280 CLINICAL FEATURES (CONT’D) proteinuria or active sediment (sens 50%), glomerulonephritis WHO CLASSIFICATION OF LUPUS NEPHRITIS NORMAL (class I) asymptomatic MESANGIAL PROLIFERATIVE (class II) mild hematuria or proteinuria FOCAL PROLIFERATIVE (class III) nephritic syn drome, proteinuria DIFFUSE PROLIFERATIVE (class IV) nephritic syndrome, nephrotic syndrome MEMBRANOUS GLOMERULONEPHRITIS (class V) nephrotic syndrome GLOMERULOSCLEROSIS (class VI) uremia SEVERITY VI >IV >III >V >II >I, consider aggressive treatment for class III, IV GI mesenteric thrombosis and vasculitis, transa minitis/hepatitis Corticosteroids could increase risk of peptic ulcer disease HEMATOLOGIC anemia of chronic disease, autoim mune hemolytic anemia, lymphopenia, thrombocytopenia NEUROLOGIC aseptic meningitis, transverse myeli tis, stroke, seizures, organic brain syndrome, psy chosis, depression, peripheral neuropathy DERMATOLOGIC photosensitivity (sens 50%), malar rash (nasolabial folds spared, sens 50%), discoid lupus (erythematous papules/plaques with central hypopigmentation, atrophic scarring involving scalp and exposed skin, sens 25%), mucosal ulcers (oral, vaginal, nasal septal), alopecia, livedo reticu laris, palpable purpura, Raynaud’s SEROLOGIC ANA (sens >99%), anti dsDNA (sens 40%), anti Smith (sens 25%), SSA/Ro, SSB/La, RNP, antiphospholipid antibody (sens 40%) CONSTITUTIONAL SYMPTOMS fatigue, fever (high grade), lymphadenopathy, weight loss, myalgia LUPUS EXACERBATIONS typically with fatigue, arthritis, mucocutaneous, renal, neurologic, and/or dermatologic involvement Individual patients usually have a fixed pattern of presentation Precipi tants include UV exposure, medication non adher ence, infections, and pregnancy Always consider other causes such as infections, medication side effects (steroids), and embolisms Systemic Lupus Erythematosus INVESTIGATIONS (CONT’D) RENAL INVESTIGATIONS BASIC CBCD, lytes, urea, Cr, ESR, CRP, ANA (sensitive), anti dsDNA (specific for SLE), C3, C4 URINE TESTS urinalysis, urine protein to Cr ratio SPECIAL INFLAMMATORY WORKUP ENA (anti Smith, spc), anti Ro/La (especially in pregnancy, associated with neonatal lupus and congenital complete BLOOD TESTS heart block), antiphospholipid antibodies (antic ardiolipin antibodies, lupus anticoagulant), cryoglobulin INFECTIOUS WORKUP serologies (Parvovirus, HBV, HCV, EBV, CMV) ARTHROCENTESIS w3Cw (Cell count with diff [>2000 WBC/mm3], Culture and Gram stain, Crys tal Cannot make definite diagnosis of systemic lupus erythematosus from arthrocentesis) MANAGEMENT SYMPTOM CONTROL cutaneous lupus (sunsc reen, hydroxychloroquine) Arthritis (NSAIDs, hydro xychloroquine, steroids, methotrexate) Nephritis and neuritis (steroids, cyclophosphamide, mycophe nolate mofetil) Serositis (NSAIDs, steroids) Throm bocytopenia (steroids, IVIG, splenectomy) Avoid exogenous estrogen TREAT UNDERLYING CAUSE rituximab SPECIFIC ENTITIES DRUG INDUCED SYSTEMIC LUPUS PATHOPHYSIOLOGY some drugs may trigger pro duction of autoantibodies (e.g ANA) which may cause or precipitate drug induced lupus in suscep tible individuals CAUSES procainamide, hydralazine, quinidine, atenolol, anti TNFa (infliximab, etanercept), capto pril, carbamazepine, chlorpromazine, enalapril, ethosuximide, hydrochlorothiazide, isoniazid, lithium, methyldopa, minocycline, minoxidil, phe nytoin, primidone, statins, sulfasalazine, trimethadione CLINICAL FEATURES compared to systemic lupus, drug induced lupus has the following features: middle age presentation, no gender difference, no ‘‘blacks,’’ acute onset, less cutaneous, renal, neurologic, and hematologic involvement, but equal joint, hepatic, and constitutional symptoms Usually anti histone antibody positive, anti Smith negative, anti dsDNA negative and normal com plement levels TREATMENTS discontinue offending drug if possible RAYNAUD’S PHENOMENON PATHOPHYSIOLOGY exaggerated vasoconstriction to cold, emotional stress, or exercise Triphasic changes from white to blue to red CAUSES primary (isolated Raynaud’s), secondary (trauma [Jack hammer, vibrations], rheumatologic [SLE, scleroderma, dermatomyositis, polymyositis, rheumatoid arthritis, mixed connective tissue disease], drugs [ergots, cocaine, b blockers, bleo mycin, vinblastine, interferon], tumors [lymphoma, 281 Systemic Lupus Erythematosus SPECIFIC ENTITIES (CONT’D) carcinoid syndrome, pheochromocytoma], occlu sive arterial disease, hyperviscosity, hypothyroid ism, Parvovirus B19, PBC) CLINICAL FEATURES usually symmetric episodes of sharply demarcated color changes of the skin and severe pain of the digits lasting 10 15 Sec ondary causes more likely if age >40, male, ulcera tions, asymmetric, involvement proximal to digits and abnormal capillary nailfold TREATMENTS avoidance (cold, stress, smoking, sympathomimetic drugs) Keep core temperature stable Terminate attacks early (place hands in warm water) Calcium channel blockers (nifedipine 10 60 mg PO TID, amlodipine 20 mg PO daily) Topical nitrates ASA Anticoagulate (if antipho spholipid antibodies or surgical interventions required) Related Topic Cutaneous Lupus Erythematosus (p 371) SCLERODERMA extensive fibrosis and some degree of inflammation of skin, blood vessels, and internal organs (GI, lungs, renal, cardiac) There are four subtypes, including diffuse systemic sclerosis (progressive systemic sclerosis), limited systemic sclerosis wCRESTw syndrome (Calcinosis, Ray naud’s phenomenon, Esophageal dysmotility, Scler odactyly, Telangiectasias), localized scleroderma (morphea, linear), and scleroderma sine scleroderma CLINICAL FEATURES Raynaud’s phenomenon may precede skin changes for years Usually involves the skin (starts from extremities extending proxi mally, progressing from edematous to fibrotic to atrophic stage Common signs include dilated capil lary loops, sclerodactyly, flexion contractures, hypo pigmentation, hyperpigmentation, ‘‘coup de sabre deformity’’, purse lip, telangiectasia), and GI hypo motility (dry mouth, dysphagia, dyspepsia, N&V, abdominal pain, constipation, diarrhea, weight loss) The lungs (pleural effusion, pulmonary fibrosis, pulmonary hypertension), kidneys (renal crisis), and heart (pericarditis) may also be involved PATHOPHYSIOLOGY SPECIFIC ENTITIES (CONT’D) major criterion is sclerodermatous skin changes proximal to the MCP joints Minor criteria include sclerodactyly, digital pitting scars, and bilateral pulmonary fibrosis Tests include antibo dies to topoisomerase I (anti SCI 70) seen more in diffuse systemic sclerosis and antibody to centro mere seen more in CREST TREATMENTS Raynaud’s (calcium channel block ers) GERD (proton pump inhibitor) Renal crisis (ACE inhibitors) Interstitial pneumonitis (steroids, azathioprine, cyclophosphamide) Pulmonary hypertension (endothelin antagonists [Bosentan]) INFLAMMATORY MYOPATHIES PATHOPHYSIOLOGY classified as polymyositis, der matomyositis, and inclusion body myositis ASSOCIATIONS dermatomyositis is associated with malignancy (GI, lung, ovarian, breast, lymphoma) in 45% of patients CLINICAL FEATURES proximal, symmetric, progres sive muscle weakness developing over weeks to months, may be associated with morning stiffness Muscle pain is not common Extramuscular mani festations include arthralgias, cardiac (conduc tion abnormalities, cardiomyopathy), respiratory (muscle weakness, aspiration, interstitial lung dis ease), skin (Gottron’s papules [dorsal aspect of MCP and IP joints/elbows/knees], heliotrope rash (over upper eyelids with periorbital edema), V rash/shawl sign [erythematous rash over upper chest/back/shoulders], periungual telangiectasia, mechanic’s hand [with darkened horizontal lines across lateral and palmar aspects of fingers/ hands]), and constitutional symptoms Reflexes are usually normal DIAGNOSIS symmetric proximal weakness, eleva tion of muscle enzymes, EMG findings consistent with inflammatory myositis, muscle biopsy consis tent with inflammatory myositis Need all four criteria for definite polymyositis, and three criteria plus skin findings for definite dermatomyositis Important to exclude other causes of myopathies Anti Jo1, anti Mi2, anti SRP TREATMENTS prednisone, methotrexate, azathiop rine, leflunomide, IVIG DIAGNOSIS DISTINGUISHING FEATURES BETWEEN STEROID MYOPATHY AND INFLAMMATORY MYOPATHIES Steroidmyopathy Inflammatory myopathies History Steroid use Other inflammatory myopathy symptoms Other steroid related symptoms Physical Neck flexor normal Neck flexor weaker Tests CK less often " CK often ", anti Jo1/anti Mi2 Ab EMG Normal Abnormal activity Stop steroid Improves Worsens 282 Seronegative Spondyloarthropathies Seronegative Spondyloarthropathies DIFFERENTIAL DIAGNOSIS OF OLIGOARTHRITIS wRICEw RHEUMATOLOGIC (>6 weeks) SEROPOSITIVE wPSSRw Polymyositis, Palindro mic rheumatism, SLE, Scleroderma, Rheumatoid arthritis SERONEGATIVE wPEARw Psoriatic arthritis, Enteric arthritis, Ankylosing spondylitis, Reactive arthritis, undifferentiated VASCULITIS polymyalgia rheumatica, Wegener’s granulomatosis, Behcet’s disease, Still’s disease INFECTIONS (30 OLIGOARTHRITIS asymmetric, usually involving hands and below waist, morning stiffness >30 ENTHESOPATHY inflammation at the sites of inser tion of ligaments, tendons, joint capsule, and fascia to bone, with both destruction and new bone for mation This results in Achilles tendonitis, plantar fasciitis, tenosynovitis, and dactylitis/sausage fingers SEROLOGY HLA B27 positive, rheumatoid factor negative BACK EXAMINATION INSPECTION swelling, erythema, atrophy, scars, and loss of thoracic kyphosis and cervical/lumbar lordosis RANGE OF MOTION check gait and flexion, exten sion, lateral bending, rotation PALPATION tenderness over spinous processes and sacroiliac joints CLINICAL FEATURES (CONT’D) Schober’s test (place mark cm below and mark 10 cm above the spine at level of PSIS/L5 with patient standing A distance increase of 3 months Shorter AM stiffness ++ +/ Resting Worsens Improves Activity Improves Worsens Sacroiliac joints ++ MANAGEMENT SYMPTOM CONTROL pain control TREAT UNDERLYING CAUSE flexion and exten sion exercises ... STEROID MYOPATHY AND INFLAMMATORY MYOPATHIES Steroidmyopathy Inflammatory myopathies History Steroid use Other inflammatory myopathy symptoms Other steroid related symptoms Physical Neck flexor... systemic sclerosis and antibody to centro mere seen more in CREST TREATMENTS Raynaud’s (calcium channel block ers) GERD (proton pump inhibitor) Renal crisis (ACE inhibitors) Interstitial pneumonitis... sclerodermatous skin changes proximal to the MCP joints Minor criteria include sclerodactyly, digital pitting scars, and bilateral pulmonary fibrosis Tests include antibo dies to topoisomerase