- Email: [email protected]
RS3PE revealing recurrent non-Hodgkin’s lymphoma
Joint Bone Spine 71 (2004) 424–426 www.elsevier.com/locate/bonsoi
Case report
RS3PE revealing recurrent non-Hodgkin’s lymphoma Olivier Gisserot *, Serge Crémades, Cécile Landais, Guénaelle Leyral, Philippe Bernard, Jean-Pierre de Jauréguiberry Internal Medicine and Oncology Department, Saint-Anne Armed Forces Teaching Hospital, 83800 Toulon Naval, France Received 18 March 2003; accepted 24 July 2003 Available online 24 September 2003
Abstract A patient meeting published criteria for remitting seronegative symmetrical synovitis with pitting edema (RS3PE) was found to have a synchronous recurrence of non-Hodgkin’s malignant lymphoma. Reported cases of RS3PE associated with hematological malignancies and other forms of cancer are reviewed. © 2003 Published by Elsevier SAS. Keywords: RS3PE; Hematological malignancy; Paraneoplastic syndrome
1. Introduction Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a condition of acute polyarthritis and edema characterized by negative tests for rheumatoid factors and a dramatic response to glucocorticoid therapy, which ensures a full recovery within 2 years. After the seminal description by McCarty in 1985 [1], it was argued that RS3PE might be a syndrome rather than a clinical entity. RS3PE may be an onset pattern of chronic inflammatory joint disease in elderly patients (rheumatoid arthritis, spondyloarthropathy, Sjögren’s disease, or pseudomyalgia rheumatica), or may develop in the wake of various malignant diseases, sometimes constituting a paraneoplastic syndrome [2,3]. We report a case of RS3PE revealing a recurrence of non-Hodgkin’s lymphoma and we discuss published data on RS3PE in patients with hematological malignancies.
2. Case-report A 65-year-old woman with a history of breast cancer on the left 19 years earlier presented in September 2001 with skin nodules and enlarged lymph nodes in the right axilla and neck. Non-Hodgkin’s lymphoma with a peripheral T-cell
* Corresponding author. E-mail address: [email protected] (O. Gisserot). © 2003 Published by Elsevier SAS. doi:10.1016/j.jbspin.2003.07.005
phenotype was found. With CHOP chemotherapy, she achieved a complete remission in late December 2001. Three months later, she was admitted for a decline in general health, a fever of 38.5 °C, symmetric acute polyarthritis predominantly affecting the distal limb joints, and severe pitting edema of the dorsum of the hands and feet, with complete functional impairment. Laboratory tests showed severe inflammation (serum fibrinogen, 10 g/l; and C-reactive protein, 250 mg/l). Findings were negative or normal from tests for infection (blood and urine cultures; radiographs of the chest, sinuses and teeth; echocardiogram; and computed tomography of the chest, abdomen and pelvis) and for immunological abnormalities (rheumatoid factors, antinuclear antibodies, antineutrophil cytoplasmic antibody, circulating immune complexes and serum complement levels). No abnormalities were seen on radiographs of the involved joints (hands, wrists, knees and feet). Joint fluid from a knee showed inflammatory properties (22 000 nucleate cells with a predominance of neutrophils) without organisms or crystals. The HLA phenotype was B–08, DR B1. The only extraarticular abnormality upon physical examination was a 1-cm lymph node on the left side of the neck. Excisional biopsy showed recurrence of the T-cell non-Hodgkin’s lymphoma. Systemic glucocorticoid therapy in a dose of 0.5 mg/kg per day ensured prompt resolution of the fever, polyarthritis and edema. Despite second-line chemotherapy, progressive neurological involvement with the lymphoma was fatal 8 months after the onset of the joint manifestations, which did not recur.
O. Gisserot et al. / Joint Bone Spine 71 (2004) 424–426
425
Table 1 Hematological malignancies and RS3PE in combination: 12 cases in the literature Age/sex
1 2 3 4 5 6 7 8
NS NS NS 60/M 75/M 63/F 60/F 64/F
Constitutional symptoms (fever, anorexia, weight loss) NS NS NS – – + – +
RS3PE revealing the malignancy
Nature of the malignancy
Response to low-dose glucocorticoid therapy
HLA
Reference
Yes Yes Yes Yes (recurrence) No Yes No Yes
T-cell NHL T-cell NHL
No No No No No No No Yes (but subsequent recurrence) No
NS NS NS NS NS NS NS A2
[2] [2] [2] [6] [6] [11] [12] [13]
9
67/?
+
Yes
NHL MDS Large-cell NHL NHL bas grade Large-cell B-cell NHL NHL
A 24/31, B 52/56 NS A2, B7 NS
[14]
10 11 12
88/M 72/M 67/M
– + –
Yes No Yes
Refractory anemia Yes CLL Yes CLL Yes
[15] [16] [17]
NHL, non-Hodgkin’s lymphoma; MDS, myelodysplastic syndrome; CLL, chronic lymphocytic leukemia; NS, not specified.
3. Discussion Our patient met the criteria for RS3PE established by McCarthy: she was an older patient, experienced sudden onset of symmetric polyarthritis and severe pitting edema of the hands and feet, and had negative tests for rheumatoid factors. Several cases of RS3PE have been reported in patients with malignancies. Of the patients with solid tumors, most had adenocarcinomas: there were four cases of prostate cancer [3], three of gastric cancer [3–5], and one each of colon cancer [3], rectal cancer [6], pancreatic cancer [7], hepatocarcinoma [8], endometrial cancer [9], ovarian cancer [10] and malignant histiocytofibroma [6]. A paraneoplastic syndrome was considered in at least three patients, whose RS3PE resolved after surgical removal of the tumor [4,7,9]. Twelve cases of RS3PE in patients with hematological malignancies have been reported (Table 1). Of these 12 patients, seven had non-Hodgkin’s lymphoma [2,6,11–14], three had myelodysplastic syndrome [2,6,15], and two had chronic lymphocytic leukemia [16,17]. Although the RS3PE revealed the hematological malignancy in most cases, it occurred during the course in a few patients. In addition to our case, there has been one report of RS3PE revealing a recurrence of a malignancy [6]. Interestingly, many patients had a decline in general health and a fever, two symptoms that are exceedingly rare in “idiopathic” RS3PE. In addition, glucocorticoid therapy was less effective than expected in RS3PE. This feature may be a useful warning signal. It has been contended that classic RS3PE not linked to cancer responds to 10 mg of prednisone-equivalent or less per day [6]. In our patient, the RS3PE responded to glucocorticoid therapy, but the dose was considerably higher. In addition, the dosage used in our patient has been reported to improve hematological malignancies, most notably lymphoproliferative diseases. The pathogenesis of RS3PE remains unclear but may involve a soluble factor produced by the tumor. IL-6 level fluctuations have been shown to parallel the joint manifesta-
tions and tumor progression [3], although this does not prove production of IL-6 by the tumor. Furthermore, HLA studies in patients with RS3PE and malignancies have found an increased prevalence of the haplotypes B7 and A2 [13,16], which may confer susceptibility to the joint condition. Thus, in a patient with RS3PE, presence of constitutional symptoms and/or failure to respond to low-dose corticosteroid therapy should alert to the possibility of malignant disease. A history of malignancy further strengthens this suspicion and should prompt a careful search for a recurrence.
References [1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
McCarty DJ, O’Duffy JD, Pearson L, Hunter JB. Remitting seronegative symmetrical synovitis with edema. RS3PE syndrome. J Am Med Assoc 1985;254:2763–7. Olive A, del Blanco J, Pons M, Vaquero M, Tean X, Catalan Group for the Study of RS3Pe. The clinical spectrum of remitting seronegative symmetrical synovitis with pitting edema. J Rheumatol 1997;24: 333–6. Sibilia J, Fries S, Schaerverbeke T. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE): a form of paraneoplastic polyarthritis. J Rheumatol 1999;26:115–20. Tada Y, Sato H, Yoshinawa S, Kimura H, Kitamura M, Kusaba T, et al. Remitting seronegative symmetrical synovitis with pitting edema associated with gastric carcinoma. J Rheumatol 1997;24:974–5. Ethiopia A, Bell D. Gastric carcinoma in association with remitting seronegative symmetrical synovitis with pitting edema. J Rheumatol 1999;26:1203–4. Paira S, Graf C, Rovearno S, Rossini J. Remitting seronegative symmetrical synovitis with pitting edema: a study of 12 cases. Clin Rheumatol 2002;21:146–9. Cantini F, Olivieri I, Salvarini C. More on remitting seronegative symmetrical synovitis with pitting edema as paraneoplastic syndrome. J Rheumatol 1998;25:188–9. Nakashima H, Tanaka Y, Shigematsu H, Kanaya S, Otsuka T, Hayashida K, et al. Remitting seronegative symmetrical synovitis with pitting edema syndrome associated with cryptogenic hepatocellular carcinoma. Clin Exp Rheumatol 1999;17:390–1.
426 [9]
[10] [11] [12]
[13]
O. Gisserot et al. / Joint Bone Spine 71 (2004) 424–426 Olivo D, Mattace R. Concurrence of benign edematous polysynovitis in the elderly (RS3PE) and endometrial adenocarcinoma. Scand J Rheumatol 1997;26:67–8. Vinci M, Malaguarnera L, Pistone G. RS3PE and ovarian cancer. Ann Rheum Dis 2001;60:429–30. Roldan MR, Martinez F, Roman J, Torres A. Non-Hodgkin’s lymphoma: initial manifestation. Ann Rheum Dis 1993;52:85–6. Goldenberg K, Rozenbaum M, Rosner I, Naschitz J, Kotler C. Remitting symmetrical seronegative synovitis with pitting edema (RS3PE) secondary to non-Hodgkin’s lymphoma. Clin Exp Rheumatol 1998; 16:767–8. Baronio M, Cerudelli B, Pascarella A, Airo P. Remitting symmetrical seronegative synovitis with pitting edema associated with B-cell nonHodgkin’s lymphoma. Clin Exp Rheumatol 2000;18:787.
[14] Yamasaki T, Takeoka Y, Nakao Y, Fusamoto H. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome with malignant lymphoma. Nippon Naika Gakkai Zasshi 2002;91: 1031–3. [15] Hernandez-Beriain JA, Cuesta-Callardo I, Segura-Garcia C. Remitting seronegative symmetrical synovitis with pitting edema: a rheumatic manifestation of myelodysplastic syndrome? Rev Rhum [Eng Ed] 1996;63:629–30. [16] Cobeta-Garcia JC, Domingo-Morera JA, Martinez-Burgui J. RS3PE syndrome and chronic lymphoid leukaemia. Clin Exp Rheumatol 1999;17:26. [17] Ekenel M, Yavuz S, Karti S, Direskeneli H, Akoglu T. Remitting seronegative symmetrical synovitis with pitting edema associated with chronic lymphocytic leukaemia. Clin Rheumatol 2000;9:247–8.
Case report
RS3PE revealing recurrent non-Hodgkin’s lymphoma Olivier Gisserot *, Serge Crémades, Cécile Landais, Guénaelle Leyral, Philippe Bernard, Jean-Pierre de Jauréguiberry Internal Medicine and Oncology Department, Saint-Anne Armed Forces Teaching Hospital, 83800 Toulon Naval, France Received 18 March 2003; accepted 24 July 2003 Available online 24 September 2003
Abstract A patient meeting published criteria for remitting seronegative symmetrical synovitis with pitting edema (RS3PE) was found to have a synchronous recurrence of non-Hodgkin’s malignant lymphoma. Reported cases of RS3PE associated with hematological malignancies and other forms of cancer are reviewed. © 2003 Published by Elsevier SAS. Keywords: RS3PE; Hematological malignancy; Paraneoplastic syndrome
1. Introduction Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a condition of acute polyarthritis and edema characterized by negative tests for rheumatoid factors and a dramatic response to glucocorticoid therapy, which ensures a full recovery within 2 years. After the seminal description by McCarty in 1985 [1], it was argued that RS3PE might be a syndrome rather than a clinical entity. RS3PE may be an onset pattern of chronic inflammatory joint disease in elderly patients (rheumatoid arthritis, spondyloarthropathy, Sjögren’s disease, or pseudomyalgia rheumatica), or may develop in the wake of various malignant diseases, sometimes constituting a paraneoplastic syndrome [2,3]. We report a case of RS3PE revealing a recurrence of non-Hodgkin’s lymphoma and we discuss published data on RS3PE in patients with hematological malignancies.
2. Case-report A 65-year-old woman with a history of breast cancer on the left 19 years earlier presented in September 2001 with skin nodules and enlarged lymph nodes in the right axilla and neck. Non-Hodgkin’s lymphoma with a peripheral T-cell
* Corresponding author. E-mail address: [email protected] (O. Gisserot). © 2003 Published by Elsevier SAS. doi:10.1016/j.jbspin.2003.07.005
phenotype was found. With CHOP chemotherapy, she achieved a complete remission in late December 2001. Three months later, she was admitted for a decline in general health, a fever of 38.5 °C, symmetric acute polyarthritis predominantly affecting the distal limb joints, and severe pitting edema of the dorsum of the hands and feet, with complete functional impairment. Laboratory tests showed severe inflammation (serum fibrinogen, 10 g/l; and C-reactive protein, 250 mg/l). Findings were negative or normal from tests for infection (blood and urine cultures; radiographs of the chest, sinuses and teeth; echocardiogram; and computed tomography of the chest, abdomen and pelvis) and for immunological abnormalities (rheumatoid factors, antinuclear antibodies, antineutrophil cytoplasmic antibody, circulating immune complexes and serum complement levels). No abnormalities were seen on radiographs of the involved joints (hands, wrists, knees and feet). Joint fluid from a knee showed inflammatory properties (22 000 nucleate cells with a predominance of neutrophils) without organisms or crystals. The HLA phenotype was B–08, DR B1. The only extraarticular abnormality upon physical examination was a 1-cm lymph node on the left side of the neck. Excisional biopsy showed recurrence of the T-cell non-Hodgkin’s lymphoma. Systemic glucocorticoid therapy in a dose of 0.5 mg/kg per day ensured prompt resolution of the fever, polyarthritis and edema. Despite second-line chemotherapy, progressive neurological involvement with the lymphoma was fatal 8 months after the onset of the joint manifestations, which did not recur.
O. Gisserot et al. / Joint Bone Spine 71 (2004) 424–426
425
Table 1 Hematological malignancies and RS3PE in combination: 12 cases in the literature Age/sex
1 2 3 4 5 6 7 8
NS NS NS 60/M 75/M 63/F 60/F 64/F
Constitutional symptoms (fever, anorexia, weight loss) NS NS NS – – + – +
RS3PE revealing the malignancy
Nature of the malignancy
Response to low-dose glucocorticoid therapy
HLA
Reference
Yes Yes Yes Yes (recurrence) No Yes No Yes
T-cell NHL T-cell NHL
No No No No No No No Yes (but subsequent recurrence) No
NS NS NS NS NS NS NS A2
[2] [2] [2] [6] [6] [11] [12] [13]
9
67/?
+
Yes
NHL MDS Large-cell NHL NHL bas grade Large-cell B-cell NHL NHL
A 24/31, B 52/56 NS A2, B7 NS
[14]
10 11 12
88/M 72/M 67/M
– + –
Yes No Yes
Refractory anemia Yes CLL Yes CLL Yes
[15] [16] [17]
NHL, non-Hodgkin’s lymphoma; MDS, myelodysplastic syndrome; CLL, chronic lymphocytic leukemia; NS, not specified.
3. Discussion Our patient met the criteria for RS3PE established by McCarthy: she was an older patient, experienced sudden onset of symmetric polyarthritis and severe pitting edema of the hands and feet, and had negative tests for rheumatoid factors. Several cases of RS3PE have been reported in patients with malignancies. Of the patients with solid tumors, most had adenocarcinomas: there were four cases of prostate cancer [3], three of gastric cancer [3–5], and one each of colon cancer [3], rectal cancer [6], pancreatic cancer [7], hepatocarcinoma [8], endometrial cancer [9], ovarian cancer [10] and malignant histiocytofibroma [6]. A paraneoplastic syndrome was considered in at least three patients, whose RS3PE resolved after surgical removal of the tumor [4,7,9]. Twelve cases of RS3PE in patients with hematological malignancies have been reported (Table 1). Of these 12 patients, seven had non-Hodgkin’s lymphoma [2,6,11–14], three had myelodysplastic syndrome [2,6,15], and two had chronic lymphocytic leukemia [16,17]. Although the RS3PE revealed the hematological malignancy in most cases, it occurred during the course in a few patients. In addition to our case, there has been one report of RS3PE revealing a recurrence of a malignancy [6]. Interestingly, many patients had a decline in general health and a fever, two symptoms that are exceedingly rare in “idiopathic” RS3PE. In addition, glucocorticoid therapy was less effective than expected in RS3PE. This feature may be a useful warning signal. It has been contended that classic RS3PE not linked to cancer responds to 10 mg of prednisone-equivalent or less per day [6]. In our patient, the RS3PE responded to glucocorticoid therapy, but the dose was considerably higher. In addition, the dosage used in our patient has been reported to improve hematological malignancies, most notably lymphoproliferative diseases. The pathogenesis of RS3PE remains unclear but may involve a soluble factor produced by the tumor. IL-6 level fluctuations have been shown to parallel the joint manifesta-
tions and tumor progression [3], although this does not prove production of IL-6 by the tumor. Furthermore, HLA studies in patients with RS3PE and malignancies have found an increased prevalence of the haplotypes B7 and A2 [13,16], which may confer susceptibility to the joint condition. Thus, in a patient with RS3PE, presence of constitutional symptoms and/or failure to respond to low-dose corticosteroid therapy should alert to the possibility of malignant disease. A history of malignancy further strengthens this suspicion and should prompt a careful search for a recurrence.
References [1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
McCarty DJ, O’Duffy JD, Pearson L, Hunter JB. Remitting seronegative symmetrical synovitis with edema. RS3PE syndrome. J Am Med Assoc 1985;254:2763–7. Olive A, del Blanco J, Pons M, Vaquero M, Tean X, Catalan Group for the Study of RS3Pe. The clinical spectrum of remitting seronegative symmetrical synovitis with pitting edema. J Rheumatol 1997;24: 333–6. Sibilia J, Fries S, Schaerverbeke T. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE): a form of paraneoplastic polyarthritis. J Rheumatol 1999;26:115–20. Tada Y, Sato H, Yoshinawa S, Kimura H, Kitamura M, Kusaba T, et al. Remitting seronegative symmetrical synovitis with pitting edema associated with gastric carcinoma. J Rheumatol 1997;24:974–5. Ethiopia A, Bell D. Gastric carcinoma in association with remitting seronegative symmetrical synovitis with pitting edema. J Rheumatol 1999;26:1203–4. Paira S, Graf C, Rovearno S, Rossini J. Remitting seronegative symmetrical synovitis with pitting edema: a study of 12 cases. Clin Rheumatol 2002;21:146–9. Cantini F, Olivieri I, Salvarini C. More on remitting seronegative symmetrical synovitis with pitting edema as paraneoplastic syndrome. J Rheumatol 1998;25:188–9. Nakashima H, Tanaka Y, Shigematsu H, Kanaya S, Otsuka T, Hayashida K, et al. Remitting seronegative symmetrical synovitis with pitting edema syndrome associated with cryptogenic hepatocellular carcinoma. Clin Exp Rheumatol 1999;17:390–1.
426 [9]
[10] [11] [12]
[13]
O. Gisserot et al. / Joint Bone Spine 71 (2004) 424–426 Olivo D, Mattace R. Concurrence of benign edematous polysynovitis in the elderly (RS3PE) and endometrial adenocarcinoma. Scand J Rheumatol 1997;26:67–8. Vinci M, Malaguarnera L, Pistone G. RS3PE and ovarian cancer. Ann Rheum Dis 2001;60:429–30. Roldan MR, Martinez F, Roman J, Torres A. Non-Hodgkin’s lymphoma: initial manifestation. Ann Rheum Dis 1993;52:85–6. Goldenberg K, Rozenbaum M, Rosner I, Naschitz J, Kotler C. Remitting symmetrical seronegative synovitis with pitting edema (RS3PE) secondary to non-Hodgkin’s lymphoma. Clin Exp Rheumatol 1998; 16:767–8. Baronio M, Cerudelli B, Pascarella A, Airo P. Remitting symmetrical seronegative synovitis with pitting edema associated with B-cell nonHodgkin’s lymphoma. Clin Exp Rheumatol 2000;18:787.
[14] Yamasaki T, Takeoka Y, Nakao Y, Fusamoto H. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome with malignant lymphoma. Nippon Naika Gakkai Zasshi 2002;91: 1031–3. [15] Hernandez-Beriain JA, Cuesta-Callardo I, Segura-Garcia C. Remitting seronegative symmetrical synovitis with pitting edema: a rheumatic manifestation of myelodysplastic syndrome? Rev Rhum [Eng Ed] 1996;63:629–30. [16] Cobeta-Garcia JC, Domingo-Morera JA, Martinez-Burgui J. RS3PE syndrome and chronic lymphoid leukaemia. Clin Exp Rheumatol 1999;17:26. [17] Ekenel M, Yavuz S, Karti S, Direskeneli H, Akoglu T. Remitting seronegative symmetrical synovitis with pitting edema associated with chronic lymphocytic leukaemia. Clin Rheumatol 2000;9:247–8.