Remitting, seronegative (A) symmetrical synovitis with pitting edema--two cases of RS3PE syndrome

The sparing effect of neurological damage on the development and progression of several arthritic conditions has been documented. We describe the first 2 cases of unilateral remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome in individuals with neurologic disorders. Case 1 suffered from birth trauma resulting in paresis of the right upper extremity and developed RS3PE syndrome in the nonaffected extremities. Case 2 developed RS3PE syndrome on the nonparetic side 7 years after a cerebrovascular accident resulting in hemiparesis.     

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome accompanied by Parkinson's disease

We encountered two cases of RS3PE (remitting seronegative symmetrical synovitis with pitting edema) syndrome accompanied by Parkinson's disease (PD). Although the etiology of RS3PE syndrome is still unknown, several possible associations, such as malignancies and viral infections, have been reported; RS3PE syndrome is thought to be an autoimmune-mediated disorder. The present patients did not have any factors which are reported to be associated with RS3PE. Whether or not the complication of PD and RS3PE syndrome is incidental needs to be further examined, and we discuss here the possible cause of association between PD and RS3PE syndrome, including dopamine agonists one of the anti-PD medications.     

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome: ultrasonography as a diagnostic tool

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical synovitis and swelling of both the upper and lower extremities. The anatomical determinant of RS3PE is predominantly extensor tenosynovitis as revealed by magnetic resonance imaging (MRI). Given the cost constraints, time, and expertise required in carrying out MRI and ease in diagnosing tenosynovitis by ultrasound, we utilized high-frequency ultrasonography (USG) for evidence of tenosynovitis of the distal tendons in patients with RS3PE. Diagnosis of tenosynovitis was made on the basis of anechoic or hypoechoic signals around the tendon sheaths in both transverse and longitudinal planes. Flexor and extensor tendons at the wrist and metacarpal heads and extensor digitorum longus (EDL) tendons at the ankle were evaluated with a 7.5–10-MHz linear probe. There were ten patients (seven males) with a mean age of 59.5 years (range: 52–78 years) and mean disease duration of 6.1 months (range: 1.5–12 months). Disease onset was acute in all of the cases. Pitting edema of the hands was present in all except two patients whereas four patients, in addition, had edema of the feet. Edema was symmetrical in seven patients. Inability to make a complete fist was noted in all. Tenosynovitis of extensor and flexor tendons at the wrist and the metacarpal heads was documented in all patients with edema of the hands. In seven cases extensor tendon tenosynovitis was more prominent compared to the flexor tendons. Tenosynovitis of EDL tendons was detected in six cases. Dramatic relief with low-dose prednisolone was noted in all patients within 6 weeks of therapy. At a mean follow-up of 10.1 months all patients had marked relief in edema of extremities and improvement in the grip strength. Our study confirms that tenosynovitis of both flexor and extensor tendons at the wrist and extensor tendons of the feet is the hallmark of RS3PE syndrome. USG is a reliable and cost-effective modality for evaluation of patients with suspected RS3PE.     

Remitting seronegative symmetrical synovitis pitting oedema after BCG instillation

Remitting seronegative symmetrical synovitis pitting oedema (RS3PE) is a distinct form of seronegative rheumatoid arthritis like polyarthritis. It is characterized by late onset symmetrical joint involvement and pitting oedema of hands and feet (JAMA 254(19):2763–2767, [1]). Polyarthritis secondary to intravesical Bacillus Calmette Guerin (BCG) therapy has been reported (Clin Rheumatol 21:536–537, [2]). To our knowledge, about 0.5% of patients receiving BCG instillation presented polyarthritis, but only one case of RS3PE has been reported (J Rheumatol 28:1699–1701, [3]). We described the second case of RS3PE following intravesical BCG instillation of bladder carcinoma.     

Remitting seronegative symmetrical synovitis with pitting oedema associated with lung malignancy

RS3PE syndrome is an inflammatory disease which affects mainly males and responds rapidly to low-dose steroids. We describe the concurrence of RS3PE and lung malignancy in a 78-year-old woman. We recommend that an underlying malignancy should always be excluded in patients with RS3PE syndrome, even when general signs and symptoms such as weight loss, anorexia and fever are absent or uncertain.     

Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome: a prospective follow up and magnetic resonance imaging study

OBJECTIVE: To determine the clinical characteristics of patients with "pure" remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome, and to investigate its relation with polymyalgia rheumatica (PMR). Magnetic resonance imaging (MRI) was used to describe the anatomical structures affected by inflammation in pure RS3PE syndrome. METHODS: A prospective follow up study of 23 consecutive patients with pure RS3PE syndrome and 177 consecutive patients with PMR diagnosed over a five year period in two Italian secondary referral centres of rheumatology. Hands or feet MRI, or both, was performed at diagnosis in 7 of 23 patients. RESULTS: At inspection evidence of hand and/or foot tenosynovitis was present in all the 23 patients with pure RS3PE syndrome. Twenty one (12%) patients with PMR associated distal extremity swelling with pitting oedema. No significant differences in the sex, age at onset of disease, acute phase reactant values at diagnosis, frequency of peripheral synovitis and carpal tunnel syndrome and frequency of HLA-B7 antigen were present between patients with pure RS3PE and PMR. In both conditions no patient under 50 was observed, the disease frequency increased significantly with age and the highest frequency was present in the age group 70-79 years. Clinical symptoms for both conditions responded promptly to corticosteroids and no patient developed rheumatoid arthritis during the follow up. However, the patients with pure RS3PE syndrome were characterised by shorter duration of treatment, lower cumulative corticosteroid dose and lower frequency of systemic signs/symptoms and relapse/recurrence. Hands and feet MRI showed evidence of tenosynovitis in five patients and joint synovitis in three patients. CONCLUSION: The similarities of demographic, clinical, and MRI findings between RS3PE syndrome and PMR and the concurrence of the two syndromes suggest that these conditions may be part of the same disease and that the diagnostic labels of PMR and RS3PE syndrome may not indicate a real difference. The presence of distal oedema seems to indicate a better prognosis.     

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome following spontaneous rupture of a gouty tophus

Abstract

A 70-year-old man with a 30-year history of gout presented with a ruptured gouty tophus over the right lateral malleolus. After the debridement of the tophus, bilateral arthralgia and pitting edema were observed in his extremities. Treatments with antibiotics and nonsteroidal antiinflammatory drugs were ineffective. However, prednisolone therapy was highly effective, and the patient’s symptoms were rapidly ameliorated. Thus, we presume that rupture of a gouty tophus or its surgical treatment might contribute to the occurrence of RS3PE syndrome; however, in our case, the etiology of the syndrome remained unknown.     

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome following spontaneous rupture of a gouty tophus

A 70-year-old man with a 30-year history of gout presented with a ruptured gouty tophus over the right lateral malleolus. After the debridement of the tophus, bilateral arthralgia and pitting edema were observed in his extremities. Treatments with antibiotics and nonsteroidal antiinflammatory drugs were ineffective. However, prednisolone therapy was highly effective, and the patient’s symptoms were rapidly ameliorated. Thus, we presume that rupture of a gouty tophus or its surgical treatment might contribute to the occurrence of RS3PE syndrome; however, in our case, the etiology of the syndrome remained unknown.     

Remitting seronegative symmetrical synovitis with pitting oedema: disease or syndrome?

OBJECTIVE--To evaluate the outcome of patients with remitting seronegative symmetrical synovitis with pitting oedema (RS3PE). METHODS--In a retrospective chart review study, we identified all the patients presenting with polyarthritis and pitting oedema in the past 20 years. We tried to recall the 24 patients with characteristics of RS3PE according to McCarty et al. Two patients had died and four could not be traced. Five could not be seen after the initial period of follow up; relevant data were obtained from their practitioner. For the remaining 13 patients, clinical, radiological, and biological evaluation was performed in our department, with the last assessment in 1993. RESULTS--The follow up period was from one to 18 years (mean 4.6 (SD 4.5) years). Eleven patients developed one or several recurrences of articular manifestations consisting of mild oligoarthritis (n = 8), definite spondyloarthropathy (n = 2), and rheumatoid arthritis (n = 1). The delay of the first recurrence was 18 months to 12 years after the first attack. Thirteen patients had no recurrence, but three of them developed remarkable features: rheumatoid factor, antinuclear antibodies (1/2000), Sjögren's syndrome. HLA B typing was performed in nine patients and revealed B7 (n = 2), B27 (n = 2) and B22 (n = 2). Isolated HLA B27 typing was performed in two other patients and was positive in one. CONCLUSION--The long term outcome of RS3PE can lead to different rheumatic diseases. RS3PE appears to be a syndrome related to the elderly onset of the rheumatic diseases, including spondyloarthropathy and rheumatoid arthritis, rather than a specific entity.     

Remitting seronegative symmetrical synovitis with pitting oedema: a study of 12 cases

Twelve patients with remitting seronegative symmetrical synovitis with pitting oedema (RS₃PE) were analysed. Eight of them had typical RS₃PE without underlying disease, and four presented associated neoplasia. The first patients experienced an excellent response to low doses of prednisone, and they all achieved complete and permanent remission. The mean treatment duration was 18 months and the mean follow-up was 4.4 years. During the follow-up, none of these patients relapsed, had fever or general health deterioration, and hand and foot radiographs did not show erosion. One of them developed a panarteritis nodosa 6 years later. Four RS₃PE patients had associated neoplasia. Two were with solid malignancies, and the other two presented haematological malignancies. In one of them RS₃PE preceded the diagnosis of malignancy. The diagnosis of RS₃PE in the other patients was subsequent to cancer. The first patients presented clinical characteristics suggestive of paraneoplastic RS₃PE, and they had a poor response to corticosteroid therapy. Two patients died, and the rest of them had a complete response to surgical resection of the tumour or to chemotherapy. 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). We observed strong contrasts with the results obtained when treating RS₃PE patients with associated neoplasia. 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. Received: 2 April 2001 / Accepted: 18 September 2001     

Seven cases of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome

Among the elderly patients with seronegative polyarthritis, McCarty et al. (1985) proposed a disease entity of "remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome", but only a few cases have been reported in Japan. Here we report 7 cases suspicious of RS3PE syndrome, 2 men and 5 women with an average age of 75.9 years, ranging from 67-82 years. Their common findings were (1) relatively acute onset, (2) polyarthritis, (3) pitting edema of the dorsum of both hands and both feet, and (4) negative rheumatoid factor and antinuclear antibody. McCarty et al. found that RS3 PE syndrome was more prevalent in men; however, in our experience, the opposite was observed. The clinical courses of all patients were good, and they were effectively treated either by small dosages of oral prednisolone, nonsteroidal antiinflammatory drugs, or Chinese herbal (Kampo) medicines. Since this syndrome might not be rare in Japan, it seems necessary to evaluate elderly patients with seronegative polyarthritis with pitting edema as RS3PE syndrome in their routine medical examinations.     

Remitting seronegative symmetrical synovitis with pitting edema in leprosy

A 67-year-old man, who had widespread and well-defined erythematous violaceous hyperkeratotic plaques on his skin, was diagnosed with borderline tuberculoid leprosy. The patient began treatment with clofazimine, rifampicin, and dapsone, but 15 days afterwards he complained of acral edema with godet sign. Magnetic resonance imaging was done, and the case was interpreted as remitting seronegative symmetrical synovitis with pitting edema. About 8 mg/day of methylprednisolone were started with excellent response.     

Remitting seronegative symmetrical synovitis with pitting edema following acute intracranial hemorrhage

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is an unusual inflammatory arthritis with unknown pathogenic mechanism, and is characterized by an acute onset of symmetrical synovitis with pitting edema of the hands or feet. Numerous diseases are associated with RS3PE, including neoplasia, infection, Parkinson’s disease, and other rheumatic diseases. Neoplasia is the most common condition associated with RS3PE. We report a case of RS3PE that occurred following acute intracranial hemorrhage in an 80-year-old man with a 20-year history of hypertension.     

Remitting seronegative symmetrical synovitis with pitting oedema syndrome, associated with prostate adenocarcinoma: a case report

Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) of the dorsum of the hands and/or feet can be observed in different inflammatory rheumatic diseases as well as in haematological and solid malignancies. McCarty et al, described this syndrome for the first time more than twenty years ago. Underlying malignancy should always be excluded in patients with RS3PE syndrome.     

Remitting seronegative symmetrical synovitis with pitting edema associated with acute myeloid leukemia

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) almost exclusively affects elderly men and can occur independently or may be associated with a vast array of clinical conditions including underlying malignancy. Patients present with a polyarthritis similar to rheumatoid arthritis. We describe a case of an elderly man presenting with RS3PE who developed acute myeloid leukemia. It is important for clinicians to be aware of this possibility and initiate appropriate investigations, particularly if systemic symptoms are prominent, to detect an occult malignancy at a potentially earlier stage.     

Remitting seronegative symmetrical synovitis with pitting edema syndrome: followup for neoplasia

OBJECTIVE: To investigate whether the remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome may represent a paraneoplastic disorder in a significant percentage of cases. METHODS: Patients diagnosed with RS3PE syndrome at the Medical College of Wisconsin before 1995 were telephoned and asked about their rheumatologic course since initial diagnosis of RS3PE and whether they had been diagnosed with any cancer. If so, permission was obtained to review tissue pathology. Criteria used for diagnosis of RS3PE syndrome included sudden onset of painful diffuse swelling of both hands associated with pitting edema of the dorsa of the hands without other synovitis or evidence of disease, negative rheumatoid factor, absence of radiologic abnormalities, and resolution within 6-12 months without sequelae. Data from the national SEER databank on population incidence of cancers in the appropriate sex, age, and ethnic groups for the years under study were used to assess relative risk for cancer. RESULTS: There were 10 patients for whom followup data were available. Four had a cancer diagnosed following recognition of the RS3PE syndrome; 1 patient developed non-Hodgkin's lymphoma initially diagnosed as hairy cell leukemia after 4 years; 1 developed acute lymphocytic leukemia with hyperdiploidy after 14 years; 1 was diagnosed with male breast cancer after 2.5 years; and 1 developed squamous cell lung cancer 12 months after RS3PE diagnosis. SEER data project an estimated rate of 2-3 cancers in a similar group of 10 patients of the same sex, age, and time period for this geographic area. CONCLUSION: The small sample size in this longterm followup precludes extrapolation to larger populations but suggests that there may be a slightly higher than expected rate of neoplasia in patients diagnosed with RS3PE syndrome. The interval between onset of RS3PE syndrome and diagnosis of cancer was fairly long, indicating that patients should be monitored for neoplasia with prudent age and sex specific surveillance for an extended period after diagnosis with RS3PE.