Poliarterite nodosa na faixa etária pediátrica: um estudo multicêntrico brasileiro
Data
2024-11-07
Autores
Fernandez, Jade Dib 
Orientadores
Terreri, Maria Teresa
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: A poliarterite nodosa (PAN) é uma doença inflamatória rara, caracterizada por evidência de vasculite necrosante que afeta predominantemente artérias de médio calibre. Pode ser subdividida em PAN cutânea e sistêmica. Devido à raridade da doença, às manifestações diversas e à escassez de estudos, existem muitos desafios para realizar o diagnóstico precoce, bem como acompanhamento e tratamento adequados da PAN, principalmente na pediatria.
Objetivos: Descrever as características clínicas, laboratoriais, histopatológicas e de imagem, bem como o tratamento e prognóstico em uma amostra da população brasileira com PAN pediátrica; avaliar a proporção de pacientes que preenchem os critérios de classificação da PAN pediátrica; estudar os fatores relacionados ao atraso diagnóstico e descrever os achados atípicos da doença.
Métodos: Trata-se de um estudo retrospectivo, multicêntrico, utilizando o registro de pacientes que tiveram o diagnóstico de PAN até os 18 anos de idade, em sete centros acadêmicos e terciários do Brasil, descrevendo características demográficas, clínicas, laboratoriais, de imagem e histopatológicas, tratamento, prognóstico e morbidades relacionadas. Os dados foram coletados em três tempos diferentes de acompanhamento: apresentação da doença, do diagnóstico ao 12° mês após o diagnóstico, e avaliação final, referente aos dados de última consulta.
Resultados: Dos 30 pacientes incluídos inicialmente no estudo, 60% foram classificados como PAN cutânea, 33% como PAN sistêmica e 7% foram classificados como deficiência de adenosina deaminase 2 (após teste confirmatório foram incluídos nos dados demográficos e excluídos das demais análises). Sete pacientes (70%) preencheram critérios de classificação para PAN sistêmica. A média de idade ao diagnóstico foi 9 anos. Em 77% dos pacientes, o diagnóstico ocorreu em até 6 meses do início dos sintomas. Em 23% dos pacientes, o diagnóstico ocorreu após 1 ano de sintomas. O diagnóstico incorreto ocorreu em 33% (10 pacientes) no início dos sintomas, com o diagnóstico inicial incluindo febre reumática (3), artrite idiopática juvenil (1), artrite idiopática juvenil e febre reumática (1), celulite (1), polimiosite (1), lúpus bolhoso (1), síndrome inflamatória multissistêmica pediátrica possivelmente associada à COVID-19 (MIS-C) (1) e doença de Kawasaki (1). Os sintomas mais frequentes foram: febre (89%), livedo reticular (60%), nódulos subcutâneos (57%), púrpura/vasculite (57%), artrite (57%), perda de peso (46%) e fadiga (46%). As manifestações de fadiga, neuropatia periférica sensitiva e miosite foram significantemente mais frequentes nos pacientes com PAN sistêmica do que nos com PAN cutânea. Algumas das manifestações atípicas descritas foram: fotossensibilidade, úlceras genitais, pseudotumor, síndrome de ativação macrofágica e choque cardiogênico. As alterações laboratoriais mais encontradas foram: elevação da proteína C reativa (PCR) (89%) e da velocidade de hemossedimentação (VHS) (71%), anemia (68%), leucocitose (60%) e aumento do anticorpo antiestreptolisina O (ASLO) (36%). As elevações de ASLO e proteinúria no início do quadro foram mais frequentes nos casos de PAN sistêmica. Na apresentação da doença, 89% dos pacientes fizeram uso de corticoide por via oral, 50% de pulsoterapia com corticoide endovenoso, 32% de ciclofosfamida endovenosa durante o tratamento de indução (indicada em 60% dos pacientes com PAN sistêmica e em 17% dos pacientes com PAN cutânea, p = 0,035), 18% de metotrexato e 14% de azatioprina; nenhum paciente recebeu micofenolato e apenas 7% dos pacientes fizeram uso de biológico. A penicilina G benzatina profilática foi usada em 25% dos pacientes e antiagregante plaquetário em 18%. Na evolução, 54% dos pacientes fizeram uso do corticoide por via oral e 25% de antiagregante plaquetário. A profilaxia com penicilina G benzatina foi indicada em 29% dos pacientes. Foram considerados em remissão com medicação dentro do primeiro ano após o diagnóstico 54% dos pacientes e 25% apresentaram recidiva. Na última consulta avaliada, após o primeiro ano do diagnóstico, 35% dos pacientes apresentaram recidiva, ocorreram dois óbitos (7%) e morbidades estavam presentes em 40% dos pacientes.
Conclusão: A PAN é uma doença rara na pediatria e com apresentação clínica variável, o que acarreta atrasos e erros no diagnóstico, com encaminhamento tardio para centros de referência. Algumas manifestações clínicas e alterações laboratoriais foram diferentes entre pacientes com PAN sistêmica e PAN cutânea. Reconhecer a doença é essencial para o tratamento precoce e melhor prognóstico.
Background: Polyarteritis nodosa (PAN) is a rare inflammatory disease characterized by necrotizing vasculitis predominantly in medium-sized arteries. It can be subdivided into cutaneous and systemic PAN. Due to its rarity, diverse manifestations, and lack of clinical studies, there are significant challenges in achieving early diagnosis of PAN and in providing adequate monitoring and treatment, particularly in pediatrics. Objectives: To describe the clinical, laboratory, imaging and histopathological characteristics, as well as the treatment and prognosis of a sample of the Brazilian pediatric population with PAN, to assess the proportion of patients meeting PAN classification criteria, to study the factors related to diagnostic delays, and to describe atypical findings of the disease. Methods: A retrospective, multicentric study was conducted using the registry of patients who were diagnosed with PAN up to 18 years of age, across seven academic tertiary centers in Brazil. The study describes their demographic, clinical, laboratory, imaging, and histopathological characteristics, treatment, prognosis and related morbidities. Data were collected at three different follow-up times: presentation of the disease, diagnosis to the 12th month after diagnosis, and final evaluation, based on the data of the last visit. Results: Of the 30 patients initially included, 60% were classified as cutaneous PAN, 33% as systemic PAN, and 7% as deficiency of adenosine deaminase 2 (after confirmatory testing they were included in the demographic data and excluded from the other analyses). Seven patients (70%) met the classification criteria for systemic PAN. The mean age at diagnosis was 9 years. In 77% of cases, the diagnosis occurred within 6 months of symptom onset, while in 23% the diagnosis was made after 1 year of symptoms. Misdiagnosis at symptom’s onset occurred in 33% (10 patients), with the initial diagnoses including rheumatic fever (3 patients), juvenile idiopathic arthritis (1), both juvenile idiopathic arthritis and rheumatic fever (1), cellulitis (1), polymyositis (1), bullous lupus (1), pediatric multisystem inflammatory syndrome possibly associated with COVID-19 (MIS-C) (1), and Kawasaki disease (1). The most frequent symptoms were fever (89%), livedo reticularis (60%), subcutaneous nodules (57%), purpura/vasculitis (57%), arthritis (57%), weight loss (46%) and fatigue (46%). Fatigue, sensory peripheral neuropathy, and myositis were statistically more frequent in patients with systemic PAN. Some of the atypical manifestations described included: photosensitivity, genital ulcers, pseudotumor, macrophage activation syndrome, and cardiogenic shock. The most common laboratory findings were elevated C- reactive protein (CPR) (89%), erythrocyte sedimentation rate (ESR) (71%), anemia (68%), leukocytosis (60%), and elevated anti-streptolysin O (ASLO, 36%). Elevations in ASLO, and proteinuria at the disease’s onset were more frequent in cases of systemic PAN. At disease presentation, 89% of patients received oral corticosteroids and 50% intravenous corticosteroid pulse therapy, 32% received intravenous cyclophosphamide as induction therapy (indicated in 60% of patients with systemic PAN and in 17% of patients with cutaneous PAN, p=0.035), 18% received methotrexate, and 14% received azathioprine; no patient received mycophenolate and only 7% of patients used biologics. Prophylactic penicillin G benzathine was prescribed in 25% of patients, and antiplatelet medication in 18%. During follow-up, 54% of patients used oral corticosteroids and 25% used antiplatelet agents. Prophylaxis with penicillin G benzathine was indicated in 29% of patients. Within the first year after the diagnosis, 54% of patients were in remission on medication, and 25% experienced relapse. At the last visit, after the one-year mark of the diagnosis, 35% of patients had experienced a relapsed, two deaths occurred (7%), and morbidities were present in 40% of patients. Conclusion: PAN is a rare disease in pediatrics, with variable clinical presentation, leading to diagnostic delays and misdiagnosis, as well as delayed referrals to specialized centers in Brazil. Some clinical manifestations and laboratory findings differed between systemic and cutaneous PAN patients. Recognizing the disease is essential for early treatment and to improve prognosis.
Background: Polyarteritis nodosa (PAN) is a rare inflammatory disease characterized by necrotizing vasculitis predominantly in medium-sized arteries. It can be subdivided into cutaneous and systemic PAN. Due to its rarity, diverse manifestations, and lack of clinical studies, there are significant challenges in achieving early diagnosis of PAN and in providing adequate monitoring and treatment, particularly in pediatrics. Objectives: To describe the clinical, laboratory, imaging and histopathological characteristics, as well as the treatment and prognosis of a sample of the Brazilian pediatric population with PAN, to assess the proportion of patients meeting PAN classification criteria, to study the factors related to diagnostic delays, and to describe atypical findings of the disease. Methods: A retrospective, multicentric study was conducted using the registry of patients who were diagnosed with PAN up to 18 years of age, across seven academic tertiary centers in Brazil. The study describes their demographic, clinical, laboratory, imaging, and histopathological characteristics, treatment, prognosis and related morbidities. Data were collected at three different follow-up times: presentation of the disease, diagnosis to the 12th month after diagnosis, and final evaluation, based on the data of the last visit. Results: Of the 30 patients initially included, 60% were classified as cutaneous PAN, 33% as systemic PAN, and 7% as deficiency of adenosine deaminase 2 (after confirmatory testing they were included in the demographic data and excluded from the other analyses). Seven patients (70%) met the classification criteria for systemic PAN. The mean age at diagnosis was 9 years. In 77% of cases, the diagnosis occurred within 6 months of symptom onset, while in 23% the diagnosis was made after 1 year of symptoms. Misdiagnosis at symptom’s onset occurred in 33% (10 patients), with the initial diagnoses including rheumatic fever (3 patients), juvenile idiopathic arthritis (1), both juvenile idiopathic arthritis and rheumatic fever (1), cellulitis (1), polymyositis (1), bullous lupus (1), pediatric multisystem inflammatory syndrome possibly associated with COVID-19 (MIS-C) (1), and Kawasaki disease (1). The most frequent symptoms were fever (89%), livedo reticularis (60%), subcutaneous nodules (57%), purpura/vasculitis (57%), arthritis (57%), weight loss (46%) and fatigue (46%). Fatigue, sensory peripheral neuropathy, and myositis were statistically more frequent in patients with systemic PAN. Some of the atypical manifestations described included: photosensitivity, genital ulcers, pseudotumor, macrophage activation syndrome, and cardiogenic shock. The most common laboratory findings were elevated C- reactive protein (CPR) (89%), erythrocyte sedimentation rate (ESR) (71%), anemia (68%), leukocytosis (60%), and elevated anti-streptolysin O (ASLO, 36%). Elevations in ASLO, and proteinuria at the disease’s onset were more frequent in cases of systemic PAN. At disease presentation, 89% of patients received oral corticosteroids and 50% intravenous corticosteroid pulse therapy, 32% received intravenous cyclophosphamide as induction therapy (indicated in 60% of patients with systemic PAN and in 17% of patients with cutaneous PAN, p=0.035), 18% received methotrexate, and 14% received azathioprine; no patient received mycophenolate and only 7% of patients used biologics. Prophylactic penicillin G benzathine was prescribed in 25% of patients, and antiplatelet medication in 18%. During follow-up, 54% of patients used oral corticosteroids and 25% used antiplatelet agents. Prophylaxis with penicillin G benzathine was indicated in 29% of patients. Within the first year after the diagnosis, 54% of patients were in remission on medication, and 25% experienced relapse. At the last visit, after the one-year mark of the diagnosis, 35% of patients had experienced a relapsed, two deaths occurred (7%), and morbidities were present in 40% of patients. Conclusion: PAN is a rare disease in pediatrics, with variable clinical presentation, leading to diagnostic delays and misdiagnosis, as well as delayed referrals to specialized centers in Brazil. Some clinical manifestations and laboratory findings differed between systemic and cutaneous PAN patients. Recognizing the disease is essential for early treatment and to improve prognosis.
Descrição
Citação
FERNANDEZ, Jade Dib. Poliarterite nodosa na faixa etária pediátrica: um estudo multicêntrico brasileiro. 2024. 86 f. Dissertação (Mestrado em Pediatria e Ciências Aplicadas à Pediatria) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2024.