Insights From the First 820 Patients From the Brazilian Multicenter Registry of Hereditary Angioedema: The Key Role of Genetic Testing and Targeted Therapies

Mariana P L Ferriani¹, José Eduardo Seneda Lemos¹, L Karla Arruda², Fernanda L Nunes¹, Marina M Dias¹, Maitê L Kolarik³, Persio Roxo-Junior⁴, Maria Fernanda Ferraro¹, Maria Eduarda T Zanetti¹, Faradiba S Serpa⁵, Herberto J Chong-Neto⁶, Fernanda G Minafra⁷, Solange O R Valle⁸, Régis A Campos⁹, Jane da Silva¹⁰, Eli Mansour¹¹, Rozana F Gonçalves¹², Eliana C Toledo¹³, Fernanda C Marcelino¹⁴, Iramirton F Moreira¹⁵, Adriana Azoubel-Antunes¹⁶, Janaira F S Ferreira¹⁷, Gabriela A C Dias¹⁸, Marcelo V Aun¹⁹, Ana Paula B M Castro²⁰, Maria L Oliva-Alonso⁸, Vanessa A Batigalia¹³, Clarissa L T S V Tavares²¹, Albertina V Capelo²², Therezinha R Moyses⁵, Nelson A Rosário Filho⁶, Lucca N P Jannuzzi²³, Nyla T M L Fragnan²³, Joanemile P Figueiredo⁹, Joice T Fonseca⁹, Ana Julia R Teixeira²⁴, Nayara M F Nasser²⁰, Natasha R Ferraroni²⁵, Leonardo O Mendonça²⁶, Márcia T Iwashita²⁶, Alex I F Prado²⁷, Melissa T Tumelero²⁸, Julianne A Machado²⁹, Tsukiyo O Kamoi³⁰, Luciana M Ferrel³¹, Adriana M S C Barbosa³², Caroline G F B de Moraes⁶, Tatielly Kruk⁶, Mariana R Figueiredo³³, Maria Stela Y Moraes³³, Adriana S Moreno¹, Luana S M Maia³⁴, Fabiola Traina³, Patricia C Ruy³, João B Pesquero³⁵, Konrad Bork³⁶, Sven Cichon³⁷, Davi C Aragon⁴, Pedro Giavina-Bianchi²⁴, Anete S Grumach²³

Affiliations

¹ Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
² Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: karla@fmrp.usp.br.
³ Department of Medical Images, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
⁴ Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
⁵ Division of Allergy and Immunology, Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória, Vitória, ES, Brazil.
⁶ Division of Allergy and Immunology, Federal University of Paraná, Curitiba, PR, Brazil.
⁷ Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
⁸ Department of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
⁹ Department of Internal Medicine, Federal University of Bahia, Salvador, BA, Brazil.
¹⁰ Allergy Clinics at Polydoro Ernani de São Thiago University Hospital of the Federal University of Santa Catarina (managed by the Brazilian Company of Hospital Services HU-UFSC-EBSERH), Florianópolis, SC, Brazil; Department of Medicine, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
¹¹ Allergy and Immunology, Department of Internal Medicine, School of Medical Sciences, University of Campinas/UNICAMP, Campinas, SP, Brazil.
¹² Division of Allergy, AlergoDiagnóstico Clinics, Belo Horizonte, MG, Brazil.
¹³ Department of Pediatrics and Pediatric Surgery, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil.
¹⁴ Department of Allergy and Immunology, Hospital Regional de Asa Norte, Brasília, DF, Brazil.
¹⁵ Department of Allergy and Immunology, Federal University of Alagoas, Maceió, AL, Brazil.
¹⁶ Department of Allergy and Immunology, Federal University of Pernambuco, Recife, PE, Brazil.
¹⁷ Department of Pediatric Allergy and Immunology, Hospital Albert Sabin, Fortaleza, CE, Brazil.
¹⁸ Division of Allergy and Immunology, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil.
¹⁹ Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, SP, Brazil; Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
²⁰ Pediatric Allergy and Immunology Division, Instituto da Criança e Adolescente, University of São Paulo School of Medicine, São Paulo, SP, Brazil.
²¹ Division of Allergy, Othorrinos E Alergistas Associados Clinic, Maceió, AL, Brazil.
²² Department of Allergy and Immunology, Gaffrée and Guinle Hospital of Federal University of the State of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
²³ Department of Clinical Immunology, Centro Universitario Faculdade de Medicina do ABC, Santo André, SP, Brazil.
²⁴ Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, SP, Brazil.
²⁵ Division of Allergy, Instituto Ferraroni, Brasília, DF, Brazil.
²⁶ Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, SP, Brazil; Division of Rare and Immunological Disorders, Rede Américas, Hospital 9 de Julho, São Paulo, SP, Brazil; Division of Clinical Immunology and Allergy, Faculdade de Medicina, Universidade de Santo Amaro, São Paulo, SP, Brazil.
²⁷ Division of Allergy, Clínica Croce, São Paulo, SP, Brazil.
²⁸ Division of Infectious Diseases and Immunology, University of Passo Fundo, Passo Fundo, RS, Brazil.
²⁹ Clinical Immunology, Federal University of Sergipe, Aracajú, SE, Brazil.
³⁰ Division of Allergy, Clínica Kamoi Milani, Curitiba, PR, Brazil.
³¹ Division of Allergy, Policlínica Tucumã-Sesacre, Rio Branco, AC, Brazil.
³² Division of Allergy and Immunology, Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil; Division of Allergy, Instituto de Alergia e Imunologia, Campo Grande, MS, Brazil.
³³ Department of Medicine, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
³⁴ Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil; Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
³⁵ Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Federal University of São Paulo, São Paulo, SP, Brazil.
³⁶ Department of Dermatology, Johannes Gutenberg University, Mainz, Germany.
³⁷ Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.

PMID: 40912615
DOI: 10.1016/j.jaip.2025.08.026

Free article

Multicenter Study

Insights From the First 820 Patients From the Brazilian Multicenter Registry of Hereditary Angioedema: The Key Role of Genetic Testing and Targeted Therapies

Mariana P L Ferriani et al. J Allergy Clin Immunol Pract. 2025 Nov.

Free article

. 2025 Nov;13(11):3104-3117.

doi: 10.1016/j.jaip.2025.08.026. Epub 2025 Sep 3.

Authors

Affiliations

¹ Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
² Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: karla@fmrp.usp.br.
³ Department of Medical Images, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
⁴ Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
⁵ Division of Allergy and Immunology, Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória, Vitória, ES, Brazil.
⁶ Division of Allergy and Immunology, Federal University of Paraná, Curitiba, PR, Brazil.
⁷ Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
⁸ Department of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
⁹ Department of Internal Medicine, Federal University of Bahia, Salvador, BA, Brazil.
¹⁰ Allergy Clinics at Polydoro Ernani de São Thiago University Hospital of the Federal University of Santa Catarina (managed by the Brazilian Company of Hospital Services HU-UFSC-EBSERH), Florianópolis, SC, Brazil; Department of Medicine, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
¹¹ Allergy and Immunology, Department of Internal Medicine, School of Medical Sciences, University of Campinas/UNICAMP, Campinas, SP, Brazil.
¹² Division of Allergy, AlergoDiagnóstico Clinics, Belo Horizonte, MG, Brazil.
¹³ Department of Pediatrics and Pediatric Surgery, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil.
¹⁴ Department of Allergy and Immunology, Hospital Regional de Asa Norte, Brasília, DF, Brazil.
¹⁵ Department of Allergy and Immunology, Federal University of Alagoas, Maceió, AL, Brazil.
¹⁶ Department of Allergy and Immunology, Federal University of Pernambuco, Recife, PE, Brazil.
¹⁷ Department of Pediatric Allergy and Immunology, Hospital Albert Sabin, Fortaleza, CE, Brazil.
¹⁸ Division of Allergy and Immunology, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil.
¹⁹ Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, SP, Brazil; Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
²⁰ Pediatric Allergy and Immunology Division, Instituto da Criança e Adolescente, University of São Paulo School of Medicine, São Paulo, SP, Brazil.
²¹ Division of Allergy, Othorrinos E Alergistas Associados Clinic, Maceió, AL, Brazil.
²² Department of Allergy and Immunology, Gaffrée and Guinle Hospital of Federal University of the State of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
²³ Department of Clinical Immunology, Centro Universitario Faculdade de Medicina do ABC, Santo André, SP, Brazil.
²⁴ Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, SP, Brazil.
²⁵ Division of Allergy, Instituto Ferraroni, Brasília, DF, Brazil.
²⁶ Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, SP, Brazil; Division of Rare and Immunological Disorders, Rede Américas, Hospital 9 de Julho, São Paulo, SP, Brazil; Division of Clinical Immunology and Allergy, Faculdade de Medicina, Universidade de Santo Amaro, São Paulo, SP, Brazil.
²⁷ Division of Allergy, Clínica Croce, São Paulo, SP, Brazil.
²⁸ Division of Infectious Diseases and Immunology, University of Passo Fundo, Passo Fundo, RS, Brazil.
²⁹ Clinical Immunology, Federal University of Sergipe, Aracajú, SE, Brazil.
³⁰ Division of Allergy, Clínica Kamoi Milani, Curitiba, PR, Brazil.
³¹ Division of Allergy, Policlínica Tucumã-Sesacre, Rio Branco, AC, Brazil.
³² Division of Allergy and Immunology, Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil; Division of Allergy, Instituto de Alergia e Imunologia, Campo Grande, MS, Brazil.
³³ Department of Medicine, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
³⁴ Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil; Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
³⁵ Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Federal University of São Paulo, São Paulo, SP, Brazil.
³⁶ Department of Dermatology, Johannes Gutenberg University, Mainz, Germany.
³⁷ Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.

PMID: 40912615
DOI: 10.1016/j.jaip.2025.08.026

Abstract

Background: Hereditary angioedema (HAE) is a rare autosomal dominant disorder with a prevalence of 1:50,000 individuals. Delayed diagnosis and deaths from asphyxia still occur.

Objective: To identify knowledge and management gaps regarding clinical, genetic, and therapeutic aspects of HAE in Brazil, aiming to improve patient care and outcomes.

Methods: A Brazilian multicenter HAE registry was established, with patients' data included by treating physicians using the REDCap (Research Electronic Data Capture) platform.

Results: Of the 820 patients with HAE enrolled, 68.8% were female. Most (72.4%) experienced HAE due to C1 inhibitor deficiency (HAE-C1INH), whereas 19.4% had HAE with normal C1INH caused by variants in the F12 gene (HAE-FXII). Onset of symptoms occurred earlier in HAE-C1INH as compared with HAE-FXII (mean 11.2 years vs 19.4 years, respectively), and time for diagnosis was shorter in patients younger than 18 years, as compared with those 18 years and older (mean 1.8 years vs 14.5 years, respectively). Regarding treatment, 52.8% received first-line on-demand therapies (icatibant or plasma-derived C1INH [pdC1INH]). Only 4.8% used first-line options for long-term prophylaxis (LTP), such as lanadelumab or subcutaneous/intravenous pdC1INH. Attenuated androgens were used for LTP in 52% of patients, with adverse effects reported for 34.8%.

Conclusions: Brazilian patients with HAE share common aspects with global patients, including predominance in women, and HAE-C1INH as the most common subtype. Available genetic testing allowed for identification of a notable proportion of HAE-FXII (19.4% of the patients). Despite recent advances, access to first-line therapies for LTP of HAE attacks remains limited.

Keywords: C1 inhibitor; Genetic testing; Hereditary angioedema; Hereditary angioedema due to C1 inhibitor deficiency; Hereditary angioedema with normal C1 inhibitor; Registry; Therapy for hereditary angioedema.

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Insights From the First 820 Patients From the Brazilian Multicenter Registry of Hereditary Angioedema: The Key Role of Genetic Testing and Targeted Therapies

Affiliations

Insights From the First 820 Patients From the Brazilian Multicenter Registry of Hereditary Angioedema: The Key Role of Genetic Testing and Targeted Therapies

Authors

Affiliations

Abstract

Publication types

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Substances

LinkOut - more resources

Full Text Sources

Miscellaneous