Tophi as first manifestation of gout

Introduction

Gout is a common disease associated with monosodium urate (MSU) crystal deposition in articular or peri-articular tissues and in the renal tract. Generally it progresses through four clinical stages if left untreated: asymptomatic hyperuricemia, acute gout, intercritical or interval gout and chronic tophaceous gout. Although gouty tophi are seen in chronic disease, tophi may be first sign of the disorder. Here, we report a twenty-year-old male with normal blood uric acid level who presented with tophi prior to any other manifestation of gout.

Case Report

A 20-year-old non-alcoholic male presented with gradually increasing multiple subcutaneous nodules on both the lateral malleoli, lateral parts of bilateral feet and toes, left palm, right elbow, helix of left ear [Figure - 1],[Figure - 2],[Figure - 3],[Figure - 4], ranging in size from 1-1.5 cm diameter since last one and half year. These nodules were firm, mobile and non-tender. Few of them had broken into the skin discharging whitish chalky particulate material. The same could be expressed out of the tophi with the help of a needle. He had intermittent mild pain in the great toes since last six months. Recently, it has spread to elbows. He did not receive any major medication except painkillers in the past.

Systemic examination was normal. Radiographs of both the feet and the hands showed soft tissue swellings with no involvement of bones. Fine Needle Aspiration Cytology (FNAC) was performed from subcutaneous nodules on the left leg using a 21-gauge needle. Light microscopy of the Giemsa and Papanicolaou (Pap) stained smears demonstrated abundant granular amorphous material and scattered stacks of slender needle shaped crystals, associated with chronic inflammatory infiltrate [Figure - 5]. Based on the above findings, a diagnosis of gouty tophi was made. Polarizing microscopy was not used as this facility was not available in our institute. On further investigations, serum uric acid was 5.8mg/dl (normal: 2.5-7 mg/dl). His blood sugar (fasting: 142 mg/dl; postmeal: 190 mg/dl) and triglycerides were raised (212 mg/dl). Ultrasound revealed bilateral nephrocalcinosis [Figure - 6]. Serum levels of calcium, phosphate, albumin, electrolytes, urea, creatinine, Parathyroid hormone, Thyroid-stimulating hormone were within normal limits. Different tests to exclude connective tissue diseases, including that for antinuclear antibody, were performed. 24-hour urine analysis and measurement of levels of calcium, sodium, uric acid, oxalate and citrate were done to rule out any other pathology.

Discussion

Gout, one of the oldest known forms of arthritis, is characterized by chronic hyperuricemia (serum urate >450 ΅mol/l or 7.0 mg/dl in men; and >350 ΅mol/l or 6.0 mg/dl in women). The hyperuricemia may be primary (due to inborn errors of purine metabolism or diminished renal excretion of uric acid) or secondary (conditions with extensive cell turnover or acquired renal disease). In 90% cases of primary gout, hyperuricemia results mostly from relative renal urate underexcretion (′relative urate underexcretors,′) while in about 10% of subjects, hyperuricemia is due to endogenous overproduction of uric acid (′urate overproducers′). ^[1],[2]

The diagnosis of gout can be made according to the American College of Rheumatology (ACR)/Wallace criteria proposed in 1977 [Table - 1]. The gold standard for diagnosis is the demonstration of urate crystals in synovial fluid or in a tophus by polarized light microscopy. The presence of six or more of the 12 criterias makes a diagnosis of gout highly likely. ^[3] But due to changing spectrum of gout, diagnosis of gout is often difficult. Identification of urate crystals in joint aspirates is often not possible. Often the clinicians have to rely on observations of intermittent monoarthritis that begins with involvement of a single joint or multiple joints in the lower extremities (most commonly the first metatarsophalangeal i.e. podagra), associated with hyperuricemia and responsiveness to colchicine. According to newly formed European League Against Rheumatism (EULAR) recommendations, classic podagra and presence of tophi have the highest clinical diagnostic value for gout. Urate crystal identification is very likely to be positive in symptomatic gout and hyperuricemia is a major risk factor for gout although some gouty patients may have normal serum uric acid levels at the time of investigation. ^[4]

Hyperuricemia is the most important risk factor for the development of gout, the risk increasing with a higher urate concentration. But the level of serum uric acid (SU) may be normal in gout, specially in diabetics and alcoholics. ^[5] However in an Indian study of 6 normouricemic patients of gout, only one consumed alcohol. ^[6] 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. ^[7] Our patient was non-alcoholic and his serum uric acid level was within normal limits. He was never suspected to have gout before. So uric acid was never measured earlier and he never received any drugs used in treatment of gout.

Tophi are deposits of MSU crystals in soft tissue that may occur in the helix of the ear, over olecranon processes, and over interphalangeal joints. They have to be differentiated from periarticular nodules like rheumatoid nodules, ganglion cysts, pigmented villonodular synovitis, synovial chondromatosis and synovial sarcoma. The clinical differential diagnoses of acute gout are pseudogout (chondrocalcinosis articularis) and septic arthritis. Calcium pyrophosphate dehydrate (CPPD) crystals are deposited in tophaceous pseudgout and they are shorter, more rhomboid than needle shaped and show positive birefringence as compared to their counterparts in gout.

Uric acid promotes calcium oxalate crystallization in urinary tract by facilitating the formation of nuclei. Sodium acid urate also nullifies the effectiveness of naturally occurring inhibitors of calcium oxa-late crystal growth. Recent prospective studies in 50000 male health professionals have confirmed that a diagnosis of gout was associated with twice the risk of incident renal calculi. ^[8] Toyoda et al., reported 18 cases with medullary nephrocalcinosis of whom seven had gouty arthritis and one had Lesch-Nyhan syndrome. ^[9] According to Kuo et al., gout should be considered as first differential diagnosis in male subjects with medullary nephrocalcinosis, whereas primary hyperparathyroidism should be considered first in females. ^[10]

Gout is often associated with hyperlipidemia (usually hypertriglyceridemia) and insulin resistance syndrome (IRS). The situation may become often tricky as the treatment of gout with a purine restricted diet that is usually rich in both carbohydrate and saturated fat may negatively influence the management of IRS.

Now FNAC is replacing other investigations due to its quick, less invasive, simpler and cost effective technique. The crystal demonstration in FNAC smears is superior to histopathology sections where crystals are more commonly lost during processing. In joint fluid analysis coincident crystals like hydroxyapatite, steroid etc in the joint fluid may cause confusion. ^[11]

Tophi generally developed after an average of 11.6 years of gouty arthritis before uric acid lowering therapy became available. ^[12] They were reported to occur in 12% of patients after 5 years, and 55% after 20 years of untreated disease. ^[13] However, they can develop without the concomitant arthritis. Iglesias et al., used the term ′gout nodulosis′ to describe the subcutaneous deposits of MSU in the absence of initial manifestation of gouty arthritis. ^[14] Recently Thissen et al., reported an 85-year-old woman who was diagnosed with tophaceous gout devoid of a prior medical history of the disease. ^[15]

Probably tissue deposition occurs long before any symptom. When we get symptomatic disease i.e. arthritis, we recognize gout. Then we do routine tests and recognize systemic manifestations such as nephrolithiasis or interstitial deposits.

To the best of our knowledge, ours is the first case report from India where tophi were the first clinical sign of gout.