Pathophysiology
Summary
Polymyositis and dermatomyositis, predominantly observed in women, are inflammatory myopathies that impact muscle fibers and present with a range of clinical symptoms.
The pathogenesis of polymyositis begins with increased expression of MHC I on the sarcolemma of striated muscle cells. This allows autoantigens to be presented to CD8+ cytotoxic T-cells, thus setting off the cascade leading to muscle fiber destruction. Muscle biopsy in polymyositis illustrates features such as inflammation, myocyte necrosis, regeneration of muscle fibers, fibrosis, and a distinctive endomysial inflammatory infiltrate, where inflammatory cells surround individual muscle fibers within the fascicle.
Dermatomyositis distinguishes itself by affecting not only the muscle fibers but also their nourishing capillaries. Its pathogenesis centers on the upregulation of type 1 interferon, leading to both myofiber and capillary injury. Muscle biopsy findings in are marked by a perimysial inflammatory infiltrate where inflammatory cells envelop the entire muscle fascicle. A notable histologic feature is the perifascicular muscle cell injury localized to one segment of the fascicle, indicative of localized microinfarcts. Dermatomyositis uniquely presents with skin manifestations, including Gottron’s papules—violaceous papules over joints and bony prominences, especially the dorsal metacarpophalangeal and interphalangeal joints of the hands, as well as a violaceous heliotrope rash on the upper eyelids. Dermatomyositis can also increase the risk of developing adenocarcinoma, particularly of the lungs and ovaries.
Both polymyositis and dermatomyositis clinically manifest with symmetric proximal muscle weakness affecting both upper & lower extremities. This manifests clinically as difficulty in arm elevation due to deltoid muscle impairment and challenges in rising from a seated position due to hip flexor weakness. Other shared clinical signs and symptoms between the two include myalgias, interstitial lung disease, increased creatine kinase, and the presence of anti-JO-1 antibodies, also known as anti-tRNA or antisynthetase antibodies.
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FAQs
Both polymyositis and dermatomyositis are inflammatory myopathies, but they differ in their underlying pathologies. In polymyositis, there's an increased expression of MHC I on the sarcolemma, leading to the activation of CD8+ cytotoxic T cells that initiate myofiber destruction, with muscle biopsies showing endomysial inflammatory infiltrate. In contrast, dermatomyositis involves the upregulation of type 1 interferon, causing injury to both muscle fibers and their feeding capillaries. Muscle biopsies in dermatomyositis display perimysial inflammatory infiltrate and perifascicular muscle cell injury.
Both polymyositis and dermatomyositis present with symmetric proximal muscle weakness, affecting both the upper and lower extremities. This results in challenges like raising arms above the head or rising from a chair. Other shared symptoms include myalgias, interstitial lung disease, and elevated levels of creatine kinase, indicating muscle cell death.
Dermatomyositis has distinct cutaneous manifestations not seen in polymyositis. Patients may exhibit a violaceous ‘heliotrope rash’ on the upper eyelids and Gottron’s papules, which are violaceous papules over joints and bony prominences. Additionally, dermatomyositis carries an increased risk of adenocarcinoma, especially in the lungs and ovaries.
Diagnosis for both conditions typically involves a muscle biopsy. In polymyositis, the biopsy may reveal endomysial inflammatory infiltrate, while in dermatomyositis, it may show perimysial inflammatory infiltrate and perifascicular muscle cell injury. The presence of anti-JO-1 antibodies, also known as anti-tRNA or antisynthetase antibodies, can also support the diagnosis for both conditions.
While the exact reasons are not fully understood, hormonal differences, particularly the influence of estrogen on the immune system, are believed to play a role in the higher prevalence of these conditions in women. Genetic predispositions combined with environmental triggers might also contribute to the onset of these diseases in females.
