What are the characteristics and management of Rett syndrome (RS) with a 3q25-26 deletion (rs3Pe)?

Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) Syndrome: Characteristics and Management

RS3PE syndrome is a distinct rheumatic inflammatory condition characterized by symmetrical polysynovitis of acute onset with pitting edema, predominantly affecting elderly individuals, with excellent response to low-dose glucocorticoids and complete remission without residual damage in most cases. 1

Clinical Characteristics

Demographics and Presentation

• Predominantly affects Caucasians over 60 years of age
• Male predominance (approximately 2:1 male-to-female ratio) 2, 3
• Acute onset of symptoms

Key Clinical Features

• Symmetrical polysynovitis (bilateral joint inflammation)
• Distinctive pitting edema of the dorsum of hands (hallmark feature)
• Negative rheumatoid factor (seronegative) 1, 2
• Joint involvement pattern:
  • Metacarpophalangeal joints (81.5%)
  • Proximal interphalangeal joints (70.4%)
  • Wrists (55.5%)
  • Shoulders (48%)
  • Knees (33.3%)
  • Ankles (25.9%) 3

Associated Features

• Carpal tunnel syndrome (reported in approximately one-third of cases) 2
• Low-titer antinuclear antibodies may be present in some patients (uncommon)
• Generally absence of erosive changes on radiographs

Differential Diagnosis

• Polymyalgia rheumatica
• Late-onset rheumatoid arthritis
• Crystal arthropathies (gout, pseudogout)
• Paraneoplastic syndromes (important to consider)
• Edema due to cardiac, renal, or hepatic causes

Diagnostic Approach

1. Clinical assessment focusing on:

   • Pattern of joint involvement
   • Presence of pitting edema
   • Age of onset
   • Acute nature of presentation

2. Laboratory investigations:

   • Rheumatoid factor (negative in RS3PE)
   • Inflammatory markers (ESR, CRP) - typically elevated
   • Antinuclear antibodies (usually negative or low-titer)
   • Basic metabolic panel to rule out other causes of edema

3. Imaging:

   • Radiographs to confirm absence of erosive changes
   • Ultrasound may show tenosynovitis and joint effusions

Management

Pharmacological Treatment

• Glucocorticoids are the mainstay of treatment:
  • Prednisone 15-20 mg/day (median 18.2 mg/day) 4
  • Treatment duration typically 3-6 months (median 5.3 months) 4
  • Gradual tapering based on clinical response

Monitoring

• Regular assessment of clinical response
• Monitoring for glucocorticoid side effects
• Vigilance for development of malignancies (rare association)

Prognosis

• Excellent prognosis with complete remission in most cases
• Low relapse rate (some patients may experience relapse but typically respond well to reinstitution of treatment) 2
• No residual joint damage in the majority of cases

Special Considerations

• Although initially described as a distinct entity, some cases may represent the initial presentation of other rheumatic conditions or paraneoplastic syndromes
• Rare associations with hematological malignancies have been reported, including T-cell lymphoma and myelodysplastic syndrome 3
• In atypical presentations (unilateral involvement, poor response to treatment), consider alternative diagnoses or underlying conditions

Clinical Pearls

• The dramatic response to low-dose glucocorticoids is a characteristic feature
• The presence of pitting edema with inflammatory arthritis in an elderly patient should prompt consideration of this diagnosis
• Despite the benign course, appropriate evaluation to rule out underlying malignancy may be warranted, especially in atypical presentations