Negligência no diagnóstico precoce de hanseníase na atenção primária: um relato de caso / Negligence in the early diagnosis of leprosy in primary care: a case report

A hanseníase é uma doença infecciosa, transmissível, de caráter crônico, com potencial grau de incapacidade, que ainda persiste como problema de saúde pública no Brasil. A demora e a falta de conhecimento técnico para realizar o diagnóstico resulta em inúmeros prejuízos aos pacientes acometidos pela doença, sendo que, a prevenção das incapacidades está relacionada diretamente com o diagnóstico precoce da doença. Com a finalidade de evitar a negligência diagnóstica e o desenvolvimento de incapacidades físicas, ressaltamos a importância do conhecimento técnico sobre o diagnóstico e o manejo da hanseníase por profissionais da saúde em qualquer nível de atenção à saúde ou especialidade.

Hansen is an infectious disease, transmissible, of a chronic nature, with serious potential for disability, which still persists as a public health problem in Brazil. The delay and the lack of technical knowledge to carry out the diagnosis with numerous prejudices to the patients affected by the disease, since the prevention of disabilities is directly related to the early diagnosis of the disease. In order to avoid diagnostic negligence and the development of physical disabilities, we highlight the importance of technical knowledge about the diagnosis and management of training by health professionals at any level of health care or special care.

Efficacy of fixed duration multidrug therapy for the treatment of multibacillary leprosy: A prospective observational study from Northern India.

BACKGROUND: In endemic regions of several countries, the prevalence of leprosy has not come down to the level of elimination. On the contrary, new cases are being detected in large numbers. Clinically, it is frequently noted that despite completion of multibacillary multidrug therapy for 12 months, the lesions remain active, especially in cases with high bacteriological indices. AIM: The present study focused on finding out the viable number of Mycobacterium leprae during the 12-month regimen of multibacillary multidrug therapy, at six and 12 months intervals and, attempting to determine their role in disease transmission. METHODS: Seventy eight cases of multibacillary leprosy cases were recruited from leprosy patients registered at The Leprosy Mission hospitals at Shahdara (Delhi), Naini (Uttar Pradesh) and Champa (Chhattisgarh), respectively. Slit skin smears were collected from these patients which were transported to the laboratory for further processing. Ribonucleic acid was extracted by TRIzol method. Total Ribonucleic acid was used for real-time reverse transcription-polymerase chain reaction (two-step reactions). A standard sample with a known copy number was run along with unknown samples for a reverse transcription-polymerase chain reaction. Patients were further assessed for their clinical and molecular parameters during 6th month and 12th month of therapy. RESULTS: All 78 new cases showed the presence of a viable load of bacilli at the time of recruitment, but we were able to follow up only on 36 of these patients for one year. Among these, using three different genes, 20/36 for esxA, 22/36 for hsp18 and 24/36 for 16S rRNA cases showed viability of M. leprae at the time of completion of 12 months of multidrug therapy treatment. All these positive patients were histopathologically active and had bacillary indexes ranging between 3+ and 4+. Patients with a high copy number of the Mycobacterium leprae gene, even after completion of treatment as per WHO recommended fixed-dose multidrug therapy, indicated the presence of live bacilli. LIMITATIONS: Follow up for one year was difficult, especially in Delhi because of the migratory nature of the population. Patients who defaulted for scheduled sampling were not included in the study. CONCLUSION: The presence of a viable load of bacilli even after completion of therapy may be one of the reasons for relapse and continued transmission of leprosy in the community.

Gene expression patterns associated with multidrug therapy in multibacillary leprosy.

Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against M. leprae. Consequently, clearance of bacilli from the body is a slow process and after 12 doses of MDT not all MB patients reduce bacillary index (BI). In this context, we recruited MB patients at the uptake and after 12-month of MDT. Patients were stratified according to the level of reduction of the BI after 12 doses MDT. A reduction of at least one log in BI was necessary to be considered a responder patient. We evaluated the pattern of host gene expression in skin samples with RNA sequencing before and after MDT and between samples from patients with or without one log reduction in BI. Our results demonstrated that after 12 doses of MDT there was a reduction in genes associated with lipid metabolism, inflammatory response, and cellular immune response among responders (APOBEC3A, LGALS17A, CXCL13, CXCL9, CALHM6, and IFNG). Also, by comparing MB patients with lower BI reduction versus responder patients, we identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7, and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT, with higher expression of genes like CYP11A1, that are associated with cholesterol metabolism in the group with the worst response to treatment. Altogether, the data presented contribute to elucidate gene signatures and identify differentially expressed genes associated with MDT outcomes in MB patients.

Necrotic erythema nodosum reaction associated with histological alterations of Lucio's phenomenon

Abstract Patients with lepromatous or borderline leprosy may present two types of vasculonecrotic reactions: Lucio's phenomenon (LP) and necrotic erythema nodosum leprosum (nENL). These are serious conditions, which mostly lead to life-threatening infectious and thrombotic complications. The authors report the case of a patient with leprosy recurrence associated with an atypical type II reaction with LP characteristics on histopathology.

Symmetrical Centrofacial Erythematous Plaques and Papules: A Clinicopathological Challenge.

Facial papular eruptions remain a diagnostic dilemma for the dermatologist with a wide range of inflammatory and infectious conditions manifesting in this manner. Here, we present a case of a 29-year-old, otherwise healthy man from North India with asymptomatic well-defined normoaesthetic symmetrical papules and plaques over the upper and mid-face of 3 months duration. Skin biopsy showed perivascular and periappendageal well-defined collections of foamy macrophages and epithelioid cells in superficial and deep dermis, characteristic of borderline lepromatous leprosy. Though acid-fast stain for lepra bacilli was negative both on lesional biopsy specimen and lesional and ear lobe slit skin smear, a 16s ribosomal ribonucleic acid (16s-r-RNA) polymerase chain reaction on skin biopsy specimen was found to be positive for lepra bacilli. A final diagnosis of borderline lepromatous leprosy in type I reaction was made and the patient received World Health Organization (WHO) multibacillary (MB) multidrug therapy along with oral steroids. This case highlights the unusual localized involvement in a case of MB leprosy lacking all the three cardinal features of leprosy, i.e. sensory loss, peripheral nerve involvement, and acid-fast bacilli positivity on biopsy or slit skin smear but diagnosed on the basis of characteristic histology and positive polymerase chain reaction results.

Necrotic erythema nodosum reaction associated with histological alterations of Lucio's phenomenon.

Patients with lepromatous or borderline leprosy may present two types of vasculonecrotic reactions: Lucio's phenomenon (LP) and necrotic erythema nodosum leprosum (nENL). These are serious conditions, which mostly lead to life-threatening infectious and thrombotic complications. The authors report the case of a patient with leprosy recurrence associated with an atypical type II reaction with LP characteristics on histopathology.

Patterns and determinants of treatment completion and default among newly diagnosed multibacillary leprosy patients: A retrospective cohort study.

BACKGROUND: Poor treatment adherence among leprosy patients contribute to relapse, development of antimicrobial resistance, and the eventual plateauing of the prevalence and incidence of leprosy not just in the Philippines, but also worldwide. For this reason, we aimed to identify the patterns and determinants affecting treatment completion and default among multibacillary leprosy patients. METHODS: We conducted a retrospective cohort study involving three large hospitals in Metro Manila, Philippines. Patients who started the World Health Organization - Multiple Drug Therapy for multibacillary leprosy between January 1, 2007 and December 31, 2013 were included in the study. Selected socio-demographic and clinical data were abstracted from the patient treatment records. Survival analysis and proportional hazards regression were used to analyze the data. RESULTS: Records of 1,034 patients with a total follow-up time of 12,287 person-months were included in the analysis. Most patients were male, younger than 45 years old, had an initial bacterial index between 1 and 4, and were residents of Metro Manila. Less than 20% had their treatment duration extended to more than 12 months. Treatment adherence of the patients was poor with less than 60% completing treatment. Most patients complete their treatment within 12 months, but treatment duration may be extended for up to three years. Patients who default from treatment usually do so a few months after initiating it. After adjusting for other variables, hospital, initial bacterial index, and non-extended treatment duration were associated with treatment completion. These factors, in addition to age, were also found to be associated with treatment default. CONCLUSION: This study provides quantitative evidence that there might be marked variations in how doctors in particular hospitals manage their patients, and these findings underscore the need to revisit and re-evaluate clinical practice guidelines to improve treatment outcomes and adherence.

Report on an unusual case of leprosy from Germany: just an exception of the rule?

CASE PRESENTATION: We report on a German leprosy patient originating from Pakistan who had a relapse more than 5 years after completion of multi-drug therapy (MDT) of his first episode of multibacillary (MB) leprosy. State-of-the-art laboratory techniques (histopathology, PGL-I serology, microscopy and DNA/RNA qPCR) were applied for laboratory confirmation and monitoring of treatment outcome. Serology indicated the relapse long before the presence of unambiguous clinical signs. At the time of diagnosis of the relapse the patient had a remarkably high bacterial load suggesting increased risk for a second relapse. Furthermore, unexpectedly prolonged excretion of viable bacilli through the upper respiratory tract for more than 3 months after onset of MDT was shown. Therefore, MDT was administered for 2 years. DISCUSSION AND CONCLUSIONS: The clinical course of the patient, as well as the prolonged excretion of viable bacilli, underlines the usefulness of laboratory assessment. Laboratory tools including up-to-date molecular assays facilitate rapid diagnosis, timely MDT, identification of individuals excreting viable bacilli and patients at risk for relapses, monitoring of treatment outcome and respective adaptation of treatment where appropriate.

Aspectos clínicos y epidemiológicos en pacientes timorenses con enfermedad de Hansen / Clinical and epidemiological aspects in Timor patients with the Hansen disease

Se realizó un estudio observacional, descriptivo y transversal de 14 pacientes con lepra, diagnosticados y atendidos en la consulta de Dermatología del Hospital Nacional Guido Valadares, en Dili, Timor Oriental, de julio a diciembre del 2015, con vistas a caracterizarles y describir algunos aspectos clínicos y epidemiológicos de la enfermedad. En la serie se obtuvo una mayor frecuencia de pacientes en el grupo etario de 26 a 35 años y del sexo masculino, la forma clínica predominante fue la multibacilar y el tiempo de evolución de los síntomas hasta que fuera establecido el diagnóstico fue de menos de un año. Igualmente, en la mayoría existieron reacciones agudas, principalmente de tipo II o eritema nudoso leproso, y diferentes grados de discapacidad.

An observational, descriptive and cross-sectional study of 14 patients with leprosy, diagnosed and assisted in the Dermatology Service of Guido Valadares National Hospital, in Dili, Timor Lester was carried out from July to December, 2015, with the aim of characterizing them and to describe some clinical and epidemiological aspects of the disease. In the series a higher frequency of patient was obtained in the age group 26 to 35 years and of the male sex, the predominant clinical form was the multibacilar and the time of clinical course of the symptoms up to reaching the diagnosis was shorter than a year. Equally, in most of them acute reactions were presented, mainly of type II or from the erythema leprosy group, and different degrees of inability.

Aspectos clínicos y epidemiológicos en pacientes timorenses con enfermedad de Hansen / Clinical and epidemiological aspects in Timor patients with the Hansen disease

Se realizó un estudio observacional, descriptivo y transversal de 14 pacientes con lepra, diagnosticados y atendidos en la consulta de Dermatología del Hospital Nacional Guido Valadares, en Dili, Timor Oriental, de julio a diciembre del 2015, con vistas a caracterizarles y describir algunos aspectos clínicos y epidemiológicos de la enfermedad. En la serie se obtuvo una mayor frecuencia de pacientes en el grupo etario de 26 a 35 años y del sexo masculino, la forma clínica predominante fue la multibacilar y el tiempo de evolución de los síntomas hasta que fuera establecido el diagnóstico fue de menos de un año. Igualmente, en la mayoría existieron reacciones agudas, principalmente de tipo II o eritema nudoso leproso, y diferentes grados de discapacidad(AU)

An observational, descriptive and cross-sectional study of 14 patients with leprosy, diagnosed and assisted in the Dermatology Service of Guido Valadares National Hospital, in Dili, Timor Lester was carried out from July to December, 2015, with the aim of characterizing them and to describe some clinical and epidemiological aspects of the disease. In the series a higher frequency of patient was obtained in the age group 26 to 35 years and of the male sex, the predominant clinical form was the multibacilar and the time of clinical course of the symptoms up to reaching the diagnosis was shorter than a year. Equally, in most of them acute reactions were presented, mainly of type II or from the erythema leprosy group, and different degrees of inability(AU)

Lepra histioide o de Wade: Presentación de un caso clínico / Wade histioid leprosy: A case report

La lepra histioide de Wade, es una forma clínico-histopatológica especial de lepra multibacilar, caracterizada por la presencia de tubérculos (lesiones papulosas o nodulares) correspondientes a lepromas formados por histiocitos de morfología fusiforme. La misma es una variante infrecuente de lepra lepromatosa, que se desarrolla generalmente como recaída, en pacientes que recibieron monoterapia con dapsona, aunque se reportó su presentación de novo. En el presente trabajo, se comunica el caso clínico de una paciente de sexo femenino de 45 años de edad, con diagnóstico tardío de lepra histioide. Además, se examinan las características principales de esta forma particular de expresión de la lepra, sus diferencias con la forma clásica de presentación, los diagnósticos diferenciales que deben considerarse y la importancia de tener a esta patología entre las sospechas diagnósticas, para comenzar el tratamiento adecuado y evitar su propagación.

Wade's hystioid leprosy is a special clinical-pathological form of multibacillary leprosy, characterized by papular and nodular lepromas that consist of spindle histiocytes. It is a variant of lepromatous leprosy. Most of the cases have been related to dapsone resistance in the context of longterm monotherapy. De novo cases, not associated with previous anti-leprosy treatment, have been less frequently reported. This article presents the case of 45 years old female, with late diagnosis of histoid leprosy. There will be explained the main features of this particular form of leprosy, its differences with the classic presentation, the differential diagnoses to be considered, and the importance of having this pathology among diagnostic suspicions to begin adecuate treatment.

Inflammatory cytokines in leprosy reactions and periodontal diseases

The inflammatory cytokines involved in the immune response to chronic periodontal disease (CPD) in the context of leprosy reactions (LR) were analyzed in 57 new cases of multibacillary leprosy (MBL). They were stratified by the presence of CPD and LR. Messenger RNA (mRNA) expression of inflammatory mediators was determined by qRT-PCR using skin biopsy and by ELISA using serum samples, maintaining 5% of significance level in ANOVA and correlation analyses. Twenty-three (40.4%) patients presented the first LR, whereas 22 (45.0%) patients presented CPD. IL-4 and IL-6 serum levels were significantly lower in patients with CPD and LR than in patients without CPD but with LR; IFN-γ serum levels were higher in patients with CPD and LR than in patients with no CPD and no LR; IL-4 serum levels were negatively correlated with TNF-α gene expression, while IL-6 serum levels were positively correlated with IFN-γ gene expression, in the skin of subjects with CPD and LR. The presence of DPC in individuals with LR immunoregulated IL-6, IFN-γ, and IL-4 concentrations. The presence of DPC decreased serum levels of IL-6 and IL-4 in reactional individuals. CPD concomitant to LR resulted in increased IFN-γ serum levels.

Enfermedad de Hansen. Una condición emergente en Chile / Hansen disease, an emergent condition in Chile

Resumen La enfermedad de Hansen (EH) es una infección secundaria a Mycobacterium leprae, de curso crónico y que afecta preferentemente la piel y los nervios periféricos. Es una condición emergente en Chile debido a la migración humana. Presentamos un caso que afectó a un trabajador inmigrante desde Haití, que presentó antes de su arribo múltiples lesiones cutáneas en placas, con hipoestesia y madarosis unilateral. El diagnóstico de la forma multibacilar se estableció por los hallazgos clínicos, la presencia de bacilos ácido-alcohol resistentes en una muestra cutánea y la detección de células inflamatorias alrededor de los terminales nerviosos y granulomas en una biopsia de piel, desde donde se amplificaron segmentos específicos de los genes rpoB y hsp65 de M. leprae. El paciente fue tratado con el esquema combinado estándar de la OMS para la forma multibacilar durante un año, con regresión parcial de las lesiones. Durante el seguimiento se detectó por RPC una disminución del número de copias del gen rpoB de M. leprae en muestras nasofaríngeas hasta el sexto mes. El registro de enfermedades de notificación obligatoria demuestra un incremento reciente de casos de EH en Chile, todos relacionados con población migrante. La enfermedad de Hansen es una nueva condición clínica y los clínicos deben estar atentos a esta posibilidad diagnóstica. Las pruebas moleculares pueden ayudar en el diagnóstico y seguimiento.

Hansen's disease (HD) is caused by Mycobacterium leprae. It has a chronic course and preferentially affects the skin and the peripheral nerves. It's an emergent infection in Chile due to migration waves. This case report affecting a migrant worker from Haiti that presented several compatible skin lesions, with hypoesthesia and unilateral madarosis that appeared before arrival. The diagnosis of a multibacillary form was established by clinical findings, presence of fast acid bacilli on a direct skin smear, and inflammatory cell surrounding nerve endings and granulomas on skin biopsy. Besides, specific rpoB and hsp65 gene segments from M. leprae were amplified from skin samples. Patient was treated with the WHO standard combined regimen for multibacillary forms during one year showing partial regression of skin lesions. Nasopharyngeal samples showed the presence of M. leprae rpoB copies detected by PCR decreasing until six months of therapy. Notifiable diseases databases showed a recent increment of cases, all related to migrant population. Hansen's disease is a new condition in Chile and clinicians should be aware of this possibility. Molecular tools may facilitate diagnosis and follow up.

Diffuse Multibacillary Leprosy of Lucio and Latapí with Lucio's Phenomenon, Peru.

Diffuse multibacillary leprosy of Lucio and Latapí is mainly reported in Mexico and Central America. We report a case in a 65-year-old man in Peru. He also had Lucio's phenomenon, characterized by vascular thrombosis and invasion of blood vessel walls by leprosy bacilli, causing extensive skin ulcers.

Wade's histoid leprosy in a 14-year-old teenage boy

Abstract Wade's histoid leprosy (HL) is a rare variant of multibacillary leprosy, with characteristic clinical, immunologic, histopathologic, and bacteriologic features. It is associated with resistance to sulfa drugs or polychemotherapy and is rarely observed in patients who have not undergone prior treatment. Clinically, HL resembles keloid or dermatofibroma. Furthermore, HL is rare in children and is difficult to diagnose even by experts. This report describes a case of HL in a 14-year-old Brazilian boy, who presented with multiple nodular and tumor-like lesions, simulating keloids. He had not undergone prior treatment with anti-leprosy drugs, which accentuates the relevance of this case report.

Unusual Presentation of Multibacillary Nodular Leprosy.

Despite India achieving the goal of elimination of leprosy as a public health problem, leprosy is still being transmitted in India. However, due to decreased clinical suspicion of leprosy and atypical case presentations, such cases may be not be diagnosed. We present a case report of an unusual presentation of multibacillary leprosy which presented as nodular lesions. This case report indicates that atypical presentations of leprosy may be missed out by primary care physicians.

Verrucous lepromatous leprosy: a rare form of presentation - Report on two cases

Leprosy skin lesions are described as hypochromic or erythematous macules, pale erythematous or reddish-brown plaques, papules, nodules, and diffuse cutaneous infiltration, depending on the clinical form of the disease. They may be accompanied by hypo or anesthesia, alopecia, and hypo or anhidrosis. Verrucous lesions are now quite uncommon in leprosy. The literature is sparse, with only 25 reported cases of this association, especially in the lepromatous pole of the disease. This work is a report on two cases of lepromatous leprosy of long evolution, coursing with vegetant verrucous lesions.

Reação reversa macular da hanseníase: relato de caso / Macular reversal reaction in leprosy: a case report

A reação reversa maculosa consiste no aparecimento abrupto de máculas hipocrômicas, ocorrendo em pacientes hansenianos dimorfos que completaram o tratamento com poliquimioterapia para hanseníase multibacilar. Em geral, surgem entre 6 a 12 meses da alta, com baciloscopia negativa e boa resposta a corticoterapia sistêmica. Ressaltamos a dificuldade em diferenciar recidiva de um episódio reacional, já que não existem critérios clínicos bem estabelecidos que possibilitem este diagnóstico, além de existirem poucos relatos em literatura. Relatamos um caso clínico com diagnóstico de reação reversa macular após período variável de alta do tratamento de hanseniase dimorfa-dimorfa. Foi feita investigação por meio de anamnese rigorosa, exame dermatológico, exame histopatológico da lesão e baciloscopia, excluindo-se os critérios de recidiva, além de analisados dados anteriores do prontuário.O paciente foi submetido a corticoterapia sistêmica,apresentando melhora das lesões. Conclui-seque a reação reversa maculosa deve ser lembrada nos diagnósticos diferenciais com hanseníase recidivada e episódios reacionais clássicos, evitando retratamentos desnecessários.

Macular reversal reaction is the abrupt onset of hypochromic lesions, occurring in borderline leprosy patients who completed treatment with multidrugtherapy for multibacillary leprosy. In general, these reactions appear 6 to 12 months after medical discharge, showing negative skin smear and good response to systemic corticosteroid therapy. We emphasize the difficulty in differentiating relapse cases from leprosy reactions, as there are no well-established clinical criteria that allow this diagnosis, and moreover there are few reports about it in the literature. We report a borderline leprosy case diagnosed with macular reversal reaction after variable period of discharge from treatment. Detailed anamnesis, dermatological and histopathological examination and bacilloscopy, analysis of previous medical records, excluding the relapse criteria, were used for the investigation. The patient was submitted to systemic corticosteroid therapy, with improvement of the lesions. It is concluded that macular reversal reaction should be considered in the differential diagnosis of relapsed leprosy and classic reactional episodes, avoiding unnecessary retreatment.

Acometimento hepático na síndrome sulfona dapsona-induzida durante tratamento de hanseníase / Hepatic involvement in sulfone dapsone-induced syndrome during treatment of leprosy

A hanseníase é uma doença endêmica no Brasil e constitui grave problema de saúde pública. Em números absolutos, o Brasil é o segundo país que mais registra novos casos da doença por ano no mundo. O tratamento da hanseníase compreende: quimioterapia específica, supressão dos surtos reacionais, prevenção de incapacidades físicas, reabilitação física e psicossocial. A síndrome sulfona é uma condição multissistêmica potencialmente grave que pode ocorrer durante o tratamento de algumas dermatoses, entre elas a hanseníase. Relatamos um caso de síndrome de hipersensibilidade à dapsona (SHD) em um paciente masculino, de 32 anos, ocorrida durante o tratamento de hanseníase multibacilar...