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studies that different forms of extra-articular rheumatoid disease such as Felty's syndrome, major vasculitis, and various forms of lung disease have different HLA ...

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Annals of the Rheumatic Diseases 1996; 55: 489-490

MATTERS ARISING Associations of HLA-DRB and HLA-DRQ genes with two and five year outcomes in rheumatoid arthritis We were interested in the results of the longitudinal study by Eberhardt and colleagues,' who examined the relationship between HLA-DRB and HLA-DRQ genes and outcomes in rheumatoid arthritis. Their results, showing a lack of relationship between HLA-DQ variants and articular disease severity, are in keeping with the results of our previous cross-sectional study that showed no influence of HILA-DQ variants on articular disease severity, in addition to demonstrating a definite relationship between homozygosity for HLADR4 and severity of articular disease. Eberhardt and-coworkers have gone on to look for a relationship between HLA variants and risk of extra-articular disease. Again, in previous studies we have looked at this relationship,3 and showed in cross-sectional studies that different forms of extra-articular rheumatoid disease such as Felty's syndrome, major vasculitis, and various forms of lung disease have different HLA associations. We consider this is an important point to make, as such associations may be lost if different forms of extra-articular rheumatoid disease are analysed together. The HLA associations in Felty's syndrome and in major forms of rheumatoid vasculitis have been particularly interesting, in that Felty's syndrome has shown an association with a particular HLA haplotype (B44-BfsC4A*3-C4B*Q0-DR4-DQB1*0301), while major rheumatoid vasculitis has shown associations with the DRB1*0401 variant of HLA-DR4 and with the C4 null allele, C4A*QO. D M GRENNAN W OLLIER

Department of Rheumatology Wrightington Hospitalfor Joint Disease Wigan WN6 9EP, United Kingdom Eberhardt K, Fex E, Johnson U, Woolheim FA. Assoications of HLA-DRB and -DQB genes with two and five year outcome in rheumatoid arthritis. Ann Rheum Dis 1996; 55: 34-9. 2 McMahon M J, Hillarby M C, Clarkson R, Hollis S, Grennan D M. Articular disease severity in rheumatoid subjects with and without Felty's syndrome. Br Rheumatol 1993; 32: 899-902. 3 Hillarby M C, Grennan D M, Clarkson R. Immunogenetic heterogeneity in rheumatoid disease as characterised by different MHC associations (DQ, Dw and C4) in articular and extra-articular subsets. Br Jf Rheumatol 1990; 30:5-9. 1

Aul-HoR's REPLY: We have read with interest the comments by Drs Grennan and Ollier regarding the relationship between HLA variants and extra-articular rheumatoid disease. We do agree that different forms of extra-articular features should be analysed separately. In our cohort, one patient developed major vasculitis, and three developed renal amyloidosis during the first

five years of disease. To date, we have not had a patient with Felty's syndrome. The number of patients is too small to permit any risk analysis, and in our paper we therefore reported only their HLA-DR-DQ pattern. Unfortunately, our genetic typing did not include the C4 null allele. KERSTIN EBERHARDT Department ofRheumatology Lund University Hospital S-221 85 Lund, Sweden

LETTER TO THE EDITOR Rheumatoid arthritis preceding the onset of polyarticular tophaceous gout Rheumatoid arthritis (RA) and gout are relatively common diseases, but their coexistence is extremely rare. The diagnosis of RA and gout is hampered because 1 0% of patients with RA have hyperuricaemia' and 30% of patients with tophaceous gout may have low titre rheumatoid factor (RF) .2 It is necessary, therefore, to meet the terms of strict criteria before concluding that a patient has both diseases. The criteria include: seropositive erosive RA, or histological confirmation of rheumatoid nodule/pannus, and recurrent attacks of gout with identification of monosodium urate (MSU) crystals. Up to December 1995, 14 cases of coexistent RA and gout as defined above were reported.'3-6 We now report another case, review the literature, and discuss possible risk factors for the development of gout in our patient. A 61 year old white woman with RA of more than 25 years duration presented in December 1994 with a swollen, painful thumb with a whitish, chalk-like discharge. Her past history included obesity and hypertension treated with hydrochlorothiazide. RA had been diagnosed based on the presence of polyarthritis in a rheumatoid distribution, and treated with different second line agents over time; at presentation she was receiving oral gold and prednisone 7-5 mg/day. Laboratory data from 1983 revealed a serum uric acid concentration of 132 mg/l and a positive RF (titre 2560). In 1984, rheumatoid nodules over the olecranon bursae, ulnar deviation of both wrists, and swan neck deformities were observed. Fluid from both knees contained 70 000/mm3 leucocytes, with predominance of polymorphonuclear cells; MSU crystals were not found. In November 1992, the patient had acute right ankle swelling; septic arthritis was suspected. Ankle radiographs showed changes compatible with chronic RA, and magnetic resonance showed a subtalar effusion, but an arthrocentesis was unsuccessful. Serum uric acid concentration was again increased (132 mg/l); blood cultures were negative. Her condition improved spontaneously and continued about the same until August 1994,

when she noted multiple subcutaneous nodules (2-3 mm in diameter) over the extensor surfaces of her upper and lower extremities. MSU crystals were demonstrated in the material drained from her thumb. Serum uric acid concentration was 118 mg/l and RF was negative. Radiographs of hands and feet revealed findings of RA and gout: collapse of both wrists, marked subluxations of the metacarpophalangeal joints bilaterally, large erosions of the distal phalanx of the thumb, and an erosion on the lateral aspect of the fifth right metatarsal head with calcified intraosseous tophi (figure). The coexistence of gout and RA in our patient is unquestionable. She had evidence of seropositive destructive RA, hyperuricaemia, acute gout, and MSU crystals. Coexistent radiographic changes of RA and gout have been described previously. 7 As RA is far more prevalent than gout, it would be expected that a patient with both disorders would be diagnosed first as having RA. However, in 10 of the 14 previously reported cases (among whom the ratio of men to women was 2-5:1) the first diagnosis was gout (table). The reason for the usual mutual exclusion of RA and gout is not clear. Hyperuricaemia may have some 'protective immunosuppressive' effect.'8 A blocking effect of RF on Fc receptors adsorbed on MSU crystal surfaces'3 and a negative correlation between serum uric acid concentration and clinical activity in RA have been demonstrated.' As noted, hyperuricaemia occurs in about 10% of RA patients,'8 and has been related to the use of aspirin and analgesics, which may affect the excretion or renal handling of uric acid. Most rheumatic diseases disproportionately affect women rather than men; however, while women are distinctly less affected by gout in premenopausal years, their frequency of gout increases afterwards. '9 Predisposing factors for gout include an underlying joint disease,20 21 use of diuretics, and renal impairment.22 Gout in women is commonly polyarticular,23 tophi





2k I

Radiographs of the right hand andfoot. Osteoporosis, marginal erosions, subluxation of the metacarpophalangeal joints, and advanced destruction of the wrist, with sparring of metacarpal bases are characteristic of RA. Gouty tophi replace thefirst and second distal phalanges (A). Erosion in the lateral aspect of the 5th metatarsal head indicates RA. Tarsometatarsal joint destruction and extensive intraosseous tophi are characteristic of gout (B).

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Letter to the editor

Case reports of coexistent gout and rheumatoid arthritis Source

Sex! Age (yr)

Age at diagnosis (yr) Gout


McCarty 19643 Owen etal, 19644 Bloch-Michelle et al, 19685 Schwartzberg et al, 19786

M:75 M:64 F:38

63 49 26

75 63 31



Wallace etal, 19797 Rizzolietal, 19798

F:73 M:58

Jessee et al, 1980' Atdjianetal, 1981'°

RF titre

Rheumatoid nodules


2560 320 320

+ +

+ +




72 58

38 70

5120 1280

M:71 M:56

61 50

64 55

640 5120

Ramanetal, 1981" Waterworth 1981'2 Gordon etal, 1985"3

F:67 M:61 M:60




61 54

64 56

320 2048

Martinez-Cordero etal, 1988"4 Spector et al, 1989"5 Wendlingetal, 1991"6 Present study





M:39 F:45 F:61

41 45 58

57 45 42

640 2560 2560


Uric acid



Response to



+ +




13 2 11-0



10 0


+ +

+ +

+ +

16 2 12-6

Yes Yes

+ +





7-2 6-4







t t




Rheumatoid nodule Synovium, pannus Synovium, pannus and MSU crystals Synovium, pannus and nodule with MSU crystals NA Menisectomy MSU crystals Rheumatoid nodule Rheumatoid nodule and MSU crystals; synovium, pannus

+ + +






Rheumatoid nodule NA NA



+ +


Rheumatoid nodule Rheumatoid nodule Rheumatoid nodule; synovium, pannus Rheumatoid nodule



NA = Not available.

appear sooner than in men,24 and interphalangeal joints are involved frequently.25 Although the coexistence of RA and gout is extremely rare, the latter should be sought in patients with inflammatory arthropathies and otherwise asymptomatic hyperuricaemia if acute or chronic gout, or both, are to

receive the patients.



in these

ABRAHAM ZONANA-NACACH GRACIELA S ALARCON Division of Clinical Immunology and Rheumatology, The University ofAlabama at Birmingham, Birmingham, Alabama, USA

WILLIAM W DANIEL Department of Radiology, The University of Iowa, Iowa City, Iowa, USA

5 Bloch-Michelle H, Benoist M, Ripauult J, Siaud J R. Arthropathy micro crystalline associees a une maladie rhumatoide. A propos de sept case. Discussion sur les liens eventuels entre les deux syndromes. [Microcrystalline arthropathy associated with rheumatoid arthritis disease. A propos of seven cases. Discussion on the possible relation between the two syndromes]. Presse Med 1968; 76: 1311-2. 6 Schwartzberg M, Lieberman D H, Gupta V P, Ehrlich G E. Rheumatoid arthritis and chronic gouty arthropathy.3AMA 1978; 240: 2658-9. 7 Wallace D J, Klinenberg J R, Morhaim D, Berlanstein B, Biren P C, Callis G. Coexistent gout and rheumatoid arthritis: case report and literature review. Arthritis Rheum 1979; 22: 81-6. 8 Rizzoli A J, Trujeque L, Bankhurst A D. The coexistence of gout and rheumatoid arthritis: case reports and a review of the literature. Rheumatol 1980; 7: 316-24. 9 Jessee E F, Toone E, Owen D S, Irby R. Coexistent rheumatoid arthritis and chronic tophaceous gout. Arthritis Rheum 1980; 23: 244-7. 10 Atdjian M, Fernandez-Madrid F. Coexistence of chronic tophaceous gout and rheumatoid arthritis. Rheumatol 198 1; 8: 989-92. 11 Raman D, Abdalla A M, Newton D R L, Haslock I. Coexistent rheumatoid arthritis and tophaceous gout: a case report. Ann Rheum Dis 1981; 40: 427-9. 12 Waterworth R F. The effect of allopurinol therapy on coexistent gout and rheumatoid arthritis. Arthritis Rheum 1981; 24: 103-4. 13 Gordon T P, Ahern M J, Reid C, RobertsThompson P J. Studies on the interaction of rheumatoid factor with monosodium urate crystals and case report of coexistent tophaceous gout and rheumatoid arthritis. Ann Rheum Dis 1985; 44: 384-9. 14 Martinez-Cordero E, Bessudo-Babani A, Trevifto-P6rez S C, Guillermo-Grajales E. Concomitant gout and rheumatoid arthritis. Rheumatol 1988; 15: 1307-11. 15 Spector A K, Christman R A. Coexistent gout and rheumatoid arthritis. Am Podiatr Med Assoc 1989; 79: 552-8.



18 19 20 21



Correspondence to: Dr Graciela S Alarcon, University Station, MEB 615/ 1813 6th Avenue South, Birmingham, AL 35294, USA. This work was partially supported by the Instituto Mexicano del Seguro Social (IMSS) (A Z-N) and the National Institute of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases, Center grant P-60-AR-20614 (G S A). We are grateful to Ms Ella Henderson for preparation of the manuscript. Agudelo C A, Turner R A, Panetti M, Pisko E. Does hyperuricemia protect from rheumatoid inflammation? A clinical study. Arthritis Rheum 1984; 27: 443-8. 2 Kozin F, McCarty D J. Rheumatoid factor in the serum of gouty patients. Arthritis Rheum 1977; 20: 1559-60. 3 McCarty D J. The pendulum of progress in gout: from crystals to hyperuricemia and back. Arthritis Rheum 1964; 7: 534-41. 4 Owen D S Jr, Toone E, Irby R. Coexistent rheumatoid arthritis and chronic tophaceous gout. JAMA 1966; 197: 123-6. 1


23 24 25

Wendling D,

Guidet M. Association goutte-

polyarthrite rheumatoide [Gout and rheumatoid arthritis in the same patient]. Semin Hop Paris 1991; 67: 1497-500. Talbott J H, Altman R D, Ts'ai-Fan Y. Gouty arthritis masquerading as rheumatoid arthritis or vice versa. Semin Arthritis Rheum 1978; 8: 77-114. Lussier A, Medicis de R. Coexistent gout and rheumatoid arthritis: a red marker? Arthritis Rheum 1979; 22: 939-40. Yu T F. Some unusual features of gouty arthritis in females. Semin Arthritis Rheum 1977: 6: 247-55. Simkin P A, Campbell F M, Larson E B. Gout in Heberden's nodes. Arthritis Rheum 1977; 20: 895-900. Strader K W, Agudelo C A. Coexistent rheumatoid nodulosis and gout. _7 Rheumatol 1986;13: 1307- 11. Macfarlane D G, Dieppe A P. Diuretic-induced gout in elderly women. Br I Rheumatol 1985; 24: 155-7. Curran J J, Renold F. Clinical manifestations of acute polyarticular gout in female patients [abstract]. Arthritis Rheum 1988; 31: R31. Meyers 0 L, Monteagudo F S E. A comparison of gout in men and women. S Afr MedJ 1986; 70: 721-3. Ter Borg E J, Rasker J J. Gout in the elderly: a separate entity? Ann Rheum Dis 1987; 46: 72-6.

Correction Can methotrexate be used as a steroid sparing agent in the treatment of polymyalgia rheumatica and giant cell arteritis? van der Veen et al (Ann Rheum Dis 1996; 55: 218-223) It is regretted that an incorrect affiliation was given for Dr H J Dinant, who is now rheumatologist at the Jan van Breemen Instituut, Amsterdam.

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Rheumatoid arthritis preceding the onset of polyarticular tophaceous gout. A Zonana-Nacach, G S Alarcón and W W Daniel Ann Rheum Dis 1996 55: 489-490

doi: 10.1136/ard.55.7.489-c

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