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Image courtesy of Inani K, Mernissi F. Pan Afr Med J. 2014 Apr 7;17:250. French. [Open access.] PMID: 25309650; PMCID: PMC4189869.

Gout for the Holidays

Lars J Grimm, MD, MHS | November 9, 2023 | Contributor Information

Gouty tophi, composed of monosodium urate crystals, are shown above in the hand of a 70-year-old patient. The skin has thinned above the subcutaneous nodules.

Gout is a crystalline-induced arthropathy and the most common form of inflammatory arthritis.[1] Once known as the "disease of kings" or "rich man's disease," gout can result from holiday-related overindulgence in certain foods and beverages.[2] This pertains not only to alcohol use but also to the consumption of shellfish, red meat, organ meat, processed foods like chips, and refined carbohydrates, especially those containing fructose. A systematic review reported that patients with gout have an increase in all-cause mortality as well as mortality from cardiovascular disease, infections, and digestive system disease.[3]

Image courtesy of Medscape | Rose Anton, MD.

Gout for the Holidays

Lars J Grimm, MD, MHS | November 9, 2023 | Contributor Information

In the above image, a hematoxylin and eosin (H&E) stain shows pale brown-gray urate crystals, which are characteristic of gout.

Gout results from the overproduction or underexcretion of uric acid, either of which may occur as a primary defect or may be secondary to an underlying disorder or due to medication.[4]

All patients with gout have preexisting hyperuricemia, but not all patients with hyperuricemia develop gout. Gout attacks are triggered by an acute change in the level of uric acid, rather than a particular level of uric acid.

It is the deposition of monosodium urate monohydrate crystals in the joints that, due to the release of inflammatory mediators, leads to the clinical presentation of gout.[5] These crystals are needle-shaped and 5-25 microns in length.[6]

Image from Medscape.

Gout for the Holidays

Lars J Grimm, MD, MHS | November 9, 2023 | Contributor Information

Secondary causes of gout are numerous and include myeloproliferative diseases, renal failure, renal tubular disorders, lead poisoning, glycogen storage disease, hyperproliferative skin disorders, and enzymatic defects. Moreover, sleep apnea is an independent risk factor for gout.[7] The classic presentation of gout is pain, edema, and inflammation.

Podagra refers to involvement of the metatarsophalangeal (MTP) joint in the first toe and is present in 50% of cases.[4] The above image demonstrates typical radiographic changes in the first MTP joint (arrow), with erosion and destruction of the joint space. Gout has a preference for peripheral locations, possibly because the cooler temperature of peripheral digits decreases urate solubility and facilitates precipitation.[4,8]

Image from Medscape.

Gout for the Holidays

Lars J Grimm, MD, MHS | November 9, 2023 | Contributor Information

The above image shows gouty involvement of the elbow, a finding that is more common in later stages of gout.

Gout attacks begin abruptly and typically reach maximal intensity within 8-12 hours. They involve activation of inflammasomes (multiprotein cytoplasmic complexes that activate caspases) and the production of interleukin 1.[9] Attacks may resolve spontaneously in a couple of weeks, and patients may return to normal between attacks. If left untreated, gout may begin to involve more joints, larger joints, or more proximal joints; attacks may also occur more frequently and last longer.[4]

Image from Medscape.

Gout for the Holidays

Lars J Grimm, MD, MHS | November 9, 2023 | Contributor Information

Radiographs are the first-line imaging modality of choice in gout.[10] Early in the disease, the radiographic appearance is usually normal. As the disorder progresses, the classic radiographic appearance of gout is punched-out periarticular lesions with overhanging edges (yellow arrow), normal bone mineral density, and hyperdense soft-tissue tophi (pink arrow). Typically, there is preservation of the joint space until late in the disease process. Involvement is asymmetrical, which helps to differentiate gout from systemic arthropathies, such as rheumatoid disease.[4,11]

Image from Wikimedia Commons | DESHAMO1.

Gout for the Holidays

Lars J Grimm, MD, MHS | November 9, 2023 | Contributor Information

The above image demonstrates a synovial toe joint tophus.

The tophi in gout typically appear hyperdense and may develop calcifications. The tophi may be readily identified on magnetic resonance imaging (MRI) as well-defined, periarticular masses that have varying signal intensities, depending on the amount of uric acid, granulation tissue, and edema present.

The findings on MRI are often nonspecific in gout, depending on the joint being imaged. Nonetheless, MRI is likely the best imaging study for the evaluation of spinal gout, owing to its ability to assess for soft-tissue changes, including inflammation, ligament or tendon rupture, bone marrow edema, and cartilage damage.[12] Ultrasonography, however, is the most sensitive imaging modality to detect tophi and is especially useful for the evaluation of peripheral joints.[4,13]

Image from Medscape.

Gout for the Holidays

Lars J Grimm, MD, MHS | November 9, 2023 | Contributor Information

Synovial fluid obtained from a patient with tophaceous gout is shown.

Formal diagnosis of gout requires aspiration of synovial fluid, which will appear clear or white in a patient with the disease. Only a small amount of fluid is typically needed for crystal analysis, and the aspiration procedure is safe, being associated with a 0.1% risk for septic arthritis.[14] Depending on the clinical circumstances, it may be important to exclude septic arthritis as the etiology of crystalline arthropathy.[4] White blood cell (WBC) counts may be elevated (<50,000 WBCs/µL) in gout, but glucose levels typically are normal, and a Gram stain should be negative.[4,15]

Image from Medscape.

Gout for the Holidays

Lars J Grimm, MD, MHS | November 9, 2023 | Contributor Information

Urate crystals are shaped like needles and exhibit negative birefringence under polarized light. The crystals appear yellow when aligned parallel to the axis of the red compensator (yellow arrow), and blue when aligned perpendicular (blue arrow). Identification of the crystals' shape and birefringence is diagnostic for gout.[4,16]

Although synovial fluid analysis is the gold standard for the diagnosis of gout, a diagnostic rule for the condition has been developed and may be helpful in the absence of such assessment. The seven variables in the diagnostic rule include the following[17-19]:

  • Male sex
  • Previous patient-reported arthritis attack(s)
  • Onset within 1 day
  • Joint redness
  • Involvement of the first MTP joint
  • Hypertension or one or more cardiovascular diseases
  • A serum uric acid level of more than 5.88 mg/dL
Image from Medscape.

Gout for the Holidays

Lars J Grimm, MD, MHS | November 9, 2023 | Contributor Information

The above image shows tophaceous deposits in a patient's ear.

Gout therapy can be divided into treatment of acute flares, flare prophylaxis, and reduction in stores of excess urate.[20]

An acute attack of gout is treated with short-term, potent anti-inflammatory agents. Low-dose colchicine, nonsteroidal anti-inflammatory agents (NSAIDs), and glucocorticoids are equally effective and can be administered orally, intramuscularly, or intra-articularly.[21]

Image from Medscape.

Gout for the Holidays

Lars J Grimm, MD, MHS | November 9, 2023 | Contributor Information

The photograph demonstrates the classic physical examination findings of gout in the great toe.

Advise patients to avoid foods that may trigger an acute attack of gout. In general, there are few purine-rich foods, but those that do have a high purine content are energy-rich foods like fish (eg, sardines), meats, and organs (eg, sweetbreads).[20] In particular, the type of purine consumed is also crucial, as hypoxanthine is the most important purine to be reduced.[22]

Unfortunately, diet and lifestyle changes are typically not sufficient treatment for gout, with lifelong therapy needed.[23,24] Allopurinol is usually the first drug of choice because of its ease of use, efficacy, and low cost. Treatment targets can typically be reached through allopurinol dose escalation, although newer medications are available.[25]

Image courtesy of Aradoini N, Talbi S, Berrada K, Abourazzak FZ, Harzy T. Pan Afr Med J. 2015 Oct 13;22:132. [Open access.] PMID: 26889313, PMCID: PMC4742039.

Gout for the Holidays

Lars J Grimm, MD, MHS | November 9, 2023 | Contributor Information

The image shown depicts chronic tophaceous gout with very large tophi.

Guidelines released in 2020 by the American College of Rheumatology strongly recommend the initiation of urate-lowering therapy for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares.[23] A urate-lowering agent (allopurinol or febuxostat is recommended) is started at a low dose, which would then be increased to maintain a urate level below 6 mg/dL. Concomitant anti-inflammatory prophylaxis for 3-6 months is strongly recommended. Urate-lowering therapy may need to be continued for life.[21]

Image from Wikimedia Commons | Mikael Häggström, MD. [CC0 1.0.]

Gout for the Holidays

Lars J Grimm, MD, MHS | November 9, 2023 | Contributor Information

Gross pathology of a large tophus is shown.

Although current guidelines do not recommend treatment of asymptomatic hyperuricemia, an increased incidence of hypertension, renal disease, hyperlipidemia, metabolic syndrome, and diabetes is associated with hyperuricemia, and it is an independent risk factor for death from cardiovascular disease.[26] It is unclear why some individuals with hyperuricemia will progress to symptomatic disease but not others.[27] An estimated 10-20% of adults in industrialized nations have asymptomatic hyperuricemia,[28] and treatment might lower the risk of renal disease, hypertension, and cardiovascular disease.[29]

When renal failure does occur, the management of gout is complicated, as abnormal renal function is related to allopurinol hypersensitivity syndrome (with allopurinol being used to reduce uric acid synthesis).[30]

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