Aspectos psicossociais associados à falha terapêutica da poliquimioterapia da hanseníase no estado de São Paulo, Brasil / Psychosocial aspects associated with therapeutic failure of multidrug therapy for leprosy in the state of São Paulo, Brazil

Na hanseníase, o fracasso na conclusão do esquema terapêutico da poliquimioterapia (PQT) é um dos motivos pela ocorrência de falhas terapêuticas, contribuindo para a transmissão continuada do bacilo, desenvolvimento de resistência aos medicamentos e necessidade de retratamento. Portanto, o objetivo deste estudo foi avaliar os componentes psicossociais dos pacientes submetidos a um ou mais tratamentos da PQT. Estudo de natureza qualitativa, realizado em Bauru, São Paulo, com 11 pacientes, por meio de entrevistas semiestruturadas: três sem retratamento e oito com retratamento. A interpretação dos dados foi realizada a partir das árvores de associação, derivada da análise de conteúdo de Bardin. Foram definidos cinco eixos temáticos: estigma social, autoestigma, relações interpessoais, atividade profissional, cuidados do paciente com a saúde e falhas na assistência profissional ao paciente. Os resultados indicaram que, apesar dos pacientes relatarem experiências de discriminação social, baixa autoestima, medo da rejeição e necessidade de sigilo do diagnóstico, os familiares funcionavam como rede de apoio. No trabalho, houve maior ocorrência de afastamentos, exonerações e benefícios trabalhistas. Falhas na assistência profissional e alguns cuidados do paciente com a saúde podem se constituírem fatores que contribuem para a necessidade de retratamento da PQT. A investigação desses componentes psicossociais pode fornecer subsídios para o planejamento das ações educativas dos profissionais de saúde a fim de evitar o retratamento da PQT, reduzir as falhas terapêuticas e favorecer à adesão ao tratamento.

Assessment of neuropathic pain in leprosy patients with relapse or treatment failure by infrared thermography: A cross-sectional study.

BACKGROUND: Neuropathic pain (NP) is one of the main complications of leprosy, and its management is challenging. Infrared thermography (IRT) has been shown to be effective in the evaluation of peripheral autonomic function resulting from microcirculation flow changes in painful syndromes. This study used IRT to map the skin temperature on the hands and feet of leprosy patients with NP. METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study included 20 controls and 55 leprosy patients, distributed into 29 with NP (PWP) and 26 without NP (PNP). Thermal images of the hands and feet were captured with infrared camera and clinical evaluations were performed. Electroneuromyography (ENMG) was used as a complementary neurological exam. Instruments used for the NP diagnosis were visual analog pain scale (VAS), Douleur Neuropathic en 4 questions (DN4), and simplified neurological assessment protocol. The prevalence of NP was 52.7%. Pain intensity showed that 93.1% of patients with NP had moderate/severe pain. The most frequent DN4 items in individuals with NP were numbness (86.2%), tingling (86.2%) and electric shocks (82.7%). Reactional episodes type 1 were statistically significant in the PWP group. Approximately 81.3% of patients showed a predominance of multiple mononeuropathy in ENMG, 79.6% had sensory loss, and 81.4% showed some degree of disability. The average temperature in the patients' hands and feet was slightly lower than in the controls, but without a significant difference. Compared to controls, all patients showed significant temperature asymmetry in almost all points assessed on the hands, except for two palmar points and one dorsal point. In the feet, there was significant asymmetry in all points, indicating a greater involvement of the lower limbs. CONCLUSION: IRT confirmed the asymmetric pattern of leprosy neuropathy, indicating a change in the function of the autonomic nervous system, and proving to be a useful method in the approach of pain.

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.

Genetic Susceptibility and Predictors of Paradoxical Reactions in Buruli Ulcer.

INTRODUCTION: Buruli ulcer (BU) is the third most frequent mycobacterial disease in immunocompetent persons after tuberculosis and leprosy. During the last decade, eight weeks of antimicrobial treatment has become the standard of care. This treatment may be accompanied by transient clinical deterioration, known as paradoxical reaction. We investigate the incidence and the risks factors associated with paradoxical reaction in BU. METHODS: The lesion size of participants was assessed by careful palpation and recorded by serial acetate sheet tracings. For every time point, surface area was compared with the previous assessment. All patients received antimicrobial treatment for 8 weeks. Serum concentration of 25-hydroxyvitamin D, the primary indicator of vitamin D status, was determined in duplex for blood samples at baseline by a radioimmunoassay. We genotyped four polymorphisms in the SLC11A1 gene, previously associated with susceptibility to BU. For testing the association of genetic variants with paradoxical responses, we used a binary logistic regression analysis with the occurrence of a paradoxical response as the dependent variable. RESULTS: Paradoxical reaction occurred in 22% of the patients; the reaction was significantly associated with trunk localization (p = .039 by Χ(2)), larger lesions (p = .021 by Χ(2)) and genetic factors. The polymorphisms 3'UTR TGTG ins/ins (OR 7.19, p < .001) had a higher risk for developing paradoxical reaction compared to ins/del or del/del polymorphisms. CONCLUSIONS: Paradoxical reactions are common in BU. They are associated with trunk localization, larger lesions and polymorphisms in the SLC11A1 gene.

Cutaneous tuberculosis due to multidrug-resistant tubercle bacilli and difficulties in clinical diagnosis.

This report describes 6 HIV-negative patients including 5 children with scrofuloderma and an adult with lupus vulgaris, out of a total of 303 cases of cutaneous tuberculosis seen during a 4½-year period, who showed a positive tuberculin test and granulomatous histopathology, but failed to respond to first-line antitubercular therapy. They were suspected to have multidrug-resistant infection as no other cause could be ascertained. Tissue aspirate or biopsy was sent for histopathology and culture. Mycobacterium tuberculosis was isolated from the aspirate in three patients and sputum in one with associated pulmonary tuberculosis. Drug susceptibility tests showed that all isolates were resistant to rifampicin and isoniazid, and one each additionally to streptomycin and ethambutol, respectively. In two, culture was unsuccessful. All were administered second-line antitubercular drugs. Clinical improvement was appreciable within 2 months as weight gain, and regression of ulcers, swellings and plaques. Two completed the recommended 24 months of therapy. Multidrug-resistant cutaneous tuberculosis should be suspected in patients with no response to first-line drugs, with clinical deterioration, and where other causes of treatment failure are not forthcoming. Owing to poor isolation rates on culture and low sensitivity of molecular tests, in such cases, a trial of second-line anti-tubercular drugs may be justified for a reasonable period of 2 months. Where facilities permit, culture and drug sensitivity tests should be done before starting treatment. Culture positivity is better from aspirated material.

High mortality associated with retreatment of tuberculosis in a clinic in Kampala, Uganda: a retrospective study.

The World Health Organization recommends for tuberculosis retreatment a regimen of isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z), and streptomycin (S) for 2 months, followed by H, R, E, and Z for 1 month and H, R, and E for 5 months. Using data from the National Tuberculosis and Leprosy Program registry, this study determined the long-term outcome under programmatic conditions of patients who were prescribed the retreatment regimen in Kampala, Uganda, between 1997 and 2003. Patients were traced to determine their vital status; 62% (234/377) patients were found dead. Having ≤ 2 treatment courses and not completing retreatment were associated with mortality in adjusted analyses.

Eccrine syringofibroadenomatosis of the reactive subtype occurring in chronic poorly-controlled psoriasis.

Eccrine syringofibroadenomatosis (ESFA) is a rare adnexal tumor with acrosyringeal differentiation. Clinically, it can be mistaken for granulomatous infections or malignancies such as squamous cell carcinoma. Despite the rarity of the condition, we recently encountered two cases of the reactive subtype, which occurred in patients with poorly controlled chronic psoriasis. Both patients presented with long-standing, thick verrucous lesions on the lower legs. The diagnosis was made after histological examination and exclusion of infectious and neoplastic disorders. As this is a reactive disorder, management is focused on treating the underlying condition. Unfortunately, psoriasis was difficult to manage in both our patients and they defaulted further treatment. It is important to recognize ESFA as it can be confused with infectious or malignant disorders.

Descrição de um caso exuberante de eritema nodoso hansênico e análise crítica dos sistemas de classificação para tratamento da hanseníase / Description of a lush case of erythema nodosum and critical analysis of classification systems for the treatment of leprosy

A hanseníase é doença endêmica e de notificação compulsória no Brasil. Há diversos sistemas de classificação para instituição da poliquimioterapia. Descreve-se caso de jovem com diagnóstico e tratamento de hanseníase paucibacilar que, após sete anos, retorna com recidiva das lesões e tratamento para multibacilar, evoluindo com eritema nodoso necrotizante.

Leprosy is an endemic and notifiable disease in Brazil. There are several classification systems for institution of multidrug therapy. We describe the case of a young man with diagnosis and treatment of paucibacillary leprosy who, after seven years, returns with lesion recurrence and treatment for multibacillary evolving necrotizing erythema nodosum.

Recidiva de hanseníase após 24 doses de poliquimioterapia multibacilar / Relapse in leprosy after 24 months o who multidrug therapy

The WHO multidrug therapy has changed the leprosy scenario since its implementation, with a low relapse rate. However, it is still a challenge the duration of treatment for effective cure in patients with high bacillary load. We report in this article a relapse in a patient 9 years after he had finished the therapy. It is also discussed the diagnostic criteria for leprosy relapse and the possibility that some patients require a longer treatment than the usually preconized.

Persister studies in leprosy patients after multi-drug treatment.

Cutaneous biopsies were collected from leprosy patients who attended the out-patient department of the Institute for treatment at different intervals, i.e., 12 months, 18 months, 24 months, 36 months, and more after beginning the multi-drug treatment therapy (M.D.T.). The patients belonged to the two drug regimens; (i) standard multibacillary (MB) M.D.T. after 12, 24, and 36 months; or (ii) standard M.D.T. + Minocycline 100 mg once a month (supervised) + Ofloxacin 400 mg once a month supervised for 12 months Biopsies were processed for mouse footpad inoculation and for estimating ATP levels by bioluminescence assay as per established methods. Viable bacilli were observed in 23.5% up to 1 year, 7.1% at 2 years, and in 3.84% at 3 years of M.D.T. by MFP and 29.4%, 10.7%, and 3.84% by ATP assay in the M.D.T. group at the same time period, respectively, but not in M.D.T. + Minocycline + Ofloxacin group after one year. The overall percentage of persisters was 5.55% by MFP and 7.14% by ATP assay up to 3 years of treatment.

Methotrexate in resistant ENL.

This is a report of a case of steroid resistant severe Type 2 reaction that was managed with methotrexate and prednisolone. Synergistic action of both the drugs in severe Type 2 reaction make them one of the preferred combinations in the absence of other agents such as thalidomide.

The relapse rate in MB leprosy patients treated with 2-years of WHO-MDT is not low.

A group of multibacillary patients is clearly at high risk for relapse following 2-yr WHO-MDT. Relapse is largely confined to BL or LL patients with a high BI initially, and occurs long after the discontinuation of therapy. This important group of patients at risk for treatment failure presents several important issues: the need to identify those at risk and the operational requirements needed for their long term follow-up. Also, this group of patients might well benefit from an alternative antimicrobial regimen from the outset, as well as upon relapse.