Case Presentation: A 69 year-old woman with recently diagnosed endometrial cancer presented with two weeks of dysphagia and progressive upper extremity weakness. On exam she was dysarthric with oral mucous retention and poor dentition; she had left supraclavicular lymphadenopathy. Neurologically, cranial nerves were intact except shoulder shrug, and shoulder girdle strength was 3+/5 bilaterally with normal distal upper and lower extremity strength. Video swallow demonstrated poor pharyngeal wall movement, reduced tongue base retraction, and a flaccid velum. Creatinine Phosphokinase (CPK) was normal at 117 U/L; one month prior it was elevated at 4456 U/L and diagnosed as idiopathic rhabdomyolysis. Aldolase was elevated and Myositis-Specific Antibodies were positive to TIF-1γ and P155/140.
Electromyography displayed a diffuse irritable myopathy. Bicep muscle biopsy revealed necrotizing myopathy with mild lymphocyte involvement. Lymph node biopsy confirmed clear cell carcinoma, gynecological in origin.
Her weakness, dyspnea, and dysphagia progressed despite prednisone and a 4-day course of IVIG. Due to disease extent and declining functional status, she was a poor chemotherapy candidate and was ultimately discharged with hospice.
Discussion: Hospitalists need to recognize the presentation of immune-mediated myopathies (IMM), as the disease is progressive and early treatment can lead to a favorable outcome. All IMMs are characterized by subacute symmetric proximal muscle weakness. In necrotizing myopathy, weakness can be prominent in neck muscles and be associated with dysphagia and respiratory muscle fatigue. Positive Myositis-Specific Antibodies are helpful in the diagnosis, but timing of results limits their utility and one-third have no detectable antibody. An elevated CPK and an EMG consistent with irritant myopathy should raise suspicion for an inflammatory myopathy—especially in the setting of a known or suspected malignancy.
Recently, the link between cancer and IMM has been clearly described, with the main clinical subtypes being polymyositis, dermatomyositis, and immune-mediated necrotizing myopathy. Cancer associated myopathy (CAM) occurs in 20% of IMM cases, with cancer diagnosis arising 3 years before or after myopathy. The diagnosis of IMM relies on clinical and pathologic findings; a biopsy of affected muscle should be obtained, though treatment should not be delayed.
In addition to targeting the malignancy, the mainstay of treatment for CAM is immunosuppression—systemic steroids and another agent, such as intravenous immunoglobulin, methotrexate, cyclosporine, and mycophenolate. Treatment duration will be prolonged and clinical improvement, not CK levels, will indicate disease activity. Weaning immunotherapy is associated with a high relapse rate, so life long steroids may be indicated.
Conclusions: Malignancy and immune mediated myopathy have a significant link that continues to be elucidated. Early recognition and treatment is key to successful management. Therefore, it is important for hospitalists to understand the disease process and to identify it properly.