Validation of the Urticaria Control Test (UCT) in Children With Chronic Urticaria.

BACKGROUND: Few validated tools exist to evaluate chronic urticaria (CU) control in children. Although the Urticaria Control Test (UCT) exhibits favorable clinometric properties in adult CU, it is not yet validated in children. OBJECTIVE: To evaluate the validity of the UCT for the assessment of pediatric CU. METHODS: Children presenting with CU were consecutively recruited and completed both the UCT and the Children's Dermatology Life Quality Index (CDLQI) at study entry. Using the CDLQI as an anchor, we assessed the internal consistency, convergent and known-groups validity, and screening accuracy of the UCT at study entry and at follow-up. RESULTS: A total of 52 children with CU were recruited. The UCT exhibited respectable internal consistency in the evaluation of CU (Cronbach's α, 0.73; 95% CI, 0.62-0.85). UCT and CDLQI scores strongly correlated (r = -0.74; P < .01). The UCT distinguished between different strata of disease severities established by the CDLQI (P < .01). Screening accuracy of the UCT was excellent in the discrimination of poorly controlled CU (area under the curve, 0.82). An optimal cutoff of less than or equal to 10 was determined for defining poorly controlled CU (sensitivity, 95.5%; specificity, 63.3%). Data at follow-up were consistent with data at study entry. Subgroup analyses of patients with chronic spontaneous urticaria were consistent with overall estimates of validity. CONCLUSIONS: The UCT is a valid tool for the assessment of pediatric CU and chronic spontaneous urticaria, as evidenced by the acceptable internal consistency, convergent and known-groups validity, and screening accuracy at multiple time points.

Cold urticaria in a pediatric cohort: Clinical characteristics, management, and natural history.

BACKGROUND: Cold urticaria (coldU) is associated with substantial morbidity and risk of fatality. Data on coldU in children are sparse. We aimed to evaluate the clinical characteristics, management, risk of associated anaphylaxis, and resolution rate of coldU in a pediatric cohort. Additionally, we sought to compare these metrics to children with chronic spontaneous urticaria (CSU). METHODS: We prospectively enrolled children with coldU from 2013-2021 in a cohort study at the Montreal Children's Hospital and an affiliated allergy clinic. Data for comparison with participants with solely CSU were extracted from a previous study. Data on demographics, comorbidities, severity of presentation, management, and laboratory values were collected at study entry. Patients were contacted yearly to assess for resolution. RESULTS: Fifty-two children with cold urticaria were recruited, 51.9% were female and the median age of symptom onset was 9.5 years. Most patients were managed with second-generation H1-antihistamines (sgAHs). Well-controlled disease on sgAHs was negatively associated with concomitant CSU (adjusted odds ratio (aOR) = 0.69 [95%CI: 0.53, 0.92]). Elevated eosinophils were associated with cold-induced anaphylaxis (coldA; aOR = 1.38 [95%CI: 1.04, 1.83]), which occurred in 17.3% of patients. The resolution rate of coldU was 4.8 per 100 patient-years, which was lower than that of CSU (adjusted hazard ratio = 0.43 [95%CI: 0.21, 0.89], p < 10-2 ). CONCLUSION: Pediatric coldU bears a substantial risk of anaphylaxis and a low-resolution rate. Absolute eosinophil count and co-existing CSU may be useful predictive factors.

Prevalence, Management, and Anaphylaxis Risk of Cold Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: Cold urticaria is a subtype of chronic inducible urticaria (CIndU) associated with significant morbidity and a risk for anaphylaxis. Few studies have assessed the prevalence, management, and prevalence of associated anaphylaxis of cold urticaria. OBJECTIVES: To evaluate the prevalence of cold urticaria among CIndU and chronic urticaria (CU) cases, to assess the management of cold urticaria, and to determine the prevalence of associated anaphylaxis. METHODS: We searched PubMed and EMBASE for studies pertaining to cold urticaria and/or CIndU published in the past 10 years. We conducted meta-analyses to evaluate the prevalence of cold urticaria among CIndU and CU cases, the management of cold urticaria with H1-antihistamines and omalizumab, and the prevalence of associated anaphylaxis. RESULTS: Twenty-two studies were included in the systematic review and 14 in the meta-analysis. The pooled prevalence of cold urticaria among patients with CU and CIndU was 7.62% (95% confidence interval [CI], 3.45% to 15.99%; I2 = 98%) and 26.10% (95% CI, 14.17% to 43.05%; I2 = 97%), respectively. Cold urticaria was managed by H1-antihistamines in 95.67% (95% CI, 92.47% to 97.54%; I2 = 38%) of patients and omalizumab in 5.95% (95% CI , 2.55% to 13.27%; I2 = 83%) of patients. The pooled prevalence of anaphylaxis among patients with cold urticaria was 21.49% (95% CI, 15.79% to 28.54%; I2 = 69%). CONCLUSIONS: Cold urticaria constitutes an appreciable proportion of CIndU and CU cases and is predominantly managed with H1-antihistamines; few patients receive omalizumab. Anaphylaxis is common, and an epinephrine autoinjector prescription may be considered.

Managing Chronic Urticaria and Recurrent Angioedema Differently with Advancing Age.

Angioedema and urticaria affect people of all ages. Accurate diagnosis and optimum management is essential for healthy aging. Older people continue to experience mast cell-mediated urticaria and angioedema, with a higher prevalence of autoimmune and a lower prevalence of autoallergic disease. Bradykinin-mediated angioedemas are more common in the elderly because of their association with angiotensin-converting enzyme inhibitor (ACEI) treatment. Acquired C1-inhibitor deficiency, another bradykinin-mediated angioedema, occurs predominantly in older people, whereas hereditary angioedema due to C1-inhibitor deficiency continues to cause symptoms, even in old age. Drug-induced angioedemas disproportionately affect older people, the most frequent users of ACEIs, aspirin, and nonsteroidal anti-inflammatory drugs. Accurate diagnosis and targeted treatment prevent unnecessary morbidity and mortality. Second-generation antihistamines with omalizumab if required are effective and well tolerated in older people with mast cell-mediated urticaria. For bradykinin-mediated angioedemas, these drugs are ineffective. C1-inhibitor replacement or blockade of kallikrein or the bradykinin B2 receptor of the contact pathway is required to treat hereditary angioedema and may be considered in other bradykinin-mediated angioedemas, if supportive treatment is insufficient. For aspirin-related angioedema and urticaria, alternative medications or, exceptionally, desensitization may be required.

Clinical Characteristics, Management, and Natural History of Chronic Inducible Urticaria in a Pediatric Cohort.

BACKGROUND: Some forms of chronic urticaria (CU) can be specifically attributed to a response to a definite trigger, referred to as chronic inducible urticaria (CIndU). We aimed to assess the demographics, clinical characteristics, comorbidities, natural history, and management of pediatric patients with CIndU. METHODS: Over a 6-year period, children presenting to the allergy clinic at the Montreal Children's Hospital (MCH) with CIndU were prospectively recruited. CU was defined as the presence of wheals and/or angioedema, occurring for at least 6 weeks. A standardized diagnostic test was used to establish the presence of a specific form of urticaria. Resolution was defined as the absence of hives for 1 year without treatment. RESULTS: Sixty-four patients presented with CIndU, of which 51.6% were male, with a median age of 12.5 (interquartile range 7.3, 15.9) years. Cold CU and cholinergic CU were the most common subtypes (60.3 and 41.3%, respectively). Basophil counts were undetectable in 48.4% of the cases, and C-reactive protein levels were elevated in 7.8% of patients. Of all cases, 71.4% were controlled with second-generation antihistamines. The resolution rate was of 45.3% (95% confidence interval 33.1-57.5%), based on per-protocol population within the 6-year course of the study. Resolution was more likely in patients who presented with well-controlled urticaria control test scores and elevated CD63 counts and in those suffering from thyroid comorbidity. CONCLUSION: The natural history of CIndU resolution in pediatric patients was relatively low and was associated with elevated CD63 levels, as well as thyroid comorbidity.

Secondary prevention measures in anaphylaxis patients: Data from the anaphylaxis registry.

BACKGROUND: Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction. METHODS: Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil. RESULTS: The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one. CONCLUSIONS: Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians.

Guia prático de atualização: medicamentos biológicos no tratamento da asma, doenças alérgicas e imunodeficiências / Practical update guide: biological drugs in the treatment of asthma, allergic diseases and immunodeficiencies

O presente guia apresenta revisão extensa sobre imunobiológicos utilizados, liberados e ainda sob estudo, para o tratamento da asma, doenças alérgicas e imunodeficiências. Além das características físico-químicas de alguns desses fármacos, são revisadas as indicações e os resultados de estudos clínicos realizados para avaliar eficácia e segurança. Separados por doença específica, são apresentados os principais agentes disponíveis e aprovados para utilização segundo as normas regulatórias nacionais.

This guide presents an extensive review of immunobiological drugs used, approved and/or under investigation for the treatment of asthma, allergic diseases and immunodeficiencies. In addition to the physicochemical characteristics of some of these drugs, their indications and results of clinical studies evaluating efficacy and safety are reviewed. The main agents available and approved for use in each specific disease according to national regulatory standards are presented.

The Burden of Chronic Urticaria from Brazilian Patients' Perspective.

INTRODUCTION: Chronic urticaria (CU), a proxy for chronic spontaneous urticaria, has been associated with a negative impact on health-related quality of life (HRQoL) and costs, but there is limited evidence on the burden of CU in Brazil. The objective of this study was to estimate the prevalence of CU and assess the burden of CU on HRQoL and healthcare resource utilization (HRU) among adults in Brazil. METHODS: This retrospective, cross-sectional study, pooled data from the 2011, 2012, and 2015 National Health and Wellness Survey in Brazil (n = 36,000). Respondents (aged ≥18 years) diagnosed with and treated for CU provided data on demographics, health history, HRQoL (mental and physical health status) on Short-Form SF-36v2, presence of psychological complaints, work impairment, activity impairment, and HRU. Generalized linear models, controlling for covariates, examined differences between those treated for CU and matched controls on the outcome variables. RESULTS: The prevalence of diagnosed CU was 0.41% (n = 249) and treated CU was 0.21% (n = 127). After adjustments, CU (currently treated for CU) was associated with worse mental functioning, physical functioning, and health utilities compared with controls (all p < 0.01). CU had over twice the odds of anxiety and sleep difficulties, over 1.5 times the work and activity impairment, twice the number of total physician visits, eight times the number of allergist visits, and twice the number of emergency room visits as controls (all p < 0.01). CONCLUSIONS: Many CU patients using prescription treatment experienced anxiety and sleep disturbances, poorer HRQoL, significant work and activity impairment, and high HRU, compared with matched general population controls. Findings suggest an unmet need for more effective treatment and management of CU in Brazil. FUNDING: Novartis Pharma AG and Genentech.

Uso a longo prazo de alternativas terapêuticas aos anti-inflamatórios não-esteroidais / Long term use of therapeutic alternatives for non-steroidal anti-inflammatory drugs

A benzidamina e o etoricoxibe são drogas que podem ser utilizadas como alternativa terapêutica em pacientes com hipersensibilidade aos anti-inflamatórios não-esteroidais (AINEs). O objetivo do estudo foi avaliar a utilização destas medicações a longo prazo em pacientes com teste de provocação negativo. Métodos: Pacientes com hipersensibilidade aos AINEs que apresentaram teste de provocação negativo foram contactados por telefone e questionados sobre a utilização posterior da drogatestada. Os pacientes que responderam que não voltaram a utilizar a droga foram questionados sobre os motivos pelo qualnão usaram. Resultados: Dos 53 pacientes testados, 50 apresentaram teste de provocação negativo. Destes, 36 foram contactados por telefone e 18 haviam utilizado novamente a droga sem qualquer reação. Dentre os que não foram expostos novamente aos medicamentos, metade não o fez porque não julgou necessário, e a outra metade por receio de uma nova reação. Conclusões: O teste de provocação oral é seguro para a determinação de alternativas terapêuticas, mas a eficácia do mesmo está diretamente relacionada ao entendimento do paciente quanto a possibilidade de novas reações. Além disso, as indicações para o teste também devem ser revistas.

Benzydamine and etoricoxib are drugs that can be used as an alternative therapy in patients with hypersensitivity to thenon-steroidal anti-inflammatory drugs (NSAIDs). The aim of the study was to evaluate the long-term use of these drugs inpatients with a negative drug provocation test. Methods: Patients with NSAIDs hypersensitivity that presented a negative drug provocation test were contacted by telephone and questioned about the subsequent use of the tested drug. The patients who answered that they had not used the drug again were questioned on the reasons for not using it. Results: Of the 53 patients tested, 50 presented a negative drug provocation test. Of these, 36 were contacted by telephone and 18 had used the drug again without any reaction. Among the ones that were not exposed again to the drugs, halfof them had not used because they didn't judge necessary, andt he other half were afraid of a new reaction. Conclusions: The drug provocation test is safe for the determination of an alternative therapy, but the effectiveness oft he test is directly related to the patient's understanding about the possibility of new reactions. Besides, the indications for the test should also be reviewed.

Reações de hipersensibilidade à insulina / Insulin hypersensitivity reactions

As reações de hipersensibilidade à insulina têm diminuído significativamente após a introdução da preparação de insulina humana. No entanto, alguns casos continuam sendo observados na prática clínica. Revisamos os principais aspectos relacionados à fisiopatologia, às manifestações clínicas, ao diagnóstico e ao tratamento das reações de hipersensibilidade a insulina. As reações à insulina podem estar relacionadas a qualquerum dos quatro mecanismos de Gell e Coombs. As manifestações clínicas surgem geralmente nas quatro primeiras semanas de tratamento e incluem mais frequentemente reações locais, mas também urticária, angioedema e anafilaxia. A sensibilização à insulina pode ser avaliada pelo teste cutâneo de leitura imediata, pesquisa de IgE sérica específica, teste intradérmico e pesquisa de IgG específica. O tratamento envolve o uso deadrenalina, anti-histamínicos e corticosteróides, dependendo do tipo e gravidade da reação. Em alguns casos a dessensibilização deve ser considerada.

Hypersensitivity reactions to the insulin have been decreesing significantly after the introduction of the preparation of human insulin. However, some cases continue being observed in clinical practice. We revised the main aspects related to the physiopathology, clinical manifestations, diagnosis and treatmentof the insulin hypersensitivity reactions. Insulin reactions can be related with any one of the four mechanisms of Gell and Coombs. Clinical manifestations usually appear in the first 4 weeks of treatment and they more frequently include local reactions, but also urticaria, angioedema and anaphylaxis. Insulin sensitization can be evaluated by the prick test, serum specific IgE, intradermal test and serum specific IgG.

Dendritic cell-tumor cell hybrid vaccination for metastatic cancer.

Dendritic cells are the most potent antigen-presenting cells, and the possibility of their use for cancer vaccination has renewed the interest in this therapeutic modality. Nevertheless, the ideal immunization protocol with these cells has not been described yet. In this paper we describe the preliminary results of a protocol using autologous tumor and allogeneic dendritic hybrid cell vaccination every 6 weeks, for metastatic melanoma and renal cell carcinoma (RCC) patients. Thirty-five patients were enrolled between March 2001 and March 2003. Though all patients included presented with large tumor burdens and progressive diseases, 71% of them experienced stability after vaccination, with durations up to 19 months. Among RCC patients 3/22 (14%) presented objective responses. The median time to progression was 4 months for melanoma and 5.7 months for RCC patients; no significant untoward effects were noted. Furthermore, immune function, as evaluated by cutaneous delayed-type hypersensitivity reactions to recall antigens and by peripheral blood proliferative responses to tumor-specific and nonspecific stimuli, presented a clear tendency to recover in vaccinated patients. These data indicate that dendritic cell-tumor cell hybrid vaccination affects the natural history of advanced cancer and provide support for its study in less advanced patients, who should, more likely, benefit even more from this approach.

Antileucotrienos em asmáticos corticodependentes – relato de seis casos / Antileukotriene in steroid dependent asthma – report of six cases

Objetivo: Descrever a experiência com o uso de antileucotrienos em seis pacientes com asma grave corticodependente, acompanhados no Serviço de Alergia e Imunopatologia do Hospital do Servidor Público Estadual de São Paulo. Pacientes e métodos: Por um período de três meses os pacientes maiores de doze anos receberam aleatoriamente zafirlucaste 20mg de 12/12h ou montelucaste 10mg/dia e os menores de 12 anos montelucaste 5mg/dia. Os parâmetros avaliados foram: necessidade do uso diário de corticosteróides sistêmicos (oral), escore clínico de sintomas, prova de função pulmonar realizada antes da introdução da medicação e após três meses de acompanhamento. Resultados: Houve melhora do escore clínico em todos os pacientes (exceto um), melhora da prova de função pulmonar em apenas três dos pacientes, porém todos reduziram de forma significativa o uso diário de corticosteróides sistêmicos. Conclusão: Concluímos que na população avaliada, os pacientes em muito se beneficiaram com o uso de antileucotrienos, sugerindo que esta medicação tenha um papel no tratamento da asma grave corticodependente, para tanto, novos estudos serão necessários.