Haploinsufficiency of A20 (HA20) is a rare, complex autosomal-dominant immune dysregulation disorder first described in 2016, caused by loss-of-function variants in TNFAIP3. Autoimmune hepatitis (AIH) is an uncommon manifestation and rarely the index presentation; in our case from Qatar, AIH was the first presentation.
A 26-year-old male with genetically confirmed HA20 (2020), first presented at 9 years of age with AIH complicated by cirrhosis (Child–Pugh A) and portal hypertension. He subsequently developed warm autoimmune hemolytic anemia and autoimmune enteropathy with chronic refractory diarrhea despite multiple antimicrobials, immunomodulators, and prolonged systemic corticosteroids. His course was complicated by recurrent severe infections, including recurrent esophageal candidiasis and recurrent lower respiratory tract infections with bronchiectasis, leading to multiple admissions for sepsis, pneumonia, and hepatic encephalopathy. Primary immunodeficiency (PID) was suspected based on pan-hypogammaglobulinemia. Intravenous immunoglobulin (IVIG) (40 g every 3 weeks) and steroid were initiated. Recently admitted twice with sepsis, pancytopenia (lymphocyte 0.1 × 103/uL, platelet [PLT] 13 × 103/uL), severe colitis, and marked weight loss (30 kg). Given advanced liver disease, vedolizumab was started for immune-mediated colitis without adequate response; total parenteral nutrition was added. Baricitinib was introduced cautiously after completing essential vaccinations (including recombinant zoster vaccine). After one week, preliminary laboratory results (though still early) suggested improvement in hematologic parameters (lymphocyte 0.7 × 103/uL, PLT 28 × 103/uL).
Childhood-onset AIH can be the initial manifestation of HA20 evolving into severe multisystem autoimmunity with immunodeficiency. Early recognition of monogenic immune dysregulation is essential. Targeting interferon signaling via the JAK–STAT pathway was suggested in HA20, and baricitinib may confer greater benefit when introduced earlier.
