Our patient is a 21-month-old male, born in Texas to consanguineous parents from Afghanistan. He presented as a newborn with petechiae, severe thrombocytopenia, and hepatitis. Family history was notable for two female siblings who had died in infancy and early childhood, one with neonatal thrombocytopenia and hemorrhage, the other with pulmonary hemorrhage and renal failure due to large vessel vasculitis.
Our patient had an extensive workup which ruled out neonatal alloimmune/autoimmune thrombocytopenia, infection, and hemophagocytic lymphohistiocytosis. Bone marrow biopsy was unrevealing. Liver biopsy showed diffuse, spotty hepatocyte necrosis, rare foci of lobular neutrophilic, and periportal lymphocytic infiltration. He met clinical and histologic criteria for autoimmune hepatitis. He was given IVIG and started on dexamethasone. The thrombocytopenia responded partially and the hepatitis worsened.
Whole-exome sequencing identified a homozygous mutation in ACP5 (p.H205Y) which was predicted to be deleterious and was not found in population databases. ACP5 deficiency causes spondyloenchodrodysplasia with immune dysregulation (SPENCD-I), a type 1 interferonopathy. This has been associated with neonatal thrombocytopenia and other autoimmune manifestations.
The serum interferon alpha level and type 1 interferon response signature were found to be elevated. We therefore initiated baricitinib at 1 mg every 12 hours and continued steroids. Thrombocytopenia normalized. The hepatitis responded only partially, and we were unable to wean steroid (Figure 1). Furthermore, the type 1 interferon signature continued to be very elevated.
We then initiated anifrolumab at 5.5 mg/kg/month intravenously and overlapped with baricitinib and systemic steroid. Two months after initiation of anifrolumab, the patient’s interferon signature normalized, liver function normalized, platelet count has remained normal, and we have been able to wean systemic glucocorticoid by over 10-fold. We are in the process of weaning baricitinib. The patient has thus far had no adverse effects from this medication regimen. He is on acyclovir and pentamidine for infectious prophylaxis, along with regular PCR monitoring for EBV, CMV, and BK virus.
There is a paucity of published experience with baricitinib and anifrolumab in this age-range. This case demonstrates the safe and effective use of these medications in this young child with SPENCD-I, a severe type 1 interferonopathy.
