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

BackgroundItchy 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 descriptionWe 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.