Sirolimus-induced improvement of immune dysregulation associated hepatosplenomegaly in common variable immunodeficiency: a case-based review

Common variable immunodeficiency (CVID) is the most common primary immune defficiency in adults. Patients with CVID present with predominant antibody deficiency and reduced serum levels of immunoglobulin class G, A and/ or M. The disease is frequently complicated by non-infectious organ involvement, including hepatosplenomegaly secondary to immune dysregulation and lymphoproliferation. Sirolimus is a mTORC1 inhibitor, used as immunosuppressant in transplant medicine, increasingly inborn errors of immunity with lymphoproliferation and autoimmunity, including CVID and monogenic CVID-like disorders. Therefore, we describe the case of a 50-year-old patient diagnosed with CVID for 5 years, on regular IVIG (intravenous immunoglobulins) replacement who developed progressive hepatosplenomegaly and cytopenias despite adequate infection preventive healthcare. The patient reported increasing abdominal enlargement, dyspnea, and fatigue. She had also noted excessive daytime and nighttime sweating, initially partly attributed to menopausal status. Physical examination confirmed marked hepatosplenomegaly. Initial evaluation excluded acute infection and overt lymphoma. Abdominal imaging revealed hepatosplenomegaly without focal lesions, raising suspicion of immune-mediated lymphoproliferation related to CVID. Sirolimus was introduced as a steroid-sparing agent for presumed immune dysregulation. During sirolimus treatment, spleen length decreased from 23 cm before initiation to 13 cm after 5 months and 12 cm after 7 months, while liver size fell from 18 cm to 15 cm. Platelet count rose from 37 to 75 × 10³/µL, and aspartate aminotransferase activity declined from 77 to 58 U/L, with alanine aminotransferase dropping from 93 to 47 U/L. Leukopenia, neutropenia, and elevated alkaline phosphatase activity, however, persisted. The patient reported improvement in constitutional and abdominal symptoms,and no serious infectious complications occurred during treatment. This case demonstrates a marked organ response and a partial platelet response to sirolimus in complicated CVID, suggesting that mTOR inhibition may be considered in carefully selected patients with CVID-associated immune dysregulation and lymphoproliferative hepatosplenic involvement, although its efficacy and safety require confirmation in larger studies.