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:10.3109/s10165-011-0556-y

Cited by 34 publications

(16 citation statements)

References 11 publications

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“…In the current study, there was no significant difference in the clinical characteristics of RS3PE between patients with and without malignancies ( Supplementary Table S3). Origuchi et al reported that RS3PE with malignancies has higher MMP-3 serum levels than RS3PE without malignancies, due to the abundant production of MMP-3 owing to malignancies [24]. In our study, there was no difference in MMP-3 levels.…”

Section: Comparison Between Rs3pe Patients With and Without Malignanciescontrasting

confidence: 49%

Comparing the Clinical and Laboratory Features of Remitting Seronegative Symmetrical Synovitis with Pitting Edema and Seronegative Rheumatoid Arthritis

Higashida-Konishi

Izumi

Hama

et al. 2021

JCM

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In seronegative arthritis with extremity edema, it is difficult to differentiate between remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) and seronegative rheumatoid arthritis (SNRA). We compared the clinical characteristics of RS3PE and SNRA in patients with and without malignancies. We retrospectively examined patients diagnosed with RS3PE (McCarty criteria) and SNRA at our hospital in 2007–2020. Malignancy was diagnosed within 2 years before or after RS3PE or SNRA diagnosis. Overall, 24 RS3PE and 124 SNRA patients were enrolled. The median ages were 79.5 and 68.5 years, and men comprised 54.2% and 37.1% of RS3PE and SNRA patients, respectively. RS3PE patients had higher inflammation levels (p = 0.004) and more incidences of malignancy (p = 0.034). Matching for age and sex, RS3PE patients had higher inflammation levels (p = 0.021) and more incidences of malignancy (p = 0.005). Overall, odds ratios (ORs) for malignancy were higher for older age (OR 1.06, p = 0.037), male sex (OR 4.34, p = 0.007), RS3PE patients (OR 4.83, p = 0.034), and patients with extremity edema (OR 4.83, p = 0.034). Inflammation levels and associated factors of malignancy were higher in RS3PE patients than in SNRA patients. Patients who are older, male, with extremity edema, or had RS3PE should be screened for malignancies.

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Section: Comparison Between Rs3pe Patients With and Without Malignanciescontrasting

confidence: 49%

Comparing the Clinical and Laboratory Features of Remitting Seronegative Symmetrical Synovitis with Pitting Edema and Seronegative Rheumatoid Arthritis

Higashida-Konishi

Izumi

Hama

et al. 2021

JCM

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“…Origuchi T that 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). 33 When we suspect of RS3PE, the possibility of malignancies cannot be entirely excluded even if the initial presentation seems not to be. There is still many rooms to learn about RS3PE but on diagnosis, associations with other rheumatologic conditions and neoplasia should be borne in mind.…”

Section: Discussionmentioning

confidence: 99%

A Case with Fever and Multiple Joint Pain

Okada

Shimizu

2014

Gen. Med.

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“…Elevated levels of vascular endothelial growth factor (VEGF) have been observed in RS3PE patients and given its potent vasodilatory effect, VEGF is speculated to play a role in RS3PE disease pathogenesis. [9] In addition to VEGF, elevated levels of interleukin-6 and matrix metalloporoteinase-3 have been observed in RS3PE patients [10,11] ; however, their role in RS3PE pathogenesis is elusive. One study showed that combination of dexamethasone and DMARD(s) could synergistically or addictively suppress VEGF production from synoviocytes of patients with rheumatoid arthritis, [12] suggesting that 5-10 mg prednisone was not enough to suppress VEGF production to prevent RS3PE in our case.…”

Section: Discussionmentioning

confidence: 99%

RS3PE Following Treatment With Combination of Hormonal Therapies Plus Ipilimumab in a Patient With Metastatic Prostate Cancer

Kim

Murphy

Aparicio

et al. 2020

Journal of Immunotherapy and Precision Oncology

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Introduction Immune checkpoint inhibitors (ICIs) are often associated with inflammatory toxicities known as immune-related adverse events (irAEs). Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is an atypical inflammatory arthritis. Herein, we report a case of RS3PE in a patient with metastatic prostate cancer who was receiving a combination of second-generation hormonal therapies plus ipilimumab. Case Presentation A 59-year-old man with metastatic prostate cancer developed sudden onset of pain and swelling of the right hand after 15 weeks of treatment with second-generation hormonal therapies plus three cycles of ipilimumab. Symptoms alternated to the left hand. Physical examination showed tender, pitting edema of the left hand with tenderness on the right second through fifth metacarpal phalangeal joints, leading to the diagnosis of RS3PE. Ipilimumab was withheld, and the RS3PE self-resolved; however, 1 month later, the patient had another flare of RS3PE. A bone scan showed active inflammation on bilateral wrists and hands. Methotrexate was initiated, and his symptoms resolved over a few days. Methotrexate was discontinued 2 months later, and RS3PE has been in complete remission. His prostate cancer progressed, and radium-223 treatment was initiated. Conclusion To the best of our knowledge, this is the first reported case of RS3PE after the combined second-generation hormonal therapy plus ipilimumab. Both rheumatologists and oncologists should be aware that RS3PE can develop as an irAE. Understanding the mechanism of ICI therapy–associated RS3PE is critical to identify predictive biomarkers and develop optimal therapeutic strategies that do not sacrifice antitumor immunity.

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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 34 publications

References 11 publications

Comparing the Clinical and Laboratory Features of Remitting Seronegative Symmetrical Synovitis with Pitting Edema and Seronegative Rheumatoid Arthritis

Comparing the Clinical and Laboratory Features of Remitting Seronegative Symmetrical Synovitis with Pitting Edema and Seronegative Rheumatoid Arthritis

A Case with Fever and Multiple Joint Pain

RS3PE Following Treatment With Combination of Hormonal Therapies Plus Ipilimumab in a Patient With Metastatic Prostate Cancer

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