Histological findings associated with treatment response in cutaneous leishmaniasis: a clinicopathological correlation study

Abstract

Background: Treatment responses to cutaneous leishmaniasis (CL) observed in Sri Lanka show variability, ranging from quick healing to delayed or failed responses to routine medication. The determinants of these differences in treatment response are not well defined. This study aimed to identify predictive features of treatment response and outcome in localized CL caused by Leishmania donovani, focusing on both clinical and histopathological findings in the patients.

Methods: Tissue sections (n = 103) derived from 3 mm punch biopsies of parasitologically confirmed patients were assessed. Patients were followed up weekly until complete healing of skin lesions and were reviewed at the end of 6 months and 1 year.

Results: Healing required 7-21 weekly doses of intralesional sodium stibogluconate (IL-SSG) (mean = 12.2 ± 0.622). Twenty-nine (28.1%) patients were identified as delayed responders. None had recurred at the end of 1 year. The demographic or clinical features (age, gender, lesion type, size, location, and lesion duration) did not significantly influence the treatment response. A heavy parasite load and acanthosis were significant predictors of a delayed response to treatment (P < 0.001). Higher parasite loads were associated with inflammation of the entire dermis (P = 0.008), more intense infiltration of macrophages (p = 0.001), and epidermal atrophy (P = 0.033). Well-formed granulomas were inversely proportional to parasite loads.

Conclusions: Histology findings proved to be better prognostic markers than clinical features for delayed responders to treatment and will aid in targeted patient management when tissue biopsies are performed in the initial diagnosis of CL.

Figure 1

Distribution of study participants (CL patients) in the district of Anuradhapura in Central Sri Lanka 26 patients (25%) were recorded as the first case from their home territory (Areas indicated in red). The geographical spread of these newly identified patients suggests that the disease is now also prevalent in urban areas which favours the existence of anthroponotic transmission cycles or a role for domestic pets as reservoir hosts on which there is a dearth of information in the local setting.

Figure 2

Different types of CL lesions found in Sri Lanka (a) Papule (b) Nodule (c) Nodule (d) Nodule (ulcerated) (e) Ulcer (f) Plaque (ulcerated)

Figure 3

Dermal and epidermal features of cutaneous leishmaniasis stained with H&E (a) to (d) x100 magnification & (e) to (h) x400 magnification (a) Granuloma formation (b) Giant cell (c) Langhan cell (horse shoe type) (d) Plasma cells (e) Acanthosis (f) Atrophy (g) Oedema (h) Parakeratosis & Follicular plugging

Figure 4

Progression of the lesion with SSG doses (a) Ulcerated nodule below the left eye healing over 7 weeks (b) Ulcerated nodule on right forearm healing over 10 weeks

Figure 5:

Association between the parasite load and the treatment response The number of treatment doses of 69 patients who did not show any LD bodies (mean=10.76, SD=2.01) when compared to the 9 patients who showed moderate level of LD bodies (mean=11.78, SD=2.54) did not demonstrate significant difference in the number of treatment doses required for complete healing, t(78)=−1.38, p>0.05. *The number of treatment doses of 69 patients who did not show any LD bodies (mean=10.76, SD=2.01) when compared to the 25 patients who showed higher level of LD bodies (mean=16.29, SD=2.66) demonstrated a significant difference in the number of treatment doses required for complete healing, t(94)=−10.61, p<0.01.