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 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.