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vertebral bodies and complete fusion (ankylosis) of the spine, causing signi
cant
loss of mobility. The same process happens at the sacroiliac joints, causing anky-
losis. Several molecular pathways have been proposed to be involved in this pro-
cess, including bone morphogenic proteins (BMPs), Wnt protein, hedgehog protein
and
fibroblast growth factors (FGFs) [
46
]. The relationship between chronic
in
ammation and new bone formation remains unclear.
The prevalence of AS ranges from 0.1 to 1 % of the population, depending on
the ethnic groups studied. Caucasians and Native Americans have the highest
prevalence, while AS is rare in Africans. Men are 3 times more likely to have AS
than women, and often have more severe disease. AS tends to run in families, with
an estimated heritability of more than 90 % [
47
]. It usually begins during adoles-
cence or early adulthood, and is life-long.
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3.1.2 Clinical Manifestations
In
ammatory back pain is the most common symptom in patients with AS. Patients
often describe pain in their lower back or the buttock, worse after rest, especially
during the second half of the night. They often report waking up in signi
fl
cant pain
and stiffness in the morning. Exercise and NSAIDs improve the back pain. The
symptoms usually fluctuate, and are often associated with fatigue.
With progression of the disease and the growth of syndesmophytes, ankylosis of
the spine becomes a more prominent feature in the disease presentation. In advanced
stages of AS, patients may develop a stooped posture, have decreased movement of
their spine, and signi
cant loss of function. Fusion of the cervical spine leads to a
forward
culty raising their head to look
straight ahead. Involvement of the thoracic spine and the chest wall may make it
dif
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flexion of the head, and patients may have dif
cult for patients to expand their chest and take deep breaths, affecting the function
of the lungs. In severe cases, patients may develop roundback, which prohibits them
from sleeping on their back. Lumbar spine involvement may make it dif
cult for
patient to bend forward and reach the
floor. Complete fusion of the spine makes
patients more susceptible to trauma and spine fractures. The extent of spine fusion
varies greatly among patients, and progression to complete fusion is not inevitable.
Complaints in the limbs are common, mainly due to enthesitis and arthritis.
fl
In
ammation of the entheses causes intermittent pain and swelling at various ten-
don insertion sites, for example, at the heel, where the Achilles tendon attaches, or
at the bottom of the foot. Hips, shoulders and collarbone joints are frequently
involved with pain, stiffness, and sometimes swelling, indicating ongoing in
fl
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am-
mation. Over time, in
ammation may causes damage, with erosion of the bone and
loss of cartilage and the joint space. Joint movements may become limited, for
example, with
fl
flexion contracture of the hips.
Paradoxically, despite the propensity to add extra abnormal bone to the spine,
patients with AS often develop osteoporosis, a condition of decreased bone density,
with increased risk of fracture. Organs other than musculoskeletal system are
affected in AS. Common manifestations include uveitis (in
fl
