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Patient: Male, 83
Final Diagnosis: Remitting seronegative symmetrical synovitis with pitting edema
Symptoms: Morning stiffness · pitting edema of the hands · shoulder and hip pain
Medication: —
Clinical Procedure: 18FDG PET/CT
Specialty: Rheumatology
Objective: Rare disease
患者：男，83岁
最终诊断：缓和性血清阴性的对称性滑膜炎伴凹陷性水肿
症状：晨僵，手部凹陷性水肿
药物处理：—
临床过程：18FDG PET/CT
所涉专业：风湿科
目的：罕见病
Background: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare condition that occurs in elderly individuals. It can present alone or in association with various rheumatic or malignant diseases.
背景：缓和性血清阴性的对称性滑膜炎伴凹陷性水肿（RS3PE）是一种发生于老年患者的罕见症状。可能单独出现，也可能伴有多种风湿性或恶性疾病。
Case Report: An 83-year-old man presented with anemia, hyper-sedimentation, and pitting edema of the back of the hands. The patient complained of pain and stiffness of the shoulder and hip girdles, especially in the morning. He was previously diagnosed with adenocarcinoma of the prostate. After 3 years of watchful waiting, treatment with goserelin, a gonadotropin releasing hormone agonist, was started, when PSA had increased to 67.9 μg/l. About 1 year before the cancer treatment, the patient also presented with sore and swollen hands, compatible with RS3PE, which remitted after a few months of prostatic cancer treatment. Thorough laboratory evaluation was performed upon admission to the Rheumatology Department and he was referred for FDG PET/CT on suspicion of metastases of the previously diagnosed prostatic cancer. PET/CT imaging revealed increased FDG up-take in the soft tissues around the shoulders and hips, but no evidence of bone metastasis or other malignant findings. A diagnosis of polymyalgia rheumatica (PMR) together with RS3PE syndrome was made and treatment with prednisolone 15 mg/d was started, which resulted in rapid resolution of the symptoms.
病例报告：患者，男，83岁。出现贫血，超沉淀，背部和手部凹陷性水肿。主诉：肩膀和髋带僵硬，在早上尤为如此。患者之前被诊断为前列腺癌。观察等待治疗3年后，患者PSA升至67.9μg/l，于是开始戈舍瑞林和促性腺激素释放激素激动剂治疗。在开始癌症治疗前1年，患者出现手部酸痛，肿胀症状，与RS3PE一致，前列腺癌治疗在几个月后症状缓解。患者被接入风湿科后进行了全面的实验室检查，因怀疑前列腺癌转移，建议做FDG PET/CT。PET/CT检查显示肩部和髋部软组织FDG吸收增多，但是未显示骨转移或者其他的恶性肿瘤。诊断为风湿性多肌痛（PMR）和RS3PE综合征，开始用药泼尼松龙15mg/d予以治疗，症状快速缓解。
Conclusions: Presence of RS3PE in relation with PMR and prostatic cancer in our patient suggests a common trigger factor. To the best of our knowledge, this is the first report of a case of RS3PE that presented twice with 2 different diagnoses in the same patient.
结论：该患者出现RS3PE及PMR和前列腺癌，这表明了一个共同的诱发因素。据我们所知，本文是第一篇报道同一位患者出现2次RS3PE且得出不同诊断的病例。
MeSH Keywords: Paraneoplastic Syndromes · Polymyalgia Rheumatica · Prostatic Neoplasms · Rheumatology
MeSH关键词：副肿瘤综合征；风湿性多肌痛；前列腺肿瘤；风湿病
Background
背景
Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare condition that has been reported as a paraneoplastic syndrome, frequently together with prostate, stomach, and colon cancers. It occurs in elderly individuals and is characterized by symmetrical distal synovitis, pitting edema of the dorsum of the hands, and seronegativity of rheumatoid factor. It responds well to low-dose steroids and remains in remission for a long time unless associated with malignancy.
缓和性血清阴性的对称性滑膜炎伴凹陷性水肿（RS3PE）是一种罕见的症状，被认为副肿瘤综合征，常伴随前列腺癌，胃癌及结肠癌。该病发生于老年人群，特点是对称的远端滑膜炎，手背凹陷性水肿，血清类风湿因子阴性。对低剂量的类固醇类药物反应较好，长期处于缓解阶段（除非与恶性肿瘤相关）。
Polymyalgia rheumatica (PMR) is characterized by inflammatory pain and stiffness of the shoulder and pelvic girdles, with biochemical evidence of inflammation. It occurs most frequently in patients over 50 years of age. However, clinical diagnosis of PMR is rather difficult due to the large differential diagnosis that can mimic PMR. Although malignant diseases can present with PMR-like syndrome, physicians should be aware of co-occurrence of both conditions at the same time. Here, we report the case of an 83-year-old man who presented twice with RS3PE; first as a paraneoplastic syndrome with adenocarcinoma of prostate and then with concurrent PMR.
风湿性多肌痛（PMR）的特点是炎症性疼痛和肩膀及骨盆带僵硬，伴炎症的生化证据。多发生于50岁以上人群。但是，由于许多鉴别诊断与PMR相似，所以临床诊断相当困难。虽然一些恶性疾病会出现与PMR相似的症状，医师们应注意多种症状同时发作。本文中报道的患者患过两次RS3PE；第一次是副肿瘤综合征伴前列腺癌，第二次同时并发了PMR。
Case Report
病例报告
An 83-year-old man was referred to the Rheumatology Department due to anemia, hyper-sedimentation, and pitting edema of the back of the hands. The patient complained of pain and stiffness of the shoulder and hip girdles, especially in the morning. On physical examination the patient had normal range of motion of the shoulder, but range of motion of the hip was limited. There were signs of arthritis in the left knee. He had no symptoms or signs of headache, visual problems, jaw claudication, scalp tenderness, or any other cranial symptoms. The patient had been diagnosed with adenocarcinoma of the prostate 4 years before the presentation of these symptoms. Prostate-specific antigen (PSA) and Gleason score were 16 μg/l and 5 (2+3), respectively, at that point of time. He was under watchful waiting for 3 years until the PSA increased to 67.9 μg/l. This triggered initiation of hormonal ablation. Therefore, treatment with injection of goserelin 10.8 mg every 3 months, together with bicalutamide 150 mg/day in the first 2 weeks, was started. After 9 months, treatment was changed to leuprorelin every 6 months and the PSA level decreased to less than 0.1 μg/l within 3 months after treatment. One year before the initiation of treatment with goserelin, the patient also had sore and swollen hands, compatible with RS3PE. This phenomenon
disappeared when PSA level fell to 0.3 μg/l.
患者，男，83岁。因贫血，超沉淀，背部和手部凹陷性水肿而被送至风湿科。主诉：肩膀和髋带僵硬，在早上尤为如此。体检发现，患者肩部活动度正常，髋部活动受限。左膝有关节炎症状。无头痛，视力问题，颌跛行，头皮触痛，或者颅神经症状。4年前，患者曾被诊断为前列腺癌。当时，患者前列腺特异性抗原（PSA）和格里森分级积分分别为16μg/l和5（2+3）。观察等待治疗3年后，患者PSA升至67.9μg/l，于是开始戈舍瑞林治疗（每3个月10.8mg），加比卡鲁胺150mg/天（前两周）。9个月后，改用亮丙瑞林（每6个月），治疗三个月PSA水平降至0.1 μg/l以下。开始戈舍瑞林治疗前一年，患者患者出现手部酸痛，肿胀症状，与RS3PE一致。PSA水平降至0.3μg/l时现象消失。
Results of laboratory evaluations are summarized in Table 1. The patient was anemic and the levels of erythrocyte sedimentation rate and C-reactive protein had increased. Bone marrow aspiration was done to rule out hematological malignancy or bone metastasis; results were normal and demonstrated normal surface antigen with normal karyotype. The result of peripheral blood smear showed hypochromic erythrocytes with a slight increase in nucleated blood cells without immature or plasma cells. The patient was referred for FDG PET/CT scan due to suspicion of metastases. FDG PET/CT is a routine examination in cases of suspected occult cancer or suspected metastases from known cancer, as well as to identify causes of rheumatologic diseases. The results of FDG PET/CT imaging visualized a strong FDG uptake in the soft tissues around the shoulders and hips, consistent with PMR (Figure 1). There was no evidence of bone metastases and no other findings suspicious for malignancies. Therefore, the patient was referred to the Rheumatology Department due to suspicion of an underlying rheumatologic condition. Ultrasound-guided puncture of the left knee was done to determine the cause of swelling in the affected joint, and the result showed a small increase in leucocytes (860×10E6/l, normal range <200×10e6 ))="" with="" no="" evidence="" of="" crystal="" deposition,="" which="" was="" compatible="" with="" arthrosis.="" temporal="" artery="" biopsy="" was="" performed="" to="" diagnose="" a="" possible="" inflammation="" and="" the="" result="" was="" negative.="" treatment="" with="" prednisolone="" 15="" mg/d="" was="" started="" with="" a="" tapering="" schedule="" of="" reducing="" 2.5="" mg="" every="" 2="" weeks.="" ca-vitamin="" d="" supplementation="" and="" alendronate="" 70="" mg="" every="" week="" were="" additionally="" prescribed="" to="" reduce="" the="" risk="" of="" osteoporosis.="" the="" patient="" became="" asymptomatic="" after="" a="" short="" period="" of="" time="" and="" all="" subsequent="" biochemistry="" test="" results="" were="" normal.="" decreasing="" the="" prednisolone="" dosage="" to="" 5="" mg/d="" resulted="" in="" recurrence="" of="" symptoms="" and="" slight="" increase="" in="" crp="" value.="" as="" a="" result,="" prednisolone="" dosage="" was="" increased="" to="" 12.5="" mg/d="" again,="" whereupon="" symptoms="" disappeared,="" and="" that="" was="" successfully="" tapered="" afterward.="" the="" prednisolone="" medication="" was="" ceased="" after="" 18="" months,="" without="" any="" related="" adverse="" effects.="" after="" 4-year="" follow-up="" in="" the="" rheumatology="" department="" and="" 8="" years="" after="" cancer="" diagnosis,="" the="" patients="" is="" still="" alive="" and="" has="" no="" symptoms="" or="" signs="" of="" pmr="" or="" rs3pe,="" without="" having="" any="" evidence="" of="" cancer="" recurrence,="" and="" psa="" level="" has="" remained="" undetectable="" (psa=""><0.1 μg/l).="" he="" also="" has="" no="" complaints="" of="" pain="" in="" the="" left="" knee="" and="" recently="" started="" to="" exercise="" at="" a="">
表1总结了实验室检查结果。患者贫血，红细胞沉降速率和C反应蛋白水平升高。进行骨髓穿刺以排除血液系统恶性肿瘤和骨转移，结果正常，核型和表面抗原均正常。外周血涂片显示低色素红细胞，有核血细胞略有增加，无未成熟细胞或者浆细胞。因怀疑前列腺癌转移，建议做FDG PET/CT。FDG PET/CT是一种对已知癌症是否有隐匿性癌或者癌转移的常规检查，且能识别风湿性疾病的病因。FDG PET/CT结果显示肩部和髋部软组织FDG吸收增多，与PMR一致（图1）。没有证据表明骨转移及其他恶性肿瘤。由于怀疑潜在的风湿性疾病，患者被接入风湿科。行超声指导的左膝穿刺术检测左膝肿胀原因，结果显示白细胞增多（860×10E6/l, 正常范围 <200×10e6 ），无证据表明晶体沉积（与关节病一致）。进行颞动脉活检以诊断炎症，结果为阴性。用药泼尼松龙15mg/d予以治疗，每两周剂量减少2.5mg，每周补充钙-维生素d和阿仑膦酸钠70mg以降低骨质疏松症的风险。很快，患者无症状，后续的化学检查结果均显示正常。泼尼松龙剂量减至5mg/d时，患者症状复发，crp值轻微增高。结果，泼尼松龙剂量再次增加，至12.5mg/d，症状消失，此后，泼尼松龙剂量再次递减。18个月后停药泼尼松龙，无任何相关的副作用。风湿科随访4年，确诊癌症后随访8年，患者仍无pmr或者rs3pe症状，无癌症复发的症状，psa水平仍无法测得（psa=""><0.1>
图1： 
Discussion
讨论
RS3PE is a rare condition in the elderly and can appear as a first presentation of various types of rheumatic and malignant diseases. It is first described by McCarthy et al. in 1985. The etiology of the RS3PE syndrome is unknown, but environmental factors and infection may affect the course of the disease. It can present alone or in association with rheumatic diseases (e.g., PMR and late-onset rheumatoid arthritis) and malignancies. Diagnosis is based on clinical features. Absence of erosive or degenerative changes plus dramatic response to low-dose corticosteroid treatment is characteristic of the disease.
RS3PE是一种罕见的发生于老年患者的疾病，可能是各种风湿性或恶性疾病的第一表现。RS3PE由McCarthy等人于1985年首次报道。病因尚不清楚，可能单独出现，也可能伴有多种风湿性疾病（如PMR和后来发作的类风湿性关节炎）和恶性肿瘤。诊断基于临床特点。缺乏腐蚀性或者退行性病变加上对低剂量的糖皮质激素治疗有显著反应是该病的特点。
PMR is the most common rheumatic disease in older individuals. It is difficult to diagnose PMR due to the wide variation in clinical picture. In addition, there are no specific tests available for PMR. Presenting symptoms, including proximal pain and stiffness, a commonly accepted characteristic of PMR, are not indicative of PMR and can occur in other rheumatologic diseases. However, distal manifestations, such as peripheral arthritis and carpal tunnel syndrome, present in half of PMR cases.
PMR是老年患者中最常见的风湿性疾病。由于许多临床症状与PMR相似，所以诊断相当困难。而且，PMR没有特异性检查。近端疼痛或者僵硬等症状是普遍接受的PMR的特征，其他风湿性疾病也可能出现这些症状。但是，外周关节炎和腕管综合征等远端症状出现在一半的PMR患者中。
Treatment with glucocorticoids is a mainstay and it results in rapid resolution of symptoms. The British Society for Rheumatology and British Health Professionals in Rheumatology recommend use of prednisolone 15 mg/d when the diagnosis is established. Subsequently, the dosage should be gradually tapered over time. All patients diagnosed with PMR should commence calcium and vitamin D supplementation to reduce risk of osteoporosis.
治疗主要为糖皮质激素，可快速缓解症状。英国风湿病协会和英国风湿病专家建议，确诊后用药泼尼松龙15mg/d。之后渐渐减少剂量。所有诊断为PMR的患者应开始补充钙和维生素以降低骨质疏松症的风险。
Several previous studies reported a PMR-like syndrome as a presenting manifestation of various malignant diseases (e.g., prostate cancer, renal cell carcinoma, and lymphoma). Other malignancies mimicking PMR include cancers of the gastrointestinal system, lungs, pancreas, uterus, and ovaries. However, PMR patients have an increased risk of malignancies. A recent cohort study by Muller et al. Showed a 69% increased risk of malignancies in PMR patients within the first 6 months after a PMR diagnosis. When our patient was referred with suspected PMR, it was obvious to suspect a condition like metastatic prostate cancer mimicking PMR, but this was not shown by the FDG PET/CT scan. The subsequent diagnosis of PMR concurrent with RS3PE was seen as an independent phenomenon. Since PMR and RS3PE presented and disappeared almost at the same time, it can be assumed that there is an association between them.
之前有一些研究报道了类似PMR综合征，将其作为多种恶性疾病的临床表现（如前列腺癌，肾细胞癌，淋巴瘤）。还有一些恶性肿瘤与OMR相似：消化系统肿瘤、肺癌、胰腺癌、子宫瘤和卵巢癌。然而，PMR患者患上恶性肿瘤的风险增加。近来，Muller等人进行了一项队列研究，结果显示在确诊PMR后6个月内，PMR患者患上恶性肿瘤的风险增加了69%。本文所述患者疑似PMR，显然可能是与PMR相似的前列腺癌转移，但是患者的FDG PET/CT检查将其排除。PMR并发RS3PE的后续诊断被视为一种独立的现象，由于PMR并发RS3PE几乎在同一时间出现或消失可以认为之间有某种联系。
RS3PE may present before, concurrent with, or after the diagnosis of malignant disease. In our case the RS3PE syndrome presented approximately 1 year before prostate cancer was estimated to need treatment, and the syndrome disappeared again after about 6 months of cancer treatment, which suggests a correlation between these 2 conditions. Considering the long disease history of prostate cancer, it might reasonably be assumed that the patient had been suffering from prostatic cancer for a very long time before the diagnosis. If the prostatic cancer was the triggering factor for RS3PE (in this case, when tumor burden was large enough), one could speculate that there are potential immunological mechanisms triggering RS3PE.
RS3PE可能在确诊恶性疾病之前、同时或者之后出现。本例患者中，RS3PE综合征出现在前列腺癌前约一年，在治疗癌症6个月后再次出现，这表明二者之间有联系。考虑到患者的几年的前列腺癌病史，在确诊之前患者应该已经经历了很长时间的前列腺癌的折磨。如果前列腺癌是RS3PE的诱因（本例，肿瘤负担足够大），则可推测存在某种潜在的免疫机制诱发了RS3PE。
Conclusions
结论
This report illustrates a rare case of RS3PE that occurred together with PMR and prostate cancer. Presence of RS3PE first, simultaneously with prostatic cancer, as a paraneoplastic syndrome, and thereafter concurrent with clinical presentation of PMR, suggests a common trigger factor for RS3PE from a prostatic cancer and PMR. It has previously been reported that there is an association between prostatic cancer and PMR as well as RS3PE. On the other hand, RS3PE was found to be correlated with prostatic cancer and PMR. However, in the presented case prostatic cancer and PMR were seen together with RS3PE, although not at the same time. In line with earlier studies, our case report suggests that PMR and RS3PE belong to the same clinical entity. To the best of our knowledge, this is the first case report of RS3PE presenting twice in 2 different diagnoses in the same patient.
本文呈现了罕见的RSEPE伴PMR和前列腺癌一例。患者先出现RS3PE，同时出现前列腺癌，作为一种副肿瘤综合征，此后在原来基础上同时并发PMR的临床表现，这表明RS3PE伴前列腺癌和PMR有一个共同的诱导因素。之前有报道称前列腺癌与PMR及RS3PE之间有联系。另一方面，有研究发现RS3PE与前列腺癌和PMR相关。但是，本例患者前列腺癌和PMR都与RS3PE同时出现（前列腺癌和PMR并非同时出现）。考虑到之前的研究，本研究表明PMR 和RS3PE属于同一种临床实体。据我们所知，本文是第一篇报道同一位患者出现2次RS3PE且得出不同诊断的病例。
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