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 ¼ .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 ¼ .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. Cancer 2013;119:825-31.

Granulomatous inflammation in secondary syphilis is rare and poses diagnostic challenges both on clinical grounds and histologically. We report a case of granulomatous syphilis in a 44-year-old woman that presented with an erythematous papulo-nodular rash involving her face, neck and upper portions of chest, back and arms that was initially diagnosed as urticaria and treated ineffectively with systemic steroids. No mucosal or genital lesions, involvement of soles and palms, or lymphadenopathy was present. Histopathologic examination revealed dense dermal perivascular and periadnexal inflammatory infiltrate composed of lymphocytes and plasma cells accompanied by prominent granulomatous inflammation. Anti-treponemal immunohistochemical study revealed spirochetes and along with positive serology, supporting the diagnosis of secondary syphilis. With an increasing number of reported syphilis cases recently, internists, infectious disease specialists, dermatologists and dermatopathologists alike should be aware of the unusual presentations of this great imitator. We also present a review of literature of cases of secondary syphilis that present in such unusual clinical and histologic phenotypes.