HLA-B27 Syndromes

What is HLA-B27 Syndromes?

Ever since the early 1970s, scientists have discovered a relationship between a gene called HLA-B27 and a disease called ankylosing spondylitis. Although this gene can be found in many people, it greatly increases the chance of developing a group of inflammation-related joint conditions, also known as spondyloarthritis. Other diseases, especially acute anterior uveitis (an inflammation of the eye), are also strongly related to the HLA-B27 gene.

Even though the HLA-B27 gene is linked to spondyloarthritis, experts are still learning about its role in causing immune system problems. It’s also found, although less often, in people suffering from conditions like inflammatory bowel disease, psoriatic arthritis (a type of arthritis affecting some people with psoriasis), and reactive arthritis (a condition causing inflammation, often in the joints).

What Causes HLA-B27 Syndromes?

Human leukocyte antigens (HLA) are specific parts of our genes located on chromosome 6, found in all cells with a nucleus. Their main job is to catch and present harmful substances, like components of viruses or other harmful microorganisms, to specialized immune cells known as cytotoxic T cells. Their role is crucial to our body’s ability to fight off diseases.

Research has shown that autoimmune diseases, where the body mistakenly attacks its own cells, are generally caused by a complex mix of environmental and genetic factors. However, in most cases, the presence of certain features in the HLA region of our genes makes a person more prone to autoimmune diseases.

A remarkable example is the HLA-B27 feature. This unique genetic marker has been shown to cause spondyloarthritis (a type of arthritis that affects the spine) in animals, even when no other disease factors are present. Although we have lots of studies on the relationship between the HLA region and disease, it is still not entirely clear how HLA-B27 makes people more likely to develop spondyloarthritis.

Risk Factors and Frequency for HLA-B27 Syndromes

The HLA-B27 allele is found more commonly in regions towards the north and is present in about 6 to 8 percent of people in the United States. However, most people carrying this allele do not develop a syndrome associated with HLA-B27. There are over 100 subtypes of HLA-B27, each with various links to a condition called spondyloarthritis.

Though having the HLA-B27 allele is not necessary for developing spondyloarthropathy, it is strongly linked to the condition. Many other genetic factors have been identified that can contribute to the development of this disease. HLA-B27 is responsible for about 30 percent of the heritability of another condition known as ankylosing spondylitis. The rate of acute anterior uveitis (a type of eye inflammation) in people with HLA-B27 can range from 40 to 82.5 percent. Interestingly, this eye condition can manifest about three years before ankylosing spondylitis starts.

An estimated 0.5 to 1% of the US population suffers from a disease called axial spondyloarthropathy.
Men often display clear signs of this disease on X-rays. However, advances in identifying cases without radiographic signs have challenged the notion that this disease is more common in males.
Typically, symptoms start to appear when people are between twenty and forty years old.
More than 20% of affected patients may also develop acute anterior uveitis.

Psoriatic arthritis affects about 6 individuals per 100,000 each year and is prevalent in 1 to 2 in every 1000 people.
It affects both genders equally.
Interestingly, it can manifest even before the appearance of psoriasis in about 10 to 15% of patients.
About one-third of people with psoriasis might develop psoriatic arthritis.
The risk increases for people with severe skin psoriasis, obesity, and psoriasis affecting the scalp, buttocks crease, and nails.

Another condition, reactive arthritis, also impacts both men and women equally and typically affects young adults. Certain bacteria that cause food poisoning and sexually transmitted infections can trigger this type of arthritis. Individuals with the HLA-B27 allele are more likely to develop chronic arthritis following these infections, especially if caused by the Shigella bacteria. However, it is thought that the prevalence rate for this condition (0.1%) might be underestimated because some people might have asymptomatic infections acting as triggers.

Signs and Symptoms of HLA-B27 Syndromes

HLA-B27 associated syndromes are a group of conditions that often have unique patterns of symptoms, important to identify when evaluating these diseases.

The main symptom of a condition known as axial spondyloarthritis is back pain due to inflammation. You can differentiate this pain from regular back pain due to its slow development over about three months, and it usually starts before the age of 45. It can cause significant pain at night, make you feel stiff in the morning, and it doesn’t improve with rest. Instead, it tends to get better with exercise. When someone has this type of back pain, they should get checked for other symptoms of spondyloarthritis, such as:

Inflammation of the eye (uveitis)
Inflammation of fingers or toes (dactylitis)
Inflammatory bowel disease
Psoriasis
Inflammation at the insertion point of a tendon (enthesitis), especially on the heel

Having a family history of the condition or responding well to anti-inflammatory medication can increase the likelihood of having spondyloarthritis. Your doctor might perform specific tests during a physical exam, like checking flexibility and pain reaction.

In other forms of spondyloarthritis that mainly affect the arms or legs, you’ll see similar symptoms, such as inflammatory arthritis, dactylitis, and enthesitis. Some people with these symptoms also have psoriatic arthritis, usually preceded by psoriasis on the skin. Negative changes in the skin and nail discoloration can correspond with developing psoriatic arthritis.

Another syndrome linked to HLA-B27 is reactive arthritis. This disease begins with a sudden onset of inflammation in multiple joints, usually after a urinary or intestinal infection. Symptoms can include inflammation of the urethra (urethritis) or eyes (uveitis).

HLA-B27 is also associated with acute anterior uveitis (AAU), a non-infectious inflammation of the eye. Young people between 20 to 40 usually get this condition. Symptoms include an abrupt start of eye pain and redness in one eye and possible vision loss. On examination, white blood cells can be seen in the front chamber of the eye, and it can cause other complications as well.

Inflammatory bowel disease, a condition involving inflamed bowels, can show up before or after any arthritis symptoms linked to the condition. This condition may cause changes in bowel habits and blood in the stool. Additionally, many patients might experience under-the-radar inflammation in their colon.

Testing for HLA-B27 Syndromes

Spondyloarthritis and other syndromes related to HLA-B27 don’t have one specific diagnostic symptom or sign. Doctors use different methods to try to diagnose these conditions. One method is using X-ray images of your sacroiliac joints (the joints in your lower back where the spine meets the pelvis). X-rays can pick up changes like damage, thickening, or fusion of these joints. However, these changes may not show up in the early stages of the disease. Sometimes, patients may have all the symptoms of the disease without any significant changes showing up on their X-ray, a condition known as non-radiographic axial spondyloarthritis.

In such cases, doctors might use other ways to find out if inflammation (swelling) is present, which is a key sign of these conditions. They might do a blood test for a substance called C reactive protein that increases in response to inflammation in the body. They could also use a specific type of MRI scan called a short tau inversion recovery (STIR) scan for this purpose. However, inflammation observed through imaging needs to be seen in the light of the patient’s overall health condition and symptoms, as such changes can occur even in healthy people or athletes.

Imaging of the lumbar spine (lower part of the spine) in spondyloarthritis patients may display a squaring of the vertebrae (bones in the spine) as an early sign. More specific signs that come up later are the formation of syndesmophytes (bony growths inside the spine) and fusion of facet joints (small joints located between and behind adjacent vertebrae). A classic late sign in these conditions is a “bamboo” spine, which is a fully fused spine that resembles a bamboo.

Doctors can also detect inflammation in the tendons, a feature of these conditions, by using power Doppler ultrasound. It gives a more detailed image of the tendons and can confirm the presence of inflammation and any damage at the tendon attachment sites.

If there is swelling in any of your joints, doctors may also use a needle to remove and analyze the fluid from the joint, a procedure known as arthrocentesis. This fluid usually contains a high number of white blood cells (cells that fight infection and disease) in people suffering from inflammatory arthritis, which spondyloarthritis is a type of.

The likelihood of having spondyloarthritis goes up if you test positive for the HLA-B27 gene. If you have symptoms of acute anterior uveitis, eyeball inflammation, including a red eye, it calls for an HLA-B27 test. In these cases, you should also see an eye specialist promptly for a confirmation and to rule out any infections.

All patients with reactive arthritis, a type of spondyloarthritis, should undergo tests for HIV and checks for intestinal and sexual diseases that can trigger their current conditions.

Treatment Options for HLA-B27 Syndromes

HLA-B27 syndromes are a group of conditions that are treated with similar types of medicines. However, the best starting treatment, or “first-line therapy,” can vary for each kind of HLA-B27 syndrome.

For adults with an active kind of HLA-B27 syndrome called ankylosing spondylitis, medical guidelines recommend using nonsteroidal anti-inflammatory drugs (NSAID) on a regular basis for treatment. Research has shown that continuous use of NSAIDs can reduce the progression of the disease, but the main aim of therapy is to control the activity of the disease. If a patient has this condition but doesn’t improve even after regular use of NSAIDs, then treatment with TNF inhibitors, which are protein blockers, is considered. Treatments like sulfasalazine and methotrexate aren’t effective for this condition.
Different TNF inhibitors can be more or less preferable depending on the patient’s other health conditions.

Similarly, if a patient has psoriatic arthritis, another type of HLA-B27 syndrome, the choice of treatment should take into account different factors, including symptoms, acuteness of the condition, and presence of skin symptoms. For example, medications that inhibit specific proteins like TNF inhibitors are preferred as a frontline treatment if the condition is active and the patient has inflammation-related issues. Alternatively, other small molecules like methotrexate and apremilast could be considered for those with milder disease involvement or if there are concerns about infections.

Another condition, acute anterior uveitis, that affects the eyes is treated initially with steroid eye drops. Steroid injections can be given if the eye drops don’t work. Oral steroids are sometimes needed and if the disease doesn’t respond to treatment or there are side effects from the steroids, other types of medications like mycophenolate mofetil, methotrexate, and azathioprine may be used. TNF inhibitors can be used in some difficult-to-treat cases.

Reactive arthritis is another type of HLA-B27 syndrome, and its treatment depends on the initial cause and severity of the condition. If it’s due to an infection in the urinary tract, antibiotics are needed to treat the underlying cause. Pain and inflammation are treated with NSAIDs and steroids if needed. If the condition becomes chronic, other treatments like sulfasalazine, methotrexate, or TNF inhibitors may be considered. Overall, something to remember is that the chosen treatment should be able to manage the condition successfully.

Peripheral arthritis, or inflammation of the joints, can be a symptom of many different health conditions. It’s important to first rule out any infections that might be causing the inflammation. For example, Lyme disease can cause symptoms that resemble peripheral spondyloarthritis, including inflammation of the knee. Viruses can also cause temporary arthritis in some patients. Rheumatoid arthritis and crystalline arthritis may also show signs similar to peripheral spondyloarthritis, but these conditions can usually be excluded through tests that analyze synovial fluid and measure certain substances in your blood.

Non-inflammatory pain in your joints, or arthralgia, is often caused by osteoarthritis, particularly in the lower back, shoulders, hips, and knees. It can cause pain and stiffness. Degenerative arthritis often appears in people over the age of 40 and usually doesn’t cause pain during the second half of the night. It often gets worse with exertion. Other possible causes for this type of pain include cancer (especially multiple myeloma), central pain syndromes, hypothyroidism (an underactive thyroid), and hypercalcemia (excessive calcium).

Uveitis, or inflammation of the eye, can also be caused by a variety of conditions. Infectious causes can include:

Herpes simplex
Herpes zoster (shingles)
CMV (cytomegalovirus)
Toxoplasmosis
Tuberculosis
Syphilis

Uveitis can also be a symptom of several other conditions, including:

Behcet disease
Vogt-Koyanagi-Harada syndrome
Relapsing polychondritis
Sjogren syndrome
Sarcoidosis
Juvenile idiopathic arthritis.

What to expect with HLA-B27 Syndromes

The creation of specialized biological treatments has greatly improved the management of inflammation caused by HLA-B27 related disease. These treatments include everything from TNF inhibitors to others that block the functions of IL-17, IL-23, and JAK/STAT pathways in your body.

Indications of a poor prognosis in psoriatic arthritis might include detectable erosions in radiographic images, a condition called dactylitis (an inflammation of an entire digit), and increased levels of certain blood markers (ESR and CRP). Joint deformities and highly active disease can majorly impact a patient’s quality of life.

Issues arising from mild to severe ankylosing spondylitis (a type of arthritis that affects the spine) can decrease physical abilities. This condition may lead to complications such as osteoporosis, cardiovascular disease, and fractures in the spine. Patients can also develop severe hip problems that may require a total hip replacement surgery and severe bending deformities of the neck spine, limiting their ability to move.

Hopefully, identifying these issues early and starting effective treatment can slow down the progression of damage seen in radiographic images and help preserve physical function. Appropriate treatment can also reduce the risk of damage to the joints in peripheral arthritis, a type of arthritis that affects the body parts furthest from the middle of your body like hands and feet.

Reactive arthritis often affects patients for three to five months, and most patients will be free of the disease within six to twelve months. In rare cases, the arthritis may become chronic, necessitating a further evaluation for any of the other related conditions, collectively called spondyloarthropathies.

Possible Complications When Diagnosed with HLA-B27 Syndromes

Ankylosing spondylitis, a type of arthritis, can lead to various complications. These can include atlantoaxial subluxation (the shifting of spinal bones), which can impair neurological functions. Other complications are spinal fractures from light injuries, severe hip arthritis leading to more hip replacements, and complications during surgery due to a stiff neck or limited chest movement. Heart-related complications are also common, such as aortic dissection (tearing of the main artery), acute coronary syndromes (a range of conditions that affect blood flow to the heart), and irregular heart rhythms. Eye complications such as glaucoma, posterior synechiae (eye adhesions), band keratopathy (corneal degradation), cystoid macular edema (swelling of the retina), and cataracts can also occur.

Just like other types of inflammatory rheumatological conditions, people with psoriasis, psoriatic arthritis, and ankylosing spondylitis have an increased risk of heart disease. Metabolic syndrome, a cluster of conditions that increase disease risk, is notably higher in people with psoriatic arthritis. Keeping the disease under control can reduce these risks. It is crucial to pay attention to manageable risk factors. Notably, starting statin treatment (cholesterol reducing medication) has shown to reduce mortality in ankylosing spondylitis patients.

Complications of Ankylosing Spondylitis:

Atlantoaxial subluxation and neurological impairment
Spinal fractures from low impact injuries
Advanced hip arthritis and increased occurrence of hip replacement surgery
Surgery complications due to rigid neck or reduced chest expension
Heart-related issues such as aortic dissection, acute coronary syndromes and irregular heartbeats
Eye complications like glaucoma, posterior synechiae, band keratopathy, cystoid macular edema, and cataracts
Increased risk of heart disease in people with psoriasis, psoriatic arthritis, and ankylosing spondylitis
High instances of metabolic syndrome in people with psoriatic arthritis
Reduced mortality rates with statin treatment in ankylosing spondylitis patients

Preventing HLA-B27 Syndromes

Physical therapy can play an important role in managing the daily complications of some illnesses. Regular aerobic exercise is highly recommended to help with this. Sometimes, lower impact activities might be more suitable, depending on what the person feels comfortable with. Regular exercise, combined with maintaining a healthy weight, can also help ease strain on the joints and increase the effectiveness of certain medicines like TNF inhibitors. These are drugs that help to reduce inflammation in the body. Additionally, it’s crucial for overall health that all patients quit smoking.

Frequently asked questions

HLA-B27 syndromes are a group of inflammation-related joint conditions, also known as spondyloarthritis, that are strongly related to the HLA-B27 gene.

The HLA-B27 allele is found in about 6 to 8 percent of people in the United States.

Signs and symptoms of HLA-B27 syndromes include: - Back pain due to inflammation, which develops slowly over about three months and typically starts before the age of 45. This pain can be differentiated from regular back pain as it tends to cause significant pain at night, stiffness in the morning, and does not improve with rest but rather gets better with exercise. - Other symptoms of spondyloarthritis, such as inflammation of the eye (uveitis), inflammation of fingers or toes (dactylitis), inflammatory bowel disease, psoriasis, and inflammation at the insertion point of a tendon (enthesitis), especially on the heel. - Family history of the condition or a positive response to anti-inflammatory medication can increase the likelihood of having spondyloarthritis. - In other forms of spondyloarthritis that mainly affect the arms or legs, similar symptoms may be present, including inflammatory arthritis, dactylitis, enthesitis, and psoriatic arthritis preceded by psoriasis on the skin. - Reactive arthritis, another syndrome linked to HLA-B27, typically begins with a sudden onset of inflammation in multiple joints, often following a urinary or intestinal infection. Symptoms can include inflammation of the urethra (urethritis) or eyes (uveitis). - Acute anterior uveitis (AAU), a non-infectious inflammation of the eye, is also associated with HLA-B27. It usually affects young people between the ages of 20 and 40 and presents with abrupt eye pain, redness in one eye, and possible vision loss. Examination may reveal white blood cells in the front chamber of the eye, and it can lead to other complications. - Inflammatory bowel disease, which involves inflamed bowels, can occur before or after any arthritis symptoms associated with HLA-B27 syndromes. Symptoms may include changes in bowel habits, blood in the stool, and under-the-radar inflammation in the colon.

The presence of the HLA-B27 allele in a person's genes is associated with HLA-B27 syndromes.

The doctor needs to rule out the following conditions when diagnosing HLA-B27 Syndromes: - Inflammatory bowel disease - Psoriatic arthritis - Reactive arthritis - Rheumatoid arthritis - Crystalline arthritis - Osteoarthritis - Cancer (especially multiple myeloma) - Central pain syndromes - Hypothyroidism (an underactive thyroid) - Hypercalcemia (excessive calcium) - Infectious causes of uveitis (such as herpes simplex, herpes zoster, CMV, toxoplasmosis, tuberculosis, and syphilis) - Other conditions causing uveitis (such as Behcet disease, Vogt-Koyanagi-Harada syndrome, relapsing polychondritis, Sjogren syndrome, sarcoidosis, and juvenile idiopathic arthritis)

The types of tests needed for HLA-B27 syndromes include: - X-ray images of the sacroiliac joints to detect changes like damage, thickening, or fusion - Blood test for C reactive protein to check for inflammation - Short tau inversion recovery (STIR) MRI scan to detect inflammation - Power Doppler ultrasound to detect inflammation in tendons - Arthrocentesis to analyze fluid from swollen joints - HLA-B27 gene test to determine likelihood of having spondyloarthritis - Tests for HIV and checks for intestinal and sexual diseases in cases of reactive arthritis

HLA-B27 syndromes are treated with a variety of medications depending on the specific condition. For ankylosing spondylitis, nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended as the first-line therapy. If NSAIDs are not effective, TNF inhibitors may be considered. Sulfasalazine and methotrexate are not effective for ankylosing spondylitis. For psoriatic arthritis, TNF inhibitors are preferred if the condition is active and there are inflammation-related issues. Methotrexate and apremilast may be considered for milder disease involvement. Acute anterior uveitis is initially treated with steroid eye drops, and other medications like mycophenolate mofetil, methotrexate, and azathioprine may be used if needed. Reactive arthritis treatment depends on the cause and severity, with antibiotics for infections, NSAIDs and steroids for pain and inflammation, and other medications like sulfasalazine, methotrexate, or TNF inhibitors for chronic cases.

When treating HLA-B27 syndromes, there can be potential side effects depending on the specific treatment being used. Some possible side effects include: - Nonsteroidal anti-inflammatory drugs (NSAIDs): These medications can cause stomach ulcers, gastrointestinal bleeding, and kidney problems. - TNF inhibitors: These protein blockers can increase the risk of infections, including serious infections like tuberculosis. They can also cause allergic reactions and injection site reactions. - Steroids: Steroids can have various side effects, including weight gain, mood changes, increased blood sugar levels, and increased risk of infections. - Methotrexate: Methotrexate can cause liver damage, lung problems, and increased risk of infections. - Sulfasalazine: Sulfasalazine can cause gastrointestinal side effects like nausea, vomiting, and diarrhea. It can also cause liver problems and blood disorders. - Mycophenolate mofetil: Mycophenolate mofetil can increase the risk of infections and can cause gastrointestinal side effects, liver problems, and blood disorders. - Azathioprine: Azathioprine can increase the risk of infections and can cause gastrointestinal side effects, liver problems, and blood disorders. It's important to note that not all patients will experience these side effects, and the benefits of treatment usually outweigh the risks. It's essential for patients to discuss potential side effects with their healthcare provider and to report any concerning symptoms.

The prognosis for HLA-B27 syndromes can vary depending on the specific condition. However, early identification and effective treatment can help slow down the progression of damage seen in radiographic images and preserve physical function. Appropriate treatment can also reduce the risk of joint damage and complications associated with these syndromes.

You should see a rheumatologist for HLA-B27 syndromes.