Erythema nodosum leprosum (ENL) or type 2 lepra reactions complicate lepromatous leprosy and borderline lepromatous leprosy. We report an 11-year retrospective case record analysis of 481 outpatients with borderline lepromatous and lepromatous leprosy at the Dhoolpet Leprosy Research Center in Hyderabad, India.. The overall prevalence of ENL was 24%, 49.4% among cases of lepromatous leprosy (LL) and 9% among cases of borderline lepromatous (BL) leprosy. Logistic regression analysis identified LL (odds ratio [OR] = 8.4, 95% confidence interval [CI] = 4.6-15.4, P < 0.001) and BL with a bacterial index > or = 4+ (OR = 5.2, 95% CI = 2.1-12.9, P = 0.001) as major risk factors. The average patient with ENL was male, 34.7 years of age, and had multiple episodes of ENL (mean = 3.1) over an 18.5-month period. Three types of ENL were identified: single acute ENL, multiple acute ENL (repeated discrete episodes), and chronic ENL (continuous episodes). Acute single ENL is rare, accounting for only 8% of cases. Chronic ENL accounted for 62.5% of the cohort. Chronic ENL was of longer duration and more severe. An age > or = 35 years was a risk factor for developing chronic ENL. Patients with chronic ENL were more compliant with multi-drug therapy, especially during the first six doses of multi-drug therapy. Distinguishing these different types of ENL would be useful for patient management and developing improved treatment of these debilitating reactions. Improved strategies for treatment and management of these reactions need to be developed.
The global leprosy situation has changed significantly over the last four decades after the introduction of multidrug therapy (MDT) in 1982 with a reduction in prevalence from over 5 million cases in the mid-1980s to less than 200,000 at the end of 2016. The programme in India also saw a reduction from a prevalence rate of 57.8/10,000 in 1983 to less than 1/10,000 by the end of 2005 when India declared to have reached the World Health Organization (WHO) target of elimination as a public health problem. Post 2005, major changes in the programme were made by the National leprosy eradication programme (NLEP) and the global leprosy programme, which may have affected the new case detection (NCD), disability, and child leprosy trends, which continue to show no appreciable regression. This article reviews the current global and Indian leprosy scenario to bring out its achievements and successes, including the impact of Leprosy Case Detection Campaigns (LCDC) on leprosy numbers. The basis and expected benefits of recent introduction of chemo and immune-prophylaxis in the programme are also discussed. It also discusses the shortcomings, the areas of concern, and the need for an inclusive strategy in the Indian leprosy programme that includes an intersectoral collaboration within the country for reaching the desired goal of leprosy eradication.
The effects of prednisolone treatment on the cellularity and cytokine (gamma interferon, interleukin-12, and inducible nitric oxide synthase) profiles of leprosy skin type 1 (reversal) reactions were studied using immunohistochemistry. Skin biopsies were taken from 15 patients with leprosy type 1 (reversal) reactions at days 0, 7, 28, and 180 after the start of steroid treatment. Prednisolone treatment had little effect at day 7, but by day 28 significant decreases were found in cytokine levels. Some patients maintained cytokine production at days 28 and 180. These results illustrate the strong Th1 profile of type 1 reactional lesions, the slow response to steroid therapy, and continuing activity at 180 days.
This study has identified T1R as being under-diagnosed in comparison with clinical assessments. Key variables for diagnosing T1R were established. This comparative masked study highlights the need for such studies in other inflammatory conditions.
To investigate genetic diversity in a bacterial population, we measured the copy numbers of simple sequence repeats, or microsatellites, in Mycobacterium leprae from patients living in and around Hyderabad, India. Three microsatellite loci containing trinucleotide or dinucleotide repeats were amplified from infected tissues, and the copy numbers were established by sequence analysis. Extensive diversity was observed in a cross-sectional survey of 33 patients, but closely related profiles were found for members of a multicase family likely to share a common transmission source. Sampling of multiple tissues from single individuals demonstrated identical microsatellite profiles in the skin, nasal cavity, and bloodstream but revealed differences at one or more loci for M. leprae present in nerves. Microsatellite mapping of M. leprae represents a useful tool for tracking short transmission chains. Comparison of skin and nerve lesions suggests that the evolution of disease within an individual involves the expansion of multiple distinct subpopulations of M. leprae.
The epineurium of the ulnar nerve can be measured with the use of HRUS, and it is often strikingly thickened in leprosy patients, especially in those with ulnar involvement.
BackgroundThe ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment in leprosy. The aim was to study correlations between clinical and histological diagnosis of reactions.Methodology/Principal FindingsThree hundred and three newly diagnosed patients with World Health Organization multibacillary (MB) leprosy from two centres in India were enrolled in the study. Skin biopsies taken at enrolment were assessed using a standardised proforma to collect data on the histological diagnosis of leprosy, leprosy reactions and the certainty level of the diagnosis. The pathologist diagnosed definite or probable Type 1 Reactions (T1R) in 113 of 265 biopsies from patients at risk of developing reactions whereas clinicians diagnosed skin only reactions in 39 patients and 19 with skin and nerve involvement. Patients with Borderline Tuberculoid (BT) leprosy had a clinical diagnosis rate of reactions of 43% and a histological diagnosis rate of 61%; for patients with Borderline Lepromatous (BL) leprosy the clinical and histological diagnosis rates were 53.7% and 46.2% respectively. The sensitivity and specificity of clinical diagnosis for T1R was 53.1% and 61.9% for BT patients and 61.1% and 71.0% for BL patients. Erythema Nodosum Leprosum (ENL) was diagnosed clinically in two patients but histologically in 13 patients. The Ridley-Jopling classification of patients (n = 303) was 42.8% BT, 27.4% BL, 9.4% Lepromatous Leprosy (LL), 13.0% Indeterminate and 7.4% with non-specific inflammation. This data shows that MB classification is very heterogeneous and encompasses patients with no detectable bacteria and high immunological activity through to patients with high bacterial loads.Conclusions/SignificanceLeprosy reactions may be under-diagnosed by clinicians and increasing biopsy rates would help in the diagnosis of reactions. Future studies should look at sub-clinical T1R and ENL and whether they have impact on clinical outcomes.
Pure neuritic leprosy has always been an enigma due to its clinical and management ambiguities. Although only the Indian Association of Leprologist's classification recognizes 'pure neuritic leprosy' as a distinct sub group of leprosy, cases nonetheless are reported from various countries of Asia, Africa, South America and Europe, indicating its global relevance. It is important to maintain pure neuritic leprosy as a subgroup as it constitutes a good percentage of leprosy cases reported from India, which contributes to more than half of global leprosy numbers. Unfortunately, a high proportion of these patients present with Grade 2 disability at the time of initial reporting itself due to the early nerve involvement. Although skin lesions are absent by definition, when skin biopsies were performed from the skin along the distribution of the affected nerve, a proportion of patients demonstrated leprosy pathology, revealing sub-clinical skin involvement. In addition on follow-up, skin lesions are noted to develop in up to 20% of pure neuritic leprosy cases, indicating its progression to manifest cutaneous disease. Over the decades, the confirmation of diagnosis of pure neuritic leprosy has been subjective, however, with the arrival and use of high-resolution ultrasonography (HRUS) for nerve imaging, we have a tool not only to objectively measure and record the nerve thickening but also to assess the morphological alterations in the nerve including echo texture, fascicular pattern and vascularity. Management of pure neuritic leprosy requires multidrug therapy along with appropriate dose of systemic corticosteroids, for both acute and silent neuritis. Measures for pain relief, self-care of limbs and physiotherapy are important to prevent as well as manage disabilities in this group of patients.
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