POLYPHARMACY, DRUG RELATED NITROSAMINE CONTAMINATION (BISOPROLOL/PROPAFENONE) AND THE LINK TO LICHEN PLANUS/SUBSEQUENT DEVELOPMENT OF KERATINOCYTE AND MUCOSAL CANCER/ORAL LEUKOPLAKIA: PRESENTATION OF THE FIRST CASE AND UPDATE ON THE NEW PATHOGENETIC VISION.

Abstract

The association between drug-induced lichen planus - whether oral/mucosal or solely cutaneous - involves a diverse range of drugs, including ACE inhibitors, diuretics, and beta blockers, as well as quinidine, NSAIDs, hydroxychloroquine, antiretroviral medications for HIV, penicillamine, TNF inhibitors, and certain medications for type 2 diabetes. The natural course of lichen planus has been also linked in certain cases to the development of squamous cell carcinoma, affecting both mucous membranes and skin, as extensively documented in the literature. However, little attention has been given to the fact that many of the medications associated with lichen planus - such as ACE inhibitors, diuretics, and beta blockers - are listed by the FDA as contaminated with carcinogenic and mutagenic nitrosamines. These compounds exhibit photocarcinogenic, carcinogenic and mutagenic properties. Their potential role in the progression of lichenoid lesions to oral leukoplakia, oral carcinomas and squamous cell carcinoma, but also strictly cutaneous located tumour has not been previously explored, yet it appears both plausible and significant. We present for the first time in the medical literature, a case of a 91-year-old patient with a 2-year history of oral lichen planus and subsequent oral leukoplakia following 2-year beta-blocker (bisoprolol) and/or anti-arrhythmic (propafenone) administration, with no history of smoking and alcohol consumption, and discuss the possible role of nitrosamines as a cofactor in the malignant transformation of ulcerative lichenoid lesions to oral leukoplakia/mucosal carcinoma. The adverse effects of these medications may be categorized into those related to 1) the active substance - potentially triggering lichen planus and those 2) linked to contaminants/carcinogens/mutagens, such as nitrosamines, which may act as primary or contributory factors in skin carcinogenesis in direction development of oral leukoplakia and oral/cutaneous carcinomas.