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.

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

  1. Stephen says:

    I was diagnosed with AS 18 years ago without MRI and without HLA-B27. Doctor was able to diagnose because of enthesitis, low-back pain and stiffness, and morning stiffness.

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    • Yes. AS can be diagnosed without MRI/ HLA- B27.

      Certain classical features like dactylitis, enthesitis along with inflammatory backache are good enough to reach a diagnosis without MRI/ HLA B27.

      in patients with long standing AS, X rays are good enough to make a diagnosis. However, they are not useful for early diagnosis.

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  2. thank you for such an informative post! can completely get a picture!

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  3. Bhavana says:

    How wonderful to have stumbled upon your blog!!

    My 40y old husband was diagnosed with AS after testing positive for HLA B27 marker. We have 2 little boys(5y and 1.7y) and Im desperate for another(girl!) He was diagnosed when our youngest was 3 mos old and he’s terrified of having already passed it on to our innocent babies-So no more kids!

    All that aside, how soon can we test our boys for this and is there any preventative action we can take? I would love to know if you are having any clinical trials/studies about AS in young patients. We live in Chennai.

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  4. Sagar Mehlawat (9971171751) says:

    Dear Sir,
    my name is sagar i’am 17yrs old and have back pain sinlosce last 6 months. my spine surgeon said that i have ankylosing spondylitis ,altough i’am HLA b27 negative and i have Vit D deficiency. then i went to a rheumatologost in army hospital. he told me every thing is normal and gave prescribed me anti inflammatory medicines. but sir i still have severe morning stiffness and pain in joints. when i workout i am alright and when i rest my whole spine and body becomes stiff.please sir give your opinion.

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    • Dear Sagar,

      As I’ve already pointed out, HLA-B 27 may be negative in some patients with ankylosing spondylitis. A MRI of the sacroiliac joints & lumbosacral spine may provide the answer to your backache. Kindly speak to your Rheumatologist about the same.

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  5. Tiffany says:

    Dear Sir, I’m 39. Lower back pain started when I was approx. 20.(1994/1995’ish??). For years it was infrequent (once a month for a day or so) and was a dull pain concentrated in a ball. Would take tylenol or a couple of Doan’s pills to alleviate the pain successfully. By 2003 pain levels and the length of time had increased. Chiropractic care, massage therapy, acupuncture, eastern medicine (herbs, etc), three years with the Florida Spine Institute with no improvement AND still no physical signs of damage. They could see inflammation (CRP levels) but nothing else. Then in 2007 began having joint pain (feet, wrists/hands, elbows, knees). Rheumatologist in Clearwater diagnosed me with AS AND RA based on history and physical exam. No positive HLAB27. Tried Humera, Methotrexate, Enbrel, etc… no miracle as I had hoped. Finally in 2011, MRI’s showed ‘L4/L5 disc bulge’. Pain has continued to worsen. Only relief is with pain relievers and muscle relaxers. In the last 6 months pain has moved into my mid-back and a couple of times seems to effect my entire rib cage. Very soar feeling which I must interpret as inflammation. Nighttime sleep is limiting. Take sleep aid and Lyrica to ward off night time pain which begins @ 3-4 am (3/4x week). Sometimes is localized in lower back but other times radiates all over my body and is very ‘nervy’ feeling (like I want to come out of my skin). Saw a new Rheumatologist and saw immediately that I was negative for the HLAB27 marker and discounted AS and possibly RA. She immediately mentioned Fibromyalgia. Based on this info. would you PLEASE give me a brief and general opinion? Especially interested in your thoughts on the MRI results as it relates to the progression of AS. No one WANTS to have A.S. but I also don’t want someone treating me that refuses to look at my full history. Thank you so much for your feedback!

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  6. ativan says:

    Greetings! Very helpful advice within this article! It’s the little changes that produce the largest changes. Thanks a lot for sharing!

    Like

  7. Amy Banham says:

    Hi Doc! Yes, I am female and my diagnosis was delayed for >8 years as I had the HLA B27 gene tested when my mother was diagnosed with AS who was HLA B27 positive. I was tested to see if I would inherit the disease but I am negative for the gene. I did have symptoms of AS back then but due to the neg blood test nothing was done. I am now 28 with grade 2 bilateral sacroiliitis on x-ray and taking DMARDS. Thanks for the post.

    Like

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