Consecutive pseudogout attacks after repetitive granulocyte colony-stimulating factor administration for neutropenia

Abstract

Several risk factors account for pseudogout development including hemochromatosis, hypothyroidism, primary hyperparathyroidism, and hypomagnesemia. 1-4 Intraarticular injection of hyaluronic acid 5 and parenteral administration of granulocyte colony-stimulating factor (G-CSF) have precipitated acute attacks in two cases. 6,7 We report another case of G-CSF related pseudogout that re-presented at a lesser intensity every time G-CSF was administered to the patient in question.A 74-year-old man developed marked swelling of left foot, ankle, and leg 5 days after receiving three doses of 300 µg of G-CSF subcutaneously for neutropenia ensued after his 4th course of chemotherapy (CEOP: cyclophosphamide, etoposide, vincristine, and prednisolone) for anaplastic large T-cell lymphoma stage IVB. On examination his left foot, ankle, and leg were red, swollen, and tender. He had had low-grade pyrexia at 37.5°C for 2 days. Deep vein thrombosis, early cellulites, and sepsis were excluded by Doppler ultrasound and skin and blood cultures. C-reactive protein was elevated at 50 mg/dl. Aspiration of the 1st metatarsophalangeal (MTP) joint did not yield fl uid. X-rays of feet, ankles, knees, and wrists revealed minor osteoarthritic changes at the 1st MTP of the left foot but no chondrocalcinosis. Health checks before the diagnosis of lymphoma had revealed normal serum urate levels and the patient had never suffered episodes of gout/pseudogout in the past. At the time of lymphoma diagnosis a 24-h urinary urate excretion was normal as well as thyroid function and serum magnesium levels. The patient received allopurinol the day before starting each chemotherapy course and for 2 weeks thereafter. This episode was considered pseudogout and treated with colchicine 500 µg four times daily for 5 days, with remission of pain and swelling.Four weeks after the 5th course of CEOP the patient was again neutropenic and to avoid treatment delay G-CSF was given as above. Pain and swelling developed at the 1st left MTP joint and ankle but to a lesser extent from the previous time, and required only 2 days of colchicine 500 µg four times a day to bring symptoms under control.Polarizing microscopy of a drop of fl uid aspirated from the left 1st MTP revealed birefringent calcium pyrophosphate dihydrate (CPPD) crystals, some free, some within neutrophils, but no urate crystals. Five weeks after the 6th course of CEOP the patient was again neutropenic, developed sepsis, and received i.v. antibiotics and G-CSF at the usual dosage to hasten improvement. Minor pain and swelling developed at the 1st left MTP and settled with naproxen 250 mg 6-hourly for 2 days.Granulocyte colony-stimulating factor improves neutrophil production and function, 8 prevents neutropenia and febrile neutropenia in patients with lymphoma, and allows dose intensity of chemotherapy. 9 Accordingly, G-CSF was given repetitively in this patient despite the severe attack after the fi rst administration but we did not use prophylactic colchicine as we were not foreseeing further attacks. S...

Calcium Pyrophosphate Deposition Disease

“…Although this association is somewhat controversial, the administration of intraarticular hyaluronan preparations may induce acute CPP crystal arthritis. 38 Other possible associations include the use of loop diuretics, 39 granulocyte–macrophage colony-stimulating factor, 40 and pamidronate. 41 …”

Pseudogout: An Autoimmune Paraneoplastic Manifestation of Myelodysplastic Syndrome

“…Our patient’s arthritis did not convalesce with antibiotics as no organism was isolated from the synovial fluid tap; albeit, positively birefringent rhomboid intracellular calcium pyrophosphate crystals were detected in the synovial fluid which confirmed the diagnosis of pseudogout. Two causes, autoimmune paraneoplastic syndrome and administration of granulocyte colony-stimulating factor (G-CSF) in MDS patients for neutropenia [ 9 , 10 ] are reported to manifest pseudogout in MDS, the former being a renowned cause. Because our patient’s multiple attacks of pseudogout involving several joints responded well to steroids, we speculated an autoimmune pathology behind it.…”

Pseudogout Attack after Pegfilgrastim Administration in Anaplastic Large Cell Lymphoma

“…The present patient developed a pseudogout attack when pegfilgrastim was administered, and the neutrophil count was over 20,000 /μL, but he did not suffer a pseudogout attack when filgrastim was administrated. Some reports have suggested that filgrastim is related to pseudogout attacks ( 3 ), but there have been no reports about any attacks with pegfilgrastim. This is likely the first such report.…”