Case Report: A Case Series of Immunobiological Therapy (Anti-TNF-α) for Patients With Erythema Nodosum Leprosum.

Patients with leprosy may experience a chronic and severe type II leprosy reaction (ENL) erythema nodosum leprosum that may not respond to thalidomide and systemic immunosuppressants or may even cause serious adverse events. We here present four patients in whom anti-TNF-α therapy was used with successful results and compare our findings with other published cases. Four patients with chronic and severe ENL who did not respond to, at least, thalidomide and steroids (high doses) were followed up at two reference centers in Brazil. A thorough laboratory investigation was performed to exclude tuberculosis and other diseases before the start of immunobiological medication. Three patients were started on etanercept, and one patient was started on adalimumab. Of all patients, three developed severe adverse events resulting from the use of classical immunosuppressants for ENL (cataracts, deep vein thrombosis, diabetes, and osteoporosis). In all cases, a reduction in the number of ENL and, at least half of the immunosuppressant dose between 6 months and 2 years, were observed. Long-term follow-up of one patient revealed a dramatic reduction in hospital admissions due to ENL, from 12 instances in 1 year (before biologic therapy) to none (after biologic therapy), along with an improvement in condyloma acuminatum. In addition, no direct adverse events were observed with biologics. Treatment with anti-TNF-α therapy may be used as an alternative in patients with chronic and severe ENL who do not respond to traditional treatment (e.g., thalidomide, steroids, and other immunosuppressants). This treatment can help reduce the frequency of ENL, the immunosuppressive burden, and the number of hospital admissions.

Dramatic secukinumab-mediated improvements in refractory leprosy-related neuritis via the modulation of T helper 1 (Th1) and T helper 17 (Th17) immune pathways.

A 39-year-old woman was diagnosed with relapsed multibacillary leprosy and refractory neuritis. Here, we describe an evident loss of therapeutic effectiveness after the third pulse of corticosteroids, which may be attributed to tachyphylaxis and the posterior modulation of interferon- γ (IFN-γ), tumor necrosis factor- α (TNF-α,) interleukin-17A (IL-17A), and IL-12/23p40 after the induction phase of secukinumab. In this case, plasma cytokine analysis showed that secukinumab induced a reduction in IL-17 concomitant with impressive clinical improvements in the patient's neural function. Interestingly, secukinumab induced reductions in cytokines related to Th1 responses and earlier stages of the Th17 response, including IL-23/12.

Non-tuberculous cutaneous mycobacterioses

Abstract Non-tuberculous mycobacteriosis, previously known as atypical, anonymous, opportunistic, or unclassified mycobacteriosis, refers to pathogenic mycobacterioses other than those caused by Mycobacterium tuberculosis and Mycobacterium leprae. These mycobacteria are known for their environmental distribution, mainly in water and soil. The incidence of non-tuberculous mycobacteriosis has been increasing in all countries and skin infections are being increasingly studied, mainly with the increase in immunosuppressive conditions and the development of new medications that affect immunological function. In the present article, a detailed narrative review of the literature is carried out to study the main non-tuberculous mycobacteriosis that cause diseases of the skin and appendages. The article also aims to present a historical context, followed by epidemiological, microbiological, and clinical characteristics of these diseases. Practical considerations about the diagnosis and treatment of non-tuberculous mycobacteriosis are detailed.

Non-tuberculous cutaneous mycobacterioses.

Non-tuberculous mycobacteriosis, previously known as atypical, anonymous, opportunistic, or unclassified mycobacteriosis, refers to pathogenic mycobacterioses other than those caused by Mycobacterium tuberculosis and Mycobacterium leprae. These mycobacteria are known for their environmental distribution, mainly in water and soil. The incidence of non-tuberculous mycobacteriosis has been increasing in all countries and skin infections are being increasingly studied, mainly with the increase in immunosuppressive conditions and the development of new medications that affect immunological function. In the present article, a detailed narrative review of the literature is carried out to study the main non-tuberculous mycobacteriosis that cause diseases of the skin and appendages. The article also aims to present a historical context, followed by epidemiological, microbiological, and clinical characteristics of these diseases. Practical considerations about the diagnosis and treatment of non-tuberculous mycobacteriosis are detailed.

The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study.

BACKGROUND: Protective effects of Bacillus Calmette-Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. METHODOLOGY/PRINCIPAL FINDINGS: We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93-13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04-4.06) were significant risk factors for COVID-19. CONCLUSIONS/SIGNIFICANCE: Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.

Leprosy detection rate in patients under immunosuppression for the treatment of dermatological, rheumatological, and gastroenterological diseases: a systematic review of the literature and meta-analysis.

BACKGROUND: Recently developed immunosuppressive drugs, especially TNF antagonists, may enhance the risk of granulomatous infections, including leprosy. We aimed to evaluate the leprosy detection rate in patients under immunosuppression due to rheumatological, dermatological and gastroenterological diseases. METHODS: We performed a systematic review of the literature by searching the PubMed, EMBASE, LILACS, Web of Science and Scielo databases through 2018. No date or language restrictions were applied. We included all articles that reported the occurrence of leprosy in patients under medication-induced immunosuppression. RESULTS: The search strategy resulted in 15,103 articles; finally, 20 articles were included, with 4 reporting longitudinal designs. The detection rate of leprosy ranged from 0.13 to 116.18 per 100,000 patients/year in the USA and Brazil, respectively. In the meta-analysis, the detection rate of cases of leprosy per 100,000 immunosuppressed patients with rheumatic diseases was 84 (detection rate = 0.00084; 95% CI = 0.0000-0.00266; I2 = 0%, p = 0.55). CONCLUSION: Our analysis showed that leprosy was relatively frequently detected in medication-induced immunosuppressed patients suffering from rheumatological diseases, and further studies are needed. The lack of an active search for leprosy in the included articles precluded more precise conclusions. TRIAL REGISTRATION: This review is registered in PROSPERO with the registry number CRD42018116275 .

A systematic review and meta-analysis of studies on the diagnostic accuracy and screening of tests to detect antimicrobial resistance in leprosy.

Although multidrug therapy is considered an effective treatment for leprosy, antimicrobial resistance is a serious concern. We performed a systematic review of studies on the diagnostic accuracy and screening of tests for antimicrobial resistance in leprosy. This review was registered in PROSPERO (CRD42020177958). In April 2020, we searched for studies in the PubMed, EMBASE, Web of Science, Scopus, Scielo, and LILACS databases. A random effects regression model was used for the meta-analysis. We included 129 studies. Molecular tests for dapsone resistance had a sensitivity of 78.8% (95% confidence interval [CI] = 65.6-87.9) and a specificity of 97.0% (95% CI = 94.0-98.6). Molecular tests for rifampicin resistance had a sensitivity and specificity of 88.7% (95% CI = 80.0-93.9) and 97.3% (95% CI = 94.3-98.8), respectively. Molecular tests for ofloxacin resistance had a sensitivity and specificity of 80.9% (95% CI = 60.1-92.3) and 96.1% (95% CI = 90.2-98.5), respectively. In recent decades, no increase in the resistance proportion was detected. However, the growing number of resistant cases is still a clinical concern.

A systematic review and meta-analysis of studies on the diagnostic accuracy and screening of tests to detect antimicrobial resistance in leprosy

Although multidrug therapy is considered an effective treatment for leprosy, antimicrobial resistance is a serious concern. We performed a systematic review of studies on the diagnostic accuracy and screening of tests for antimicrobial resistance in leprosy. This review was registered in PROSPERO (CRD42020177958). In April 2020, we searched for studies in the PubMed, EMBASE, Web of Science, Scopus, Scielo, and LILACS databases. A random effects regression model was used for the meta-analysis. We included 129 studies. Molecular tests for dapsone resistance had a sensitivity of 78.8% (95% confidence interval [CI] = 65.6−87.9) and a specificity of 97.0% (95% CI = 94.0−98.6). Molecular tests for rifampicin resistance had a sensitivity and specificity of 88.7% (95% CI = 80.0−93.9) and 97.3% (95% CI = 94.3−98.8), respectively. Molecular tests for ofloxacin resistance had a sensitivity and specificity of 80.9% (95% CI = 60.1−92.3) and 96.1% (95% CI = 90.2−98.5), respectively. In recent decades, no increase in the resistance proportion was detected. However, the growing number of resistant cases is still a clinical concern(AU).

Dramatic secukinumab-mediated improvements in refractory leprosy-related neuritis via the modulation of T helper 1 (Th1) and T helper 17 (Th17) immune pathways

Abstract A 39-year-old woman was diagnosed with relapsed multibacillary leprosy and refractory neuritis. Here, we describe an evident loss of therapeutic effectiveness after the third pulse of corticosteroids, which may be attributed to tachyphylaxis and the posterior modulation of interferon- γ (IFN-γ), tumor necrosis factor- α (TNF-α,) interleukin-17A (IL-17A), and IL-12/23p40 after the induction phase of secukinumab. In this case, plasma cytokine analysis showed that secukinumab induced a reduction in IL-17 concomitant with impressive clinical improvements in the patient's neural function. Interestingly, secukinumab induced reductions in cytokines related to Th1 responses and earlier stages of the Th17 response, including IL-23/12.

The challenge of concomitant infections in the coronavirus disease 2019 pandemic era: Severe acute respiratory syndrome coronavirus 2 infection in a patient with chronic Chagas disease and dimorphic leprosy.

Coronavirus disease 2019 (COVID-19) was first officially described in Brazil on February 26th, 2020. The accumulation of reports of concomitant infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pathogens that cause diseases endemic to tropical countries, such as dengue and chikungunya fever, has started to draw attention. Chagas disease and leprosy remain public health problems in many developing countries, such as Brazil. In this manuscript, we describe a case of concomitant leprosy, Chagas disease, and COVID-19, highlighting the cutaneous manifestations of SARS-CoV-2 infection and the clinical behavior of household contacts who previously received prophylactic Bacillus Calmette-Guérin vaccines.

The interference of polypharmacy and the importance of clinical pharmacy advice in the treatment of leprosy: a case-control study.

INTRODUCTION: Although supervised doses are essential for reducing leprosy treatment failure, the impact of specific drug interactions has rarely been assessed. This study aimed to estimate the risk of leprosy treatment suspension in patients receiving polypharmacy. METHODS We performed this case-control study in which the primary outcome was defined as the need to discontinue multibacillary leprosy treatment for at least one supervised dose, and the main risk factor was the detection of polypharmacy. Multivariate analysis by logistic regression was used for calculating odds ratio (OR). RESULTS: This study included 103 patients, of whom 43 needed to discontinue leprosy treatment (hemolysis = 26, hepatitis = 2, hemolysis associated with hepatitis = 6, and suspected treatment resistance = 9) and the rest did not. The severity of drug interactions had no effect on treatment discontinuation. Patients who used five or more drugs in addition to leprosy treatment had almost a 4-fold greater risk of treatment suspension (OR, 3.88; 95% confidence interval: 1.79-9.12; p < 0.001). The number of drugs used also positively influenced the occurrence of hemolysis (p < 0.001). No patient presented evidence of molecular resistance to rifampicin, dapsone, or ofloxacin treatment, as evidenced by genetic sequencing detection of rpoB, folp1, and gyrA mutations. CONCLUSIONS: Polypharmacy has deleterious effects on the already difficult-to-adhere-to treatment of leprosy and polypharmacy induces hemolysis. Additional measures must be taken to avoid the undesirable effects of inadequate polypharmacy.

The interference of polypharmacy and the importance of clinical pharmacy advice in the treatment of leprosy: a case-control study

Abstract INTRODUCTION: Although supervised doses are essential for reducing leprosy treatment failure, the impact of specific drug interactions has rarely been assessed. This study aimed to estimate the risk of leprosy treatment suspension in patients receiving polypharmacy. METHODS We performed this case-control study in which the primary outcome was defined as the need to discontinue multibacillary leprosy treatment for at least one supervised dose, and the main risk factor was the detection of polypharmacy. Multivariate analysis by logistic regression was used for calculating odds ratio (OR). RESULTS: This study included 103 patients, of whom 43 needed to discontinue leprosy treatment (hemolysis = 26, hepatitis = 2, hemolysis associated with hepatitis = 6, and suspected treatment resistance = 9) and the rest did not. The severity of drug interactions had no effect on treatment discontinuation. Patients who used five or more drugs in addition to leprosy treatment had almost a 4-fold greater risk of treatment suspension (OR, 3.88; 95% confidence interval: 1.79-9.12; p < 0.001). The number of drugs used also positively influenced the occurrence of hemolysis (p < 0.001). No patient presented evidence of molecular resistance to rifampicin, dapsone, or ofloxacin treatment, as evidenced by genetic sequencing detection of rpoB, folp1, and gyrA mutations. CONCLUSIONS: Polypharmacy has deleterious effects on the already difficult-to-adhere-to treatment of leprosy and polypharmacy induces hemolysis. Additional measures must be taken to avoid the undesirable effects of inadequate polypharmacy.

The challenge of concomitant infections in the coronavirus disease 2019 pandemic era: Severe acute respiratory syndrome coronavirus 2 infection in a patient with chronic Chagas disease and dimorphic leprosy

Abstract Coronavirus disease 2019 (COVID-19) was first officially described in Brazil on February 26th, 2020. The accumulation of reports of concomitant infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pathogens that cause diseases endemic to tropical countries, such as dengue and chikungunya fever, has started to draw attention. Chagas disease and leprosy remain public health problems in many developing countries, such as Brazil. In this manuscript, we describe a case of concomitant leprosy, Chagas disease, and COVID-19, highlighting the cutaneous manifestations of SARS-CoV-2 infection and the clinical behavior of household contacts who previously received prophylactic Bacillus Calmette-Guérin vaccines.