Onset Of Gout Research Articles

Clinical manifestations of Korean female gouty patients.

In an endeavor to analyse the clinical characteristics of female gout, we reviewed 36 women with gout. Twenty-seven (75%) developed the first symptomatic episode of gout after the onset of the menopause. The mean age at onset of gout was 54.3 years (range 15-87 years). Twenty-two patients (61%) had hypertension, 17 (47%) had renal insufficiency, 13 (36%) used diuretics and 10 (28%) were taking cyclosporine for a renal allograft. Tophaceous gout occurred in 10 patients (27%) and polyarticular involvement was seen in 16 (44%) at initial presentation. Five of nine premenopausal patients were taking cyclosporine and four had renal insufficiency. A comparison with a control group of 72 randomly selected male patients with gout showed that the female patients were frequently receiving diuretics at the time of the attack and had significantly lower mean uric acid excretion, whereas significantly more male patients showed heavy alcohol consumption and precipitating events for an acute attack compared with the female patients. There were no significant differences between the sexes for onset age, hypertension, renal insufficiency, distribution of joint involvement, tophi and mean serum uric acid concentration. The female patients in this study had a lower mean age at onset of gout than in previous studies, which was attributed to the inclusion of renal transplantation patients. Transplantation gout patients receiving cyclosporine lower the mean age at onset of female gout and this is an emerging problem in female gout.

Characterization of E-selectin expression, leucocyte traffic and clinical sequelae in urate crystal-induced inflammation: an insight into gout.

The self-limiting response to urate crystals allows the exploration of events involved in both the onset and resolution of gout. Using i.v. injected radiolabelled anti-E-selectin monoclonal antibody 1.2b6 together with differentially radiolabelled neutrophils, mononuclear cells and albumin, we have characterized the expression of E-selectin in relation to leucocyte traffic, microvascular permeability and clinical sequelae following intracutaneous injection of monosodium urate crystals. We found that the inflammatory response in this model involved several distinct phases. First, E-selectin expression increased over 2-6 h in the context of increases in neutrophil and mononuclear cell accumulation, and albumin leakage. Secondly, leucocyte accumulation rapidly declined despite persisting E-selectin expression. Thirdly, E-selectin expression peaked at approximately 8 h and then fell despite an increase in clinically detectable erythema and induration. Lastly, these clinical manifestations of inflammation resolved despite the continued presence of urate crystals in the tissues. The further dissection of mechanisms regulating these phases will lead to a better understanding of events in both the pathogenesis and resolution of gout. Of broader significance, this inflammatory model may yield information about the protective events that underly resolution of inflammation, and provide insights into factors which determine chronicity.

Hyperuricemia and gout among heart transplant recipients receiving cyclosporine

purpose: To determine the frequency and characteristics of hyperuricemia and gouty arthritis among cyclosporine-treated heart transplant recipients. patients and methods: One hundred ninetysix surviving adult heart or heart/lung transplant recipients were evaluated. Medical records were reviewed to determine peak serum uric acid levels after transplantation, and to evaluate potential risk factors for hyperuricemia. Patients were surveyed by postal questionnaire for a history of gouty arthritis, with positive responses evaluated by telephone interview and/or examination of the patient. results: Hyperuricemia occurred in 72% of male and 81% of female patients and was not correlated with cyclosporine level, presence of hypertension, or degree of renal insufficiency. Eleven (6%) patients had gout prior to transplantation; 14 (8%) had onset of definite gout and seven (4%) had probable gout a mean of 17 months after transplantation. Polyarticular arthritis and/or tophi developed in six (43%) of the posttransplant-onset definite gout group within a mean of 31 months. conclusion: Both hyperuricemia and gouty arthritis occur with increased frequency among cyclosporine-treated heart or heart/lung transplant recipients. The clinical course of gout in these patients is often accelerated, with management complicated by the patients' renal insufficiency and interaction with transplant-related medications.

Precocious Familial Gout with Reduced Fractional Urate Clearance and Normal Purine Enzymes

Gout is primarily a disease of middle-aged males and is unusual in females and adolescent males. We describe 21 young men and women (mean age 28 years) referred because of precocious onset of gout or hyperuricaemia. Fifteen patients had a family history, but known hereditary causes of primary or secondary hyperuricaemia were excluded. A high proportion (14/21) also had reduced renal function, but there was no clear relationship between this and the hyperuricaemia. Only two patients were hypertensive. A striking abnormality was that the uric acid clearance relative to creatinine [FEur] was subnormal (mean 4.4 +/- 1.4 per cent) in 15/21 patients, including all seven females. A dominantly inherited defect in renal tubular urate handling, leading to a reduced endogenous urate clearance, is the most likely explanation for the hyperuricaemia in this group. Only six patients, all male had a normal [FEur] (mean 8.6 +/- 1.0 per cent). The results confirm that young men and women with gout-or hyperuricaemia disproportionate to the renal dysfunction-should always be investigated, not only for purine defects, but also for abnormalities of renal urate handling. Since the abnormality described here was found also in symptomless subjects, the families of such patients must also be studied. Early identification is important since treatment may ameliorate the renal damage. Although rare, the number of such patients seen in a single referral unit suggests that this type of renal tubular defect in urate handling is more common than suspected and may only come to attention through an isolated episode of precocious gout, when renal function may already be impaired.

Clinical aspects of gouty patients in Taiwan.

The mean age of the onset of gout in Taiwan is 49.6 years old. This is very similar to Japan. The female cases made up 5.78% of total cases. This is very similar to the world average of about 5%. As far as laboratory findings are concerned, uric acid had a significant correlation with BUN, creatinine, cholesterol and triglyceride. In our occupation study we found that gout occurs in almost every class of society and no particular group has any immunity.

Withdrawal of longterm antihyperuricemic therapy in tophaceous gout.

After longterm treatment (mean duration 7.2 years) with antihyperuricemic drugs, ten tophaceous gouty patients requested withdrawal of the medication because they had not felt any arthritic pains for years, the tophi had disappeared, and they disliked the idea of taking the medicine daily for the rest of their lives. Five patients (Group I) had no recurrence of either arthritis or tophi during follow-up for 18 to 52 months (average duration 33 months). Five patients (Group II) had a recurrence of arthritis 5 to 29 months (average 15.8 months) after cessation of therapy and two of them developed tophi again at 29 months and resumed treatment. Group II patients tended toward obesity, more severe hyperuricemia and an earlier age onset of gout, as compared with Group I patients. The creatinine concentration determined before, during, and after treatment showed no change. On the basis of the present findings it seems justified to withdraw medication in cases of tophaceous gout in remission when aggravating factors such as obesity and severe hyperuricemia are absent. Attacks of gout and tophi are likely to recur, but so far in our series the duration of the symptom-free period without medication is almost three years for Group I patients, who are now considered as "asymptomatic hyperuricemics".

The Clinical Spectrum of Gouty Arthritis in Women

We reviewed crystal-proved gouty arthritis in 23 women. Twenty-one (91%) developed gout after menopause onset. Tophaceous gout occurred in six (26%), polyarticular involvement in 13 (57%); 70% manifested an underlying arthropathy, usually osteoarthritis. We studied 75 men with crystal-proved gout for comparison. Women developed gout significantly later compared with men, more often were receiving diuretics before gout onset, and more frequently manifested renal insufficiency and monoarticular involvement. These differences were significant when controlled for the women's later age at onset. Significantly more men than women had alcoholism and an identifiable precipitating event for acute attacks. There were no significant differences in race, age, family history of gout, disease duration, hypertension, distribution of joint involvement, tophi, or mean serum urate concentration. Gout in women is overwhelmingly postmenopausal, apparently associated with diuretic therapy and renal insufficiency independent of the effects of age. Articular characteristics in men and women are remarkably similar.

Hypoxanthine-guanine phosphoribosyltransferase in human lymphoblastoid cells: confirmation of four structural variants and demonstration of a new variant (HPRT Ann Arbor).

An inherited deficiency of hypoxanthine-guanine phosphoribo-syltransferase (HPRT) has been described in two distinct clinical syndromes. A virtually complete deficiency of enzyme activity is associated with patients having the Lesch-Nyhan syndrome (1) while a partial deficiency of enzyme activity leads to hyperuricemia and an early onset of gout (2).

Human hypoxanthine-guanine phosphoribosyltransferase. Detection of a mutant allele by restriction endonuclease analysis.

We have developed a method for the direct analysis of a hypoxanthine-guanine phosphoribosyltransferase (HPRT) allele associated with a deficiency of enzyme activity and an early onset of gout. The functionally abnormal enzyme coded for by this mutant allele (HPRTToronto) differs from the normal enzyme by an arginine-to-glycine substitution at position 50. A single base change in the codon for arginine 50 can explain this substitution. Direct analysis of this point mutation is based on the observation that it abolishes a Taq I recognition site in HPRT DNA. As predicted, DNA from individuals with the HPRTToronto allele exhibited an abnormal restriction pattern when digested with Taq I and probed with HPRT complimentary DNA: a normal 2.0-kb fragment is replaced by a 4.0-kb fragment. The 4.0/2.0-kb restriction fragment variation was used to detect the HPRTToronto allele in a heterozygote that was otherwise normal with respect to the classical techniques used to diagnose heterozygosity in HPRT deficiency.

Renal function in gout: V. Factors influencing the renal hemodynamics

Renal hemodynamics as measured by inulin clearance (C inulin) and para-aminohippurate clearance ( Cpah) was evaluated in 149 patients with primary gout over intervals of two to 22 years. In over 30 per cent of the patients plasma urate was >10 mg/dl and urinary uric acid >800 mg/min. A linear trend in decreasing frequency of hyperuricemia and excessive uricosuria is significantly related to the patient's age at the onset of gout. Group I consisted of 84 patients with uncomplicated gout in both clearance studies. C inulin and Cpah were somewhat lower in patients ≥ 50 years of age with longer duration of gout. Further reduction in clearances was minimal at the second clearance study in intervals of approximately 10 years. Group II included 27 patients who had no associated disease at the time of the first clearance study but in whom associated disease had developed by the time of the second clearance study. A striking reduction in C inulin and Cpah was noted, especially in those 50 years old or above. There were 38 patients in group III with associated diseases at the time of both clearance studies. They had lower C inulin and Cpah at the time of the first study, particularly the older patients. Further reduction during the second study was less striking than that in group II. Analyses of variance suggest that various coexisting vascular diseases with associated nephropathy have the most significant impact on the status of renal function in gout, with aging the second most important and duration of gout, the third.

Some unusual features of gouty arthritis in females

Gouty arthritis in females is relatively infrequent, although the sex ratio may be somewhat altered in different races. A positive family history is relatively prevalent among females whose onset of gout is premenopausal. In those patients with a postmenopausal onset, the incidence of diuretic-associated gout is high. The bimodal distribution of serum urate might be related to some variance of genetic transmission in female gout. Hypertension and coronary heart disease are common coexisting conditions, as is true of gouty arthritis in males. Chronic urinary tract infection dating from previous pregnancies is a frequent complication. The relative prevalence of proteinuria and diminished renal function leads to increased hyperuricemia, with a tendency to a low urinary uric acid output. This explains in part the higher incidence of extensive tophaceous deposition but lower incidence of renal calculi. Diuretics are associated with a higher urine pH, likewise, they reduce the urinary uric acid excretion. This also may contribute to the lower incidence of renal calculi. There may be some statistical support for the low fertility rate among the gouty females. Only two females became pregnant after the onset of gouty arthritis. All other pregnancies occurred before the onset of arthritis. Even then, abnormal pregnancies were relatively frequent. Some hormonal malfunction among the gouty females cannot be discounted. Both renal calculi and tophi are frequent in female gout associated with blood dyscrasias. They may manifest early, preceding the first attack of acute gouty arthritis. In both the male and female secondary gout, the primary underlying disease governs the uric acid metabolism and the clinical symptomatology of gout. The predominant role in pathogenesis is the excessive rate of uric acid production, and its disposal is governed by the different stages of the underlying disease and the treatment. Thus, secondary gout in females appears to be somewhat different from primary gout in females, but not different from secondary gout in males.