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

BACKGROUND: Pemphigus is a rare autoimmune vesiculobullous disorder caused by autoantibodies targeting desmosomes. While paraneoplastic pemphigus is known to be associated with malignancy, the cancer risk in non-paraneoplastic pemphigus remains unclear, particularly in Asian populations. OBJECTIVES: This study aims to assess the risk of subsequent malignancies in pemphigus patients compared to matched controls in Taiwan. METHODS: Using Taiwan's National Health Insurance Research Database, a retrospective cohort study was conducted and included 357 pemphigus patients and 1,428 matched controls from 2000 to 2015. Covariates including age and sex, were adjusted using multivariable Cox regression. Adjusted hazard ratios (HRs) 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. Risks of different subsequent cancers were estimated between patients with pemphigus and the control group. RESULTS: Overall cancer risk was not significantly elevated in the pemphigus group (aHR 1.103; p = 0.342). In the sex-stratified analysis, male patients had a higher risk of malignancy compared with female patients (aHR 1.703; p = 0.039). However, after adjusting for covariates in the multivariable Cox regression model, sex was not an independent risk factor for subsequent malignancy (aHR 1.129; p = 0.321 and aHR 1.074; p = 0.367, respectively). Lymphatic and haematopoietic malignancies were correlated with the highest risk in pemphigus patients (aHR 2.903; p < 0.001). Median follow-up durations were 6.37 years in the pemphigus cohort and 6.45 years in the control cohort, yielding an overall median follow-up duration of 6.4 years. CONCLUSIONS: Pemphigus was not associated with an overall increased risk of subsequent malignancy. Sex was not an independent risk factor; however, males exhibited a higher cancer risk compared with females. Among specific cancer types, lymphatic and haematopoietic malignancies showed the strongest association with pemphigus.