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Histoid leprosy is a rare variant of leprosy with a unique clinical presentation and bacilli rich histology. These patients are large reservoirs for disease and vectors for spread, making prompt diagnosis and treatment crucial. To date, no consensus on treatment and duration exists. This paper aims to investigate the efficacy, safety, and duration of varying treatment regimens in patients with histoid leprosy. A systematic PubMed review of all articles published before January 2020 containing the key words histoid leprosy. All patients included must have completed their prescribed treatments with comment on outcomes and treatment duration. The review generated 165 articles containing 62 cases that met inclusion criteria. A majority of cases reported excellent clinical outcomes with limited adverse events. Regimens included variations of rifampicin, dapsone, clofazimine, minocycline, ofloxacin, and sulforthormadine with most treatment duration lasting 12 or 24 months. Existing literature is limited to case reports or case series and may be subject to publication bias of successful cases. Many reports lack quantifiable data regarding outcomes and rely on clinical judgment. Continued observation for complete clearance or relapse was limited. The findings demonstrate that multibacillary-multidrug therapy is an efficacious and safe treatment for histoid leprosy. No significant differences were observed between 12 and 24 months of treatment. There remains no consensus on treatment duration for histoid leprosy.

Background Leprosy or Hansen's disease is a chronic infection caused by Mycobacterium leprae (M. leprae) or Mycobacterium lepromatosis (M. lepromatosis). In Europe, most of the leprosy cases are imported. However, occasionally a case is diagnosed in one of the old endemic foci. Leprosy is often not suspected because it is no longer emphasized in the medical curricula. Attention shifted from leprosy to tuberculosis and human immunodeficiency virus infections in the late 20th century, whereby the WHO leprosy programme was toned down in the conviction that leprosy was all but eliminated. The result of unawareness is a harmful doctor's delay. Material and methods This paper focusses on clinical diagnosis, complications and treatment based on literature and experience. Results It mentions the value of laboratory tests in classification, follow-up and detection of relapses. It discusses the etiopathology. Conclusion This is a position statement.

A leprosy reaction resembling Sweet syndrome was first described in 1987. This cutaneous manifestation can be classified as the type 2 reaction which arises from antigen-antibody interaction. It can occur in patients with diagnosed or undiagnosed leprosy, and men with borderline leprosy tend to exhibit this type of reaction. Triggering factors may include WHO multibacillary treatment or prescription antibiotics. Several reports of this clinical phenomenon have been published, making physicians consider it as part of this spectrum of the disease. Treatment regime can include systemic steroids and thalidomide.

Leprosy (causative, Mycobacterium leprae) continues to be the persisting public health problem with stable incidence rates, owing to the emergence of dapsone resistance that being the principal drug in the ongoing multidrug therapy. Hence, to overcome the drug resistance, structural modification through medicinal chemistry was used to design newer dapsone derivative(s) (DDs), against folic acid biosynthesis pathway. The approach included theoretical modeling, molecular docking, and molecular dynamic (MD) simulation as well as binding free energy estimation for validation of newly designed seven DDs, before synthesis. Theoretical modeling, docking, and MD simulation studies were used to understand the mode of binding and efficacy of DDs against the wild-type and mutant dihydropteroate synthases (DHPS). Principal component analysis was performed to understand the conformational dynamics of DHPS-DD complexes. Furthermore, the overall stability and negative-binding free energy of DHPS-DD complexes were deciphered using Molecular Mechanics/Poisson-Boltzmann Surface Area technique. Molecular mechanics study revealed that DD3 possesses higher binding free energy than dapsone against mutant DHPS. Energetic contribution analysis portrayed that van der Waals and electrostatic energy contributes profoundly to the overall negative free energy, whereas polar solvation energy opposes the binding. Finally, DD3 was synthesized and characterized using Fourier-transform infrared spectroscopy, UV, liquid chromatography-mass spectrometry, and proton nuclear magnetic resonance techniques. This study suggested that DD3 could be further promoted as newer antileprosy agent. The principles of medicinal chemistry and bioinformatics tools help to locate effective therapeutics to minimize resources and time in current drug development modules.

Background Leprosy reactions are immunologically mediated conditions and a major cause of disability before, during and after multidrug therapy. Little data has been published on the epidemiology of leprosy reactions in Bangladesh. Objectives To describe the pattern and prevalence of leprosy reactions in the post elimination stage. Methods A descriptive retrospective cross-sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients the periods between 2004 and 2013. Results Of the 670 leprosy patients 488 (73.38%) were males and 182 (27.37%) were females. The prevalence of reaction was 300 (44.78%) with a male: female ratio of 3.55:1. The age specific cumulative reactions cases at >40 years was high 115 (38.33%) among all age groups. The prevalence of reaction was found to be 166 (55.33%) for the reversal reaction, 49 (16.57%) for the erythema nodosum leprosum and 85 (28.33%) for the neuritis. Borderline tuberculoid was the most common 106 (35.33%) group in reversal reaction while lepromatous leprosy was the most common 37 (12.33%) in erythema nodosum leprosum. More than half of the patients 169 (56.33%) had reactions at the time of presentations while 85 (28.33%) and 46 (15.33%) of patients developed reaction during and after multidrug therapy respectively. The reversal reaction group presented with ≥ 6 skin lesions in 96 (57.83%) and ≥ 2 nerves involvement in 107 (64.46%) patients. The erythema nodosum leprosum presented chiefly as papulo-nodular 45 (91.84%) lesions followed by pustule-necrotic 4 (8.16%) lesions, neuritis 33 (67.35%), fever 24 (48.98%), lymphadenitis 6 (12.24%), arthritis 5 (10.20%) and iritis 2 (4.08%). Bacterial index ≥ 3 had been demonstrated in 34 (60.71%) patients of erythema nodosum leprosum. Conclusion The incidence of leprosy reaction seemed to be more than three times common in borederline tuberculoid (52.33%) than in lepromatous leprosy (14%). Reactions with nerve function impairment and disability still occur among multibacillary patients during and after multidrug therapy. Early detection and management of leprosy reaction is 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 health care services. This article is protected by copyright. All rights reserved.

Background Type 2 lepra reaction (T2R) is a difficult-to-manage condition in leprosy, and an effective and safe steroid-sparing agent is needed for its management. The World Health Organization proposes clofazimine and recommends pentoxifylline for T2R. Our study was done to compare the effectiveness and safety of clofazimine and pentoxifylline therapy in patients with T2R. Methods Twenty patients with T2R were randomized equally. Group A received pentoxifylline 400 mg t.d.s, group B received clofazimine 100 mg t.d.s. for 12 weeks. Both groups received prednisolone 40 mg o.d., tapered over 12 weeks. The effectiveness parameters were days needed for resolution of cutaneous and systemic manifestations, relapses, cutaneous score, systemic score, and average daily prednisolone intake. Safety parameters were spontaneously appearing adverse events and laboratory parameter changes. Results The cutaneous scores in the clofazimine (P

Background The treatment of Mycobacterium avium complex (MAC) requires prolonged, multidrug therapy, which is often not well tolerated. In solid organ transplant (SOT) recipients, drug–drug interactions complicate treatment further. Failure or intolerance requires the use of salvage regimens, and clofazimine is one of the drugs that can be used. No data are available on the safety and tolerability of clofazimine for the treatment of MAC in SOT recipients. Methods Retrospective review of all SOT recipients treated for MAC infection with clofazimine at a large transplant center between 2006 and 2013. Results Five SOT recipients received clofazimine as salvage therapy. Transplanted organs were lungs in 3 patients, and kidney and liver in 1 patient each. Infection was diagnosed at a median of 22 months (range 4–57) post transplant. Sites of infection were the lungs in 2 patients, and septic arthritis, mesenteric, and disseminated disease in 1 patient each. All patients received standard anti-MAC therapy for a median of 26 weeks (range 18–45) before starting clofazimine. Indications for use of clofazimine included a lack of response to previous therapy (3 patients), and poor tolerance of other regimens (3 patients). All patients received at least 2 additional drugs besides clofazimine. Median duration of clofazimine-containing regimen was 8 months (range 2–18). Clofazimine was discontinued because of gastrointestinal intolerance in 1 of the 5 patients. The most common adverse event from clofazimine was skin discoloration, in 60% of patients. No hepatotoxicity or hematologic toxicity occurred. Microbiological clearance and resolution of clinical disease was documented in 2 of 5 patients; and 2 of the 5 patients died of other causes while on therapy. Conclusions Clofazimine appears safe and may be considered as a salvage therapeutic option in SOT recipients with MAC infection who are intolerant or unresponsive to standard therapy. The small sample size does not allow conclusions regarding efficacy.

Objective This study was conducted to evaluate the effectiveness of uniform multi-drug therapy (UMDT) in patients with multibacillary (MB) leprosy. Methods Newly detected MB leprosy patients were treated with six months of UMDT as recommended by the World Health Organization (WHO). The effectiveness of treatment was evaluated by clinical status and skin smear tests. Results At the start, 114 patients were recruited, examined, and treated. These patients were re-examined and followed annually for up to six years. A total of 75 (65.8%) patients completed six years of follow-up. Dropouts were attributable to death, severe drug reactions, and other reasons. The mean ± standard deviation bacteriological index (BI) of all patients decreased from 3.01 ± 1.50 before treatment to 0.02 ± 1.84 at the end of year 6, reflecting a mean annual decrease of 0.50. The rate of smear negativity in all patients was 98.7% at the end of year 6 of follow-up. A total of 53 leprosy reactions were observed. One patient relapsed 13 months after the cessation of treatment. Conclusions A 6-month administration of UMDT is effective in MB leprosy patients. The changes in BI values and the frequency of leprosy reactions were similar to those cited in reports in the literature of patients treated with 1- or 2-year regimens of MDT. However, further research should be conducted to confirm the present results.

Background Lepromatous leprosy is associated with suppressed cell-mediated immunity (CMI). This results in failure of the body to mount an efficient immune response and may render chemotherapy ineffective. The lack of sufficient response may mimic drug resistance. Three case reports in which the immunity was stimulated by administering Injection BCG are presented. All three patients were initially anergic and showed no reaction at the Mantoux testing site, showing an inability to mount type IV hypersensitivity and characterized by live bacilli in smears. Following 1-4 doses of Injection BCG, all three showed dead bacilli in smears. Case reports The first case, a 61-year-old man with lepromatous leprosy who continued to show live bacilli in smears after prolonged chemotherapy, was administered a total of four BCG injections, following which he achieved clearance. The second, a 40-year-old man with borderline lepromatous leprosy and severe type 2 reactions, achieved bacterial clearance and control of severe reactions following a single injection. The third, a 67-year-old man with histoid leprosy, achieved effective bacterial killing with a single dose of Injection BCG. Results All three patients achieved good results when chemotherapy was combined with Injection BCG. Following Injection BCG, all three showed a reaction at the Mantoux testing site. Conclusions Suppressed CMI may be responsible for the lack of response in recalcitrant cases of lepromatous leprosy. These case reports would lead to the trend in combination therapy (immunotherapy combined with chemotherapy) for such cases, and help lower the tendency for inappropriate diagnosis of drug-resistant leprosy.

Aim: Leprosy classically presents with cutaneous and neural involvement. Rheumatological manifestations arefrequent, although often under-recognized. At times, these may present to a rheumatology clinic prior to thediagnosis of leprosy. Herein, we present our experience with patients referred with various rheumatological dis-orders who were subsequently diagnosed as having leprosy.Methods: This retrospective study (January 2001–September 2010) was carried out at the Department of Clini-cal Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, in northern India.Patients who were confirmed as having leprosy were included. Details regarding demographic and clinical pre-sentations were collected.Results: Forty-four cases (30 male, mean age 40 ± 13.6 years and mean disease duration 18.7 ± 24.3 months)were identified. Musculoskeletal manifestations included arthritis ( n = 22), swollen hands and feet syndrome(SHFS) (n = 11), tenosynovitis (n = 9), painful swollen feet (n = 9), arthralgias (n = 7) and vasculitis ( n = 1).Distribution of joints mimicked rheumatoid arthritis ( n = 14) and spondyloarthropathy (n = 7). Arthritis and/or tenosynovitis were part of spontaneous onset lepra reaction in 28 cases. Other clinical manifestations were:paresthesias (n = 28), erythematous nodules (n = 25) and anesthetic patches ( n = 7). Thirty-one patients hadthickened nerves (ulnar n = 28, common peroneal n = 21). Eight patients did not have any cutaneous manifes-tations and had presented with SHFS and arthritis or tenosynovitis. These were labeled as pure neuritic leprosy.Most of the patients responded to multidrug anti-leprosy therapy and glucocorticoids.Conclusion: Rheumatological presentations of leprosy may mimic RA, spondyloarthropathy or vasculitis. Pureneuritic variety and spontaneous type 2 lepra reaction pose unique diagnostic challenges. Increased awarenessmay avoid delay in diagnosis.Key words: arthritis, lepra reaction, leprosy, pure neuritic leprosy, swollen hand foot syndrome, tenosynovitis.

Objective: The aim of this study was to evaluate the prevalence of Candida spp. and presence of oral lesions in Brazilian leprosy patients under multidrug therapy (MDT). Methods: Thirty-eight individuals (18 males and 20 females, median age 53 years) clinically and microbiologically diagnosed as leprosy (lepromatous variant), and under MDT for at least 45 days were studied. The control group constituted by 38 healthy individuals (median age 53.5), matched to the test group in relation to age, gender and oral conditions. Oral rinses were collected and the Candida identification was performed by phenotypic tests. The existence of Candida dubliniensis among the isolates was analyzed using a validated multiplex PCR assay. Twenty-nine leprosy patients were examined intra-orally for the presence of lesions. Data were analyzed by z- and Mann–Whitney tests (α = 5%). Results: Yeast carriage rate between leprosy patients (65.8%) and controls (47.4%) was similar (P = 0.099), and no significant difference between yeast counts was observed (P = 0.1004). Candida albicans was the most frequently isolated species in both groups. In the leprosy group, Candida tropicalis and Candida parapsilosis were also identified. In the control group, we additionally identified Candida tropicalis, Candida glabrata and Candida kefyr. Candida dubliniensis was not detected. No leprosy-related oral lesion was registered. Conclusion: Within the limits of the study, we concluded that Brazilian leprosy patients under MDT showed similar levels of carriage and Candida species distribution in relation to the controls.

Several forms of arthritis and rheumatism can sometimes complicate leprosy. However, its presentation as an acute onset arthritis is unusual. We report two adult male naïve patients who presented to our rheumatology outpatient clinic with acute onset inflammatory polyarthritis, skin rash and mild sensory neurodeficit. Borderline lepromatous leprosy (in type I lepra reaction) was diagnosed. We also refer to 19 case records of Hansen arthritis in the clinic database (1998-2007) from approximately 35,000 patients and a community study to highlight the missed diagnosis of Hansen's disease and its unusual association with rheumatoid arthritis. In countries like India where leprosy is endemic, this disease also merits attention in rheumatology clinics.

Leprosy is rare in Australia, particularly in the southern states. We report two cases of leprosy in southern Australia that presented to the dermatology outpatients' department within a 4-month period. The presentation of the first case was complex, making the correct diagnosis difficult. Both cases involved immigrants from South-East Asia, were classified as multi-bacillary leprosy as defined by the World Health Organization, and were commenced on the recommended multiple drug therapy. The ensuing clinical course was complicated, with both cases developing Type 1 leprosy reactions. The first case also developed the rare but serious dapsone-induced delayed hypersensitivity reaction.

This study included 200 randomly selected multibacillary leprosy cases who had completed 1 year of fixed World Health Organization recommended multidrug therapy (WHO-MDT) without prior dapsone (DDS) monotherapy. The time interval after release from treatment varied from a few months to 8 years. All cases were clinically reviewed in 2006 by comparison with their old clinical records. Reactions, particularly reversal reactions, occurred frequently among patients who had completed MDT within the last 3 years. It was difficult to distinguish relapse cases and late reversal reactions in skin smear-negative multibacillary cases. Based on bacteriological and histological analyses, one patient was confirmed to have relapsed 1 year after release from treatment. The overall relapse rate was 0.5%. No drug resistance mutations were detected by polymerase chain reaction or dot blot hybridization. The present study indicates that it is important to follow up patients for several years after completion of MDT in order to detect possible lepra reactions and relapses.

In analysis of longitudinal data, the variance matrix of the parameter estimates is usually estimated by the 'sandwich' method, in which the variance for each subject is estimated by its residual products. We propose smooth bootstrap methods by perturbing the estimating functions to obtain 'bootstrapped' realizations of the parameter estimates for statistical inference. Our extensive simulation studies indicate that the variance estimators by our proposed methods can not only correct the bias of the sandwich estimator but also improve the confidence interval coverage. We applied the proposed method to a data set from a clinical trial of antibiotics for leprosy.

Background Several clinical and laboratory observations point to the possible microscopical affection of normal-looking skin in leprosy. Objective This study was carried out to verify the microscopical affection of apparently normal-looking skin in different types of leprosy. Patients and methods The study included 50 patients with different clinical types of leprosy. Biopsies from both skin lesions and normal-looking skin were obtained from each patient and examined for microscopical evidence of leprosy. Results Microscopical affection of normal-looking skin was detected in 52% of our cases, with higher incidence of affection towards the lepromatous end of the disease. Conclusion Our findings underscore that the incidence of microscopical affection of normal-looking skin in leprosy is much higher on the lepromatous end of the spectrum of leprosy than on the tuberculoid end; during treatment, the leprosy granulomas may disappear from the normal skin before the clinical lesions. Moreover, the microscopic picture of indeterminate leprosy can be observed in the normal-looking skin of patients with tuberculoid leprosy or lepromatous leprosy, and this description appears not to be confined to the entity known as indeterminate leprosy.

A retrospective study of 531 leprosy patients was undertaken to study the profile of reactions in the post Multi-Drug-Therapy period in a tertiary hospital in Delhi. BT was the most common group. The prevalence of reactions was found to be 8.09% for the Type 1 and 4.70% for the Type 2 reactions for a male:female ratio of 2.2. The Type 1 reaction was most frequently observed in the BB group followed by BL, BT and LL groups respectively. More than half of the patients had reactions at the time of presentation. In only 39.8% of the patients did reaction follow Multi-Drug-Therapy. In 4.5% of the patients with Type 1 reactions (T1R), concomitant infections were noted. The most common presentation of T1R was cutaneous lesions (74.41%) followed by cutaneous lesions and neuritis (53.6%), neuritis alone (12.1%), and only edema of hands and feet (7.31%) respectively. The Type 2 reactions (T2R) presented chiefly as papulo-nodular (92%) lesions followed by pustulonecrotic (8%) lesions. Associated neuritis was found in 40% and periosteitis and iritis in 8% and 4%, respectively. In 8.6% of the patients with T2R, precipitating factors could be observed. The prevalence of deformities in patients with reaction was 25%, and was more common in females. Deformities were observed in 23.25% of the T1R patients and 28% of the T2R patients.

A 25-year-old Thai housewife had a history of tuberculosis of the lymph nodes for six years that had been successfully treated with a course of anti-TB drugs. She developed several red, circumscribed, infiltrative plaques composed of umbilicated papules and pustules on her face and upper part of the body with cervical lymphadenopathy six months later. A pus smear from the lesion grew acid fast bacilli (AFB). Histopathological examination showed a mixed cell granuloma suggestive of infection. A T cell study showed a low CD4 count, and multi skin tests indicated cutaneous anergy. Culture from a biopsy specimen taken from the skin lesion grew M.chelonae; the cultures from blood, urine, and bone marrow. The lesions were not responsive to an anti TB drug given for 2 months based upon the results of the AFB positive pus smear before the culture and sensitivity reports were obtained. Since then the patient was treated with antibiotics according to the results of the sensitivity tests. A combination of amikacin and clarithromycin was started and hyperthermic therapy was later added with a partial response. Based upon the sensitivity test, kanamycin was introduced but had to be stopped because of ototoxicity. Sparfloxacin was used with an effective result but was discontinued for economic reasons. Finally, clarithromycin in combination with clofazimine and cryotherapy were given for a year before the lesions healed completely. It took a three years duration for the total course of treatment for this patient. She is still in remission after two years of follow-up period. This extensive cutaneous M.chelonae infection needed a prolonged combination of antibiotics with the addition of cryotherapy for the non-responsive lesions.

Thalidomide was marketed in the late-1950s as a sedative and tranquilliser of exceptionally low general toxicity, but in 1961 it was implicated separately by Lenz and MacBride as the cause of the epidemic of congenital malformations that had been puzzling the world for some years. It is a very potent teratogen in humans, but in few other mammalian species; damage to the embryo is produced at specific stages of gestation, but the mechanism of embryopathic action is still not understood. Following the withdrawal of the drug worldwide, it was consigned to the history of medical tragedies. In 1965, however, Sheskin discovered that it was effective in treating erythema nodosum leprosum, a distressing complication of leprosy. As the drug is neither an antibiotic nor an analgesic, its action was assumed to be immunosuppressive. In Brazil the drug was used widely with few regulatory controls, since when more than 100 cases of congenital malformation have appeared. Sheskin's discovery led to the experimental use of thalidomide in many other indications thought to possess some immunological component. In some cases, e.g. Behçet's syndrome, graft-versus-host disease and aphthous ulceration in HIV-positive patients, the drug has been shown to possess some efficacy. And there is some evidence that it inhibits the replication of one of the immunodeficiency viruses. The AIDS community in the US has exerted much pressure on the FDA to allow the drug on to the market, although the use of a potent immunosuppressive drug of unknown mechanism in an immunodeficiency condition raises further questions. Thalidomide is not always beneficial; its use is associated with an increased mortality in epidermal necrolysis. In 1991, D'Amato confirmed it possessed antiangiogenic properties and this led to further trials in malignant conditions. Results were mixed, but those in multiple myeloma gave some grounds for optimism. In 1998, the FDA announced its extraordinary decision to grant marketing approval for thalidomide.

Thalidomide is approved in the United States for treating erythema nodosum leprosum, a complication of leprosy. The present study determined the single-dose oral pharmacokinetics and dose proportionality from 50 to 400 mg of Celgene's commercial Thalomid thalidomide formulation in an open-label, single-dose, three-way crossover study. Fifteen healthy subjects were given 50, 200, and 400 mg of thalidomide on three occasions, and blood samples were collected over 48 hours. Pharmacokinetic parameters were determined using noncompartmental methods, and dose proportionality was assessed by linear regression of dose-normalized Cmax and AUC0-infinity. No serious or unexpected adverse events occurred. The most common adverse events were dizziness, somnolence, headache, and nausea. One patient was discontinued because of pharyngitis. There was a significant deviation from proportionality for Cmax with increases being less than proportional than changes in dose. AUC0-infinity increased proportionally with dose, suggesting that the overall amount of thalidomide absorbed, as well as its clearance, is independent of dose over the range used. V/F was found to increase with dose. This was most likely due to the terminal rate constant, which is used to calculate V/F, actually representing the absorption process rather than elimination (i.e., flip-flop phenomenon). The terminal rate constant (absorption rate constant) for the highest dose was 50% less than for the other two lower doses. The less than proportional increases in Cmax were most likely due to thalidomide's low aqueous solubility. Thalidomide shows reasonable dose proportionality with respect to AUC from 50 to 400 mg.

Objective To determine effective treatment strategies for patients with refractory canine leproid granuloma syndrome. Design Multi-institutional retrospective/prospective case series using client-owned dogs. Procedure Seven dogs (four Boxers, one Dobermann, one Bullmastiff and one Bullmastiff cross-bred; ages 3 to 11 years) with leproid granulomas were treated successfully using a variety of treatment regimens. These cases were recruited because: lesions were either widely distributed over the dog; progressive, despite routine therapy, or were associated with particularly disfiguring lesions. The treatment regimen evolved during the course of the clinical study. Results Combination therapy using rifampicin (5 to 15 mg/kg p.o., every 24 h) and clarithromycin (8 to 24 mg/kg p.o. daily; dose divided every 8 or every 12 h) was used most frequently and proved to be effective and free from side effects. Total daily doses of clarithromycin in excess of 14 mg/kg were considered optimal and long treatment courses, in the order of 1 to 3 months, were used. Combination therapy using rifampicin (25 mg/kg; that is, higher than the recommended dose) and clofazimine was effective in one case, but resulted in hepatotoxicity. A topical formulation of clofazimine in petroleum jelly was used as an adjunct to oral rifampicin and doxycycline in another patient treated successfully. Conclusion Based on our evolving clinical experience, a combination of rifampicin (10 to 15 mg/kg p.o., every 24 h) and clarithromycin (15 to 25 mg/kg p.o. total daily dose; given divided every 8 to 12 h) is currently recommended for treating severe or refractory cases of canine leproid granuloma syndrome. Treatment should be continued (typically for 4 to 8 weeks) until lesions are substantially reduced in size and ideally until lesions have resolved completely. A topical formulation, containing clofazimine in petroleum jelly may be used as an adjunct to systemic drug therapy. Further work is required to determine the most cost effective treatment regimen for this condition.

A 28-year-old man from the Philippines presented with multiple papules and plaques symmetrically distributed on the arms and legs. This was associated with worsening paraesthesia of the hands and feet. A right common peroneal nerve decompression had been performed 2 years earlier. He was diagnosed with multibacillary leprosy on skin biopsy and subsequently treated with oral rifampicin, clofazamine and dapsone.

Changes in Mycobacterium leprae-induced lymphoproliferative responses and mediator release by leprosy patients’ lymphocytes were followed during multiple drug therapy (MDT). At the time of diagnosis, multibacillary (MB) patients who did not develop reactions responded to both sonicated M. leprae and synthetic disaccharide coupled to bovine serum albumin (ND-BSA) antigens, but those who would later develop reactions did not respond, even in the presence of added cytokines. The paucibacillary (PB) group initially had high responses to sonicated M. leprae but no response to ND-BSA, even in the presence of added cytokines. In the first year of treatment, the supernatants of PB patients’ cell cultures contained factors that enhanced the phytohaemagglutinin (PHA) response of normal cells. In contrast, those MB patients who did not develop reactions at a later stage produced culture supernatants that were inhibitory. Interestingly, the MB patients who later developed reactions during treatment, and did not initially respond to M. leprae, produced supernatants containing enhancing factors, like those of the PB group. Later on in the treatment, all patients had the same patterns: when response to M. leprae decreased from its highest level, inhibitory factors were produced. Further studies revealed that the supernatants which inhibited the PHA response of normal cells contained the active form of transforming growth factor-β1 (TGF-β1), whatever the disease type or treatment status of the donor. These TGF-β1 levels correlated directly with the degree of inhibition. Similarly, supernatants that neither inhibited nor enhanced PHA responses contained the highest levels of interleukin-10 (IL-10), while those from treated patients that enhanced contained the lowest levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ). These cytokine correlations transcended the conventional disease classification, and imply that all patients pass through a sequence of patterns of immune response during treatment. These treatment-induced changes may explain occasional reports of response patterns at variance with the ‘immunological spectrum’ of leprosy. BB, borderlineBL, borderline lepromatousBT, borderline tuberculoidIFN-γ, interferon gammaIL-4, interleukin-4IL-10, interleukin-10MB, multibacillaryPB, paucibacillaryRT–PCR, reverse transcriptase–polymerase chain reactionLL, polar lepromatousTGF-β1, transforming growth factor-β1TT, tuberculoid.

Background: Recurrent immune-mediated scleritis after adequate treatment of leprosy is not well documented in the literature. We describe an Australian resident with unilateral intra-ocular lepromatous leprosy who had persistent non-infectious scleritis. Methods: A man of Anglo-Indian ancestry initially presented with lepromatous leprosy and unilateral ocular involvement. The affected eye had an interstitial keratitis and a granulomatous anterior uveitis that responded to antileprotics and anti-inflammatory agents. Despite systemic cure with triple antileprotic therapy, he developed recurrent scleritis that required multiple scleral patch grafts for scleral thinning and, subsequently, an enucleation. Histology failed to demonstrate persistent infection, rather a chronic non-granulomatous scleritis, which was probably immune mediated. Results/Conclusions: This case demonstrates an ocular complication of leprosy that is infrequently reported. Patients with ocular involvement by leprosy are at risk of developing recurrent scleritis despite systemic cure with antileprotics.

SUMMARY A 38-year-old Indonesian man presented with a single anaesthetic plaque on his right forearm and no other sensory changes. His clinical presentation was consistent with tuberculoid leprosy, but histopathology of a skin biopsy from the lesion showed borderline lepromatous disease. The patient was treated with multidrug therapy for multibacillary disease. Seven months after initiation of treatment his solitary skin anaesthetic plaque became tumid, and he developed multiple small plaques on his arms, legs and face, without evident neuritis. He was clearly in a reversal reaction (type 1), which slowly resolved with treatment of prednisone.

A 26-year-old man presented with persistent redness of the face over the past 2 years and thickening of the ears for a year. The current state was preceded by three to four episodes of epistaxis, 2–3 months previously. The patient had not received any treatment. Cutaneous examination revealed indurated (infiltrated) plaques on the face and ears over an apparently normal-looking skin, and numerous, small, ill-defined, slightly hypopigmented, shiny macules all over the body. They were bilateral and symmetric (Fig. 1a,b). There was no variation in the cutaneous sensations of temperature, touch, and pain. The patient showed loss of the lateral eyebrows and conjunctival congestion. Examination of the nerves revealed enlargement of the ulnar, radial, posterior tibial, and right common peroneal nerves; however, there was no tenderness of the nerves. Systemic examination was within normal limits. Examination of a slit-skin smear (under oil immersion), prepared from a representative lesion (plaque), demonstrated an abundance of solid and uniform-staining acid-fast bacilli, occurring either singly or in parallel clumps/globii, in an average field (6+). Furthermore, a scraping mount (10% KOH) prepared from the lesion on the back was negative. Figure 1. (a, b) Histoid leprosy Download figure to PowerPoint Hematoxylin and eosin-stained sections prepared from a biopsy taken from a plaque revealed a conspicuous granuloma composed of peculiar spindle-shaped histiocytes. Several of the granulomas were present in the mid and lower dermis. They were characterized by whorled, criss-cross, or parallel patterns. Solid and uniform-staining, slender, rod-like (length three times that of the breadth) acid-fast bacilli were found scattered throughout the section. A few histiocytes closely packed with acid-fast bacilli, together with lymphocytic infiltrates, were also seen. There was a prominent eosinophilic stained clear zone just below the epidermis. It was free from acid-fast bacilli as well as the inflammatory infiltrate (Fig. 2a,b). A definitive diagnosis of untreated lepromatous leprosy (LL) changing to histoid leprosy (de novo) was made. Figure 2. (a, b) Histoid leprosy depicting granuloma formed by histiocytes displaying whorl-wind, criss-cross or interlacing pattern, and a clear zone beneath the epidermis (H&E ×40) Solid and uniform staining acid fast bacilli, – slender, rod-like, length 3 times that of breadth found scattered throughout the granuloma (H&E ×100) Download figure to PowerPoint

Background. Tumor necrosis factor-alpha (TNF) is an important mediator of immunologic responses to chronic infections. Method. Sera from 25 patients with acute reactions (6 with type 1 upgrading, 8 with type 1 downgrading, and 11 with type 2 reaction) were assayed for TNF before treatment and after clinical remission of the acute episode. The results were compared with serum TNF levels in healthy controls and fresh pauci-and multibacillary leprosy patients. Results. TNF levels in acute reactions were higher than in the control groups (significant only in upgrading reaction). In type 1 reaction, serum TNF concentrations fell to approximately the levels of the control patients following treatment and clinical remission. In type 2 reaction, however, levels of TNF were seen to rise further (became statistically significant) as a result of therapy induced clinical remission. Conclusions. The rise in TNF-A level in reactions in leprosy is significant and indicates its active role in immunopathogenesis. The corresponding decline in TNF-a levels seen following regression of type 1 (lepra) reactions was not observed in the case of type 2 (ENL) reaction. This probably reflects the enhancement of cellular immunity in such cases and/or an attempt by the immunologic process to overcome specific inhibitors.

Background Leprosy and vitiligo are common affections in the West Indies. Vitiligo frequently occurs in lepromatous patients, an observation rarely reported in the literature. Methods We studied the prevalence of vitiligo in patients affected by leprosy by performing a retrospective study between 1978 and 1999 in the French West Indies (Martinique). Results Eleven patients presented with vitiligo among 101 with lepromatous (multibacillary) leprosy. None presented with vitiligo among the 364 with the tuberculoid (paucibacillary) form. The mean age of the vitiligo patients was 55.4 years at vitiligo onset. The sex ratio was 0.8. Vitiligo occurred 19 years after the diagnosis of leprosy, with a range from 3 to 42 years. The prevalence of vitiligo in lepromatous patients was 10.9%, compared to 0% in tuberculoid patients. Such an increase in prevalence compared with that in the general population (0.34%) was shown to be highly significant (P

We report a 35-year-old HIV-positive male affected by lepromatous leprosy which, to our knowledge, is the first case of its kind in Spain. The relationship between the two conditions is discussed.

It has been reported previously that Mycobacterium leprae modulated CD2 on human peripheral blood T lymphocytes and that this modulation was accompanied by a marked reduction in the proliferative response of these cells to mitogens and antigens. In this study, we report that treatment of peripheral blood mononuclear cells from healthy individuals with Dharmendra preparation of M. leprae inhibited their ability to form rosettes with sheep red blood cells. Flow cytometric analysis of Dharmendra lepromin-treated cells showed that, in addition to CD2, CD4 and CD8 were modulated while the surface expression of CD3 was not affected. The specificity of CD2 modulation was confirmed by similar effects of Dharmendra lepromin on thymocytes and lymph node cells from human CD2 transgenic mice. The modulatory effect of Dharmendra lepromin was not observed at lower temperatures. Dharmendra lepromin treatment of activated T cells resulted in reduced binding of monoclonal antibodies to IL-2R and D66 epitope of CD2. The modulatory effects were not observed with Dharmendra preparation of BCG or other preparations of M. leprae. Our results indicate that certain M. leprae factor(s) specifically modulate(s) CD2, CD4, CD8 and IL-2R but not CD3 on T lymphocytes. The suppressive effect of Dharmendra lepromin on the T-cell proliferative response reported earlier may be explained by its modulatory effect on a number of T-cell surface molecules.

Dapsone is an efficient anti-inflammatory and antimycobacterial agent. It is one of the main constituents of multidrug therapy (MDT). It acts by interference with folate metabolism. Dapsone-induced photosensitivity is a rare, non-dose-related adverse effect of the sulfone and can occur in patients with inflammatory skin disorders treated with dapsone. So far, only 12 cases seem to have been reported in the literature. We report a case of dapsone-induced photosensitivity in an Indian patient with leprosy.