Role of intravenous cyclophosphamide in the treatment of severe neuropsychiatric systemic lupus erythematosus

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Purpose

We assessed the outcome of 31 patients with severe neuropsychiatric (NP) systemic lupus erythematosus (NPSLE) treated with intravenous cyclophosphamide (IV-CYC), and identified clinical predictors of response to therapy.

Methods

The authors performed a retrospective chart review and classified patients by NP manifestation and response to therapy as measured by serial anatomic imaging and neurodiagnostic studies coupled with clinical assessment of improvement.

Results

Neuropsychiatric manifestations occurred with the following frequencies: organic brain syndromes (OBS) 55%, stroke syndromes 35%, peripheral or mononeuropathy 32%, seizures 29%, psychiatric symptoms 26%, transverse myelitis 16%, cranial neuropathies 13%, other 16%. Most patients had multiple NP manifestations, with a median of two. Ninety percent of patients had failed therapy with corticosteroids with or without cytotoxic drugs prior to treatment with IV-CYC. Eight patients received synchronous plasmapheresis along with IV-CYC. After treatment with IV-CYC, NP deficits substantially improved in 61% (group I), stabilized in 29% (group S), and progressively deteriorated in 10% (group P). Patients in group I had significantly fewer NP manifestations than combined group S+P, two versus four, and a lower frequency of OBS, 37% versus 83%.

Conclusions

Intravenous Cyclophosphamide appears to be an effective treatment for some patients with severe NPSLE refractory to other forms of therapy. Higher number of NP manifestations and presence of OBS may predict poor outcome and identify a group of patients for whom early aggressive therapy may be indicated.

References (43)

  • AustinHA et al.

    Therapy of lupus nephritis: controlled trial of prednisone and cytotoxic drugs

    NEJM.

    (1986)
  • SteinbergAD et al.

    Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only

    Arthritis Rheum.

    (1991)
  • McCuneWJ et al.

    Clinical and immunologic effects of monthly administration of intravenous cyclophosphamide in severe systemic lupus erythematosus

    NEJM.

    (1988)
  • McCuneWJ et al.

    Intravenous cyclophosphamide therapy of severe SLE

    Rheum Dis Clin North Am.

    (1989)
  • WalportMJ et al.

    Reversal of aplastic anemia secondary to systemic lupus erythematosus by high-dose intravenous cyclophosphamide

    BMJ.

    (1982)
  • WinklerA et al.

    High-dose intravenous cyclophosphamide treatment of systemic lupus erythematosus-associated aplastic anemia

    Arthritis Rheum.

    (1988)
  • LaingTJ

    Gastrointestinal vasculitis and pneumatosis intestinalis due to systemic lupus erythematosus: successful treatment with pulse intravenous cyclophosphamide

    Am J Med.

    (1988)
  • VonFeldtJM et al.

    The use of cyclophosphamide in the treatment of CNS lupus

    Arthritis Rheum.

    (1991)
  • BoumpasDT et al.

    Pulse cyclophosphamide for severe neuropsychiatric lupus

    Q J Med.

    (1991)
  • KlippelJH

    Is aggressive therapy effective for lupus?

    Rheum Dis Clin North Am.

    (1993)
  • TanEM et al.

    The 1982 revised criteria for the classification of systemic lupus erythematosus

    Arthritis Rheum.

    (1982)
  • RitchlinCT et al.

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

    Arthritis Rheum.

    (1992)
  • AisenAM et al.

    MR imaging of systemic lupus erythematosus involving the brain

    Am J Neuroradiol.

    (1985)
  • SingerJ et al.

    Diagnostic criteria for neuropsychiatric systemic lupus erythematosus: the result of a consensus meeting

  • KayeBR et al.

    Central nervous system systemic lupus erythematosus mimicking progressive multifocal leukoencephalopathy

    Ann Rheum Dis.

    (1992)
  • FeinglassEJ et al.

    Neuropsychiatric manifestations of systemic lupus erythematosus: diagnosis, clinical spectrum, and relationship to other features of the disease

    Medicine.

    (1976)
  • BoumpasDT et al.

    Neuropsychiatric lupus: a case for guarded optimism

    J Rheumatol.

    (1993)
  • SchroederJO et al.

    Synchronization of plasmapheresis and pulse cyclophosphamide in severe systemic lupus erythematosus

    Ann Int Med.

    (1987)
  • FutrellN et al.

    Central nervous system disease in patients with systemic lupus erythematosus

    Neurology.

    (1992)
  • WinfieldJB et al.

    Intrathecal IgG synthesis and blood-brain barrier impairment in patients with systemic lupus erythematosus and central nervous system dysfunction

    Am J Med.

    (1983)
  • BluesteinHG et al.

    Cerebrospinal fluid antibodies to neuronal cells: association with neuropsychiatric manifestations of systemic lupus erythematosus

    Am J Med.

    (1981)
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