1299 “NAVAJO ARTHRITIS” RECONSIDERED Relationship to HLA-B27 ROBERT G. RATE, HAROLD G. MORSE, MARK D. BONNELL, and TIMOTHY T. KUBERSKI “Navajo arthritis” was described in 1971 as an acute, self-limited, asymmetric polyarthritis of unknown etiology seen in Navajo Indian patients. This description was before published accounts relating HLA-B27 to certain seronegative arthropathies. Review of 92 cases of arthritis seen between 1977 through 1979 in adult Navajo Indians revealed 16 cases of complete Reiter’s syndrome, 6 cases of incomplete Reiter’s syndrome, and 7 cases of ankylosing spondylitis. The phenotype frequency of HLA-B27 in this Navajo population is 36% and, of the Reiter’s syndrome and ankylosing spondylitis patients tested, 85% were found to be HLA-B27 positive. We suggest that “Navajo arthritis” may not be a unique form of arthritis affecting only the Navajo, but a variant of either Reiter’s syndrome or ankylosing spondylitis. In 1971, Muggia, Bennahum, and Williams described 21 cases of an acute, self-limited, asymmetric polyarthritis of unknown etiology in Navajo patients (I). The entity was termed “Navajo arthritis” and felt to be a distinct syndrome. Our recent clinical experience From the Public Health Service Indian Hospital, Keams Canyon, Arizona, and the National Institute of Arthritis, Metabolism, and Digestive Diseases, Epidemiology and Field Studies Branch, 1440 East Indian School Road, Phoenix, Arizona. Supported in part by the Indian Health Service under provisions of PL 94-437, Title 11, Section 201(d). Additional funds provided by NIAMDD. Robert G. Rate, MD: Public Health Service Indian Hospital; Harold G. Morse, MD: Public Health Service Indian Hospital; Mark D. Bornell, MD: Public Health Service Indian Hospital; Timothy T. Kuberski, MD: NIAMDD. Address reprint requests to Dr. T. Kuberski, NIAMDD, Epidemiology and Field Studies Branch, 1440 East Indian School Road, Phoenix, Arizona 85014. Submitted for publication June 2, 1980; accepted in revised form July 29, 1980. Arthritis and Rheumatism, Vol. 23, No. 11 (November 1980) with arthritis in Navajos and the finding of a high frequency of HLA-B27 in this population (2) suggested to us ,hat the previously reported cases of “Navajo arthritis” may in fact have been HLA-B27-related forms of arthritis. This report summarizes 3 years experience with arthritis in Navajos at the Keams Canyon Indian Hospital (KCIH), a 38-bed hospital located in northeastern Arizona which provides medical care for approximately 6,000 Navajos. The objective of this study was to examine the arthritides seen by us in Navajo Indians, particularly the proven and probable HLA-B27related forms, and to compare these with the previously described cases of “Navajo arthritis.” PATIENTS AND METHODS The charts of all adult ( 2 1 5 years) KCIH Navajo patients with a discharge diagnosis of arthritis during the 3-year period 1977 through 1979 were reviewed. ’Ihe diagnosis of rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, osteoarthritis, and gout were made using established criteria (3). Gonococcal arthritis was diagnosed in patients with arthritis from whom Neisseria gonorrhea had been isolated. The diagnosis of Reiter’s syndrome was considered established when the classic triad of arthritis, conjunctivitis, and urethritis occurred. Incomplete Reiter’s syndrome was based on the presence of arthritis in addition to either conjunctivitis or urethritis. HLA typing was done using the microlymphocytotoxicity method (4) at the discretion of the attending physician. Statistical analysis was done using the Chi-square test. RESULTS The charts of 121 adult Navajo patients with arthritis were reviewed for the 3-year period. Table 1 is the compilation of our results, compared to those reported by Muggia et al from the Gallup Indian Medical RATE ET AL 1300 Table 1. Discharge diagnoses of adult Navajo patients with arthritis who were seen at Keams Canyon Indian Hospital (KCIH) 1977-79 compared to discharge diagnoses at Gallup Indian Medical Center (GIMC), 1969 Number of patients Diagnosis KCIH GIMC Gout Rheumatic fever Gonococcal Rheumatoid Osteoarthritis Reiter’s syndrome Incomplete Reiter’s syndrome Ankylosing spondylitis Undetermined origin 4 0 2 17 35 16 6 7 5 1 8 9 23 18 1 0 0 39 Total 92 99 Center (GIMC) in 1969. Not included in the data from KCIH in Table 1 are 21 patients with traumatic arthritis, 5 with septic arthritis, and 3 with arthritis grouped under collagen vascular disease (these diagnoses were not reported in the GIMC series). In comparing the two series, there are significant dserences in the number of patients seen with arthritis of acute rheumatic fever, gonococcal arthritis, and osteoarthritis. However, the most significant difference is between those patients having HLA-B27 related arthropathies. There were 22 patients with Reiter’s syndrome (complete and incomplete) and 7 with ankylosing spondylitis seen at KCIH, while only 1 patient with Reiter’s syndrome was reported from GIMC (P < 0.001). Also significant was that only 5 of our cases were classified as undetermined origin, whereas 39 were so classified at GIMC (P < 0.001). Of the 22 patients with Reiter’s syndrome seen at KCIH, 21 were tested for HLA-B27 and 18 (86%) were positive. Eighty percent (4 of 5) of the ankylosing spondylitis patients tested for HLA-B27 were positive. Thus, of those patients tested who had either Reiter’s syndrome or ankylosing spondylitis, 85% (22 of 26) were HLA-B27 positive. A comparison of the various findings observed in the Reiter’s syndrome, ankylosing spondylitis, and arthritis of undetermined origin patients at KCIH and the “Navajo arthritis” patients from GIMC is given in Table 2. Male predominance, similar age range, and predilection for knee involvement were seen in both groups. We were able to obtain followup information and HLA typing on only 1 of our 5 patients with arthritis of undetermined origin. This 27-year-old woman presented in early 1979 with peripheral arthritis involving her knees and hips. Subsequent to the chart review, she developed signs and symptoms which fulfill criteria for the diagnosis of ankylosing spondylitis. This patient was found to be HLA-B27 positive. Interestingly, a diagnosis of Reiter’s syndrome has been made in her 5-year-old daughter, who is also HLA-B27 positive (5). DISCUSSION Recent observations associating HLA-B27 with certain forms of arthritis, particularly Reiter’s syndrome and ankylosing spondylitis (6,7), have expanded knowledge concerning these arthritides. The phenotype frequency of HLA-B27 in the Navajo population served by the Keams Canyon Indian Hospital has been shown to be about 36% (2). This is approximately five times the HLA-B27 frequency for whites (7). The report in 1971 (1) which described “Navajo arthritis” as being a distinct, previously undescribed example of an acute, selflimited arthritis was before the published observations associating HLA-B27 with certain forms of arthritis (6,7). Because we had encountered patients who clinically had “Navajo arthritis” and discovered that many were HLA-B27 positive, we began to examine the hy- Table 2. Reiter’s syndrome, ankylosing spondylitis, and arthritis of undetermined origin in adult Navajos, Keams Canyon Indian Hospital, 1977-79, compared to “Navajo arthritis” patients, Gallup Indian Medical Center, 1969 Form of arthritis No. of patients No. of men (%) Age range Knee involvement (70) 22 7 18-86 32-76 27-7 1 18-86 15 (68) 3 (43) 4 (80) 22 (65) 15-68 21 (100) Reiter’s syndrome Ankylosing spondylitis Undetermined origin KCIH totals 34 22 (loo) 7 (100) 3 (60) 32 (94) Patient with “Navajo arthritis” reported from GIMC 21 16 (76) 5 1301 “NAVAJO ARTHRITIS” pothesis that our patients with “Navajo arthritis” might have been, in many cases, HLA-B27 related arthritis. The patients reported in 1971 with “Navajo arthritis” (1) were characterized by the “preponderance of males and the absence of a chronic course, residual deformities, morning stiffness, rheumatoid nodules, lupus cells or positive tests for rheumatoid factor.” The clinical findings were described as “typically lasting a few days or several weeks, marked by the rapid onset of asymmetric distribution of acutely painful, red, swollen joints with a predilection for the knee. This is followed by rapid and complete resolution leaving no residual deformities or clinical symptoms.” Except for the presence of conjunctivitis and/or urethritis, this description characterizes many of our Reiter’s syndrome patients and, similarly, could have been observed early in the course of a few of our ankylosing spondylitis patients. Except for the uniform self-limited nature (1-3 weeks) of “Navajo arthritis,” this characterization also is compatible with the description of some incomplete Reiter’s syndrome patients who are HLA-B27 positive and have peripheral arthritis with no urethritis or conjunctivitis (8). The description of “Navajo arthritis” is also consistent with the heterogeneous group of arthritides associated with HLA-B27 termed “reactive arthritis” (9). Based on our experience, Reiter’s syndrome is comparatively common among the Navajo, as is incomplete Reiter’s syndrome. Presumably this is related to the high frequency of HLA-B27 in the Navajo population served by our hospital. In the report by Muggia et a1 (1) describing “Navajo arthritis,” only one patient (1%) with Reiter’s syndrome was observed in the 99 arthritis patients seen during 1 year, and 39 (39%) were found to have arthritis of undetermined origin. In our series of 92 patients with similar diagnoses seen over 3 years, there were 16 (17%) cases of Reiter’s syndrome, 6 (7%) incomplete Reiter’s syndrome, 7 (8%) ankylosing spondylitis, and 5 (5%) cases of arthritis of undetermined origin. Eighty-five percent of our Reiter’s syndrome and ankylosing spondylitis patients tested were found to be HLA-B27 positive. Certainly some of the differences observed in the various forms of arthritis are due to differences in the type of patients seen; KCIH is community based, whereas GIMC is a referral hospital. The patient population differences probably account for the greater number of cases of arthritis associated with rheumatic fever (in addition to a decreasing incidence) and the fewer cases of osteoarthritis seen at GIMC. Nevertheless, the Navajo is a relatively homogeneous American Indian population (lo), and we have no reason to believe that the Navajos seen at KCIH differ substantially from Navajos seen elsewhere. This suggests that a large proportion of the patients described with “Navajo arthritis” may have been patients with HLA-B27 associated arthritis, particularly incomplete Reiter’s syndrome or “reactive” arthritis. This hypothesis could be confirmed (or refuted) only if the 21 cases of “Navajo arthritis” were evaluated again and HLA typing performed. If these 21 patients represented a random sampling of our Navajo population, only 7 or 8 would be expected to be HLA-B27 positive. If some, or all, of the patients had Reiter’s syndrome, about 17 or 18 of the 21 would be expected to be HLA-B27 positive. With the advantage of new information and techniques that can be applied to the study of arthritis, we suggest that “Navajo arthritis” is not a unique form of arthritis affecting only the Navajo, but probably represents variants of classic Reiter’s syndrome or ankylosing spondylitis. ACKNOWLEDGMENTS The authors thank the Navajo and Hopi tribes for their cooperation in this study; Dr. Peter Bennett for his advice; and Theona Vyvial of Arizona Blood Services for her assistance in the histocompatibility antigen typing. We also appreciate the invaluable help of the staff at the Keams Canyon Indian Hospital. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the Indian Health Service. REFERENCES 1. Muggia AL, Bennahum DA, Williams RC Jr: Navajo arthritis-an unusual, acute, self-limited disease. Arthritis Rheum 14:348-355, 1971 2. Morse HG, Rate RG, Bonnell MD, Kuberski TT: High frequency of HLA-B27 and Reiter’s syndrome in Navajo Iridians. J Rheumatol (in press) 3. Bennett PH, Burch TA: New York symposium on population studies in the rheumatic diseases: new diagnostic criteria. Bull Rheum Dis 17:453458, 1967 4. Terasaki PI, McClelland JD: Microdroplet assay of human serum cytotoxins. Nature 204:998-1000, 1964 5. Morse HG, Rate RG, Bonnell MD, Kuberski TT: Reiter’s syndrome in a five-year-old girl. Arthritis Rheum 23:960961, 1980 6. Schlosstein L, Terasaki PI, Bluestone R, Pearson CM: High association of an HL-A antigen, W27, with ankylosing spondylitis. N Engl J Med 288:704-706, 1973 7. Morris R, Metzger AL, Bluestone R, Terasaki PI: HL-A W27-ia clue to the diagnosis and pathogenesis of Reiter’s syndrome. N Engl J Med 290554-556, 1974 RATE ET AL 1302 8. Arnett FC, McClusky OE, Schacter BZ Lordon RE: Incomplete Reiter’s syndrome: discriminating features and HL-A W27 in diagnosis. Ann Intern Med 84:8-12, 1976 9. Aho K, Ahvonen P, Lassus A, Severs K, Tiilikainen A: Yersinia arthritis and related diseases: clinical and i m m u nogenetic implications, Infection and Immunology in the Rheumatic Diseases. Edited by DC Dumonde. London, Blackwell Scientific Publications, 1976, pp 341-344 10. Vogt EZ: Navajo, Perspectives in American Indian Culture Change. Edited by EH Spicer. Chicago, The University of Chicago Press, 1961, pp 278-336 New Approaches-Internal Medicine A course in new approaches to Internal Medicine will be held February 8-14, 1981 at the Wildwood Inn in Snowmass, Colorado. The objective of this course is to present the definition, pathogenesis, appropriate diagnostic approach, and best current management of problems commonly seen in general medical practice. Workshops and “Meet the Professor” sessions will be included. Registration is $250. Physicians practicing in Colorado may attend for $190. For further information, contact the Office of Postgraduate Medical Education, The University of Colorado School of Medicine, 4200 East Ninth Avenue, Denver, CO 80262, or call (303) 3945241.