# A systematic review of adverse effects associated with systemic corticosteroids in the management of leprosy

## TL;DR

This review summarizes the harmful effects of corticosteroids used to treat leprosy, showing they cause serious issues like infections and metabolic problems, especially in patients with severe reactions.

## Contribution

The study provides the first comprehensive overview of corticosteroid adverse effects in leprosy, emphasizing the need for safer treatment options and better monitoring.

## Key findings

- Metabolic complications, including lipodystrophy, were the most common adverse effects, affecting one-third of patients.
- Infections, particularly tuberculosis, accounted for 75% of corticosteroid-related deaths, especially in those with erythema nodosum leprosum.
- Cataracts and osteoporosis were strongly associated with erythema nodosum leprosum in corticosteroid-treated patients.

## Abstract

Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and Mycobacterium lepromatosis (M. lepromatosis), primarily affecting the skin and peripheral nervous system. Leprosy is complicated by immune-mediated reactions which are risk factors for nerve damage and disability. Systemic corticosteroids are the mainstay of therapy; however, prolonged use in chronic or recurrent reactions carries significant risks but the evidence on the short- and long-term adverse effects of corticosteroids in leprosy is limited. We conducted a systematic review to evaluate corticosteroid-associated adverse effects in leprosy affected individuals.

Eight electronic databases were searched (including PubMed, Embase and LILACS) without language or year restriction for studies reporting adverse effects associated with systemic corticosteroid use in individuals with leprosy. Eligible studies included randomised controlled trials, observational studies, case series and case reports. Data variability was assessed using Stata software.

A total of 111 studies were included; of which 22 were randomised controlled trials. Due to heterogeneity, findings were synthesised narratively. The most frequently reported adverse effects were metabolic complications, with approximately one-third of individuals developing corticosteroid-induced lipodystrophy. Infections were the second most common adverse effect (15.5%), followed by gastritis (12.6%). Infections accounted for three-quarters of corticosteroid-associated mortality, predominantly due to tuberculosis, with 88.2% of corticosteroid-associated mortalities occurring in individuals with erythema nodosum leprosum (ENL). There was an association between ENL and the development of cataract and osteoporosis, with 69.7% of cataract cases and 84.4% of osteoporosis cases occurring among individuals with ENL.

This systematic review illustrates the range and severity of adverse effects affecting individuals with leprosy who received systemic corticosteroids. Although this review is limited by study heterogeneity, publication bias, and the scarcity of long-term data, it highlights the need for corticosteroid stewardship, structured pharmacovigilance and further research for safer therapeutic alternatives to corticosteroids for leprosy reactions.

Leprosy is a neglected tropical disease that causes stigmatising disability and is associated with significant reduction in quality of life. The infectious organism and the body’s immune response to it causes nerve damage often with severe, painful episodes called leprosy reactions. Leprosy reactions are the major risk factor for disability and are treated with corticosteroids. Corticosteroids are used in many inflammatory conditions with well recognised adverse effects, but data on these adverse effects in individuals with leprosy are limited.

We conducted a systematic review to characterise the nature and frequency of the adverse effects associated with corticosteroid use in people with leprosy. Our review found that adverse effects affected many organ systems and some were particularly frequent and severe in individuals who required prolonged treatment. Our results highlight the importance of monitoring patients with leprosy who are prescribed corticosteroids and reveal significant gaps within existing literature to inform future research. Strengthening pharmacovigilance of corticosteroid use and monitoring practices could help improve care.