eMedicine Specialties > Ophthalmology > Metabolic Disorders

Gout

Andrew A Dahl, MD, Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine

Updated: Feb 19, 2009

Introduction

Background

Gout is one of the oldest diseases in the medical literature and has been characterized as a condition caused by indiscretions of diet and alcohol. Since the time of the Greeks, many authors have written about gout as the result of personal excess. However, among the abstinent was John Milton, who lived a life of rigorous self-discipline and yet, to his anger and despair, suffered from what commonly was regarded as just punishment of the dissolute.

Gout, the king of diseases and the disease of kings, is an illness that produces signs and symptoms secondary to elevated levels of uric acid salts in the serum and the resulting deposition of these salts within target organs, primarily the joints of the extremities, the kidneys, and the urinary collecting system.

Rarely, gout can produce significant ocular findings. The incidence of age-related macular degeneration (ARMD) is higher in patients with gout.

Frequency

United States

Unknown

International

Unknown

Mortality/Morbidity

During an attack, the patient is incapacitated by pain in the affected area.

Race

No racial predilection is known.

Sex

Males are affected more commonly than females.

Age

The onset of this condition generally occurs in patients aged 30-50 years.

Clinical

History

With joint involvement, patients experience pain in the distal extremities. With kidney stones, patients experience acute flank pain.

Physical

The classic attack of acute primary gouty arthritis occurs in a portly middle-aged man and produces fairly sudden inflammation of a single joint, most commonly the metatarsal-phalangeal joint of the great toe, resulting in intense pain, tenderness, and swelling.

The folklore surrounding gout has also involved the eye, and, prior to the 20th century, a myriad of common and unusual ocular symptoms were falsely ascribed to the gout. All manifestations of gout in the eye are secondary to deposition of urate crystals within the ocular tissue.

• Conjunctival nodules containing needlelike crystals have been described within the interpalpebral areas, sometimes associated with a mild marginal keratitis.
• Band keratopathy with refractile, yellow crystals in the deep corneal epithelial cells and at the level of the Bowman membrane are not uncommon.
• Symptoms of visual blurring from the corneal haze or foreign body sensation due to epithelial breakdown can be treated with scraping of the epithelium and removal of the crystals.
• Gout rarely can be associated with anterior uveitis and has been mentioned by Duke-Elder in his textbook as a cause of hemorrhagic iritis.
• Scleritis and tenonitis also have been described.
• In addition to the cornea, urate crystals have been described clinically in the iris, anterior chamber, lens, and sclera, and, on postmortem examination, in the tarsal cartilage and in the tendons of extraocular muscles.
• Uric acid nodules called tophi have been described in the eyelids.

Causes

Attacks are caused by the deposition of monosodium urate monohydrate within the joint space. Precipitating factors can include emotional stress, dehydration, surgery, and thiazide diuretics. Attacks tend to be recurrent and usually are self-limited. Recurrent attacks of acute gouty arthritis can result in chronic arthritis with limitation of joint mobility.

Uric acid levels may be elevated as a result of primary gout. Primary gout is an autosomal dominant error of metabolism. Primary gout can occur secondarily from increased production of uric acid or decreased excretion of uric acid. The latter is seen in chronic renal disease.

• Excessive uric acid production primarily occurs in patients on chemotherapy for malignancies, especially those of the hematopoietic or lymphatic systems. This can be expected because uric acid is the metabolic end product of purines, which are present in high concentration in cell nuclei.
• Decreased levels of serum uric acid have been found in patients with demyelinating disease.

Other causes of secondary gout include chronic lead poisoning, polycystic kidney disease, systemic cyclosporine therapy, various antimitotic chemotherapeutic agents, sarcoidosis, psoriasis, and hyperparathyroidism.

Differential Diagnoses

Keratopathy, Band

Other Problems to Be Considered

Conjunctival calcinosis

Workup

Laboratory Studies

• Serum uric acid is used in helping to diagnose this condition and in monitoring the treatment process.

Treatment

Medical Care

For urate crystals within the ocular tissue, treatment is directed at reducing both hyperuricemia and ocular inflammation.

Diet

Reduction of purine intake in the diet can moderate both the frequency and the severity of attacks of gout.

Medication

Treatment involves hydration, colchicine for prevention and acute treatment, nonsteroidal and steroidal anti-inflammatory drugs, uricosuric agents (eg, probenecid), and antihyperuricemic drugs (eg, allopurinol), which are effective in inhibiting xanthine oxidase, the enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid.

Anti-inflammatory agents

Modify the immune system to diverse stimuli.

Colchicine

Decreases leukocyte motility and phagocytosis in inflammatory responses.

Dosing

Adult

1-1.2 mg PO qd for acute attacks of gouty arthritis; 0.5-0.6 mg PO qd as maintenance dose

Pediatric

Not established

Interactions

Sympathomimetic agent toxicity and effect of CNS depressants are significantly increased with colchicine

Contraindications

Documented hypersensitivity; severe renal, hepatic, GI, or cardiac disorders; blood dyscrasias

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Risk of renal failure, hepatic failure, permanent hair loss, bone marrow suppression, numbness or tingling in hands and feet, disseminated intravascular coagulopathy, and decreased sperm count

Uricosuric agents

Inhibit renal tubular reabsorption of urates, causing increase in urinary excretion of urates.

Probenecid

The generic name is 4-[(dipropylamine) sulfonyl)] benzoic acid. Inhibits tubular secretion of penicillin, and usually increases penicillin plasma levels by any route the antibiotic is given. A 2-fold to 4-fold elevation has been demonstrated for various penicillins. Used in treatment of hyperuricemia associated with gout and gouty arthritis. Also used as an adjuvant to therapy with penicillin or ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whichever route the antibiotic is given.

Dosing

Adult

0.5 g PO qd

Pediatric

Not established

Interactions

Salicylates at high dosages, and nitrofurantoin, may decrease effects of probenecid; probenecid increases levels/toxicity of methotrexate, beta-lactam antibiotics, acyclovir, thiopental, clofibrate, dyphylline, pantothenic acid, ketorolac, benzodiazepines, rifampin, sulfonamide, dapsone, zidovudine, sulfonylureas

Contraindications

Documented hypersensitivity; known blood dyscrasia or uric acid kidney stones; coadministration of ketorolac as levels/toxicity of ketorolac are significantly increased

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Crosses placental barrier; use of any drug in women of childbearing potential requires anticipated benefit be weighed against possible hazards; caution in history of peptic ulcer

Allopurinol (Zyloprim)

Inhibit xanthine oxidase, the enzyme that synthesizes uric acid from hypoxanthine. Reduces the synthesis of uric acid without disrupting the biosynthesis of vital purines.

Dosing

Adult

200-400 mg/d PO in divided doses

Pediatric

<10 years: 10 mg/kg/d PO divided bid/tid; not to exceed 400 mg/d
>10 years: 200-400 mg/d PO

Interactions

Alcohol decreases effects; increases incidence of skin rash when used concurrently with ampicillin and amoxicillin; large amounts of vitamin C acidify urine and may cause kidney stone formation; allopurinol inhibits metabolism of azathioprine and mercaptopurine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Not for use in asymptomatic hyperuricemia; reduce dose in renal insufficiency; monitor liver function and perform complete blood counts before initiating therapy and periodically thereafter

Febuxostat (Uloric)

Xanthine oxidase inhibitor. Prevents uric acid production and lowers elevated serum uric acid levels. Indicated for long-term management of hyperuricemia associated with gout.

Dosing

Adult

40 mg PO qd initially; after 2 wk, if serum uric acid levels are not <6 mg/dL, increase to 80 mg/d

Pediatric

Not established

Interactions

Coadministration with xanthine oxidase substrate drugs (eg, azathioprine, mercaptopurine, theophylline) may increase plasma concentration of these substrates, resulting in toxicity

Contraindications

Documented hypersensitivity; coadministration with azathioprine, mercaptopurine, or theophylline

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Increased gout flares frequently observed during initiation of therapy (use prophylactic therapies such as NSAIDs or colchicine); higher rate of thromboembolic events observed in patients treated with febuxostat compared with allopurinol in clinical trials (monitor for signs and symptoms of MI and stroke); may increase liver transaminase levels; common adverse effects include nausea, arthralgia, and rash

Follow-up

Further Outpatient Care

• Monitor uric acid levels.

Deterrence/Prevention

• Reduction of purine intake in the diet can moderate both the frequency and the severity of attacks of gout.

Complications

• Complications include distal joint pain and kidney stones.

Prognosis

• The prognosis is favorable with diet and medication control of uric acid.

Patient Education

• Inform the patient of the importance of both diet control and medication.
• For excellent patient education resources, visit eMedicine's Arthritis Center. Also, see eMedicine's patient education article Gout.

Miscellaneous

Medicolegal Pitfalls

• Patients with atypical band keratopathy should be questioned regarding symptoms of gouty arthritis or nephrolithiasis.

References

1. Bernad B, Narvaez J, Diaz-Torne C, et al. Clinical image: corneal tophus deposition in gout. Arthritis Rheum. Mar 2006;54(3):1025. [Medline].

2. Choi HK, Atkinson K, Karlson EW, et al. Alcohol intake and risk of incident gout in men: a prospective study. Lancet. Apr 17 2004;363(9417):1277-81. [Medline].

3. Choi HK, Curhan G. Gout: epidemiology and lifestyle choices. Curr Opin Rheumatol. May 2005;17(3):341-5. [Medline].

4. Coassin M, Piovanetti O, Stark WJ, et al. Urate deposition in the iris and anterior chamber. Ophthalmology. Mar 2006;113(3):462-5. [Medline].

5. Fishman RS, Sunderman FW. Band keratopathy in gout. Arch Ophthalmol. Mar 1966;75(3):367-9. [Medline].

6. Fuchs E. Gout. Graefes Arch Ophth. 1895;21:229.

7. Kim KY, Ralph Schumacher H, Hunsche E, et al. A literature review of the epidemiology and treatment of acute gout. Clin Ther. Jun 2003;25(6):1593-617. [Medline].

8. Klein R, Klein BE, Tomany SC, et al. Association of emphysema, gout, and inflammatory markers with long-term incidence of age-related maculopathy. Arch Ophthalmol. May 2003;121(5):674-8. [Medline].

9. Knapp CM, Constantinescu CS, Tan JH, et al. Serum uric acid levels in optic neuritis. Mult Scler. Jun 2004;10(3):278-80. [Medline].

10. Margo CE. Use of standard hematoxylin-eosin to stain gouty tophus specimens. Arch Ophthalmol. Apr 2004;122(4):665. [Medline].

11. Mcwilliams JR. Ocular findings in gout; report of a case of conjunctival tophi. Am J Ophthalmol. Dec 1952;35(12):1778-83. [Medline].

12. Morris WR, Fleming JC. Gouty tophus at the lateral canthus. Arch Ophthalmol. Aug 2003;121(8):1195-7. [Medline].

13. Slansky HH, Kubara T. Intranuclear urate crystals in corneal epithelium. Arch Ophthalmol. Sep 1968;80(3):338-44. [Medline].

14. Wyngaarden JB. Gout. In: The Metabolic Basis of Inherited Disease. 1966:667-728.

Keywords

gout, uric acid, urate crystals, ocular tissue, kidneys, kidney stones, urinary collecting system, joint inflammation, joint destruction, tophus, tophi, alcohol, uric acid salts, uric acid metabolism, uric acid nephropathy, chronic tophaceous gout, tophaceous gout, gouty arthritis, primary gout, secondary gout, acute gout, chronic gout, polyarticular gout, hyperuricemia, acute monoarticular arthritis, polyarticular arthritis

Contributor Information and Disclosures

Author

Andrew A Dahl, MD, Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine
Andrew A Dahl, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Richard W Allinson, MD, Associate Professor, Department of Surgery, Texas A&M University Health Science Center; Senior Staff Ophthalmologist, Scott and White Clinic
Richard W Allinson, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

R Christopher Walton, MD, Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, Assistant Dean for Graduate Medical Education, University of Tennessee College of Medicine; Consulting Staff, Regional Medical Center, Memphis Veterans Affairs Medical Center, St Jude Children's Research Hospital
R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Research in Vision and Ophthalmology, and Retina Society
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

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