Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression

Abstract Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA.

Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression.

BACKGROUND: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). OBJECTIVE: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. METHODS: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. RESULTS: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. STUDY LIMITATIONS: Small sample size and limited length of follow-up. CONCLUSIONS: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03327116.

Estudo dos indivíduos e suas variáveis clínico-histopatológicas relacionadas ao aumento do risco de reação hansênica durante poliquimioterapia em área endêmica do nordeste do Brasil / Study of individuals and their clinical-histopathological variables related to the increased risk of leprosy reaction during multidrug therapy in endemic area of the northeast of Brazil / Estudio de individuos y sus variables clínico-histopatológicas relacionadas con el aumento del riesgo de reacción a la lepra durante el tratamiento multimedicamentoso en una zona endémica del noreste de Brasil

Introdução: a hanseníase apresenta potencial incapacitante secundário às reações hansênicas. Existe considerável número de indivíduos com episódios recorrentes de reação durante o tratamento. Objetivo: identificar características clínicas e histopatológicas que diferenciem pacientes com reação hansênica ou não. Método: estudo prospectivo de julho/2015 a dezembro/2016, com avaliação de indivíduos com diagnóstico novo de hanseníase atendidos no serviço de dermatologia do Complexo Hospitalar Clementino Fraga, na cidade de João Pessoa, Paraíba, Brasil. Os sujeitos foram classificados segundo os critérios de Ridley-Jopling/Madrid e por classificação operacional. Realizaram exame histopatológico no momento do diagnóstico e após 12 meses, e reavaliados após 6 e 12 meses do diagnóstico. Resultados: o grupo sem reação apresentou maior número de lesões com nítida delimitação. Observou-se predomínio das formas multibacilares entre indivíduos com reação. Quanto ao grau de incapacidade, o grupo com reação apresentou maior número de indivíduos com grau de incapacidade maior que zero. No grupo sem reação, encontrou-se menor frequência de fatores predisponentes. Notou-se correlação positiva do índice baciloscópico de biópsia cutânea com a ocorrência de reações. Discussão: a ausência de delimitação periférica das lesões pode se correlacionar com o surgimento de reação hansênica. O predomínio de reação entre os indivíduos que apresentavam grau de incapacidade maior que zero sugere associação de deficiência física e doença multibacilar. A ausência de fatores predisponentes aponta menor risco de reação hansênica. Observou-se correlação positiva do índice baciloscópico da biópsia com a ocorrência das reações. Conclusão: a significativa prevalência de reações graves enfatizam a importância do estudo contínuo da hanseníase e a necessidade de identificar precocemente as características clínicas sugestivas de reações hansênicas.(AU)

Introduction: leprosy reactions have the potential to cause disabilities. Many individuals experience recurrent episodes of reaction during treatment. Objective:to identify clinical and histopathological characteristics that differentiate patients with leprosy reactions from those without leprosy reactions. Method: this is a prospective study conducted from July 2015 to December 2016, evaluating individuals newly diagnosed with leprosy and treated at the dermatology service of the Clementino Fraga Hospital Complex in João Pessoa, Paraíba, Brazil. The subjects were classified according to the Ridley-Jopling/Madrid criteria and operational classification. They underwent a histopathological examination at the time of diagnosis and 12 months later, and were reassessed 6 and 12 months after the diagnosis. Results: the group without a reaction had a greater number of lesions with clear delimitation. Individuals with a reaction showed a predominance of multibacillary forms. The group with a reaction had a greater number of individuals with a degree of disability greater than zero. A positive correlation was observed between the bacilloscopic index and the occurrence of reactions. Discussion: the lack of clear boundaries around the lesions may be linked to the onset of a leprosy reaction. The higher incidence of reactions in individuals with some degree of physical disability indicates a correlation between disability and multibacillary disease. Additionally, a positive correlation was found between the bacilloscopic index of the biopsy and the occurrence of reactions. Conclusion: the high incidence of severe reactions underscores the need for ongoing studies on leprosy and the identification of early clinical characteristics that suggest leprosy reactions.(AU)

Amiloidose nodular - relato de rara apresentação da amiloidose localizada cutânea / Nodular amyloidosis - report of a rare presentation of cutaneous localized amyloidosis

Contexto: Amiloidose é um grupo de doenças caracterizadas pelo depósito de proteínas fibrilares, denominadas substância amiloide. Podem ser divididas em formas localizadas ou sistêmicas, sendo que dentre as localizadas, a forma nodular é a mais rara. Descrição do caso: Relatamos o caso de amiloidose primária localizada cutânea nodular que se apresentou com nódulos violáceos no dorso, e placas acastanhadas na região cervical há 8 anos sem evidências de envolvimento sistêmico. Discussão: Como cerca de 1% a 7% dos casos de amiloidose nodular localizada cutânea podem evoluir com envolvimento sistêmico, o seguimento dos pacientes faz-se necessário. O tratamento não é obrigatório, a retirada das lesões pode ser feita se o paciente o desejar, contudo as recidivas são frequentes. Conclusões: Mesmo possuindo baixa prevalência, a amiloidose nodular deve ser reconhecida pelo risco de progredir para acometimento sistêmico e associação com discrasias plasmocitárias, como mieloma múltiplo.

Assessment of reflectance confocal microscopy for monitoring treatment of actinic keratosis and field cancerization with daylight photodynamic therapy.

Actinic keratosis (AK) is the most common pre-malignant cutaneous lesion of the skin, often associated with field cancerization. Daylight photodynamic therapy (DL-PDT) is used as treatment, showing good histological results. Reflectance confocal microscopy (RCM) may be useful as a non-invasive, real-time approach to monitor treatment, however, there is a lack of data on the correlation between RCM and histopathological findings in AK patients treated with DL-PDT. To correlate histological and RCM findings and evaluate the efficacy of DL-PDT in patients with AK and field cancerization treated with DL-PDT. Patients with field cancerization and a minimum of six AK lesions on the face were included in the study. A single session combining methyl aminolevulinate followed by two-hour daylight exposure of the face was performed. RCM and biopsy were performed before and after three months of the intervention to compare efficacy between patients using the Wilcoxon test, and concordance of the findings based on the different methods was analysed using the Kappa test. Twenty-four patients completed the study. An improvement in photodamage and a decrease in the number of AK lesions (45.3% reduction) was observed. Regression in atypia and dysplasia was observed via histopathology and RCM, however, there was poor agreement between the methods. No changes were observed after treatment for inflammation, fibroplasia and acantholysis. Concordance between histological and RCM findings was poor, suggesting that RCM cannot replace the histopathological examination, however, it may be used as an adjuvant test for follow-up of patients. Despite this, DL-PDT proved to be an effective method for treating AK.

Areata-Like Lupus as a Clinical Manifestation of Cutaneous Lupus Erythematosus.

Introduction: Lupus erythematosus (LE) is a chronic autoimmune disease that frequently causes hair loss and scalp lesions. Hair loss can be scarring and nonscarring, diffuse, or patchy. The nonscarring patchy alopecia is usually related to systemic LE (SLE) and may simulate alopecia areata (AA), reason why it is named areata-like lupus. Our case was diagnosed with areata-like lupus but did not meet criteria for SLE. Case Report: A 63-year-old woman presented with irregular nonscarring patchy alopecia in the temporal and frontoparietal scalp. Trichoscopy showed exclamation mark hairs, vellus hairs, and sparse yellow dots. Histology revealed epidermal vacuolar interface dermatitis, lymphohistiocytic infiltrate around the bulbs of anagen follicles, and eccrine glands. Direct immunofluorescence showed deposits of C3, IgA, and IgG in the basement membrane zone. Discussion: Patients with cutaneous LE can also manifest as nonscarring patchy alopecia that is clinically similar to AA, despite the absence of systemic manifestations. Areata-like lupus is secondary to the lupus autoimmune infiltrate that affects the skin including the hair follicles. Trichoscopy, histology, and direct immunofluorescence are important to differentiate this form of alopecia from AA, which is believed to have a higher incidence in lupus patients.

Lichen planopilaris and frontal fibrosing alopecia: review and update of diagnostic and therapeutic features.

Lichen planopilaris and frontal fibrosing alopecia are primary scarring alopecias where diagnosis can be suggested by clinical and trichoscopy features, especially in the early stages, but scalp biopsy is the standard exam for definitive diagnosis. Frontal fibrosing alopecia is considered a variant of lichen planopilaris, as the histopathological findings are similar, with a perifollicular lymphohistiocytic infiltrate, sometimes with a lichenoid pattern. A thorough clinical examination, trichoscopy and photographic documentation are essential to assess the evolution and therapeutic response. To date, there are no validated treatments or guidelines for these diseases, but there are recommendations that vary with the individual characteristics of each patient. This article presents a comprehensive review of the literature, including an update on topics related to the diagnosis, follow-up, histopathological aspects and available treatments for lichen planopilaris and frontal fibrosing alopecia, highlighting their similarities, differences and peculiarities.

Lichen planopilaris and frontal fibrosing alopecia: review and update of diagnostic and therapeutic features

Abstract Lichen planopilaris and frontal fibrosing alopecia are primary scarring alopecias where diagnosis can be suggested by clinical and trichoscopy features, especially in the early stages, but scalp biopsy is the standard exam for definitive diagnosis. Frontal fibrosing alopecia is considered a variant of lichen planopilaris, as the histopathological findings are similar, with a perifollicular lymphohistiocytic infiltrate, sometimes with a lichenoid pattern. A thorough clinical examination, trichoscopy and photographic documentation are essential to assess the evolution and therapeutic response. To date, there are no validated treatments or guidelines for these diseases, but there are recommendations that vary with the individual characteristics of each patient. This article presents a comprehensive review of the literature, including an update on topics related to the diagnosis, follow-up, histopathological aspects and available treatments for lichen planopilaris and frontal fibrosing alopecia, highlighting their similarities, differences and peculiarities.