Association between pemphigus and subsequent malignancy: a nationwide population-based study in Taiwan

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BACKGROUND: Pemphigus is a rare autoimmune vesiculobullous disorder caused by autoantibodies targeting desmosomes. Paraneoplastic pemphigus is known to be associated with malignancy; however, the cancer risk in nonparaneoplastic pemphigus remains unclear, particularly in Asian populations. OBJECTIVES: To assess the risk of subsequent malignancies in patients with pemphigus compared with a matched control group in Taiwan. METHODS: Using Taiwan's National Health Insurance Research Database, a retrospective cohort study was conducted and included 357 patients with pemphigus and 1428 matched control participants from 2000 to 2015. Covariates including age and sex were adjusted using multivariable Cox regression. Adjusted hazard ratios (aHRs) were calculated after controlling for age, sex and comorbidity. Comorbidities were assessed using the Revised Charlson Comorbidity Index, with higher scores indicating greater comorbidity burden. Subsequent overall risk of cancer and risks for specific cancers were estimated for patients with pemphigus and the control group. RESULTS: Overall cancer risk was not significantly elevated in the pemphigus group [aHR 1.10, 95% confidence interval (CI) 0.66-1.47, P = 0.34]. In the sex-stratified analysis, male patients had a higher risk of malignancy compared with female patients (aHR 1.70, 95% CI 1.02-2.30, P = 0.04). However, after adjusting for covariates in the multivariable Cox regression model, sex was not an independent risk factor for subsequent malignancy (male and female patients, aHR 1.13, 95% CI 0.68-1.51, P = 0.32 and aHR 1.07, 95% CI 0.64-1.44, P = 0.37, respectively). Lymphatic and haematopoietic malignancies were correlated with the highest risk in patients with pemphigus (aHR 2.90, 95% CI 1.73-3.88, P < 0.001). Median follow-up durations were 6.37 years (range 0.10-15.89) in the pemphigus group and 6.45 years (range 0.15-15.89) in the control group, yielding an overall median follow-up duration of 6.40 years (0.15-15.91). CONCLUSIONS: Pemphigus was not associated with an overall increased risk of subsequent malignancy. Sex was not an independent risk factor; however, male patients exhibited a higher cancer risk compared with female patients. Among specific cancer types, lymphatic and haematopoietic malignancies showed the strongest association with pemphigus.

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