From the Guidelines
Systemic therapy for Rosai-Dorfman disease (RDD) should be individualized, with corticosteroids such as prednisone being the first-line treatment, and consideration of immunomodulatory agents, cytotoxic chemotherapy, or targeted therapies like sirolimus or MEK inhibitors for steroid-resistant or relapsing cases. The choice of therapy depends on the disease extent, organ involvement, and patient comorbidities, as RDD can range from self-limiting to chronically progressive disease requiring long-term management 1.
First-Line Treatment
Corticosteroids, such as prednisone at 1 mg/kg/day for several weeks with a slow taper based on clinical response, are often used as the first-line systemic therapy for RDD 1. This approach is supported by several case reports and case series showing responses in orbital, CNS, and bone RDD and AHA-associated disease 1.
Second-Line Treatment
For steroid-resistant or relapsing cases, immunomodulatory agents like methotrexate (10-25 mg weekly), azathioprine (1-3 mg/kg/day), or mycophenolate mofetil (1-2 g/day) may be used 1. More aggressive cases might require cytotoxic chemotherapy with regimens such as vinblastine, cyclophosphamide, or cladribine 1.
Targeted Therapies
Recently, targeted therapies have shown promise, including sirolimus (rapamycin) at 2-5 mg daily with dose adjustments to maintain trough levels of 5-15 ng/mL, and MEK inhibitors like cobimetinib for MAPK pathway-activated cases 1. Anti-CD20 monoclonal antibodies like rituximab (375 mg/m² weekly for 4 weeks) have been used in some cases 1.
Treatment Duration and Monitoring
Treatment duration varies based on clinical response, typically continuing for 6-12 months or longer with regular monitoring of disease activity 1. The management algorithm for patients with RDD should consider recurrence after interruption of steroids or when steroids are contraindicated, and nucleoside analogs like cladribine and clofarabine may be considered in severe or refractory cases 1.
Some key points to consider in the management of RDD include:
- Observation may be considered for uncomplicated adenopathy or asymptomatic cutaneous RDD 1.
- Surgical resection may be considered for unifocal extranodal disease or symptomatic cranial, spinal, sinus, or airway disease 1.
- Radiotherapy may be considered for refractory or symptomatic disease not amenable to resection, recurrent after resection, or with a contraindication to systemic therapy 1.
From the Research
Systemic Therapy Options for Rosai-Dorfman Disease
The following systemic therapy options have been utilized in the treatment of Rosai-Dorfman disease:
- Corticosteroids: led to a response in 56% of cases 2
- Cladribine: overall response rate of 67% 2
- Methotrexate: used alone or in combination with other agents, led to partial or complete resolution of disease in over half of the cases 3
- Pegylated interferon: stabilized systemic and ocular disease in a patient with multi-organ involvement 4
- Chemotherapy: role continues to be based on small case series and case reports 5
- Radiation therapy: used in cases of steroid-resistant disease, with reported complete remission in a patient with laryngeal Rosai-Dorfman disease 6
Treatment Approaches
Treatment approaches for Rosai-Dorfman disease may involve:
- Surgical excision: commonly utilized as a first-line treatment 2
- Systemic therapies: used in cases of symptomatic disease, extranodal involvement, or vital organ compression 5
- Multi-disciplinary approach: essential for managing the unique diagnostic and management challenges of Rosai-Dorfman disease 4