Coexistent Gout and Rheumatoid Arthritis
Adam Spector DPM*
Robert A. Christman DPM†

Gout and rheumatoid arthritis are relatively common entities individually; however, the coexistence of these two conditions has been reported rarely in the literature. The authors present a case that was followed for 20 years. The patient was seen by the acknowledged internist and podiatrist. Criteria for the evaluation and diagnosis of each disease entity are discussed and correlated to the case reported. Various theories and research attempting to explain the negative coexistence of gout and rheumatoid arthritis are presented.

Gout and rheumatoid arthritis rarely coexist in the same patient. As separate disease entities in the US, they are relatively common. Rheumatoid arthritis affects 2% to 3% of the population, with a female-to-male ratio of 3:1, while gout affects 0.25% of the population, with 90% of the cases occurring in males.1 It has been suggested that, since 10% of all rheumatoid arthritis patients are hyperuricemic, there should be approximately 10,000 cases of coexistent gout and rheumatoid arthritis reported in the US.2 But, in fact, there have been few cases reported in the medical literature since 1881, with only five cases adequately meeting the criteria for diagnosis of rheumatoid arthritis and gout.2-15 With two possible exceptions, these patients were all middleaged men in whom gout was the primary diagnosis, followed by the development of rheumatoid arthritis. In an extensive review of the podiatric literature, no previously reported cases were found.

The following is the history of a patient who presented with strong evidence for having both disease processes. The patient initially had clinically evident rheumatoid arthritis, and he developed gouty arthritis nearly 20 years later. Also described in this article will be the specific diagnostic criteria necessary in differentiating the two diseases, which can have similar presentations. The various theories explaining their prevailingly negative association with one another are reviewed.

Case Report

A 33-year-old Caucasian male police officer initially sought treatment by his internist in August 1967 because of pain, swelling, and weakness in his left wrist, which made it difficult for him to pull the trigger of his gun. He had no other symptoms and there was no family history of arthritis. His serum uric acid was 5.7 mg/100 ml, a rheumatoid slide test showed positive results, and both antinuclear antibody and C-reactive protein results were negative. Radiographs of his wrists did not show any abnormalities. He was treated with phenylbutazone, 100 mg four times a day for 1 week, which provided some relief.

During the following 2 years, he experienced recurrent acute morning flare-ups of pain and stiffness, primarily in his hands and wrists. He again sought medical evaluation. Physical findings were within normal limits, except for the evaluation of the joints. Both wrists were swollen, warm, and tender, and muscle strength was decreased. The left wrist was more painful, but there was diminished

flexion, which was associated with dorsal pain, in both wrists. Further examination revealed swelling and stiffness of both knees and feet; his metatarsophalangeal and interphalangeal joints were swollen, but were not tender to palpation. Subcutaneous nodules were present along the olecranon eminence of both elbows and on the posterior aspect of the Achilles tendon at the level of the right ankle joint. Laboratory results included a serum uric acid level of 6 mg/100 ml, a negative lupus erythematosus preparation, a 6 mm/hr Wintrobe sedimentation rate, and a positive rheumatoid slide test. Results of serologic tests for syphilis were negative. Conventional radiographs showed slight generalized osteopenia without erosions in the hands and wrists.

Initially, indomethacin, 25 mg four times a day, was prescribed, and then phenylbutazone, 100 mg four times a day, but these did not help significantly. Eventually the patient was given a course of gold therapy, while being monitored with frequent laboratory evaluations. The results of the evaluations were within normal limits. He responded well, although occasional flare-ups requiring additional drug therapy, such as naproxen or fenoprofen, were noted. He had an urticarial rash on the buttock and lower back areas, thought to be secondary to the fenoprofen, which was resolved with diphenhydramine hydrochloride and prednisone. He spent the next 9 years relatively asymptomatic; the subcutaneous nodules in the elbows disappeared, although he still maintained a positive latex slide test result for rheumatoid arthritis.

The patient's medical history was further complicated in 1975, when, at age 41, he was hospitalized for flank pain and spontaneously passed a 2mm calculus consisting of calcium, oxalate, and uric acid, which had been lodged in his right ureter. Subsequently, he was prescribed allopurinol, 300 mg daily, which he has taken since that time.

In 1979, the patient's arthritic flare-ups recurred. He presented to his internist with a chief complaint of plantar foot pain that was greatest under the metatarsal heads. He also had severe, persistent left shoulder pain. On examination, his hands showed swelling and stiffness of the metacarpophalangeal and proximal interphalangeal joints. His knees and ankles were swollen. Neither foot was erythernatous or edematous and there was only minimal tenderness to palpation. Subcutaneous nodules were palpated at the left proximal aspect of the Achilles tendon and there were nodules on the elbows. There were no obvious joint changes on radiographs. Results of routine laboratory studies were essentially within normal limits. His serum uric acid was 4.7 mg/100 ml, sedimentation rate was 10 mm/hr, and latex rheumatoid slide test showed positive results. A monthly regimen of gold, 50 mg intramuscularly, along with tolmetin sodium, 400 mg three times a day, and allopurinol, 300 mg daily, allowed him to function with less stiffness and swelling.

In the fall of 1986, after the patient continued to complain of persistent foot pain, he was referred to a podiatrist. The patient reported acute episodes of discomfort and diffuse plantar foot pain, mainly in the balls of both feet. He also had posterior heel pain that was aggravated by shoes. Examination revealed swelling and tenderness in both ankles and all metatarsophalangeal joints of the feet, with a sausage-like swelling of the right fourth toe. Radiographs of the feet revealed erosions along the medial and lateral aspects of both fifth metatarsal heads and the medial aspect of the left second metatarsal head (Fig. 1). Pre-erosive changes were noted along the medial aspects of all remaining lesser metatarsal heads and the hallux interphalangeal joints. There was mild joint space narrowing of the left second and the right second, third, and fifth metatarsophalangeal joints.

Figure 1. A, Left foot. Erosions are present along the medial and lateral aspects of the second and fifth metatarsophalangeal joints. Pre-erosive changes are evident along the third metatarsal head subchondral bone plate. There is mild joint space narrowing of the second metatarsophalangeal joint. B, Right foot. Erosions are found predominantly at the fifth metatarsophalangeal joint. Mild, even joint space narrowing can be seen at the second, third, and fifth metatarsophalangeal joints.

A well circumscribed increased soft tissue density was evident adjacent to the right Achilles tendon enthesis and posterior calcaneus (Fig. 2). This subcutaneous nodule was surgically removed from the posterior heel area. Histologic evaluation of the nodule demonstrated granulornatous foci with central zones of cell necrosis, surrounded by a palisade of proliferated mononuclear cells and peripheral fibrosis, with chronic inflammatory cell infiltration (Fig. 3). These findings confirmed the presence of a rheumatoid nodule. Physical therapy, local corticosteroid injections, and orthoses produced some relief of his acute forefoot symptomatology.

The joint symptoms were stable until the fall of 1987, when the patient presented with general joint pain, stiffness, and malaise; he was further evaluated by his internist and a rheumatologist. His elbows, wrists, hands, knees, and feet were affected. There was normal range of motion and no pain with movement of either elbow, but there was swelling and tenderness on palpation, and nodules were present bilaterally. His grip strength was decreased; significant wrist synovitis was demonstrated, more marked in the right extremity. The hands showed a bulging effusion in the left third proximal interphalangeal joint, and swelling and variable tenderness in the right first, second, and fifth metacarpophalangeal joints and left second and fifth distal interphalangeal joints. Both ankles and feet were similarly affected as before.

Radiographs of the hands revealed mild periarticular and generalized osteoporosis, as well as marginal erosions at the left first and second and the right second and fifth metacarpophalangeal joints

Figure 2. Right heel. A well circumscribed increased soft tissue density is located retrocalcaneally. This mass was excised and histologically proven to be a rheumatoid nodule.

Figure 3. Histologic specimen of the right heel soft tissue mass demonstrates findings consistent with a rheumatoid nodule.

(Fig. 4). C-shaped erosions with overhanging edges were evident along the medial margins of both second proximal phalangeal bases and the medial and lateral margins of the left third proximal interphalangeal joint. An increased soft tissue density and volume were evident at all affected joints. There also were erosions along the ulnar styloid process bilaterally and the anterolateral aspect of the right distal radius. There was mild hypertrophic spurring of the tibial spines and patellae bilaterally.

Figure 4. Marginal joint erosions are present at both second, the left first, and the right fifth metacarpophalangeal joints. Mild joint space narrowing is evident at all metacarpophalangeal joints, with subluxation of the left first metacarpophalangeal joint. Well defined, C-shaped erosions with overhanging edges are seen along the radial aspects of both second digit proximal phalangeal bases and the left third interphalangeal joint. Increased soft tissue density and volume are identified with each of these latter sites, probably representing gouty tophi.
Radiographs of both feet revealed considerable progression of the joint disease (Fig. 5). There was symmetrical, bilateral involvement of all lesser metatarsophalangeal joints and hallux interphalangeal joints. The erosions were predominantly located medially. Significant, even joint space narrowing was evident at the affected joints, with subluxation of the left third and fourth metatarsophalangeal joints. The medially-located hallux interphalangeal joint erosions were well defined, with evidence of sclerotic margins and marginal new bone formation (Fig. 6). Nodular soft tissue masses were adjacent to these erosions. His serum uric acid was 5.3 mg/100 ml, the results of the latex slide test were again positive for rheumatoid arthritis, the latex rheumatoid titer was 1:640, the Wintrobe sedimentation rate was 28 mm/hr, and the slide test for antinuclear antibody showed negative results. Aspiration of the left third proximal interphalangeal joint of the hand revealed intracellular sodium urate crystals. Gold therapy was discontinued, and he was given hydroxychloroquine, 200 mg twice a day, following ophthalmologic approval and instructions. Allopurinol was increased from 300 to 400 mg/day and he also was given 75 mg of indomethacin twice a day. Within I month, he was free of pain and stiffness.

Figure 5. A, Left foot (1 year later). There are significant erosions involving all lesser metatarsophalangeal joints. In addition to even joint space narrowing, there are subluxations of the third and fourth metatarsophallangeal joints. Well defined, C-shaped erosions with sclerotic margins present along the medial aspect of the hallux interphalangeal joint. B, Right foot (1 year later). Similar findings as in the left foot, except there are no subluxations, and the hallux interphalangeal and fourth metatarsophalangeal joints are affected to a lesser degree.

Figure 6. The soft tissue densities adjacent to the hallux interphalangeal joint erosions probably represent gouty tophi.

Discussion

The presence of intracellular monosodium urate crystals in affected joint fluids or tophi is of paramount importance in diagnosing gout. McCarty 6 demonstrated crystals obtained from joints where gouty attacks had occurred in 109 patients; he found that the high correlation of crystals, rather than hyperuricemia, was the key diagnostic feature of the disease.

Additional criteria can help to clinically identify gouty arthritis. Classically, the joints are asymmetrically involved. Pain in one joint is described as being "out-of-phase" with the other joints.6 There usually is more than one acute, painful flare-up of monarthric arthritis, in which maximal inflammation develops within 1 day. Joint redness and eccentric soft tissue swelling commonly are seen, and the first metatarsophalangeal and tarsal joints of the foot are the most likely to develop symptoms. Joint fluids should have negative cultures for microorganisms. Radiographic findings include intraarticular and extra-articular bony erosions, with frequent sclerotic margins and overhanging edges, but no early narrowing of joint spaces.1,16 The presence of hyperuricemia can be a contributing factor but is not critical in establishing the diagnosis of gout, as many reported cases and studies have shown.6, 12, 13, 15 Another criterion is responsiveness to treatment with colchicine.2

Iii the case presented, the patient satisfied the criteria described. He had multiple acute flare-ups in his wrists and fingers, from which monosodium urate crystals were obtained. There was considerable eccentric soft tissue swelling. The radiographic findings were classic for gout, including punched out erosions with sclerotic margins, overhanging edges (Martel's sign), and minimal joint space narrowing. Serum uric acid levels were consistently not elevated; however, this could be explained by his taking allopurinol for kidney stones. Also notable in this patient was that, although he became refractory to gold, he did respond to allopurinol and indomethacin. Finally, the passing of urate stones may precede the first attack of arthritis in many gouty patients, which occurred in this case.1, 10

The most important prerequisite for the diagnosis of rheumatoid arthritis is the histologic confirmation of the presence of subcutaneous nodules or a positive latex rheumatoid factor titer of at least 1:320. Rheumatoid arthritis is further identified by morning stiffness and arthritic symptoms lasting longer than 6 weeks in duration. There is symmetric joint involvement, fusiform soft tissue swelling, and, commonly, wasting of the interosseous muscles of the hand. Radiologically, there is moderate-to-severe osteoporosis, with- symmetric loss of joint space early in the disease; later, marginal joint erosions develop, rarely with sclerotic borders. Malalignment or subluxation also can occur. Other criteria may include characteristic histologic changes in rheumatoid arthritis joint synovium, poor mucin precipitate from synovial fluid, and elevated sedimentation rate and C-reactive protein values.1, 16

The patient had symmetric joint symptoms, consisting of morning stiffness and fusiform soft tissue swelling, that persisted for 20 years or more. Additionally, he demonstrated decreased grip strength. Marginal joint erosions at multiple metacarpophalangeal and metatargophalangeal joints, as seen on conventional radiographs, were interpreted as being compatible with rheumatoid arthritis. A subcutaneous nodule excised from the right heel area was histologically consistent with that of a rheumatoid nodule. He also had nodules on both elbows that were strongly suggestive of rheumatoid arthritis, although this was not confirmed histologically. But, most importantly, he had a significantly elevated positive titer of 1:640 for rheumatoid factor.

The question could be raised as to whether this patient had gout all along. Diagnosing rheumatoid arthritis and gout can be confusing, because they can present with many common features. Chronic tophaceous gout can simulate rheumatoid arthritis and can fulfill the American Rheumatism Association criteria as well; it can present with long-term joint swelling, large subcutaneous nodules, and symmetric polyarthritis, which is the initial presentation in 5% of gouty patients.7, 10,13 Both gout and rheumatoid arthritis can present with morning stiffness, joint erosions, ulnar deviations of the fingers, poor mucin precipitate from synovial fluid, and synovial membrane thickening with similar histopathologic changes.5, 11, 15, 17

Schwartzberg et al 10 and Baraf et al 18 found that gout could produce a rheumatoid-like chronic synovitis in the wrists because of the continued presence of the crystals within the joint. Kozin and McCarty 17 found 30% of patients with chronic tophaceous gout and 10% of patients with acute gout to have rheumatoid factor present in low titers (less than 1:320). Other researchers also found positive titers of rheumatoid factor, but in a smaller percentage of patients.18, 19, 20 Complicating matters is that significant pulmonary or hepatic disease can contribute to a falsely positive rheumatoid factor titer.11 In addition, rheumatoid arthritis patients may be hyperuricemic, while gout patients may not be.1 Other causes of hyperuricemia are alcohol ingestion, dehydration, chronic renal failure, and mild lactic acidosis, all of which can be misleading in differentiating between gout and rheumatoid arthritis.

Although the possibility that chronic tophaceous gout can masquerade as rheumatoid arthritis should not be overlooked, the coexistence of gout and rheumatoid arthritis is well documented in the patient. Although positive rheumatoid factor has been found in low titers in some patients with gout, the patient had a significantly elevated rheumatoid factor titer of 1:640. Additionally, intracellular monosodium urate crystals were not present until 20 years after the onset of arthritic symptoms. He had no pulmonary or hepatic disease that would yield a false-positive rheumatoid factor titer. Erosive changes in the joints were judged by both a rheumatologist and a radiologist to be characteristic of rheumatoid arthritis and gout. Excision of a subcutaneous rheumatoid nodule was confirmed histologically. It should be noted that the gold therapy worked initially, which may be further evidence of the early existence of rheumatoid arthritis.

Why there are so few cases of coexistent rheumatoid arthritis and gout reported in the literature is still unclear. Various theories involving genetic, immunologic, and biochemical factors have been proposed to explain the apparent negative association between these two disease processes. Rizzoli et al 11 explained the rarity of cases by proposing that the genetic predisposition for both gout and rheumatoid arthritis in the same patient produces a fatal immunogenetic linkage that does not allow those patients to survive. Most of the research, however, has focused on the immunosuppressive effect of hyperuricemia over the expression of rheumatoid inflammation. Lussier 21 and Lussier and deMedicis 22 showed that the inflammatory polyarthritis in Freund's adjuvant-injected rats was significantly reduced in the presence of diet-induced hyperuricemia. In the evaluation by Agudelo et al 23 of rheumatoid arthritis patients with a history of hyperuricemia (but not gout), improvement of rheumatoid arthritis flare-ups coincided with the development of hyperuricemia, and exacerbation of symptoms occurred after normalization of serum uric acid levels in a few select patients. The anti-inflammatory effect of the hyperuricemic state possibly can be explained on a biochemical basis. Within the affected joints of rheumatoid arthritis patients, there is increased activity of free oxygen radicals. Uric acid, in high concentrations, functions as both an anti-oxidant and a free radical scavenger to reduce the number of rheumatoid factor-producing cells stimulated by aggregated immunoglobulin G, and thus decreases rheumatoid inflammation. Thiol compounds, such as gold salts and D-penicillamine, also have antioxidant effects and may function similarly.23

In other experiments, Kozin and McCarty 24 investigated the properties of uric acid crystals and discovered that they would bind antigens such as immunoglobulin G and alter their early recognition by monocytes and macrophages. This binding blocked the activation of T and B lymphocytes, preventing rheumatoid inflammation from occurring.

These studies could explain how gout inhibits the development of rheumatoid arthritis, yet they do not explain how rheumatoid arthritis could suppress episodes of gout, which might have occurred in this patient. Gordon et all 15 performed in vitro experiments with purified monoclonal rheumatoid factor with specificity for immunoglobulin G (rheumatoid factor bound to antigenic determinants on the exposed Fc portion of adsorbed immunoglobulin G on the monosodium urate crystal surface). This blocked the interaction of crystal-bound immunoglobulin G with Fc receptors and was thought to modify gouty inflammation in patients with rheumatoid arthritis. Other possible theories explaining this phenomenon have included the following: inhibition of crystal deposition by possible connective tissue alterations in rheumatoid arthritis, impaired phagocytic function of neutrophils in rheumatoid joint fluid, and synovial hypocomplementemia.25, 26, 27

Conclusion

The coexistence of rheumatoid arthritis and gout is rare. While the majority of previous reports describe gout as the initial disease followed by rheumatoid arthritis, the opposite occurred in the patient reported here. The criteria for both rheumatoid arthritis and gout were satisfied; most importantly, the patient exhibited a high serum rheumatoid factor titer, a histologically confirmed rheumatoid nodule, and intracellular monosodium urate crystals in joint fluid. Various studies explaining the negative association between the two diseases were described, but further studies are needed to fully clarify the etiology. It is possible that the incidence of both diseases in the same patient is greater than that previously reported. However, differentiation between the two diseases can be difficult because of their similar presentations, and because nonsteroidal anti -inflammatory drugs, as well as gold, can treat both diseases successfully, eliminating the need for a specific diagnosis. It should be noted that the usual doses of allopurinol may not prevent bone destruction. It is imperative to carefully reevaluate arthritic patients who do not respond to current drug regimens, because reevaluation can lead to changes in diagnosis and medications.

Acknowledgment. Mark D. Sussman, DPM, and Israel Spector, MD, for providing information about their patient.

_____________________________________________
* Submitted during fourth year, Pennsylvania College of Podiatric Medicine, Philadelphia, PA.
t Fellow, American College of Podiatric Radiologists; Director of Radiology and Assistant Professor, Department of Medicine, Pennsylvania College of Podiatric Medicine, Eighth at Race Street, Philadelphia, PA 19107.


References

1. RODMAN GP, SCHUMACHER HR, EDS: Primer on the Rheumatic Diseases, 8th Ed, Arthritis Foundation, Atlanta, 1983.

2. WALLACE DJ, KLINENBERG JR, MORHAIM D, ET AL: Coexistent gout and rheumatoid arthritis. Case report and literature review. Arthritis Rheum 22: 81, 1979.

3. HUTCHINSON J: Parts of joints showing the changes of gout and rheumatoid arthritis in the same patient. Pathol Soc Lond Trans 32: 193, 1881.

4. CECIL R: Influential factors in recovery from rheumatoid arthritis. Ann Intern Med 8: 45, 1934.

5. TALBOTT JH: The diversity of gouty arthritis and its complication. Ann Intern Med 31: 555, 1949.

6. MCCARTY DJ, JR: The pendulum of progress in gout: from crystals to hyperuricernia and back. Arthritis Rheum 7: 534, 1964.

7. OWENS DS, JR, TOONE E, IRBY R: Coexistent rheumatoid arthritis and chronic tophaceous gout. JAMA 197: 953, 1966.

8. CACIOPPI JT, MORRISSEY JB, BACON AS: Condyle destruction concomitant with advanced gout and rheumatoid arthritis. Oral Surg 25: 919, 1968.

9. KATZ W: Rheumatic Disease: Diagnosis and Management, JB Lippincott, Philadelphia, 1977.

10. SCHWARTZBERG M, LIEBERMAN DH, GUPTA VP, ET AL: Rheumatoid arthritis and chronic gouty arthropathy. JAMA 240: 2658, 1978.

11. RIZZOLI AJ, TRUJEQUE L, BANKHURST AD: The coexistence of gout and rheumatoid arthritis. J Rheumatol 7: 316, 1980.

12. JESSEE EF, TOONE E, OWENS DS, ET AL: Coexistent rheumatoid arthritis and chronic tophaceous gout. Arthritis Rheum 23: 244,1980.

13. ADTJIAN M, FERNANDEZ-MADRID F: Coexistence of chronic tophaceous gout and rheumatoid arthritis. J Rheumotol 8: 989,1981.

14. RAMAN D, ABDALLA AM, NEWTON DRL, ET AL: Coexistent rheumatoid arthritis and tophaceous gout: a case report. Ann Rheum Dis 40: 427,1981.

15. GORDON TP, AHERN MJ, REID C, ET AL: Studies on the interaction of rheumatoid factor with monosodium urate crystals and case report of coexistent tophaceous gout and rheumatoid arthritis. Ann Rheum Dis 44: 384, 1985.

16. RESNICK D, NiWAYAMA G: Diagnosis of Bone and Joint Disorders, 2nd Ed, WB Saunders, Philadelphia, 1988.

17. KOZIN F, MCCARTY DJ: Rheumatoid factor in the serum of gouty patients. Arthritis Rheum 20: 1559, 1977.

18. BARAF HSB, CALDWELL DS, REYNOLDS P, ET AL: Gouty arthritis: prevalence of chronic synovitis, polyarticular attacks and positive serologic tests for rheumatoid factor (Abstr). Arthritis Rheum 21: 544, 1978.

19. GIGANTE D, GIACOMELLO A: Rheumatoid factors in the serum of gouty patients. Arthritis Rheum 23: 379, 1980.

20. STOCKMAN A, SCOTT JT: RF activity in sera from gouty patients. Arthritis Rheum 21: 741, 1978.

21. LUSSIER A: Inhibition of adjuvant - induced arthritis in hyperuricemic rats. Arthritis Rheum 18: 414, 1975.

22. LUSSIER A, DEMEDICIS R: Coexistent gout and rheumatoid arthritis: "a red marker?" (letter). Arthritis Rheum 22: 939, 1979.

23. AGUDELO CA, TURNER RA, PANETTI M, ET AL: Does hyperuricemia protect from rheumatoid inflammation? A clinical study. Arthritis Rheum 27: 443, 1984.

24. KOZIN F, MCCARTY DJ: Protein adsorption of monosodiurn urate, calcium pyrophosphate dihydrate and silica crystals. Arthritis Rheum 19: 433, 1976.

25. SCHUMACHER HR: Pathogenesis of crystal induced synovitis. Clin Rheum Dis 3: 105, 1977.

26. TURNER RA, SCHUMACHER HR, MYERS AR: Phagocytic function of polymorphonuclear leukocytes in rheumatic diseases. J Clin Invest 52: 1632, 1973.

27. SCOTT JT: Gout. Ann Rheum Dis 42 (suppl): 16,1983.

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