Epidemiologic characteristics of leprosy reactions.

An 8-year prospective study of a cohort of 176 newly diagnosed leprosy patients was conducted to examine the possible influence of age, sex, multidrug therapy (MDT), and duration of illness on the risk of either type 1 or type 2 reactions. Patients were enrolled over a 5-year period (1984-1989) and followed for a minimum of 3 years. All reactions studied were severe enough to warrant hospital admission. Overall, 45% of this cohort developed a reaction; 32% of patients considered at risk developed type 1 reactions, and 37% of patients considered at risk developed type 2 reactions. Despite the predominance of men among the leprosy patients, type 1 reactions occurred with significantly greater frequency in women, and did not appear to be influenced by age of onset of leprosy. Individuals experiencing one type 1 reaction were not likely to experience a recurrence, suggesting that the immunologic mechanisms of this reaction may be limited or regulated by genetic or immunologic factors. Type 2 reactions, on the other hand, occurred with equal frequency in both males and females, but were highly associated with onset of leprosy in the second decade of life. Individuals who experienced type 2 reactions often had one or more recurrence of the reaction. No increased risk was seen for either reaction with longer duration of leprosy or longer duration of treatment. The mechanisms by which these differences relate to the pathogenesis of leprosy reactions remains unclear, but future studies of clinical and immunological parameters of leprosy reactions may benefit from stratification of data by gender and age of onset of leprosy in addition to the routine grouping of results by leprosy classification.

Studies of human leprosy lesions in situ using suction-induced blisters: cell changes with IgM antibody to PGL-1 and interleukin-2 receptor in clinical subgroups of erythema nodosum leprosum.

To examine the immunopathogenesis of type 2 erythema nodosum leprosum (ENL) reactions in leprosy, we studied cellular and soluble immunologic components of skin lesions in 57 patients with reactions (19 acute ENL and 38 chronic ENL), 61 active patients without reactions, and 33 control patients whose leprosy had been treated and cured. Cells, IgM antibody to PGL-1 and Tac peptide levels were obtained from fluid aspirated from blisters induced by suction directly over representative skin lesions. During ENL reactions: a) the lesions in chronic ENL showed a decreased number of CD8+ (T-suppressor) cells and increased helper/suppressor ratio as compared to those in acute ENL and non-reactional leprosy; b) Tac peptide and IgM antibody to PGL-1 levels were elevated in the chronic ENL lesions; c) and systemic administration of corticosteroids appeared to cause a reduction in the intralesional CD4+ cell population and IgM antibody to PGL-1 but did not change CD8+ cell population and the levels of Tac peptide in the lesions. The elevated levels of Tac peptide were localized in the skin lesions while increased levels of IgM anti-PGL-1 seemed to be filtered from the peripheral blood. We conclude that spontaneous lymphocyte activation in situ, primarily of decreased CD8+ and relatively increased CD4+ cells, are important features of chronic, recurrent ENL reactions and may be an intermittent or cyclic phenomenon during the reaction. Understanding the mechanisms of these spontaneous changes in immunity in leprosy will enlarge our knowledge of reactions and of the underlying determinants of delayed type hypersensitivity and cell-mediated immunity in leprosy, which in turn will allow us to realize the potential for artificially manipulating these responses as proposed with vaccines or immunotherapy.

Studies of human leprosy lesions in situ using suction-induced blisters. 2. Cell changes and soluble interleukin 2 receptor (Tac peptide) in reversal reactions.

To examine the pathogenesis of type 1 (reversal) reactions in leprosy, we studied cellular and soluble immunologic components of skin lesions in 10 patients with reactions, 24 active patients without reactions, and 33 control patients whose leprosy had been treated and cured. Cells and Tac-peptide levels were obtained from fluid aspirated from blisters induced by suction directly over representative skin lesions. During reversal reactions: a) the lesions contained an increased number and percentage of CD4+ (T-helper) cells; b) Tac-peptide levels were elevated in half of the lesions; c) the increases in Tac peptide and CD4+ cells were directly correlated; and d) systemic administration of corticosteroids appeared to cause a reduction in the intralesional CD4+ cell population. These findings were localized to the skin, and do not represent simple filtration of these components from the peripheral blood. We conclude that spontaneous lymphocyte activation in situ, primarily of CD4+ cells, is an important feature of reversal reactions, and may be an intermittent or cyclic phenomenon during the reaction. Findings in active patients without reactions are consistent with the hypothesis that differing states of immunologic equilibrium have been established in different portions of the leprosy spectrum. In reversal reactions we may, therefore, be examining immunologic processes set in motion when a pre-existing equilibrium has been upset by spontaneous, natural events. The mechanism of such spontaneous changes in immunity in leprosy is of considerable interest, not only to understand the reaction, but also to examine the underlying determinants of delayed-type hypersensitivity and cell-mediated immunity in leprosy and the potential for artificially manipulating these responses, as proposed with vaccines or immunotherapy.

Cell changes and soluble interleukin-2 receptors (Tac peptide) in leprosy reversal reactions using suction-induced blisters.

The cellular contents and soluble interleukin-2 receptor (IL-2R) [Tac peptide] of skin blisters induced by suction over 7 reversal reaction (RR) patients were examined using immunoperoxidase and ELISA techniques respectively. The helper T activity (CD4+ cells) and helper:suppressor ratio were significantly greater in borderline lepromatous (BL) lesions with RR than in quiescent BL lesions. Interestingly, the intracutaneous levels of Tac peptide were elevated and directly correlated with the increases in CD4+ cells. The systemic administration of corticosteroids revealed a reduction in the numbers of CD4+ cells in the lesions. These results indicate that RRs are manifestations of a spontaneous increase in delayed type hypersensitivity (DTH) and possibly cell mediated immunity (CMI) in leprosy patients. The mechanism of such changes in immunity is of considerable value in understanding reversal reactions and the underlying determinants of DTH and CMI in leprosy and this in turn will have a bearing on the potential for proposed vaccines or immunotherapy.

Studies of human leprosy lesions in situ using suction-induced blisters. 1. Cellular components of new, uncomplicated lesions.

The cellular contents of blisters induced by suction over new, uncomplicated leprosy lesions, and in the skin of cured, control patients, have been examined with enzyme- and immuno-histochemical staining over a period of 4 days. The total cellularity of the blisters varied over a wide range, not correlated with the type of leprosy. Mononuclear cells predominated at all times studied, with nearly equal percentages of monocytes and T lymphocytes. The T-helper: suppressor ratio was significantly greater in BT than in BL and LL lesions at 48 hr. Suction blisters offer a painless, quantitative, reproducible, multiple-sampling method for obtaining cells from the cutaneous infiltrates of leprosy for phenotyping or functional analysis.