What Caused This Forearm Nodule?

A 48-year-old man presented with a progressively enlarging tumor on his right wrist. He had previously developed a similar lesion that caused perforation of his skin and healed with atrophic scarring. Beneath the skin, material appeared to be nearly extruded (Figure 1 and Figure 2). 

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Tophaceous Gout

Gout is characterized by the deposition of monosodium urate in and around joints. It results from not only hyperuricemia caused by excessive uric acid production or reduced uric acid elimination, but also the inflammation in response to the deposited urate. The progression of gout is as follows:^1-3 

• Asymptomatic hyperuricemia 

• Deposition of monosodium urate crystals 

• Acute gout characterized by an arthritis attack 

• Intercritical period, occurring after resolution of the acute gout attack when the joints appear to return to normal 

• Chronic gout, an advanced stage including polyarticular arthritis and bony erosions associated with gout duration, joint effusion, patient age, synovial hypertrophy, and tophi 

Gout is a lifelong condition. Ideally, it is optimal to establish a definitive diagnosis of gout by documenting the presence of monosodium urate crystals in the serum, joint fluid, or tissues, including the skin. Diagnostic clinical criteria for gout include 2 of the following:⁴ 

• At least 2 attacks, each of which resolved within 2 weeks of painful joint swelling 

• Observation or a history of podagra (involvement of the first metatarsal of the great toe) or the presence of a tophus 

• Prompt response (within 48 hours) after starting treatment with colchicine 

An acute gout flare typically presents with monoarticular joint involvement. The joint is not only erythematous, but also painful or swollen, or both. A classic site of joint involvement is the first metatarsophalangeal joint of the great toe.⁵ 

Dermatologic manifestations of gout caused by monosodium urate deposits include nodular tophi, draining tophi, and chronic ulcers. Tophi on the ears and the finger pads are rare. Uncommon clinical presentations of gout include:^1,6-12 

• Disseminated cutaneous gout, in which there are widespread dermal and subcutaneous tophi at an extra-articular body site 

• Gouty nodulosis, a rare presentation of gout in a person who does not have any prior history of acute gouty arthritis and often has a normal uric acid level 

• Miliarial gout, characterized by tiny milia-like papules containing tophaceous material 

• Panniculitis, characterized by indurated subcutaneous nodules in nonjoint areas, with or without ulcerations 

• Perforating gout, in which there is transepidermal elimination of urate deposits 

Monosodium urate is water soluble. Skin biopsy specimens are usually placed in formalin (an aqueous solution of formaldehyde) and processed in the standard fashion using routine automated processing that contains water in the early solutions used. The urate crystals are dissolved when the tissue is treated in this manner and appear as amorphous eosinophilic deposits in the dermis after hematoxylin-eosin staining.⁶ 

To preserve the monosodium urate crystals, the skin biopsy specimen should be placed in absolute ethanol or Carnoy’s solution (ferric chloride, absolute alcohol, chloroform, and glacial acetic acid). When processing the tissue, it is fixed in absolute ethanol, then transferred to a solution of equal parts xylene and paraffin, and then into paraffin. If the tissue is stained with a 20% silver nitrate stain (de Galantha stain), the crystals will appear black using a light microscope and demonstrate negative birefringence when examined using a polarized light microscope.⁶ 

Gout is classified as either primary, when caused by inborn errors of metabolism, or secondary, when caused by disease associated with increased production or decreased excretion of uric acid. Some examples of genetic conditions that can cause gout are Lesch-Nyhan syndrome (hypoxanthine-guanine phosphoribosyltransferase deficiency when homozygous), fructose 1-phosphate aldolase deficiency, phosphoribosylpyrophosphate synthetase superactivity, and von Gierke disease (glucose-6-phosphatase deficiency). Numerous medical conditions can predispose an individual to gout, including hematologic disorders, renal insufficiency, and tumor lysis syndrome.^1,2,5,13 

Medications can be associated with hyperuricemia, including low-dose aspirin, cyclosporin, diuretics (loop and thiazide types), ethambutol, levodopa, nicotinic acid, and pyrazinamide.¹ 

Lifestyle behaviors or dietary factors can also predispose a person to gout, including alcohol use (especially beer), consumption of high-fructose sweeteners (nondiet sodas), dehydration, high-purine foods (meats and shellfish), and obesity. However, the urate lowering effects were generally minor after dietary interventions, such as low-calorie or low-purine diets. Therefore, to successfully lower urate concentration, lifestyle and dietary modifications alone are not usually adequate interventions.^1,2,5,13 

The differential diagnosis of an acute gout flare includes: 

• Cellulitis 

• Osteoarthritis 

• Palindromic rheumatism, a rare type of inflammatory migratory arthritis affecting only 1 or 2 joints characterized by joint inflammation, pain, and swelling that suddenly appears and resolves spontaneously or several days after the attack until the next flare, which occurs in different joints 

• Pseudogout from calcium pyrophosphate deposition disease 

• Septic arthritis 

• Trauma 

In patients with tophaceous gout, the differential diagnosis includes calcinosis cutis, dactylitis (from psoriatic arthritis or reactive arthritis), osteomyelitis, and rheumatoid arthritis.^1,5,14 Cutaneous tophi on the ear and periungual region can mimic squamous cell carcinoma.^1,15 Our patient’s lesions mimicked a mycetoma.¹⁶ 

Management for acute gout flare includes colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids (either administered orally, intravenously, or intraarticularly). For patients with recurrent episodes of gout, it is recommended that they keep “the pill in their pocket” so they can initiate treatment as soon as they experience symptoms. In addition, these medications can be used for gout prophylaxis in the treat-to-avoid symptoms approach to management. Alternative agents for gout flare management include IL-1 inhibitors, such as anakinra, canakinumab, and rilonacept, or corticotropin.^2,5,13 

The xanthine oxidase inhibitor allopurinol is the first-line therapy for patients being managed as treat-to-target to maintain a serum urate concentration of less than 6 mg/dL. Alternative urate-lowering agents include the xanthine oxidase inhibitor febuxostat and uricosuric drugs, such as benzbromarone, probenecid, and pegloticase.^2,5,13 

The patient had lost much of the function of his right wrist. The tophus was asymptomatic. More than half of the patients with gout stop their urate-lowering drug within 1 year after initiation.⁵ Similarly, he was not interested in any additional investigation or treatment of his gout. 

Gout results from hyperuricemia and the deposition of monosodium urate crystals in and around joints. It can be associated with inborn errors of metabolism, diseases that either increase the production or decrease the elimination of uric acid, medications, and certain dietary and lifestyle practices. Acute attacks typically affect a single joint, such as podagra occurring on the first metatarsal of the great toe. Tophaceous gout can have various dermatologic manifestations, including nodules with or without draining, ulcers, disseminated cutaneous gout, gouty nodulosis, miliarial gout, panniculitis, and perforating gout. Colchicine, NSAIDs, and corticosteroids are first-line agents that can be used for management of an acute gout attack; IL-1 inhibitors and corticotropin are alternative drugs. Chronic management of hyperuricemia often entails the use of urate-lowering agents; treatment may also include uricosuric drugs. 

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Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of The Dermatologist or HMP Global, their employees, and affiliates. 

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