Should prophylaxis against Pneumocystis jirovecii pneumonia be considered in selected patients with leprosy reactions?

Leprosy reactions often require prolonged high-dose steroids or immunosuppressive drugs, putting patients at risk of Pneumocystis jirovecii pneumonia (PJP). However, no PJP cases are reported, possibly due to dapsone treatment for leprosy. In patients with leprosy reactions not receiving dapsone because of toxicity or resistance and requiring long-term immunosuppression, PJP prophylaxis should be considered.

Time to revisit the purported link of leprosy reactions with infective triggers: An unnecessary economic burden for patients.

Existing literature on factors triggering leprosy reactions is based only on case reports and case series, and thus probably gives a biased view. We undertook a case-control study to investigate such purported trigger factors in 42 leprosy reaction patients and 40 non-reactional controls, and the cost of investigations required for the same. Detailed history, clinical evaluation and investigations for triggers were carried out. Infections (typhoid, dental caries) were the most common triggers found, followed by pregnancy. Trigger factors were commoner in the type 2 reaction (T2R) group compared to type 1 (T1R) reaction group. There was however no statistical difference between the two groups. The average estimated cost of investigations was higher in the reactional group and this difference was statistically significant. Hence, except for essential investigations required for initiating steroids, an extensive battery of investigations is unjustified unless the medical history suggests a definitive infective trigger.

Chronic type 2 reaction in lepromatous leprosy with underlying Plasmodium falciparum infection: A case report.

Tropical diseases prevalent in leprosy-endemic areas may alter the immunological patient response and also complicate the presentation of leprosy reactional episodes. The introduction of anti-malarial drugs in our case produced a subsidence of reaction. With dwindling manpower skilled in leprosy, the reactional episodes are very often treated with non-steroidal anti-inflammatory drugs, steroids and thalidomide, neglecting the possibility of other co-existing infections, tropical or other. Our case emphasises the importance of history, examination and balanced investigation in the context of tropical diseases in endemic areas before injudicious intervention.

Cytokines profile in pure neural leprosy.

Introduction: Pure Neural Leprosy (PNL) is a form of this long time known disease that affects only the peripheral nervous system. Since it is a rare form of the disease, its pathophisiology is still poorly understood. Objective: Describe the cytokines profile in patients with PNL. Methods: 30 Patients diagnosed with PNL in the Souza Araujo Outpatient Clinic and with cytokines evaluated were selected. They were evaluated by neurologists and diagnosed after a nerve biopsy. Serum levels of IL-1 ß, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-ϒ, CXCL-10/IP-10 and TGF-ß were evaluates at the moment of the diagnosis. Results: Neural thickening was a common clinical finding in this groups of patients. Small and medium sensitive fibers signs and symptoms were present in 92% of the patients and motor involvement in 53%. 43% of patients presented neuropathic pain and no one had neuritis TGF-beta, IL-17, CCl-2 and IP-10. CCL-2 levels were associated with demyelinating patters and IP-10 and IL-1o were associated with axonal patterns at NCS. Discussion: PNL patients' cytokine profile appears to be different of other clinical forms of leprosy, with the presence of cytokines described in both tuberculoid and lepromatous leprosy. High levels of CCl-2 may be related to the presence of silent neuritis as well as the presence of IL-10. PNL is unique a form of leprosy, therefore, understanding its immunological profiles essential to better understand the disease itself.

Xenophagy as a Strategy for Mycobacterium leprae Elimination during Type 1 or Type 2 Leprosy Reactions: A Systematic Review.

BACKGROUND: Mycobacterium leprae is an intracellular bacillus that causes leprosy, a neglected disease that affects macrophages and Schwann cells. Leprosy reactions are acute inflammatory responses to mycobacterial antigens, classified as type1 (T1R), a predominant cellular immune response, or type2 (T2R), a humoral phenomenon, leading to a high number of bacilli in infected cells and nerve structures. Xenophagy is a type of selective autophagy that targets intracellular bacteria for lysosomal degradation; however, its immune mechanisms during leprosy reactions are still unclear. This review summarizes the relationship between the autophagic process and M. leprae elimination during leprosy reactions. METHODS: Three databases, PubMed/Medline (n = 91), Scopus (n = 73), and ScienceDirect (n = 124), were searched. After applying the eligibility criteria, articles were selected for independent peer reviewers in August 2023. RESULTS: From a total of 288 studies retrieved, eight were included. In multibacillary (MB) patients who progressed to T1R, xenophagy blockade and increased inflammasome activation were observed, with IL-1ß secretion before the reactional episode occurrence. On the other hand, recent data actually observed increased IL-15 levels before the reaction began, as well as IFN-γ production and xenophagy induction. CONCLUSION: Our search results showed a dichotomy in the T1R development and their relationship with xenophagy. No T2R studies were found.

Leprosy Reactions: Experience in the Puerto Rico Hansen's Disease Population.

OBJECTIVE: Hansen's disease (HD) is a chronic granulomatous infection endemic in the tropics. Its main clinical manifestations involve the cutaneous, nervous, and musculoskeletal systems. Leprosy reactions (LR) are systemic inflammatory and immune-mediated complications of HD. These include reversal reactions (RR), erythema nodosum leprosum (ENL), and Lucio phenomenon. These reactions significantly increase disease-related morbidity and disability. We aimed to determine the number and type of LR, their association to hosts' immune responses (Ridley Jopling classification), timing of development, and treatment of HD patients in Puerto Rico. METHODS: A retrospective medical record review was performed on 291 HD patients containing LR status data available from the Dermatology Service at the Hispanic Alliance for Clinical & Translational Research. RESULTS: Our data revealed that 83 (29%) patients developed LR, of which 31% had RR and 69% had ENL. Most LR were observed in patients in the lepromatous border (97%): Borderline lepromatous leprosy (BL) and Lepromatous Leprosy (LL). Most patients with RR and ENL had a single episode (83% and 62%, respectively), and those that received multi-drug therapy (MDT) had a reaction onset occurring most frequently within the first year of MDT and after the first year of MDT, respectively. Prednisone was the first line treatment used to manage both types of LR. CONCLUSION: Most lepromatous reactions occur within the lepromatous border. ENL was the most common LR. Prompt recognition and management of these immunologic reactions is essential to prevent long term nerve function impairment.

Prediction of the occurrence of leprosy reactions based on Bayesian networks.

Introduction: Leprosy reactions (LR) are severe episodes of intense activation of the host inflammatory response of uncertain etiology, today the leading cause of permanent nerve damage in leprosy patients. Several genetic and non-genetic risk factors for LR have been described; however, there are limited attempts to combine this information to estimate the risk of a leprosy patient developing LR. Here we present an artificial intelligence (AI)-based system that can assess LR risk using clinical, demographic, and genetic data. Methods: The study includes four datasets from different regions of Brazil, totalizing 1,450 leprosy patients followed prospectively for at least 2 years to assess the occurrence of LR. Data mining using WEKA software was performed following a two-step protocol to select the variables included in the AI system, based on Bayesian Networks, and developed using the NETICA software. Results: Analysis of the complete database resulted in a system able to estimate LR risk with 82.7% accuracy, 79.3% sensitivity, and 86.2% specificity. When using only databases for which host genetic information associated with LR was included, the performance increased to 87.7% accuracy, 85.7% sensitivity, and 89.4% specificity. Conclusion: We produced an easy-to-use, online, free-access system that identifies leprosy patients at risk of developing LR. Risk assessment of LR for individual patients may detect candidates for close monitoring, with a potentially positive impact on the prevention of permanent disabilities, the quality of life of the patients, and upon leprosy control programs.

Clinico-Epidemiological Trends of Leprosy at a Tertiary Care Centre of South Rajasthan: A 10-Year Retrospective Study.

Background: Leprosy is a major public health problem in India, which affects many people every year and has significantly high new case detection rates in certain districts and blocks. According to the National Leprosy Elimination Program (NLEP) report of March 2019, there were a total of 1.14 lakhs new cases of leprosy in India with an Annual New Case Detection Rate (ANCDR) of 8.1 per 100,000 population. Aim: The present study aimed at determining the epidemiological and clinical profile of leprosy patients from a tertiary level teaching hospital in South Rajasthan. Materials and Methods: A retrospective, record-based study was carried out on patients registered in the leprosy clinic of a tertiary level teaching hospital of South Rajasthan during a period of ten years (2010-2019). Data regarding the demographic profile, clinical features, treatment given, and complications were analysed. Results: A total of 1372 patients registered in the leprosy clinic during a period of 10 years were evaluated. There were 1007 (73.4%) males and 365 (26.6%) females with a male-female ratio of 2.76:1. The majority of patients 671 (48.9%) belonged to the middle age group (21-40 years). Multibacillary leprosy was the most common clinical type seen in 1109 patients (80.8%). Borderline leprosy was the most common morphological type, determined in 625 (45.6%) patients, of which BL (21.0%) was the most common group. 16.7% patients presented with leprosy reaction at the time of initial diagnosis. Type 1 reaction was seen in 91(6.6%) and type 2 reaction in 138 (10.1%) patients. Grade I disability was observed in 347 (25.3%) patients whereas grade II disability was seen in 456 (33.2%) patients. 54 patients (3.9%) had a definite history of contact in the family. 28 patients defaulted during the study period. Yearly trend of epidemiological and operational parameters was observed, and the parameters were compared with the national data. Conclusion: Persistent high proportion of multibacillary cases and grade 2 disability indicates that leprosy continues to be a significant health care problem despite statistical elimination. There is a clear need to strengthen early detection, treatment and regular follow-up of these cases in both high and low endemic settings.

Leprosy Reactions and Neuropathic Pain in Pure Neural Leprosy in a Reference Center in Rio de Janeiro - Brazil.

Introduction: Leprosy reactions are complications that can occur before, during, or after multidrug therapy (MDT) and are considered a major cause of nerve damage. Neuritis is an inflammatory process that causes nerve function impairment associated with pain and tenderness along the nerve. Neuritis can be found in both type 1 and type 2 reactions and may also be the sole manifestation of a leprosy reaction. The objective of this study is to describe the incidence of leprosy reactions and its association with neuropathic pain in pure neural leprosy (PNL) patients. Methods: We selected 52 patients diagnosed with PNL and 67 patients with other clinical forms of leprosy. During the MDT the patients visited the clinic monthly to take their supervised dose. The patients were instructed to return immediately if any new neurological deficit or skin lesions occurred during or after the MDT. Results: Of the PNL patients, 23.1% had a leprosy reaction during or after the MDT, while this was 59.7% for patients with the other clinical forms of leprosy. There was an association between having PNL and not having any reaction during and after the MDT, as well as having PNL and having neuritis after the MDT.There was also an association between having previous neuritis and having neuropathic pain in the other clinical forms of leprosy group, although this association was not present in the PNL group. Discussion: Our data suggest that PNL is a different form of the disease, which is immunologically more stable. In addition, PNL patients have more neuritis than the classical leprosy skin reactions. In PNL there was no association between acute neuritis and neuropathic pain, suggesting that these patients may have had silent neuritis. Understanding and identifying neuritis is essential to reduce disability and the impact on public health.

Analysis of therapeutic effectiveness and adverse effects of long-term corticosteroids among leprosy patients with reactions: A retrospective cohort study.

Objectives: Main therapy for leprosy reactions is 12 weeks corticosteroids according to World Health Organization recommendations, but recovery cannot be achieved and recurrence occurs. Long duration of administration was thought to provide better clinical improvement. Evidence of the efficacy of corticosteroids in leprosy reactions is still lacking, and optimal dose and duration of therapy vary, while the need for long-term high-dose corticosteroids makes it difficult to avoid adverse effects. Methods: This is a retrospective cohort study analyzing the difference between therapeutic effectiveness and adverse effects of 12 weeks and >12 weeks corticosteroids, involving all new leprosy patients without age restriction, at Cipto Mangunkusumo Hospital and Cakung Community Health Center in Indonesia during 1 January 2015-31 December 2017. Secondary data were collected from medical records, and observations carried out until December 2018. Therapeutic effectiveness was assessed from clinical improvement to corticosteroids discontinuation, without 3 months recurrence after first cycle was completed. Adverse effects were assessed by all corticosteroids-related side effects. Results: Of 195 patients, 57 (29.2%) used 12 weeks corticosteroids, and 138 (70.8%) for >12 weeks. Effectiveness occurred in 38 (66.7%) of 12 weeks group and 106 (76.8%) of >12 weeks group (relative risk = 0.604, 95% confidence interval = 0.307-1.189, p = 0.143). Of 145 patients, adverse effects occurred in 12 (31.6%) of 12 weeks group and 70 (65.4%) of >12 weeks group (relative risk = 0.244, 95% confidence interval = 0.111-0.538, p < 0.001). Of 171 adverse effects, 37.4% were mild such as dyspepsia, skin disorders, and lipodystrophy, while 62.6% were severe in the form of neuropsychiatric disorders, eye disorders, cardiovascular disease, gastrointestinal bleeding, metabolic-hormonal abnormalities, and reactivation of infections. Conclusion: There is no effectiveness difference in the form of clinical improvement without 3 months recurrence, between 12 weeks and >12 weeks corticosteroid, while longer administration causes 4 times more events.

Immunology of leprosy.

Leprosy is a disease caused by Mycobacterium leprae (ML) with diverse clinical manifestations, which are strongly correlated with the host's immune response. Skin lesions may be accompanied by peripheral neural damage, leading to sensory and motor losses, as well as deformities of the hands and feet. Both innate and acquired immune responses are involved, but the disease has been classically described along a Th1/Th2 spectrum, where the Th1 pole corresponds to the most limited presentations and the Th2 to the most disseminated ones. We discuss this dichotomy in the light of current knowledge of cytokines, Th subpopulations and regulatory T cells taking part in each leprosy presentation. Leprosy reactions are associated with an increase in inflammatory activity both in limited and disseminated presentations, leading to a worsening of previous symptoms or the development of new symptoms. Despite the efforts of many research groups around the world, there is still no adequate serological test for diagnosis in endemic areas, hindering the eradication of leprosy in these regions.

Magnitude dos episódios reacionais na hanseníase em serviço ambulatorial especializado / Magnitude of reactional episodes in leprosy in a specialized outpatient service

O objetivo do estudo é caracterizar os episódios reacionais segundo os dados sociodemográficos, clínicos e epidemiológicos de pacientes com hanseníase em um município hiperendêmico do estado do Piauí, Brasil, no período de 2013 a 2017. Para tanto, um estudo descritivo, transversal e retrospectivo utilizou-se os casos de hanseníase, notificados no Sistema de Informação de Agravos de Notificação (SINAN), juntamente com a ficha de dispensação de medicamentos do local em estudo. Foram realizadas análise univariada, por meio de estatística descritiva simples, e análise bivariada, utilizando o Qui-quadrado de Pearson para associar as va-riáveis quantitativas com a variável resposta do estudo, que é o momento da reação hansênica. A significância estatística foi fixada em p<0,05. Observou-se que a maioria dos episódios reacionais ocorreram durante o tratamento para hanseníase. Homens, pardos, pessoas com ensino fundamental completo ou incompleto, pedreiros, moradores da zona urbana, indivíduos dimorfos, multibacilares e com presença de grau 0 de incapacidade física, predominaram no aparecimento de reação. A reação que prevaleceu foi a do tipo 1, seguida pelo tipo 2, e em última, a reação mista. Diante disso, com-preende-se que as vulnerabilidades individuais, sociais e econômicas impactam diretamente no desenvolvimento de reação hansênica.(AU)

The objective of the study is to characterize the reactional episodes according to the sociodemographic, clinical and epidemiological data of patients with leprosy in a hyperendemic municipality in the state of Piauí, Brazil, from 2013 to 2017. For that, a study descriptive, cross-sectional and retrospective, leprosy cases notified in the Disease Information System were used of Notification (SINAN), together with the medication dispensing form place under study. Univariate analysis was performed using simple descriptive statistics, and bivariate analysis, using Pearson's Chi-square to associate the quantitative variables with the study response variable, which is the moment of the leprosy reaction. Statistical significance was set at p<0.05. It was observed that most reactional episodes occurred during treatment for leprosy. Men, browns, people with complete or incomplete elementary education, bricklayers, residents of the urban area, dimorphic, multibacillary individuals and with the presence of degree zero of physical disability, were the ones that predominated in the appearance of reaction. The reaction that prevailed was type 1, followed by type 2 and, finally, the mixed reaction. In view of this, it is understood that individual, social and economic vulnerabilities directly impact the development of leprosy reaction.

Host-Related Laboratory Parameters for Leprosy Reactions.

Leprosy reactions are acute inflammatory episodes that complicate the course of a Mycobacterium leprae infection and are the major cause of leprosy-associated pathology. Two types of leprosy reactions with relatively distinct pathogenesis and clinical features can occur: type 1 reaction, also known as reversal reaction, and type 2 reaction, also known as erythema nodosum leprosum. These acute nerve-destructive immune exacerbations often cause irreversible disabilities and deformities, especially when diagnosis is delayed. However, there is no diagnostic test to detect or predict leprosy reactions before the onset of clinical symptoms. Identification of biomarkers for leprosy reactions, which impede the development of symptoms or correlate with early-onset, will allow precise diagnosis and timely interventions to greatly improve the patients' quality of life. Here, we review the progress of research aimed at identifying biomarkers for leprosy reactions, including its correlation with not only immunity but also genetics, transcripts, and metabolites, providing an understanding of the immune dysfunction and inflammation that underly the pathogenesis of leprosy reactions. Nevertheless, no biomarkers that can reliably predict the subsequent occurrence of leprosy reactions from non-reactional patients and distinguish type I reaction from type II have yet been found.

Comparison between nerve conduction study and high-resolution ultrasonography with color doppler in type 1 and type 2 leprosy reactions.

OBJECTIVE: To analyze the role of high-resolution ultrasonography with color Doppler (HRUS with CD) to diagnose inflammatory activity (IA) in nerves of leprosy patients under type 1 (RT1) and 2 (RT2) reactions compared to Nerve Conduction Studies (NCS). METHODS: Leprosy patients with signs or symptoms suggestive of neuritis (RT1 and RT2) without corticosteroids use were selected. They were evaluated by NCS and subsequently by HRUS with CD. Subacute segmental demyelination and the presence of blood flow, respectively, were considered signs of IA. The two methods were compared for their ability to diagnose patients with leprosy reactions. RESULTS: A total of 257 nerves from 35 patients were evaluated. NCS and HRUS with CD diagnosed IA in 68% and 74% of patients, respectively. When both methods were used concomitantly, the diagnosis rate was 91.4%. HRUS with CD was particular helpful when there was minimal neurophysiological compromise in NCS or when motor potentials were not detected. CONCLUSION: HRUS with CD was able to detect leprosy reactions, especially when combined with NCS. It was especially useful in two opposite situations: nerves with only minor changes and those without motor response in NCS. SIGNIFICANCE: Our data shows the usefulness of HRUS and CD, similar to NCS, as a tool to diagnose leprosy reactions.

Comparison between nerve conduction study anf high-resolution ultrasonography with color doppler in type 1 and type 2 leprosy

Objective: To analyze the role of high-resolution ultrasonography with color Doppler (HRUS with CD) to diagnose inflammatory activity (IA) in nerves of leprosy patients under type 1 (RT1) and 2 (RT2) reactions compared to Nerve Conduction Studies (NCS). Methods: Leprosy patients with signs or symptoms suggestive of neuritis (RT1 and RT2) without corticosteroids use were selected. They were evaluated by NCS and subsequently by HRUS with CD. Subacute segmental demyelination and the presence of blood flow, respectively, were considered signs of IA. The two methods were compared for their ability to diagnose patients with leprosy reactions. Results: A total of 257 nerves from 35 patients were evaluated. NCS and HRUS with CD diagnosed IA in 68% and 74% of patients, respectively. When both methods were used concomitantly, the diagnosis rate was 91.4%. HRUS with CD was particular helpful when there was minimal neurophysiological compromise in NCS or when motor potentials were not detected. Conclusion: HRUS with CD was able to detect leprosy reactions, especially when combined with NCS. It was especially useful in two opposite situations: nerves with only minor changes and those without motor response in NCS. Significance: Our data shows the usefulness of HRUS and CD, similar to NCS, as a tool to diagnose leprosy reactions.

Mycobacterium leprae: Pathogenesis, diagnosis, and treatment options.

Mycobacterium leprae is known to cause leprosy, a neurological and dermatological disease. In the past 20 years, 16 million leprosy cases have been recorded and more than 200,000 new cases were registered each year, indicating that the disease is still progressing without hindrance. M. leprae, an intracellular bacterium, infects the Schwann cells of the peripheral nervous system. Several types of leprosy have been described, including indeterminate, tuberculoid, borderline tuberculoid, mid-borderline, borderline lepromatous and lepromatous, and three different forms of leprosy reactions, namely type 1, 2 and 3, have been designated. Microscopic detection, serological diagnostic test, polymerase chain reaction and flow tests are employed in the diagnosis of leprosy. The recommended treatment for leprosy consists of rifampicin, dapsone, clofazimine, ofloxacin and minocycline and vaccines are also available. However, relapse may occur after treatment has been halted and hence patients must be educated on the signs of relapse to allow proper treatment and reduce severity. In this review, we depict the current understanding of M. leprae pathogenicity, clinical aspects and manifestations. Transmission of leprosy, diagnosis and treatment are also discussed.

Chronic aspects of leprosy-neglected but important.

The chronic aspects of leprosy are discussed here. They are a consequence of the peripheral nerve damage that affects many patients during their lifetime with leprosy. The peripheral nerve damage leaves people unable to feel and with weakness in their hands and feet. They are at risk of damaging their hands and feet, causing the disabilities and deformities that characterise late leprosy. More than 200 000 new leprosy patients are diagnosed globally each year. Better data are needed from cohort studies to estimate the number of patients developing nerve damage and modelling studies are needed to estimate the number of patients who develop disabilities. For some of them, this will be a lifelong disability. Nerve damage is caused by inflammation in leprosy-affected nerves. Patients with nerve damage of <6-mo duration need treatment with steroids. About 66% of multibacillary patients will develop nerve damage. Plastic graded monofilaments can be used to detect nerve damage in leprosy and diabetic clinics. Assessing nerve damage and treating patients with steroids in leprosy programmes needs to be strengthened. The World Health Organization has a successful programme for supplying antibiotics for treating leprosy infection to national leprosy programmes. They should take responsibility for providing steroids to national programmes since this is a core part of the treatment for >66% of multibacillary patients. Patients need to be asked about neuropathic pain symptoms and treated if necessary. Treated leprosy patients are at risk of developing ulcers in their feet. Treatment and prevention needs to be improved through health education, providing protective footwear and patient empowerment.

Evaluation of monocyte subsets and markers of activation in leprosy reactions.

Understanding host immune pathways associated with tissue damage during reactions are of upmost importance to the development of immune intervention strategies. The participation of monocytes in leprosy reactions was evaluated by determining the frequency of monocyte subsets and the degree of cellular activation through the expression of MHCII and the co-stimulatory molecules CD40, CD80, CD86. Leprosy subjects with or without reactions were included in this cross-sectional study. Peripheral blood mononuclear cell were isolated and stained ex vivo to determine monocyte subsets and the degree of cellular activation by flow cytometry. Intermediate monocytes were increased in leprosy patients with reactions when compared to patients without reactions. Although no difference was detected in the frequency of monocyte subsets between type 1 and 2 reactions, the expression of CD80 was increased in monocytes from patients with type 1 reactions and CD40 was higher in paucibacillary subjects presenting type 1 reactions. Moreover, CD86 and MHC II expression were higher in intermediate monocytes when compared to the other subsets in leprosy reaction types 1 and 2. Intermediate monocyte activation with CD86 and MHCII expression is involved with both type 1 and 2 reactions, whereas CD80 and CD40 expression is related to type 1 reactions.

Whole blood profiling of leprosy type 1(reversal) reactions highlights prominence of innate immune response genes.

BACKGROUND: The major factors contributing for nerve damage and permanent disabilities in leprosy are type 1 or reversal reactions (RR) and type 2 or erythema nodosum leprosum (ENL). Gene profiling of leprosy reactions have shown that different pathways are activated during the course of reactions, which is consistent with the exacerbated immune response exhibited by these patients. METHODS: We used qPCR to screen a panel of 90 genes related to the immune response in leprosy in RNA-derived peripheral leukocytes of patients with (N = 94) and without leprosy reactions (N = 57) in order to define expression signatures correlated to RR or ENL. RESULTS: Our results show that there is a marked signature for RR in the blood, comprising genes mostly related to the innate immune responses, including type I IFN components, autophagy, parkins and Toll like receptors. On the other hand, only Parkin was differentially expressed in the ENL group. CONCLUSIONS: The data put together corroborates previous work that brings evidence that an acute uncontrolled exacerbated immune response designed to contain the spread of M. leprae antigens might be cause of RR pathogenesis. Identifying a blood profile useful to predict leprosy reactions prior to its development might help to reduce the morbidity associated to this disabling disease.