A Phase Two Randomised Controlled Double Blind Trial of High Dose Intravenous Methylprednisolone and Oral Prednisolone versus Intravenous Normal Saline and Oral Prednisolone in Individuals with Leprosy Type 1 Reactions and/or Nerve Function Impairment
Open Access
- 12 April 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Neglected Tropical Diseases
- Vol. 5 (4), e1041
- https://doi.org/10.1371/journal.pntd.0001041
Abstract
Leprosy Type 1 reactions are a major cause of nerve damage and the preventable disability that results. Type 1 reactions are treated with oral corticosteroids and there are few data to support the optimal dose and duration of treatment. Type 1 reactions have a Th1 immune profile: cells in cutaneous and neural lesions expressing interferon-γ and interleukin-12. Methylprednisolone has been used in other Th1 mediated diseases such as rheumatoid arthritis in an attempt to switch off the immune response and so we investigated the efficacy of three days of high dose (1 g) intravenous methylprednisolone at the start of prednisolone therapy in leprosy Type 1 reactions and nerve function impairment. Forty-two individuals were randomised to receive methylprednisolone followed by oral prednisolone (n = 20) or oral prednisolone alone (n = 22). There were no significant differences in the rate of adverse events or clinical improvement at the completion of the study. However individuals treated with methylprednisolone were less likely than those treated with prednisolone alone to experience deterioration in sensory function between day 29 and day 113 of the study. The study also demonstrated that 50% of individuals with Type 1 reactions and/or nerve function impairment required additional prednisolone despite treatment with 16 weeks of corticosteroids. The study lends further support to the use of more prolonged courses of corticosteroid to treat Type 1 reactions and the investigation of risk factors for the recurrence of Type 1 reaction and nerve function impairment during and after a corticosteroid treatment. Controlled-Trials.comISRCTN31894035 Leprosy is caused by a bacterium and is curable with a combination of antibiotics known as multi-drug therapy that patients take for six or 12 months. However a significant proportion of leprosy patients experience inflammation in their skin and/or nerves, which may occur even after successful completion of multi-drug therapy. These episodes of inflammation are called leprosy Type 1 reactions. Type 1 reactions are an important complication of leprosy because they may result in nerve damage that leads to disability and deformity. Type 1 reactions require treatment with immunosuppressive agents such as corticosteroids. The optimum dose and duration of corticosteroid therapy remains unclear. We conducted a study to see if it would be safe to use a large dose of a corticosteroid called methylprednisolone for three days at the start of a 16 week corticosteroid treatment regime of prednisolone in patients with leprosy Type 1 reactions and leprosy patients with nerve damage present for less than six months. We did this by comparing individuals who were given methylprednisolone followed by prednisolone and those who received just prednisolone. In this small study we did not see any significant difference in the frequency of adverse events due to corticosteroid treatment in the two groups. We did not demonstrate a significant difference in improvement in individuals in the methylprednisolone group (who received a larger dose of corticosteroids) than those in the prednisolone treated group. Overall approximately 50% of individuals required more prednisolone in addition to the 16 week course of treatment to prevent further nerve damage or reactions. This suggests that it would be worthwhile investigating longer treatment courses with corticosteroids and other immunosuppressive drugs.Keywords
This publication has 22 references indexed in Scilit:
- Global leprosy situation, 2009.2009
- Development and Validation of a Severity Scale for Leprosy Type 1 ReactionsPLoS Neglected Tropical Diseases, 2008
- Age Is an Important Risk Factor for Onset and Sequelae of Reversal Reactions in Vietnamese Patients with LeprosyClinical Infectious Diseases, 2007
- Clinical outcomes in a randomized controlled study comparing azathioprine and prednisolone versus prednisolone alone in the treatment of severe leprosy type 1 reactions in NepalTransactions of the Royal Society of Tropical Medicine and Hygiene, 2004
- Steroid prophylaxis for prevention of nerve function impairment in leprosy: randomised placebo controlled trial (TRIPOD 1)BMJ, 2004
- Immunohistochemical Analysis of Cellular Infiltrate and Gamma Interferon, Interleukin-12, and Inducible Nitric Oxide Synthase Expression in Leprosy Type 1 (Reversal) Reactions before and during Prednisolone TreatmentInfection and Immunity, 2001
- Corticosteroids or ACTH for acute exacerbations in multiple sclerosisEmergencias, 2000
- Effects of pulse methylprednisolone on inflammatory mediators in peripheral blood, synovial fluid, and synovial membrane in rheumatoid arthritisArthritis & Rheumatism, 1997
- Tumour necrosis factor-alpha (TNF-α) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactionsClinical and Experimental Immunology, 1995
- Corticosteroid pulse therapy in active rheumatoid arthritisSeminars in Arthritis and Rheumatism, 1993