Ankylosing spondylitis

Definitions & Key takeaways

Ankylosing spondylitis (AS) is a form of arthritis that primarily affects the spine. This chronic condition can lead to fusion of the vertebrae, resulting in a rigid spine. AS can also affect the sacroiliac joints, peripheral joints, and digits, and in severe cases, it can lead to disability. Some of the symptoms seen in AS include back pain, postural abnormalities, buttock pain, and pain in the peripheral joints such as the hips, knees, and ankles.

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Introduction0:00–0:46

With ankylosing spondylitis, ankylosing refers to the stiffening and fusion of the bones. Sponddylo refers to the spine, while itis refers to inflammation.
So ankylosing spondylitis is a chronic inflammatory condition that primarily affects the spine, causing it to become stiffer over time.
Ankylosing spondylitis, along with psoriatic, reactive and enteropathic arthritis, belongs to a group of autoimmune conditions called seronegative spondyloarthropathies.
The phrase seronegative means that there's no rheumatoid factor present, which is an autoantibody commonly found in other autoimmune conditions such as rheumatoid arthritis.
But first, let's focus on physiology. Normally, foreign pathogens in the gastrointestinal tract activate the immune system through a process known as antigen presentation.

Physiology0:46–0:46

Physiology0:46–2:16

Typically, this security system involves dendritic cells. These cells act like immune scouts, constantly gathering intelligence on potential threats.
When dendritic cells detect a pathogen, such as a virus or bacterial components, they capture it through phagocytosis and break it down into smaller pieces known as antigens.
Next, they transport the antigens into the endoplasmic reticulum, where they bind them to special molecules called the Major histocompatibility Complex class one or MHC class one.
From here, the antigen MHC1 complex travels through the Golgi complex to the cell surface, where it acts like a serving platter.
The dendritic cells present the foreign antigens to CD8 positive T cells. When CD8 positive T cells, also known as cytotoxic T cells, bind the antigen MHC class one complex, they become activated.
This activation marks the start of their mission to locate and destroy the invader. Once they find it, they release cytotoxic granules to eliminate the threat.
Now, the exact underlying mechanism of ankylosing spondylitis remains a mystery, but we believe it involves a disregulated immune response in genetically predisposed individuals.

Pathology2:16–5:15

In most cases, these individuals carry the HLAB27 gene, which results in the production of a misfolded HLAB27 MHC class one molecule.
These misfolded proteins accumulate in the endoplasmic reticulum, causing intracellular stress. In response, dendritic cells and macrophages begin production of interleukin 23.
Which activates TH17 cells to produce interleukin 17. Ultimately, this sparks macrophages to produce cytokines like interleukin 6 and tumor necrosis factor alpha, which together result in joint inflammation, or in other words, arthritis.
Another possible important mechanism why ankylosing spondylitis might occur is molecular mimicry. You can think of molecular mimicry like a thief dressing up in a police uniform to sneak past security.
In other words, just like the thief looks like an officer, the foreign molecule mimics the structure of the body's own molecules, tricking the immune system into attacking its own tissue.
In ankylosing spondylitis, certain bacterial products in the gastrointestinal tract look like peptides normally found in the joints.
When these peptides break through the intestinal mucosa, dendritic cells capture them, break them down, and present them on their surface using MHC1 molecules.
But here's the thing, since the endoplasmic reticulum is creating misfolded HLAB27 MHC1 proteins, this antigen MHC1 complex is strange and confuses the body's immune system.
Instead of fighting a specific pathogen in the gut, the immune system misguides CD8 positive cytotoxic T cells against similar looking peptides in the joints, eventually causing inflammation.
Regardless of the underlying mechanism, the immune system primarily targets the intervertebral and facet joints of the spine, as well as the sacroiliac joints.
First, the immune system triggers inflammation and subsequent fibrin accumulation. As more layers of fibrin build up, they create a tough fibrous band around the outside of the joints, limiting their range of motion.
Meanwhile, the immune system activates osteoclasts to breakdown bone tissue, creating small erosions. At the same time, osteoblasts are working to form new bone, creating small bony outgrowths at the joint edges called syndesmophytes.
As a result, the affected joints become stiff and immobile. Keep in mind that inflammation can also affect the surrounding structures, including places where tendons and ligaments attach to the bone.
This is also known as enthesitis. So the most common manifestations of ankylosing spondylitis include articular manifestations related to the spine and sacroiliac involvement.
The spine involvement results in spine immobility and chronic lower back pain. Which is often referred to as inflammatory back pain.

Signs and symptoms5:15–5:40

Inflammatory back pain refers to back pain that starts before the age of 40, has no clear cause, improves with movement, and doesn't improve with rest.
Next, the sacroiliac involvement can cause hip, buttock, and sometimes groin pain, which could radiate down to the knee.
Less commonly, inflammation can affect shoulders, knees and ankles. Finally, some individuals can present with enthesitis, which most commonly affects the Achilles tendon.

Diagnosis5:40–5:40

Diagnosis5:40–6:09

But ankylosing spondylitis doesn't affect just the joints. It can also cause extra-articular manifestations, including eye discomfort from uveitis, inflammatory bowel disease, and psoriasis.
Now, let's talk about diagnosis, which primarily relies on clinical manifestations and imaging findings. Typically, an X-ray of the spine is enough to recognize the bamboo spine sign, which occurs as the new bone forms along joints.

Treatment6:09–6:49

However, in the early stages, this sign could be absent. In those cases, an MRI is helpful because it can detect erosions and inflammation much earlier than an X-ray.
Additionally, an X-ray of the pelvis could reveal a narrowing of the sacroiliac joints, suggesting sacroiliitis. Finally, don't forget to order genetic testing because the HLAB27 gene is present in up to 90% of individuals with ankylosing spondylitis.
Finally, the treatment involves non-pharmacologic and pharmacologic management. Non-pharmacologic management mainly focuses on active physical therapy to reduce stiffness and improve mobility.

Review6:49–7:58

On the flip side, pharmacologic management primarily includes anti-inflammatory medications such as NSAIDs. If NSAIDs fail to improve symptoms and reduce inflammation, you should consider therapy with monoclonal antibodies such as adalimumab, golimumab, and infliximab.
Alright, as a quick recap, ankylosing spondylitis is a chronic inflammatory condition that primarily affects the spine and sacroiliac joints, causing them to become stiffer over time.
We believe it occurs due to a dysregulated immune response in genetically predisposed individuals who carry the HLAB27 gene.
Misfolded HLA B27 proteins cause intracellular stress and subsequent activation of immune cells that eventually result in joint inflammation.
Additionally, molecular mimicry between gut bacteria and joint peptides might confuse the immune system, causing it to misguide CD8 positive T cells against its own tissues, leading to joint damage.