Lymphopenia and Treatment-Related Infectious Complications in ANCA-Associated Vasculitis

Abstract

SummaryBackground 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, 0.3-1.03 10 9 /L), or severe (lymphocyte count # 0.3310 9 /L) lymphopenia and neutropenia (neutrophil count # 1.5310 9 /L).Results One hundred patients had a mean age of 57615 years and a Birmingham vasculitis activity score of 7.763.6. 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.

Lymphocytopenia Is an Independent Predictor of Unfavorable Functional Outcome in Spontaneous Intracerebral Hemorrhage

“…Lymphocytopenia was defined according to common definitions (L<1000·10 9 /L). [16][17][18] We assessed patient characteristics, for example, history of stroke, cardiovascular comorbidity, nicotine or alcohol abuse, by standardized mailed questionnaires. We conducted a semiquantitative phone interviews-performed by physicians trained and certified for data collection on disability and quality of life-with patients or their closest relatives if the questionnaire did not return within 2 to 4 weeks.…”

Outcomes of Elderly Patients with Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis Treated with Immunosuppressive Therapy

“…Infection was the leading cause of death in this cohort as in other studies [12] and all deaths attributable to severe infections occurred early in the treatment course (within the first 6 months) [3,4,6], when disease activity was greatest, and the highest doses of corticosteroids were used coupled with cyclophosphamide [4,5,8,10,14]. Another study also reported significantly higher rates of severe infections associated with severe lymphopenia (p < 0.001), independent of other risk factors [10].…”

“…Another study also reported significantly higher rates of severe infections associated with severe lymphopenia (p < 0.001), independent of other risk factors [10]. In addition, lower estimated glomerular filtration rate (eGFR) and longer duration of glucocorticoid use was also shown to be associated with poorer outcomes [8,10,12].…”

“…It is associated with dose-dependent toxicity resulting in leukopenia and increased susceptibility to infections [5,6,8,10]. It has been argued that doses of cyclophosphamide should be adjusted according to age and renal function to help minimise toxicity [4,11].…”

What can we do to Prevent Infections in Adult Patients with Rheumatic Diseases?

“…Prolonged corticosteroid treatment has been identified as one of the underlying factors [9]. Biological therapies increase the possibility of serious infections, with varying effects on the safety profile depending on their mechanism of action.…”