Ankylosing Spondylitis: Have you missed your diagnosis, as you were HLA-B27 negative?

Doctors as well as patients have equated ankylosing spondylitis with HLA-B27 since a long time. In fact, many of the patients call Ankylosing spondylitis ‘HLA-B27 disease’

This is good as far as awareness is concerned. But, on the flip side, many patients have missed the diagnosis, as they were HLA-B27 negative. This is particularly important, as the average delay in the diagnosis of Ankylosing spondylitis is 8- 11 yrs. The delay for women is even more than that of men. This is quite unacceptable as the first 10 years are the most important for a patient as the treatment can be initiated before permanent limitations of spinal mobility and deformity has set in.

Although HLA-B27 gene is the most important gene predisposing to Ankylosing spondylitis, studies have shown that it contributes only 20-30% of the total genetic risk. No doubt HLA-B27 is a strong risk factor for the development of Ankylosing spondylitis, but that does not mean that it is a must for diagnosis.

So, then how important is HLA-B27 for a diagnosis of Ankylosing spondylitis?
Only about 80-90% of the patients with AS have the HLA-B27 gene. That means that the rest could miss the diagnosis if one would totally depend on HLA-b27 for a diagnosis.
The converse of this is also interesting. Only 1% of people with HLA-B27 develop the disease. So, HLA-B 27 alone cannot be equated with AS in somebody with backache.

Low back pain is a relatively common symptom that may be associated with a variety of conditions other than AS. The single most important feature that raises the suspicion of AS is inflammatory backache. The characteristics of inflammatory backache are –(1) morning stiffness of > 30 minutes, (2) improvement in back pain with exercise but not with rest, (3) awakening because of back pain during the second half of the night only, and (4) alternating buttock pain.

Role of MRI
MRI of the sacroiliac joints is one of the best investigations for a definitive & early diagnosis of AS. HLA-B27 is not diagnostic of AS, but can only guide us towards a diagnosis. MRI of the SI joints can give a definite diagnosis by actually showing the inflamed SI joints. Though, MRI is a costly, time-consuming investigation; its utility in confirming the diagnosis in a particular individual cannot be understated.

All in all, let us not diagnose AS with HLA-B27 alone. Definitive history of inflammatory backache/ other features & MRI of the sacroiliac joints can be the best guide for the diagnosis.

References:
1. Brown MA, Kennedy LG, MacGregor AJ, et al. Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthritis Rheum 1997; 40: 1823–28.
2. Feldtkeller E, Khan MA, van der Heijde D, van der Linden S, Braun J. Age at disease onset and diagnosis delay in HLA-B27negative vs. positive patients with Ankylosing spondylitis. Rheumatol Int 2003; 23:61–6.
3. Blum U, Buitrago-Tellez C, Mundinger A, et al. Magnetic resonance imaging (MRI) for detection of active sacroiliitis – a prospective study comparing conventional radiography, scintigraphy, and contrast enhanced MRI. J Rheumatol 1996; 23:2107–2115.

Do have a look at this video to understand this better–