CASE REPORT

In January 1995 a 69 year old woman was admitted to our institute with severe pain and stiffness of the shoulders, hips, and ankles lasting up to two months, which did not respond to cortisone (prednisone 15 mg/day). Laboratory findings showed inflammation was increased and tumour markers were all negative. Table 1 reports the laboratory data. Erythrocyte sedimentation rate, C reactive protein, gammaglobulins, alanine aminotransferase were increased, whereas other parameters were normal. Rheumatoid factor was repeatedly absent.

Serum autoantibodies (antinuclear, antimitochondrial, anti-smooth muscle, antineutrophil cytoplasmic, extractable nuclear antigen antibodies) were evaluated owing to the rheumatological findings, but were negative, as were the tumour markers assessed (CA 19.9, carcinoembryonic antigen, α fetoprotein, and mammalian carcinoma antigen). Radiological findings of the hands, wrists, hips, ankles, and feet disclosed an increase in the space between the cutaneous surface and the bones, showing a soft tissue swelling. The patient was discharged in February 1995 with a diagnosis of benign oedematous polysynovitis and, after treatment with prednisone 15 mg/day her symptoms improved rapidly for about six months. In September 1995 the patient was readmitted to our division with the same symptoms as described above but, additionally, with ovarian swelling. Leucopenia and anaemia were present, and values of lactic dehydrogenase, alanine aminotransferase, creatinine, and blood urea nitrogen (or azotaemia) had increased (table 1).

Because of the suspected ovarian tumour the patient was admitted to the institute of obstetrics and gynaecology of our hospital. Examination showed diffuse articular pain and myalgia and limited motion of ankles, hips, wrists, and shoulders. A tenosynovitis of muscle tendons of the hands as well as a pitting oedema of hands, feet, ankles, and knees were also present bilaterally.

We performed a pelvic ultrasonography and showed that the uterus had a normal density, but the ultrasound findings of the right ovary were compatible with a tumour. Computed tomography of the abdomen and pelvis confirmed the presence of an irregular pelvic mass in the right adnexal site with maximum diameter of 5 cm associated with a retroperitoneal adenopathy affecting the lumboaortic lymph nodes with a moderate ascites in the Douglas pouch. The serum Ca 125 level was much higher than normal and the interleukin 6 serum concentration was increased (table 1).

Surgical intervention allowed debulking and the biopsy specimen showed the presence of a serous cystoadenocarcinoma, moderately differentiated (FIGO stage IIb, grading G2). The pitting oedema, the absence of muscular pain, laboratory findings, and the muscle biopsy ruled out a diagnosis of polymyositis-dermatomyositis. In addition, the absence of eosinophilia and involvement of the palmar fascia excluded other characteristic diseases associated with neoplasms. After debulking, the patient underwent cytoreductive chemotherapy (CisPlatinum 75 mg/m², Adriblastin 30 mg/m2, and cyclophosphamide 750 mg/m² (PAC schedule), for four cycles of 28 days). Subsequently, owing to a positive response, the patient had a total hysterectomy. In October 1995 the patient was discharged with treatment with prednisone 20 mg/day, which was tapered to 10 mg/day after the first month. From November 1995 the rheumatological symptoms were absent, and in January 1996 the patient suspended the prednisone treatment and underwent six cycles of adjuvant PAC based chemotherapy. To date, the patient is alive and none of the previously reported symptoms have reappeared.

DISCUSSION

Several cases of RS3PE have been reported.8-12 This syndrome has been recognised since 1985, and an association with a malignancy was found in only two cases. It is probably related to HLA-B7 (relative risk 9.5)3 ,13 ,14 and to HLA-A2 haplotypes15 and affects more men than women (sex ratio M:F=2:1) and the elderly. Our patient showed all the symptoms and signs of RS3PE: she was elderly, had a symmetrical polysynovitis, pitting oedema over the major joints, seronegativity for rheumatoid factor, symmetrical involvement of the sheath of the flexor muscle tendons of the hands, morning stiffness, spreading pain, and partial ankylosis of the shoulder. Some authors have reported a rapid response to low doses of steroids, with a progressive and complete recovery. In our patient, the signs indicating that this was not a simple RS3PE were the coexisting neoplasm, the poor response to the steroids given, and the disappearance of symptoms after total hysterectomy and lymphadenectomy. The clinical findings of RS3PE before the discovery of the neoplasm and its disappearance after the hysterectomy suggest a definite association between oncological and rheumatological diseases, even though a linkage has not yet been demonstrated. In fact, the remission of RS3PE with chemotherapy against the tumour might be due to the efficacy of this treatment on immunological and inflammatory diseases. However, findings leading to a diagnosis of RS3PE, which is not responsive to steroids, may predict the presence of a neoplasm at an early stage before its clinical manifestation. If this were the case RS3PE would behave as other “sentry” syndromes found in rheumatology—for example, neurological findings before a clear diagnosis of systemic lupus erythematosus, or respiratory disease before the renal involvement in Wegener's disease. We found that the serum interleukin 6 concentration was higher than normal, as previously reported in the association with prostatic adenocarcinoma.7

Our experience suggests that a diagnosis of RS3PE, not responsive to low doses of steroids, may indicate an association with a neoplasm before the clinical manifestation of the latter, allowing a fundamental advance in the diagnosis and treatment of the malignancy.