Activated status of basophils in chronic urticaria leads to interleukin-3 hyper-responsiveness and enhancement of histamine release induced by anti-IgE stimulus

Background Basophils and mast cells are the main target cells in chronic idiopathic urticaria (CIU). Besides the basopenia, intrinsic defects of the anti-IgE cross-linking signalling pathway of basophils have been described in CIU. Objectives We sought to investigate the profile of expression of activation markers on basophils of patients with CIU and to explore the effect of interleukin (IL)-3 priming upon anti-IgE cross-linking stimuli through expression of activation markers and basophil histamine releasability. Methods Evaluation of the surface expression of Fc epsilon RI alpha, CD63, CD203c and CD123 on whole blood basophils of patients with CIU undergoing autologous serum skin test (ASST) was performed by flow cytometry. The effect of pretreatment with IL-3 in the anti-IgE response was analysed by the expression of basophil activation markers and histamine release using enzyme-linked immunosorbent assay. Results Blood basophils of patients with CIU were reduced in number and displayed increased surface expression of Fc epsilon RI alpha, which was positively correlated with the IgE serum levels. Upregulation of expression of both surface markers CD203c and CD63 was verified on basophils of patients with CIU, regardless of ASST response. High expression of IL-3 receptor on basophils was detected only in ASST+ patients with CIU. Pretreatment with IL-3 upregulated CD203c expression concomitantly with the excreting function of blood basophils and induced a quick hyper-responsiveness to anti-IgE cross-linking on basophils of patients with CIU compared with healthy controls. Conclusions Basophils of patients with CIU showed an activated profile, possibly due to an in vivo priming. Functionally, basophils have high responsiveness to IL-3 stimulation, thereby suggesting that defects in the signal transduction pathway after IgE cross-linking stimuli are recoverable in subjects with chronic urticaria.

Sociodemographic and clinical characteristics, causal factors and evolution of a group of patients with chronic urticaria-angioedema

CONTEXTO E OBJETIVO: Urticária-angioedema crônico é enfermidade freqüente, complexa e multicausal. O objetivo foi estudar as características sociodemográficas, clínicas, os fatores causais, agravantes e a evolução da enfermidade. TIPO DE ESTUDO E LOCAL: Descritivo e prospectivo, realizado no ambulatório de Dermatologia da Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp). MÉTODOS: Foram avaliados pacientes com diagnóstico de urticária-angioedema crônico através de dados sociodemográficos, anamnese, exames dermatológico, clínico e laboratorial, com ênfase nos fatores causais, agravantes e na evolução da enfermidade. RESULTADOS: 125 pacientes foram incluídos, 95 mulheres e 30 homens. Predominaram mulheres de 30 a 40 anos e homens de 10 a 20 anos. A idade média foi de 35 anos para as mulheres e 32 anos para os homens. Predominaram pacientes de raça branca, residentes em zona urbana e casados. O tempo médio de doença foi de 45,6 meses e de cada lesão foi de 5,6 horas. A metade dos casos tinha surtos diariamente e associação de urticária com angioedema. Não houve horário preferencial de aparecimento dos surtos, mas o noturno foi o horário de piora mais citado. A causa foi esclarecida em 37,6%, predominando as infecções. O estresse foi o agravante mais referido. O tempo médio de acompanhamento foi de 11,7 meses e 60% evoluíram para o controle, 32% melhoraram, 9% mantiveram-se inalterados e um caso piorou. CONCLUSÕES: Urticária-angioedema ocorreu mais em mulheres de meia-idade. A causa foi esclarecida em um terço dos pacientes e metade deles teve controle da doença em aproximadamente um ano.

Individual IL-3 priming is crucial for consistent in vitro activation of donor basophils in patients with chronic urticaria

The in vivo autologous serum skin test (ASST) is the diagnostic gold standard to detect autoantibodies against FcεRI or IgE itself, as well as other autoreactive serum components, in patients with chronic spontaneous urticaria (CU). Coincubation of patient sera with donor basophils and measuring their degranulation in vitro could be a safe alternative but has shown inconsistent results.

Allergy - 5: Allergy and the skin: eczema and chronic urticaria

Eczema is common, occurring in 15%-20% of infants and young children. For some infants it can be a severe chronic illness with a major impact on the child's general health and on the family. A minority of children will continue to have eczema as adults. The exact cause of eczema is not clear, but precipitating or aggravating factors may include food allergens (most commonly, egg) or environmental allergens/irritants, climatic conditions, stress. and genetic predisposition. Management of eczema consists of education; avoidance of triggers and allergens; liberal use of emollients or topical steroids to control inflammation; use of antihistamines to reduce itch; and treatment of infection if present. Treatment with systemic agents may be required in severe cases, but must be supervised by an immunologist. Urticaria (hives) may affect up to a quarter of people at some time in their lives. Acute urticaria is more common in children, while chronic urticaria is more common in adults. Chronic urticaria is not life-threatening, but the associated pruritus and unsightly weals can cause patients much distress and significantly affect their daily lives. Angioedema coexists with urticaria in about 50% of patients. It typically affects the lips, eyelids, palms, soles and genitalia. Management of urticaria is through education; avoidance of triggers and allergens (where relevant); use of antihistamines to reduce itch; and short-term use of corticosteroids when antihistamine therapy is ineffective. Referral is indicated for patients with resistant disease.

Chronic autoimmune urticaria as the first manifestation of juvenile systemic lupus erythematosus

Chronic urticaria (daily or almost daily symptoms lasting for more than six weeks) is characterized by wheals and erythema, with or without itching. A few case reports have shown chronic autoimmune urticaria at the beginning of systemic lupus erythematosus (SLE), particularly in adults. However, the prevalence of this manifestation in a lupus paediatric population was not studied. During 27 consecutive years, 5419 patients were followed up at our University Hospital and 271 (5%) had juvenile SLE (American College of Rheumatology criteria). Two of them (0.7%) had chronic and painless autoimmune urticaria as the first manifestation of juvenile SLE, and were reported herein. One case was a five-year old female with continuous widespread urticaria (duration 120 days), antinuclear antibodies (ANA) 1:640 (dense fine speckled pattern) and elevated complement levels. The juvenile SLE diagnosis was established after one year. The other case was a 13-year old female who had chronic widespread urticaria (lasting 45 days), ANA 1:160 (fine speckled pattern) and normal complement levels. The juvenile SLE diagnosis was established after three years. In conclusion, chronic autoimmune urticaria is very rare and may be the first lupus manifestation, particularly associated with the presence of autoantibodies. This study reinforces the importance of a rigorous follow-up in children and adolescents suffering from autoimmune urticaria due to the possibility of connective tissue disorders, such as paediatric lupus. Lupus (2011) 20, 763-766.

Urticaria unresponsive to antihistaminic treatment: An open study of therapeutic options based on histopathologic features

Background: The non- or low-sedating H1 receptor antagonists represent the basic therapy for urticaria. Objective: To test an alternative approach to patients unresponsive to conventional treatment. Materials and methods: A total of 22 patients with chronic urticaria unresponsive to conventional antihistamine treatment were enrolled for this study. They had uncontrolled urticaria even using multiple combinations of antihistamines on maximum doses and corticosteroids in short cycles (prednisone 20-40 mg, per os once a day, 3-7 days per month). Cutaneous biopsies of the urticaria lesions were taken. These findings were classified as: (I) a mixture of perivascular dermal inflammatory infiltrate composed of lymphocytes, monocytes and neutrophils and/or eosinophils; (II) inflammatory infiltrate composed chiefly of neutrophils; and (III) inflammatory infiltrate composed mainly of eosinophils. According to histology, the patients were submitted to one of the following therapeutic schemes: class A - antihistamine treatment plus dapsone; class B - colchicine or dapsone; class C montelukast. Results: Four patients in class A, 08 in class B and seven in class C displayed complete control of urticaria after 12 weeks of treatment; one patient in class B and two in class C did not respond to treatment. Two years after discontinuation, 16 patients are still free of urticaria. Conclusions: This study suggests an alternative approach for treating unresponsive chronic urticaria.

Management of Childhood Urticaria: Current Knowledge and Practical Recommendations

Urticaria, defined by the presence of wheals and/or angioedema,is a common condition in children, prompting parents to consult physicians. For its successful management, paediatric-specific features must be taken into account, regarding the identification of eliciting triggers and pharmacological therapy. This review systematically discusses the current best-available evidence on spontaneous acute and chronic urticaria as well as physical and other urticaria types in children. Potential underlying causes, namely infections, food and drug hypersensitivity, autoreactivity and autoimmune or other conditions, and eliciting stimuli are considered, with practical recommendations for specific diagnostic approaches. Second-generation antihistamines are the mainstay of pharmacological treatment aimed at relief of symptoms, which require dose adjustment for paediatric use. Other therapeutic interventions are also discussed. In addition, unmet needs are highlighted, aiming to promote research into the paediatric population, ultimately aiming at the effective management of childhood urticaria.

Natural anti-FcepsilonRIalpha autoantibodies may interfere with diagnostic tests for autoimmune urticaria.

IgG autoantibodies against the alpha-chain of the high affinity IgE receptor are claimed to play a pathogenetic role in autoimmune urticaria. The best methods for detection of functional autoantibodies are currently the autologous serum skin test and the basophil histamine release assay. A simplified and feasible screening test would facilitate the diagnosis of autoimmune urticaria. Here we offer an explanation for the difficulties in establishing a screening test for autoantibodies directed against the alpha-chain of the high affinity IgE receptor in autoimmune urticaria. Identical autoantibodies in chronic urticaria patients and healthy donors belonging to the natural autoantibody repertoire were found by sequence analysis of anti-alpha-chain autoantibodies isolated by repertoire cloning from antibody libraries. These natural autoantibodies bound to the receptor and triggered histamine release but only if IgE was previously removed from the receptor. Diagnostic assays used for detection of antibodies directed against the IgE receptor may require signal comparison with and without the artificial removal of IgE, immune complexes, and complement in order to avoid false positive or negative results. After IgE removal diagnostic tests will detect natural autoantibodies against the high affinity IgE receptor regardless of whether they are pathogenic or not.

Allergo-immunologie. 2 : Les réactions allergiques aux anti-inflammatoires non stéroïdiens [Allergic reactions to nonsteroidal anti-inflammatory drugs]

Allergy to nonsteroidal antiinflammatory drugs (NSAIDs) is a very common affliction, especially among patients with asthma and chronic urticaria. These reactions are most often of a non-immunological nature but related to pharmacologic intolerance and linked to arachidonic acid metabolism and leukotriene release. Therefore, crossed reactions implying all non-selective and semi-selective NSAIDs constitute the rule, especially during respiratory reactions to NSAIDs and for patients with chronic urticaria. In isolated acute urticaria, crossed reactions are difficult to predict so caution is necessary. Tolerance induction is possible, especially when aspirin has to be administered in small doses as antiplatelet agent. Finally, acetaminophen and selective NSAIDs as celecoxib are well tolerated by most of these patients. L'allergie aux anti-inflammatoires non stéroïdiens (AINS) est très fréquente, en particulier chez les asthmatiques ou dans l'urticaire chronique. Il s'agit en général de réactions non immunologiques, mais dues à une intolérance pharmacologique liée au métabolisme de l'acide arachidonique et à la formation de leucotriènes. Ainsi, les réactions croisées impliquant tous les AINS non sélectifs et semi-sélectifs sont la règle, surtout lors de réactions respiratoires aux AINS et dans l'urticaire chronique. Lors d'urticaire aiguë isolée, les réactions croisées sont difficiles à prédire, ainsi la prudence s'impose. Une induction de tolérance est possible, en particulier lorsque l'aspirine est nécessaire à dose faible, comme antiagrégant plaquettaire. Enfin, le paracétamol et les AINS sélectifs sont supportés par la grande majorité de ces patients.

Qualidade de vida em urticária crônica: inquérito em ambulatório público universitário, Botucatu (Brasil)

OBJETIVO: Avaliar o impacto da urticária crônica na qualidade de vida dos pacientes de ambulatório universitário a partir do questionário DLQI (Dermatology Life Quality Index). MÉTODOS: Inquérito sobre o impacto na qualidade de vida infligido pela urticária crônica a partir do questionário DLQI validado para a língua portuguesa. Pacientes foram entrevistados durante suas consultas em ambulatório especializado, entre maio de 2009 e maio de 2010, em serviço público brasileiro (Botucatu-SP). Os escores do DLQI foram analisados segundo subgrupos: idade, gênero, escolaridade, tempo de doença e presença de angioedema. RESULTADOS: Foram entrevistados 100 pacientes com urticária crônica. Predominou o gênero feminino (86%), a idade média foi de 41,8 anos, duração média da doença foi de seis anos e angioedema ocorreu em 82% dos pacientes. O escore médio do DLQI foi de 13,5, caracterizando grave impacto à qualidade de vida, superior a hanseníase, psoríase, eczema atópico e carcinoma basocelular. Presença de angioedema se associou a maiores escores: 14,5 x 9,9 (p < 0,01). Pacientes do gênero feminino referiram maior impacto quanto ao vestuário, já o gênero masculino referiu quanto ao tratamento, trabalho e estudo (p < 0,05). CONCLUSÃO: Urticária crônica inflige grave comprometimento da qualidade de vida nos pacientes avaliados em serviço universitário brasileiro, especialmente nos portadores de angioedema.

CD63 e CD123 expressão, autoanticorpos IgG e acurácia do teste do soro autólogo em pacientes com urticária crônica

Introduction: The autologous serum skin test (ASST) may suggest an autoimmune etiology in chronic urticaria (CU). A new laboratory technique called basophil activation test (BAT) has been currently employed for its diagnosis. Objective: To analyze ASST in relation to BAT as well as to evaluate interleukin 3 (IL3) receptors (CD123) and non-specific immunoglobulin G (IgG) autoantibodies bound to basophils in patients with chronic urticaria. Methods: We studied 33 adults with CU and mean age of 42.5 + 14 years. After stimulation by serum from patients with CU, CD63 expression on basophils from one atopic donor was analyzed by flow cytometry. Furthermore, we investigated CD123 and IgG autoantibody expressions. Results: The odds ratio (OR) between ASST and BAT was 1.00 (95% confidence interval [CI]: 0.22 to 4.5). The ASST for autoimmune CU diagnosis showed an accuracy of 54.5%, sensitivity of 66%, specificity of 33%, positive predictive value of 63%, and negative predictive value of 36%. There was no statistical difference between the studied groups as to mean non-specific IgG and CD123 expressions (for a p < 0.05). Discussion: This study demonstrated that ASST has low accuracy in the diagnosis of autoimmune CU. Concerning other analyzed aspects, there was no statistical difference between positive ASST and negative ASST. Conclusions: Due to insufficient studies in this area and the relevance of this issue, further investigation is required.

Estudo da associação entre urticária crônica idiopática e autoimunidade tireóidea: aspectos clínicos, positividade do teste do soro autólogo da pele e expressão gênica do receptor de TSH

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Adesão ao tratamento da urticária crônica

Este trabalho apresenta o estudo de caso de uma mulher encaminhada ao serviço de psicologia de um hospital universitário com diagnóstico de urticária crônica. A queixa principal foi de que, apesar da adesão ao tratamento, os sintomas permaneciam. O objetivo foi auxiliar a cliente na instalação de novos repertórios e na generalização de padrões adequados já instalados, buscando melhor controle da urticária. Realizaram-se dez sessões de atendimento ambulatorial utilizando-se o modelo construcional, da abordagem analítico-comportamental, por meio de análises funcionais de episódios relatados pela cliente. Resultados indica-ram multicausalidade no desencadeamento e manutenção dos sintomas. O treino em análise de contingências favoreceu melhor controle dos fatores ambientais. A cliente aderiu adequadamente ao uso do medicamento após estabelecer relações funcionais entre sintomas e estressores ambientais, promovendo redução dos sintomas e melhor controle da doença. Concluiu-se que o atendimento auxiliou na melhora da qualidade de vida da cliente, destacando-se a relevância da adesão ao tratamento.