INTERNAL MED Flashcards
UVEITIS (IRITIS)
o Anterior = inflammation of iris (iritis) or ciliary body (cyclitis)
o Posterior = choroid inflammation
ETIOLOGIES = systemic inflammatory diseases (spondyloarthropathies, sarcoid, Behcets), or Infectious (CMV, syphilis, TB, toxoplasmosis), trauma, etc.
SIGNS/SYMPTOMS
o Anterior = Unilateral ocular pain, redness, photophobia, excessive tearing
- Anterior usually occurs after blunt trauma
o Posterior = blurred / decreased vision
- floaters, absent symptoms of anterior involvement
- no pain
so anterior uveitis = pain
posterior uveitis = blurry/decreased vision, no pain
PHYSICAL EXAM
- CILIARY INJECTION (LIMBIC FLUSH)
- Consensual photophobia
- visual changes (if posterior)
- Inflammatory cells (WBC) + flare (protein) within aqueous humor
TREATMENT
- steroids
Anterior = topical steroids, Scopolamine, topical cycloplegics
Posterior = systemic steroids
MARCUS GUNN PUPIL (RELATIVE AFFERENT PUPILLARY DEFECT)
during swinging flashlight test: when light is shone into unaffected eye, the affected eye will also constrict
when light shone into affected eye = dilates, or only slightly constricts (so does other eye)
Test = perform the “SWINGING FLASHLIGHT TEST”
RAPD = ray (light) in affected pupil = dilates
ex: Left Afferent Pupillary Defect = When it is directed at the left eye, both pupils are 3 mm. When swung to the right eye, both pupils constrict to 2.5 mm. When swung back to the left eye, both pupils dilate back to 3 mm
Seen in OPTIC NEURITIS
ARGYLL-ROBERTSON PUPIL
pupil constricts with accommodation (switching from near to far) but DOES NOT react to bright light
MC CAUSE = NEUROSYPHILIS***
VISUAL PATHWAY DEFECT
a blindness or reduction in vision in one half of the visual field due to damage of the optic pathways in the brain.
decreased vision or blindness in half the visual field. can occur in one eye or both eyes
homonymous hemianopsia = both right sides or both left sides of visual fields are decreased/blind
(due to damage of optic tract on one side); if damage on the optic tract on the left side = goes to the left side of both eyes = then lose vision on right side of both eyes
if damage to optic tract on the right side = goes to the right side of both eyes = then lose vision in the left side of both eyes
if damage at the optic chiasm (where cross-over occurs) = goes to the inner vision of both eyes = then lose vision on lateral sides of both eyes = bitemporal heteronymous hemianopsia
if damage at the optic nerve = supplies both the inner and outer vision of the same eye –> monocular blindness
ACUTE SINUSITIS
The major organisms associated with bacterial acute sinusitis is streptococcus pneumonia, H. influenzae, and M. Catarrhalis.
With the patients history of anaphylaxis with penicillin, the best choice is D bactrim
LYME DISEASE
multi-system bacterial infection
- symptoms may not be obvious for days or weeks after the tick bite
- deer tick: Borrelia burgdorferi (gram negative spirochete)
- MC = Ixodes scapularis tick, MC sources = White-tailed deer and White-footed mice
- MC in spring and summer
- MC in Northeast, Midwest + Mid-Atlantic regions of US
highest likelihood of transmission = tick is engorged and/or has been attached for at least 72 hours
SYMPTOMS
- early localized = ERYTHEMA MIGRANS = the characteristic rash of lyme disease = expanding, warm, annular, erythematous rash - salmon color and expands over a few days or weeks. Center of rash = lighter color - “bull’s eye” appearance - central clearing. Lesion usually expands slowly over days to weeks; may be accompanied by viral-like syndrome: headaches, fever, malaise or lymphadenopathy
- 80-90% of ppl with lyme dz will develop erythema migrans rash
- early disseminated symptoms (1-12 weeks) = RHEUMATOLOGIC = arthritis (especially in large joints). NEUROLOGIC = headache, meningitis, weakness, CN palsies (ex: CN VII/facial nerve palsy). CARDIAC = AV Block, pericarditis
- may have multiple erythema migrans lesions
- late disease = persistent synovitis, persistent neurological symptoms, subacute encephalitis. Acrodermatitis chronica atrophicans = bluish discoloration of extremities (seen in Europe)
DIAGNOSIS = clinical: especially in early Lyme disease = based on presence of EM rash, hx of tick bite and arthritis; patients with EM rash are often seronegative in early stage
- Serologic testing = ELISA. if positive = Western blot
TREATMENT = Doxycycline 100mg BID x 10-21 days.
- if Kid < 8 or Pregnant = Amoxicillin x 14-21 days
- if Doxy CI and PCN allergy = Azithromycin or Erythromycin
Late/severe disease = IV Ceftriaxone if patient is experiencing 2nd/3rd degree AV heart block, syncope, dyspnea, chest pain, CNS disease (meningitis)
NEED FOR PREVENTATIVE TREATMENT?
- IDSA recommends preventive treatment with abx only in people who meet ALL of the following criteria:
⦁ the attached tick is identified as an adult or nymphal deer tick
⦁ the tick is estimated to have been attached for > 36 hours - Antibiotic treatment can begin within 72 hours of tick removal; the patient can take doxycycline if not pregnant, not breastfeeding and not < 8 years old (given amoxicillin); if allergic to PCN and doxy is CI = give azithromycin or erythromycin
- if the patient meets all of the above criteria = single dose of 200mg for adults, and 4mg/kg in children > 8
- if allergic to doxy = no prophylaxis is given
MOLLUSCUM CONTAGIOUSUM
benign viral infection of the skin
highly contagious*
POXVIRUS (poxviridae family)
MC in children, sexually active adults, and immunocompromised patients (HIV)
SPREAD VIA
⦁ skin to skin contact (MC)
⦁ Fomites
usually asymptomatic**
RISK FACTORS ⦁ children sharing baths ⦁ athletes sharing gym equipment ⦁ camp / school / public recreational places (pools) ⦁ *** swimming pools *** ⦁ sexual activity / HIV
CLINICAL MANIFESTATIONS
- In children = common on face / trunk / extremities
- In adults = common in pubic / genital region
⦁ ** Discrete 2-5mm, UMBILICATED, DOME-SHAPED, FLESH-COLORED, WAXY PAPULES
⦁ ** CENTRAL UMBILICATION **
- May express material if squeezed
- can be single or multiple
DIAGNOSIS
⦁ clinical (appearance)
⦁ may biopsy if uncertain
- will show keratin in central depression
- molluscum bodies, or Henderson-Paterson bodies are seen on histologic examination findings
- consider STD work-up in adults / adolescents
TREATMENT
⦁ NONE!!! will spontaneously resolve on its own - in about 3-6 months
⦁ other options = curettage, cryotherapy, cantharidin, podophyllin (for HPV warts), cautery, Imiquimod, TCA (trichloracetic acid), topical retinoids, Cimetidine (antiviral; usually antihistamine - H2 blocker, Tagamet - used for PUD/GERD)
ROSACEA
Chronic acneiform disorder of facial pilosebaceous units
- increased reactivity of capillaries to heat
- onset: 30-50 years old
- predominantly affects females
EXACERBATING ROSACEA FACTORS ⦁ hot liquids ⦁ spicy foods ⦁ alcohol ⦁ exposure to sun & heat ⦁ exercise
CLINICAL PRESENTATION OF ROSACEA
⦁ redness to cheeks, nose and chin
⦁ burning or stinging with episodes
⦁ skin dryness, edema
The nose, cheeks, forehead, chin, and glabella are the most commonly affected areas.
Clinical features include flushing, telangiectasias, erythema, papules and pustules, and rhinophyma.
More than 50% of patients with rosacea have ocular manifestations, and ocular findings may be the first manifestation of rosacea in some patients.
Variable erythema and telangiectasia are seen over the cheeks and the forehead. Inflammatory papules and pustules may be predominantly observed over the nose, the forehead, and the cheeks.
Prominence of sebaceous glands may be noted, with the development of thickened and disfigured noses (rhinophyma) in extreme cases. Unlike acne, patients generally do not report greasiness of the skin; instead, they may experience drying and peeling. The absence of comedones is another helpful distinguishing feature.
Rhinophyma may occur as an isolated entity, without other symptoms or signs of rosacea. Rhinophyma can be disfiguring
Manifestations of ocular rosacea range from minor irritation, foreign body sensation, dryness, and blurry vision to severe ocular surface disruption and inflammatory keratitis. Patients frequently describe a gritty feeling, and they commonly experience Blepharitis and conjunctivitis. Other ocular findings include lid margin and conjunctival telangiectasias, eyelid thickening, eyelid crusts and scales, chalazia and hordeolum, punctate epithelial erosions, corneal infiltrates, corneal ulcers, corneal scars, and vascularization
Ocular rosacea is most frequently diagnosed when patients also suffer from cutaneous disease. However, ocular signs and symptoms may occur prior to cutaneous manifestations in 20% of patients with rosacea
4 SUBTYPES OF ROSACEA ⦁ erythematotelangiectatic rosacea ⦁ papulopustular rosacea ⦁ phymatous rosacea (large nose) ⦁ ocular rosacea
TREATMENT FOR ROSACEA
- to minimize precipitating factors
- TOPICAL ANTIBIOTICS = 1st line therapy for mild to moderate patient
use gel or creams
Azelaic acid
Metronidazole - most common
Erythromycin
Clindamycin
Brimonidine (Mirvaso) = alpha -2 agonist = vasoconstrictor; best for facial flushing / persistent redness) - brimonidine can also be used for acute angle closure glaucoma
Topical Ivermectin cream (Soolantra) = for ppl who get papulopustular acneiform rosacea due to being immunologically sensitive to mites
SYSTEMIC ANTIBIOTICS = for mod/severe rosacea
⦁ Tetracycline
⦁ Doxycycline / Minocycline
⦁ Erythromycin
FACIAL REDNESS/FLUSHING TX = BRIMONIDINE (MIRVASO)
PAPULOPUSTULAR DISEASE TX = metronidazole, azelaic acid, ivermectin (soolantra) = 1st line; can try sodium sulfacetamide
can do oral antibiotics for mod/severe = tetracyclines (doxy/tetra), oral metronidazole, oral ivermectin, sodium sulfacetamide
ACNE VULGARIS
ACNE = eruption VULGARIS = common
= “common eruption” of skin that occurs when hair follicles (pores) get blocked up/plugged with dead skin cells or oil
once the hair follicle is blocked ==> forms red raised bump on the skin
Acne = particularly common among teenagers because of skin changes that occur during puberty
- affects males more during puberty
- affects females more during later years
DIFFERENT TYPES OF ACNE
⦁ mild acne = whiteheads + blackheads
⦁ moderate acne = pustules
⦁ severe acne = cysts + nodules
3 MAIN LAYERS OF SKIN
⦁ epidermis (5 sublayers) = “Come Lets Get Some Beer”
- stratum corneum = outermost
- stratum lucidum = in palms + feet (thicker)
- stratum granulosum
- stratum spinosum = thickest layer
- stratum basale
⦁ dermis
- connective tissue
- sweat glands
- nerve endings
- lymphatic vessels
- blood vessels
- sebaceous glands - secretes sebum (oil) - helps transport nutrients and lubricates the skin
- hair follicles (shaft, root, bulb)
When arrector pili muscle contracts, sebum gets squeezed out
- Sebum softens the hair shaft and prevents it from getting brittle
- Sebum prevents moisture loss in the skin
- sebum is also slightly acidic, so helps to deter pathogens
⦁ hypodermis
- made of fat and connective tissue that anchors the skin to the underlying muscle
CAUSE OF ACNE - not fully understood - combination of factors
⦁ keratin plugs
⦁ sebum
⦁ bacterial overgrowth
- 4 factors involved ⦁ follicular hyperkeratinization ⦁ increased sebum production ⦁ Propionibacterium acnes within the follicle ⦁ inflammation
1) KERATIN PLUGS
- dead keratinocytes (dead skin cells) + keratin + melanin
- when hair follicles and keratinocytes overproduce keratin (hyperkeratosis), –> leads to more keratin plugs forming –> blocks opening of hair follicle (pore)
- clogged sebaceous glands due to increased proliferation of follicular keratinocytes
2) SEBUM
- released by sebaceous glands in response to increased androgen hormone production that is released during puberty
- also causes blockage of pore, just like keratin plug
- increased sebum production due to increased androgens - MC after puberty, or when increased androgen levels with PCOS or Cushing’s disease
3) BACTERIAL OVERGROWTH
- when excess of keratin plugs or sebum or both ==> can start to fill up a hair follicle (pore), but doesn’t quite plug it up all the way
- if hair follicle is still open to the surface of the skin (open comedo = blackhead)
- blackheads are black because the melanin in keratin plug gets oxidized when exposed to air - becomes darker than normal
- bacteria = Propionibacterium acnes (now called CUTIBACTERIUM ACNES) = always present in follicle - part of normal skin flora, usually don’t cause problems
- if follicle gets completely plugged up with keratin and sebum, then bacterium gets closed off
==> closed comedo where the bacteria continues to grow, as bacteria feasts on keratin and sebum. Bacteria overgrowth as it has nowhere else to go
Triglycerides in the sebum (large component of sebum) particularly is what the bacteria love to thrive on
- P. acne produces lipase, which converts sebum into inflammatory fatty acids that damages healthy cells –> leads to an inflammatory response
- bacterial overgrowth attracts immune cells, which start attacking bacteria ==> white pus (whitehead) with surrounding red inflammation
CAUSES OF ACNE
- genetic + environmental factors
⦁ hyperkeratosis (genetic component)
⦁ hormones (ex: PCOS - increased androgen levels) (ex: Cushing’s disease = increased androgens)
⦁ products (can block pores)
⦁ behaviors (ex: wearing a headband) (ex: excessive face washing –> irritation –> more acne)
⦁ psychological stress –> increased cortisol –> increased sebum secretion
⦁ certain foods (dairy or chocolate)
acne can affect one’s physical appearance / confidence –> leads to more stress –> leads to more acne / etc.
wearing a headband / helmet / hat etc = contact acne (ACNE VENENATA)
HORMONES - increased androgen levels
Acne vulgaris is thought to be an insulin-like growth factor 1 mediated disease
⦁ Milk products
⦁ hyperglycemia
⦁ smoking
- can all lead to increased insulin-like growth factor 1
Insulin-like growth factor is thought to activate the 5-alpha-reductase enzyme for conversion of testosterone to dihydrotestosterone. It also stimulates androgen release by the adrenal gland and gonads as well as androgen receptor signal transduction. These factors together may stimulate the eruption of acne lesions.
Elevated testosterone and exogenous supplementation of testosterone have also been associated with acne formation. Because hormone levels are elevated and labile in adolescents, this is a significant cause of acne in teens
Androgens, not estrogens, stimulate the growth and secretion of the sebaceous glands. In teenagers, comedonal acne correlates with the rise of dehydroepiandrosterone (DHEA) serum levels.
androgens are what kick off the sebaceous glands -> increased sebum production. DHEA (precursor of testosterone) is what increases sebum production –> seborrhea.
No androgens = no acne
ACNE VULGARIS MC OCCURS ON LOCATIONS OF ⦁ face / neck ⦁ shoulders ⦁ chest ⦁ back - sites of oil glands
- COMEDONES = small, noninflammatory bumps from clogged pores
⦁ blackheads = open comedones (incomplete blockage)
⦁ whiteheads = closed comedones (complete blockage)
4 TYPES OF ACNE VULGARIS (based on severity)
⦁ type I (mild acne) = no scarring, and has few small comedones, may have some papules / pustules
⦁ type II (moderate acne) = no scarring, larger comedones / larger amounts of papules / pustules
⦁ type III (moderately severe acne) = some scarring, have papular and pustular acne
⦁ type IV (severe) = severe scarring and nodulocystic acne - invades deeper into the dermis
TREATMENT - depends on severity
⦁ type I (mild acne)
- topicals such as benzoyl peroxide or salicylic acid - decreases P. acne concentration, removes the top keratin layer, reduces inflammation. SE = erythema / dermatitis
- topical abx = clindamycin or erythromycin
- ** CLINDAMYCIN can be used with BENZOYL PEROXIDE to reduce resistance ***
- topical retinoids - help to alter pilosebaceous glands –> antibacterial, decreases comedone formation, reduces inflammation
- OCPs = decreases androgen –> reduces sebum production
⦁ mild to moderate = topical retinoids, topical antibiotics, benzoyl peroxide
⦁ type II (moderate acne) = topical retinoids, oral abx such as doxycycline / minocycline / bactrim
- spironolactone for hormonal regulation
⦁ type III and IV = isotretinoin (Accutane) = oral retinoid = synthetic vitamin A derivative - affects sebum secretion
- SE = teratogenicity
Spironolactone = decreases androgen –> reduces sebum production
ISOTRETINOIN - affects all 4 MOA of acne!
- teratogen
- photosensitivity - specifically to UVA
- labs = CBC, lipid panel, LFTs
- hepatitis (increased LFTs)
- increased triglycerides / cholesterol
- arthralgias
- leukopenia (CBC)
- premature long bone closure
- dry skin
- monitor for SE of increased depression / suicidality
- 2 pregnancy tests prior to initiation of treatment + monthly pregnancy tests / labs, 2 forms of contraception - used at least 1 month prior to starting Accutane and 1 month after d/c accutane
the effect of most phototoxic medications is through their activation by UVA light (which comprises 95% of all UV light we receive from the sun).
TREATMENT FOR ACNE SCARS
- retinoids, peels, microdermabrasion, lasers
PSORIASIS
H
ECZEMA
H
SERONEGATIVE SPONDYLOARTHROPATHIES
SERONEGATIVE SPONDYLOARTHROPATHIES
Seronegative = RF not found in the blood
⦁ Young male predominance: < 40 ⦁ inflammatory arthritis ⦁ uveitis and sacroiliitis ⦁ + HLA-B27 gene susceptibility ⦁ Negative ANA and RF ⦁ + Enthesitis = inflammation where ligaments and tendons insert into bone
⦁ PEAR = Psoriatic Arthritis, Enteropathic Arthritis (IBD), Ankylosing Spondylitis, and Reiter’s or Reactive Arthritis
HUNTINGTON’S DISEASE
- Human Basal Ganglia - consists of Putamen and Caudate nucleus
- Autosomal dominant - so if one parent has huntington’s - kid has 50% of getting huntington’s
- affects motor function, cognition and behavior
- mean age of onset = 40
- mean duration of illness = 20 years - is slowly progressive and neurodegenerative
- MOA = causes brain cells to waste away
- most live until mid 60’s - early 70’s; however if more progressive = can be fatal much sooner
CHARACTERIZED BY:
⦁ Behavioral / Psychological changes
⦁ Chronic progressive chorea
⦁ Dementia
HTT (huntingtin gene) is affected, which encodes the protein huntingtin - on chromosome 4
HD expands the CAG trinucleotide in HTT gene (cytosine - adenine - guanine ) = glutamine - sequence is repeated longer than usual
MRI Findings with HD = Atrophy of caudate & putamen (neostriatem) = most prominent on MRI = can actually see this disease in an MRI
- also see ventricular enlargement
SIGNS/SYMPTOMS
SYMPTOMS (ADULT ONSET)
⦁ Chorea affects the limbs and trunk
⦁ Dystonia (involuntary contractions of muscles)
⦁ Rigidity
⦁ Postural instability
⦁ Myoclonus (quick, involuntary muscle jerk)
⦁ Nystagmus
SYMPTOMS (JUVENILE ONSET) ⦁ Very rare ⦁ Bradykinesia ⦁ Rigidity ⦁ Quicker progression
EARLY PSYCHOLOGICAL MANIFESTATIONS - behavioral changes: personality, cognitive, intellectual and psychiatric - including irritability ⦁ Depression ⦁ Personality changes - Memory loss - Impulsive behavior - Moodiness - Antisocial behavior - Emotional outbursts
OTHER EARLY SIGNS
⦁ lack of initiative
⦁ loss of spontaneity
⦁ inability to concentrate
EARLY PHYSICAL SIGNS
⦁ fidgeting
⦁ restlessness
LATER PHYSICAL SIGNS
⦁ chorea - rapid, involuntary or arrhythmic movement of the face, neck, trunk and limbs initially. Chorea worsens with voluntary movements and stress. Usually disappears with sleep
⦁ dystonic posturing
⦁ progressive rigidity
⦁ akinesia (absence/loss of control of voluntary movement)
⦁ dementia - most develop dementia before 50y/o
- Also experience gait abnormalities / ataxia = often irregular and unsteady. Incontinence. Facial grimacing
Death = often due to aspiration from pneumonia - due to discoordinated swallowing, or suicide.
PHYSICAL EXAM
- restlessness
- fragility
- quick, involuntary hand movements
- brisk DTRs
DIAGNOSTIC STUDIES
CT SCAN = cerebral and caudate nucleus atrophy and increased ventricular size
- MRI = similar findings
⦁ MRI - shows caudate atrophy & increased ventricular size
⦁ Genetic Testing
- sensitive & specific
- easy confirmation of clinical diagnosis, diagnosis of atypical patients, and presymptomatic testing in at-risk individuals (confirmation of HD)
TREATMENT
- treatment of symptoms only - no medication available to change the course of HD/stop disease progression
- usually fatal within 15-20 years
- treatment directed at downregulating dopaminergic neurotransmission
- To suppress the chorea
⦁ Tetrabenazine or Deutetrabenazine (VAMT Inhibitor) = inhibits presynaptic vesicular monoamine transporter type 2- inhibits dopamine transport –> dopamine depletion. SE = depression - can add neuroleptic, or can switch to FGA or SGA by adding neuroleptic and tapering off VAMTI)
⦁ Neuroleptics (antipsychotics) - deplete cerebral dopamine (Neuroleptics (antipsychotics) act by blocking dopamine transmission, and have the potential benefit of treating both chorea and certain psychiatric symptoms such as agitation and psychosis
⦁ Risperidone (Risperdal)
⦁ Olanzapine (Zyprexa)
⦁ Aripiprazole (Abilify)
Anticonvulsants
⦁ Clonazepam (Klonopin)
⦁ Valproic Acid (Depakote)
Antidepressants for depression
⦁ Fluoxetine (Prozac)
⦁ Sertraline (Zoloft)
⦁ Nortriptyline (Aventyl, Pamelor)
- SE from many of the drugs used to treat HD may include hyper-excitability, fatigue, and restlessness
- Antipsychotic meds may cause SE that mimic the signs of Parkinson’s disease - include involuntary twitching in the face & body (tardive dyskinesia)
PARKINSON’S DISEASE
- PD is a progressive neurodegenerative disorder that is characterized by:
⦁ resting & postural Tremor
⦁ Rigidity
⦁ Akinesia (or bradykinesia)
⦁ Postural instability
TRAP = tremor (resting & postural), rigidity, akinesia (or bradykinesia), postural instability
PD tends to affect older populations - usually hits around age 60, but younger onset can occur
- *UNILATERAL - usually tremor starts in hand, but can also affect foot / leg
- Gait = shuffling - arms don’t swing
- Resting Tremor (unlike essential tremor - tremor with action)
PD = Leading cause of neurologic disease in patients over 65 - usually begins after age 50, but can occur at earlier stages
- the earlier the onset of symptoms = worse prognosis
PATHOPHYSIOLOGY
-Dopamine depletion from the basal ganglia - results in the major disruption in connections to the thalamus & motor cortex
loss of dopaminergic nerve terminals in substantia nigra - primarily D1 + D2 receptors are relevant in PD (5 types of dopamine receptors: D1-D5)
- Also relative increase in cholinergic interneuron activity occurs due to degeneration of dopamine pathways, which contributes especially to tremor
LEWY BODIES - believed to be the pathological hallmark of PD
- not specific to PD
- found in up to 10% of brains of older adults
- Lewy bodies are generally thought to be toxic, but some studies have suggested that they may actually be neuroprotective (defense mechanism)
- lewy bodies appear
POSSIBLE CAUSES / RISK FACTORS FOR PD ⦁ primary cause = unknown ⦁ family history ⦁ genetics - Parkin gene was found with early-onset Parkinson's ⦁ immunologic & inflammatory factors ⦁ aging
FACTORS THAT REDUCE THE RISK OF PD ⦁ caffeine intake ⦁ moderate to vigorous physical activity ⦁ statin use & lipid levels...? (unsure) ⦁ NSAID use...? (unsure)
SIGNS/SYMPTOMS
⦁ Tremor
- occurs in 75% of ppl with PD
- tremor = the most visible manifestation with PD***** - usually affects distal segment of limbs - mainly hands & feet
- called “pill rolling”
- tremor = usually unilateral & appears at rest, disappears with movement & sleep
⦁ Rigidity
- resistance to movement - “cog-wheeling” or ratchet-like movements
- rigidity starts unilaterally - then progresses to involve both sides of the body
⦁ Akinesia
- (bradykinesia)
- The most debilitating symptom of PD*****
- slowness in initiating & performing movements
- difficulty in sudden, unexpected stopping of voluntary muscles
- difficulty turning
- feel frozen in place, especially when moving through a doorway or preparing to turn
⦁ Postural Instability
- lean forward to maintain center of gravity
- take small “shuffling” steps without swinging the arms
- prone to fall, especially backwards
OTHER SYMPTOMS OF PARKINSON'S DISEASE ⦁ Emotional and voluntary facial movements become limited and slow leading to a “mask like” facies - lack expression ⦁ Loss of blinking reflex ⦁ Tongue, palate and throat muscles become rigid --> leads to drooling ⦁ Uncontrolled sweating ⦁ Sebaceous gland secretion - Seborrhea ⦁ Micrographia (small writing) ⦁ Hypophonia (weak voice due to diminishing vocal muscles) ⦁ Depression ⦁ Orthostatic hypotension ⦁ Constipation ⦁ Impotence ⦁ Urinary incontinence ⦁ Dementia
DIAGNOSIS OF PD
- practical diagnosis of PD during life is based on clinical impression
- no physiologic tests or blood tests can confirm the diagnosis
- neurodiagnostic testing with computerized imaging is almost always unrevealing
- GOLD STANDARD for diagnosis = Neuropathologic Examination (…after pt has died)
- 2/3 cardinal manifestations of PD must be present to make the diagnosis of idiopathic PD
⦁ tremor
⦁ bradykinesia
⦁ rigidity
RATING SCALE FOR PD
UPDRS = Unified Parkinson’s Disease Rating Scale
⦁ I. Mentation / Behavior / Mood
⦁ II. Activities of Daily Living (subjective)
⦁ III. Motor Examination (objective)
⦁ IV. Complications of Therapy
TREATMENT
PD TREATMENT - catered towards increased dopamine levels - as normally high concentrations of dopamine in the basal ganglia is reduced in Parkinsonism
- Pharm tx = given in attempts to restore dopamine activity in brain, as well as manage SE of dopaminergic therapy
1) LEVODOPA / CARBIDOPA (SINEMET)
“GOLD STANDARD OF TREATMENT” = traditionally used 1st line, very effective
- Sinemet tends to be less effective with prolonged use in some patients - build up tolerance over time, which is why you ideally want to hold off on Sinemet for as long as you can
- effectiveness substantially decreases after the 3rd year of treatment, and may return to pre-treatment levels in 6-7 years
- Sinemet completely or partially relieves akinesia, rigidity, and tremor in about 80% of PD patients. It is the preferred initial treatment in patients over 70, particularly those with dementia
- MOA
- Levodopa = metabolic precursor to dopamine. Dopamine cannot cross the BBB, but Levodopa can. After crossing the BBB, Levodopa is decarboxylated into dopamine
- Dopamine is then stored in presynaptic neurons until stimulated for release
- Carbidopa = decarboxylase inhibitor - prevents Levodopa from being converted into dopamine in the periphery - keeps Levodopa around longer centrally so that plasma levels of Levodopa remain high so that more is available to enter the brain. Carbidopa therefore also helps to prevent some SE (like N/V) that is caused by dopamine in the periphery
- which is why Levodopa/Carbidopa combo (Sinemet) is more beneficial
SE of Sinemet = ⦁ low BP (opposite of MAOB inhibitors)
⦁ dizziness ⦁ HA ⦁ insomnia ⦁ arrhythmia
⦁ GI effects - N / V / D / C
⦁ hair loss ⦁ Dyskinesias*** - (80%) - more common when used in younger patients
⦁ confusion ⦁ anxiety ⦁ vivid dreams / hallucination
To try & prevent these SE - try giving Sinemet in smaller doses more frequently
- reduce or stop evening dose if severe psychiatric effects occur
2) MAOB- INHIBITORS
⦁ SELEGILINE (Eldepryl, Zelapar) (older & more SE)
⦁ RASAGILINE (Azilect)
MOA = - stops the breakdown of dopamine; MAOB breaks down dopamine, so MAOB-inhibitors prevent the breakdown of dopamine
- MAOB inhibitors enhance levadopa levels
- **Often used 1st line in patients with mild PD/slow progression PD, and want to delay need for Levodopa…Has neuroprotection
- Can also be used as adjunctive therapy with Sinemet to decrease “wearing off effect”
3) DOPAMINE AGONISTS ⦁ Bromocriptine (Parlodel); Pergolide (Permax) = older = ergo derivatives ⦁ Pramipexole (Mirapex) ⦁ Ropirinole (Requip) ⦁ Rotigotine (Neupro) = patch
- moderate symptoms in younger patients may be treated with dopamine agonists as first line**
MOA
- stimulates dopamine receptors in the substantia nigra
- effective in delaying motor complications during the first 1-2 years of treatment
- improvement in impaired movements & disability
- may delay the need for levadopa/carbidopa
***Dopamine agonists are typically avoided in the ELDERLY due to significant SE
Rotigotine (Neupro) = transdermal patch - available because of diminished ability to swallow with PD
4) COMT INHIBITORS
⦁ ENTACAPONE (COMTAN)
⦁ TOLCAPONE (TASMAR)
*** - COMT inhibitors reduces the need for levadopa/carbidopa, but CAN ONLY BE USED in patients who are taking levadopa / carbidopa - but often able to decrease Sinemet dose
MOA
- COMT breaks down levodopa in the periphery. COMT inhibitors prevent the breakdown of levodopa in the periphery, therefore increasing the levodopa concentration, leading to more dopaminergic stimulation of the brain (COMT inhibits MAOB from degrading levodopa)
Entacapone (Comtan) used more than Tolcapone (BBW for hepatotoxicity - have to check LFTs every 2 weeks x 6 months & need written documentation of consent)
STALEVO = combo of Levadopa / Carbidopa (sinemet) + Entacapone
5) AMANTADINE (SYMMETREL)
MOA = unknown - thought to inhibit NMDA receptors to potentiate dopaminergic responses
Indications = for mild symptoms or for treatment of levodopa induced dyskinesia (given in addition to levodopa/carbidopa to treat SE of dyskinesia)
*USE AMANTADINE WITH CAUTION IN RENAL DYSFUNCTION
- Amantadine induced Levido Reticularis (rash - that pale ppl get - purplish splotches)
6) ACETYLCHOLINE-BLOCKING AGENTS
Block acetylcholine = anticholinergic drugs (sympathetic
⦁ TRIHEXYPHENIDYL (ARTANE)
⦁ BENZTROPINE (COGENTIN) - reverses extrapyramidal symptoms SE from antipsychotics
Can give anticholinergics to restore balance between dopamine (low) and acetylcholine (which is now relatively high - has not increased, but is high compared to dopamine - which levels should be balanced).
- used primarily for tremor, but also helps with rigidity
- no effect on akinesias
- drugs differ in potency
- if patient does not respond to one drug, a trial with another is warranted**
CONTRAINDICATIONS TO ANTICHOLINERGICS
⦁ BPH
⦁ Obstructive GI disease
⦁ Angle closure glaucoma (also a CI to Sinemet)
MYASTHENIA GRAVIS
- Autoimmune peripheral nerve disorder - characterized by weakness + fatigue of skeletal muscle
- HLA-DR3
MOA = Inefficient skeletal muscle neuromuscular transmission due to developing autoimmune autoantibodies against acetylcholine (nicotinic) receptors (AchR-Ab) at neuromuscular junction —> this leads to a destruction of ACh receptors = a decrease in the number of acetylcholine receptors available because of AchR-Ab binding.
- This leads to progressive weakness with repeated muscle use, and recovery after periods of rest
- 10-20% of patients are antibody negative - they may have antibodies directed against another target - muscle specific receptor tyrosine kinase (MuSK)
- T cells then bind to acetylcholine receptors and activate B cells
- most patients (75%) with MG have thymic abnormalities: HYPERPLASIA OR THYMOMA*** or other autoimmune disorders
EPIDEMIOLOGY
- prevalence has been increasing over past 5 decades
- BIMODAL DISTRIBUTION = early peak in 2nd/3rd decades (female predominance), and late peak in 6th-8th decade (male predominance)
CLINICAL PRESENTATION
- 2 categories = 1) Ocular + 2) Generalized muscle weakness
o OCULAR WEAKNESS
⦁ usually the 1st presenting symptom, and is more severe than generalized
⦁ weakness of EOM –> DIPLOPIA, PTOSIS (more prominent in upward gaze)
⦁ weakness is worsened with repeated EOM use; pupils are spared
⦁ “Curtain Sign = The clinical examiner might also try to elicit the “curtain sign” in a patient by holding one of the person’s eyes open, which in the case of MG will lead the other eye to close
o GENERALIZED MUSCLE WEAKNESS
⦁ least in the morning; worsened with repeated muscle use throughout the day; relieved with rest
⦁ have normal sensation and normal DTRs
⦁ BULBAR (OROPHARYNGEAL WEAKNESS) = Jaw weakness, especially with prolonged chewing. Dysphagia, Dysarthria. Weakness of orbicularis oris muscle –> “Myasthenic Sneer” - lost their smile, patient appears expressionless
⦁ RESPIRATORY MUSCLE WEAKNESS = may lead to respiratory failure / risk of aspiration = Myasthenic crisis
⦁ weight of head overcomes extensors –> results in “dropped head syndrome”
⦁ limbs have proximal weakness - arms are more affected than legs
⦁ wrist and finger extensors and foot dorsiflexors involved
CLINICAL COURSE
- early-on symptoms are transient = fine in the morning, but worse later in the day or when tired or have exercised
- maximal extent of disease seen in 77% of patients after 3 years
DIAGNOSIS
- serology - Acetylcholine receptor antibodies
- however 40-50% have seronegative MG = have Ab to MuSK. (muscle-specific tyrosine kinase)
- A small % are double seronegative
Electrodiagnostic studies
- Rapid Nerve Stimulation (RNS) - with MG, action potential will eventually tire out, and not reach threshold
- Single Fiber Electromyography (SFEMG) - shows jittering of individual muscle fibers
- Pharmacological Testing = injection of IV Edrophonium (Tensilon) = an indirect cholinergic agonist (i.e., it inhibits acetylcholinesterase to transiently elevate synaptic acetylcholine levels
- can be difficult to determine if weakness/respiratory failure is from myasthenic crisis (severe MG) or cholinergic crisis (result of too much acetylcholine from acetylcholinesterase inhibitors)
o If flaccid paralysis improves with Tensilon = Myasthenic crisis
o If flaccid paralysis worsens with Tensilon = cholinergic crisis (weakness, N/V, pallor, sweating, salivation, diarrhea, miosis, bradycardia, respiratory failure) - Ice pack Test = place ice pack on eyelid x 10 minutes –> leads to improvement of ptosis in ocular MG
- according to uptodate: serological studies & electrodiagnostic studies = most reliable
Tensilon test and ice pack test = sensitive, but too many false-positive results
All patients should have a CT to rule out thymic enlargement or thymoma with MG. Xray may detect enlargement/thymoma, however, a negative xray does not rule this out…
TREATMENT
- 1st line = Pyridostigmine or Neostigmine = Acetylcholinesterase Inhibitors - increases acetylcholine receptors by decreasing breakdown via acetylcholinesterase.
SE = abdominal cramps, diarrhea, cholinergic crisis (weakness, N/V, pallor, sweating, salivation, diarrhea, miosis, bradycardia, respiratory failure)
- Edrophonium (Tensilon) = only for diagnostic purposes, not for tx of MG
- 2nd line tx = Immunosuppression = Plasmapharesis or IVIG in myasthenic crisis for rapid response.
- For chronic immunosuppression = Steroids. Can also use Azathioprine or Cyclosporine as alternatives
- Thymectomy if thymoma present
- Avoid Fluoroquinolones + Aminoglycosides = may exacerbate Myasthenia
GUILLAIN-BARRE SYNDROME
- Acquired inflammatory DEMYELINATING POLYRADICULONEUROPATHY of peripheral nerves
PATHOPHYSIOLOGY = - usually provoked by preceding infection - acute immune-mediated demyelination and axonal degeneration that slows nerve impulses –> leads to symmetric weakness and paresthesias. A post-infection immune response cross-reacts with peripheral nerve components * Causes generation of antibodies to gangliosides that cause axonal injury or immune response to myelin. Usually presents 2-4 weeks after infection
***PRECEDED BY INFECTION
- usually Campylobacter Jejuni (MC)
Others = respiratory or GI infections, CMV, EBV, HIV, mycoplasma
- small % of GBS result from immunizations, surgery, trauma + bone marrow transplant
CLINICAL MANIFESTATIONS
- ASCENDING WEAKNESS + PARESTHESIAS - usually SYMMETRIC
- decreased DTR (LMN lesion)
- may involve muscles of respiration or bulbar muscles (swallowing abnormalities); CN VII palsy
- Autonomic dysfunction –> Tachycardia, Hypo or hypertension, Breathing difficulties
⦁ Symmetric (Bilateral) ASCENDING muscle weakness with ABSENT / DECREASED DTRs; weakness usually starts in proximal legs
⦁ severe respiratory muscle weakness - 30% of patients require ventilator support
⦁ Paresthesias in hands/feet = common (80%); sensory abnormalities on examination are frequently mild
⦁ Often prominent severe back pain
⦁ Dysautonia (70%) = ANS doesn’t work properly => tachycardia, bradycardia, urinary retention, HTN alternating with hypotension, orthostatic hypotension, ileus, loss of sweating
DIAGNOSIS
o Lumbar Puncture (LP) - normal or xanthochromia (yellow)
- will show elevated CSF protein** (> 400)
- will have normal WBC count in CSF
- will have normal glucose
= known as ALBUMINOCYTOLOGICAL DISSOCIATION
- high protein usually seen after 1-3 weeks of symptom onset
o Electrophysiologic studies = decreased motor nerve conduction velocities and amplitude
TREATMENT
- Plasmapheresis (best if done early) = removes harmful circulating auto-antibodies that cause demyelination. Equally as effective as IVIG
- IVIG = suppresses harmful inflammation/auto-Abs, and induces remyelination. Most recover within months
Uptodate = When both therapies are equally available and there are no contraindications for either, we suggest treatment with IVIG.
- Mechanical ventilation if respiratory failure develops
PROGNOSIS
- 60% have full recovery in 1 year; 10-20% have permanent disability
MULTIPLE SCLEROSIS
**The MOST common acquired disease of myelin
Autoimmune, inflammatory, demyelinating disease of the CNS
- Axon degeneration of WHITE MATTER of the brain, spinal cord and optic nerve
MC in women + young adults (20-40)
- myelin (sheath) function = increases the speed at which impulses propagate along the myelinated fiber
MS = autoimmune dz in which the body mistakenly directs antibodies + WBCs against proteins in the myelin sheath
- this results in inflammation + injury to the sheath and ultimately to the nerves that it surrounds
- Result = multiple areas of scarring (sclerosis)
The areas of demyelination are found scattered in the white matter of the
⦁ brain
⦁ spinal cord
⦁ optic nerve
- this damage can eventually slow or block nerve signals that control muscle coordination, strength, sensation, and vision
- initiating cause is unknown - thought to have genetic + environmental causes
PATHOGENESIS
- auto-immune mediated inflammatory demyelination + axonal injury
o peri-vascular infiltration by lymphocytes + monocytes
o MCH (major histocompatibility complex) antigen expression
o HLA-DR2 = increases risk
- MS is characterized by relapses followed (in most cases) by some degrees of recovery (relapsing - remitting = RRMS)
- this eventually progresses to a continual disease
AREAS COMMONLY AFFECTED BY MS
⦁ Optic nerve (optic neuritis)
⦁ Corticobulbar tracts = affects speech + swallowing
⦁ Corticospinal tracts = affects muscle strength
⦁ Cerebellar tracts = affects gait + coordination
⦁ Spinocerebellar tracts = affects balance
⦁ Longitudinal fasciculus = affects conjugate gaze + EOMs
⦁ Posterior cell columns of spinal cord = affects proprioception + vibratory sense
EPIDEMIOLOGY
- incidence rate is increasing
- usually occurs between ages 15-50*
- more frequent in women*
- genetic link - established by higher incidence in monozygotic twins
Geographical factors = more common in countries with temperate climates (Europe, southern canada, northern US, southeastern Australia); reason is unknown
- Northern latitude populations = very high incidence*** (no populations with a high risk for MS exist between 40N and 40S)
Environmental Factors = many viruses + bacteria have been suspected of causing MS - most recently EBV**
- some studies have suggested that developing an infection at a critical period of exposure may lead to conditions conducive to the later development of MS (a decade or more later)
SYMPTOMS OF MS
⦁ Lhermitte’s Symptoms = weakness / numbness / tingling / unsteadiness in a limb (barber chain phenomenon - an electrical sensation that runs down the back and into the limbs. In many patients, it is elicited by bending the head forward
⦁ unilateral visual impairment
⦁ fatigue
⦁ spastic paraparesis (spastic partial paralysis of lower limbs)
⦁ diplopia
⦁ disequilibrium
⦁ muscle weakness
⦁ sphincter disturbance - such as urinary urgency or hesitancy
⦁ dysarthria
⦁ mental disturbance - such as depression
SIGNS OF MS ⦁ Optic Neuritis = often the initial episode/sign of MS - pale disc, large cup to disc ratio ⦁ ophthalmoplegia ⦁ nystagmus ⦁ spasticity or hyperreflexia ⦁ Babinski sign ⦁ absent abdominal reflexes ⦁ labile or changed mood
1) SENSORY DEFICITS
- pain
- fatigue
- numbness
- paresthesias in limbs
- muscle cramping
TRIGEMINAL NEURALGIA = chronic pain disorder that affects the trigeminal nerve; Symptoms include facial pain, difficulty in chewing, speaking, and brushing
UHTOFF’S PHENOMENON = worsening of symptoms with heat = exercise, fever, hot tubs
LHERMITTE’S SIGN = neck flexion causes shock pain that radiates from spine down the leg
2) OPTIC NEURITIS
- Marcus Gunn Pupil - during swinging flashlight test = affected eye dilates with light and constricts without light
3) MOTOR = UPPER MOTOR NEURON INVOLVEMENT
- spasticity
- positive (upwards) Babinski
4) SPINAL CORD SYMPTOMS
- Bladder, Bowel or Sexual dysfunction
5) CHARCOT’S NEUROLOGIC TRIAD
- Nystagmus
- Staccato speech
- Intentional tremor
The majority of patients have resolution of their initial symptoms, but then fall into the following pattern:
⦁ RRMS (Relapsing–Remitting MS) - there is an interval of months to years after the initial episode before new symptoms develop or original symptoms reoccur
⦁ RRMS = type of MS seen in the majority of patients
- Infection, fever, + trauma can precipitate or trigger exacerbations
- relapses are more likely during the 2-3 months after pregnancy (immune system decreases while pregnant, so not attacking myelin, then after pregnancy, comes back)
- as the disease progresses, there is an increasing disability with weakness, spasticity, ataxia, impaired vision, and urinary incontinence
4 TYPES OF MS
- “Benign” MS = no disability occurs, return to normal between attacks
- RRMS = Relapsing-Remitting MS = never new disability between attacks, but progressively deteriorating
- SPMS = Secondary Progressive MS = no new disability between attacks but progressively deteriorating = just like RRMS, but then eventually progresses to a steady increase in disability
- PPMS = Primary Progressive MS = steady increase in disability, even without attacks
DIAGNOSIS
- MRI - IV Gadolinium enhances acute lesions
MRI of head or cervical cord = clinically definite in 85% of MS patients
- hx, PE, neurological exam, signs/symptoms
CT = not helpful
CSF can be helpful when an MRI is not confirmatory = usually normal, but can show - high protein, high lymphocytes, high IgG, myelin antibodies, and oligoclonal bands
o test results can be altered in a variety of inflammatory neurologic disorders, so CSF results are not specific for MS; do CSF if hx/PE/signs/symptoms = suspicious of MS, but MRI is negative
- DEFINITIVE DIAGNOSIS OF MS*
- requires intermittent or progressive CNS symptoms supported by the evidence of 2 or more CNS white matter lesions occurring in an appropriately aged patient**
- must indicate involvement from different parts of CNS at different times
PROBABLE DIAGNOSIS OF MS
- multifocal white matter disease, but only 1 clinical attack…or a history of at least 2 clinical attacks but signs of only 1 lesion
KURTZKE EXPANDED DISABILITY STATUS SCALE (EDSS) = used to measure disease progression by assigning a severity score (0-10) to patient’s clinical status
TREATMENT
1) STEROIDS = mainstay of tx for acute attacks
- helps to reduce inflammation + improve nerve conduction. Long term administration of steroids does not alter the course of the disease, however, and long term use can have harmful SE
2) PLASMAPHARESIS (plasma exchange) = treatment for acute exacerbations that are not responsive to steroids; Plasma is removed from blood, to remove antibodies to myelin, mixed with albumin, then put back in
IMMUNE MODIFIERS
⦁ Interferon 1a
⦁ Interferon 1b
⦁ Glatiramer acetate
DRUGS FOR PROGRESSIVE MS = IMMUNOSUPRRESSANTS ⦁ Glatiramer acetate (Copaxone) ⦁ Dimethyl fumarate (Tecfidera) ⦁ Fingolimod (Gilenya) ⦁ Teriflunomide (aubagio) ⦁ Natalizumab (Tysabri) ⦁ Alemtuzumab (Lemtrada) ⦁ Miloxantrone
Amantadine (anti-viral - also used in parkinsons) = helpful for fatigue in MS
ADHD
has to affect them in different areas of their life, in multiple settings: school/work, home, etc.
Manifests in childhood with symptoms of hyperactivity, impulsivity and/or inattention
- some genetic component as well as environmental factors. Increased chance of sibling having ADHD, and even higher chance of twin having ADHD
Symptoms affect cognitive, academic, behavioral, emotional and social functioning
these patients experience their emotion in a more intense fashion; may seem to be an “inappropriate reaction” to a stress
Now realizing that ADHD can manifest in adults who didn’t show symptoms as a child; instead of school functioning issues, impulsivity/inability to follow through with tasks at work, multiple job changes, unhappiness at work/failure at work; mostly productivity
ADHD = one of the most common disorders of childhood
Having oppositional defiant disorder / uconduct disorder = more likely to also have ADHD. Same with kids who have anxiety disorder and learning disabilities
More prevalent in males
ADHD = frequently associated with other psychiatric disorders
NEUROPATHOGENESIS OF ADHD
- brain imaging reveals decreased activation in areas of basal ganglia & anterior frontal lobe
- major NTs involved in ADHD = Dopamine & NE*****
- Most of dopamine sensitive neurons = located in the frontal lobe
- Dopamine system = associated with reward, attention, STM tasks, planning, motivation, taking risks or being impulsive
- Dopamine limits and selects sensory information arriving from the thalamus to the forebrain
The sensory information gets unorganized and unfiltered; it’s difficult for ppl with ADHD to filter info and store it properly –> so move around a lot, or are doing other things while listening or looking elsewhere but still able to process what’s going on
Too little dopamine (like parkinson’s) - so need medication that will increase dopamine
FRONTAL LOBE = ability to project future consequences resulting from current actions, and being able to choose between good and bad decisions (or even between better and best choices).
- Frontal lobe also allows for the override + suppression of socially unacceptable responses, and the determination of similarities + differences between things/events
- the impulsivity will decrease with behavioral interventions and as the person ages
DIFFERENCE IN BRAIN FUNCTION OF THOSE WITH ADHD
- decreased activation in areas of basal ganglion and anterior frontal lobe
- there is an increase in dopamine transporter activity –> clears dopamine from the synapse too quickly
- Hypoactivity of dopamine, norepinephrine, and epinephrine in the prefrontal cortex
THE BASIS OF TREATMENT OF ADHD WITH METHYLPHENIDATE***
⦁ increases extracellular dopamine + NE in the brain
⦁ changes the areas of function in the frontal lobe
⦁ in patients without ADHD, methylphenidate does NOT have the same effect on the frontal lobe function
CRITERIA FOR DIAGNOSIS
- NEED 6+ SYMPTOMS OF INATTENTION OR 6+ SYMPTOMS OF HYPERACTIVITY/IMPULSIVITY***
- There are 9 symptoms in each category; need at least 6/9 symptoms of inattention or 6/9 symptoms of hyperactivity / impulsiveness
- Symptoms must be present of at least 6 MONTHS
- The majority of the time, children have symptoms of BOTH subtypes
- Need 5+ for age 17 or older
- Symptoms should be inappropriate for the given age**
- symptoms negatively impact social & academic or occupational activities
- symptoms developed PRIOR to age 12**
- symptoms present in 2+ settings
- symptoms present for at least 6 months**
- symptoms not better explained by other psych disorders
ADHD INATTENTIVE SYMPTOMS
⦁ Easily distracted; miss details, frequently switch from one activity to another, forget things. Easily distracted when multiple things are happening simultaneously
⦁ Difficulty maintaining focus on one task or learning something new
⦁ Failure to give close attention to detail; misses details, may make careless mistakes
⦁ Failure to listen when spoken to directly, Failure to follow instructions
⦁ Difficulty organizing tasks and activities; difficulty completing assignments
⦁ Reluctance to engage in tasks that require sustained mental effort
⦁ Forget things or lose things needed to complete activities and tasks (pencil); (did my hw, but I lost it - very common with ADHD).
⦁ Forgetfulness in daily activities
⦁ Becomes bored with a task after a few minutes, unless doing something enjoyable
ADHD IMPULSIVE-HYPERACTIVITY SYMPTOMS
⦁ Fidgetiness with hands and feet or squirms in seat
⦁ Constantly in motion; may often leave their seat - difficulty remaining seated in class
⦁ Has trouble sitting for long periods (ex: doing homework, dinner, school)
⦁ Difficulty doing quiet tasks
⦁ Often talks excessively or non-stop
⦁ Excessive talking and blurting out answers before questions have been completed
⦁ Impatience
⦁ Excessive running or climbing in inappropriate situations; Dashes around, touching or playing with everything in sight
⦁ Restlessness
⦁ Blurts out appropriate or inappropriate comments; shows unrestrained emotions
⦁ Difficulty in engaging in quiet activities
⦁ Is often “on-the-go” or acts as if “driven by a motor”
⦁ Difficulty awaiting turns (while waiting in line)
⦁ Interrupting and intruding on others; Interrupts the conversation or activities of others
MEDICAL EVALUATION FOR ADHD
- Parents + Teacher need to fill out form - such as the Vanderbilt form
- Refer for vision & hearing tests* - r/o that kid isn’t just having difficulty seeing or hearing at school
- Complete hx, ROS, and PE to rule out other causes / psych illnesses
- If history suggests, may consider the following
⦁ blood lead level
⦁ TSH
⦁ sleep study
⦁ neurology consult if concern for seizures or other neurologic disorder
Poor sleep quality can lead to ADHD-like symptoms or learning disabilities; so ask about snoring, look in mouth (tonsils), large neck, obesity, etc.
DIAGNOSIS + TREATMENT OF ADHD IN ADULTS
- diagnosis should be made by a mental health professional
- symptoms often continue into adulthood, and can have significant effects on social & occupational functioning
- same meds used for adults + kids with ADHD
often kids with ADHD are able to come off the med as an adult due to decrease in symptoms; unsure if changes in brain development or whether due to adaptation to ADHD over time
ADHD TREATMENT
TREATMENT OF ADHD
1) = Behavior modification
2) Sympathomimetic medications = Stimulants = PHARM TREATMENT OF CHOICE
⦁ Ritalin (Methylphenidate) = Concerta
⦁ Adderall (Amphetamine; Dextroamphetamine)
⦁ Focalin (Dexmethylphenidate)
- Stimulants increase dopamine + NE neurotransmitters by blocking NE and dopamine reuptake. These are decreased in ADHD, so blocking their reuptake reduces symptoms
- The fast release of dopamine causes euphoria and can be addictive, which is why it is imperative to have a slow release of dopamine -> helps with focus and attention = what the ADHD stimulant meds do
- Behavioral Therapy Treatment = has NOT been shown to reduce symptoms in the absence of a concurrent stimulant Rx for a patient that truly has a diagnosis of ADHD
- other alternative treatments, such as cognitive treatment, dietary modification and multivitamins have NOT been shown to be effective in controlled studies
CRITERIA FOR INITIATION OF THERAPY
⦁ Complete diagnostic assessment that confirms ADHD
⦁ ≥ 6 years old
⦁ Parental consent
⦁ School is cooperative (if dosing during school hours)
⦁ No previous sensitivity to the chosen medication
⦁ Normal heart rate and BP
⦁ No history of seizure disorder (if so refer to neurology to treat ADHD too)
⦁ Does not have Tourette syndrome, Autism spectrum disorder, anxiety disorder, or substance abuse among household members
if there is a hx of substance abuse in household members, can prescribe a non-stimulant therapy
PRETREATMENT WORK UP
o need a comprehensive medical evaluation (above info) + EKG to r/o arrhythmia
o document pretreatment height / weight / BP / HR
o document the presence of any of the following symptoms PRIOR to treatment
⦁ general appetite
⦁ sleep pattern
⦁ headaches
⦁ abdominal pain
o assess for substance use or abuse
⦁ need treatment for this before starting ADHD meds
ADHD PHARMACOTHERAPY
Choice of Agent (If patient and parents agree to medications)
o Stimulants are first line agent
⦁ Methylphenidate (Ritalin) (Concerta)
⦁ Dextroamphetamine (Adderall)
- Dexmethylphenidate (Focalin)
o Atomoxetine (Strattera) is an alternative (non stimulant)
CONSIDERATIONS THAT MAY AFFECT MEDICATION CHOICE IN ADHD
⦁ Daily duration of coverage needed
⦁ Completion of homework or driving after school?
⦁ Ability of child to swallow pills or capsules
⦁ Time of day when target symptoms occur
⦁ Desire to avoid administration at school
⦁ Coexisting tic disorder (avoid stimulants)**
⦁ Coexisting emotional or behavioral condition
⦁ Potential adverse effects
⦁ History of substance abuse in patient or household member (avoid stimulants)
⦁ Expense (short acting stimulants are least expensive)**
SHORT ACTING STIMULANTS: o METHYLPHENIDATE - Ritalin + Methylin = short acting -available in tablet, chewable tablet or liquid - onset of action = 20-60 minutes - duration of action = 3-5 hrs
o SHORT ACTING AMPHETAMINES = Adderall
LONG ACTING STIMULANTS: o METHYLPHENIDATE - Metadate ER, Methylin ER & Ritalin SR - onset of action: 20-60 minutes - duration of action = 8hrs
CONCERTA = osmotic release = Immediate release on the outside then uses an osmotic pump to slowly release medication
QUILLIVANT = liquid DAYTRANA = patch
o LONG ACTING AMPHETAMINES
- Vyvanse (Lisdexamfetamine)
- Dextroamphetamine SR
- Amphetamine-dextroamphetamine (Adderall XR)
Methylphenidate, dexmethylphenidate and amphetamines are equally effective
Have similar side effect profiles
Short acting agents
⦁ Initial rx in children < 6 (short acting methylphenidate = ritalin or methylin)*******
⦁ Or can be used to determine optimal dosing before switching to a long acting agent
Longer acting preparation
⦁ May be used initially in age > 6
⦁ Starting at the lowest dose and titrating up
Dose Titration: know that the initial dose is not necessarily the effective dose, so need to titrate up, and education patient/parents that drug won’t be effective until reach effective dose, but important to start on lower dose initially
NONSTIMULANT MEDS o Atomoxetine (Strattera) = alternative (non-stimulant) = 2nd line = SNRI = blocks NE reuptake - only increases NE release, not dopamine
- for children > 6
- may take 1-2 weeks before see effects*** (unlike stimulants - will know pretty quickly)
- also can’t take “pill holiday” with strattera the way you can with stimulants
- Similar efficacy and SE profile as stimulants, however, SE occur less often with Strattera, and there are less addictive properties
FOLLOW UP
EVALUATE FOR THESE SIDE EFFECTS AT EACH FOLLOW UP
⦁ Decreased appetite*
⦁ Poor growth* (take summer drug holidays)
⦁ Dizziness (monitor BP)
⦁ Insomnia/Nightmares
⦁ Mood lability (can occur when drug is wearing off - consider switching to longer acting or increasing to BID or TID)
⦁ Rebound
⦁ Tics
⦁ Psychosis
⦁ Diversion and misuse
REASONS FOR TREATMENT FAILURE
- not sticking to medication regimen
- possibility of medication diversion (giving it to another person - selling it)
- are treatment goals / expectations realistic?
- is there a comorbid psychiatric diagnosis?
o Can try another stimulant medication
o if pt fails multiple stimulants or experiences intolerable side effects = try Atomoxetine (Strattera) or an alpha-2 adrenergic (Clonodine - Cataprex) (Guanfacine - Tenex)
DRUG HOLIDAYS
- discontinuation of stimulant medication on weekends or during the summer
- decide on a case by case basis
- not an option for atomoxetine (strattera) or alpha-2 adrenergic agonists because of the extended half life**
MAINTENANCE OF THERAPY
- once on a stable dose - follow up in office every 3-6 months
- continue to monitor weight / BP / HR (SE of decreased appetite, hypertension, tachycardia)
TERMINATION OF THERAPY
- May abruptly discontinue stimulants or atomoxetine (strattera)***
- for alpha-2 adrenergic agonists + TCAs = should taper off over several weeks*
both ritalin & adderall can cause anxiety, weight loss, psychosis and heart problems in at risk pts. High potential for addiction and abuse
DEXTROAMPHETAMINE (DEXEDRINE)
- previously used for OTC diet pill
- among the most effective treatments for ADHD***
- sudden death in ppl that have heart problems or cardiac defects (like ritalin + adderall)
LISDEXAMFETAMINE (VYVANSE)
- is converted to dextroamphetamine after oral ingestion
- is less addictive*** but is still a schedule II drug like rest
- amphetamines cause release of catecholamines (primarily dopamine + NE) from their storage sites in presynaptic nerve terminals
ATOMOXETINE (STRATTERA)
- non-stimulant - was initially the only approved non-stimulant treatment until Intuniv
- non-stimulant - so DOESN’T WORK ON DOPAMINE, only works on NE*** - but therefore also why its less effective than a stimulant
- was initially tested for depression, but didn’t do much
**BBW - INCREASED RISK OF SUICIDAL BEHAVIOR IN PTS < 25 **
- may not be as effective as stimulant meds
- is expensive
MOST COMMON SE
⦁ dry mouth, insomnia, nausea, decreased appetite, constipation, decreased libido/ED, urinary hesitancy, dizziness, sweating
- RISK OF SUICIDAL IDEATION IN CHILDREN AND ADOLESCENTS*
- so need to weight risk vs benefits, and should be monitored closely for suicidal thinking and behavior
- families/caregivers should be advised of the need for close observation & communication with the provider
GUANFACINE (INTUNIV)
- alpha-2 adrenergic agonist - antihypertensive
- but also approved for treatment of ADHD
**so if pt has ADHD + HYPERTENSION = give Guanfacine (Intuniv)
SE can become hypotensive
*Caution with KIDNEY OR LIVER DISEASE **
BUPROPION (WELLBUTRIN)
- alternative treatment for ADHD (as well an antidepressant and to quit smoking)
- SE = anxiety & insomnia
- DON’T give in bulimics - can lower the seizure threshold
- can be used as add on therapy with SSRI to prevent sexual SE
- increases dopamine
ESSENTIAL TREMOR
Essential Familial Tremor (Benign)
- MOST COMMON CAUSE OF TREMORS*
- inherited; Autosomal dominant inherited disorder of unknown etiology
- ranges from cosmetic to disabling
- affects both sides of the body symmetrically (whereas PD = unilateral + occurs at rest)
- MORE PROMINENT WITH ACTION THAN WITH REST* (unlike PD) = INTENTIONAL TREMOR**
- frequency of tremor is constant
- amplitude may vary
WHICH BODY PARTS ARE AFFECTED
⦁ neck & head muscles
⦁ muscles of the voice
⦁ muscles of the arms & hands
THE TREMOR IS AGGRAVATED BY
⦁ stress
⦁ sleep deprivation
⦁ stimulants
- Alcohol shortly RELIEVES the essential tremor
- Essential tremor usually starts earlier than PD
CLINICAL MANIFESTATIONS
1) Intentional Tremor = postural, bilateral ACTION tremor of the hands, forearms, head, neck or voice
- MC in upper extremities and head; usually spares legs
- WORSENED with emotional stress
- WORSENED with intentional movement
o Finger to Nose test = tremor increases as target is approached
Tremor is shortly RELIEVED with ALCOHOL*
2) No abnormal physical findings
- no significant neurologic findings besides tremor
ESSENTIAL TREMOR TREATMENT
- treatment not usually needed
⦁ Propranolol (Indurol) - BB** - may help if severe or situational (Atenolol /Tenormin - BB of choice for those with asthma or bronchospasm)
⦁ Mysoline (Primidone) = barbiturate - anticonvulsant / sedative = given if no relief with Propranolol, given instead of Propranolol, or given with Propranolol
⦁ Gabapentin (Neurontin) - anticonvulsant
⦁ Alprazolam (benzo) = 3rd line
Remeron (Mirtazapine) = antidepressant + for tremor
- don’t give BB to someone who is depressed! or to someone with low blood sugars
- usually start with BB - sometimes can combine BB + anticonvulsant
- some ppl take medicine daily, others just during stressful situations
SURGICAL TREATMENT
- must have failed 2-3 medications to qualify for surgical treatment of essential tremor
- surgery can be debilitating
- DBS - Deep Brain Stimulation = electrodes are placed in thalamic ventral intermediate nucleus (stereotactic methods) - electrodes are then connected to a pulse generator in the chest wall
ANOREXIA NERVOSA
- Refusal to maintain a minimally normally body weight - fueling a relentless desire for thinness
- Morbid fear of fatness or gaining weight, even though the patient is underweight
2 types = Restrictive and Binge / Purge
DSM IV CRITERIA FOR ANOREXIA NERVOSA
⦁ Restriction of energy intake relative to requirements ==> leading to significantly low body weight for her age / sex / developmental trajectory & physical health
⦁ Fear of weight gain
⦁ Severe body image disturbance in which body image is the predominant measure of self-worth with denial of the seriousness of the illness
MC age of onset = mid teens
90% of patients = Women (60% = 15-24y/o)
Frequently seen in athletes, dancers, or other conditions requiring thinness
60% incidence of depression
CLINICAL MANIFESTATIONS
- Exhibits behaviors targeted at maintaining a low weight or certain body image
- Excess water intake, food-related obsessions (hoarding, collecting)
RESTRICTIVE TYPE = reduced calorie intake, dieting, fasting, excessive exercise, diet pills
BINGE/PURGE TYPE = primarily engages in self-induced vomiting, diuretic / laxative / enema use
binge/purge anorexia vs bulimia = For those with binge-purge anorexia, what they are doing results in a net intake lower than their output for long enough to become, or maintain, a too-low weight. For those with bulimia, the net input is enough to maintain or gain weight.
SIGNS/SYMPTOMS ⦁ dry skin ⦁ cold intolerance / hypothermia (hypothyroidism) ⦁ blue hands / feet ⦁ constipation ⦁ bloating ⦁ delayed puberty ⦁ primary or secondary amenorrhea ⦁ fainting ⦁ orthostatic hypotension ⦁ lanugo hair ⦁ scalp hair loss ⦁ early satiety ⦁ weakness / fatigue ⦁ short stature ⦁ osteopenia ⦁ breast atrophy ⦁ atrophic vaginitis ⦁ pitting edema ⦁ cardiac murmurs / sinus bradycardia
DIAGNOSIS
- BMI = 17.5 kg or weight < 85% of ideal weight
PHYSICAL EXAM
- emaciation (abnormally thin / weak)
- hypotension
- bradycardia
- skin / hair changes (ex: lanugo - fine hairs), dry skin, brittle hair
- salivary gland hypertrophy
- amenorrhea (no periods)
- arrhythmias
- osteoporosis
o Vital signs - include Orthostatic vitals
o Skin + Extremity evaluation =dryness, bruising, lanugo
o Cardiac Exam = Bradycardia, Arrhythmia, MVP** (heart muscle shrinks but the valves don’t)
o Abdominal Exam
o Neuro Exam - evaluate for other causes of weight loss or vomiting (brain tumor)
LABS
- leukocytosis (elevated WBC count; normal 4-11,000)
- leukopenia (decreased WBC count)
- anemia
- hypokalemia
- increased BUN (dehydration)
- hypothyroidism
TREATMENT
o medical stabilization: hospitalization if < 75% of ideal body weight, or if patients have medical complications; electrolyte imbalances may lead to cardiac abnormalities, dehydration, arrested growth/development, etc
o Psychotherapy = CBT, supervised meals, weight monitoring
o Pharmacotherapy: if depressed = SSRIs, or atypical antipsychotics - Olanzapine (Zyprexa) - (may also help with weight gain)
o Nutrition
- Goal = to regain 90-92% of ideal body weight
- Inpatient treatment varies by facility
+ oral liquid nutrition
+ nasogastric tube feedings
+ gradual caloric increase with “regular” food - but take it easy during first 2 weeks - so don’t get heart failure + pitting edema
ANOREXIA OUTCOME
o 50% = good outcome - return of menses & weight gain
o 25% = intermediate outcome - some weight regained
o 25% = poor outcome
⦁ associated with later age of onset
⦁ longer duration of illness
⦁ lower minimal weight
⦁ Overall mortality rate = 6.6%. 1/5 anorexia deaths are due to suicide
BULIMIA NERVOSA
Bulimia patients (vs anorexia) = patients with bulimia have NORMAL WEIGHT or are OVERWEIGHT
- more common in females
- average onset = late teens
- concerned about body image
- 2 types: Purging and Non-Purging
EPIDEMIOLOGY
- occurs in 1-5% of high school girls
- occurs in as high as 10% in college women
DSM IV CRITERIA FOR BULIMIA / clinical manifestations
1) Recurrent BINGE EATING: an episode of binge eating is characterized by BOTH of the following
⦁ Recurrent episodes of eating a large amount of food in a small amount of time (2hrs) = (larger amount of food than what most individuals would eat in a similar period of time)
⦁ A sense of a lack of control over eating during the episode
- **Occurs at least weekly x 3 months
2) Recurrent inappropriate COMPENSATORY BEHAVIORS to prevent weight gain
o Purging Type
⦁ self-induced vomiting
⦁ misuse of laxatives, diuretics, enemas, other meds
o Non-Purging Type ⦁ reduced calorie intake ⦁ dieting ⦁ fasting ⦁ excessive exercise ⦁ diet pills
3) The binge eating & inappropriate compensatory behaviors both occur, on average, at least 1x per week x 3 months
4) Self evaluation is influenced by body shape and weight
5) the disturbance does not occur exclusively during periods of anorexia nervosa
SIGNS/SYMPTOMS OF BULIMIA NERVOSA ⦁ mouth sores ⦁ pharyngeal trauma ⦁ dental caries / teeth pitting / enamel erosion ⦁ Russell's Sign = Calluses on back of knuckles/fingers from sticking hand in mouth to gag ⦁ Heartburn / chest pain ⦁ Esophageal rupture ⦁ Impulsivity: stealing / alcohol abuse / drugs / tobacco ⦁ Muscle cramps ⦁ weakness ⦁ bloody diarrhea ⦁ bleeding or easy bruising ⦁ irregular periods ⦁ fainting ⦁ swollen parotid glands** - Bilateral Parotid Sialadenosis - parotid gland hypertrophy ⦁ Hypotension
parotid gland hypertrophy - attempt to increase saliva release in order to buffer acidity from vomiting
HISTORY
⦁ maximum height & weight
⦁ exercise habits: intensity & hours/week
⦁ stress levels
⦁ habits & behaviors: smoking / alcohol / drugs / sexual activity
⦁ eating attitudes & behaviors
⦁ ROS (review of systems)
PHYSICAL EXAM - BULIMIA
All previous elements +
⦁ Parotid Gland Hypertrophy (if purging type)
⦁ Erosion of teeth enamel (caries) (if purging type)
LABS
- metabolic alkalosis from vomiting
- may have hypokalemia (from vomiting)
- may have hypomagnesemia (from vomiting)
- electrolyte imbalance may lead to cardiac arrhythmias
TREATMENT FOR BULIMIA
o CBT** is effective! (not very effective with anorexia, but IS effective for bulimia)
o Pharmacotherapy = high success rate (unlike anorexia)
⦁ SSRIs - Fluoxetine (Prozac)** - up to 67% reduction in binge eating, and 56% reduction in vomiting - has been shown to reduce binge-purge cycle, but may have CV SE if electrolyte abnormalities are present
⦁ TCAs
⦁ Topiramate (Topamax) - reduced binge eating by 94% and average weight loss of 6.2 kg (seizure med that is also used to treat migraines, and now bulimia)
⦁ Ondansetron (Zofran) - 24mg/day (often food is associated with vomiting - helps prevent nausea/urge to throw up after - Sublingual available - Dwight prefers this)
**do NOT give Wellbutrin (Bupropion) = (miscellaneous antidepressant) - can lower seizure threshold in bulimics
FEMALE ATHLETE TRIAD
⦁ Eating disorders
⦁ Osteopenia or Osteoporosis (stress fractures)
⦁ Amenorrhea or Oligomenorrhea
Osteopenia = when your bones are weaker than normal but not so far gone that they break easily, which is the hallmark of osteoporosis
Amenorrhea = no menstruation Oligomenorrhea = abnormal menstruation
ERYTHEMA NODOSUM
- extremely tender red nodules that develop on the shins
- painful, erythematous, inflammatory nodules seen on anterior shins
- range in colors from pink, red, purple
- usually bilateral
- may also occur on other parts of body
- An idiopathic inflammatory skin condition; commonly associated with
⦁ ESTROGEN EXPOSURE - OCPs, Pregnancy
⦁ certain medications = SULFA related drugs, OCPs, estrogen
⦁ Infections: MC STREP, TB, Sarcoidosis, Mono, Coccidioidomycosis - fungal
⦁ IBD (crohns + UC)
⦁ leukemia
⦁ Behcets
Erythema nodosum is generally self-limiting and resolves spontaneously within a few weeks. Treat underlying cause
- can give NSAIDS for pain
- if persistent = give STEROIDS
IBS (irritable bowel syndrome)
LARGE BOWEL DISORDER
- chronic, functional idiopathic disorder with NO organic cause
HALLMARK = ABDOMINAL PAIN ASSOCIATED WITH ALTERED DEFECATION / BOWEL HABITS (diarrhea, constipation, or alternation between the two)
PAIN OFTEN RELIEVED WITH DEFECATION
- not autoimmune mediated that we know of; no fever/no weight loss/no elevated WBC/no red flags/no elevated Sed rate/CRP
- more of a spectrum of an irritating bowel - can have diarrhea, constipation, mucus, etc.
OLDER TERMS OF IBS ⦁ Spastic colon ⦁ Spastic colitis ⦁ Mucous colitis ⦁ Functional bowel disease
IBS = a functional GI disorder that is a variable combination of chronic or recurrent GI symptoms that are not explained by structural or biochemical abnormalities
⦁ IBS is a diagnosis of exclusion
⦁ 25% of patients get post-enteric infections (small bowel infxn), and 7% go on to develop true IBD
EPIDEMIOLOGY
o females > males
o younger (late teens - early 20’s)
SYMPTOMS OF IBS
Continuous or recurrent symptoms for at least 3 months of:
⦁ abdominal pain or discomfort
⦁ pain relieved by defecation (also with UC - IBD)
⦁ pain with a change in frequency or form of stools
And a varying pattern of defecation with 3 or more of the following:
⦁ altered stool frequency
⦁ altered stool form
⦁ altered stool passage (straining, urgency, incomplete evacuation/sensation of rectal fullness)
⦁ abdominal distention & bloating
⦁ passage of mucus
ASSOCIATED SYMPTOMS OF IBS ⦁ FATIGUE*** (96%) ⦁ back ache (75%) ⦁ early satiety (73%) ⦁ nausea ⦁ headache ⦁ irritable bladder ⦁ functional dyspepsia
DIAGNOSIS OF IBS
- diagnosis is based on symptoms
- Rome IV Criteria = Most commonly used
Abdominal discomfort/pain with 2/3 of the following for at least 3 of the past 12 months (not necessarily consecutive)
⦁ relief with defecation (also seen in ulcerative colitis - IBD)
⦁ onset associated with change in stool frequency
⦁ onset associated with change in stool formation - Manning Criteria
⦁ pain relieved by defecation
⦁ more frequent stools associated with pain onset
⦁ looser stools associated with pain onset
⦁ abdominal distention
⦁ passage of mucus
⦁ feeling of incomplete evacuation
TREATMENT - Which category does the patient belong in? ⦁ bloating & pain predominant ⦁ constipation predominant ⦁ diarrhea predominant ⦁ anxiety associated ⦁ depression associated
- pick which category the patient most falls under, treat that first
1) Lifestyle changes: Smoking cessation, low fat / unprocessed food diet. Avoid sorbitol or fructose, cruciferous veggies, get enough sleep / exercise
2) Diarrhea = Anticholinergics/spasm (Dicyclomine****) or antidiarrheal (Loperamide / Immodium****)
3) Constipation = laxatives, fiber, stool softeners
4) Pain management
OSMOSIS
- pattern of recurrent bouts of abdominal pain + abnormal bowel motility (constipation or diarrhea or a mixture of both)
- often the abdominal pain improves after a bowel movement**
vs IBD = inflammation, ulcers, other damage to the bowel
IBS = no inflammation, no ulcers, no damage to the bowel
IBS = a FUNCTIONAL DISORDER
not well understood MOA; so focused on symptoms
SYMPTOMS
⦁ Abdominal Pain
- many ppl with IBS have VISCERAL HYPERSENSITIVITY - the sensory nerve endings in the bowel have an abnormally strong response to stimuli, such as stretching during and/or after a meal
⦁ Abnormal Bowel Motility
- eating foods with short-chain carbs often trigger the symptoms
- unabsorbed short-chain carbs act as solutes and draw water across intestinal wall and into the lumen; This triggers visceral hypersensitivity (causes abdominal pain), but also the excess water can cause the intestine to spasm –> Diarrhea, if excess water is not reabsorbed back into the body
- Additionally, the unabsorbed short-chain carbohydrates remaining get metabolized by bacterial flora –> Gas, which can trigger even more bloating, spasm or pain
EPIDEMIOLOGY
- more common in women
RISK FACTORS
- Acute gastroenteritis (ex: Norovirus or Rotavirus)
- Stress
both can be triggers for developing IBS
TREATMENT (since MOA is unclear, treatment targets the symptoms)
- diet modification (avoid certain foods like apples, beans and cauliflower = all have short-chain carbohydrates)
- for Constipation = soluble fiber, stool softeners, laxatives
- for Spasms & Pain = anti-diarrheals or antimuscarinic
- manage stress, anxiety and depression
GERD
- NOT A DISEASE!!!
- GERD is a syndrome - understand, diagnose and treat
- you can prevent the “complications” and improve quality of life
- a compilation of symptoms that occurs with a variety of syndromes
GERD = mucosal damage produced by the abnormal reflux of gastric contents into the esophagus
Transient relaxation of the LES (incompetency) –> gastric acid reflux –> esophageal mucosal injury
- rule out angina pectoris first**
4 Major Physiologic Mechanisms that protect against Esophageal Acid Injury
1) clearance mechanisms of the esophagus
2) mucosal integrity of the esophagus
3) LES competence (sealing off the esophagus from gastric contents)
4) Gastric Emptying (so that levels aren’t so high of chyme to get close to LES)
primary barrier to GERD = LES (lower esophageal sphincter)**
The LES normally works in conjunction with the diaphragm. If the barrier is disrupted, acid goes from the stomach to the esophagus
ETIOLOGIES OF GERD - combination of factors - ⦁ Increased gastric acid ⦁ Hiatal hernia ⦁ incompetent LES ⦁ decreased esophageal clearance / esophageal motility disorders ⦁ decreased gastric emptying ⦁ medications (alpha agonists, theophylline, sedatives, NSAIDS)
CLASSIC GERD SYMPTOMS
⦁ Heartburn (pyrosis) - substernal burning / discomfort = hallmark*** - often postprandial (MC 30-60 minutes after eating)
- increased with supine position / bending down
- often relieved with antacids
⦁ Regurgitation - bitter, acidic fluid in the mouth when lying down or bending over
⦁ Dysphagia
⦁ Cough at night (acid aspirates into the lungs and causes lung irritation / cough)
⦁ Regurgitation of partially digested food
Extraesophageal Manifestations of GERD PULMONARY ⦁ asthma - bronchospasm from acid contact with lungs ⦁ aspiration pneumonia ⦁ chronic bronchitis ⦁ pulmonary fibrosis
ENT ⦁ hoarseness ⦁ laryngitis / pharyngitis ⦁ chronic cough ⦁ globus sensation - feel like something's in throat ⦁ dysphonia ⦁ sinusitis ⦁ subglottic stenosis ⦁ laryngeal cancer
OTHER
⦁ non-cardiac chest pain
⦁ dental erosion
ORAL/LARYNGOPHARYNGEAL SIGNS OF GERD
- edema / hyperemia of larynx
- vocal cord erythema / polyps / granulomas / ulcers
- hyperemia & lymphoid hyperplasia of posterior pharynx
- interarytenoid changes
- dental erosion
- subglottic stenosis
- laryngeal cancer
ALARM SYMPTOMS
- dysphagia / odynophagia
- weight loss
- bleeding (suspect malignancy / cancer)
HIATAL HERNIA - an etiology of GERD
- herniation of a portion of the stomach adjacent to the esophagus through an opening in the diaphragm
⦁ sliding - esophageal gastric junction slides up past diaphragm
⦁ paraesophageal (rolling) - fundus of the stomach ends up above the diaphragm
hiatal hernia = stomach has slipped above the diaphragm
o food lodges in the pouch (hernia) –> inflammation of the mucosa, and reflux of the food up to the esophagus, and dysphagia
o often due to an incompetent gastro-esophageal sphincter
o contributing factors to hiatal hernia
⦁ shortening of the esophagus
⦁ weakness of diaphragm
⦁ increased abdominal pressure (pregnancy)
⦁ extreme obesity –> increased abdominal pressure from fat
DIAGNOSIS
1) clinical diagnosis based on history
2) Endoscopy** = often used 1st if persistent symptoms or complications of GERD
3) Esophageal Manometry = measures strength / coordination of esophagus:
- will show decreased LES pressure
4) 24hr ambulatory pH monitoring = gold standard* (rarely used) = only needed if symptoms persistent
TREATMENT GOALS FOR GERD
1) Lifestyle Modifications
- avoid large meals; eat small meals
- avoid acidic foods (citrus/tomato), alcohol, caffeine, chocolate, onions, garlic, peppermint
- avoid fatty or spicy foods
- avoid lying down within 3-4 hrs after a meal
- elevate head of bed 4-8 inches
- avoid meds that may potentiate GERD (alpha agonists, theophylline, sedatives, NSAIDS)
- avoid tight clothing around waist
- lose weight
- stop smoking
2) RX TREATMENT as needed
- Antacids - OTC acid suppressants/antacids = appropriate initial therapy. about 1/3 of pts with heartburn related symptoms use this at least BIW
- H2-receptor blockers (antagonists) - Cimetidine (Tagamet), Ranitidine, Famotidine (Pepcid)
- PPIs - Omeprazole (Prilosec), Pantoprazole (protonix), esomeprazole (nexium)
Omeprazole = warn patients of B12 deficiency
3) Antireflux Surgery = reduces hiatal hernia, repairs diaphragm, strengthens GE junction, and strengthens the antireflux barrier via gastric wrap. 75-90% effective at alleviating symptoms of heartburn and regurgitation
o reduce hiatal hernia
o restore intra-abdominal esophagus
o approximate diaphragmatic crurae - stitch tighter diaphragm around esophagus
o perform Nissen Fundoplication = wrap the fundus of stomach around esophagus/stitch
After surgery, 10% of pts have solid food dysphagia, 2-3% have permanent symptoms, 7-10% have gas/bloating/diarrhea/nausea/early satiety. Within 3-5 years, 52% of patients are back on anti-reflux meds….so surgery not that successful?
Complications of GERD ⦁ erosive esophagitis ⦁ strictures ⦁ Barrett's esophagus ⦁ Esophageal adenocarcinoma
DON’T LET PATIENTS GET TO THESE STAGES - don’t let GERD turn into one of these
BARRET’S ESOPHAGUS
Complication of GERD
Esophageal squamous epithelium is replaced by precancerous metaplastic columnar cells from the cardia of the stomach (these cells are more used to the acidic environment - coping mechanism for GERD), however, columnar cells don’t belong in the esophagus…
Barrett’s esophagus = precancerous, however, it can progress to ADENOCARCINOMA
- Acid damages the lining of esophagus and causes chronic esophagitis
- Damaged area heals in a metaplastic process and abnormal columnar cells replace squamous cells
- This specialized intestinal METAPLASIA can progress to dysplasia and adenocarcinoma
In GERD, acid and food splash into esophagus repeatedly. The stomach acid can damage some of the cells/tissue of the esophagus
- Sometimes METAPLASIA can occur in the esophagus = BARRETT’S ESOPHAGUS - the normally squamous cells turn into columnar. Not cancerous at first, just abnormal (dysplastic) but can become cancerous = why its important to reduce reflux to prevent Barrett’s esophagus
DIAGNOSIS
The following techniques are used in the diagnosis and assessment of Barrett esophagus:
⦁ Esophagogastroduodenoscopy (EGD): The procedure of choice for the diagnosis of Barrett esophagus
⦁ Biopsy: The diagnosis of Barrett esophagus requires biopsy confirmation of specialized intestinal metaplasia (SIM) in the esophagus
⦁ Ultrasonography: When high-grade dysplasia or cancer is found on surveillance endoscopy, endoscopic ultrasonography (EUS) is advisable to evaluate for surgical resectability
TREATMENT
- Once Barrett esophagus has been identified, patients should undergo periodic surveillance endoscopy to identify histologic markers for increased cancer risk (dysplasia) or cancer that is at an earlier stage and is amenable to therapy.
DYSPLASIA = THE BEST HISTOLOGIC MARKER FOR CANCER RISK
The management options for high-grade dysplasia include the following:
⦁ Surveillance endoscopy, with intensive biopsy at 3-month intervals until cancer is detected
⦁ Endoscopic ablation: In most major medical centers, ablation is first-line therapy
⦁ Surgical resection: While studies have shown surgery to be efficacious in the control of GERD symptoms, no good evidence indicates that surgical therapy provides regression in Barrett esophagus
Pharmacologic treatment for Barrett esophagus should be the same as that for GERD, although most authorities agree that treatment should employ a proton pump inhibitor (PPI) instead of an H2-receptor antagonist, due to the relative acid insensitivity of patients with Barrett esophagus. While PPIs have been found to be better than H2-receptor antagonists at reducing gastric acid secretion, the evidence as to whether PPIs induce regression of Barrett esophagus remains inconclusive
The diet for patients with Barrett esophagus is the same as that recommended for patients with GERD. Patients should avoid the following: ⦁ Fried or fatty foods ⦁ Chocolate, Peppermint ⦁ Alcohol ⦁ Coffee ⦁ Carbonated beverages ⦁ Citrus fruits or juices ⦁ Tomato sauce, Ketchup, Mustard, Vinegar ⦁ Aspirin and other NSAIDS
PYELONEPHRITIS
UTI - often goes along with cystitis; MC cause = E.coli. MC cause in sexually active women = staph saprophyticus
- will have pyuria
PRESENTATION ⦁ flank pain, abdominal pain, pelvic pain ⦁ N/V ⦁ fever > 99.8F ⦁ may have CVA tenderness ⦁ +/- symptoms of cystitis
LABS
- UA may show white cell casts; send urine for culture and sensitivities
- CBC
- Pregnancy test in females
TREATMENT o Mild to Moderate ⦁ rehydrate patient & give parenteral dose of antibiotics in ER - observe 8-12 hrs ⦁ IV ABX = Ceftriaxone ⦁ Discharge pt on fluoroquinolone x 7d
o Severe Illness - requiring hospitalization
⦁ high fever, pain, marked debility
⦁ inabililty to maintain oral hydration or take oral meds
⦁ pregnant
⦁ concerns about patient compliance
CYSTITIS
colonization of vaginal introitus from fecal flora –> ascends to bladder via urethra (cystitis) –> ascends to kidneys causing pyelonephritis
- this route is much more difficult in males due to much longer urethra
MOST COMMON ORGANISM OF UTIs
⦁ E. coli
- other organisms = Proteus & Klebsiella
UTIs = much less common in men
Men with UTIs = get much bigger work up because they aren’t as common in men
UTI PRESENTATION ⦁ dysuria ⦁ frequency ⦁ urgency ⦁ suprapubic pain ⦁ hematuria
PYELONEPHRITIS
- symptoms of cystitis may or may not be present with pyelonephritis
- chills
- flank pain with costovertebral angle tenderness
- Nausea + Vomiting
DIAGNOSTIC TESTS
CYSTITIS
- UA is a MUST! - look for positive leukocytes and/or positive nitrites
- if uncertain about diagnosis or resistance is possible = do urine culture
- ALL MALES with cystitis = need a culture
FOR PYELONEPHRITIS
- UA
- urine culture + sensitivity
TREATMENT FOR WOMEN WITH CYSTITIS
⦁ Nitrofurantoin
⦁ Bactrim
⦁ can give phenozopyridine (pyridium) - analgesic agent - turns urine dark orange
-reserve fluoroquinolones for other uses in case resistance is built
TREATMENT FOR MEN WITH CYSTITIS
- ddx = prostatitis, urethritis secondary to STI, Urinary tract abnormality, nephrolithiasis
⦁ Bactrim
⦁ Fluoroquinolone
- want to cover possible prostatitis (also treat with either bactrim or cipro for acute or chronic)
- men = usually have longer lengths of abx
TREATMENT FOR PYELONEPHRITIS
- outpatient (mild to moderate illness / can keep meds down) = Fluoroquinolone (cipro or levaquin) if resistance is low. Others = bactrim or augmentin
- inpatient treatment = fluoroquinolone + aminoglycoside
CARDIAC TAMPONADE
- a pericardial effusion that causes significant pressure on the heart –> restricts cardiac ventricular filling –> decreases cardiac output
-
BECK’S TRIAD
1) distant / muffled heart sounds
2) increased JVP
3) systemic hypotension
PULSUS PARADOXUS = upon inspiration = > 10mmHg decrease in systolic BP = decreased pulses with inspiration - because increased filling of the right side of the heart during inspiration and decreased left sided ventricular filling –> pulsus paradoxus
PATHOPHYSIOLOGY
- fluid is putting pressure on the heart itself, so that the heart can’t fully stretch out or relaxing between contractions. Chambers can’t properly fill with blood => decreased cardiac output => hypotension. Tries to compensate with tachycardia
During inspiration = increased pressure in the lungs, negative pressure in the heart => increased venous return to the right atrium; the right ventricle expands slightly into the pericardial space to accomodate for increased volume
With tamponade = with increased pressure on the heart, the right ventricle isn’t able to expand into the pericardial space, and therefore pushes over into left ventricle - the interventricular septum is pushed over into the left ventricle => decrease in LV diastolic volume => decreased stroke volume => decreased systolic BP during inspiration
- Dyspnea, fatigue, peripheral edema, shock, hypotension, reflex tachycardia, cool extremities
DIAGNOSIS = ECHO = see presence of effusion + diastolic collapse of cardiac chambers (due to pericardial fluid pressure pushing on relaxed chamber –> collapse)
- ECHO = TEST OF CHOICE FOR TAMPONADE**
TREATMENT = PERICARDIOCENTESIS (immediate)
- pericardial window if drainage is recurrent
Malignant pericardial effusions are common, just not commonly symptomatic; mortality probably from other aspects of the patient’s disease
- MC = lung cancer + breast cancer
- EKG = ELECTRICAL ALTERNANS
seen with cardiac tamponade and severe pericardial effusion
Presents with left or right sided failure, pulsus paradoxus, and big heart on CXR (bottle shaped heart = with pericardial effusion &a cardiac tamponade)
TREATMENT
- need an Echo + Cytology for pericardiocentesis
- Pericardiocentesis = catheter drainage of pericardial fluid
- medical management
- onocology input: chemotherapy
- CT surgery input: subxiphoid pericardial window or balloon pericardiotomy - especially for recurrent effusions in patients with good performance status
SIADH
- Syndrome of Inappropriate ADH
- SMALL CELL LUNG CANCER
- lots of ADH –> lots of water retention –> HYPONATREMIA
Na+ < 120 = anorexia, irritability, N/V, constipation, muscle weakness, myalgia
Na+ < 110 = seizure, coma / death, abnormal reflexes, papilledema
decreased BUN / osmolarity (dilute from water absorption)
increased urine osmolarity & sodium levels (concentrated urine)
TREATMENT
- treat underlying tumor
- limit fluid intake to 500-1000mL/day
- furosemide (lasix)
- parenteral sodium replacement with severe neurological symptoms
- monitor electrolytes: Mg, K, Ca
SVC SYNDROME
- seen with Bronchogenic Carcinoma
- SVC syndrome = dilated neck veins, prominent chest veins, facial plethora
- SOB = MC symptom** (also have facial / arm swelling) + varicose veins across chest/neck
- MC with small cell carcinoma (oat cell)
usually from lung cancer
- could also be from lymphoma, breast cancer, mediastinal tumors
CLINICAL MANIFESTATIONS
- facial edema
- symmetric or asymmetric upper extremity edema also common
- SOB common, but not hypoxic
only a relative emergency, even with CNS symptoms
- mainly from Bronchogenic carcinoma, but can be from Pancoast tumor too
Supra-azygos SVC obstruction (obstruction above junction of SVC & azygos vein = causes arm/neck/chest vein distention & edema of face/arms) vs Infra-azygos SVC obstruction (more severe symptoms - obstruction in SVC)
DIAGNOSIS
- need pulse ox & CXR
- Chest CT to outline the mass that will need therapy
- oncology involved = chemo for small cell, lymphoma and germ cell
- radiation for almost all else
- heparin or steroids
- SVC stenting…new
LIPOMA
- benign SUBCUTANEOUS tumor of adipose tissue
- soft, rounded and movable against overlying skin
Lipomas are composed of fat cells that have the same morphology as normal fat cells
MC locations = trunk or extremities
- soft
- symmetric
- painless
- easily mobile
- palpable mass in subcutaneous tissue
TREATMENT
- no treatment needed; may perform surgical removal for cosmetic reasons
**Some individuals have Familial Lipoma Syndrome = an autosomal dominant trait appearing in early adulthood, where an individual may have hundreds of Lipomas
A lipoma is a benign tumor composed of adipose tissue (body fat). It is the most common benign form of soft tissue tumor. Lipomas are soft to the touch, usually movable, and are generally painless.
Many lipomas are small (under one centimeter diameter) but can enlarge to sizes greater than six centimeters. Lipomas are commonly found in adults from 40 to 60 years of age, but can also be found in younger adults and children. Some sources claim that malignant transformation can occur, while others say this has yet to be convincingly documented.
VITILIGO
PATHOPHYS = autoimmune mechanism - formation of antibodies to melanocytes
- autoimmune destruction of melanocytes leads to skin depigmentation
- onset = usually early in life (age 20-30)
CLINICAL MANIFESTATIONS
⦁ irregular discrete macules and patches of total depigmentation
⦁ lesions primarily occur on the face, upper trunk, fingertips, dorsum of hands, armpits, genitalia, bony prominences, perioral region, and body folds
** acral areas **
⦁ hair may be white in involved areas
- often occurs in the context of other autoimmune conditions such as
⦁ ** Pernicious anemia ***
⦁ ** Hashimoto’s thyroiditis ****
⦁ DM type I
⦁ Addison’s disease
⦁ SLE
** Patients with other autoimmune disorders have an increased likelihood of vitiligo **
DIAGNOSIS
⦁ usually clinical
⦁ can use woods lamp to locate areas of hypopigmentation
Workup should include laboratory tests such as thyroid function tests, hemoglobin A1c levels, complete blood count, and anti-nuclear antibody testing among others.
TREATMENT
- re-pigmentation can be achieved to variable degrees with
⦁ topical steroids = 1st line
⦁ calcineurin inhibitors ( ** Tacrolimus ** = protopic) = 2nd line
⦁ Psoralens = light-sensitive drug that absorbs UV
⦁ UVA / UVB
Calcineurin = enzyme that activates T-cells of the immune system
⦁ calcineurin inhibitor (cyclosporine + tacrolimus) = inhibits T cells - inhibits immune system
Protopic doesn’t cause skin thinning/atrophy like topical steroids, however, there is a possible link between Tacrolimus (protopic) and lymphoma
- treatment is a long process that requires patient commitment
- may need psychological support
LICE
Ectoparasites that live on the body and feed on human blood after piercing the skin.
⦁ Pediculosis capitus: head lice
⦁ Pediculosis corporis: body lice
⦁ Pediculosis pubis: pubic lice
Very common
Body and scalp lice are about 1-3 mm long
Unable to jump or fly
Gray-brown to red-brown.
Host specific- cannot live off host more than 24-48 hrs - need blood
Life Cycle: unhatched egg (nit), three molt stages(growing), adult reproductive stage, death.
⦁ nits hatch after 1 week
⦁ take 1 week to become mature louse
⦁ mature louse lay eggs x 1 month
Females lay their eggs along the hair shafts –150-300 eggs per life span. They live 30-50 days.
Feed on human host blood. Spit has anticoagulant in it to help promote feeding –> increased histamine release –> pruritus
TRANSMISSION = person to person usually; can also spread through fomites (hats, headsets, clothing, bedding) but not as common
Body lice: Act a little different. Can live up to 14 days off of host. Transferred mostly through infested clothes, blankets.
Pubic Lice: Spread through intimate contact.
Head Lice: Incidence is higher among girls. Being spread from combs and hats is not the usual mode. It is mostly hair to hair contact.
CLINICAL PRESENTATION OF LICE
⦁ intense pruritus* (make take 2-6 weeks to develop after exposure) - especially occipital area
⦁ popular urticaria near lice bites**
⦁ nits = white oval-shaped egg capsules at base of hair shafts - must be removed with a comb
⦁ itching + scratching can lead to secondary cellulitis - secondary skin infection commonly staph
⦁ pubic lice = should prompt eval for other STIs
⦁ typical lesion of body lice = macule at bite site that may develop vesicles/wheals
⦁ nocturnal pruritus** = common
DIAGNOSIS = Observation of:
⦁ Eggs (nits)
⦁ Nymphs
⦁ Mature lice
Commonly found behind ears and on back of the neck
Wood lamp of area
⦁ Yellow-green fluorescence of lice/nits
TREATMENT
- 2 mechanisms
o Neurotoxicity
⦁ Permethrin (Nix) = 1st line
- sodium channel blocker –> paralysis
- capitus = permethrin shampoo - leave on x 10 min
- pubis / corporis = permethrin lotion x 8-10 hrs
- permethrin = safe in children 2+ y/o, safe during pregnancy
⦁ Lindane = 2nd line
- SE = Neurotoxic*** - headaches / seizures - do not use after showering - increased absorption through open pores, and teratogenic! (don’t use during pregnancy or while breastfeeding), and not for use in children < 2
⦁ Malathion
⦁ Ivermectin - lotion or oral; must be repeated in 1 week, as it does not kill unhatched lice. Oral ivermectin can be used in refractory cases
o Suffocation via “coating”
⦁ benzyl alcohol lotion (Ulesfia)
- MOA = louse asphyxiation. It does not destroy their eggs; a 2nd treatment is needed again after 7 days
- Spinosaid (Natroba) = promotes hyperexcitation + death by paralysis
Environmental control = treat all ppl in contact with infested patient (especially sexual partners), then use nit combs to get rid of unhatched eggs
Bedding/clothing = laundry in hot water + dryer
Toys that can’t be washed = place in air-tight plastic bags x 14 days
BASAL CELL CARCINOMA
MC type of skin cancer in the US
- MC in fair-skinned ppl with prolonged sun exposure
- Xeroderma pigmentosum = genetic disorder with inability to repair damage caused by UV light exposure
⦁ Lifetime risk of developing a BCC is 30%….one of the most common malignancies in humans
⦁ Incidence increases with age (55-75 y/o show 100-fold higher incidence than those <20)
⦁ Incidence is rising across all subgroups
⦁ Particularly common in Caucasians
⦁ Very uncommon in dark-skinned populations
⦁ States closer to the equator have much higher incidence
BCC arises from the - BASAL LAYER of the epidermis
is caused by DNA damage of keratinocytes
- rarely metastasizes, however, can be locally invasive and cause destructive of skin + surrounding structures, including the bone
- SLOW GROWING - locally invasive. VERY low incidence of metastasis
Etiology = exess UV radiation exposure
CLINICAL APPEARANCE
- Flat, firm area with Small / Translucent / Pearly white / Waxy papule, “shiny” with Telangiectasias** over the surface that slowly enlarges, and development of a Central Ulceration*** and with rolled edges
⦁ 70% of BCCs occur on the face (consistent with solar radiation)
⦁ majority are “nodular” but can also have superficial or morpheaform
DIAGNOSIS
- shave bx or punch bx
- see basophilic palisading cells on histology
TREATMENT FOR BCC
- ED+C = used MC in non-facial tumors with low risk of recurrence
- surgical excision = for tumors with either low or high tumor recurrence
- MOHS = for facial involvement/difficult/recurrent cases
- radiation therapy
- Cryotherapy = only for small and superficial BCC
- topical 5-FU = efudex or Imiquimoid (aldara) = only for small and superficial BCC.
MOHS PROCEDURE
⦁ Technique where thin layers of tumor tissue are removed and then examined microscopically
⦁ The procedure is repeated until the entire tumor is removed (no abnormal cells seen under microscopy)
⦁ After Mohs’ recurrence rates are <1%!
SUMMARY
- BCC = most frequent skin cancer (4x more common than SCC)
- Mets = rare (< 1% of cases), but does lead to local destruction of tissue
Gorlin Syndrome (Nevoid BCC Syndrome) = genetic disorder (autosomal dominant) that is characterized by a broad face + rib malformations + extraordinary predisposition to BCCs
SQUAMOUS CELL CARCINOMA
arises from the malignant proliferation of the keratinocytes of the epidermis
- Malignancy of keratinocytes of skin / mucous membranes
HYPERKERATOSIS + ULCERATION
2nd MC skin cancer worldwide (after BCC)
- SCCs often begin as AKs
- HPV infection**
⦁ may be associated with HPV types 16 / 18 / 31 / 33 / 35 - Sun + Environmental exposure
- Xeroderma Pigmentosum (genetic disorder = inability to repair damage caused by UV exposure - also a cause of BCC)
- Chronic wounds
MC locations = lips, hands, neck, head
Bowen’s Disease = SCCIS (slow growing, rarely metastasize)
AK –> Bowen’s Dz (SCCIS) –> SCC
⦁ typically presents as chronic, asymptomatic, nonhealing, slowly enlarging erythematous patch with sharp but irregular outline (scaling + crusting may be present)
Invasive SCC = flesh-colored nodule that enlarges and often undergoes ulceration and crusting
CLINICAL PRESENTATION = Red, elevated thickened nodule with adherent white scaly or crusted, bloody margins***
with multiple AKs = 10% risk of malignant transformation
DIAGNOSIS
- BIOPSY - see atypical keratinocytes and malignant cells with large, pleomorphic, hyperchromatic nuclei in the epidermis, extending into the dermis
- May form nodules with laminated centers
AK TREATMENT
- cryotherapy
- Efudex or Aldara
- Curettage
- chemical peels (TCA)
- laser
- photodynamic therapy
if non-hypertrophic = LN2
if hypertrophic = surgical curettage - send these to path
multiple AKs = Efudex or Imiquimod (aldara)
Bowen’s disease treatment (SCCIS)
⦁ Surgical excision of lesion
⦁ cryotherapy
⦁ efudex x 6 weeks under occlusion
Advanced SCC
⦁ TREATMENT OF CHOICE = WIDE LOCAL SURGICAL EXCISION
⦁ other options = ED+C, Mohs, radiation therapy
KAPOSI’S SARCOMA
- vascular tumor associated with HHV-8 (herpes virus) = KS - associated herpesvirus (KSHV)
- 4 forms of Kaposi’s Sarcoma
⦁ Classic = affects older men of Mediterranean & Jewish origin
⦁ Endemic or African = found in all parts of equatorial Africa, particularly in sub-saharan Africa. This is not typically associated with immune deficiency
⦁ Organ transplant associated
⦁ AIDS related (KS prevalence was much higher before antiretroviral therapy)
- KS = highly variable clinical course
- NOT just a skin problem - also affects oral cavity, GI tract and respiratory tract
- Skin findings ⦁ papules most often ⦁ elliptical along skin tension lines ⦁ multiple colors ⦁ may be surrounded by yellow halo
TREATMENT o Local treatment ⦁ surgery ⦁ radiation therapy ⦁ cryotherapy & laser therapy ⦁ intralesional therapy ⦁ topical therapy - imiquimod
o Systemic Treatments
⦁ chemotherapy
⦁ immunomodulators
IMPETIGO
- common, contagious, superficial skin infection
- highly contagious, superficial vesiculopustular skin infection
Typically occurs at sites of superficial skin trauma (ex: insect bite)
- primarily occurs on exposed surfaces (ex: ** FACE ** or extremities)
RISK FACTORS
⦁ warm / humid conditions
⦁ poor personal hygiene
CAUSE
⦁ strep pyogenes (GABHS)
⦁ staph aureus - produces exfoliative toxin A
⦁ combo
- high incidence in children
- self limiting (will eventually go away), but if not treated = may last weeks to months
- Post-strep Glomerulonephritis may follow impetigo**
⦁ Occurring most commonly in children age 5-12 years
⦁ Patients develop symptoms 3- 6 weeks after streptococcal impetigo
⦁ Symptoms of PSGN include gross hematuria, facial edema, renal insufficiency, brown colored urine, and hypertension
PE
⦁ nonbullous and/or bullous
⦁ have vesicles and bullae containing clear yellow or slightly turbid fluid without surrounding erythema
⦁ superficial small vesicle or pustules 1-3 cm lesions
⦁ golden-yellow, honey crusted lesions
TYPES OF IMPETIGO
⦁ NONBULLOUS = impetigo contagiosa = vesicles, pustules = characteristic “honey colored crust” = MC type. Is associated with regional lymphadenopathy. MC etiology = ** STAPH AUREUS ** (2nd MC = GABHS)
⦁ BULLOUS = vesicles rapidly form large bullae –> lead to think “varnish-like crusts”. Have fever, diarrhea
- MC = ** STAPH AUREUS**
- this form of impetigo is rare - usually seen in newborns / young children if at all
⦁ ECTHYMA = ulcerative pyoderma caused by
** GABHS ** - heals with scarring. Not common
TREATMENT
⦁ BACTROBAN (MUPIROCIN) OINTMENT - mild = MC treatment - apply TID x 10 days
⦁ Bacitracin
⦁ Wash area gently with soap / water. good skin hygiene
If extensive disease or having systemic symptoms (fever) = systemic abx
⦁ oral abx - ** Cephalexin (Keflex**), dicloxacillin (especially effective against Staph), clindamycin, erythromycin, azithromycin, clarithromycin
⦁ In severe cases = oral antibiotics to cover for MRSA = Bactrim, doxycycline, clindamycin
HSV
HERPES SIMPLEX VIRUS 1 + 2
- HSV I + HSV 2
- can occur anywhere on the body
CLINICAL MANIFESTATIONS
- prodromal symptoms x 24 hours prior = Burning, Paresthesias, Tingling
- Get painful, grouped vesicles on an erythematous base
- HSV-1 = usually oral and HSV -2 = usually genital, however, both can interchange
PRIMARY INFECTION
- can be symptomatic or asymptomatic
- can be spread by direct contact or fluid
- Symptoms occur 3-7 days after contact
⦁ Tenderness
⦁ Pain
⦁ Mild paresthesias or burning
⦁ Grouped vesicles on an erythematous base
⦁ Centers become depressed
⦁ Crusts form and heal without scaring
⦁ The virus enters the nerve endings, runs through peripheral nerves to dorsal root ganglia
- ACUTE HERPETIC GINGIVOSTOMATITIS = primary infection in children. Get sudden onset of fever, anorexia, GINGIVITIS (gum swelling, friable / bleeding gums), vesicles in mouth / tongue / lips, grey / yellow lesions
- > 90% of US population are infected with HSV-1
- ACUTE HERPETIC PHARYNGOTONSILLITIS = primary infection in adults. Vesicles that rupture –> ulcerative lesions with grayish exudates in posterior pharyngeal mucosa
- HERPES LABIALIS = cold sore / fever blister with stress or illness. Secondary infection from HSV - 1 MC
- GENITAL HSV = most often HSV -2, but can be HSV-1 as well. Genital HSV seen in 25% of population
- HERPES KERATITIS = usually unilateral. see DENDRITIC ULCERS on slit lamp.
- Bell’s Palsy = associated with HSV-1
- HSV esophagitis = small deep ulcers seen primarily in immunocompromised
- Herpetic Whitlow = HSV infection of nail or finger
- Encephalitis = HSV is the MC cause of encephalitis
RECURRENT INFECTION
- local skin trauma, especially ultraviolet
- systemic changes (fever, infection, stress)
Type I
⦁ oral + labial herpes simplex
⦁ Whitlow fingers
type II = genital
⦁ primary
⦁ recurrent
⦁ may mimic zoster in sacral distributions
DIAGNOSIS
- inspection = clinical diagnosis
- PCR = most sensitive + specific test for HSV*
- Tzanck smear = see multinucleated giant cells***** and intranuclear inclusion bodies
- Direct immuno-fluorescence antibody
- culture (viral)
TREATMENT
⦁ cool compresses
⦁ air or heat lamp - dry of lesions
⦁ Penciclovir (denavir) = topical
⦁ Famciclovir (Famvir) or Valacyclovir (Valtrex)
⦁ Acyclovir = less expensive, but have to take more often
⦁ pain control PRN
- IV antivirals for encephalitis
Acyclovir: 400 mg PO TID or 200 mg PO 5x/day x 7-10 days (cheaper but more pills)
Famciclovir: 500 mg TID x 7-10 days
Valacyclovir: 1000 mg PO BID x 7-10 days
The usual duration of treatment is 7 to 10 days
Can also do chronic suppressive therapy:
⦁ Acyclovir 400mg BID
⦁ Valacyclovir 500mg QD
VARICELLA (CHICKEN POX)
Caused by HHV-3 - Varicella Zoster Virus
Chicken Pox = Primary varicella infection
Transmission = respiratory droplets, direct contact
The virus spreads mainly by touching or breathing in the virus particles that come from chickenpox blisters, and possibly through tiny droplets from infected people that get into the air after they breathe or talk
10-20 day incubation period
It takes about 2 weeks (from 10 to 21 days) after exposure to a person with chickenpox or shingles for someone to develop chickenpox
Usually lasts 5-7 days
- highly contagious!
⦁ is highly contagious from 2 days before onset of rash until all lesions have crusted
A person with chickenpox can spread the disease from 1 to 2 days before they get the rash until all their chickenpox blisters have formed scabs (usually 5-7 days).
RASH
- appears on face + trunk (chest / back), then spreads to extremities
- CENTRIPETAL RASH = lesions mostly distributed on face / trunk / proximal extremities, less so on distal extremities
(smallpox = centrifugal - mostly face + extremities)
⦁ vesicles - “dew drops on a rose petal” = clusters of vesicles on erythematous base
⦁ pruritic
⦁ become pustules + crust over
vesicles are in ** DIFFERENT STAGES **
- have macules, papules, vesicles, pustules, and crusted lesions
SYMPTOMS - may begin to show 1-2 days prior to rash ⦁ fever ⦁ malaise ⦁ headache ⦁ decreased appetite
- more severe presentation may occur in adults
Some people who have been vaccinated against chickenpox can still get the disease. However, the symptoms are usually milder with fewer red spots or blisters and mild or no fever. Though uncommon, some vaccinated people who get chickenpox will develop illness as serious as chickenpox in unvaccinated persons.
Chickenpox can be spread from people with shingles to others who have never had chickenpox or received the chickenpox vaccine. This can happen if a person touches or breathes in virus from shingles blisters
If a person vaccinated for chickenpox gets the disease, they can still spread it to others.
For most people, getting chickenpox once provides immunity for life. However, for a few people, they can get chickenpox more than once, although this is not common.
The best way to prevent chickenpox is to get the chickenpox vaccine. Children, adolescents, and adults should get two doses of chickenpox vaccine.
Chickenpox vaccine is very safe and effective at preventing the disease. Most people who get the vaccine will not get chickenpox. If a vaccinated person does get chickenpox, it is usually mild—with fewer red spots or blisters and mild or no fever. The chickenpox vaccine prevents almost all cases of severe disease.
TREATMENT
- usually self-limiting
- Calamine lotion and colloidal oatmeal baths may help relieve some of the itching
- Keeping fingernails trimmed short may help prevent skin infections caused by scratching blisters
- if symptomatic
⦁ benadryl for pruritus
⦁ tylenol for fever
Do not use aspirin or aspirin-containing products to relieve fever from chickenpox. The use of aspirin in children with chickenpox has been associated with Reye’s syndrome, a severe disease that affects the liver and brain and can cause death
- Systemic
⦁ Acyclovir (Zovirax)
Acyclovir, an antiviral medication, is licensed for treatment of chickenpox. The medication works best if it is given within the first 24 hours after the rash starts. Other antiviral medications that may also work against chickenpox include valacyclovir and famciclovir
CDC recommends two doses of chickenpox vaccine for children, adolescents, and adults. Children should receive two doses of the vaccine—the first dose at 12 through 15 months old and a second dose at 4 through 6 years old
VARICELLA ZOSTER (SHINGLES)
- more than 60% are > 50 y/o
- involves dermatomes
- reactivation of varicella virus in cutaneous nerves from earlier varicella
- triggering factors
- unilateral, very painful
- flu like prodrome
COMPLICATIONS OF ZOSTER
⦁ Postherpetic neuralgia
⦁ Temporary motor paresis
Common locations ⦁ Thoracic ⦁ Trigeminal ⦁ Lumbosacral ⦁ Cervical
SHINGLE LESIONS ⦁ Papules to vesicles-bullae ⦁ Pustules to crusts ⦁ Erythematous, edematous base with superimposed clear vesicles, sometimes hemorrhagic ⦁ Vesicle is oval or round ⦁ Can have regional lymphadenopathy
TREATMENT
- famvir, valtrex or acyclovir 800mg 5xd for 7-10 days
- oral steroids are controversial
- antibiotic cream to prevent secondary infections
- if extremely painful = - Ultram PO (tramadol)
- burrow’s solution or cool tap water compresses
CONTACT DERMATITIS
- direct exposure to a substance –> allergy or irritation
- most common plant causes in North America = Oleoresin Urushiol = found in Poison ivy, poison oak, poison sumac, skin of mangoes, gingko fruit
- may spread from pets or from oils trapped under fingernails
Other common allergens
⦁ Nickel (jewelry, buttons, belts)
⦁ Formaldehyde, quanternium-15 (clothing, nail polish)
⦁ perfumes, cosmetics
⦁ preservatives (topical medications, cosmetics)
⦁ rubber + chemicals in shoes
⦁ topical hydrocortisone, topical antibiotics (neomycin, bacitracin), topical meds (benzecaine, thimerosol)
⦁ Laundry detergents - may be a rare cause
CLINICAL PRESENTATION
⦁ intense pruritus
⦁ rash
⦁ papular, erythematous lesions
⦁ papules from fluid in the epidermis and in severe cases produces vesicles & serous oozing
- exposure may have been as far back as 2 weeks ago
- may develop a rxn to products that you have used for months to years
TREATMENT
o Plant-based Contact Dermatitis
⦁ symptomatic therapy - oatmeal baths, cool/wet compresses, Calamine lotion, Burrow’s or domeboro solution for weeping lesions, Zanfel soap
⦁ Antihistamines - used for sedation, as this is NOT due to histamine release
⦁ Topical Corticosteroids: high potency = Clobetasol
⦁ Systemic Steroids if needed for large areas, face or genitals = give 2-3 week taper of prednisone
o Treatment of Contact Dermatitis
⦁ remove offending agent
⦁ topical symptomatic therapy
⦁ medium to high potency topical steroids = Clobetasol cream
⦁ Systemic steroids in severe cases (> 10% BSA) = medrol dose pack or prednisone taper
⦁ Burrow’s solution for weeping blisters
⦁ Antihistamines for treatment of pruritus
⦁ treat any recognized secondary bacterial infections
if contact dermatitis is caused by an irritant, the reaction is usually immediate
if caused by an allergen, rxn may be delayed
DYSHIDROSIS / DYSHIDROTIC ECZEMA
POMPHOLYX
- Cause = unknown
- Vesicular eruption on the skin of hands + feet - marked by intense itching***
- vesicles are deep
- scaling, fissures and lichenification may follow
TRIGGERS ⦁ sweating ⦁ emotional stress ⦁ warm / humid weather ⦁ pollen ⦁ metals (nickel / cobalt / chromium salts in objects and/or food)
- Association with seasonal allergies
dyshidrotic eczema blisters are known to erupt more frequently during the spring allergy season. The blisters may last up to three weeks before they begin to dry and can sometimes be large and painful. As the blisters dry, they may turn into skin cracks or cause the skin to feel thick and spongy, especially if you’ve been scratching the area
Dyshidrotic eczema usually appears in adults ages 20 through 40 but it can also affect children
People with contact dermatitis, atopic dermatitis or hay fever, are at higher risk of developing dyshidrotic eczema
Dyshidrotic eczema seems to run in families, so if you have a close relative with this form of eczema, your chance of also developing it is increased.
CLINICAL MANIFESTATION
⦁ pruritic “tapioca like” tense vesicles on soles, palms and fingers (common on lateral digits)
Characterized by a pruritic vesicular eruption comprised of clear, deep-seated vesicles without erythema erupting on the lateral aspects of fingers, the central palm, and plantar surfaces.
The eruption has been described as resembling tapioca pudding. The onset may be acute, recurrent, or chronic.
TREATMENT
⦁ High potency topical steroids - ointments preferred; may need to be given with occlusion
⦁ hydration of skin with emollient cream
⦁ cold compresses, Burrow’s solution, Tar soaks
PERICARDIAL EFFUSION
- Abnormal accumulation of fluid in the pericardial sac
- Increased fluid in the pericardial space
- Fluid can be ⦁ serous ⦁ serosanguinous ⦁ blood ⦁ pus ⦁ chyle (lymph fluid)
CAUSES OF PERICARDIAL EFFUSION
⦁ Disturbance in the equilibrium between the production and reabsorption of pericardial fluid
⦁ Develops during any inflammatory pericardial disease
ETIOLOGIES = PERICARDITIS (viral - coxsackie, bacterial, TB, etc), malignancy, infection, radiation, dialysis/uremia - renal failure, collagen vascular disease - aortic dissection extending into the pericardium, chest trauma, myxedema (hypothyroidism),
- 15-50ml of fluid is the usual amount of fluid within the pericardium
- Symptoms don’t necessarily depend on the amount of fluid; The amount of fluid can vary
o a small amount of fluid (80 mL) can rapidly be very symptomatic
o a large amount of fluid (2 L) may build up over time and be less symptomatic - symptoms may be related to the underlying cause
⦁ ex: fever if secondary to infection
⦁ night sweats/cough with TB
⦁ weight loss with cancer - without tamponade, the signs and symptoms of an effusion may be very subtle
PHYSICAL EXAM
- **DISTANT (MUFFLED) HEART SOUNDS - fluid interferes with sound conduction
EKG OF PERICARDIAL EFFUSION
⦁ Electrical Alternans = Tall short Tall short Tall short (QRS waves) - this can also occur on an EKG with deep breathing = due to cyclic shifts with beats as heart swings in fluid
⦁ LOW VOLTAGE QRS = suggests a large effusion or tamponade
⦁ Tachycardia (to make up for decreased cardiac output)
- OTHER DIAGNOSTIC STUDIES FOR PERICARDIAL EFFUSION -
⦁ **Echocardiogram = shows increased pericardial fluid - used to assess for tamponade
⦁ CXR = cardiomegaly - enlarged cardiac silhouette & water bottle shaped heart* - (usually not seen until advanced stages/tamponade)
TREATMENT OF PERICARDIAL EFFUSION
⦁ small effusions can be monitored
⦁ with large effusions & tamponade = Pericardiocentesis - fluid is drained
⦁ with reoccurrences = pericardiectomy
- the majority of fluid pools in the apex, so when draining (pericardiocentesis) = aim for the apex; bedside echo done to guide needle; enter through subxiphoid space - aim for apex of heart
- pericardial fluid analysis: gram stain - bacterial & fungal cultures, cytology, AFB stain - detects mycobacterium (TB), PCR for specific viruses (CMV)
ventricular free-wall rupture or aortic dissection = actively bleeding = don’t want to do pericardiocentesis to drain the pericardium, because the fluid is actually helping stop some of the bleeding. These conditions go to surgery instead
RECURRENT EFFUSION TREATMENT
- generally patients with cancer have recurrent effusions
⦁ pericardiectomy = surgical removal of part or most of pericardium (also done for chronic pericarditis)
⦁ pericardial window - fluid can drain into chest cavity
⦁ pericardiodesis = steroids, tetracyclines or antineoplastic drugs injected into the pericardial space causing sclerosis - scar the pericardium
CONTRAINDICATIONS TO PERICARDIOCENTESIS o Acute MI associated with LV free wall rupture o Aortic dissection o Bleeding disorder / coagulopathy o Underlying severe pulmonary HTN
Pericardial effusion = cannot remove fluid as quickly as it comes in; can start putting pressure on the heart itself, preventing it from fully stretching out or relaxing between contractions
- Electrical Alternans + low QRS voltage
- this can lead to cardiac tamponade - in which there is so much pressure that the cardiac chambers can’t properly fill will blood, causing a decrease in cardiac output. to compensate –> tachycardia
PILONIDAL CYSTS
- Cyst near the natal cleft of the buttocks that often contains hair or skin debris
- tender abscess with drainage on or near the GLUTEAL CLEFT near the midline of the coccyx or sacrum with small MIDLINE PITS
- usually happens when hair punctures the skin and becomes embedded
MC in white males who are obese, hairy patients; can occur from prolonged sitting or local trauma
- occurs in hairy, young men**
- rare in patients > 40
CLINICAL PRESENTATION
- pain
- erythema + swelling of the skin
- drainage of foul smelling pus or blood from the opening of the skin
RISK FACTORS
- obesity
- prolonged sitting
- local trauma / irritation
TREATMENT / PREVENTION
1) I+D the cyst - may need to leave open or pack
2) if cyst reoccurs = surgery (excision of cyst + tracts)
3) Antibiotics - usually only given in the setting of cellulitis = Cefazolin (1st gen) + Metronidazole (Flagyl)
ILEUS
- temporary absence of the normal contractile movements to the intestinal wall
- Decreased peristalsis WITHOUT structural obstruction - non-mechanical factors affect the motor activity of the GI tract
ETIOLOGIES OF ILEUS
⦁ Postoperative State—especially abdominal when intestine’s have been manipulated
⦁ Drugs: opioids and anticholinergics
⦁ Hypothyroidism
⦁ Diabetes
⦁ Electrolyte disorders—hypokalemia, hypercalciemia
⦁ Intestinal peritonitis
⦁ Severe Medical Illness: Kidney failure, Pancreatitis
CLINICAL MANIFESTATIONS
- bloating
- nausea
- vomiting
- crampy abdominal pain - pain precedes vomiting when associated with acute surgical etiology
- severe constipation
- obstipation = severe constipation
- abdominal distention
- loss of appetite - may not be able to tolerate oral diet
DIAGNOSIS OF ILEUS ⦁ XRAYS = 1ST LINE - see uniformly distended loops of small + large bowel (due to air) as well as air in the rectum with no transition zone ⦁ electrolytes ⦁ CBC ⦁ CMP including magnesium
- CT or Upper GI series may be performed if high suspicion and negative abdominal films
TREATMENT OF ILEUS
- NPO (nothing by mouth) or dietary restriction - advancing to clear liquids as tolerated
- IV fluids to maintain hydration
- correct electrolyte abnormalities
- stop drugs that will make ileus worse (d/c opioids and use other meds for pain) / treat underlying cause
- Occasionally an NG tube if moderate vomiting
AML
AUER RODS
ALL
OCCURS IN CHILDREN
CML
PHILADELPHIA CHROMOSOME (Philadelpha CreaM cheese)
CLL
no clear distinguishing features except increased lymphocytes
MULTIPLE MYELOMA
BENCE JONES PROTEIN
PATHOPHYSIOLOGY OF ATHEROSCLEROSIS
Atherosclerosis = The formation of fibrofatty lesions in the intimal lining of large and medium sized arteries
Roles of Endothelium (lining of blood vessels)
⦁ Acts as a barrier between stuff that’s in the blood and the rest of the blood vessel wall, so stuff can’t just pass through to the vessel walls
⦁ Another really important function = secretes proteins onto its surface that prevent clotting
3 LAYERS OF ARTERIES
1) Tunica intima
2) Tunica media
3) Tunica externa or adventitia
- there is an internal and external elastic membrane between the layers
- internal elastic membrane is between the tunica intima & tunica media
- external elastic membrane is between the tunica media & tunica externa/adventitia
- innermost = endothelium. So endothelium, tunica intima, internal elastic membrane, tunica media, external elastic membrane, and tunica externa
STEPS OF ATHEROSCLEROSIS
1) irritant present (LDL, toxins, HTN)
2) damage to endothelium
3) plaque buildup –> fatty streak
4) oxidation of plaque –> monocytes recruited –> macrophages –> die –> foam cells –> release signals (cytokines) –> inflammation –> further endothelium damage
5) foam cell signals –> 1 of them is to smooth muscle cells which deposit calcium in fatty streak/plaque buildup –> leads to further hardening of plaque –> arteriosclerosis
6) smooth muscle cells also secrete a fibrous cap over the plaque buildup so not exposed to blood. Bulge is now occluding / blocking off part of the artery
7) if fibrous cap ruptures, now exposed to blood, clot can start building on top of plaque, and further occlude blood vessel
ETIOLOGY
⦁ NON-MODIFIABLE RISK FACTORS OF ATHEROSCLEROSIS
o Age
o Family Hx of Premature CAD - genetic alteration in lipid metabolism
o Male Sex
o Post-menopausal Females (estrogen)
- Atherosclerosis increases with age - starts at childhood
- Men’s rate of atherosclerosis is higher than women’s. Once women are post-menopausal, however, their rate of atherosclerosis goes back up to being equal to men’s
⦁ MODIFIABLE RISK FACTORS OF ATHEROSCLEROSIS
o hypercholesterolemia - high LDL
o Cigarette smoking - toxins –> increased endothelial damage (1 ppd = 2x damage to endothelium
o obesity
o visceral fat
o hypertension - increases risk of CAD x 2
o DM - increases risk of CAD > 2x, if both DM & HTN = 8x
⦁ NON-TRADITIONAL RISK FACTORS o elevated CRP o elevated homocysteine o lipoprotein a o infectious agents o inflammation
CRP = C-reactive protein
- marker for systemic inflammation
- elevated CRP levels are associated with vascular disease
HOW TO REDUCE CRP LEVELS ⦁ exercise ⦁ decreased stress ⦁ statins ⦁ fibrates ⦁ TZDs
HOMOCYSTEINE
- derived from animal protein
- how to lower homocysteine levels = increase vitamin B6/B12/Riboflavin
- function of homocysteine = inhibits elements of the anticoagulant cascade by impairing fibrinolysis –> impairs ability to break down clots –> endothelial damage
- elevated homocysteine levels are associated with
⦁ endothelial damage
⦁ vascular inflammation
⦁ local ischemia of the arterial wall
-however, studies have shown that there isn’t that much of a benefit to increasing vitamin B6/B12/riboflavin levels, because while homocysteine levels are decreased, it is more related to genetic metabolism, so the lowering of homocysteine will not be significant enough to prevent endothelial damage
LIPOPROTEIN A
- lipoprotein A is similar to LDL
- it is an independent risk factor for premature CVD
- lipoprotein A binds to macrophages and promotes foam cell formation and the deposition of cholesterol in atherosclerotic plaques
- would check lipoprotein A levels in patients with premature CAD or a positive family history
- Ways to reduce lipoprotein A = Niacin + Statin. Don’t generally manage with just niacin, usually a statin is added
INFECTIOUS AGENTS
⦁ Chlamydia pneumonia
⦁ Herpes virus
⦁ CMV
- endothelial cells damaged by irritant. Inflammatory cells migrate over. Lipids accumulate in intima. Monocytes –> Macrophages. Macrophages release free radicals which oxidizes the LDL. Macrophages eat oxidized cholesterol (toxic to macrophages) –> die and become foam cells –> accumulate –> further inflammation. Muscle cells proliferate to form fibrous cap to wall off plaque/foam cells –> occludes/blocks off part of the artery
ENDOTHELIAL CELL INJURY
- elevated LDL
- smoking
- mechanical stress from hypertension
- immune mechanisms - anything that will cause infection or inflammation
Endothelial loss and exposure of subendothelial tissue to blood components leads to platelet aggregation + fibrin deposition
TYPES OF ATHEROSCLEROTIC LESIONS
⦁ Fatty Streak
⦁ Fibrous Atheromatous Plaque
⦁ Complicated Lesion
Fatty Streak
- first visible lesions that develop as early as the first year of life
- fatty streaks form from accumulation of LDL particles in arterial intima. The LDL particles induce an inflammatory reaction
- Monocytes, Lymphocytes, Mast Cells, Neutrophils flow into arterial walls. Monocytes mature into Macrophages
- The macrophages engulf the lipoprotein particles and become foam cells
- fatty streaks are generally pretty flat and don’t cause too much obstruction. Not until they chronically build up to form plaque/fibrous scar tissue
Fibrous Atheromatous Plaque
- fatty streaks develop into fibroatheromas
- early fibroatheromas develop in late adolescence and early adulthood
- plaques form due to the accumulation of foam cells, inflammatory cells, and normal arterial cells between the endothelial lining and medial arterial wall
- cell necrosis occurs and leads to further inflammation/distortion of normal intimal structure
- cell necrosis –> lipid rich necrotic core forms from dead & dying cells and extracellular lipids
- fibrous tissue forms around necrotic core & under the endothelium = fibrous cap
- advancing atheroma - occurs in late adulthood, where the fibrous cap of the fibroatheroma thins due to weakening. Thin caps may rupture and thrombose
- a thrombus that is at high risk of rupturing is called a VULNERABLE PLAQUE
- vulnerable plaques when ruptured can cause thrombosis and lead to MI/stroke
Complex Lesions
- calcium deposition makes the artery more hard/brittle = less mobile–> high risk of rupture
- cycles of thin cap rupture, thrombosis, and healing may occur and can be clinically silent
- calcium deposits can accumulate into large nodules. If ruptured, become sites for thrombosis
- more unstable because both old and new - both central necrotic core & also building smooth muscle cells –> calcium –> more likely to dislodge
CLINICAL MANIFESTATIONS
- narrowing of the blood vessel takes place (plaque buildup) –> increased BP
- stiffening and decreased vessel compliance (calcium) –> increased BP
- plaque hemorrhage or rupture
- thrombosis & formation of emboli from damage to vessel endothelium
- aneurysm (balloon formation in vessel) formation due to weakening of vessel wall (collection of blood –> more susceptible to clot formation)
SIZE MATTERS
⦁ Larger Arteries (like the aorta) - more susceptible to thrombus formation & weakening of the vessel wall (rupture)
⦁ Medium sized arteries (like the coronary & cerebral arteries) - more susceptible to ischemia (reduced blood supply and therefore oxygen supply) & infarction (tissue death due to inadequate supply of oxygen) due to vessel occlusion
THE MOST COMMONLY AFFECTED ARTERIES ARE o heart o brain o kidneys o lower extremities o small intestine
RHEUMATIC HEART DISEASE / RHEUMATIC FEVER
Rheumatic heart disease is caused by rheumatic fever, an inflammatory disease that can affect many connective tissues, especially in the heart, joints, skin, or brain. The heart valves can be inflamed and become scarred over time. This can result in narrowing or leaking of the heart valve making it harder for the heart to function normally
Caused by infection of the throat with group A streptococcus bacteria. The condition is characterized by fever and painful, tender joints. Treatment involves use of antibiotics such as penicillin, NSAIDS such as aspirin and bed rest.
A possible complication of strep throat infection or scarlet fever that can cause a wide range of secondary symptoms from joint inflammation to heart valve damage.
MITRAL REGURGITATION
BLOWING HOLOCYSTOLIC (PANCYSTOLIC) MURMUR DURING SYSTOLE @ apex
- Radiates to the axilla
Widely Split S2
PARONYCHIA
Infection of the nail margin
Superficial inflammation of the lateral + posterior folds of the nail surrounding fingernail or toenail
MC occurs after skin trauma (biting nails, cuticle damage) - infection in the skin around the fingernails or toenails often caused by ingrown nails
MC bacterial agent = STAPH AUREUS (especially if rapid)
- others = GABHS
- Candida if slow growing
CLINICAL MANIFESTATION
- painful, red, swollen area around the nail at the cuticle site / around the base or the sides of the nail.
MANAGEMENT
- warm soaks (to reduce pain + swelling)
- ABX (cephalexin / Keflex)
- I+D (to drain pus)
***Most important thing = differentiate paronychia from a felon (entire finger is swollen, red, and very tender = starting to compromise vascular flow to the area)
FELON
closed space infection of the fingertip pulp
a paronychia can progress into a felon
pulp space infection in a CLOSED COMPARTMENT - comprising the pulp space of the tip of the digit
- swollen, exquisitely tender, erythematous
- the edema from a felon can compromise arterial supply and lead to necrosis of the fingertip
TX = I+D, antibiotics, and referral to hand surgeon for definitive treatment
ONYCHOMYCOSIS
= Tinea Unguium = fungal nail infection
- vast majority of fungal nail infections = caused by TRICHOPHYTON RUBRUM (type of dermatophyte)
- most of the time due to dermatophytes
Most common location = distal subungual region
- seldom are all nails affected
- toenails = much more common than fingernails
Seen more with fake nails, pedicures, not changing out of sweaty boots
- Nail infection by various fungi (ex: tinea, candida). Occurs MC on great toe
RISK FACTORS FOR ONYCHOMYCOSIS
⦁ DIABETES*** (fungus likes to eat sugar, so with tinea or candida etc = check blood sugar)
⦁ older age
⦁ swimming
⦁ increased skin moisture (occlusive gear)
⦁ tinea pedis
⦁ psoriasis
⦁ immunodeficiency (HIV)
⦁ PVD (peripheral vascular disease)
⦁ living with family members who have onychomycosis
PRESENTATION
- brittle
- lusterless
- hypertrophic
Begins with whitish, yellowish or brownish discoloration in one region of the nail, then gradually spreads to involve the entire width of the nail plate
⦁ nail plate then starts to break away or is picked away by the patient
⦁ mostly cosmetic concern, but can cause physical discomfort for some
- Opaque, thickened, discolored, cracked nail with subungual hyperkeratinization
DIAGNOSIS
- nail dystrophies often clinically indistinguishable from onychomycosis
- nail dystrophies can occur with psoriasis, eczematous conditions, senile ischemia, trauma and lichen planus
- onychomycosis = responsible for only 50-60% of abnormal appearing nails, so HAVE to make the diagnosis before treating
⦁ KOH prep - Woods lamp = green fluorescence if microsporum
⦁ nail culture - often performed when patients have a negative KOH exam; culture takes 4-6 weeks. Dermatophyte Test Medium
⦁ Nail plate Biopsy = most sensitive test - clip nail just distal to nail bed, place in 10% formalin**
TREATMENT
- treatment is recommended in the following groups
⦁ patients with hx of cellulitis of the LE who have an ipsilateral toenail onychomycosis
⦁ patients with diabetes who have additional risk factors for cellulitis (prior cellulitis, venous insufficiency, PAD, edema)
⦁ patients with discomfort or pain
⦁ patients who desire tx for cosmetic reasons
- onychomycosis can trigger cellulitis
TREATMENT
- topical therapies = generally ineffective - unable to penetrate nail plate
- there is a high rate of treatment failure & recurrence even with oral therapy
⦁ Oral Terbinafine (Lamisil) - success = about 75% = treatment of choice - has greater efficacy and fewer SE than alternative oral regimens**
⦁ Alternatives = Itraconazole (Sporanox), Griseofulvin, and Fluconazole (Diflucan)
TERBINAFINE (LAMISIL)
- associated with hepatotoxicity
**Careful with the liver - no alcohol!
and don’t take with a statin - will make LFTs skyrocket
Treatment Monitoring
- can cause increased LFTs, hepatotoxicity, hepatic failure
- assess LFTs prior and during course of treatment
- CANNOT USE WITH STATINS***
recurrence rate = 20-50%; high rate of treatment failure & recurrence with oral therapy
Tinea vs Candida
- both infections are fungal
- ringworm is a dermatophyte = a type of fungi that can cause skin, hair, or nail infections.
- Candida is a yeast
IBD (INFLAMMATORY BOWEL DISEASE)
- consists of both Crohn’s Disease and Ulcerative Colitis
- highest incidence of IBD in Jewish population
- Geographic distribution of IBD = highest = North America (US/Canada), Europe, and Australia
- Peak age incidence = 20’s (10-30)
- Sex incidence: Ulcerative Colitis more prevalent in males, Crohn’s more prevalent in females
EPIDEMIOLOGY
- IBD is common in developed nations; is infrequent in countries with poor sanitation
- North America & Europe rates highest
- most common in 2nd & 3rd decades, but can affect any age
- Males about = to females, however, UC slightly more common in males, Crohns slightly more common in females
ETIOLOGIC THEORIES OF IBD ⦁ Infectious ⦁ Immunologic ⦁ Genetic ⦁ Dietary ⦁ Environmental ⦁ Vascular ⦁ Neuromotor ⦁ Allergic ⦁ Psychogenic
- not really known, perhaps a combination of multiple factors
PATHOPHYSIOLOGY
- IBD = a defect in the function of the intestinal lumen
- breakdown of the defense barrier of the gut –> leading to exposure of the mucosa to microorganisms or their products
- this results in a chronic inflammatory process that is mediated by T cells (so more likely to get C. dif, giardia, staph, etc.)
ULCERATIVE COLITIS (IBD)
- AUTOIMMUNE
- mucosal ulceration in the colon
- primarily involves the mucosal layer, and occasionally the submucosa of the colon, but MOSTLY just the mucosal layer - more superficial than Crohn’s disease (transmural)
ULCERATIVE COLITIS = involves the mucosal surface of the colon - with the formation of crypt abscesses
- UC ALWAYS INCLUDES THE RECTUM, and then the inflammation spreads proximally
⦁ Distal Colitis = Proctitis (inflammation of rectum) or Proctosigmoiditis (inflammation of rectum & sigmoid colon)
⦁ Extensive Colitis (Pancolitis) = Mild to mod, severe
***UC is UNIFORMLY CONTINUOUS and CIRCUMFERENTIAL ; NO SKIP LESIONS (unlike Crohns)
o 50% of UC = Rectosigmoid (Proctosigmoiditis)
o 30% = to the splenic flexure (left sided colitis)
o 20% = extends proximally (pancolitis)
The top of the mucosa sheds off –> abscesses form. Always starts in the rectum, then spreads proximally
On imaging - shows granular mucosa - more mottled appearance of colon. If biopsied = lots of inflammatory mediators are present
CLINICAL COURSE OF ULCERATIVE COLITIS
- consists of cycles of flares + remissions
- more common in nonsmokers*
- the disease severity may actually be lower in active smokers, and may worsen in patients who stop smoking (onset occasionally appears to coincide with smoking cessation)
⦁ smoking is bowel protective in UC - smoking attacks the immune system, and since UC is autoimmune, prevents the body’s own immune system from attacking the mucosa of the GI tract - higher risk of developing cancer - this is related to the extent/duration/age of diagnosis of UC
SIGNS/SYMPTOMS
Mild/Moderate UC
⦁ Hallmark = bloody diarrhea
⦁ lower abdominal cramps (that is relieved with defecation) - (occurs in IBS too)
⦁ fecal urgency
Severe UC ⦁ rectal bleeding ⦁ LLQ cramps ⦁ severe diarrhea ⦁ fever ⦁ anemia (from blood loss) ⦁ hypoalbuminemia (from protein loss) ⦁ hypovolemia (dehydrated)
SYSTEMIC ASSOCIATIONS
- arthritis
- erythema nodosum***** (inflammation of the fat cells under the skin, resulting in tender red nodules or lumps that are usually seen on both shins) - usually resolves
by 6 weeks
- pyoderma gangrenosum
- uveitis, episcleritis
- fever, sweats, weight loss, malaise, fatigue
- sclerosing cholangitis (disease of the bile ducts - causes inflammation + obstruction)
LABS
o CBC
⦁ anemia
⦁ leukocytosis
o Sed Rate & CRP (inflammation)
⦁ elevated sed rate
⦁ elevated CRP
The sedimentation rate increases when more inflammation is present in the body of the person whose blood was sampled because inflammation alters certain substances on the surfaces of the red blood cells, making them tend to adhere together and more rapidly fall to the bottom of the test tube
MILD ULCERATIVE COLITIS
- Stools: < 4/day
- Pulse: < 90
- Hematocrit: normal (about 36-48); 45% for men, 40% for women
- Weight loss: none
- Temperature: normal
- ESR: < 20
- Albumin: normal (3.5 - 5.5)
hematocrit = ratio of RBCs to total volume of blood
MODERATE ULCERATIVE COLITIS
- Stools: 4-6/day
- Pulse: 90-100
- Hematocrit: 30-40
- Weight Loss: 1-10%
- Temperature: 99-100
- ESR: 20-30 (normal = 0-22/men; 0-29/women)
- Albumin: 3-3.5
SEVERE ULCERATIVE COLITIS
- Stools: > 6/day (mostly bloody)
- Pulse: > 100
- Hematocrit: < 30
- Weight loss: > 10%
- Temperature > 100
- ESR: > 30
- Albumin: < 3
DIAGNOSIS = SIGMOIDOSCOPY (best choice)
- the diagnosis is usually based on clinical presentation -
- also done based on exclusion of bacterial and parasitic infection, and from sigmoidoscopic demonstration of inflammation
o presence of bloody diarrhea (differentiates from Crohns)
o plain abdominal xrays
o sigmoidoscopy**
o CT scan
MC type of IBD = UC**
- causes inflammation and ulceration of the mucosa and/or submucosa of the large intestine ONLY, which sets it apart from Crohns disease
ETIOLOGIES
- autoimmune
- idiopathic - most likely an immune reaction to GI tract flora
- cytotoxic T cells often found in the epithelium lining the colon - destroy the endothelium of the intestinal area
- some patients have p-ANCA in their blood (antibodies that target antigens in body’s own neutrophils) - perhaps an immune reaction occurs to gut bacteria that have structural similarities to our own cells –> causing antibodies to gut bacteria to target neutrophils
** p-ANCA **
CAUSES
- combination of environmental stimuli + genetic predisposition***
- MC in Caucasians and Jews
- MC age : 15-35
CLINICAL MANIFESTATIONS
⦁ CIRCUMFERENTIAL & CONTINUOUS inflammation - goes around the entire lumen. Starts in the rectum and spreads upward without any breaks (“skip lesions”)
⦁ MC pain = LLQ (rectum) / colicky
⦁ Tenesmus = feeling of incomplete defecation
⦁ BLOODY DIARRHEA = HALLMARK - severe and frequent diarrhea with blood (as cells of colon are destroyed, can’t absorb water properly –> diarrhea)
⦁ stools with mucus / pus, hematochezia
⦁ Smoking DECREASES risk for UC
⦁ Uniform inflammation
⦁ Pseudopolyps
⦁ “Stovepipe Sign” = loss of haustral markings with barium studies
DIAGNOSIS = SIGMOIDOSCOPY = test of choice in acute UC - can see ulcers / take biopsies
⦁ don’t do Colonoscopy with acute UC = risk of perforation
⦁ don’t do barium enema / xray with acute UC = risk of toxic megacolon
but can do CT scans, MRI, and barium enemas
- see “stovepipe” sign = loss of haustral markings
TREATMENT
⦁ 5-ASA = 5-Aminosalicylic acids = anti-inflammatory agents = good for flares and remission
- Mesalamine (oral) = best for maintenance
- Mesalamine topical (rectal suppositories or enemas) = effective in distal colon
- Sulfasalazine = works primarily in colon. *Higher SE profile. **Give FOLIC ACID with sulfasalazine
Other TX options = Immunosuppressors
⦁ Steroids = for acute flares only (long term risks = osteoporosis, increased infections, weight gain, edema, cataracts, etc)
⦁ Azathioprine or Cyclosporine
⦁ Biologics - Infliximab, Adalimumab etc)
⦁ Colectomy - surgical removal of colon - generally cures the disease since UC only affects the colon
- surgery is curative, unlike with crohns
CROHNS (IBD)
- not technically classified as an autoimmune disease, like UC, but rather an immune-related disorder - in which rather than antibodies to own cells
- in crohns = thought to be triggered by some foreign pathogen in GI tract
- this is what is supposed to happen…however, the response is exaggerated inflammation that ends up damaging cells in intestinal tract
- thought that some defect in epithelial barrier more easily lets pathogens through –> activates immune system –> unregulated inflammation / cell destruction
- immune cells spread down deep into intestinal wall layers and form granulomas (big masses of immune cells that are trying to encapsulate foreign pathogens)
- eventually, ulcers form from inflammation and cellular damage –> ulcers appear as craters in intestinal wall
- genetic factor: family hx of crohns = increased risk of developing crohns
- Transmural inflammation (involves ileitis, ileocolitis, and colitis). Crohns disease can affect the GI tract from the mouth to the anus, and goes all the way through the GI wall
TRANSMURAL (spans entire intestinal wall, from mucosa to serosa)
- with formation of fistulas, narrowing of the lumen, and obstruction
- can involve any segment of the GI tract
⦁ Ileocolitis = 45% (most common to affect ileum & colon)
⦁ Ileitis = 28% (just ileum)
⦁ Colitis = 15% (just colon)
⦁ Gastroduodenitis = 7% (stomach & duodenum)
⦁ Jejunoileitis = 5% (jejunum & ileum)
***Usually RECTAL SPARING (doesn’t affect the rectum, unlike ulcerative colitis)
SKIP LESIONS - can have healthy tissue between areas of inflammation along the GI tract
** Cigarette smoking is strongly associated with the development of Crohns disease (unlike Ulcerative Colitis, where smoking is protective). Smoking with Crohn’s leads to resistance of medical therapy and early disease relapse
- Involves ANY SEGMENT of the GI tract, from mouth to anus…spares the rectum
- MC in terminal ileum –» RLQ pain (UC = LLQ)
CLINICAL MANIFESTATIONS
- presentation depends on the site & severity of inflammation
- insidious onset usually
- Intermittent bouts of low grade fever
- diarrhea (usually no bleeding, unlike ulcerative colitis)
- RLQ pain
- postprandial pain is common
- RLQ mass
- Perianal disease (abscess, fistulas, strictures, Granulomas, etc)
- Often nocturnal bowel movements
- night sweats
- weight loss
- Skin lesions (primarily erythema nodosum) - may precede intestinal symptoms
- pallor
Pts often chronically ill
SYSTEMIC ASSOCIATIONS
- arthritis
- erythema nodosum***** (inflammation of the fat cells under the skin, resulting in tender red nodules or lumps that are usually seen on both shins) - usually resolves
by 6 weeks
- pyoderma gangrenosum
- uveitis, episcleritis
- fever, sweats, weight loss, malaise, fatigue
- sclerosing cholangitis (disease of the bile ducts - causes inflammation + obstruction)
- **malabsorption –> Iron + B12 deficiency (especially if small intestine is involved)
- With children or adolescents = presentation is often insidious with weight loss, failure to grow or develop secondary sex characteristics. Arthritis, or fever of unknown origin
- weight loss more common with crohns
PHYSICAL EXAM - abdominal distention - abnormal bowel sounds - tenderness in the area of involvement - Perianal region ⦁ abscesses ⦁ fistulas ⦁ skin tags ⦁ anal strictures
LABS o CBC ⦁ anemia ⦁ leukocytosis o Sed Rate + CRP ⦁ both elevated - reflect acute phase o CMP ⦁ electrolyte disturbances ⦁ decreased serum albumin ⦁ prolonged clotting time o ASCA (immune proteins present with IBD) ⦁ serum anti-saccharomyces cerevisiae antibody = highly specific, but not very sensitive
RADIOGRAPHY
- Barium Contrast studies = most commonly used for upper & lower GI tract = better for finding complications (strictures/fistulas)
⦁ Can see “cobblestoning”, “skip lesions”, psudodiverticula, dilated bowel, fistulas communicating to adjacent bowel/mesentary/bladder/vagina
- Histology from endoscopic biopsy
WITH CROHNS DISEASE = small bowel involvement, rectum spared, bleeding absent, perianal disease, focal lesions, segmental distribution, asymmetrical involvement, fistulae, granulomas, and endoscopic differences
“string sign” where inflammation has eroded through wall. “cobblestoning” appearance
- a fistula can form (passageway between 2 organs) - can be entero-enteric, entero-vesical, retroperitoneal, and entero-cutaneous
- perianal fistula & abscess & skin tags (perianal disease) = complications of Crohns disease
- ** “STRING SIGN” ***
- ** COBBLESTONE APPEARANCE ***
- ** SKIP LESIONS ***
- ** ASCA antibodies ***
- **PERIANAL DISEASE ***
TREATMENT o 5-Aminosalicylic Acid Agents ⦁ Sulfasazine ⦁ Mesalamine ⦁ Pentasa o Antibiotics o Corticosteroids o Anti-TNF therapy ⦁ Infliximab (Remicade) o Immunomodulating Drugs ⦁ Azathioprine ⦁ Mercaptopurine ⦁ Methotrexate
- surgery = non-curative, unlike ulcerative colitis
ABSENCE SEIZURES (PETIT MAL) = type of generalized seizure disorder
- Non-convulsive
- Generalized, non-convulsive epileptic events
- expressed mainly as disturbances in consciousness = “petit mal seizures”
- MC in childhood and cease in adulthood (by 20y/o)
- **Can evolve into generalized motor seizures
- onset + termination of attacks = abrupt
- impairment is so brief that patient is unaware of it
- lasts about 10 seconds
Examples
⦁ Brief lapse of consciousness; patient usually unaware of attacks**
⦁ blank stare - brief staring episodes**
⦁ eyelid twitching**
⦁ motionless
⦁ stop talking in mid sentence
⦁ can have mild clonic, tonic, or atonic components
may be clonic (jerking), tonic (stiffness) or atonic (loss of postural tone)
⦁ may have automatisms
⦁ no postictal period**
TREATMENT
- *1st line for absence seizures = Ethosuxamide (Zarontin)
- 2nd line = Valproic acid (SE = hepatitis, pancreatitis)
- Can also use Lamotrigine (Lamictal) or Benzos (Lorazepam - Ativan) (Diazepam - Valium); Lorazepam = most effective
Ethosuxamide (Zarontin) = blocks calcium channels –> motor cortex depression –> elevates the stimulation threshold which decreases neuronal firing. Only used in absence seizures
Valproic Acid (Depakote) = increases effects of GABA --> increased CNS inhibition. Also inhibits glutamate / NMDA receptor-mediated neuronal excitation - SE = Pancreatitis, Hepatotoxicity*
Lamotrigine (Lamictal) = blocks sodium + calcium channels –> decreases glutamate and aspartate release. Also inhibits glutamate’s effects on NMDA receptor –> decreased neuronal activity
- SE = SJS*, HA, diplopia
ex: little kid blowing on piece of paper - then has seizure; after seizure - automatically resumes activities
EEG = shows bilateral symmetric 3hz spike + wake action or may be normal
MYOCLONIC SEIZURES
- type of generalized seizure
Sudden, brief, sporadic involuntary twitching
NO LOSS OF CONSCIOUSNESS***
- rapid recurrent brief muscle jerks: can occur bilaterally, unilaterally, synchronously, or asynchronously
- can range from small movements of face or hands to bialteral spasms that simultaneously affect the head / limbs / trunk
- may terminate into generalized tonic-clonic (grand mal) seizure
- can occur at any time
- often cluster shortly after waking or while falling asleep***
TREATMENT
- valproic acid (Depakote)
MOA = increases GABA (inhibitory NT in CNS)
- Clonazepam (Klonopin)
ATONIC SEIZURES
- “drop attacks”
- sudden loss of postural tone
- occur most often in children with diffuse encephalopathies
- characterized by sudden loss of muscle tone - may result in falls with self-injury
- can occur in a repetitive, rhythmic and successive manner
FEBRILE SEIZURES
- **Most common cause of convulsions in children **
- occur between ages 3 months - 6 years
- temperature usually > 38 (100.4)
- chance of recurrence = greatest if first seizure occurs before 1 year or there is a family hx
- not associated with, nor do they cause mental impairment, poor school performance, or behavioral problems
- these are provoked
2 types of febrile seizures
⦁ simple
⦁ complex
- body becomes stiff + arms/legs begin twitching
- lose consciousness
- blood test, imaging, and EEG generally not needed
- treat with Benzos (lorazepam or diazepam), phenobarbitol, or Depakote (valproic acid)
TONIC-CLONIC SEIZURES
- “grand mal” seizures - major motor seizure - involves all extremities & is characterized by sudden loss of consciousness
- may either be primary (arises from deep brain structure) or could be a focal seizure with secondary generalization
TONIC = characterized by sudden loss of consciousness. Become rigid and fall to ground. Respiration is arrested. Usually lasts for less than a minute
CLONIC = jerking of body musculature. may last 2-3 minutes, followed by stage of altered level consciousness
tongue & lips may be bitten
urinary & fecal incontinence
patient may be injured
Immediately following Tonic-Clonic seizure
- May recover consciousness
- may drift into sleep
- may have further convulsions without recovery of consciousness between attacks = STATUS EPILEPTICUS
POST-ICTAL PHASE ⦁ headache ⦁ disorientation ⦁ confusion ⦁ drowsiness ⦁ nausea ⦁ soreness of muscles
need to monitor their kidney function for muscle breakdown - creatinine levels
SECONDARY-GENERALIZED SEIZURES
- seizure that becomes generalized (spreads from focal to both sides of brain)
- 30% of people with focal epilepsy progress to secondary generalized
- usually last 1-3 minutes, but may take longer for patient to recover
- may begin with aura, or simple focal seizure
SIGNS/SYMPTOMS ⦁ stiffening of muscles ⦁ loss of consciousness ⦁ tongue/cheek may be bitten ⦁ tonic/clonic phases
consciousness returns slowly, and person may be drowsy, confused, or agitated
DIAGNOSIS
⦁ EEG
⦁ MRI
TREATMENT
- Valproic acid
- Phenytoin
- Carbamazepine
- Lamotrigine
FOCAL SEIZURES
o Focal = partial seizures - limited to part of one cerebral hemisphere - can be whole hemisphere or part of it
⦁ focal seizures with impairment of consciousness
⦁ focal seizures without impairment of consciousness
o Generalized = involve the cerebral cortex of both sides of the brain ⦁ Absence (petit mal) ⦁ Tonic-clonic (grand mal) ⦁ myoclonic ⦁ tonic ⦁ clonic ⦁ atonic (drop) ⦁ febrile seizure ⦁ post-traumatic epilepsy
FOCAL SEIZURES - initial discharge arises from focal, unilateral area of the brain without impaired consciousness o Jacksonian March = motor o sensory o autonomic o psychic
Jacksonian March = travel through the primary motor cortex in succession, affecting corresponding muscles, often beginning with fingers - felt as tingling sensation…then affects hands and moves up to arm/etc.
- other symptoms often associated with Jacksonian seizure = sudden head/eye movements, tingling, numbness, smacking of lips, sudden muscle contractions
- Without impaired consciousness = prodrome or aura = warning sign of impending seizure
- Todd’s Paralysis = post-ictal temporary unilateral paralysis lasting 30min-36 hours
- can progress very quickly from a seizure with no change of consciousness to a seizure in which consciousness is altered, as in a staring spell, automatisms, or can progress to a generalized seizure (tonic-clonic) seizure
Patient may not recall aura, but EEG will show focality before progression
for focal that progresses to tonic/clonic = carbamazepine (tegretol) or oxcarbamazepine
FOCAL SEIZURES WITH IMPAIRED CONSCIOUSNESS
- unresponsiveness
- 70-80% arise from the temporal lobe
- many evolve from simple focal seizures (simple focal followed by impaired consciousness)
- some may present with impairment of consciousness at onset (rather than progressed)
- present with automatisms (often chewing, lip smacking, picking at clothes, fumbling around)
- Most common type of seizure = focal seizure with impaired consciousness*
- clinical signs/symptoms & supporting EEG indicate involvement of one hemisphere at onset. Lasts from 30 seconds - 2 minutes. Confusion & tiredness may follow for about 15 minutes, and may take hours to feel fully normal
STATUS EPILEPTICUS
- any seizure lasting > 30 min or a prolonged flurry of seizures without recovery of consciousness between seizures
- life threatening! especially if generalized tonic-clonic status
- if patient arrives to ED still seizing, assume they have Status Epilepticus and treat accordingly
Causes of Status Epilepticus
⦁ drug noncompliance or sudden withdrawal from seizure med
⦁ fever
⦁ drug or alcohol withdrawal
Remember ABCs
- airway - roll to side, head tilt, oral airway
- breathing - oxygen, intubation
- circulation - cardiac monitor, maintain BP
blood draw for glucose, electrolytes, calcium, magnesium, CBC, drugs of abuse, AED levels (anti-epileptic drug levels)
1ST LINE TX = BENZOS = Ativan (Lorazepam) or Valium (Diazepam) - once you’ve stabilized the airway!!!!
- If Benzo doesn’t work = try Phenytoin
- if phenytoin doesn’t work = Phenobarbital
- start IV:
⦁ Ativan (Lorazepam)
⦁ Fosphenytoin or phenytoin
if above not effective after 20 minutes = Phenobarbital or Depacon
- if still not working = general anesthesia with ventilator & neuromuscular junction blockade
WORKUP and TREATMENT FOR SEIZURES
EEG = most important diagnostic test for seizure activity***
- important for classifying seizures correctly, identifying epileptic syndromes, and making therapeutic decisions
- in order to be completely diagnostic, the EEG MUST be obtained during seizure activity
40-50% show epileptiform abnormalities in their initial EEG. capture of epileptiform activity is enhanced by sleep deprivation for 24 hours so that patients sleep during a portion of EEG recording
IMAGING
- *MRI = study of choice
- MRI should be obtained in all patients over 20 who are suspected of having epilepsy - for possbility of underlying neoplasm
- should be obtained in ALL children with partial seizures, abnormal neurologic findings, or focal slow wave abnormalities on EEG
- MRI identifies structural brain pathology
CT = alternative choice
LABS
- baseline
- AED levels (anti-epileptic drug) levels
- CBC
- CMP
- TSH
- drug screen (blood or urine)
- blood sugar levels
- LP if indicated
- EKG
TREATMENT OF SEIZURES
- if provoked = treatment is directed to the provoking factor
- if unprovoked =
⦁ first seizure = usually no treatment; treatment can be initiated if risk of recurrence is high
⦁ second seizure = diagnosis of epilepsy is established + risk of third seizure is high - most physicians treat at this stage. In children, some wait for 3rd seizure
1) Absence Seizures
⦁ 1st line = ETHOSUXIMIDE (ZARONTIN - only works for absence)
⦁ 2nd line - Valproic Acid (SE- Hepatitis, Pancreatitis)
⦁ Lamotrigine (Lamictal) (SE - SJS)
2) Grand Mal Seizures (Tonic-Clonic)
⦁ Valproic Acid (pancreatitis, hepatitis)
⦁ Phenytoin (erythema multiforme / SJS, gingival hyperplasia, hirsutism, hypotension, arrhythmias with rapid admin),
⦁ Carbamazepine (SE = hyponatremia, SIADH, SJS)
3) Status Epilepticus
⦁ 1st line = Benzos (Lorazepam / Diazepam)
⦁ 2nd line = Phenytoin
⦁ 3rd line = Phenobarbital
4) Myoclonus
⦁ Valproic Acid
⦁ Clonazepam
⦁ Febrile = Phenobarbital
*NEUROLOGY REFERRAL for medication, surgery, ketogenic diet, vagal nerve stimulator, biofeedback
Alternative Therapies (these do NOT replace drugs) ⦁ Biofeedback ⦁ Ketogenic Diet = high fat low carb diet - body burns fat instead of glucose for energy ⦁ Vagal Nerve Stimulation = implant device to stimulate vagus nerve & abort seizure
KETOGENIC DEIT = high in fat, low in carbs. Usually used in children refractory to AEDs
SURGERY OPTIONS
- anterior temporal lobectomy
- corpus callosotomy
- amygdala-hippocampectomy
- vagus nerve stimulation
EDUCATION
- avoid sleep deprivation & alcohol use
- avoid jobs that involve working at heights, near heavy machinery, flames, or burners
- restrictions on careers = firefighters, commercial drivers, airline pilots
- never swim alone
- most sports are permitted
- caution on: hand gliding, scuba, mountain climbing, skydiving
CYSTIC FIBROSIS
- “smaller than other children their age”
- “hacking” cough
- bronchodilators
- cough so forceful it occasionally causes him to vomit
- “bulky + frothy stools” - due to formula intolerance - due to lack of pancreatic enzymes - so food just goes right through –> “frothy”
- nasal polyps**
MC cause of Bronchiectasis is CF
- Bronchiectasis = bronchial dilation due to transmural inflammation –> destruction of muscular / elastic tissues of bronchial wall
WHAT IS CF? - Autosomal recessive disease of the Exocrine gland system. Defective chloride channels result in highly viscous secretions - decrease in chloride secretion leads to relative dehydration + abnormal mucociliary clearance
- autosomal recessive - so both parents must at least be a carrier = 1/32 adults - Caucasian
- CF = obstructive disease (like asthma and COPD)
- genetic condition that affects the lungs…but the name cystic fibrosis refers to the effects on the pancreas (cysts + excess CT that replaces normal tissue in an organ)
CF = autosomal recessive; CFTR gene codes for CFTR protein
- need to inherit 2 mutated CFTR genes (so both parents need to have been carriers)
- CF = more common in European descent
CFTR protein is a channel protein = pumps chloride ions into various secretions; the chloride ions help draw water into the secretions to thin the secretion
⦁ phenylalanine is deleted from 508th amino acid –> becomes misfolded
- this causes lack of CFTR channel protein on epithelial surface = can’t pump chloride ions out into secretions –> SECRETIONS ARE LEFT OVERLY THICK
EFFECT ON MECONIUM
- in Newborns, the thickened secretion can apply to meconium (first stool) in which the stool becomes THICK + STICKY and gets stuck in the intestines and not come out = MECONIUM ILEUS (surgical emergency)
PANCREATIC INSUFFICIENCY
- Most prominent effect of CF in childhood
- thick secretions block the pancreatic duct, and therefore prevent pancreatic digestive enzymes from making it to the small intestines –> proteins + fat NOT absorbed
⦁ over time –> leads to poor weight gain and FTT (failure to thrive)
⦁ Steatorrhea (fat containing stools - float)
⦁ Pancreas gets damaged - backed up digestive enzymes degrade the cells that line the pancreatic duct –> local inflammation –> can lead to acute pancreatitis and with repeated episodes, chronic pancreatitis. Development of CYSTS and FIBROSIS of pancreas
- *Protein + Fat Malabsorption
- failure to thrive, hypoalbuminemia, vitamin ADEK deficiency, steatorrhea
Liver disease
- cholestatic jaundice, steatohepatitis, portal hypertension —-» CIRRHOSIS
ENDOCRINE DYSFUNCTION
- pancreas destruction can damage the endocrine function of the pancreas –> lead to insulin-dependent diabetes
CLINICAL MANIFESTATIONS
- lung problems usually don’t develop until later in childhood; the cilia typically do a good job of keeping lungs clean by moving mucus (catches debris / bacteria) and moves it back up to the pharynx
- in CF, becomes difficult for the cilia to clear THICK MUCUS –> mucociliary action becomes defective –> Bacteria chronically colonizes the lungs
- With a sudden increased bacterial load --> CF Exacerbation ⦁ Cough ⦁ Fever ⦁ Changes on CXR - Requires antibiotics
MC Bacteria
⦁ In 1st decade of life: Staph Aureus (gram +) and H. flu (gram -) = MC
⦁ In 2nd + 3rd decade of life: Pseudomonas (gram -) = MC
⦁ Staph Aureus & Pseudomonas = big players
⦁ kids = staph; adults = pseudomonas
chronic infection –> destruction of bronchi –> bronchiectasis –> creates obstructive lung disease
FLOW CHART
1) abnormal CFTR –>
2) impaired mucociliary clearance –>
3) infection & inflammation –>
4) bronchiectasis & lung damage –>
5) functional airway impairment
- Chronic bacterial infections and therefore inflammation –> BRONCHIECTASIS (airway wall damage which leads to permanent dilation of the bronchi)
- Occasionally if the inflammation erodes into a blood vessel –> can even have HEMOPTYSIS
Repeated CF exacerbations can lead to RESPIRATORY FAILURE = leading cause of death in CF
OTHER CF RELATED ISSUES
⦁ Infertility in Men = male CF patients commonly lack vas deferens
⦁ Digital clubbing
⦁ Nasal polyps
⦁ Allergic Bronchopulmonary Aspergillosis - hypersensitivity rxn to Aspergillus Fumigatus
CLINICAL FEATURES OF CF - Respiratory Insufficiency ⦁ pulmonary fibrosis ⦁ obstruction ⦁ frequent infections ⦁ chronic sinusitis ⦁ nasal polyps
- Pancreatic Insufficiency
⦁ malabsorption of fats + proteins (steatorrhea = fat in stool) (meconium ileus = bowel obstruction - not pooping - dehydrated)
⦁ failure to thrive
DIAGNOSIS
- CXR
- pulse ox
- CBC with diff
- sputum studies of possible
- sweat chloride testing - measures amount of chloride in the sweat after small electrical stimulation
- PPD if worried about TB
- consult with pediatric pulmonologist
o newborn screening
⦁ IRT = detects Pancreatic Enzyme IRT (immunoreactive trypsinogen) = released into the blood when the pancreas is damaged
⦁ DNA testing
⦁ sweat chloride test (not done on newborns - difficult to perform on babies < 48 hrs)
- CF can be detected through sweat chloride test = standard for diagnosis of CF
- Elevated sweat chloride > 60 = positive result
- parents often first notice that baby tastes salty when they kiss their baby
The lack of normal CFTR functions alters chloride conductance in the sweat gland –> excessively high sweat sodium & chloride levels in sweat
Hyponatremia, hypochloremic metabolic alkalosis
DIAGNOSIS OF CF
⦁ Sweat Chloride test = not done on babies < 48 hrs
⦁ IRT Assay - newborn screening
⦁ DNA Assay - newborn screening
⦁ typical pulmonary + GI symptoms as well as positive Fam hx
TREATMENT
PANCREATIC TREATMENT
⦁ pancreatic enzyme supplements
⦁ fat soluble vitamin supplements (ADEK)
⦁ high calorie/high protein diet
- Pulmonary Treatment
⦁ Chest physiotherapy - loosens mucus by banging on the chest
⦁ inhalers - Other Mediations
⦁ N-Acetylcysteine - cleaves disulfide bonds in mucus glycoproteins (loosens)
⦁ Dornase Alfa Nuclease - cuts up nucleic acid in mucus (loosens) - PFTs often done to monitor the disease
- Lung transplant may be needed; due to chronic infections and loss of pulmonary function over time
- test for CF at birth, but 2% are missed - so even if test is negative - check for other clues
TREATMENT
- Tobramycin + Piperacillin or Ticarcillin (Aminoglycoside + antipseudomonal penicillin)
- nebulized bronchodilators
- oxygen therapy as needed
- chest physiotherapy
- mucolytics
- steroids (prn)
⦁ common SE of aminoglycoside (tobramycin/gentamycin) = nephro/ototoxicity
⦁ sinusitis = very prevalent in CF population
⦁ problem with using Cipro for pseudomonal coverage = risk of tendon rupture
- primary morbidity with CF = from progressive obstructive lung disease
- advances in pulmonary medicine/development of pancreatic enzyme replacement meds have increased survival in CF patients (median survival = 31 years)
- often diagnosed at birth in hospital (17%) because of meconium ileus** - CF is suspected if meconium is not passed in 24 hours (obstruction) - signs also include abdominal distention + thick/sticky meconium with enema exam
- failure to thrive, respiratory compromise, both
- some patients are not diagnosed until adulthood
BRONCHIECTASIS
I
PJP
K
SARCOIDOSIS
- granulomatous disorder of unknown etiology -
- Chronic, multisystem, inflammatory, granulomatous disorder of unknown etiology
- Disordered immune regulation in genetically predisposed individuals exposed to certain environmental antigens
- characterized by presence of noncaseating GRANULOMAS in involved organs (granulomas = collection of immune cells that have walled off foreign substances that they are unable to eliminate)
- These granulomas take up space and disrupt the normal structure / function of tissues –> variety of clinical manifestations
- Granulomas may eventually resolve or may undergo fibrosis
PATHOPHYSIOLOGY
- Exaggerated T cell response to a variety of antigens or self-antigens –> CENTRAL immune cell ACTIVATION + PERIPHERAL immune cell DEPRESSION
- T cell accumulation –> Granuloma formation
Granulomas in sarcoidosis are characteristic of the disease and generally have elevated levels of
1-ALPHA-HYDROXYLASE
Increased prevalence in ⦁ Afro-Americans ⦁ Northern Europeans ⦁ Females ⦁ onset usually 20-40; typically affects YOUNG ADULTS
- presents with
⦁ bilateral hilar lymphadenopathy*** (CXR)
⦁ pulmonary reticular opacities
⦁ skin, joint, eye lesions, etc.
CLINICAL MANIFESTATIONS
- ***50% = asymptomatic - found incidentally on CXR
- varies with stage of disease + organ involvement
- Most complications are PULMONARY (90%)
⦁ dry (nonproductive) cough
⦁ dyspnea
⦁ chest pain - LYMPHADENOPATHY
⦁ painless intrathoracic lymphadenopathy
⦁ hilar nodes - paratracheal node involvement** - SKIN
⦁ Erythema Nodosum** - bilateral tender red nodules on anterior shins (from inflammation of fat); usually resolves spontaneously in 2-4 weeks. Also seen in coccidioidomycosis. Increased incidence in northern Europeans - not common in Afro-Americans.
⦁ Lupus Pernio* - violaceous, raised discoloration of nose, ear, cheek and chin (resembles a frost bite)
⦁ Maculopapular rash = MC derm manifestation
⦁ Subcutaneous nodules and waxy nodular lesions may be seen
⦁ Calcinosis cutis refers to firm, skin-colored or white-yellow papules, nodules, or plaques under the skin that are caused by deposition of calcium salts. The condition is often seen in patients with disrupted calcium and phosphate metabolism, such as those with sarcoidosis.
⦁ PAROTID GLAND ENLARGEMENT* - VISUAL
⦁ Anterior Uveitis - inflammation of iris / ciliary body –> BLURRY VISION***, ocular discomfort, photophobia, ciliary flush, floaters
⦁ conjunctivitis - tearing, erythema
⦁ may develop cataracts, glaucoma, blindness - MYOCARDIAL
⦁ arrhythmias - secondary to conduction system involvement
⦁ cardiomyopathies - RHEUMATOLOGIC
⦁ arthralgias**
⦁ hepatosplenomegaly - NEUROLOGIC (5%)
⦁ CN palsies (especially CN 7 - facial palsy)
⦁ diabetes insipidus
⦁ hypothalamic / pituitary lesions
CONSTITUTIONAL SYMPTOMS
⦁ fever***
⦁ malaise / fatigue
⦁ weight loss
- lung involvement occurs in over 90% of patients + is staged according to CXR
PULMONARY PRESENTATION
⦁ dyspnea
⦁ cough (dry, nonproductive)
⦁ chest pain
DIAGNOSIS
1) clinical / radiologic findings
2) NCGs = non-caseating granulomas
3) exclusion of other diseases
o Tissue Biopsy = Noncaseating Granulomas***
- noncaseating = no central necrosis in granuloma. Mainly contains multinucleated giant cells + T cells
BIOPSY = BEST DIAGNOSIS - skin, lymph nodes, etc.
o CXR =
⦁ BILATERAL HILAR LYMPHADENOPATHY
⦁ Right paratracheal lymphadenopathy = also common
⦁ CXR = almost always abnormal
⦁ INTERSTITIAL LUNG DISEASE - reticular opacities, fine/ground glass opacities,
- Stage I = bilateral hilar lymphadenopathy (BHL)
- Stage II = BHL + interstitial lung disease (ILD)
- Stage III = ILD
- Stage IV = Fibrosis
o PFTs = restrictive pattern - seen with advanced disease
- MC finding = ISOLATED DECREASED DLCO = diffusing capacity of lungs for carbon monoxide
o CT
o Gallium scan = “panda sign”
o Bronchoalveolar lavage - to rule out infectious causes: Have increased T cells in the lungs**
- Increased CD4, Decreased CD8
(bronchoscope goes down throat into lungs - fluid is squirted out and then recollected)
LAB STUDIES
⦁ Increased ACE** (50-80%) - granulomas (specifically T cells) secrete ACE (angiotensin converting enzyme)
⦁ Hypercalcuria / Hypercalcemia* = granulomas (specifically macrophages) increase vitamin D production –> increased calcium levels**
⦁ Eosinophilia**
⦁ Leukopenia
⦁ Cutaneous Anergy** = 70% have diminished skin test reactivity to common skin allergens ==> peripheral immune suppression due to central immune system activation)
- get a false negative PPD
TREATMENT
⦁ OBSERVATION
- a large number of patients undergo spontaneous remission within 2 years or have a benign clinical course. No easy way to assess severity - so difficult to develop treatment guidelines - so no specific treatment exists. F/U with periodic evaluations, CXRs, PFTs, etc.
⦁ STEROIDS = treatment of choice*** when treatment is needed; MOA = reduces granuloma formation and fibrosis. ACE levels fall with steroids
Indications for treatment
⦁ worsening pulmonary symptoms (cough, dyspnea, chest pain/discomfort, hemoptysis)
⦁ deteriorating lung function
⦁ progressive CXR changes
⦁ MTX = alternative to steroids or steroid-refractory dz
⦁ Hydroxychloroquine = for chronic disfiguring skin lesions
⦁ NSAIDS = for MSK symptoms and erythema nodosum
⦁ Lung transplant in severe cases
good prognosis = stage I, erythema nodosum
bad prognosis = interstitial lung disease, lupus pernio
CLASSIC SARCOID PRESENTATION = young patient with respiratory and constitutional symptoms, blurred vision and erythema nodosum**
LOFGREN’S SYNDROME TRIAD
1) Erythema Nodosum
2) Bilateral Hilar Lymphadenopathy
3) Polyarthralgias + Fever
- Lofgren’s Syndrome triad = common presentation of sarcoidosis in Northern Europeans, but not African Americans (don’t typically get erythema nodosum)
- Lofgren’s Syndrome = associated with a good prognosis and spontaneous remission
SARCOIDOSIS = RESTRICTIVE LUNG DISEASE
PERTUSSIS = WHOOPING COUGH
- HIGHLY CONTAGIOUS secondary infection to BORDATELLA PERTUSSIS (gram negative)
- rarely seen now due to widespread vaccination
- gram negative coccobacillus
- MC seen in children < 2
CLINICAL MANIFESTATIONS
- 7-10 day incubation period
- Catarrhal phase –> Paroxysmal phase –> Convalescent phase
1) CATARRHAL PHASE
- upper respiratory symptoms x 1-2 weeks
- most contagious*** during this phase
2) PAROXYSMAL PHASE
- severe paroxysmal coughing fits with INSPIRATORY WHOOPING SOUND after cough fits
- post-coughing emesis may be present
“cough so hard they vomit”
coughing fits may occur spontaneously, or can be provoked by laughing, yawning, etc**
- coughing often lasts 2-4 weeks, scattered rhonchi
- may develop subconjunctival hemorrhage from increased pressure with coughing fits
3) CONVALESCENT PHASE
- resolution of cough (may last up to 6 weeks)
DIAGNOSIS
- PCR of NASOPHARYNGEAL SWAB* = gold standard
- done in first 3 weeks of symptom onset
LABS
- Lymphocytosis = 60-80% lymphocytes on differential (normal = 15-40%)
- WBC count may be as high as 50,000 (normal = 4,500 - 11,000)
TREATMENT
1) mainstay of treatment = SUPPORTIVE THERAPY - oxygen, nebulizers, mechanical ventilation as needed
2) Antibiotics used to decrease contagiousness - however, abx only shortens the duration of infection if given in the first 7 days of symptom onset, and most patients don’t present as Pertussis in the Catarrhal phase
⦁ ERYTHROMYCIN, or azithromycin. Macrolides = treatment of choice
- Macrolides may increase risk of infantile pyloric stenosis in infants < 1 month
⦁ Bactrim = 2nd line if allergic to macrolides
COMPLICATIONS OF PERTUSSIS
- *Pneumonia
- encephalopathy
- otitis media
- sinusitis
- seizures
Increased mortality in infants due to apnea and cerebral hypoxia associated with coughing fits
WERNICKE-KORSAKOFF SYNDROME
Wernicke–Korsakoff syndrome is the combined presence of Wernicke encephalopathy and alcoholic Korsakoff syndrome. Due to the close relationship between these two disorders, people with either are usually diagnosed with WKS, as a single syndrome.
- caused by deficiency of Thiamine (vitamin B1)
- results from CHRONIC ALCOHOLISM = MC
ETIOLOGIES
- 1) CHRONIC ALCOHOLISM = Alcohol interferes with active gastrointestinal transport, and chronic liver disease leads to decreased activation of thiamine pyrophosphate from thiamine, as well as decreased capacity of the liver to store thiamine
- 2)
most thiamine deficiencies = due to alcoholism - leads to poor absorption/metabolism/storage of thiamine. Get thiamine from pork, whole grains, oatmeal, potatoes
WKS CHARACTERIZED BY
⦁ Confusion**
⦁ Amnesia
⦁ Confabulation = most distinguishing feature**- fabricated/distorted memories
other features ⦁ acute weakness ⦁ paralysis of EOMs* ⦁ nystagmus**** ⦁ ataxia (lack of muscle control)**** ⦁ peripheral neuropathy ⦁ diplopia*
Confusion Amnesia Confabulation Ataxia Nystagmus
DDX = temporal lobe epilepsy, temporal lobe infarction, concussion, transient global amnesia, anoxic encephalopathy, alzheimers, third ventricle tumor, HSV sequela
DIAGNOSIS OF WKS ⦁ symptoms ⦁ CBC (to rule out infection) ⦁ Coag panel (to rule out bleeding disorder) ⦁ Serum/urine drug test = for toxins ⦁ Liver enzymes ⦁ CT scan (to rule out other diagnoses) ⦁ MRI = will show acute lesions of Wernicke's area
TREATMENT OF WKS
⦁ supplemental thiamine - start with IV or IM followed by supplemental oral doses
⦁ important to start thiamine treatment BEFORE giving any glucose, as encephalopathy will worsen with glucose
HHV #1-8
HUMAN HERPES VIRUS FAMILY
HHV 1 = oropharyngeal
HHV 2 = genital
HHV 3 = varicella zoster
HHV 4 = Epstein barr (infectious mononucleosis)
HHV 5 = Cytomegalovirus (CMV)
HHV 6 = Roseola
HHV 7 = Pityriasis Rosea
HHV 8 = Kaposi’s Sarcoma
HYPOTHYROIDISM
HYPOTHYROIDISM: T3/T4 = LOW; TSH = HIGH
- too little thyroid hormone
- More common in women than men
- incidence increases with age
- MC cause of Hypothyroidism = Hashimoto’s Thyroiditis
- 3 types of Hypothyroidism
⦁ PRIMARY HYPOTHYROIDISM = the thyroid gland is the problem - not making enough thyroid hormones
- have low T3/T4 but elevated TSH to try and stimulate the gland (not working) (T3/T4 = low, TSH/TRH = high)
- Iodine deficiency (MC cause in poor countries); follicular cells in the thyroid gland need iodine in order to produce T3 and T4
- Hashimoto’s Thyroiditis = MC cause of Hypothyroidism in developed countries - autoimmune disorder = develop antibodies to thyroid gland: Anti-thyroid peroxidase and Anti-thyroglobulin. Damage to thyroid gland causes the thyroid to respond with hypertrophy and hyperplasia (increase size + cells) = GOITER - to compensate (enlargement of thyroid gland). Eventually, the thyroid gland function gets destroyed altogether.
- Post partum Thyroiditis
- Iatrogenic - Iodine-131 therapy or Thyroidectomy = was hyperthyroid; had surgery -removed part of thyroid gland and now hypothyroidism. Or radioiodine therapy damages too many follicular cells of thyroid gland
- Drug Induced = Lithium, Amiodarone, Antithyroid drugs
Cretinism is a form of hypothyroidism that occurs in neonates and infants.
- Congenital = agenesis (absent), dysgenesis (underdeveloped), hypoplastic (too small)
- have symptoms of excessive sleeping; but if not corrected quickly enough = at risk for mental retardation and intellectual disabilities and DELAYED PHYSICAL GROWTH / SHORT HEIGHT - due to effect of thyroid hormone on brain and sympathetic nervous system development
- Adult Onset = normal aging
⦁ SECONDARY HYPOTHYROIDISM (central hypothyroidism) = problem with anterior pituitary - not enough TSH
- usually occurs because of a tumor in anterior pituitary that compresses the gland + prevents TSH production
- Neoplasm
- Surgery
- Post partum Necrosis
- Cushing’s
- Radiation
⦁ TERTIARY HYPOTHYROIDISM = problem with hypothalamus - not secreting enough TRH (tumor?)
- Hypothalamus dysfunction
- Hemochromatosis (too much iron - form clots in thyroid)
- Sarcoidosis
PATHOPHYSIOLOGY
1) Hypothalamus detects low levels of thyroid hormone in blood –> releases TRH (thyrotropin releasing hormone)
2) TRH acts on the Anterior Pituitary –> TSH
3) TSH stimulates thyroid gland to release T4 (free)
T4 is converted to T3 in order to have metabolic effects on body
- T3 speeds up the basal metabolic rate => produce more proteins and burn more energy (sugar / fat)
- T3 also increases cardiac output, stimulates bone resorption, and activates the sympathetic nervous system
So Hypothyroidism ==> decreased basal metabolic rate
SYMPTOMS OF HYPOTHYROIDISM ⦁ fatigue* ⦁ cold intolerance* (body producing less heat) ⦁ weakness ⦁ lethargy* ⦁ weight gain* ⦁ constipation ⦁ myalgias ⦁ arthralgias ⦁ menstrual irregularities
- weight gain despite loss of appetite - due to decreased basal metabolic rate
- LDL cholesterol levels increase in patients with hypothyroidism.
Decreased expression of low density lipoprotein receptors causes patients with hypothyroidism to have hypercholesterolemia.
Hypothyroidism can lead to menstrual abnormalities, most commonly menorrhagia
SIGNS OF HYPOTHYROIDISM ⦁ dry, course skin* ⦁ hoarse voice ⦁ brittle nails ⦁ periorbital/peripheral edema (myxedema)* ⦁ delayed reflexes / slow reaction time ⦁ bradycardia (decreased metabolism) ⦁ mental slowness
bradycardia, mental slowness, lethargy and constipation = due to decreased effect of thyroid hormones on sympathetic nervous system (T3)
Increased TSH –> stimulates fibroblasts in skin and soft tissues –> deposition of glycosaminoglycans (proteins) into space between cells –> MYXEDEMA = swelling in skin and soft tissues, like the tongue
Hypothyroidism may be a reversible cause of dementia.
Patients with primary hypothyroidism can have galactorrhea due to increased amounts of thyrotropin-releasing hormone which stimulates prolactin.
DIAGNOSIS
- serum levels of TSH, T3/T4
⦁ all hypothyroidism = T3/T4 LOW
⦁ in primary hypothyroidism, TSH = high
⦁ if secondary cause, TSH = low or normal
- TSH is HIGH - indicates that thyroid hormone production is insufficient. T3/T4 = LOW
TREATMENT
- LEVOTHYROXINE = synthetic T4
usually give 100-200 mcg daily
start with 50-100 mcg/day
In elderly, start with 25-50 mcg/day, then increase by 25 mcg every 2-3 weeks
- Levothyroxine should be taken on an empty stomach - wait 30 minutes before eating
- Monitor response with clinical features & TSH
MONITORING
- In patients with an intact hypothalamus-pituitary axis: Monitor TSH serially
- In patients with pituitary insufficiency: Monitor T3/T4
- Normal TSH values = 0.4 - 4.0
- if already being treated for hypothyroidism, TSH should be 0.5 - 3.0
- Normal Thyroxine levels (T4) = 4.5 - 11
- T3 = Triiodothyrodinine (normal = 100-200)
With age, thyroid binding may decrease, and serum albumin may decline…therefore Levothyroxine dosage may need to be reduced over time
HYPOTHYROIDISM = seen in Hashimoto’s Thyroiditis, Myxedema, & Subclinical Hypothyroidism
The Wolff-Chaikoff effect refers to an acute adaptive response to high doses of iodine, increased intracellular iodide blocks the organic-binding and coupling reactions in the thyroid, functionally turning off the thyroid; the Wolff-Chaikoff effect is used to prepare the thyroid for surgery.
- Wolff-Chaikoff effect results in Hypothyroidism
SUMMARY
Hypothyroidism is a common disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as cold intolerance, fatigue, and weight gain. In children, hypothyroidism leads to delays in growth and intellectual development, which is called cretinism in severe cases. Treatment typically involves thyroid hormone replacement.
SUBCLINICAL HYPOTHYROIDISM
T3/T4 = normal, but TSH is mildly elevated
MYXEDEMA COMA
people with poorly managed hypothyroidism undergo a stressful situation such as an infection or surgery
essentially extreme hypothyroidism
⦁ mental slowness => altered consciousness / confusion
⦁ decreased body temperature => hypothermia
⦁
Severe hypothyroidism can lead to myxedema heart, a form of dilated cardiomyopathy.
SCABIES
also known as the seven-year itch
- a contagious skin infestation by the mite Sarcoptes scabiei
- mites are transmitted through prolonged, close skin-skin contact or fomites (clothing / bedding)
- mites cannot survive off of human body for > 4 days (head lice = 24-48 hrs, but body lice = 2 weeks)
Female mites BURROW INTO SKIN to lay eggs, feed and defecate
- scybala = fecal particles that precipitate a hypersensitivity reaction in the skin
SYMPTOMS
⦁ ** SEVERE ITCHINESS **
⦁ pimple-like rash
⦁ may see tiny burrows in the skin
⦁ symptoms can be present across most of the body, but MC areas = wrists, between fingers, and along waistline
⦁ itch = worst at night and after hot shower
- Intensely pruritic lesions = papules, vesicles and LINEAR BURROWS*** commonly found in intertriginous zones (web spaces between fingers/toes)
- usually spares the neck and face
- linear burrows at wrist, ankles, finger webs, axillary folds, genitalia
- intense pruritus with minimal skin findings and increased intensity at night**
Red itchy pruritic papules or nodules on the scrotum, glans or penile shaft, and body folds = pathognomonic for scabies
Infected patients may remain without symptoms for up to 4-6 weeks**
Common locations for infestation = crowded living conditions - dorms, prisons, army barracks
DIAGNOSIS
- often a clinical diagnosis
- skin scraping (15 blade) of unscratched papule / burrow region to identify mites / eggs
- CBC will show eosinophilia…
TREATMENT
⦁ Permethrin topical (Elimite, Nix) = drug of choice** - apply topically from neck down x 8-14 hrs, then shower
- repeat in 1 week
- permethrin = safe in pregnancy
⦁ Lindane (neurotoxin) = cheaper than permethrin…but
- do NOT use after bath/shower - can cause SEIZURES d/t increased absorption through open pores
- teratogenic - so don’t use in pregnant or breastfeeding women, or in children < 2
⦁ 6-10% sulfur in petroleum jelly for pregnant women and infants
⦁ oral ivermectin if extensive
⦁ place all clothing / bedding in plastic bag for at least 72 hrs, then wash / dry in heat
**also need to treat household members and intimate partners **
NEVOID BASAL CELL CARCINOMA SYNDROME (GORLIN SYNDROME)
Consider nevoid basal cell carcinoma syndrome (NBCCS) in any young patient with multiple basal-cell carcinomas (BCC), or with BCC and palmar pitting.
a rare autosomal dominant disorder affecting multiple systems. It is caused by inherited mutations in the PTCH1 or SUFU genes, with increased penetrance in Caucasians.
Diagnosis of NBCCS is a clinical determination, based on the presence of 2 major or 1 major + 2 minor criteria.
Major criteria:
⦁ More than 2 instances of basal cell carcinoma (BCCs), or 1 BCC in a patient younger than 20 years old
⦁ Odontogenic keratocysts of the jaw
⦁ Three or more palmar or plantar pits
⦁ Bilamellar calcification of the falx cerebri
⦁ Bifid, fused, or markedly splayed ribs
⦁ First-degree relative with NBCCS
Minor criteria: ⦁ Macrocephaly ⦁ Ovarian fibroma or medulloblastoma ⦁ Congenital malformations – cleft lip or palate, frontal bossing, etc ⦁ Skeletal abnormalities ⦁ Radiological abnormalities
Autosomal dominant genetic disorder characterized by a broad face, rib malformations, and a predisposition to BCCs
NEVUS SEBACEOUS
A nevus sebaceous is a congenital plaque typically occurring on the face or scalp. Removal is recommended before adolescence as these masses are responsive to hormones.
a congenital, hairless plaque that typically occurs on the face or scalp. Such nevi are present at birth, affecting males and females of all races equally. The condition is named for an overgrowth of sebaceous glands.
Skin growths such as benign tumors and basal cell carcinoma can arise within these sebaceous nevi, usually in adulthood. Rarely, sebaceous nevi can give rise to sebaceous carcinoma. However, the rate of such malignancies is now known to be less than was previously estimated. Still, removal is normally recommended before adolescence.
painless lesion
area of alopecia
underlying skin is orange in color and nodular
MALIGNANT OTITIS EXTERNA
- A severe form of otitis externa that presents in diabetic and immunocompromised patients
- An invasive infection of the external auditory canal and skull base
- **typically occurs in the elderly + patients with DM (most likely uncontrolled) + immunocompromised / HIV
- MC bacterial agent = ** PSEUDOMONAS ** (gram negative rod / bacilli)
- 2nd MC cause = staph aureus
Malignant otitis externa, or necrotizing external otitis, is an uncommon form of otitis that occurs primarily in immunocompromised patients and early diabetic patients, particularly when DM is being poorly managed. It typically begins as a case of acute otitis externa, which is characterized by ear pain, swelling of the ear canal, and occasionally decreased hearing.
CLINICAL MANIFESTATIONS
⦁ otalgia - pain more severe than with otitis externa
⦁ otorrhea
Unlike acute otitis externa, malignant otitis externa is potentially fatal and commonly presents with severe, deep pain, greenish foul smelling discharge and hearing loss.
COMPLICATIONS ⦁ Osteomyelitis of the base of the skull ⦁ Mastoiditis ⦁ TMJ osteomyelitis ⦁ Cranial nerve palsies
MOE is caused by extension of the outer ear infection into the bony ear canal and soft tissues deep to the bony canal and can result in skull base osteomyelitis and multiple cranial nerve palsies.
DIAGNOSIS ⦁ otoscopy = see granulation in the inferior portion of the EAC ⦁ Elevated ESR ⦁ Positive culture ⦁ Imaging
TREATMENT = - no role for topical abx!!
The offending pathogen is almost always Pseudomonas aeruginosa and, unlike acute otitis externa, malignant otitis externa requires oral or intravenous antibiotics.
The initial treatment of malignant otitis externa is CIPROFLOXACIN***
⦁ CIPRO bid po x 6-8 weeks
⦁ pip/tazo (as pseudomonas is growing more resistant)
⦁ steroids to reduce itching / inflammation
GENERALIZED ANXIETY DISORDER
GAD = EXCESSIVE ANXIETY OR WORRY FOR
6+ MONTHS ABOUT VARIOUS ASPECTS OF LIFE
Excessive, persistent, and unreasonable anxiety about everyday things
Can range from mild (able to function socially and hold down a job) to severe (completely debilitated)
- feelings of anxiety may worsen or improve over time
GAD is not episodic (like panic disorder)
GAD is not situational (like phobias)
GAD is not focal
Associated with >/= 3 of the following symptoms ⦁ fatigue ⦁ restlessness ⦁ difficulty concentrating ⦁ muscle tension ⦁ sleep disturbance** (common - can have significant impact on physical well-being) ⦁ irritability ⦁ shakiness ⦁ headaches
= NOT due to medical illness
GAD = more common in FEMALES
onset of symptoms = usually in early 20’s
SIGNS/SYMPTOMS ⦁ can't relax ⦁ startle easily ⦁ have difficulty concentrating ⦁ trembling ⦁ irritability ⦁ sweating
- may have stomach pain from eating too much or not eating enough (due to anxiety)
Generalized anxiety disorder (GAD) involves persistent and excessive worry pertaining to multiple events or domains that continues for > 6 months
Anxiety is not related to a specific focus, but rather is generalized to most issues
GAD is the most common psychiatric illness seen by primary care providers.**
DSM-5 DIAGNOSTIC CRITERIA FOR GAD
o Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance).
o The individual finds it difficult to control the worry.
o The anxiety and worry are associated with three (or more) of the following six symptoms (with at least some symptoms having been present for more days than not for the past 6 months): Note: Only one item is required in children.
- present for 90+ days out of 180 days
- adults = 3+ symptoms
- children = 1+ symptom
⦁ Restlessness or feeling keyed up or on edge.
⦁ Being easily fatigued.
⦁ Difficulty concentrating or mind going blank.
⦁ Irritability.
⦁ Muscle tension
⦁ Sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying sleep).
The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of
The disturbance is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g., hyperthyroidism).
EVERYDAY ANXIETY VS ANXIETY DISORDER
- Everyday Anxiety
⦁ worry about paying bills, landing a job, a romantic breakup, other important life events
⦁ embarrassment or self-consciousness in an uncomfortable or awkward social situation
⦁ nerves/sweating before a big test, business presentation, stage performance, etc.
⦁ realistic fear of a dangerous object, place or situation
⦁ anxiety, sadness or difficulty sleeping immediately after a traumatic event
- Anxiety Disorder
⦁ constant worry that causes significant distress + interferes with daily life
⦁ avoiding social situations for fear of being judged / embarrassed / humiliated
⦁ out of the blue panic attacks, preoccupation with the fear of having another panic attack
⦁ irrational fear or avoidance of an object / place / situation that poses little or not threat of danger
⦁ recurring nightmares / flashbacks / emotional numbing related to a traumatic event that occurred several months or years before
Anxiety is not related to a specific person, situation, or event in generalized anxiety disorder.
At least 80% of patients with GAD have had at least one other anxiety disorder in their lifetime.
Patients with GAD are at increased risk of developing other conditions such as depression and bipolar disorder.
CAUSE = uncertain, but thought to be a combination of genetic + environmental factors
GABA and serotonin levels are DECREASED in patients with generalized anxiety disorder.
⦁ MOST IMPORTANT = decreased GABA levels*****
do have decreased serotonin as well
Norepinephrine levels are INCREASED in patients with generalized anxiety disorder
GAD-7 scale = out of 21 points = 0 / 1 / 2 / 3 on 7 questions regarding feelings of anxiety in past 2 weeks
TREATMENT FOR GAD
- 1st line = Combo or Monotherapy of
⦁ Psychotherapy (CBT) - alone or with SSRI
⦁ SSRI: Paroxetine (Paxil), Sertraline (Zoloft), Escitalopram (Lexapro)
*****SSRI of choice = Paxil; sertraline is more activating - has more stimulation, which is not good for GAD…unless patient also has significant depression
⦁ SNRI = alternative to 1st line - Effexor (venlafaxine) or Duloxetine (Cymbalta)
SNRI of choice = Effexor
- 2nd line =
⦁ Buspirone (Buspar) - can be used solo or with SSRI
= stimulates serotonin receptors, and blocks dopamine receptors. May take several weeks to see clinical improvement - ** Buspirone does NOT cause sedation**
- SE = nausea, RLS, EPS, dizziness
⦁ Benzo’s (low dose)
- short half life = alprazolam (Xanax) (11.2 hrs) or lorazepam (Ativan) (12 hrs) - longer half life = diazepam (valium) (45-100 hrs) or flurazepam (dalmane) (74-90hrs)
Benzos = short term use only) - used in interim until SSRI takes effect or for acute exacerbations / anxiety attacks / panic attacks (not used long-term due to abuse potential)
⦁ TCAs
⦁ Beta-Blockers
⦁ Pregabalin (Lyrica)
DYSGRAPHIA
- WRITING DISABILITY - a learning disability that results from the difficulty in expressing thoughts in writing
- DSM -5 uses the phrase “an impairment in written expression learning disorder” rather than dysgraphia
- dysgraphia is more than just bad handwriting
In Dysgraphia = Have Difficulties With:
⦁ handwriting
⦁ grammar + syntax
⦁ formulating, expressing, and organizing ideas in writing
⦁ spelling “encoding” = the ability to use sound-letter relationships effectively
DYSCALCULIA
- MATH DISABILITY - difficulty performing math calculations
SIGNS/SYMPTOMS
- difficulty understanding number lines
- difficulty carrying + borrowing numbers
- difficulty with word problems
STRATEGIES
- allow use of fingers and scratch paper
- use diagrams and draw out math concepts
- provide peer assistance
- suggest use of graph paper
HALO NEVUS
Halo nevi are areas of depigmentation surrounding a nevus. These are benign but are associated with
⦁ vitiligo
⦁ Turner syndrome
⦁ malignant melanoma
A halo nevus, also known as a Sutton nevus or leukoderma acquisitum centrifugum, is an area of depigmentation surrounding a nevi. Because of this appearance, it is described as a “halo” effect surrounding a nevus. Halo nevi are a benign skin condition and is believed to be caused by the destruction of melanocytes by CD8+ T lymphocytes. In some cases, the pigmentation can spontaneously re-appear. Halo nevi have not been shown to be associated with basal cell or squamous cell carcinoma. These lesions need to be monitored regularly for any changes. Halo nevi are associated with vitiligo, Turner syndrome, and malignant melanoma.
AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD)
- congenital condition in which the kidneys become filled with hundred of cysts (fluid-filled sacs)
Polycystic kidney disease is an inherited renal disorder resulting in bilaterally enlarged kidneys with cysts in the renal cortex and medulla.
- Cysts cause the kidneys to become larger than normal, and to quit functioning over time
- Cysts develop both in the cortex (outer layer) and medulla (inner layer) of both kidneys
- The cysts accumulate fluid, and therefore grow larger over time, causing the kidneys themselves to enlarge
Blood vessels that supply nephrons can become compressed by neighboring cysts –> leads to starvation of the nephron due to lack of oxygen
Poorly perfused Kidneys respond by activating the RAAS (Renin - Angiotensin - Aldosterone System) due to thinking the lack of blood flow is due to a lack of volume –> leads to sodium retention to therefore increase volume (water retention) –> hypertension
Cysts can also compress the collecting system, causing urinary stasis in the kidneys
- can result in kidney stones / infections
usually have a history of frequent UTIs or hx of kidney stones
MOST COMMON CLINICAL SYMPTOMS OF ADPKD
⦁ acute abdominal flank pain
⦁ back pain
⦁ hematuria - micro at first, gross hematuria may occur
⦁ non-specific dull lumbar pain
⦁ sharp localized pain - from cyst rupture, infection, or passage of renal stone
COMMON COMPLICATIONS WITH ADPKD
⦁ UTIs (will have low grade fever)
⦁ Pyelonephritis (inflammation of kidneys, usually due to bacterial infxn) - flank pain
⦁ Cyst infections
⦁ HTN*
⦁ renal insufficiency due to compression leads to renal failure
- patients eventually die from renal failure or consequences of HTN
TYPES OF ADPKD
⦁ Autosomal Dominant PKD (ADPKD) = “adult PKD” since symptoms usually manifest in adulthood
- caused by PKD1 gene mutation - codes for Polycystin 1 protein –> causes a more severe case that has an earlier onset, shorter life expectancy
- or caused by PKD2 gene mutation - codes for Polycystin 2 protein –> causes a less severe case that has a later onset, longer life expectancy
Polycystin 1 + Polycystin 2 allow for calcium channel influx into renal tubules that prevents abnormal cell proliferation. Mutations in PKD1 + PKD2 results in dysfunctioning polycystin proteins, allowing cells to proliferate rapidly –> cysts. H2O channels are also completely open to allow fluid to fill cysts, and then compress surrounding tissue
can become septic with upper urinary tract infection
can do a UA and not find anything = better to do blood cultures + ultrasound
PHYSICAL EXAM
⦁ Enlarged kidneys - may be palpable
⦁ HTN
A combination of abdominal mass + HTN suggests ADPKD
The cysts produce EPO, so Hgb and hematocrit are not affected
UA = hematuria maybe, perhaps mild proteinuria
COMMON ASSOCIATIONS WITH ADPKD
⦁ Multiple, asymptomatic hepatic cysts (30%)*
- can also develop cysts in seminal vesicles or pancreas
⦁ Mitral valve prolapse (25%)*
⦁ Aortic Root dilation (can lead to heart failure)
⦁ Cerebral aneurysms (10%) - Berry aneurysms, usually in circle of willis, subarachnoid hemorrhage
⦁ Diverticulosis
** ASSOCIATED WITH HEPATIC CYSTS **
- benign hepatic cysts
- berry aneurysms
- MVP
DISEASE PROGRESSION OF ADPKD
- renal function impairment is variable
- 50% of ADPKD progresses to ESRF (end stage renal failure) by age 60
ASSOCIATIONS OF POOR PROGNOSIS ⦁ ADPKD1 gene ⦁ Male sex ⦁ Black race ⦁ HTN ⦁ Early age of clinical presentation ⦁ Episodes of gross hematuria
DIAGNOSIS
⦁ ** ULTRASOUND ** - multiple cysts throughout parenchyma, have renal enlargement, increased cortical thickness, and bilateral renal involvement. US = initial test (no radiation, no dye, cheap)
⦁ Can do CT - usually done afterwards to differentiate cysts once found on ultrasound
DIAGNOSTIC CRITERIA FOR ADPKD1
⦁ at least 2 cysts in 1 kidney, or 1 cyst in each kidney in an at-risk patient younger than 30
⦁ at least 2 cysts in each kidney in an at-risk patient aged 30-59
⦁ at least 4 cysts in each kidney for an at-risk patient aged 60+
Symptoms that indicate cyst infection = flank pain, fever, leukocytosis
If cyst infection suspected = run blood cultures. UA will be clear because cysts don’t communicate with urinary tract. CT may show increased wall thickness of infected cyst
Gross hematuria = usually caused by rupture of cyst into renal pelvis
hematuria should resolve within about 7 days with bed rest + hydration. If recurrent, indicative of Renal cell carcinoma. Recurrence indicates need for cancer workup
really difficult to treat!
TREATMENT FOR ADPKD
- aimed at preventing complications (infections/etc) and preserving renal function
o Treat the HTN (** ACEI )
o Treat the Infection - need gram negative coverage; all following abx penetrate cyst walls and attain therapeutic levels - 2 weeks of abx
⦁ Bactrim
⦁ Chloramphenicol (grey baby syndrome)
⦁ Ciprofloxacin (fluoroquinolones bbw - tendon rupture)
o Dialysis - for ESRF
o Transplant - for ESRF
o Bilateral Nephrectomy prior to transplantation in patients with enlarged kidneys or a history of frequent and persistent UTIs
HTN is associated with ADPKD because of cyst-induced ischemia, which activates RAAS. BP can be lowered with cyst decompression
CENTRAL VS PERIPHERAL VERTIGO
CENTRAL VERTIGO
⦁ Tinnitus / hearing loss = Absent
⦁ Nystagmus = vertical - can be horizontal, vertical, rotary and bidirectional
⦁ Nystagmus duration = more than 1 minute
⦁ CNS symptoms + neurological findings - unable to walk, severe instability
⦁ not usually nauseous
⦁ duration = constant
⦁ onset = slow / gradual
⦁ intensity = mild
⦁ minimal change with head position
⦁ recovery = months +
CAUSES OF CENTRAL VERTIGO ⦁ meningitis ⦁ encephalitis ⦁ vertebral basilar insufficiency ⦁ cerebellar hemorrhage ⦁ temporal lobe epilepsy ⦁ tumors
Central (neurologic) causes of vertigo include brainstem vascular disease, arteriovenous malformations, tumors, multiple sclerosis, and vertebrobasilar migraine.
Central vertigo is associated with a more gradual onset and vertical nystagmus. Unlike peripheral vertigo, it does not present with auditory symptoms. Central vertigo is commonly associated with motor, sensory, or cerebellar deficits.
PERIPHERAL VERTIGO
⦁ may have tinnitus / hearing loss
⦁ nystagmus = horizontal (NEVER VERTICAL)
⦁ nystagmus duration = less than 1 minute
⦁ no CNS symptoms / neurological findings - able to walk
⦁ often have nausea
⦁ duration = intermittent
⦁ onset = sudden
⦁ intensity = severe
⦁ worsened with head positioning
⦁ recovery = days to weeks
CAUSES OF PERIPHERAL VERTIGO ⦁ BPPV ⦁ Acute otitis media ⦁ Labyrinthitis (vestibular neuronitis) ⦁ Meniere's ⦁ Vestibular neuritis ⦁ Trauma
Peripheral (inner ear) causes of vestibular dysfunction include labyrinthitis, benign paroxysmal positional vertigo, endolymphatic hydrops (Ménière syndrome), vestibular neuritis, and head injury
Peripheral vertigo is associated with sudden onset, nausea/vomiting, tinnitus, hearing loss, and nystagmus (typically horizontal with a rotatory component)
CARPAL TUNNEL SYNDROME
carpal tunnel syndrome = nerve entrapment disorder
that results in the COMPRESSION of the MEDIAN NERVE, which makes its way through the wrist through a narrow passageway called the carpal tunnel
Median nerve branches off from medial + lateral cords of brachial plexus
The median nerve provides sensation to the thumb (shared by radial nerve), index finger, middle finger, and half of the ring finger (shared by ulnar nerve)
- back of hand (dorsal) = radial nerve
The median nerve innervates the palmar surfaces and nail beds of the first three digits (thumb, index and middle fingers) and half of ring finger
Only the median nerve goes through the carpal tunnel
The median nerve and 9 tendons pass through the carpal tunnel. These tendons are 4 of flexor digitorum superficialis, 4 of flexor digitorum profundus and 1 tendon of flexor pollicis longus.
The median nerve innervates the thenar muscles of the hand, also called the LOAF muscles (first two Lumbricals, Opponens pollicis, Abductor pollicis brevis, and Flexor pollicis brevis) and pronator teres in the forearm. Weakness of these muscles results in diminished hand-grip strength and clumsiness, exhibited by this patient in the form of her troubles with jars.
CAUSE
- compression of median nerve occurs typically due to inflammation of surrounding tendons + tissues
- -> swelling (edema) –> increased fluid in very tight space –> puts pressure on median nerve
SYMPTOMS
⦁ initially can cause dull ache or discomfort in wrist / thumb / index / middle / half of ring finger
⦁ pain / numbness / tingling in thumb, index, middle, and ring finger
⦁ “pins + needles” type pain - sharp - “Paresthesias” - can extend up the forearm
⦁ can cause MUSCLE WEAKNESS –> clumsiness with holding small objects / turning doorknobs + keys / fine motor tasks ie buttoning a shirt
⦁ WORSE AT NIGHT - due to normal wrist flexion while sleeping
Increased pain with wrist flexion
Decreased pain with hand shaking
Feels better when arms are held down - increases circulation, as carpal tunnel pressure inhibits blood flow to the median nerve
- ** in severe situations - THENAR MUSCLE ATROPHY - thenar muscles at base of the thumb can start to waste away due to loss of sensation
- why??? - because thenar muscles are innervated by the RECURRENT BRANCH of the median nerve, which arises from the median nerve after it passes through the carpal tunnel - so is completely compressed off
unlike the PALMAR BRANCH of the median nerve, which branches off upstream of the carpal tunnel, and is not compressed, which is why the center of the palm remains unaffected (full sensation)
CARPAL TUNNEL = USUALLY BILATERAL - because usually both hands are involved in repetitive stress (ex: typing) that causes inflammation in both wrists
CARPAL TUNNEL = WORSE AT NIGHT after full day of using hands, and because of natural wrist flexion while sleeping
RISK FACTORS ⦁ obesity* ⦁ pregnancy* ⦁ diabetes* ⦁ underlying conditions: ex - Rheumatoid Arthritis (RA) ⦁ hypothyroidism ⦁ typing / piano player / job that requires a lot of hand work = repetitive strain injury to transverse carpal ligament ⦁ trauma
** dislocation of the LUNATE bone can cause carpal tunnel syndrome **
DIAGNOSIS
⦁ electrophysiologic tests - nerve conduction studies show decreased conduction velocity in the median nerve.
⦁ symptoms
⦁ physical tests = Tinel’s + Phalen’s test
Tinel = Tap on median nerve
Phalen = upside down praying x 1 min –> numbness
Durkan’s Test = manually compress median nerve x 30 seconds
TREATMENT
⦁ behavior modification
⦁ NSAIDS
⦁ volar wrist supports / splints - night splints first, can progress to day + night splints if needed
⦁ PT - stretching / exercises to help relieve symptoms
⦁ steroid injections
** definitive tx = Surgical division of TRANSVERSE CARPAL LIGAMENT - to open up carpal tunnel and relieve pressure on median nerve
Transverse carpal ligament forms the roof of the carpal tunnel
PRONATOR SYNDROME (VS CARPAL TUNNEL)
Pronator syndrome = also median nerve compression, but not in the carpal tunnel, but in the PROXIMAL FOREARM***
median nerve compression in proximal forearm
May develop paresthesias in same distribution as carpal tunnel, but Pronator Syndrome = associated more with PROXIMAL FOREARM PAIN than hand / wrist pain
NOT ASSOCIATED WITH PAIN AT NIGHT (unlike carpal tunnel)
HYPERTROPHIC CARDIOMYOPATHY
HOCM = hypertrophic obstructive cardiomyopathy
= broad term used to describe disease of the myocardium
cardiomyopathy = “heart muscle disease”
Primary cardiomyopathy = disease of heart muscle develops on its own
Secondary Cardiomyopathy = when cardiomyopathy develops in order to compensate for other diseases such as HTN or valve diseases (aortic stenosis)
Hypertrophic = heart muscle walls become thick , heavy, and hyper-contractile ==> essentially muscle becomes much larger - as new sarcomeres are added in parallel to each other
Usually the LV is most affected with hypertrophic cardiomyopathy == however, the hypertrophy is ASYMMETRICAL, meaning the interventricular septum grows larger relative to the LV free wall (border side)
LEADS TO
1) less LV space due to wall hypertrophy –> less blood can fill into the LV
2) LV muscle becomes more stiff / less compliant –> can’t stretch out as much –> also leads to less filling
With less filling of LV –> less blood pumped out from LV to the body = decreased SV (stroke volume - the volume of blood pumped from the left ventricle per beat) –> Heart Failure (when heart fails to pump enough blood to the body)
Hypertrophic cardiomyopathy has a thick interventricular septum that is too close to the anterior mitral leaflet, which causes outflow obstruction.
HYPERTROPHIC CARDIOMYOPATHY = A TYPE OF DIASTOLIC HEART FAILURE (because the decreased filling of the LV occurs during diastole)
Hypertrophic cardiomyopathy is classified as a diastolic dysfunction.
In some cases, the left interventricular septum enlargement gets in the way of the outflow tract of blood through the aortic valve
- > this causes the velocity of blood to increase as it goes through a narrowing to get to the aortic valve
- > this causes the mitral valve leaflet to pull down to try and decrease the velocity ===> ** VENTURI EFFECT **
- > this creates an even further obstruction
- which is why it is sometimes called a HOCM (Hypertrophic OBSTRUCTIVE Cardiomyopathy)
MURMUR
⦁ *** CRESCENDO - DECRESCENDO SYSTOLIC MURMUR = anytime blood is going through a narrowing - gets louder as blood is first rushing out, then gets softer (also seen in Aortic Stenosis)
- murmur best heard at LEFT LOWER STERNAL BORDER / APEX - radiates to the axilla
The intensity of the murmur can change, however, depending on the intensity of the obstruction
⦁ If patient Squats or does Handgrip = the systemic vascular resistance increases => venous return increases = makes it harder for blood to be ejected => increases afterload ==> more blood in the LV that helps to stretch it out –> less obstructed => diminished murmur
⦁ If patient Stands or does Valsalva maneuver = venous return decreases ==> decreases preload (LV pressure after diastole, before systole) => less blood in the LV to stretch it out –> more obstruction => murmur intensity increases
**MURMUR = LOUDER WITH VALSALVA MANEUVER **
** HARSH SYSTOLIC CRESCENDO-DECRESCENDO MURMUR ** - best heard at LLSB (left lower sternal border)
DECREASED MURMUR INTENSITY ⦁ squatting ⦁ handgrip ⦁ laying supine = increased venous return - increased LV volume preserves outflow more, as the increased fluid pushes the septum out of the way and decreases SAM of the mitral valve (systolic anterior motion)
INCREASED MURMUR INTENSITY
⦁ standing
⦁ Valsalva maneuver
⦁ dehydration
⦁ ** BIFID PULSE ** = may have 2 pulses felt - due to venturi effect of mitral valve leaflet moving closer to interventricular septum hypertrophy -> increased obstruction mid-systole
DECREASED COMPLIANCE
- with larger muscle mass, the ventricle becomes less compliant / decreased ability to stretch when filled with blood
==> may hear S4 HEART SOUND = sign of LVH
S3 heart sound = may be pathological or normal. Can occur normally in children, pregnant women and athletes, however, can also be a sign of heart failure
- S3 occurs right after S2 = delayed closure of aortic valve
S4 = almost always abnormal - can occur with aortic stenosis, HTN, and now HOCM
- occurs before S1 = produced by blood striking the hypertrophied LV
An S4 heart sound is commonly associated with hypertrophic cardiomyopathy.
- may have mitral regurgitation
- may have S4
- may have S3
- may have ** PULSUS BISFERIENS **
ISCHEMIA
⦁ increased heart muscle requires more oxygen, but hypertrophied LV has decreased amount of oxygenated blood —> develop dangerously fast arrhythmias
===> HYPERTROPHIC CARDIOMYOPATHY = MC CAUSE OF SUDDEN DEATH IN YOUNG INDIVIDUALS, ESPECIALLY YOUNG ATHLETES
typically asymptomatic until sudden cardiac death
or have symptoms only with exercise
SYMPTOMS
⦁ dyspnea** = MC initial complaint (90%)
⦁ syncope
⦁ angina / exertional chest pain (75%)
⦁ fatigue
⦁ arrhythmias (Afib, VT, VF) - palpitations, syncope, sudden cardiac death (ischemia)
Hypertrophic cardiomyopathy can cause syncope during exercise and may lead to sudden death in young athletes due to VENTRICULAR ARRHYTHMIA
PATHOPHYSIOLOGY
- Subaortic outflow obstruction - narrowed LV outflow tract secondary to
1) hypertrophied septum + 2) systolic anterior motion of mitral valve / papillary muscle displacement
systolic anterior motion seen with
⦁ increased contractility (ex: Digoxin, beta agonists, exercise)
⦁ decreased LV volume (ex: decreased venous return - standing, dehydration, Valsalva maneuver)
CAUSES OF HYPERTROPHIC CARDIOMYOPATHY
⦁ majority of primary cases = inherited - autosomal dominant mutation of single nucleotide (missense mutation)
Autosomal dominant mutations in β-myosin heavy chains are the most common cause of hypertrophic cardiomyopathy.
** mutation in the β-myosin heavy chain **
** or mutation in cardiac myosin binding protein-C **
Autosomal dominant = children of a parent with HCM have a 50% chance of also having HCM
FINDINGS OF HISTOLOGY = ** myocyte disarray ** - myofibers don’t line up properly
⦁ Another cause = Friedrich’s Ataxia - autosomal recessive neurodegenerative disease - often develop hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy can be associated with Friedreich’s ataxia, an autosomal recessive inherited disease that causes progressive damage to the nervous system and manifests initially with gait disturbance, but does not affect cognitive function.
Secondary hypertrophic cardiomyopathy = can develop from essential HTN or aortic stenosis
Hypertrophic cardiomyopathy is a genetic and inherited form of heart disease. It causes enlargement of the heart wall, in particular, the septum, which leads to left ventricular outflow obstruction. Patients with hypertrophic cardiomyopathy can be characterized by syncope, shortness of breath, and chest pain
Exam = pulsus bisferiens = second pulse is felt
Cardiac examination will also show a loud, harsh, crescendo-decrescendo systolic murmur over the lower left sternal edge with radiation to the axilla. This murmur is accentuated by a Valsalva maneuver (forceful expiration against a closed airway)
DIAGNOSIS
⦁ ** echo **
- see asymmetrical wall thickness, especially septal thickness
- see systolic anterior motion of mitral valve leaflets
- see small LV size
- see dynamic outflow obstruction
- may see mitral regurgitation
⦁ EKG - LVH, may also have atrial enlargement
⦁ CXR - cardiomegaly
TREATMENT
⦁ avoid dehydration + extreme exertion / exercise
⦁ ** BETA BLOCKERS = 1ST LINE ** - helps slow down heart rate - allow enough time to completely fill and prevents arrhythmias from lack of oxygen to heart muscle
⦁ CCB (verapamil or diltiazem) if BB don’t work (non-dihydropyridines)
⦁ Disopyramide
- all 3 are negative inotropes = decrease force/speed of contractions + increase ventricular diastolic filling time
- do NOT give Digoxin (increases contractility)
- do NOT give Nitrates (decreases LV volume)
- do NOT give Diuretics (decreases LV volume)
⦁ Surgery
- Myomectomy = resection of hypertrophied septum = usually done in patients with severe, refractory symptoms despite medical management
Beta blockers, calcium channel blockers, or cessation of high intensity athletics are all possible managements of hypertrophic cardiomyopathy.
⦁ Alcohol Septal Ablation = alternative to surgical management with good outcomes = “ a medical myomectomy” - use ethanol to destroy extra myocardial tissue
*** do NOT give Digoxin!!! - contraindicated because it can increase the contractility –> which can then increase the obstruction as blood is forced out of the ventricle
- ** ATHLETES ****
- *MURMUR = LOUDER WITH VALSALVA MANEUVER**
The murmur is accentuated when the patient stands up from a squatting position and with the valsava maneuver. The murmur decreases in intensity when the patient lays supine.
CUSHING’S SYNDROME
- named after Harvey Cushing
- an Endocrine disorder with ** ELEVATED CORTISOL LEVELS ** in the blood
Women more affected than men (4:1)
- Hypothalamic - Pituitary - Adrenal Axis = Hypothalamus –> CRH –> Anterior Pituitary –> ACTH –> Adrenal Glands (Adrenal Cortex - Zona Fasciculata) –> Cortisol
Adrenal Cortex = outer part of the adrenal gland - is subdivided into 3 layers
⦁ Zona Glomerulosa= mineralocorticoid (aldosterone)
⦁ Zona Fasciculata = middle + widest zone - takes up the majority of the volume of the adrenal gland - Glucocorticoids (Cortisol)
⦁ Zona Reticularis = secretes androgens (DHEAS)
ACTH stimulates cells in Zona Fasciculata to secrete CORTISOL
- Glucocorticoid (Lipid-soluble hormone) = not soluble in water, so most Cortisol is bound to carrier protein called Cortisol-Binding Globulin
- only about 5% of Cortisol is unbound (free)
- ** only a small fraction of the free cortisol is biologically active ** -
Excess free cortisol is dumped into the kidneys and excreted into the urine
FUNCTIONS OF CORTISOL
1) Free Cortisol is part of the Circadian Rhythm - Cortisol levels naturally peak in the morning - “get up and go”
Cortisol levels drop at night getting ready to sleep
2) During times of stress, the body needs plenty of energy, so Cortisol ** INCREASES GLUCONEOGENESIS ** - synthesis of new glucose molecules, as well as proteolysis and lipolysis (breakdown of protein and fat) to convert into glucose for energy
3) Cortisol maintains Blood Pressure - Cortisol increases sensitivity of peripheral blood vessels to catecholamines (epinephrine, NE) ==> narrows blood vessel lumen ==> increased BP during times of stress
4) Cortisol dampens inflammatory and immune response by decreasing the production and the release of inflammatory mediators (prostaglandins, interleukins)
- also inhibits the proliferation of T lymphocytes
5) Cortisol receptors are present in the brain - unsure of this effect, but may affect things like mood and memory (which explains certain symptoms of Cushing’s Syndrome)
Levels of free cortisol must remain in a normal range - so body uses negative feedback to control range - so high levels of Cortisol sends a message to hypothalamus and pituitary gland to decrease levels of CRH and ACTH. Decreased CRH will also then decrease release of ACTH from pituitary gland
Zona Fasciculata then gets less stimulation from ACTH to make Cortisol, and eventually Cortisol levels go back down to normal range again
- In Cushing’s Syndrome - CORTISOL LEVELS ARE CONSTANTLY HIGHER THAN NORMAL RANGE **
- so have exaggerated effects
CLINICAL MANIFESTATIONS OF CUSHING’S
⦁ severe muscle / bone / skin breakdown (due to protein / fat breakdown)
⦁ elevated blood glucose levels (gluconeogenesis) –> leads to high insulin levels
Insulin specifically targets Adipocytes in the center of the body –> Activates Lipoprotein Lipase –> enzyme that helps those central adipocytes accumulate more fat molecules
Cortisol excess can cause Insulin resistance –> DM
⦁ CENTRAL / TRUNCAL OBESITY + thin extremities
⦁ HYPERTENSION - for 2 reasons
1) amplified effect of catecholamines on blood vessels
2) cortisol starts to cross-react with mineralocorticoid receptors due to similar structure (usually binds to mineralocorticoids, such as aldosterone- released by Zona Glomerulosa)
- vasoconstriction –> elevated BP
- retained Na+ –> increased volume –> elevated BP
⦁ Inhibits Gonadotropin Releasing Hormone (GnRH) - which messes up ovarian + testicular function
⦁ Dampens Inflammatory + Immune response –> makes people more susceptible to infections
⦁ Impairs normal brain function
CAUSES OF CUSHING’S SYNDROME
Iatrogenic administration of exogenous corticosteroids = MC cause of Cushing syndrome.
- Endogenous
⦁ MC Endogenous cause = Cushing’s Disease = Pituitary Adenoma (benign tumor of pituitary gland)–> excess ACTH
Pituitary Adenoma (benign) doesn't invade other tissues - just grows in size and secretes excess ACTH - over-stimulation of zona fasciculata ==> grows larger and secretes excess cortisol
⦁ Ectopic sources of ACTH (MC = small cell lung cancer) - excess ACTH coming from somewhere other than pituitary gland = Paraneoplastic Syndrome**
- Small cell Lung Cancer
- or Medullary Thyroid Cancer
ACTH secreting pituitary adenoma (Cushing disease) and paraneoplastic ACTH secretion (eg, small cell lung cancer, bronchial carcinoids) causing Cushing syndrome, result in increased ACTH, resulting in bilateral adrenal hyperplasia.
⦁ Adrenal Gland tumor (Adrenal adenoma - benign) or (Adrenal carcinoma - malignant) or Adrenal Hyperplasia - make excess cortisol - suppresses CRH + ACTH production
- adrenal gland without tumor ends up shrinking due to excess cortisol -> negative feedback, however, net release of cortisol is still significantly elevated
- cortisol levels are always elevated with primary adrenal disorder in Cushing’s Syndrome, regardless of low or high dose dexamethasone test
- Exogenous
⦁ Excess / Prolonged steroid use - often used to treat autoimmune or inflammatory disorders
Exogenous steroids are so structurally similar to Cortisol that they mimic its actions on various tissues
- can cause negative feedback on hypothalamus and pituitary gland –> decreased CRH and ACTH –> shuts down cortisol production from zona fasciculata
- over time, the lack of stimulation from hypothalamus / pituitary gland can cause zona fasciculata to shrink / become atrophic
- since zona fasciculata is the widest portion of the adrenal cortex, it can have a significant effect on the size of adrenal glands
The administration of exogenous corticosteroids that causes Cushing syndrome results in decreased ACTH, which in turn causes bilateral adrenal atrophy.
SYMPTOMS OF CUSHING’S SYNDROME
⦁ muscle wasting/weakness / thin extremities
⦁ thin skin / easy bruising
⦁ abdominal striae
⦁ hyperpigmentation
⦁ acanthosis nigricans
⦁ hirsutism
⦁ oily skin / acneiform rash
⦁ fractures - due to osteoporosis (breakdown) (osteoblast activity is inhibited)
⦁ central / truncal obesity
⦁ moon fascies (fat redistribution)
⦁ buffalo hump (fat redistribution)
⦁ supraclavicular fat pads
⦁ hypertension
⦁ hypokalemia
⦁ hyperglycemia (can lead to DM / increased risk for CV disease)
⦁ increased vulnerability to infections
⦁ poor wound healing
⦁ amenorrhea / oligomenorrhea (decreased GnRH)
⦁ increased libido
⦁ psychiatric / mental disturbances (depression, mania, psychosis)
** Associated with Acanthosis Nigricans ** - along with diabetes, obesity, gastrointestinal stromal tumors
CENTRAL OBESITY + HIRSUTISM + MOON FACIES + BUFFALO HUMP
1) Redistribution of Fat (truncal obesity, moon facies, buffalo hump, supraclavicular fat pads)
2) Catabolism of Protein (wasting of extremities, skin atrophy - bruising, striae, hyperpigmentation, increased infections)
3) Hypertension, weight gain, osteoporosis, hypokalemia, acanthosis nigricans
4) Mental (depression / mania / psychosis)
5) Androgen Excess (Hirsutism, oily skin, acneiform rash, amenorrhea / oligomenorrhea, increased libido)
Muscle weakness is a feature of Cushing syndrome due to cortisol-mediated break down of muscle to produce amino acids for gluconeogenesis.
DIAGNOSIS
⦁ measure free (unbound) Cortisol in 24hr urine sample
- assess total amount of cortisol excreted in urine over 24-hr period
⦁ can also do blood or saliva test at night to see if there is a normal daily rise and fall of cortisol levels
⦁ if Cortisol > 125 = Cushing’s
⦁ ** DEXAMETHASONE SUPPRESSION TEST ** = given low dose of dexamethasone - should suppress ACTH production in pituitary gland, which should then cause a decrease in serum cortisol levels
- if due to endogenous excess cortisol, then cortisol levels will remain elevated / unchanged
Patients with Cushing syndrome caused by cortisol-producing adrenal tumor will show no change in cortisol levels following dexamethasone suppression test.
Primary adrenal adenoma, hyperplasia, or carcinoma causing Cushing syndrome, results in decreased ACTH. This leads to atrophy of the uninvolved adrenal gland.
⦁ ACTH levels - would have low ACTH levels with adrenal tumors, but would be elevated with pituitary adenomas (Cushing disease) and ectopic ACTH production
- if ACTH levels are high = then given a HIGH dose of dexamethasone to distinguish between ectopic ACTH or pituitary adenoma; ectopic ACTH typically will NOT respond even to high doses of dexamethasone, and serum cortisol will continue to remain elevated, whereas serum cortisol would decrease with high dexamethasone injection with pituitary adenoma
If a 24-hour urine free cortisol is elevated (>125), a late night salivary cortisol is elevated, and/or there is an inadequate suppression of cortisol with 1 mg overnight dexamethasone test in a patient suspected of Cushing syndrome, the next step would be to measure ACTH
⦁ IMAGING
- MRI of pituitary gland
- CT of adrenal glands
- CT of chest / abdomen / pelvis if seems to be ectopic site of ACTH production
⦁ normal cortisol levels = < 5 at night, and between 10-20 in the morning
- (> 10 = cushing’s syndrome)
⦁ normal ACTH levels = 10-60 in the morning
⦁ normal 24hr urine free cortisol levels = < 90/24 hrs
Cushing syndrome and disease is diagnosed with a dexamethasone suppression test. If ACTH levels are normal or elevated, but <100 pg/mL, the patient has Cushing disease (pituitary adenoma). If ACTH levels are low and cortisol levels are not suppressed by high dose dexamethasone, the patient has Cushing syndrome - likely due to adrenal adenoma
If high-dose dexamethasone suppresses cortisol production, the cause is Cushing disease as the pituitary remains somewhat responsive to the regulatory axis. If cortisol levels are not suppressible at high or low doses, the culprit is either an ectopic ACTH source or an alternative, unregulated cortisol source.
If Cushing Disease, a high-dose overnight dexamethasone suppression test would show low cortisol the morning after
The diagnosis is typically established with an elevated 24-hour urinary free cortisol level. The most common cause is exogenous administration of glucocorticoids. However, when the source of excess cortisol is an adrenal adenoma that secretes excess cortisol primarily, this negatively feedbacks and reduces pituitary secretion of ACTH
** DIAGNOSIS ** = The initial test should be to confirm the hypercortisol state by performing either a 24 hour urinary free cortisol, evening salivary cortisol, or AM blood cortisol tests. Once that is confirmed, then ACTH levels should be obtained. Low ACTH levels would indicate an adrenal etiology. A high dose dexamethasone test would differentiate between pituitary and ectopic etiologies. A negative dexamethasone test (cortisol remains elevated) would indicate an ectopic tumor whereas a positive dexamethasone test (cortisol decreases) would indicate a pituitary etiology.
TREATMENT
- if due to exogenous medication
⦁ gradually decrease drug
⦁ avoid sudden steroid withdrawal - can cause adrenal crisis (life threatening), as adrenal glands might be atrophied, and may need months to fully recover, so body relies on exogenous steroids for cortisol
- if endogenous
⦁ Pituitary Adenoma (Cushing Disease) = surgical excision of adenoma (Transsphenoidal surgery)
⦁ Ectopic ACTH secreting tumor or adrenal tumor ==> tumor removal
- or Adrenal Steroid Inhibitors = Ketoconazole or Metyrapone
Metyrapone is a drug used in Cushing syndrome as it inhibits 11-beta-hydroxylase ( steroid hydroxylase found in the zona glomerulosa and zona fasciculata), thereby inhibiting glucocorticoid synthesis.
⦁ Iatrogenic steroid therapy –> GRADUAL steroid taper (to prevent Addisonian Crisis)
ADDISON’S DISEASE = PRIMARY ADRENAL INSUFFICIENCY
PRIMARY ADRENAL INSUFFICIENCY (ADDISON’S DISEASE) = Adrenal gland is not able to produce enough hormones that the body needs - particularly ALDOSTERONE + CORTISOL
PRIMARY ADRENAL INSUFFICIENCY = the Adrenal Cortex gets progressively damaged over time
ADDISON’S DISEASE = LOW CORTISOL + LOW ALDOSTERONE
Called PRIMARY because the problem is with the adrenal gland itself rather than a problem elsewhere / other hormone acting on the adrenal gland
Addison’s Disease can develop Acutely or Chronicly
JOHN F. KENNEDY had Addison’s disease - diagnosed at age 30
ADRENAL GLAND ANATOMY
- 2 adrenal glands that sit on top of the kidneys
- inner layer of adrenal gland = medulla
- outer layer of adrenal gland = cortex
- adrenal cortex has 3 layers
⦁ Zona Glomerulosa (outermost) –> Aldosterone
⦁ Zona Fasciculata –> Cortisol
⦁ Zona Reticularis (innermost - connects to medulla) –> Androgens (DHEAS = dehydroepiandrosterone = precursor to testosterone)
ALDOSTERONE (released in Zona Glomerulosa of Adrenal Cortex)
- part of RAAS - which leads to K+ excretion and Na+ absorption, which leads to decreased K+, increased Na+, increased blood volume and increased BP
CORTISOL (released in Zona Fasciculata of Adrenal Cortex)
- needed in times of emotional + physical stress
- Hypothalamus –> CRH –> Pituitary Gland –> ACTH –> Adrenal Gland (zona fasciculata of adrenal cortex) –> Cortisol
⦁ Cortisol promotes gluconeogenesis in the liver from fat and protein
⦁ Cortisol gets muscle to break down into protein into glucose, and adipose tissue into fat into glucose
So Cortisol –> High blood glucose levels***
CAUSES OF ADDISON’S DISEASE
⦁ In developed countries - MC Cause = Autoimmune destruction of Adrenal Cortex (70-90%) –> leads to adrenal atrophy
⦁ In developing countries - MC Cause = Tuberculosis - infection spreads from lungs to adrenal glands, causing inflammation + destruction of adrenal cortex
- Other infections = HIV, fungal, CMV –> causes Adrenal Calcification
⦁ Metastatic Carcinoma - cancer spreads from somewhere else to Adrenal Cortex
⦁ Waterhouse-Friderichsen = thrombosis or hemorrhage in the adrenal gland / trauma
⦁ Medications: KETOCONAZOLE***, Rifampin, Phenytoin, Barbiturates
⦁ Long-term exogenous intake of high-dose steroids –> adrenal atrophy (= SECONDARY Adrenocortical Insufficiency)
** BY THE TIME PATIENT IS SHOWING SYMPTOMS OF ADDISON’S DISEASE = ABOUT 90% OF ADRENAL CORTEX HAS BEEN DESTROYED **
SYMPTOMS - depends on which layers of Adrenal Cortex have been destroyed
o Zona Glomerulosa destroyed (Aldosterone)
⦁ High K+ levels (also elevated Ca+ + BUN)
⦁ Low Na+ levels
⦁ Low blood volume
⦁ Low BP
⦁ High H+ levels –> normal anion gap Metabolic Acidosis (in distal tubule, sodium is usually retained in exchange for H+ excretion, so with Na+ excretion, H+ is retained –> acidosis)
---> Leads to ⦁ Cravings for Salty Foods ⦁ Dizziness that worsens with standing ⦁ Nausea / Vomiting ⦁ Fatigue
o Zona Fasciculata destroyed (Cortisol)
⦁ Hypoglycemia during times of stress
⦁ weak / tired / disoriented during stress
⦁ Decreased Cortisol
⦁ Elevated ACTH (normal 20-100)
⦁ overactive pituitary gland –> Elevated Propiomelanocortin (precursor to ACTH) but also a precursor to Melanin Stimulating Hormone
–> Excess Melanin Stimulating Hormone –> ** EXCESS MELANIN PRODUCTION –> HYPERPIGMENTATION ** particularly sun-exposed areas and joints (elbows / knees / knuckles)
o in some extreme cases of Primary Adrenal Insufficiency, the Zona Reticularis is affected as well –> Androgen levels fall
- this does NOT affect men much, because majority of testosterone is released by Testes in Men
- this DOES affect women, because testosterone source for women is from adrenal glands
⦁ women = loss of pubic / armpit hair
⦁ women = loss of sex drive
⦁ amenorrhea
Sometimes associated with VITILIGO - autoimmune
*** Sometimes the symptoms of Addison’s disease are missed or ignored until a major stressor, such as infection / surgery / injury occurs, which suddenly causes symptoms to become severe
= ** ADDISONIAN CRISIS **
- Body develops sudden increased need for Aldosterone and Cortisol, and therefore symptoms are significantly elevated
ADDISONIAN CRISIS = ACUTE PRIMARY ADRENAL INSUFFICIENCY - usually occurs when the majority of zona glomerulosa and zona fasciculata are destroyed
- can cause
⦁ sudden pain in back, abdomen, or legs
⦁ severe vomiting + diarrhea –> dehydration
⦁ low blood pressure –> loss of consciousness
⦁ can be FATAL if left untreated
DIAGNOSIS OF ADDISON’S DISEASE
⦁ Low plasma cortisol (and aldosterone) with elevated ACTH
- low ACTH + low cortisol = secondary adrenocortical insufficiency (pituitary)
⦁ ACTH Stimulation Test *** - synthetic ACTH (cosyntropin) given IM –> then measure Aldosterone and Cortisol levels at 30 + 60 min
- Cortisol levels should double…if cortisol levels are low and don’t increase/double with synthetic ACTH ===> adrenal insufficiency
- this helps to figure out how well the adrenal glands are working
TREATMENT
⦁ ** steroids - replacement of cortisol with
** IV HYDROCORTISONE ** (preferred)
- can give prednisone if pt not responding to HC
⦁ *** hormones - take cortisol, aldosterone and androgen hormones - typically taken for life
FLUDRICORTISONE = synthetic mineralocorticoid (aldosterone)
⦁ stopping the hormones can cause Addisonian Crisis
ADDISONIAN CRISIS (ADRENAL CRISIS)
Sudden worsening of adrenal insufficiency due to a “stressful event” - surgery / trauma / volume loss / hypothermia / MI / fever / sepsis / hypoglycemia / steroid withdrawal
A normal response to stress = 3x increase in cortisol
- these patients are unable to increase cortisol during times of extreme stress to meet demands of body
CAUSES
⦁ Abrupt withdrawal of steroids = MC CAUSE** - instead of gradually tapering off steroids
⦁ Undiagnosed Addison’s disease patients who experience significant “stress”
⦁ Exacerbation of known Addison’s disease (did not increase steroid treatment during stress)
⦁ Bilateral adrenal infarction (usually due to hemorrhage)
*** Sometimes the symptoms of Addison’s disease are missed or ignored until a major stressor, such as infection / surgery / injury occurs, which suddenly causes symptoms to become severe
= ** ADDISONIAN CRISIS **
- Body develops sudden increased need for Aldosterone and Cortisol, and therefore symptoms are significantly elevated
ADDISONIAN CRISIS = ACUTE PRIMARY ADRENAL INSUFFICIENCY - usually occurs when the majority of zona glomerulosa and zona fasciculata are destroyed
- can cause
⦁ sudden pain in back, abdomen, or legs
⦁ severe vomiting + diarrhea –> dehydration
- nausea / vomiting / fever / weakness / lethargy / coma
⦁ low blood pressure –> loss of consciousness
⦁ can be FATAL if left untreated
- shock (hypovolemia / hypotension)
ALL SAME SYMPTOMS AS WITH ADDISON’S DISEASE, BUT MORE SEVERE
⦁ High K+ levels (also elevated Ca+ + BUN)
⦁ Low Na+ levels
⦁ Low blood volume
⦁ Low BP
⦁ High H+ levels –> normal anion gap Metabolic Acidosis
---> Leads to ⦁ Cravings for Salty Foods ⦁ Dizziness that worsens with standing ⦁ Nausea / Vomiting ⦁ Fatigue
⦁ Hypoglycemia during times of stress
⦁ Anorexia / weight loss
⦁ weak / tired / disoriented during stress
⦁ Decreased Cortisol
⦁ Elevated ACTH
⦁ overactive pituitary gland –> Elevated Proopiomelanocortin (precursor to ACTH) but also a precursor to Melanin Stimulating Hormone
–> Excess Melanin Stimulating Hormone –> ** EXCESS MELANIN PRODUCTION –> HYPERPIGMENTATION ** particularly sun-exposed areas and joints (elbows / knees / knuckles)
o in some extreme cases of Primary Adrenal Insufficiency, the Zona Reticularis is affected as well –> Androgen levels fall
- this does NOT affect men much, because majority of testosterone is released by Testes in Men
- this DOES affect women, because testosterone source for women is from adrenal glands
⦁ women = loss of pubic / armpit hair
⦁ women = loss of sex drive
⦁ amenorrhea
TREATMENT OF ADDISONIAN/ADRENAL CRISIS
⦁ IV fluids*** (hypotension + dehydration) - normal saline, D5NS if hypoglycemic
- reverse electrolyte disorder - Na, K, glucose, calcium
⦁ IV glucose
⦁ IV Hydrocortisone if known Addison’s, IV Dexamethasone if undiagnosed
- can then be switched to oral medication once stable and out of crisis
WATERHOUSE-FRIDERICHSON SYNDROME
- can also cause Addisonian Crisis (in addition to Addison’s disease or Primary Adrenal Insufficiency)
Waterhouse Friderichson Syndrome = when a sudden increase in blood pressure causes blood vessels in adrenal cortex to rupture
- this fills the adrenal glands with blood and leads to tissue ischemia –> adrenal gland failure
MONONUCLEOSIS
Mononucleosis caused by the Epstein-Barr virus commonly presents with fever, hepatosplenomegaly, pharyngitis, and lymphadenopathy.
