Lecture 7: Connective Tissue Diseases Flashcards
Homogenous/diffuse ANA staining patterns may be associated with what 3 underlying conditions?
- Drug-induced SLE**
- Sjogren’s syndrome
- SLE
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What does the centromere pattern of ANA staining refer to and what condition is it seen in?
- Presence of 30-60 uniform speckles distributed throughout the nucleus of resting cells
- Limited systemic sclerosis (CREST)
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A nucleolar pattern of ANA staining may be seen in which 2 conditions?
- Diffuse systemic sclerosis
- SLE
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What are 3 positive serology findings seen in SLE; which is most specific and correlates with disease activity?
- (+) ANA
- (+) anti-ds DNA –> correlates w/ disease activity; most specific
- (+) Sm (Smith)
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What will be seen with complement activity during active SLE?
↓ C3 or C4 due to ↑ consumption
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Anti-Phospholipid Antibody Syndrome (APS) arises in association with what?
- 1/3 of SLE pt’s (secondary APS)
- Can also be present w/o a dx of SLE (primary APS)
Of the 3 types of antiphospholipid antibodies, what is the significance of Type One?
Causes biologic false-(+) tests for syphilis
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Of the 3 types of antiphospholipid antibodies, what is the significance of Type Two; how is it detected?
- Lupus anticoagulant
- Risk factor for venous and arterial thrombosis and miscarriage
- Causes prolongation of aPTT
- Presence is confrmed by an abnormal dilute Russell viper venom time (DRVVT)
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Of the 3 types of antiphospholipid antibodies, what is the significance of Type Three?
- Anti-cardiolipin antibodies
- Directed at a serum co-factor Beta2GPI
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Which 2 serology findings if positive correlates with lupus-like syndrome/drug-induced?
- (+) ANA
- (+) Anti-histone antibodies (95%)
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Neonatal lupus affects children born of mothers with which serum antibodies?
Anti Ro (SSA) or La (SSB) Abs
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Which complication may arise in children with neonatal lupus?
Permanent complete heart block
What are 4 treatment strategies/drugs used for SLE?
- Avoid sun exposure, wear sunscreen
- NSAIDs
- Corticosteroids (topical or systemic)
- Hydroxychloroquine
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What is the hallmark finding of Scleroderma (systemic sclerosis)?
- Thickening and hardening of the skin
- Microangiopathy and fibrosis of the skin and visceral organs
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Which antibodies are specific to diffuse cutaneous scleroderma?
- (+) Anti-Scl 70 –> aka Anti-(DNA) topoisomerase I
- Anti-RNA polymerase III
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Which antibody is specific to the limited cutaneous type of scleroderma?
(+) Anti-centromere
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Which type of imaging may be appropriate for working up Scleroderma?
- CXR
- Barium swallow if indicated
- Hand x-rays may show distal tuft resorption and calcinosis
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Which manifestations of disease are more pronounced in the limited cutaneous type of Scleroderma?
- Vascular manifestations i.e., digital ischemia and progressive Pulmonary artery HTN
- Think is limited to pulmonary a.; while diffuse is all over and caused interstitial lung disease
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A patient with diffuse cutaneous systemic sclerosis (scleroderma) in renal crisis may have what lab finding?
Hemolytic anemia
What is localized scleroderma and most often affects whom?
- Benign skin conditions; most often affects children
- Discreet areas of discolored skin induration; patches = morphea
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Deficiency of which nutrients is common in systemic sclerosis patients with GI involvement?
Fat + protein + B12 + vitamin D
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Which esophageal manifestations may be seen with systemic sclerosis?
Strictures, Barret esophagus –> ↑ risk of esophagal adenocarcinoma
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Which disease manifestations of the stomach may be seen in systemic sclerosis?
- Gastric Antral Vascular Ectasia (GAVE) aka Watermelon stomach
- Gastroparesis
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Which biliary disease manifestation may be seen with systemic sclerosis; what is the associated antibody?
Primary biliary cirrhosis –> anti-Mitochondrial Ab
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What is the primary cause of morbidity and mortality in patients with systemic sclerosis?
Pulmonary involvement
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What type of pulmonary involvement is seen in the diffuse type of systemic sclerosis and how is it diagnosed/confirmed?
- Interstitial lung disease
- Dx by pulmonary function test (PFT)
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What type of pulmonary disease is seen in the limited type of systemic sclerosis and how is it diagnosed?
- Pulmonary artery hypertension (PAH)
- Right heart catheter to confirm dx: mean pulm. artery pressure of 25 mmHg or greater
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There is an increased incidence of which lung malignancy in those with systemic sclerosis?
Bronchoalveolar carcinoma
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Which MSK and endocrine are often seen with systemic sclerosis?
- Carpal tunnel syndrome
- Hypothyroid from thyroid fibrosis
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Sjögren syndrome has strong association with what malignancy?
B-cell Non-Hodgkin lymphoma
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What are the sicca sx’s associated with Sjögren syndrome; increased risk for what complication?
- Immune-mediated destruction of lacrimal and salivary glands
- Dry eyes + mouth (xerostomia) + vaginal dryness + tracheobronchial dryness
- ↑ incidence of oral infections (candida) + dental caries
- Parotid or other major salivary gland enlargement
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What type of biopsy is essential for the diagnosis of Sjögren syndrome; what is seen?
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Lip biopsy –> reveals characteristic lymphoid foci in accessory salivary glands
What serological findings are characteristic of Sjögren syndrome?
- Hypergammaglobulinemia
- (+) Anti SSA/Ro
- (+) Anti SSB/La = never present without Ro
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Which type of medicated drops may help the dry eye sx’s of Sjögren syndrome?
Cyclosporine drops
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Which 2 medications may help the sicca manifestations of Sjögren syndrome?
Pilocarpine and Cevimeline
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Inflammatory myopathies are associated with what muscle sx’s?
- Myalgias
- Symmetric bilateral proximal muscle weakness
- Difficulty rising from a chair or bathtub or climbing stairs
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What is the characteristic biopsy finding of Dermatomyositis?
Perimysial and perivascular inflammation, perifascicular atrophy
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What are the most common malignancies associated with Dermatomyositis?
- Ovarian: check transvaginal US, CT abd/pelvis, CA-125
- Lung
- Pancreatic
- Stomach
- Colorectal
- NHL
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Which serology findings will be positive in Polymyositis?
- Elevated serum CK
- Anti-Jo-1
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What are the steps to tx of the inflammatory myopathies, DM and PM?
- Step 1: Glucocorticoids (3-4 wks, then tapered very gradually)
- Step 2: Approximately 75% of pt’s require additional therapy with other immunosuppressive drugs
- Step 3: IV immunoglobulin
- Step 4: a trial of one of the following: rituximab, cyclosporine, cyclophosphamide, or tacrolimus
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Which sex and ethnicity are most often affected by Inclusion Body Myositis (IBM)?
Males > F; more often Caucasians
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What are characteristic sign/sx’s of Inclusion Body Myositis (IBM); what are the serum CK levels like?
- Finger flexion or quadriceps weakness
- CK is mild** or **normal
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What is the characteristic finding on muscle biopsy in Inclusion Body Myositis (IBM); which autoantibodies may be present?
- Endomysial inflammation, rimmed vacuoles, invasion of non-necrotic muscle fibers
- Anti-cN1A autoantibodies
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What are the characteristic gross vascular lesions of Takayasu Arteritis; what is seen histologically?
- Long smooth tapered stenosis
- Granuloma w/ some giant cells, fibrosis in chronic stages
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What are some of the complications of Takayasu Arteritis?
- 50% have pulmonary involvement
- Retinopathy, Renal artery stenosis, Aortic dilations, Aortic regurgitation, Aneurysm, and Aortic rupture
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How is diagnosis of Takayasu Arteritis made; what is the tx?
- Dx: MRI or CT angiography
- Tx: Glucocorticoids
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What is a characteristic fundoscopic finding in pt with Takayasu Arteritis?
Copper-wiring
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What is the triad of Behcet Syndrome?
- Recurrent mouth ulcers
- Genital ulcers
- Eye inflammation (uveitis)
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What is Pathergy seen in the setting of Behcet Syndrome?
Pustules at site of sterile needle pricks
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Which HLA is Behcet Syndrome associated with?
HLA-B51
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What are 2 vessel complication which may arise in the setting of Behcet Syndrome?
- Large vessel = aneurysms
- Venous impairment —> DVT
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Polyarteritis nodosa may be associated with what infectious agent?
HBV
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Which neurological manifestations may be seen in the setting of Polyarterisitis Nodosa?
- Peripheral nerve: 80% have vasculitis nephropathy
- Mononeuritis multiplex: foot drop
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Which organ system is characteristically spared in Polyarteritis Nodosa?
Lungs
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How is diagnosis of Polyarteritis made; what is seen?
- Bx: infiltration and destruction of blood vessels by inflammatory cells –> fibrinoid necrosis, NO granulomas
- Angiogram: microaneurysms
If patient with Polyarteritis Nodosa is ANCA negative, what should you check for?
HBsAg and HBeAg
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Which serum marker is positive in granulomatosis with Polyangiitis (Wegener’s)?
C-ANCA aka PR3-ANCA
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What are the 3 hallmarks of granulomatosis with Polyangiitis (Wegener’s)?
- Granulomatous inflammation
- Necrotizing vasculitis
- Segmental glomerulonephritis (hematuria/RBC/proteinuria)
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What are the upper and lower respiratory tract manifestations which may be seen in setting of granulomatosis with Polyangiitis (Wegener’s); what may be seen on CXR?
- 90% have nasal involvement: saddle nose, crusting, bleeding, obstruction
- Lung: Asx nodule –> alveolar hemorrhage
- CXR: infiltrate/nodules/cavitary lesions
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Which serum marker is positive in some cases of eosinophilic granulomatosis with Polyangiitis (Churg-Strauss)?
MPO-ANCA aka P-ANCA
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What is the hallmark of eosinophilic granulomatosis with Polyangiitis (Churg-Strauss)?
Asthma + Eosinophilia –> Vasculitis
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What is the characteristic finding on angiography of Thromboangiitis Obliterans (aka Buerger Disease)?
“Corkscrew” appearance
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Which finding on nailfold capillaroscopy is characteristic of secondary raynaud’s?
Distorted with widened and irregular looop, dilated lumen and areas of vascular “dropout”
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Which arteries most often affected in Giant Cell Arteritis (aka Temporal arteritis)?
- Cranial arteries (temporal/facial/opthalmic)
- Aortic arch
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Which HLA is associated with Giant Cell Arteritis (aka Temporal arteritis)?
HLA-DR4
What are the signs/sx’s and characteristic lab findings of Giant Cell Arteritis (aka Temporal arteritis)?
- HA + jaw claudication + PMR + visual abnormalitis (amaurosis fugax or diplopia)
- ↑↑ ESR (>50 mm/h)
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What is the gold standard for diagnosis of Giant Cell Arteritis (aka Temporal Arteritis); what is seen?
- Temporal artery bx: need a 1.0 cm segment
- Segmental granulomatous vasculitis w/ multinucleated giant cells
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What is an important thing to remember about the tx of Giant Cell Arteritis (aka Temporal Arteritis)?
Start corticosteroids (before biopsy!) –> dramatic improvement
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What are the signs/sx’s of Polymyalgia Rheumatica and what is it associated with?
- Proximal severe symmetrical morning and daylong stiffness, soreness, and pain in shoulder, neck, and pelvic girdles
- “Feelings” of weakness as a result of pain (as opposed to PM), no true weakness
- Associated with Giant Cell Arteritis (aka Temporal Arteritis)
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What is seen on muscle biopsy and in the serum of patient with Polymyalgia Rheumatica?
- NO inflammation on muscle bx
- Muscle enzymes and EMG = normal
- ↑↑↑ ESR and CRP
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What are the cardiopulmonary complications which may arise in SLE?
- Pleuritis + pericarditis + myocarditis + endocarditis
- Pt’s also at ↑ risk of MI usually due to accelerared atherosclerosis
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Which complication may arise in the eye associated with SLE/APS?
Retinopathy: cotton wool spots
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Which antibody is seen in cases of polymyositis w/ pneumonitis + arthritis?
Anti-Jo-1
Henoch-Schonlein Purpura is associated with what underlying signs/sx’s?
- Palpable purpura: NO thrombocytopenia
- Arthritis
- Abdominal pain
- Glomerulonephritis
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