clinical approach to connective tissue and vasculitides Flashcards
Systemic Lupus Erythematosus general characteristics
Multisystem Inflammatory autoimmune disorder ◦ Autoantibodies to nuclear antigens Immune complexes type III hypersensitivity Spontaneous remissions and relapses Severity varies Heterogeneous (varies from pt to pt F>M African Americans and Hispanics >Caucasians Socioeconomic factors ( poverty, w/o insurance) Genetic and environmental factors ◦ Sex hormones/X linked? ◦ UV light ◦ Viruses (EBV)
SLE diagnosis
Constitutional: ◦ fatigue, fever, malaise, weight loss Cutaneous: ◦ rashes (especially malar “butterfly” rash ), photosensitivity , vasculitis, alopecia, oral ulcers Arthritis: ◦ inflammatory, symmetric, non erosive Hematologic: ◦ anemia (may be hemolytic), neutropenia, thrombocytopenia, lymphadenopathy, splenomegaly, venous or arterial thrombosis Cardiopulmonary: ◦ *Pericarditis Substernal, constant, “crushing” or sharp chest pain that is worse with cough or deep inspiration (pleuritic) Worse when supine, better with sitting upright/leaning forward Pericardial friction rub can be auscultated Diffuse ST elevation on ECG ◦ Pleuritis , myocarditis ◦ Libman Sacks endocarditis ◦ Pts are also at increased risk of myocardial infarction usually due to accelerated atherosclerosis Nephritis: ◦ classification is primarily histologic GI: ◦ peritonitis, vasculitis Neurologic: ◦ organic brain syndromes, seizures, psychosis , cerebritis
labs to order with SLE
CBC (Complete Blood Count) ESR (Erythrocyte Sedimentation Rate) ANA and ANA subtypes (staining pattern) Antibodies to ◦ dsDNA (double stranded DNA) important ◦ Sm (Smith) important ◦ Ro/SS A ◦ La/SS B ◦ Histone Complement levels (C3, C4, CH50) Antiphospholipid Ab ◦ Anti cardiolipin antibody ◦ Lupus anticoagulant Urinalysis
what is seen in SLE serology
(+) ANA (+) anti ds DNA Correlates with disease activity (+) Sm (smith) Does NOT correlate with disease activity Complement activation promotes inflammation ◦ C3 or C4 ↓ meaning increased consumption Suggests disease activity Returns towards normal when in remission
SLE treatment
Avoid sun exposure, wear sunscreen NSAIDs Glucocorticoids (topical or systemic ) [colloquial synonym “ Hydroxychloroquine
Others: Azathioprine Methotrexate Mycophenolate mofetil Cyclophosphamide IVIG (intravenous immunoglobulin) Plasmapheresis Monoclonal antibodies
what to worry about in SLE in early years
Infection especially with opportunistic organisms
Active SLE meaning kidney or central nervous disease
what to worry about in the later years of SLE
Accelerated athersclerosis
-Myocardial infarction
Thromboembolic events
management and preventative measures of SLE
Minimize other conventional risk factors for atherosclerosis ◦ eg , hypercholesterolemia, hypertension, obesity, and inactivity). Avoid smoking Influenza vaccination every year Pneumococcal vaccination every 5 years SLE patients have a higher risk of developing malignancy ◦ (especially lymphoma, lung cancer, and cervical ◦ preventive cancer screening recommendations should be followed With corticosteroid use ◦ Monitor for avascular necrosis of bone affecting most commonly the hips and knees ◦ Long term use, monitor for osteoporosis
percentage of Antiphospholipid antibody presentations
Primary APS:
-patients that have it without SLE
Secondary APS:
-1/3 of SLE patients
what are the 3 types of antiphospholipid antibodies
Type One Causes biologic false positive tests for syphilis Non treponemal tests (RPR and VRDL)
Type two: Lupus anticoagulant Risk factor for venous and arterial thrombosis and miscarriage
Type three: Anti cardiolipin antibodies Directed at a serum cofactor beta 2glycoprotein I Beta2GPI
what is the treatment of APS
Anticoagulation continued indefinitely
what appears on the retina of SLE/APS?
Cotton wool spots
Characteristics of Drug induced lupus and what drugs can cause this?
Promote demethylation of DNA No renal or neurologic symptoms (+) ANA (+) Anti histone antibodies (95 Some associated medications that can cause it: Hydralazine Isoniazid (INH) Minocycline TNF inhibitors Quinidine Chlorpromazine Methyldopa Procainamide
Sulfa antibiotics lead to SLE flare
Characteristics of Pregnancy and neonatal lupus? what abs are associated, and what types of symptoms?
Neonatal “lupus" ◦ Affects children born of mothers with Anti Ro (SSA) or La (SSB) Abs 1-2 % Can potentially happen in Sjogren pts too ◦ Transient Rashes Thrombocytopenia Hemolytic anemia Arthritis ◦ Permanent complete heart block
Discoid lupus erythematosus
Variant of cutaneous lupus Independent or manifestations of SLE Most commonly occurs on the head Characterized by ◦ well defined inflammatory plaques that evolve into atrophic, disfiguring scars ◦ Concern over the appearance of skin lesions desire treatment Diagnosis ( Dx ◦ Clinical exam and biopsy (histology) Treatment ( Tx ): ◦ Photoprotection \+ ◦ topical anti inflammatory agents or systemic antimalarial drugs ◦ In particular, early treatment of DLE is essential to minimize scarring.
characteristics of generic scleroderma
30 60 yo F>M Progressive Localized, Limited (CREST), Diffuse Hallmark of SSc : ◦ Thickening and hardening of the skin ◦ Microangiopathy & fibrosis of the skin & visceral organs ◦ Obliteration of eccrine sweat and sebaceous glands dry itchy skin Affects: ◦ Multisystem : lungs , GI, kidney, MSK, and heart Skin Secondary Raynaud phenomenon in virtually all pts Usually first symptom in Caucasian patients Changes in skin pigmentation (hyper/hypo) first symptom in AA > than Raynaud’s Dx : See serology slide + physical exam Tx : No approved disease modifying therapy. ◦ Goal is to control symptoms and slow progression to improve quality of life and prolong survival
Localized scleroderma
Children Discreet areas of discolored skin induration NO Raynaud’s NOT systemic Histologically indistinguishable from Systemic Patches = Morphea Coalesced patches = generalized morphea
Limited cutaneous systemic sclerosis
AKA CREST Syndrome ◦ Cutaneous calcinosis ◦ Raynaud’s Long standing ischemic ulceration of fingertips ◦ Esophageal dysmotility GERD ◦ Sclerodactaly ◦ Telangiectasia
Indolent course (delayed onset and slow progression) Vascular manifestations are more pronounced (than dcSSc ) ◦ Digital ischemia ◦ Progressive Pulmonary Artery HTN (PAH) Presents as shortness of breath Renal Crisis is uncommon Dx : Physical Exam, Serology, EGD/Barium swallow ( Eval esophagus), Echocardiogram/Right heart catheterization ( Eval for PAH). ◦ Dx typically made in advanced disease Patient may present with arthralgias and positive ANA and misdiagnosed as having SLE early in disease.
Diffuse cutaneous systemic sclerosis
Phases ◦ Inflammatory edematous phase fibrotic phase ◦ Skin induration, hyper/hypo pigmentation loss of body hair and impaired sweating ◦ Fibrotic joints stiffness Soft tissue swelling, erythema, pruritus Fatigue, stiffness, malaise Arthralgia, muscle weakness, carpal tunnel Raynaud ( later than in limited) Internal organ involvement ◦ Renal crisis May see hemolytic anemia on labs during renal crisis ◦ Interstitial Lung Disease
what is the primary cause of morbidity and mortality for scleroderma?
Primary cause of morbidity and mortality
◦
Aspiration pneumonia (GERD)
◦
Interstitial lung disease
Diffuse:
Chronic dry cough, dyspnea, fine “ velcro ” crackles (rales)
Diagnose by pulmonary function test PFT and Lung CT
◦
Pulmonary artery hypertension (PAH)
Limited:
2D Echocardiogram or Right heart catheterization
(gold standard) = elevated pulm artery pressure
Exertional dyspnea, syncope, angina, right heart failure
◦
Increased incidence of bronchoalveolar carcinoma
(new name adenocarcinoma in situ form of non small cell lung
cancer [NSCLC])
