Acute gout at engraftment following hematopoietic transplantation
Authors: Rammurti T Kamble, Shan Guo, Carlos A. Ramos, George Carrum
Journal: American Journal of Hematology (2011)

Acute exacerbation of gout or pseudogout has been reported following administration of granulocyte colony stimulating factor (G-CSF) in a healthy donor undergoing stem cell mobilization [1] and in drug-induced cytopenia [2, 3]. Release of proinflammatory cytokines along with rapid cell turnover have been implicated [3-5]. Acute gout exacerbations at engraftment following autologous or allogeneic hematopoietic stem cell transplantation have not been reported; we herein report five consecutive such patients. Between January 2005 and April 2011, a total of 292 hematopoietic transplants (allogeneic = 120, autologous = 172) were performed in adults. Following approval from the Institutional Review Board, their medical records were examined. Twenty-three (7.8%) patients had a history of gout. Of these, five (21.7%) patients developed acute gout during the course of transplant. All five patients had prior established diagnosis of symptomatic gout and were receiving allopurinol prophylaxis. Patients, disease, and transplant characteristics are summarized in Table I. All but one patient were males with median age of 57 years (range = 47–69) and received peripheral stem cell graft with median of 5.45 × 106 CD34+ cells/kg (range = 3.2–7.32). The median time to engraftment for neutrophils [absolute neutrophil count (ANC) of 500 for 3 consecutive days] and platelets (untransfused platelets of more than 20,000 × 3 days) was 15 days (range = 12–17) and 11 days (range = 10–16), respectively. Acute gout preceded engraftment by a median of 2 days (range = 1–3 days) in three patients; two patients had acute gout 1 to 2 days following engraftment (patients #4, 5). The median white blood cell count, ANC and platelet count at the time of acute gout were 2.51 × 103/μL (range = 1.64–5.47), 917/μL (range = 721–3938) and 25 × 103/μL (range = 20–37), respectively. The median serum uric acid level at the onset of acute gout was 5.1 mg/dl (range = 3.1–9.1). In all patients, the clinical presentation of gout was typical of their previous attacks, and in view of their thrombocytopenia, we did not perform diagnostic joint aspiration, using established diagnostic criteria instead [6, 7]. Of the five patients, two were receiving G-CSF at the time of their exacerbation (patients #4, 5). One patient received G-CSF after the acute gout attack on Day 16 (patient #3) and two patients received no G-CSF. Neither of the two patients who received autologous transplant had acute gout during stem cell mobilization. There were no characteristics of the patients, their disease or transplant type that were consistently related to gout exacerbation in this small series. Treatment of acute gout included a short course of systemic steroids in all five patients; three patients also received colchicin. The decision to use colchicin in our patients was based on their quick response to treatment with this agent in previous episodes. Given its myelosuppressive potential, colchicin should generally be reserved for patients who are refractory to steroids. Acute gout can manifest in context of normal uric acid levels, precipitated by trauma, surgery, dehydration, starvation, dietary alcohol, and drugs. Several of the hematopoietic transplant supportive drugs (that can either increase or decrease uric acid levels) including allopurinol, cyclosporine, tacrolimus, low dose aspirin, and loop diuretics among others can promote acute gout. All five patients received allopurinol and variable doses of intravenous furosemide. We do not know why in all five patients gout was precipitated by hemopoietic engraftment. Possible explanations include release of proinflammatory cytokines such as interleukin-1(IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha [5, 8, 9]. These cytokines may peak at Day 12 of hematopoietic transplant [9]. In addition, monosodium urate monohydrate crystals induced release of proinflammatory cytokines from neutrophils have been demonstrated [4]. Thus, gout exacerbation may occur at engraftment even without G-CSF administration and must be considered in the differential diagnosis of joint pain in these patients. Rammurti T Kamble*, Shan Guo*, Carlos A. Ramos*, George Carrum*, * Center of Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital, Houston, TX.