Background

Gout is the most prevalent inflammatory arthropathy in men caused by elevated serum uric acid levels leading to the precipitation of urate crystals and, subsequently causing acute and/or chronic inflammation, as well as potential destruction of surrounding tissue.⁽¹⁾ Uric acid is produced as a result of purine metabolism via the actions of xanthine oxidase, which converts hypoxanthine and xanthine. However, this enzyme is also known to generate oxygen-free radicals, which can lead to endothelial damage.⁽²⁾ Numerous epidemiological studies have shown a connection between hyperuricemia and the development of various conditions, including cardiovascular disease (CVD), diabetes, chronic kidney disease (CKD), and other metabolic disorders. Of particular interest, the correlation between hyperuricemia and heart failure has been the subject of significant attention for many years.⁽³⁾ Large studies have shown the association between hyperuricemia and increased incidence of cardiovascular diseases.

Herein, we report on a patient with chronic untreated gout presenting with signs and symptoms of decompensated global dilated cardiomyopathy, chronic kidney disease and hypertension.

Case Report

A 40-year-old male presented to the emergency room with complaints of bilateral lower limb edema for 2 months duration, dyspnea, orthopnea and oliguria for 2 weeks duration. He also gives history of multiple joint pains for 5 years associated with diffuse painful nodular swellings over bony prominences since 2 years. He is a non-alcoholic and non-smoker. Past medical history includes no other comorbidities. On admission, the patient was conscious and oriented. He was afebrile, with blood pressure 170/100 mmHg and oxygen saturation (SpO₂) 90% on room air. Physical examination revealed tachycardia, bilateral pitting pedal oedema and elevated JVP (jugular venous pressure). Systemic examination revealed soft heart sounds with gallop rhythm and bilateral crepitations in lower lung fields. He was noted to have multiple nodular swellings, predominantly on the first and second metatarsophalangeal joints in lower limbs, proximal and distal interphalangeal joints of hands, left elbow joint and also subcutaneous nodules noted on the anterior aspect of right lower limb. The joint swellings were deformed and ulcerated with marked yellow tophi nodules as in figure 1.

Figure 1: Marked inflamed, ulcerated tophi nodules in left foot.

Laboratory investigations revealed anemia with hemoglobin 10.5gm/dl, deranged RFT with urea 81.5mg/dl, and creatinine 3.38mg/dl. Urine routine showed albuminuria. Serum uric acid level is 9mg/dl. Serum calcium is 8.57mg/dl (corrected calcium 8.9mg/dl with serum albumin 3.53mg/dl), phosphorous 4.66mg/dl, S.PTH (Parathyroid hormone) is 122.5 pg/ml, 25OH vitamin D is 20.83ng/ml. NT- ProBNP levels are 800pg/ml and cardiac troponin I levels were normal.

Radiological investigations revealed cardiomegaly with hilar congestion and right mild pleural effusion on chest X-ray. Ultrasound abdomen showed bilateral chronic medical renal disease and no evidence of nephrolithiasis. Echocardiogram revealed dilated right and left ventricles with Ejection Fraction 32%.

X-ray images of affected joints revealed punched-out erosions with overhanging bony margins in the first metatarsophalangeal joints as well as in proximal and distal interphalangeal joints of both hands as in figure 2.

A punch biopsy of joint swelling was taken, histopathological examination revealed needle shaped crystals forming nodular aggregates with surrounding dense inflammation as shown in figure 3.

Figure 2: X-ray image of affected joints

Figure 3: Histopathological examination showing needle shaped crystals forming nodular aggregates with surrounding dense inflammation

Patient was admitted and treated with Intravenous Furosemide, vasodilators and spironolactone. Once stabilised he was started on oral febuxostat 40mg and a short course of oral steroids to reduce inflammation and pain. On follow-up after 2 weeks there is resolution of pedal edema, pain and inflammation of joint swellings.

Discussion

The case we reported here is of a patient with chronic, untreated gout clinically presented as heart failure, on evaluation he was diagnosed with dilated cardiomyopathy and chronic kidney disease. Untreated gout that persisted for an extended period caused deformities in the fingers and toes with notable tophi on both extremities. Our patient has striking similarities with Petra Sulentic's case.⁽⁴⁾ including DCM presentation, but with the difference that our patient also had CKD with secondary hyperparathyroidism and Vitamin D insufficiency.

Despite the reported high levels of serum uric acid concentration in patients with heart failure, the root cause of evaluated cardiomyopathy is still remains unidentified. While there is ample evidence to suggest that uric acid is a marker for a range of cardiovascular diseases such as congestive heart failure, coronary heart disease, hypertension, atherosclerosis, stroke and chronic kidney disease, it has not yet been definitively established that hyperuricemia is a causal factor for different categories of cardiovascular diseases. The core pathogenesis of hyperuricemia-related heart failure is the up-regulated activity of xanthine oxidase enzyme and the consequent increased production of reactive oxygen free radicals, which results in a cluster of pathophysiological cardiovascular effects. Therefore, xanthine oxidase itself may serve as a novel and promising therapeutic target and xanthine oxidase inhibition may potentially lead to improved clinical outcomes in heart failure. Several studies have reported a beneficial effect of the gout medication allopurinol (as well as its metabolite oxypurinol) on endothelial and myocardial function in individuals with hyperuricemia.⁽⁵⁾ Few studies have indicated that treatment with allopurinol can lead to improvements in both LV hypertrophy, endothelial function and also reported improved clinical outcomes in patients with hyperuricemia-related heart failure.⁽⁶⁾ Currently, there is no randomized controlled trial (RCT) that has compared the effects of xanthine oxidase inhibitors with uricosurics on clinical cardiovascular events. Therefore, large-scale trials are warranted to establish which medication is more effective in this regard and also newer treatment modalities needed to be addressed to curtail further disease progression and devastating complications.

Conclusion

To our knowledge, cardiomyopathy was associated with gout in only very few cases reported worldwide till now as shown in table 1. Though the presentation is rare, larger studies are required to examine the relationship between gout severity and heart failure. In recent epidemiological studies, it has been discovered that high levels of serum urate can increase the risk of chronic kidney disease and cardiovascular events which yields regulation of urate concentration necessary.⁽⁹⁾ Hence early identification of the disease, periodic monitoring of uric acid levels and aggressive management with uric acid lowering therapies are needed to prevent disfigurement and deformities of joints, cardiovascular and renal complications. Also, patients with gouty arthritis should be educated regarding the avoidance of purine rich foods especially of animal origin as studies implied that acute purine intake increases the risk of recurrent gout attacks by almost five times in patients with gout.⁽¹⁰⁾

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