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

Origuchi, Tomoki; Arima, Kei; Kawashiri, Shin‐ya; Tamai, Mami; Yamasaki, Satoshi; Nakamura, Hideki; Takahashi, Toshiaki; Aramaki, Toshiyuki; Furuyama, Masako; Miyashita, Taiichiro; Kawabe, Yojiro; Iwanaga, Naoki; Terada, Kaoru; Ueki, Yukitaka; Fukuda, Takaaki; Eguchi, Katsumi; Kawakami, Atsushi

doi:10.1007/s10165-011-0556-y

Cited by 22 publications

(17 citation statements)

References 13 publications

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“…However, the symptoms disappeared as the tumor size was rapidly decreased by gefitinib therapy. Especially given that paraneoplastic RS3PE syndrome is refractory to steroids although non-paraneoplastic RS3PE syndrome is normally responsive to steroids [ 6 ], the present case further supported the possible hypothesis that paraneoplastic RS3PE syndrome might be caused by tumor-induced VEGF.…”

Section: Discussionsupporting

confidence: 79%

A Case of Paraneoplastic Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome Improved by Chemotherapy

et al. 2017

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The patient was a 69-year-old male who had started experiencing acute-onset pain in both shoulder joints and edema of both hands and feet. His symptoms progressively worsened within 1 month. Laboratory data indicated elevated CRP and erythrocyte sedimentation rate despite the normal range of antinuclear antibodies and rheumatoid factor and normal organ function. Furthermore, imaging data of the hand indicated synovitis without bone erosions. Meanwhile, chest CT revealed a lung tumor, leading to a diagnosis of primary lung adenocarcinoma with EGFR mutation (cT2aN3M0, stage IIIB). Based on these findings, he was diagnosed as suffering from paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Thereafter, his symptoms disappeared as the tumor size was rapidly decreased by gefitinib therapy for lung adenocarcinoma. Currently, RS3PE syndrome can be classified as a vascular endothelial growth factor (VEGF)-associated disorder. Given that his symptoms improved by chemotherapy, the present case further supported the possible hypothesis that paraneoplastic RS3PE syndrome might be caused by tumor-induced VEGF. Therefore, the present case suggested that the symptoms of acute-onset joint pain accompanied by pitting edema in elderly patients should be considered suspicious for a malignant tumor, thereby warranting a detailed full-body examination.

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Section: Discussionsupporting

confidence: 79%

A Case of Paraneoplastic Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome Improved by Chemotherapy

et al. 2017

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“…In the same report, tumor necrosis factor α and interleukin-1 levels were not different Additional Japanese reports showed elevated VEGF levels in one patient with sarcoidosis and RS3PE, with subsequent reduction after glucocorticoid treatment [45], one patient with angioimmunoblastic T cell lymphoma [28], and another patient with RS3PE and myasthenia gravis [58]. In addition, interleukin-6 and matrix metalloproteinase-3 have been reportedly elevated in RS3PE patients with neoplasia versus those without as well [59,60]. It is postulated that neoplasia, other medical conditions, and drugs may trigger production of VEGF and other molecules, which in turn result in polyarthritis/polysynovitis and subcutaneous pitting edema of the extremities by inducing vascular permeability in RS3PE syndrome [61].…”

Section: Advances Of Pathogenic Study In Rs3pementioning

confidence: 90%

RS3PE: Clinical and Research Development

Altman

Yao

2015

Curr Rheumatol Rep

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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.

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“…As a result, VEGF contributes to a neoplasm's ability to grow, invade, and metastasize [37]. Other biomarkers that maybe elevated in patients with RS3PE include matrix metalloproteinase 3 (MMP3) and interleukin-6 [38].…”

Section: Discussionmentioning

confidence: 99%

Nivolumab induced remitting seronegative symmetrical synovitis with pitting edema in a patient with melanoma: a case report

et al. 2018

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Background: Novel immune checkpoint inhibitors have been often utilized for different types of malignancies as salvage therapy with varying success. One obstacle to immune checkpoint inhibitor use is the higher incidence of immune-mediated side effects that can prompt discontinuation of therapy. Remitting seronegative symmetrical synovitis with pitting edema has been described with immune checkpoint inhibitors only once previously. We report a case of a patient who developed remitting seronegative symmetrical synovitis with pitting edema related to immune checkpoint inhibitor therapy and stress that these symptoms can be managed without cessation of immune checkpoint inhibitor therapy. Case presentation: We present a 70-year-old white man who presented with 4 months of progressive inflammatory arthritis with pitting edema. He had been started on nivolumab therapy for his metastatic melanoma with excellent response prior to symptom onset. The symptoms started in his knees and subsequently involved both hands and feet. On evaluation, he was wheelchair bound and completely dependent for all activities of daily living. Evaluation revealed negative serological testing and plain film imaging. Ultrasound demonstrated diffuse flexor tenosynovitis and soft tissue swelling, and a diagnosis of remitting seronegative symmetrical synovitis with pitting edema was made. He was treated with orally administered corticosteroids (0.5 mg/kg per day) which improved his symptoms significantly and allowed him to regain prior independent functioning. His corticosteroids were tapered (0.15 mg/kg per day) but not discontinued and his nivolumab treatment was not interrupted. In follow up he continued to have stable control of his melanoma as well as his remitting seronegative symmetrical synovitis with pitting edema. Conclusions: In conclusion we present the first case of nivolumab-induced remitting seronegative symmetrical synovitis with pitting edema that is controlled by maintenance low-dose orally administered corticosteroids allowing for continuation of nivolumab therapy. Clinicians who encounter mild-to-moderate immune checkpoint inhibitor immune-mediated adverse effects can consider maintaining immune checkpoint inhibitor therapy with concomitant low-dose corticosteroids rather than abrupt cessation of the immune checkpoint inhibitor.

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

Cited by 22 publications

References 13 publications

A Case of Paraneoplastic Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome Improved by Chemotherapy

A Case of Paraneoplastic Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome Improved by Chemotherapy

RS3PE: Clinical and Research Development

Nivolumab induced remitting seronegative symmetrical synovitis with pitting edema in a patient with melanoma: a case report

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