Leprosy reactions in postelimination stage: the Bangladesh experience.

BACKGROUND: Leprosy reactions are immunologically mediated conditions and a major cause of disability before, during and after multidrug therapy (MDT). Little data have been published on the epidemiology of leprosy reactions in Bangladesh. OBJECTIVES: To describe the pattern and prevalence of leprosy reactions in the postelimination stage. METHODS: A descriptive retrospective cross-sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients in the period between 2004 and 2013. RESULTS: Of the 670 patients with leprosy, 488 (73.38%) were males and 182 (27.37%) were females. The prevalence of reaction was in 300 (44.78%) patients with a male:female ratio of 3.55 : 1. The age-specific cumulative reaction cases at >40 years were 115 (38.33%) among all age groups. The prevalence of reaction was found to be in 166 (55.33%) patients for the reversal reaction, 49 (16.57%) for the erythema nodosum leprosum (ENL) and 85 (28.33%) for the neuritis. Borderline tuberculoid was most common (106, 35.33%)in the reversal reaction group, while lepromatous leprosy was most common (37, 12.33%) in ENL group. More than half of the patients (169, 56.33%) had reactions at the time of presentations, while 85 (28.33%) and 46 (15.33%) patients developed reaction during and after MDT, respectively. The reversal reaction group presented with ≥six skin lesions in 96 (57.83%) patients and ≥two nerve function impairments (NFIs) in 107 (64.46%) patients. The ENL was present chiefly as papulo-nodular lesions in 45 (91.84%) patients followed by pustule-necrotic lesions in four (8.16%), neuritis in 33 (67.35%), fever in 24 (48.98%), lymphadenitis in six (12.24%), arthritis in five (10.20%) and iritis in two (4.08%). Bacterial index ≥3 had been demonstrated in 34 (60.71%) patients in ENL group. CONCLUSION: The incidence of leprosy reaction seemed to be more than three times common in borderline tuberculoid (52.33%) group than in lepromatous leprosy (14%) group. Reactions with NFI and disability still occur among multibacillary patients during and after MDT. Early detection and management of leprosy reaction are very important in preventing disability and deformity, and patients should be educated to undergo regular follow-up examinations. Developing reinforced new therapies to curb leprosy reactions is crucial for improving leprosy healthcare services.

Sphingolipids as new biomarkers for assessment of delayed-type hypersensitivity and response to triptolide.

BACKGROUND: Hypersensitivity diseases are associated with many severe human illnesses, including leprosy and tuberculosis. Emerging evidence suggests that the pathogenesis and pathological mechanisms of treating these diseases may be attributable to sphingolipid metabolism. METHODS: High performance liquid chromatography-tandem mass spectrometry was employed to target and measure 43 core sphingolipids in the plasma, kidneys, livers and spleens of BALB/c mice from four experimental groups: control, delayed-type hypersensitivity (DTH) model, DTH+triptolide, and control+triptolide. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify potential biomarkers associated with variance between groups. Relationships between the identified biomarkers and disease markers were evaluated by Spearman correlation. RESULTS: As a treatment to hypersensitivity disease, triptolide significantly inhibit the ear swelling and recover the reduction of splenic index caused by DTH. The sphingolipidomic result revealed marked alterations in sphingolipid levels between groups that were associated with the effects of the disease and triptolide treatment. Based on this data, 23 potential biomarkers were identified by OPLS-DA, and seven of these biomarkers correlated markedly with the disease markers (p<0.05) by Spearman correlation. CONCLUSIONS: These data indicate that differences in sphingolipid levels in plasma and tissues are related to DTH and treatment with triptolide. Restoration of proper sphingolipid levels may attribute to the therapeutic effect of triptolide treatment. Furthermore, these findings demonstrate that targeted sphingolipidomic analysis followed by multivariate analysis presents a novel strategy for the identification of biomarkers in biological samples.

Corticosteroid pulse therapy for leprosy complicated by a severe type 1 reaction.

A 24-year-old Vietnamese woman presented with a 3-month history of non-itchy erythematous plaques on the face, trunk and limbs. Borderline lepromatous leprosy was confirmed by clinical findings, acid-fast bacilli on skin biopsy specimen and skin smear and a history of exposure. Around the twentieth day of World Health Organization (WHO) multibacillary standard treatment (rifampin 600 mg per month, dapsone 100 mg per day, clofazimine 300 mg per month and 50 mg per day for 1 year), she developed fever, general malaise, blurred vision, cough, nausea, epigastric pain, and arthralgia. The skin lesions also became swollen. During hospitalization, her illness was complicated by retrobulbar optic neuritis, secondary bacterial pneumonia, pleuritis, ascites, hepatitis, antral gastritis, progressive normocytic anemia, and peripheral sensory loss. The patient recovered after receiving systemic steroid pulse therapy (prednisolone equivalent dose 1250 mg) with systemic antibiotics (cefuroxime), adjustment of her anti-lepromatous therapy, and supportive care. She resumed the WHO multibacillary regimen uneventfully. This patient presented with a diverse type 1 reaction, which is a complex immune response in leprosy. We found that the judicious use of high dose steroids followed by a slow tapering course is beneficial in managing patients with a severe type 1 reaction. At the 1-year follow up, the patient had generalized skin hyperpigmentation resulted from long-term clofazamine use and numbness on feet without other systemic sequelae.

Delayed-type hypersensitivity reactions followed by erythema nodosum leprosum.

Reported herein are 13 borderline lepromatous (BL) or subpolar lepromatous (LLs) patients who presented with or developed delayed-type hypersensitivity (DTH) reactions after initiation of antibacterial therapy, but who subsequently developed erythema nodosum leprosum (ENL), the DTH to ENL group. During the same time, three LLs patients had ENL followed by relapse-associated DTH, a significant (p < 0.05) difference in sequence of the two conditions. The DTH to ENL group had statistically significant higher biopsy indexes at the time of diagnosis of the DTH reaction compared with two DTH control groups, 7 multibacillary patients presenting with DTH reactions and 15 BL or LLs who developed DTH reactions after starting treatment but had no ENL. DTH-associated histologic changes were less well developed in the DTH to ENL group than in either of the two control groups. In the DTH to ENL group, 77% required prednisone in addition to thalidomide to achieve a complete remission in contrast to only 10% of 21 ENL clinical controls. In the DTH to ENL group, the classical histologic ENL pattern was present in only 31% of these patients, in contrast to 88% of 33 ENL histologic controls. In 9 of 9 of the DTH to ENL patients studied, after the ENL remitted, Mycobacterium leprae-sonicate-stimulated lymphocyte transformation tests gave stimulation indexes within the range of our tuberculoid (TT) and borderline tuberculoid (BT) patients, in contrast to absent responses in 6 ordinary, longterm-treated patients who had had ENL.

Leprosy reversal reaction in HIV-positive patients.

We report two cases of leprosy in HIV-infected patients who, by their clinical, histological and immunological features, enhance the evidence that HIV-positive leprosy does not differ from nonHIV-positive leprosy. Moreover, extensive studies of reversal reactions in HIV-positive patients might be of great interest in determining the exact pathogenesis of this leprosy reactional state.

Evidence for prevention of borderline leprosy reactions by dapsone.

68 patients were included in a prospective study of the treatment of borderline leprosy. 34 were treated with dapsone 5 mg daily, and 34 with 50 mg daily. Reversal reactions developed in 11 of those on 5 mg daily and in 3 of those on 50 mg daily. The statistically significant difference between the two treatment groups indicates that, contrary to previous teaching, dapsone given in higher dosage does not predispose patients to reversal reactions and indeed may prevent them.