The Silent Epidemic: A Scoping Review of Chronic Pain Etiology and Management Strategies in Transfusion-Dependent Thalassemia.

Advances in transfusion regimens and iron chelation have transformed transfusion-dependent thalassemia (TDT) into a chronic condition, revealing chronic pain as an important but under-recognized morbidity. Despite its substantial effect on health-related quality of life, pain in TDT remains poorly characterized and is rarely addressed in clinical protocols. We systematically searched PubMed/MEDLINE, EMBASE, Scopus, Google Scholar, and the Cochrane Library from inception to January 2026 for original studies, reviews, and guidelines addressing chronic pain in TDT. Two independent reviewers screened studies, extracted data, and synthesized evidence on prevalence, pathogenesis, and management. Chronic pain affects approximately 32% to 55% of adults with TDT, and more than 90% of affected patients report moderate-to-severe pain. Its pathogenesis is multifactorial, with major contributors including thalassemia-associated osteoporosis, chelation-related arthropathy, extramedullary hematopoiesis, iron-overload-related endocrinopathies, and treatment-associated abdominal pain, particularly with deferasirox. Management remains empirical and fragmented. Bisphosphonates, including zoledronic acid, may improve skeletal pain, whereas NSAID and opioid use is often limited by hepatic and renal comorbidities. A disease-specific approach should combine correction of metabolic abnormalities, targeted anti-resorptive therapy, validated pain assessment, and cautious pharmacological treatment. Chronic pain is a major but neglected component of the contemporary TDT phenotype. Randomized trials and standardized clinical guidelines are needed to support effective pain management and improve quality of life.