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Ankylosing Spondylitis

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Description: Ankylosing spondylitis is a chronic inflammatory disease primarily affecting the spine and sacroiliac joints, leading to pain and potentially severe spinal fusion and rigidity.
Type: Ankylosing spondylitis is an inflammatory disease primarily affecting the spine and sacroiliac joints. It is considered a type of seronegative spondyloarthropathy. The disease has a strong genetic component, with a notable association with the HLA-B27 gene. However, it is not inherited in a simple Mendelian fashion; instead, it follows a complex polygenic pattern with contributions from multiple genes and environmental factors.
Signs And Symptoms: The signs and symptoms of ankylosing spondylitis often appear gradually, with peak onset between 20 and 30 years of age. Initial symptoms are usually a chronic dull pain in the lower back or gluteal region combined with stiffness of the lower back. Individuals often experience pain and stiffness that awakens them in the early morning hours.As the disease progresses, loss of spinal mobility and chest expansion, with a limitation of anterior flexion, lateral flexion, and extension of the lumbar spine are seen. Systemic features are common with weight loss, fever, or fatigue often present. Pain is often severe at rest but may improve with physical activity. Inflammation and pain may recur to varying degrees regardless of rest and movement.
AS can occur in any part of the spine or the entire spine, often with pain localized to either buttock or the back of the thigh from the sacroiliac joint. Arthritis in the hips and shoulders may also occur. When the condition presents before the age of 18, AS is more likely to cause pain and swelling of large lower limb joints, such as the knees. In prepubescent cases, pain and swelling may also manifest in the ankles and feet where heel pain and enthesopathy commonly develop. Less common occurrences include ectasia of the sacral nerve root sheaths.About 30% of people with AS will also experience anterior uveitis causing eye pain, redness, and blurred vision. This is thought to be due to the association that both AS and uveitis have with the presence of the HLA-B27 antigen. Cardiovascular involvement may include inflammation of the aorta, aortic valve insufficiency or disturbances of the heart's electrical conduction system. Lung involvement is characterized by progressive fibrosis of the upper portion of the lung.
Prognosis: Prognosis is related to disease severity. AS can range from mild to progressively debilitating and from medically controlled to refractory. Some cases may have times of active inflammation followed by times of remission resulting in minimal disability while others never have times of remission and have acute inflammation and pain, leading to significant disability. As the disease progresses, it can cause the vertebrae and the lumbosacral joint to ossify, resulting in the fusion of the spine. This places the spine in a vulnerable state because it becomes one bone, which causes it to lose its range of motion as well as putting it at risk for spinal fractures. This not only limits mobility but reduces the affected person's quality of life. Complete fusion of the spine can lead to a reduced range of motion and increased pain, as well as total joint destruction which could lead to a joint replacement.Osteoporosis is common in ankylosing spondylitis, both from chronic systemic inflammation and decreased mobility resulting from AS. Over a long-term period, osteopenia or osteoporosis of the AP spine may occur, causing eventual compression fractures and a back "hump". Hyperkyphosis from ankylosing spondylitis can also lead to impairment in mobility and balance, as well as impaired peripheral vision, which increases the risk of falls which can cause fracture of already-fragile vertebrae. Typical signs of progressed AS are the visible formation of syndesmophytes on X-rays and abnormal bone outgrowths similar to osteophytes affecting the spine. In compression fractures of the vertebrae, paresthesia is a complication due to the inflammation of the tissue surrounding nerves.
Organs commonly affected by AS, other than the axial spine and other joints, are the heart, lungs, eyes, colon, and kidneys. Other complications are aortic regurgitation, Achilles tendinitis, AV node block, and amyloidosis. Owing to lung fibrosis, chest X-rays may show apical fibrosis, while pulmonary function testing may reveal a restrictive lung defect. Very rare complications involve neurologic conditions such as the cauda equina syndrome.
Onset: Ankylosing spondylitis often begins in late adolescence or early adulthood, commonly between the ages of 15 and 30. Early symptoms typically include chronic pain and stiffness in the lower back and hips, particularly in the morning or after periods of inactivity.
Prevalence: Ankylosing spondylitis (AS) is a form of inflammatory arthritis that primarily affects the spine and sacroiliac joints. The prevalence of ankylosing spondylitis varies geographically and among different populations. It is estimated to affect approximately 0.1% to 1.8% of the global population. The condition tends to be more common in males than females and typically manifests in late adolescence to early adulthood.
Epidemiology: Between 0.1% and 0.8% of people are affected. The disease is most common in Northern European countries, and seen least in people of Afro-Caribbean descent. Although the ratio of male to female disease is reportedly 3:1, many rheumatologists believe the number of women with AS is underdiagnosed, as most women tend to experience milder cases of the disease. The majority of people with AS, including 95 per cent of people of European descent with the disease, express the HLA-B27 antigen and high levels of immunoglobulin A (IgA) in the blood. In 2007, a team of researchers discovered two genes that may contribute to the cause of AS: ARTS-1 and IL23R. Together with HLA-B27, these two genes account for roughly 70 percent of the overall number of cases of the disease.
Intractability: Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the spine and sacroiliac joints. While it is not curable, it is not entirely intractable. Treatment options such as nonsteroidal anti-inflammatory drugs (NSAIDs), biologics like TNF inhibitors, physical therapy, and lifestyle modifications can help manage symptoms, reduce inflammation, and improve quality of life. Early diagnosis and a comprehensive treatment plan are key to controlling the disease effectively.
Disease Severity: Ankylosing spondylitis is a chronic inflammatory disease that primarily affects the spine and sacroiliac joints, leading to pain and stiffness. The severity of the disease can vary widely among individuals. In some cases, the disease may progress slowly with mild symptoms, while in others, it can lead to severe pain, loss of spinal mobility, and even fusion of the vertebrae (ankylosis).

Currently, there are no specific nanotechnology-based treatments widely used for ankylosing spondylitis. However, research in nanomedicine is ongoing, aiming to improve drug delivery systems for better efficacy and reduced side effects.
Healthcare Professionals: Disease Ontology ID - DOID:7147
Pathophysiology: Ankylosing spondylitis (AS) is a systemic rheumatic disease, meaning it affects the entire body. 1–2% of individuals with the HLA-B27 genotype develop the disease.Tumor necrosis factor-alpha (TNF α) and interleukin 1 (IL-1) are also implicated in ankylosing spondylitis. Autoantibodies specific for AS have not been identified. Anti-neutrophil cytoplasmic antibodies (ANCAs) are associated with AS, but do not correlate with disease severity.Single nucleotide polymorphism (SNP) A/G variant rs10440635 is close to the PTGER4 gene on human chromosome 5 has been associated with an increased number of cases of AS in a population recruited from the United Kingdom, Australia, and Canada. The PTGER4 gene codes for the prostaglandin EP4 receptor, one of four receptors for prostaglandin E2. Activation of EP4 promotes bone remodeling and deposition (see prostaglandin EP4 receptor § Bone) and EP4 is highly expressed at vertebral column sites involved in AS. These findings suggest that excessive EP4 activation contributes to pathological bone remodeling and deposition in AS and that the A/G variant rs10440635a of PTGER4 predisposes individuals to this disease, possibly by influencing EP4's production or expression pattern.The association of AS with HLA-B27 suggests the condition involves CD8 T cells, which interact with HLA-B. This interaction is not proven to involve a self-antigen, and at least in the related reactive arthritis, which follows infections, the antigens involved are likely to be derived from intracellular microorganisms. There is, however, a possibility that CD4+ T lymphocytes are involved in an aberrant way, since HLA-B27 appears to have a number of unusual properties, including possibly an ability to interact with T cell receptors in association with CD4 (usually CD8+ cytotoxic T cell with HLAB antigen as it is a MHC class 1 antigen).
"Bamboo spine" develops when the outer fibers of the fibrous ring (anulus fibrosus disci intervertebralis) of the intervertebral discs ossify, which results in the formation of marginal syndesmophytes between adjoining vertebrae.
Carrier Status: Ankylosing spondylitis does not have a carrier status. It is a chronic inflammatory disease that primarily affects the spine and sacroiliac joints. It is associated with the HLA-B27 gene in many, but not all, cases. Having the HLA-B27 gene increases the risk but does not guarantee that an individual will develop the disease. The condition is complex and likely involves a combination of genetic and environmental factors.
Mechanism: Ankylosing spondylitis (AS) is a type of inflammatory arthritis that primarily affects the spine and sacroiliac joints.

Mechanism:
Ankylosing spondylitis involves chronic inflammation of the entheses, which are the sites where ligaments and tendons attach to bones. This inflammation can lead to pain, stiffness, and ultimately ankylosis, which is the fusion of the bones. The exact cause of AS is not entirely understood, but genetic, environmental, and immunological factors are involved.

Molecular Mechanisms:
1. **Genetic Factors:** The HLA-B27 gene is strongly associated with AS. Around 90-95% of people with AS possess this gene, although not everyone with HLA-B27 will develop AS. HLA-B27 may misfold within the endoplasmic reticulum, triggering an unfolded protein response that results in chronic inflammation.

2. **Cytokines and Inflammatory Pathways:** Pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), and interleukin-23 (IL-23) play pivotal roles in the inflammatory process. These cytokines promote the activation and survival of inflammatory cells such as T cells, macrophages, and neutrophils, contributing to the chronic inflammation seen in AS.

3. **Microbiome Interactions:** There is evidence suggesting that gut microbiota might interact with the immune system in a way that influences the development of AS. Dysbiosis, or an imbalance in gut microbiota, may exacerbate immune responses and inflammation.

4. **Bone Remodeling Pathways:** As inflammation persists, it can stimulate pathways that lead to bone formation at entheses, mediated by molecules like bone morphogenetic proteins (BMPs) and the Wnt signaling pathway. Over time, this leads to new bone formation and fusion of the joints.

Research into these pathways is ongoing, with the aim of developing targeted therapies to inhibit specific molecules and pathways involved in the disease.
Treatment: There is no cure for AS, but treatments and medications can reduce symptoms and pain.
Compassionate Use Treatment: Compassionate use treatment for ankylosing spondylitis (AS) may include access to investigational drugs or biologics that are not yet approved by regulatory agencies but are used under special circumstances. This generally applies to patients who have severe disease and have not responded to standard treatments. Patients often gain access through clinical trials or expanded access programs.

Off-label treatments and experimental therapies for ankylosing spondylitis may include:

1. **Biologic agents**: While several biologics are approved for AS, others that are approved for related conditions like rheumatoid arthritis might be used off-label. Examples include rituximab and abatacept.

2. **Janus kinase (JAK) inhibitors**: These are primarily approved for rheumatoid arthritis but are being investigated for AS. Tofacitinib and upadacitinib are examples sometimes used off-label.

3. **IL-17 and IL-23 inhibitors**: These biologics target specific cytokines involved in inflammatory pathways. Secukinumab (an IL-17A inhibitor) is approved for AS, while others like ixekizumab and ustekinumab (an IL-12/23 inhibitor) might be used off-label or are under investigation.

4. **Stem cell therapy**: Although highly experimental, mesenchymal stem cell therapy is being researched for its potential to modulate immune responses and repair tissue damage.

5. **Small molecule inhibitors**: Such as apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, approved for psoriatic arthritis, might be considered.

Patients and healthcare providers should weigh the potential benefits and risks of these treatments and consider involvement in clinical trials whenever possible for access to the latest therapies.
Lifestyle Recommendations: Lifestyle recommendations for ankylosing spondylitis include:

1. Regular Exercise: Engaging in low-impact activities such as swimming, walking, and stretching to maintain flexibility and strength.
2. Good Posture: Practicing good posture to prevent deformities and maintain spine alignment.
3. Balanced Diet: Following an anti-inflammatory diet rich in fruits, vegetables, whole grains, and omega-3 fatty acids.
4. Smoking Cessation: Avoiding smoking, as it can exacerbate symptoms and overall health.
5. Sleep Quality: Using a firm mattress and pillow to support proper spine alignment.
6. Stress Management: Incorporating relaxation techniques such as yoga, meditation, or deep breathing exercises.
7. Ergonomic Adjustments: Making workplace and home modifications to reduce strain on the back.

Consult with healthcare providers for personalized recommendations.
Medication: Medications for AS may be broadly considered either "disease-modifying" or "non-disease-modifying". Disease-modifying medications for ankylosing spondylitis aim to slow disease progression and include drugs like tumor necrosis factor (TNF) inhibitors. Non-disease-modifying medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), primarily address symptoms like pain and inflammation but do not alter the course of the disease.
Repurposable Drugs: For ankylosing spondylitis, several repurposable drugs that might be considered include:

1. **NSAIDs (Nonsteroidal Anti-Inflammatory Drugs):** Commonly used to reduce inflammation and pain; examples include ibuprofen and naproxen.
2. **TNF inhibitors (Tumor Necrosis Factor inhibitors):** Originally developed for other inflammatory conditions like rheumatoid arthritis, they can be effective in ankylosing spondylitis; examples include infliximab, adalimumab, and etanercept.
3. **IL-17 inhibitors:** Secukinumab and ixekizumab are examples of IL-17 inhibitors that were initially developed for other conditions but can be used for ankylosing spondylitis.

These treatments can help manage symptoms and slow disease progression. Always consult a healthcare professional for advice tailored to individual health needs.
Metabolites: Information on specific metabolites involved in ankylosing spondylitis (AS) is still an area of active research. However, some studies have suggested potential metabolic alterations that play a role in the disease. For example, abnormalities in amino acid metabolism, lipid metabolism, and energy metabolism have been observed in AS patients.

Regarding nanotechnology (nan), its application in ankylosing spondylitis primarily focuses on developing targeted drug delivery systems and diagnostic tools. Nanoparticles can potentially deliver anti-inflammatory drugs directly to affected joints, thereby reducing systemic side effects and improving therapeutic outcomes. Additionally, nanotechnology-based imaging techniques could enhance early diagnosis and monitoring of disease progression.
Nutraceuticals: Nutraceuticals for ankylosing spondylitis may include:

1. **Omega-3 Fatty Acids:** Found in fish oil, these can help reduce inflammation.
2. **Curcumin:** An active compound in turmeric, known for its anti-inflammatory properties.
3. **Vitamin D:** Important for bone health, as deficiency is common in autoimmune disorders.
4. **Glucosamine and Chondroitin:** Often used for joint support, though evidence for effectiveness is mixed.

Always consult a healthcare professional before starting any new supplementation.
Peptides: Ankylosing spondylitis is a type of arthritis that primarily affects the spine, although other joints can be involved. Research into peptides for ankylosing spondylitis is ongoing, with some studies exploring the potential of peptide-based therapies to modulate the immune response and reduce inflammation. Nanotechnology is also being investigated in the context of ankylosing spondylitis for its potential to deliver drugs more effectively, increase bioavailability, and reduce side effects. Nanoparticles may be engineered to target specific cells or tissues, offering a promising approach for future treatments.