Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Current Rheumatology Reports
Published in: Current Rheumatology Reports 8/2015

01-08-2015 | Orphan Diseases (B Manger, Section Editor)

RS3PE: Clinical and Research Development

Authors: Hongbin Li, Roy D. Altman, Qingping Yao

Published in: Current Rheumatology Reports | Issue 8/2015

Login to get access

Abstract

Remitting seronegative symmetrical synovitis with pitting edema or RS3PE is a rare elderly-onset rheumatic syndrome. Although there are overlapping clinical manifestations between RS3PE, elderly-onset rheumatoid arthritis, and polymyalgia rheumatica, RS3PE has distinct characteristics. RS3PE can be associated with neoplasia and various rheumatic conditions, suggesting that it may be heterogeneous, and is considered as a paraneoplastic rheumatic disease. The pathogenesis of RS3PE may involve vascular endothelial growth factor and infection in RS3PE based upon limited data. Patients with RS3PE without concomitant malignancy respond well to small doses of glucocorticoids and carry good prognosis.
Literature
1.
McCarty DJ, O’Duffy JD, Pearson L, Hunter JB. Remitting seronegative symmetrical synovitis with pitting edema. RS3PE syndrome. JAMA. 1985;254:2763–7.PubMedCrossRef
2.
Bhakta BB, Pease CT. Late-onset rheumatoid arthritis: is pitting oedema of the hands at onset a good prognostic indicator? Br J Rheumatol. 1997;36:214–9.PubMedCrossRef
3.
Mavragani CP, Moutsopoulos HM. Rheumatoid arthritis in the elderly. Exp Gerontol. 1999;34:463–71.PubMedCrossRef
4.
Schaeverbeke T, Vernhes JP, Bannwarth B, Dehais J. Is remitting seronegative symmetrical synovitis with pitting oedema (RS3PE syndrome) associated with HLA-A2? Br J Rheumatol. 1995;34:889–90.PubMedCrossRef
5.
Russell EB. Remitting seronegative symmetrical synovitis with pitting edema syndrome: followup for neoplasia. J Rheumatol. 2005;32:1760–1.PubMed
6.
7.
8.
Varshney AN, Kumar N, Tiwari A, et al. Unilateral RS3PE in a patient of seronegative rheumatoid arthritis. Case Rep Rheumatol. 2013;2013:923797.PubMedCentralPubMed
9.
Nygaard U, Vestergaard C, Koppelhus U. Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) of hands and feet in an 83-year-old man. Acta Derm Venereol. 2013;93:491–2.PubMedCrossRef
10.
Ozsahin M, Ataoglu S, Turan H. Unilateral RS3PE with young-onset rheumatoid arthritis. Semin Arthritis Rheum. 2011;40:e1.PubMedCrossRef
11.
Keenan RT, Hamalian GM, Pillinger MH. RS3PE presenting in a unilateral pattern: case report and review of the literature. Semin Arthritis Rheum. 2009;38:428–33.PubMedCrossRef
12.••
Kimura M, Tokuda Y, Oshiawa H, et al. Clinical characteristics of patients with remitting seronegative symmetrical synovitis with pitting edema compared to patients with pure polymyalgia rheumatica. J Rheumatol. 2012;39:148–53. This is a comparative study between RS3PE and PMR.PubMedCrossRef
13.
Bucaloiu ID, Olenginski TP, Harrington TM. Remitting seronegative symmetrical synovitis with pitting edema syndrome in a rural tertiary care practice: a retrospective analysis. Mayo Clin Proc. 2007;82:1510–5.PubMedCrossRef
14.
Okumura T, Tanno S, Ohhira M, Nozu T. The rate of polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome in a clinic where primary care physicians are working in Japan. Rheumatol Int. 2012;32:1695–9.PubMedCentralPubMedCrossRef
15.
Yao Q, Su X, Altman RD. Is remitting seronegative symmetrical synovitis with pitting edema (RS3PE) a subset of rheumatoid arthritis? Semin Arthritis Rheum. 2010;40:89–94.PubMedCrossRef
16.
Sugihara T, Ishizaki T, Hosoya T et al. Structural and functional outcomes of a therapeutic strategy targeting low disease activity in patients with elderly-onset rheumatoid arthritis: a prospective cohort study (CRANE). Rheumatology (Oxford) 2014 Oct 8. pii:keu395. [Epub ahead of print].
17.
Cantini F, Salvarani C, Olivieri I, et al. Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome: a prospective follow up and magnetic resonance imaging study. Ann Rheum Dis. 1999;58:230–6.PubMedCentralPubMedCrossRef
18.
Agarwal V, Dabra AK, Kaur R, et al. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome: ultrasonography as a diagnostic tool. Clin Rheumatol. 2005;24:476–9.PubMedCrossRef
19.
Gisserot O, Cremades S, Landais C, et al. RS3PE revealing recurrent non-Hodgkin’s lymphoma. Joint Bone Spine. 2004;71:424–6.PubMedCrossRef
20.
Tunc SE, Arslan C, Ayvacioglu NB, et al. Paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome): a report of two cases and review of the literature. Rheumatol Int. 2004;24:234–7.PubMedCrossRef
21.
Paira S, Graf C, Roverano S, Rossini J. Remitting seronegative symmetrical synovitis with pitting oedema: a study of 12 cases. Clin Rheumatol. 2002;21:146–9.PubMedCrossRef
22.
23.
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;16:767–8.PubMed
24.
Cobeta-Garcia JC, Domingo-Morera JA, Martinez-Burgui J. RS3PE syndrome and chronic lymphoid leukaemia. Clin Exp Rheumatol. 1999;17:266–7.PubMed
25.
Chiappetta N, Gruber B. Remitting seronegative symmetrical synovitis with pitting edema associated with acute myeloid leukemia. J Rheumatol. 2005;32:1613–4.PubMed
26.
Ekenel M, Yavuz S, Karti S, et al. Remitting seronegative symmetrical synovitis with pitting oedema associated with chronic lymphocytic leukaemia. Clin Rheumatol. 2000;19:247–8.PubMedCrossRef
27.
Manganelli P, Delsante G, Bianchi G, et al. Remitting seronegative symmetrical synovitis with pitting oedema in a patient with myelodysplastic syndrome and relapsing polychondritis. Clin Rheumatol. 2001;20:132–5.PubMedCrossRef
28.
Tabeya T, Sugaya T, Suzuki C et al. A case of angioimmunoblastic T-cell lymphoma with high serum VEGF preceded by RS3PE syndrome. Mod Rheumatol. 2013.
29.
Sibilia J, Friess S, Schaeverbeke T, et al. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE): a form of paraneoplastic polyarthritis? J Rheumatol. 1999;26:115–20.PubMed
30.
Ethiopia A, Bell D. Gastric carcinoma in association with remitting seronegative symmetrical synovitis with pitting edema. J Rheumatol. 1999;26:1203–4.PubMed
31.
Tada Y, Sato H, Yoshizawa S, et al. Remitting seronegative symmetrical synovitis with pitting edema associated with gastric carcinoma. J Rheumatol. 1997;24:974–5.PubMed
32.
Mattace-Raso FU, van der Cammen TJ. Remitting seronegative symmetrical synovitis with pitting oedema associated with lung malignancy. Age Ageing. 2007;36:470–1.PubMedCrossRef
33.
Olivo D, Mattace R. Concurrence of benign edematous polysynovitis in the elderly (RS3PE syndrome) and endometrial adenocarcinoma. Scand J Rheumatol. 1997;26:67–8.PubMedCrossRef
34.
Smitten AL, Simon TA, Hochberg MC, Suissa S. A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis. Arthritis Res Ther. 2008;10:R45.PubMedCentralPubMedCrossRef
35.•
Gross RL, Schwartzman-Morris JS, Krathen M, et al. A comparison of the malignancy incidence among patients with psoriatic arthritis and patients with rheumatoid arthritis in a large US cohort. Arthritis Rheumatol. 2014;66:1472–81. This is a new study of malignancy rate in rheumatoid arthritis.PubMedCentralPubMedCrossRef
36.
Yamada T, Nakajima A, Inoue E, et al. Incidence of malignancy in Japanese patients with rheumatoid arthritis. Rheumatol Int. 2011;31:1487–92.PubMedCrossRef
37.
Muller S, Hider SL, Belcher J, et al. Is cancer associated with polymyalgia rheumatica? A cohort study in the general practice research database. Ann Rheum Dis. 2014;73:1769–73.PubMedCentralPubMedCrossRef
38.
39.•
Manger B, Schett G. Paraneoplastic syndromes in rheumatology. Nat Rev Rheumatol. 2014;10:662–70. This is a recent review of malignancies in rheumatology where the concept of paraneoplastic syndromes were defined, including RS3PE.PubMedCrossRef
40.
Hegazi MO, Saleh F, Al Rashidi A, Yaktien MM. Synovitis with pitting edema as the presenting manifestation of systemic lupus erythematosus. Lupus. 2014;23:1069–72.PubMedCrossRef
41.
Sugisaki K, Hirose T. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome following spontaneous rupture of a gouty tophus. Mod Rheumatol. 2008;18:630–3.PubMedCrossRef
42.
Fietta P, Manganelli P. Sjogren’s syndrome presenting as remitting seronegative symmetric synovitis with pitting edema (RS3PE): comment of the article by Choi et al. J Korean Med Sci. 2003;18:921.PubMedCentralPubMedCrossRef
43.
Billey T, Navaux F, Lassoued S. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) as the first manifestation of periarteritis nodosa. Report of a case. Rev Rhum Engl Ed. 1995;62:53–4.PubMed
44.
Koeger AC, Karmochkine M, Chaibi P. RS3PE syndrome associated with advanced ankylosing spondylitis. J Rheumatol. 1995;22:375–6.PubMed
45.
Matsuda M, Sakurai K, Fushimi T, et al. Sarcoidosis with high serum levels of vascular endothelial growth factor (VEGF), showing RS3PE-like symptoms in extremities. Clin Rheumatol. 2004;23:246–8.PubMedCrossRef
46.
Magy N, Michel F, Auge B, et al. Amyloid arthropathy revealed by RS3PE syndrome. Joint Bone Spine. 2000;67:475–7.PubMed
47.
Kato T, Ubara Y, Sawa N, et al. An abrupt onset of seropositive polyarthritis with prominent distal tenosynovitis concomitant with bronochiolitis obliterans organizing pneumonia (BOOP): consideration of the relationship with RS3PE syndrome. Intern Med. 2004;43:143–7.PubMedCrossRef
48.
Sakoda H, Ito S, Kanda H, et al. Association between type 1 diabetes mellitus and remitting seronegative symmetrical synovitis with pitting edema: a case report. Diabetes Res Clin Pract. 2011;91:e43–4.PubMedCrossRef
49.
50.
Smyth D, Rehman R, Remund K, Egan J. Remitting seronegative symmetrical synovitis with pitting oedema associated with rifampicin. Ir J Med Sci. 2011;180:585–6.PubMedCrossRef
51.
Mainali NR, Schmidt TR, Alweis R, George DL. Novel development of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome due to insulin therapy. Am J Case Rep. 2014;15:119–22.PubMedCentralPubMedCrossRef
52.
El Mahou S, Popa L, Constantin A, et al. Remitting seronegative symmetrical synovitis pitting oedema after BCG instillation. Clin Rheumatol. 2006;25:566–7.PubMedCrossRef
53.
Perandones CE, Colmegna I, Arana RM. Parvovirus B19: another agent associated with remitting seronegative symmetrical synovitis with pitting edema. J Rheumatol. 2005;32:389–90.PubMed
54.
Torres A, Cuende E, De Pablos M, et al. Remitting seronegative symmetrical synovitis with pitting edema associated with subcutaneous Streptobacillus moniliformis abscess. J Rheumatol. 2001;28:1696–8.PubMed
55.
Mittal K, Ebos J, Rini B. Angiogenesis and the tumor microenvironment: vascular endothelial growth factor and beyond. Semin Oncol. 2014;41:235–51.PubMedCrossRef
56.
Ku DD, Zaleski JK, Liu S, Brock TA. Vascular endothelial growth factor induces EDRF-dependent relaxation in coronary arteries. Am J Physiol. 1993;265:H586–92.PubMed
57.
Arima K, Origuchi T, Tamai M, et al. RS3PE syndrome presenting as vascular endothelial growth factor associated disorder. Ann Rheum Dis. 2005;64:1653–5.PubMedCentralPubMedCrossRef
58.
Horai Y, Honda M, Nishino A, et al. Anti-citrullinated protein antibody-positive rheumatoid arthritis associated with RS3PE syndrome-like symptoms and an elevated serum vascular endothelial growth factor level in a patient with myasthenia gravis. Intern Med. 2014;53:895–8.PubMedCrossRef
59.
Oide T, Ohara S, Oguchi K, et al. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome in Nagano, Japan: clinical, radiological, and cytokine studies of 13 patients. Clin Exp Rheumatol. 2004;22:91–8.PubMed
60.
Origuchi T, Arima K, Kawashiri SY, et al. High serum matrix metalloproteinase 3 is characteristic of patients with paraneoplastic remitting seronegative symmetrical synovitis with pitting edema syndrome. Mod Rheumatol. 2012;22:584–8.PubMedCrossRef
61.
Baumgartner I, Rauh G, Pieczek A, et al. Lower-extremity edema associated with gene transfer of naked DNA encoding vascular endothelial growth factor. Ann Intern Med. 2000;132:880–4.PubMedCrossRef
62.
van Schaardenburg D, Breedveld FC. Elderly-onset rheumatoid arthritis. Semin Arthritis Rheum. 1994;23:367–78.PubMedCrossRef
63.
Finnell JA, Cuesta IA. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome: a review of the literature and a report of three cases. J Foot Ankle Surg. 2000;39:189–93.PubMedCrossRef
64.
65.
Metadata
Title
RS3PE: Clinical and Research Development
Authors
Hongbin Li
Roy D. Altman
Qingping Yao
Publication date
01-08-2015
Publisher
Springer US
Published in
Current Rheumatology Reports / Issue 8/2015
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-015-0525-0

Other articles of this Issue 8/2015

Current Rheumatology Reports 8/2015 Go to the issue

Psoriatic Arthritis (O FitzGerald and P Helliwell, Section Editors)

Contribution of the IL-17 Pathway to Psoriasis and Psoriatic Arthritis

Imaging (P Conaghan, Section Editor)

Imaging in Giant Cell Arteritis

Osteoarthritis (MB Goldring, Section Editor)

Implementation of Functional Genomics for Bench-to-Bedside Transition in Osteoarthritis

Osteoarthritis (MB Goldring, Section Editor)

Novel Insights into Osteoarthritis Joint Pathology from Studies in Mice

Infections and Arthritis (K Winthrop, Section Editor)

HCV Treatments and Their Integration Into Rheumatology

Osteoarthritis (MB Goldring, Section Editor)

Medical Plant Extracts for Treating Knee Osteoarthritis: a Snapshot of Recent Clinical Trials and Their Biological Background

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits