Viewpoints
13 February 2025
Early Access
To prophylax or not to prophylax? The role of trimethoprim/sulfamethoxazole as a prophylactic agent in systemic vasculitis: the case of antineutrophil cytoplasmic antibody- associated vasculitis and giant cell arteritis
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
911
Views
256
Downloads
Authors
Inflammatory rheumatic and musculoskeletal diseases, including systemic vasculitis, increase the risk of infection due to immunosuppressive treatments and disease-related immune dysfunction. In this viewpoint, we focused on patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and giant cell arteritis (GCA). We critically reviewed the literature on infectious risks and the role of trimethoprim/sulfamethoxazole (TMP/SMX) as a prophylactic agent in these conditions. In AAV, serious infections from opportunistic (e.g., Pneumocystis jirovecii) and non-opportunistic pathogens are especially common, peaking in the first year post-diagnosis. TMP/SMX is crucial for prevention, as its use significantly reduces the incidence of Pneumocystis jirovecii pneumonia (PJP) and other serious infections. In GCA, although the risk of PJP is low, the overall infection risk is high and correlates with glucocorticoid dosage. However, evidence supporting the routine use of TMP/SMX in GCA is limited, warranting further investigation through randomized clinical trials.
Altmetrics
Downloads
Download data is not yet available.
Citations
Mehta B, Pedro S, Ozen G, Kalil A, Wolfe F, Mikuls T, et al. Serious infection risk in rheumatoid arthritis compared with non-inflammatory rheumatic and musculoskeletal diseases: a US national cohort study. RMD Open 2019; 5: e000935. DOI: https://doi.org/10.1136/rmdopen-2019-000935
Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised international Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum 2013; 65: 1-11. DOI: https://doi.org/10.1007/s10157-013-0869-6
Rathmann J, Jayne D, Segelmark M, Jönsson G, Mohammad AJ. Incidence and predictors of severe infections in ANCA-associated vasculitis: a population-based cohort study. Rheumatology 2021; 60: 2745-54. DOI: https://doi.org/10.1093/rheumatology/keaa699
Sánchez Álamo B, Moi L, Bajema I, Faurschou M, Flossmann O, Hauser T, et al. Long-term outcomes and prognostic factors for survival of patients with ANCA-associated vasculitis. Nephrol Dial Transplant 2023; 38: 1655-65. DOI: https://doi.org/10.1093/ndt/gfac320
Vassilopoulos A, Vassilopoulos S, Kalligeros M, Shehadeh F, Mylonakis E. Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy: a systematic review and meta-analysis. Front Med 2023; 10: 1110548. DOI: https://doi.org/10.3389/fmed.2023.1110548
Berti A, Ottone M, Sartorelli S, Treppo E, Bettiol A, Padoan R, et al. POS1176 hospitalization rates, features, and discharge diagnoses of a large nationwide cohort of ANCA-associated vasculitis. Ann Rheum Dis 2023;82:920-1. DOI: https://doi.org/10.1136/annrheumdis-2023-eular.6039
Flossmann O, Berden A, De Groot K, Hagen C, Harper L, Heijl C, et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis 2011; 70: 488-94. DOI: https://doi.org/10.1136/ard.2010.137778
Waki D, Nishimura K, Yoshida T, Tanaka N, Mizukawa K, Fukushima M, et al. Protective effect of different doses of trimethoprim-sulfamethoxazole prophylaxis for early severe infections among patients with antineutrophil cytoplasmic autoantibody-associated vasculitis. Clin Exp Rheumatol 2021; 39: 142-8. DOI: https://doi.org/10.55563/clinexprheumatol/p34lkr
Ghembaza A, Vautier M, Cacoub P, Pourcher V, Saadoun D. Risk factors and prevention of Pneumocystis jirovecii pneumonia in patients with autoimmune and inflammatory diseases. Chest 2020; 158: 2323-32. DOI: https://doi.org/10.1016/j.chest.2020.05.558
Green H, Paul M, Vidal L, Leibovici L. Prophylaxis of Pneumocystis pneumonia in immunocompromised non-HIV-infected patients: systematic review and meta-analysis of randomized controlled trials. Mayo Clin Proc 2007; 82: 1052-9. DOI: https://doi.org/10.4065/82.9.1052
Ward MM, Donald F. Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality. Arthritis Rheum 1999; 42: 780-9. DOI: https://doi.org/10.1002/1529-0131(199904)42:4<780::AID-ANR23>3.0.CO;2-M
Honda N, Tagashira Y, Kawai S, Kobayashi T, Yamamoto M, Shimada K, et al. Reduction of Pneumocystis jirovecii pneumonia and bloodstream infections by trimethoprim-sulfamethoxazole prophylaxis in patients with rheumatic diseases. Scand J Rheumatol 2021; 50: 365-71. DOI: https://doi.org/10.1080/03009742.2020.1850854
Schmajuk G, Jafri K, Evans M, Shiboski S, Gianfrancesco M, Izadi Z, et al. Pneumocystis jirovecii pneumonia (PJP) prophylaxis patterns among patients with rheumatic diseases receiving high-risk immunosuppressant drugs. Semin Arthritis Rheum 2019; 48: 1087-92. DOI: https://doi.org/10.1016/j.semarthrit.2018.10.018
Park JW, Curtis JR, Kim MJ, Lee H, Song YW, Lee EB. Pneumocystis pneumonia in patients with rheumatic diseases receiving prolonged, non-high-dose steroids-clinical implication of primary prophylaxis using trimethoprim-sulfamethoxazole. Arthritis Res Ther 2019; 21: 207. DOI: https://doi.org/10.1186/s13075-019-1996-6
Park JW, Curtis JR, Moon J, Song YW, Kim S, Lee EB. Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids. Ann Rheum Dis 2018; 77: 644-9. DOI: https://doi.org/10.1136/annrheumdis-2017-211796
Kronbichler A, Kerschbaum J, Gopaluni S, Tieu J, Alberici F, Jones RB, et al. Trimethoprim-sulfamethoxazole prophylaxis prevents severe/life-threatening infections following rituximab in antineutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis 2018; 77: 1440-7. DOI: https://doi.org/10.1136/annrheumdis-2017-212861
Nettleton E, Sattui SE, Wallace Z, Putman M. Incidence of Pneumocystis Jiroveci pneumonia in patients with ANCA-associated vasculitis initiating therapy with rituximab or cyclophosphamide. Arthritis Care Res 2024; 76: 288-94. DOI: https://doi.org/10.1002/acr.25222
Ho JMW, Juurlink DN. Considerations when prescribing trimethoprim-sulfamethoxazole. CMA 2011; 183: 1851-8. DOI: https://doi.org/10.1503/cmaj.111152
Grimwade K, Swingler GH. A daily low dose of cotrimoxazole for preventing opportunistic infections in adults with HIV Available from: https://www.cochrane.org/CD003108/HIV_a-daily-low-dose-of-cotrimoxazole-for-preventing-opportunistic-infections-in-adults-with-hiv.
Park JW, Curtis JR, Jun KI, Kim TM, Heo DS, Ha J, et al. Primary prophylaxis for pneumocystis jirovecii pneumonia in patients receiving rituximab. Chest 2022; 161: 1201-10. DOI: https://doi.org/10.1016/j.chest.2021.11.007
Odler B, Riedl R, Gauckler P, Shin JI, Leierer J, Merkel PA, et al. Risk factors for serious infections in ANCA-associated vasculitis. Ann Rheum Dis 2023; 82: 681-7. DOI: https://doi.org/10.1136/ard-2022-223401
Mendel A, Behlouli H, de Moura CS, Vinet É, Curtis JR, Bernatsky S. Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the United States of America: a retrospective cohort study. Arthritis Res Ther 2023; 25: 133. DOI: https://doi.org/10.1186/s13075-023-03114-7
Canadian Rheumatology Association. Canadian Rheumatology Association annual scientific meeting RBC convention centre (and virtually) Winnipeg, Manitoba, Canada February 28-March 2, 2024. J Rheumatol 2024;jrheum.2024-0330. DOI: https://doi.org/10.3899/jrheum.2024-0330
Emmi G, Bettiol A, Gelain E, Bajema IM, Berti A, Burns S, et al. Evidence-based guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis. Nat Rev Rheumatol 2023; 19: 378-93. DOI: https://doi.org/10.1038/s41584-023-00958-w
Chung SA, Langford CA, Maz M, Abril A, Gorelik M, Guyatt G, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol 2021; 73: 1366-83. DOI: https://doi.org/10.1002/art.41773
Hellmich B, Sanchez-Alamo B, Schirmer JH, Berti A, Blockmans D, Cid MC, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis 2024; 83: 30-47. DOI: https://doi.org/10.1136/ard-2022-223764
Thorpe C, Hickson R, Aspinall S, Darebail V, Zhao X, Thorpe J, Cao B, et al. Receipt of antimicrobial prophylaxis in U.S. medicare beneficiaries initiating immunosuppressive medications for ANCA vasculitis. Available from: https://acrabstracts.org/abstract/receipt-of-antimicrobial-prophylaxis-in-u-s-medicare-beneficiaries-initiating-immunosuppressive-medications-for-anca-vasculitis/.
El-Sadr WM, Murphy RL, Yurik TM, Luskin-Hawk R, Cheung TW, Balfour HH, et al. Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. Community program for clinical research on AIDS and the AIDS clinical trials group. N Engl J Med 1998; 339: 1889-95. DOI: https://doi.org/10.1056/NEJM199812243392604
Eliopoulos GM, Huovinen P. Resistance to trimethoprim-sulfamethoxazole. Clin Infect Dis 2001; 32: 1608-14. DOI: https://doi.org/10.1086/320532
Hellmich B, Agueda A, Monti S, Buttgereit F, De Boysson H, Brouwer E, et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis 2020; 79: 19-30. DOI: https://doi.org/10.1136/annrheumdis-2019-215672
Tomelleri A, van der Geest KSM, Khurshid MA, Sebastian A, Coath F, Robbins D, et al. Disease stratification in GCA and PMR: state of the art and future perspectives. Nat Rev Rheumatol 2023; 19: 446-59. DOI: https://doi.org/10.1038/s41584-023-00976-8
Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med 2017; 377: 317-28. DOI: https://doi.org/10.1056/NEJMoa1613849
Mahr AD, Jover JA, Spiera RF, Hernández-García C, Fernández-Gutiérrez B, LaValley MP, et al. Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Arthritis Rheum 2007; 56: 2789-97. DOI: https://doi.org/10.1002/art.22754
Proven A, Gabriel SE, Orces C, O’Fallon WM, Hunder GG, Michael O’Fallon W, et al. Glucocorticoid therapy in giant cell arteritis: duration and adverse outcomes. Arthritis Rheum 2003; 49: 703-8. DOI: https://doi.org/10.1002/art.11388
Albrecht K, Huscher D, Buttgereit F, Aringer M, Hoese G, Ochs W, et al. Long-term glucocorticoid treatment in patients with polymyalgia rheumatica, giant cell arteritis, or both diseases: results from a national rheumatology database. Rheumatol Int 2018; 38: 569-77. DOI: https://doi.org/10.1007/s00296-017-3874-3
Schmidt J, Smail A, Roche B, Gay P, Salle V, Pellet H, et al. Incidence of severe infections and infection-related mortality during the course of giant cell arteritis: a multicenter, prospective, double-cohort study. Arthritis Rheum 2016; 68: 1477-82. DOI: https://doi.org/10.1002/art.39596
Therkildsen P, de Thurah A, Nielsen BD, Faurschou M, Baslund B, Hansen IT, et al. The one-year infection risk among patients diagnosed with giant cell arteritis: use of antibiotics and hospitalisations. Rheumatology 2025; 64: 740-6. DOI: https://doi.org/10.1093/rheumatology/keae107
Durand M, Thomas SL. Incidence of infections in patients with giant cell arteritis: a cohort study. Arthritis Care Res 2012; 64: 581-8. DOI: https://doi.org/10.1002/acr.21569
Calderón-Goercke M, Loricera J, Aldasoro V, Castañeda S, Villa I, Humbría A, et al. Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice. Semin Arthritis Rheum 2019; 49: 126-35. DOI: https://doi.org/10.1016/j.semarthrit.2019.01.003
Berger CT, Greiff V, John S, Koenig KF, Bigler MB, Recher M, et al. Risk factors for pneumocystis pneumonia in giant cell arteritis: a single-centre cohort study. Clin Exp Rheumatol 2015; 33: S-122-5.
Kermani TA, Ytterberg SR, Warrington KJ. Pneumocystis jiroveci pneumonia in giant cell arteritis: a case series. Arthritis Care Res 2011; 63: 761-5. DOI: https://doi.org/10.1002/acr.20435
Cettomai D, Gelber AC, Christopher-Stine L. A survey of rheumatologists’ practice for prescribing pneumocystis prophylaxis. J Rheumatol 2010; 37: 792-9. DOI: https://doi.org/10.3899/jrheum.090843
Anumolu N, Henry K, Sattui SE, Putman M. Is there a role for Pneumocystis jiroveci pneumonia prophylaxis in giant cell arteritis or polymyalgia rheumatica? Semin Arthritis Rheum 2023; 58: 152154. DOI: https://doi.org/10.1016/j.semarthrit.2022.152154
Katsuyama T, Saito K, Kubo S, Nawata M, Tanaka Y. Prophylaxis for Pneumocystis pneumonia in patients with rheumatoid arthritis treated with biologics, based on risk factors found in a retrospective study. Arthritis Res Ther 2014; 16: R43. DOI: https://doi.org/10.1186/ar4472
How to Cite
To prophylax or not to prophylax? The role of trimethoprim/sulfamethoxazole as a prophylactic agent in systemic vasculitis: the case of antineutrophil cytoplasmic antibody- associated vasculitis and giant cell arteritis. (2025). Reumatismo. https://doi.org/10.4081/reumatismo.2025.1791
Copyright (c) 2025 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
