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How dangerous are norovirus infections in patients with rheumatic diseases treated with biologics and DMARDs? Follow-up on a local outbreak and comparison with a control cohort
  1. Christoph Fiehn,
  2. Nikolaus Miehle
  1. ACURA Center for Rheumatic Diseases, Baden-Baden, Germany
  1. Correspondence to Professor Christoph Fiehn, ACURA Center for Rheumatic Diseases, Rotenbachtalstr. 5, Baden-Baden 76530, Germany; c.fiehn{at}

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Norovirus causes acute gastroenteritis and is highly contagious. In healthy individuals, the symptoms, which mostly are heavy vomiting and diarrhoea, resolve spontaneously after a couple of days. However, in transplantation medicine norovirus infections attained much attention currently, as it was found that immunocompromised transplant recipients are at risk of developing chronic norovirus infections.1 ,2 Although exact numbers are missing, the estimated rate for this complication is 17%–18% in children and adults after allogeneic haematopoietic stem cell or renal transplantation. These patients show prolonged diarrhoea, eventually with weight loss, and chronic norovirus shedding in the stool for up to years.3–7 The patients often have the need for nutritional support and even fatal outcomes were described.3 ,8 Immune recovery was associated with the eventual clearance of the virus in some patients.3 ,9 So far, no cases of chronic norovirus infection in patients who received immunomodulating drugs because of rheumatic diseases were described.

The objective of this work was to investigate whether chronic norovirus infections may also occur in immunosuppressed patients with rheumatic diseases.

In November 2012, within the span of a few days, 47 patients of our institution's Departments of Rheumatology and Psychosomatic Disorders (20% of all inpatients) developed acute gastroenteritis with documented faecal norovirus excretion as detected by ELISA (R-Biopharm, Darmstadt, Germany). The rapid spread of the outbreak through the institution was mediated by a frequently used elevator, which, although superficially cleaned, was contaminated by the vomit of a patient who had a community acquired norovirus infection. All symptomatic patients were tested and in the majority norovirus was found. Six weeks later, all patients with positive testing were sent a questionnaire and were asked to return a stool sample. In all, 41 patients (rate of return 87%) agreed.

A total of 24 out of 41 patients had inflammatory rheumatic diseases (Group A) including the following diagnoses: rheumatoid arthritis (n=15), ankylosing spondylitis (n=3), psoriatic arthritis (n=2), systemic lupus erythematosus (n=2), polymyalgia rheumatica (n=1) and Sjögren's syndrome (n=1). The remaining 17 patients had psychosomatic disorders or fibromyalgia (Group B).

Overall, 13 patients in Group A had been taking biologics (4× rituximab, 3× abatacept, 2× tocilizumab, 2× adalimumab, 1× certolizumab, 1× belimumab) and 16 disease modifying antirheumatic drugs (DMARDs) (9× methotrexate, 3× leflunomide, 2× antimalarials, and 1× azathioprine or ciclosporine A, respectively). The mean prednisone dose was 8.2±5.6 mg/day. Once their acute gastrointestinal (GI) symptoms had resolved, patients resumed their medications.

Patients in both groups reported that the severe symptoms of their infection disappeared spontaneously after 2–3 days. There was no significant difference between the two groups (table 1).

Table 1

Characteristics of patients with either inflammatory rheumatic diseases (Group A) or psychosomatic diseases/fibromyalgia (Group B) with acute norovirus infection during an outbreak in a hospital with departments for rheumatology and for psychosomatic diseases. There was no significant difference in the clinical course of norovirus infection between both groups (Fisher's exact test)

Eight and four of the patients in Groups A and B, respectively, received intravenous volume replacement. Complications included atrial fibrillation (n=1) and Mallory–Weiss syndrome (n=1) in Group A and an increase in serum creatine by more than 20% in one patient in each group. Five and four of the patients in Groups A and B (21% and 24%), respectively, continued to have GI symptoms (bloating and irregular bowel movements) after 6 weeks, but all had a negative stool test for norovirus.

In conclusion, norovirus infections are associated with significant subjective impairment of well-being and its outbreak in rheumatology hospitals should be prevented by strict hygienic measures. However, compared with a control group with psychosomatic disorders, the course of the disease was not more severe or prolonged in patients receiving biologics or DMARDs because of rheumatic diseases. Moreover, persistent norovirus excretion was not found in our population. The restriction of this investigation is the lack of treatment with highly immunosuppressive drugs such as cyclophosphamide and the loss to follow-up of six out of 47 patients. Therefore, immunosuppressed patients with acute norovirus infections should still be monitored carefully.


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  • Contributors Both authors contributed by planning the study, data sampling and documentation. CF wrote the text of the manuscript.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics Committee, University of Heidelberg, Germany.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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