What is the treatment for Rosai-Dorfman syndrome?

Treatment of Rosai-Dorfman Syndrome

Most patients with Rosai-Dorfman disease do not require treatment, as the disease is often self-limited, particularly for nodal and cutaneous forms; however, symptomatic or life-threatening disease should be managed with surgical excision for isolated lesions, corticosteroids for systemic disease, and consideration of targeted therapies for refractory cases. 1

Initial Management Decision

The first critical decision is determining whether treatment is necessary at all:

• Observation alone is appropriate for asymptomatic nodal disease and isolated cutaneous lesions without functional impairment, as spontaneous resolution occurs in many cases 1, 2
• Active intervention is required when disease causes airway obstruction, neurologic compression, end-organ compromise, or significant symptoms 1
• Extranodal disease generally does not respond durably to steroids alone and requires more aggressive management 1

Treatment Algorithm by Disease Severity

For Localized, Symptomatic Disease

Surgical excision is the primary treatment for isolated lesions causing symptoms or organ dysfunction 1, 2:

• Indicated specifically for airway obstruction, neurologic compression from CNS lesions, or large masses causing end-organ compromise 1
• Remains the mainstay for symptomatic disease based on extensive clinical experience 2
• Recurrence after surgery occurs in approximately 30% of initially treated patients 3

For Systemic or Multifocal Disease

Corticosteroids are first-line systemic therapy 1, 3:

• Prednisone or dexamethasone have demonstrated efficacy in orbital involvement, bone lesions, and RDD with autoimmune hemolytic anemia 1
• Response rate is approximately 56% when used as first-line treatment 3
• However, extranodal disease typically does not show durable responses to steroids alone 1

For Refractory or Aggressive Disease

When corticosteroids fail or disease is life-threatening, escalate to:

Radiotherapy for specific indications 1:

• Refractory soft tissue disease
• Orbital disease with visual compromise
• Resistant airway obstruction
• Palliation of local symptoms

Systemic immunomodulatory agents 1, 3:

• Cladribine shows 67% overall response rate and is the most commonly used systemic agent 3
• Thalidomide and lenalidomide have demonstrated efficacy in refractory cases 1
• Rituximab may be effective for refractory disease 1

Targeted therapies for molecularly-defined disease 1:

• MEK inhibitors for patients with MAP2K1 mutations (identified in some cases with Erdheim-Chester overlap) 3
• Imatinib has shown promising results in specific cases 1
• Consider targeted-capture, next-generation sequencing of lesional tissue for mutations in RAF-RAS-MEK-ERK pathway (KRAS, MAP2K1) in severe or refractory cases 4

Anti-TNF-α therapy represents an emerging option 5:

• Methotrexate combined with infliximab successfully treated RDD with cutaneous involvement and arthritis 5
• TNF-α overexpression is implicated in RDD pathogenesis 5

Critical Prognostic Factors

Poor prognosis indicators requiring aggressive management 1:

• Kidney involvement (40% mortality rate) 4
• Liver involvement
• Lower respiratory tract disease
• Overall mortality ranges 7-12% in large series, primarily from direct disease complications, infections, or amyloidosis 1

Favorable prognosis is expected for nodal and cutaneous disease 1

Essential Baseline Evaluation

Before initiating treatment, obtain 4:

• Complete blood count with differential, serum immunoglobulins, inflammatory markers (ESR)
• Complete metabolic panel, coagulation parameters, LDH
• PET/CT for disease staging (or whole-body MRI/ultrasound as alternatives)
• Targeted genetic sequencing for RAF-RAS-MEK-ERK pathway mutations in severe/refractory cases
• Bone marrow biopsy if cytopenias or abnormal peripheral blood smear present

Common Pitfalls

• Delayed diagnosis is common, with median time from symptom onset to diagnosis of 7 months and median of 2 biopsies required 3
• Misdiagnosis occurs frequently, particularly with cutaneous disease mimicking other dermatologic conditions 6
• Undertreatment of extranodal disease with steroids alone leads to poor durable responses 1
• Failure to recognize overlap with Erdheim-Chester disease, which has distinct molecular features and treatment implications 3