Risk factors for serious infection during treatment with cyclophosphamide and high-dose corticosteroids for systemic lupus erythematosus.
OBJECTIVE
To determine risk factors for serious infection during treatment with cyclophosphamide (CYC) and high-dose corticosteroids in systemic lupus erythematosus (SLE).


METHODS
Records of 100 SLE patients who had received CYC were examined for documentation of serious infections that occurred during CYC therapy and the subsequent 3 months.


RESULTS
Infection occurred in 45 of 100 patients during CYC therapy. Patients with infection were more likely to have multiple organ disease (49% versus 29%; P = 0.04), a lower nadir in the white blood cell (WBC) count (2,818 versus 3,558 cells/microliter; P = 0.02), and a higher maximum corticosteroid dose (195 versus 73 mg; P < or = 0.01) than patients without infection. Infection occurred with equal prevalence in those who received intravenous (IV) (39%) or oral (40%) CYC, but was more common with use of sequential IV and oral therapy (68%). By multivariate analysis, the strongest association with infection was a WBC nadir < or = 3,000 cells/microliter (odds ratio [OR] 2.8, 95% confidence interval [95% Cl] 1.4-5.5) and use of sequential IV and oral CYC (OR 2.3, 95% Cl 1.2-4.3). Infection occurred in more CYC-treated patients taking concomitant steroids than in those treated with high-dose steroids alone (45% versus 12%; P = 0.001). Fatal and opportunistic infections during CYC therapy were associated with a low WBC nadir and a high maximum corticosteroid dose.


CONCLUSIONS
The risk of serious infection in patients with SLE is influenced by the inclusion of CYC in the treatment regimen. The likelihood of infection in this setting is enhanced by CYC-induced reductions in the total WBC count < 3,000 cells/microliter and by sequential IV and oral therapy. Both of these factors may be indicators of aggressive cytotoxic treatment, underscoring the need for close observation during treatment to minimize the risk of serious infection.
Pryor
B D
BD
Washington University School of Medicine, St. Louis, Missouri, USA.
Bologna
S G
SG
Kahl
L E
LE
D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D001424:Bacterial Infections / Q000453:epidemiology* / Q000401:mortality; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000453:epidemiology / Q000401:mortality; D009894:Opportunistic Infections / Q000453:epidemiology* / Q000401:mortality; D012189:Retrospective Studies; D012307:Risk Factors; D014777:Virus Diseases / Q000453:epidemiology / Q000401:mortality
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide