Background/Purpose:

Immune dysregulation associated with SLE leads to a substantially high background risk of infection. This risk of infection further increases with the use of immunosuppressive drugs like cyclophosphamide. Our objective was to determine the incidence and types of infections (especially pneumocystis jirovecii (PCJ) )  in SLE patients treated with cyclophosphamide, and to identify  relative contribution of other variables like patient demographics, steroid dose, other immunosuppressive agents, baseline white blood cell(WBC) count and absolute neutrophil count(ANC) to the risk of infection.

Methods:

We did retrospective chart review of SLE patients presented to our institute over the last 10 years, who have received at least 6 doses of monthly cyclophosphamide infusions(induction phase) and were followed up for 6 months post-induction(maintenance phase) for lupus nephritis. The timings and types of infection, cumulative steroid dose, and maintenance phase immunosuppressive regimen were recorded.  Statistical analyses were done using SAS software(SAS Institute, Cary, NC).

Results:

Majority (90.5%) of the 31 patients with complete records were female.  Mean age was 31.4 years (15- 50 years), 50% Hispanic, 23.8% African American, 11.9% Asian and 14.3% were Caucasian.  None of our patients were on routine prophylaxis for infections including PCJ.

There were 42 episodes of infection in 31 patients. Different types of infection were UTI, URI, line sepsis, bacterial pneumonia, PCJ mucocutaneous infections (fungal/ viral/ bacterial) and viral gastroenteritis.

Incidence of infection was significantly higher among Hispanic patients (p value 0.0425).

As expected, the rate of infection was found to be significantly higher during the induction phase (65.9%) compared to the maintenance phase (34.1%) (p value=0.0041).

Cumulative steroid dose during the induction phase was associated with significantly higher rates of infection (Table 1).

Incidence of infection during maintenance phase tends to be higher in patients on quarterly cyclophosphamide infusion compared to those on daily oral azathioprine or mycophenoalte mofetial.

We did not find any association between baseline WBC count or ANC and risk of infection. 

Conclusion:

In our cohort of SLE patients we found higher infection rates among Hispanics.

Patients with higher cumulative steroid dose during monthly cyclophosphamide infusions are at the highest risk of infection.  Surprisingly only one episode of PCJ was found in our cohort despite absence of routine prophylaxis.

Maintenance treatment with quarterly cyclophosphamide was associated with higher rates of infection as compared to azathioprine or mycophenolate.

Our study limitations include retrospective review, modest numbers and short duration of follow-up.  Larger prospective studies with long-term follow-up are needed to confirm our results.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cyclophosphamide-and-cumulative-steroid-dose-associated-with-higher-risk-of-infections-in-patients-with-lupus-nephritis/