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Ankylosing Spondylitis

Updated : January 19, 2024





Background

A chronic, inflammatory condition of the axial spine known as AS (ankylosing spondylitis) can cause a variety of clinical indications & symptoms. The most typical symptoms of the condition are growing spinal stiffness and persistent back pain. The condition is characterised by involvement of the spine, sacroiliac (SI) joints, digits, peripheral joints, and entheses.

AS is characterised by reduced spinal mobility, peripheral arthritis, buttock, and hip pain, enthesitis, postural irregularities & dactylitis (sometimes known as “sausage digits”). This illness may damage extraskeletal organs. The most prevalent extraarticular symptoms of AS are psoriasis (10%), acute anterior uveitis (25%–35%), and inflammatory bowel disease (up to 50%). A higher risk of heart disease is also linked to AS.

The systemic inflammation that is present in AS has been hypothesized to be the reason for this elevated risk. Because lower spinal movement and decreased chest wall expansion predispose patients to a restrictive pulmonary pattern, pulmonary problems are also linked to AS. Finally, AS puts persons at least twice as likely to suffer a vertebral brittle fracture. Additionally, these patients have a higher chance of suffering from cauda equina syndrome, spinal cord damage, or atlantoaxial subluxation.

 

Epidemiology

About 80 percent of patients with ankylosing spondylitis experience their first symptoms before the age of 30, and the disease is frequently identified in those under the age of 40. Less than 5 percent of patients over the age of 45 visit the doctor. Men are more likely than women to have AS. Family members of patients who are impacted are at higher risk.

Anatomy

Pathophysiology

Ankylosing spondylitis is a sneaky-onset chronic inflammatory condition. The condition is characterized by progressive musculoskeletal and frequent extra-skeletal symptoms and signs. Each patient’s progression rate will be different.

Enthesitis with persistent inflammation, especially CD4 & CD8 T cells and macrophages, is the main pathogenesis of spondyloarthropathies. By causing swelling, fibrosis, & ossification at enthesitis sites, cytokines, especially TNF-α (tumour necrosis factor) & TGF-β (transforming growth factor), are also crucial in the inflammatory process.

Etiology

In spite of the fact that the cause of ankylosing spondylitis is still largely unknown, there appears to be a connection between the incidence of AS & HLA-B27 in a specific community. There are between 5% and 6% of HLA-B27 positive individuals who also have AS.

The incidence of HLA-B27 differs among racial groups in the United States. HLA-B27 prevalence rates were 1.1 percent across non-Hispanic Blacks, 7.5 percent across non-Hispanic Whites, & 4.6 percent across Mexican-Americans, , based on a 2009 study.

 

Genetics

Prognostic Factors

Although significant physical handicap is infrequent, younger age of start is linked to worse function outcomes in ankylosing spondylitis sufferers. Most patients continue to function normally and can still work. When compared to the general population, patients with the severe, chronic condition die more frequently, primarily as a result of cardiovascular problems.

Clinical History

Physical Examination

Physical examination

Chronic spinal involvement can eventually result in decreased range of motion (ROM) and vertebral body fusion. Unification of the neck in a hunched forward-flexed position is possible when the cervical and upper thoracic spine are involved (kyphosis). The patient’s mobility and ability to stare directly ahead may both be severely restricted in this position.

Articular manifestations

Concentrate the medical examination on the axial & peripheral joints’ active and passive ROM. Joint pain in the SI region is typical. The pain and swelling of tendons & ligamentous insertions are common symptoms of peripheral enthesitis.

Spine

In highly developed AS, the spine is stiff, or kyphosis, which causes a hunched posture, is present. Indirect signs of sacroiliitis & spondylitis may be seen earlier in the disease’s progression, such as SI discomfort (caused by indirect or direct compression) or a restricted range of motion in the spine. A malformation of the spine may occur in some patients, most frequently with a decrease of lumbar lordosis as well as an accentuation of thoracic kyphosis.

Peripheral joints and entheses

33 percent of patients experience peripheral enthesitis. These lesions may be accompanied by swelling at the ligament or tendon insertion and are unpleasant and tender to the touch. The insertions of the plantar fascia as well as the Achilles tendon on the calcaneus are the two most frequent & distinctive peripheral locations of enthesitis. Due to biomechanical stress, certain anatomical regions might be more vulnerable to enthesitis. Check patients carefully for palpable tenderness.

A portion of the involvement of the peripheral joints is due to enthesitis & synovitis. 33 percent of patients have peripheral joint disease, which most often affects the hips. The first ten years of the disease’s progression commonly see hip involvement, which is typically bilateral.

There may also be involvement in the following joints:

  • Temporomandibular joint
  • Symphysis pubis
  • Manubriosternal joints
  • Costosternal junctions
  • Costovertebral joints
  • Shoulder girdle

Rarely are peripheral joints implicated. They participate in an asymmetric oligoarticular pattern when they do.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Differential diagnosis

It’s important to screen out other diseases and ailments because they can mimic ankylosing spondylitis (AS). Among them are, but not restricted to:

  • DISH (Diffuse idiopathic skeletal hyperostosis)
  • Rheumatoid arthritis
  • Lumbar spinal stenosis
  • Mechanical low back pain

Although each of these illnesses shares features with AS, it is important to rule out or rule them in based on their distinctions. The beginning of symptoms can be used to distinguish between physical back pain and AS because the former can occur at any age while the latter usually does so before around 40. In contrast to AS, discomfort subsides with rest, and morning stiffness is minimal and transient. Like AS, mechanical back pain is not linked to extraskeletal symptoms or peripheral arthritis. A shrinking of the spinal canal known as lumbar spinal stenosis places stress on the spine. Similar to AS, it may manifest as persistent back discomfort & morning stiffness.

In contrast to AS, LSS typically manifests in people above the age of 60, is not accompanied by peripheral arthritis and extraskeletal symptoms, and has inconsistent NSAID response. Similar to AS, rheumatoid arthritis (RA) is a chronic inflammatory illness of the joints that frequently manifests in patients 40 years of age or younger as developing back pain & morning stiffness. Peripheral arthritis, in contrast to AS, is particularly frequent in RA. Rheumatoid nodules are another distinguishing feature of RA, but they are not typically seen in AS.

A degenerative condition known as diffuse idiopathic skeletal hyperostosis causes bone formation in the spine, most commonly in the anterior longitudinal ligaments, paravertebral tissues, & peripheral portion of the annulus fibrosus. Comparable to AS, the DISH may exhibit a history of back discomfort & postural abnormalities. The DISH does not exhibit inflammatory traits such morning stiffness or improvements with exercising but not with rest, in contrast to AS, which is an inflammatory condition. On radiographs, DISH also lacks any indication of sacroiliitis.

 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

History

The following are significant elements of the patient’s condition that point to ankylosing spondylitis (AS):

  • Symptoms that first appear around age 40
  • Beginning of low back discomfort slowly
  • Symptoms continuing for more than three months.
  • A worsening of symptoms in the morning or after inactivity
  • Exercise can help symptoms get better.

General symptoms

Back pain with inflammation, peripheral enthesitis, arthritis, as well as constitutional & organ-specific extra-articular signs are some of the symptoms of AS. Systemic characteristics are frequent in AS since it is a systemic inflammatory illness. Individuals with AS most frequently complain of stiffness and chronic pain. More than 70% of patients say they experience everyday stiffness and pain.

Another frequent issue is fatigue, which affects about 65 percent of AS patients. The majority of patients say their exhaustion is moderately severe. Greater discomfort, stiffness, and reduced functional capacity are all linked to higher levels of fatigue. When a disease is active, a fever & weight loss could develop.

Inflammatory back pain

The most frequent symptom and initial symptom in about 75 percent of patients is inflammatory back pain. The SI and gluteal regions often experience dull, poorly localised discomfort.

Insidious onset over months or years, typically with at least three months of symptoms prior to presentation, are some indications of inflammatory back pain. The majority of patients have moderate chronic conditions or sporadic flare-ups followed by remissions. Rarely is the spinal illness continuously active. The lumbosacral area is typically where the pain first appears, and it frequently starts unilaterally & intermittently. However, when the condition worsens, it becomes more chronic, bilateral, and moves closer to the spine, ossifying the annulus fibrosus and causing it to fuse (bamboo spine). Patients frequently report morning stiffness that lasts for at least thirty min, symptoms that get better with light exercise, and widespread, non-specific pain radiating into both buttock. A distinguishing symptom not typically seen in people with physical back pain is stiffness & pain that wakes them early in the morning.

There have been suggested diagnostic standards for inflamed back pain. When all five of the following conditions are met, the sensitivity is 79.6% as well as the specificity is 72.4%:

  • Pain at night.
  • Enhancement through exercise.
  • Age at onset is under 40 years.
  • With rest, nothing has changed.

Peripheral arthritis and enthesitis

Involvement of the peripheral musculoskeletal system occurs in 30 – 50percent of individuals. The primary pathological process that involves inflammation at the location where tendons and ligaments attach to bone is known as peripheral enthesitis. This frequently moves from osteitis and erosion to ossification, leaving behind recognisable radiological indications of periosteal new bone development.

Sites like these are frequently involved:

  • Iliac crest
  • Inferior and superior poles of the patella
  • Tibial tuberosity
  • The fifth metatarsal head’s base
  • Plantar fascia insertion on the calcaneus or metatarsal heads
  • Insertion of the Achilles tendon

The following are some further locations of involvement:

  • Distal ulna
  • Lateral epicondyle
  • Distal scapula
  • Costochondral junctions
  • Ischial tuberosity
  • Greater trochanter

Staging

Treatment Paradigm

The major treatment objectives should be to reduce stiffness and pain preserve functional capacity and axial spine motion and avoid spinal problems. Physical therapy, posture training, & regular exercise should all be considered non-pharmacologic therapies. Long-term, daily non-steroidal anti-inflammatory drug therapy is the first line of treatment.

If NSAIDs are ineffective, TNF-Is (tumour necrosis factor inhibitors), such as etanercept, adalimumab, or infliximab, might be added to them or used in place of them. 4 to 6 weeks after starting an NSAID and 12 weeks after starting a TNF-I should be used to evaluate the patient’s response. Although regional steroid injections may be an option, systemic glucocorticoids are not advised.

Referrals to specialists can be necessary depending on the clinical profile of the patient, probable sequelae, and extra-articular disease symptoms. Dermatologists, gastroenterologists, & ophthalmologists can help with associated non-musculoskeletal characteristics of AS, while rheumatologists can help with a formal diagnosis, therapy, & monitoring.

by Stage

by Modality

Chemotherapy

Radiation Therapy

 

 

Surgical Interventions

 

 

Hormone Therapy

 

 

Immunotherapy

 

 

Hyperthermia

 

 

Photodynamic Therapy

 

 

Stem Cell Transplant

 

 

Targeted Therapy

 

 

Palliative Care

 

 

Medication

 

 

 

aspirin

4 g orally daily in divided doses as needed



certolizumab pegol 

400

mg

Solution

Subcutaneous (SC)

every 2 weeks



golimumab 

50

mg

Subcutaneous (SC)

every month


Or
2 mg/kg IV at weeks 0 and 4, then every 8Weeks



adalimumab-aacf 

40

mg

Solution

Subcutaneous (SC)

every 2 weeks



esomeprazole/naproxen  

Take one tablet orally twice a day, ensuring a minimum interval of 30 minutes before meal



diclofenac 

diclofenac potassium- 25 mg orally 4-5 times daily
diclofenac sodium- 50 mg orally every 12 hours



azapropazone 

1.2 gm orally each day in 2 to 4 divided doses



sulindac 

Take 150 mg to 200 mg two times a day orally
The maximum dose is 400 mg
Take the minimum efficient amount for the shortest duration possible



Dose Adjustments

Limited data is available

meclofenamate 

Take a dose of 200 to 400 mg orally daily divided into 3 to 4 equal doses



 

sulindac 

Take 150 mg to 200 mg two times a day orally
The maximum dose is 400 mg
Take the minimum efficient amount for the shortest duration possible



 

azapropazone 

For more than 60 years, 300 mg twice daily



Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK470173/

Ankylosing Spondylitis

Updated : January 19, 2024




A chronic, inflammatory condition of the axial spine known as AS (ankylosing spondylitis) can cause a variety of clinical indications & symptoms. The most typical symptoms of the condition are growing spinal stiffness and persistent back pain. The condition is characterised by involvement of the spine, sacroiliac (SI) joints, digits, peripheral joints, and entheses.

AS is characterised by reduced spinal mobility, peripheral arthritis, buttock, and hip pain, enthesitis, postural irregularities & dactylitis (sometimes known as “sausage digits”). This illness may damage extraskeletal organs. The most prevalent extraarticular symptoms of AS are psoriasis (10%), acute anterior uveitis (25%–35%), and inflammatory bowel disease (up to 50%). A higher risk of heart disease is also linked to AS.

The systemic inflammation that is present in AS has been hypothesized to be the reason for this elevated risk. Because lower spinal movement and decreased chest wall expansion predispose patients to a restrictive pulmonary pattern, pulmonary problems are also linked to AS. Finally, AS puts persons at least twice as likely to suffer a vertebral brittle fracture. Additionally, these patients have a higher chance of suffering from cauda equina syndrome, spinal cord damage, or atlantoaxial subluxation.

 

About 80 percent of patients with ankylosing spondylitis experience their first symptoms before the age of 30, and the disease is frequently identified in those under the age of 40. Less than 5 percent of patients over the age of 45 visit the doctor. Men are more likely than women to have AS. Family members of patients who are impacted are at higher risk.

Ankylosing spondylitis is a sneaky-onset chronic inflammatory condition. The condition is characterized by progressive musculoskeletal and frequent extra-skeletal symptoms and signs. Each patient’s progression rate will be different.

Enthesitis with persistent inflammation, especially CD4 & CD8 T cells and macrophages, is the main pathogenesis of spondyloarthropathies. By causing swelling, fibrosis, & ossification at enthesitis sites, cytokines, especially TNF-α (tumour necrosis factor) & TGF-β (transforming growth factor), are also crucial in the inflammatory process.

In spite of the fact that the cause of ankylosing spondylitis is still largely unknown, there appears to be a connection between the incidence of AS & HLA-B27 in a specific community. There are between 5% and 6% of HLA-B27 positive individuals who also have AS.

The incidence of HLA-B27 differs among racial groups in the United States. HLA-B27 prevalence rates were 1.1 percent across non-Hispanic Blacks, 7.5 percent across non-Hispanic Whites, & 4.6 percent across Mexican-Americans, , based on a 2009 study.

 

Although significant physical handicap is infrequent, younger age of start is linked to worse function outcomes in ankylosing spondylitis sufferers. Most patients continue to function normally and can still work. When compared to the general population, patients with the severe, chronic condition die more frequently, primarily as a result of cardiovascular problems.

Physical examination

Chronic spinal involvement can eventually result in decreased range of motion (ROM) and vertebral body fusion. Unification of the neck in a hunched forward-flexed position is possible when the cervical and upper thoracic spine are involved (kyphosis). The patient’s mobility and ability to stare directly ahead may both be severely restricted in this position.

Articular manifestations

Concentrate the medical examination on the axial & peripheral joints’ active and passive ROM. Joint pain in the SI region is typical. The pain and swelling of tendons & ligamentous insertions are common symptoms of peripheral enthesitis.

Spine

In highly developed AS, the spine is stiff, or kyphosis, which causes a hunched posture, is present. Indirect signs of sacroiliitis & spondylitis may be seen earlier in the disease’s progression, such as SI discomfort (caused by indirect or direct compression) or a restricted range of motion in the spine. A malformation of the spine may occur in some patients, most frequently with a decrease of lumbar lordosis as well as an accentuation of thoracic kyphosis.

Peripheral joints and entheses

33 percent of patients experience peripheral enthesitis. These lesions may be accompanied by swelling at the ligament or tendon insertion and are unpleasant and tender to the touch. The insertions of the plantar fascia as well as the Achilles tendon on the calcaneus are the two most frequent & distinctive peripheral locations of enthesitis. Due to biomechanical stress, certain anatomical regions might be more vulnerable to enthesitis. Check patients carefully for palpable tenderness.

A portion of the involvement of the peripheral joints is due to enthesitis & synovitis. 33 percent of patients have peripheral joint disease, which most often affects the hips. The first ten years of the disease’s progression commonly see hip involvement, which is typically bilateral.

There may also be involvement in the following joints:

  • Temporomandibular joint
  • Symphysis pubis
  • Manubriosternal joints
  • Costosternal junctions
  • Costovertebral joints
  • Shoulder girdle

Rarely are peripheral joints implicated. They participate in an asymmetric oligoarticular pattern when they do.

Differential diagnosis

It’s important to screen out other diseases and ailments because they can mimic ankylosing spondylitis (AS). Among them are, but not restricted to:

  • DISH (Diffuse idiopathic skeletal hyperostosis)
  • Rheumatoid arthritis
  • Lumbar spinal stenosis
  • Mechanical low back pain

Although each of these illnesses shares features with AS, it is important to rule out or rule them in based on their distinctions. The beginning of symptoms can be used to distinguish between physical back pain and AS because the former can occur at any age while the latter usually does so before around 40. In contrast to AS, discomfort subsides with rest, and morning stiffness is minimal and transient. Like AS, mechanical back pain is not linked to extraskeletal symptoms or peripheral arthritis. A shrinking of the spinal canal known as lumbar spinal stenosis places stress on the spine. Similar to AS, it may manifest as persistent back discomfort & morning stiffness.

In contrast to AS, LSS typically manifests in people above the age of 60, is not accompanied by peripheral arthritis and extraskeletal symptoms, and has inconsistent NSAID response. Similar to AS, rheumatoid arthritis (RA) is a chronic inflammatory illness of the joints that frequently manifests in patients 40 years of age or younger as developing back pain & morning stiffness. Peripheral arthritis, in contrast to AS, is particularly frequent in RA. Rheumatoid nodules are another distinguishing feature of RA, but they are not typically seen in AS.

A degenerative condition known as diffuse idiopathic skeletal hyperostosis causes bone formation in the spine, most commonly in the anterior longitudinal ligaments, paravertebral tissues, & peripheral portion of the annulus fibrosus. Comparable to AS, the DISH may exhibit a history of back discomfort & postural abnormalities. The DISH does not exhibit inflammatory traits such morning stiffness or improvements with exercising but not with rest, in contrast to AS, which is an inflammatory condition. On radiographs, DISH also lacks any indication of sacroiliitis.

 

History

The following are significant elements of the patient’s condition that point to ankylosing spondylitis (AS):

  • Symptoms that first appear around age 40
  • Beginning of low back discomfort slowly
  • Symptoms continuing for more than three months.
  • A worsening of symptoms in the morning or after inactivity
  • Exercise can help symptoms get better.

General symptoms

Back pain with inflammation, peripheral enthesitis, arthritis, as well as constitutional & organ-specific extra-articular signs are some of the symptoms of AS. Systemic characteristics are frequent in AS since it is a systemic inflammatory illness. Individuals with AS most frequently complain of stiffness and chronic pain. More than 70% of patients say they experience everyday stiffness and pain.

Another frequent issue is fatigue, which affects about 65 percent of AS patients. The majority of patients say their exhaustion is moderately severe. Greater discomfort, stiffness, and reduced functional capacity are all linked to higher levels of fatigue. When a disease is active, a fever & weight loss could develop.

Inflammatory back pain

The most frequent symptom and initial symptom in about 75 percent of patients is inflammatory back pain. The SI and gluteal regions often experience dull, poorly localised discomfort.

Insidious onset over months or years, typically with at least three months of symptoms prior to presentation, are some indications of inflammatory back pain. The majority of patients have moderate chronic conditions or sporadic flare-ups followed by remissions. Rarely is the spinal illness continuously active. The lumbosacral area is typically where the pain first appears, and it frequently starts unilaterally & intermittently. However, when the condition worsens, it becomes more chronic, bilateral, and moves closer to the spine, ossifying the annulus fibrosus and causing it to fuse (bamboo spine). Patients frequently report morning stiffness that lasts for at least thirty min, symptoms that get better with light exercise, and widespread, non-specific pain radiating into both buttock. A distinguishing symptom not typically seen in people with physical back pain is stiffness & pain that wakes them early in the morning.

There have been suggested diagnostic standards for inflamed back pain. When all five of the following conditions are met, the sensitivity is 79.6% as well as the specificity is 72.4%:

  • Pain at night.
  • Enhancement through exercise.
  • Age at onset is under 40 years.
  • With rest, nothing has changed.

Peripheral arthritis and enthesitis

Involvement of the peripheral musculoskeletal system occurs in 30 – 50percent of individuals. The primary pathological process that involves inflammation at the location where tendons and ligaments attach to bone is known as peripheral enthesitis. This frequently moves from osteitis and erosion to ossification, leaving behind recognisable radiological indications of periosteal new bone development.

Sites like these are frequently involved:

  • Iliac crest
  • Inferior and superior poles of the patella
  • Tibial tuberosity
  • The fifth metatarsal head’s base
  • Plantar fascia insertion on the calcaneus or metatarsal heads
  • Insertion of the Achilles tendon

The following are some further locations of involvement:

  • Distal ulna
  • Lateral epicondyle
  • Distal scapula
  • Costochondral junctions
  • Ischial tuberosity
  • Greater trochanter

The major treatment objectives should be to reduce stiffness and pain preserve functional capacity and axial spine motion and avoid spinal problems. Physical therapy, posture training, & regular exercise should all be considered non-pharmacologic therapies. Long-term, daily non-steroidal anti-inflammatory drug therapy is the first line of treatment.

If NSAIDs are ineffective, TNF-Is (tumour necrosis factor inhibitors), such as etanercept, adalimumab, or infliximab, might be added to them or used in place of them. 4 to 6 weeks after starting an NSAID and 12 weeks after starting a TNF-I should be used to evaluate the patient’s response. Although regional steroid injections may be an option, systemic glucocorticoids are not advised.

Referrals to specialists can be necessary depending on the clinical profile of the patient, probable sequelae, and extra-articular disease symptoms. Dermatologists, gastroenterologists, & ophthalmologists can help with associated non-musculoskeletal characteristics of AS, while rheumatologists can help with a formal diagnosis, therapy, & monitoring.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

aspirin

4 g orally daily in divided doses as needed



certolizumab pegol 

400

mg

Solution

Subcutaneous (SC)

every 2 weeks



golimumab 

50

mg

Subcutaneous (SC)

every month


Or
2 mg/kg IV at weeks 0 and 4, then every 8Weeks



adalimumab-aacf 

40

mg

Solution

Subcutaneous (SC)

every 2 weeks



esomeprazole/naproxen  

Take one tablet orally twice a day, ensuring a minimum interval of 30 minutes before meal



diclofenac 

diclofenac potassium- 25 mg orally 4-5 times daily
diclofenac sodium- 50 mg orally every 12 hours



azapropazone 

1.2 gm orally each day in 2 to 4 divided doses



sulindac 

Take 150 mg to 200 mg two times a day orally
The maximum dose is 400 mg
Take the minimum efficient amount for the shortest duration possible



Dose Adjustments

Limited data is available

meclofenamate 

Take a dose of 200 to 400 mg orally daily divided into 3 to 4 equal doses



sulindac 

Take 150 mg to 200 mg two times a day orally
The maximum dose is 400 mg
Take the minimum efficient amount for the shortest duration possible



azapropazone 

For more than 60 years, 300 mg twice daily



 

 

https://www.ncbi.nlm.nih.gov/books/NBK470173/