Inflammatory Muscle Disease

Classification by Bohan and Peter:

1. Adult polymyositis (PM)
2. Adult dermatomyositis (DM)
3. PM/DM associated with malignancy (12% of all myositis patients; 50% of myositis patients >age 65 years)
4. Childhood (juvenile) DM
5. PM/DM associated with other connective tissue disorders (11% to 40% of all myositis patients)
6. Sporadic inclusion body myositis (s-IBM) has recently been added to this list of idiopathic inflammatory myopathies and may be one of the most common accounting for 16% to 28% of all inflammatory myopathies.

• Polymyositis (PM) and dermatomyositis (DM) are characterized by proximal muscle weakness, elevated muscle enzymes, and abnormal electromyogram.
• The typical skin manifestations of DM include heliotrope rash, Gottron’s papules, and abnormal nailfold capillaries. Skin ulcerations and anti-155/140 antibodies signal the presence of an associated underlying malignancy.
• Myositis-specific autoantibodies can predict extramuscular manifestations, response to therapy, and prognosis.
• The antisynthetase syndrome is characterized by myositis, interstitial lung disease (ILD), arthritis, mechanic’s hands, and Raynaud’s phenomenon.
• Inclusion body myositis should be considered in patients over age 50 with proximal and distal muscle weakness, neuropathic features, and poor response to steroid therapy.

Major diagnostic criteria for PM/DM:

Proximal motor weakness: Weakness occurs earliest and insidiously over 3 to 6 months. It occurs most severely around the shoulder/pelvic girdles and neck flexors.

Elevated serum muscle enzymes: Creatine kinase (CK) is elevated in almost all patients at some time during the course of active disease. Other markers of muscle damage include elevated levels of aldolase, myoglobin, aspartate and alanine aminotransferase (AST and ALT), and lactate dehydrogenase (LDH). Myoglobinuria can be seen in active disease.

Abnormal neurodiagnostic studies: The electromyogram (EMG) in PM/DM has a good sensitivity (85%) but low specificity (33%). It shows a typical but not specific pattern consisting of:

1) increased insertional activity with spontaneous fibrillations;

2) myopathic low amplitude and short duration polyphasic motor unit action potentials (MUAPs);

3) complex repetitive discharges. Nerve conduction velocity (NCV) studies are normal in the idiopathic inflammatory myopathies, with the exception of inclusion-body myositis in which neuropathic disease can develop along with the myopathy.

Muscle biopsy: Muscle biopsy should be performed in most cases to confirm the suspected diagnosis.

Characteristic rash of dermatomyositis: Skin biopsy shows an interface dermatitis similar to systemic lupus erythematosus (SLE)

Magnetic resonance imaging (MRI) scanning of the muscle can be helpful to direct muscle biopsy with a sensitivity of 96% to 100%. Areas of inflamed muscle demonstrate increased signal on T2-weighted images with fat suppression (STIR images) but not T1-weighted images, denoting areas of edema/inflammation. In chronic disease, MRI can also show fatty degeneration on T1-weighted images which is unlikely to improve with medications.

Amyopathic dermatomyositis

Occasionally, the cutaneous manifestations of DM occur in the absence of clinically apparent muscle involvement. Such is referred to as clinically amyopathic dermatomyositis (CADM). Perhaps half or more of such patients will develop muscle disease over time, but a significant proportion will manifest skin-limited disease only. This form can be associated with malignancy whereas other patients may develop extramuscular manifestations such as rapidly progressive interstitial lung disease even in the absence of myositis. Over half of these patients have anti-MDA-5 (anti-CADM-140) autoantibodies

Extramuscular or extradermatologic manifestations of PM/DM

Constitutional symptoms: fatigue, low-grade fever, weight loss

Musculoskeletal: arthralgias/arthritis (20% to 70%); associated with antisynthetase antibody syndrome

Pulmonary: interstitial lung disease (70% of patients with antisynthetase antibodies); aspiration pneumonia; respiratory muscle weakness; pulmonary hypertension (ILD: anti-MDA-5, anti-Ro52, anti-PM-Scl, anti-Synthetase )

Gastrointestinal: esophageal dysmotility (10% to 30%); reflux due to lower esophageal sphincter weakness (15% to 50%); rectal incontinence due to sphincter ani weakness; intestinal perforation due to vasculitis (primarily in juvenile DM)

Cardiac: ECG abnormalities (dysrhythmias, conduction blocks); myocarditis

Vascular: vasculitis (juvenile DM), skin ulcerations (juvenile DM); livedo reticularis, Raynaud’s phenomenon (20% to 40%)

Other: manifestations of other connective tissue diseases when PM/DM occurs in “overlap” syndromes or in association with mixed connective tissue disease (MCTD)

Association between PM/DM and underlying neoplastic disease (anti-TIF1-gamma, anti-NXP2)

Associated cancers are present in about 10% to 20% of adult (not juvenile) patients with PM/DM and over 50% of patients who develop PM/DM after age 65 years old. Most have DM (80%) with the remainder having PM (20%). The malignancy is present at onset of myositis or within the first year in 68%. If associated with a malignancy, the cancer almost always occurs within 3 years of myositis onset. Cancers reported in association with PM/DM include, among others, breast, lung, pancreas, stomach, colon, ovary, and Hodgkin’s lymphoma. Taiwanese patients also have nasopharyngeal and cervical tumors.

--> Ulcerative skin lesions in an adult DM patient are highly associated with an underlying malignancy.

Therapy options

Pdn, MTX, AZA, HC, Cyc, calcineurin inhibitors, MMF, IVIG, plasmapheresis, RTX

Myositis-specific Autoantibodies

Differential Diagnosis of Myopathies

Pubmed

UpToDate

Images

Video

Web:

Focal muscular atrophies - Medscape

myositis.org

Dermatomyositis - NINDS NIH

Inflammatory Myopathy - NINDS NIH Inflammatory Myopathies

Myositis ossificans

Antibodies in Myositis

Cancer Therapy Advisor

Inclusion Body Myositis

Amyopathic dermatomyositis - NIH