Hereditary epidermolysis bullosa: clinical-epidemiological profile of 278 patients at a tertiary hospital in São Paulo, Brazil

Abstract Background Epidermolysis bullosa (EB) is a group of rare hereditary diseases, characterized by fragility of the skin and mucous membranes. Epidemiological data on EB in Brazil are scarce. Objectives To describe epidemiological aspects of patients with EB diagnosed in the Dermatology Department of a tertiary hospital, from 2000 to 2022. Methods An observational and retrospective study was conducted through the analysis of medical records. The evaluated data included clinical form, sex, family history, consanguinity, age at diagnosis, current age, time of follow-up, comorbidities, histopathology and immunomapping, presence of EB nevi and squamous cell carcinomas (SCC), cause of and age at death. Results Of 309 patients with hereditary EB, 278 were included. The most common type was dystrophic EB (DEB), with 73% (28.4% dominant DEB, 31.7% recessive DEB and 12.9% pruriginous DEB). Other types were junctional EB with 9.4%, EB simplex with 16.5% and Kindler EB with 1.1%. Women accounted for 53% and men for 47% of cases. Family history was found in 35% and consanguinity in 11%. The mean age at diagnosis was 10.8 years and the current age was 26 years. The mean time of follow-up was nine years. Esophageal stenosis affected 14%, dental alterations affected 36%, malnutrition 13% and anemia 29%. During diagnostic investigation, 72.6% underwent histopathological examination and 92% underwent immunomapping. EB nevi were identified in 17%. Nine patients had SCC. Eleven patients died. Study limitations Insufficient data included to medical records, loss to follow-up, and unavailability of genetic testing. Conclusions In this study, dystrophic EB predominated and the need for multidisciplinary care for comorbidities and complications was highlighted.

Advantages of whole-exome sequencing over immunomapping in 67 Brazilian patients with epidermolysis bullosa

Abstract Background Epidermolysis bullosa (EB) is characterized by skin fragility and blistering. In Brazil, the diagnosis is usually obtained through immunomapping, which involves a skin biopsy. Most recently, whole exome sequencing (WES) has become an important tool for the diagnosis of the subtypes of EB, providing information on prognosis as well as allowing appropriate genetic counseling for the families. Objective To compare the results of immunomapping and molecular analysis and to describe the characteristics of a Brazilian cohort of patients with EB. Methods Patients were submitted to clinical evaluation and WES using peripheral blood samples. WES results were compared to those obtained from immunomapping testing from skin biopsies. Results 67 patients from 60 families were classified: 47 patients with recessive dystrophic EB (DEB), 4 with dominant DEB, 15 with EB simplex (EBS), and 1 with junctional EB (JEB). Novel causative variants were: 10/60 (16%) in COL7A1 associated with recessive DEB and 3 other variants in dominant DEB; one homozygous variant in KRT5 and another homozygous variant in PLEC, both associated with EBS. Immunomapping was available for 59 of the 67 patients and the results were concordant with exome results in 37 (62%), discordant in 13 (22%), and inconclusive in 9 patients (15%). Study limitations Even though EB is a rare disease, for statistical purposes, the number of patients evaluated by this cohort can still be considered limited; other than that, there was a significant difference between the proportion of types of EB (only one case with JEB, against more than 50 with DEB), which unfortunately represents a selection bias. Also, for a small subset of families, segregation (usually through Sanger sequencing) was not an option, usually due to deceased or unknown parent status (mostly the father). Conclusion Although immunomapping has been useful in services where molecular studies are not available, this invasive method may provide a misdiagnosis or an inconclusive result in about 1/3 of the patients. This study shows that WES is an effective method for the diagnosis and genetic counseling of EB patients.

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.

Bullous lesions following phototherapy in a newborn

ABSTRACT A male infant presented with progressive jaundice immediately after birth. Fecal acholia and choluria associated with extensive bullous skin lesions in his trunk, abdomen, and upper and lower limbs developed during phototherapy. Several diagnostic hypotheses were presented, including neonatal porphyria, hemochromatosis, Alagille syndrome, and neonatal lupus. A 24-hour urine sample for the dosage of urinary porphyrins was collected, showing high results (1823.6µg in 100mL). At 50 days of life, fluorescence spectroscopy using a Wood's lamp revealed simultaneous bright red fluorescence of urine-stained diapers and sample blood. A definitive diagnosis of congenital erythropoietic porphyria was made following identification of a mutation of the uroporphyrinogen synthetases III gene on genetic testing. The patient was subsequently maintained in a low light environment since then, resulting in improvement of the lesions. Congenital erythropoietic porphyria is a disease of the group of porphyrias that presents shortly after birth with blistering occurring in regions exposed to the sun or other ultraviolet light. Atrophic scars, mutilated fingers, and bright red fluorescence of the urine and teeth may also be observed. There is no specific treatment, and prophylaxis comprising a total avoidance of sunlight is generally recommended. A high degree of suspicion is required for diagnosis. An early diagnosis can lead to less damage. Here, we present the case of a newborn with congenital erythropoietic porphyria diagnosed after presenting with bullous lesions secondary to phototherapy.

Consensus on the treatment of hidradenitis suppurativa - Brazilian Society of Dermatology

Abstract: Hidradenitis suppurativa is a chronic immune mediated disease of universal distribution that causes great damage to the quality of life of the affected individual, whose prevalence is estimated at 0.41% in the Brazilian population. The objective of this work was update on physiopathogenesis, diagnosis and classification of hidradenitis suppurativa and to establish therapeutic recommendations in the Brazilian reality. It was organized as a work group composed of eight dermatologists from several institutions of the country with experience in the treatment of hidradenitis suppurativa and carried out review on the topic. Recommendations were elaborated and voted by modified Delphi system and statistical analysis of the results was performed. The Brazilian consensus on the clinical approach of hidradenitis suppurativa had the support of the Brazilian Society of Dermatology.

Consensus on the diagnostic and therapeutic management of chronic spontaneous urticaria in adults - Brazilian Society of Dermatology

Abstract: Background: Urticarias are frequent diseases, with 15% to 20% of the population presenting at least one acute episode in their lifetime. Urticaria are classified in acute ( ≤ 6 weeks) or chronic (> 6 weeks). They may be induced or spontaneous. Objectives: To verify the diagnostic and therapeutic recommendations in chronic spontaneous urticaria (CSU), according to the experience of Brazilian experts, regarding the available guidelines (international and US). Methods: A questionnaire was sent to Brazilian experts, with questions concerning diagnostic and therapeutic recommendations for CSU in adults. Results: Sixteen Brazilian experts answered the questionnaire related to diagnosis and therapy of CSU in adults and data were analyzed. Final text was written, considering the available guidelines (International and US), adapted to the medical practices in Brazil. Diagnostic work up in CSU is rarely necessary. Biopsy of skin lesion and histopathology may be indicated to rule out other diseases, such as, urticarial vasculitis. Other laboratory tests, such as complete blood count, CRP, ESR and thyroid screening. Treatment of CSU includes second-generation anti-histamines (sgAH) at licensed doses, sgAH two, three to fourfold doses (non-licensed) and omalizumab. Other drugs, such as, cyclosporine, immunomodulatory drugs and immunosuppressants may be indicated (non-licensed and with limited scientific evidence). Conclusions: Most of the Brazilian experts in this study partially agreed with the diagnostic and therapeutic recommendations of the International and US guidelines. They agreed with the use of sgAH at licensed doses. Increase in the dose to fourfold of sgAH may be suggested with restrictions, due to its non-licensed dose. Sedating anti-histamines, as suggested by the US guideline, are indicated by some of the Brazilian experts, due to its availability. Adaptations are mandatory in the treatment of CSU, due to scarce or lack of other therapeutic resources in the public health system in Brazil, such as omalizumab or cyclosporine.

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.

PHACE syndrome: clinical manifestations, diagnostic criteria, and management

Abstract: Infantile hemangioma can be linked to other organ malformations. In 1996, PHACE syndrome was first defined as the association of large and segmental infantile hemangioma, usually on the face, head, or cervical region, with malformations of the posterior fossa of the brain, arterial anomalies of the central nervous system, coarctation of the aorta, cardiac defects, and ocular abnormalities. Over 300 cases of PHACE syndrome have been reported, and it is cconsidered one of the most common neurocutaneous vascular disorders in childhood. Knowledge of the features and locations of lesions that imply a greater risk of systemic involvement is crucial for the diagnosis and proper management of PHACE syndrome patients. This review highlights the diagnostic criteria for PHACE syndrome, the imaging workup for extracutaneous involvement, the treatment of infantile hemangioma, and the importance of a multidisciplinary approach in the management of these patients.

Tuberous sclerosis complex: review based on new diagnostic criteria

Abstract: Tuberous sclerosis complex is a multisystemic, autosomal dominant genetic disorder with complete penetrance, that can evolve with hamartomas in multiple organs, such as skin, central nervous system, kidney and lung. Due to the wide phenotypic variability, the disease is often not recognized. Tuberous sclerosis complex affects one in 10,000 newborns and most patients are diagnosed during the first 15 months of life. The diagnostic criteria for tuberous sclerosis were reviewed in 2012, at the second International Tuberous Sclerosis Complex Consensus Conference. The diagnosis is based on genetic criteria, by the identification of inactivating pathogenic mutation of tumor suppressor genes TSC1 and TSC2, and clinical criteria, including cutaneous, renal, pulmonary, cardiac and neurological manifestations. The treatment of tuberous sclerosis complex consists, mainly, in management of the symptoms caused by hamartomas and in prevention of organ failure. Multidisciplinary approach is recommended, in order to obtain better clinical outcomes.

Propranolol for treatment of infantile hemangiomas / Tratamento de hemangiomas infantis com propranolol

Infantile hemangioma is the most common vascular tumor in early childhood. Propranolol has been successfully used recently in a limited number of children with Infantile hemangioma. We present 6 cases of Infantile hemangioma, at a single dermatological center, which responded to oral propranolol with good results.

O hemangioma da infância é o tumor vascular mais comum nessa faixa etária. Mais recentemente, propranolol oral tem sido usado com sucesso em um número limitado de crianças com hemangioma da infância. Nós apresentamos 6 casos de hemangioma da infância, provenientes de um único centro dermatológico, que apresentaram boa resposta ao tratamento com propranolol oral.