Incomplete Kawasaki disease preceding the diagnosis of AICDA deficiency (hyper-IgM syndrome type 2)

Abstract

Abstract Background Activation-induced cytidine deaminase (AICDA) deficiency is a rare autosomal recessive inborn error of immunity caused by biallelic pathogenic variants in AICDA . It is characterised by defective immunoglobulin class-switch recombination, resulting in recurrent bacterial infections and impaired antigen-specific antibody responses. Prominent lymphoid hyperplasia, often manifesting as persistent lymphadenopathy, is a characteristic clinical feature. Although immune dysregulation is increasingly recognised in AICDA deficiency, Kawasaki Disease (KD) has not previously been reported as its presenting manifestation. We describe a child with genetically confirmed AICDA deficiency who experienced an episode clinically consistent with incomplete KD before recognition of her underlying immune disorder. Case presentation A six-year-old girl of Chinese ethnicity first presented at 18 months of age with persistent fever and cervical lymphadenopathy, without other classical mucocutaneous features of KD. Laboratory investigations revealed markedly elevated inflammatory markers, leukocytosis, thrombocytosis, anaemia and hypoalbuminaemia. Echocardiography demonstrated dilatation of the left anterior descending coronary artery and mild pericardial effusion leading to a diagnosis of incomplete KD. She responded well to intravenous immunoglobulin and aspirin, with subsequent normalisation of the coronary artery abnormalities. During the following two years, she developed recurrent respiratory infections, Salmonella gastroenteritis and persistent lymphadenopathy, prompting further immunological evaluation. Immunological evaluation demonstrated elevated IgM with low IgG and IgA levels, impaired vaccine-specific antibody responses, and absent switched memory B cells. Genetic testing identified compound heterozygous pathogenic variants in AICDA , confirming the diagnosis of autosomal recessive AICDA deficiency. The patient responded well to immunoglobulin replacement therapy and antimicrobial prophylaxis. Conclusion This case describes incomplete KD as the initial presenting manifestation of AICDA deficiency. Although a causal relationship cannot be established, this observation raises a possibility that immune dysregulation associated with AICDA deficiency may contribute to susceptibility to hyperinflammatory vasculitis. Importantly, the subsequent combination of recurrent bacterial infections, persistent lymphadenopathy, and hyper-IgM immunoglobulin profile should raise suspicion of AICDA deficiency, allowing timely immunological evaluation, genetic diagnosis, and appropriate long-term management.