We report a case of reactivation of pseudogout by granulocyte colony-stimulating factor (G-CSF) in a patient receiving chemotherapy for ovarian cancer. To our knowledge, this is the first report of this side effect of G-CSF.

A 70-year-old woman was treated with 9-aminocamptothecin (9-AC) on a National Cancer Institute phase II trial for refractory epithelial ovarian carcinoma. 9-Aminocamptothecin was administered in 14-day cycles at 47 µg/m² body surface area per hour over 72 hours. Treatment with G-CSF (5 µg/kg) was started on day 5 of each cycle and was continued for 8 days. At evaluation for her third cycle, the patient reported pain and swelling in the right leg that had worsened since day 9 of the second cycle (Figure 1). Examination showed a swollen, warm, and tender right leg. Deep venous thrombosis was excluded by Doppler ultrasonography, and pelvic vascular compression and venous clot were excluded by computed tomography of the pelvis. These symptoms resolved, but before the fourth cycle of therapy, similar symptoms developed in the left leg. A left knee effusion was detected. The patient's right leg was normal on examination. Radiography of the knees showed bilateral chondrocalcinosis, a moderate left-knee effusion, and a small right-knee effusion. Arthrocentesis of the left knee yielded inflammatory fluid with 12 000 leukocytes/mm³, 94% of which were neutrophils, and calcium pyrophosphate dihydrate crystals. No urate crystals were detected, and the patient's serum uric acid, calcium, and magnesium levels and thyroid function were normal. The patient then reported a history of pseudogout for which she had been treated 15 years earlier. She responded to intrarticular glucocorticoids and thereafter received colchicine, 0.6 mg twice daily.

View larger version (13K): [in this window] [in a new window]   Figure 1. Granulocyte count during second and third cycles of 9-aminocamptothecin therapy. * = Granulocyte colony-stimulating factor therapy began; = joint symptoms began.

Granulocyte colony-stimulating factor stimulates neutrophil production [1] and enhances induction of neutrophil function in vitro [2]. Pseudogout involves the phagocytosis of calcium pyrophosphate dihydrate crystals elaborated into the joint space, causing release of lysosomal enzymes and a chemotactant glycoprotein, thus producing and maintaining an inflammatory response [3].

Our patient twice developed similar symptoms 4 days after starting G-CSF. We believe that the increase in neutrophil count and responsiveness caused by G-CSF led to this patient's recurrent episodes of pseudogout. We suggest that exacerbation of pseudogout is a side effect that should be considered before G-CSF therapy is initiated.