Immune reconstitution inflammatory syndrome accompanied by transient immune and chromosomal abnormality after azathioprine exposure in utero

Azathioprine (AZA) is widely used during pregnancy to manage autoimmune diseases; however, concerns regarding fetal immunological vulnerability persist. Although neonatal lymphocytopenia and chromosomal abnormalities have been reported following prenatal AZA exposure, little is known about immune recovery in infants after congenital infections in these infants. Here, we describe an infant with congenital cytomegalovirus (CMV) infection, who was born to a mother treated with azathioprine for systemic lupus erythematosus and developed hemophagocytic lymphohistiocytosis (HLH) during immune reconstitution during lymphocytopenia. The preterm infant presented with lymphocytopenia, anemia, thrombocytopenia, and congenital CMV infection. Despite initiating antiviral therapy, immune reconstitution inflammatory syndrome (IRIS) developed, thus fulfilling the diagnostic criteria for HLH, including increased alanine aminotransferase, ferritin, triglycerides, and soluble interleukin-2 receptor levels. A chromosomal analysis revealed mosaicism with 46,XX and i [18](q10) in the bone marrow cells. In the absence of definitive HLH treatment, such as corticosteroids or other immunosuppressive therapies, fever, splenomegaly, and laboratory abnormalities resolved spontaneously, and the chromosomal alterations normalized. This indicates that prenatal AZA exposure induces transient immunosuppression, leading to the development of IRIS. Our case highlights the necessity of vigilant immunological surveillance in neonates exposed to AZA in utero.