BACKGROUND
McCarty and colleagues first described RS3PE syndrome with 10 cases characterized by symmetrical synovitis in peripheral joints and pitting edema on the dorsum of the hands, primarily affecting the elderly.1 Ages of the eight male and two female patients ranged from 59 to 82 years. Seven of the 10 patients could pinpoint the onset of disease to the hour. The patients showed little or no benefit from NSAIDs, and radiographic examination revealed no erosions of the affected joints.
Four additional cases with features similar to those of McCarty's original 10 cases were described by Chaouat and Le Parc.4 All four patients experienced disease onset at an advanced age, and all exhibited symmetrical polysynovitis with distal pitting edema that resolved in 6 to 18 months. Three of the four patients required hospitalization because of their initial disability. As with McCarty's original 10 patients, RF was absent. Chaouat and Le Parc's patients went into remission without use of disease-modifying antirheumatic drugs (DMARDs).
In a subsequent study, Russell, Hunter, Pearson, and McCarty reviewed an additional 13 cases of RS3PE that confirmed the original findings.5 Ages of the patients (eight men and five women) ranged from 45 to 81 years with a mean of 68 years. All patients had asymptomatic residual flexion contractures of the fingers and wrists and negative results for RF on latex fixation testing. No erosions were observed on radiographic examination of the affected joints. Use of low-dose corticosteroids resulted in dramatic clinical improvement, and all patients went on to complete remission without relapse.
DISCUSSION
The term synovitis (rather than arthritis) is used in RS3PE because patients present with symmetrical polysynovitis of the joints and fl exor digitorum sheaths associated with pitting edema of the dorsum of the hands and feet.1 Although the etiology of pitting edema is unknown, Olivieri and colleagues note that on MRI, marked extensor tenosynovitis appears to be primarily responsible for the edema affecting the subcutaneous and peritendinous soft tissue.6
The presentation of arthritis and edema of the hands and feet is unusual but will often lead the clinician to consider a number of commonly known differentials. Patients often report shoulder-girdle pain as well.7 When the symptoms are considered together, the clinician will most likely place LORA and PMR high on the list of differentials.
Based on a multicenter study, a team led by Olivé proposed the following diagnostic criteria for RS3PE: patient age older than 50 years; pitting edema of both hands; polyarthritis with sudden onset; absence of RF; and lack of radiographic evidence of joint destruction.8
In a comparison of rheumatoid arthritis (RA) and RS3PE syndrome, RS3PE is distinguished by its remitting nature, absence of joint destruction, and negative serology. In the rare case of RA with pitting edema, the edema often occurs unilaterally and in conjunction with seropositivity to RF. Patients with LORA (development of RA after age 60 years) often have large-joint involvement and an elevated ESR.9 Other distinguishing features of RS3PE include a higher incidence in males than females, persistent seronegativity, and predictable remission.5 While differentiation can be difficult, dramatic response to low-dose corticosteroids and long-term remission after withdrawal will allow for definitive diagnosis of RS3PE.
RS3PE can also be easily confused with PMR. In a retrospective study of 245 cases of PMR, Salvarani, Gabriel, and Hunder reported the prevalence of swelling with pitting edema in the distal extremities to be 8%.10 Both PMR and RS3PE are seronegative, seen at an advanced age, and respond dramatically to low-dose corticosteroids. In addition, both diseases may manifest with sudden onset of symptoms and an elevated ESR, but PMR is often seen in females whereas RS3PE is more frequently seen in males. The major distinguishing feature is symmetrical pitting edema.5 Although differentiation from PMR is difficult, both RS3PE and PMR must be included in the differential diagnosis in an elderly patient who develops an acute inflammatory syndrome, morning stiffness, shoulder-girdle pain, and hand edema.
Serum antibodies can also be a distinguishing feature in RA, RS3PE, and PMR. Results of serology are positive for RF in 80% of all RA cases but negative for RF in RS3PE and PMR. Additionally, human leukocyte antigen (HLA) typing is different in all three diseases. In RA, the HLA type is DR1.4, while in RS3PE, it is B7, and in PMR it is DR3.4.5 Table 1 shows a comparison of RS3PE with RA and PMR.
Some patients with features of RS3PE also have a paraneoplastic disorder associated with solid tumors and hematologic disorders. Researchers have found a higher prevalence of cancer in patients with RS3PE than in patients matched by age and sex living in the same geographic area.2 While cases of gastric carcinoma have been identified in patients with RS3PE, other paraneoplastic disorders associated with RS3PE include endometrial carcinoma and pancreatic carcinoma.11-13 In other cases, as with the patient described, RS3PE has been associated with several hematologic malignancies, including chronic lymphoid leukemia; non-Hodgkin lymphoma; acute lymphocytic leukemia; and precancerous disorders, such as myelodysplastic syndromes.13-15 An appropriate diagnostic workup is required to rule out a paraneoplastic disorder when the diagnosis of RS3PE is being considered.
CONCLUSION
The prompt recognition of RS3PE is important because of its impact on treatment options. No DMARDs are required for RS3PE; instead, RS3PE is very responsive to low-dose corticosteroids. Distinguishing RS3PE from PMR in older patients is important in view of the duration of corticosteroid treatment required. Finally, the diagnosis of RS3PE in an older patient should heighten the suspicion of an underlying malignant disease and mandates a thorough evaluation to rule out this possibility.16 JAAPA
Linda Sekhon is Assistant Professor, Department of Physician Assistant Studies, Duquesne University, Pittsburgh, Pennsylvania. The author has indicated no relationships to disclose relating to the content of this article.
REFERENCES
1. McCarty DJ, O'Duffy JD, Pearson L, Hunter JB. Remitting seronegative symmetrical synovitis with pitting edema: RS3PE syndrome. JAMA. 1985;254(19):2763-2767.
2. Bucaloiu I, Olenginski T, Harrington TM. Remitting seronegative symmetrical synovitis with pitting edema syndrome in a rural tertiary care practice: a retrospective analysis. Mayo Clinic Proc. 2007;82(12):1510-1515.
3. Kundu AK. Syndrome of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE). J Assoc Physicians India. 2007;55:227-230.
4. Chaouat D, Le Parc JM. The syndrome of seronegative symmetrical synovitis with pitting edema (RS3PE sydrome): a unique form of arthritis in the elderly? Report of 4 additional cases. J Rheumatol. 1989;16(9):1211-1213.
5. Russell EB, Hunter JB, Pearson L, McCarty DJ. Remitting, seronegative, symmetrical synovitis with pitting edema—13 additional cases. J Rheumatol. 1990;17(5):633-639.
6. Olivieri I, Salvarani C, Cantini F. Remitting distal extremity swelling with pitting edema: a distinct syndrome or a clinical feature of different infl ammatory rheumatic diseases? J Rheumatol. 1997;24(2):249-252.
7. Dudler J, Gerster JC, So A. Polyarthritis and pitting oedema. Ann Rheum Dis. 1998;58(3):142-147.
8. Olivé A, del Blanco J, Pons M, et al. The clinical spectrum of remitting seronegative symmetrical synovitis with pitting edema. The Catalán Group for the Study of RS3PE. J Rheumatol. 1997;24(2):333-336.
9. Schnell A. The clinical features of rheumatic infection on the old. Acta Med Scand. 1941;106(4):345-351.
10. Salvarani C, Gabriel S, Hunder GG. Distal extremity swelling with pitting edema in polymyalgia rheumatica: report on nineteen cases. Arthritis Rheum. 1996;39(1):73-80.
11. Tada Y, Sato H, Yoshizawa S, et al. Remitting seronegative symmetrical synovitis with pitting edema associated with gastric carcinoma. J Rheumatol. 1997;24(5):974-975.
12. Olivo D, Mattace R. Concurrence of benign edematous polysynovitis in the elderly (RS3PE syndrome) and endometrial adenocarcinoma. Scand J Rheumatol. 1997;26(1):67-68.
13. Cantini F, Olivieri I, Salvarani C. More on remitting seronegative symmetrical synovitis with pitting edema as paraneoplastic syndrome. J Rheumatol. 1998;25(1):188-189.
14. Cobeta-Garcia JC, Domingo-Morera JA, Martinez-Burgui J. RS3PE syndrome and chronic lymphoid leukaemia. Clin Exp Rheumatol. 1999;17(2):266-267.
15. Goldenberg K, Rozenbaum M, Rosner I, et al. Remitting symmetric seronegative synovitis with pitting edema (RS3PE) secondary to non-Hodgkin's lymphoma. Clin Exp Rheumatol. 1998;16(6):767-768.
16. Sayarlioglu M. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) and malignancy. Eur J Gen Med. 2004;1(2):3-5.