Ankylosing Spondylitis

Ankylosing Spondylitis

1. ANKYLOSING SPONDYLITIS Guided By Mr.P.Raut Presented By Gayatri R.Kachh

2. OVERVIEW Introduction of A.S. Epidemiology of A.S Characteristics Pathological Features of A.S. Symptoms of A.S. Structural Damage in A.S. Causes of A.S. HLA-B27 Pathogenesis of HLA-B27 Diagnosis of A.S. Treatment of A.S. Humira Pen Therapy( Adalimumab ) for A.S. Quality of Life Conclusion References

3. Introduction Ankylosing Spondylitis is a Rheumatic disease of unknown cause that primarily affects the back bone or spine . The name is derived from the Greek words ‘ Ankylos ” meaning fusion and “ Spondylos ” meaning vertebra. “ Itis ” denotes inflammation of the body part. The name therefore describes the inflammatory process in the spinal joints It is considered to be one of a group of diseases called the Spondylo-Arthropathies AS is a chronic, progressive immune-mediated inflammatory disorder that results in ankylosis of the vertebral column and sacroiliac joints Also referred to as the Bekhterev-Strumpell syndrome after the first doctor to actually study the disease. Aka Strumpell -Marie(or Marie- Strumpell ) disease after his wife, the first officially noted case study

4. Epidemiology of A.S. First documented AS case was reported in 1691 Unknown cause First signs of Ankylosing Spondylitis were unearthed in the skeletal remains of a 5000 year old Egyptian mummy The incidence of AS may be underestimated due to unreported cases HLA-B27 gene is associated with AS Age of onset typically between 15 and 35 years 2-3 times more frequent in men than in women M ore common in whites than in nonwhites

5. Characteristics Pathological Features of A.S. Chronic inflammation in: Axial structures (sacroiliac joint, spine, anterior chest wall, shoulder and hip) Possibly large peripheral joints, mainly at the lower limbs ( oligoarthritis ) Entheses ( enthesitis ) Bone formation particularly in the axial joints Serronegative Presence of HLA-B27

6. Symptoms of A.S. Axial manifestations: Chronic low back pain With or without buttock pain Inflammatory characteristics: Occurs at night (second part), Sleep disturbance,Morning stiffness Limited lumbar motion Onset before age of 40 years Other common symptoms seen during the early stages of disease include: Anorexia Malaise Low grade fever Weight loss Fatigue

7. Structural Damage in A.S. Most striking feature of AS = New bone formation in the spine with: Spinal syndesmophytes Ankylosis Both can be seen on conventional radiography Bamboo Spine: Repeated process of healing and bone formation leads to the formation of Syndesmophytes i.e. “Bone Bridges”

8. Causes of A.S. The exact cause of ankylosing spondylitis is unknown, but genes are thought to play a part. The tendency for developing ankylosing spondylitis is believed to be genetically inherited, and the majority (nearly 90%) of patients with ankylosing spondylitis is born with the HLA-B27 gene . The HLA-B27 gene appears only to increase the tendency of developing ankylosing spondylitis One can likely to get AS if you have a history of it in your family. Studies show that almost nine out of ten people with AS have the gene called HLA-B27 . Researchers currently think that exposure to certain environmental triggers can lead to the development of AS in people with the gene. But these triggers are unknown.

9. HLA-B27 Human leukocyte antigens (HLAs) are proteins that help the body's immune system tell the difference between its own cells and foreign, harmful substances . The human leukocyte antigen (HLA) is not a single antigen, but is rather a group of proteins that are located on the surface of White Blood Cells (WBCs). The HLA is the human version of a complex that is known as the major histocompatibility complex . A variation of the  HLA-B  gene called  HLA-B27  increases the risk of developing ankylosing spondylitis . Mechanism of HLA-B27 action in AS patients may still involve peptide handling (the canonical function of HLA-B27 as a MHC class I molecule).

10. Pathogenesis of HLA-B27 HLA-B27 is the strongest associated gene in AS. Recent Genome Wide Association Studies (GWAS) have implicated several other genes associated with AS thus affirming the complex, oligogenic nature of the disease HLA-B27 consists of a heavy chain having three a domains, which non-covalently binds short peptides and β 2 -microglobulin (β 2 M ) Although the HLA-B27 has remained a center of extensive research, the mechanism whereby HLA-B27 confers susceptibility to AS is not well defined. Current hypotheses regarding the pathogenesis of AS have sought to incorporate HLA B27 into mechanistic models.

11. Diagnosis of A.S. MRI X-Ray CT-Scan Several Lab test are also performed such as measuring the concentration of CRP and ESR in the blood samples of A.S. Patients. There is no direct test to diagnose AS

12. Treatment of A.S. There is not yet a cure for AS. However, there are effective treatment options that can relieve pain and improve your condition The general approach is a conservative treatment plan that includes: medication, physical therapy, and exercise Drugs like. Local steroid injection To single inflamed joints, entheses , bursae Beware of weight bearing enthesis Not more than 3 injections a yr NSAIDs Spinal stiffness, pain Persistent synovitis or enthesopathy Caution in elderly, peptic ulcer COX II inhibitors Oral or systemic steroids Short courses for intolerable symptoms Uveitis May result in osteoporosis Precipitate heart failure DMARDS & TNF Blocker(Anti-TNF) These are some most frequently used drugs in A.S. Condition

13. Right Posture, Swimming, Daily workouts are some of the physical therapies. In severe cases of AS, surgery can be an option in the form of joint replacements, particularly in the knees and hips Daily Workouts Surgery

14. Humira Pen Therapy( Adalimumab ) for A.S. HUMIRA ( adalimumab ) is a recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF). HUMIRA is a medicine called a Tumor Necrosis Factor (TNF) blocker . Adalimumab is produced by recombinant DNA technology in a mammalian cell expression system and is purified by a process that includes specific viral inactivation and removal steps. It consists of 1330 amino acids and has a molecular weight of approximately 148 kilodaltons . Adalimumab binds specifically to TNF-alpha and blocks its interaction with the p55 and p75 cell surface TNF receptors.

15. Quality of Life with A.S. AS=23.7 years 90.2 83.1 62.4 54.1 20 40 60 80 100 Stiffness Pain Fatigue Poor Sleep N=175 Percentage of Patients (%) Bad Quality Pain Sleep problems Fatigue Loss of mobility and dependency Loss of social life Effect employability Higher rate of mortality

16. CONCLUSION Ankylosing spondylitis has been a challenging disorder with few therapeutic options. In previous studies, patients receiving traditional therapies such as NSAIDs and DMARDs have received only mild to moderate benefit. Importantly, no intervention has been shown to alter progressive loss of spinal mobility . The need for new alternatives for treating these patients is substantial. The pathogenesis of AS is poorly understood. HLA-B27 stands as the earliest and most robust genetic marker associated with a rheumatic disease Researchers are currently exploring the pathogenic role of inflammatory cellular infiltrates, including various cytokines such as TNF α Use TNF inhibitor like Adalimumab ( Humira ). However, these treatments are of limited benefit. Emerging biological therapies target the inflammatory processes underlying AS, and thus, may favourably alter the disease process while providing relief of symptoms.

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