Postdiarrheal arthropathy of Yersinia pseudotuberculosis ANDREW CHALMERS,* MD; ROBERT E. KAPROVE,* MD; WILLIAM J. REYNOLDS, MD; MURRAY B. UROWITZ, MD

Two patients with acute gastroenteritis in whom polyarthritis subsequently developed were found to have positive serologic results for Yersinia pseudotuberculosis. With resolution of the arthropathy the antibody titres decreased. While the patient without the histocompatibility antigen HLA-B27 had an acute, self-limited arthritis, the patient with this antigen had a more chronic arthritis. Serologic typing and stool culture for V. pseudotuberculosis should be done in cases of postdysenteric arthritis. Deux patients qui ont souffert de gastroenterite aigu. et chez qui une polyarthrite est par Ia suite apparue ont eu une 6preuve serologique positive a Versinia pseudotuberculosis. Avec Ia resolution de l'arthropathie, les titres d'anticorps ont diminue. Alors que le patient sans antigene d'histocompatibilite HLA-B27 a pr6sent6 une arthrite aigue evoluant vers Ia guerison, le patient ayant cet antig&ne a presente une forme d'arthrite plus chronique. La recherche de Y. pseudotuberculosis par epreuve s6rologique et culture des selles devrait .tre faite dans les cas d'arthrite consecutive a une dysenterie. While the arthritis associated with Yersinia enterocolitica infection has received considerable attention from Europe1-6 and less frequently from North America,7 that due to the related organism Y. pseudotuberculosis has seldom been reported.2'8 Y. pseudotuberculosis, a common pathogen of birds and rodents,9 has also been responsible for cases in humans of mesenteric adenitis,'0 septi" acute gastroenteritis,'2 erythema nodosum" and acute polyarthritis.1 In this paper two different presentations of the arthropathy of Y. pseudotuberculosis draw attention to circumstances when cultural and serologic evidence of Y. pseudatuberculosis infection should be sought.

Case reports Case 1 On Feb. 3, 1977, after eating the same meal, a 30-year-old woman and three relatives had explosive diarrhea containing blood and mucus, which lasted 48 hours, From the division of rheumatology, University of Toronto and the rheumatic disease units, Toronto Western and Wellesley hospitals, Toronto *Former fellow, Canadian Arthritis and Rheumatism Society Reprint requests to: Dr. Murray B. Urowitz, 561A Rheumatic disease unit, Wellesley Hospital, 160 Wellesley St. E, Toronto, Ont. M4Y 1J3

then subsided spontaneously. The three relatives had no complications, but a fever developed 4 days later in our patient and painful, red lesions appeared over both tibiae. The lesions turned purple, then gradually disappeared over the next 3 days. Pain and swelling then developed in several metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, both knees and the right ankle. Cervical cultures for Neisseria gonorrhoeae were negative. The joint pain and swelling persisted. On Feb. 20, 1977 she was admitted to hospital. She denied previous ocular or bowel symptoms, urethral discharge, photosensitivity, Raynaud's phenomenon and alopecia. The second and third right MCP joints, second and third lefi PIP joints, left wrist, elbow, ankle and knee were all tender and swollen. Roentgenography of the joints showed only soft tissue swelling; the sacroiliac joints appeared normal. The hemoglobin value was 13.8 g/dL; leukocyte count, 8.3 X 109/L (normal differential); and erythrocyte sedimentation rate, 59 mm/h (Westergren). Urinalysis gave normal results. Synovial fluid contained 5000 leukocytes that were mononuclear in type, and culture of the synovial fluid was negative. Hepatitis-associated antigen, latex fixation and antinuclear antibody tests gave negative results. Tests for the histocompatibility antigen HLA-B27 gave negative results. A Widal agglutination test was negative. Two days after admission antibodies to Y. pseudotuberculosis type 2 were present in a titre of 1:400. (The relatives' serum contained none.) Stool cultures for Yersinia, Salmonella and Shigella were negative. Over the subsequent 5 days the arthritis subsided without therapy and serum obtained during the convalescent stage 2 weeks later contained no antibodies to Y. pseudotuberculosis. Case 2 Within a few days of experiencing low back pain, a 30-year-old man had the simultaneous onset of conjunctivitis, a painful urethral discharge and loose stools containing blood and mucus. He had one episode of painless hematuria. Associated with these symptoms were pain and swelling of both knees, one toe, and the fifth PIP and second metatarsophalangeal joint on the left side, and pain in the right heel. The diagnosis was Reiter's disease. The bowel symptoms resolved in 2 weeks and the joint symptoms over 4 months. Six years later, in April 1976, the patient again experienced low back pain. Physical examination and roentgenography of the spine and sacroiliac joints yielded normal results. HLA-B27 was demonstrated. Four months later iritis developed in the left eye. The following month the back pain became more severe and he noted pain in the left groin and general malaise. In November 1976 he attended a dinner,

following which a number of people experienced mild diarrhea. Unlike the others, he noted blood in his stool. Colonoscopy and rectal biopsy revealed acute nonspecific ulcerations. Results of a Widal test were negative. Steroids in oral form, steroid enemas and salicylazosulfapyridine were administered. The patient was improved after 1 week and steroid treatment was tapered. One month later dactylitis of the left fourth finger and heel pain developed. On Jan. 27, 1977 he was hospitalized with dactylitis of the left fourth finger and the left third toe, and with arthritis of the second left MCP joint and both shoulders. Hemoglobin concentration was 12.1 g/dL, leukocyte count was 8.5 X 109/L and erythrocyte sedimentation rate was 70 mm/h. Results of barium enema examination, sigmoidoscopy and rectal biopsy were normal. Reactivation of Reiter's disease was diagnosed. He was treated with phenylbutazone and his condition improved, but within 3 weeks the arthritis recurred. Gastrointestinal rcentgenograms obtained on readmission were normal. Y. pseudotuberculosis type 2 antibody was present in a titre of 1:200. Prednisone (20 mg/d) was started and provided relief of pain. The antibody titre 1 month later, after clinical improvement, was 1:100. Six months after onset of the recurrence, low-grade arthritis persisted. The antibody titre was less than 1:100. (At the Canadian National Refererice Centre this titre is considered negative for Y. enterocolitica and Y. pseudotuberculosis.)

Discussion Both an acute and a chronic postinfectious arthropathy have been described in association with Y. enterocolitica infections."2"4 However, only acute arthritis has been described following Y. pseudotuberculosis infection,1 this organism being considered a rare cause of arthritis.' The clinical signs in patient 1 were typical of those previously associated with infection due to Y. enterc'colitica.""5 She had acute gastroenteritis followed by erythema nodosum and, 3 to 4 days later, acute polyarthritis. Stool cultures were not done during the acute phase, but the presence of a positive titre for Y. pseudotuberculasis type 2 antibody then and a negative titre when the joint pain resolved strongly supported the correct diagnosis. That serum of the relatives who had only gastroenteritis contained no such antibodies is consistent with previous reports of the short-lived nature of the serologic reaction in individuals with enteritis alone and the higher, more persistent titres associated with the arthritis."

CMA JOURNAL/MARCH 4, 1978/VOL. 118 515

Our second patient, in whom HLA- to Y. enterocolitica and Y. pseudotuberB27 had previously been demonstrated, culosis has risen.17 However, reports of had well documented Reiter's dis- disease associated with Y. enterocolitica ease following acute gastroenteritis. are greater in number than those of After a recurrence of the gastroenter- infection caused by Y. pseudotubercuitis acute arthritis and low back pain losis. This may be owing either to a developed and was associated with greater incidence of enterocoliticaelevated titres of antibodies to Y. related infection, or to a greater awarepseudotuberculosis. When his condition ness of syndromes associated with Y. improved, the antibody titre decreased. enterocolitica. In 1976, only eight isoThe postinfectious arthritis caused lates of Y. pseudotuberculosis were sent by Y. enterocolitica in patients with to the reference centre and none reHLA-B27 has usually been chronic presented human infection. However, and a high incidence of relapse, six of the eight were from animals iritis, sacroiliitis, spondylitis and Reit- slaughtered for human consumption.18 er's disease. This contrasts with the Greater awareness of the relations of acute self-limited arthritis produced by Y. pseudotuberculosis infection to postY. enterocolitica in individuals without dysenteric arthritis, spondylitis and HLA-B27.'4 Our first patient, who Reiter's disease should lead to increased had acute self-limited arthritis fol- recognition of its association with these lowing infection by Y. pseudotuber- conditions. culosis, did not have HLA-B27, but We thank Dr. Sandu Toma, of the Canaour second patient, who had a history dian National Reference Centre for Yerof Reiter's disease, had a more chronic sinia enterocolitica and Yersinia arthritis, with a slower reduction in tuberculosis (Ontario Provincial pseudoPublic the titre of Y. pseudotuberculosis anti- Health Laboratory), for doing the serobody. It will be interesting to see if logic tests. this pattern is maintained in larger series of patients with arthritis follow- References ing Y. pseudotuberculosis infection. 1. AHVONEN P. SIEVERS K, AHO K: Arthritis associated with Yersinia enterocolitica infecY. pseudotuberculosis grows well on tion. Acta Rheum Scand 15: 232, 1969 media used to grow lactose-fermenting 2. AHVONEN P: Human yersiniosis in Finland. II. Clinical features. Ann Gun Res 4: 39, Escherichia coli and less well on other 1972 media, including those used to grow 3. A.vp.si.sor. B, DAMGAARO K, WINBLAO S: Clinical symptoms of infection with Yersinia Salmonella and Shigella. Therefore culenterocolitica. Scand J Inject Dis 3: 37, 1971 tures for Y. pseudotuberculosis should 4. LAITINEN 0, TUUHEA J, AHVONEN P: Polyarthritis associated with Yersinia enterocolitica be specifically requested. If appropriinfection. Clinical features and laboratory findings in nine cases with severe ately cultured, this organism is easy to symptoms. Ann Rheum Dis 31: 34, 1972 joint identify. 5. WINBLAD S: Arthritis associated with Yersinia enterocolitica infections. Scand J Inject Because the abdominal pain and Dis 7: 191, 1975 diarrhea caused by Y. pseudotubercu6. LEINo R, KALLIOMAKI JL: Yersiniosis as an internal disease. Ann Intern Med 81: 458, losis are generally self-limited, by the 1974 time arthropathy develops stool cul7. JACOBS JC: Yersinia enterocolitica arthritis. Pediatrics 55: 236, 1975 tures are usually negative. This was 8. wETzLER TF, HUBERT wT: Pasteurella pseuexemplified by our first case. For this dotuberculosis in North America, in international Symposium on Pseudotuberculosis, reason serologic identification should Paris, 1967. Symposia Series in immunological Standardization, Vol. 9: Proceedings, be attempted. Because of shared antiwhite Plains, Phiebig, 1968, pp 33-44 gens with Salmonella groups B and D 9. WEBER 1, FINLAYSON NB, MARK JBD: Mesenteric lymphadenitis and terminal ileitis due and with F. coli, crossreactivity may to Yersinia pseudotuberculosis. N Engi J Med occur; thus, determination of serotypes 283: 172, 1970 HNATKO DI, ROOIN AE: Pasteurella pseudoand antibody titres requires techniques 10. tuberculosis infection in man. Can Med Assoc involving adsorption with appropriate J 88: 1108, 1963 YAMAIHIRO 11. KM. GOLDMAN RH, HARRIS D, antigens?6 Since no commercial antiet al: Pasteurella pseudotuberculosis. Acute gens or antisera are available to date, sepsis with survival. Arch Intern Med 128: 1971 these determinations should be per- 12. 605, VANTRAPPEN G, PONETI-rE E, GEBOEs K, et al: formed by a reference laboratory. At Proceedings: Yersinia enteritis and enterocolitis. Gut 17: 392, 1976 the Canadian National Reference Centre HANNUK5ELA M, AHvONEN P: Skin manifesfor Y. enterocolitica and Y. pseudo- 13. tations in human yersiniosis. Ann Clin Res 7: 368, 1975 tuberculosis, a titre of 1:100 is con14. ALO K, AHvONEN P, LAssus A, et al: HL-A sidered positive. 27 in reactive arthritis: a study of yersinia arthritis and Reiter's disease. Arthritis Rheum Sera should be cultured in the usual 17: 521, 1974 15. SOLEM JH, LAssEN I: Reiter's disease folmanner during the convalescent phase lowing Yersinia enterocolitica infection. Scand to demonstrate a reduction in the antiI Inject Dis 3: 83, 1971 PAFF JR, TRIPLE1-r DA, SAARI TN: Clinical body titre. For Y. enterocolitica anti- 16. and laboratory aspects of Yersinia body several samples over several tuberculosis infections, with a report pseudoof two cases. I Gun Pathol 66: 101, 1976 months have been required to show this 17. TOMA Am 5: Survey of the incidence of Yersinia reduction.6 Since a national reference enterocolitica in the province of Ontario. Can I Public Health 64: 477, 1973 service was established in Ontario for 18. ToMA 5, DEIDRIcK VR: Incidence of Yeridentification of both these organisms, sinia enterocolitica and Y. pseudotuberculosis infections in Canada; 1975 semiannual report the incidence of reported infection due (C). Can Med Assoc 1 114: 16. 1976 516 CMA JOURNAL/MARCH 4, 1978/VOL. 118

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