Hydrochlorothiazide and cutaneous T cell lymphoma: Prospective analysis and case series

Background: Mycosis fungoides (MF) and leukemic Sézary syndrome (SS) are the most common cutaneous T cell lymphomas (CTCL), but their etiology remains unknown. After patients were observed with hydrochlorothiazide (HCTZ)-associated CTCL, HCTZ was examined as a putative chronic antigen in a cohort of prospectively staged patients. METHODS: Demographic and drug exposure data was examined from 1443 confirmed MF and SS patients. Hypertensive CTCL patients were divided into HCTZ users or nonusers for statistical analysis by chi-square and t tests. Causality in a case series was rated by the Naranjo Adverse Drug Reaction Probability Scale. RESULTS: A total of 815 of 1443 MF and SS patients (56.5%) were hypertensive; 205 (25.2%) were taking HCTZ at initial staging. Comparing stage of patients who were using or not using HCTZ, the most significant difference was between stage I and stage IV (odds ratio of 0.45; 95% confidence interval of 0.25-0.78, P =.003), demonstrating reduced likelihood of being stage IV in patients who were on HCTZ. Seventy-seven percent of the MF patients on HCTZ were stage I. A total of 125 patients of 196 (63.8%) started HCTZ prior to developing CTCL lesions, and 35 of 121 (28.0%) started within 1 year of first skin rash. Thirty-six of 125 patients (28.8%) experienced complete or partial remissions after discontinuing HCTZ. A monoclonal T cell receptor rearrangement was detected more frequently in the hypertensive stage I patients not taking HCTZ as compared with those who were (55.3% vs 69.1%, P =.032). Three patients were rechallenged and developed MF lesions that resolved or improved with discontinuation. CONCLUSIONS: HCTZ is commonly prescribed and may be a putative antigen in a small subset of early MF patients. Careful drug histories and a trial off medication are warranted.