Systemic lupus erythematosus cyclophosphamide

Cyclophosphamide is active against rheumatoid arthritis when given orally at dosages of 2 mg/kg/d but not when given intravenously. It is used regularly to treat systemic lupus erythematosus, vasculitis, Wegener s granulomatosis, and other severe rheumatic diseases. 

Clinical Use. Cyclophosphamide (Cytoxan, Neosar) is an anticancer alkylating agent that is commonly used in a variety of neoplastic disorders (see Chapter 36). This drug may also be helpful in suppressing the immune response in certain autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.12 43 High doses of cyclophosphamide are also used to prevent tissue rejection in patients receiving bone marrow transplants and other organ transplants. 

Cyclophosphamide reportedly caused a type I hypersensitivity reaction in a patient with systemic lupus erythematosus (38). 

A 72-year-old man with autoimmune thrombocytopenia had taken prednisone (30 mg/day) for 1 year, when he was found to have systemic lupus erythematosus (46). Prednisone was continued and he started to take chloroquine (250 mg/day) and monthly cyclophosphamide (0.75 g/m ). Three weeks after the first bolus of cyclophosphamide, he complained of fever and dyspnea, and chest X-rays showed bilateral pulmonary infiltrates. Despite prompt medical management, he died 5 days after admission with cytomegalovirus-induced interstitial pneumonia. 

In another study in patients with Wegener s granulomatosis there was an 11-fold increase in the incidence of lymphomas compared with the general population (41). In contrast, previous exposure to cyclophosphamide did not appear to be associated with a significantly higher risk of cancer in patients with systemic lupus erythematosus, but the number of cases was very low (48). 

It has been suggested that cyclophosphamide can contribute to the risk of cervical dysplasia. In a retrospective study of 110 patients with systemic lupus erythematosus, cervical dysplasia was significantly more frequent in patients who had received intravenous cyclophosphamide (10 of 61) than in a control group who did not receive cyclophosphamide (two of 49) (55). In addition, cervical pathology worsened during cyclophosphamide therapy in all four patients with pre-existing cervical dysplasia, and one patient developed in situ cervical carcinoma. 

Wang CL, Wang F, Bosco JJ. Ovarian failure in oral cyclophosphamide treatment for systemic lupus erythematosus. Lupus 1995 4(1) 11-14. 

McDermott EM, Powell RJ. Incidence of ovarian failure in systemic lupus erythematosus after treatment with pulse cyclophosphamide. Ann Rheum Dis 1996 55(4) 224-9. 

Mok CC, Lau CS, Wong RW. Risk factors for ovarian failure in patients with systemic lupus erythematosus receiving cyclophosphamide therapy. Arthritis Rheum 1998 41(5) 831-7. 

Thong BY, Leong KP, Thumboo J, Koh ET, Tang CY. Cyclophosphamide type I hypersensitivity in systemic lupus erythematosus. Lupus 2002 ll(2) 127-9. 

Pryor BD, Bologna SG, Kahl LE. Risk factors for serious infection during treatment with cyclophosphamide and high-dose corticosteroids for systemic lupus erythematosus. Arthritis Rheum 1996 39(9) 1475-82. 

Garcia-Porrua C, Gonzalez-Gay MA, Perez de Llano LA, Alvarez-Ferreira J. Fatal interstitial pneumonia due to cytomegalovirus following cyclophosphamide treatment in a patient with systemic lupus erythematosus. Scand J Rheumatol 1998 27(6) 465-6. 

Ortmann RA, Klippel JH. Update on cyclophosphamide for systemic lupus erythematosus. Rheum Dis Clin North Am 2000 26 363-375. 

Clearly, a complete evaluation for the presence of lung disease and pulmonary hypertension should be done so that appropriate therapy can be initiated early in the course of disease. Other rheumatologic conditions that may predispose to development of PAH are rheumatoid arthritis and systemic lupus erythematosus, especially in patients with Raynauds phenomenon. For patients in whom there is a reason to suspect acute inflammation or vasculitis, response to immunomodu-lation therapy may at least partially treat pulmonary hypertension (62). This may be particularly relevant in the lupus or mixed-connective tissue patient population. In particular, pulmonary hypertension also markedly improved in a series of patients who were responders to cyclophosphamide therapy. In the appropriate lupus patient who does not have fulminant systemic disease, one may have to consider lung biopsy to assess for inflammation and vasculitis. 

Four patients (two with systemic lupus erythematosus, one with Sjogren s syndrome, and one with Wegener s granulomatosis) developed liver injury when given cyclophosphamide and 3 of them had liver cell necrosis. All had previously been treated with azathioprine and 2 of them had received cyclophosphamide previously without apparent liver damage. It was suggested that azathioprine and eyelophosphamide may have interacted. However, in a retrospective study of eardiac transplant recipients, substitution of cyclophosphamide for azathioprine was associated with improvement in liver ftmetion tests in 29 patients with suspected azathioprine-induced liver impairment. ... 

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