GO TO CMA Home
GO TO Inside CMA
GO TO Advocacy and Communications
GO TO Member Services
GO TO Publications
GO TO Professional Development
GO TO Clinical Resources

GO TO What's New
GO TO Contact CMA
GO TO Web Site Search
GO TO Web Site Map


CMAJ
CMAJ - May 30, 2000JAMC - le 2 mai 2000

Rheumatology: 4. Acute monoarthritis

Jolanda Cibere

CMAJ 2000;162(11):1577-83

Rheumatology series · Série sur la rheumatologie
Clinical basics · Principes cliniques
Contents
The case
Mrs. R, a 72-year-old woman with a history of osteoarthritis of the knees, consults her physician because she has a fever, malaise and a swollen, painful right knee. She is unable to bear weight on her right leg because of the pain. Two years earlier she experienced gastrointestinal bleeding while taking nonsteroidal anti-inflammatory drugs for osteoarthritis; currently, she is taking only acetaminophen as needed for pain. Mrs. R is otherwise healthy and has not travelled recently. During examination the physician finds that Mrs. R is slightly confused. Her pulse rate is 80 beats/min and regular; her blood pressure is normal, and her temperature is 37.9°C. Her right knee is warm, erythematous, swollen and tender. Flexion ranges from 10° to 80° with pain. Her leukocyte count is above normal at 14.8 × 109 cells/L (normal range: 4­11 × 109 cells/L). Her serum uric acid level, measured at an earlier office visit, was slightly above normal at 450 µmol/L (normal range: 90­360 µmol/L).

[Contents]

Acute monoarthritis is a potential medical emergency that must be investigated and treated promptly. Common diagnoses include crystal-induced arthritis and mechanical complications of osteoarthritis, fractures and ligamentous or meniscal injury; less common causes are ischemic necrosis (osteonecrosis), hemarthrosis or tumour. However, first and foremost, acute monoarthritis should be considered septic until proven otherwise.

An accurate diagnosis of acute monoarthritis depends on a good history and physical examination that are supplemented by the appropriate investigations. In particular, the physician must verify that the patient has arthritis, as manifested by joint swelling, and that the arthritis is limited to a single joint.1,2 Determining whether the arthritis is inflammatory or mechanical in nature and whether the disease is acute or chronic will then help the physician arrive at a presumptive diagnosis.

Investigations should include joint aspiration of synovial fluid for a leukocyte count, Gram's stain, cultures and an examination for crystals; radiographs of the joint may also be required. Occasionally, a radionuclide scan, computed tomography (CT) or magnetic resonance imaging (MRI) is useful. Treatment is based on the underlying diagnosis, but antibiotics are sometimes required until septic arthritis is excluded.

If acute monoarthritis is apparent from the history and physical examination the most common differential diagnoses are infectious arthritis, crystal-induced arthritis and trauma-induced arthritis3 (Fig. 1 [available in PDF format only]); these can be differentiated by history, physical examination and synovial fluid analysis4 (Table 1).

[Contents]

Causes

Infectious arthritis

Acute monoarthritis should be considered infectious until proven otherwise.5,6,7 Septic arthritis is usually caused by an infectious agent that is spread through the blood system. It often affects the knee and is characterized by systemic symptoms of sepsis (e.g., fever and malaise), as well as swelling, warmth and local pain in the involved joint, sometimes so severe that the patient refuses to allow even passive movement. Redness around the joint is an important clue, limiting diagnosis to either infectious or crystal-induced arthritis.

The inflammatory response may be blunted in immunocompromised patients (such as those taking immunosuppressants); patients with rheumatoid arthritis, diabetes mellitus or HIV; intravenous drug users and those with prosthetic joints. However, suspicion of infectious arthritis in these patients should be maintained, despite limited physical signs, until infection has been excluded.

Staphylococcus aureus causes most nongonococcal cases of septic arthritis in adults.5,6,7,8 However, gonococcal infections are the most common cause of septic arthritis in sexually active young adults.9,10 These cases are often characterized by migratory arthritis and associated with tenosynovitis and maculopapulovesicular skin lesions before manifesting as a monoarthritis.

Although arthritides caused by mycobacteria and fungi are usually chronic in nature, they can also resemble acute monoarthritis. If the patient's history suggests prior tuberculosis, recent exposure to tuberculosis or an immunodepressed state, mycobacterial or fungal arthritis should be considered.

Viruses such as hepatitis B, HIV and human parvovirus and the spirochete Borrelia burgdorferi, which causes Lyme disease, rarely cause acute monoarthritis; they more commonly manifest as acute or chronic oligoarthritis.

Crystal-induced arthritis

Crystal-induced arthritis is another main cause of acute monoarthritis. Gout, which is caused by monosodium urate crystals in the synovial fluid, can give rise to acute arthritis in any joint, but predominantly affects the first metatarsophalangeal joints, midfoot, ankles or knees. Pseudogout, caused by calcium pyrophosphate dihydrate crystal deposition, affects mainly the knees and wrists, but can occur in the first metatarsophalangeal and other joints as well.

An important clue in the diagnosis of crystal-induced arthritis is a history of acute attacks of monoarthritis that resolved spontaneously. Crystal-induced arthritis is characterized by redness around the joint, and it can present with fever, mimicking infectious arthritis. With gout the pain is often so severe that patients complain of an inability to tolerate the weight of a light bed sheet on the involved joint.

Tophi — deposits of urate crystals — in soft tissues is highly suggestive of chronic gout. Tophi appear as soft, subcutaneous nodules usually on fingers and toes, around the elbows and, classically, on the helix of the ear. They can be differentiated from rheumatoid nodules by their asymmetric distribution, yellow–white appearance and occasional overlying skin erythema.

Noninflammatory monoarthritis

Trauma causing fractures (or microfractures), as well as ligamentous or meniscal injuries, can lead to acute monoarthritis. It is often associated with mild-to-moderate joint swelling, and the pain is characteristically exacerbated on movement and relieved at rest. Although a history of trauma is usually evident, this may not be the case for patients with osteoporosis. The pain of traumatic arthritis is felt within seconds to minutes of the trauma, in contrast to the pain of infectious and crystal-induced arthritis which often develops over hours. Acute hemarthrosis (bleeding into a joint) should be suspected in patients with bleeding disorders and in those taking anticoagulants.

Other noninflammatory causes of monoarthritis include osteoarthritis and osteonecrosis. Osteoarthritis occurs mostly in elderly patients, is usually chronic and is characterized by pain with activity. Joint swelling is minimal but can be present when an acute exacerbation of pain occurs. Osteonecrosis, also called avascular or ischemic necrosis, results from bone death secondary to an impaired blood supply.11–13 The femoral head is commonly involved, leading to hip-joint arthritis, but any other joint can be affected. Symptoms include pain, especially when bearing weight, limping and the eventual restricted movement of the involved joint. Osteonecrosis should be considered in young people with risk factors such as corticosteroid use, hemoglobinopathies or sickle cell disease, as well as in alcoholic and elderly diabetic patients.

Tumour-associated monoarthritis is rare in adults but should be suspected in patients with chronic, progressive monoarthritis with no clear underlying diagnosis.

A popliteal or Baker's cyst — a swelling behind the knee caused by escape of synovial fluid — can occur with septic arthritis, chronic inflammatory arthritis, osteoarthritis or arthritis associated with internal derangement. The prevalence of popliteal cysts ranges from 4.7% among orthopedic patient populations14 to 47.5% among patients with rheumatoid arthritis.15 The prevalence of cysts among patients with septic arthritis is unknown. Because of the correlation between popliteal cysts and knee-joint effusions,16 it is thought that cysts may develop as a result of a persistent knee effusion. A 1-way valve prevents popliteal cyst fluid from returning to the knee joint, and the increasing pressure may cause the cyst to rupture. When this occurs the associated pain and swelling in the calf mimics deep venous thrombosis, which is often wrongly diagnosed and treated. A crescentic hematoma below the medial or lateral malleoli of the ankle supports a diagnosis of a ruptured popliteal cyst; however, the best clue is sudden onset of calf pain.

[Contents]

Diagnosis

Joint aspiration and analysis of synovial fluid

Arthrocentesis is mandatory if infectious arthritis is even considered17 and is also usually required for the diagnosis of crystal-induced arthritis and hemarthrosis. Joint aspiration and the synovial fluid leukocyte count may also be helpful in differentiating inflammatory from noninflammatory arthritis. Therapeutic indications for joint aspiration include draining of a tense effusion to relieve pain and improve function, as well as draining of pus or blood to avoid permanent joint damage.17 Synovial fluid analysis should include a cell count and differential leukocyte count, Gram's staining, culture and an examination for crystals. If Gram's staining is not immediately available a request for the procedure should be made, at least for patients with high leukocyte counts.

The leukocyte count in the synovial fluid is helpful in distinguishing inflammatory from noninflammatory conditions but is not helpful to differentiate between the various causes of inflammatory monoarthritis.4 Inflammatory arthritis is characterized by a synovial fluid leukocyte count > 1 × 109 cells/L; the leukocyte count will be lower in a noninflammatory arthritis. Although septic arthritis should be suspected if the leukocyte count is > 100 × 109 cells/L, it may be lower. A polymorphonuclear (PMN) cell count > 85% suggests infectious or crystal-induced arthritis. A predominant mononuclear infiltrate occurs with chronic infections and chronic inflammation.

Synovial fluid should be examined for crystals using a polarized light microscope. Monosodium urate crystals are needle-shaped and strongly negatively birefringent under polarized light; calcium pyrophosphate dihydrate crystals are rhomboid or rod shaped, only weakly birefringent and, therefore, more difficult to see. An examination of synovial fluid for crystals (especially calcium pyrophosphate dihydrate crystals) should be done promptly because crystals can dissolve when synovial fluid is stored. In addition, if the analysis is not performed by an experienced examiner, it may be falsely reported as negative. Other pathogenic crystals such as calcium apatite crystals can be identified with certainty only under an electron microscope; under a light microscope they appear as debris. A positive alizarin red stain will confirm that this debris contains calcium crystals, although the stain is not specific for calcium apatite crystals. Acute monoarthritis is likely crystal-induced if microscopy reveals crystals not only in the synovial fluid but also intracellularly. However, the presence of intracellular crystals does not exclude infection. If infection is suspected synovial fluid cultures are still necessary.

Gram's staining and culture may be falsely negative if the patient has been taking antibiotics. However, joint aspiration may still reveal the causative organism and should be performed.

If nongonococcal infection is suspected, blood and urine samples should be obtained for culture. For gonococcal infection, in addition to blood and urine cultures, cervical, urethral, rectal and pharyngeal cultures are necessary.

Blood in synovial fluid may result from a traumatic tap or a true hemarthrosis. With true hemarthrosis the synovial fluid is uniformly red and the supernatant is yellow–brown (xanthochromic), whereas with a traumatic tap the synovial fluid is less uniformly red and often contains streaks of clotted blood.

Synovial biopsy

A synovial biopsy may be indicated if the diagnosis is unclear after initial investigations. Synovial biopsy is usually diagnostic in monoarthritis infections caused by Mycobacteria, Neisseria and Chlamydia spp. and infiltrative diseases such as sarcoidosis, amyloidosis and malignancies. Therefore, synovial biopsy specimens should be sent not only for pathologic evaluation but for mycobacterial, neisserial and chlamydial culture as well.4

Radiologic investigations

Although plain radiographs are not always necessary in the investigation of acute monoarthritis they can be helpful to establish the diagnosis of monoarthritis and provide a baseline for follow-up (Table 2).1,18–20 If infectious arthritis is suspected a plain radiograph of the joint should be obtained to diagnose a concomitant osteomyelitis and to provide a baseline from which to monitor treatment.21 A patient with septic arthritis who does not respond to antibiotic treatment (i.e., with less joint pain and swelling and greater range of motion ) in 5–7 days or who has persistent positive synovial fluid cultures should undergo radiographic evaluation for osteomyelitis with repeat plain radiographs; if plain radiography is inconclusive radionuclide scan, CT or MRI may be required.5,18–20,22

Chondrocalcinosis on plain radiographs supports the diagnosis of calcium pyrophosphate deposition disease. However, septic arthritis must still be ruled out. If acute gout is confirmed by synovial fluid analysis radiographic evaluation is not necessary, but if a patient has chronic tophaceous gout the plain radiograph may show typical joint erosions with sclerotic margins and overhanging edges.

Other indications for plain radiographs are suspected fractures and bony lesions, such as primary or metastatic malignancy, and any other cause of acute monoarthritis that eludes diagnosis.1 If plain radiographs are inconclusive CT is used to evaluate bony lesions,19,22 and MRI is the method of choice for diagnosing early osteonecrosis and soft-tissue injury.11–13,20,22 Popliteal cysts are best identified and differentiated from deep venous thrombosis with duplex ultrasonography.15,23

[Contents]

Management

Infectious arthritis

Confirmed bacterial arthritis should be treated with prompt antibiotic therapy and repeat joint drainage to minimize joint destruction. The choice of antibiotic is based on risk factors, such as the patient's age and immunocompetence, whether the infection was hospital acquired, as well as the results of Gram's staining, if available (Fig. 1).7 If nongonococcal arthritis is suspected antibiotics against S. aureus and streptococci should be used; in the immunocompromised patient Gram-negative and anaerobic bacteria should also be targeted.3,7,8 All antibiotics should be given intravenously. Although the duration of treatment depends on the patient's response, generally, intravenous antibiotics should be continued for at least 2 weeks and followed by 2–4 weeks of oral antibiotics.21

Suspected gonococcal arthritis is treated with ceftriaxone (1 g/day, intramuscularly or intravenously). If the organism is reported to be sensitive to penicillin, either ampicillin (1 g every 6 h, intravenously) or penicillin G (10 million U daily in divided doses, intravenously) should be given. Parenteral therapy should be maintained until there is clinical improvement of skin and joints (usually 2–4 days) and followed by oral antibiotics to complete a 7-day treatment.9

Infectious joint effusions require drainage to minimize joint destruction. Joint effusions tend to reaccumulate rapidly, particularly in nongonococcal arthritis and, therefore, must be aspirated at least daily.3 Joints that are easily accessible can be drained by needle aspiration, and the synovial fluid aspirate should be sent for serial leukocyte counts and cultures.5 The leukocyte count is an indicator of the patient's progress and should gradually decrease with antibiotic treatment. Similarly, culture results should be negative after a few days of antibiotic treatment, and cultures can then be discontinued unless clinically indicated. Arthroscopic or open drainage is indicated for patients with underlying joint pathology, for joints that are difficult to aspirate and for patients who have a poor response to antibiotics.5

The treatment of a popliteal cyst requires the treatment of the underlying knee effusion. In septic knee arthritis repeated knee aspiration prevents an increase in joint pressure and a further accumulation of fluid in the cyst. Intra-articular injection of corticosteroids will reduce inflammation and, therefore, joint effusion, but this should only be done after septic arthritis has been eradicated or excluded.

Crystal-induced arthritis

Acute crystal-induced arthritis can be treated with nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids or, rarely, colchicine.24 The sooner the drug therapy is initiated, the quicker the patient will respond. NSAIDs are used as first-line agents because they are usually well tolerated and easy to administer; they are given at high doses and tapered over 5–10 days. NSAIDs should be avoided or used cautiously in patients with renal dysfunction and those at high risk for gastrointestinal bleeding (e.g., elderly patients, patients with peptic ulcer disease and those taking anticoagulants or corticosteroids).25–27 They should also be used cautiously in patients with congestive heart failure, because of the risk of exacerbating fluid overload, and in those with any cardiovascular disease that may impair ability to cope with acute blood loss.27

If NSAIDs are contraindicated corticosteroids are a safe alternative. The most convenient route of administration is intra-articular, but a short course of oral prednisone can be given at a dosage of 30–50 mg daily, tapered rapidly over 5–10 days.28 Rarely, parenteral corticosteroids are necessary. Single-dose intramuscular adrenocorticotropic hormone is also effective,29 although corticosteroids are generally preferred. Oral colchicine is used infrequently now because of its toxicity, especially in the elderly. Management of acute crystal-induced arthritis in elderly or debilitated patients sometimes requires a brief hospital stay for systemic symptoms suggesting sepsis.30

The long-term management of gout involves treating hyperuricemia through risk modification and, once the acute episode of gout has been well controlled, drug therapy. Allopurinol is the drug of choice — 300 mg daily with dose reduction for renal insufficiency. Indications for allopurinol are shown in Table 3;31when it is initiated it is essential to prescribe low-dose NSAIDs or colchicine concurrently to prevent acute attacks of gout. Colchicine prophylaxis consists of 0.6 mg once or twice daily and should be continued until the patient has been attack free for 6 months or until the tophi have lysed. For patients with allopurinol allergy, uricosuric agents such as probenecid or sulfinpyrazone could be considered if the urinary uric acid excretion is less than 800 mg/day. Alternatively, the patient could undergo allopurinol desensitization.32

[Contents]

Treating our patient

Mrs. R's arthritis was presumed to be septic, and she was admitted to hospital for treatment. Fluid from the right knee was aspirated, blood and urine samples were obtained for culture and the patient was started on intravenous cloxacillin and gentamicin. Synovial fluid analysis revealed 45 — 109 leukocytes/L with 93% PMNs; Gram's staining was negative, but intracellular calcium pyrophosphate dihydrate crystals were identified. On the second day all cultures were still negative and a radiograph of the knee showed calcification of the menisci and hyaline cartilage. The diagnosis was changed to acute pseudogout. Antibiotics were stopped and corticosteroids were injected into the affected knee. Mrs. R's symptoms improved quickly, and she was discharged with a referral for outpatient physiotherapy.

[Contents]

Key points
  • Acute monoarthritis should be considered infectious until proven otherwise.
  • A red joint can indicate infectious arthritis or crystal-induced arthritis.
  • A history of acute attacks of monoarthritis that resolve spontaneously is indicative of crystal-induced arthritis.
  • Patients with crystal-induced arthritis can also present with fever, mimicking infectious arthritis.
  • Arthrocentesis is mandatory if infectious arthritis is suspected.
  • Synovial fluid analysis should include a cell count and differential leukocyte count, Gram's staining, culture and an examination for crystals.
  • Synovial fluid should be examined for crystals promptly.
  • If infectious arthritis is suspected a plain radiograph of the joint should be obtained to diagnose concomitant osteomyelitis and to monitor ongoing treatment.
  • Bacterial arthritis should be treated promptly with antibiotics (after all cultures have been obtained), and the joint should be drained to minimize joint destruction.
  • Arthroscopic or open drainage is indicated in patients with underlying joint pathology, in those whose joints are difficult to aspirate and in patients who have a poor response to antibiotics.
  • Treatment of a popliteal cyst involves treating the underlying knee pathology.
  • Acute crystal-induced arthritis is treated with NSAIDs, corticosteroids or, rarely, colchicine.
  • When allopurinol is initiated, it is essential to prescribe low-dose NSAIDs or colchicine concurrently to prevent acute attacks of gout.

Competing interests: None declared.

Comments Send a letter to the editor
Envoyez une lettre à la rédaction

[Contents]

Dr. Cibere is a Medical Research Council of Canada Clinician Scientist Fellow at the University of British Columbia, and is with the Arthritis Research Centre of Canada, Vancouver, BC

This article has been peer reviewed.

This series has been reviewed and endorsed by the Canadian Rheumatology Association.

The Arthritis Society salutes CMAJ for its extensive series of articles on arthritis. The Society believes that this kind of information is crucial to educating physicians about this devastating disease.

Series editor: Dr. John M. Esdaile, Professor and Head, Division of Rheumatology, University of British Columbia, and Scientific Director, Arthritis Research Centre of Canada, Vancouver, BC.

Reprint requests to: Dr. Jolanda Cibere, Arthritis Research Centre of Canada, 895 W 10th Ave., Vancouver BC V5Z 1L7; fax 604 879-3791; jcibere@bc.arthritis.ca

References
  1. McCune WJ, Golbus J. Monarticular arthritis. In: Kelley WN, Ruddy S, Harris ED Jr, Sledge CB, editors. Textbook of rheumatology. 5th ed. Philadelphia: W.B. Saunders; 1997. p. 371-80.
  2. Ensworth S. Rheumatology: 1. Is it arthritis? CMAJ 2000;162(7):1011-6. [MEDLINE]
  3. Baker DG, Schumacher HR Jr. Acute monoarthritis. N Engl J Med 1993;329:1013-20. [MEDLINE]
  4. Schumacher RH Jr. Synovial fluid analysis and synovial biopsy. In: Kelley WN, Ruddy S, Harris ED Jr, Sledge CB, editors. Textbook of rheumatology. 5th ed. Philadelphia: W.B. Saunders; 1997. p. 609-25.
  5. Goldenberg DL, Reed JI. Bacterial arthritis. N Engl J Med 1985;312:764-71. [MEDLINE]
  6. Mikhail IS, Alarcon GS. Nongonococcal bacterial arthritis [review]. Rheum Dis Clin North Am 1993;19:311-31. [MEDLINE]
  7. Goldenberg DL. Septic arthritis. Lancet 1998;351:197-202. [MEDLINE]
  8. Cimmino MA. Recognition and management of bacterial arthritis. Drugs 1997;54:50-60. [MEDLINE]
  9. Cucurull E, Espinoza LR. Gonococcal arthritis [review]. Rheum Dis Clin North Am 1998;24:305-22. [MEDLINE]
  10. Manshady BM, Thompson GR, Weiss JJ. Septic arthritis in a general hospital 1966–1977. J Rheumatol 1980;7:523-30. [MEDLINE]
  11. Chang CC, Greenspan A, Gershwin ME. Osteonecrosis: current perspectives on pathogenesis and treatment. Semin Arthritis Rheum 1993;23:47-69. [MEDLINE]
  12. Mankin HJ. Nontraumatic necrosis of bone (osteonecrosis). New Engl J Med 1992;326:1473-9. [MEDLINE]
  13. Bullough PG, DiCarlo EF. Subchondral avascular necrosis: a common cause of arthritis. Ann Rheum Dis 1990;49:412-20. [MEDLINE]
  14. Sansone V, DePonti A, Paluello GM, Del Maschio A. Popliteal cysts and associated disorders of the knee. Critical review with MR imaging. Int Orthop 1995;19:275-9. [MEDLINE]
  15. Andonopoulos AP, Yarmenitis S, Sfountouris H, Siamplis D, Zervas C, Bounas A. Baker's cyst in rheumatoid arthritis: an ultrasonographic study with a high resolution technique. Clin Exp Rheumatol 1995;13:633-6. [MEDLINE]
  16. Miller TT, Staron RB, Koenigsberg T, Levin TL, Feldman F. MR imaging of Baker cysts: association with internal derangement, effusion and degenerative arthropathy. Radiology 1996;201:247-50. [MEDLINE]
  17. Canoso JJ. Aspiration and injection of joints and periarticular tissues. In: Klippel JH, Dieppe PA, editors. Rheumatology. 2nd ed. London: Mosby International; 1998. p. 2.12.1.
  18. Alazrake N. Radionuclide techniques. In: Resnick D, editor. Bone and joint imaging. 2nd ed. Philadelphia: W.B. Saunders Company; 1996. p. 141-50.
  19. Andre M, Resnick D. Computed tomography. In: Resnick D, editor. Bone and joint imaging. 2nd ed. Philadelphia: W.B. Saunders Company; 1996. p. 70-83.
  20. McEnery KW, Murphy WA Jr. Magnetic resonancy imaging. In: Resnick D, editor. Bone and joint imaging. 2nd ed. Philadelphia: W.B. Saunders Company; 1996. p. 84-93.
  21. Goldenberg DL. Bacterial arthritis. In: Kelley WN, Ruddy S, Harris ED Jr, Sledge CB, editors. Textbook of rheumatology. 5th ed. Philadelphia: W.B. Saunders; 1997. p. 1435-49.
  22. Peterfy CG. Imaging techniques. In: Klippel JH, Dieppe PA, editors. Rheumatology. 2nd ed. London: Mosby International; 1998. p. 2.14.1-18.
  23. Mack LA, Scheible W. Diagnostic ultrasonography. In: Resnick D, editor. Bone and joint imaging. 2nd ed. Philadelphia: W.B. Saunders Company; 1996. p. 94-9.
  24. Emmerson BT. The management of gout. N Engl J Med 1996;134:445-51.
  25. Fries JF. NSAID gastropathy: the second most deadly rheumatic disease? Epidemiology and risk appraisal. J Rheumatol 1991;28(Suppl):6-10.
  26. Lichtenstein DR, Syngal S, Wolfe MM. Nonsteroidal anti-inflammatory drugs and the gastrointestinal tract. The double-edged sword. Arthritis Rheum 1995;38:5-18. [MEDLINE]
  27. Griffin MR. Epidemiology of nonsteroidal anti-inflammatory drug-associated gastrointestinal injury. Am J Med 1998;104:23S-9S.
  28. Groff GD, Franck WA, Raddatz DA. Systemic steroid therapy for acute gout: A clinical trial and review of the literature. Semin Arthritis Rheum 1990;19:329-36. [MEDLINE]
  29. Axelrod D, Preston S. Comparison of parenteral adrenocorticotropic hormone with oral indomethacin in the treatment of acute gout. Arthritis Rheum 1988;31:803-5. [MEDLINE]
  30. Doherty M. The management of acute pseudogout in the elderly. In: Klippel JH, Dieppe PA, editors. Rheumatology. 2nd ed. London: Mosby International; 1998. p. 8.19.4-5.
  31. Agudelo CA. Crystal deposition diseases. In: Weisman MH, Weinblatt ME, editors. Treatment of the rheumatic diseases: companion to the textbook of rheumatology. Philadelphia: W.B. Saunders; 1995. p. 279.
  32. Fam AG, Lewtas J, Stein J, Paton TW. Desensitization to allopurinol in patients with gout and cutaneous reactions. Am J Med 1992;93:299-302. [MEDLINE]

© 2000 Canadian Medical Association or its licensors