ANKYLOSING SPONDYLITIS IN AFRICAN BLACKS

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1366 ANKYLOSING SPONDYLITIS IN AFRICAN BLACKS IAN. CHALERS Over a period of years in a large African teaching hospital, only 8 patients with ankylosing spondylitis were seen.

1 1366 ANKYLOSING SPONDYLITIS IN AFRICAN BLACKS IAN. CHALERS Over a period of years in a large African teaching hospital, only 8 patients with ankylosing spondylitis were seen. This small number supports the impression that the disease is rare in African blacks. Patients tended to be relatively old and to have severe disease. None had iritis or a positive family history. The HLA- B7 antigen was found in only 1 patient. Ankylosing spondylitis is believed to be rare in African blacks (1,). A search of the English language literature conducted in 1976 revealed only 11 cases reported from Africa south of the Sahara during the preceding 16 years (3). The author and his colleagues reported 3 additional cases, which were the only black patients with ankylosing spondylitis seen over % years in a hospital serving approximately million people. Another recent report () documents a single example of the disease seen at Ahmadu Bello University Hospital in Northern Nigeria over a period of 3 years. Because reports of ankylosing spondylitis from Africa have been few and often brief, no clear picture of its spectrum or of contrasts with the disease in other races has emerged. In addition to the 3 patients previously reported (3), the author has seen more, making a total of 8 patients observed over a -year period at King Edward VIII Hospital, Durban, South Africa. On the basis of this series, some interesting features of an- From the Department of edicine, University of Natal and the King Edward VIII Hospital, Durban, South Africa. Ian. Chalmers, B, RCP, FRCP(C): Lecturer in edicine and Specialist Physician; presently Assistant Professor of edicine (Rheumatology), emorial University of Newfoundland. Address reprint requests to Ian. Chalmers, B, St. Clare s ercy Hospital, St. John s, Newfoundland AlC B8, Canada. Submitted for publication December 17, 1979; accepted in revised form August 13, kylosing spondylitis in the black population served by this institution have become apparent. PATIENTS AND ETHODS The patients were seen between August 197 and August 1978 at King Edward VIII Hospital. This institution is a secondary and tertiary referral center for an African black population of approximately million and, through its outpatient department and peripheral clinics, provides primary care for about 300,000 people. Annual black outpatient attendances and inpatient admissions number approximately 800,000 and 80,000, respectively. The hospital is government owned and operated and is funded from tax revenues. Patients are charged a nominal attendance fee based on income. No patient is turned away on the basis of inability to pay, but long waiting times and large crowds do act as a deterrent. Patients also tend to seek help from traditional practitioners before resorting to western-style medicine. This phenomenon would tend to exclude those with mild or short-lived symptoms. The author requested referral of rheumatic problems from his colleagues throughout the hospital. They were informed of his special interest in ankylosing spondylitis and responded generously and enthusiastically. Clinic and ward records were also checked from time to time. Each patient was personally examined by the author. edical and family histories were obtained in as much detail as possible, and attempts were made to contact relatives for corroboration. This was possible in only one patient, whose two adult sons agreed to be interviewed. Routine hematologic and biochemical tests were carried out in the hospital laboratory. HLA antigens were determined by r.. G. Hammond of the Natal Institute of Immunology (). (Because the Hospital Administration had requested restraint in the use of expensive investigations, only the B7 antigen was sought in patients -8.) Appropriate radiographs were made of clinically involved sites. Each patient fulfilled the New York criteria for definite ankylosing spondylitis (6). There were no patients with possible or probable disease, other seronegative spondyl- Arthritis and Rheumatism, Vol. 3, No. 1 (December 1980)

2 ~ ANKYLOSING SPONDYLITIS IN AFRICAN BLACKS 1367 Table 1. Demographic features of 8 African black spondylitics Duration of disease by history Patients Sex Age (years) (Years) F ? arthropathies, or disorders of calcium and phosphorus metabolism. Individuals with degenerative spinal disease, idiopathic osteoporosis, tuberculous spondylitis, or ankylosing hyperostosis of the spine were excluded from the study. Because of the relatively advanced age of the patients in this series, ankylosing hyperostosis was specifically considered and excluded in each case, according to the criteria of Resnick et a1 (7). RESULTS Demographic features of the patients are given in Table 1. ean age at onset was 1 years and at pre- sentation 3 years. The age of onset of patient 8 is unknown because he had no back symptoms. The sex ratio of 7 men to 1 woman is as expected. All patients denied the occurrence of ankylosing spondylitis or other rheumatic diseases in family members. Objective confirmation of the family history was available only for patient 3; adult sons who were interviewed and examined had no clinical evidence of ankylosing spondylitis, and concurred with their father on its absence in other relatives. Table lists the patients clinical features, erythrocyte sedimentation rates, and HLA-B7 status. Other laboratory values were negative or normal, or were deranged by concurrent but unrelated diseases. With the exception of patient 8, all gave histories of ascending back pain, morning stiffness, and progressive immobility. Patients 1, 3, and 8 appeared to have burnt-out disease at the time of presentation and had no evidence of peripheral joint involvement. In the remaining patients, the disease was active and peripheral joints were affected. No patient gave a history suggestive of eye inflammation, and none had objective evidence of present or past iritis. Table. Clinical and selected laboratory findings in 8 African black spondylitics Patients ~ Chest ex- Peripheral Spinal Spinal pansion joint HLAtenderness mobility (cms) involvement Deformity ESR* B7 Other features Nil Nil 0 Nil Severe kyphosis 0 - Stroke; urinary tract infections: no evidence of cauda equina lesion Neck only 1.0 Left hip Nil 38 - Nil Sacroiliac, thoracic, lumbar Nil Cervical Sacroiliac, Lumbar, Nil 0 Nil Nil 0 Hips, knees Nil 0 Hips, knees, ankles, sternoclavicular joints, right elbow Nil 0 Hips,knees Severe kyphosis 17 - Congestive cardiomyopathy Flattened spinal curves; 7 + Rheumatic mitral valve hip and knee flexion disease; no aortic insufcontractures ficiency Nil 10 - Apical lung fibrosis; no evidence of tuberculosis Slight kyphoscoliosis; 60 - Hypertension right hip flexed and abducted; left hip flexed and adducted; both knees flexed 7 Sacroiliac, Slight residual 0 Hips, knees, Severe kyphosis Nil lumbar, mobility of ankles, elbows, thoracic, neck only wrists 8 Nil Neck only * Erythrocyte sedimentation rate: mm/ 1 hour, Westergren method. 1. Nil Nil 8 - Hepatocellular carcinoma; asymptomatic spondylitis discovered during investigation

1368 CHALERS Table 3. Radiologic abnormalities in 8 African black spondylitics._ Patients Sacroiliac ioints Lumbar spine Thoracic spine Cervical spine Penpheral joints I 3 6 1 8 Joint space widening.

3 1368 CHALERS Table 3. Radiologic abnormalities in 8 African black spondylitics._ Patients Sacroiliac ioints Lumbar spine Thoracic spine Cervical spine Penpheral joints I Joint space widening. erosions, sclerosis Joint space widening: erosions. sclerosis Bamboo spine Bamboo spine Bamboo spine Anterior and lateral Normal Normal syndesmoph ytes: vertebral body squanng Bamboo spine Bamboo spine Bamboo spine Flattened lumbar curve. Flattened thoracic curve Early syndesmophytes. vertebral body squaring; apophyseal joint early ankylosis syndesmophytes Bamboo spine Bamboo spine Bamboo spine Bamboo spine Bamboo spine Bamboo spine Vertebral body squaring; arkedly increased Early syndesmophytes early syndesmophytes thoracic kyphosis; no obvious syndesmophytes Advanced syndesmophyte formation from TI0 to SI Not examined visible on anteroposterior abdominal film; no lateral views available Normal Normal (including clinically involved left hip) Normal Loss ofjoint space and erosions in hips and knees, large erosions in relation to patellar tendon insertions trosive disease of knees; other involved joints radiologically normal of hips Erosive disease of knees; other involved joints radiologically normal Not examined Only patient had the HLA-B7 antigen, giving a positivity rate of 1.%. Radiologic abfiormalities are enumerated in Table 3. Patient 8 was not examined extensively because he was severely ill with malignant disease. Six patients had total spinal involvement, and radiologic changes were commensurate with the clinical abnormalities. Six patients had moderate or marked residual disability after treatment, including patients with chronic peripheral arthritis. DISCUSSION The finding of only 8 patients with ankylosing spondylitis in a hospital serving an African black population of million supports the impression of rarity of the disease in this group. It is of interest to consider a comparable white population in which one would anticipate finding,000 affected persons. This number is derived from the widely accepted prevalenke figure of 0.1% (8), which may be an underestimate (9,lO). Of course, not all of these hypothetical sufferers would be under medical care, let alone hospitalized for severe disease. Even though the two figures are not strictly comparable, however, they are nevertheless impressively different. The most interesting feature of this series of patients is that only one (patient ) possessed the HLA- B7 antigen. Since the first reports of a strong association between ankylosing spondylitis and this histocompatibility antigen (1 l,l), it has been recognized that this relationship may vary in populations other than whites of European origin. Thus, in American blacks with ankylosing spondylitis, about 0% have been found to carry HLA-B7 (13,1). The prevalence of HLA-B7 in the black American population at large is %, compared with 8% for their white compatriots (1), and the disease is about one-third as frequent in the former as in the latter (I). In African blacks, HLA- B7 is extremely rare (1), which is certainly true for the population from which the present study group was drawn (). It appears, therefore, that the great rarity of HLA-B7 in African blacks relates to a very low (but as yet undetermined) prevalence of ankylosing spondylitis and to an association between antigen and disease that may be even more tenuous than that seen in American blacks. Because of the small size of the present series, however, one cannot be sure that the positivity rate is significantly different from that seen in American blacks. These observations are nevertheless compatible with the view that ankylosing spondylitis in the latter population is largely determined by the white contribution to their gene pool (I). The weakening of the association between HLA- B7 and ankylosing spondylitis in black populations is explicable if one assumes less interracial variation in other etiologic factors. With increasing rarity of the antigen, there is a decline in the number of B7-positive cases and a consequent drop in the prevalence of the disease as a whole. B7-negative disease prevalence is less variable, so that as HLA-B7 prevalence declines,

4 ANKYLOSING SPONDYLITIS IN AFRICAN BLACKS 1369 the relative preponderance of patients who do not carry the antigen increases. This in no way negates the importance of HLA-B7 as a marker of disease susceptibility for individuals carrying the antigen, but the diagnostic value of the ant,igen in low prevalence populations is diluted. It is unfortunate that full tissue typing was not feasible during the latter part of this study. Therefore, it is impossible to comment on other possible associations such as that reported by Khan et a1 (16), who found twice the expected frequency of HLA-B7 in a series of B7-negative American black spondylitics. HLA-B7 was found in 1 of the 3 initial patients studied (patient ), but this antigen is common in the general African population (,1) so its relevance in this case is uncertain. Woodrow and Eastmond (17) have suggested that genes for psoriasis and ulcerative colitis may code for susceptibility to ankylosing spondylitis in the absence of HLA-B7 and, since the former two diseases are also almost unknown in Africans, their rarity may provide an additional explanation for the rarity of ankylosing spondylitis in this population. In addition to the lack of disease association with B7, the patients in this series show several other differences from the average white subject described in standard rheumatology texts (1 8,19). First, they were relatively old, their mean age at presentation being 3 years in contrast with the usual patient who is a late adolescent or young adult male (19). The age at presentation does not, of course, give a reliable indication of the age of onset, but it is worth noting that other investigators (16,17) have found the mean age of onset to be later in B7-negative patients than in those carrying the antigen. It may also be relevant that patient was both the youngest patient in the series and the only one to possess HLA-B7. A second point of difference is the absence of positive family histories of ankylosing spondylitis or related conditions. Similar observations have been made in relation to other B7-negative spondylitic populations (16,17). However, it is acknowledged that there was no objective confirmation of family histories other than in patient 3, and it is also possible that the apparent absence of family history is a random phenomenon imposed by the small size of the series. The patients reported in this study appeared to have disease of unusual severity, even allowing for its long duration in several cases. A study of only hospital patients inevitably introduces selection bias in which a more severe disease involvement is seen. Nevertheless, such a study lends credence to the view that absence of HLA-B7 does not confer immunity from severe disease (0). None of these patients had evidence of iritis, past or present. It is now believed that the occurrence of iritis in patients with ankylosing spondylitis is related to the presence of HLA-B7 and does not represent a complication of the disease per se (1). Therefore, it is not surprising that eye inflammation was not seen in this series of largely B7-negative cases. This study has provided an indication of the pattern of ankylosing spondylitis in an African population, notably the lack of association with HLA-B7. The late age of presentation and absence of positive family history concur with similar findings by other authors, but the true prevalence of the disease and accurate assessment of the spectrum of disease severity will require formal epidemiologic study. ACKNOWLEDGENTS The author thanks all his colleagues who assisted him in his search for cases and referred their patients to him, and r. ike Hammond of the Natal Institute of Immunology for the HLA antigen determinations. REFERENCES 1. Baum J, Ziff : The rarity of ankylosing spondylitis in the black race. Arthritis Rheum 1:1-18, Khan A: Race-related differences in HLA associations with ankylosing spondylitis and Reiter s disease in American blacks and whites. J Natl ed Assoc 70:1, Chalmers I, Seedat YK, udaliar Y: Ankylosing spondylitis in three Zulu men negative for the HLA B7 antigen. S Afr ed J 67-69, ulley GP: Ankylosing spondylitis in blacks. Lancet 1:109, Hammond G, Appadoo B, Brain P: HLA and cancer in South African Negroes. Tissue Antigens 9: 1-7, Bennett PH, Wood PNH: Third International Symposium on Population Studies of the Rheumatic Diseases. Amsterdam, Excerpta edica Foundation, 1968, p 6 7. Resnick D, Niwayama G, Utsinger P, Shapiro R: Newer concepts in ankylosing hyperostosis of the spine. Arthritis Rheum 19:818, Kellgren JH: The epidemiology of rheumatic disease. Ann Rheum Dis 3:109-1, Calin A, Fries JF: Striking prevalence of ankylosing spondylitis in healthy W7 positive males and females. N Engl J ed 93:83-839, Cohen L, ittal KK, Schmid FR, Rogers LF, Cohen KL: Increased risk for spondylitis stigmata in apparently healthy HL-AW7 men. Ann Intern ed 8:l-7, 1976

5 1370 CHALERS 11. Brewerton DA, Caffrey, Hart FD, James DCO, Nich- 011s A, Sturrock RD: Ankylosing spondylitis and HL-A7. Lancet 1:90-907, Schlosstein L, Terasaki PI, Bluestone R, Pearson C: High association of an HL-A antigen, W7, with ankylosing spondylitis. N Engl J ed 88:70-706, Good AE, Kawanishi H, Schultz JS: HLA B7 in blacks with ankylosing spondylitis or Reiter s syndrome. N Engl J ed 9: , Khan A, Kushner I, Braun WE: Low incidence of HLA-B7 in American blacks with spondyloarthropathies. Lancet 1:83, Payne R, Feldman, Cann H, Bodmer JG: A comparison of HLA data of the North American black with African black and North American Caucasoid populations. Tissue Antigens 9: 13-17, Khan A, Kushner I, Braun WE A subgroup of ankylosing spondylitis associated with HLA-B7 in American blacks. Arthritis Rheum Woodrow JC, Eastmond CJ: HLA B7 and the genetics of ankylosing spondylitis. Ann Rheum Dis , oll JH: Ankylosing spondylitis, Copeman s Textbook of the Rheumatic Diseases. Fifth edition. Edited by JT Scott. Edinburgh, Churchill Livingstone, 1978, pp Bluestone R: Ankylosing spondylitis, Arthritis and Allied Conditions. Ninth edition. Edited by DJ ccarty. Philadelphia, Lea and Febiger, 1979, pp Khan A, Kushner I, Braun WE: Comparison of clinical features in HLA-B7 positive and negative patients with ankylosing spondylitis. Arthritis Rheum , Brewerton DA: HL-A7 and acute anterior uveitis. Ann Rheum Dis 3 (Suppl 1):33-3, 197 International Leukemia arker Conference The International Leukemia arker Conference will be held February 1-18, 1981 in Vienna, Austria, and will consist of 3 symposia and 8 workshops. Topics will include hybridoma antibodies in leukemia research, subset specific markers of normal and malignant leukocytes, and the clinical relevance of leukocyte marker studies. For further information please write Dr. W. Knapp, c/o Weiner edizinische Akademie, Alser Strasse, A-1090 Vienna, Austria.

Ankylosing Spondylitis*

Ankylosing Spondylitis* JOHN BAUM, M.D. Professor of Medicine, Pediatrics, and Preventive Medicine and Community Health, University of Rochester School of Medicine, Rochester, New York Within the last