Update on skin allergy.

Skin diseases with an allergic background such as atopic dermatitis, allergic contact dermatitis, and urticaria are very common. Moreover, diseases arising from a dysfunction of immune cells and/or their products often manifest with skin symptoms. This review aims to summarize recently published articles in order to highlight novel research findings, clinical trial results, and current guidelines on disease management. In recent years, an immense progress has been made in understanding the link between skin barrier dysfunction and allergic sensitization initiating the atopic march. In consequence, new strategies for treatment and prevention have been developed. Novel pathogenic insights, for example, into urticaria, angioedema, mastocytosis, led to the development of new therapeutic approaches and their implementation in daily patient care. By understanding distinct pathomechanisms, for example, the role of IL-1, novel entities such as autoinflammatory diseases have been described. Considerable effort has been made to improve and harmonize patient management as documented in several guidelines and position papers.

A high-affinity natural autoantibody from human cord blood defines a physiologically relevant epitope on the FcepsilonRIalpha.

Natural Abs represent the indigenous immune repertoire and are thus present at birth and persist throughout life. Previously, human autoantibodies to the alpha domain of the high-affinity IgE receptor (FcepsilonRIalpha) have been isolated from Ab libraries derived from normal donors and patients with chronic urticaria. To investigate whether these anti-FcepsilonRIalpha Abs are present in the germline repertoire, we constructed a phage Fab display library from human cord blood, which represents the naive immune repertoire before exposure to exogenous Ags. All isolated clones specific to the FcepsilonRIalpha had the same sequence. This single IgM Ab, named CBMalpha8, was strictly in germline configuration and had high affinity and functional in vitro anaphylactogenic activity. Inhibition experiments indicated an overlapping epitope on the FcepsilonRIalpha recognized by both CBMalpha8 and the previously isolated anti-FcepsilonRIalpha Abs from autoimmune and healthy donors. This common epitope on FcepsilonRIalpha coincides with the binding site for IgE. Affinity measurements demonstrated the presence of Abs showing CBMalpha8-like specificity, but with a significantly lower affinity in i.v. Ig, a therapeutic multidonor IgG preparation. We propose a hypothesis of escape mutants, whereby the resulting lower affinity IgG anti-FcepsilonRIalpha Abs are rendered less likely to compete with IgE for binding to FcepsilonRIalpha.

The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease

The basophil activation test (BAT) has become a pervasive test for allergic response through the development of flow cytometry, discovery of activation markers such as CD63 and unique markers identifying basophil granulocytes. Basophil activation test measures basophil response to allergen cross-linking IgE on between 150 and 2000 basophil granulocytes in <0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In addition to clinical history, skin prick test, and specific IgE determination, BAT can be a part of the diagnostic evaluation of patients with food-, insect venom-, and drug allergy and chronic urticaria. It may be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment or in the natural resolution of allergy. Basophil activation test may use fewer resources and be more reproducible than challenge testing. As it is less stressful for the patient and avoids severe allergic reactions, BAT ought to precede challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. In this EAACI task force position paper, we provide an overview of the practical and technical details as well as the clinical utility of BAT in diagnosis and management of allergic diseases.

Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma.

Nerve growth factor (NGF) serum levels were measured in 49 patients with asthma and/or rhinoconjunctivitis and/or urticaria-angioedema. Clinical and biochemical parameters, such as bronchial reactivity, total and specific serum IgE levels, and circulating eosinophil cationic protein levels, were evaluated in relation to NGF values in asthma patients. NGF was significantly increased in the 42 allergic (skin-test- or radioallergosorbent-test-positive) subjects (49.7 +/- 28.8 pg/ml) versus the 18 matched controls (3.8 +/- 1.7 pg/ml; P < 0.001). NGF levels in allergic patients with asthma, rhinoconjunctivitis, and urticaria-angioedema were 132.1 +/- 90.8, 17.6 +/- 6.1, and 7.6 +/- 1.8 pg/ml (P < 0.001, P < 0.002, and P < 0.05 versus controls), respectively. Patients with more than one allergic disease had higher NGF serum values than those with a single disease. When asthma patients were considered as a group, NGF serum values (87.6 +/- 59.8 pg/ml) were still significantly higher than those of control groups (P < 0.001), but allergic asthma patients had elevated NGF serum levels compared with nonallergic asthma patients (132.1 +/- 90.8 versus 4.9 +/- 2.9 pg/ml; P < 0.001). NGF serum levels correlate to total IgE serum values (rho = 0.43; P < 0.02). The highest NGF values were found in patients with severe allergic asthma, a high degree of bronchial hyperreactivity, and high total IgE and eosinophil cationic protein serum levels. This study represents the first observation (that we know of) that NGF is increased in human allergic inflammatory diseases and asthma.

Polissensibilização alimentar : um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Alergia a beta-lactâmicos : uma revisão sistemática

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Urticária crónica, associação a tiroidite autoimune : revisão a propósito de um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Contact dermatitis from shoes: an update

Contact dermatitis is a common inflammatory skin condition characterized by erythematous and pruritic skin lesions that occur after contact with a foreign substance. There are two forms of contact dermatitis: irritant and allergic. Irritant contact dermatitis is caused by the non–immune-modulated irritation of the skin by a substance, leading to skin changes. Allergic contact dermatitis is a delayed hypersensitivity reaction in which a foreign substance comes into contact with the skin; skin changes occur after reexposure to the substance. A medical condition referred to as “shoe dermatitis” is a form of contact dermatitis caused by the contact of the foot with parts of the shoe due to these materials. Shoe dermatitis is a diagnostic and therapeutic challenge and is a common type of contact dermatitis. It is imperative the foot and ankle physician become familiar with recognizing signs and symptoms of shoe dermatitis so that their patients can be accurately diagnosis and appropriately treated to avoid secondary infections and disability. This review will first present causative factors for the etiology of shoe contact dermatitis supported by clinical-based evidence as found in the medical literature. Secondly, a description of the signs and symptoms of shoe contact dermatitis will be presented in a narrative fashion. Finally, both treatment options and preventative measures to avoid shoe.

Alergias a alimentos ou a derivados usados como excipientes em medicamentos

Aditivos químicos têm como principal objetivo melhorar os produtos industrializados, como fármacos, conferindo-lhes cor, aroma, textura, conservação, entre outros. Os aditivos utilizados na indústria farmacêutica são denominados excipientes, completando a massa ou o volume especificado no medicamento. São considerados substâncias inativas, uma vez que não apresentam propriedades curativas ou preventivas de doenças ou dos seus sintomas. No âmbito deste trabalho, foi realizado uma revisão bibliográfica sobre os excipientes naturais e sintéticos mais usados na indústria farmacêutica, agrupando-os mediante a sua função específica. Assim, foi feita uma breve descrição sobre alguns dos excipientes mais utilizados nas formulações farmacêuticas, nomeadamente os antioxidantes, os corantes, os edulcorantes e os conservantes, que visam garantir a conservação do produto em condições viáveis. Uma vez que os excipientes são considerados substâncias inativas, são vistos como inofensivos para a saúde. No entanto, é cada vez mais evidente que os excipientes não são sempre inertes e podem apresentar riscos para o desenvolvimento de reações alérgicas, podendo promover alterações mais prejudiciais. As reações alérgicas associadas aos excipientes são consideradas raras, visto que são incorporadas baixas concentrações destes em formulações farmacêuticas, tendo surgido, no entanto, diversos casos associados aos diferentes excipientes anteriormente referidos. Dependendo do excipiente e da sensibilidade do indivíduo, as alergias podem originar dermatites de contacto, prurido, urticária, edema, reações anafiláticas, entre outros. É importante salientar que o excesso de aditivos pode originar problemas de saúde, normalmente em indivíduos suscetíveis e na população pediátrica, sendo necessário aplicar cuidados adicionais que promovam uma maior vigilância e orientação no uso de medicamentos.