High serum matrix metalloproteinase 3 is characteristic of patients with paraneoplastic remitting seronegative symmetrical synovitis with pitting edema syndrome

Recently, it was reported that remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome could be complicated with solid tumors. In a retrospective, multicenter study between October, 2003 and September, 2010, we investigated the characteristics of patients with paraneoplastic RS3PE syndrome who fulfilled following criteria: (1) bilateral pitting edema of hands or feet or both, (2) sudden onset of polyarthritis, and (3) age >50?years, (4) seronegativity for rheumatoid factor (RF). A total of 33 cases fulfilled the above criteria. Eight patients (seven men and one woman) developed cancer within 2?years of RS3PE syndrome onset. There was no significant difference between the neoplastic and nonneoplastic groups in the proportions of patients with fever, symmetrical polyarthritis, pitting edema, and good response to corticosteroids. Serum matrix metalloproteinase 3 (MMP-3) level (median 437.3?ng/ml) in the paraneoplastic RS3PE patients was significantly higher than that in patients without neoplasia (median 114.7?ng/ml) (p?相似文献   

High serum matrix metalloproteinase 3 is characteristic of patients with paraneoplastic remitting seronegative symmetrical synovitis with pitting edema syndrome

Abstract

Recently, it was reported that remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome could be complicated with solid tumors. In a retrospective, multicenter study between October, 2003 and September, 2010, we investigated the characteristics of patients with paraneoplastic RS3PE syndrome who fulfilled following criteria: (1) bilateral pitting edema of hands or feet or both, (2) sudden onset of polyarthritis, and (3) age >50 years, (4) seronegativity for rheumatoid factor (RF). A total of 33 cases fulfilled the above criteria. Eight patients (seven men and one woman) developed cancer within 2 years of RS3PE syndrome onset. There was no significant difference between the neoplastic and nonneoplastic groups in the proportions of patients with fever, symmetrical polyarthritis, pitting edema, and good response to corticosteroids. Serum matrix metalloproteinase 3 (MMP-3) level (median 437.3 ng/ml) in the paraneoplastic RS3PE patients was significantly higher than that in patients without neoplasia (median 114.7 ng/ml) (p < 0.05). We found that high serum MMP-3 is characteristic of patients with paraneoplastic RS3PE syndrome.     

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.     

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.     

Oedematous polyarthritis and myopericarditis as presenting features of periarteritis nodosa

Remitting symmetrical seronegative synovitis with pitting edema (RS3PE) syndrome is a rare type of seronegative polyarthritis occurring in the elderly. It can be associated to various diseases. We report a case of RS3PE syndrome associated with myopericarditis, leading to the diagnosis of polyarteritis nodosa in a 71-year-old patient admitted to the hospital for a febrile acute polyarthritis with pitting edema of the hands associated with a marked inflammatory syndrome. On second day of hospitalization, a sustained chest pain led to the diagnosis of myopericarditis. Muscular biopsy showed necrotizing vasculitis, characteristic of polyarteritis nodosa. The coexistence of RS3PE and myopericarditis has never been described in the literature. Its association with polyarteritis nodosa is also very rare and only one case has been previously reported.     

An abrupt onset of seropositive polyarthritis with prominent distal tenosynovitis concomitant with bronochiolitis obliterans organizing pneumonia (BOOP): consideration of the relationship with RS3PE syndrome

A 64-year-old Japanese woman with a two-week history of polyarthralgia and persistent cough was diagnosed as seropositive polyarthritis and fulfilled the criteria of early rheumatoid arthritis (RA). In addition, inflammatory pitting edema of the distal extremities was apparent, suggestive of the remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. A number of investigations including hand MRI, bone scintigraphy and HLA typing supported a diagnosis of RS3PE syndrome rather than RA. Chest computed tomography revealed concomitant evidence of bronchiolitis obliterans organizing pneumonia (BOOP). Treatment with 30 mg of prednisolone daily immediately ameliorated the polyarthritis and the BOOP. Seropositive polyarthritis with distal pitting edema may be categorized as both RA and the RS3PE syndrome.     

Remitting seronegative symmetrical synovitis with pitting edema of the hands: ultrasound, color doppler ultrasound, and magnetic resonance imaging findings

OBJECTIVE: To assess the value of gray-scale ultrasound (US), color Doppler ultrasound (CDUS), contrast-enhanced CDUS, and magnetic resonance imaging (MRI) in the diagnostic evaluation of the hands in patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE). METHODS: Eight patients (5 men, 3 women; mean +/- SD age 69.3 +/- 7.2 years) with clinical diagnosis of RS3PE syndrome underwent US, CDUS, contrast-enhanced CDUS, and MRI. US was performed with a linear array transducer operating at 12 MHz. The US contrast agent (SHU 508; Levovist, Schering, Germany) was intravenously infused in a concentration of 300 mg/ml at a rate of 1 ml/minute. RESULTS: All patients showed symmetric subcutaneous edema and synovitis of tendons and finger joints on both US and MRI. Vascularity was detected subcutaneously in tendon sheaths and in the joint synovia on CDUS and MRI. Detection of increased vascularity was improved after contrast administration compared with unenhanced CDUS (P < 0.01). CONCLUSION: Ultrasound, CDUS, contrast-enhanced CDUS, and MRI are valuable tools in the diagnostic evaluation of involved anatomic structures in patients with RS3PE. Contrast-enhanced CDUS is superior to CDUS in assessment of inflammatory edema, effusion, and synovitis.     

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

We analyzed the rate of polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome, both characterized as seronegative inflammatory arthritis in elderly, in an outpatient unit where primary care physicians are working in Japan to better understand the epidemiological characteristics of the diseases in Japan. Consecutive outpatients who newly visited at Department of General Medicine, Asahikawa Medical University Hospital, Japan, between April 2004 and March 2010 were analyzed. Each parameter such as age, sex, diagnosis, and biochemical examination was investigated. During the 6?years, 10 or 3 patients were diagnosed as PMR or RS3PE syndrome, respectively. The patients with PMR were 7 women and 3 men, and the average age at diagnosis was 69. Out of all patients aged over 50 (n?=?3,347), the rate of PMR was 0.22% in men or 0.36% in women, respectively. On the other hand, RS3PE syndrome was diagnosed in 3 men (76, 76, and 81?years old). The rate of patients with RS3PE syndrome was 0.09% among outpatients aged over 50 indicating that the rate of PMR in an outpatient clinic in Japan is not far from previous findings reported from western countries. When compared with PMR, the rate of RS3PE syndrome was approximately one-third, providing for the first time the rate of RS3PE syndrome when compared with PMR. These epidemilogical data might help us pick up the diseases in primary care setting in Japan.     

Parvovirus B19: another agent associated with remitting seronegative symmetrical synovitis with pitting edema

A number of conditions have been associated with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) and the controversy of whether this should be considered a syndrome rather than a disease continues. There are few reports on the role of infectious agents in the etiology of RS3PE, and human parvovirus B19 has not previously been linked to this syndrome. We describe a patient with RS3PE syndrome in association with positive serology and viremia for parvovirus B19. A 9-year followup failed to uncover another cause for RS3PE.     

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 following intravesical bacillus Calmette-Guérin instillation

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare syndrome of undetermined etiology occurring in the elderly. We describe the first case of RS3PE in a HLA-B27 positive 65-year-old man following intravesical bacillus Calmette-Guérin (BCG) instillation for bladder carcinoma. He developed symmetrical arthritis and synovitis involving wrists, knees, ankles, and metatarsophalangeal joints, with marked pitting edema of the dorsa of both hands and feet, fever, and elevated acute phase reactants. Right knee effusion revealed nonspecific sterile inflammatory fluid. He responded dramatically to nonsteroidal antiinflammatory drugs. BCG instillation may have triggered active symmetrical synovitis via local T cell activation and a T-helper-1 (Th-1)/Th-2 inflammatory profile.     

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.     

Magnetic resonance imaging findings in a case of remitting seronegative symmetrical synovitis with pitting edema

We describe a case of remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome) in a 66-year-old man. This report discusses magnetic resonance imaging findings of RS3PE syndrome and the changes after steroid therapy.     

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.     

Sarcoidosis with high serum levels of vascular endothelial growth factor (VEGF), showing RS3PE-like symptoms in extremities

We report a patient with sarcoidosis who showed edema in the distal portion of all extremities, particularly the legs, as seen in remitting seronegative symmetrical synovitis with pitting edema (RS3PE). Magnetic resonance imaging demonstrated diffuse abnormal intensity in subcutaneous tissues of both legs, and skin biopsy led to a diagnosis of sarcoidosis. Vascular endothelial growth factor (VEGF) showed a high serum level, which decreased soon after starting oral prednisolone, in parallel with an improvement in the limb edema. In this patient VEGF as well as infiltration by sarcoid granuloma in the skin might have played an important role in the pathogenesis of RS3PE-like symptoms in the extremities. When painful pitting edema is seen predominantly in the distal portion of all extremities, sarcoidosis as well as RS3PE should be considered as a possible diagnosis.Abbreviations ACE Angiotensin converting enzyme - RS3PE Remitting seronegative symmetrical synovitis with pitting edema - VEGF Vascular endothelial growth factor     

Gastric carcinoma in association with remitting seronegative symmetrical synovitis with pitting edema.

We describe an elderly woman who developed remitting seronegative symmetrical synovitis with pitting edema (RS3PE). In addition to typical findings, she had increased alkaline phosphatase; and investigations revealed metastatic gastric carcinoma. The literature relating to RS3PE in association with neoplasia is reviewed.     

Paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome): a report of two cases and review of the literature

We report two cases of paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE) associated with prostatic adenocarcinoma. One of the patients was positive for Helicobacter pylori and the other had secondary bone metastases. In the latter, the clinical picture of RS3PE developed after surgical intervention for the primary lesion. On physical examination, while the hands and feet were swollen in the first patient, pitting edema was present only at the feet of the other. All joints of the affected hands and feet were painful. Serological tests including rheumatoid factor, antinuclear antibody, and human leukocyte antigen B27 were all negative. Response to low-dose corticosteroid treatment was delayed in the first patient, but the symptoms were relieved better in the second one.     

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.     

Dynamic gadolinium-enhanced fat-suppressed T1-weighted MRI (chemical shift selective images) for remitting seronegative symmetrical synovitis with pitting edema

A 75-year-old man suddenly suffered from polyarthralgia and pitting edema in his distal extremities. Laboratory tests revealed inflammation, negative rheumatoid factor, and positive B7 human leukocyte antigen typing. Severe synovitis was observed in dynamic gadolinium-enhanced fat-suppressed (DGEFS) T1-weighted images of his right hand. Our diagnosis was remitting seronegative symmetrical synovitis with pitting edema (RS₃PE syndrome). He responded dramatically to low-dose corticosteroids, after which his synovitis remarkably improved as observed with DGEFS imaging. DGEFS imaging is useful for distribution of synovitis in patients with RS₃PE syndrome as well as assessing the efficacy of treatment.     

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.