Fatal Infections in Systemic Lupus Erythematosus

Hellmann, David B.; Petri, Michelle; Whiting-O'Keefe, Quinn E.

doi:10.1097/00005792-198709000-00002

Cited by 220 publications

(116 citation statements)

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“…Because the presence of multiple organ disease, lower WBC nadir, and a higher maximum steroid dose all significantly correlated with opportunistic infection, we cannot identify a single mechanism for this finding. Other studies have similarly found an association between opportunistic infection and corticosteroid dose (13,17). Hellmann et al additionally reported an association between the use of cytotoxic agents and death secondary to opportunistic infection in SLE patients (17).…”

Section: Discussionmentioning

confidence: 91%

“…Other studies have similarly found an association between opportunistic infection and corticosteroid dose (13,17). Hellmann et al additionally reported an association between the use of cytotoxic agents and death secondary to opportunistic infection in SLE patients (17).…”

Section: Discussionmentioning

confidence: 91%

“…Few studies have provided detailed information regarding infection rates and risk factors during treatment with the cytotoxic agent CYC (1). In one study, cytotoxic therapy of unspecified type was significantly correlated with death from infection, particularly oppor-tunistic infection (17). The cytotoxic agent azathioprine has been implicated as an infection risk factor in several studies (12,15), but exonerated in others (7,13).…”

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confidence: 99%

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Risk factors for serious infection during treatment with cyclophosphamide and high‐dose corticosteroids for systemic lupus erythematosus

Pryor

Bologna

Kahl

1996

Arthritis & Rheumatism

213

122

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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 (4Wo versus 2Wo; P = OM), a lower nadir in the white blood cell (WBC) count (2,818 versus 3,558 celldpl; P = 0.02), and a higher maximum corticosteroid dose (195 versus 73 mg; P S 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 $3,000 cells/pl (odds ratio [OR] 2.8, 95% confidence interval [95% CI] 1.4-5.5) and use of sequential IV and oral CYC (OR 23, 95% CI 12-43), 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 ma)rimum corticosteroid dose.Conelusion. Submitted for publication July 12, 1995; accepted in revised form March 11, 1996. the treatment regimen. The likelihood of infection in this setting is enhanced by CYC-induced reductions in the total WBC count C3, OOO cells/pl 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.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 99%

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Risk factors for serious infection during treatment with cyclophosphamide and high‐dose corticosteroids for systemic lupus erythematosus

Pryor

Bologna

Kahl

1996

Arthritis & Rheumatism

213

122

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“…Routine blood studies were performed, along with tests for C3 and C4 complement levels and anti-doublestranded DNA. An SLE activity index was calculated using a scale developed by Hellman and associates (30).…”

Section: Methodsmentioning

confidence: 99%

Quantitative electroencephalography: A new approach to the diagnosis of cerebral dysfunction in systemic lupus erythematosus

Ritchlin

Chabot

Alper

et al. 1992

Arthritis & Rheumatism

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Objective. Neuropsychiatric manifestations are common in patients with systemic lupus erythematosus (SLE), but accurate diagnosis is often difficult. We conducted a prospective study to determine the utility of neurometric quantitative electroencephalography (QEEG) as an indicator of cerebral dysfunction in SLE patients. Methods. Fifty-two SLE patients were divided into 4 groups based on the results of neuropsychiatric evaluations. These included patients with objective evidence of neuropsychiatric SLE (NPSLE), patients with neuropsychiatric symptoms, patients with no evidence of NPSLE, and patients with a prior history of NPSLE. All QEEG findings were compared with data in an age-regressed normative database and with findings in an independent sample of normal subjects.Results. QEEG sensitivity was 87%, and specificity was 75%. QEEG results were abnormal in 74% of the SLE patients with neuropsychiatric symptoms and in 28% of the patients with no evidence of active NPSLE. QEEG profiles varied as a function of the severity and type of neuropsychiatric manifestation present. Within this patient population, QEEG was more sensitive than magnetic resonance imaging, computed tomography scanning, or conventional EEG.Conclusion. Neurometric QEEG may be a sensitive indicator of cerebral dysfunction in patients with NPSLE and can differentiate patients with diverse neuropsychiatric manifestations. When combined with a careful clinical history and evaluation, QEEG provides information that may be useful for the early detection of NPSLE and for serial evaluation of disease activity and treatment efficacy.Neurologic and psychiatric manifestations of systemic lupus erythematosus (SLE) are common, occurring at any time during the illness, and often in the absence of generalized disease activity. Estimates of the prevalence of neuropsychiatric SLE (NPSLE) vary between 24% and 75% (1-7). This variability is partially due to the lack of uniform diagnostic criteria for determining central nervous system (CNS) involve-

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“…As an alkylating agent, CTX is not only toxic to cells that are in active cell cycle, but is also a carcinogen and mutagen. At doses used for lupus nephritis in humans, CTX therapy results in a reduction in peripheral lymphocytes (12) and an increased risk of some infections (13,14). In addition, prolonged therapy commonly results in ovarian failure (15), azoospermia (16), and an increased rate of various malignancies (17).…”

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confidence: 99%

Cutting Edge: Reversal of Murine Lupus Nephritis with CTLA4Ig and Cyclophosphamide

Daikh

Wofsy

2001

The Journal of Immunology

188

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Cyclophosphamide (CTX) prevents progression of nephritis and prolongs survival in (NZB × NZW)F1 (B/W) mice and is used to treat humans with lupus nephritis. To compare the efficacy of CTLA4Ig with CTX and determine whether there is an incremental benefit to combining CTLA4Ig with CTX, we treated B/W mice with CTX, CTLA4Ig, or both agents. In mice with mild renal disease, treatment delayed the onset of proteinuria and prolonged survival in all groups. In mice with advanced renal disease, treatment with both agents reduced proteinuria in 71% of mice, whereas mice treated with either agent alone had no such improvement. Survival was also markedly improved among mice treated with both agents. Thus, combination treatment with CTX and CTLA4Ig is more effective than either agent alone in reducing renal disease and prolonging survival of B/W mice with advanced nephritis. This striking reversal of proteinuria is unprecedented in animal models of SLE.

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Fatal Infections in Systemic Lupus Erythematosus

Cited by 220 publications

References 0 publications

Risk factors for serious infection during treatment with cyclophosphamide and high‐dose corticosteroids for systemic lupus erythematosus

Risk factors for serious infection during treatment with cyclophosphamide and high‐dose corticosteroids for systemic lupus erythematosus

Quantitative electroencephalography: A new approach to the diagnosis of cerebral dysfunction in systemic lupus erythematosus

Cutting Edge: Reversal of Murine Lupus Nephritis with CTLA4Ig and Cyclophosphamide

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