Fatal streptococcal toxic shock syndrome in a patient with rheumatoid arthritis treated with etanercept

I. Uthman, A. Husari, Z. Touma and S. S. Kanj

Departments of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon

Correspondence to: I. W. Uthman, American University of Beirut Medical Center, PO Box: 113-6044, Hamra, Beirut 1103 2090, Lebanon. E-mail: iuthman{at}aub.edu.lb

SIR, We report the case of a 24-yr-old female with a 5-yr history of severe seropositive rheumatoid arthritis (RA) treated only with chloroquine and prednisone. Over the last 2 yr she had been maintained on prednisone 25 mg. Her physical exam revealed Cushingoid features in addition to persistent active joint inflammation in the small joints of the hands and wrists. In view of the severity of her disease it was decided to start her on methotrexate and etanercept. She received her first dose of etanercept 25 mg subcutaneously; the next day she started to complain of nausea, vomiting and diarrhoea associated with fever. She was managed with intravenous fluid and electrolyte replacement. Two days later she presented to the emergency room with fever, hypotension (blood pressure 80/50 mmHg) and generalized lethargy. She reported a history of a fall a few hours before with trauma to her right lower extremity. Her physical exam revealed swelling and erythema over the right knee and thigh. She was managed with fluid replacement and broad spectrum antibiotics. Her condition rapidly deteriorated and she went into shock with further drop in her blood pressure, tachycardia, tachypnoea and anuria. She was intubated, mechanically ventilated and was transferred to the intensive care unit. Her blood pressure did not pick up despite full-dose inotropes and flush fluids. Her right lower extremity rapidly became mottled with sloughing of the overlying skin. She had a cardiac arrest around 12 h after her admission to the emergency room. Two blood cultures revealed streptococcus group A.

The rapid development of a streptococcal toxic shock syndrome shortly after the initiation of etanercept therapy in a young patient with chronic RA raises the question of whether this was a coincidental occurrence or whether the etanercept caused exacerbation of an active subclinical infection. The chronic steroid therapy with 25 mg of prednisone daily should also be considered as an additional contributing factor in masking the infection. In our review of the literature only two cases of fatal sepsis associated with tumour necrosis factor alpha (TNF-{alpha}) blockers were reported [1, 2]. Baghai et al. [1] reported a case of fatal pneumococcal sepsis occurring in a 37-yr-old woman with rheumatoid arthritis treated with etanercept, and Herrlinger et al. [2] reported the case of a 40-yr-old woman who after six infusions of infliximab for perianal Crohn's disease developed staphylococcal pneumonia resulting in fatal adult respiratory distress syndrome. Kroesen et al. [3] reviewed patient charts and records of the infectious disease unit for serious infections in patients with RA in the 2 yr preceding anti-TNF-{alpha} therapy and during therapy. Serious infections affected 18.3% of patients treated with infliximab or etanercept. In several cases, only a few signs or symptoms indicated the severity of developing infections and sepsis; therefore a high level of suspicion of infection is necessary in patients under anti-TNF-{alpha} therapy.

Our experience with TNF-{alpha} blockers at the American University of Beirut Medical Center (a tertiary-care teaching hospital, one of the largest medical centres in Lebanon), dates back to October 2000; up to the present time around 90 patients with various rheumatic diseases have received this drug [4]. No serious infections in our series have been reported except for a case of miliary tuberculosis [5]. A thorough screening for any latent infections, besides tuberculosis, is warranted in patients prior to the initiation of TNF-{alpha} blocker therapy.

The authors have declared no conflicts of interest.

References

  1. Baghai M, Osmon DR, Wolk DM, Wold LE, Haidukewych GJ, Matteson EL. Fatal sepsis in a patient with rheumatoid arthritis treated with etanercept. Mayo Clin Proc 2001;76:653–6.[ISI][Medline]
  2. Herrlinger KR, Borutta A, Meinhardt G, Stange EF, Fellermann K. Fatal staphylococcal sepsis in Crohn's disease after infliximab. Inflamm Bowel Dis 2004;10:655–6.[CrossRef][ISI][Medline]
  3. Kroesen S, Widmer AF, Tyndall A, Hasler P. Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF-alpha therapy. Rheumatology 2003;42:617–21.[Abstract/Free Full Text]
  4. Uthman I, Mroueh K, Arayssi T, Nasr F, Masri A-F, Uthman I. The use of tumor necrosis factor neutralization strategies in rheumatologic disorders other than rheumatoid arthritis in Lebanon. Semin Arthritis Rheum 2004;33:422–3.[CrossRef][ISI][Medline]
  5. Uthman I, Kanj N, El-Sayad J, Bizri A-B. Miliary tuberculosis after infliximab therapy in Lebanon. Clin Rheumatol 2004;23:279–80.[CrossRef][ISI][Medline]
Accepted 8 April 2005





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