{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:59:26Z","timestamp":1790863166495,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T00:00:00Z","timestamp":1616198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: The human anti-IL-6 receptor antibody tocilizumab (TCZ) has been approved for the treatment of rheumatoid arthritis (RA) and giant cell arteritis (GCA). It is observed that CRP levels drop quickly after starting TCZ treatment. This may lead to misinterpretation of laboratory results when accessing the patient with infectious disease while on TCZ. We conducted this study to report cases treated with tocilizumab who developed serious infections with special reference to levels of CRP and to review the literature on the effect of tocilizumab on acute phase response (APR) during infections. Methods: The files of RA and GCA patients hospitalized in the Tel Aviv medical center between 2009\u20132019 were reviewed. Cases of patients with RA and GCA treated with tocilizumab who were hospitalized due to severe infections were reviewed with special emphasis on the duration of treatment, type of infection, and APR. Results: We identified nine admissions. Seven patients were treated with tocilizumab for RA, two for GCA. The diagnosis was pneumonia in three cases, osteomyelitis in one, cellulitis in one, endocarditis due to Whipple disease in one, abscess of cervix uteri in one, meningitis in one, and perforated diverticulitis in one. The mean CRP levels on admission were 4.75 mg\/L (normal range, up to 5 mg\/L). All cases were diagnosed correctly on admission. Conclusions: CRP levels may not correctly reflect the severity of infectious diseases during tocilizumab treatment. Increased awareness of the masking effect of tocilizumab on the APR during infection is needed in order to avoid a delay in the diagnosis.<\/jats:p>","DOI":"10.3390\/life11030258","type":"journal-article","created":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T22:00:37Z","timestamp":1616364037000},"page":"258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The Effect of Tocilizumab on Inflammatory Markers in Patients Hospitalized with Serious Infections. Case Series and Review of Literature"],"prefix":"10.3390","volume":"11","author":[{"given":"Mark","family":"Berman","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronen","family":"Ben-Ami","sequence":"additional","affiliation":[{"name":"Infectious Disease Unit, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlomo","family":"Berliner","sequence":"additional","affiliation":[{"name":"Tel Aviv Medical Center, Internal Medicine E Department, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Anouk","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Broyde","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Borok","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ori","family":"Elkayam","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1177\/1759720X10378372","article-title":"The role of interleukin 6 in the pathophysiology of rheumatoid arthritis","volume":"2","author":"Srirangan","year":"2010","journal-title":"Adv. Musculoskelet Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.2165\/00003495-200969050-00007","article-title":"Tocilizumab: A review of its use in the management of rheumatoid arthritis","volume":"69","author":"Oldfield","year":"2009","journal-title":"Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1056\/NEJMoa1613849","article-title":"Trial of Tocilizumab in Giant-Cell Arteritis","volume":"377","author":"Stone","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1136\/ard.2008.092866","article-title":"Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): Evidence of safety and efficacy in a 5-year extension study","volume":"68","author":"Nishimoto","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/ncprheum0338","article-title":"Interleukin 6: From bench to bedside","volume":"2","author":"Nishimoto","year":"2006","journal-title":"Nat. Clin. Pract. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0969-2126(99)80023-9","article-title":"The physiological structure of human C-reactive protein and its complex with phosphocholine","volume":"7","author":"Thompson","year":"1999","journal-title":"Structure"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5294","DOI":"10.4049\/jimmunol.160.11.5294","article-title":"Testosterone and IL-6 requirements for human C-reactive protein gene expression in transgenic mice","volume":"160","author":"Szalai","year":"1998","journal-title":"J. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1385\/IR:24:2:163","article-title":"C-Reactive Protein, Inflammation, and Innate Immunity","volume":"24","author":"Mortensen","year":"2001","journal-title":"Immunol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1084\/jem.154.5.1703","article-title":"C-reactive protein is protective against Streptococcus pneumoniae infection in mice","volume":"154","author":"Mold","year":"1981","journal-title":"J. Exp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5652","DOI":"10.1128\/IAI.68.10.5652-5656.2000","article-title":"Human C-reactive protein is protective against fatal Salmonella enterica serovar typhimurium infection in transgenic mice","volume":"68","author":"Szalai","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.clim.2005.08.004","article-title":"C-reactive protein: Ligands, receptors and role in inflammation","volume":"117","author":"Marnell","year":"2005","journal-title":"Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1136\/bmj.332.7545.838","article-title":"Infections","volume":"332","author":"Healy","year":"2006","journal-title":"Br. Med. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1093\/rheumatology\/keg263","article-title":"Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF\u03b1 therapy","volume":"42","author":"Kroesen","year":"2003","journal-title":"Rheumatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/S0749-0704(02)00022-2","article-title":"Infections in the immunocompromised rheumatologic patient","volume":"18","author":"Greenberg","year":"2002","journal-title":"Crit. Care Clin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jcrc.2017.07.025","article-title":"Accuracy of C-Reactive protein as a bacterial infection marker in critically immunosuppressed patients: A systematic review and meta-analysis","volume":"42","author":"Moraes","year":"2017","journal-title":"J. Crit. Care"},{"key":"ref_16","first-page":"339","article-title":"Impaired immune and acute-phase responses in interleukin-6-deficient mice","volume":"368","author":"Kopf","year":"1994","journal-title":"Nat. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R141","DOI":"10.1186\/ar3455","article-title":"Integrated safety in tocilizumab clinical trials","volume":"13","author":"Schiff","year":"2011","journal-title":"Arthritis Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1093\/rheumatology\/ker223","article-title":"Risk of infections in rheumatoid arthritis patients treated with tocilizumab","volume":"51","author":"Lang","year":"2011","journal-title":"Rheumatology"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nguyen, M.T.T., P\u00f8denphant, J., and Ravn, P. (2013). Three cases of severely disseminated Staphylococcus aureus infection in patients treated with tocilizumab. BMJ Case Rep.","DOI":"10.1136\/bcr-2012-007413"},{"key":"ref_20","first-page":"0220125835","article-title":"The absence of typical pneumonia symptoms in a patient with rheumatoid arthritis during tocilizumab and steroid treatment","volume":"2012","author":"Yanagawa","year":"2012","journal-title":"BMJ Case Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3109\/s10165-008-0111-7","article-title":"Masked early symptoms of pneumonia in patients with rheumatoid arthritis during tocilizumab treatment: A report of two cases","volume":"19","author":"Fujiwara","year":"2009","journal-title":"Mod. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bari, S.F., Khan, A., and Lawson, T. (2013). C reactive protein may not be reliable as a marker of severe bacterial infection in patients receiving tocilizumab. BMJ Case Rep., 2013.","DOI":"10.1136\/bcr-2013-010423"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"280","DOI":"10.7861\/clinmedicine.17-3-280","article-title":"Lesson of the month 1: Septic arthritis with normal acute phase reactants and white cell count in a patient receiving tocilizumab","volume":"17","author":"Conway","year":"2017","journal-title":"Clin. Med."},{"key":"ref_24","first-page":"1678","article-title":"Immunosuppression may mask severe infection. Septic arthritis in tocilizumab treatment yielded only modest acute-phase reaction","volume":"109","author":"Ljung","year":"2012","journal-title":"Lakartidningen"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3109\/s10165-011-0459-y","article-title":"Diagnostic features of mild cellulitis phlegmon in patients with rheumatoid arthritis treated with tocilizumab: A report of two cases","volume":"21","author":"Hirao","year":"2011","journal-title":"Mod. Rheumatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.2169\/internalmedicine.54.3103","article-title":"Fatal Complication of Legionella pneumophila Pneumonia in a Tocilizumab-treated Rheumatoid Arthritis Patient","volume":"54","author":"Arinuma","year":"2015","journal-title":"Intern. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"660","DOI":"10.3109\/s10165-011-0449-0","article-title":"Recurrent allergic bronchopulmonary aspergillosis in a patient with rheumatoid arthritis treated with etanercept and tocilizumab","volume":"21","author":"Honda","year":"2011","journal-title":"Mod. Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.annder.2017.03.011","article-title":"\u00c9rysip\u00e8le sans fi\u00e8vre ni syndrome inflammatoire lors d\u2019un traitement par tocilizumab","volume":"144","author":"Henry","year":"2017","journal-title":"Ann. Dermatol. V\u00e9n\u00e9r\u00e9ologie"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.reuma.2016.10.008","article-title":"Necrotizing fasciitis in a patient receiving tocilizumab for rheumatoid arthritis\u2014Case report","volume":"14","author":"Bernardes","year":"2018","journal-title":"Reumatol. Cl\u00ednica"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.2169\/internalmedicine.54.3956","article-title":"Mycobacterium abscessus Pulmonary Infection under Treatment with Tocilizumab","volume":"54","author":"Kobayashi","year":"2015","journal-title":"Intern. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.2169\/internalmedicine.55.5981","article-title":"Cytomegalovirus Reactivation Induced Acute Hepatitis and Gastric Erosions in a Patient with Rheumatoid Arthritis under Treatment with an Anti-IL-6 Receptor Antibody, Tocilizumab","volume":"55","author":"Komura","year":"2016","journal-title":"Intern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Manabe, S., Yanagi, H., Ozawa, H., and Takagi, A. (2017). Necrotising soft tissue infection without systemic toxicity in a patient with rheumatoid arthritis treated with tocilizumab. BMJ Case Rep., 2017.","DOI":"10.1136\/bcr-2017-222826"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3109\/s10165-011-0505-9","article-title":"Necrotizing fasciitis in a patient with rheumatoid arthritis treated with tocilizumab","volume":"22","author":"Yoshida","year":"2011","journal-title":"Mod. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.jiac.2019.02.005","article-title":"Disseminated nocardiosis with Nocardia brasiliensis bacteremia in a patient with rheumatoid arthritis using tocilizumab","volume":"25","author":"Yamate","year":"2019","journal-title":"J. Infect. Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Williams, C.J., Foote, A., and Choi, P. (2019). Pseudomonas meningoencephalitis masquerading as a stroke in a patient on tocilizumab. BMJ Case Rep., 12.","DOI":"10.1136\/bcr-2018-227296"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1186\/1752-1947-5-499","article-title":"Severe sepsis caused by Aeromonas hydrophila in a patient using tocilizumab: A case report","volume":"5","author":"Okumura","year":"2011","journal-title":"J. Med Case Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.jos.2015.06.018","article-title":"Pyogenic spondylodiscitis following anti-interleukin-6 therapy in a patient with rheumatoid arthritis (implication of hematogenous infection risk in degenerative intervertebral discs): A case report and review of the literature","volume":"21","author":"Tsujimoto","year":"2016","journal-title":"J. Orthop. Sci."},{"key":"ref_38","first-page":"951","article-title":"Streptococcal lung abscesses from a dental focus following tocilizumab: A case report","volume":"30","author":"Bel","year":"2012","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jbspin.2012.10.015","article-title":"An unusual complication of tocilizumab therapy: MRI appearances of thenar eminence pyomyositis","volume":"80","author":"Raine","year":"2013","journal-title":"Jt. Bone Spine"},{"key":"ref_40","first-page":"245","article-title":"Tropheryma Whipplei infection mimicking giant cell arteritis flare in a patient treated with interleukin-6 receptor blocker tocilizumab","volume":"124","author":"Razanamahery","year":"2020","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/j.cmi.2020.05.030","article-title":"Tuberculosis sepsis after tocilizumab treatment","volume":"26","author":"Reisinger","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_42","first-page":"577","article-title":"Necrotizing fasciitis in a rheumatoid arthritis patient treated with tocilizumab","volume":"51","year":"2011","journal-title":"Rheumatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1093\/rheumatology\/ket379","article-title":"Polyarticular late infection of total joint arthroplasties in a patient with rheumatoid arthritis treated with anti-interleukin-6 therapy","volume":"53","author":"Wakabayashi","year":"2013","journal-title":"Rheumatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1080\/14397595.2018.1515059","article-title":"Comparison of the clinical characteristics and severity of community-acquired pneumonia between patients with rheumatoid arthritis treated with tocilizumab and those treated with TNF inhibitor","volume":"29","author":"Nagai","year":"2019","journal-title":"Mod. Rheumatol."},{"key":"ref_45","first-page":"905","article-title":"Serious infection across biologic-treated patients with rheumatoid arthritis: Results from the British Society for Rheumatolgy Biologics Register for Rheumatoid Arthritis","volume":"77","author":"Rutherford","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1080\/14397595.2017.1366007","article-title":"Prodromal signs and symptoms of serious infections with tocilizumab treatment for rheumatoid arthritis: Text mining of the Japanese postmarketing adverse event-reporting database","volume":"28","author":"Atsumi","year":"2018","journal-title":"Mod. Rheumatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/rheumatology\/kex336","article-title":"Interleukin-6 flags infection in tocilizumab-treated giant cell arteritis","volume":"57","author":"Berger","year":"2017","journal-title":"Rheumatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1007\/s00296-020-04705-2","article-title":"Utility of the neutrophil-to-lymphocyte ratio for predicting bacterial infection in patients with rheumatoid arthritis receiving Tocilizumab","volume":"40","author":"Nagai","year":"2020","journal-title":"Rheumatol. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1097\/INF.0b013e318295a3d0","article-title":"Procalcitonin","volume":"32","author":"Gaensbauer","year":"2013","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"696","DOI":"10.3109\/s10165-009-0223-8","article-title":"Neutrophil CD64 as a marker of infection in patients treated with tocilizumab","volume":"19","author":"Matsui","year":"2009","journal-title":"Mod. Rheumatol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/3\/258\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:38:40Z","timestamp":1760161120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/3\/258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,20]]},"references-count":50,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["life11030258"],"URL":"https:\/\/doi.org\/10.3390\/life11030258","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,20]]}}}