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
