RHEUMATOLOGY Flashcards
MORPHEA
“localized scleroderma”, or “circumscribed scleroderma”
involves isolated patches of hardened skin with no internal organ involvement.
DIAGNOSIS
⦁ history + physical exam
⦁ Anti-ANA, Anti-centromere antibody (to rule out CREST), Anti-SCL 70 (Topoisomerase I) (to rule out diffuse sclerosis)
TREATMENT
⦁ steroids (topical to thin area, systemic to prevent further progression)
⦁ immunosuppressants (cyclosporine, azathioprine)
CREST SYNDROME
= LIMITED CUTANEOUS SYSTEMIC SCLEROSIS
= LIMITED SCLERODERMA
- An autoimmune condition
= MC type of Scleroderma
⦁ Calcinosis cutis ⦁ Raynaud's phenomenon ⦁ Esophageal dysmotility ⦁ Sclerodactyly ⦁ Telangiectasias
= less severe form of systemic sclerosis
- causes damage to skin and blood vessels and leads to fibrosis
Calcinosis Cutis = deposition of calcium in the skin
Raynaud’s = spasm of arteries in the fingers
Esophageal Dysmotility = difficulty swallowing –> heartburn
Sclerodactyly = tightening of the skin over the fingers
Telangiectasias = small dilated blood vessels on the skin surface
Symptoms include esophageal dysmotility, resulting in heartburn and dysphagia, as well as many skin findings including digital ulcers, tightened facial features and symmetrical skin thickening.
PATHOPHYSIOLOGY
- normally when there’s an infection in the body, macrophages will flood to the area to destroy the pathogen
- macrophages will also present a part of the antigen to naïve T cells, which mature into helper T cells (CD4+ T cells) –> recruit more immune cells
- helper T cells release cytokines –> increase activity of macrophages, and attract nearby neutrophils
- also release more cytokines –> recruit fibroblasts to repair damaged tissue after infection resolves to lay down new collagen
CAUSE OF CREST SYNDROME
⦁ unknown
- patients in the first 1-2 years of the condition have higher numbers of T cells in their skin on the hands and face, particularly near blood vessels
CLINICAL MANIFESTATIONS
Limited scleroderma affects the skin of the face, hands, and neck. The skin on other areas of the body is not affected.
1) CALCINOSIS CUTIS
- T helper cells release cytokines, which attract more immune cells (macrophages, neutrophils), which cause a lot of INFLAMMATION in the skin
- so much inflammation causes the TISSUE TO DIE (necrosis)
- when tissue dies, calcium in the cytosol binds to the cell membrane fragments and builds up in the skin –> CALCINOSIS CUTIS
- patients report hands bumps on fingers
2) RAYNAUD’S PHENOMENON
- episodic dramatic vasoconstriction of arterial blood vessels in the hands –> cold/pale fingertips
- patients reports that fingers change color or turn white / pale from time to time, especially when cold
** Raynaud’s phenomenon = typically the first thing patient’s with CREST syndrome notice **
3) ESOPHAGEAL DYSMOTILITY
- difficulty swallowing
- heartburn
- may have to drink water with every bite to make sure that food makes it down properly
4) SCLERODACTYLY
- the inflammation in the skin also damages blood vessels –> poor blood flow –> ischemia –> more damage to the skin, particularly in the hands + fingers
- the severe ischemia + tight skin in the fingers can cause ischemic ulcers and even finger loss if left untreated
- the body tries to repair the damage by activating fibroblasts –> lays down bundles of collagen
- T helper cells also release more cytokines –> keeps the fibroblasts functioning
- the collagen buildup in fingers + hands –> sclerodactyly
early on, the fingers may be swollen and painful, but over time, become thick and tight
5) TELANGIECTASIAS
- due to vascular damage –> tiny dilated capillaries - usually on the skin of the hands
- telangiectasias of skin and mucous membranes
May notice red spots on their hands, as well as perhaps the face and neck
** greatest concern = pulmonary fibrosis - leads to pulmonary hypertension **
Because CREST syndrome is defined as a limited scleroderma, there is limited involvement of the skin that is typically confined to the face and fingers.
DIAGNOSIS
⦁ history + physical exam
⦁ ** association with ANTI-CENTROMERE ANTIBODY **
⦁ in many cases, positive serum antinuclear antibody (ANA) as well.
- Anti-centromere antibody in serum will confirm CREST syndrome in about 60% of patients
A diagnosis of CREST syndrome is typically made when at least three of the five classic signs are described in a patient.
TREATMENT
⦁ no cure
⦁ steroids* or DMARDs*
⦁ immunosuppressants - cyclosporine, azathioprine
⦁ smoking cessation
⦁ symptomatic treatment for esophageal reflux PPIs), pulmonary HTN and Raynaud’s phenomenon (CCBs, Prostacyclin - vasodilators) and sclerodactyly (MTX)
The progression of CREST syndrome can be slowed with the use of immunosuppressants.
DIFFUSE SCLERODERMA
= DIFFUSE SYSTEMIC SCLEROSIS
= SCLERODERMA
Scleroderma, also known as systemic sclerosis, is a chronic systemic autoimmune disease characterized by hardening of the skin.
Scleroderma is an autoimmune disorder characterized by fibroblast activation and collagen deposition.
Systemic connective tissue disorder = thickened skin (sclerodactyly), lungs, heart, kidneys + GI tract
Develop TIGHT, SHINY, THICKENED SKIN (localized or generalized) due to fibrous collagen buildup
Diffuse scleroderma is rapidly progressing form and affects a large area of the skin and one or more internal organs, frequently the kidneys, esophagus, heart and/or lungs.
Scleroderma is a multisystem, autoimmune disease of no known cause, resulting in vascular abnormalities, fibrosis, and characteristic symmetrical skin thickening.
- Scleroderma more commonly affects FEMALES
- often develops in patients between the age of 40-50
PATHOPHYSIOLOGY - Scleroderma involves a symptomatic triad of ⦁ autoimmunity ⦁ non-inflammatory vasculopathy ⦁ collagen deposition with fibrosis.
Scleroderma is caused by fibroblast activation leading to collagen deposition, resulting from autoimmune damage to mesenchymal tissue.
Limited systemic sclerosis is characterized by cutaneous manifestations and some involvement of the GI tract (esophageal dysmotility) and vascular symptoms (vasculitis and telangiectasias)… WHEREAS
Diffuse systemic sclerosis results involves more systemic components including pulmonary involvement, renal involvement, and usually has a more rapid progression than the limited form, resulting in a poorer prognosis.
The pathophysiologic changes in systemic sclerosis are primarily due to increased production of ground substance by fibroblasts, cells that are sensitive to FGF, causing the systemic fibrosis pattern seen in the disease.
The fibrosis causes skin thickening leading to sclerodactyly, esophageal thickening leading to esophageal dysmotility, pulmonary fibrosis and pulmonary hypertension, and possible renal fibrosis leading to renal failure. There is also some suspected endothelial cell change leading to the vasculitis and telangiectasias.
CLINICAL MANIFESTATIONS
⦁ On the skin, scleroderma usually manifests with pitting in the fingertips / digital ulcers and as puffy, taut skin free of wrinkles.
⦁ Diffuse scleroderma is associated with widespread skin involvement, rapid progression and early visceral involvement.
⦁ Systemic sclerosis can affect much of the GI tract, with the ESOPHAGUS being the most common portion affected, frequently resulting in DYSPHAGIA.
⦁ GI involvement of scleroderma includes heartburn and dysphagia (of both solids and liquids) because of esophageal dysmotility from smooth muscle conversion to collagen
⦁ dyspnea, due to interstitial pulmonary fibrosis
⦁ renal disease
⦁ tightened facial features
⦁ polyarthralgia.
The clinical symptoms such as dysphagia, heartburn, digital ulcerations, the presence of Raynaud’s phenomenon, and pruritus are common in scleroderma (systemic sclerosis).
The most common cause of death in scleroderma is sclerosis of pulmonary tissue causing pulmonary arterial hypertension.
Findings on lung exam may represent an early finding of interstitial pulmonary fibrosis, a complication of systemic sclerosis that can be fatal.
DIAGNOSIS
⦁ Anti-scl-70 antibodies (Anti - topoisomerase I antibody)
- typically seen in patients with diffuse systemic sclerosis, but not seen in CREST (limited cutaneous systemic sclerosis)
⦁ serum ANA - anti nuclear antibodies
TREATMENT
⦁ Raynaud’s = Calcium Channel Blockers (CCBs)
⦁ Sclerodactyly = Methotrexate (MTX)
⦁ Esophageal Reflux = Proton Pump Inhibitors (PPIs)
⦁ Steroids (Prednisone) or DMARDs
⦁ Immunosuppressants (Cyclosporine, Azathioprine)
FIBROMYALGIA
- Pain of fibrous tissue + muscle
- CHRONIC condition that affects WOMEN > men
- MC = Middle-Aged Women
- Causes widespread muscle pain + extreme tenderness + sleep disturbances
NORMAL PATHOPHYSIOLOGY
1) When something painful happens (ex: cut on finger) => specific pain receptor sensory neuron (“Nocireceptor”) converts the pain into an electrical signal
- Nocireceptors are the first neurons and are found in skin, joints, and walls of organs
2) electrical signal travels up to brain to dorsal root ganglion of spinal cord –> cell body –> releases SUBSTANCE P
If sensory neuron pain is > inhibitory neuron’s ability to inhibit pain (releases serotonin / norepinephrine), then signal travels up spinal cord to the brain, where pain is perceived
3) where damage occurs, epithelial cells release “Nerve Growth Factor” –> which attracts nearby Mast Cells –> release even more Nerve Growth Factor
- Nerve Growth Factor functions
⦁ boosts growth of nocireceptors (pain receptors)
⦁ makes nocireceptors more sensitive to pain***
⦁ makes nocireceptors produce even more substance P
CAUSE OF FIBROMYALGIA
- unknown, but there seems to be a problem with how the brain perceives pain signals
- thought that patients with fibromyalgia have
⦁ lower levels of serotonin (involved in inhibiting pain signals)
⦁ higher levels of substance P
⦁ higher levels of nerve growth factor
- both substance P + nerve growth factor are involved in propagating the pain signals
leads to a HYPERSENSITIVITY TO PAIN****
⦁ Fibromyalgia tends to run in families - so thought to have a genetic link as well
⦁ Environmental factors such as child abuse are also linked to fibromyalgia, as well as depression / anxiety
CLINICAL MANIFESTATIONS ⦁ **** WIDESPREAD MUSCLE PAIN ****(chronic) ⦁ excessive muscle tenderness in body ⦁ fatigue ⦁ stiffness / painful + tender joints ⦁ difficulty concentrating "fibro fog" / haziness ⦁ sleep difficulties ⦁ issues with memory ⦁ headache
- symptoms may worsen with stress
** Increased incidence of fibromyalgia with RHEUMATOID ARTHRITIS, LUPUS, and ANKYLOSING SPONDYLITIS **
DIAGNOSIS
⦁ pain in 7+ areas of the body + symptom severity scale must be at least 5/12
OR
⦁ pain in 5+ areas of the body + symptom severity scale of at least 9/12
⦁ Duration = MUST BE AT LEAST 3 MONTHS
⦁ Pain cannot be due to another disorder
DIAGNOSIS
⦁ DIFFUSE PAIN IN 11 / 18 TRIGGER POINTS
⦁ > 3 MONTHS
⦁ WIDESPREAD PAIN
- Muscle Biopsy = “Moth Eaten” appearance of type I muscle fibers, muscle damage
LABS - need to order these to rule out issues with ⦁ B12 ⦁ Hypothyroidism ⦁ Vitamin D ⦁ Magnesium
TREATMENT
- exercise (SWIMMING PREFERRED) - due to relaxing effect of water on muscles, or water aerobics
⦁ can also try fast walking, biking
- relaxation techniques
- good sleep hygiene
- if conservative therapy fails = can use MEDICATION
⦁ TCAs (Amitriptyline)
⦁ SNRIs (increase serotonin + NE) - duloxetine (Cymbalta), Milnacipran (Savella) = FDA approved to treat fibromyalgia
⦁ SSRIs
⦁ Anticonvulsants
⦁ Pregabalin (Lyrica) = FDA approved for fibromyalgia!!!
⦁ Gabapentin (Neurontin)
GOUT
GOUT = inflammatory condition in which MONOSODIUM URATE CRYSTALS deposit in joints due to hyperuricemia (excess uric acid in blood)
- uric acid deposition in areas of decreased blood flow, / lower temperatures like the joints and kidney tubules
Gout is MC caused by UNDEREXCRETION of uric acid in 90% of cases.
- gout attacks = secondary to purine-rich foods (alcohol, liver, seafood, yeasts) - causing rapid changes in uric acid concentrations
- medication causes = Diuretics (thiazides, loop), ACEI, Pyrazinamide, Ethambutol, Aspirin, ARBs
exception = Losartan - actually decreases uric acid levels
- MC in men (especially > 30y/o); if seen in women = usually postmenopausal
STEM - awakened at night by pain - usually in big toe- feeling like toe is on fire
- sometimes affects heel, calf, ankle, knee, wrist, elbow
- pain resembles dislocated bone
- followed by chillness, shivering, slight fever which grows more violent every hour
- can’t even endure the weight of bedsheet
- swelling can last for days or even weeks
MC affects MTP joint - metatarsophalangeal joint - big toe; painful joint inflammation in first MTP joint
CLINICAL MANIFESTATIONS
1) Acute Gouty Arthritis ⦁ severe joint pain / tender ⦁ heat ⦁ erythema (red) ⦁ swelling ⦁ stiffness - happens within hours - PODAGRA = 1st MTP joint involvement = MC - knees, feet, ankles also common
** joints are affected ASYMMETRICALLY **
2) Tophi Deposition = chronic arthropathy - collection of solid uric acid in soft tissues (**helix of ear, eyelids, Achilles tendon) occurs after 10-20 years of chronic hyperuricemia
Over time, repeated gouty attacks can cause destruction of the joint tissue, and lead to ARTHRITIS**
- TOPHI = permanent deposits of uric crystals
3) Uric Acid Nephrolithiasis + Nephropathy = uric acid stones - associated with low urine volume and acidic urine pH; may cause glomerulonephritis; may lead to renal failure
= at an increased risk of kidney stones made of uric acid + urate nephropathy (crystals deposit in kidney)
Secondary gout may be caused by renal insufficiency leading to uric acid underexcretion.
gout = Monosodium Urate Crystals in joint space
- over time, joint space is damaged
- precipitates out where areas are more cool in temperature (big toe)
- tophi may also form in the joint space (similar to heberden’s node)
- PODAGRA = first MTP joint = most commonly affected
- due to decreased excretion and/or increased production of uric acid, and increased purine intake
anything with high PURINE levels (meats, cheeses, fermented yeasts, alcohol, etc)
- purines are converted into uric acid (a molecule that can be excreted through the urine)
RISK FACTORS FOR GOUT
⦁ increases with age
⦁ female sex hormones increase urinary excretion of uric acid (so lack of estrogen contributes to gout)
⦁ meat
⦁ seafood
⦁ dehydration (decreased clearance)
⦁ alcohol (increased production + decreased clearance)
⦁ obesity
⦁ diabetes
⦁ chemo / radiation
⦁ genetic predisposition for increased uric acid
⦁ chronic kidney disease (decreased excretion)
⦁ medications (thiazide diuretics, aspirin, etc)
⦁ states of increased cell turnover: cancer, psoriasis, chemotherapy / radiation - induces tumor lysis syndrome –> increased uric acid production
CLINICAL PRESENTATION OF GOUT
- looks like an infection!
- severe pain
- redness/warmth
- swelling/disability
- onset more at night***
- overlying skin becomes tense
Inflammation due to presence of WBCs, which migrate to the site to eliminate uric acid - release proinflammatory cytokines
Von Gierke disease is a glycogen storage disorder associated with gout which causes underexcretion and overproduction of uric acid. Results from G6PD (glucose-6-phosphatase deficiency).
DIAGNOSIS OF GOUT ⦁ clinical diagnosis ⦁ serum uric acid levels ⦁ Arthrocentesis = synovial fluid analysis = **** NEGATIVELY BIREFRINGENT**** - Needle-shaped urate crystals
In gout, monosodium urate crystals appear YELLOW under parallel light.
In gout, monosodium urate crystals appear BLUE under perpendicular light.
Gout is caused by precipitation of needle shaped, negative birefringent, monosodium urate crystals.
⦁ Radiographs = “mouse/rat bite” “punched out erosions” (takes a long time to show on xray)
⦁ increased ESR + WBC during acute attack
- serum uric acid levels = initial test
- arthrocentesis = definitive diagnosis
o Female uric acid level: normal = 2.5 - 6.0
o Male uric acid level: normal = 3.5 - 7.0
TREATMENT OF GOUT - RX FOR ACUTE GOUT
- resolves in a few days to weeks
1) NSAIDS = USUAL FIRST CHOICE**
⦁ Naproxen, Ibuprofen, Indomethacin (1st line)
- beware of GI and CV effects
- do NOT use aspirin - aspirin increases serum uric acid
2) Colchicine (2nd line) - was main RX for many years - helps with inflammation by inhibiting WBC migration - used first if patient has renal failure***
- low dose regimen is effective, and has fewer SE, however, can cause GI upset, neutropenia, and peripheral neuropathy
- colchicine not used as often due to SE of diarrhea**
Do NOT use IV Colchicine!!! - serious / fatal SE
3) Glucocorticoids
⦁ Intraarticular injections often quickly resolve symptoms
⦁ oral steroids if multiple joints are involved, if can’t use NSAIDS/colchicine, or if severe renal disease
PROPHYLACTIC TREATMENT FOR HYPERURICEMIA
1) Diet - reduce intake of purines (reduce meat / seafood / alcohol) Increase dairy products
2) Xanthine Oxidase Inhibitors
⦁ ALLOPURINOL (first choice of drug to lower serum urate levels) - inhibits xanthine oxidase => inhibits conversion of purines to uric acid, so it decreases uric acid production
- SE = take with meals to prevent gastric irritation / diarrhea; arthralgias, rash (HSN / SJS); Caution in renal disease
- do not give Allopurinol for acute gout - as may exacerbate it. only for prevention.
⦁ Febuxostat (Uloric)* = xanthine oxidase inhibitor that is safer in patients with renal disease**
o Uricosuric Drugs
⦁ Probenecid = increases uric acid excretion in urine
- SE = gouty attack, GI upset, stone formation
⦁ Colchicine = only rx that can be used for both acute and chronic gout
PREVENTING RECURRENT ATTACKS
1) lifestyle changes = weight loss, stay well hydrated, decrease alcohol
2) Diet = decrease meat / fish, increase dairy
3) Lower Serum Uric Acid = Uricosuric agents (increases excretion- probenecid) + Xanthine Oxidase Inhibitors (decreases synthesis - allopurinol)
PSEUDOGOUT = CHONDROCALCINOSIS = CALCIUM PYROPHOSPHATE DIHYDRATE DEPOSITION DISEASE (cppdd disease)
Pseudogout = Chondrocalcinosis, or calcium pyrophosphate dihydrate crystal deposition disease in joints / soft tissue –> inflammation + bone destruction
Pseudogout = a rheumatologic disorder with varied symptoms and signs arising from the accumulation of crystals of calcium pyrophosphate dihydrate in the connective tissues.
RISK FACTORS
- Pseudogout MC affects people older than 50 y/o
- MC in females (unlike gout, mc = males)
CLINICAL MANIFESTATIONS
⦁ asymptomatic
⦁ red / swollen / tender joint (resembles gout)
⦁ MC location = KNEE
⦁ Other locations = wrist, MCP joint, elbows, MTP
Pseudogout (chondrocalcinosis) typically affects larger joints, classically presenting in the knee joint.
- can be monoarticular or polyarticular (affect just 1 joint or can affect multiple joints)
- can present as an Acute or Chronic inflammatory arthritis, that causes pain in one or more joints
ASSOCIATIONS
⦁ can be associated with osteoarthritis
⦁ can be associated with hypothyroidism
⦁ can be associated with hemochromatosis
⦁ can be associated with hypo / hyperparathyroidsm
DIAGNOSIS
- As gout and pseudogout are clinically similar, differentiation requires examination of synovial fluid from affected joints.
It is important to aspirate a new-onset acutely inflamed joint to rule out septic arthritis.
⦁ Arthrocentesis = synovial fluid analysis =
- * POSITIVELY BIREFRINGENT**
- LINEAR + RHOMBOID***-shaped urate crystals
- Appears Blue under parallel polarized light (unlike gout = yellow under parallel, blue under perpendicular)
⦁ Elevated WBC + ESR
⦁ XRAY = Chondrocalcinosis (calcification of articular cartilage) - linear radiodensities on xray
TREATMENT (same as acute gout tx)
- asymptomatic = no tx
⦁ 1ST LINE = ** Intraarticular STEROIDS**- reduce inflammation + pain
⦁ NSAIDS - help relieve pain + inflammation (Naproxen / Indomethacin / Ibuprofen) - no aspirin
⦁ Colchicine - reduces leukocyte degranulation - relieves pain + inflammation
- colchicine = for acute tx or for prophylaxis
SJOGRENS SYNDROME
- named after Dr. Henrik Sjogren
A common AUTOIMMUNE disorder in which the body’s immune cells start attacking own exocrine glands
Exocrine glands = pour secretions into a duct
typically occurs in WOMEN, age 40-60
*** INCREASED INCIDENCE OF
NON-HODGKIN’S LYMPHOMA **
= TYPE IV HYPERSENSITIVITY RXN (T - cells)
- type II = IgG or IgM
- type I = IgE
PATHOPHYSIOLOGY
- normally immune cells attack foreign pathogens in the body
- Macrophages (antigen presenting cells) latch onto pathogens and engulf them
- pieces of the pathogen (antigens) are then presented on a MHC II (major histocompatibility complex - class II molecule)
- helper T cell (CD4+ cell) binds to the MHC II presented antigen –> activates the T cell –> releases proinflammatory cytokines –> recruits more immune cells –> INFLAMMATION
CAUSE OF SJOGRENS SYNDROME
⦁ unknown, but seems to be related to both genetic and environmental factors
⦁ Genetic = seems to be linked to specific HLA genes:
1) HLA-DRW52 (MC - 85% of cases) = think DRy Why
2) HLA-DQA1
3) HLA-DQB1
⦁ Environmental = infection of exocrine glands - infection can damage cells of lacrimal and/or salivary glands and expose cell components to immune cells which then recognize exocrine gland cells as foreign
T cell gets inappropriately activated against own exocrine gland cells –> Activates B cell –> produce Anti-Nuclear Antibodies (ANAs) = antibodies against nuclear antigens
** 2 types of ANAs (anti-nuclear antibodies) formed in Sjogren’s Syndrome
⦁ Anti-Ro (Anti-SSA antibody)
⦁ Anta-La (Anti-SSB antibody) = most specific
Cytokines –> inflammation of exocrine gland tissue
Antibodies –> damage of exocrine gland tissue
Fibroblasts deposit collage in place of damaged tissue
Leads to a loss of secretory cells in the exocrine glands
PRIMARY SJOGRENS SYNDROME
- occurs alone = ** SICCA SYNDROME **
- SICCA syndrome = very similar to sjogrens syndrome, except no arthritic symptoms, and more commonly involves other locations - vaginal dryness, myositis, kidney disease, hepatobiliary disease, brain, etc.
SECONDARY SJOGRENS SYNDROME
- occurs along with other autoimmune conditions such as Rheumatoid Arthritis or SLE or polymyositis
CLINICAL MANIFESTATIONS - MC affects the salivary glands + lacrimal glands - usually presents in middle-aged women ⦁ dry eyes** ⦁ dry mouth** ⦁ fatigue** ⦁ joint pain**
if affects eyes ⦁ dry eyes = *** KERATOCONJUNCTIVITIS SICCA *** - blurry vision - redness - itching - burning
if affects mouth ⦁ dry mouth = xerostomia ⦁ PAROTID ENLARGEMENT**** - difficulty tasting - difficulty swallowing - cracks / fissures in the mouth - recurrent dental caries (cavities)
==> develop enlargement of salivary glands (MC parotid) to compensate for dryness
⦁ if affects nose / respiratory passages
- ulceration / perforation of nasal septum
- crusting / bleeding
⦁ if affects larynx
- difficulty speaking
⦁ some patients may also experience dryness of the skin and vagina
COMPLICATIONS
- swelling of glands –> can compress nerves / be painful
- dryness of epithelial linings can make infections more likely
** sjogrens syndrome = has increased incidence of
⦁ ** NON-HODGKIN’S LYMPHOMA ** (B-cell)
⦁ Interstitial nephritis
⦁ pneumonitis
Patients with Sjögren syndrome are at greater risk for extranodal marginal zone B-cell lymphoma, which presents in late disease as UNILATERAL parotid gland enlargement.
DIAGNOSIS
- based on decrease in exocrine gland secretion
⦁ Sialometry = measures saliva flow
⦁ positive Schirmer test = decreased tear production
⦁ Blood = anti-Ro / Anti La antibodies (anti SSA/SSB)
⦁ will also have positive RF (rheumatoid factor)
⦁ may have positive ANA
⦁ confirmatory = lip or salivary gland biopsy - see increased lymphocytic infiltration of CD4+ cells, plasma cells and macrophages, and thickening of inner duct wall
SCHIRMER TEST = paper strips inserted into lower eyelids; tear secretion is measured
- < 5mm of moisture collected on filter paper in 5 min = highly likely diagnosis of sjogrens syndrome
- while not all patients with sjogrens disease have anti-SSA / anti-SSB antibodies, the presence of autoantibodies is associated with greater severity and longer duration of the disease
TREATMENT
- there is no definitive cure for Sjögren syndrome.
- immunosuppressants = ex: steroids
- symptomatic therapy
⦁ artificial tear drops
⦁ NSAIDS for joint inflammation
⦁ good dental hygiene to prevent caries
⦁ ** PILOCARPINE ** - (cholinergic = parasympathetic –> direct stimulation of muscarinic receptors –> increases lacrimation and salivation
SE of cholinergic drugs = diaphoresis, flushing, sweating, bradycardia, diarrhea, N/V, incontinence, blurred vision
SLUDD-C = salivation, lacrimation, urination, defecation, digestion, constriction of pupil
POLYMYALGIA RHEUMATICA
Disorder that causes MUSCLE PAIN + JOINT STIFFNESS
immune-mediated disease = immune system attacks own body
While myalgia = muscle pain, polymyalgia rheumatica is mostly inflammation around joints, while muscles are usually spared
PATHOPHYSIOLOGY
- immune system starts attacking own cells, which are recognized as foreign
- helper T cells bind to MHC class I molecules that are displaying “foreign” cells
- helper T cells release pro-inflammatory cytokines –> recruit macrophages
- interleukins trigger B cells to release antibodies against targeted antigens
PR is associated with both genetic + environmental factors
⦁ genetics: HLA-DR4 = more likely to develop PR, especially after Adenovirus or Parvovirus B19 infection
- muscles are actually spared on biopsy
- structures surrounding joints are affected: tendons / bursae ==> causes referred pain in the muscle** due to inflammation of nearby nerves in the muscle
Inflammatory cytokines circulate in blood, go to brain and can cause fever / fatigue / malaise
** STRONG ASSOCIATION WITH GCA / TEMPORAL ARTERITIS ** - stem patient may also have headache
SYMPTOMS OF POLYMYALGIA RHEUMATICA
⦁ often affects women > 50 (like with GCA)
⦁ pain / stiffness of proximal joints/muscles = neck, shoulder, hip
⦁ muscle strength = unchanged!
⦁ typically starts on one side, but progresses to both sides within weeks
⦁ **** symptoms more severe in the MORNING **** improves throughout the day, worsens at night
⦁ pain / stiffness lasts for > 30 minutes / > 1 hr
⦁ ** IMPROVES WITH ACTIVITY **
⦁ difficult to get out of bed, get up from chair, lifting arms, combing hair, putting on coat
⦁ can also cause low-grade fever, fatigue, anorexia –> weight loss
⦁ may develop GCA - headache, temporal pain, jaw claudication, fever, vision problems - even blindness
DIAGNOSIS OF POLYMYALGIA RHEUMATICA
⦁ elevated ESR > 50
⦁ elevated CRP
⦁ CK = normal (muscle not actually being damaged helps to differentiate between PR and polymyositis
⦁ normocytic normochromic anemia (like GCA)
TREATMENT
⦁ low doses of STEROIDS- Prednisone 10-20mg qd
(whereas GCA = high dose steroids - 60mg qd)
⦁ NSAIDS
⦁ methotrexate
⦁ exercise / healthy diet - to help improve flexibility of affected joints
Patient will present as → a 62-year-old female complaining of headaches, muscle pain, and weakness. She has no history of headaches but has now started experiencing them every morning for the past two weeks. She reports feeling very weak and tired in the mornings and cannot even raise her arms to brush her hair. Physical exam shows that she has normal strength and normal range of movement. Passive range of motion is limited in all directions and she has difficulty rising out of the exam room chair. Erythrocyte sedimentation rate is elevated.
- ** How to differentiate between PMR + Polymyositis
- both have proximal involvement that is worse in morning and improves with activity
- PMR = pain / stiffness in proximal JOINTS
- Polymyositis = proximal MUSCLE weakness, but usually painless
- PMR = ESR very elevated, no elevated CK
- Polymyositis = ESR elevated (but not > 50), but elevated CK! and Aldolase! + anti-jo, anti-srp, anti-mi2
- PMR = acute onset
- Polymyositis = progressive*
DERMATOMYOSITIS
- An inflammatory condition that involves both the SKIN and the MUSCLES
- Idiopathic Inflammatory Myopathy
- An AUTOIMMUNE disease - immune cells gone rogue and start attacking own cells of the skin and muscles
More common in WOMEN
- usually occurs in 4th/5th decades, but may also occur at any age
NORMAL PATHOPHYSIOLOGY
- B lymphocytes create antibodies against a specific part of foreign pathogens (ANTIGENS)
- the base of antibodies bind to antigens
- the body of antigens are recognized by complement proteins
Complement proteins = small group of proteins made by the liver. They activate one another in an enzymatic cascade
When 2 antibodies bind to an antigen, their bodies or constant regions get bound by C1 protein
⦁ C1 binds to the constant region (Fc) of 2 antibodies attached to pathogen
⦁ C1 cleaves C2 and C4 –> half portions bind to antigen and create enzymatic complex that cleaves C3 into C3a and C3b
⦁ C3a joins the enzymatic complex (part of C2 + C4)
- the C2/C4/C3a now cleaves C5 into C5a and C5b
⦁ C3b + C5b float off into the blood to attract more immune cells to the area
⦁ C5a, C6, C7, C8, and multiple C9 proteins join together on surface of antigen to form MEMBRANE ATTACK COMPLEX (MAC)
⦁ MAC attacks pathogenic cells by forming a channel in the cell membrane of the pathogen –> allows water to flow in via osmosis (greater solute concentration inside cell) –> cell lysis
DERMATOMYOSITIS PATHOPHYSIOLOGY
- immune cells confuse cells of skin + muscle as foreign pathogens
” molecular mimicry “ - host protein is mimicking a foreign or tumor protein
when normal proteins trigger an immune response, that protein = “Autoantigen”
- These autoantigens are then picked up by B lymphocytes, which start producing antibodies against them
In Dermatomyositis, autoantigens are found in endothelial cells of capillaries in muscle + skin cells, as well as antigens coming from destroyed muscle / skin cells
1) Autoantibodies attach to capillary endothelial cells lining the perimysium (sheath of CT around bundles of muscle fibers)
2) Once bound, autoantibodies activate the complement cascade –> MAC –> endothelial cells lyse
3) complement proteins also attract more inflammatory cells to the area, ie macrophages
4) Autoantibodies also bind to small soluble antigens that are released from damaged muscle / skin cells ==> form antigen / antibody complexes
- these complexes are not removed from bloodstream very quickly –> move around blood stream for some time –> attack to various blood vessel walls –> activate complement –> MAC –> further damage
5) Damage to blood vessels –> tissue ischemia in affected muscle and skin tissue
TRIGGER FOR DERMATOMYOSITIS = unknown
- certain genetic + environmental factors
- genetic predisposition to HLA-DR3 or HLA-DR5 (human leukocyte antigen) - may develop dermatomyositis after infection (coxsackie virus) or specific tumor antigens (ovarian / lung /breast / gastric / genitourinary CA)
The cause is unknown, but it may result from an initial viral or bacterial infection
Dermatomyositis is commonly associated with bronchogenic, ovarian and breast cancer.
Dermatomyositis is an immunologic disease that damages small blood vessels, which contributes to muscle injury.
Dermatomyositis is an autoimmune condition involving the muscle and skin, caused by CD4 T-cells that cause perimysial inflammation and atrophy
Individual muscle fibers are grouped into bundles called “Fascicles”
- Fascicles are then bound together and protected by CT layer called “Perimysium”
INFLAMMATION OF THE PERIMYSIUM MEDIATED BY CD4+ T-CELLS (helper T cells) AND ANTIBODY ACTIVATION CAUSES MUSCLE FIBER WEAKNESS + OTHER DERMATOMYOSITIS SYMPTOMS
CLINICAL MANIFESTATIONS
- Muscle involvement
⦁ SYMMETRIC BILATERAL PROXIMAL muscle weakness**
⦁ muscle atrophy
⦁ muscle pain / tenderness
- typically affects large muscle groups (shoulder / hip)*
- can cause difficulty getting out of chair
- difficulty combing hair
- difficulty climbing stairs
- difficulty reaching for high objects
Proximal muscle weakness in dermatomyositis is seen first
- In severe cases, the muscles of pharynx of esophagus can be affected –> at risk for aspiration / aspiration pneumonia
⦁ Dysphagia
⦁ Dysphonia - ** LUNG / CARDIAC INVOLVEMENT ***
- high risk of developing interstitial lung disease due to pulmonary inflammation
- risk of developing respiratory failure due to diaphragm / intercostal muscle weakness
- risk of developing CHF, MI, Myocarditis –> can lead to arrhythmias / conduction defects
- Skin involvement
⦁ ** HELIOTROPE RASH ** = purplish rash on upper eyelids
⦁ ** SHAWL SIGN / RASH ** = rash also may affect shoulders / upper chest / back, resembling a shawl - or V-sign = just anterior neck / upper chest
⦁ less commonly = butterfly malar rash (just like SLE)
o Difference between SLE malar rash + DM malar rash
-SLE malar rash = excludes nasolabial folds
-dermatomyositis malar rash = includes nasolabial folds
⦁ ** GOTTRON’S SIGN ** = flat, red, scaly papules over the backs of fingers, KNUCKLES, elbows or knees
⦁ Erythroderma
- scaly, erythematous rash over the knuckles
- rashes are PHOTOSENSITIVE - worsen in sunlight
- rashes may be itchy, painful, may bleed
⦁ Periungual telangiectasias
⦁ “mechanic’s hands” = rough / cracked dry skin
DIAGNOSIS
- combination of skin + muscle findings
- physical exam: test muscle strength
- Autoantibodies
⦁ ANA
⦁ Anti-Mi2 (strong association with Gottron papules)
⦁ Anti-Jo1
⦁ Anti-SRP antibodies (signal recognition particle) = may be in DM, but almost exclusively found in PM)
⦁ increased muscle enzymes (creatinine kinase)* (aldolase)** (lactate dehydrogenase)
⦁ abnormal electromyogram
⦁ muscle biopsy = inflammation of perimysium, perifascicular involvement, perivascular involvement
** Anti-Mi2 = specific to DERMATOMYOSITIS **
⦁ INCREASED CK, ALDOLASE, ESR, LACTATE DEHYDROGENASE
MOST APPROPRIATE 1ST STEP = CREATININE KINASE
anti-Mi2 antibodies show a strong association with prominent Gottron papules in dermatomyositis.
TREATMENT
- suppress immune response
⦁ steroids - Prednisone or Methylprednisolone- usually 9-12 months initially
⦁ MTX - may also be used as adjunct to steroid
⦁ Azathioprine - can also be adjunct to steroid
⦁ Rituximab - often tried if steroid + MTX or steroid + Azathioprine fails
⦁ Antimalarial meds (Hydroxychloroquine or Chloroquine) - may be helpful for skin rashes
⦁ sun avoidance / wear protective clothing
⦁ IVIG = has been shown to help with treatment resistant dermatomyositis - not shown to be effective for polymyositis
MTX + Azathioprine = alternatives to steroids in diabetic patients
POLYMYOSITIS
- An inflammatory condition that affects the MUSCLES(not the skin - unlike dermatomyositis)
- Idiopathic Inflammatory Myopathy of various muscles throughout the body
- An AUTOIMMUNE disease - immune cells gone rogue and start attacking own cells of the muscles
More common in WOMEN
- usually occurs in 4th/5th decades, but may also occur at any age
NORMAL PATHOPHYSIOLOGY
- B lymphocytes create antibodies against a specific part of foreign pathogens (ANTIGENS)
- the base of antibodies bind to antigens
- the body of antigens are recognized by complement proteins
Complement proteins = small group of proteins made by the liver. They activate one another in an enzymatic cascade
When 2 antibodies bind to an antigen, their bodies or constant regions get bound by C1 protein
⦁ C1 binds to the constant region (Fc) of 2 antibodies attached to pathogen
⦁ C1 cleaves C2 and C4 –> half portions bind to antigen and create enzymatic complex that cleaves C3 into C3a and C3b
⦁ C3a joins the enzymatic complex (part of C2 + C4)
- the C2/C4/C3a now cleaves C5 into C5a and C5b
⦁ C3b + C5b float off into the blood to attract more immune cells to the area
⦁ C5a, C6, C7, C8, and multiple C9 proteins join together on surface of antigen to form MEMBRANE ATTACK COMPLEX (MAC)
⦁ MAC attacks pathogenic cells by forming a channel in the cell membrane of the pathogen –> allows water to flow in via osmosis (greater solute concentration inside cell) –> cell lysis
POLYMYOSITIS PATHOPHYSIOLOGY
- immune cells confuse cells of muscle as foreign pathogens
” molecular mimicry “ - host protein is mimicking a foreign or tumor protein
when normal proteins trigger an immune response, that protein = “Autoantigen”
- These autoantigens are then picked up by B lymphocytes, which start producing antibodies against them
In Polymyositis, autoantigens are found in endothelial cells of capillaries in muscle cells, as well as antigens coming from destroyed muscle cells
1) Autoantibodies attach to capillary endothelial cells lining the endomysium (sheath of CT around single muscle fiber)
2) Once bound, autoantibodies activate the complement cascade –> MAC –> endothelial cells lyse
3) complement proteins also attract more inflammatory cells to the area, ie macrophages
4) Autoantibodies also bind to small soluble antigens that are released from damaged muscle cells ==> form antigen / antibody complexes
- these complexes are not removed from bloodstream very quickly –> move around blood stream for some time –> attack to various blood vessel walls –> activate complement –> MAC –> further damage
5) Damage to blood vessels –> tissue ischemia in affected muscle tissue
*** however, Vascular injury DOES NOT have a major role in the pathogenesis of polymyositis.
TRIGGER FOR POLYMYOSITIS = unknown
- certain genetic + environmental factors
- genetic predisposition to HLA-DR3 or HLA-DR5 (human leukocyte antigen) - may develop polymyositis after infection (coxsackie virus) or specific tumor antigens (ovarian / lung /breast / gastric / genitourinary CA)
The cause is unknown, but it may result from an initial viral or bacterial infection
Polymyositis is commonly associated with bronchogenic, ovarian and breast cancer.
Polymyositis is an immunologic disease that damages small blood vessels, which contributes to muscle injury.
Unlike Dermatomyositis (CD4+ T cells / Perimysium), Polymyositis is ENDOMYSIAL INFLAMMATION WITH CD8+ T-CELLS
- Within a muscle, the CT layer that surrounds and individual muscle fiber is called the endomysium - ensheaths each individual fiber and protects it
- CD8+ T-cells (cytotoxic T cells) attack and inflame this layer ==> muscle fiber weakness
CLINICAL MANIFESTATIONS
- Muscle involvement
⦁ SYMMETRIC BILATERAL PROXIMAL muscle weakness**
⦁ muscle atrophy
⦁ muscle pain / tenderness
- typically affects large muscle groups (shoulder / hip)*
- can cause difficulty getting out of chair
- difficulty combing hair
- difficulty climbing stairs
- difficulty reaching for high objects
Proximal muscle weakness in polymyositis is seen first
- In severe cases, the muscles of pharynx of esophagus can be affected –> at risk for aspiration / aspiration pneumonia
⦁ Dysphagia
⦁ Dysphonia - ** LUNG / CARDIAC INVOLVEMENT ***
- high risk of developing interstitial lung disease due to pulmonary inflammation
- risk of developing respiratory failure due to diaphragm / intercostal muscle weakness
- risk of developing CHF, MI, Myocarditis –> can lead to arrhythmias / conduction defects
DIAGNOSIS
- physical exam: weakened muscle strength
- Autoantibodies
⦁ ANA
⦁ Anti-SRP antibodies (signal recognition particle) = may present in both, but almost exclusively found in Polymyositis patients
⦁ Anti-Jo1
⦁ increased muscle enzymes (creatinine kinase)*** (lactate dehydrogenase) (aldolase)
⦁ abnormal electromyogram (uses electrical energy to show muscular activity - helps differentiate myopathies from neurological conditions such as MG)
⦁ muscle biopsy = inflammation of endomysium
⦁ NOT Anti-Mi2 (specific to dermatomyositis)
Aldolase is a protein (called an enzyme) that helps break down certain sugars to produce energy. It is found in high amount in muscle tissue.
MOST APPROPRIATE 1ST STEP = CREATININE KINASE
TREATMENT
- suppress immune response
⦁ steroids - Prednisone or Methylprednisolone- usually 9-12 months initially.
** Steroids = 1ST LINE **
⦁ MTX - can also be used as adjunct to steroid
⦁ Azathioprine - can also be adjunct to steroid
⦁ Rituximab - often tried if steroid + MTX or steroid + Azathioprine fails
⦁ Antimalarial meds (Hydroxychloroquine or Chloroquine) - may be helpful for skin rash
MTX + Azathioprine = alternatives to steroids in diabetic patients
REACTIVE ARTHRITIS (REITER’S SYNDROME)
- AUTOIMMUNE RESPONSE to an INFECTION in another part of the body
- usually starts 2-3 weeks after the initial infection
- Inflammation of a joint that usually occurs after an infection
- Usually affects MALES more
⦁ Typically occurs after a sexually transmitted disease or gastroenteritis
Falls under the category of
SERONEGATIVE SPONDYLOARTHROPATHIES = autoimmune inflammatory joint diseases
- Seronegative = means that Rheumatoid Factor is absent from the blood
All cells contain MHC (major histocompatibility complex) - 2 classes
⦁ Class I = found on most cells of the body - contains a self-antigen for immune cells to recognize / not attack
⦁ Class II = found specifically on phagocytic cells, like macrophages - destroy and digest foreign pathogens. Once a macrophage destroys a bacterium, it presents a small piece of that antigen and travels to lymph nodes to be recognized by T lymphocytes - CD4 helper T cell binds to foreign antigen; then swaps out with B cell, which starts producing a ton of antibodies
B cells prevent foreign pathogen from attacking, and also “tag” the antigen for destruction by other immune cells
CLINICAL MANIFESTATIONS
1) ARTHRITIS - asymmetric inflammation
2) CONJUNCTIVITIS / UVEITIS
3) URETHRITIS / CERVICITIS
MC in 20-40 y/o, especially males
- occurs 1-4 weeks after infection (usually sexually transmitted or dysenteric infection)
**MC INFECTION = CHLAMYDIA**
Others = after Gonorrhea
GI Infections = after Salmonella, Shigella, E. coli, Campylobacter, Yersinia
All are GRAM NEGATIVE = have lipopolysaccharides - produce strong immune response
MOST patients with Reactive Arthritis have specific HLA-B27 gene => has codes to make MHC Class I receptors
- HLA-B27 gene = PEAR - associated with Psoriatic Arthritis, Enteropathic Arthritis, Ankylosing Spondylitis, and Reactive Arthritis
HLA B27 DISEASE ASSOCIATIONS
Ankylosing Spondylitis >90% = most common
Reactive Arthritis 85%
Reiter’s Syndrome 80%
Inflammatory Bowel Disease 50% (enteropathic)
Psoriatic Arthritis 50%
Whipple’s Disease 30%
MC tissues affected = joint spaces (reactive arthritis), but can also affect tissues of the urethra and conjunctiva (Reiter’s syndrome)
CLINICAL MANIFESTATIONS
- Triad -
1) conjunctivitis / uveitis
2) urethritis
3) arthritis (especially lower extremities)**
“can’t see, can’t pee, can’t bend my knee”
or “can’t see, can’t pee, can’t climb a tree”
- other tissues that can be affected = cervix in women and the pericardium of the heart
When triad occurs = called REITER’S SYNDROME - but the triad is pretty uncommon. MC just affects the joints space = reactive arthritis
SYMPTOMS
o PAIN and SWELLING of a single large joint = MC the knee, but can also affect ankles, hips, and small joints in the feet; sometimes affects multiple joints
o Painful urination (urethritis)
o Redness of the eyes (conjunctivitis)
o painful sex (cervicitis)
o chest pain and fevers (pericarditis)
- get sausage toes / fingers
- KERATODERMA BLENNORRHAGICUM*** = hyperkeratotic lesions on palms / soles = psoriatic-like papulosquamous lesions
- Circinate balanitis - inflammation of tip of penis
DIAGNOSIS
- usually diagnosed based on previous infection and clinical exam
- Positive HLA B27 (80%)
- increased WBC (10,000-20,000)
- increased ESR
- normochromic anemia
- increased IgG
- Synovial Fluid = shows increased WBC (1000-8000)
TREATMENT = NSAIDS = mainstay of tx (joint pain)
- Antibiotics to treat infection that caused this
- if no response to NSAIDS = MTX, Sulfasalazine, Steroids, Anti-TNF agents (biologics)
Antibiotic use during precipitating disease decreases the incidence of Reiter’s disease or Reactive Arthritis
Diagnosing reactive arthritis may be challenging because symptoms may present after the triggering infection has been cured
SUMMARY
Reactive arthritis, originally referred to as Reiter’s arthritis is classified as an autoimmune condition that develops in response to an infection in another part of the body (cross-reactivity). The manifestations of reactive arthritis include the following triad of symptoms: an inflammatory arthritis of large joints, inflammation of the eyes in the form of conjunctivitis or uveitis, and urethritis in men or cervicitis in women. Reactive arthritis is an RF-seronegative, HLA-B27-linked arthritis often precipitated by genitourinary or gastrointestinal infections. The most common triggers are intestinal infections (with Salmonella, Shigella or Campylobacter) and sexually transmitted infections (with Chlamydia trachomatis).
SYSTEMIC LUPUS ERYTHEMATOSIS (SLE)
Lupus = latin for wolf erythematosus = reddening of the skin systemic = affects multiple organs of the body
Lupus = AUTOIMMUNE DISEASE - immune system starts attacking own body’s cells
With Lupus, essentially any tissue or organ can be targeted
CAUSE OF LUPUS
⦁ combination of genetic + environmental factors
PATHOPHYSIOLOGY OF LUPUS
- some risk factor, ex: sun exposure, causes damage to cells –> programmed cell death (apoptosis) –> contents of cell are released (DNA, histones, etc) into the body
- People with lupus have susceptibility genes, which causes their immune system to think these inner cell contents are foreign invaders (Nuclear Antigens)
- Susceptibility genes also cause less effective clearance of apoptotic cell contents - takes longer to clear cell contents from body, so end up having nuclear antigens build up
- B-cells then start production of antibodies against Nuclear Antigens = ANTI-NUCLEAR ANTIBODIES (ANA)
- ANA (anti-nuclear antibodies) bind to nuclear antigens –> form antigen-antibody complexes
- These antigen-antibody complexes then float off in the blood and can stick to blood vessel walls (damage vessels) or deposit at any tissue/organ site, like the skin / kidneys / joints / heart / etc.
- Deposited complexes initiate a LOCAL INFLAMMATORY REACTION –> Complement system –> deposition of channels in cell walls –> water enters cell via osmosis –> cell lysis
TYPE III HYPERSENSITIVITY REACTION = when tissues become damaged as a result of immune complexes
TRIGGERS FOR LUPUS ⦁ Sun exposure (UV radiation) ⦁ smoking ⦁ viruses ⦁ bacteria ⦁ medications (hydralazine, procainamide, isoniazid) ⦁ sex hormones (estrogen)
- Which may be why lupus is MC in women
- 10X MC in women of childbearing age than men
but only 2-3x MC in younger women / > 65 than men
Onset = usually in 20s-40s
MC in African Americans, Hispanics, Native Americans
PATHOPHYSIOLOGY
1) environmental trigger –> damages cells –> apoptosis
2) release of “nuclear antigens” = person’s immune cells recognizes own cells as foreign–> attack
3) person’s genetics cause decreased clearance of cell contents from body –> increased “nuclear antigens” –> antibodies produced (anti-nuclear antigen)
4) Antibody-antigen complex –> deposit in blood stream / organs/tissues –> inflammation –> symptoms
Sometimes immune cells also attack other cells: RBCs, WBCs –> Phagocytosis / destruction –> other symptoms = TYPE II HYPERSENSITIVITY REACTION
LUPUS = TYPE III HYPERSENSITIVITY REACTION
- Type III hypersensitivity occurs when there is an accumulation of immune complexes (antigen-antibody complexes) that are not cleared away by immune cells, causing an inflammatory reaction like the one seen in lupus nephritis which is a type of nephritic syndrome.
SYMPTOMS
** Classic Presentation of Lupus = woman of childbearing age presenting with Fever + Joint pain + Rash **
actual diagnosis of lupus is difficult because there are a wide variety of symptoms that could present, and can affect a wide variety of people of different age/gender
o General ⦁ Fever ⦁ Joint pain ⦁ Weight loss ⦁ Fatigue
o SKIN - after sun exposure
⦁ “butterfly” malar rash - over cheeks but spares nasolabial folds (unlike dermatomyositis + rosacea)
⦁ discoid rash - chronic raised erythematous rash on face with scaling and scarring (seal)
⦁ photosensitivity –> other rashes from sun exposure
o MUCOSA (inner membrane of various tissues) ⦁ ulcers in mouth or nose
o SEROSA (outer membrane of tissues)
⦁ Pleuritis (inflammation of lining around lungs)
⦁ Pericarditis (inflammation of lining around heart)
- can also cause Endocarditis or Myocarditis
*** Libman-Sacks endocarditis - nonbacterial - verrucous vegetations form on both sides of mitral valve leaflets. (LSE with SLE) –> mitral regurgitation (holosystolic murmur) or mitral stenosis
o JOINTS
⦁ arthritis (inflammation of joints)
*** specifically needs to affect 2+ joints to meet criteria
o KIDNEYS
⦁ may develop renal disorders
- abnormal urine protein levels
- glomerulonephritis
o BRAIN
⦁ neurological disorders
- seizures
- psychosis
o BLOOD
⦁ anemia if RBCs targeted
⦁ leukopenia if WBCs / immune cells targeted
⦁ thrombocytopenia if platelets targeted
autoimmune hemolytic anemia is a type of chronic anemia common in systemic lupus erythematosus.
Common causes of death in patients with SLE are cardiovascular disease, infections, and end-stage renal disease
DIAGNOSIS
- need 4+ / 11 diagnostic criteria need to be met
1) malar rash
2) discoid rash
3) photosensitivity
4) ulcers in mucosa
5) serositis (pleuritis / pericarditis)
6) arthritis
7) renal disorders: proteinuria > 0.5 /cellular casts
8) neurological disorders
9) blood disorders
10) ANA (anti-nuclear antibodies) in the blood
- large proportion of people with Lupus test positive for ANA = very SENSITIVE test to lupus
- but NOT SPECIFIC test - positive ANA also seen in various other autoimmune diseases
** best INITIAL test = ANA ** - not specific!
- positive Rheumatoid Factor
11) Other antibodies
⦁ Anti-Smith (targets small ribonucleoproteins - snRNPs) = more specific to lupus
⦁ Anti-dsDNA (targets double-stranded DNA) - seen more during periods of active disease = more specific to lupus: indicative of poor RENAL prognosis
⦁ Anti-phospholipid (targets proteins bound to phospholipids - doesn’t actually target phospholipids)
- less specific for lupus
1) anticardiolipin antibody = associated with false positive syphilis test
2) Lupus Anticoagulant - increased thrombosis, but paradoxically increases PT/PTT
3) B2-glycoprotein I antibody = women who have this antibody may have frequent MISCARRIAGES + livedo reticularis - with Anti-phospholipid antibody syndrome** = can put patient in hypercoagulable state - more prone to clot formation –> Arterial + Venous Thrombosis: DVTs, hepatic vein thrombosis, stroke, etc.
- need to be on lifelong anticoagulants
Anti-cardiolipin antibodies may cause a false positive test for syphilis in antiphospholipid antibody syndrome associated with systemic lupus erythematosus.
- Anti-dsDNA antibodies are indicative of a POOR RENAL PROGNOSIS in systemic lupus erythematosus.
*** Will also have DECREASED complement due to formation of immune complexes (used up complement)
Diagnostic criteria for systemic lupus erythematosus:
RASH OR PAIN
1/2) Rash (malar or discoid)
6) Arthritis (not osteoarthritis - age related)
5) Serositis (pleuritis / pericarditis)
9) Hematologic disorders (e.g. cytopenias)
4) Oral/nasopharyngeal ulcers
7) Renal disease
3) Photosensitivity
10) Antinuclear antibodies
11) Immunologic disorder or Immunoglobulins (anti-dsDNA, anti-Sm, antiphospholipid)
8) Neurological disorders (e.g. seizures, psychosis)
- joint pain / fever / malar rash / serositis / cardiovascular / renal / retinitis / oral ulcers / alopecia
SLE places patients at increased risk for OSTEONECROSIS. High-dose steroids for SLE treatment adds to this risk. So do lipid-lowering agents
TREATMENT
- Lupus is characterized by periods of flares and periods of remission
- so treatment aimed at preventing flares, and limiting severity when flares occur
o Prevention
⦁ avoid sun-exposure (hats / long-sleeve clothes)
o Reducing Severity
⦁ Mild cases = NSAIDS
⦁ Hydroxychloroquine
⦁ Cyclophosphamide - used for patients with active glomerulonephritis
⦁ ** STEROIDS ** - to limit immune response
⦁ Immunosuppressants - MTX, Azathioprine
NEONATAL LUPUS
The leading cause of congenital complete heart block is neonatal lupus due to the presence of SLE in the mother.
Complete heart block is characterized by separate rates for the atria and ventricles.
The leading cause of congenital complete heart block is neonatal lupus.
Neonatal lupus can occur in babies born to mothers who have an autoimmune disease (usually SLE) and have antibodies to SSA and SSB (also known as Ro and La).
However, the mother can have these autoantibodies without having symptoms of lupus at the time of pregnancy. These autoantibodies cross the placenta and are believed to be the cause of damage to the fetal heart.
EKG shows complete heart block (complete dissociation of the atrial and ventricular rhythms) - p waves and QRS waves are not synced up
During pregnancy, fetal bradycardia may be the only sign of neonatal lupus. At birth, the infant can have various degrees of heart block, including complete heart block.
DISCOID LUPUS
Discoid lupus erythematosus is a chronic skin condition of sores with inflammation and scarring of the face, neck, ears, and scalp and at times on other body areas.
These lesions develop as a red, inflamed patch with a scaling and crusty appearance that then scar over
. The center areas may appear lighter with a rim darker than the normal skin.
- often lack hair on scalp due to scarring / follicular plugging
The most common areas affected by DLE are the face and scalp.
- The development of systemic manifestations is RARELY seen in discoid lupus erythematosus.
CLASSIC PRESENTATION:
- scaly lesions and scars on face that developed after sun-exposure. Lesions have varying degrees of edema, erythema, and scaling.
DIAGNOSIS
⦁ Antinuclear antibodies are positive in nearly 1/3 of the patients with discoid lupus erythematosus.
Histological examination of the skin in DLE shows immunoglobulins and complement three deposits at the junction of the dermis and epidermis.
TREATMENT
⦁ topical steroids
⦁ topical calcineurin inhibitors if steroids don’t work
DRUG-INDUCED LUPUS
- similar to SLE, however, due to certain drugs
SHIPP ⦁ sulfonamides ⦁ hydralazine ⦁ isoniazid ⦁ procainamide ⦁ phenytoin ⦁ quinidine
DIAGNOSIS
⦁ Anti-histone antibodies
TREATMENT
⦁ d/c offending drug
⦁ initiate steroids if needed
- usually resolves with drug discontinuation
- not associated with kidney / CNS damage or alopecia
