Manifestations Of Gout Research Articles

Gouty arthritis and uric acid metabolism.

Important observations have continued to expand our understanding of gout. The increased risk of gout in black Americans has been linked more closely with the development of hypertension, and an increasing prevalence in African blacks and in England may have a similar association, possibly through the use of diuretics. The association of gout and insulin resistance appears to be related to fat distribution, and the link with hyperlipidemia may be related to genetic factors. The relationship between gout and renal disease and the frequency of gout in patients with renal failure continue to be areas of controversy. The mechanism and a possible therapeutic approach to the hyperuricemia associated with cyclosporine therapy are better understood. The potential for antibodies against urate crystals to potentiate further crystallization may explain some of the uncertainties about gouty attacks. Unusual manifestations of gout, including more cases of spinal involvement, were reported. The role of formalin in dissolving urate crystals in pathologic specimens was further clarified, and the use of atomic force microscopy to detect crystals was reported. Corticosteroids are increasingly accepted in treating acute gout, and the role of colchicine in acute and intercritical gout has come under increasing scrutiny. Urate-lowering drugs appear to be cost effective in patients with more than one or two attacks per year.

Isolated or dominant lesions of the patella in gout: a report of seven patients.

Isolated or dominant osteolytic lesions of the patella are an unusual manifestation of gout. We present seven patients who had such patellar lesions unilaterally (six patients) or bilaterally (one patient) and analyze the radiologic characteristics to determine whether they can be differentiated from those of other osteolytic lesions of the patella. The lesions were uniformly characterized by a geographic pattern of bone destruction in the superolateral aspect of the patella. Five lesions were each accompanied by a peripatellar soft tissue mass, four of which contained calcification. It therefore appears that an osteolytic lesion of the superolateral portion of the patella, especially when associated with a peripatellar calcified soft tissue mass, should alert one to the possible diagnosis of gout. Awareness of this possibility may obviate the need for invasive diagnostic procedures.

Tophi as the initial manifestation of gout. Report of six cases and review of the literature

Tophi as the initial manifestation of gout. Report of six cases and review of the literature

Tophi as the Initial Manifestation of Gout

The development of tophi in the absence of prior episodes of gouty arthritis is unusual. We present six such cases and review 26 previously published cases. These patients differ from those with typical gout in that they were older, more likely to be women, and usually had predominant or exclusive finger involvement. Most had renal insufficiency and many were receiving an anti-inflammatory or diuretic. Although several possibilities for the lack of gouty arthritis in the presence of tophi exist, usually no clear explanation is found.

Influence of antihyperuricemic therapy on the clinical and radiographic progression of gout

Ten years ago, we studied the clinical and radiographic manifestations of gout in 60 patients and described 3 patterns of disease. To determine the consequences of management over a 10-year period, we recently reassessed the 39 available patients of this population. We found that although reduced tophaceous deposition on physical examination correlated with normalization of the serum urate concentration, no correlation existed between radiographic changes and mean serum urate concentrations. Progression of gouty changes on radiography reflected progressive deformity on physical examination. We have described the radiographic changes that occurred in a well-characterized population of subjects with gout over 10 years and determined that serum urate concentrations alone may not provide an effective means of monitoring the progression of tophaceous disease in bone.

Tophaceous Deposition in the Finger Pads Without Gouty Arthritis

Tophi are rarely observed in patients without a prior history of gouty arthritis. We describe four patients whose initial manifestation of gout was tophaceous deposition in an unusual location, the finger pad. None of these patients had a history of acute gouty arthritis and none had tophi elsewhere. All four patients were postmenopausal women with decreased renal function; all were taking diuretics. We conclude that tophaceous gout without arthritis may be more common than previously recognized and that tophi may deposit in the finger pad. We recommend prompt aspiration and crystal analysis of white subcutaneous finger pad deposits in hyperuricemic patients even without a history of gouty arthritis.

The radiologic manifestations of gout.

The radiologic manifestations of gout.

Gout and uric acid nephropathy: some new aspects in diagnosis and treatment.

It has been recognized that primary disorders of uric acid metabolism result from impaired renal excretion or increased endogenous production of uric acid. It has also been found that these two mechanisms do not comprise two distinct syndromes, but may each constitute a group of syndromes. Contrary to earlier as well as currently published reports we conclude from our clinical and experimental experience that the fraction of so-called over-producers is less than 1% of all patients with primary hyperuricaemia and gout. A procedure for the diagnosis of uric acid overproduction is suggested. The manifestation of hyperuricaemia and gout mainly depends on renal uric acid clearance and is greatly influenced by dietary habits in most of the patients. An impaired renal uric acid excretion results in an increased intestinal excretion; this partly compensates for the defect. Normalization of serum uric acid should be achieved by dietary regimens with or without additional drug treatment, but not by drug treatment alone. With drug treatment xanthine oxidase inhibitors are preferable to uricosurics; no other xanthine oxidase inhibitor besides Allopurinol has been in clinical trial, however. Due to the enhancement of uric acid clearance with uricosurics, there are groups of patients who should not be treated with these drugs. Fixed combinations of Allopurinol and uricosurics should not be used. Drugs which have uricosuric as well as other pharmacologic properties are under investigation. So far they have not reached general clinical application.

Gout in the spine and sacro-iliac joints: radiological manifestations.

It is well known that deposits of urates in soft tissues occur commonly in gout, particularly in para-articular areas and in articular cartilages of the limbs. Involvement of the spine and sacro-iliac joints by such deposits, however, has been regarded as being relatively unusual and has attracted little attention in the literature. As we were impressed by the frequency of episodes of acute back pain in our patients with gouty arthritis, established definitely on clinical and biochemical grounds, we undertook a radiological investigation of the spine and sacro-iliac joints in a series of 54 subjects. It was suspected that their episodes of pain were clinical manifestations of gout, and 12 of the group had suffered one or more attacks. Of these 12 subjects, eight were found to have radiological abnormalities. In six subjects, evidence of sacro-iliitis was demonstrated, which is comparable to the report of Resnick and Reinke [8], and in two patients vertebral lesions corresponded to those describe by Jaffe [5]. Hyperostotic spondylosis was present in no fewer than 29 of the series. Although lacking histological confirmation of the lesions demonstrated radiologically, we believe that our suspicions have been confirmed.

Diffuse idiopathic skeletal hyperostosis and new bone formation in male gouty subjects. A radiologic study.

Ninety-nine males with gout were identified and their radiographs examined for features of vertebral hyperostosis and entheseal changes (diffuse idiopathic skeletal hyperostosis, DISH). Of patients over the age of 45 years 43% fulfilled criteria for diagnosis of DISH. New bone formation in other regions of the skeleton was also common. The overhanging margin sign, seen in well developed tophi, was noted only in patients with prominent new bone formation elsewhere in their skeleton. Some of the radiologic manifestations of gout may be modified by a co-existent tendency, in these patients, to form new bone. It is suggested that a common metabolic factor, possibly hyperinsulinaemia, underlies the association of gout and hyperostosis.

Panniculitis of the legs with urate crystal deposition

Dark red nodules that drained an opaque amber liquid developed on the extensor surfaces of both legs in a 69-year-old woman receiving furosemide and spironolactone for congestive heart failure. In addition to asymptomatic cholelithiasis, the serum amylase, lipase, and uric acid levels were elevated. Other skin signs and joint manifestations of gout were absent. A biopsy revealed a granuloma with the needle-like crystals characteristic of gout.

Panniculitis of the Legs With Urate Crystal Deposition

• Dark red nodules that drained an opaque amber liquid developed on the extensor surfaces of both legs in a 69-year-old woman receiving furosemide and spironolactone for congestive heart failure. In addition to asymptomatic cholelithiasis, the serum amylase, lipase, and uric acid levels were elevated. Other skin signs and joint manifestations of gout were absent. A biopsy revealed a granuloma with the needle-like crystals characteristic of gout. ( Arch Dermatol 113:655-656, 1977)

Nutritional state and purine metabolism.

Hyperuricemia and gout are multifarious disorders of purine metabolism with heredity as genetic base and exogenic environmental factors which are prevailing of alimentary nature including overcaloric and fatty nutrition and alcohol consumption. These latter factors may be able to induce the manifestation of clinical gout.

Weaver's Bottom

<h3>To the Editor.—</h3> I have just read "Ischiogluteal Bursitis: The Pain in the Arse" (227:551, 1974) by Swartout and Compere. This syndrome, ischiogluteal bursitis (weaver's bottom), has been described in several editions of<i>Christopher's Minor Surgery</i>(Philadelphia, W. B. Saunders Co). Ischiogluteal bursitis is one of the manifestations of gout and responds to treatment with colchicine, an opiate, and uricosuric drugs. It is well to remember that gout may affect any joint or bursa. I remember because I suffer from gout, and I have sat on weaver's bottom!

Hyperglutamatemia in primary gout

The mean plasma glutamate concentration, determined by column chromatography, was found to be 80 ± 27 μmol/liter in 62 gouty subjects with distinct hyperuricemia, and 79 ± 14 μmol/liter in 12 distinctly hyperuricemic but asymptomatic young sons of gouty subjects, as compared to 53 ± 16 μmol/ liter and 56 ± 15 μmol/liter in their normouricemic counterparts (p < 0.001). Hyperglutamatemia is thus a frequent and early manifestation of primary gout with distinct hyperuricemia, appearing before the onset of symptoms and apparently in conjunction with the onset of hyperuricemia. Erythrocyte to plasma ratios for molal concentrations of glutamate averaged 3.7 ± 1.3 in normal men and were maintained at about that level (mean, 3.2 ± 1.0) in gouty subjects. After oral glutamate loading, there was a disparate increase in plasma glutamate to a mean peak of 283 ± 141 μmol/liter in gouty subjects as compared to a normal mean peak of 150 ± 59 μmol/liter (p = 0.01); after glutamine loading the respective figures for plasma glutamate were 147 ± 49 versus 96 ± 28 μmol/liter (0.05 > p > ?0.02). The data support the view that catabolism of glutamate is somewhat impaired in many patients with primary gout. Whether this is due to a deficiency in glutamate dehydrogenase activity, as postulated by Pagliara and Goodman, remains to be determined. The abnormalities in glutamine metabolism previously described in many patients with primary gout could be secondary to the abnormalities in glutamate metabolism and, for reasons discussed, both appear to be compatible with a polygenic and multifactorial origin in most cases of primary gout.

The overhanging margin of bone: a roentgenologic manifestation of gout.

Characteristic but not diagnostic of gout are “punched-out lytic lesions” of articular bone. Such erosions, appearing as sharply marginated lucent pockets or as discrete subchondral “pseudocysts” which seem unconnected to the joint, are commonly observed in rheumatoid arthritis and in other chronic joint diseases. There is a type of erosion, however, that is typical of gout and seems to be relatively rare in rheumatoid arthritis (1). The purpose of this communication is to describe this finding and emphasize its diagnostic value. Roentgenologic Description At the periphery of the erosion there is an elevated bone margin which appears to hang over the tophaceous nodule as though it were displaced by it (Figs. 1 and 2). This margin characteristically has a thin shell-like configuration and is continuous with the adjacent bone contour; its close relationship to a tophus is usually evident. This type of lesion is most commonly observed in the hand or foot. Comment In a retrospective review of the available roentgenograms of 78 randomly selected cases of gout with bone erosion, there were 31 patients (40 per cent) in whom this finding was manifest. It was noted in the foot in 17 cases, in the hand in 3 others, and in both the hand and the foot in 11 cases. It tended to occur in patients with severe disease but was also observed in instances where there were only a few bone erosions. Many of the patients in this series had roentgenograms of a limited number of joints. It is possible that in patients with more complete radiologic joint surveys this type of lesion will be found to be more widely prevalent. Certain aspects of the differential diagnosis deserve comment. The outward dis-placement of the overhanging margin away from the bone contour is an important feature. Similar erosions without such displacement are common in rheumatoid arthritis (Fig. 3), as well as in gout. One may postulate that this displacement reflects the gradual increase in size of the urate nidus, which grows by multicentric deposition of urate crystals. As this progresses, bone resorption at the interface with the tophus develops into a discrete erosion and, concomitantly, periosteal bone apposition at the outer aspect of the involved cortex causes the over-hanging margin of bone. The tophus usually appears as a relatively discrete, soft-tissue nodule adjacent to the erosion. In rheumatoid arthritis, on the other hand, the erosions are associated with a diffuse soft-tissue swelling of the entire joint and their localization, apparently influenced by the anatomy of the joint in question, follows a more predictable pattern (2) (Fig. 3). Other radiologic features which serve to differentiate the lesions of gout from those of rheumatoid arthritis have been emphasized elsewhere (1, 3). Department of Radiology University Hospital

Genetics of an X-Linked Disorder of Uric Acid Metabolism and Cerebral Function

Extract: A syndrome of mental retardation, spastic cerebral palsy, choreoathetosis, and self-destructive biting has recently been described in children with elevated concentrations of uric acid in the blood. It is the purpose of this report to describe genetic studies which support an X-linked recessive mode of transmission. Two new pedigrees have been constructed following the study of propositi. Patients D.B. and G.W. were studied at 5 years of age; the concentration of uric acid in the plasma was 9.9 and 11.7 mg% respectively. The excretion of uric acid in the urine of patient D. B. ranged from 546 to 847 mg per 24 hours, with a mean excretion of uric acid of 3.02 mg per mg of creatinine. The specific activity of the uric acid in the urine after administration of glycine-U-C14 was maximal in the first 12 hours and amounted to 118 cpm per mg. Cumulative recovery of radioactivity in uric acid amounted to 1.97 percent in 7 days. The difference between patient and controls is of the order of magnitude of 200 times. Genetic transmission in an X-linked pattern was suggested from study of pedigrees (fig. 4 and fig. 5). Among the relatives of D. B., there were 15 affected individuals, all males. In the family of G.W., the disease was observed exclusively in males and, in each instance, transmission was through a female. In a trait transmitted as an X-linked recessive, one-fourth of the daughters an all sons of carrier females are expected to be affected. In this test of the hypothesis, the observed proportion of affected and unaffected grandsons did not differ significantly from this expectation. The results of testing with Xga antiserum indicated that throughout most of the kindred the X chromosome carrying the pathologic hyperuricemic gene also carried the silent Xg gene. Recombination must be invoked to explain case III-15, who was Xg (a+) and had an Xg (a+) son and an involved son. Neither the concentration of uric acid in the plasma nor the excretion of uric acid in the urine were useful in the detection of the abnormal gene. However, these data suggest that there may be some abnormality in uric acid metabolism in the heterozygote, but that it is not regularly possible to detect the presence of the abnormal gene by measuring the excretion of uric acid in the urine. The adult males were all found to excrete less uric acid than any of the groups of females. The observations recorded provide further confirmation for the concept that the disorder under study is a distinct disease entity. Genetic data accumulating indicate that the disorder is inherited in an X-linked recessive pattern. Speculation: This condition has now been observed to present all the clinical manifestations of gout, including hyperuricemia, urinary tract crystals and calculi, renal failure, arthritis and tophi. It differs in the age of onset and the involvement of the central nervous system. Most gout in adults appears to be renal in origin; some reflects an overproduction of uric acid. The overproduction of uric acid in this condition greatly exceeds that of any form of gout in adults. It appears likely that the mechanism of overproduction will be found likewise to be different. In the presence of X-linked transmission, it should be possible to develop methods which detect the heterozygous carrier.

Unusual manifestations of gout.

Unusual manifestations of gout.

Sacroiliac Gout

One patient had acute, recurrent, sacroiliac gouty arthritis, and two others had clinically inactive, tophaceous involvement of the sacroiliac joint. In a retrospective roentgenographic study, changes characteristic of gout were found in the sacroiliac joints of seven of 95 gouty patients. Equivocal changes were found in an additional five gouty patients. Involvement was found only in patients in whom other manifestations of gout had been present for many years. Gout of the axial skeleton appears to be more frequent than is commonly thought.

A Non-Articular Manifestation of Gout

A Non-Articular Manifestation of Gout