Transepidermal Elimination in Cutaneous Leishmaniasis: a Multiregional Study

Background: Transepidermal elimination has been documented in a myriad of infectious diseases; however, its occurrence in cutaneous leishmaniasis has not been evaluated.

Methods: Skin biopsies (n = 212) with cutaneous leishmaniasis in Lebanon (n = 46), Syria (n = 53), Saudi Arabia (n = 45) and Pakistan (n = 68) were evaluated. Clinical data collected included age, gender, eruption type (papule, nodule, verrucous or scar), duration and anatomic location. Histopathologically, multiple parameters were recorded including Ridley's parasitic index and pattern, transepidermal elimination, interface changes, ulceration and necrosis. Transepidermal elimination was defined as the presence of amastigotes in the epidermis in all layers, limited to the basal layer or present in a perforating plug. All cases were confirmed by polymerase chain reaction (PCR) analysis followed by restriction fragment length polymorphism analysis for molecular subspeciation.

Results: Leishmania tropica was identified in 88.2% and Leishmania major in 11.8% of all cases. Transepidermal elimination was observed in 28.3% of cases (29 perforating plug, 19 all layers and 12 basal layer) with a significant prevalence of L. major in this group (35 vs. 2%, p < 0.001). Cases with transepidermal elimination were associated with interface changes and higher parasitic index (p < 0.001) but not with an increased ulceration rate (p > 0.05). Multivariate analysis showed that transepidermal elimination was independently predicted by L. major [OR (95% confidence interval) = 80 (9-712); p < 0.001], parasitic index [OR = 3.4 (2.1-5.3); p < 0.001], interface changes [OR = 6.24 (2.2-17.8); p < 0.001] and necrosis [OR = 0.2 (0.1-0.8);p = 0.026].

Conclusions: We report the largest multiregional cutaneous leishmaniasis series with a 28.3% documented transepidermal elimination incidence of which 48% were perforating plug; a significant prevalence of L. major was also identified in the transepidermal elimination group. The association of transepidermal elimination with interface changes and a higher parasitic index, without an increased ulceration rate, may reflect a unique biologic alteration in the epidermis, serving to facilitate the extrusion of the parasites through the skin.