Correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy.

BACKGROUND: In leprosy, sensory function of nerves is evaluated with monofilaments test and the motor function with voluntary muscle test, however electroneuromyography is considered as the gold-standard tool. OBJECTIVES: This study aimed: i) to evaluate the correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy; and ii) to identify the prevalence of leprosy neuropathy and the most compromised peripheral nerves in leprosy. METHODS: We analysed the data from a nested case-control study that identified 166 patients diagnosed with leprosy neuropathy confirmed by electromyography. This study was designed for an analysis of correlation between the diagnostic tests. RESULTS: The most prevalent type of the neural damage was the sensory and motor multiple mononeuropathy, observed in 62 (37.3%) cases. The highest prevalence was the ulnar nerve in 67 (40.3%) cases. Agreement specified by nerves was moderate, ranging from k = 0.58 in the deep peroneal nerve to k = 0.41 in the posterior tibial nerve). Overall agreement between the clinical tests and electroneuromyography was very poor. Monofilaments test with k = 0.02 (95% CI 0.00-0.12) and voluntary muscle test with 0.16 (95% CI 0.04 to 0.28, P = 0.01). CONCLUSIONS: There is a low to moderate correlation between clinical tests (monofilaments and voluntary muscle tests) and the electroneuromyography examination. The most prevalent type of neural impairment was the sensory and motor multiple mononeuropathy, and the most affected nerve was the ulnar.

Widespread nasal carriage of Mycobacterium lepraeamong a healthy population in a hyperendemic region of northeastern Brazil.

A case-control study was conducted to determine the presence ofMycobacterium lepraeDNA in nasal secretions of leprosy cases and nonleprosy individuals in Fortaleza, Brazil. It included 185 cases identified by physicians at the Dona Libânia National Reference Centre for Sanitary Dermatology (CDERM). A control group (Co) (n = 136) was identified among individuals from CDERM not diagnosed as leprosy cases. To augment the spatial analysis of M. leprae specific repetitive element (RLEP) positive prevalence, an external group (EG) (n = 121), a convenience sample of healthy students, were included. Polymerase chain reaction for the RLEP sequence was conducted for all participants. Prevalence of RLEP positivity for cases and Co were 69.2% and 66.9%, respectively, significantly higher than for EG (28.1%), and reported elsewhere. Male sex, belonging to a lower socioeconomic status (D/E), history of a previous contact with a case and being older, were associated with being a leprosy case. Our geographical analysis demonstrated that the bacillus is widespread among the healthy population, with clusters of RLEP positive multibacillary cases concentrated in distinct areas of the city. Our results suggest that in endemic areas, as in Fortaleza, surveillance for both nonhousehold leprosy contacts and members of the general population living in cluster areas should be implemented.

Results from the clinical trial of uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): decrease in bacteriological index.

BACKGROUND: Many believe that the regular treatment for multibacillary (MB) leprosy cases could be shortened. A shorter treatment allowing uniformity in treatment for all cases renders case classification superfluous and therefore simplifies leprosy control. OBJECTIVE: To evaluate the association between treatment duration and the trend in bacteriological index (BI) decrease over time among patients given Uniform MDT (UMDT) compared to those given regular MDT (RMDT). METHODS: An open-label randomised clinical trial to compare the present routine treatment with one lasting six month. Patient intake was from March 2007 to February 2012. To evaluate the trend of BI as a function of time, a multilevel linear with mixed effects model was fixed to the two study groups and also four groups after stratification by BI, less than 3 and 3 or more. RESULTS: The BI fall was higher among those taking RMDT, this difference however was not statistically significant. CONCLUSION: The results presented here support the possibility of use of UMDT in the field, but further follow up is still needed for a final conclusion.

Patient profile and treatment satisfaction of Brazilian leprosy patients in a clinical trial of uniform six-month multidrug therapy (U-MDT/CT-BR).

OBJECTIVE: To describe the profile of patients who participated in the Randomised Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR) and determine the level of satisfaction with a uniform therapy regimen, especially among paucibacillary patients. DESIGN: This is a descriptive cross-sectional epidemiologic study nested in the wider U-MDT/CT-BR. The study was conducted using a convenience sample composed of patients from the Dona Libânia Dermatology Centre in Fortaleza, Ceará and from the Alfredo da Matta Foundation in Manaus, Amazonas in Brazil. The absolute and relative frequencies of categorical variables and the median age were calculated. Hypothesis testing was done using the Chi-squared and Mann-Whitney tests with a 0.05 level of significance. RESULTS: Of the 859 patients included in the clinical trial, 342 were interviewed. The majority of patients were male (58.2%) and multibacillary (78.3%) with a median age of 42 (7-65) years. Most of the interviewees had not completed primary education (48.0%), earned an income below three times the minimum wage (53.8%), were non-smokers (85.1%), did not regularly consume alcohol (88.3%), had not experienced any leprosy-related discrimination (69.2%) and showed a basic knowledge of the disease. With regards to paucibacillary patients, 87.8% and 90.9% of the PB U-MDT and PB R-MDT groups, respectively, indicated that they had not thought of defaulting treatment at any time. On a satisfaction scale of 1-5 (with five as the highest score), 92.7% of PB U-MDT and 100.0% of PB R-MDT patients gave a mark between three and five. CONCLUSIONS: The data suggest that the introduction of clofazimine into the therapeutic regimen did not diminish the level of treatment satisfaction among PB patients.

Infections in the era of immunobiologicals.

Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.

Monkeypox: What the Dermatologist Needs to Know.

Monkeypox, an endemic disease in some African countries, has provoked public health activeness on a global scale that even the World Health Organization (WHO), invoking international health regulations, declared it a public health emergency of international concern (PHEIC). The WHO called attention of member states to exert maximum surveillance over the disease, its patients, and contact persons in order to standardize control measures. A need was directed to provide complete knowledge about the disease, allowing the administration of prior diagnoses as well as isolation and more effective epidemiologic control measures. An updated review on monkeypox emphasized upon having the fundamental aspects of the lesions caused by the disease, and appropriate management of patients upon clinical and epidemiologic evaluation.

Late relapses in leprosy patients in Brazil: 10-year post-trial of uniform multidrug therapy (U-MDT/CT-BR).

BACKGROUND: Leprosy is a neglected dermato-neurologic, infectious disease caused by Mycobacterium leprae or M. lepromatosis. Leprosy is treatable and curable by multidrug therapy/MDT, consisting of 12 months rifampicin, dapsone and clofazimine for multibacillary/MB patients and for 6 months for paucibacillary/PB patients. The relapse rate is considered a crucial treatment outcome. A randomized Controlled Clinical Trial (U-MDT/CT-BR) conducted from 2007‒2012 compared clinical outcomes in MB patients after 12 months regular MDT/R-MDT and 6 months uniform MDT/U-MDT in two highly endemic Brazilian areas. OBJECTIVES: To estimate the 10 years relapse rate of MB patients treated with 6 months U-MDT. METHODS: The statistical analyses treated the data as a case-control study, sampled from the cohort generated for the randomized trial. Analyses estimated univariate odds ratio and applied logistic regression for multivariate analysis, controlling the confounding variables. RESULTS: The overall relapse rate was 4.08 %: 4.95 % (16 out of 323) in the U-MDT group and 3.10 % (9 out of 290) in the regular/R-MDT group. The difference in relapse proportion between U-MDT and R-MDT groups was 1.85 %, not statistically significant (Odds Ratio = 1.63, 95 % CI 0.71 to 3.74). However, misdiagnosis of relapses, may have introduced bias, underestimating the force of the association represented by the odds ratio. CONCLUSIONS: The relapse estimate of 10 years follow-up study of the first randomized, controlled study on U-MDT/CT-BR was similar to the R-MDT group, supporting strong evidence that 6 months U-MDT for MB patients is an acceptable option to be adopted by leprosy endemic countries worldwide. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00669643.

Epidemiological profile of rosacea in dermatology outpatient clinics in Brazil: an observational report from the Brazilian study group on rosacea.

BACKGROUND: Rosacea prevalence varies worldwide and there is a lack of information in Brazil. OBJECTIVES: To describe the epidemiological profile of rosacea in subjects who consulted in dermatological outpatient clinics in Brazil. MATERIALS & METHODS: A cross-sectional study was conducted in 13 dermatological outpatient clinics across the country. Patients with rosacea diagnosis were eligible for the study according to the investigator's clinical assessment. Clinical, social and demographic data were collected. The overall and regional rosacea prevalence was calculated, and association with baseline characteristics was analysed. RESULTS: A total of 3,184 subjects were enrolled, and rosacea prevalence was 12.7%. The southern region of Brazil presented a higher prevalence, followed by the southeast. The subjects in the rosacea group were older than those without rosacea (52.5 ±14.9 vs. 47.5 ±17.5; p<0.001). Moreover, the rosacea group was associated with Fitzpatrick's phototypes I and II, Caucasian ethnicity, a family history of rosacea, and facial erythema, however, no association with gender was found. The most prevalent clinical sign and clinical subtype in rosacea patients were erythema and erythematotelangiectatic, respectively. CONCLUSION: Rosacea is highly prevalent in Brazil, mostly in the southern region, associated with phototypes I and II and a family history.

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.

Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique.

This publication is an update of the "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.

Primary results of clinical trial for uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): reactions frequency in multibacillary patients.

SETTINGS: Many believe that the regular treatment for multibacillary (MB) leprosy cases could be shortened. A shorter treatment, allowing for uniform treatment for all cases, makes case classification superfluous and therefore simplifies leprosy control. OBJECTIVE: To evaluate the association of the treatment duration with the frequency of reactions among MB patients. METHODS: An open-label randomised clinical trial to compare the present routine treatment with one lasting six months. Patients were recruited between March 2007 and February 2012. We analysed the frequency of first reaction with the Kaplan-Meier method and of recurrent reaction with a Poisson regression, using the treatment group and baciloscopic index level (BI) as independent variables. Logistic regression was used to evaluate the statistical association of different reaction types and the treatment group. RESULTS: Among those with BI < 3, we found a statistical significant difference of reaction frequencies between the treatment groups from 6 to 18 months since the beginning of treatment. This difference disappears at 2 years after the start of treatment. Multiple reactions were associated with the treatment group and with BI > or = 3. No specific types of reactions were associated with treatment duration. CONCLUSION: Although this is the first report of U-MDT/CT-BR, the results presented here support the possibility of use of UMDT in the field.

A clinical trial for uniform multidrug therapy for leprosy patients in Brazil: rationale and design.

Leprosy will continue to be a public health problem for several decades. The World Health Organization (WHO) recommends that, for treatment purposes, leprosy cases be classified as either paucibacillary or multibacillary (MB). A uniform leprosy treatment regimen would simplify treatment and halve the treatment duration for MB patients. The clinical trial for uniform multidrug therapy (U-MDT) for leprosy patients (LPs) in Brazil is a randomised, open-label clinical trial to evaluate if the effectiveness of U-MDT for leprosy equals the regular regimen, to determine the acceptability of the U-MDT regimen and to identify the prognostic factors. This paper details the clinical trial methodology and patient enrolment data. The study enrolled 858 patients at two centres and 78.4% of participants were classified as MB according to the WHO criteria. The main difficulty in evaluating a new leprosy treatment regimen is that no reliable data are available for the current treatment regimen. Relapse, reaction and impaired nerve function rates have never been systematically determined, although reaction and impaired nerve function are the two major causes of nerve damage that lead to impairments and disabilities in LPs. Our study was designed to overcome the need for reliable data about the current treatment and to compare its efficacy with that of a uniform regimen.

Brazilian clinical trial of uniform multidrug therapy for leprosy patients: the correlation between clinical disease types and adverse effects.

This study sought to verify the correlation between leprosy types and the adverse effects of treatment drugs. This quantitative, prospective, nested study was developed at the Dona Libânia Dermatology Centre in Fortaleza, Brazil. Data were collected from November 2007-November 2008. During this period, 818 leprosy patients were diagnosed and began treatment. Forty patients with tuberculoid leprosy (TT) were selected. Twenty patients followed a standard therapy of dapsone and rifampicin and 20 were administered dapsone, rifampicin and clofazimine (U-MDT). Twenty patients with borderline lepromatous (BL) and lepromatous leprosy (LL) were also selected and treated with U-MDT. All of the subjects received six doses. With the exception of haemolytic anaemia, there was a low incidence of adverse effects in all the groups. We did not observe any differences in the incidence of haemolytic anaemia or other side effects across groups of patients with TT, BL or LL treated with U-MDT.

Mycobacterium leprae virulence-associated peptides are indicators of exposure to M. leprae in Brazil, Ethiopia and Nepal.

Silent transmission of Mycobacterium leprae, as evidenced by stable leprosy incidence rates in various countries, remains a health challenge despite the implementation of multidrug therapy worldwide. Therefore, the development of tools for the early diagnosis of M. leprae infection should be emphasised in leprosy research. As part of the continuing effort to identify antigens that have diagnostic potential, unique M. leprae peptides derived from predicted virulence-associated proteins (group IV.A) were identified using advanced genome pattern programs and bioinformatics. Based on human leukocyte antigen (HLA)-binding motifs, we selected 21 peptides that were predicted to be promiscuous HLA-class I T-cell epitopes and eight peptides that were predicted to be HLA-class II restricted T-cell epitopes for field-testing in Brazil, Ethiopia and Nepal. High levels of interferon (IFN)-γ were induced when peripheral blood mononuclear cells (PBMCs) from tuberculoid/borderline tuberculoid leprosy patients located in Brazil and Ethiopia were stimulated with the ML2055 p35 peptide. PBMCs that were isolated from healthy endemic controls living in areas with high leprosy prevalence (EChigh) in Ethiopia also responded to the ML2055 p35 peptide. The Brazilian EChigh group recognised the ML1358 p20 and ML1358 p24 peptides. None of the peptides were recognised by PBMCs from healthy controls living in non-endemic region. In Nepal, mixtures of these peptides induced the production of IFN-γ by the PBMCs of leprosy patients and EChigh. Therefore, the M. leprae virulence-associated peptides identified in this study may be useful for identifying exposure to M. leprae in population with differing HLA polymorphisms.

Genotyping of Mycobacterium leprae present on Ziehl-Neelsen-stained microscopic slides and in skin biopsy samples from leprosy patients in different geographic regions of Brazil.

We analysed 16 variable number tandem repeats (VNTR) and three single-nucleotide polymorphisms (SNP) in Mycobacterium leprae present on 115 Ziehl-Neelsen (Z-N)-stained slides and in 51 skin biopsy samples derived from leprosy patients from Ceará (n = 23), Pernambuco (n = 41), Rio de Janeiro (n = 22) and Rondônia (RO) (n = 78). All skin biopsies yielded SNP-based genotypes, while 48 of the samples (94.1%) yielded complete VNTR genotypes. We evaluated two procedures for extracting M. leprae DNA from Z-N-stained slides: the first including Chelex and the other combining proteinase and sodium dodecyl sulfate. Of the 76 samples processed using the first procedure, 30.2% were positive for 16 or 15 VNTRs, whereas of the 39 samples processed using the second procedure, 28.2% yielded genotypes defined by at least 10 VNTRs. Combined VNTR and SNP analysis revealed large variability in genotypes, but a high prevalence of SNP genotype 4 in the Northeast Region of Brazil. Our observation of two samples from RO with an identical genotype and seven groups with similar genotypes, including four derived from residents of the same state or region, suggest a tendency to form groups according to the origin of the isolates. This study demonstrates the existence of geographically related M. leprae genotypes and that Z-N-stained slides are an alternative source for M. leprae genotyping.

Lucius phenomenon: the importance of a primary dermatological care.

Leprosy presents a varied clinical spectrum. Lucius phenomenon is a rare leprosy reaction characterized by erythematous, painful, slightly infiltrated macules and hemorrhagic bullae that progress to ulceration. This case report describes a patient whose diagnosis of leprosy occurred in the presence of Lucius phenomenon. Late diagnosis and delay in the implementation of specific therapy contributed to an unfavorable outcome, highlighting the importance of early identification and treatment of this disease, as well as its complications.

Human Genetic Susceptibility of Leprosy Recurrence.

Host genetic susceptibility to leprosy has been intensively investigated over the last decades; however, there are no studies on the role of genetic variants in disease recurrence. A previous initiative identified three recurrent cases of leprosy for which none of the M. leprae strains, as obtained in the first and the second diagnosis, had any known genomic variants associated to resistance to Multidrug therapy; in addition, whole genome sequencing indicated that the same M. leprae was causing two out of the three recurrences. Thus, these individuals were suspected of being particularly susceptible to M. leprae infection, either as relapse or reinfection. To verify this hypothesis, 19 genetic markers distributed across 11 loci (14 genes) classically associated with leprosy were genotyped in the recurrent and in three matching non-recurrent leprosy cases. An enrichment of risk alleles was observed in the recurrent cases, suggesting the existence of a particularly high susceptibility genetic profile among leprosy patients predisposing to disease recurrence.

Infections in the era of immunobiologicals

Abstract Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.