Coexistent Solid Malignancies in Pemphigus: A Population-Based Study

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Abstract

Importance

The association of pemphigus vulgaris and pemphigus foliaceus with comorbid malignancies is yet to be firmly established.

Objective

To estimate the association between pemphigus and a wide range of nonhematologic malignancies using one of the largest cohorts of patients with pemphigus to date.

Design, Setting, and Participants

For this cross-sectional study, we used the computerized database of Clalit Health Services, the largest public health care provider organization in Israel insuring 4.4 million individuals in the settings of general community clinics, primary care and referral centers, and ambulatory and hospitalized health care. The study included 1985 patients with pemphigus and 9874 control patients and was conducted from January 2004 to December 2014.

Main Outcomes and Measures

The prevalence of 17 different solid malignancies was compared between patients diagnosed with pemphigus and age-, sex-, and ethnicity-matched control patients; χ2 and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The association was examined following a sensitivity analysis that included only cases treated with long-term pemphigus-specific medications (corticosteroids, immunosuppressants, or rituximab), and following the adjustment for several confounding factors.

Results

Overall, the total sample included 11 859 eligible patients, of whom 1985 were patients with pemphigus (mean [SD] age at presentation, 72.1 [18.5] years; 1188 women [59.8%]). In patients with pemphigus compared with control patients, there was a greater prevalence of esophageal cancers (0.4% vs 0.1%; odds ratio [OR], 2.9; 95% CI, 1.1-7.4) and laryngeal cancers (0.6% vs 0.3%; OR, 2.0; 95% CI, 1.0-4.1). No significant associations between pemphigus and other solid malignancies were observed. Estimates were not altered significantly after controlling for comorbidities, health care overutilization, immunosuppressive therapy, and other malignancy-specific risk factors (ie, smoking and alcohol abuse in laryngeal cancer, gastroesophageal reflux disease in esophageal cancer).

Conclusions and Relevance

Significant associations were observed between pemphigus and solid malignancies of the larynx and the esophagus. Physicians treating patients with pemphigus should be aware of these findings. Further observational studies are warranted to establish this association in other cohorts.

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