Haploinsufficiency of A20 (HA20) is a monogenic autoinflammatory disorder caused by heterozygous loss-of-function variants in TNFAIP3, resulting in dysregulated NF-κB activation. Clinical presentations are heterogeneous and often mimic Behçet disease with mucosal ulceration, fever, and systemic inflammation. Although cutaneous involvement is recognized, deep soft tissue abscesses as an initial manifestation in early infancy are rare. We present a 14-month-old boy whose evaluation for recurrent gluteal abscesses beginning at age 3 months led to the diagnosis of HA20.
A 3-month-old boy was hospitalized for a painful right gluteal abscess. Prior infections included a febrile urinary tract infection and hand-foot-mouth disease. His mother initially noted a diaper rash before a progressive gluteal mass developed. He was treated with an incision and drainage, clindamycin, and amoxicillin-clavulanate with resolution; however, a new gluteal abscess recurred, prompting prescription for antibiotics, but improved with Epsom salt baths. Cultures were negative or yielded only skin commensals. Between episodes, he remained well without oral ulcers, gastrointestinal symptoms, or failure to thrive. Immunologic evaluation showed elevated quantitative immunoglobulins, normal neutrophil oxidative burst, and normal CD18/CD11b expression. Lymphocyte subsets demonstrated a persistently elevated CD8 and decreased CD4 T cell counts with an inverted CD4:CD8 ratio. Given persistent inflammation without a clear infectious etiology, a targeted immunodeficiency panel was obtained and identified a heterozygous, likely pathogenic TNFAIP3 variant (c.152_155delinsACAAA; p.Phe51TyrfsTer50), consistent with HA20.
HA20 has a variable clinical presentation, but recurrent oral ulcers are the most consistent feature, seen in >70% of patients, with a median onset of ∼6 years old. This case expands the phenotypic range, highlighting deep soft tissue abscesses as an early presenting sign, even without mucosal involvement. An inverted CD4:CD8 ratio, as seen in this patient, is frequently reported in HA20. Although our patient has not developed additional inflammatory manifestations, early genetic diagnosis was essential. Further evaluation, including expanded T/B cell phenotyping and inflammatory cytokines, may guide future targeted therapies such as TNF-inhibitors, IL-1 antagonists, and JAK inhibitors.
A20 haploinsufficiency should be considered in infants with recurrent soft tissue abscesses and unexplained inflammation. Early diagnosis facilitates tailored immunomodulatory treatment and may prevent disease progression.
