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Year : 2019  |  Volume : 65  |  Issue : 3  |  Page : 188-189

Remitting symmetrical seronegative synovitis and pitting edema syndrome with concomitant adenocarcinoma of the lung

Department of Internal Medicine, Division of Rheumatology, Kayseri City Hospital, Kayseri, Turkey

Date of Web Publication18-Jul-2019

Correspondence Address:
S Karahan
Department of Internal Medicine, Division of Rheumatology, Kayseri City Hospital, Kayseri
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpgm.JPGM_237_19

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How to cite this article:
Karahan S. Remitting symmetrical seronegative synovitis and pitting edema syndrome with concomitant adenocarcinoma of the lung. J Postgrad Med 2019;65:188-9

How to cite this URL:
Karahan S. Remitting symmetrical seronegative synovitis and pitting edema syndrome with concomitant adenocarcinoma of the lung. J Postgrad Med [serial online] 2019 [cited 2023 Feb 4];65:188-9. Available from:

Remitting symmetrical seronegative synovitis and pitting edema (RS3PE) syndrome is a rheumatologic disease affecting elderly patients accompanied by symmetric synovitis of small joints of the hand and/or foot, which is characterized by pitting edema in the dorsum of the hand and/or foot.[1] In RS3PE syndrome, antinuclear antibody (ANA), rheumatoid factor (RF), and anticyclic citrullinated peptide (Anti-CCP) autoantibodies are negative. Although some clinical signs may differentiate from polymyalgia rheumatica (PMR) and late-onset rheumatoid arthritis (RA), some clinicians may be confused in the differential diagnosis. RS3PE syndrome usually responds to low-dose steroid therapy.[1] In this article, we present a patient with symmetrical seronegative synovitis in the small joints of his hands and feet and pitting edema in the dorsii of his hands and feet with concomitant adenocarcinoma of the lung.

A 55-year-old male patient was admitted with complaints of pain in the small joints of his hands and feet; and swelling in his hands and feet for 2 weeks. The patient's past medical history was unremarkable. However, he had lost weight (about 10 kg) in the last 4 months. On physical examination, cardiac auscultation was normal and breath sounds were decreased in right middle and upper zones. Musculoskeletal examination revealed arthralgia of the hand and foot joints and pitting edema, more prominent in both feet [Figure 1]. On laboratory evaluation, the patient's leukocyte count (WBC) was 12,400/μL, erythrocyte sedimentation rate (ESR) was 61mm/1st h, C-reactive protein (CRP) was 108 mg/L with normal liver and kidney function tests. Among the autoimmune parameters, RF, anti-CCP, extractable nuclear antigen (ENA) profile tests, and HLA-B27 tests were negative. Musculoskeletal ultrasonography of the hand and wrist regions revealed synovial hypertrophy in various small joints of the hands, especially in radiocarpal and metacarpofalangel joints, with various stages of Doppler activity in these areas. The patient was diagnosed as having RS3PE syndrome and malignancy screening was performed. The chest tomography of the patient revealed a mass lesion of 2 × 3 cm in the right middle-upper zones with ground glass appearance [Figure 2]. Tranbsronchial biopsy was performed and the histopathological examination was diagnostic of adenocarcinoma of the lung.
Figure 1: Significant pitting edema of the patient's right foot

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Figure 2: Chest tomography revealed a mass of 2 × 3 cm in the right middle-upper zones with ground glass appearance

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The patient did not have any pain in the joints of his hands and feet after being treated with oral methylprednisolone 16 mg/day for 15 days. Pitting edema also disappeared and acute phase reactants regressed: ESR 26 mm/1st hr and CRP 12 mg/dL. The patient was referred to the oncology services for treatment of his lung malignancy.

RS3PE syndrome was first described in 1985 by Mc Carthy et al in eight elderly male and two female patients with pitting edema and acute onset symmetric polysinovitis on the dorsum in both hands and feet.[1] These swellings, which usually accompanied by pitting, show a “boxing glove” appearance because of the affected wrist and metacarpophalangeal joints. Although RS3PE syndrome was initially considered as a variant of RA, it is now known that this disease can be separated from both RA and PMR with some sharp borders.[2] The following features help differentiate RS3PE from RA: pitting edema in the feet and hands, lack of subcutaneous nodules, RF and/or anti-CCP negative, no radiographic erosion, no specificity to any HLA-DR locus specific to RA, and an excellent dramatic response to steroid therapy. RS3PE syndrome is a rare disease (0.09% incidence), the etiology is unknown and males are more frequently affected than females. Tenosynovitis is observed especially with the inflammation of the flexor and extensor tendons of the hands and no pannus is observed in this sites. Unlike RA, RS3PE syndrome is accompanied in 20% of cases with a concomitant malignancy.[3]

In general, idiopathic RS3PE patients do not show either general health deterioration or fever and they do respond to low doses of steroids (10 mg/day). In patients with RS3PE the presence of systemic symptoms along with resistance to low doses of corticosteroid therapy should alert the physician to the possible presence of malignancy.[4] RS3PE has also been described after autoimmune diseases such as Sjögren syndrome, ankylosing spondylitis, polyarteritis nodosa, and the use of certain drugs, such as dipeptidyl peptidase inhibitors and rifampin.[3]

Although various factors are mentioned in etiopathogenesis, vascular endothelial growth factor (VEGF) is believed to play a critical role. VEGF levels have been shown to be elevated in patients having edema such as in RA, PMR, temporal arthritis and also RS3PE syndrome.[5] It has been postulated that the vascular permability increase due to the overproduction of this neoangiogenesis factor may be trigger RS3PE syndrome and other rheumatic entities.[6]

Declaration of patient consent

The authors certify that appropriate patient consent was obtained.

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Conflicts of interest

There are no conflicts of interest.

 :: References Top

Olivieri I, Salvarini C, Cantini F. RS3PE: An overview. Clin Exp Rheumatol 2000;18(4 Suppl 20):S53.  Back to cited text no. 1
dos Santos JM, Florentin JP, Ricarte SP. Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) syndrome in an elderly Spanish patient: Ruling-out polymyalgia rheumatica and management. Egypt Rheumatol. [In press].  Back to cited text no. 2
Li H, Altman RD, Yao Q. RS3PE: Clinical and research development. Curr Rheumatol Rep 2015;17:49.  Back to cited text no. 3
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.  Back to cited text no. 4
Smets P, Devauchelle-Pensec V, Rouzaire PO, Pereira B, Andre M, Soubrier M. Vascular endothelial growth factor levels and rheumatic diseases of the elderly. Arthritis Res Ther 2016;18:283.  Back to cited text no. 5
Sakamoto T, Ota S, Haruyama T, Ishihara M, Natsume M, Fukasawa Y, et al. A case of paraneoplastic remitting seronegative symmetrical synovitis with pitting edema syndrome improved by chemotherapy. Case Rep Oncol 2017;10:1131-7.  Back to cited text no. 6


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2004 - Journal of Postgraduate Medicine
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