Ankylosing Spondylitis; Causes, Symptoms, Diagnosis, Treatment

Ankylosing spondylitis  (Bechterew’s disease or Marie Struempell disease as it is also known) (AS) is a chronic progressive inflammatory arthropathy or seronegative spondyloarthropathy or inflammatory form of arthritis that causes vertebrae in the spine to fuse together. This limits flexibility in the spine and may cause a person to have a hunched-forward posture. It is a form of chronic, degenerative arthritis that affects the spine and sacroiliac joints and often other joints of the body.

Ankylosing spondylitis is a chronic inflammatory rheumatic disorder that primarily affects the axial skeleton. Sacroiliitis is its hallmark, accompanied by inflammation of the entheses (points of union between tendon, ligament, or capsule and bone) and formation of syndesmophytes, leading to spinal ankylosis in later stages. The pathogenesis of AS is poorly understood. [Rx]However, immune-mediated mechanisms involving human leucocyte antigen (HLA)-B27, inflammatory cellular infiltrates, cytokines (for example, tumor necrosis factor α and interleukin 10), and genetic and environmental factors are thought to have key roles. The detection of sacroiliitis by radiography, magnetic resonance imaging, or computed tomography in the presence of clinical manifestations is diagnostic for AS, although the presence of inflammatory back pain plus at least two other typical features of spondyloarthropathy (for example, enthesitis and uveitis) is highly predictive of early AS. Non-steroidal anti-inflammatory drugs (NSAIDs) effectively relieve inflammatory symptoms and are presently first line drug treatment.[Rx]

Causes of Ankylosing Spondylitis

The exact cause of ankylosing spondylitis is unclear. It is thought to be an autoimmune disease – where the body’s own immune system attacks the body’s tissues causing inflammation and tissue damage.

Genetic (inherited) factors appear to influence the development of AS. Approximately 90% of people diagnosed with AS have a gene called HLA-B27. However, only about 10 – 15% of people with the gene will go on to develop AS. Approximately one in five individuals with AS also has a relative with the condition.

Causes And / Or Aggravation

Symptoms of Ankylosing Spondylitis

General symptoms-

• Difficulty bending the spine
• Pain in the hips and difficulty walking- dull diffuse type of pain
• Pain in the heels and soles of the feet- pain in worse in morning and night and better after a warm shower
• Bent-over posture
• Straightening of the normal curvature of the spine
• Fever – In the early stages of disease, there may be mild fever, loss of appetite and general discomfort
• Loss of appetite, weight loss
• Fatigue decreased energy
• Eye swelling, redness, and pain
• Sensitivity to light
• Difficulty taking a deep breath (because expanding the chest is difficult and painful)
• Heart failure
• Pain and stiffness. Constant pain and stiffness in the low back, buttocks, and hips that continue for more than three months. Back pain from ankylosing spondylitis is inflammatory in nature
• The stiffness is often worst in the morning and after you have been inactive for a while

• Bone fusion resulting in a rigid spine. These changes may be mild or severe and may lead to a stooped-over posture
• Pain in ligaments and tendons.

• Stiffness and pain in the morning affecting the sacroiliac joint area and spine.
• Aching in the lower back which can disrupt sleep.
• Pain radiating down the legs and into the groin.
• Pain is worse during and after rest e.g. in the mornings.
• Exercise eases the pain and stiffness.
• Aches and pains in the buttocks, neck, shoulders, hips and upper back.
• Symptoms may flare up and then disappear.
• Severe cases may cause feelings of illness, weight loss, and fatigue.
• Back pain relieved by movement and exercise
• Difficulty bending the spine
• Pain in the hips and difficulty walking
• Pain in the heels and soles of the feet
• Bent-over posture
• Straightening of the normal curvature of the spine
• Fever
• Loss of appetite, weight loss
• Fatigue decreased energy
• Eye swelling, redness and pain
• Sensitivity to light
• Difficulty taking a deep breath (because expanding the chest is difficult and painful)

Treatment of Ankylosing Spondylitis

Non-Surgical Treatment

• Bed rest for first 24 hours. Additional bed rest will be determined by the severity of the problem. Recent medical studies indicate that staying more active is better for back disorders than prolonged bed rest.
• Use a firm mattress (place a bed board under the mattress if needed).
• Massage may help. Be sure the person is well-trained or massage could cause more harm than help.
• Wear a special back support device.
• Other options are available depending on the degree of injury, such as surgery (if disk damaged), electrical nerve stimulation, acupuncture, special shoes, etc.
• Stress reduction techniques, if needed.
• Non-Prescription Pain Relievers – Naproxen, acetaminophen, and ibuprofen each reduce inflammation and pain. Though these drugs are available over-the-counter, they are potent and taking more than the recommended dose can harm health. A doctor can help with advice about the right kind of non-prescription pain reliever to take.
• Cold and Heat – Applying a cold pack to the painful part of the back contracts inflamed muscle and relieves pain. This treatment helps a great deal when the disk has recently ruptured and swelling is at its greatest. A heating pad or warm pack helps with residual pain.
• Continued Physical Activity – Though pain or weakness seem like good reasons to rest the back, excessive bed-rest worsens the symptoms of a slipped disc. Moving around too little allows muscles to grow weaker and prevents the body from healing. Periods of rest interspersed with periods of normal activity throughout the day keep the back muscles in shape.
• Prescription Remedies –  If over-the-counter drugs fail to ease slipped disc pain, the doctor will turn to prescription medications.  These can include narcotics, such as hydrocodone or codeine. While they can do away with pain, narcotics are very addictive and induce a mental fogginess that can itself be dangerous.  More narrowly-focused medicines designed to target damaged nerves that create chronic pain may be a better choice, as they have fewer undesirable side effects. Gabapentin and Cymbalta are two drugs that act in different ways to minimize nerve pain. These drugs are less addictive than narcotics.
• Nutrition – In order to restore the disc we also are going to need to include different substances in our diet. There are a lot of supplements on the market, of course. If you wish to try them, that’s fine. I personally don’t like them. I have tried one with glucosamine and chondroitin, but I didn’t feel any different. So, if you have the opportunity to take these with the food or from more natural sources, it will be great. You can find these substances in seafood and animal cartilages and by digesting them we ensure the building blocks for the connecting tissue for our joints and spine. Also, we will need more Omega 3 fatty acids, which can be supplied from cold pressed oils, fatty fish, flax seeds, chia and many more. Vitamins from the B group are very beneficial for people with herniated discs and all kinds of issues with the peripheral nervous system. Vitamins B1, B6 and B12 nourish the nerves and help them recover from the disk accident. Usually, doctors prescribe them as a part of the treatment, but it is worth mentioning anyway.
• A good massage – A massage is one of the natural methods of relieving pain. Individuals who get a massage weekly for several months stand a better chance of alleviating back pain. A good massage provides a person with many health benefits that lessen back pain. A massage triggers the release of endorphins. Endorphins aid in decreasing anxiety and relieving pain. They offer a relaxation effect by softening muscles that are injured preventing cramping.
• Undertaking yoga – Yoga is an applicable strategy for keeping the level of back pain at minimal levels. Taking yoga sessions often is very an effective method of dealing with back pain. With yoga, there is a high likelihood of proper body functions. The use of pain prescriptions is also diminished. Patients suffering from back pain related issues do not have to rely on these prescriptions to manage pain. Incorporating laughter in yoga is a good way of exercising. Yoga incorporates simple yet appropriate exercises that enhance the stretching of muscles. Laughter with yoga stimulates relieving of pain. It facilitates increased uptake of oxygen, little anxiety, and production of endorphins. All these variables play an essential role in diminishing back pain.
• Adjusting sleeping position – A simple sleeping mistake can immensely contribute to back pain. A poor sleeping position can cause stress and tension on the muscles contributing to back pain. Altering one’s sleeping position and adopting a style that does not exert a lot of stress on the back is a recommended tactic. Nurturing sleeping habits such as assuming a reclining position, using wedge-shaped cushions and getting adjustable beds from reputable medical institutions are easy techniques to endorse. If a reclining position does not suit an individual, the other two techniques can be embraced.
• Heat therapy – Several considerations should be observed when using heat therapy. The right temperature ought to be set so as to ensure a patient does not face risks associated with too much exposure to heat. The key objective should be to ensure enough access to heat to the muscles to yield benefits for the patient. The adoption of heat therapy for easing back pain is determined by the magnitude of pain a person is experiencing. In cases where relatively low back pain is encountered, short heat therapy sessions are recommended. On the other hand, if an individual is experiencing prolonged back pain, long heat therapy sessions are the most applicable.
• Taking hot baths – This is a form of heat therapy that aims at relieving back pain. It guarantees permeation of heat into the muscles leading to reduced pain. Many individuals opt for this method since they believe it achieves competent results. Hot baths initiate a fast process of blood supply to stiff neck and back muscles. When this happens, the muscles relax and stretch leading to decreased back pain. To avoid interference with one’s sleeping patterns, a hot bath should be taken several hours before retiring to bed.
• Aquatic therapy – This natural technique involves physical therapy in a pool. Individuals get the best out of this therapy by relying on the resistance of water. Consistency in undertaking this therapy is what ascertains getting back pain relief. Integrating aquatic therapy in an individual’s life for the better part of the week enhances the reduction of back pain quickly.
• Enlighten others – Individuals have the power to devise their own natural strategies that aid them in coping with back pain. The strategies can also be a good remedy for others going through similar circumstances. An individual can use social media platforms to equip others with important tips on how to keep back pain at bay. Further, becoming a member of associations that address back pain issues enables better communication of the knowledge gained from personal experience.

Medication

The major types of medications used to treat ankylosing spondylitis are pain-relievers and drugs aimed at stopping or slowing the progression of the disease. All of these have potentially serious side effects. Pain-relieving drugs come in two major classes:

•  Nonsteroidal anti-inflammatory drugs (NSAIDs) – NSAIDs including the Coxib class are the first-line drugs for ankylosing spondylitis. A recent study reported that ankylosing spondylitis is associated with the prostaglandin E receptor 4 (PTGER4) gene. This receptor is associated with bone absorption; NSAIDs inhibit prostaglandin production, thus reducing the absorption¹²⁾. The mainstay of therapy in all seronegative spondyloarthropathies are anti-inflammatory drugs, which include NSAIDs such as ibuprofen, phenylbutazone, diclofenac, indomethacin, naproxen and COX-2 inhibitors, which reduce inflammation and pain. Indomethacin is a drug of choice. 2012 research showed that those with AS and elevated levels of acute phase reactants seem to benefit most from continuous treatment with NSAIDs.
• Analgesics – Acetaminophen and opioid-(like) agents are often used 1) for patients who complain of pain even after administration of NSAIDs and TNF-α inhibitors or 2) when other therapeutic options are not available.
• Glucocorticoids – Although local glucocorticoid injection can be considered for skeletal muscle inflammation such as enthesitis, systematic administration of steroids is not generally recommended⁶⁾
• Antidepressants – such as tricyclics and serotonin and norepinephrine reuptake inhibitors have been commonly prescribed for chronic low back pain, but their benefit for nonspecific low back pain is unproven, according to a review of studies assessing their benefit.
• Calcium & vitamin D3 – to improve bones health and healing fracture.
• Glucosamine & Diacerein – can be used to tightening the loose tension and regenerate cartilage or inhabit the further degeneration of cartilage.
• Corticosteroid- to healing the nerve inflammation and clotted blood in the joints.
• Dietary supplement -to remove the general weakness & improved the health.
• Muscle Relaxants – If the muscles around the slipped disc experience painful spasms, a muscle relaxant such as Valium may be useful. The drawback to drugs like these is that they do not limit their power to the affected nerve. Instead, they have a generally relaxing effect and will interfere with daily activities. Such as cyclobenzaprine (Flexeril), might be prescribed to relieve the discomfort associated with muscle spasms. However, these medicines might cause confusion in older people. Depending on the level of pain, prescription pain medicines might be used in the initial period of treatment.
• Steroids – If inflammation is severe, a doctor may also prescribe a steroid. Steroids, such as cortisone, reduce swelling quickly. A cortisone shot directly in the affected area will have an immediate effect on the displaced disc.
• Counter-irritants – such as creams or sprays applied topically stimulate the nerves in the skin to provide feelings of warmth or cold in order to dull the sensation of pain. Topical analgesics reduce inflammation and stimulate blood flow.
• Nerve Relaxant — Pregabalin or gabapentin and anti-inflammatory drugs help to relieve pain and stiffness, allowing for increased mobility and exercise. There are many common over-the-counter medicines called non-steroidal anti-inflammatory drugs (NSAIDs). They include aspirin, ibuprofen, and naproxen.
• Disease-modifying anti-rheumatic drugs (DMARDs) – Although the administration of DMARDs (e.g., sulfasalazine and methotrexate) is not recommended for axial diseases such as back pain, sulfasalazine is worth considering for treatment of peripheral arthritis ^Rx. Disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine can be used in people with peripheral arthritis. For axial involvement, the evidence does not support sulfasalazine. Other DMARDs, such as methotrexate, did not have enough evidence to prove their effectiveness. Generally, systemic corticosteroids were not used due to lack of evidence. Local injection with a corticosteroid can be used for certain people with peripheral arthritis.
• TNF-α inhibitors – In 1995, Braun and coworkers^rx) isolated TNF-α from ankylosing spondylitis patients via sacroiliac arthrocentesis. Thus, it was recognized that TNF-α is an important inflammatory mediator in this disease, which dramatically facilitated the development of biological agents.
• Infliximab (Remicade) – Infliximab is a chimeric monoclonal antibody against TNF-α and is the first developed biological agent, consisting of 75% of human and 25% of mouse sequences ^rx). This antibody directly binds to TNF-α and neutralizes it. It is administered by intravenous injections at 5 mg/kg body weight. For the first administration, the same dose of infliximab is injected twice with an interval of 2 weeks and then the drug is administered every 6 weeks. Baraliakos et al.^Rx reported a drug survival rate (patients who completed 8 years of treatment) of 48% and 88% of partial remission or low disease activity after 8-year follow-up. It was also reported that the potency was similar when the treatment was interrupted for 3 years and then resumed.
• Etanercept (Enbrel) – Etanercept is a soluble blocker of TNF-α. This fusion protein binds TNF-α, which hinders interactions between TNF-α and TNF-α receptor located on other cells. Etanercept is generally administered by subcutaneous injection of 25 mg twice a week ^Rx. Martĺn-Mola et al.^Rxreported that 63% of the enrolled patients completed 5 years of etanercept administration without any serious complications, while Baraliakos reported a drug survival rate of 62%, partial remission in 31% of patients, and complete remission in 44% of patients in a 7-year follow-up study. Similar to infliximab, etanercept was effective when the medication was interrupted and then resumed; the drug survival rate was slightly higher in the etanercept group than in the infliximab group.
• Adalimumab (Humira) – Like infliximab, adalimumab is a monoclonal antibody against TNF-α but its sequence is 100% human. Adalimumab is administered by subcutaneous injections of 40 mg once per 2 weeks. Sieper et al.^Rx reported a drug survival rate of 65%, partial remission according to Ankylosing Spondylitis Disease Activity Score (ASDAS) in 51% of patients, and ASDAS inactive disease in 61% of patients in a 5-years follow-up study. Similar to the long-term follow-up results for infliximab, favorable outcomes of long-term follow-up were demonstrated with remission achieved after 12 weeks of administration.
• Anti-tumor necrosis factor therapy —A group of medicines known as anti-tumor necrosis factor agents (anti-TNF agents or TNF inhibitors) are often effective in the treatment of AS. Examples of anti-TNF medications include infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab. People who do not respond to one anti-TNF treatment may respond to another. Improvement in symptoms is common and may occur within a few weeks of starting the drugs.
• Who should use anti-TNF therapy? – Not every patient with AS needs anti-TNF therapy. In general, people with the active disease in the spine who have not responded fully to NSAIDs may be candidates (see ‘How do I know how active my ankylosing spondylitis is?’ above). Your clinician may also recommend a glucocorticoid (cortisone-like drug) injection into painful or swollen joints before starting an anti-TNF drug if these areas continue to bother you despite using NSAIDs (see ‘Glucocorticoids (steroids)’ below). The decision to use anti-TNF therapy depends upon several factors that should be discussed with your clinician.
• Secukinumab — Secukinumab (brand name: Cosentyx) may be an alternative treatment option for some people who do not respond adequately to anti-TNF therapy.
• Glucocorticoids (steroids) — Some clinicians may also recommend a glucocorticoid injection into particularly painful or swollen joints, especially if only one or two areas are causing the most pain. In some cases, a glucocorticoid injection into the sacroiliac joint may help provide relief in patients who have sacroiliac pain that has not responded to other therapies.
• Bisphosphonates – Oral bisphosphonates are commonly used for fracture prevention in ankylosing spondylitis. Bisphosphonates also have an anti-inflammatory action and may have an effect on disease activity. Intravenous pulses of the bisphosphonate pamidronate have been investigated in several studies and have produced significant clinical improvements in some but not all studies.^rx

Clinical Trials

[dropshadowbox align=”none” effect=”lifted-both” width=”auto” height=”” background_color=”#ffffff” border_width=”3″ border_color=”#dddddd” ]

Physical therapy involves three main components: education, passive treatments, and active treatments. A physical therapist uses passive treatments to relax you and your body and to decrease acute pain or inflammation. They’re called passive because you don’t have to actively participate. If you’re experiencing acute pain, you’ll most likely start with passive treatments as your body heals and/or adjusts to the pain. However, the goal of physical therapy is to get into active treatments. These are therapeutic exercises that strengthen your body so that your spine has better support.

Passive Treatments for Ankylosing Spondylitis

Your physical therapist may give you passive treatments such as:

Deep Tissue Massage  – This technique targets spasms and chronic muscle tension that perhaps builds up through daily life stress. You could also have spasms or muscle tension because of strains or sprains. The therapist uses direct pressure and friction to try to release the tension in your soft tissues (ligaments, tendons, muscles).

Hot and Cold Therapies  – Your physical therapist will alternate between hot and cold therapies. By using heat, the physical therapist seeks to get more blood to the target area because an increased blood flow brings more oxygen and nutrients to that area. Blood is also needed to remove waste byproducts created by muscle spasms, and it also helps to heal. Cold therapy, also called cryotherapy, slows circulation, helping to reduce inflammation, muscle spasms, and pain. You may have a cold pack placed upon the target area, or even be given an ice massage. Another cryotherapy option is a spray called fluoromethane that cools the tissues. After cold therapy, your therapist may work with you to stretch the affected muscles.

Electrical stimulation – This can be performed within the clinic and if extremely successful, a TENS unit can be issued to a patient for home use. E-stim stimulates your muscles through variable (but safe) intensities of electrical current. It helps to reduce muscle spasms, and it may increase your body’s production of endorphins, your natural pain killers. It may also drive out inflammation, bring in healing properties, relax, and re-educate the muscles involved. The e-stim unit in the clinic is of a professional standard; the equipment is relatively large. However, a smaller machine for at “at home” use is also available. Electrical stimulation is a helpful therapy.

Yoga  – Yoga is a great natural pain reliever for ankylosing spondylitis,” Ostrowski says. “You need to start with very basic poses and be patient, but if you work with an instructor who can modify the yoga positions for you, you can really benefit from this form of exercise.” A review of studies published in January 2016 in the Journal of Orthopedics & Rheumatology examined the impact of yoga on low back pain and found that it was safe and can help reduce both disability and pain.

Omega-3 fats and inflammation – Foods that contain omega-3 fats have been found to help reduce the inflammation associated with some forms of arthritis. These effects are modest compared with medication.

Omega-3 fats have few side effects and may have other health benefits, such as reduced heart disease. Foods rich in omega-3 fats include

• fish – the oily fish such as salmon and sardines have greater amounts of omega-3 fats
• linseeds and linseed (flaxseed) oil
• canola (rapeseed) oil
• walnuts
• foods fortified with omega-3, such as margarine and eggs
• some fish oil supplements.
• Potassium Rich Foods

Potassium is known to decrease inflammation if it is present in the body in adequate amounts. Foods that contain potassium in high amounts are bananas, almonds, apricots, and broccoli.

Vitamin D –  You must correct the vitamin D deficiency in your body if you are suffering from ankylosis. Bones need Vitamin D in greater amounts when they are affected by a disease.

Home Remedies For Ankylosing Spondylitis

• Use Ginger, Black Pepper or any good digestive with your meals. It will help detoxify your body.
• 1 tablespoonful of Turmeric should be consumed once every day, after boiling it in milk for half an hour.
• Constipation must be avoided at all costs. Constipation may increase pain in Ankylosing spondylitis.
• Herbs have divine healing powers and they have the ability to cure any disease of the root. They were gifted to us by God when he created life. So believe in God if you want to get rid of your problems!
• Ayurvedic herbs are unique natural remedies for Ankylosing spondylitis. Ayurvedic principles are different in many ways From modern medicine for example – Drinking water From a copper pan after keeping it overnight is also very useful in Rheumatoid arthritis and Ankylosing spondylitis.
• Consuming castor oil at night with milk or alone is a very useful herbal remedy for arthritis, especially rheumatoid arthritis and ankylosing spondylitis.
• Improve your nutrition as the first step. It plays an important role to fight diseases. When nothing works, nutrition works a lot !
• Use herbal juices like Aloe vera juice (Kumari Saar) and Amla Juice ( Amla Saar) in routine. Amla is the richest source of natural Vitamin C. Vitamin C improves the natural immunity of the body. 100 gm of Amla juice contains 30 times more vitamin C than 100 gm of oranges.

Homeopathic treatment for Ankylosing Spondylitis

Homeopathy treats the person as a whole. A Remedy is selected after full individualizing examination and case analysis which includes a medical history of the patient, physical and mental constitution etc.

• Phosphorus – The rigidity of nape of the neck. Pressure on shoulders. Swelling of the neck. Engorgement of axillary glands and of those of nape of the neck and of the neck. Paralyzes sensation in the upper sacrum and lower lumbar vertebrae. Contusive pain in loins and back (as if the back were broken), especially after having been seated a long time Sensitiveness of spinous processes of dorsal vertebrae to pressure.
• Silicea – The stiffness of nape, with a headache. Swelling of glands of nape, in the neck, and under the axillae (with suppuration), sometimes with indurations…Stitches between the hips.Coccyx painful, as after a long carriage ride.- Stinging in os coccyx on rising, painful to pressure. -Scabby elevation on the coccyx, above fissure of nates- Inflammatory abscess in the lumbar region (on the psoas muscle).- Weakness and paralytic stiffness in back, loins, and nape.
• Aurum Metallicum – Serious or advanced rheumatism with marked stiffness. Rheumatism with stiffness or spasms of the chest wall. Severe spasm or tearing pains. Pains also described as “paralytic.” An important remedy in ankylosing spondylitis. Wandering arthritis; moving spot to spot from one week to next. Worse: Night. Morning in bed. Hip pain worse rising from a seat or from walking.
• Sulfur – The stiffness of the neck, in nape, with a paralytic, sprained pain. A child cannot hold head up neck muscles so weak. Tetters on nape. Swelling and inflammation of glands of nape and of the neck. Swelling and suppuration of axillary glands. Cracking in vertebrae of the neck, especially on bending backward.
• Maintain a healthy weight – If you are overweight or obese, the extra load on your joints may be exacerbating your symptoms, especially if your affected joints include those of the hip, knee or spine. There is also a clear link between being overweight and an increased risk of developing osteoarthritis.

What can the athlete do?

• Keep themselves fit and healthy
• Maintain an optimum weight to place as little strain on the spine as possible
• Have a good diet
• Maintain a good posture and mobility
• Avoid sudden twisting and turning movements
• Use a heat pack or warm bath to reduce pain and stiffness
• Exercise such as swimming can be great for ankylosing spondylitis as it places very little strain on the spine and joints.
• Other exercises for mobility and back strength can also be beneficial.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971137/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570004/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1766729/
4. https://www.ncbi.nlm.nih.gov/books/NBK470173/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077878/
6. https://en.wikipedia.org/wiki/Ankylosing_spondylitis
7. https://en.wikipedia.org/wiki/Spondylitis
8. https://www.spondylitis.org/Ankylosing-Spondylitis
9. https://bestpractice.bmj.com/topics/en-us/366
10. https://bestpractice.bmj.com/topics/en-gb/366/treatment-algorithm
11. https://www.sciencedirect.com/topics/medicine-and-dentistry/ankylosing-spondylitis
12. https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/ankylosing-spondylitis
13. https://www.sciencedirect.com/science/article/pii/S1521694202902457
14. https://www.sciencedaily.com/releases/2014/12/141209120027.htm
15. https://www.sciencedaily.com/releases/2014/10/141020090000.htm
16. https://www.sciencedaily.com/releases/2005/06/050613063413.htm
17. https://www.science.gov/topicpages/b/background+ankylosing+spondylitis
18. https://www.science.gov/topicpages/r/ra+ankylosing+spondylitis
19. https://www.niams.nih.gov/health-topics/ankylosing-spondylitis
20. https://clinicaltrials.gov/ct2/show/NCT01302730
21. https://clinicaltrials.gov/ct2/show/NCT00081562
22. https://books.google.com/books/about/Ankylosing_Spondylitis.html?
23. https://books.google.com/books/about/Ankylosing_Spondylitis.html?
24. https://books.google.com/books/about/Ankylosing_Spondylitis_Axial_Spondyloart.html?
25. https://www.springer.com/gp/book/9780857291790
26. https://www.springer.com/gp/book/9781447142997
27. https://www.webmd.com/back-pain/guide/ankylosing-spondylitis
28. https://www.webmd.com/arthritis/what-is-ankylosing-spondylitis
29. https://www.nhs.uk/conditions/ankylosing-spondylitis/
30. https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/ankylosing-spondylitis
31. https://www.arthritis.org/about-arthritis/types/ankylosing-spondylitis/