Comparing the Clinical and Histological Diagnosis of Leprosy and Leprosy Reactions in the INFIR Cohort of Indian Patients with Multibacillary Leprosy

Diana N J Lockwood,Wim Van Brakel,W Cairns S Smith,Sujai Suneetha,Peter Nicholls,Loretta Das,Pramila Barkataki

doi:10.1371/journal.pntd.0001702

Abstract

BackgroundThe ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment in leprosy. The aim was to study correlations between clinical and histological diagnosis of reactions.Methodology/Principal FindingsThree hundred and three newly diagnosed patients with World Health Organization multibacillary (MB) leprosy from two centres in India were enrolled in the study. Skin biopsies taken at enrolment were assessed using a standardised proforma to collect data on the histological diagnosis of leprosy, leprosy reactions and the certainty level of the diagnosis. The pathologist diagnosed definite or probable Type 1 Reactions (T1R) in 113 of 265 biopsies from patients at risk of developing reactions whereas clinicians diagnosed skin only reactions in 39 patients and 19 with skin and nerve involvement. Patients with Borderline Tuberculoid (BT) leprosy had a clinical diagnosis rate of reactions of 43% and a histological diagnosis rate of 61%; for patients with Borderline Lepromatous (BL) leprosy the clinical and histological diagnosis rates were 53.7% and 46.2% respectively. The sensitivity and specificity of clinical diagnosis for T1R was 53.1% and 61.9% for BT patients and 61.1% and 71.0% for BL patients. Erythema Nodosum Leprosum (ENL) was diagnosed clinically in two patients but histologically in 13 patients. The Ridley-Jopling classification of patients (n = 303) was 42.8% BT, 27.4% BL, 9.4% Lepromatous Leprosy (LL), 13.0% Indeterminate and 7.4% with non-specific inflammation. This data shows that MB classification is very heterogeneous and encompasses patients with no detectable bacteria and high immunological activity through to patients with high bacterial loads.Conclusions/SignificanceLeprosy reactions may be under-diagnosed by clinicians and increasing biopsy rates would help in the diagnosis of reactions. Future studies should look at sub-clinical T1R and ENL and whether they have impact on clinical outcomes.

Highlights

Diagnosing leprosy and the immunological reactions that complicate this disease is not always straightforward
Borderline Tuberculoid (BT) was the main clinical diagnosis, comprising 59.5% of the patients, but 41% were reclassified after histological diagnosis: 24 (13%) to Borderline Lepromatous (BL), two to Lepromatous Leprosy (LL) and 32 and 15 to indeterminate and no significant lesion (NSL) respectively
Patients in the BL group were re-classified after histological diagnosis, with 17 going to BT, nine to LL and two and three to indeterminate and NSL respectively

Summary

Introduction

Diagnosing leprosy and the immunological reactions that complicate this disease is not always straightforward. Leprosy skin lesions can have a very variable appearance and the presence of inflammation which is associated with immune reactions is not always obvious. Patients with definite clinical evidence of MB leprosy were recruited to the cohort. All patients had a skin biopsy on recruitment. [1] The serological studies showed that LAM IgG1 antibody levels were significantly elevated in patients with skin reactions and nerve function impairment (NFI). [2] The immuno-histological studies in skin biopsies have shown a significant association between the presence of three cytokine proteins, TNF-a, iNOS and TGF-b, and Type 1 Reactions (T1R) in skin and nerve damage. The aim was to study correlations between clinical and histological diagnosis of reactions

Methods

Results

Discussion

Conclusion