Objective: Allopurinol is the most commonly used urate‐lowering therapy in gout. Allopurinol hypersensitivity syndrome (AHS) is a rare but potentially fatal adverse event. Dosing guidelines based on creatinine clearance have been proposed based on the recognition that dosages of ≥300 mg/day may be associated with AHS, particularly in patients with renal impairment. However, the relationship between the allopurinol starting dose and AHS is unknown. This study was undertaken to determine the relationship between allopurinol dosing and AHS.Methods: A retrospective case–control study of patients with gout who developed AHS between January 1998 and September 2010 was undertaken. For each case, 3 controls with gout who were receiving allopurinol but did not develop AHS were identified. Controls were matched with cases for sex, diuretic use at the time of initiating allopurinol, age (±10 years), and estimated glomerular filtration rate (estimated GFR). Starting dose and dose at the time of the reaction in cases were compared between cases and controls.Results: Fifty‐four AHS cases and 157 controls were identified. There was an increase in the risk of AHS as the starting dose of allopurinol corrected for the estimated GFR increased. For the highest quintile of starting dose per estimated GFR, the odds ratio was 23.2 (P < 0.01). Receiver operating characteristic analysis indicated that 91% of AHS cases and 36% of controls received a starting dose of allopurinol of ≥1.5 mg per unit of estimated GFR (mg/ml/minute).Conclusion: Our findings indicate that starting allopurinol at a dose of 1.5 mg per unit of estimated GFR may be associated with a reduced risk of AHS. In patients who tolerate allopurinol, the dose can be gradually increased to achieve the target serum urate level.

Objective. To determine whether MPO contributes to oxidative stress and disease activity in RA and whether it produces hypochlorous acid in SF. Methods. Plasma and where possible SF were collected from 77 RA patients while 120 healthy controls supplied plasma only. MPO and protein carbonyls were measured by ELISAs. 3-Chlorotyrosine in proteins and allantoin in plasma were measured by mass spectrometry. Results. Plasma MPO concentrations were significantly higher in patients with RA compared with healthy controls [10.8 ng/ml, inter-quartile range (IQR): 7.2–14.2; P < 0.05], but there was no significant difference in plasma MPO protein concentrations between RA patients with high disease activity (HDA; DAS-28 >3.2) and those with low disease activity (LDA; DAS-28 ≤3.2) (HDA 27.9 ng/ml, 20.2–34.1 vs LDA 22.1 ng/ml, 16.9–34.9; P > 0.05). There was a significant relationship between plasma MPO and DAS-28 (r = 0.35; P = 0.005). Plasma protein carbonyls and allantoin were significantly higher in patients with RA compared with the healthy controls. MPO protein was significantly higher in SF compared with plasma (median 624.0 ng/ml, IQR 258.4–2433.0 vs 30.2 ng/ml, IQR 25.1–50.9; P < 0.0001). The MPO present in SF was mostly active. 3-Chlorotyrosine, a specific biomarker of hypochlorous acid, was present in proteins from SF and related to the concentration of MPO (r = 0.69; P = 0.001). Protein carbonyls in SF were associated with MPO protein concentration (r = 0.40; P = 0.019) and 3-chlorotyrosine (r = 0.66; P = 0.003). Conclusion. MPO is elevated in patients with RA and promotes oxidative stress through the production of hypochlorous acid.

Objective: There is evidence supporting a therapeutic range for methotrexate polyglutamate (MTXGlu) concentrations in the treatment of rheumatoid arthritis (RA). Knowledge of the pharmacokinetics of MTXGlu_1–5 is required for optimal timing of blood sampling. The aim of this study was to determine the time to steady state and the half‐life of accumulation of red blood cell (RBC) MTXGlu_1–5 in patients with RA commencing oral MTX, and the time for RBC MTXGlu_1–5 to become undetectable and the half‐life of elimination of RBC MTXGlu_1–5 in patients ceasing treatment with oral MTX.Methods: Ten patients beginning treatment and 10 patients stopping treatment with low‐dose oral MTX were recruited. Blood samples were initially collected weekly, with gradual extension to monthly collection over the study period. RBC MTXGlu_1–5 concentrations were assayed by high‐performance liquid chromatography. Results were analyzed using a first‐order exponential method.Results: The median times to reach steady state in RBCs (defined as 90% of the maximum concentration) were 6.2, 10.6, 41.2, 149, and 139.8 weeks, respectively, for MTXGlu₁, MTXGlu₂, MTXGlu₃, MTXGlu₄, and MTXGlu₅. The median half‐life of accumulation for RBC MTXGlu_1–5 ranged from 1.9 weeks to 45.2 weeks. The median times for MTXGlus to become undetectable in RBCs were 4.5, 5.5, 10, 6, and 4 weeks, respectively, for MTXGlu₁, MTXGlu₂, MTXGlu₃, MTXGlu₄, and MTXGlu₅. The median half‐life of elimination for RBC MTXGlu_1–5 ranged from 1.2 weeks to 4.3 weeks.Conclusion: There is wide interpatient variability of RBC MTXGlu_1–5 accumulation and elimination in adults with RA. These data also suggest that after a dose change, >6 months are required for RBC MTXGlu_1–5 to reach steady state. Such delays in achieving steady state suggest that more rapid dose escalation or subcutaneous administration from the outset should be considered.

Objective.: To determine the epidemiology, clinical features, and microbiology of adult native joint septic arthritis in Canterbury, New Zealand, over a 5-year period in individuals with and without an underlying rheumatic disorder.Methods.: Patients with native joint septic arthritis were identified retrospectively and classified by Newman’s criteria. The clinical characteristics were described and comparisons made between those with and without underlying rheumatic disease.Results.: Two hundred forty-eight cases of native joint septic arthritis (mean age 60, range 16–97 yrs) were identified with an overall incidence rate of 12.0/100,000/year (95% CI 10.6–13.6). Yearly incidence increased with age to a maximum of 73.4/100,000 in those > 90 years of age. Septic arthritis was iatrogenic in 16.9% of cases while 27% had an underlying inflammatory arthritis including gout (14.9%), calcium pyrophosphate disease (8.5%), and rheumatoid arthritis (4%). Few patients were taking immunosuppressant therapy, with just 1 taking a biological agent.Staphylococcus aureuswas the most commonly identified organism. Those with underlying inflammatory arthritis were significantly older (73.6 yrs vs 55.6 yrs; p < 0.001), more likely to be female (55.2% vs 26.0%; p < 0.001), and to have septic polyarthritis (16.4% vs 4.4%; p = 0.002). The 30-day mortality was 2%, increasing to 6% at 90 days.Conclusion.: The incidence of septic arthritis in Canterbury, New Zealand, is higher than in previous studies. Crystal arthropathy commonly coexisted with infection although autoimmune arthritis and immunosuppression was less of a factor than anticipated.