Gouty Attacks Research Articles

Pseudomelanosis Duodeni Revisited

Purpose: A 70-year-old African American man was admitted to the hospital with an acute gouty arthritis attack. He had ischemic cardiomyopathy status post heart transplantation, Gout, hypertension, and chronic renal insufficiency. His list of medications included Sirolimus, Mycophenolate mofetil, prednisone, hydralazine, ferrous sulfate, colchicine, and allopurinol. With higher doses of corticosteroids the patient's symptoms had improved, however, hemoglobin level was found to be low. His Physical exam was remarkable for a positive test for occult blood in the stool. Blood tests revealed hemoglobin level of 8.6 g/dl, hematocrit of 26.6 per cent, iron level of 32 mcg/dl, Iron-binding capacity of 118 mcg/dl, Iron saturation of 27 per cent and ferritin of 1273 ng/ml. Esophagogastroduodenoscopy revealed small black and brown pigmentations over the antrum of the stomach, duodenal bulb, and descending duodenum. Pathological evaluation of the pigmented duodenal mucosa showed normal villous architecture and iron containing pigments compatible with pseudomelanosis duodeni. In spite of stopping the hydralazine and continuing iron supplementation, the patient's anemia persisted. Pseudomelanosis duodeni is a rare condition characterized by scattered pigmentations throughout the duodenal mucosa composed mainly of iron. The condition is strongly associated with hypertension and oral iron intake. Once iron is coupled with sulfur, the compound accumulates in the macrophages of the lamina propria and gives the black pigmentations seen on endoscopy. The clinical significance of diagnosing this condition has yet to be determined. In our patient, anemia can be attributed to a number of factors including chronic renal insufficiency and immunosuppressive therapy. Pseudomelanosis duodeni might be contributing to the anemia by interfering with iron absorption. However, the available evidence is not enough to support this theory or to justify the use of parentral iron in these patients especially given the fact that most of these patients' anemia is not strictly related to iron deficiency.Figure

Management of gout: Primary care approach

AbstractGreat strides have been made in understanding gout as a disease over the centuries. Despite these advances, reports suggest that the management of gout is relatively suboptimal at the primary care level. This article reviews important considerations in the management of gout and provides an evidence-based approach for the management of acute and chronic gouty arthritis at the primary care level. Recurrent monoarticular pain and swelling should raise the suspicion of gout and the demonstration of urate crystals in synovial fluid during a clinical episode confirms the diagnosis. Acute gouty attacks should be managed with appropriate doses of non-steroidal anti-inflammatory drugs (NSAIDs) or colchicines or steroids. Recurrent attacks of gout, presence of tophi and urate stones necessitate urate-lowering drugs. Prophylactic anti-inflammatory agents for up to six months should be added at initiation of urate-lowering therapy to reduce flares of acute attacks. Gout management requires lifelong commitmen...

Author’s reply

I thank Dr Perry for his interest in my article. I agree with him that if the manifestations of the side effects of allopurinol are mild, then desensitisation can be attempted at a lower dose. However, isolated asymptomatic hyperuricaemia does not warrant the use of allopurinol. One must distinguish the difference between gout and hyperuricaemia. Dr Perry’s references on the rheumatology guidelines for the management of gout apply to cases of gout and not to hyperuricaemia.1 In fact, the indications for allopurinol therapy are tophaceous gout, major uric acid overproduction (proven by urinary excretion >53 mmol/24 hours) frequent gouty attacks, recurrent uric acid renal calculi and prevention of acute urate nephropathy in patient receiving cytotoxic therapy for malignancies.2 In a study by Khoo3 a total of 13 patients were admitted for severe cutaneous adverse reactions to allopurinol during a three-year period. Almost 92% of them suffered from allopurinol hypersensitivity reactions, which included four patients with Stevens-Johnson syndrome. Allopurinol hypersensitivity syndrome, in contrast to other purely cutaneous drug eruptions, deserves special attention because of its multi-organ involvement, the liver and kidneys being most commonly affected. It was interesting to note that none of the 13 patients had clear clinical indications for allopurinol therapy. Asymptomatic hyperuricaemia is not uncommon, affecting an estimate of 5–8% of the population. As the risks, morbidity and mortality outweigh the benefits, it should only be prescribed when it is truly indicated.

Gout

Because of the changing dietary habits of an aging population, hyperuricemia is frequently found in combination with other metabolic disorders. Longstanding elevation of the serum uric acid level can lead to the deposition of monosodium urate crystals, causing gout (arthritis, urate nephropathy, tophi). In Germany, the prevalence of gouty arthritis is estimated at 1.4%, higher than that of rheumatoid arthritis. There are no German guidelines to date for the treatment of gout. Its current treatment is based largely on expert opinion. Selective literature review on the diagnosis and treatment of gout. Asymptomatic hyperuricemia is generally not an indication for pharmacological intervention to lower the uric acid level. When gout is clinically manifest, however, acute treatment of gouty arthritis should be followed by determination of the cause of hyperuricemia, and long-term treatment to lower the uric acid level is usually necessary. The goal of treatment is to diminish the body's stores of uric acid crystal deposits (the intrinsic uric acid pool) and thereby to prevent the inflammatory processes that they cause, which lead to structural alterations. In the long term, serum uric acid levels should be kept below 360 micromol/L (6 mg/dL). The available medications for this purpose are allopurinol and various uricosuric agents, e.g., benzbromarone. There is good evidence to support the treatment of gouty attacks by the timely, short-term use of non-steroidal anti-inflammatory drugs (NSAID), colchicine, and glucocorticosteroids.

Serum Urate During Acute Gout

To study the frequency of normal serum urate (SU) levels during acute gout in the largest studies of acute gout treatment to date. Data collected from 2 randomized controlled clinical trials assessing the efficacy of etoricoxib or indomethacin for 7 days in acute gout were used to assess SU levels during acute gouty attacks. Efficacy was similar with both agents, so both groups were combined for analysis. A total of 339 patients were enrolled in the 2 studies; 94% were male; mean age was 50.5 years. At baseline, 14% of patients had a "true" normal SU (<or=6 mg/dl) and 32% had SU<or=8 mg/dl during acute gout. Baseline mean SU was 7.1 versus 8.5 mg/dl (p<0.001) in those taking allopurinol versus nonusers. Patients taking chronic allopurinol were more likely to have lower SU at baseline compared to those not taking chronic allopurinol (p<0.001) during the acute attack. A normal SU level at presentation does not exclude an acute gouty attack. In the largest studies of acute gout to date, attacks still occurred despite SU levels being below 6.8 mg/dl, the saturation level for urate. This may be attributed to persistence of tophi and an increased body uric acid pool. Additional studies are needed to determine the correlation between SU and the body uric acid pool as well as the relationship to timing of changes during acute gout.

Total Knee Arthroplasty Failure and Gouty Arthropathy

We present a patient with gout and a total knee arthroplasty that failed secondary to infection. The English literature records only 5 other cases of gouty attacks after total knee arthroplasty. Symptoms, presentation, and laboratory tests do not definitively differentiate between infection and gout, but crystals in the joint aspirate are diagnostic. This case stresses the importance of recognizing crystalline arthropathy as a source of a painful knee and as a complicating factor during revision surgery.

Gout: new advances in the diagnosis and management of an old disease

Gout is a monosodium urate crystal deposit disease, occurring as a consequence of hyperuricemia. Very importantly, the formation of crystals is reversible and they slowly dissolve when serum urate levels became normal, so the disease can be considered curable. The identification of urate crystals in synovial fluid allows simple unequivocal diagnosis; diagnosis based on clinical features and hyperuricemia is often inaccurate, even if patients fit the American College for Rheumatology Classification Criteria. Several recent publications show that gout is frequently misdiagnosed, and management often falls below reasonable standards. The main aim of treatment is to dissolve the deposited crystals, freeing the patient of the disease; this is usually achieved by allopurinol, and new drugs will be available soon. Crystal deposit is silent but signaled by the occurrence of gouty attacks, for which treatment is effective, and can be avoided with adequate prophylaxis. Alterations related to the so-called metabolic...

Colchicine for pericarditis: hype or hope?

Colchicine has been effectively used in the treatment of several inflammatory conditions, such as gouty attacks, serositis related to familial Mediterranean fever, Behçet syndrome, and more recently also in acute and recurrent pericarditis. Growing evidence has shown that the drug may be useful to treat an acute attack and may be a way to cope with the prevention of pericarditis in acute and recurrent cases and after cardiac surgery. Nevertheless, clinicians are often sceptical about the efficacy of the drug, and concerns have risen on possible side effects and tolerability. In this review, we analyse current evidence to support the use of the drug, as well as possible harms and risks related to drug interactions, reaching the conclusion that colchicine is safe and useful in recurrent pericarditis, if specific precautions are followed, although less evidence supports its use for the treatment of acute pericarditis, where colchicine remains optional and there is a need for further multicentre confirmatory studies. This paper also reviews specific dosing and precautions for the clinical use.

Colchicine for the Treatment of Pericarditis

Colchicine has been effectively used in the treatment of several inflammatory conditions, such as gouty attacks, serositis related to familial Mediterranean fever, Behçet syndrome and more recently, in acute and recurrent pericarditis. Colchicine concentrates in white blood cells, particularly polymorphonuclear cells, inhibiting tubulin polymerization, thus interfering with migration and phagocytosis, and reducing the inflammatory cycle. Although the exact number of responders is unknown, the drug has been successfully used for the treatment and prevention of recurrences and to taper corticosteroids in patients with recurrent pericarditis in several retrospective studies and an open-label, randomized trial, where the recurrence rate was halved in the treatment arm. Less evidence supports the use of the drug for the treatment of acute pericarditis, where colchicine remains optional and requires further multicenter confirmatory studies. At present, colchicine has been recommended by the 2004 European guidelines on the management of pericardial diseases for acute (class IIa) and recurrent pericarditis (class I), but its use is still unlabeled and informed consent is required for prescription. A careful monitoring of possible contraindications, drug interactions and side effects is necessary. The aim of this paper is to review the evidence that supports the use of the drug in acute and recurrent pericarditis, as well as dosing and precautions for clinical use.

Die Behandlung des akuten Gichtanfalls

In a patient with often recurring acute gouty attacks over a longer period, these attacks decayed in each case easily after prescription of the particular homeopathic remedy which is adapted to the individual pathology. The attacks were treated continuously ineffective before with remedies of the homeopathic drug treasure and with non-steroidal anti-inflammatory drugs by self-treatment through the patient himself. Observations and conclusions about the homeopathic treatment of acute gouty attacks rounds off the case.

Willingness to Pay for a Cure in Patients with Chronic Gout

Gout is a chronic painful inflammatory arthritis. The authors interviewed patients with chronic stable gout to assess their hypothetical willingness to pay (WTP) to be cured of their gout. Patients with gout were asked how much money they would be willing to pay every month out of pocket or as a co-pay to cure their gout. To assess determinants of WTP amounts, the authors performed stepwise multivariable linear regression analysis, controlling for demographics, health status, and relative concern about gout. Of the 78 patients, 70 (90%) were male, 54 (69%) were Caucasian, 21 (27%) were African American, and 32 (41%) had annual incomes < $25,000. The median WTP amount was $25 ($0, $75) per month, and the mean (s) was $52 ($74) per month (range, $0-$350); 23 (30%) patients were unwilling to pay any amount. Patients who rated their gout as their top health concern were willing to pay a median of $63 ($25, $100) per month. In multivariable analysis, gout as the top health concern, greater frequency of gouty attacks over the past 1 y, and younger age were significantly associated with WTP amounts (R(2) =0:19 ). Many patients with chronic gout would be willing to pay money every month in perpetuity to be cured of their gout. Younger patients, patients whose main health concern is gout, and patients with frequent attacks are willing to pay the most.

The future of the IL-1 receptor antagonist anakinra: from rheumatoid arthritis to adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis

Background: IL-1 receptor antagonist (IL-1Ra) is a naturally occurring IL-1RI-binding molecule that blocks the biologic effects of the proinflammatory cytokine IL-1. A recombinant form of human IL-1Ra, anakinra (Kineret), has been approved for use in rheumatology initially to manage rheumatoid arthritis (RA) patients that are refractory to more conventional forms of treatment. Objective: This review summarizes the experience with anakinra in the treatment of patients with rheumatic diseases emphasizing its beneficial effects in novel applications. Methods: English-language trials of anakinra were searched using MEDLINE and abstracts from rheumatology scientific meetings. Results/conclusions: In the treatment of patients with RA anakinra is effective but inferior to TNF-α blocking agents. Over the last few years it has become increasingly evident that anakinra is highly effective and safe in patients with systemic-onset juvenile idiopathic arthritis, adult-onset Still's disease, hereditary autoinflammatory syndromes, Schnitzler's syndrome and recently in gouty attacks.

Gouty attacks occur frequently in postoperative gastric bypass patients

Both obesity and surgery are known risk factors for instigating gouty attacks. We describe the incidence and management of postoperative gouty attacks after bariatric surgery. We performed a retrospective, multi-institutional review of 411 consecutive laparoscopic gastric bypass patients and identified all patients with postoperative gouty attacks. Of the 411 patients reviewed, 21 (5.1%) had had a previous diagnosis of gout. Of these 21 patients, 7 (33.3%) had had an acute attack postoperatively. No patient who had never had a preoperative episode developed gout. In 4 of the 7 (57.1%) patients, the attack was severe enough to require treatment with corticosteroids. Monoarticular attacks occurred in 5 (71.4%) of the 7 patients, and polyarticular attacks occurred in 2 (28.6%). The joints involved included the toes, ankles, and wrists. One patient presented with cervical gout and developed polyarticular gout that required a significant rehabilitation stay. The morbidity of postoperative gouty attacks in bariatric surgery patients is significant. Patients with a history of gout should given prophylactic treatment and closely monitored.

Gout and the postoperative bariatric surgery patient

Gout is an important associated disease of our bariatric surgery population because the underlying cause, hyperuricemia, intersects all those conditions that predispose to the flares: morbid obesity, postoperative state, metabolic syndrome and the associated dietary habits, hypertension and treatment with diuretics, sudden starvation diet, high-protein postoperative diet, insulin resistance/type II diabetes, advancing age, and renal insufficiency, to name a few [ [1] Chen S.Y. Chen C.L. Shen M.L. Manifestations of metabolic syndrome associated with male gout in different age strata. Clin Rheumatol. 2007; 26: 1453-1457 Crossref PubMed Scopus (31) Google Scholar ]. Furthermore, acute gouty exacerbations in the postoperative setting can lead to marked disability, thus setting the stage for potential cardiopulmonary complications. As the age limits and criteria for obesity surgery expand, this timely report has demonstrated that so might the incidence of postoperative acute attacks of gout. Gouty attacks occur frequently in postoperative gastric bypass patientsSurgery for Obesity and Related DiseasesVol. 4Issue 1PreviewBoth obesity and surgery are known risk factors for instigating gouty attacks. We describe the incidence and management of postoperative gouty attacks after bariatric surgery. Full-Text PDF

An unusual case of gout in the wrist: the importance of monitoring medication dosage and interaction. A case report

BackgroundGouty arthritis of the wrist is uncommon although gout itself is the most common inflammatory arthritis in older patients. Some known risk factors for the development of gout include trauma, alcohol use, obesity, hyperuricaemia, hypertension and diabetes mellitus. As well, certain medications have been shown to promote the development of gout. These include thiazide diuretics, low dose salicylates and cyclosporine. We present a case of gouty wrist pain possibly precipitated by a medication dosage increase as well as medication interactions.Case presentationA 77 year old male presented with right wrist pain. Redness and swelling was present at the dorsal aspect of his wrist and range of motion was full with pain at end range upon examination. One week prior, his anti-hypertensive medication dosage had been increased. The patient's situation continued to worsen. Radiographic examination revealed changes consistent with gouty arthritis.ConclusionIt is important for clinicians treating joint conditions to be aware of patients' comorbidities, medication usage and changes in dosages. Education of patients with gout is of prime importance. Clinicians should educate patients that gout may occur at any joint in the body not only the lower limb. Patients should be aware of the signs and symptoms of an acute gouty attack and be made aware that changes in certain medication dosages may precipitate an attack. Awareness of radiographic changes associated with gout is still of importance although these changes are not seen as frequently as they have been in the past due to better control of the disease.

The inflammasome, autoinflammatory diseases, and gout

IL-1beta is a cytokine with major roles in inflammation and innate immune responses. IL-1beta is produced as an inactive proform that must be cleaved within the cell to generate biologically active IL-1beta. The enzyme caspase-1 catalyzes the reaction. Recent work showed that caspase-1 must be activated by a complex known as the inflammasome. The inflammasome comprises NALP, which is an intracellular receptor involved in innate immunity, and an ASC adapter that ensures caspase-1 recruitment to the receptor. The most extensively described inflammasome to date is formed by the NALP3 receptor within monocytes. Mutations involving the NALP3 gene cause hereditary periodic fever syndromes in humans. Increased inflammasome activity responsible for uncontrolled IL-1beta production occurs in these syndromes. Inhibition of the IL-1beta pathway by IL-1 receptor antagonist (anakinra) is a highly effective treatment for inherited periodic fever syndromes. A major role for inflammasome activity in the development of gout attacks was established recently. Urate monosodium crystals are specifically detected via the NALP3 inflammasome, which results in marked IL-1beta overproduction and initiation of an inflammatory response. This finding opens up new possibilities for the management of gouty attacks.

Discussion Following Cases 1 and 2

In both the case of acute gouty attack presented by Dr. Arthur L. Weaver (Case 1; Patient NZ)1 and the case of acute gout and bacterial infection that I presented (Case 2; Patient PA),2 the outcome ultimately was positive. However, these 2 cases illustrate several potential decision points at which care could be improved.

Case 1: Differential Diagnosis of an Acute Gouty Attack

Case 1: Differential Diagnosis of an Acute Gouty Attack

Excellent response to the clinical treatment of tophaceous gout

Gout continues to be a health problem around the world, and the treatment may turn into a real challenge when the patient presents a certain degree of chronic renal failure (CRF). We discuss a case of tophaceous gout in a 68-year-old male patient without urolithiasis and with uric acid (UA) underexcretion and CRF (creatinine clearance of 42 ml/min). Uricosuric treatment with benzbromarone and urinary alkalinization was administered, and acute gouty attacks improved substantially. Subsequently, allopurinol was added to the treatment to accelerate tophi reduction in the hands, feet, elbows and knees. After 30 months of treatment, serum UA declined from 10 to 3.2 mg/dl. Urinary UA excretion of 0.44 g/24 h in the baseline rose to 0.85 g/24 h, returning to the baseline value after 30 months. UA clearance tripled, rising from 3.05 ml/min before treatment to 9.48 ml/min, and remained at this level. It is worth stressing that even in cases of severe tophaceous gout, the response to clinical treatment may be satisfactory with substantial reduction of tophi and full acute gouty attack remission even in patients presenting a certain degree of CRF.

Gout, Have We Met before? No, Not Like This?

Extra-articular symptoms could be the first manifestation of gouty arthritis (GA); polyarticular GA can mimic an infectious arthritis; infection can complicate GA. A 66-year-old male with a history of gout presented with high fever and excruciating bilateral calf pain for 1 day. Examination revealed chronic knee effusions; range of motion in both knees was limited by calf pain. Joint aspiration showed negatively birefringent intracellular crystals and normal gram stain. While receiving empiric antibiotics fever continued and he developed bilateral knee, right ankle, and shoulder pain. After demonstration of urate crystals and exclusion of infection, antibiotics were discontinued and steroids initiated. Fever, calf pain, and polyarthritis quickly resolved. Polyarticular gouty attack is an uncommon presentation of gout, and can mimic several other conditions. An exceptional presentation of this entity is excruciating calf pain, probably caused by tenosynovitis or referred pain preceding an acute polyarticular gouty attack.