Rare Complications After Treatment of Hyper IgE Syndrome with Allogeneic Hematopoietic Stem Cell Transplantation
Marija Simić, Borko Gobeljić, Milanka Tešić, Gordana Petrović, Stefan Kotlajić, Milan Rodić, Srđan PašićIntroduction
Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by high serum IgE levels combined with atopic dermatitis, staphylococcal skin infections, recurrent sinopulmonary infections, musculoskeletal deformities, and vasculopathy.
Case Report
An 8-year-old girl was diagnosed with hyper-IgE syndrome at the age of 5, based on elevated IgE levels and the presence of atopic dermatitis, recurrent suppurative otitis with cholesteatomas, recurrent pneumonias, craniosynostosis, osteopenia, and dilation of the coronary arteries. Clinical exome sequencing identified a heterozygous pathogenic variant in the STAT3 gene. At the age of 8, she underwent an allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related donor. A myeloablative reduced-toxicity conditioning regimen was used, and cyclosporine was administered as graft-versus-host disease prophylaxis. The source of stem cells was bone marrow. Neutrophil engraftment occurred on day +11, while platelet engraftment was delayed due to multiple complications. In the posttransplant period, she experienced Pseudomonas aeruginosa sepsis, engraftment syndrome, necrotizing pneumonia caused by Legionella pneumoniae with a residual abscess, adenoviral colitis, BK+ hemorrhagic cystitis, and encephalopathy and polyneuropathy most likely resulting from CMV reactivation. Donor lymphocyte infusions (DLI) were administered from day +30 to accelerate immune reconstitution. On day +60, due to a decline of donor chimerism, the CD3+ cell dose was increased. In total, she received eight doses of donor CD3+ T cells. All complications were successfully treated by day +100, except for the residual “cold” lung abscess and partially recovered polyneuropathy. Percutaneous surgical drainage of the abscess was performed, followed by an additional ten-week antibiotics course. Osteoporosis is being treated with vitamin D and pamidronate. Ten months after allogeneic HSCT, the girl has complete donor chimerism, satisfactorily recovered immunity, no recent bacterial infections, and significantly improved polyneuropathy.
Key Messages for Clinical Practice
HSCT represents an acceptable curative option for the treatment of HIES, but further research remains needed to improve our understanding and management of this disease.