Clinical diagnosis
Case 79
【Progress】She was given corticosteroids (predonine 15mg) which induced gradually improvement of symptoms. The doses of corticosteroids were scheduled to be quickly tapered. Five days later, she was discharged.
【Discussion】
Remitting seronegative symmetric synovitis with pitting edema (RS3PE) is characterized as follows: negative rheumatoid factor; sudden onset of polyarthritis; (symmetric) pitting edema at dorsum of bilateral hands and feet; general malaise: radiographs showing no bone erosion (1-3). RS3PE usually occurs in aged persons with more than 50 years. RS3PE has a benign clinical course because of the good response (remitting) to low-dose corticosteroids.
Recent studies revealed that RS3PE is caused by production of vascular endothelial growth factor (VEGF) induced by Interleukin 6 (4, 5). VEGF induces proliferation of vascular endothelial cells, enhances angiogenesis and accelerates permeability of vessel wall leading to arthritis, tenosynovitis and edematous upper and lower extremities. It can occur pleural and pericardial effusions (4 – 7). However, the pathogenesis of RS3PE in what triggers to produce Interleukin 6 and VEGF is not known. VEGF production plays a central role in angiogenesis, related to formation of tumor neo-vascularization. In fact, RS3PE is reported to have a greater weight loss (28.5 to 54.4%) associated with malignant tumor as para-neoplastic syndrome (6, 7). However, paraneoplastic RS3PE has a poor response to treat with corticosteroids, only resolving with successful treatment of underlying malignancy (6, 7).
The main differential diagnosis is polymyalgia rheumatica (PMR) which very mimics in terms of polyarthritis of shoulder and pelvic girdle with systemic symtoms of fever, malaise, fatigue and weight loss (8). However, PMR requires more protracted and higher corticosteroids, whereas RS3PE can be tapered more rapidly with persisting remission (2-3).
As imaging diagnosis, MRI and echo show edema of subcutaneous and peritendinous soft tissue, and symmetric polysynovitis of metacarpophalangeal, interphalangeal, tarsal and metatarsophalangeal joints (8 – 10)
In our patient aged 64 years, although she did not own malignant tumor indicating to be idiopathic, she presented to have polymyalgia, marked weight loss, and pitting edema at bilateral hands and feet. MRI showed synovitis of MP and PIP joints and tenosynovitis of both flexor and extensor tendon (Figs 1 to 4). She had suffered from these symptoms for two months before her coming to us because of no effectiveness of NSAIDs, indicating a relatively acute onset.
【Summary】
We present a sixty four-year-old female with R3SPE which is relative acute onset of polyarthritis, malaise and pitting edema at bilateral hands and feet. MRI showed synovitis of MP and PIP joints and tenosynovitis of both flexor and extensor tendon. We should keep in mind that MRI show edema of subcutaneous and peritendinous soft tissue, and symmetric polysynovitis of metacarpophalangeal, interphalangeal, tarsal and metatarsophalangeal joints that is caused by production of VEGF and Interleukin 6. VEGF induces proliferation of vascular endothelial cells, enhances angiogenesis and accelerates permeability of vessel wall.
【References】
1.McCarty DJ,et al. Remitting seronegative symmetrical synovitis with pitting edema. RS3PE syndrome. JAMA. 1985;254:2763–7. doi: 10.1001/jama.1985.03360190069027. [PubMed] [Cross Ref]
2.Yao Q, et al. Is remitting seronegative symmetrical synovitis with pitting edema (RS3PE) a subset of rheumatoid arthritis? Semin Arthritis Rheum. 2010;40:89–94. doi: 10.1016/j.semarthrit.2008.11.006. [PubMed] [Cross Ref]
3.Keenan RT, Hamalian GM, Pillinger MH. RS3PE presenting in a unilateral pattern: Case report and review of the literature. Semin Arthritis Rheum. 2009;38:428–33.
4.Cohen T. Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem. 1996 12;271(2):736-41.
5.Yanamoto S. Idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome associated with bilateral pleural and pericardial effusions: a case report. J Med Case Rep. 2016; 10: 198. Published online 2016 Jul 20. doi: 10.1186/s13256-016-0983-7 PMCID: PMC4955210
6.Ciro Manzo. The paraneoplastic meaning of R3SPE (remitting seronegative simmetrical synovitis with pitting edema) syndrome. J Med Oncl Ther 2016; 1 (2): 72-75
7.Sayarlioglu M. Remitting Seronegative Symmetrical Synovitis With Pitting Edema (RS3PE) Syndrome and Malignancy. European Journal of General Medicine 2004; 1(2):3-5
8.Cantini F, et al. Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome: a prospective follow up and magnetic resonance imaging study. Ann. Rheum. Dis. 1999 :58: 230-236
9.Unlu Z, Orguc S, Ovali GY, et al. MRI findings in a case of remitting seronegative symmetrical synovitis with pitting edema. Clin Rheumatology 2005; 24: 648-51.
10.Takeguchi T, Sugawara Y, Kikuchi K, et al. RS3PE: Scintigraphic and Magnetic resonance imaging findings. Clinical Nuclear Medicine. 2003; 28: 766-69
2017.11.8