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OBJECTIVES: To determine the relative severity and compare the clinical expression of spondyloarthropathy (SpA) in men and women. METHODS: A clinical study was conducted in 43 women and 40 men who made up 80% of all individuals identified as having SpA in a community-wide epidemiologic study of Alaskan Eskimos. The study included interviews, physical, laboratory, radiographic and electrocardiographic examinations, record reviews, and functional assessments. A measure of relative severity was developed to evaluate disease impact in individual patients. The results in men and women were compared. RESULTS: No significant differences between men and women were found in many features, including the age of onset, frequency of inflammatory joint swelling or inflammatory back pain, physical signs of sacroiliitis, presence of skin changes, or positive family history of SpA. Women were less likely to have sacroiliac joint fusion, advanced spinal changes, uveitis, severe cardiac conduction and valvular abnormalities, and elevated erythrocyte sedimentation rates. According to our relative severity measure, a smaller proportion of women had severe disease than men. CONCLUSION: Although as many women as men were affected by SpA in the communities studied, severe disease was seen more often in men and a number of disease manifestations were more frequent or more marked in men. These discrepancies in disease severity and expression may contribute to the underdiagnosis of SpA in women and the long standing impression that SpA is a disease predominantly of men.

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OBJECTIVE: To define the clinical spectrum and disease manifestations of spondyloarthropathy (SpA) as seen in a community, rather than a referral setting. METHODS: Eighty percent (83/104) of all individuals identified as having SpA in a community wide epidemiologic study of Alaskan Eskimos and 83 age and sex matched controls from the same regions participated in a 5 year clinical study. The study included baseline and followup interviews, physical, radiographic, and electrocardiographic examinations, record reviews, and functional assessment. The medical records of an additional 83 age and sex matched controls were reviewed and followed over the same 5 year period. RESULTS: The spectrum of disease varied from very mild undifferentiated SpA (USpA) to incapacitating ankylosing spondylitis (AS). Most cases were mild. Overlapping clinical features were common in the different syndromes; 10% of the cases met more than 1 set of disease criteria. Axial signs and symptoms were more frequent in patients with AS, but occurred in over half of the patients with USpA and reactive arthritis (ReA) also. Peripheral joint involvement was noted in 85% of the AS cases, usually early in the course of disease. The patterns of joint involvement and enthesopathy were similar in SpA subjects with different syndromes and significantly different from those in control subjects. Patients with AS had a higher frequency of uveitis and of aortic root disease than patients with other syndromes. CONCLUSION: The results illustrate the extent of shared clinical features in the different SpA syndromes, and describe the frequency of different features associated with SpA in patients and matched controls in a community setting. ReA and USpA were more prevalent and less severe than AS in these populations.

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OBJECTIVE: To compare the prevalence of rheumatoid arthritis (RA) in related, but geographically separate, indigenous circumpolar populations. METHODS: Cases were identified by community survey in Russia and by examination of cases located through arthritis registries, a computerized patient information database, and query of local health care providers in Alaska. All possible cases were verified by examination and application of the American College of Rheumatology 1987 criteria. RESULTS: The prevalence rates of RA (age standardized to US population of 1980) varied from 0.62% in the Alaskan Yupik to 1.78% in the Alaskan Inupiat. The Russian Chukchi rate was 0.73% and that of the Siberian Eskimo was 1.42%. CONCLUSION: The Alaskan Yupik Eskimo and Chukchi natives had prevalence rates of RA within the usual range of North American Caucasian groups, in contrast to the Russian Siberian Eskimo and the Alaskan Inupiat Eskimo of the Barrow region, whose high rates approached those of unrelated North American native groups living in very different environments. The Alaskan Inupiat rate was significantly higher than that of the Alaskan Yupik (OR = 2.51, 95% CI 1.25-5.07; p = 0.013), but statistical inferences are limited in the Russian study populations by the small case numbers. The high prevalence rates probably have a genetic basis, although an environmental influence cannot be excluded.

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BACKGROUND: Undiagnosed cases of seronegative spondyloarthropathy (Spa) are often observed during epidemiologic studies. OBJECTIVE: To determine the extent of and the reasons for the underdiagnosis of Spa. METHODS: We studied 2 groups of Alaskan native patients with Spa using a standardized protocol that included an interview, physical examination, medical record review, and radiographic and laboratory examinations. One group consisted of patients identified in a communitywide epidemiologic study; the other group consisted of patients from related but geographically separate populations who had been diagnosed by a specialist in the hospital or a specialty clinic. All cases met the current classification criteria for Spa. The clinical and demographic features of the cases in the 2 groups were compared. RESULTS: Fifty-five (72%) of the 76 community cases that we identified in the epidemiologic study had not been diagnosed previously as Spa. Among the undiagnosed patients were 34 (94%) of the 36 women, 11 (65%) of the 17 patients with ankylosing spondylitis, 12 (36%) of the 33 patients with reactive arthritis, and 24 (100%) of those with undifferentiated Spa. The community and specialty clinic patient groups were similar in age of onset of joint and back pain and in overall symptoms. The specialty clinic group had a higher proportion of men, more severe disease, and a higher frequency of iritis. CONCLUSIONS: The diagnosis of Spa was missed more often than not in the primary care setting, probably because most of the cases were of mild or moderate severity and did not fit the classic descriptions of spondyloarthropathic disorders. The higher proportion of men among the specialty clinic cases probably reflects provider expectation as well as a slightly milder disease course in women.

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OBJECTIVE: To assess the role of HLA-B27 and other class I histocompatibility antigens in overall risk and clinical manifestations of spondyloarthropathy (SpA) in Alaskan Eskimos. METHODS: Class I antigens were studied in 104 patients with SpA and in 111 controls. The frequencies of HLA-A, B, and Cw antigens were determined in patients with SpA with various clinical manifestations and compared to frequencies observed in controls. RESULTS: Only HLA-B27 differed significantly in cases and controls. Except for B27, no association of particular antigens with specific syndromes or disease features was found. Patients with B27 had more extraarticular manifestations than patients who lacked B27 antigen. Patients putatively homozygous for B27 did not appear to have more severe disease than those who were heterozygotic. B27 was most closely associated with ankylosing spondylitis [odds ratio (OR) = 210], less so with reactive arthritis (OR = 12.9) and undifferentiated SpA (OR = 4.6). CONCLUSION: Observations in other population groups that implicated B27 cross reactive group (CREG) and other A, B, and Cw antigens as risk factors for developing SpA were not confirmed in Alaskan Eskimos. Nor were CREG or other B antigens either alone or in combination with B27 associated with specific clinical syndromes. Only HLA-B27 was strongly associated with disease and with extraarticular manifestations.

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AIMS: To compare the nature and frequency of spondylarthropathy in geographically separated but genetically related populations with a high prevalence of HLA-B27. METHODS: Using a common questionnaire and disease criteria, cases were ascertained through cross-sectional community surveys in Russia and by examination and study of possible cases identified through rheumatic disease registries and the Native Health Service's computerized patient care data system in Alaska. RESULTS: Similar overall prevalences of spondyloarthropathy (2.0-3.4%) and a similar spectrum of disease were found, including reactive arthritis, ankylosing spondylitis and undifferentiated spondylarthropathy. Psoriatic arthritis was very rare. CONCLUSION: No predisposition to one particular form of spondyloarthropathy was observed; genetic and microbial settings for a spectrum of disease were present. Among adults positive for the presence of HLA-B27 the prevalence of all types of spondylarthropathies was estimated to be 4.5%, all populations combined, and the prevalence of AS was estimated to be 1.6%.

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For epidemiologic studies of spondyloarthropathy in circumpolar peoples of Chukotka, Russia and Alaska, we gathered demographic, physical and laboratory data to provide a background for evaluating and comparing factors that may influence susceptibility and clinical expression of disease. The study groups included the Chukchi and Siberian Eskimo of Russia and the Inupiat and Yupik Eskimo of Alaska. The 4 groups were remarkably similar in population structure, educational attainment, mean hemoglobin concentrations and frequency of the Class I histocompatibility antigen HLAB27. The Alaskan and Chukotkan groups were similar in mean height, but the Alaskans had higher body weights and significantly greater body mass indexes, probably a reflection of a shift away from traditional lifestyle and diet. Differences in the frequencies of ABO and MN blood group antigens were also apparent, with higher frequencies of blood group M in the Alaskan populations, particularly the Inupiat.

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Parallel epidemiologic studies of spondyloarthropathy in aboriginal circumpolar populations were carried out by U.S. and Russian investigators. These complementary studies used the same data collection instrument and disease criteria to facilitate comparisons. During three expeditions to Siberia, Russian investigators collected cross-sectional data from four settlements of Eskimos and Chukchi Indians on the Chukotka peninsula for a study of disease prevalence. U.S. researchers collected cross-sectional data from Eskimos in four Alaskan regions for studies of prevalence and longitudinal data for studies of clinical manifestations, natural history, disease impact, and health care utilization. The aims of these studies were to describe the spectrum of spondyloarthropathy in these populations, and to lay the groundwork for investigations of the role of specific genetic and environmental factors in the pathogenesis and expression of disease. These studies were carried out with a minimum disruption to the native people.

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BACKGROUND: During a case-control study, data necessary for fulfilling diagnostic and classification criteria for spondyloarthropathy were collected from 121 patients. OBJECTIVE: To study the potential impact of differences between patient recall and the medical record on diagnosis and clinical characterization of spondyloarthropathy as a model of chronic disease. METHODS: The study was conducted among four Alaskan Eskimo populations served by the Alaska Native Health Service. Two sets of historical data were compiled for each subject, one acquired during the interview and the other derived from the medical record. Paired items from the interview and the medical record were analyzed to determine discrepancies and consequent effects on diagnosis, classification, and disease characterization. RESULTS: Significant differences were observed in the reporting of genitourinary or diarrheal illnesses preceding or associated with arthritis, the occurrence of eye inflammation in association with joint pain, the occurrence of joint pain and back pain together, and the age at onset of back pain all of which are important to the diagnosis and classification of spondyloarthropathy. In contrast, for information needed to establish the probable inflammatory nature of back pain, patient interview was more helpful than the medical records, which did not provide adequate details to differentiate inflammatory from mechanical back pain. CONCLUSIONS: Patient recall bias can substantially affect diagnosis and clinical assessment of chronic disease, as exemplified by spondyloarthropathy. Reliance on records alone, however, may lead to underestimation of features that require subjective appraisal by the patient.

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OBJECTIVE: To estimate the prevalence of spondyloarthropathies (SpA) in 2 Alaskan Eskimo populations, using improved methodology for case ascertainment and new, more inclusive classification criteria. METHODS: Through existing rheumatic disease registries, health care providers and the Alaska Area Native Health Service (AANHS) computerized patient information system, we identified all native residents of the 2 study regions with a diagnosis of any inflammatory arthritis or problems characteristic of SpA, such as iritis or persistent back pain. Individuals with such diagnoses or problems were evaluated in clinic, according to a standardized protocol (interview, examination), and by medical record review, pelvic radiography and laboratory tests. Each case was evaluated according to standard diagnostic criteria for the individual disease entities and by the Amor and European Spondylarthropathy Study Group (ESSG) preliminary classification criteria for SpA. RESULTS: We identified 104 cases of SpA in the combined Eskimo populations, an overall prevalence of 2.5% in adults aged 20 and over. Both undifferentiated (USpA) and reactive SpA were more common than ankylosing spondylitis (AS). CONCLUSION: Using the new criteria and a more effective approach to case ascertainment we found the prevalence of SpA to be about twice that found in our earlier studies of adult Eskimo populations. The prevalence of SpA was very similar in men and women. Despite the known high prevalence (25-40%) of HLA-B27 in the study populations we did not find the prevalence of any form of SpA to be as strikingly high as that of AS (6-10%) for the Canadian Haida.

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OBJECTIVE: To characterize the features of rheumatoid arthritis (RA) in Tlingit Indians, to identify the HLA-DR alleles associated with RA in the Tlingit, and to determine whether disease severity or specific clinical manifestations correlate with the presence of specific HLA antigens. METHOD: Thirty-seven Tlingit patients with RA and 75 controls were evaluated clinically; comparative HLA studies were carried out in 33 patients and 62 controls. RESULTS: The results of this clinical study of RA in the Tlingit confirms that the disease found in them is classical RA, characterized by an early age of onset, a high frequency of nodules, serum rheumatoid factor (RF) and antinuclear antibodies (ANA); an often severe clinical course, with a high frequency of erosive disease and frequent need for surgical joint repair, and an often positive family history. In Tlingit volunteers who did not have RA we also found an increased prevalence of RF and ANA. Neither HLA-DR1 nor DR4 was found to be associated with RA in the Tlingit. The commonest DR antigen in patients with RA was DR14. The most frequent DRB1 allele was DRB1*1402 (Dw16). CONCLUSION: The Tlingit population had a very high frequency of the DRB1*1402 allele, which shares key sequence homology with DRB1*0401 (Dw4) and DRB1*0101 (Dw1), associated with RA in other racial groups. No correlations were found between specific HLA-DRB1 alleles or combinations of alleles and specific disease features or severity.

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OBJECTIVE: To evaluate the preliminary classification criteria proposed by the European Spondylarthropathy Study Group (ESSG) in Alaskan Eskimo populations. METHODS: We examined, interviewed, and reviewed the records of 104 Eskimo patients with spondylarthropathy and 75 with other rheumatic disorders, and evaluated them according to the proposed criteria. RESULTS: We found an overall sensitivity of 88.5% and a specificity of 89.3%, which is similar to the reported values in European populations. CONCLUSION: The ESSG criteria performed well in a population very different from that in which they were developed, and deserve further evaluation as a much-needed and useful epidemiologic tool.

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A review of rheumatic diseases in the southeast coastal Indians of Alaska revealed high frequencies of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Both prevalence and incidence rates of RA were significantly higher and the peak age of incidence was younger in the southeast Alaskan Indian population than in Alaskan Eskimo groups and the United States population in general. The prevalence of SLE in the Alaskan Indian population was about twice that reported for most white populations. The frequency of seronegative spondyloarthropathic disorders was similar in the Alaskan Indian and Eskimo populations. Comparable studies of the prevalence of spondyloarthropathy in general have not been carried out in white populations. The prevalence rate of ankylosing spondylitis, one of the major types of spondyloarthropathy, did not differ significantly in the SE Indians from rates in predominantly white US populations.

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In a Yupik Eskimo population, the prevalence, incidence and clinical features of rheumatoid arthritis (RA) were similar to those described for the United States population in general. More frequent than RA were seronegative spondyloarthropathic disorders, many of which could not be classified by existing disease criteria. Of the adult patients with spondyloarthropathy only half could be classified as having Reiter's syndrome (RS), ankylosing spondylitis (AS) or psoriatic spondylitis. The remaining patients had many signs and symptoms consistent with spondyloarthropathy, but they either did not meet the diagnostic criteria for any specific disease or had features pathognomonic of more than one. The clinical manifestations of the patients who did not meet standard disease definitions are summarized and compared to those of the patients with RS, AS and psoriatic spondylitis. Because of the many shared features, we believe that these as yet unclassified disease states belong with AS and RS in a single spondyloarthropathic disease spectrum and should be defined and recognized as such.

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We analyzed the demographic, clinical, laboratory and histologic features of 13 patients who were diagnosed as having polyarteritis nodosa associated with hepatitis B virus infection over a 12-year period, 1974 to 1985. All 13 patients were Yupik Eskimos and resided in southwest Alaska, an area hyperendemic for hepatitis B virus infection. The annual incidence of hepatitis B virus-associated polyarteritis nodosa for this population is 7.7 cases per 100,000 population. All patients presented with multisystem disease, and all had biopsy or angiographic findings consistent with polyarteritis nodosa. All 13 were positive for hepatitis B surface antigen and hepatitis B e antigen at diagnosis. Two untreated patients and two of five patients who received corticosteroids died, vs. none of six who received corticosteroids plus cyclophosphamide. None of the patients who survived the initial bout of polyarteritis nodosa has relapsed after a mean follow-up of 55 months, but all have become chronic HBsAg carriers. In eight patients, clinical or serologic evidence indicated that polyarteritis nodosa followed recent hepatitis B virus infection. We concluded that hepatitis B virus-associated polyarteritis nodosa is a serious, life-threatening complication that occurs early in the course of hepatitis B virus infection, is ameliorated by immunosuppressive therapy and can be prevented by hepatitis B vaccine.

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We reviewed rheumatic diseases in an Inupiat Eskimo population and found a high frequency of seronegative spondyloarthritides. Most cases of juvenile arthritis, which occurred with particularly high incidence in male children (47.4/100,000), appeared to belong in the spondyloarthropathic category. Both Reiter's disease and undifferentiated spondyloarthropathy were common disorders in adults. The prevalence of ankylosing spondylitis (0.2%) was less than expected in a population with a high percentage of HLA-B27 positive individuals. The prevalence rates of rheumatoid arthritis (1.0%), gout (0.3%), and other rheumatic diseases were similar to those of the United States population in general.

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Six cases of hepatitis B-associated vasculitis occurred during a four-year period in Eskimos living in southwest Alaska, an area hyperendemic for hepatitis B. All showed positive results in tests for hepatitis B surface antigen (HBsAg), and all five patients tested for hepatitis B e antigen (HBeAg) showed positive values. Two patients died of the disease. Of three who recovered, two had positive values for HBsAg and HBeAg when tested two years later. In the villages of four patients, the prevalence of hepatitis B virus (HBV) infection ranged from 18.2% to 73.1%. Serological evidence of HBsAg was found in 22% and antibody to HBsAg (anti-HBs) in 30% of close relatives of the patients. Two patients had no previous serological evidence of infection with HBV, indicating that vasculitis followed recent infection. The results provide epidemiologic evidence of the clinical association between HBV infection and vasculitis.

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