Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique.

This publication is an update of the "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.

Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique

Abstract This publication is an update of the "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.

Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology.

BACKGROUND: Atopic dermatitis is a highly prevalent inflammatory and pruritic dermatosis with a multifactorial etiology, which includes skin barrier defects, immune dysfunction, and microbiome alterations. Atopic dermatitis is mediated by genetic, environmental, and psychological factors and requires therapeutic management that covers all the aspects of its complex pathogenesis. OBJECTIVES: The aim of this article is to present the experience, opinions, and recommendations of Brazilian dermatology experts regarding the therapeutic management of atopic dermatitis. METHODS: Eighteen experts from 10 university hospitals with experience in atopic dermatitis were appointed by the Brazilian Society of Dermatology to organize a consensus on the therapeutic management of atopic dermatitis. The 18 experts answered an online questionnaire with 14 questions related to the treatment of atopic dermatitis. Afterwards, they analyzed the recent international guidelines on atopic dermatitis of the American Academy of Dermatology, published in 2014, and of the European Academy of Dermatology and Venereology, published in 2018. Consensus was defined as approval by at least 70% of the panel. RESULTS/CONCLUSION: The experts stated that the therapeutic management of atopic dermatitis is based on skin hydration, topical anti-inflammatory agents, avoidance of triggering factors, and educational programs. Systemic therapy, based on immunosuppressive agents, is only indicated for severe refractory disease and after failure of topical therapy. Early detection and treatment of secondary bacterial and viral infections is mandatory, and hospitalization may be needed to control atopic dermatitis flares. Novel target-oriented drugs such as immunobiologicals are invaluable therapeutic agents for atopic dermatitis.

Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology

Abstract: BACKGROUND: Atopic dermatitis is a highly prevalent inflammatory and pruritic dermatosis with a multifactorial etiology, which includes skin barrier defects, immune dysfunction, and microbiome alterations. Atopic dermatitis is mediated by genetic, environmental, and psychological factors and requires therapeutic management that covers all the aspects of its complex pathogenesis. OBJECTIVES: The aim of this article is to present the experience, opinions, and recommendations of Brazilian dermatology experts regarding the therapeutic management of atopic dermatitis. METHODS: Eighteen experts from 10 university hospitals with experience in atopic dermatitis were appointed by the Brazilian Society of Dermatology to organize a consensus on the therapeutic management of atopic dermatitis. The 18 experts answered an online questionnaire with 14 questions related to the treatment of atopic dermatitis. Afterwards, they analyzed the recent international guidelines on atopic dermatitis of the American Academy of Dermatology, published in 2014, and of the European Academy of Dermatology and Venereology, published in 2018. Consensus was defined as approval by at least 70% of the panel. RESULTS/CONCLUSION: The experts stated that the therapeutic management of atopic dermatitis is based on skin hydration, topical anti-inflammatory agents, avoidance of triggering factors, and educational programs. Systemic therapy, based on immunosuppressive agents, is only indicated for severe refractory disease and after failure of topical therapy. Early detection and treatment of secondary bacterial and viral infections is mandatory, and hospitalization may be needed to control atopic dermatitis flares. Novel target-oriented drugs such as immunobiologicals are invaluable therapeutic agents for atopic dermatitis.

Up-regulation of HMGB1 and TLR4 in skin lesions of lichen planus.

Lichen planus (LP) is a chronic, mucocutaneous inflammatory disease of an unknown aetiology. The disease has been associated with certain viruses, and the factors such as DAMPs (damage-associated molecular patterns) and PAMPs (pathogen-associated molecular patterns) may also contribute to the inflammatory response in LP. HMGB1 (high mobility group box 1 protein) is one of the major DAMPs that induces inflammation and could trigger LP disease. The present study was aimed to examine TLR4, RAGE and HMGB1 production in epidermis or dermis by immunohistochemistry and the respective expression of these targets in the skin lesions of patients with LP. Moreover, we measured HMGB1 serum levels by ELISA. The results showed similar profile of expression by HMGB1 and TLR4, which are decreased at epidermis and up-regulated at dermis of skin lesions of LP patients that was sustained by intense cellular infiltration. RAGE expression was also increased in dermis of LP. Although there is increased RAGE protein levels, a decreased RAGE transcript levels was detected. Similar HMGB1 serum levels were detected in the LP and control groups. This study demonstrates that HMGB1 and TLR4 could contribute to the inflammatory LP process in skin.

Staphylococcus aureus enterotoxins modulate IL-22-secreting cells in adults with atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory immune-mediated skin disease characterized by skin colonization by Staphylococcus aureus. Interleukin (IL)-22, in cooperation with IL-17, triggers antimicrobial peptide elaboration and enhances certain immunological responses. In AD, IL-22 is related to epidermal hyperplasia, keratinocyte apoptosis, and inhibition of antimicrobial peptide (AMP) production. We aimed to evaluate the impact of staphylococcal enterotoxins on the Tc22/Th22 induction in the peripheral blood of AD patients and on CD4+/CD8+ T cells expressing IL-22 in AD skin. Our study showed inhibition of the staphylococcal enterotoxins A and B (SEA and SEB) response by Th22 (CD4+IL-22+IL-17A-IFN-γ-) cells in AD patients. In contrast, Tc22 (CD8+IL-22+IL-17A-IFN-γ-) cells were less susceptible to the inhibitory effects of staphylococcal enterotoxins and exhibited an enhanced response to the bacterial stimuli. In AD skin, we detected increased IL-22 transcript expression and T lymphocytes expressing IL-22. Together, our results provide two major findings in response to staphylococcal enterotoxins in adults with AD: dysfunctional CD4+ IL-22 secreting T cells and increased Tc22 cells. Our hypothesis reinforces the relevance of CD8 T cells modulated by staphylococcal enterotoxins as a potential source of IL-22 in adults with AD, which is relevant for the maintenance of immunological imbalance.

Skin barrier in atopic dermatitis: beyond filaggrin.

Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis, where changes in skin barrier and imbalance of the immune system are relevant factors. The skin forms a mechanic and immune barrier, regulating water loss from the internal to the external environment, and protecting the individual from external aggressions, such as microorganisms, ultraviolet radiation and physical trauma. Main components of the skin barrier are located in the outer layers of the epidermis (such as filaggrin), the proteins that form the tight junction (TJ) and components of the innate immune system. Recent data involving skin barrier reveal new information regarding its structure and its role in the mechanic-immunological defense; atopic dermatitis (AD) is an example of a disease related to dysfunctions associated with this complex.

Skin barrier in atopic dermatitis: beyond filaggrin

Abstract: Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis, where changes in skin barrier and imbalance of the immune system are relevant factors. The skin forms a mechanic and immune barrier, regulating water loss from the internal to the external environment, and protecting the individual from external aggressions, such as microorganisms, ultraviolet radiation and physical trauma. Main components of the skin barrier are located in the outer layers of the epidermis (such as filaggrin), the proteins that form the tight junction (TJ) and components of the innate immune system. Recent data involving skin barrier reveal new information regarding its structure and its role in the mechanic-immunological defense; atopic dermatitis (AD) is an example of a disease related to dysfunctions associated with this complex.

Reactions to the different pigments in tattoos: a report of two cases.

Tattoos are defined as the intentional or accidental deposit of pigment into the skin. These pigments have been associated with various dermatoses such as allergic contact dermatitis, lichenoid dermatitis, photoinduced reactions, and granulomatous, sarcoid and pseudolymphomatous reactions. The objective of this report was to describe the various types of reactions to pigments and the importance of recognizing them clinically. Two cases are reported: one of lichenoid dermatitis resulting from a reaction to the red pigment of a tattoo and the other of a pseudolymphoma resulting from a reaction to red and lilac pigments and a photo-induced reaction to a yellow pigment. Removal generally requires multiple forms of treatment, most of which fail to remove the colors completely.

Reações aos diferentes pigmentos de tatuagens: relato de dois casos / Reactions to the different pigments in tattoos: a report of two cases

A tatuagem é definida como deposição de pigmento intencional ou acidental na pele. Os pigmentos têm sido associados a diversas dermatoses, como a dermatite de contato alérgica, a dermatite liquenoide e as reações fotoinduzidas, granulomatosas, sarcoídeas e pseudolinfomatosas. Enfocam-se os diversos tipos de reações aos pigmentos e a importância de reconhecê-los clinicamente. São relatados dois casos: um de dermatite liquenoide sobre o pigmento vermelho e outro de pseudolinfoma sobre os pigmentos vermelho e lilás e de reação fotoinduzida sobre o amarelo. A remoção geralmente requer múltiplos tratamentos, e a maioria não retira as cores completamente.

Tattoos are defined as the intentional or accidental deposit of pigment into the skin. These pigments have been associated with various dermatoses such as allergic contact dermatitis, lichenoid dermatitis, photoinduced reactions, and granulomatous, sarcoid and pseudolymphomatous reactions. The objective of this report was to describe the various types of reactions to pigments and the importance of recognizing them clinically. Two cases are reported: one of lichenoid dermatitis resulting from a reaction to the red pigment of a tattoo and the other of a pseudolymphoma resulting from a reaction to red and lilac pigments and a photo-induced reaction to a yellow pigment. Removal generally requires multiple forms of treatment, most of which fail to remove the colors completely.

Comparação entre duas loções hidratantes de diferentes pHs na melhora da hidratação da pele e na redução do prurido / Comparison between two moisturizing lotions with diff erent pHs in skin moisture improvement and pruritus reduction

Introdução: A dermatite atópica (DA) afeta aproximadamente 15% da população e é uma das doenças infl amatórias crônicas mais comuns da infância. O prurido e a xerose intensa da pele são os seus sintomas mais importantes. A restauração dos elementos da barreira de proteção epidérmica através do uso de emolientes é essencial para o tratamento da doença. Objetivo: Avaliar a melhora do prurido, a hidratação cutânea e xerose em dois grupos de pacientes utilizando hidratantes idênticos (aveia coloidal, Glicerol e petrolato), mas com diferentes pHs em pacientes com DA. Materiais e Métodos: Vinte e um pacientes, com idades entre 7 a 54 anos, com DA moderada a grave e prurido, foram divididos aleatoriamente em dois grupos. Os grupos foram trocados após 30 dias. Resultados: Os resultados foram avaliados após 60 dias. A melhora no prurido, na xerose e na hidratação foram avaliadas pelo médico, pelo paciente e por corniometria. Não houve diferença estatística em ambos os grupos, sendo então os dados avaliados como de um único grupo ao fi nal. A redução do prurido foi observada por 59% dos pacientes e por 52% dos clínicos, e da xerose por 52% dos pacientes e 43% dos clínicos. O nível de hidratação da pele nas áreas com eczema aumentou em 79%, em comparação com o início do tratamento. Conclusão: Hidratantes contendo aveia coloidal, glicerol e petrolato com pH próximo ao da pele normal mostraram-se apropriados na melhora do prurido em pacientes com DA.

Introduction: Atopic dermatitis (AD) affects approximately 15% of the population and is one of chronic infl ammatory diseases more common in childhood. Intense pruritus and skin xerosis are the most important symptoms of the disease. Restoration of epidermal barrier protection elements through the use of emollients is essential for disease treatment. Objective: To evaluate the improvement in pruritus, skin hydration, and xerosis in two groups of patients using the same moisturizer (colloidal oatmeal, glycerol and petrolatum), but with different pH values in patients with AD. Materials and Methods: Twenty-one patients aged 7 to 54 years with AD moderate to severe and pruritus were randomly divided in two groups. The groups were switched after 30 days. Results: The results were assessed after 60 days. Improvement in pruritus, xerosis, and hydration were evaluated by the physician, the patient, and by corneometry. There was no statistical difference in the two groups; therefore, data were evaluated as belonging to a single group at the end. Decrease in pruritus was observed by 59% of patients and 52% of physicians; xerosis reduction was observed by 52% of patients and 43% of physicians. The level of skin hydration in areas with eczema has increased by 79% compared with baseline period. Conclusion: Moisturizers containing colloidal oatmeal, glycerin, and petrolatum with pH close to the one in normal skin showed to be appropriate to improve pruritus in patients with AD.

Caso para diagnóstico / Case for diagnosis

A necrose gordurosa do subcutâneo do recém-nascido é paniculite rara e auto-limitada, caracterizada por placa eritematosa extensa com nódulos amolecidos no dorso de recém-nascidos a termo ou pós-termo. São fatores desencadeantes de relevância a pré-eclâmpsia materna, asfixia perinatal e hipercalcemia. Relata-se caso de necrose gordurosa do recém-nascido associado a pré-eclâmpsia materna e asfixia perinatal.

Subcutaneous fat necrosis of the newborn is an uncommon self-limited panniculitis characterized by large erythematous patches and soft nodules on the back of full-term or post-term infants. Maternal pre-eclampsia, birth asphyxia and hypercalcemia are relevant triggers. We describe a case of subcutaneous fat necrosis in a newborn related to maternal pre-eclampsia and birth asphyxia.

Erupção liquenóide: secundária ao uso de adalimumabe? / Lichenoid eruption: secondary to adalimumab?

O adalimumabe é um anticorpo recombinante monoclonal IgG1, completamente humano, que se liga especificamente ao fator de necrose tumoral alfa (TNF-a) e neutraliza sua atividade. Relatamos aqui um caso de erupção liquenóide secundária ao uso de adalimuma-be em uma paciente com artrite reumatóide. O quadro melhorou após a suspensão do adalimumabe, com recidiva à reintrodução do medicamento e nova melhora após a suspensão definitiva deste. Embora a paciente estivesse recebendo, concomitantemente ao adalimumabe, metotrexate, corticosteróides e outras drogas, não houve suspensão ou modificação das medicações, exceto o adalimumabe durante todo o período. A ocorrência de erupção liquenóide com o uso do adalimumabe é um evento não esperado, uma vez que, na imunopatologia do líquen plano, o papel do TNF-a parece ser o de propagador da doença. Desse modo, esperaria-se que drogas anti-TNF-a pudessem ser usadas no tratamento do líquen plano e não que atuassem como indutoras desta condição.

Adalimumab is a recombinant, fully human IgG1 monoclonal antibody that binds specifically to human TNF-a and neutralizes the activity of this cytokine. We report herein the case of a lichenoid eruption with the use of adalimumab in a patient with rheumatoid arthritis. The eruption improved after interruption of adalimumab, with recurrence at the reintroduction and improvement again with definitive suspension. Although this patient was receiving concomitant adalimumab with methotrexate, corticosteroids and other drugs, these medications except the adalimumab were not discontinued or modified at any moment during the period. The occurrence of lichenoid eruption with adalimumab is a not expected event since the function of the TNF-a in the immunopathology of lichen planus seems to be as a propagator of disease. This way, we would expect that drugs with anti-TNF-a effect would not act as inductors of lichen planus but could be used in its treatment.

Dermatose neutrofílica febril aguda (Síndrome de Sweet): uma causa a ser considerada no diagnóstico diferencial dos distúrbios inflamatórios cutâneos associados a processos febris / Acute febrile neutrophilic dermatosis (Sweet syndrome): a cause to be considered in the differential diagnosis of inflammatory skin disorders associated with febrile processes

A dermatose neutrofílica febril aguda, também denominada síndrome de sweet, é uma doença inflamatória rara, caracterizada por febre, mialgia, artralgia, neutrofilia, placas eritematosas bem demarcadas e dolorosas. O exame histológico demonstra um denso exsudato dérmico de neutrófilos, muitas vezes com intensa leucocitoclasia e edema de derme papilar. A doença está localizada freqüentemente em áreas fotoexpostas. Foi descrita pela primeira vez por Robert Sweet, em 1964 e, desde então, vários casos foram relatados. Freqüentemente está associada a neoplasias, principalmente à leucemia, e pode ser desencadeada por medicamentos, infecções e até gestação. Apesar destas associações descritas, sua fisiopatologia ainda não está bem definida. A vasculite é secundária a toxinas liberadas por neutrófilos, e as citocinas são importantes no desencadeamento da dermatose. Este trabalho relata o caso de uma mulher de 37 anos de idade, com quadro de Síndrome de Sweet, que se iniciou por surgimento de febre, cefaléia, alterações gastrointestinais e uso de medicamentos sintomáticos para o quadro descrito.

Acute febrile neutrophilic dermatosis (Sweet's Syndrome) is a rare inflammatory disease that is characterized by fever, myalgias, arthralgias, neutrophilia, and painful well-demarcated erythematous plaques. The histological examination shows a dense dermal infiltrate of neutrophils, often with intense leukocytoclasia and papillary dermal edema. It frequently affects areas exposed to light. It was originally described by Robert Sweet in 1964. Since then, hundreds of patients have been reported. It may occur in the absence of other diseases but is often associated with malignant conditions, including leukemia, and may be precipitated by drugs, infections and also pregnancy. Although these described associations, its physiopathology is not well defined Vasculitis occurs secondary to noxious products released from neutrophils. As for the etiopathogenesis, cytokines are important in precipitating this dermatosis. Systemic glucocorticoids are used in the treatment; however, prolonged use may be necessary to suppress the recurrences. This paper reports a 37-year-old female presenting Sweet?s Syndrome who presented with sudden onset of fever, headache, gastrointestinal tract symptoms and use of symptomatic medicine for the described case.

Erythema elevatum diutinum as a first clinical manifestation for diagnosing HIV infection: case history

CONTEXTO: O eritema elevatum diutinum é uma dermatose crônica, rara, variante clínica da vasculite leucocitoclástica, provavelmente mediada por imunocomplexos. Está sendo incluído no grupo das dermatoses específicas associadas à infecção pelo HIV. Em geral, associa-se a outros processos infecciosos, auto-imunes e neoplásicos. RELATO DE CASO: Relatamos o caso de um paciente em que a manifestação cutânea de eritema elevatum diutinum foi a primeira evidência clínica para diagnóstico da infecção pelo HIV. O tratamento foi feito com dapsona e se obteve regressão parcial das lesões após 15 dias, mesmo antes de o esquema anti-retroviral ser prescrito. CONCLUSÃO: Frente ao diagnóstico de eritema elevatum diutinum, deve-se investigar a infecção pelo HIV, principalmente nas apresentações clínicas atípicas e exacerbadas.

Erythema elevatum diutinum as a first clinical manifestation for diagnosing HIV infection: case history.

CONTEXT: Erythema elevatum diutinum is a chronic and rare dermatosis that is considered to be a variant of leukocytoclastic vasculitis. It is probably mediated by immune complexes. It is generally associated with autoimmune, neoplastic and infectious processes. Recently, it has been added to the group of specific dermatoses that are associated with HIV. CASE REPORT: We report on the case of a patient who had erythema elevatum diutinum as the first clinical evidence for diagnosing HIV infection. Dapsone was used in the treatment of this patient, and partial regression of the lesions was achieved within 15 days, even before anti-retroviral therapy was prescribed. CONCLUSION: When there is a diagnosis of erythema elevatum diutinum, HIV infection should be investigated, especially in atypical and exacerbated clinical manifestations.

Cisticercose cutânea, muscular e cerebral / Skin, muscle and brain cysticercosis

A cisticercose representa a infestaçäo do tecido humano pelas formas císticas intermediárias da Taenia solium. É adquirida por auto ou heteroinfestaçäo. O cisticerco aloja-se em numerosos órgäos ou tecidos, sendo os mais comuns a pele, o tecido celular subcutâneo, os músculos, o cérebro e os olhos. A doença adquire importância clínica devido às suas complicaçöes potencialmente letais, a partir do envolvimento de órgäos vitais. Este artigo relata um caso de uma paciente apresentando acometimento cutâneo disseminado com nódulos subcutâneos, calcificaçöes no tecido muscular e calcificaçöes intracranianas. A paciente apenas apresentava manifestaçöes clínicas cutâneas, sem sintomas ou sinais de acometimento do sistema nervoso central.