Friday, February 16, 2007

Diagnosing Behcet's -- Part 2 (HLA testing)

I'm taking a look at the different types of information that doctors use in diagnosing a case of Behcet's disease. As a reminder, there are no specific blood test results, lab results or biopsy results that will definitely tell a doctor that you have Behcet's. Each of the posts that I make over the next few days will only provide a small piece of the puzzle. You need a doctor who's experienced in Behcet's diagnosis and treatment to pull all of the pieces together. The American Behcet's Disease Association maintains a Doctors' Registry on their website that lists patient-recommended doctors across the U.S. You can access the list here.

The following information is adapted from Essential Guide to Behcet's Disease, c.2003 J Zeis. References (appearing in parentheses) can be provided on request.

\\ HLA blood testing can help in diagnosis of Behcet's disease, although patients need to understand that the results are not specific to Behçet's (they also appear in people with other illnesses, and in people who are perfectly healthy), the test is expensive, it may not be covered by health insurance, and the final report can take weeks to arrive.

HLA stands for human leukocyte antigen. HLA types are inherited from both parents. The HLA types that appear on your test results will never change during your lifetime-just as your blood type (A, B, AB or O) always stays the same. HLA testing is used most often to see if organ donors and organ recipients are compatible, and it is also used for genetic counseling. Research over several decades has shown that HLA-B5 is found more often in the blood of Behçet's patients in Japan, Italy, Korea and Turkey, than in healthy people.(11) Zouboulis (1999) states that HLA-B51 presents a high risk for Behçet's disease in "a small geographic area of the Mediterranean Sea countries and Southern Asia."(146) HLA-B51, HLA-B52, HLA-B5101, and HLA-DR3 have also been implicated in Behçet's studies from various countries(11,14,40).

There is apparently no relationship between HLA results and Behçet's disease for patients in the US(12) and the UK(13). It should be noted, however, that a patient's ethnic background is more important in HLA typing than whether s/he is a resident of a Western country like the US.

While blood for an HLA test is drawn in the same way as standard blood tests, the HLA blood sample is usually forwarded to a specialized lab for processing. Your doctor may request that the lab produce results for HLA-A, HLA-B, HLA-C and/or HLA-D types. Your test results will arrive showing all of the HLA types that appear in your blood. Contrary to popular belief, your results won't show up stating that you "tested positive (or negative) for Behcet's", or "tested positive (or negative) for HLA-B5 or B51". For example, my doctor asked for HLA-A and HLA-B tests to be performed, and my report showed the following:

HLA AB Type: A2, A23; B7, B50

HLA-C and HLA-D testing was not performed (although I wish it had been, because new HLA links to various diseases are being found every year).

You can tell from my test results that I don't carry either of the typical HLA types that are common to Behçet's disease (B5 or B51). However, several research studies mention the possible involvement of HLA-A2 in situations where BD has shown up in more than one family member(189,191) - which may apply in my case. It's important to ask your doctor what the full results are from your HLA test, so that you can have a copy in your own records at home for future reference. Even if you don't carry any of the typical BD-type results, researchers have found links between some HLA results and other autoimmune and/or rheumatic diseases. For example, the following HLA types have been linked to cases of multiple sclerosis -- A3, DR15, DRB1, DRB5, DQB1; and lupus -- B8, DR3. If doctors are on the borderline between diagnosing you with Behcet's, MS, or lupus (or a combination of 2 of them, which is also possible), your total HLA "picture" will give them more information to work with.

"What does all of this HLA lingo mean to me, as a Behçet's patient?"
It means that there's much more to a Behçet's diagnosis than a simple test. If you have an HLA blood test that shows HLA-B5, B51, B5101, or DR3, there is a higher probability that Behçet's will be your diagnosis, than if those results hadn't shown up. However, Lee (2001), gives a general idea of the odds with the following statement: "In humans, Behçet's disease occurs in only 1 of 1000 individuals who have the HLA-B51 phenotype."(188)

It's important to know that you don't have to show ANY of the typical Behcet's-related HLA types in order to be diagnosed with Behçet's: physicians base a diagnosis on a combination of observed physical signs and symptoms, their personal experience in treating Behçet's patients, the patient's medical history, and the patient's test results.


  1. Dear Joanne,

    I look forward to reading your blog in more depth later. But for now, I'm glad I found it. As a journalist/writer, I see right away that you are a serious, and good, reporter! I will catch up on all of this soon. Thank you for putting your story and this complicated information out there. Best, Laura

  2. My 15 year old daughter has suffered from genital sores every time that she's had a cold for the last year and a half (4 times) and the gynecologist was sharp enough to suggest Behcet's. We just got her blood work back, today, and she is HLA-B51 positive. She doesn't have mouth sores (or at least none that she has been aware of) but I find it interesting that as her mother, I have had tens of mouth ulcers, and had genital sores once as a kid, making me think that I may have a mild version of it.
    I have read that the medicine for gout has been used to treat Behcet's, which interests me, since it helps reduce acid, and the miracle cure for my mouth ulcers was, you guessed it, Nexium, an acid reducer! Every time I got a cold for the first 34 years of my life, I would lose my voice for 3-6 weeks, and harbored a mouth full of ulcers. When I began to take Nexium, they went away. I have been free from multiple mouth ulcers ever since! I wonder if the same effect might work on genital ulcers. I wonder why I only had genital ulcers once... Dawn

  3. You stated that "Contrary to popular belief, your results won't show up stating that you "tested positive (or negative) for Behcet's", or "tested positive (or negative) for HLA-B5 or B51"; however, this is not always the case. I just got my HLA-B51 back today and it said "Positive for -HLA-B51, results out-of-range...This patient is positive for the genetic marker associated with Behcet's Disease". I just wanted to point out that some people do see this on their lab results.
    Thanks for all the great information! I truly appreciate it!

  4. That was great information. I am just now doing some research for my son, and came across this.My son has MS since 2005, recently added Uvietis.The blood work at U of M says he has the we go to the Reumatologist..and what will they do there? & Just because he has that HLA-B51,does that mean he will get it?

  5. My son of 20, has had 6 years of testing for various diseases... His symptoms have been severe 'shock' like nerve pain that has got progresively worse oveer these years. A week ago I mentioned to the Doctor (neurologist) that he has had bad mouth ulcers for the last one and a half months and gets them frequently. He was immediately sent for HLA B51 tests (results pending). He has also had a few stomach upsets (diahrrea today) We have been searching the world looking for help as nothing that he has been prescribed to date has helped with the nerve pain. Just interested to hear what anyone has to say about all this. By the way, live in South Africa, white, with English and Afrikaans ancestors and a father who was adopted (no idea of ancestors on his side)

  6. i have b55 and b46 no 51. i have behcets but they are thinking i may have something alongside behcets due to severity of my pain and symptoms

    what are the b55 and b46 associated with do you have any idea?