Resposta humoral contra lipoproteínas de alta densidade em doentes com psoríase

RESUMO: Este é o primeiro estudo que mostra a existência de IgG aHDL e aApoA-I em doentes com psoríase. É também a primeira vez que se identificam anticorpos aApoE associados a psoríase ou a qualquer patologia humana. Estes anticorpos são mais elevados na psoríase grave e têm capacidade de bloquear o efeito anti-inflamatório das HDL in vitro, o que sugere fortemente o seu papel patogénico. Concluímos que esta investigação sugere uma nova explicação mecanística para a associação entre psoríase e aterosclerose e também novos candidatos a biomarcadores de risco cardiovascular na psoríase que permitirão a estratificação do risco, orientando as atitudes de vigilância e as intervenções terapêuticas.ABSTRACT: Psoriasis is an immunomediated disease with a prevalence of 2-3%. It is the most prevalent chronic inflammatory disease in humans. Historically it was considered as a disease affecting only the skin, and sometimes the joints. However, in the last decades the association of psoriasis with various comorbidities was recognized. These include type II diabetes, hypertension, dyslipidemia, obesity, anxiety, depression, metabolic syndrome, subclinical atherosclerosis and cardiovascular disease (coronary artery disease and cerebrovascular disease). These comorbidities cause a considerable negative socioeconomical impact as well as loss of quality of life. Despite intensive investigation the causes and mechanisms of such associations are yet to be clarified. Psoriasis is associated with classic risk factors for cardiovascular disease but it is also an independent risk factor. It´s inclusion on the Framingham Risk score would lead to the reassignment of most psoriasis patients to a higher risk class, hence to actual changes in the therapeutic strategies and goals for these patients. The chronic inflammatory and oxidative processes occurring in psoriasis are very similar to those underlying atherosclerosis and are certainly implicated in the pathogenesis of the psoriatic plaques on the skin and the atheroma plaques on the arteries, with a parallel evolution. Our group had previously identified anti-HDL antibodies in autoimmune and non-autoimmune diseases, e.g., lupus erythematosus and type 2 diabetes, and associated these antibodies with a hampered HDL function. This project aimed at investigating the presence of anti-HDL antibodies in patients with psoriasis, suggesting a new mechanistic explanation for the association between psoriasis and atherosclerosis as well as providing potential biomarkers for the assessment of cardiovascular risk in these patients. We enrolled 67 consecutive patients with plaque psoriasis from our outpatient clinic, as well as 50 healthy blood donors with matching age and sex. Epidemiologic and clinical data were recorded. IgM and IgG anti-HDL (aHDL), anti-apolipoprotein A-I (aApoA-I), anti-apolipoprotein E (aApoE) and anti-paraoxonase 1 (aPON1) antibodies as well as vascular adhesion molecules (VCAM-1), Il-6 and TNF-α were assessed by ELISA. The plasma lipid profile was determined by standard enzymatic techniques. Apolipoprotein A-I (ApoA-I) and Apolipoprotein E (ApoE) were measured by immunoturbidimetric assays. Paraoxonase 1 (PON1) activity was assessed by quantification of nitrophenol formation by spectrophotometry. Nitric oxide metabolites (NOx) were measured using the Griess reaction. The biologic activity of the antibodies was assessed in vitro by the blockade of HDL inhibition of VCAM-1 expression on HUVECs previously stimulated with TNF- α. In the psoriasis group we found elevated BMI (p=0.043), hypertension (p=0.005), cardiovascular disease (p=0.07), diabetes (p=0.07) and dyslipidemia (p<0.001). Patients with psoriasis had higher titres of IgG (but not IgM) aHDL (p<0.001). They also had higher IgG aApoA-I (p=0.001) and aApoE antibodies (p<0.001). IgG aHDL antibodies titres directly correlated with aApoA-I antibodies (rS=0.432, p < 0.001) and aApoE antibodies (rS=0.339, p<0.001). Patients with severe psoriasis, defined as baseline PASI>10, had higher IgG aHDL and aApoE titres (p=0.010 and p=0.018, respectively) but there was no association with age or disease duration. There was no statistical difference in aPON1 levels between patients and controls. Regarding apoprotein levels, patients had increased ApoE (p=0.031) and decreased ApoA-I (p<0.001) levels. There were no differences in inflammation or oxidation markers. The functional in vitro study performed in HUVECs stimulated with TNF-α, showed that IgG aHDL isolated from patients were capable of blocking the inhibitory effect of HDL on the expression of VCAM-1 in the endothelium. To my knowledge, this is the first report showing the presence of aHDL and aApoA-I antibodies in patients with psoriasis. It is also the first report of aApoE in psoriasis and in human pathology. These antibodies were associated with increased disease severity and they block the anti-inflammatory effect of HDL in vitro, which strongly suggest they may play a role in the pathogenesis of atherosclerosis in psoriasis. They may also fulfil the clinical need for biomarkers of cardiovascular risk associated with psoriasis that would help to stratify patients for future prevention and therapeutic approaches

Neurotequeoma Celular em Criança: Descrição de um Caso Invulgar e Breve Revisão da Literatura

Neurothekeoma is a rare benign neoplasm of uncertain histogenesis. Progresses in immunohistochemistry have brought new insights into its cellular differentiation and origin, recognizing the possibility of a fibrohystiocitic lineage. Also, it has been subclassified histopathologically as either myxoid, cellular, or mixed type, depending on the amount of myxoid matrix and on immunohistochemical analysis. Few cases of cellular neurothekeoma have been reported. Most of them are found on the head, neck and upper extremities and mostly in young female adults. On review of literature we have not found reports regarding dermoscopic features of neurothekeoma. Herein we report an uncommon case of cellular neurothekeoma on the axilla of a 7–year-old girl, with description of its dermoscopic findings.O neurotequeoma é uma neoplasia benigna, rara, cuja histiogénese permanece incerta. Os avanços nos estudos com a imunohistoquímica, no entanto, permitiriam o reconhecimento de uma possível origem na linhagem fibrohistiocitária. Histopatologicamente são reconhecidas três variantes de acordo com a quantidade de matriz mixóide e com a análise imunohistoquímica: mixóide, celular ou misto. Os raros casos reportados, localizaram-se sobretudo na cabeça, pescoço e membros superiores, em mulheres jovens. Na revisão da literatura não há referência às características dermatoscópicas do neurotequeoma. Neste contexto, descrevemos o caso invulgar de um neurotequeoma celular, localizado na axila de uma criança de 7 anos, do sexo feminino, e respectivos achados dermatoscópicos

Pseudoainhum numa Doente com Doença Mista do Tecido Conjuntivo: Uma Associação Incomum

The term pseudoainhum is used to describe constricting band(s) around one or more digits in relation to several congenital or acquired diseases. Systemic sclerosis, keratoderma, psoriasis, Reynolds syndrome among others, has been reported to be associated with pseudoainhum development. We report a case of a 54 years old woman with annular constricting bands and micronychia on the fourth and fifth digits of her both hands associated with bilateral distal acrosclerosis. Raynaud’s phenomenon with some years of evolution and, more recent, fatigue and recurrent inflammatory polyarthritis and also antinuclear and anti-U1 nuclear ribonucleoprotein antibodies were present. Therefore, the diagnoses of pseudoainhum with a likely association with mixed connective tissue disease were proposed. Whenever in the presence of pseudoainhum, a detailed workup, including autoimmune disorders screening, is mandatory in order to rule out possible associated syndromes or underlying diseases. The authors present this case as the association between pseudoainhum and mixed connective tissue disease has not been previously reported in the literature.Peudoainhum representa a formação de anéis constritivos em redor de um ou vários dedos. Pode ser congénito ou adquirido e, neste caso, pode estar associado a várias dermatoses como esclerose sistémica, queratodermias, psoríase, síndrome de Reynolds, entre outras. É apresentado o caso de uma mulher de 54 anos que foi referenciada por lesões digitais anulares constritivas e microníquia no quarto e quinto dedos das mãos associadas a acroesclerose distal bilateral. Salientava-se ainda a presença de fenómeno de Raynaud há vários anos e, mais recentes, fadiga e poliartralgias recorrentes de carácter inflamatório e ainda de anticorpos antinucleares e anticorpo anti-U1 ribonucleoproteína. Desta forma, foi considerado o diagnóstico de pseudoainhum associado a uma provável doença mista do tecido conjuntivo. É sabido que perante um caso de pseudoainhum, uma investigação etiológica aturada deve ser levada a cabo incluindo o despiste de doenças autoimunes. A associação de pseudoainhum com a doença mista do tecido conjuntivo não está descrita na literatura, razão pela qual este caso é apresentado

ALERGIA A PROTEÍNAS DE LEITE DE VACA EM IDADE PEDIÁTRICA – ABORDAGEM DIAGNÓSTICA E TERAPÊUTICA

Cow’s milk protein allergy is an increasingly prevalent and more prolonged disease. Cow’s milk protein allergy is the most common food allergy in infants with a prevalence of approximately 2% to 3%. It may develop even in exclusively breastfed infants. It can manifest through a wide variety of symptoms depending on whether the type of immune response is IgE or non-IgE mediated. Symptoms and signs related to cow’s milk protein allergy may involve many different organ systems, mostly the skin and the gastrointestinal tract. Among the skin manifestations, urticaria and angioedema are likely the most common, followed by atopic dermatitis, pruritus, diffuse erythema and maculopapular rash. Cow’s milk protein allergy is suspected clinically in a large number of children. An incorrect diagnostic workup often leads to unnecessary dietary restrictions that may affect growth and development of children. This article presents a practical approach for the diagnosis and management of suspected cow’s milk protein allergy according to age and symptom severity.A alergia a proteínas do leite de vaca é uma patologia cada vez mais prevalente e de duração mais prolongada. Constitui a alergia alimentar mais comum na primeira infância, atingindo 2 a 3% dos lactentes e crianças. Pode apresentar-se logo após o nascimento, inclusive em lactentes alimentados exclusivamente com leite materno. A apresentação clínica é heterogénea e inespecífica e depende do tipo de resposta imunológica ser IgE ou não IgE mediada. Pode atingir vários órgãos e sistemas, mais frequentemente a pele e o sistema gastrintestinal. Dentre as manifestações cutâneas, a urticária e o angioedema são as mais comuns, seguidas da dermite atópica, prurido, eritema generalizado e exantema máculo-papular. O elevado número de crianças alvo de suspeita clínica e a realização de um diagnóstico incorrecto da alergia a proteínas do leite de vaca, leva, muitas vezes, a dietas de evicção desnecessárias e até prejudiciais ao seu crescimento e desenvolvimento. Neste artigo é revista a marcha diagnóstica na suspeita de alergia a proteínas do leite de vaca e a abordagem terapêutica de acordo com a gravidade das manifestações e a idade das crianças

Congenital Ichthyoses: 11 Cases from the Pediatric Dermatology Multidisciplinary Consultation of the Centro Hospitalar e Universitário de Lisboa Central

Introdução: As ictioses são um grupo heterogéneo de distúrbios genéticos hereditários que ocorrem devido a um defeito da queratinização e consequente disrupção da função de barreira cutânea. Embora raras, elas apresentam-se como um desafio clínico, em particular face ao correto diagnóstico e opções terapêuticas. Este estudo teve como objectivo principal caracterizar clinica e genotipicamente os casos de ictioses congénitas não sindrómicas e avaliar possível relação genótipo-fenótipo face aos dados mais recentes na literatura.Métodos: Realizámos um estudo retrospetivo onde foram incluídos todos os casos com diagnóstico clinico e confirmação genética de ictioses congénitas não sindrómicas da Consulta Multidisciplinar de Dermatologia Pediátrica do Hospital D. Estefânia do Centro Hospitalar e Universitário de Lisboa Central.Resultados: Foi analisado um total de 11 doentes com idades compreendidas entre os 20 meses e os 16 anos de idade. Quatro tinham a forma recessiva ligada ao X com mutação no gene da esteróide-sulfatase sendo que três deles manifestaram-se tipicamente pelo aparecimento ao nascimento de descamação poligonal cinza-acastanhada de distribuição generalizada e um com manifestações mais ligeiras compatíveis de xerose e eczema. Os restantes sete doentes tinham uma forma autossómica recessiva, quatro deles com mutação no gene TGM1, dois no ALOX12B e um no CYP4F22. Relativamente à evolução e prognóstico, verificou-se que o mesmo gene mutado foi responsável por um amplo espectro de manifestações clínicas, confirmando a dificuldade em estabelecer uma relação genótipo-fenótipo para estes doentes.Conclusão: Os avanços na área da genética têm sido fundamentais para a melhor compressão da fisiopatologia e evolução clínica das ictioses congénitas. No entanto, dado o amplo espectro fenotípico associado a uma mutação no mesmo gene, o estabelecimento de uma relação genótipo-fenótipo que possibilitaria um correto prognóstico, nem sempre é possível. Embora raras, os autores salientam a importância de mais estudos de modo a melhorar a qualidade de vida dos doentes com estas genodermatoses.Introduction: Congenital ichthyoses are a heterogeneous group of hereditary genetic disorders that occur due to a defective keratinization and consequent disruption of the skin barrier function. Although rare, they are presented as a diagnostic and therapeutic challenge. This study aimed to characterize clinically and genotypically the cases of non-syndromic congenital ichthyoses and to evaluate possible genotype-phenotype relation based on the most recent data in the literature.Methods: We performed a retrospective study in which all cases with clinical diagnosis and genetic confirmation of non-syndromic congenital ichthyoses were included in the Pediatric Dermatology Multidisciplinary Consultation of Hospital D. Estefânia of the Centro Hospitalar e Universitário de Lisboa Central.Results: A total of 11 patients aged between 20 months and 16 years were analyzed. Four had the X-linked recessive form with a mutation in the steroid-sulphatase gene, three of which typically manifested by the appearance at birth of generalized gray polygonal desquamation and one with milder manifestations of xerosis and eczema. The remaining seven patients had an autosomal recessive form, four of them mutated in the TGM1 gene, two in ALOX12B and one in CYP4F22. Regarding the evolution and prognosis, the same mutated gene was responsible for a broad spectrum of clinical manifestations, emphasizing the difficulty in establishing a genotype-phenotype relationship for these patients.Conclusion: Advances in genetics have been fundamental for better compression of the pathophysiology and clinical evolution of congenital ichthyoses. However, given the broad phenotypic spectrum associated with a mutation in the same gene, the establishment of a genotype-phenotype relationship, that would allow a correct prognosis, is not always possible. Although rare, the authors emphasize the importance of further studies in order to improve the quality of life of patients with these genodermatoses

Manifestações Cutâneas das Rasopatias

Rasopathies are a group of developmental diseases associated with mutations in the RAS/MAPK pathway. In the recent years, the study of intracellular signaling pathways allowed the characterization of this heterogeneous group of genetic disorders, with pleomorphic clinical manifestations, depending on the mutated gene. Rasopathies may be associated with cognitive impairment, cardiovascular disease, facial dysmorphism and cutaneous findings, as well as an increased risk of neoplasia. This group includes the Noonan syndrome, LEOPARD syndrome, neurofibromatosis type 1, Legius syndrome, Costello syndrome and cardiofaciocutaneous syndrome. It is important to recognize the cutaneous findings of rasopathies, which can help to establish the clinical diagnosis.As rasopatias são doenças do desenvolvimento associadas a mutações da via RAS/MAPK. Nos últimos anos, o estudo das vias de sinalização intracelular permitiu a caraterização deste grupo de doenças genéticas, com manifestações clínicas variáveis e dependentes do gene afetado. As rasopatias podem associar-se a alterações do desenvolvimento cognitivo, doenças cardiovasculares, dismorfismo facial e manifestações cutâneas, assim como a um risco aumentado de neoplasias. Entre estas doenças incluem-se a síndrome de Noonan, a síndrome de LEOPARD, a neurofibromatose tipo 1, a síndrome de Legius, a síndrome de Costello e a síndrome cardio-facio-cutânea. O conhecimento das suas manifestações cutâneas é importante, uma vez que pode ajudar a estabelecer o diagnóstico clínico

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Portuguese recommendations for the treatment of atopic dermatitis with biologic therapy and JAK inhibitors in adult patients

Funding Information: Disclosure and potential conflicts of interest: TT has received research grants and/or consulting fees from AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Samsung-Bioepis, Sandoz and Sanofi. MG has received research grants and/or consulting fees from Abbvie, Leo, Lilly, Novartis, Pfizer, Sanofi and Takeda. MJPL has received research grants and/or consulting fees from AbbVie, Almirall, Janssen, Leo-Pharma, Lilly, Novartis, Pfizer, Sanofi and Viatris. CC has received research grants and/or consulting fees from Janssen, Sanofi-Genzyme, Procter&Gamble, Astellas, Galderma, Leo-Pharma and Mylan. MS has received research grants and/or consulting fees from Janssen, Novartis and Pfizer. PMB has received research grants and/ or consulting fees from AbbVie, Pfizer, Janssen, LEO Pharma, Novartis, Sanofi, Teva, Bayer and L’Oreal. LR, JR, RC, AM and PF have no conflicts of interest to declare. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2021/11/dic.2021-9-5-COI.pdf Publisher Copyright: Copyright: Copyright © 2021 Torres T, Gonçalo M, Paiva Lopes MJ, Claro C, Ramos L, Selores M, Mendes Bastos P, Rocha J, Carvalho R, Mota A, Filipe P on Behalf of the Atopic Dermatitis Group of the Portuguese Society of Dermatology and Venereology. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.Atopic dermatitis is a highly prevalent chronic, immune-mediated inflammatory skin disease with a significant burden on patients, families and healthcare systems. This article presents recommendations developed by the Atopic Dermatitis Group of the Portuguese Society of Dermatology and Venereology addressing several clinical questions that arise in the management and care of moderate-to-severe atopic dermatitis with biologic agents and Janus kinase (JAK) inhibitors based on the available evidence. The recommendations were generated after a thorough evaluation of existing guidelines on the treatment of atopic dermatitis, publications concerning new biologics and JAK inhibitors not yet incorporated into existing guidelines, and expert-based recommendations. It also includes considerations on atopic dermatitis severity, indications for initiating biologic agents and JAK inhibitors, parameters to be considered in the treatment choice, in particular treatment goals, and recommendations for the use, screening and monitoring of these therapies.publishersversionpublishe

Hausdorff Distance evaluation of orthodontic accessories' streaking artifacts in 3D model superimposition

The aim of this study was to determine whether image artifacts caused by orthodontic metal accessories interfere with the accuracy of 3D CBCT model superimposition. A human dry skull was subjected three times to a CBCT scan: at first without orthodontic brackets (T1), then with stainless steel brackets bonded without (T2) and with orthodontic arch wires (T3) inserted into the brackets' slots. The registration of image surfaces and the superimposition of 3D models were performed. Within-subject surface distances between T1-T2, T1-T3 and T2-T3 were computed and calculated for comparison among the three data sets. The minimum and maximum Hausdorff Distance units (HDu) computed between the corresponding data points of the T1 and T2 CBCT 3D surface images were 0.000000 and 0.049280 HDu, respectively, and the mean distance was 0.002497 HDu. The minimum and maximum Hausdorff Distances between T1 and T3 were 0.000000 and 0.047440 HDu, respectively, with a mean distance of 0.002585 HDu. In the comparison between T2 and T3, the minimum, maximum and mean Hausdorff Distances were 0.000000, 0.025616 and 0.000347 HDu, respectively. In the current study, the image artifacts caused by metal orthodontic accessories did not compromise the accuracy of the 3D model superimposition. Color-coded maps of overlaid structures complemented the computed Hausdorff Distances and demonstrated a precise fusion between the data sets