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Idiopathic Inflammatory Myopathies
05 November 2004
CLASSIFICATION OF INFLAMMATORY DISEASES OF MUSCLE
Idiopathic Inflammatory Myopathies Polymyositis Dermatomyositis Juvenile (childhood) dermatomyositis Myositis associated with collagen vascular disease Myositis associated with malignancy Inclusion body myositis
Myopathies caused by infection HIV HTLV Influenza Bornholm Disease Toxoplasmosis Others: see chart
Myopathies caused by drugs and toxins
Unusual idiopathic inflammatory myopathy variants Eosinophilic myositis: 1. Eosinophilic fasciitis 2. Eosinophilic mono/multiplex myositis 3. Eosinophilic polymyositis 4. Eosinophilia – myalgia syndrome Myositis ossificans Focal myositis Giant cell myositis
Idiopathic Inflammatory Myopathies
3 major categories: Polymyositis Dermatomyositis Inclusion body myositis Each individually defined clinically, histologically and pathogenically. DM is not PM with a rash; IBM is not PM with rimmed vacuoles and inclusions. Incidence is 1 per 100,000 per year.
Dermatomyositis
Bimodal: 5 –15, 30-45. Female predominance.
Subacute onset with predilection for truncal and proximal muscles. 30% dysphagia Heliotrope rash Gottren’s papules V sign Shawl sign Dilated nailbed capillaries Mechanic’s hands Subcutaneous calcification (50% of children) 1/3 Raynaud’s phenomenon
Cardiac: often ECG abnormalities, rarely clinical manifestations. Pulmonary: 10% interstitial lung disease involving lung bases 50% Jo-1 (Histidyl transfer RNA synthetase) aspiration pneumonia as a complication of weakness. GIT: vasculitis especially in childhood DM. Joints: symmetrical arthritis involving large and small joints. Vasculitis Malignancy: 25% more than 40 yo Female usually breast or ovary Male usually lung or colon.
BLOOD WORK: 40% ANA: especially with overlap syndromes 10% Jo-1: interstitial lung disease, arthritis, moderate response to treatment and poor long term prognosis. SRP and Mas not seen in DM 20% Mi2 exclusive to DM: acute onset, florid rash, good response to treatment, favorable prognosis.
MUSCLE BIOPSY: Humorally mediated microangiopathy. Perifascicular atrophy Microvacuolated fibres CD4 cells Deposition of membrane attack complex on small vessels.
PROGNOSIS: Older age Associated interstitial lung disease Underlying malignancy Cardiac disease Late / inadequate treatment. Jo-1
Polymyositis
Usually >20 yo Female predominance
Frequently myalgia 1/3 dysphagia
Cardiac: often ECG abnormalities, rarely clinical manifestations. Pulmonary: 20% interstitial lung disease involving lung bases 50% Jo-1 (Histidyl transfer RNA synthetase) aspiration pneumonia as a complication of weakness. GIT: vasculitis especially in childhood DM. Joints: symmetrical arthritis involving large and small joints. Vasculitis Malignancy: 15% more than 40 yo Female usually breast Male usually lung or colon.
BLOOD WORK: 25% ANA: especially with overlap syndromes 20% Jo-1: interstitial lung disease, arthritis, moderate response to treatment and poor long term prognosis. 4% SRP: acute onset, severe weakness, myalgia, myocarditis, resistant to immunosuppression, poor prognosis with 25% 5 year survival.
MUSCLE BIOPSY: Endomysial inflammation Variability in fibre size Scattered necrotic and regenerating muscle fibres CD8 cells No immune deposits
PROGNOSIS: Older age Associated interstitial lung disease Underlying malignancy Cardiac disease Late / inadequate treatment. Jo1 and SRP antibodies.
Inclusion Body Myositis
Usually >50 yo Males predominate.
Insidious onset Slowly progressive, often asymmetrical weakness involving proximal and distal muscles. Predilection or quadriceps, volar forearm, ankle dorsiflexors and flexor pollicis longus. 40% dysphagia 33% mild facial weakness 30% peripheral neuropathy
15% associated autoimmune disorders: SLE, Sjogren’s, scleroderma, thrombocytopenia, sarcoidosis.
BLOOD WORK: CK is only normal or mildly elevated. Antibodies are usually absent.
MUSCLE BIOPSY: Endomysial inflammation CD8 cells Eosinophilic cytoplasmic inclusions Muscle fibres with rimmed vacuoles lined with granular material Amyloid deposition seen with Congo red staining. May occasionally have red ragged fibres. May require repeat muscle biopsies to make diagnosis.
PROGNOSIS: Life expectancy not altered for age matched controls. Does not respond
well to immunosuppression. Myositis Workup
Myopathy vs muscular dystrophy vs myositis. Exclude drug and infectious etiology. Clinical features consistent with which type of myositis. Check for malignancy: PV, breast, PR, sigmoidoscope, LN.
UCE, Ca, Mg, PO4 Muscle enzyme: CK (most sensitive & specific marker for muscle destruction), enolase, aldolase, AST, ALT, LDH. FBE, ESR. ANA, ENA. HIV (HTLV, Influenza, Tox, Coxsackie) Urinary myoglobin
ECG
CXR
EMG: increased insertional activity Fibrillation, fasciculations. Pseudomyotonia and complex repetitive discharges. Reduced amplitude, polyphasic motor unit potentials. Early recruitment.
Muscle biopsy
Academic value studies: Myositis specific antibodies. MRI High resolution ultrasound Myosin Scintigraphy
Treatment
Steroids (1 mg/kg/d prednisolone) First line treatment. IBM generally nonresponsive DM: 50% complete response Further 30% have partial response. PM: 30% complete response Further 50% have partial response. Associated osteoporosis prevention is now recommended: Caltrate & calcitriol Alendronate.
SECOND LINE TREATMENT:
Azathioprine (2-3 mg/kg/d) 64% beneficial response in conjunction with steroids for both PM & DM. Side effects: 12% fever, abdo pain, nausea, vomiting. Leukopenia, hepatotoxicity, pancreatitis, teratogenic, oncogenic.
Intragam (2 mg/kg mthly for at least 3 mths) Proven in DM Some benefit in IBM Possible benefit in IBM. Side effects: flu like illness, rash, aseptic meningitis, renal failure.
Methotrexate (7.5 mg weekly) 80% DM & PM showed some improvement. Avoid in those with interstitial lung disease. Side effects: alopecia, stomatitis, interstitial lung disease, teratogenic, oncogenic, hepatotoxic.
THIRD LINE TREATMENT: Cyclophosphamide Chlorambucil Cyclosporine Tacrolimus (FK 506) Plasmapharesis Leukapharesis Total body irradiation Thymectomy |
