Case Report: Sustained immune and pulmonary recovery three years after hematopoietic stem cell transplantation for ITCH E3 ubiquitin ligase deficiency

Background Itchy E3 ubiquitin ligase deficiency (ITCH deficiency) is a rare monogenic immune dysregulation syndrome characterized by early-onset multisystem autoimmunity and significant morbidity and mortality. Only one prior case report has described a patient treated with hematopoietic stem cell transplantation (HSCT) with clinical improvement, and no established disease-modifying or curative therapy algorithm exists. Case description We describe a female patient who presented in early childhood with chronic lung disease requiring tracheostomy and long-term mechanical ventilation and later developed progressive muscle weakness. She was diagnosed with steroid-responsive juvenile polymyositis and subsequently accumulated multiple autoimmune manifestations including autoimmune hepatitis, enteropathy, psoriasis, inflammatory arthritis, and Sjögren’s-like parotitis. Genetic testing ultimately identified compound heterozygous pathogenic variants in ITCH . Despite prolonged treatment with multiple immunosuppressive and biologic therapies, she remained prednisone dependent with poor disease control and substantial treatment-related morbidity. At 20 years of age, she underwent allogeneic hematopoietic stem cell transplantation. Following transplantation, she achieved sustained resolution of autoimmune disease activity, was successfully weaned from all immunosuppressive therapy, and was decannulated from chronic mechanical ventilation, with marked improvement in functional status and quality of life. Conclusions This is the second reported case demonstrating the benefit of hematopoietic stem cell transplant (HSCT) in ITCH deficiency and provides evidence of durable multisystem clinical remission and recovery of long-standing pulmonary and musculoskeletal disease. These findings support consideration of HSCT as a therapeutic option in carefully selected patients with severe, refractory autoimmune manifestations due to ITCH deficiency and raise the possibility that earlier consideration in the disease course may mitigate cumulative disease- and treatment-related morbidity.