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

five years ofdisease. To date, we have not had when she noted multiple subcutaneous a patient with Felty's syndrome. The number nodules (2-3 mm in diameter) over the MATTERS of patients is too small to permit any risk extensor surfaces of her upper and lower analysis, and in our paper we therefore extremities. MSU crystals were demon- ARISING reported only their HLA-DR-DQ pattern. strated in the material drained from her Unfortunately, our genetic typing did not thumb. Serum uric acid concentration was include the C4 null allele. 118 mg/l and RF was negative. Radiographs ofhands and feet revealed findings of RA and KERSTIN EBERHARDT : collapse of both wrists, marked Associations ofHLA-DRB Department ofRheumatology Lund University Hospital subluxations of the metacarpophalangeal and HLA-DRQ genes with S-221 85 Lund, Sweden joints bilaterally, large erosions of the distal two year phalanx of the thumb, and an erosion on the and five lateral aspect ofthe fifth right metatarsal head outcomes in with calcified intraosseous tophi (figure). rheumatoid The coexistence of gout and RA in our patient is unquestionable. She had evidence We were interested in the results of the of seropositive destructive RA, hyper- longitudinal study by Eberhardt and uricaemia, acute gout, and MSU crystals. colleagues,' who examined the relationship LETTER TO Coexistent radiographic changes of RA and between HLA-DRB and HLA-DRQ genes gout have been described previously. 7 As RA and outcomes in . Their THE EDITOR is far more prevalent than gout, it would be results, showing a lack of relationship expected that a patient with both disorders between HLA-DQ variants and articular would be diagnosed first as having RA. disease severity, are in keeping with the However, in 10 of the 14 previously reported results of our previous cross-sectional study Rheumatoid arthritis cases (among whom the ratio of men to women was 2-5:1) the first diagnosis was gout that showed no influence of HILA-DQ preceding the onset of variants on articular disease severity, in (table). addition to demonstrating a definite re- polyarticular tophaceous The reason for the usual mutual exclusion lationship between homozygosity for HLA- gout of RA and gout is not clear. Hyperuricaemia DR4 and severity of articular disease. may have some 'protective immunosup- effect.'8 A effect of RF on Eberhardt and-coworkers have gone on to arthritis (RA) and gout are pressive' blocking Rheumatoid Fc receptors adsorbed on MSU crystal look for a relationship between HLA variants relatively common diseases, but their co- and risk of extra-articular disease. Again, in existence is rare. The of surfaces'3 and a negative correlation between extremely diagnosis serum uric acid concentration and clinical previous studies we have looked at this RA and gout is hampered because 1 0% of relationship,3 and showed in cross-sectional patients with RA have hyperuricaemia' and activity in RA have been demonstrated.' As studies that different forms of extra-articular 30% of with noted, hyperuricaemia occurs in about 10% patients tophaceous gout may of RA and has been related to the rheumatoid disease such as Felty's syndrome, have low titre rheumatoid factor (RF).2 It is patients,'8 major vasculitis, and various forms of lung necessary, therefore, to meet the terms of use of aspirin and analgesics, which may disease have different HLA associations. We criteria before that a affect the excretion or renal handling of uric strict concluding patient acid. Most rheumatic diseases dispropor- consider this is an important point to make, has both diseases. The criteria include: tionately affect women rather than men; as such associations may be lost if different seropositive erosive RA, or histological forms of extra-articular rheumatoid disease confirmation of rheumatoid however, while women are distinctly less nodule/pannus, affected gout in years, are analysed together. and recurrent attacks of gout with identifi- by premenopausal The HLA associations in Felty's syndrome cation of monosodium urate (MSU) crystals. their frequency of gout increases after- and in major forms of rheumatoid vasculitis wards. '9 Predisposing factors for gout include Up to December 1995, 14 cases of 21 have been particularly interesting, in that as defined above an underlying joint disease,20 use of coexistent RA and gout Gout in Felty's syndrome has shown an association We now another diuretics, and renal impairment.22 were reported.'3-6 report women is commonly polyarticular,23 tophi with a particular HLA haplotype (B44-Bfs- case, review the literature, and discuss C4A*3-C4B*Q0-DR4-DQB1*0301), while possible risk factors for the development of major rheumatoid vasculitis has shown gout in our patient. associations with the DRB1*0401 variant of A 61 year old white woman with RA of HLA-DR4 and with the C4 null allele, more than 25 years duration presented in C4A*QO. December 1994 with a swollen, painful thumb with a whitish, chalk-like discharge. D M GRENNAN W OLLIER Her past history included obesity and hyper- Department ofRheumatology tension treated with hydrochlorothiazide. RA .. 174 Joint Disease Wrightington Hospitalfor had been diagnosed based on the presence of v, lvM"i Wigan WN6 9EP, United Kingdom in a rheumatoid distribution, and treated with different second line 1 Eberhardt K, Fex E, Johnson U, Woolheim FA. agents Assoications of HLA-DRB and -DQB genes over time; at presentation she was receiving with two and five year outcome in rheumatoid oral gold and prednisone 7-5 mg/day. arthritis. Ann Rheum Dis 1996; 55: 34-9. 2 McMahon M J, Hillarby M C, Clarkson R, Laboratory data from 1983 revealed a 2k Hollis S, Grennan D M. Articular disease serum uric acid concentration of 132 mg/l I severity in rheumatoid subjects with and and a positive RF (titre 2560). In 1984, without Felty's syndrome. Br Rheumatol rheumatoid nodules over the olecranon 1993; 32: 899-902. 3 Hillarby M C, Grennan D M, Clarkson R. bursae, ulnar deviation of both wrists, and Immunogenetic heterogeneity in rheumatoid swan neck deformities were observed. Fluid disease as characterised by different MHC from both knees contained 70000/mm3 associations (DQ, Dw and C4) in articular and extra-articular subsets. Br Jf Rheumatol leucocytes, with predominance of poly- 1990; 30:5-9. morphonuclear cells; MSU crystals were not found. In November 1992, the patient had acute Aul-HoR's REPLY: We have read with interest right ankle swelling; was sus- Radiographs ofthe right hand andfoot. the comments by Drs Grennan and Ollier pected. Ankle radiographs showed changes Osteoporosis, marginal erosions, subluxation of regarding the relationship between HLA compatible with chronic RA, and magnetic the metacarpophalangealjoints, and advanced variants and extra-articular rheumatoid resonance showed a subtalar effusion, but an destruction of the wrist, with sparring of metacarpal bases are characteristic ofRA. disease. We do agree that different forms of arthrocentesis was unsuccessful. Serum uric Gouty tophi replace thefirst and second distal extra-articular features should be analysed acid concentration was again increased (132 phalanges (A). Erosion in the lateral aspect of separately. In our cohort, one patient mg/l); blood cultures were negative. Her the 5th metatarsal head indicates RA. developed major vasculitis, and three condition improved spontaneously and Tarsometatarsaljoint destruction and extensive developed renal amyloidosis during the first continued about the same until August 1994, intraosseous tophi are characteristic ofgout (B). 490 Letter to the editor

Case reports ofcoexistent gout and rheumatoid arthritis Source Sex! Age at diagnosis (yr) RF titre Rheuma- Tophi MSU Uric Response Histopathology Age toid acid to (yr) Gout RA nodules Synovial Tophi colhicine McCarty 19643 M:75 63 75 2560 + + + t Rheumatoid nodule Owen etal, 19644 M:64 49 63 320 + + + 13 2 Yes Synovium, pannus Bloch-Michelle F:38 26 31 320 + 11-0 Synovium, pannus et al, 19685 and MSU crystals Schwartzberg M:39 39 23 5120 + + + 10 0 Yes Synovium, pannus et al, 19786 and nodule with MSU crystals Wallace etal, 19797 F:73 72 38 5120 + + + 16 2 Yes NA Rizzolietal, 19798 M:58 58 70 1280 + + + 12-6 Yes Menisectomy MSU crystals Jessee et al, 1980' M:71 61 64 640 + + + 7-2 Yes Rheumatoid nodule Atdjianetal, 1981'° M:56 50 55 5120 + + + + 6-4 Rheumatoid nodule and MSU crystals; synovium, pannus Ramanetal, 1981" F:67 63 50 256 + + t Rheumatoid nodule Waterworth 1981'2 M:61 61 64 320 + + t Rheumatoid nodule Gordon etal, 1985"3 M:60 54 56 2048 + + + t Yes Rheumatoid nodule; synovium, pannus Martinez-Cordero M:37 27 30 1280 + + 8-9 Rheumatoid nodule etal, 1988"4 Spector et al, 1989"5 M:39 41 57 640 + + 4-5 Rheumatoid nodule Wendlingetal, 1991"6 F:45 45 45 2560 + t Yes NA Present study F:61 58 42 2560 + + + 13-2 NA NA = Not available. appear sooner than in men,24 and inter- 5 Bloch-Michelle H, Benoist M, Ripauult J, 16 Wendling D, Guidet M. Association goutte- phalangeal joints are involved frequently.25 Siaud J R. micro crystalline polyarthrite rheumatoide [Gout and rheuma- associees a une maladie rhumatoide. A Although the coexistence of RA and gout propos toid arthritis in the same patient]. Semin Hop de sept case. Discussion sur les liens eventuels Paris 1991; 67: 1497-500. is extremely rare, the latter should be sought entre les deux syndromes. [Microcrystalline 17 Talbott J H, Altman R D, Ts'ai-Fan Y. Gouty in patients with inflammatory arthropathy associated with rheumatoid arthritis masquerading as rheumatoid arthritis and otherwise asymptomatic hyperuricaemia arthritis disease. A propos of seven cases. or vice versa. Semin Arthritis Rheum 1978; 8: Discussion on the possible relation between 77-114. if acute or chronic gout, or both, are to the two syndromes]. Presse Med 1968; 76: 18 Lussier A, Medicis de R. Coexistent gout and receive the correct treatment in these 1311-2. rheumatoid arthritis: a red marker? Arthritis patients. 6 Schwartzberg M, Lieberman D H, Gupta V P, Rheum 1979; 22: 939-40. Ehrlich G E. Rheumatoid arthritis and 19 Yu T F. Some unusual features of gouty arthritis chronic gouty arthropathy.3AMA 1978; 240: in females. Semin Arthritis Rheum 1977: 6: ABRAHAM ZONANA-NACACH 2658-9. GRACIELA S ALARCON 247-55. 7 J Division ofClinical Immunology and Wallace D J, Klinenberg R, Morhaim D, 20 Simkin P A, Campbell F M, Larson E B. Gout , Berlanstein B, Biren P C, Callis G. Coexistent in Heberden's nodes. Arthritis Rheum 1977; The University ofAlabama at Birmingham, and Birmingham, USA gout rheumatoid arthritis: case report and 20: 895-900. Alabama, literature review. Arthritis Rheum 1979; 22: 21 Strader K W, Agudelo C A. Coexistent 81-6. WILLIAM W rheumatoid nodulosis and gout. _7 Rheumatol DANIEL 8 Rizzoli A J, Trujeque L, Bankhurst A D. The 1986;13: 1307-11. Department ofRadiology, The University ofIowa, coexistence of Iowa USA gout and rheumatoid arthritis: 22 Macfarlane D G, Dieppe A P. Diuretic-induced City, Iowa, case reports and a review of the literature. _ gout in elderly women. Br I Rheumatol 1985; Rheumatol 1980; 7: 316-24. Correspondence to: Dr Graciela S 24: 155-7. Alarcon, 9 Jessee E F, Toone E, Owen D S, Irby R. 23 Curran J J, Renold F. Clinical manifestations of University Station, MEB 615/ 1813 6th Avenue Coexistent South, Birmingham, AL 35294, USA. rheumatoid arthritis and chronic acute polyarticular gout in female patients tophaceous gout. Arthritis Rheum 1980; 23: [abstract]. Arthritis Rheum 1988; 31: R31. 244-7. 24 Meyers 0 L, Monteagudo F S E. A comparison 10 Atdjian M, Fernandez-Madrid F. Coexistence ofgout in men and women. S AfrMedJ 1986; This work was partially supported by the Instituto of chronic tophaceous gout and rheumatoid 70: 721-3. Mexicano del Seguro Social (IMSS) and arthritis. Rheumatol (A Z-N) _ 198 1; 8: 989-92. 25 Ter Borg E J, Rasker J J. Gout in the elderly: the National Institute of Health (NIH), National 11 Raman D, Abdalla A M, Newton D R L, a separate entity? Ann Rheum Dis 1987; 46: Institute of Arthritis and Musculoskeletal and Skin Haslock I. Coexistent rheumatoid arthritis 72-6. Diseases, Center grant P-60-AR-20614 (G S A). and tophaceous gout: a case report. Ann We are grateful to Ms Ella Henderson for Rheum Dis 1981; 40: 427-9. preparation of the manuscript. 12 Waterworth R F. The effect of allopurinol therapy on coexistent gout and rheumatoid arthritis. Arthritis Rheum 1981; 24: 103-4. 1 Agudelo C A, Turner R A, Panetti M, Pisko E. 13 Gordon T P, Ahern M J, Reid C, Roberts- Correction Does hyperuricemia protect from rheumatoid Thompson P J. Studies on the interaction of ? A clinical study. Arthritis rheumatoid factor with monosodium urate Can methotrexate be used as a steroid Rheum 1984; 27: 443-8. crystals and case report of coexistent sparing agent in the treatment of 2 Kozin F, McCarty D J. Rheumatoid factor in tophaceous gout and rheumatoid arthritis. the serum of gouty patients. Arthritis Rheum Ann Rheum Dis 1985; 44: 384-9. polymyalgia rheumatica and giant cell 1977; 20: 1559-60. 14 Martinez-Cordero E, Bessudo-Babani A, arteritis? 3 McCarty D J. The pendulum of progress in Trevifto-P6rez S C, Guillermo-Grajales E. van der Veen et al (Ann Rheum Dis 1996; 55: gout: from crystals to hyperuricemia and Concomitant gout and rheumatoid arthritis. 218-223) back. Arthritis Rheum 1964; 7: 534-41. Rheumatol 1988; 15: 1307-11. 4 Owen D S Jr, Toone E, Irby R. Coexistent 15 Spector A K, Christman R A. Coexistent gout It is regretted that an incorrect affiliation was given rheumatoid arthritis and chronic tophaceous and rheumatoid arthritis. Am Podiatr Med for Dr H J Dinant, who is now rheumatologist at gout. JAMA 1966; 197: 123-6. Assoc 1989; 79: 552-8. the Jan van Breemen Instituut, Amsterdam.