Lecture 22: Connective Tissue Disorders and Vasculitides Flashcards
What is Systemic Lupus Erythematosus and who does it commonly affect?
- multisystem inflammatory autoimmune disorder of autoAbs to nuclear antigens (Type 3 hypersensitivity)
- forms immune complexes
- African Americans/Hispanics > Caucasians
- F > M
What are Cutaneous, Arthritis, Hematologic, Cardiopulmonary, and Nephritis features of Systemic Lupus Erythematosus?
Cut: Malar “Butterfly” rash and photosensitivity
- over cheeks/nasal bridge (spares nasolabial folds)
A: inflammatory, symmetric, non-erosive
H: thrombosis
Cardio: PERICARDITIS
- constant, substernal “crushing” or sharp chest pain
- inc. risk of MI due to accelerated atherosclerosis
N: classification via histologic
What are 4 findings of Systemic Lupus Erythematosus serology?
- ANA (+)
- anti-DS DNA and Smith antibodies
- DS DNA correlates with disease activity
- decreased levels of C3/C4 = inc. consumption (returns towards normal during remission)
What kind of endocarditis is associated with SLE?
LIBMAN-SACKS ENDOCARDITIS
- caused by immune deposits collecting on heart valves
- NOT INFECTIOUS
What are 4 common treatments for SLE? (A, N, G, H)
- avoid sun exposure (use sunscreen)
- NSAIDS
- glucocorticoids (topical or systemic)
- hydroxychloroquine
What are two causes of Early Year SLE Mortality vs Later Year SLE Mortality?
Early: infections and kidney/CNS disease
Late: accelerated atherosclerosis and thromboembolic events
What are the 3 types of Antiphospholipid Antibodies? When should they be measured?
Type 1: causes false-positive syphilis test
- test for Treponemal Abs if syphilis is suspected
Type 2: Lupus anticoagulant
- inc. venous/arterial thrombosis and miscarriage
- inc. aPTT time, abnormal DRVVT
Type 3: Anti-cardiolipin Abs to Beta2GPI
measure on two occasions 12 weeks apart and treat APS via anticoagulants INDEFINITELY
What is the retinopathy associated with SLE and Antiphospholipid Syndrome?
Cotton Wool Spots
What is Lupus-like Syndrome (Drug-induced Lupus) and what two tests are it positive for?
What happens when suspected pts. take sulfa antibiotics?
- promotes demethylation of DNA with NO RENAL/CNS symptoms
- positive for ANA and ANTI-HISTONE Abs (95%)
- sulfa antibiotics cause SLE FLARE
What are the two antibodies found in mothers who give birth to children with Neonatal Lupus?
What is a serious complication of Neonatal Lupus?
- mothers will have the Anti Ro (SSA) or La (SSB) Abs
- Permanent complete heart block is a major complication that can occur in utero, at birth, or in the neonatal period
What is Discoid Lupus Erythematosus (DLE) and how can it be treated? (2)
- occurs independent or as a manifestation of SLE most commonly on the HEAD
- well-defined inflammatory plaques that can become atrophic, disfiguring scars
T: photoprotection and topical anti-inflammatory agents or systemic antimalarial drugs
What is Scleroderma, how does it differ between Caucasians and African Americans, and what is its treatment?
- thickening/hardening of skin with fibrosis of skin/visceral organs and obliteration of eccrine/sebaceous glands causing dry itchy skin
- Caucasians: secondary Raynauds FIRST
- African Amer: pigmentation change THEN Raynauds
T: no approved therapy; focus on control/slowing of symptoms
What is the difference between Localized, Limited, and Diffuse Scleroderma?
Localized: children with morphea (patches)
- discreet discoloration of skin
- no Raynauds and NOT systemic
Limited: fingers, toes, face, distal extremities
- CREST SYNDROME; indolent and slow progress
- Raynauds and Pulmonary Artery Hypertension
- digital ischemia
Diffuse: systemic (proximal extremities and trunk)
- early organ involvement (WORST PROGNOSIS)
- interstitial lung disease and renal crisis
What is CREST Syndrome and what is it commonly associated with?
- associated with Limited Cutaneous Systemic Scleroderma
C - cutaneous calcinosis R - Raynauds (longstanding) E - Esophageal dysmotility (GERD) S - sclerodactaly T - telangiectasia
What is the primary cause of Morbidity and Mortality in patients with Scleroderma?
What are the two manifestations seen in Diffuse and Limited Scleroderma and how are they diagnosed?
- most common cause is PULMONARY involvement
Diffuse = Interstitial Lung Disease
- fine velcro crackles (rales), chronic dry cough
- dx with pulmonary function test (PFT)/Lung CT
Limited = Pulmonary Artery Hypertension
- exertional dyspnea, angina, right heart failure
- dx with 2D echocardiogram or right heart cath.
inc. risk of bronchoalveolar carcinoma
What are two Renal manifestations of Scleroderma?
- Chronic Kidney Disease
- Renal Crisis
- malignant HTN, hemolytic anemia, prog. renal insuff.
- high dose of glucocorticoids can induce crisis
What are 3 common GI manifestations of Scleroderma?
- Barrett esophagus - inc. risk of esophageal AdenoC
- GAVE Syndrome = Watermelon Stomach
- gastric antral vascular ectasia
- Primary biliary cirrhosis/cholangitis
What is a common MSK and Thyroid manifestation of Scleroderma?
MSK = Carpal Tunnel Syndrome
Thyroid = Hypothyroid (thyroid fibrosis)
What is the difference in serology between Limited and Diffuse Scleroderma?
What should you pay particular attention to when taking the history/physical of a pt. believed to have Scleroderma?
Limited: positive for anti-CENTROMERE Abs
Diffuse: positive for anti-SCL70 and anti-RNA POLY III
- anti-SCL70 = anti-DNA TOPOISOMERASE I
- should pay special attention to BLOOD PRESSURE since it is a heralding feature of renal disease
Who is Sjogren’s Syndrome normally seen in, what symptoms does it present with, and what cancer it is strongly associated with?
- seen in Postemenopausal females (Mid 50’s)
- causes SICCA symptoms (destruction due to inflammatory processes)
- dry eyes, mouth (inc. candida and dental caries)
- keratoconjunctivitis sicca (foreign body sensation)
- strongly associated with MALT Lymphoma
What test is used to measure quality of the tears secreted by patients with Sjogren’s Syndrome?
Schirmer test
What are 4 serological findings of Sjogren’s Syndrome and what biopsy should be performed and why?
ANA (+), Rhematoid Factor (+), Anti-Ro/La (+), polyclonal hypergammaglobulinemia
- do a LIP BIOSPY to see lymphoid foci in accessory salivary glands (ESSENTIAL FOR DIAGNOSIS)
What is the treatment for Sjogren’s Syndrome and what drugs should be avoided by the patient?
- treatment is symptomatic, should have regular check-ups with dentist and ophthalmologist
- avoid ATROPINIC drugs and DECONGESTANTS (will further dry out the patient)
What weaknesses are characteristic of Inflammatory Myopathies and what enzymes will be elevated? (2)
- occurs more in females and African Americans
- see Systemic Bilateral Proximal Muscle weakness (difficulty rising from a chair or bathtub)
- muscle enzymes will be elevated (creatine kinase and aldolase) while ESR/CRP are often normal
Dermatomyositis (DM)
What is it and who is it seen in, what biopsy and serology are characteristic of it, and what is it at an increased risk of developing?
- muscle weakness (proximal –> distal) WITHOUT sensory symptoms seen in 7-15 yo and 30-60 yo (binodal distribution)
- perifascicular atrophy (biopsy) and Anti Jo-1 antibodies (serology)
- increased risk of OCCULT MALIGNANCY
What are 4 characteristic skin lesions of Dermatomyositis? (GP, HR, PE, V)
- Gottron’s patches/papules (overlying knuckles)
- Heliotrope rash (purple, periorbital edema)
- Periungal erythema
- V-neck erythema (Poikiloderma or “Shawl Sign”)
Polymyositis (PM)
What is it and who is it seen in, what biopsy/serology/labs are characteristic of it, and how is it treated?
- subacute proximal muscle weakness in 30-50 yo with NO SKIN CHANGES (vs. DM)
- endomysial inflammation (biospy), Anti Jo-1 (serology), and elevated CK (labs)
- treat with Glucocorticoids
Inclusion Body Myositis (IBM)
What is it and who is it seen in, what biopsy/serology/labs are characteristic of it, and how is it treated?
- finger/quadriceps weakness in white MALES 40-50 yo
- endomysial inflammation/rimmed vacuoles (biospy), mild or normal CK (labs), anti-cN1A autoabs (serology)
- treatment is SUPPORTIVE
What are 3 Systemic Vasculitides of SMALL vessels? (HSP, GS, GPA)
Henoch-Schonlein Purpura, Goodpasture Syndrome, Granulomatosis with Polyangiitis
What are 2 Systemic Vasculitides that vary in vessels? (EGPA, BS)
Eosinophilic Granulomatosis with Polyangiitis and Behcet Syndrome
What are 3 Systemic Vasculitides of MEDIUM vessels? (TO, PN, KD)
Thromboangiitis Obliterans (Buerger Disease), Polyarteritis Nodosa, and Kawasaki Disease
What are 2 Systemic Vasculitides of LARGE vessels? (TA, GCA)
Takayasu Arteritis and Giant Cell Arteritis
Henoch-Schonlein Purpura (IgA Vasculitis)
What is it and who does it affect, what is its tetrad (PP/A/AP/RD), and how is it treated?
- common in small vessels of KIDS
T: palpable purpura (no thrombocytopenia), arthritis, abdominal pain, and renal disease (IgA deposits)
T: supportive and glucocorticoids
Goodpasture Syndrome (Anti-Glomerular Basement Membrane)
What is it, what does it affect, and how is it treated?
- small vessel deposits of anti-basement membrane autoantibodies (commonly glomerular and pulmonary capillaries)
- pulmonary hemorrhage can cause death if not treated
T: plasmapheresis, glucocorticoids
Granulomatosis w/Polyangiitis (Wegener’s Granulomatosis)
What is it and who does it affect, what are 3 common hallmarks (G, NV, G) and what physical finding does it commonly present with?
What is a major serological finding of GPA?
- affects small vessels of MALES > 40 yo
H: Granulomatous inflammation, Necrotizing vasculitis, and glomerulnephritis
PF: Saddle Nose w/crusting and bleeding due to Respiratory Tract involvement (90% nasal)
Serology: ANCA (+)
Eosinophilic Granulomatosis w/Polyangiitis (Churg-Strauss Syndrome)
What is it, what does it look like, and what is a major serological finding of EGPA?
- affects small/medium vessels of RESPIRATORY Tract
H: asthma and eosinophilia with granuloma vasculitis
- high eosinophils in circulating blood
- palpable purpura and systemic necrosis
Serology: ANCA (+)
Behcet Syndrome
What are two complications it can cause, what is its common Triad for SMALL vessels, and what is a major serological finding of it?
- multisystem involvement that can cause Large Vessel aneurysms and DVT
Triad: recurrent mouth ulcers, genital ulcers, and uveitis (eye inflammation)
Serology: HLA-B51 (+)
use low dose glucocorticoids to treat
Thomboangiitis Obliterans (Buerger Disease)
What is it and who does it affect, how does it progress, and what is its treatment?
- segmental MEDIUM vessel disease in young MALES < 35 yo
- occurs in SMOKERS; treat by STOPPING SMOKING
- thrombosis of distal –> proximal vessels than can cause loss of digits and has a CORKSCREW appearance on angiography
Polyarteritis Nodosa
What does it affect and what is it associated with, what does it cause in the Periphery/Renal/Lung, and what does a biopsy reveal?
- affects segmental MEDIUM vessels of MALES and is associated with HBV –> check for serological HBV markers
- Vaculitis Neuropathy (“foot drop”), Renin-mediated HTN, but SPARES the LUNGS
- biopsy shows fibrinoid necrosis (inflammatory cells) WITHOUT granulomas
Kawasaki Disease
What is it and who does it affect, what is a common physical manifestation, and what causes morbidity?
- affects MEDIUM vessels of MALES < 5 yo (mainly Japan)
- common physical finding is STRAWBERRY TONGUE
- also fever, LAD, rash
- morbidity from CORONARY involvement (either aneurysm or myocardial infarction that can occur years later)
Takayasu Arteritis
What is it and who does it affect, what does it look like on biopsy, and what does it look like on angiography?
- affects LARGE vessels (AORTA) in females < 40 yo (adolescent girls and young women in Asia)
- called “pulseless disease” because it obliterates the peripheral pulses (but collaterals prevent limb loss)
Biopsy: granuloma with some GIANT CELLS
Angiography: long smooth tapered stenosis (athersclerosis = focal irregular lesions)
What is a common eye manifestation of Takayasu Arteritis and what is it caused by?
- causes Copper Wiring Retinopathy due to renal artery stenosis = HYPERTENSION
Giant Cell Arteritis (Temporal Arteritis)
What is it and who does it affect, what are common clinical symptoms (JC/PR), and what is seen on biopsy?
- affects LARGE vessels (cranial arteries and aorta) in women > 50 yo
- headache, JAW CLAUDICATION, Polymyalgia Rheumatica, visual abnormalities (start glucocorticoids to prevent blindness!!)
- ESR greatly increased, HLA-DR4 serology
Biopsy: temporal artery (GOLD STANDARD) with granulomatous vasculitis and MULTINUCLEATED Giant Cells
What is Polymyalgia Rheumatica (PMR) and what two findings are elevated?
- associated with GCA and is a stiffness, soreness, or muscle pain with FEELINGS of weakness as a result of pain (no TRUE objective weakness)
- everything will be normal save for elevated ESR and CRP (no muscle inflammation, no muscle enzyme inflammation)
What is the difference between Primary and Secondary Raynauds Phenomenon?
Primary: benign, symmetric, exaggerated response to cold
- females 15-30 yo
Secondary: occurs BECAUSE of something else
- unilateral; mainly > 30 yo
- MORE SEVERE –> ischemia
