- Email: [email protected]
Development of recurrent pseudoseptic arthritis in a patient with rheumatoid arthritis receiving TNF-alpha blocker
Letters to the editor / Joint Bone Spine 73 (2006) 763–768
clinical status deteriorated in 16% of cases [9]. The ossified plaques adhere to the spinal cord, requiring painstaking dissection to avoid neurological compromise. Therefore, simple laminectomy is the recommended procedure [10]. Laminectomy should be performed at all the affected levels. Preoperative CT is invaluable for planning the extent of the procedure. 4. Conclusion In conclusion, arachnoiditis ossificans is a rare condition that probably represents the end-stage of adhesive arachnoiditis. CT is the best investigation for establishing the diagnosis and evaluating the extent of the lesions before laminectomy. MRI may disclose spinal cord abnormalities. References [1]
Kahler RJ, Knuckey NW, Davis S. Arachnoiditis ossificans and syringomyelia: a unique case report. J Clin Neurosci 2000;7:66–8. [2] Lucchesi AC, White WL, Heiserman JE, Flom RA. Review of arachnoiditis ossificans with a case report. BNI Q 1998;14:4–8. [3] Capron I, Gille M, Guiot S, Lindemans I, Duprez T, Goffin J. Myélopathie dorsale révélant une arachnoïdite spinale chronique dorsolombaire ossifiante. Rev Neurol 2000;156:395–8. [4] Laitt R, Jackson A, Sherwood I. Patterns of chronic adhesive arachnoiditis following Myodil myelography: the significance of spinal canal stenosis and previous surgery. Br J Radiol 1996;69:693–8. [5] Petty PG, Hudgson P, Hare WSC. Symptomatic lumbar spinal arachnoiditis: fact or fallacy? J Clin Neurosci 2000;7:395–9. [6] Dullerud R, Molrand TJ. Adhesive arachnoiditis after radiculography with dimer-X and depo-medrol. Radiology 1976;119:153–5. [7] Frizzel B, Kaplan P, Dussault R, Sevick R. Arachnoiditis ossificans: MR imaging features in five patients. AJR 2001;177:461–4. [8] Manabe Y, Shiro Y, Warita H, Hayashi T, Nakashima H, Abe K. Fluctuating monoplegia due to insufficiency by spinal arachnoiditis ossificans. J Neurol Sci 2000;178:163–6. [9] Whittle IR, Dorsch NW, Segelov IN. Symptomatic arachnoiditis ossificans: report of two cases. Acta Neurochir (Wien) 1982;65:217–26. [10] Shiraishi T, Crock HV, Reynolds A. Spinal arachnoiditis ossificans: observations on its investigation and treatment. Eur Spine J 1995;4:60–3.
Soulef Kriaa Chiraz Hafsa Mohamed Zbidi* Ahmed Laifi Mondher Golli Amor Gannouni Radiology Department, Fattouma-Bourguiba Hospital, Monastir, Tunisia E-mail address: [email protected] (M. Zbidi). Received 22 November 2005; accepted 30 January 2006 Available online 28 July 2006 *Corresponding
author.
1297-319X/$ - see front matter © 2006 Published by Elsevier Masson SAS. doi:10.1016/j.jbspin.2006.01.024
767
Development of recurrent pseudoseptic arthritis in a patient with rheumatoid arthritis receiving TNF-alpha blocker Keywords: Etanercept; Pseudoseptic arthritis; Rheumatoid arthritis; TNF-alpha blocker
TNF is a proinflammatory cytokine that plays a central role in the pathophysiology of rheumatoid arthritis (RA). Blocking the action of TNF-alpha with monoclonal antibodies directed against TNF-alpha has been shown to yield fast and impressive responses in patients with RA [1]. On the other hand, case reports have been published identifying TNF-alpha blockers as a possible cause of rheumatoid nodules, lung injury, glomerulonephritis as well as cutaneous vasculitis [2–5]. We present a case with RA who developed recurrent pseudoseptic arthritis while on TNF-alpha blocker (etanercept). We also discussed the possible mechanisms of TNF-alpha blocker induced pseudoseptic arthritis. 1. Case report A 25-year-old Turkish girl with a 5-year history of seropositive, erosive RA was admitted to our hospital because of swollen and painful left knee joint associated with fever. She had been receiving etanercept 25 mg twice per week for 4 months in addition to leflunomide 20 mg/day, sulphasalazine 2 g/day, hydroxychloroquine 200 mg/day, prednisolone 5 mg/day. On examination, there was swelling and pain in her left knee joint without arthritis in her other joints. There were also deformities in the hand joints attributed to RA. Erythrocyte sedimentation rate and C-reactive protein were 90 mm/h and 28 mg/dl (N = 0–0.8), respectively. Synovial fluid obtained from the left knee was purulent appearance. The patient was referred to Orthopaedic Department for an urgent surgical lavage. Leukocyte count of synovial fluid was 85,500 per mm3 consisting of 90% neutrophils and 10% lymphocytes. A clinical diagnosis of septic arthritis was made, and parenteral antibiotics were started subsequent to obtaining blood and synovial fluid cultures. All the drugs prescribed for RA had to be withdrawn. Direct examination of the fluid revealed no crystals or micro organism. Cultures of blood and synovial fluid for aerobic and anaerobic micro organism, as well as brucella and mycobacterium, were negative. Glucose level of synovial fluid was 20 mg/dl. Rheumatoid factor was 101 IU/ml (N<15). Antinuclear antibody was negative. Antibiotic (cefazoline) was withdrawn 10 days after admission. All drugs as well as etanercept were restarted. Six months later, she was admitted again to our department due to fever and swollen left knee and pain. Synovial fluid was once again purulent in appearance. Leukocyte count of synovial fluid was 55,500 per mm3. Direct examination of the fluid revealed no crystals or any microorganisms. Cultures of blood and synovial fluid for aerobic and anaerobic microorganisms, as well as brucella and mycobacterium, were negative. We resorted to no changes in the treatment regimen, though we increased the dosage of prednisolone to 20 mg/day. After resolution of arthritis, the dosage was decreased gradually. Four weeks later, the patient
768
Letters to the editor / Joint Bone Spine 73 (2006) 763–768
was readmitted with arthritis in the left knee and fever. Microbiological analysis was still negative. No leukocyte count of synovial fluid was made due to fluid insufficiency. Erythrocyte sedimentation rate and C-reactive protein were 45 mm/h and 27.3 mg/dl, respectively. The patient reported that she had been injecting etanercept 50 mg once a week rather than 25 mg twice a week for the past 3 months. However, she complained that the number of monoarthritis attacks increased after the beginning of this dosage. Furthermore, she noticed that every etanercept injection led to increase in pain and swelling in the left knee. She had spontaneously increased the dosage of prednisolone to relive her pains during the painful periods. While the patient’s other drugs were continued, etanercept was discontinued, taking a probable relationship between etanercept and appearance of arthritis into consideration. The patient has remained in a remission period with the abovementioned treatment regimen for over 6 months. 2. Discussion A general attitude of rheumatologists is to think of septic arthritis in a patient with RA presenting with monoarthritis associated with significantly increased synovial fluid leukocyte. However, familial Mediterranean fever (FMF) septic arthritis, crystal arthropathies and the exacerbation of the RA itself can cause severe monoarthritis [6,7]. Our patient neither had any symptoms related with FMF, nor did we observe any microcrystal in the synovial fluid samples. If an RA patient presents with a monoarthritis associated with very high leukocyte count in the synovial fluid, it is mostly considered as either septic arthritis, especially while on TNF-alpha blocker, or exacerbation of RA itself. Since total synovial fluid leukocyte count during the exacerbation of RA only rarely reaches 50,000 per mm3 [7], we thought it could be possibly be septic arthritis and so commenced an empirical antibiotic treatment while waiting for the microbiological results. But no organisms were isolated throughout the evaluation. Our patient used a few other drugs in addition to etanercept, which is why it may be hard to blame etanercept for the pseudoseptic arthritis. On the other hand, there are no data attributing pseudoseptic arthritis to leflunomide, sulphasalazine or hydroxychloroquine, or a combination of all. It is interesting to note that monoarthritis attacks increased in frequency upon starting 50 mg of etanercept once a week. This curious observation may lead us to think of a probable relationship between TNF-alpha blocker and pseudoseptic arthritis. Vega and Gonzalez [8] reported three patients with RA who developed pseudoseptic arthritis and sterile left calf abscess while receiving TNF-alpha blocker. Two of the patients had monoarthritis and fever. The other one had an episode of sterile muscular abscess. Leukocyte counts of synovial fluid were 58,600 and 84,000 mm3 in these two patients. Synovial cultures were negative as in our case. They suggested that TNF-alpha blocker use may have contributed to pseudoseptic arthritis [8]. We could not explain the emergence of monoarthritis while she was on TNF-alpha blocker, considering the absence of synovitis in the other joints. According to some recent reports, TNF-alpha blockers may lead to development of rheumatoid
nodules [2], lung injury [3], glomerulonephritis [4,5] as well as vasculitis [5] in patients with RA while they are in remission period. Experimental trials have documented those patients using etanercept revealed antibodies to the TNF–TNF receptor complex. It is plausible that the TNF–cytokine receptor immune complexes deposit in tissues, activating the complement system and generating C5a anaphylatoxin, which attracts neutrophils. The neutrophils exacerbate the tissue damage by releasing lysosomal enzymes and by generating leukotriene B4, which enhances the influx of neutrophils [9,10]. Although we do not rule out the possibility that pseudoseptic arthritis could be due to RA, it can be a secondary event to TNFalpha blocker. This case is the second of its kind published on the pseudoseptic arthritis secondary to TNF-alpha blocker use. We believe further case reports might help clarify a possible relationship between pseudoseptic arthritis and TNF-alpha blockers. References [1] Elliot MJ, Maini RN, Feldmann M, Long-Fox A, Charles P, Bijl H, et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (ca2) versus placebo in rheumatoid arthritis. Lancet 1994;344:1105–10. [2] Kekow J, Welte T, Kellner U, Pap T. Development of rheumatoid nodules during anti-tumor necrosis factor α therapy with etanercept. Arthritis Rheum 2002;46:843–4. [3] Peno-Green L, Lluberas G, Kingsley T, Brantley S. Lung injury linked to etanercept therapy. Chest 2002;122:1858–60. [4] Doulton TWR, Tucker B, Reardon J, Velasco N. Antineutrophil cytoplasmic antibody-associated necrotizing crescentic glomerulonephritis in a patient receiving treatment with etanercept for severe rheumatoid arthritis. Clin Nephrol 2004;62:234–8. [5] Roux CH, Brocq O, Albert C, Breuil V, Euller-Ziegler L. Cutaneous vasculitis and glomerulonephritis in a patient taking the anti-TNF-alpha agent etanercept for rheumatoid arthritis. Joint Bone Spine 2004;71: 444–5. [6] Garcia-Gonzalez A, Weisman MH. The arthritis of familial Mediterranean fever. Semin Arthritis Rheum 1992;22:139–50. [7] Kreyb PR, Bailen DA. Synovial fluid leukocytosis. Am J Med 1979;67: 436–42. [8] Vega AJL, Gonzalez D. Anti-TNF-alpha and pseudoseptic arthritis in rheumatoid arthritis. Ann Rheum Dis 2005;64(Suppl III):206. [9] Galaria NA, Werth VP, Schumacher HR. Leukocytoclastic vasculitis due to etanercept. J Rheumatol 2000;27:2041–4. [10] Yancey KB, Lawley TJ. Circulating immune complexes: their immunohistochemistry, biology, and detection in selected dermatologic and systemic diseases. J Am Acad Dermatol 1984;10:711–31.
Cengiz Korkmaz* Timuçin Kaşifoğlu Division of Rheumatology, Department of Internal Medicine, Eskişehir Osmangazi University Medical Faculty, Vişnelik M. Alifuat Güven C. Akasya S. 11/11, 26020 Eskişehir, Turkey E-mail address: [email protected] (C. Korkmaz). Received 30 December 2005; accepted 20 February 2006 Available online 18 October 2006 *Corresponding
author.
1297-319X/$ - see front matter © 2006 Eksevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2006.02.011
clinical status deteriorated in 16% of cases [9]. The ossified plaques adhere to the spinal cord, requiring painstaking dissection to avoid neurological compromise. Therefore, simple laminectomy is the recommended procedure [10]. Laminectomy should be performed at all the affected levels. Preoperative CT is invaluable for planning the extent of the procedure. 4. Conclusion In conclusion, arachnoiditis ossificans is a rare condition that probably represents the end-stage of adhesive arachnoiditis. CT is the best investigation for establishing the diagnosis and evaluating the extent of the lesions before laminectomy. MRI may disclose spinal cord abnormalities. References [1]
Kahler RJ, Knuckey NW, Davis S. Arachnoiditis ossificans and syringomyelia: a unique case report. J Clin Neurosci 2000;7:66–8. [2] Lucchesi AC, White WL, Heiserman JE, Flom RA. Review of arachnoiditis ossificans with a case report. BNI Q 1998;14:4–8. [3] Capron I, Gille M, Guiot S, Lindemans I, Duprez T, Goffin J. Myélopathie dorsale révélant une arachnoïdite spinale chronique dorsolombaire ossifiante. Rev Neurol 2000;156:395–8. [4] Laitt R, Jackson A, Sherwood I. Patterns of chronic adhesive arachnoiditis following Myodil myelography: the significance of spinal canal stenosis and previous surgery. Br J Radiol 1996;69:693–8. [5] Petty PG, Hudgson P, Hare WSC. Symptomatic lumbar spinal arachnoiditis: fact or fallacy? J Clin Neurosci 2000;7:395–9. [6] Dullerud R, Molrand TJ. Adhesive arachnoiditis after radiculography with dimer-X and depo-medrol. Radiology 1976;119:153–5. [7] Frizzel B, Kaplan P, Dussault R, Sevick R. Arachnoiditis ossificans: MR imaging features in five patients. AJR 2001;177:461–4. [8] Manabe Y, Shiro Y, Warita H, Hayashi T, Nakashima H, Abe K. Fluctuating monoplegia due to insufficiency by spinal arachnoiditis ossificans. J Neurol Sci 2000;178:163–6. [9] Whittle IR, Dorsch NW, Segelov IN. Symptomatic arachnoiditis ossificans: report of two cases. Acta Neurochir (Wien) 1982;65:217–26. [10] Shiraishi T, Crock HV, Reynolds A. Spinal arachnoiditis ossificans: observations on its investigation and treatment. Eur Spine J 1995;4:60–3.
Soulef Kriaa Chiraz Hafsa Mohamed Zbidi* Ahmed Laifi Mondher Golli Amor Gannouni Radiology Department, Fattouma-Bourguiba Hospital, Monastir, Tunisia E-mail address: [email protected] (M. Zbidi). Received 22 November 2005; accepted 30 January 2006 Available online 28 July 2006 *Corresponding
author.
1297-319X/$ - see front matter © 2006 Published by Elsevier Masson SAS. doi:10.1016/j.jbspin.2006.01.024
767
Development of recurrent pseudoseptic arthritis in a patient with rheumatoid arthritis receiving TNF-alpha blocker Keywords: Etanercept; Pseudoseptic arthritis; Rheumatoid arthritis; TNF-alpha blocker
TNF is a proinflammatory cytokine that plays a central role in the pathophysiology of rheumatoid arthritis (RA). Blocking the action of TNF-alpha with monoclonal antibodies directed against TNF-alpha has been shown to yield fast and impressive responses in patients with RA [1]. On the other hand, case reports have been published identifying TNF-alpha blockers as a possible cause of rheumatoid nodules, lung injury, glomerulonephritis as well as cutaneous vasculitis [2–5]. We present a case with RA who developed recurrent pseudoseptic arthritis while on TNF-alpha blocker (etanercept). We also discussed the possible mechanisms of TNF-alpha blocker induced pseudoseptic arthritis. 1. Case report A 25-year-old Turkish girl with a 5-year history of seropositive, erosive RA was admitted to our hospital because of swollen and painful left knee joint associated with fever. She had been receiving etanercept 25 mg twice per week for 4 months in addition to leflunomide 20 mg/day, sulphasalazine 2 g/day, hydroxychloroquine 200 mg/day, prednisolone 5 mg/day. On examination, there was swelling and pain in her left knee joint without arthritis in her other joints. There were also deformities in the hand joints attributed to RA. Erythrocyte sedimentation rate and C-reactive protein were 90 mm/h and 28 mg/dl (N = 0–0.8), respectively. Synovial fluid obtained from the left knee was purulent appearance. The patient was referred to Orthopaedic Department for an urgent surgical lavage. Leukocyte count of synovial fluid was 85,500 per mm3 consisting of 90% neutrophils and 10% lymphocytes. A clinical diagnosis of septic arthritis was made, and parenteral antibiotics were started subsequent to obtaining blood and synovial fluid cultures. All the drugs prescribed for RA had to be withdrawn. Direct examination of the fluid revealed no crystals or micro organism. Cultures of blood and synovial fluid for aerobic and anaerobic micro organism, as well as brucella and mycobacterium, were negative. Glucose level of synovial fluid was 20 mg/dl. Rheumatoid factor was 101 IU/ml (N<15). Antinuclear antibody was negative. Antibiotic (cefazoline) was withdrawn 10 days after admission. All drugs as well as etanercept were restarted. Six months later, she was admitted again to our department due to fever and swollen left knee and pain. Synovial fluid was once again purulent in appearance. Leukocyte count of synovial fluid was 55,500 per mm3. Direct examination of the fluid revealed no crystals or any microorganisms. Cultures of blood and synovial fluid for aerobic and anaerobic microorganisms, as well as brucella and mycobacterium, were negative. We resorted to no changes in the treatment regimen, though we increased the dosage of prednisolone to 20 mg/day. After resolution of arthritis, the dosage was decreased gradually. Four weeks later, the patient
768
Letters to the editor / Joint Bone Spine 73 (2006) 763–768
was readmitted with arthritis in the left knee and fever. Microbiological analysis was still negative. No leukocyte count of synovial fluid was made due to fluid insufficiency. Erythrocyte sedimentation rate and C-reactive protein were 45 mm/h and 27.3 mg/dl, respectively. The patient reported that she had been injecting etanercept 50 mg once a week rather than 25 mg twice a week for the past 3 months. However, she complained that the number of monoarthritis attacks increased after the beginning of this dosage. Furthermore, she noticed that every etanercept injection led to increase in pain and swelling in the left knee. She had spontaneously increased the dosage of prednisolone to relive her pains during the painful periods. While the patient’s other drugs were continued, etanercept was discontinued, taking a probable relationship between etanercept and appearance of arthritis into consideration. The patient has remained in a remission period with the abovementioned treatment regimen for over 6 months. 2. Discussion A general attitude of rheumatologists is to think of septic arthritis in a patient with RA presenting with monoarthritis associated with significantly increased synovial fluid leukocyte. However, familial Mediterranean fever (FMF) septic arthritis, crystal arthropathies and the exacerbation of the RA itself can cause severe monoarthritis [6,7]. Our patient neither had any symptoms related with FMF, nor did we observe any microcrystal in the synovial fluid samples. If an RA patient presents with a monoarthritis associated with very high leukocyte count in the synovial fluid, it is mostly considered as either septic arthritis, especially while on TNF-alpha blocker, or exacerbation of RA itself. Since total synovial fluid leukocyte count during the exacerbation of RA only rarely reaches 50,000 per mm3 [7], we thought it could be possibly be septic arthritis and so commenced an empirical antibiotic treatment while waiting for the microbiological results. But no organisms were isolated throughout the evaluation. Our patient used a few other drugs in addition to etanercept, which is why it may be hard to blame etanercept for the pseudoseptic arthritis. On the other hand, there are no data attributing pseudoseptic arthritis to leflunomide, sulphasalazine or hydroxychloroquine, or a combination of all. It is interesting to note that monoarthritis attacks increased in frequency upon starting 50 mg of etanercept once a week. This curious observation may lead us to think of a probable relationship between TNF-alpha blocker and pseudoseptic arthritis. Vega and Gonzalez [8] reported three patients with RA who developed pseudoseptic arthritis and sterile left calf abscess while receiving TNF-alpha blocker. Two of the patients had monoarthritis and fever. The other one had an episode of sterile muscular abscess. Leukocyte counts of synovial fluid were 58,600 and 84,000 mm3 in these two patients. Synovial cultures were negative as in our case. They suggested that TNF-alpha blocker use may have contributed to pseudoseptic arthritis [8]. We could not explain the emergence of monoarthritis while she was on TNF-alpha blocker, considering the absence of synovitis in the other joints. According to some recent reports, TNF-alpha blockers may lead to development of rheumatoid
nodules [2], lung injury [3], glomerulonephritis [4,5] as well as vasculitis [5] in patients with RA while they are in remission period. Experimental trials have documented those patients using etanercept revealed antibodies to the TNF–TNF receptor complex. It is plausible that the TNF–cytokine receptor immune complexes deposit in tissues, activating the complement system and generating C5a anaphylatoxin, which attracts neutrophils. The neutrophils exacerbate the tissue damage by releasing lysosomal enzymes and by generating leukotriene B4, which enhances the influx of neutrophils [9,10]. Although we do not rule out the possibility that pseudoseptic arthritis could be due to RA, it can be a secondary event to TNFalpha blocker. This case is the second of its kind published on the pseudoseptic arthritis secondary to TNF-alpha blocker use. We believe further case reports might help clarify a possible relationship between pseudoseptic arthritis and TNF-alpha blockers. References [1] Elliot MJ, Maini RN, Feldmann M, Long-Fox A, Charles P, Bijl H, et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (ca2) versus placebo in rheumatoid arthritis. Lancet 1994;344:1105–10. [2] Kekow J, Welte T, Kellner U, Pap T. Development of rheumatoid nodules during anti-tumor necrosis factor α therapy with etanercept. Arthritis Rheum 2002;46:843–4. [3] Peno-Green L, Lluberas G, Kingsley T, Brantley S. Lung injury linked to etanercept therapy. Chest 2002;122:1858–60. [4] Doulton TWR, Tucker B, Reardon J, Velasco N. Antineutrophil cytoplasmic antibody-associated necrotizing crescentic glomerulonephritis in a patient receiving treatment with etanercept for severe rheumatoid arthritis. Clin Nephrol 2004;62:234–8. [5] Roux CH, Brocq O, Albert C, Breuil V, Euller-Ziegler L. Cutaneous vasculitis and glomerulonephritis in a patient taking the anti-TNF-alpha agent etanercept for rheumatoid arthritis. Joint Bone Spine 2004;71: 444–5. [6] Garcia-Gonzalez A, Weisman MH. The arthritis of familial Mediterranean fever. Semin Arthritis Rheum 1992;22:139–50. [7] Kreyb PR, Bailen DA. Synovial fluid leukocytosis. Am J Med 1979;67: 436–42. [8] Vega AJL, Gonzalez D. Anti-TNF-alpha and pseudoseptic arthritis in rheumatoid arthritis. Ann Rheum Dis 2005;64(Suppl III):206. [9] Galaria NA, Werth VP, Schumacher HR. Leukocytoclastic vasculitis due to etanercept. J Rheumatol 2000;27:2041–4. [10] Yancey KB, Lawley TJ. Circulating immune complexes: their immunohistochemistry, biology, and detection in selected dermatologic and systemic diseases. J Am Acad Dermatol 1984;10:711–31.
Cengiz Korkmaz* Timuçin Kaşifoğlu Division of Rheumatology, Department of Internal Medicine, Eskişehir Osmangazi University Medical Faculty, Vişnelik M. Alifuat Güven C. Akasya S. 11/11, 26020 Eskişehir, Turkey E-mail address: [email protected] (C. Korkmaz). Received 30 December 2005; accepted 20 February 2006 Available online 18 October 2006 *Corresponding
author.
1297-319X/$ - see front matter © 2006 Eksevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2006.02.011