Scleroderma Three major disease subsets: Based on extent of skin dz Diffuse disease - skin abnormalities extending to the proximal extremities (AKA - PSS) Limited disease AKA "CREST" syndrome 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 Pseudosclerodactyly IDDM, Hypothyroidism Drugs: Tryptophan, bleomycin, pentazocine, vinyl chloride, solvents Eosinophilic fasciitis Overlap Conditions Scleroderma-like conditions Eosinophil myalgia syndrome (tryptophan) Porphyria cutanea tarda

ACR Systemic Sclerosis Preliminary Classification Criteria* Major Criterion Proximal 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 80% females Age: 50% are < 40 yrs @ onset (20-50) 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 Etiology: unknown? Autoimmune disorder suggested by the presence of characteristic autoantibodies such as ANA, anti-centromere and anti-SCL-70 antibodies. Pathology: 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 Cold PSS

PSS - Clinical 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 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. 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.

Pulmonary Manifestations of PSS Dyspnea Pulmonary HTN only in CREST Interstitial fibrosis (fibrosing alveolitis) High resolution CT vs Galium Scan Major cause of death RARE: Pulmonary embolism Pulmonary vasculitis

Cardiac Findings in PSS Myocardial fibrosis Dilated cardiomyopathy Cor pulmonale Arrhythmias Pericarditis Myocarditis Congestive heart failure

Arthralgia/Arthritis Comparison CREST v. PSS  Feature Limited+ CREST Diffuse+ PSS  Calcinosis ++ +  Arthralgia/Arthritis  ++  ++++  Pulmonary fibrosis  +  Pulmonary HTN  0  Tend friction rubs +++  Renal crisis  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 Raynauds: warmth, skin protection, vasodilator therapy CREST: none PSS: none proven Penicillamine: controversy Cytoxan: for lung disease? Steroids have no value

Polymyositis Dermatomyositis 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 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 Primary idiopathic dermatomyositis Primary idiopathic polymyositis Adult PM/DM associated with neoplasia Childhood Dermatomyositis (or PM) often associated with vasculitis Myositis associated with collagen vascular disease

MYOPATHY: HISTORICAL CONSIDERATIONS Age/Sex/Race Acute vs. Insidious Onset Distribution: Proximal vs. Distal Pain? Drugs/Pre-existing Conditions Neuropathy Systemic Features

MYOPATHIIES Toxic/Drugs Infectious Inflammatory Myopathies Congenital Etoh, Cocaine, Steroids, Plaquenil, Penicilamine, Colchicine, AZT, Lovastatin, Clofibrate, Tryptophan, Taxol, Emetine Infectious Coxackie A9, HBV, HIV, Stept., Staph, Clostridial, Toxoplasma, Trichinella Inflammatory Myopathies Congenital Neuropathic/Motor Neuron Disorders Endocrine/Metabolic

NONMYOPATHIC CONSIDERATIONS Fibromyalgia/Fibrositis/Myofascial Pain Disorder Polymyalgia Rheumatica Caucasians, > 55 yrs, M=F ESR > 100, normal strength, no synovitis RA SLE Adult Still's Disease

INFLAMMATORY MYOSITIS Immunopathogenesis 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-B8/DR3 in childhood DM DR3 and DRW52 with t-RNA synthetase Ab

DERMATOMYOSITIS 5 Skin Features Heliotrope Rash: over eyelids 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 Physical Examiniation: Motor Strength (Gowers sign), Neurologic Exam Acute phase reactants unreliable Muscle Enzymes CPK: elevated >65%; >10% MB fraction is possible Muscle specific- Aldolase, Troponin, Carb. anhydraseIII 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 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 Magnetic Resonance Imaging - detects incr. water signal, fibrous tissue, infiltration, calcification Investigational: Tc-99m Scans, PET Scans Serologic Tests: ANA (+) 60%, Abs against t-RNA synthetases

INFLAMMATORY MYOSITIS Biopsy Findings 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

Autoantibodies in PM/DM Ab Freq (%) Clinical Syndrome ANA 50 Myositis U1-RNP 15 SLE + myositis Ku <5 PSS + myositis Mi2 30 Dermatomyositis PM1 PSS – PM overlap Jo-1 25 Arthritis+ ILD+ arthritis SS-B (La) SLE,Sjogrens, ILD, PM PL-12,7 ILD + PM

INFLAMMATORY MYOSITIS NORMAL/NOT INVOLVED: Face Uncommon Renal RES: LN, spleen, liver (enzymes from muscle) NOT UNCOMMON RA-like arthritis Fever/chills/night sweats Myalgias

MALIGNANCY & MYOSITIS 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 1st, 30% neoplasm 1st, and 10% contemporaneously Avoid invasive, expensive searches for occult neoplasia

PM/DM Complications PULMONARY Aspiration pneumonitis Infectious pneumonitis Drug induced pneumonitis Intercostal, diagphragm involvement Fibrosing alveolitis RARE: Pulmonary vasculitis Pulmonary neoplasia CARDIAC Elev. CPK-MB Mitral Valve prolapse AV conduction disturbances Cardiomyopathy Myocarditis

PM/DM Diagnosis Symmetric progressive proximal weakness Elevated muscle enzymes (CPK, LFTs) Muscle biopsy evidence of myositis EMG: inflammatory myositis Characteristic dermatologic findings

INFLAMMATORY MYOSITIS Treatment Early Dx, physical therapy, respiratory Rx Corticosteroids : 60-80 mg/day 80% respond within 12 weeks Steroid resistant Methotrexate Azathioprine IVIG, Cyclosporin, Chlorambucil: unproven No response to apheresis

PROGNOSIS 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 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: EtOH, Cocaine, K+ deficiency, infection, PM/DM, infection (clostridial, staph, strept), exertion/exercise, cytokines

INCLUSION BODY MYOSITIS 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 CD8+ lymphs. Tubulofilamentous inclusion bodies on electron microscopy Role for amyloid?

Inflammatory Myositis Polymyositis (PM) and dermatomyositis (DM) are types of idiopathic inflammatory myopathy (IIM). IIM are characterized clinically by proximal muscle weakness Etiology: There is now known etiology. Demographics: PM is more common than DM in adults. Peak incidence occurs between 40 and 60 yrs. F:M 2:1 Muscles: Proximal muscle weakness, dysphagia, aspiration. respiratory failure or death. Skin: Gottron's papules, heliotrope rash, "V" neck rash, periungual erythema, "Mechanic's hands", calcinosis Dx: Muscle enzymes (CPK, aldolase), EMG, Biopsy Rx: Steroids, MTX, Azathioprine, IVIG