Inflammatory My Opa Thies

The Physician's Guide to Laboratory Test Selection and Interpretation
Inflammatory Myopathies
Diagnosis
Indications for Testing Symmetrical proximal muscle weakness Criteria for Diagnosis Bohan and Peter criteria for diagnosis of PM and DM Bohan and Peter Criteria for Diagnosis of PM and DM Proximal muscle weakness, usually symmetrical Elevated serum muscle enzymes (CK, aldolase) Electromyographic abnormalities Common myopathic potential (low amplitude, short duration and polyphasic action potentials) Characteristic triad myopathic potentials, fibrillations, positive sharp waves, increased insertional activity, complex repetitive discharges Muscle biopsy findings typical of PM or DM necrosis, phagocytosis, regeneration, inflammation Dermatological features of DM, Gottrons sign or papules, or heliotrope rash
Definite diagnosis requires four criteria with rash for DM and without rash for PM Probable diagnosis requires three criteria with rash for DM and without rash for PM
Laboratory Testing Initial screening tests Creatine kinase (CK) elevated, but consider other causes for elevations >100-fold ESR or CRP elevated during active phases of disease Calcium should be normal TSH rule out thyroid disease Antibody testing ANA positive in 50-80% of patients Anti-histidyl-tRNA synthetase (Jo-1) testing Found in 18-36% of patients satisfying myositis criteria not useful in confirming diagnosis; more common in PM Nearly all Jo-1-positive patients have lung involvement (antisynthetase syndrome) and moderate to severe disease Relationship between Jo-1 antibody titer and disease activity reported but not confirmed Jo-1 antibodies rarely found in any other disease states Overlap syndromes Other myositis-specific antibodies Anti-synthetase antibodies predictive of lung involvement, not usually found in IBM In addition to Jo-1, less common markers include the following Anti-PL7 (threonyl-tRNA synthetase) Anti-PL-12 antibodies (anti-alanyl-tRNA synthetase) Anti-EJ (glycyl-ts RNA) Anti-OJ (anti-isoleucyl-tRNA synthetase) Anti-KS (asparaginyl tRNA synthetase) Anti-HA (tyrosyl tRNA synthetase) Anti-Zo (phenylalanyl tRNA synthetase) Non-synthetase antibodies
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Anti-signal recognition particle (anti-SRP) myocardial involvement frequent; severe, rapidly progressive myositis with high CK Anti-p155/140 may be found in juvenile DM Other myositis-associated autoantibodies rare in juvenile disease Anti-HMGCR Anti-MDA5 Anti-Mi-2 Anti-140 Anti-SA5 Anti-MJ (NXP-2) Myositis-associated antibodies Anti-PM-Scl scleroderma-polymyositis Anti-U1 RNP/anti-U3 RNP Anti-Ku Anti-pLA Anti-topo Anti-RO (SSA) Anti-5bKDa Anti-hPMS1 Nonspecific tests Aldolase, AST, ALT, LD, serum myoglobin variably elevated Histology Muscle biopsy is gold standard for diagnosis Usually performed on proximal muscles of the leg but not in end-stage muscles MRI may be helpful in choosing muscle Open biopsy preferred larger sample DM Demonstrate perivascular and perimysial inflammation (B-cells, macrophages and CD4+ cells) T-cells usually absent Distinct muscle pathology PM Demonstrates CD8+ T-cell invasion of non-necrotic muscle; uniform expression of MHC-1 at surface of muscle IBM Rimmed vacuoles with amyloid and filamentous masses; cytochrome oxidase negative fibers Uniform expression of MHC-1 at surface of muscle Immunohistochemistry SM1-31 antibody best detected antibody but not specific for IBM Other Testing EMG changes consistent with myopathy, including increased spontaneous and insertional activity with fibrillation potential, complex repetitive discharges, positive repetitive discharges, positive sharp waves, early recruitment and small polyphasic motor unit potentials Abnormal in 70-90% of patients Not specific for inflammatory myopathies Amyopathic DM may have only subtle myopathy on EMG Imaging Studies
Ultrasound muscle edema with alteration of normal architecture May visualize subcutaneous calcifications CT fatty infiltration suggests chronic disease MRI very sensitive for detection of muscle edema Differential Diagnosis Weakness alone Endocrine myopathies Thyroid disease (hyper- and hypo-) Cushing syndrome Drug-related myopathies Statins Steroids Diuretics Colchicine Hydroxychloroquine Alcohol Growth hormone Amyloidosis Sarcoidosis Neuropathies Polymyalgia rheumatica Metabolic myopathies Lipid storage disorders Mitochondrial diseases Neuromuscular transmission disorders Myasthenia gravis Spinal stenosis Paraneoplastic syndromes Eaton-Lambert syndrome Muscular dystrophies Limb-girdle dystrophy Facioscapulohumeral dystrophy Duchenne muscular dystrophy Motor neuron disorders Spinal muscular atrophy Amyotrophic lateral sclerosis Lou Gehrig disease Vasculitis/polyarteritis nodosa Weakness (with or without rash) Viral Enterovirus (eg, polio) Influenza Parvovirus B19 Human T-lymphotropic virus type 1 Hepatitis B virus HBV Bacterial/parasitic Toxoplasmosis
Trichinella spiralis (trichinosis) Borrelia burgdorferi Lyme disease Other connective tissue diseases Systemic lupus erythematosus Systemic sclerosis scleroderma Mixed connective tissue disease Other inflammatory disease Inflammatory bowel disease Celiac disease Rash without weakness Psoriasis Eczema
Screening
All adult patients with DM should be evaluated for malignancy Breast/pelvic exam in females; testicular exam in males Tests to consider Urinalysis (utero/renal cancer) CA-125 (ovarian cancer) Stool for occult blood (colorectal cancer) Chest x-ray (lung cancer) Mammography (breast cancer) CT of abdomen and pelvis American Academy of Dermatology recommends reevaluation for malignancy every 6-12 months for first 2 years following diagnosis CK myoglobin, and LD levels are most useful in monitoring therapeutic response
Monitoring
Clinical Background
Inflammatory myopathies are a group of chronic autoimmune disorders characterized by inflammation and degeneration of skeletal muscles. The original Bohan and Peter criteria classify inflammatory myopathies into dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM). Epidemiology Adults Incidence 4-10/1,000,000 Age DM bimodal peaks Childhood 50-70 years PM age of onset typically >20 years Rare in childhood IBM >50 years Sex DM and PM M<F; 1:2 IBM M>F; 2:1 Ethnicity
DM unknown PM some studies suggest higher prevalence in African Americans compared to general U.S. population IBM higher prevalence in Caucasians Children Incidence 2-3/1,000,000 (rare) Age DM more common in children; mean onset is 7 years (25% present at <4 years) PM rare in children Juvenile myositis (JM) children 2-18 years Sex M<F, 1:2.3 Pathophysiology DM microangiopathy affecting skin and muscle with deposition of complement-causing lysis of endomysial capillaries and muscle ischemia PM and IBM T-cells invade muscle fibers, leading to necrosis Clinical Presentation General features Musculoskeletal progressive muscle weakness (usually symmetrical and proximal) Pharyngeal and neck flexion muscles frequently involved, leading to dysphagia and/or myalgia Arthralgias/arthritis wrists, knees, small joints of hands Constitutional fever, weight loss Pulmonary fibrosing alveolitis, aspiration pneumonia Gastrointestinal esophageal dysfunction, dysphagia Cardiovascular myocarditis, pericarditis, valvular disease, rhythm disturbances Renal rarely present; myoglobinuria, glomerulonephritis Dermatologic Raynaud phenomenon; common rashes, calcinosis over bony prominences DM Characteristic photosensitive rash accompanied by symmetrical, subacute, proximal muscle weakness Rash usually precedes muscle symptoms Blue-purple rash symmetrical distribution Violaceous discoloration of upper eyelids with periorbital edema (heliotrope rash) Erythema of metacarpophalangeal proximal and distal joints Raised violaceous rash (Gottron sign) or scaly erythematous plaques over dorsal surface of bony prominences (Gottron papules) considered pathognomonic for DM Macular erythema over the lower neck and upper chest in a V-distribution (V-sign), over upper back (Shawl sign), or over upper thighs (Holster sign) Telangiectasias at base of fingernails, cuticular overgrowth and periungual erythema Cancer-associated myositis Most commonly associated with DM Increased risk of malignancy (20-25%) in the following types (most risk in first 2-3 years after diagnosis) Ovarian Breast Melanoma
Non-Hodgkin lymphoma Vasculitic skin changes More common in children Subcutaneous nodules, periungual infarcts, digital ulcerations Amyopathic DM is a subgroup Characteristic cutaneous findings of DM >6 months without muscle involvement May progress to DM No evidence of muscle disease Some risk for lung disease, malignancy May have fatigue electromyography (EMG) may demonstrate subtle myopathy PM Dominated by muscular presentation Usually subacute presentation May be associated with other autoimmune diseases Diagnosis of exclusion rule out the following Rash Neuromuscular disease Endocrinopathy Muscular dystrophy Known biochemical muscle disorder Drug-induced myopathy IBM Associated with other autoimmune diseases 20% of the time Small muscles in hand frequently involved May involve proximal muscles, but distal weakness is more common Quadriceps also heavily involved Asymmetric distribution common Extramuscular disease less common; dysphagia is the exception May be misdiagnosed as PM Antisynthetase syndrome association of PM and DM; found almost exclusively in middle-aged women and characterized by the following Low-grade fevers Interstitial pneumonitis (major determinant of morbidity and mortality) Hyperkeratosis, cracking of lateral and palmar aspects of the fingers (mechanic's hands) Raynaud phenomena Inflammatory polyarthritis Presence of antinuclear antibodies known as anti-synthetases JM Skin rash usually first sign (no skin symptoms in PM) Dermatomyositis form most common symptom; polymyositis extremely rare Other symptoms are similar to adult DM & PM Cutaneous calcinosis more common in DM when compared to adults
Lab Tests
Indications for Laboratory Testing Tests generally appear in the order most useful for common clinical situations. For test-specific information, refer to the test number in the ARUP Laboratory Test Directory on the ARUP Web site at www.aruplab.com. Test Name and Number Creatine Kinase, Total, Serum or Plasma 0020010 Method: Quantitative Enzymatic Lactate Dehydrogenase, Serum or Plasma 0020006 Method: Quantitative Enzymatic Anti-Nuclear Antibodies (ANA), IgG by ELISA with Reflex to ANA, IgG by IFA 0050080 Method: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody Recommended Use Initial testing Evaluate for presence of muscle disease Monitor therapeutic response Monitor therapeutic response Limitations Follow Up
Screening test for inflammatory myopathies to rule out connective tissue disease Pattern may be helpful in distinguishing from other connective tissue diseases All ELISA results reported as "Detected" are further tested by IFA ANA ELISA screen is designed to detect antibodies against dsDNA, histone, SS-A (Ro), SS-B (La), Smith, snRNP/Sm, Scl Screen for inflammatory myopathies
ANA ELISA assays have been reported to have lower sensitivities for antibodies associated with nucleolar and specked ANA-IFA patterns
Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present
Jo-1 Antibody, IgG 0099592 Method: Semi-Quantitative Multiplex Bead Assay Myositis-Specific Panel (15 Antibodies) 2005176 Method: Qualitative Enzyme Immunoassay/ Immunoprecipitation Thyroid Stimulating Hormone with reflex to Free Thyroxine 2006108 Method: Quantitative Electrochemiluminescent Immunoassay
Assist in diagnosis of polymyositis and dermatomyositis Profile includes anti-PM-Scl, anti-Ku, anti-U1RNP, anti-U2RNP, anti-SRP, anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, anti-OJ, SSA-52 kd, P140, P155/140, U3 RNP Fibrillarin Rule out thyroid disease as etiology of muscle weakness
Sedimentation Rate, Westergren (ESR) 0040325 Method: Visual Identification C-Reactive Protein 0050180
Nonspecific test for inflammation
Nonspecific test for inflammation
Method: Quantitative Immunoturbidimetry Calcium, Serum or Plasma Rule out hypercalcemia as etiology 0020027 of muscle weakness Method: Quantitative Spectrophotometry Myoglobin, Serum 0020224 Method: Quantitative Electrochemiluminescent Immunoassay Additional Tests Available Test Name and Number Thyroid Stimulating Hormone 0070145 Method: Quantitative Chemiluminescent Immunoassay Aldolase, Serum 0020012 Method: Quantitative Enzymatic Alanine Aminotransferase, Serum or Plasma 0020008 Method: Quantitative Enzymatic Aspartate Aminotransferase, Serum or Plasma 0020007 Method: Quantitative Enzymatic RNP (U1) (Ribonucleic Protein) (ENA) Antibody, IgG 0050470 Method: Semi-Quantitative Multiplex Bead Assay Comments If elevated, indicator of active disease May be useful in monitoring therapy
Non-specific testing
Signal Recognition Particle (SRP) Antibody 2002098 Method: Immunoprecipitation PM/Scl-100 Antibody, IgG, by Immunoblot with Reflex to ANA IFA 2003040 Method: Semi-Quantitative Immunoblot/Semi-Quantitative Indirect Fluorescent Antibody Urinalysis, Complete 0020350 Method: Reflectance Spectrophotometry/Microscopy Cancer Antigen 125 0080462 Method: Quantitative Electrochemiluminescent Immunoassay General References Alexanderson H, Lundberg IE. Inflammatory muscle disease: clinical presentation and assessment of patients.Curr Rheumatol Rep. 2007; 9 (4) :273-279. Baer AN. Differential diagnosis of idiopathic inflammatory myopathies.Curr Rheumatol Rep. 2006; 8 (3) :178-187. Feldman BM, Rider LG, Reed AM, Pachman LM. Juvenile dermatomyositis and other idiopathic inflammatory myopathies of childhood.Lancet. 2008; 371 (9631) :2201-2212. Greenberg SA. Inflammatory myopathies: evaluation and management.Semin Neurol. 2008; 28 (2) :241-249. Harris BT, Mohila CA. Essential muscle pathology for the rheumatologist.Rheum Dis Clin North Am. 2011; 37 (2) :289-308, vii. Huber AM. Idiopathic inflammatory myopathies in childhood: current concepts.Pediatr Clin North Am. 2012; 59 (2) :365-380. Khan S, Christopher-Stine L. Polymyositis, dermatomyositis, and autoimmune necrotizing myopathy: clinical features.Rheum Dis Clin North Am. 2011; 37 (2) :143-58, v. Lynch MC, Cohen JA. A primer on electrophysiologic studies in myopathy.Rheum Dis Clin North Am. 2011; 37 (2) :253-68, vii. Mammen AL. Dermatomyositis and polymyositis: Clinical presentation, autoantibodies, and pathogenesis.Ann N Y Acad Sci. 2010; 1184 :134-153. Rider LG, Miller FW. Deciphering the clinical presentations, pathogenesis, and treatment of the idiopathic inflammatory myopathies.JAMA. 2011; 305 (2) :183-190. Solorzano GE, Phillips LH. Inclusion body myositis: diagnosis, pathogenesis, and treatment options.Rheum Dis Clin North Am. 2011; 37 (2) :173-83, v. Wedderburn LR, Rider LG. Juvenile dermatomyositis: new developments in pathogenesis, assessment and treatment.Best Pract Res Clin Rheumatol. 2009; 23 (5) :665-678.
References from the ARUP Institute for Clinical and Experimental Pathology Jaskowski TD, Schroder C, Martins TB, Mouritsen L, Hill HR. Comparison of three commercially available enzyme immunoassays for the screening of autoantibodies to extractable nuclear antigens.J Clin Lab Anal. 1995; 9 (3) :166-172. Reviewed by Tebo, Anne E., PhD. Assistant Medical Director, Immunology at ARUP Laboratories; Assistant Professor of Pathology (Clinical), University of Utah Diagnostic Algorithm(s) PDF algorithm(s) available at www.arupconsult.com. Connective Tissue Disease Testing Algorithm Related Content Connective Tissue Diseases Inflammatory Bowel Disease - IBD Lymphoma Phenotyping Mixed Connective Tissue Disease - MCTD Paraneoplastic Neurological Syndromes Scleroderma - Systemic Sclerosis Systemic Lupus Erythematosus - SLE Thiopurine Methyltransferase Activity - TPMT Trichinella spiralis
Last Update: October 2012

Inflammatory My Opa Thies

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The Physician's Guide to Laboratory Test Selection and Interpretation

The Physician's Guide to Laboratory Test Selection and Interpretation

The Physician's Guide to Laboratory Test Selection and Interpretation

The Physician's Guide to Laboratory Test Selection and Interpretation

The Physician's Guide to Laboratory Test Selection and Interpretation

The Physician's Guide to Laboratory Test Selection and Interpretation

The Physician's Guide to Laboratory Test Selection and Interpretation

The Physician's Guide to Laboratory Test Selection and Interpretation

Nonspecific test for inflammation

Nonspecific test for inflammation

The Physician's Guide to Laboratory Test Selection and Interpretation

The Physician's Guide to Laboratory Test Selection and Interpretation

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