Dermatomyositis etiopathogenesis : a rebel soldier in the muscle

Dermatomyositis and polymyositis are associated with cancer, but previous nationwide studies have not had sufficient cases to test the association between myositis and specific cancer types. Our aim was to investigate the risk of specific cancer types in individuals with dermatomyositis and polymyositis. We did a pooled analysis of published national data from Sweden, Denmark, and Finland. All patients with dermatomyositis and polymyositis (> or =15 years old) were identified by discharge diagnosis from the Swedish National Board of Health (1964-83), Danish Hospital Discharge Registry (1977-89), and Finnish National Board of Health (1969-85). Personal details were matched to national cancer registries, to identify all cases of cancer up to 1987 in Sweden, 1995 in Denmark, and 1997 in Finland, and to national death registries for the same periods. We calculated standardised incidence ratios (SIR) for individual cancer sites for dermatomyositis and polymyositis separately, using national cancer rates by country, sex, age, and date. We identified 618 cases of dermatomyositis, of whom 198 had cancer. 115 of the 198 developed cancer after diagnosis of dermatomyositis. This disease was strongly associated with malignant disease (SIR 3.0, 95% CI 2.5-3.6), particularly ovarian (10.5, 6.1-18.1), lung (5.9, 3.7-9.2), pancreatic (3.8, 1.6-9.0), stomach (3.5, 1.7-7.3), and colorectal (2.5, 1.4-4.4) cancers, and non-Hodgkin lymphoma (3.6, 1.2-11.1). 137 of the 914 cases of polymyositis had cancer, which developed after diagnosis of polymyositis in 95. Polymyositis was associated with a raised risk of non-Hodgkin lymphoma (3.7, 1.7-8.2), and lung (2.8, 1.8-4.4) and bladder cancers (2.4, 1.3-4.7). In both dermatomyositis and polymyositis, risk of malignant disease was highest at time of myositis diagnosis. Our results provide evidence that dermatomyositis is strongly associated with a wide range of cancers. The overall risk of malignant disease is also modestly increased among patients with polymyositis, with an excess for some cancers.

Since dermatomyositis (DM) is associated with an increased risk of malignancy, accurate identification of patients likely to harbor cancers is important. Using immunoprecipitations from radiolabeled cell lysates, several groups recently showed that anti-transcription intermediary factor 1γ (anti-TIF-1γ) antibodies are associated with malignancy in DM. We undertook this study to develop sensitive, specific assays to detect antibodies against TIF-1γ and nuclear matrix protein NXP-2 and to evaluate their association with malignancy in DM. To detect anti-TIF-1γ antibodies, immunoprecipitations were performed using lysates made from HeLa cells overexpressing TIF-1γ, with detection by immunoblotting. Anti-NXP-2 antibodies were assayed by immunoprecipitation using (35) S-methionine-labeled NXP-2 generated by in vitro transcription/translation. We analyzed patient sera from DM cohorts seen at the Stanford University Dermatology Clinic (n = 111) and the Johns Hopkins Myositis Center (n = 102). A total of 17% and 38% of patients had antibodies against NXP-2 and TIF-1γ, respectively. Reactivity against either NXP-2 or TIF-1γ identified 83% of patients with cancer-associated DM. In addition to older age and male sex, cancer was associated with antibodies to NXP-2 or TIF-1γ on multivariate analysis (odds ratio 3.78 [95% confidence interval 1.33-10.8]). Stratification by sex revealed that anti-NXP-2 was specifically associated with cancer in males (odds ratio 5.78 [95% confidence interval 1.35-24.7]). These studies demonstrate that anti-NXP-2 and anti-TIF-1γ antibodies are frequent DM specificities (found in 55% of patients) and are present in most patients with cancer-associated DM. Copyright © 2013 by the American College of Rheumatology.

Anti-p155 autoantibody, which was recently described in adult patients with dermatomyositis (DM), seems to be associated with cancer in this population. We performed a systematic review and meta-analysis to ascertain the accuracy of anti-p155 testing for the diagnosis of cancer-associated myositis. We searched relevant databases, with no restrictions on study design or language, for original studies that included adult patients with probable/definite DM or amyopathic DM who were evaluated for neoplasm and anti-p155 status. Pooled sensitivity and specificity were calculated using a bivariate model. We computed the diagnostic odds ratio (OR), likelihood ratios (LRs) for positive and negative test results, positive and negative predictive values, and the summary receiver operating characteristic (SROC) curve. Statistical heterogeneity between studies was assessed using the I(2) statistic, and 95% confidence intervals (95% CIs) were computed for the parameters studied. Six studies including a total of 312 adult patients with DM were selected. The pooled sensitivity of anti-p155 for diagnosing cancer-associated DM was 78% (95% CI 45-94%), and specificity was 89% (95% CI 82-93%). The diagnostic OR was 27.26 (95% CI 6.59-112.82), and LRs for positive and negative test results were 6.79 (95% CI 4.11-11.23) and 0.25 (95% CI 0.08-0.76), respectively. Heterogeneity was substantial except with regard to the LR for a positive test result. The area under the SROC curve was 0.91 (95% CI 0.88-0.93). Taking the pooled prevalence of 17% as pretest probability, anti-p155 had a positive predictive value of 58% and a negative predictive value of 95%. Our findings indicate that anti-p155 autoantibody determination is useful for diagnosing cancer-associated myositis and guiding disease management. Copyright © 2012 by the American College of Rheumatology.