Tumour necrosis factor-alpha (TNF-alpha) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactions.

Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (reversal reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-alpha mRNA and TNF-alpha protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-alpha mRNA are significantly increased in reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-alpha mRNA and TNF-alpha protein levels are higher in reactional nerves then reactional skin. In both reactional skin and nerve TNF-alpha mRNA is more abundant than TNF-alpha protein; this may reflect the rapid turnover of TNF-alpha protein in an immunologically dynamic situation, such as is seen in reversal reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy reversal reaction may be regarded as a useful model of tissue immunopathology in which TNF-alpha is generated as part of the host response to infection, but also produces local tissue damage.

Clinical features and outcome of reversal (type 1) reactions in Hyderabad, India.

A retrospective survey of the notes on all patients attending Dhoolpet Leprosy Research Center, India, during 1985 was done to establish the frequency, timing, and clinical features of reversal (type 1) reactions; 494 case notes were examined and clinical evidence of a reversal reaction was found in 44 cases (10.9%). Reactions were most common in borderline patients, with 11.4% and 14.8% of borderline tuberculoid (BT) and borderline lepromatous (BL) patients developing reactions, respectively. Presentation in reaction was frequent with 47.5% of reactional patients having signs of a reversal reaction at the time of their first visit to the Dhoolpet clinic; 50% of skin reactions developing in patients on antileprosy treatment occur within the first month of treatment. Neurological reactions occur later and over a longer time course. Late reactions may occur up to 6 1/2 years after the start of treatment. Further reactional episodes occurred in 31.8% of the patients, and may be repeated. Steroid treatment produced improvement of both skin lesions and neuritis, but improvement in clinical signs and symptoms occurred in only 50% of the neuritic episodes.