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Research ArticleArticle

Severe Infection in Antineutrophil Cytoplasmic Antibody-associated Vasculitis

Aladdin J. Mohammad, Mårten Segelmark, Rona Smith, Martin Englund, Jan-Åke Nilsson, Kerstin Westman, Peter A. Merkel and David R.W. Jayne
The Journal of Rheumatology August 2017, jrheum.160909; DOI: https://doi.org/10.3899/jrheum.160909
Aladdin J. Mohammad
From Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Orthopedics, Clinical Epidemiology Unit, and Section of Nephrology, Lund; Department of Medicine and Nephrology, Linköping University, Linköping, Sweden; Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge, UK; Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts; Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Supported by research grants from The Faculty of Medicine, Lund University, Governmental Funding of Clinical Research within National Health Service (ALF-medel), The Swedish Rheumatism Association (Reumatikerförbundet) and The Swedish Medical Association (Svenska Läkarsällskapet). D.R. Jayne is supported by the Cambridge Biomedical Research Centre. A.J. Mohammad, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Segelmark, MD, PhD, Department of Medicine and Nephrology, Linköping University; R. Smith, MA, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Englund, MD, PhD, Lund University, Department of Clinical Sciences Lund, Orthopedics, Clinical Epidemiology Unit, and Clinical Epidemiology Research and Training Unit, Boston University School of Medicine; J.Å. Nilsson, BSc, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology; K. Westman, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Nephrology; P.A. Merkel, MD, MPH, Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania; D.R. Jayne, FMedSci, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital. Address correspondence to Dr. A.J. Mohammad, Department of Rheumatology, Skåne University Hospital, Lund SE-221 85, Sweden. E-mail: Aladdin.mohammad@med.lu.se. Accepted for publication May 10, 2017.
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Mårten Segelmark
From Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Orthopedics, Clinical Epidemiology Unit, and Section of Nephrology, Lund; Department of Medicine and Nephrology, Linköping University, Linköping, Sweden; Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge, UK; Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts; Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Supported by research grants from The Faculty of Medicine, Lund University, Governmental Funding of Clinical Research within National Health Service (ALF-medel), The Swedish Rheumatism Association (Reumatikerförbundet) and The Swedish Medical Association (Svenska Läkarsällskapet). D.R. Jayne is supported by the Cambridge Biomedical Research Centre. A.J. Mohammad, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Segelmark, MD, PhD, Department of Medicine and Nephrology, Linköping University; R. Smith, MA, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Englund, MD, PhD, Lund University, Department of Clinical Sciences Lund, Orthopedics, Clinical Epidemiology Unit, and Clinical Epidemiology Research and Training Unit, Boston University School of Medicine; J.Å. Nilsson, BSc, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology; K. Westman, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Nephrology; P.A. Merkel, MD, MPH, Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania; D.R. Jayne, FMedSci, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital. Address correspondence to Dr. A.J. Mohammad, Department of Rheumatology, Skåne University Hospital, Lund SE-221 85, Sweden. E-mail: Aladdin.mohammad@med.lu.se. Accepted for publication May 10, 2017.
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Rona Smith
From Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Orthopedics, Clinical Epidemiology Unit, and Section of Nephrology, Lund; Department of Medicine and Nephrology, Linköping University, Linköping, Sweden; Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge, UK; Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts; Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Supported by research grants from The Faculty of Medicine, Lund University, Governmental Funding of Clinical Research within National Health Service (ALF-medel), The Swedish Rheumatism Association (Reumatikerförbundet) and The Swedish Medical Association (Svenska Läkarsällskapet). D.R. Jayne is supported by the Cambridge Biomedical Research Centre. A.J. Mohammad, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Segelmark, MD, PhD, Department of Medicine and Nephrology, Linköping University; R. Smith, MA, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Englund, MD, PhD, Lund University, Department of Clinical Sciences Lund, Orthopedics, Clinical Epidemiology Unit, and Clinical Epidemiology Research and Training Unit, Boston University School of Medicine; J.Å. Nilsson, BSc, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology; K. Westman, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Nephrology; P.A. Merkel, MD, MPH, Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania; D.R. Jayne, FMedSci, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital. Address correspondence to Dr. A.J. Mohammad, Department of Rheumatology, Skåne University Hospital, Lund SE-221 85, Sweden. E-mail: Aladdin.mohammad@med.lu.se. Accepted for publication May 10, 2017.
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Martin Englund
From Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Orthopedics, Clinical Epidemiology Unit, and Section of Nephrology, Lund; Department of Medicine and Nephrology, Linköping University, Linköping, Sweden; Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge, UK; Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts; Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Supported by research grants from The Faculty of Medicine, Lund University, Governmental Funding of Clinical Research within National Health Service (ALF-medel), The Swedish Rheumatism Association (Reumatikerförbundet) and The Swedish Medical Association (Svenska Läkarsällskapet). D.R. Jayne is supported by the Cambridge Biomedical Research Centre. A.J. Mohammad, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Segelmark, MD, PhD, Department of Medicine and Nephrology, Linköping University; R. Smith, MA, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Englund, MD, PhD, Lund University, Department of Clinical Sciences Lund, Orthopedics, Clinical Epidemiology Unit, and Clinical Epidemiology Research and Training Unit, Boston University School of Medicine; J.Å. Nilsson, BSc, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology; K. Westman, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Nephrology; P.A. Merkel, MD, MPH, Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania; D.R. Jayne, FMedSci, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital. Address correspondence to Dr. A.J. Mohammad, Department of Rheumatology, Skåne University Hospital, Lund SE-221 85, Sweden. E-mail: Aladdin.mohammad@med.lu.se. Accepted for publication May 10, 2017.
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Jan-Åke Nilsson
From Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Orthopedics, Clinical Epidemiology Unit, and Section of Nephrology, Lund; Department of Medicine and Nephrology, Linköping University, Linköping, Sweden; Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge, UK; Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts; Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Supported by research grants from The Faculty of Medicine, Lund University, Governmental Funding of Clinical Research within National Health Service (ALF-medel), The Swedish Rheumatism Association (Reumatikerförbundet) and The Swedish Medical Association (Svenska Läkarsällskapet). D.R. Jayne is supported by the Cambridge Biomedical Research Centre. A.J. Mohammad, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Segelmark, MD, PhD, Department of Medicine and Nephrology, Linköping University; R. Smith, MA, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Englund, MD, PhD, Lund University, Department of Clinical Sciences Lund, Orthopedics, Clinical Epidemiology Unit, and Clinical Epidemiology Research and Training Unit, Boston University School of Medicine; J.Å. Nilsson, BSc, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology; K. Westman, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Nephrology; P.A. Merkel, MD, MPH, Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania; D.R. Jayne, FMedSci, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital. Address correspondence to Dr. A.J. Mohammad, Department of Rheumatology, Skåne University Hospital, Lund SE-221 85, Sweden. E-mail: Aladdin.mohammad@med.lu.se. Accepted for publication May 10, 2017.
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Kerstin Westman
From Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Orthopedics, Clinical Epidemiology Unit, and Section of Nephrology, Lund; Department of Medicine and Nephrology, Linköping University, Linköping, Sweden; Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge, UK; Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts; Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Supported by research grants from The Faculty of Medicine, Lund University, Governmental Funding of Clinical Research within National Health Service (ALF-medel), The Swedish Rheumatism Association (Reumatikerförbundet) and The Swedish Medical Association (Svenska Läkarsällskapet). D.R. Jayne is supported by the Cambridge Biomedical Research Centre. A.J. Mohammad, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Segelmark, MD, PhD, Department of Medicine and Nephrology, Linköping University; R. Smith, MA, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Englund, MD, PhD, Lund University, Department of Clinical Sciences Lund, Orthopedics, Clinical Epidemiology Unit, and Clinical Epidemiology Research and Training Unit, Boston University School of Medicine; J.Å. Nilsson, BSc, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology; K. Westman, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Nephrology; P.A. Merkel, MD, MPH, Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania; D.R. Jayne, FMedSci, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital. Address correspondence to Dr. A.J. Mohammad, Department of Rheumatology, Skåne University Hospital, Lund SE-221 85, Sweden. E-mail: Aladdin.mohammad@med.lu.se. Accepted for publication May 10, 2017.
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Peter A. Merkel
From Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Orthopedics, Clinical Epidemiology Unit, and Section of Nephrology, Lund; Department of Medicine and Nephrology, Linköping University, Linköping, Sweden; Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge, UK; Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts; Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Supported by research grants from The Faculty of Medicine, Lund University, Governmental Funding of Clinical Research within National Health Service (ALF-medel), The Swedish Rheumatism Association (Reumatikerförbundet) and The Swedish Medical Association (Svenska Läkarsällskapet). D.R. Jayne is supported by the Cambridge Biomedical Research Centre. A.J. Mohammad, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Segelmark, MD, PhD, Department of Medicine and Nephrology, Linköping University; R. Smith, MA, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Englund, MD, PhD, Lund University, Department of Clinical Sciences Lund, Orthopedics, Clinical Epidemiology Unit, and Clinical Epidemiology Research and Training Unit, Boston University School of Medicine; J.Å. Nilsson, BSc, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology; K. Westman, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Nephrology; P.A. Merkel, MD, MPH, Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania; D.R. Jayne, FMedSci, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital. Address correspondence to Dr. A.J. Mohammad, Department of Rheumatology, Skåne University Hospital, Lund SE-221 85, Sweden. E-mail: Aladdin.mohammad@med.lu.se. Accepted for publication May 10, 2017.
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David R.W. Jayne
From Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Orthopedics, Clinical Epidemiology Unit, and Section of Nephrology, Lund; Department of Medicine and Nephrology, Linköping University, Linköping, Sweden; Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge, UK; Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts; Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Supported by research grants from The Faculty of Medicine, Lund University, Governmental Funding of Clinical Research within National Health Service (ALF-medel), The Swedish Rheumatism Association (Reumatikerförbundet) and The Swedish Medical Association (Svenska Läkarsällskapet). D.R. Jayne is supported by the Cambridge Biomedical Research Centre. A.J. Mohammad, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology, and Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Segelmark, MD, PhD, Department of Medicine and Nephrology, Linköping University; R. Smith, MA, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital; M. Englund, MD, PhD, Lund University, Department of Clinical Sciences Lund, Orthopedics, Clinical Epidemiology Unit, and Clinical Epidemiology Research and Training Unit, Boston University School of Medicine; J.Å. Nilsson, BSc, Lund University, Department of Clinical Sciences Lund, Section of Rheumatology; K. Westman, MD, PhD, Lund University, Department of Clinical Sciences Lund, Section of Nephrology; P.A. Merkel, MD, MPH, Penn Vasculitis Center, Division of Rheumatology and Department of Biostatistics and Epidemiology, University of Pennsylvania; D.R. Jayne, FMedSci, Vasculitis and Lupus Clinic, Addenbrooke’s Hospital. Address correspondence to Dr. A.J. Mohammad, Department of Rheumatology, Skåne University Hospital, Lund SE-221 85, Sweden. E-mail: Aladdin.mohammad@med.lu.se. Accepted for publication May 10, 2017.
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Abstract

Objective To compare the rate of severe infections after the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with the rate in the background population, and to identify predictors of severe infections among patients with AAV.

Methods The study cohort was 186 patients with AAV diagnosed from 1998 to 2010, consisting of all known cases in a defined population in southern Sweden. For each patient, 4 age- and sex-matched reference subjects were randomly chosen from the background population. Using the Skåne Healthcare Register, all International Classification of Diseases codes of infections assigned from 1998 to 2011 were identified. Severe infections were defined as infectious episodes requiring hospitalization. Rate ratios were calculated by dividing the rate in AAV by the rate among the reference subjects.

Results The rate ratio for all severe infections was 4.53 (95% CI 3.39–6.00). The highest rate ratios were found for upper respiratory tract: 8.88 (3.54–25.9), Clostridium difficile: 5.35 (1.54–23.8), nonspecific septicemia 4.55 (1.60–13.8), and skin 5.35 (1.69–19.8). Of the severe infections, 38.4% occurred within 6 months of diagnosis, 30.2% from 7–24 months, and 31.4% after 24 months. High serum creatinine and older age at diagnosis were associated with severe infection (p < 0.001). Of those with severe infection, 46.5% died during followup compared to 26% of patients without severe infection (p = 0.004).

Conclusion Patients with AAV have markedly higher rates of severe infection compared with the background population, especially patients with older age and impaired renal function. The risk of severe infection is particularly high in the first 6 months following the diagnosis of vasculitis.

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Severe Infection in Antineutrophil Cytoplasmic Antibody-associated Vasculitis
Aladdin J. Mohammad, Mårten Segelmark, Rona Smith, Martin Englund, Jan-Åke Nilsson, Kerstin Westman, Peter A. Merkel, David R.W. Jayne
The Journal of Rheumatology Aug 2017, jrheum.160909; DOI: 10.3899/jrheum.160909

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Severe Infection in Antineutrophil Cytoplasmic Antibody-associated Vasculitis
Aladdin J. Mohammad, Mårten Segelmark, Rona Smith, Martin Englund, Jan-Åke Nilsson, Kerstin Westman, Peter A. Merkel, David R.W. Jayne
The Journal of Rheumatology Aug 2017, jrheum.160909; DOI: 10.3899/jrheum.160909
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