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Veterinary Research Communications Apr 2024Canine leishmaniosis is a vector-borne disease caused by Leishmania infantum, and clinical manifestations of infection range from absent or severe to fatal and result...
Canine leishmaniosis is a vector-borne disease caused by Leishmania infantum, and clinical manifestations of infection range from absent or severe to fatal and result from immune-mediated mechanisms. In dogs, the most common clinical signs of leishmaniosis include skin lesions and lymphadenomegaly. However, the presence of other nontypical signs has been described, and diagnosing these cases can be challenging. The aim of the present short communication was to describe the impact of the formation of circulating immunocomplexes due to L. infantum in a dog with leishmaniosis affected by a massive venous thrombus of the caudal vena cava and external iliac veins. On admission, the dog presented bilateral cutaneous vasculopathy of the thigh and renal disease due to L. infantum infection. Two weeks after starting anti-Leishmania treatment based on meglumine antimoniate and allopurinol administration, the animal developed acute claudication of the hind limbs with the presence of a thrombus in the caudal vena cava and the external iliac veins and a high level of circulating immunocomplexes detected by enzyme-linked immunosorbent assay. Exacerbation of the humoral immune response, along with deposition of circulating immune complexes in the tissues and the concurrent presence of kidney and liver damage, might have contributed to an imbalance in haemostasis in this patient. Future studies should evaluate and analyse the pathological mechanisms contributing to thrombosis in dogs with leishmaniosis.
PubMed: 38630425
DOI: 10.1007/s11259-024-10370-8 -
Nephrology (Carlton, Vic.) Apr 2024Gout affects 15%-30% of individuals with advanced kidney disease. Allopurinol which is rapidly and extensively metabolised to an active metabolite, oxypurinol, is the...
Gout affects 15%-30% of individuals with advanced kidney disease. Allopurinol which is rapidly and extensively metabolised to an active metabolite, oxypurinol, is the most commonly prescribed urate-lowering therapy. Oxypurinol is almost entirely eliminated by the kidneys (>95%) and has an elimination half-life of 18-30 h in those with normal kidney function. However, oxypurinol pharmacokinetics are poorly understood in individuals with kidney failure on peritoneal dialysis. This study characterised the elimination of oxypurinol and urate in people with gout receiving peritoneal dialysis. Oxypurinol steady-state oral clearance (CL/F), elimination half-life as well as kidney (CL) and peritoneal (CL) clearances for oxypurinol and urate were calculated from the plasma, urine and dialysate concentration data for each individual. Our results demonstrate that oxypurinol and urate are removed by peritoneal dialysis, accounting for more than 50% of oxypurinol and urate clearances. An allopurinol dose about 50%-60% lower than the usual dose used for a patient with normal kidney function will provide adequate urate-lowering therapy.
PubMed: 38626950
DOI: 10.1111/nep.14306 -
The Journal of Rheumatology Jun 2024This report evaluates rheumatologists' stated adherence to and agreement with the 2020 American College of Rheumatology (ACR) Guideline for the Management of Gout.
OBJECTIVE
This report evaluates rheumatologists' stated adherence to and agreement with the 2020 American College of Rheumatology (ACR) Guideline for the Management of Gout.
METHODS
A 57-item questionnaire was administered to a sample of US rheumatologists. Stated adherence scores were based on several guideline recommendations reported to be followed by rheumatologists in practice, whereas stated agreement scores were based on whether respondents always followed the recommendations.
RESULTS
All 201 rheumatologists approached completed the questionnaire. The mean overall stated adherence score was 11.5 (maximum 15), whereas the mean overall stated agreement score was 7.7 (maximum 14). Less experienced rheumatologists (≤ 8 yrs; n = 49) were likely to claim adherence to more individual ACR recommendations than those with more experience (> 8 yrs; n = 152; mean stated adherence score: 12.3 vs 11.3; ≤ 0.05). Rheumatologists who claimed to see ≤ 75 patients with gout in 6 months (n = 66) had a mean stated adherence score of 12.1 vs 11.2 for those who claimed to have seen > 75 patients ( ≤ 0.05). Approximately 78% of rheumatologists claimed to follow the guideline for initiating urate-lowering therapy (ULT), and 89% were likely to prescribe allopurinol as a first-line ULT. Claimed adherence to recommendations for dosing was lower (febuxostat: 43%; allopurinol: 39%). Rheumatologists from academic settings were more likely to prescribe an interleukin-1 inhibitor for gout flares.
CONCLUSION
The self-reported practice of the surveyed US rheumatologists was generally concordant with the 2020 ACR Guideline for the Management of Gout. However, there were gaps in guideline knowledge and stated adherence among rheumatologists, mainly concerning the dosing of treatment regimens.
PubMed: 38621796
DOI: 10.3899/jrheum.2023-0981 -
Arthritis Research & Therapy Apr 2024Little is known about long-term clinical outcomes or urate-lowering (ULT) therapy use following pegloticase discontinuation. We examined ULT use, serum urate (SU),...
BACKGROUND/PURPOSE
Little is known about long-term clinical outcomes or urate-lowering (ULT) therapy use following pegloticase discontinuation. We examined ULT use, serum urate (SU), inflammatory biomarkers, and renal function following pegloticase discontinuation.
METHODS
We conducted a retrospective analysis of gout patients who discontinued pegloticase using the Rheumatology Informatics System for Effectiveness (RISE) registry from 1/2016 to 6/2022. We defined discontinuation as a gap ≥ 12 weeks after last infusion. We examined outcomes beginning two weeks after last dose and identified ULT therapy following pegloticase discontinuation. We evaluated changes in lab values (SU, eGFR, CRP and ESR), comparing on- treatment (≤ 15 days of the second pegloticase dose) to post-treatment.
RESULTS
Of the 375 gout patients discontinuing pegloticase, median (IQR) laboratory changes following discontinuation were: SU: +2.4 mg/dL (0.0,6.3); eGFR: -1.9 mL/min (- 8.7,3.7); CRP: -0.8 mg/L (-12.8,0.0); and ESR: -4.0 mm/hr (-13.0,0.0). Therapy post-discontinuation included oral ULTs (86.0%), restarting pegloticase (4.5%), and no documentation of ULT (9.5%), excluding patients with multiple same-day prescriptions (n = 17). Oral ULTs following pegloticase were: 62.7% allopurinol, 34.1% febuxostat. The median (IQR) time to starting/restarting ULT was 92.0 days (55.0,173.0). Following ULT prescribing (≥ 30 days), only 51.0% of patients had SU < 6 mg/dL. Patients restarting pegloticase achieved a median SU of 0.9 mg/dL (IQR:0.2,9.7) and 58.3% had an SU < 6 mg/dL.
CONCLUSION
Pegloticase treats uncontrolled gout in patients with failed response to xanthine oxidase inhibitors, but among patients who discontinue, optimal treatment is unclear. Based on this analysis, only half of those starting another ULT achieved target SU. Close follow-up is needed to optimize outcomes after pegloticase discontinuation.
Topics: Humans; Uric Acid; Retrospective Studies; Gout; Biomarkers; Kidney; Polyethylene Glycols; Urate Oxidase
PubMed: 38609967
DOI: 10.1186/s13075-024-03318-5 -
Frontiers in Pharmacology 2024Accumulating evidence suggests that hyperuricemia is a pathological factor in the development and progression of chronic kidney disease. However, the potential benefit...
Accumulating evidence suggests that hyperuricemia is a pathological factor in the development and progression of chronic kidney disease. However, the potential benefit afforded by the control of uric acid (UA) is controversial. Individual studies show discrepant results, and most existing meta-analysis, especially those including the larger number of studies, lack a placebo or control group as they aim to compare efficacy between drugs. On these grounds, we performed a me-ta-analysis restricted to studies including the action of any anti-gout therapies referenced to a control or placebo arm. This approach allows for a clearer association between UA reduction and renal effect. Of the twenty-nine papers included, most used allopurinol and febuxostat and, therefore, solid conclusions could only be obtained for these drugs. Both were very effective in reducing UA, but only allopurinol was able to significantly improve glomerular filtration rate (GFR), although not in a dose-dependent manner. These results raised doubts as to whether it is the hypouricemic effect of anti-gout drugs, or a pleiotropic effect, what provides protection of kidney function. Accordingly, in a correlation study that we next performed between UA reduction and GFR improvement, no association was found, which suggests that additional mechanisms may be involved. Of note, most trials show large inter-individual response variability, probably because they included patients with heterogeneous phenotypes and pathological characteristics, including different stages of CKD and comorbidities. This highlights the need to sub classify the effect of UA-lowering therapies according to the pathological scenario, in order to identify those CKD patients that may benefit most from them. CRD42022306646 https://www.crd.york.ac.uk/prospero/.
PubMed: 38601468
DOI: 10.3389/fphar.2024.1373258 -
The Journal of Pediatric Pharmacology... Apr 2024Allopurinol-induced drug reaction syndrome with eosinophilia and systemic symptoms (A-DRESS) is a well-described condition in adults, whereas it is uncommon among...
Allopurinol-induced drug reaction syndrome with eosinophilia and systemic symptoms (A-DRESS) is a well-described condition in adults, whereas it is uncommon among children. We describe a case of A-DRESS in a 16-year-old male with steroid-dependent nephrotic syndrome. He presented a life-threatening clinical course with persisting fever, skin rash, eosinophilia, lymphadenopathy, distributive shock, and herpesvirus 6 detection. The withdrawal of allopurinol and a combination of intravenous immunoglobulins (IVIGs) and systemic corticosteroids led to the patient's recovery without sequelae. Drug reaction with eosinophilia and systemic symptoms (DRESS) in pediatrics is rare and can present in a severe form. Early diagnosis and timely treatment are critical for prognostic purposes. This report suggests the potentially crucial role of IVIG in the treatment of patients with A-DRESS.
PubMed: 38596415
DOI: 10.5863/1551-6776-29.2.195 -
ACR Open Rheumatology Apr 2024Self-monitored point-of-care urate-measuring devices are an underexplored strategy to improve adherence to urate-lowering therapy and clinical outcomes in gout. This...
OBJECTIVE
Self-monitored point-of-care urate-measuring devices are an underexplored strategy to improve adherence to urate-lowering therapy and clinical outcomes in gout. This study observed patient-led urate self-monitoring practice and assessed its influence on allopurinol adherence, urate control, and health-related quality of life.
METHODS
People with gout (n = 31) and prescribed allopurinol self-monitored their urate concentrations (HumaSens2.0) at baseline and thereafter monthly for 12 months (3 months per quarter). Adherence to allopurinol was measured using medication event monitoring technology (Medication Event Monitoring System cap). Time spent below the target urate concentration (<0.36 mmol/L) was determined. Health-related quality of life was measured using a survey (EuroQoL EQ-5D-5L). Gout flares were recorded. Two-tailed Spearman correlation and the Wilcoxon matched-pairs signed-rank test (P < 0.05) were used for statistical comparisons.
RESULTS
Most participants were male (94%) and had urate concentrations below the target (74%) at baseline. Overall, seven participants demonstrated repeated periods of "missed doses" (two or fewer allopurinol doses missed consecutively) and "drug holidays" (three or more missed doses). Most participants (94%) persisted with allopurinol. Time spent within the target urate concentration increased 1.3-fold (from 79% to 100%; P = 0.346), and the incidence of gout flares decreased 1.6-fold (from 8 to 5; P = 0.25) in the final quarter compared to that in the first quarter of the study. Health-related quality of life was reduced for participants reporting at least one gout flare (median utility values 0.9309 vs 0.9563, P = 0.04).
CONCLUSION
Patient-led urate self-monitoring may support the maintenance of allopurinol adherence and improve urate control, thus reducing the incidence of gout flares. Further research on patient-led urate self-monitoring in a randomized controlled study is warranted.
PubMed: 38591107
DOI: 10.1002/acr2.11666 -
Rheumatology Advances in Practice 2024To examine the cross-sectional association between health literacy and gout characteristics.
OBJECTIVES
To examine the cross-sectional association between health literacy and gout characteristics.
METHODS
In a primary care cohort of adults living with gout, the prevalence of poor health literacy was defined using the Single-Item Literacy Screener (SILS). Multiple logistic regression was used to obtain adjusted odds ratios (ORs) for the cross-sectional associations between health literacy and individual gout characteristics (frequency of flares, age at gout onset, history of oligo-/polyarticular flares, allopurinol use, allopurinol dose and serum urate level) with 95% CIs and adjustment for age, sex, deprivation and further education.
RESULTS
Of 551 participants [mean age 54.4 years (s.d. 11.2), 498 (90.4%) male], 163 (30.1%) reported two or more flares in the previous 12 months. Fifty-one (9.4%) had poor health literacy. Poor health literacy was associated with having two or more flares in the preceding 12 months [adjusted OR 4.10 (95% CI 2.04, 8.19)] and a history of oligo-/polyarticular flares [OR 1.93 (95% CI 1.06, 3.55)]. No associations were identified between health literacy and age at gout onset [OR 0.99 (95% CI 0.96, 1.01)], allopurinol use [OR 0.88 (95% CI 0.46, 1.65)] or dose [OR 1.00 OR (95% CI 1.00, 1.00)] or serum urate [most recent serum urate OR 1.0 (95% CI 1.00, 1.00)].
CONCLUSIONS
Frequent flares and a history of oligo-/polyarticular flares were associated with poor health literacy. Since health literacy is an important determinant of health outcomes, it is important to consider health literacy when providing information and education to people with gout.
PubMed: 38584855
DOI: 10.1093/rap/rkae034 -
Clinical and Translational Allergy Apr 2024
Correction to HLA-A*24:02 increase the risk of allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) in HLA-B*58:01 carriers in Korean population; A multicenter cross-sectional case-control study.
PubMed: 38578246
DOI: 10.1002/clt2.12351 -
International Journal of Hematology Jun 2024Guidelines recommend rasburicase for high-risk patients to prevent tumor lysis syndrome (TLS). However, little information is available on the incidence and outcome of...
Guidelines recommend rasburicase for high-risk patients to prevent tumor lysis syndrome (TLS). However, little information is available on the incidence and outcome of TLS in AML patients. We analyzed 145 patients with AML who underwent induction therapy before the approval of rasburicase to evaluate the incidence of TLS and the necessity of rasburicase as prophylaxis. Three patients had already developed clinical TLS (CTLS) at diagnosis of AML, and another three developed CTLS after the initiation of chemotherapy. In patients without TLS at diagnosis of AML, the risk for developing TLS was classified as high in 44 patients, intermediate in 41 and low in 57, according to the current guidelines. Allopurinol alone was administered to prevent hyperuricemia in all patients. All three patients who developed CTLS after diagnosis of AML were at high risk of TLS, and had elevated serum creatinine levels and a WBC count greater than 200,000 per microliter at diagnosis of AML. Allopurinol may be insufficient to prevent TLS in high-risk patients with renal dysfunction at diagnosis of AML, especially those with a high tumor burden and a WBC count of 200,000 or more, which indicates that prophylactic administration of rasburicase should be considered.
Topics: Humans; Tumor Lysis Syndrome; Urate Oxidase; Leukemia, Myeloid, Acute; Male; Female; Middle Aged; Allopurinol; Aged; Adult; Induction Chemotherapy; Aged, 80 and over; Hyperuricemia; Adolescent; Incidence; Young Adult
PubMed: 38575822
DOI: 10.1007/s12185-024-03752-w