Acquired Angioedema due to C1-Inhibitor Deficiency: A Challenging Condition.

BACKGROUND: Acquired deficiency of C1 inhibitor (AAE-C1-INH) is a very rare cause of recurrent angioedema, with few cases reported in the literature. We aimed to describe a series of patients with AAE-C1-INH who were diagnosed and received care at angioedema reference centers in Brazil, affiliated to the Brazilian Group of Studies on Hereditary Angioedema. METHODS: Fourteen patients from 8 Brazilian Angioedema Reference Centers, diagnosed with AAE-C1-INH, were included in this study. Clinical data collected included sex, date of birth, date of onset of symptoms, date of diagnosis, plasma levels of antigenic and/or functional C1-INH, levels of C4 and C1q, location and treatment of angioedema attacks, long-term prophylaxis, associated diseases, and definitive treatment. RESULTS: Fourteen patients were identified with AAE-C1-INH. Most patients (10/14; 71.4%) were female. The median age at onset of symptoms was 56.5 years (range, 14-74 years; interquartile range [IQR], 32-64 years), and median age at diagnosis was 58.0 years (range, 20-76 years; IQR, 38-65 years), with a median time until diagnosis of 2 years (range, 0-6 years; IQR, 1-3 years). The most common manifestations were cutaneous (face, eyelids, lips, trunk, hands, feet, and genitals). Most patient had low levels of C4 (13/14; 92.8%) and of antigenic C1-INH (8/14; 57.1%). Four had decreased functional activity of C1-INH (4/7; 57.1%) and C1q levels were low in 5 patients (5/12; 41.6%). Underlying diseases were identified in all 14 patients, with lymphoma of the splenic marginal zone and monoclonal gammopathy of undetermined significance being the most frequent. Nine patients (64.2%) needed long-term prophylactic treatment for recurrent angioedema and 5 patients (46.7%) required treatment for angioedema attacks. Most of them (12/14; 85.7%) had resolution of angioedema. CONCLUSION: Therapy of AAE-C1-INH aims to control symptoms; however, diagnosis and treatment of the underlying disease, when present, should be an important target and may lead to the resolution of angioedema in patients with AAE-C1-INH.

Outcome of SARS-CoV-2 Infection in 121 Patients with Inborn Errors of Immunity: A Cross-Sectional Study.

PURPOSE: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many unresolved questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and identify factors influencing the infection. METHODS: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. RESULTS: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n = 53). The infection was mostly asymptomatic (n = 21) and mild (n = 66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex-related susceptibility, and there was a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. CONCLUSION: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. However, the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19. The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).

Validity, reliability, and interpretability of the Brazilian urticaria control test.

Background: The urticaria control test (UCT) is a patient-reported outcome measure designed to determine the current level of disease control in patients with chronic urticaria (CU). Recently, a Brazilian UCT was developed, but its validity and reliability are unknown. Method: The clinimetric properties of the Brazilian UCT short form (UCTsh) and its long form (UCTlg) were determined in 130 patients with CU. In parallel, the urticaria activity scores (UAS) that covers 7 days (UAS7) and 28 days (UAS28) were used to assess disease activity. Subsequently, the results were analyzed statistically to determine the validity, reliability, and interpretability of the Brazilian UCT versions. Results: A total of 107 female (82%) and 23 male patients with CU completed both versions of the Brazilian UCT. Both of the Brazilian UCT versions showed excellent internal consistency reliability. In addition, the Brazilian UCT results showed strong correlations with UAS7 and UAS28 results, which indicated high levels of convergent validity. The test-retest reliability was examined in a subsample of 27 patients with CU and was found to be excellent. Notably, the results of both Brazilian UCT versions correlated extensively, which suggested that the UCTsh can replace the UCTlg without changing the UCT results. Conclusion: The Brazilian UCT is a valid and reliable tool for assessing disease control. To facilitate the use of the Brazilian UCT in global studies and to put a stronger focus on the specificity, we propose that the same cutoff values for well-controlled disease should be used as identified in the original publication of the UCT, i.e., ≥12 points for the UCTsh.

Omalizumab in Chronic Spontaneous Urticaria: A Brazilian Real-Life Experience.

BACKGROUND: Current guidelines on chronic spontaneous urticaria (CSU) suggest a treatment based on a 3-step approach that aims at total symptom control, starting with H1-antihistamines. However, a significant number of patients present an antihistamine-resistant urticaria that must be treated with an alternative third-line therapy such as omalizumab. METHODS: Patients with a history of CSU who did not respond to treatment with high doses of modern antihistamines were treated with 150 or 300 mg of omalizumab every 4 weeks. The response to treatment was recorded as complete (CR), partial (PR) or no response. A dose adjustment was proposed according to response. RESULTS: We treated 47 CSU patients with omalizumab (40 females), of whom 39.5% had evidence of autoimmunity. The average number of treatments was 11.4 (range 2-87). All patients had been refractory to high-dose modern antihistamines. A CR was seen in 84.6% of patients who started with 300 mg and in 60% of those who started with 150 mg. Only 1 patient had no response to both the 150- and 300-mg doses. In 6 of the PR patients with 150 mg, a higher dose of 300 mg was proposed and 4 had a CR. Four patients discontinued the treatment. No severe adverse events were reported in the patients who finished the study. DISCUSSION: Although good results were seen in both groups, CR rates were higher in those under a high-dose initial treatment. Our data strongly suggest that the therapy should be individualized.

Prevalence and severity of asthma and related symptoms in 6- to 7-year-old schoolchildren of Rio de Janeiro using of the ISAAC questionnaire by telephone survey.

OBJECTIVE: To evaluate the prevalence and severity of asthma and its association with sex in 6- to 7-year-old schoolchildren from the city of Rio de Janeiro (RJ), obtained by a telephone survey. METHODS: A cross-sectional study using the International Study of Asthma and Allergies in Childhood (ISAAC) Written Questionnaire for Asthma adapted and validated by telephone interviews was conducted. The random sample was recruited systematically, without replacement, taking into account the proportion of school classes and students in each regional coordination of the Municipal Secretariat of Education, which supplied the students' telephone numbers. The data were collected by a polling company from May to July 2010. Prevalence ratios (PRs) and 95% confidence intervals (95% CI) were compared using the difference in proportions test suitable for large samples to analyze the association between asthma and sex. RESULTS: In total, 3216 interviews from parents/caregivers of children were analyzed; 51.4% of the children were males. Mothers were the primary respondents (71.9%). The prevalence rates of "wheezing ever" and "wheezing in the last 12 months" were 52.2% and 20.9%, respectively, and were significantly higher among boys (PR: 1.10, 95% CI: 1.03-1.18 and PR: 1.27, 95% CI: 1.10-1.45). The same pattern was observed for "asthma ever" (PR: 1.44, 95% CI: 1.12-1.85) and for "severe asthma" (PR: 1.42, 95% CI: 1.11-1.82). CONCLUSION: The prevalence of asthma was high among RJ's students. Most of the indicators of the disease were more prevalent among boys. Our results were similar to those observed in other Brazilian and international centers using the traditional ISAAC protocol. The use of this method can be an alternative for epidemiological studies of childhood asthma especially in areas where the telephone coverage is high.

A real-world study of hereditary angioedema patients due to C1 inhibitor deficiency treated with danazol in the Brazilian Public Health System.

Introduction: Hereditary angioedema (HAE) due to C1 inhibitor (C1-INH) deficiency is an ultra-rare autosomal dominant inherited disease that affects 1 in 67,000 people in the world. The attacks are based on subcutaneous and submucosal edema that can lead to death if not properly managed. Considering the lack of information on the clinical management of Brazilian patients with HAE, this study aimed to identify and characterize patients with HAE-C1-INH that used danazol prophylactic treatment in the Brazilian Public Health System (SUS) and the healthcare resource utilization (HCRU). Methods: This was an observational retrospective database study with patients treated with danazol from January 2011 until December 2021 within the SUS. The HAE cohort included patients with 12 years or older with at least one record for ICD-10 D84.1, one claim for danazol record, and at least 6 months of available history in the database. Results: Our study included 799 patients treated in the SUS, with a mean (SD) age at danazol initiation of 40 years (16). The number of patients with HAE showed a similar distribution over this 10-year period analyzed with the highest number of patients in 2015 (n = 509) and 2016 (n = 480). A total of 253 (32%) patients had a record of at least one attack. Of those, 45 (17.8%) had at least one procedure HAE-related hospital admission, and 128 (50.6%) had at least one HAE-related hospital admission. The mean (SD) hospitalization length of stay was 5 (8) days. Over 14% (n = 36) of HAE patients with attack (n = 253) had at least one HAE-related ICU admission. Conclusion: This database study is the strategy used to allow us to find and describe the characteristics of patients with HAE who use danazol for long-term prophylaxis in the SUS and identify HCRU outcomes of interest such as hospitalizations, inpatient, and outpatient settings. The high rate of attacks, hospitalizations, and general resource uses highlights the necessity to increase awareness of new strategies and accurate approaches to treat HAE patients. Therefore, our findings are important indicators that our health system and guidelines need to be revised and improved to properly diagnose, treat, and assist patients with HAE.

Epidemiological characterization of rare diseases in Brazil: A retrospective study of the Brazilian Rare Diseases Network.

BACKGROUND: The Brazilian Policy for Comprehensive Care for People with Rare Diseases was implemented in 2014; however, national epidemiological data on rare diseases (RDs) are scarce and mainly focused on specific disorders. To address this gap, University Hospitals, Reference Services for Neonatal Screening, and Reference Services for Rare Diseases, all of which are public health institutions, established the Brazilian Rare Diseases Network (RARAS) in 2020. The objective of this study was to perform a comprehensive nationwide epidemiological investigation of individuals with RDs in Brazil. This retrospective survey collected data from patients receiving care in 34 healthcare facilities affiliated with RARAS in 2018 and 2019. RESULTS: The survey included 12,530 participants with a median age of 15.0 years, with women representing 50.5% of the cohort. Classification according to skin color demonstrated that 5044 (47.4%) participants were admixed. Most had a confirmed diagnosis (63.2%), with a predominance of phenylketonuria (PKU), cystic fibrosis (CF), and acromegaly. Common clinical manifestations included global developmental delay and seizures. The average duration of the diagnostic odyssey was 5.4 years (± 7.9 years). Among the confirmed diagnoses, 52.2% were etiological (biochemical: 42.5%; molecular: 30.9%), while 47.8% were clinical. Prenatal diagnoses accounted for 1.2%. Familial recurrence and consanguinity rates were 21.6% and 6.4%, respectively. Mainstay treatments included drug therapy (55.0%) and rehabilitation (15.6%). The Public Health System funded most diagnoses (84.2%) and treatments (86.7%). Hospitalizations were reported in 44.5% of cases, and the mortality rate was 1.5%, primarily due to motor neuron disease and CF. CONCLUSION: This study marks a pioneering national-level data collection effort for rare diseases in Brazil, offering novel insights to advance the understanding, management, and resource allocation for RDs. It unveils an average diagnostic odyssey of 5.4 years and a higher prevalence of PKU and CF, possibly associated with the specialized services network, which included newborn screening services.

Are pediatricians familiar with hereditary angioedema?

Background: Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of subcutaneous or mucosal edema caused by excess bradykinin. The aim of the present study was to assess the knowledge of pediatricians about hereditary angioedema. Methods: An online survey with 12 HAE-related and 14 demographics-related questions was e-mailed to all pediatricians who were members of the Brazilian Society of Pediatrics (n = 17 145) once a week during the months of June and July 2021. The electronic questionnaire assessed clinical manifestations, diagnosis, and treatment of hereditary angioedema in children and adolescents. Results: Four hundred and fifty-five pediatricians responded to the questionnaire (2.6%), of whom 55 (12.1%) were board certified in Allergy and Immunology (A/I), while 400 (87.9%) were not (N-A/I). Three hundred and sixty-eight (80.9%) were female, 289 (55.7%) were under 50 years of age, 286 (62.9%) graduated from Medical School more than 10 years previously, 83 (18.2%) held an MSc/PhD degree, and 253 (55.6%) were living in the Southeast Region of Brazil. The median number of correct answers to the questions related to HAE among A/I was 7 out of 12 (58.3%), with median ranging from 4.5 to 8 correct answers, while for N-A/I it was 3 (25%), with median ranging from 2.5 to 4 correct answers (p < 0.001). Conclusion: Knowledge about HAE among Brazilian pediatricians, whether board certified in Allergy and Immunology or not, was unsatisfactory. HAE is a rare disease, largely unknown among physicians; therefore, increasing awareness may lead to improvement in diagnosis and treatment.

Validity and reproducibility of the asthma core International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire obtained by telephone survey.

OBJECTIVE: To assess the reproducibility and validity of the International Study of Asthma and Allergies in Childhood (ISAAC) asthma written questionnaire (IAWQ) for 6- to 7-year-old children administered to their parents/caregivers through a telephone interview. METHODS: Our study included 100 children selected from three health units in Rio de Janeiro, Brazil. In total, 50 asthmatic and 50 non-asthmatic children were evaluated; all participants were required to own a household telephone line. Initially, telephone interviews were conducted with the parents/caregivers using the IAWQ. After 2 weeks, parents/caregivers were invited to complete the IAWQ under supervision provided by the researchers. After fifteen days, the telephone interviews were repeated. The reproducibility between the two telephone interviews was assessed using kappa (κ) coefficients; the construct validity was assessed by comparing the answers obtained in the initial telephone interview in both groups according to the clinical diagnosis of asthma performed by a specialist using sensitivity and specificity coefficients. RESULTS: Overall, data from 75 children (39 asthmatics) were analyzed, as 25 patients were excluded from the study (11 did not answer phone calls and the responding parents/caregivers for 14 patients were not the same in all study phases). Perfect agreement was observed for the indicator "wheezing in the last 12 months" (κ = 1), while substantial agreement was observed for the "wheezing with exercise," "speech limited by wheezing," and "asthma ever" indicators (κ range, 0.7-0.8). The sensitivity and specificity for "wheezing within the last 12 months" were 64.1% (95% confidence interval (CI), 47.2-78.8) and 88.9% (95% CI, 73.9-96.9), respectively. For the "asthma ever" indicator, the sensitivity and specificity were 87.2% (95% CI, 77.6-95.7) and 100% (95% CI, 90.3-1), respectively. Questionnaire specificity was high for all asthma severity indicators. CONCLUSIONS: The IAWQ for children aged 6-7 years adapted for telephone interviews showed good reproducibility and adequate validity with an ability to distinguish between asthmatic and non-asthmatic participants. Thus, this method could be utilized in epidemiological studies on childhood asthma in locations where telephone lines are available.

Validation and reproducibility of the International Study of Asthma and Allergies in Childhood (ISAAC) Written Atopic Eczema Questionnaire for telephone survey in children aged 6-7 years.

BACKGROUND: The prevalence of atopic eczema is unknown in many countries. The International Study of Asthma and Allergies in Childhood (ISAAC) is an epidemiological landmark in the study of allergic diseases. OBJECTIVE: To validate and assess the reproducibility of the ISAAC Written Atopic Eczema Questionnaire (WAEQ) for children aged between 6 and 7 years by telephone contact. METHODS: Observational study through interviews with guardians of children aged 6 to 7 years using the ISAAC atopic eczema module questionnaire in three different phases separated by 2 weeks: telephone interviews in the first and third contacts and in-person interviews under supervision in the second contact. Reproducibility was estimated using the Kappa index and validation using the sensitivity and specificity coefficients. RESULTS: Data from 88 children (32 from the atopic eczema group) were analyzed. Reproducibility showed almost perfect agreement for the questions "Recurrent pruritic lesions" and "Lesions in typical locations" (Kappa between 0.81-0.82), while a substantial agreement was observed for all other indicators (Kappa variation between 0.66 and 0.78). The validation showed high specificity (≥ 80.4%) and sensitivity (≥ 87.5%) for all questions, except those related to chronicity and medical diagnosis (34.4% and 40.6%, respectively). STUDY LIMITATIONS: Non-random selection, no sample size calculation, participants from a tertiary hospital and study period coincident with the Coronavirus pandemic. CONCLUSIONS: Our results showed that the ISAAC atopic eczema module questionnaire by telephone interviews has good reproducibility and high agreement with the clinical diagnosis of atopic eczema. It may be an appropriate alternative tool in epidemiological studies of childhood atopic eczema, especially in periods of social isolation.

Hereditary angioedema: a disease seldom diagnosed by pediatricians.

OBJECTIVES: To describe the hereditary angioedema to improve awareness of this condition and reduce diagnostic delay. DATA SOURCES: Relevant articles in the MEDLINE database through PubMed. DATA SYNTHESIS: Hereditary angioedema is rare and has an autosomal dominant pattern of inheritance. Its onset occurs mainly in childhood, but there is an important delay in the diagnosis. In the most frequent phenotype, there is a quantitative and/or functional deficiency in the C1esterase inhibitor protein, which regulates the activation of the complement, contact and fibrinolysis systems with greater formation of bradykinin, the main mediator of angioedema. There is a third type, the hereditary angioedema with a normal C1 inhibitor level, which is rare in children. Clinical manifestations are characterized by recurrent angioedema attacks, mainly in the extremities, abdomen and upper airways, which can progress to asphyxia and death. The main triggers are mechanical trauma, infections and stress. The diagnosis is attained by patient clinical picture and decreased serum levels of C4 and C1esterase inhibitor or its function. In hereditary angioedema with a normal C1 inhibitor, there is no change in these parameters, thus requiring a genetic study. Treatment is based on the use of attack medications and long and short-term prophylaxis. CONCLUSIONS: Hereditary angioedema is little known by pediatricians due to the significant delay in diagnosis of this condition, whose onset usually begins in childhood. The presence of recurrent angioedema that does not respond to treatment with antihistamines, corticosteroids and adrenaline should increase the diagnostic suspicion.

Hereditary angioedema: how to approach it at the emergency department?

Angioedema attacks are common causes of emergency care, and due to the potential for severity, it is important that professionals who work in these services know their causes and management. The mechanisms involved in angioedema without urticaria may be histamine- or bradykinin-mediated. The most common causes of histamine-mediated angioedema are foods, medications, insect sting and idiopathic. When the mediator is bradykinin, the triggers are angiotensin-converting enzyme inhibitors and factors related to acquired angioedema with deficiency of C1-inhibitor or hereditary angioedema, which are less common, but very important because of the possibility of fatal outcome. Hereditary angioedema is a rare disease characterized by attacks of edema that affect the subcutaneous tissue and mucous membranes of various organs, manifesting mainly by angioedema and abdominal pain. This type of angioedema does not respond to the usual treatment with epinephrine, antihistamines and corticosteroids. Thus, if not identified and treated appropriately, these patients have an estimated risk of mortality from laryngeal edema of 25% to 40%. Hereditary angioedema treatment has changed dramatically in recent years with the development of new and efficient drugs for attack management: plasma-derived C1 inhibitor, recombinant human C1-inhibitor, bradykinin B2 receptor antagonist (icatibant), and the kallikrein inhibitor (ecallantide). In Brazil, plasma-derived C1 inhibitor and icatibant have already been approved for use. Proper management of these patients in the emergency department avoids unnecessary surgery and, especially, fatal outcomes.

Hereditary angioedema: Report of the dental treatment of 12 Brazilian patients.

OBJECTIVE: The aim of this study was to report on clinical experience in Brazil in the dental treatment and the oral conditions of a group of patients with hereditary angioedema (HAE). STUDY DESIGN: The study analyzed demographic data, type of HAE, intensity of attacks, long-term and short-term prophylaxis, dental procedures, and occurrence of crises after the procedures were performed. Radiographic evaluation of the number of teeth and bone loss was also performed. RESULTS: Data from 12 patients were collected; most were women, presenting with C1-INH-HAE type I and a history of severe attacks. All patients reported use of regular medications (long-term prophylaxis), mostly attenuated androgens, to prevent/attenuate HAE attacks. These patients had several missing teeth and alveolar bone loss. Tooth extraction was the most common procedure. In half the patients, the procedures had been performed without modification in long-term prophylaxis. The others were treated with an additional prophylaxis protocol (short-term prophylaxis), particularly those who underwent tooth extraction. None of the study patients developed HAE attacks after dental procedures. CONCLUSION: The occurrence and intensity of a possible HAE attack after dental procedures are unpredictable, but with careful preliminary screening by dental and immunology teams and the use of therapeutic prophylaxis, the risk could be minimized.

Síndrome da urticária de contato ­ uma revisão / Contact urticaria syndrome - a review

A síndrome da urticária de contato (SUC), a urticária de contato (UCO) e a dermatite de contato por proteínas (DCP) são entidades descritas sob o rótulo de reações cutâneas imediatas por contato. Geralmente as urticas surgem 20-30 minutos após a exposição por contato com uma substância, e desaparecem por completo em algumas horas, sem deixar lesão residual.Entretanto, a SUC pode apresentar sintomas generalizados graves. Estima-se uma prevalência, entre trabalhadores europeus, entre 5-10%, enquanto na população geral estima-se de que seja de 1-3%. Os mecanismos envolvidos na patogênese da SUC não foram totalmente elucidados. Uma abordagem inicial, para melhorar a sua compreensão, pode ser dividir esta condição em urticária não imunológica (UCNI) e imunológica (UCI). A primeira não necessita de sensibilização prévia ao alérgeno, enquanto a segunda necessita. O diagnóstico da SUC necessita de uma anamnese detalhada e exame físico seguido de teste cutâneo com as substâncias suspeitas. O afastamento do agente desencadeante é o melhor tratamento. Para isso é necessário o diagnóstico apropriado e precoce, a confecção de relatórios ocupacionais e o desenvolvimento de medidas preventivas.

Contact urticaria syndrome (CUS), contact urticaria, and protein contact dermatitis (PCD) are entities described under the umbrella term of immediate contact skin reactions (ICSR). Generally, hives appear 20-30 minutes after contact with the offending substance, and disappear completely in a few hours, without leaving residual lesions. However, the CUS may be associated with severe systemic symptoms. A prevalence of 5-10% has been estimated among European workers; in the general population it is 1-3%. The mechanisms involved in CUS pathogenesis have not been fully elucidated. An initial approach to improving its understanding involves dividing this condition into non-immune and immune contact urticaria. The former does not require prior sensitization to the allergen, while the latter does. Diagnosis of CUS is established by a detailed history and physical examination, followed by skin tests with suspected substances. Removal of the triggering agent is the best treatment. This requires early proper diagnosis, occupational reporting, and development of preventive measures.

Angioedema hereditário com deficiência do Inibidor de C1 ­ Armadilhas no diagnóstico, tratamento e compreensão / Hereditary angioedema with C1 inhibitor deficiency: traps in the diagnosis, treatment, and understanding

Angioedema hereditário (AEH) é uma condição rara, subdiagnosticada e de elevada morbimortalidade, devido ao caráter de suas manifestações clínicas. O AEH se diferencia do angioedema histaminérgico por não responder aos anti-histamínicos, corticosteroides ou epinefrina. Por esse motivo, é extremamente importante o diagnóstico dessa situação, a fim de instituir a terapia adequada. Tal afecção deve ser suspeitada a partir da história clínica de episódios imprevisíveis e recorrentes de edema que quando se manifesta sob a forma de edema laríngeo, pode levar a óbito por asfixia, se não for adequadamente tratado. Relatamos o caso de uma paciente de 18 anos que, apesar de previamente diagnosticada com AEH tipo 1, ao procurar um serviço de emergência devido a crise de angioedema, não dispunha de medicação específica nem apresentou plano de ação com as opções possíveis para crises. Este caso reforça a necessidade de maior divulgação da doença, além da conscientização de pacientes e familiares sobre a doença e eventuais crises, assim como o acesso as medicações.

Hereditary angioedema (HAE) is a rare, underdiagnosed condition with high morbidity and mortality due to the characteristics of its clinical presentation. HAE differs from histaminergic angioedema by not responding to antihistamines, corticosteroids, or epinephrine. Therefore, early diagnose is crucial to initiate adequate therapy. HAE is suspected in patients with a clinical history of unpredictable and recurrent episodes of edema. When laryngeal edema occurs, it can lead to death from asphyxiation if not treated properly. We report the case of an 18-year-old patient previously diagnosed with HAE type 1 who sought emergency care during an angioedema attack. However, the patient was not taking any specific medication and did not have an action plan to manage attacks. This case highlights the importance of increasing awareness about the disease, educating patients and their families about the disease and potential attacks, and ensuring access to medications.

Biomarcadores na urticária crônica: qual o seu papel? / Biomarkers of chronic urticaria: what are their role?

A urticária é uma doença com comprometimento universal, e debilitante para a maioria dos pacientes. Caracteriza-se pela ocorrência de episódios de urticas, angioedema ou ambos, determinados pela ativação de mastócitos e outras células inflamatórias com a liberação de vários mediadores. Apresenta etiologia complexa com fenótipos e terapias bem específicas. A urticária crônica possui evolução recorrente e imprevisível, podendo estender-se por anos. Caracteristicamente possui maior prevalência no sexo feminino, com pico de ocorrência entre 20 e 40 anos. A doença pode ser diferenciada pela gravidade, impacto na qualidade de vida do paciente e resposta terapêutica. Biomarcador é uma característica clínica ou laboratorial mensurável de algum estado ou condição biológica, o qual pode influenciar ou prever a incidência de desfecho ou doença. O objetivo deste artigo é realizar uma revisão dos principais biomarcadores promissores e com melhor evidência relacionados à duração, atividade da doença e resposta terapêutica.

Urticaria is a disease of global importance that can be debilitating for most patients. It is characterized by episodes of wheals, angioedema, or both, determined by the activation of mast cells and other inflammatory cells with the release of several mediators. The etiology is complex, involving specific phenotypes and therapies. Chronic urticaria has a recurrent and unpredictable course that can last for years. The prevalence is typically higher in females, with a peak incidence between 20 and 40 years of age. The disease can be classified by severity, impact on quality of life, and therapeutic response. A biomarker is a measurable clinical or laboratory characteristic of a biological state or condition that can influence or predict the incidence of outcome or disease. This study provides a review of the main biomarkers considered promising and with the best evidence related to duration, disease activity, and therapeutic response.

Coexistência de doenças autoimunes: oportunidade para a associação de imunobiológicos? / Coexisting autoimmune diseases: an opportunity to associate immunobiologicals?

O tratamento das doenças autoimunes com imunobiológicos é uma opção segura na prática clínica. A simultaneidade na ocorrência de doenças imunomediadas em um mesmo indivíduo pode determinar a necessidade da associação dos imunobiológicos para controle dos sintomas e melhora da qualidade de vida dos doentes. Relatamos o caso de uma paciente com artrite reumatoide em uso de etanercepte, que necessitou da associação de omalizumabe para o tratamento de urticária crônica espontânea.

Autoimmune diseases can be safely treated in clinical practice with immunobiologicals. The simultaneous occurrence of multiple immune-mediated diseases in the same individual could require a combination of immunobiologicals to control symptoms and improve quality of life. We report the case of a patient with rheumatoid arthritis who was receiving etanercept and required additional omalizumab for chronic spontaneous urticaria.

O omalizumabe no tratamento da urticária no contexto da pandemia de COVID-19 / Omalizumab as urticaria treatment in the context of the COVID-19 pandemic

O início da pandemia de COVID-19 foi marcado por incertezas diante do desconhecimento sobre a doença. Uma série de dúvidas relacionadas ao uso de imunobiológicos no contexto da pandemia foi levantada, inclusive em relação ao tratamento com omalizumabe em pacientes com urticária crônica (UC). Este estudo teve como objetivo analisar os dados relacionados à gravidade da COVID-19 e a evolução da urticária em pacientes em terapia com omalizumabe acompanhados por especialistas no Brasil. Foi realizada análise retrospectiva de dados de pacientes com UC tratados com omalizumabe entre julho/2020 e junho/2021 que apresentaram COVID-19. Foram avaliados dados relacionados às características clínicas dos pacientes e evolução da urticária durante a infecção pelo SARS-CoV2. Foram incluídos 28 pacientes em tratamento com omalizumabe, sendo 27 com urticária crônica espontânea (UCE), dos quais 25% tinham alguma urticária induzida associada. A maior parte dos pacientes (71%) estavam utilizando doses quadruplicadas de anti-histamínicos modernos de 2ª geração associados ao omalizumabe. Todos os pacientes estavam com os sintomas controlados. Entre os sintomas apresentados durante a COVID-19, os mais frequentes foram: febre (43%), cefaleia (36%), mal-estar (32%), hipo/anosmia (29%) e tosse (21%). Quatro pacientes foram hospitalizados, um deles em unidade de terapia intensiva. Um paciente relatou piora dos sintomas da UC durante a COVID-19. Cinco (18%) pacientes apresentaram piora dos sintomas da UC após a resolução da COVID-19. Todos os pacientes se recuperaram da COVID-19 sem sequelas graves. O OMA não pareceu aumentar o risco de COVID-19 grave e poderia ser usado com segurança em pacientes com UC.

The beginning of the COVID-19 pandemic was marked by uncertainty due to lack of knowledge about the disease. Questions were raised about the use of immunobiologicals in the pandemic context, including omalizumab for patients with chronic urticaria (UC). This study assessed COVID-19 severity and the clinical course of urticaria in Brazilian patients on omalizumab therapy who were monitored by specialists. We retrospectively analyzed data from chronic urticaria patients treated with omalizumab between July, 2020 and June, 2021 who presented with COVID- 19. Clinical characteristics and the course of urticaria during SARS-CoV2 infection were analyzed. The sample consisted of 28 patients treated with omalizumab, 27 of whom had chronic spontaneous urticaria (UCE) and 25% of whom had associated chronic inducible urticaria. Most of the patients (71%) were using quadruple doses of second-generation antihistamines associated with omalizumab. The symptoms of all patients were controlled. The most frequent symptoms during COVID-19 were: fever (43%), headache (36%), malaise (32%), hypo/anosmia (29%) and cough (21%). Four patients were hospitalized, including 1 in intensive care. One patient reported worsening chronic urticaria symptoms while infected with COVID-19. Five (18%) patients experienced worsening chronic urticaria symptoms after recovery from COVID-19. All patients recovered from COVID-19 without serious sequelae. Omalizumab did not appear to increase the risk of severe COVID-19 and can be safely used in patients with chronic urticaria.

Vacinação e exercício: imunologia em ação em tempos de pandemia / Vaccination and exercise: immunology in action in pandemic times

A COVID-19 é a enfermidade causada pelo SARS-CoV-2, descrita em 2019, em Wuhan. Desde então, causou a morte de milhões de pessoas. A doença caracteriza-se entre sintomas gripais e gastrointestinais, podendo evoluir com gravidade. A importância de compreender como melhorar a eficácia da vacinação levou à investigação de fatores que podem influenciar a resposta imune. A prática de exercícios foi identificada como um fator que pode melhorar a função imunológica e, portanto, ser um potencial adjuvante para respostas imunes. O treinamento crônico, ou altos níveis de atividade física durante um período prolongado (mês/ anos) e, separadamente, o exercício agudo ­ a realização de uma única sessão de exercício (minutos/horas), são dois segmentos relacionados à resposta imunológica ao exercício físico. O exercício agudo é conhecido por gerar efeitos de curto prazo sobre o sistema imune, mas parecem existir efeitos contrastantes entre sessões de exercícios moderados e exercícios prolongados. Na ausência de uma medicação profilática ou tratamento efetivo, a existência de vacinas e associação com a prática de exercícios, particularmente em populações em risco de disfunção imunológica, como idosos, deve ser estimulada. Assim, nesta revisão os autores buscam dissertar e hipotetizar sobre os efeitos do exercício nas respostas à vacinação. Enfim, a prática de exercícios se apresenta como adjuvante dos efeitos imunológicos sobre a vacinação, todavia, com o andamento da vacinação global para SARS-CoV-2, serão necessários estudos com acompanhamento regular para que possamos avaliar a correlação entre a atividade física e a resposta imunológica a estes imunizantes.

COVID-19 is a disease caused by SARS-CoV-2, which was first described in Wuhan in 2019. Since then, it has caused the death of millions of people. COVID-19 is characterized by flulike and gastrointestinal symptoms and may become severe. The importance of understanding how to improve vaccination effectiveness has led to the investigation of factors that may influence immune response. Exercise has been associated with improved immune function and, therefore, may be a potential adjuvant to vaccine-induced immune responses. Chronic training (high levels of physical activity over a prolonged period [months/ years]) or acute exercise alone (engaging in a single exercise session [minutes/hours)] are two segments related to the immune response to physical exercise. Acute exercise is known to have short-term effects on the immune system, but there seems to be contrasting effects between moderate exercise sessions and prolonged exercise. In the absence of prophylactic medication or effective treatment, vaccination plus exercise, particularly in populations at risk for immune dysfunction such as older adults, should be encouraged. Thus, in this review, we aimed to discuss and hypothesize the effects of exercise on vaccination responses. Exercise is presented as an adjuvant to improve the immunological effects of vaccination; however, as the COVID-19 vaccination advances worldwide, studies with regular monitoring will be necessary to evaluate the correlation between physical activity and the immune response to these vaccines.