Successful Treatment of Recurrent Autoimmune Cytopenias in the Context of Sinus Histiocytosis With Massive Lymphadenopathy Using Sirolimus

Abstract

Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease (RDD), is a non-neoplastic, lymphoproliferative disorder that usually resolves spontaneously or with minimal conventional chemotherapy. Rarely, SHML can be associated with autoimmune findings. Such cases are often treatment resistant and have high rates of morbidity and mortality. We present a case of a patient with long-standing autoimmunity in the context of SHML, dependent on standard-treatment until he was transitioned to novel monotherapy with sirolimus. Sirolimus treatment resulted in a complete remission, now sustained after discontinuation of all treatments for over 23 months, with no observable long-term sequelae.

Sirolimus—A targeted therapy for Rosai‐Dorfman disease

“…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 in murine models. [5][6][7][8] This is the first case report to demonstrate a response in lymphadenopathy to sirolimus therapy in two patients with RDD.…”

“…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 . 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 in murine models .…”

Treatment of benign cephalic histiocytosis with topical 1% rapamycin ointment

“…Topical rapamycin has been used to treat a variety of dermatologic conditions, most notably facial angiofibromas in tuberous sclerosis . The oral form of rapamycin has been used to treat the systemic histiocytoses Erdheim‐Chester disease (in combination with prednisone) and Rosai‐Dorfman disease …”

Highlights of the Management of Adult Histiocytic Disorders: Langerhans Cell Histiocytosis, Erdheim-Chester Disease, Rosai-Dorfman Disease, and Hemophagocytic Lymphohistiocytosis

“…Sirolimus at a dose of 2.5 mg/m 2 for 18 months is has been used by some clinicians. 20 Rituximab 375 mg/m 2 once a week × 4 doses is recommended for those with immune-related RDD. Low-dose methotrexate combined with 6-mercaptopurine or single-agent cladribine are recommended for patients with severe RDD.…”