Dermatomyositis
Dermatomyositis is an idiopathic inflammatory disease characterized by skeletal muscle weakness, inflammation, and various skin problems101. It can occur spontaneously as a drug reaction or paraneoplastic phenomenon102. The histopathologic and typical cutaneous changes in DM include hyperkeratosis, epidermal basal cell vacuolar degeneration, thinning of the epidermis and dermal mucin deposition and perivascular infiltrate composed of CD4+ lymphocytes103. Dermatomyositis eventually causes damage to both parenchyma and blood vessels, which results in the histologic appearance of perimysial, perifascicular atrophy in muscle as well as keratinocyte injury in the skin104. Dermatomyositis indicates persistent skin changes and includes a heliotrope rash, macular violaceous erythema (shawl sign, v-neck rash, holster sign), and an erythematous rash that may be distributed all over the joints. Pruritic papules (Gottron’s sign and Gottron’s papules) are a characteristic rash initiated on the extensor surfaces of the small joints of the hands. Pruritic papules along with heliotrope rash seem to be a disease-specific cutaneous manifestation105
Pathogenesis: The histopathological findings of DM in muscle fiber include perifascicular atrophy, swelling of endothelial cells, capillary necrosis, up-regulation of major histocompatibility complex (MHC) I, and occurrence of an inflammatory cell infiltration composed of T lymphocytes, macrophages, and plasma cells106. The Inflammatory cell infiltration in DM is composed of CD4+T lymphocyte, including interferon-α (IFNα) producing plasmacytoid dendritic cells (pDCs), Th-1 cells produced by IFN-y and Interleukin (IL)-17 released by the Th17 cells, mainly distributed in the perivascular localization mostly in the perimysium. The production of Th17 cells by Interleukin (IL)-17, in turn, activates the release of proinflammatory Th1 cytokines such as IL-2, IL-1, IL-6, thus results in the proliferation of MHC class I expression on muscle fibers. The up-regulation of MHC I may directly cause muscle damage via stimulation of a cytotoxic T cell host response107. IL-15 also stimulates the activation of cytotoxic CD8+ lymphocytes which stimulates the proliferation of myoblast endothelial cells104. The active involvement of the CD40/CD40 ligand (CD40L) system within the skin has been recently implicated in the pathogenesis of DM. There are elevated levels of CD40+ cells (which includes keratinocytes and mononuclear cells in the dermis) and CD4+ CD40L+ T lymphocytes have been reported in the skin biopsies from a patient with DM. Stimulation of CD40/CD40L system may be responsible for the up-regulation of several proinflammatory molecules, including IL-6, IL-15, IL-8 and MCP-1 causing keratinocyte apoptosis and inflammation at the basal cell layers and support an autoimmune etiology of dermatomyositis106.
Clinical incidence : Fifteen cases of dermatomyositis were reported with anti-PD-1/PD-L1 immunotherapy out of which nine cases were associated with nivolumab102, 108-114, four cases with pembrolizumab114-117, one with atezolizumab118, and one with durvalumab119 immunotherapy. Most of the patients with DM had raised muscle enzymes (e.g., creatine kinase, aldolase) and inflammatory markers (e.g., C-reactive protein). Several auto-antibodies associated with dermatomyositis include anti-synthetase (anti-Jo-1), anti-transcription intermediary factor-1-gamma (TIF1γ)110, 111. A case with paraneoplastic dermatomyositis had been reported after the initiation of nivolumab therapy109.
Treatment: The potent treatment of dermatomyositis included systemic corticosteroids, prednisone methylprednisolone, topical triamcinolone 0.1% cream to involved areas, and clobetasol 0.05% ointment. Several cases were reported, where patients received IV immunoglobulin treatment (IVIG) 102, 110, 117.