Lymphopenia and treatment-related infectious complications in ANCA-associated vasculitis

Clin J Am Soc Nephrol. 2013 Mar;8(3):416-23. doi: 10.2215/CJN.07300712. Epub 2012 Dec 6.

Abstract

Background and objectives: ANCA-associated vasculitis (AAV) is treated with potent immunosuppressive regimens. This study sought to determine risk factors associated with infections during first-intention therapy.

Design, setting, participants, & measurements: This retrospective study involved two separate cohorts of consecutive cases of AAV seen from 2004 to 2011 at two university hospitals. The following were assessed: vasculitis severity; therapy; and periods with no, moderate (lymphocyte count, 0.3-1.0× 10(9)/L), or severe (lymphocyte count ≤ 0.3×10(9)/L) lymphopenia and neutropenia (neutrophil count ≤ 1.5×10(9)/L).

Results: One hundred patients had a mean age of 57±15 years and a Birmingham vasculitis activity score of 7.7±3.6. Therapy consisted of pulse methylprednisolone (59%), cyclophosphamide (85%), methotrexate (6%), and plasmapheresis (25%) in addition to oral corticosteroids. During follow-up, 53% of patients experienced infection and 28% were hospitalized for infection (severe infection). Only 18% experienced neutropenia, but 72% and 36% presented moderate and severe lymphopenia for a total duration of <0.1%, 73%, and 8% of the treatment follow-up, respectively. Lower initial estimated GFR, longer duration of corticosteroid use, and presence of lymphopenia were risk factors of infections. The rate was 2.23 events/person-year in the presence of severe lymphopenia compared with 0.41 and 0.19 during periods with moderate or no lymphopenia (P<0.001). Similarly, the rate of severe infections was 1.00 event/person-year with severe lymphopenia and 0.08 and 0.10 with moderate and no lymphopenia (P<0.001). This association remained independent of other risk factors.

Conclusions: Lymphopenia is frequent during the treatment of AAV, and its severity is associated with the risk of infectious complications.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / diagnosis
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / drug therapy*
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / immunology
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / mortality
  • Chi-Square Distribution
  • Communicable Diseases / chemically induced*
  • Communicable Diseases / diagnosis
  • Communicable Diseases / immunology
  • Communicable Diseases / mortality
  • Cyclophosphamide / adverse effects
  • Female
  • Hospitals, University
  • Humans
  • Immunocompromised Host*
  • Immunosuppressive Agents / adverse effects*
  • Kaplan-Meier Estimate
  • Linear Models
  • Lymphocyte Count
  • Lymphopenia / chemically induced*
  • Lymphopenia / diagnosis
  • Lymphopenia / immunology
  • Lymphopenia / mortality
  • Male
  • Methotrexate / adverse effects
  • Methylprednisolone / adverse effects
  • Middle Aged
  • Multivariate Analysis
  • Neutropenia / chemically induced
  • Neutropenia / immunology
  • Plasmapheresis
  • Quebec
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide
  • Methylprednisolone
  • Methotrexate