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Prevalence of HLA-B27 in patients with back pain attending a pain clinic
Pain, 44 (1991) 147-149 a 1991 Elsevier Science Publishers ADONIS 030439599100068Q
147 B.V. 03043959/91/$03.50
PAIN 01725
Prevalence of HLA-B27 in patients with back pain attending a pain clinic M. O’Connor
and C.J. Glynn
Oxford Regional Pain Relief Unit, Abingdon Hospital, Abingdon, Oxfordrhire OX14 IAG (U.K.), and Nuffield John Radcliffe Hospital, Oxford OX3 9D U (U.K.) (Received
15 March
1990, revision received 5 July 1990, accepted
3 August
Depariment
of Anaesthetics,
1990)
101 patients presenting to a pain clinic with low back pain were tested for HLA-B27 status. Eight Summary (7.9%) of the patients were positive for HLA-B27. This prevalence is similar to that recorded in the general population and suggests that few patients referred to our clinic with back pain have undiagnosed spondyloarthropathies. Key words: Low back pain;
HLA-B27;
Ankylosing
spondylitis;
Spondyloarthropathies
Results
Introduction Spondyloarthropathies are underdiagnosed; in particular ankylosing spondylitis (AS) has a probable prevalence of 1% in the general population and 98% of these individuals are HLA-B27 positive [l]. The present study was undertaken to determine the prevalence of HLAB27 in patients with chronic back pain attending a pain clinic.
101 patients were studied. Eight were HLA-B27 positive and 93 were negative. None of the other characteristics of the patients were different between groups (Table I).
TABLE
Methods 101 patients presenting to the pain clinic back pain who had not been diagnosed as from AS were tested for HLA-B27 status. duration and radiation of pain, history of myelography and surgery, and clinical signs termined from the notes.
I
AGE, SEX AND CHARACTERISTICS POSITIVE AND NEGATIVE PATIENTS
with low suffering Age, sex, previous were de-
Statistical analysis Prevalences of HLA-B27 were compared by a z test, which has a power of 0.86 to detect a doubling of the prevalence in the patients compared with the local population. Student’s t test was used to compare the characteristics of HLA-B27 positive and negative patients.
Correspondence to: Dr. Michael O’Connor, Department Anaesthetics, Princess Margaret Hospital, Okus Road, Swindon 4JU, U.K.
of SNl
OF
PAIN
Values are expressed as mean (and standard deviation). square brackets express percentage within each group.
IN
HLA-B27
Numbers
HLA-B27
Number Age at onset of pain (years) Sex Male Female Duration of pain (years) Radiation of pain One leg Both legs Signs Absent or abnormal sensation Loss of power Abnormal reflexes Myelography Laminectomy
Positive
Negative
8 39.5
(8.8)
93 44.5 (14.4)
2 [25%] 6 [75%] 3.6 (2.2)
37 [40X] 56 [60%] 8.1 (7.5)
3 1
[38%] [13%]
47 18
(51%] [19%]
2
12581
14
[15%]
1 1 3 1
[13%] [13%] [38&l [13%]
1 7 33 27
11%1 WI [36%] [29%]
in
148
Discussion
The HLA antigens are found on chromosome 6. There are 4 genetic regions designated HLA A. B, C and D and a large number of alleles have been found at each region. More than 40 diseases have been associated with particular HLA types. Some of the strongest associations are between HLA-B27 and the spondyloarthropathies: AS, psoriatic arthritis, reactive arthritis (including Reiter’s syndrome) and HLA-B27 associated peripheral arthropathy. 20% of HLA-B27 positive individuals have symptomatic AS [l]. In the local area 8.2% of the population have the HLA-B27 antigen. Understanding of AS has improved considerably over the last few years. It used to be thought to be a rare disease with a prevalence of 1 in 2000 and a 10 to 1 male to female ratio [13]. More recent studies suggest a prevalence of about 1% of the general population and an equal male to female ratio [l]. The prevalence of undiagnosed AS is high (possibly 90% of those with the disease) because the disease is still considered to be rare. it has an undramatic evolution and because of difficulty in reading and interpreting radiographs [l]. In particular the diagnosis is often missed in women because of a low index of suspicion and a different clinical presentation with a less severe illness. more peripheral joint involvement, less rapid progression, less dramatic spinal changes and more cervical involvement [8]. There is a typical delay in diagnosis in women of 10 years [7,10,11]. Calin has suggested that patients can be screened for AS by the presence of characteristic pain symptoms [2,3]: (1) persistence for longer than 3 months: (2) age at onset less than 40 years; (3) insidious onset; (4) association with morning stiffness; and (5) improvement with exercise. Such a questionnaire is unlikely to be so useful in a pain clinic population; for example, all our patients had had pain persisting for more than 3 months. Although tissue typing for HLA-B27 is not generally thought to be helpful in the routine investigation of an individual with suspected AS [4], it can be used to screen groups of patients. Jajic [S] determined the HLA status in 652 patients with back pain attending a rheumatology clinic and 302 subjects with no symptoms. 42.4% of the back pain patients were HLA-B27 positive compared with 12.2% of the control subjects (P < 0.001). Of the HLA-B27 positive patients 46.3% had AS. Jajic argued that the determination of HLA-B27 status is therefore of diagnostic, prognostic and therapeutic significance. However, neither Grahame et al. [6] nor Sandstrom et al. [12] found an increased HLA-B27 prevalence in patients with back pain attending orthopaedic clinics. The results of the present study indicate that the prevalence of HLA-B27 in patients with back pain
attending the pain clinic 15 Gmilar to that in cwthctpaedic clinics and in the c~~n~Inunit~. There are s number of facts that might help to explain this finding. Back pain is common: in Great Britain 375.000 people a year. a proportion approaching 19 of the population, have ;I period of certified sickness incapacity because of back pain [14]. Many people are able to continue at work with back pain and these figures therefore underestimate the problem. Dunnell and Cartwright f5] reported that in a 14 dav period 21% of adults experience back pain. By contrast in 1987 only 55 new patients with back pain were referred to this clinic from a district population of 543,600. Considerable selection must therefore occur in determining which patients find their way to a pain clinic. The patients seen in pain clinics are often those with severe pain in whom no certain diagnosis has been made and who have failed to respond to conventional therapy. By contrast, the back pain of AS is not necessarily severe. It may be that patients who have early or undiagnosed AS have pain that responds well to nonsteroidal anti-inflammatory drugs and these patients are managed by their General Practitioners, while patients with diagnosed rheumatological disorders such as AS are referred to rheumatology rather than pain clinics.
Acknowledgements
The authors thank Mr. Charles Stiller of the Childhood Cancer Research Group, University of Oxford, for his help with the statistical analysis.
References
1 Calin. A. and Fries, J.F., Striking prevalence
of ankylosing spondylitis in ‘healthy’ W27 positive males and females. A controlled study, New Engl. J. Med., 293 (1975) 835-839. 2 Calin, A., Kaye. B., Sternberg. M.. Anteil, B. and Ghan, M.. The prevalence and nature of back pain in an industrial complex. A questionnaire and radiographic and HLA analysis, Spine, 5 (1980) 201-205. Calin, A.. Porta, J.. Fries, J.F. and Schurman, D.J., Clinical history as a screening test for ankylosing spondylitis, JAMA, 237 (1977) 2613-2614. Dieppe, P.A.. Doherty, M., Macfarlane. D.G. and Maddison. P.J., Rheumatological Medicine. Churchill Livingstone, Edinburgh, 1985. Dunnell, K. and Cartwright, A., Medicine Takers, Prescribers and Hoarders, Routledge and Kegan Paul, London. 1972, pp. 8-12. Grahame, R.. Calin. A., Tudor, M. et al., HL-A 27 as a diagnostic aid. In: Prof. 7th Int. Congr. of Internal Medicine, Tel Aviv. 1974. Hill, H.F.H., Hill. A.G.S. and Bodmer, J.G., Clinical diagnosis of ankylosing spondylitis in women in relation to presence of HLA827. Ann. Rheum. Dis.. 35 (1976) 267-270. Jajic, I.. The role of HLA-B27 in the diagnosis of low back pain, Acta Orthop. Stand., 50 (1979) 411-413. Marks. S.H., Barnett, M. and Calin, A., Ankylosing spondylitis in women and men: a case control study, J. Rheumatol., 10 (1983) 624-628.
149 10 McBryde. Jr., A.M. and McCollum, D.E., Ankylosing spondylitis in women. The disease and its prognosis, N.C. Med. J.. 34 (1973) 34-37. 11 Resnick, D., Dwosh, I.L., Goergen, T.G. et al., Clinical and radiographic abnormalities in ankylosing spondylitis: a comparison of men and women, Radiology, 119 (1976) 293-297. 12 Sandstrom, J., Andersson, G.B.J. and Rydberg, L., HLA-B27 as a
diagnostic screening tool in chronic low back pain, Stand. J. Rehab. Med., 16 (1984) 27-28. 13 West, H.F., The aetiology of ankylosing spondylitis, Ann. Rheum. Dis., 8 (1949) 143-148. 14 Working Group on Back Pain, Report to Secretary of State for Social Services and Secretary of State for Scotland, Her Majesty’s Stationery Office, London, 1979.
147 B.V. 03043959/91/$03.50
PAIN 01725
Prevalence of HLA-B27 in patients with back pain attending a pain clinic M. O’Connor
and C.J. Glynn
Oxford Regional Pain Relief Unit, Abingdon Hospital, Abingdon, Oxfordrhire OX14 IAG (U.K.), and Nuffield John Radcliffe Hospital, Oxford OX3 9D U (U.K.) (Received
15 March
1990, revision received 5 July 1990, accepted
3 August
Depariment
of Anaesthetics,
1990)
101 patients presenting to a pain clinic with low back pain were tested for HLA-B27 status. Eight Summary (7.9%) of the patients were positive for HLA-B27. This prevalence is similar to that recorded in the general population and suggests that few patients referred to our clinic with back pain have undiagnosed spondyloarthropathies. Key words: Low back pain;
HLA-B27;
Ankylosing
spondylitis;
Spondyloarthropathies
Results
Introduction Spondyloarthropathies are underdiagnosed; in particular ankylosing spondylitis (AS) has a probable prevalence of 1% in the general population and 98% of these individuals are HLA-B27 positive [l]. The present study was undertaken to determine the prevalence of HLAB27 in patients with chronic back pain attending a pain clinic.
101 patients were studied. Eight were HLA-B27 positive and 93 were negative. None of the other characteristics of the patients were different between groups (Table I).
TABLE
Methods 101 patients presenting to the pain clinic back pain who had not been diagnosed as from AS were tested for HLA-B27 status. duration and radiation of pain, history of myelography and surgery, and clinical signs termined from the notes.
I
AGE, SEX AND CHARACTERISTICS POSITIVE AND NEGATIVE PATIENTS
with low suffering Age, sex, previous were de-
Statistical analysis Prevalences of HLA-B27 were compared by a z test, which has a power of 0.86 to detect a doubling of the prevalence in the patients compared with the local population. Student’s t test was used to compare the characteristics of HLA-B27 positive and negative patients.
Correspondence to: Dr. Michael O’Connor, Department Anaesthetics, Princess Margaret Hospital, Okus Road, Swindon 4JU, U.K.
of SNl
OF
PAIN
Values are expressed as mean (and standard deviation). square brackets express percentage within each group.
IN
HLA-B27
Numbers
HLA-B27
Number Age at onset of pain (years) Sex Male Female Duration of pain (years) Radiation of pain One leg Both legs Signs Absent or abnormal sensation Loss of power Abnormal reflexes Myelography Laminectomy
Positive
Negative
8 39.5
(8.8)
93 44.5 (14.4)
2 [25%] 6 [75%] 3.6 (2.2)
37 [40X] 56 [60%] 8.1 (7.5)
3 1
[38%] [13%]
47 18
(51%] [19%]
2
12581
14
[15%]
1 1 3 1
[13%] [13%] [38&l [13%]
1 7 33 27
11%1 WI [36%] [29%]
in
148
Discussion
The HLA antigens are found on chromosome 6. There are 4 genetic regions designated HLA A. B, C and D and a large number of alleles have been found at each region. More than 40 diseases have been associated with particular HLA types. Some of the strongest associations are between HLA-B27 and the spondyloarthropathies: AS, psoriatic arthritis, reactive arthritis (including Reiter’s syndrome) and HLA-B27 associated peripheral arthropathy. 20% of HLA-B27 positive individuals have symptomatic AS [l]. In the local area 8.2% of the population have the HLA-B27 antigen. Understanding of AS has improved considerably over the last few years. It used to be thought to be a rare disease with a prevalence of 1 in 2000 and a 10 to 1 male to female ratio [13]. More recent studies suggest a prevalence of about 1% of the general population and an equal male to female ratio [l]. The prevalence of undiagnosed AS is high (possibly 90% of those with the disease) because the disease is still considered to be rare. it has an undramatic evolution and because of difficulty in reading and interpreting radiographs [l]. In particular the diagnosis is often missed in women because of a low index of suspicion and a different clinical presentation with a less severe illness. more peripheral joint involvement, less rapid progression, less dramatic spinal changes and more cervical involvement [8]. There is a typical delay in diagnosis in women of 10 years [7,10,11]. Calin has suggested that patients can be screened for AS by the presence of characteristic pain symptoms [2,3]: (1) persistence for longer than 3 months: (2) age at onset less than 40 years; (3) insidious onset; (4) association with morning stiffness; and (5) improvement with exercise. Such a questionnaire is unlikely to be so useful in a pain clinic population; for example, all our patients had had pain persisting for more than 3 months. Although tissue typing for HLA-B27 is not generally thought to be helpful in the routine investigation of an individual with suspected AS [4], it can be used to screen groups of patients. Jajic [S] determined the HLA status in 652 patients with back pain attending a rheumatology clinic and 302 subjects with no symptoms. 42.4% of the back pain patients were HLA-B27 positive compared with 12.2% of the control subjects (P < 0.001). Of the HLA-B27 positive patients 46.3% had AS. Jajic argued that the determination of HLA-B27 status is therefore of diagnostic, prognostic and therapeutic significance. However, neither Grahame et al. [6] nor Sandstrom et al. [12] found an increased HLA-B27 prevalence in patients with back pain attending orthopaedic clinics. The results of the present study indicate that the prevalence of HLA-B27 in patients with back pain
attending the pain clinic 15 Gmilar to that in cwthctpaedic clinics and in the c~~n~Inunit~. There are s number of facts that might help to explain this finding. Back pain is common: in Great Britain 375.000 people a year. a proportion approaching 19 of the population, have ;I period of certified sickness incapacity because of back pain [14]. Many people are able to continue at work with back pain and these figures therefore underestimate the problem. Dunnell and Cartwright f5] reported that in a 14 dav period 21% of adults experience back pain. By contrast in 1987 only 55 new patients with back pain were referred to this clinic from a district population of 543,600. Considerable selection must therefore occur in determining which patients find their way to a pain clinic. The patients seen in pain clinics are often those with severe pain in whom no certain diagnosis has been made and who have failed to respond to conventional therapy. By contrast, the back pain of AS is not necessarily severe. It may be that patients who have early or undiagnosed AS have pain that responds well to nonsteroidal anti-inflammatory drugs and these patients are managed by their General Practitioners, while patients with diagnosed rheumatological disorders such as AS are referred to rheumatology rather than pain clinics.
Acknowledgements
The authors thank Mr. Charles Stiller of the Childhood Cancer Research Group, University of Oxford, for his help with the statistical analysis.
References
1 Calin. A. and Fries, J.F., Striking prevalence
of ankylosing spondylitis in ‘healthy’ W27 positive males and females. A controlled study, New Engl. J. Med., 293 (1975) 835-839. 2 Calin, A., Kaye. B., Sternberg. M.. Anteil, B. and Ghan, M.. The prevalence and nature of back pain in an industrial complex. A questionnaire and radiographic and HLA analysis, Spine, 5 (1980) 201-205. Calin, A.. Porta, J.. Fries, J.F. and Schurman, D.J., Clinical history as a screening test for ankylosing spondylitis, JAMA, 237 (1977) 2613-2614. Dieppe, P.A.. Doherty, M., Macfarlane. D.G. and Maddison. P.J., Rheumatological Medicine. Churchill Livingstone, Edinburgh, 1985. Dunnell, K. and Cartwright, A., Medicine Takers, Prescribers and Hoarders, Routledge and Kegan Paul, London. 1972, pp. 8-12. Grahame, R.. Calin. A., Tudor, M. et al., HL-A 27 as a diagnostic aid. In: Prof. 7th Int. Congr. of Internal Medicine, Tel Aviv. 1974. Hill, H.F.H., Hill. A.G.S. and Bodmer, J.G., Clinical diagnosis of ankylosing spondylitis in women in relation to presence of HLA827. Ann. Rheum. Dis.. 35 (1976) 267-270. Jajic, I.. The role of HLA-B27 in the diagnosis of low back pain, Acta Orthop. Stand., 50 (1979) 411-413. Marks. S.H., Barnett, M. and Calin, A., Ankylosing spondylitis in women and men: a case control study, J. Rheumatol., 10 (1983) 624-628.
149 10 McBryde. Jr., A.M. and McCollum, D.E., Ankylosing spondylitis in women. The disease and its prognosis, N.C. Med. J.. 34 (1973) 34-37. 11 Resnick, D., Dwosh, I.L., Goergen, T.G. et al., Clinical and radiographic abnormalities in ankylosing spondylitis: a comparison of men and women, Radiology, 119 (1976) 293-297. 12 Sandstrom, J., Andersson, G.B.J. and Rydberg, L., HLA-B27 as a
diagnostic screening tool in chronic low back pain, Stand. J. Rehab. Med., 16 (1984) 27-28. 13 West, H.F., The aetiology of ankylosing spondylitis, Ann. Rheum. Dis., 8 (1949) 143-148. 14 Working Group on Back Pain, Report to Secretary of State for Social Services and Secretary of State for Scotland, Her Majesty’s Stationery Office, London, 1979.