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.