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.

Macular hypopigmentation, hair loss and follicular spongiosis: A distinct clinicopathological entity.

BACKGROUND: Hypopigmented macules are seen in a variety of disorders and the diagnosis rests on clinicopathological correlation. However, some cases are difficult to classify and pose a diagnostic challenge. AIM: To describe the clinical and histopathological features of patients with hypopigmented macules and follicular spongiosis on histopathology. MATERIALS AND METHODS: We undertook a retrospective analysis of clinical and histopathological findings in 12 patients who presented with clinically nondiagnostic hypopigmented macules and showed follicular spongiosis on skin biopsy, at All India Institute of Medical Sciences, New Delhi, India between January 2015 and October 2016. The findings were compared with 12 patients with "unclassified" hypopigmented macules, who did not show follicular spongiosis on skin biopsy. RESULTS: A total of 12 patients with hypopigmented macules showed spongiosis affecting the follicular epithelium on histopathology. There were eight men and four women, most in their second decade (mean age 19.1 ± 8.05 years), presenting with hypopigmented macules most commonly on the upper limbs, for a mean duration of 6.33 ± 5.10 months. Clinically evident lesional hair loss was seen in all patients, and follicular prominences in seven (58%) patients. Histological features suggestive of other diagnosis, namely leprosy, mycosis fungoides or sarcoidosis were not seen in any biopsy. Alcian blue stain revealed an minimal amount of mucin in one biopsy. Clinically apparent hair loss and follicular prominences were found to be statistically significantly associated with histological evidence of follicular spongiosis (P < 0.001 and 0.003, respectively). LIMITATIONS: Our study is limited by its retrospective design and small sample size. CONCLUSIONS: Patients with hypopigmented macules and follicular spongiosis on histopathology may represent a distinct clinicopathological entity that is associated with lesional hair loss and follicular prominences. It is probably a variant of an endogenous dermatitis similar to pityriasis alba.

Dapsone as a potential treatment option for Henoch-Schönlein Purpura (HSP).

Henoch-Schönlein Purpura (HSP, IgA vasculitis) is an immunoglobulin A (IgA) mediated disorder characterized by systemic vasculitis with variable presentation, frequently affecting the skin, mucous membrane, joints, kidneys, and rarely lungs and the central nervous system. Interestingly, enhanced production of interleukin-8 (IL-8) levels are found during active disease and increased levels have been reported in supernatants from human umbilical venous endothelial cells after stimulation with sera from patients affected by HSP. While corticosteroid therapy is currently the recommended treatment for HSP, dapsone, an anti-leprosy agent, has also recently been suggested to have therapeutic efficacy due to its ability to suppress IL-8. Moreover, in addition to IL-8 suppression, dapsone has been reported to exert various anti-inflammatory effects by inhibiting the generation of toxic free radicals, myeloperoxidase mediated halogenation that converts H2O2 to HOCl, leukocyte chemotaxis, production of tumor necrosis factor, and other anti-inflammatory molecules. This review aims to provide a solid hypothesis for the pathogenesis of vasculitis in HSP. Moreover, we highlight potential mechanistic actions of dapsone in hopes that dapsone may be considered as an alternative viable treatment for patients affected by HSP.

Clinico-pathological features of erythema nodosum leprosum: A case-control study at ALERT hospital, Ethiopia.

BACKGROUND: Leprosy reactions are a significant cause of morbidity in leprosy population. Erythema nodosum leprosum (ENL) is an immunological complication affecting approximately 50% of patients with lepromatous leprosy (LL) and 10% of borderline lepromatous (BL) leprosy. ENL is associated with clinical features such as skin lesions, neuritis, arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. ENL is treated mainly with corticosteroids and corticosteroids are often required for extended periods of time which may lead to serious adverse effects. High mortality rate and increased morbidity associated with corticosteroid treatment of ENL has been reported. For improved and evidence-based treatment of ENL, documenting the systems affected by ENL is important. We report here the clinical features of ENL in a cohort of patients with acute ENL who were recruited for a clinico-pathological study before and after prednisolone treatment. MATERIALS AND METHODS: A case-control study was performed at ALERT hospital, Ethiopia. Forty-six LL patients with ENL and 31 non-reactional LL matched controls were enrolled to the study and followed for 28 weeks. Clinical features were systematically documented at three visits (before, during and after predinsolone treatment of ENL cases) using a specifically designed form. Skin biopsy samples were obtained from each patient before and after treatment and used for histopathological investigations to supplement the clinical data. RESULTS: Pain was the most common symptom reported (98%) by patients with ENL. Eighty percent of them had reported skin pain and more than 70% had nerve and joint pain at enrolment. About 40% of the patients developed chronic ENL. Most individuals 95.7% had nodular skin lesions. Over half of patients with ENL had old nerve function impairment (NFI) while 13% had new NFI at enrolment. Facial and limb oedema were present in 60% patients. Regarding pathological findings before treatment, dermal neutrophilic infiltration was noted in 58.8% of patients with ENL compared to 14.3% in LL controls. Only 14.7% patients with ENL had evidence of vasculitis at enrolment. CONCLUSION: In our study, painful nodular skin lesions were present in all ENL patients. Only 58% patients had dermal polymorphonuclear cell infiltration showing that not all clinically confirmed ENL cases have neutrophilic infiltration in lesions. Very few patients had histological evidence of vasculitis. Many patients developed chronic ENL and these patients require inpatient corticosteroid treatment for extended periods which challenges the health service facility in resource poor settings, as well as the patient's quality of life.

A Case of Subcutaneous Phaeohyphomycosis Associated with Leprosy.

BACKGROUND: Subcutaneous phaeohyphomycosis is an infection caused by melanized fungi and is increasingly reported among immunosuppressive patients. The most commonly cited etiologic agent is Exophiala jeanselmei, followed by Alternaria spp. We present a case of subcutaneous phaeohyphomycosis in a 48-yearold woman, with a history of lepromatous leprosy, using corticosteroid in immunosuppressive doses due to a type 2 repetitive reaction leprosy outbreak. RESULT AND DISCUSSION: The diagnosis was confirmed by fine-needle aspiration of the secretion, with subsequent direct mycological observations, culture and molecular analysis. The species agent was identified by culture and nucleotide sequences of ribosomal DNA as Exophiala dermatitidis.

Terapia con corticosteroides en pacientes de lepra borderline tuberculoide coinfectados con VIH y con reacción de reversión: estudio clínico / No disponible

Antecedentes: El Mycobacterium leprae y el VIH causan enfermedades de tipo infecciosas muy preocupantes para la sanidad mundial. Son especial motivo de preocupación cuando los pacientes se coinfectan con ambos agentes patógenos. El objetivo de este estudio es evaluar los episodios de reacción de reversión (RR) y el efecto del uso de corticosteroides sobre el tratamiento de pacientes de lepra borderline tuberculoide co-infectados con el virus de inmunodeficiencia humana (VIH). Métodos: Este trabajo es un estudio retrospectivo de cohortes en el que se observan las respuestas a la terapia con corticoides y sus manifestaciones clínicas. Se analizan variables durante y después de la multiterapia farmacológica de la Organización Mundial de la Salud (OMS) entre el primer y último día de la toma de prednisona, con un máximo de hasta 6 meses posteriores a haber iniciado la terapia corticosteroidea. Resultados: Se incluye un total de 22 casos VIH-positivos y 28 VIH-negativos. La pérdida de sensibilidad y el engrosamiento neural eran estadísticamente significativos mientras que las lesiones ulceradas sólo se detectaron en el grupo coinfectado. La mayoría de pacientes fueron diagnosticados de lepra en fase de leprorreacción RR y seis pacientes manifestaron RR como un síndrome inflamatorio de restitución inmunológica. De promedio, ambos grupos recibieron dosis similares de corticosteroides (diferencia de 0·1 mg/kg/día). Conclusiones: Las manifestaciones clínicas de ambos grupos fueron similares y la mejoría general fue debida a la administración de corticoides. Registro del ensayo: Este trabajo fue presentado y aprobado por el Ethics Committee on Research of the Oswaldo Cruz Institute el 8 de agosto de 2011 (registro 616/11)

Background: Mycobacterium leprae and HIV cause infectious diseases of great concern for the public health care sector worldwide. Both are especially worrisome diseases when patients become co-infected and exhibit the expected clinical exuberance. The objective of this study was to evaluate episodes of reversal reaction (RR) and the effect of the use of corticosteroids on the treatment of borderline tuberculoid leprosy patients co-infected with the human immunodeficiency virus (HIV). Methods: This is a retrospective cohort study in which the clinical manifestations of the patients and their responses to corticosteroid therapy were observed. Variables were analysed during and after multidrug therapy between the first and last days of prednisone, which occurred up to a maximum of 6 months after initiating corticosteroid therapy. Results: A total of 22 HIV-positive and 28 HIV-negative cases were included. Loss of sensitivity and neural thickening were statistically significant while clinically ulcerated lesions were only observed in the co-infected group. Most patients were diagnosed with leprosy in the presence of RR and six patients manifested RR as an immune reconstitution inflammatory syndrome. On average, both groups received similar doses of corticosteroids (difference of 0·1 mg/kg/day).Conclusions: It is of special interest that the clinical manifestations in both groups were found to be similar and that overall improvement occurred as a result of corticosteroid therapy.Trial registration This work was submitted to and approved by the Ethics Committee on Research of the Oswaldo Cruz Institute on August 8, 2011 (registration 616/11)

The Medical Treatment of Vitiligo: An Historical Review.

Discolorations of the skin, such as vitiligo, were recognized thousands of years ago. White spots caused by vitiligo and other disorders have caused significant social opprobrium to those disfigured by these pigmentary disorders, throughout history and still in the present day. Treatments have been desperately sought with only partial success. Recent advances suggest that vitiligo and other pigmentary disorders might soon be curable.

Guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis: An Indian perspective.

BACKGROUND: Stevens-Johnson syndrome and toxic epidermal necrolysis are severe, life-threatening mucocutaneous adverse drug reactions with a high morbidity and mortality that require immediate medical care. The various immunomodulatory treatments include systemic corticosteroids, cyclosporine, intravenous immunoglobulin, cyclophosphamide, plasmapheresis and tumor necrosis factor-α inhibitors. AIM: The ideal therapy of Stevens-Johnson syndrome/toxic epidermal necrolysis still remains a matter of debate as there are only a limited number of studies of good quality comparing the usefulness of different specific treatments. The aim of this article is to comprehensively review the published medical literature and frame management guidelines suitable in the Indian perspective. METHODS: The Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) assigned the task of preparing these guidelines to its special interest group on cutaneous adverse drug reactions. The group performed a comprehensive English language literature search for management options in Stevens-Johnson syndrome/toxic epidermal necrolysis across multiple databases (PubMed, EMBASE, MEDLINE and Cochrane) for keywords (alone and in combination) and MeSH items such as "guidelines," "Stevens-Johnson syndrome," "toxic epidermal necrolysis," "corticosteroids," "intravenous immunoglobulin," "cyclosporine" and "management." The available evidence was evaluated using the strength of recommendation taxonomy and graded using a three-point scale. A draft of clinical recommendations was developed on the best available evidence which was also scrutinized and critically evaluated by the IADVL Academy of Dermatology. Based on the inputs received, this final consensus statement was prepared. RESULTS: A total of 104 articles (meta-analyses, prospective and retrospective studies, reviews [including chapters in books], previous guidelines [including Indian guidelines of 2006] and case series) were critically evaluated and the evidence thus gathered was used in the preparation of these guidelines. RECOMMENDATIONS: This expert group recommends prompt withdrawal of the culprit drug, meticulous supportive care, and judicious and early (preferably within 72 h) initiation of moderate to high doses of oral or parenteral corticosteroids (prednisolone 1-2 mg/kg/day or equivalent), tapered rapidly within 7-10 days. Cyclosporine (3-5 mg/kg/day) for 10-14 days may also be used either alone, or in combination with corticosteroids. Owing to the systemic nature of the disease, a multidisciplinary approach in the management of these patients is helpful.

Asociación de Mycobacterium leprae viable con leprorreacciones / No disponible

La hipótesis de trabajo es que el Mycobacterium leprae (M. leprae) viable desempeña un papel crucial en la precipitación de la reacción tipo 1 (T1R) en lepra. Materiales y métodos: Se estudiaron un total de 165 nuevos pacientes multibacilares. Para demostrar la presencia de M. leprae se emplearon tres técnicas en las lesiones en reacción T1R (+), como son el crecimiento en la almohadilla plantar (MFP), detección inmunohistoquímica de la proteína secretora M. leprae Ag85, y 16s rRNA - empleando RT-PCR in situ. Como controles, se emplearon biopsias de BEC y lesiones sin reacción T1R (-). Hallazgos: Un número significativamente mayor de homogeneizados de biopsia de lesión obtenidos al inicio, de casos T1R (+) han presentado crecimiento en MFP, demostrando la presencia de bacterias viables comparado con T1R (-) (P = 0·005). En contraste, pocas biopsias BEC resultaron positivas tanto en T1R (+) como en T1R (-). Con respecto a Ag85, mientras que la positividad total fue más elevada en T1R (+) (74%), la positividad de la tinción (Grado ≥ 2+) era significativamente mayor en el grupo T1R (+) BT-BB 11/20 (55%). En las muestras de biopsias en casos de T1R recurrentes, tanto el Ag 85 como el 16s rRNA, la positividad (62% y 100%) fue mayor en el grupo T1R (+). Se propone que las bacterias viables son componentes esenciales en las T1R y la diferencia en la calidad de los bacilos y no la cantidad o la ratio de inactivos/viables desempeña un papel en la precipitación de T1R. En conclusión, los hallazgos demuestran que los bacilos «metabólicamente activos» de M. leprae son un componente/requisito fundamental de la T1R y la proteína secretora Ag 85, quizás sea el precipitador de T1R (AU)

The working hypothesis is that, viable Mycobacterium leprae (M. leprae) play a crucial role in the precipitation of Type 1 reaction (T1R) in leprosy. Material and Methods: A total of 165 new multibacillary patients were studied. To demonstrate presence of viable M. leprae in reactional lesion (T1R+), three tests were used concurrently viz. growth in the mouse foot pad (MFP), immunohistochemical detection of M. leprae secretory protein Ag85, and 16s rRNA - using in situ RT- PCR. Mirror biopsies and non reactional lesions served as controls T1R (-). Findings: A significantly higher proportion of lesion biopsy homogenates obtained at onset, from T1R (+) cases have shown unequivocal growth in MFP, proving the presence of viable bacteria, as compared to T1R (-) (P , 0·005). In contrast, few Mirror biopsies were positive in both T1R (+) and T1R (-). With respect to Ag85, while the overall positivity was higher in T1R (+) (74%), however the intensity of staining (Grade ≥ 2+) was disproportionately higher in T1R (+) BT-BB lesions 11/20 (55%). In the rebiopsies obtained during a repeat episode of T1R, Ag 85 as well as 16s rRNA, positivity (62% & 100%) was higher in T1R (+). It is inferred therefore «viable» bacteria are an essential component in T1R and difference in the quality of bacilli, not the quantity or the ratio of dead to viable play a role in the precipitation of T1R. In conclusion, the findings show that «metabolically active» M. leprae is a component/prerequisite and the secretory protein Ag 85, might be the trigger for precipitation of T1R (AU)

Tiña eritrodérmica y enfermedad de Hansen: Una asociación infrecuente / No

Las infecciones micóticas, uno de los motivos de consulta más frecuentes en la práctica dermatológica, son más frecuentes en pacientes inmunocomprometidos, incluyendo a los afectados de lepra, no solo por la presencia de esta condición sino también debido al consumo de corticoesteroides que se indican en los estados reaccionales. Presentamos el caso de un paciente de sexo masculino de 51 años de edad, con lesiones que inician 10 años antes, cómo manchas rojas dolorosas en brazos. Se automedica con dexametasona más clorfeniramina VO con mejoría parcial de las mismas pero, hace tres meses aparecen manchas pruriginosas, descamativas, no dolorosas, que no mejoran con la medicación citada, diseminándose a todo el cuerpo. Se realiza el diagnóstico de enfermedad de Hansen concomitante con una tiña eritrodérmica

Fungal infections, one of the most frequent reasons for consultation in dermatological practice, are more common in immunocompromised patients, including those suffering from leprosy, not only by the presence of this condition but also due to the use of corticosteroids given in the reactional states. We report the case of a male patient of 51 years of age, with injuries that begin 10 years before, with painful red spots on arms. He self-medicate with oral dexamethasone and chlorpheniramine with partial improvement of the lesions, but three months ago itchy scaly, not painful, spots appear and do not improve with the medication