Dermatology and Global Health Meet Pharmacogenomics: Cutaneous Leishmaniasis

To date, neither dermatology nor global health has received adequate attention in the pharmacogenomics literature. Yet, the skin diseases are very common worldwide and in addition, the skin is frequently afflicted by many infectious diseases that constitute a public health problem. Cutaneous leishmaniasis is a complex vector-borne protozoan infection endemic worldwide in the tropics and the subtropics. It afflicts predominantly low socioeconomic groups who are least able to afford effective drug therapies. It has a diverse clinical spectrum and disease expression that depends on Leishmania protozoan species, vector virulence factors and host immune responses. Despite a myriad of therapeutic options, treatment outcomes are vastly variable and characterized by poor drug efficacy and toxicity. Epidemiological studies and inter-ethnic differences in disease presentation suggest genetic susceptibility. Indeed, the family and association studies have identified HLA- and non-HLA gene associations. Progress in leishmaniasis susceptibility gene identification has important implications for defining prognostic markers, identifying novel molecular targets for drug development, and pharmacogenetics-guided stratified therapy. Importantly, the genetic markers that determine those at risk of progressing to the destructive mucocutaneous variant have significant implications for drug selection and allocation. Pharmacogenetic profiling will also impact drug trials of cutaneous leishmaniasis which hitherto have been characterized by poor study design. This paper details the progress and recent developments in host genetics in both the mouse model and human studies of cutaneous leishmaniasis, and discusses the difficulties of extrapolating findings to other clinical phenotypes and endemic regions because of disease complexity and heterogeneity.