PI3Kδ syndrome (APDS) manifests as immunodeficiency and immunodysregulation, including inflammatory bowel disease (IBD). We report a case of a 12-year-old female with APDS1 (heterozygous PIK3CD p.Glu1021Lys variant), with a familial background—mother with APDS1 diagnosis with adolescent-onset symptoms—and personal history of recurrent respiratory infections, bronchiectasis, failure to thrive, and developmental delay since age three. She exhibits a combined immunodeficiency with a HyperIgM phenotype, chronic EBV/CMV viremia, and autoimmune cytopenias. Persistent lymphoproliferation in cervical, axillary, and abdominal lymph nodes, along with chronic splenomegaly, is present. Intravenous immunoglobulin and cotrimoxazole prophylaxis is required.
At age 10, abdominal CT showed cecal wall thickening and increased size of intra-abdominal lymph nodes, though she remained asymptomatic. Malignancy and infections were ruled out, and sirolimus was initiated. At age 11, she developed chronic bloody diarrhea, intermittent fever, weight loss, elevated liver enzymes, and high inflammatory markers (erythrocyte sedimentation rate 75 mm/h, C-reactive protein 7 mg/L, calprotectin 287 ug). Endoscopy revealed upper gastrointestinal tract with edema, erythema, and mild colitis in the sigmoid and rectum. Biopsies: colitis with minimal chronic features. Meprednisone (1 mg/kg/day) led to clinical improvement, but symptoms recurred during tapering despite therapeutic sirolimus levels. After 6 months, a repeat endoscopy showed moderate colitis and severe rectal ulcerations. Biopsy revealed malakoplakia and marked T cell infiltration (images available). She was considered refractory to corticosteroids and sirolimus. Due to lack of access to leniolisib in Argentina and the complexities surrounding hematopoietic stem cell transplantation in APDS, abatacept was initiated as a targeted therapy for T cell–mediated dysregulation plus a long course of oral ciprofloxacin (1 g/daily). After three monthly IV doses (500 mg), she achieved complete clinical and laboratory remission—including autoimmune cytopenias, transaminitis, and inflammation markers. Treatment continued for six months; follow-up endoscopic results are pending but remain asymptomatic.
Immunodysregulation in APDS is a challenge and tailored therapies like abatacept could be considered as an alternative treatment.
