Sirolimus—A targeted therapy for Rosai‐Dorfman disease

Abstract

To the Editor: Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare histiocytic disorder characterized by a benign proliferation of S100-positive histiocytic cells within the sinus of the lymph nodes and the lymphatic vessels of internal organs.1 Though considered a self-limiting condition with spontaneous regression of disease seen in up to 50% of cases,2 massive lymphadenopathy, rapid progression, and extranodal involvement do warrant treatment with drugs, such as corticosteroids, vinca alkaloids, anthracycline, and antimetabolites.3 Sirolimus was first reported to be used in RDD by Cooper et al, wherein a 20-month-old child diagnosed with RDD continued to have multiple autoimmune manifestations that were refractory to other drugs. They achieved complete resolution of autoimmunity within 1 month of treatment and the patient remained in remission 23 months after stopping sirolimus.4 Sirolimus inhibits the possible dysregulation of the PI(3)K/Akt/mTOR pathway, which is important for the normal development of histiocytic precursors, leading to significant reduction in these cells, as has been shown in vitro and inmurinemodels.5–8 This is the first case report to demonstrate a response in lymphadenopathy to sirolimus therapy in two patients with RDD. Patient 1, a 12-year-old female, presented to us with fever and massive tender bilateral cervical lymphadenopathy. A diagnosis of RDD was made on lymph node biopsy. Chest and abdomen imaging revealed mediastinal and mesenteric lymphadenopathy. There was no extranodal organ involvement. Epstein Barr virus polymerase chain reaction (EBV PCR) was negative. Anti-nuclear antibody and Coombs test were negative. Double-negative T cells were normal, which ruled out autoimmune lymphoproliferative disease (ALPS). She had elevated immunoglobulin G levels. She received oral steroids for 1 year at various dosing regimens but showed poor response