Bacterial Infection in the Limbs of Patients with Rheumatoid Arthritis during Biological Agent Therapy


Biological therapies in rheumatoid arthritis (RA) are known to increase the risk of serious infections. The present study was performed to evaluate the clinical features of bacterial infections occurring in the limbs during biological therapies in patients with RA. By March 2011, 11 RA patients (14 limbs) treated with biological agents at our institution required hospitalization due to bacterial infections occurring in the limbs. These patients had an average age of 53.7 years old. Infections occurred an average of 19 months after biological treatment. Two limbs in one patient were treated with infliximab, eight limbs in six patients were treated with etanercept, one limb in one patient was treated with adalimumab, and three limbs in three patients were treated with tocilizumab. Cellulitis occurred in 7 limbs, late infections after total knee arthroplasty occurred in two limbs, early infections after orthopedic surgery occurred in three limbs, and septic arthritis occurred in two limbs. Four cases had comorbidities—liver cirrhosis and diabetes mellitus in one and three cases, respectively. All patients were treated using corticosteroid with an average dose of 4.6 mg daily. Seven limbs required surgical treatment. All patients finally recovered. Ten limbs continued treatment with biological agents. Care must be taken regarding bacterial infection in the limbs of RA patients treated by using biological agents, particularly those with comorbidities. Further studies are required to confirm means of preventing such infections in daily practice.

Share and Cite:

H. Yamanaka, K. Goto and M. Suzuki, "Bacterial Infection in the Limbs of Patients with Rheumatoid Arthritis during Biological Agent Therapy," Open Journal of Rheumatology and Autoimmune Diseases, Vol. 2 No. 3, 2012, pp. 47-52. doi: 10.4236/ojra.2012.23010.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] D. L. Scott, K. A. Grindulis, G. R. Struthers, B. L. Coulton, A. L. Popert and P. A. Bacon, “Progression of Radiological Changes in Rheumatoid Arthritis,” Annals of the Rheumatic Diseases, Vol. 43, No. 1, 1984, pp. 8-17. doi:10.1136/ard.43.1.8
[2] T. Takeuchi, H. Yamanaka, E. Inoue, H. Nagasawa, M. Nawata, K. Ikari, K. Saito, N. Sekiguchi, E. Sato, H. Kameda, S. Iwata, T. Mochizuki, K. Amano and Y. Tanaka, “Retrospective Clinical Study on the Notable Efficacy and Related Factors of Infliximab Therapy in a Rheumatoid Arthritis Management Group in Japan: One-Year Outcome of Joint Destruction (RECONFIRM-2J),” Modern Rheumatology, Vol. 18, No. 5, 2008, pp. 447-452. doi:10.1007/s10165-008-0077-5
[3] L. Klareskog, D. van der Heijde, J. P. de Jager, A. Gough, J. Kalden, M. Malaise, M. E. Martin, K. Pavelka, J. Sany, L. Settas, J. Wajdula, R. Pedersen, S. Fatenejad, M. Sanda, et al., “Therapeutic Effect of the Combination of Etanercept and Methotrexate Compared with Each Treatment Alone in Patients with Rheumatoid Arthritis: Double-Blind Randomized Controlled Trial,” Lancet, Vol. 363, No. 9410, 2004, pp. 675-681. doi:10.1016/S0140-6736(04)15640-7
[4] F. C. Breedveld, M. H. Weisman, A. F. Kavanaugh, S. B. Cohen, K. Pavelka and R. van Vollenhoven, “The PREMIER Study: A Multicenter, Randomized, Double-Blind Clinical Trial of Combination Therapy with Adalimumab Plus Methotrexate versus Methotrexate Alone or Adalimumab Alone in Patients with Early, Aggressive Rheumatoid Arthritis Who Had Not Had Previous Methotrexate Treatment,” Arthritis Care & Research, Vol. 54, No. 1, 2006, pp. 26-37. doi:10.1002/art.21519
[5] N. Nishimoto and N. Takagi, “Assessment of the Validity of the 28-Joint Disease Activity Score Using Erythrocyte Sedimentation Rate (DAS28-ESR) As a Disease Activity Index of Rheumatoid Arthritis in the Efficacy Evaluation of 24-Week Treatment with Tocilizumab: Subanalysis of the SATORI Study,” Modern Rheumatology, Vol. 20, No. 6, 2010, pp. 539-547. doi:10.1007/s10165-010-0328-0
[6] M. Schiff, “Abatacept Treatment for Rheumatoid Arthritis,” Rheumatology, Vol. 50, No. 3, 2011, pp. 437-449. doi:10.1093/rheumatology/keq287
[7] G. Camussi, E. Albano, C. Tetta and F. Bussolio, “The Molecular Action of Tumor Necrosis Factor-Alpha,” European Journal of Biochemistry, Vol. 202, No. 1, 1991, pp. 3-14.
[8] F. M. Brennan and I. B. McInnes, “Evidence That Cytokines Play a Role in Rheumatoid Arthritis,” Journal of Clinical Investigation, Vol. 118, No. 11, 2008, pp. 3537-3545. doi:10.1172/JCI36389
[9] P. Emery, P. Durez and M. Dougados, “The Impact of T-Cell Co-Stimulation Modulation in Patients with Undifferentiated Inflammatory Arthritis or Very Early Rheumatoid Arthritis: A Clinical and Imaging Study of Abata- cept,” Annals of the Rheumatic Diseases, Vol. 69, No. 3, 2010, pp. 510-516. doi:10.1136/ard.2009.119016
[10] J. Listing, A. Strangfeld, S. Kary, R. Rau, U. von Hinueber, M. Stoyanova-Scholz, E. Gromnica-Ihle, C. Anatoni, P. Herzer, J. Kekow, M. Schneider and A. Zink, “Infections in Patients with Rheumatoid Arthritis Treated with Biologic Agents,” Arthritis Care & Research, Vol. 52, No. 11, 2005, pp. 3403-3412. doi:10.1002/art.21386
[11] M. Gilson, L. Gossec, X. Mariette, D. Gherissi, M. H. Guyot, J. M. Berthelot, D. Wendiling, C. Michelet, P. Dellamonica, F. Tubach, M. Dougados and D. Salmon, “Risk Factors for Total Joint Arthroplasty Infection in Patients Receiving Tumor Necrosis Factor α-Blockers: A Case-Control Study,” Arthritis Research & Therapy, Vol. 12, No. 4, 2010, p. R145. doi:10.1186/ar3087
[12] F. C. Arnett, S. M. Edworthy, D. A. Bloch, D. J. Mc-Shane, J. F. Fries, N. S. Cooper, L. A. Healey, S. R. Kaplan, M. H. Liang, H. S. Luthra, et al., “The American Rheumatism Association 1987 Revised Criteria for the Classification of Rheumatoid Arthritis,” Arthritis Care & Research, Vol. 31, No. 3, 1988, pp. 315-324. doi:10.1002/art.1780310302
[13] W. G. Dixon, K. Watson, M. Lunt, L. Hyrich, et al., “Rates of Serious Infection, Including Site-Specific and Bacterial Intracellular Infection, in Rheumatoid Arthritis Patients Receiving Anti-Tumor Necrosis Factor Therapy,” Arthritis Care & Research, Vol. 54, No. 8, 2006, pp. 2368-2376. doi:10.1002/art.21978
[14] J. B. Galloway, K. L. Hyrich, L. K. Mercer, W. G. Dixon, B. Fu, A. P. Ustianowski, K. D. Watson, M. Lunt, et al., “Anti-TNF Therapy Is Associated with an Increased Risk of Serious Infections in Patients with Rheumatoid Arthritis Especially in the First 6 Months of Treatment: Updated Results from the British Society for Rheumatology Biologics Register with Special Emphasis on Risks in the Elderly,” Rheumatology, Vol. 50, No. 1, 2011, pp. 124-131. doi:10.1093/rheumatology/keq242
[15] J. T. Giles, S. J. Bartlett, A. C. Gelber, S. Nanda, K. Fontaine, V. Ruffing and J. Bathon, “Tumor Necrosis Factor Inhibitor Therapy and Risk of Serious Postoperative Orthopedic Infection in Rheumatoid Arthritis,” Arthritis Care & Research, Vol. 55, No. 2, 2006, pp. 333-337. doi:10.1002/art.21841
[16] C. Bibbo and J. W. Goldberg, “Infectious and Healing Complications after Elective Orthopaedic Foot and Ankle Surgery during Tumor Necrosis Factor-Alpha Inhibition Therapy,” Foot Ankle International, Vol. 25, No. 5, 2004, pp. 331-335.
[17] A. A. Broeder, M. C. Creemers, J. Fransen, E. D. Jong, D. J. R. D. Rooij, A. Wymenga, M. D. Waal-Malefijt and F. H. J. V. D. Hoogen, “Risk Factors for Surgical Site Infections and Other Complications in Elective Surgery in Patients with Rheumatoid Arthritis with Special Attention for Anti-Tumor Necrosis Factor: A Large Retrospective Study,” Journal of Rheumatology, Vol. 34, No. 4, 2007, pp. 653-655.
[18] A. Strangfeld and J. Listing, “Bacterial and Opportunistic Infections during Anti-TNF Therapy,” Best Practice & Research Clinical Rheumatology, Vol. 20, No. 6, 2006, pp. 1181-1195. doi:10.1016/j.berh.2006.08.010
[19] T. Bongarts, A. Sutton, M. Sweeting, I. Buchan, E. Matteson and V. Montori, “Anti-TNF Antibody Therapy in Rheumatoid Arthritis and the Risk of Serious Infections and Malignancies,” Journal of the American Medical Association, Vol. 295, No. 19, 2006, pp. 2275-2285.
[20] J. D. Greenberg, G. Reed, J. M. Kremer, E. Tindall, A. Kavanaugh, C. Zheng, W. Bishai, M. C. Hochberg, et al., “Association of Methotrexate and Tumor Necrosis Factor Antagonists with Risk of Infectious Outcomes Including Opportunistic Infections in the CORRONA Registry,” Annals of the Rheumatic Diseases, Vol. 69, No. 2, 2008, pp. 380-386. doi:10.1136/ard.2008.089276
[21] H. H. Lee, I. H. Song and M. Friedrich, “Cutaneous Side-Effects in Patients with Rheumatoid Diseases during Application of Tumor Necrosis Factor-α Antagonists,” British Journal of Dermatology, Vol. 156, No. 3, 2007, pp. 486-491. doi:10.1111/j.1365-2133.2007.07682.x
[22] C. Vestergaard, C. Johansen, K. Otkjaer, M. Deleuran and L. Iversen, “Tumor Necrosis Factor-Alpha-Induced CTACK/ CCL27 (Cutaneous T-Cell-Attracting Chemokine) Production in Keratinocytes Is Controlled by Nuclear Factor Kappa B,” Cytokine, Vol. 29, No. 2, 2005, pp. 49-55. doi:10.1016/j.cyto.2004.09.008
[23] J. A. Hamilton and P. P. Tak, “The Dynamics of Macrophage Lineage Populations in Inflammatory and Autoimmune Disease,” Arthritis & Rheumatism, Vol. 60, No. 5, 2009 1210-1221. doi:10.1002/art.24505
[24] D. M. Grennan, J. Gray, J. Loudon and S. Fear, “Methotrexate and Early Postoperative Complications in Patients with Rheumatoid Arthritis Undergoing Elective Orthopaedic Surgery,” Annals of the Rheumatic Diseases, Vol. 60, No. 3, 2001, pp. 214-217. doi:10.1136/ard.60.3.214
[25] D. Lacaille, D. P. Guh, M. Abarahamowicz, A. H. Anis and J. M. Esdaile, “Use of Nonbiologic Disease-Modifying Anti-Rheumatic Drugs and Risk of Infection in Patients with Rheumatoid Arthritis,” Arthritis Care & Research, Vol. 59, No. 8, 2008, pp. 1074-1081. doi:10.1002/art.23913

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.