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SHOAIB AHMED SHARIEF

Technical Seminar

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RHEUMATOID ARTHRITIS

(R.A)

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CONTENTS : 1. History2. Introduction3. Epidemiology4. Causes5. Signs and Symptoms6. Diagnosis7. Treatment8. Conclusion9. Path Forward10.References

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History of R.A1858 – Dr. Alfred Baring Garrod,

named the condition Rheumatoid Arthritis.

In the 1920’s, physicians suspected the cause of RA was bacterial infection, they used gold and malaria drugs.

1940- Scientists discovered that RA was associated with a malfunction of the immune system.

1949 – Dr. Phillip Hench treated arthritic patients successfully with Cortisone.

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What is Rheumatoid Arthitis (R.A)?Rheumatoid arthritis is an autoimmune disease in which the normal immune response is directed against an individual's own tissue, including the joints, tendons, and bones, resulting in inflammation and destruction of these tissues.

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Epidemiology.. Who gets R.A??

ANYONE CAN GET R.A◦From babies to the very old

Common Age to Start: 20’s to 50’s

Sex: Females more common than males 3:1

1% of Indian population is affected with R.A

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Causes :The exact cause of RA is unknown.Suspected causes are:1. Bacterial Infection2. Genetic Marker3. Stress4. Viral Infection Other suspects include female

hormones. Smoking.

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How does it start?RA usually starts off slowly (insidious)

over weeks to months and progresses (70%)

It can come on overnight (acute) but this is rare (10%)

It can come on over a few weeks (subacute – 20%)

In the initial stages of each joint involvement, there is warmth, pain, and swelling, with corresponding decrease of range of motion of the affected joint.

Progression of the disease results in reducible and later fixed deformities.

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Joints affected

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http://www.umm.edu/graphics/images/en/17128.jpg

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Normal jointRheumatoi

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http://img.webmd.com/dtmcms/live/webmd/consumer_assets/site_images/articles/health_and_medical_reference/joints_bones_and_muscles/arthritis_basics_normal_joint.JPG

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What happens in the JOINTS?In RA, for some unknown reason, the

immune system considers its own joint tissues as foreign.

WBC that normally protect the body, migrate to the joint cavity.

Synovium becomes inflammed and engorged with fluid, causing synovitis.

Lymphocytes, Macrophages, continue to enter the joint cavity and multiply, differentiate, and release inflammatory mediators, cytokines, leukotrienes, and prostaglandins.

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Continued…Within weeks the synovium becomes

thickened.The mass of synovial tissue that spreads

over the top of cartilage in a rheumatoid joint is called a Pannus, made of white blood cells: macrophages, B&T Cells, neutrophils, plasma cells, NK cells, and T Helper cells.

These cells produce the Rheumatoid Factor, prostaglandins, cytokines and other mediators.

Over time, the chemicals from the cells damage cartilage, ligaments, tendons, and bone.

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Tumor Necrosis Factor (TNF)

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TNF is a potent inflammatory cytokine

TNF is produced mainly by macrophages and monocytes

TNF is a major contributor to the inflammatory and destructive changes that occur in RA

Blockade of TNF results in a reduction in a number of other pro-inflammatory cytokines (IL-1, IL-6, & IL-8)

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Macrophage

Any Cell

Trans-Membrane Bound TNF

TNF Receptor

Soluble TNF

How Does TNF Exert Its Effect?

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Any Cell

Trans-Membrane Bound TNF

TNF Receptor

Soluble TNF

How Are the Effects of TNF Naturally Balanced?

Soluble Receptor

Macrophage

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Established R.ARheumatoi

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http://t0.gstatic.com/images?q=tbn:ANd9GcTuR85lK2XKocig-Sut0u1LP3BrEF9aXmUYf9sAt4acgxa36SKIOuQmWA

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Real images of affected joints..

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http://t3.gstatic.com/images?q=tbn:ANd9GcRDNkPcY3zheYEWvL5Fk5xsg8iGiojZmXaO74GOO_4uNotthMhMeAAqZA

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Signs & Symptoms :• Fatigue.• Stiffness, especially in early morning

and after sitting a long period of time.• Low Grade Fever, Weakness.• Muscle pain and pain with prolonged

sitting.• Rheumatoid nodules.• Deformity of joints over time.Joints are usually

◦Swollen◦Warm

◦NOT RED

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http://lh3.ggpht.com/RBG1yD3ab-uyQdaCaEmH1B8r5MCchN5Y3e9WAJFn6LrzD2tdfTV1bYhKgBjjEvyYWdbN=s133

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Diagnosis :Rheumatoi

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Anti-CCP antibody test.Complete blood count.Synovial fluid test.Imaging Studies1. X-Ray2. M.R.I Scan3. C.A.T Scan4. Bone Scan

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Treatment :

Medications

Disease Modifying

Anti Rheumatic

Drugs (DMARDs):

Eg. Methotrexa

te Biologic

al Therapi

es (Biologics

) : Eg. Inflixima

b

Anti-inflammatory medications :

Eg. Asprin, Nonsteroidal

Anti-Inflammatory

Drugs (NSAIDs)-such as

ibuprofen .

Physical therapy

Healthy Diet

Surgery

Removal of the

joint lining

(Synovectomy)

Total joint replaceme

nt

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Trans-Membrane Bound TNF

Soluble TNF

Strategies for Reducing Effects of TNF!!.

Macrophage

Monoclonal Antibody :

InfliximabRheumatoi

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Biological Therapies (Biologics)

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Chimeric (murine & human) monoclonal antibody directed against TNF-αRheu

matoid

Arthritis

http://lh6.ggpht.com/_K-9oRygAfTpS3Y7yX8j6lYqZAnkhCXmLu1q9-iQQeHO2XUSz0qdwAmK_UGM9_J1EtEX=s122

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ConclusionRheumatoi

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R.A is a chronic disease of unknown cause affecting the joints and other tissues resulting in deformity of joints over time.

RA patients today can live a healthy and productive life. Today’s medicines used can relieve pain and swelling and in some cases put the disease in remission, preventing bone damage or deformity.

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Path forward :-Rheumatoi

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New drugs are emerging with increased efficacy but long term risks unknown.

It is only a matter of time when researchers will find the reason why the body’s immune system attacks the synovial lining of the joints which causes this disorder known as Rheumatoid Arthritis.

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References

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Arthritis Foundation. “Disease Center.” Arthritis Foundation. 2004. 24 Aug. 2005. <http://www.arthritis.org/conditions/DiseaseCenter/RA/ra_overview.asp>. 

Arthritis Foundation. Good Living with Rheumatoid Arthritis. Atlanta: Arthritis Foundation, 2004. 

Lahita, Robert G. M.D. Rheumatoid Arthritis – Everything You Need to Know. New York: Avery, 2001

Mayo Clinic. “Rheumatoid Arthritis.” Mayo Clinic.com. Mayo Foundation for Medical Education and Research. 8 April. 2005. 10 Oct. 2005 http://www.mayoclinic.com/invoke.cfm?id=DS00020>.

National Institute of Arthritis and Musculoskeletal and Skin Diseases. “Questions and Answers About Juvenile Rheumatoid Arthritis.” National Institute of Health. 2001 July. 10 Oct. 2005. <http://www.niams.nih.gov/hi/topics/juvenile_arthritis/juvarthr.htm>.

Oxford Journals. “Alfred Baring Garrod.” Heberden Historical Series. British Society for Rheumatology. 2001. 28 Oct. 2005. <http://rheumatology.oxfordjournals.org/cgi/content/full/40/10/1189?eaf>.

Parham, Peter. The Immune System. New York: Garland Science Publishing, 2005. Shlotzhauer, Tammi L. M.D. and James McGuire M.D. Living with Rheumatoid Arthritis. Baltimore: John Hopkins University Press, 2003.

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Thank you all..

!!