Grand Rounds Vol 10 pages 71–73

Specialities: Rheumatology

Article Type: Case Report

DOI: 10.1102/1470-5206.2010.0015

� 2010 e-MED Ltd

Remitting seronegative symmetrical

synovitis with pitting oedema

Anna J. Hartley, Jessica Manson and Ali S.M. Jawad

Rheumatology Department, The Royal London Hospital, London, E1 4DG, UK

Corresponding address: Anna J. Hartley, Rheumatology Department,

Mile End Hospital, Bancroft Road, London, E1 4DG, UK.

Email: annahartley@hotmail.co.uk

Date accepted for publication 16 August 2010

Abstract

Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) is a rare rheumatologic

condition frequently missed but easily treated. We describe a case of RS3PE and explore the

literature surrounding this arthritis.

Keywords

RS3PE; peripheral oedema; synovitis; rheumatology.

Introduction

Acute swelling of the hands and feet with pitting oedema can present to various specialities.

It rarely presents directly to the rheumatologists but often to the admitting physicians, care of the

elderly or, when complicated by carpal tunnel syndrome, to the orthopaedic surgeons. Cases of

remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) are probably more

common than documented but under or misdiagnosed. We describe a case of RS3PE presenting

via the orthopaedic surgeons.

Case report

A sixty year old HGV driver presented to the orthopaedic surgeons with an 18-month history of

carpal tunnel symptoms in his left hand. He had a past medical history of ischaemic heart disease

and bilateral knee replacements. He was mainly on cardiac medications. At this initial assessment,

he was found to have numbness of his left index and middle finger, but his hands were otherwise

normal. He was listed for elective carpal tunnel decompression.

Over the following weeks, he developed bilaterally painful and swollen hands. No other joints

were affected and he felt otherwise well. He had had no recent infections, nor any history of

psoriasis or inflammatory bowel disease.

On examination his hands were red, diffusely swollen and tender with synovitis of the joints

and pitting oedema over the dorsal aspects. The acute swelling had caused cracking of the

skin (Fig. 1). Distal pulses were present and capillary refill was less than 2 seconds in all fingers,

but his hands were cool. Sensation was normal but movement was limited because of the swelling

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and pain. He was afebrile with no other tender or swollen joints and no further oedema.

Cardiovascular, respiratory and abdominal examinations were unremarkable.

Blood results are shown in Table 1. Radiographs of both hands and feet were normal with no

erosions.

On representation to the orthopaedic doctors, his carpal tunnel decompression was cancelled

because of the new swelling in his hands. He was referred for an urgent vascular assessment.

After vascular compromise was excluded, he was referred to the rheumatologists where the

clinical diagnosis of RS3PE was made and prednisone 15mg was commenced with immediate

reduction in swelling. Unfortunately, weaning of steroids caused a relapse with worsening carpal

tunnel syndrome. Increasing the steroid dose once again resulted in a resolution of symptoms,

and the dose was weaned more gradually thereafter. Carpal tunnel surgery was planned on both

hands. Computed tomography (CT) of chest-abdomen-pelvis was performed which ruled out

underlying malignancy.

Discussion

In 1985, McCarty first described RS3PE in JAMA[1]. He reported 8 men and 2 women who

presented with bilateral swelling of the hands and feet with pitting oedema. Clinically, they had a

symmetrical polysynovitis and flexor tenosynovitis of the distal joints. They were all rheumatoid

factor negative and had no erosions on radiographs. McCarty also looked retrospectively at a case

series of 52 patients with definite rheumatoid arthritis. He concluded that at least three patients

had features of RS3PE and therefore hypothesised that RS3PE was maybe more a syndrome rather

than a disease.

Fig. 1. Swelling of the hands and cracking of the skin.

Table 1. Blood results

Haemoglobin 13.9 g/dL Sodium 141mmol/L

White cell count 9.6�109/L Potassium 4.4mmol/L

Neutrophils 6.1�109/L Urea 6.2mmol/L

Platelets 311�109/L Creatinine 91 mmol/L

Erythrocyte sedimentation rate 10mm/h Albumin 47 g/L

C-reactive protein 13mg/L Bilirubin 8 mmol/L

Antinuclear antibody Negative Alkaline phosphatase 93 IU/L

Rheumatoid factor Negative Alanine transaminase 14 IU/L

Corrected calcium 2.61mmol/L

72 A.J. Hartley et al.

Over the next few years there were numerous case reports and case series focussing on RS3PE.

The cases were mainly men over 50 years old with symmetrical synovitis affecting hands and feet

with pitting oedema and negative rheumatoid factor. Many cases started suddenly with patients

recalling the onset of swelling to the exact hour.

The pathogenesis of RS3PE has not yet been fully explored. One study implicates vascular

endothelial growth factor (VEGF) which causes synovial hypervascularity, inflammation and

vascular permeability leading to subcutaneous oedema. The levels of VEGF decreased on initiation

of steroid treatment[2].

Knowledge of RS3PE is relatively limited to small case series and retrospective studies. They

have debated whether RS3PE is a paraneoplastic phenomenon, a disease or syndrome or with

regard to the latter, an extension of polymyalgia rheumatic (PMR).

RS3PE has been linked to malignancy[3]. One striking series reported six cases presenting

simultaneously with RS3PE and an adenocarcinoma. The symptoms of RS3PE resolved with

steroids, but 5 patients died within 11 months as a result of disseminated malignancy[4]. Reports

also suggest that RS3PE that is resistant to steroids is more likely to be related to an underlying

malignancy[5]. This was the reason for the CT chest-abdomen-pelvis in our case.

There are case reports of RS3PE with most rheumatologic conditions. In 1995, Schaeverbeke

reviewed all patients who had presented with RS3PE over the preceding 20 years[6]. In this study

of 24 patients, he discovered that there were 8 reports of an oligoarthritis, 2 spondyloathro-

pathies and 1 rheumatoid arthritis developing in the years after RS3PE. One patient developed an

antinuclear antibody (ANA) of 1/2000 and one became rheumatoid factor positive.

In 1985, McCarty hypothesised that RS3PE may be part of rheumatoid arthritis. The literature

also points to an association with PMR. Twelve percent of patients with PMR may have distal

swelling with 39% having purely distal relapses[7]. However, cases of pure RS3PE appear to need a

shorter duration of lower dose steroids than cases of PMR[8].

RS3PE is a rare rheumatologic entity made rarer because of under diagnosis. Knowledge of its

existence avoids unnecessary investigations and treatment. Most patients have prompt resolution

of symptoms with steroids.

Teaching points

RS3PE presents mainly in men more than 50 years old, with pitting oedema and synovitis of the

hands and often the feet. Patients are rheumatoid factor negative and have no erosions on

radiographs. With low dose steroids, it usually improves rapidly. There is still much to be learnt

about RS3PE but on diagnosis, associations with other rheumatologic conditions and neoplasia

should be borne in mind.

References

1. McCarty DJ, O’Duffy JD, Pearson L, Hunter JB. RS3PE syndrome. JAMA 1985; 254: 2763–7.

doi:10.1001/jama.254.19.2763.

2. 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. doi:10.1136/

ard.2004.032995.

3. Russell EB. Remitting seronegative symmetrical synovitis with pitting edema syndrome:

followup for neoplasia. J Rheumatol 2005; 32: 1760–1.

4. 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.

5. 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.

6. Schaeverbeke T, Fatout E, Marce S, et al. Remitting seronegative symmetrical synovitis with

pitting oedema: disease or syndrome?. Ann Rheum Dis 1995; 54: 681–4.

7. Salvarani C, Cantini F, Macchioni P, et al. Distal musculoskeletal manifestations in polymyalgia

rheumatica: a prospective follow up study. Arthritis Rheum 1998; 41: 1221–6.

8. 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.

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