Scleroderma Three major disease subsets Based on extent
Scleroderma Three major disease subsets: Based on extent of skin dz n n Diffuse disease - skin abnormalities extending to the proximal extremities (AKA - PSS) Limited disease AKA "CREST" syndrome ] n Calcinosis, Raynauds, Esophageal dysmotility Sclerodactyly, Telangiectasias Localized Scleroderma Morphea: manifests as focal patches ] Linear scleroderma: band-like (linear) areas of thickening. (Coup de Sabre) ]
Other causes of Tight Skin n Pseudosclerodactyly ] IDDM, Hypothyroidism Drugs: Tryptophan, bleomycin, pentazocine, vinyl chloride, solvents n Eosinophilic fasciitis n Overlap Conditions n Scleroderma-like conditions n äEosinophil myalgia syndrome (tryptophan) äPorphyria cutanea tarda
ACR Systemic Sclerosis Preliminary Classification Criteria* n Major Criterion ] Proximal n Scleroderma Minor Criteria ] Sclerodactyly ] Digital pitting or scars or loss of finger pad ] Bibasilar pulmonary fibrosis * One major and two minor required for diagnosis
Scleroderma: Onset n n 80% females Age: 50% are < 40 yrs @ onset (20 -50) ] n n n Incidence 20/million/year Raynauds Swollen or puffy digits Loss of skin folds, no hair growth Digital pulp sores/scars Arthralgias >> Arthritis
Scleroderma A disorder of Collagen, Vessels n n n Etiology: unknown? Autoimmune disorder suggested by the presence of characteristic autoantibodies such as ANA, anticentromere and anti-SCL-70 antibodies. Pathology: ] ] n Early dermal changes lymphocytic infiltrates primarily of T cells Major abnormality is collagen accumulation with fibrosis. Small to medium-sized blood vessels, which show bland fibrotic change. Small thrombi may form on the altered intimal surfaces. Microvascular disease Cold Normal PSS
PSS - Clinical n Skin: Skin thickening is most noticeable in the hands, looking swollen, puffy, waxy. ] Thickening extends to proximal extremity, truncal and facial skin thickening is seen. ] Raynaud's phenomenon is present. ] Digital pits or scarring of the distal digital pulp ] n Musculoskeletal: Arthralgias and joint stiffness are common. Palpable tendon friction rubs associated with an increased incidence of organ involvement. ] Muscle weakness or frank myositis can be seen. ]
PSS - Clinical Gastrointestinal: Esophageal dysmotility, dysphagia, malabsorptive or blind loop syndrome, constipation. n Renal: Kidney involvement is an ominous finding and important cause of death in diffuse scleroderma. A hypertensive crisis (AKA renal crisis) may herald the onset of rapidly progressive renal failure. n
Pulmonary Manifestations of PSS n n n Dyspnea Pulmonary HTN only in CREST Interstitial fibrosis (fibrosing alveolitis) High resolution CT vs Galium Scan ] Major cause of death ] n RARE: Pulmonary embolism ] Pulmonary vasculitis ]
Cardiac Findings in PSS Myocardial fibrosis n Dilated cardiomyopathy n Cor pulmonale n Arrhythmias n Pericarditis n Myocarditis n Congestive heart failure n
Comparison CREST v. PSS Feature Limited+ CREST Diffuse+ PSS Calcinosis ++ + Arthralgia/Arthritis ++++ Pulmonary fibrosis + ++ Pulmonary HTN + 0 Tend friction rubs 0 +++ Renal crisis 0 + Centromere Ab* +++ +/0 Anti-Scl 70 Ab + ++ * Ab: antibody + Relative percentages: +++++ 81 -100%; ++++ 61 -80%; +++ 41 -60%; ++ 21 -40%; + 1 -20%
Treatment of Scleroderma Localized: none n Raynauds: warmth, skin protection, vasodilator therapy n CREST: none n PSS: none proven n ] Penicillamine: controversy ] Cytoxan: for lung disease? ] Steroids have no value
Polymyositis Dermatomyositis n n n n F: M = 2: 1 Acute onset Weakness (+ myalgia): Proximal > Distal Skeletal muscle: dysphagia, dysphonia Sx: Rash, Raynauds, dyspnea 65% elevated CPK, aldolase 50% ANA (+) 90% +EMG; 85% + muscle biopsy
Proposed Criteria for Myositis 1. 2. 3. 4. 5. n n Symmetric proximal muscle weakness Elevated Muscle Enzymes (CPK, aldolase, AST, ALT, LDH) Myopathic EMG abnormalities Typical changes on muscle biopsy Typical rash of dermatomyositis PM Dx is Definite w/ 4/5 criteria and Probable w/3/5 criteria DM Dx Definite w/ rash and 3/4 criteria and Probable w/ rash and 2/4 criteria
Polymyositis Classification Bohan & Peter 1. 2. 3. 4. Primary idiopathic dermatomyositis Primary idiopathic polymyositis Adult PM/DM associated with neoplasia Childhood Dermatomyositis (or PM) ä often associated with vasculitis 5. Myositis associated with collagen vascular disease
MYOPATHY: HISTORICAL CONSIDERATIONS n n n n Age/Sex/Race Acute vs. Insidious Onset Distribution: Proximal vs. Distal Pain? Drugs/Pre-existing Conditions Neuropathy Systemic Features
MYOPATHIIES n Toxic/Drugs ] n Infectious ] n n Etoh, Cocaine, Steroids, Plaquenil, Penicilamine, Colchicine, AZT, Lovastatin, Clofibrate, Tryptophan, Taxol, Emetine Coxackie A 9, HBV, HIV, Stept. , Staph, Clostridial, Toxoplasma, Trichinella Inflammatory Myopathies Congenital Neuropathic/Motor Neuron Disorders Endocrine/Metabolic
INFLAMMATORY MYOSITIS Immunopathogenesis n n n n Infiltrates - T cells (HLA-DR+) & monocytes Muscle fibers express class I & II MHC Ags T cells are cytotoxic to muscle fibers t-RNA antibodies: role? FOUND IN <50% OF PTS Infectious etiology? Viral implicated HLA-B 8/DR 3 in childhood DM DR 3 and DRW 52 with t-RNA synthetase Ab
DERMATOMYOSITIS 5 Skin Features 1. Heliotrope Rash: over eyelids n 2. 3. 4. 5. Seldom seen in adults Gottrons Papules: MCPs, PIPs, MTPs, knees, elbows V-Neck Rash: violaceous/erythema anterior chest w/ telangiectasias Periungual erythema, digital ulcerations Calcinosis
Calcinosis
DIAGNOSTIC TESTING n n n Physical Examiniation: Motor Strength (Gowers sign), Neurologic Exam Acute phase reactants unreliable Muscle Enzymes ] ] n CPK: elevated >65%; >10% MB fraction is possible Muscle specific- Aldolase, Troponin, Carb. anhydrase. III AST > LDH > ALT Beware of incr. creatinine (ATN) and myoglobinuria Electromyogram: increased insertional activity, amplitude, polyphasics, associated neuropathic changes, incremental/decremental MU changes
DIAGNOSTIC TESTING n Muscle Biopsy (an URGENT not elective procedure) Call the neuropathologist! 85% Sensitive. ] Biopsy involved muscle (MRI guided) ] Avoid EMG/injection sites or sites of trauma ] n n n Magnetic Resonance Imaging - detects incr. water signal, fibrous tissue, infiltration, calcification Investigational: Tc-99 m Scans, PET Scans Serologic Tests: ANA (+) 60%, Abs against t-RNA synthetases
INFLAMMATORY MYOSITIS Biopsy Findings n n n Inflammatory cells Edema and/or fibrosis Atrophy/ necrosis/ degeneration Centralization of nuclei Variation in muscle fiber size Rarely, calcification
Anti-synthetase syndrome: ILD, fever, arthritis, Raynauds, Mechanics hands
MALIGNANCY & MYOSITIS n n n Controversial Reports range from 10 -25% If real, men over age 50 yrs at greatest risk Common tumors: Breast, lung, ovary, stomach, uterus, colon 60% the myositis appears 1 st, 30% neoplasm 1 st, and 10% contemporaneously Avoid invasive, expensive searches for occult neoplasia
PM/DM Complications n n n PULMONARY Aspiration pneumonitis Infectious pneumonitis Drug induced pneumonitis Intercostal, diagphragm involvement Fibrosing alveolitis RARE: ] ] Pulmonary vasculitis Pulmonary neoplasia n n n CARDIAC Elev. CPK-MB Mitral Valve prolapse AV conduction disturbances Cardiomyopathy Myocarditis
PM/DM Diagnosis Symmetric progressive proximal weakness n Elevated muscle enzymes (CPK, LFTs) n Muscle biopsy evidence of myositis n EMG: inflammatory myositis n Characteristic dermatologic findings n
INFLAMMATORY MYOSITIS Treatment n n Early Dx, physical therapy, respiratory Rx Corticosteroids : 60 -80 mg/day ] n 80% respond within 12 weeks Steroid resistant Methotrexate ] Azathioprine ] n n IVIG, Cyclosporin, Chlorambucil: unproven No response to apheresis
PROGNOSIS n n n n Poor in pts. with delayed Dx, low CPK, early lung or cardiac findings, malignancy Neoplasia in 10% of adults PT for muscle atrophy, contractures, disability Kids: 50% remission, 35% chr active disease Adult < 20 yrs. do better than >55 yrs. Adults: Mortality rates betw. 28 -47% @ 7 yrs. Relapses & functional disability are common Death: due to malignancy, sepsis, pulm. or cardiac failure, and complications of therapy
RHABDOMYOLYSIS n n n Injury to the sarcolemma of skeletal muscle with systemic release of muscle macromolecules such as CPK, aldolase, actin, myoglobin, etc Maybe LIFE-THREATENING: from hyperkalemia, met. acidosis, ATN from myoglobinuria Common causes: Et. OH, Cocaine, K+ deficiency, infection, PM/DM, infection (clostridial, staph, strept), exertion/exercise, cytokines
INCLUSION BODY MYOSITIS n n n n Bimodal age distribution, maybe hereditary Slow onset, progressive weakness Painless, distal and proximal weakness Normal or mildly elevated CPK Poor response to corticosteroids Dx: light microscopy may be normal or show CD 8+ lymphs. Tubulofilamentous inclusion bodies on electron microscopy Role for amyloid?
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