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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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Hereditary angioedema (HAE) is an autosomal dominant disease mostly due to the deficiency of C1 inhibitor (C1-INH). HAE with normal C1-INH was first described in 2000 and associated with mutations in the coagulation factor XII in 2006. Both diseases are associated with high bradykinin production, resulting in increased vascular permeability. Gastrointestinal edema due to HAE can be misdiagnosed as acute abdomen and unnecessary surgical procedures may be performed. The present study evaluates the prevalence of surgical procedures and/or acute abdomen in HAE patients with the coagulation factor XII mutation. It is a retrospective study where patients were diagnosed with recurrent angioedema without urticaria, normal C1-INH levels, and positive family history of angioedema. All patients were evaluated for the known mutations located at exon 9 of the F12 gene. Medical records were evaluated and questionnaires were applied to 52 patients with normal C1-INH levels (age range 13–76 years; 47/52, 90.38% women; 5/52, 9.61% men). F12 mutation was present in 32/52 patients (61.5%). Acute abdominal pain was diagnosed in 16/52 (30.76%) patients, appendicitis in 9/16 (56.2%), and undetermined diagnosis in 7/16 (43.7%). Among patients diagnosed with acute abdominal pain, 13/16 (81.2%) underwent surgery and 3/16 (18.7%) improved without surgical intervention. We conclude that many HAE patients with coagulation factor XII mutation were misdiagnosed with acute abdomen and subjected to unnecessary invasive procedures. It is critical to disseminate information about this rare mutation in patients with otherwise normal C1-INH activity, in order to speed up diagnosis and avoid misconduct. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary angioedema (HAE) with C1 inhibitor (C1-INH) deficiency is a rare autosomal dominant disease. Although the first symptoms can appear in childhood, the diagnosis's delay has a strong impact on the patient's quality of life. We analyzed clinical and laboratory characteristics and the drug therapy of pediatric patients with HAE in Brazil. Methods: Medical records from 18 reference centers of HAE patients under 18 years of age were evaluated after confirmed diagnosis was performed by quantitative and/or functional C1-INH. Results: A total of 95 participants (51 M:44 F; mean age: 7 years old) out of 17 centers were included; 15 asymptomatic cases were identified through family history and genetic screening. Angioedema attacks affected the extremities (73.5%), gastrointestinal tract (57%), face (50%), lips (42.5%), eyelids (23.7%), genitals (23.7%), upper airways (10%), and tongue (6.3%). Family history was present in 84% of patients, and the mean delay in the diagnosis was 3.9 years. Long-term prophylaxis (51/80) was performed with tranexamic acid (39/80) and androgens (13/80); and short-term prophylaxis (9/80) was performed with tranexamic acid (6/80) and danazol (3/80). On-demand therapy (35/80) was prescribed: icatibant in 7/35, fresh frozen plasma in 16/35, C1-INH plasma-derived in 11/35, and tranexamic acid in 12/35 patients. Conclusions: This is the first study on HAE pediatric patients in Latin America. Clinical manifestations were similar to adults. Drugs such as androgens and tranexamic acid were indicated off-label, probably due to restricted access to specific drugs. Educational programs should address pediatricians to reduce late diagnosis and tailored child therapy. [ABSTRACT FROM AUTHOR]