A 46-year-old woman presented for medical evaluation due to a 2-month history of increasing difficulty in ambulation, especially getting up out of a chair or climbing stairs. She had also noticed swelling and discoloration of both upper eyelids (as depicted) and some small erythematous papules on the dorsum of several fingers on both hands. Routine blood work was within normal limits except for an elevated erythrocyte sedimentation rate (ESR).
E. All of the above
This patient has presented with several of the classic features of dematomyositis (DM), a rare immune-mediated disease most commonly affecting the musculoskeletal system and skin. Her symptoms and blood work point to an inflammatory myopathy, and the heliotrope and Gottron papules are typical cutaneous manifestations of the disorder. She lacked a poikilodermatous rash involving the chest, shoulders, and/or upper back.
DM has long been considered a sign of underlying malignancy, although the rate of neoplasia in published series from assorted investigational sites has varied widely: from just over 10% to nearly 50%.[1-10] Published series agree, however, that malignancy can precede, present concomitant with, or follow the diagnosis of DM. Published series also concur that, all other factors being equal, DM patients with an associated malignancy generally have a poorer prognosis due to accelerated cancer progression. Nonetheless, since over 60% have detectable malignancy at the time of DM diagnosis (or within 3 months thereof), a relatively extensive workup is indicated at initial presentation. Moreover, since the risk of malignancy remains elevated for up to 5 years [6,10] and the initial workup may be falsely negative in up to 15% of patients, yearly reexaminations are indicated.
A wide variety of malignancies have been associated with DM, most commonly: bronchogenic carcinoma; Non-Hodgkin lymphoma; and cancers of the breast, colorectal region, lung, ovary, pancreas, and stomach.[6,9,10] Asian patients with DM are at risk for nasopharyngeal carcinoma. While there are contradictory results with regard to age, gender, and absolute CPK and ESR measurements, other factors do seem to be more consistently suggestive of malignancy-associated DM. These include the rapidity of onset and severity of DM at the time of presentation, and the presence of periungual telangiectasia and skin necrosis.[2,8,10,11]
Because DM is an autoimmune disease, a variety of autoantibodies have been detected in affected patients. These include antibodies directed against: Jo-1 (most common); Mi-2; p155/140; U1 snRNP, PM-Scl, and Ku (overlap syndromes); CADM-140; SRP (refractory disease); PL-7 and PL-12; and SSA. Interestingly, and with notable exception, there is an overall paucity of autoantibody formation in DM associated with cancer.
Finding the anti-155/140-kDa antibody, however, is highly specific and moderately sensitive for DM associated with cancer; conversely, lack of this antibody carries a strong negative predictive value.[12,13] Aside from autoantibody screening, elevated levels of and serial increases in select tumor markers, such as CA-125 and CA 19-9, have been found to be strongly suggestive of malignancy in association with DM.
What tests should be performed on the newly diagnosed DM patient in order to screen for cancer? Certainly there is no disagreement about routine, low-cost, noninvasive maneuvers: detailed history and physical examination, complete blood cell count, complete chemistry panel, urinalysis, stool guiac, chest x-ray, mammogram in women, and prostate-specific antigen (PSA) testing in men. Assuming that the routine screening is entirely negative, the question then becomes: what more should be done? There is no doubt that more extensive evaluation may disclose malignancy missed by the "typical" screening protocol. Two valid approaches have been advocated: CT of chest, abdomen, and pelvis, combined with gastrointestinal endoscopy in older patients or whole body fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT scanning. In a recent 3-year prospective study of 55 patients screened within 6 months of diagnosis, both approaches had about a 93% predictive value, equivalent sensitivity and specificity, and equivalent false-positive and false-negative rates; a combination of these 2 methods did not significantly increase the predictive value.
Because ovarian carcinoma is associated with DM, it is important to adequately screen for this tumor. As has been pointed out previously, a pelvic exam and pelvic CT may be insufficient to detect this cancer.[16,17] Therefore, in newly diagnosed female DM patients, serial CA-125 measurements and a transvaginal ultrasound should be performed to insure thorough evaluation.
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