Gabriel Natalia, Marcelino Fernanda, Ferriani Mariana P L, Arruda L Karla, Campos Regis A, Gonçalves Rozana F, Chong-Neto Herberto, Rosario Filho Nelson, Valle Solange O R, Pesquero Joao B, Grumach Anete S
Clinical Immunology, Faculdade de Medicina, Centro Universitario FMABC, Santo André, Brazil.
Hospital Regional da Asa Norte (HRAN), Brasília, Brazil.
Front Allergy. 2022 Feb 17;3:846968. doi: 10.3389/falgy.2022.846968. eCollection 2022.
HAE with normal C1 inhibitor (HAE-nC1-INH) has been identified as a bradykinin mediated angioedema. Estrogens are one of the main trigger factors. Pregnancy in HAE with C1 inhibitor deficiency showed variable course, however, few reports are available for HAE-nC1-INH. We evaluated the course of pregnancies in women diagnosed with HAE-nC1-INH.
Women with diagnosis of HAE-nC1-INH according to the following criteria: clinical manifestations similar to HAE-C1-INH, normal biochemical evaluation and family history were included. A questionnaire about pregnancies was applied after consent. Genetic evaluation for known mutations was performed in all patients.
A total of 45 pregnancies occurring in 26 HAE-nC1-INH patients were evaluated (7/26 patients with variant). Spontaneous abortion was reported in 8/45 (17.8%) pregnancies. Onset of attacks started before the pregnancy in 18/26 patients; during the pregnancy in 2/26; and after the pregnancy in 6/26. HAE attacks occurred in 24/37 pregnancies (64,7%): during the 1st trimester in 41.7%; 2nd trimester in 12.5%; 3rd trimester in 20.8%; 1st and 3rd trimesters in 4.2% and during the whole pregnancy in 20.8%. Among 15/18 patients who had attacks before pregnancy, symptoms persisted with worsening in 9/15; improvement in 4/15; no change in 1/15, and no response in 1/15.
The occurrence of abortion in HAE-nC1-INH was similar to the expected for not affected women. The 1st trimester of the pregnancy was more symptomatic for HAE-nC1-INH women. Considering the strong relevance of estrogens in HAE-nC1-INH, pregnancy could worsen the course of disease.
C1抑制剂正常的遗传性血管性水肿（HAE-nC1-INH）已被确定为一种缓激肽介导的血管性水肿。雌激素是主要触发因素之一。C1抑制剂缺乏的HAE患者怀孕时病情变化不一，然而，关于HAE-nC1-INH的报道较少。我们评估了诊断为HAE-nC1-INH的女性的妊娠过程。
纳入符合以下标准诊断为HAE-nC1-INH的女性：临床表现与HAE-C1-INH相似、生化评估正常且有家族史。征得同意后应用关于妊娠的问卷。对所有患者进行已知突变的基因评估。
共评估了26例HAE-nC1-INH患者的45次妊娠（7/26例患者有变异）。8/45次（17.8%）妊娠报告有自然流产。18/26例患者在妊娠前发作开始；2/26例在妊娠期间；6/26例在妊娠后。24/37次妊娠（64.7%）发生HAE发作：妊娠早期占41.7%；妊娠中期占12.5%；妊娠晚期占20.8%；妊娠早期和晚期占4.2%，整个妊娠期间占20.8%。在妊娠前发作的15/18例患者中，9/15例症状持续且加重；4/15例改善；1/15例无变化，1/15例无反应。
HAE-nC1-INH患者自然流产的发生率与未受影响女性的预期相似。妊娠早期对于HAE-nC1-INH女性症状更明显。考虑到雌激素在HAE-nC1-INH中的密切相关性，怀孕可能会使病情恶化。
