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Dermatomyositis

The onset of weakness in DM is usually acute to subacute, worsening over several weeks. It is more common in females than males. The weakness is proximal and typically symmetrical. Difficulty with swallowing and with speech may occur along with neck weakness sometimes leading to head drop. A characteristic purplish- colored (heliotrope) skin rash occurs over the eyelids and upper chest (in a V-pattern if anterior and in a shawl pattern if posterior), the dorsal metacarpal and interphalangeal joints, and the extensor surface of the elbows, knuckles (Gottron papules), knees, and ankles. The nails may be involved and show dilated capillary loops at the base of the nails [2, 5, 6, 8]. In children, the rash may be more severe and there can sometimes be subcutaneous calcifications. About 6% of patients have no skin abnormalities. There is also a small group of patients that have skin manifestations of DM with no evidence of muscular involvement [5]. Other systemic manifestations include interstitial lung disease, cardiac abnormalities, and malignancies. Malignancies include lung, ovarian, and various GI cancers (pancreas, stomach, colon/rectal). Juvenile DM is associated with a high incidence of leukemia and lymphoma [13].

Evaluation after neuromuscular examination includes screening laboratory studies considering other causes of muscle weakness, including the muscular dystrophies, metabolic myopathies (Pompe’s disease, McArdle’s disease), mitochondrial myopathies, and thyroid-related myopathies. An acute or subacute onset is much more typical of inflammatory myopathy [10]. The creatine kinase (CK) and aldolase levels are typically elevated, up to 50 times the upper limit of normal, though normal values can also occur. Electrodiagnostic studies reveal normal nerve conduction velocities. The needle electrode exam acutely shows evidence of “myopathic” motor units with brief duration, low amplitude, polyphasic units. EMG also shows evidence of increased insertional activity with spontaneous positive waves and fibrillations seen prominently. There is early recruitment of motor units. Complex repetitive discharges may be identified. This activity may occur in any muscle, including paraspinous groups. The EMG may be helpful in identifying muscle suitable for biopsy [2, 5, 6, 8]. Magnetic resonance imaging of the muscle may show changes suggesting active inflammation, edema, and fatty infiltration. It can also help in identifying muscles suitable for biopsy [11]. Muscle biopsy shows evidence of perivascular, perimysial, and perifascicular inflammation. There is deposition of membrane attack complex (MAC) around small blood vessels that is seen early. Inflammatory infiltrates consist of macrophages, B cells, and CD4+ plasmacytoid dendritic cells. There is evidence of perifascicular atrophy (which is the classic pathological finding in DM) and decrease in capillary density at the periphery of the fascicle. Invasion of non-necrotic muscle fibers is not prominent in DM. Electron microscopy has shown tubuloreticular inclusions in the intramuscular arterioles and capillaries (Fig. 12.1a-e) [2, 5, 6, 8].

A number of myositis-specific antibodies may be associated with both DM and, in some cases, PM. Anti-Mi-2 autoantibody is associated with classical DM associated with typical skin lesions. Its presence is associated with a good response to treatment and a lower incidence of underlying cancer. The anti-TIF-1 gamma

(transcriptional intermediary factor 1) antibody is predictive of malignancy. NXP-2 (nuclear matrix protein 2) may be positive in younger patients with subcutaneous calcinosis but also suggests a high incidence of malignancy. The anti-Jo antibody (anti-histidyl-transfer RNA synthetase) occurs in both PM and DM. Patients with this antibody may develop an anti-synthetase syndrome consisting of fever, arthralgia, Raynaud’s phenomena, interstitial lung disease, seronegative arthritis, mechanics hands (roughening and cracking of skin), and a rash that differs from the typical rash of DM. Interstitial lung disease is common, seen in 75-90% of cases [3].

The cause of DM is not known, but there appears to be an autoimmune pathogenesis. Membrane attack complex is activated and is deposited on endothelial cells. This leads to necrosis and reduction of endomysial capillaries and ischemia. There is muscle fiber destruction that resembles microinfarcts. The hypoperfusion related to these changes leads to the perifascicular atrophy seen in tissue biopsies. Release of proinflammatory cytokines upregulates adhesion molecules on endothelial cells. This facilitates migration of B cells, CD+4 T cells, and plasmacytoid dendritic cells to perimysial and endomysial spaces. There are also molecular biomarkers of type 1 interferon in both muscle and skin of patients with DM [5, 8].

 
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