Systematic Review Reveals BT Leprosy and Type 1 Reactions as Primary L-IRIS Presentations
A recent systematic review published in the Indian Journal of Sexually Transmitted Diseases and AIDS in December 2025 identifies leprosy-associated immune reconstitution inflammatory syndrome (L-IRIS) as a major clinical challenge, frequently surfacing as borderline tuberculoid leprosy and acute type 1 reactions during early immune recovery.
Despite nearly 200,000 new leprosy cases annually, the clinical intersection of leprosy and human immunodeficiency virus (HIV) remains under-recognized due to a lack of validated biomarkers and standardized diagnostic criteria. To bridge this gap, Abey Anil and colleagues from the Department of Skin and STD at Vinayaka Mission’s Kirupananda Variyar Medical College and Hospitals conducted the scoping review to map the epidemiological patterns and therapeutic gaps in leprosy-associated immune reconstitution inflammatory syndrome (L-IRIS).
Therefore, the scoping review analyzed 18 original studies published between January 2003 and June 2025, specifically focusing on adults with HIV-leprosy coinfection. By searching major databases like PubMed, Embase, and the Cochrane Library and excluding animal or pediatric research, investigators synthesized evidence on primary clinical outcomes and inflammatory reactions. Key clinical endpoints included multidrug therapy (MDT) response rates, histopathological shifts, and secondary complications such as persistent neuritis.
Key clinical findings of the Review Include:
Geographic Clustering: The review shows that Brazil, India, and French Guiana account for the vast majority of documented cases, mirroring regions where high dual-disease burdens meet robust surveillance.
Clinical Phenotype: Borderline tuberculoid (BT) leprosy was the most prevalent clinical form, with type 1 reactions (T1R) identified as the primary immune event in 74% of evaluated case series.
Temporal Association: Most inflammatory events were unmasked or worsened 2 to 6 months after starting antiretroviral therapy (ART), with a median diagnosis window of 8 to 12 weeks post-initiation.
Immunological Surge: Clinical IRIS often coincided with CD4+ T-cell counts rising from below 100 cells/μL to 200-250 cells/μL, alongside a surge in activated CD8+ T cells reaching up to 77% at the peak of the reaction.
Histopathological Evolution: Post-treatment biopsies revealed a dramatic transition from poorly formed or absent granulomas to robust granulomatous inflammation characterized by CD68⁺ activated macrophage infiltration.
The results suggest that while clinical outcomes are generally favorable when combining standard multidrug therapy with systemic corticosteroids, significant complications such as ulceration occur in up to 22% of patients during intense reversal reactions
Thus, the review conclude healthcare providers should prioritize early dermatological and neurological monitoring for unmasking reactions in patients starting HIV therapy in endemic regions to mitigate the risk of permanent nerve damage
While the review provides a robust framework for understanding L-IRIS, the evidence remains limited regarding marginalized groups and pregnant women, highlighting an attractive opportunity for future research into validated biomarkers and long-term relapse rates
Reference
Anil A, Vellaisamy SG, Manickam N, Gopalan K. Reactivations, paradoxical reactions, and immune reconstitution in human immunodeficiency virus-associated leprosy: A scoping review of global case patterns, immunopathogenesis, and therapeutic gaps. Indian J Sex Transm Dis 2025;46:112-8.
