RHEUMATOID ARTHRITIS AND ITS MANAGEMENT

A Thesis Submitted to Open International University for Complementary Medicines (Pakistan Campus) affiliated to Open International University for Complementary Medicines (OIUCM) Colombo in Fulfillment of the Requirements for the Degree of

Doctor of Alternative Medicines, MD (Alt.Med)

BY

HOMOEOPATHIC DR.WALI KHAN DHMS, RHMP, M.Sc (Biochemistry)

drsarhadi@gmail.com

Rheumatoid Arthritis and Its Management

Rheumatoid Arthritis and Its Management

APPROVAL

Name: Degree: Title of Thesis:

Dr.Wali Khan Doctor of Alternative Medicine, MD (Alt.Med) Rheumatoid Arthritis and its Management

Examining Committee:

Chairman:

Prof.Dr.Mendis

Signature and Seal: _____________________________________________

Supervisor:

Prof.Dr.Indrapala

Signature and Seal: _______________________________________________ Date of Approval: _____________________________________________

I dedicate this humble effort, the fruit of my thoughts and study to my affectionate father and mother who groomed and inspired me to higher ideas of life.

Acknowledgement
It is the day of great pleasure for me that with the blessing of Almighty Allah and my continuous hard work I have achieved my target to complete this thesis. I am very thankful to Homoeopathic Professor Dr Inamullah Mirza Ex-President National Council for Homoeopathy (Govt: Pakistan) for providing me this opportunity to complete this thesis. He always responded quickly whenever, I called him for guidance. I am also thankful to Assistant Professor Dr.Roshan Ali PhD (Biotechnology) Department of Biochemistry Khyber Medical University Peshawar Khyber Pakhtunkhwa for his generous guidance. I am also thankful to my mother and grand mother who always prayed for my success in all fields of life and after death. I am very thankful to Mr.Fazal Rahim junior clerk NTFP Department Bajaur Agency who worked day and night on computer for typing this thesis.

Homoeopathic Doctor Wali Khan M.Sc (Biochemistry) DHMS drsarhadi@gmail.com

Rheumatoid Arthritis and Its Management

Preface
There are over 400,000 people with rheumatoid arthritis (RA) in the UK.Although this makes it a common disorder, there are numerous other conditions ahead of it in terms of numbers, and indeed as causes of excess mortility.What this does not capture however, is the dreadful morbidity associated with the disease. The synovitis.Four of RA affects multiple sites causing widespread pain, and the subsequent destruction of the joints can lead to severe disability affecting all aspects of motor function from walking to fine movements of hand.Further-more,RA is not simply a disease of the joints but can affect many other organs causing, for example, widespread vasculitis or severe lung fibrosis. More recently it has become apparent that RA is associated with an increased prevalence of coronary artery disease and significant increased risk of premature mortality. Fortunately there are a considerable number of disease-modifying and antiinflammatory agents which can significantly reduce the impact of RA.Some of these, for example corticosteroids,sulphasalazine or methotrexate,have been available for many years, and rheumatologists are well used to balancing the benefits and sideeffects of these drugs. More recently, targeted disease-modifying and antiinflammatory therapies, particularly the anti-TNF agents, have emerged, and have proved effective in many patients. While it is encouraging that there is such a wide range of treatment available, the choice brings with it difficult questions concerning the best sequencing of therapy. Moreover, the newer drugs are expensive. The high impact of the disease and the need to make best use of the available treatment RA a highly suitable subject for the rheumatologists and other professionals. This venture is a modest attempt to present to the reader a Synopses of a veritable disease which is generally not taken as a serious cause for concern. Most often it is reckoned as an ailment of trivial significance, despite, its wide and wild effects upon general health and well being of the peoples. Statistics with respect to the magnitude, extent and prevalence of the disease in Pakistan are too inadequate. And III

practically speaking there is no reliable data base is available on the topic Rheumatoid Arthritis. The salient features highlighted in this article show the way for forward planning and study in greater depth. A comparative study of the various therapies, briefly discussing their merits and demerits has also been sufficiently incorporated the value and worth of any type of medical treatment must necessary rest upon: Simplicity Efficacy and adequacy Economy in cost Harmlessness Availability of expertise Popularity Duration of treatment till cure Commitment and dedication of the professionals No opinion has been expressed about the preference of one thereby over the other, this being a matter for the experts from every discipline to decide in particular and individual cases. The opening chapters of this article present over all view and explain what Rheumatoid Arthritis is? The scope of this dissert under the guide lines provided by the Open International University for Complementary Medicines Colombo (OIUCM), has been kept in view and dealt with accordingly. Appropriate and effective management of Rheumatoid Arthritis is based upon: Etiology Epidemiology Immunopathogenesis Diagnosis Prognosis Treatment under various therapies Prevention and Cure

IV

Rheumatoid Arthritis and Its Management

The desertion has been prepared in fulfillment of pre-requisite and as a part of curriculum exercise toward the accomplishment of the MD degree programme the OIUCM.

Homoeopathic Doctor Wali Khan M.Sc (Biochemistry), DHMS

Table of Contents:
Dedication Acknowledgment Preface List of Abbreviations CHAPTER -1 1.1 Complementary and alternative medicines: 1.2 Alternative Medicine CHAPTER - 2 2.1 Introduction to rheumatoid arthritis CHAPTER - 3 3.1Signs and Symptoms of Rheumatoid arthritis 3.2 Joints 3.3 Deformities 3.3.1 Hands and wrists 3.3.2 Feet and ankles 3.3.3 Knee 3.3.4 Cervical Spine 3.4 Skin 3.5 Lungs 3.6 Kidneys 3.7 Heart and blood vessels. 3.8 Other 3.8.1 Musculoskeletal 3.8.2 Ocular 3.8.3 Hepatic 3.8.4 Hematological. 3.8.5 Neurological 3.8.6 Constitutional symptoms 3.8.7Osteoporosis 3.8.8 Lymphoma CHAPTER - 4 4.1 Diagnosis 4.1.1 Physical Examination 4.1.2 Imaging 4.1.3 Blood tests CHAPTER - 5 5.1 Rheumatoid arthritis classification criteria

Page # i ii iii ix
1 1 3 7 7 9 9 10 11 11 11 12 12 13 14 14 15 15 15 15 16 16 16 17 17 17 18 18 18 23 24 27 27

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Rheumatoid Arthritis and Its Management

5.2 Types of Rheumatoid Arthritis 5.3 Juvenile Rheumatoid Arthritis 5.4 Palindromic Rheumatoid Arthritis 5.5 Pannus Rheumatoid Arthritis 5.6 Seronegative Rheumatoid Arthritis 5.7 Seropositive Rheumatoid Arthritis CHAPTER- 6 6.1 Differential diagnoses 6.2 Diseases with Symptoms Similar to Rheumatoid Arthritis 6.3 Monitoring progression CHAPTER- 7 7.1 Pathophysiology and causes 7.2 Possible infectious triggers 7.3 Psychological factors 7.4 Continued abnormal immune response 7.5 Role of vitamin D CHAPTER - 8 8.1 Complications CHAPTER- 9 9.1 Rheumatoid arthritis and pregnancy 9.2 Rheumatoid arthritis makes it difficult to conceive CHAPTER-10 10.1 Management of Rheumatoid Arthritis under various therapies 10.2 Disease modifying anti-rheumatic drugs (DMARDs) 10.3 Traditional small molecular mass drugs 10.4 Agents biological 10.5 DMARDs for Treatment of Rheumatoid Arthritis 10.6 Anti-inflammatory agents and analgesics 10.7 Surgery. 10.8 Non-Pharmacological Treatment. 10.9 Other therapies 10.9.1 Homeopathic Treatment of Rheumatoid Arthritis

29 31 32 33 35 36 37 37 40 40 42 42 43 44 44 45 48 48 49 49 49 51 52 53 53 56 57 62 64 64 65 66 VII

71 10.9.2 Acupuncture for Rheumatoid Arthritis 10.9.3 Ayurveda for Rheumatoid Arthritis. 10.9.4 Reflexology. 10.9.5 Yoga Treatment of Rheumatoid Arthritis. CHAPTER- 11 11.1 Prognosis: 11.2 Prognostic factors 11.3 Mortality CHAPTER-12 12. Epidemiology CHAPTER -13 13. History CHAPTER- 14 14. Photographs 15. References 72 75 76 79 79 81 81 81 82 82 83 83 84 84 115

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Rheumatoid Arthritis and Its Management

List of Abbreviations
ANA ACR ALT AST ACPAs CAM CBC CCP CRP CNHC DNA DAS DIP DMARs ESR EULAR EBV FDA IV IL LFTs MMPs MCH MTP MCP MCV MRI MTX NIH NHIS NSAIDs PIP POCT RA RF ROM SA Antinuclear Antibody American College of Rheumatology Alanine Transaminase Aspartate Transaminase Anticitrullinated Protein Antibodies Complementary Alternative Medicine Complete Blood Count Cyclic Citrullinated Peptide C-Reactive Protein Complementary and Natural Healthcare Council Deoxy Ribonucleic Acid Disease Activity Score Distal Interphalangeal Disease Modifying Anti Rheumatic Drugs Erythrocyte Sedimentation Rate European League Against Rheumatism Epstein-Barv Virus Food and Dietary Allowance Intravenous Inter Leukin Liver Function Tests Matrix Metalloproteases Major Histocompatibility Complex Metatarsophalangeal Metacarpophalangeal Muted Citrullinated Vimentin Magnetic Resonance Image Methotrexate National Institute of Health National Health Interview Surveys Non Steroidal Anti Inflammatory Drugs proximal interphalangeal Point of Care Test Rheumatoid Arthritis Rheumatoid Factor Range of Motion Subjective Assessment IX

SC SSZ SLE TB TCM TNF T IAs VDR WBC WHM WHO

Subcutaneous Sulfasalazine Systemic lupus erythematosus Tuberculosis Traditional Chinese Medicines Tumor necrosis factor Transient Ischemic Attack Vitamin D Receptor White Blood Cell Western Herbal Medicines World Health Organization

Rheumatoid Arthritis and Its Management

CHAPTER - 1
1.1 COMPLEMENTARY AND ALTERNATIVE MEDICINES:

General Considerations. Definition CAM is defined by the Nation Institutes of Health (NIH) as a group of diverse health care systems, practices, and products that are not presently considered to be part of conventional medicine. CAM therapies may be used along an alternative to conventional therapies or in addition to conventional, mainstream medicine to treat condition and promote will being. Classification CAM modalities have been classified by NIH into five major categories. Include botanicals, dietary supplements, probiotics, vitamins, minerals, certain diets and nutritional practices, and more. Energy medicine involves the use of energy fields, such as magnetic fields or biocides (energy fields that some believe surround and penetrate the human body).Examples include Raieki, external qigong and therapeutic touch. Manipulative and body-based practices. Use manipulation or movement of one or more body parts (e.g., massage, chiropractic, Feldenkrais method and other "body work systems). Mind-body medicine uses a variety of techniques design to enhance the integration between mind and body, such as biofeedback, meditation, art and music therapy, hypnosis and guided imagery. Whole medical systems are built on complete systems of theory and practice that have evolved apart from and often earlier than the conventional medical approach used in the United States. Systems such as traditional oriental medicine, acupuncture, homeopathy, naturopathy, Ayurvede, and Tibetan medicine often use one or more of the methods listed above.

The Centers for Disease Control and Prevention conducted National Health interview Surveys (NHIS) in 2002 and 2007.Overall, 23,000 American adults from diverse populations were asked about their use of CAM in the 2007survey. Thirty-eight present reported using some form of CAM in the previous 12 months, essentially unchanged form 36% in 2002. The most commonly used CAM therapies were non- vitamin,nonmineral nature products (17.7%), with fish oil, gluscosamine, Echinacea, flaxseed and ginseng being most common; deep breathing exercises (12.7%); meditation (9.4%). Chiropractic or osteopathic manipulation (8.6%); massage (8.3%); and yoga (6.1%).CAM use was higher levels of educations, who were not poor, who live in the West and who have quit cigarette smoking. The most common conditions for which and adults used CAM were similar to those seen in most primary care offices; musculoskeletal complaints, such as back, neck, and joint pain. Funding for biomedical research in this filed increased when the NIH established the Office of alternative Medicine in 1992 with an annual budget of $2 million. In 1998, its role was expanded as the National Center for Complementary and Alternative Medicine (NCCAM).NCCAMs budget for fiscal year 2009 was $2 million. Although some CAM modalities are not easily evaluated using randomized control trial methodology, the 2005 Institute of Medicine report recommends that conventional and CAM treatments both be held to similar standards of safety and efficacy.

Rheumatoid Arthritis and Its Management

1.2

Alternative Medicine

Orthodox and holistic approaches to medicine Alternative medicine is based on holistic principles. Conventional medicine is based on very detailed and specific scientific knowledge. Health is seen as simply an absence of symptoms, ill-health as a malfunction in the body or mind system that has to be corrected. The emphasis is on fighting, conquering and destroying disease with use of drugs, surgery or sometimes hard treatment of the mind. The mind and body are seen as separate entities and are treated by different disciplines, the spirit is ignored. The focus is on symptoms of disease and it is the symptoms that will be treated while other needs of the person will largely ignored. An imbalance in the relationship between doctor and patient may be created Aims to deal with the patient as a whole, not merely with physical symptoms. Holistic Practioners: They assume a person exists on many levels and take into account not only the body but also the mind and spirit (the animating vital principle) of an individual. The mind and spirit are not seen simply as part of the body; each is considered to be a complete system, constantly interacting with one another and of equal importance. The three systems, that is mind body and spirit, can be said to be integrated principles of the whole. Holistic practitioners believe the mind, body and spirit of an individual tend naturally towards a state of balance, known in the West as homeostasis.

For example, prolonged stress may unbalance the mind that causes the body to react with various symptoms, such as pain or fatigue. The spirit, too, may become unbalanced and depression may occur. 3

Holistic practitioners tend to focus on the underlying cause rather than on symptoms of an aliment. When there is a problem Any treatment provided aims Holistic practitioners would almost certainly suggest that to control symptoms would not be able to deal with the underlying disturbances that are creating these symptoms. Not only do drugs prevent elimination of impurities but that they might add toe toxins already prevalent. Surgery is thought to destroy homeostasis and is seen as necessary only in the last resort. While it is accepted that a vieus may trigger an illness, it is thought there is probably a state of susceptibility to disease already prevalent n the individual owing to an imbalance in the mind, which cannot be treated with surgery. Alternative Therapies in the west Alternative therapies come from all over the world. Some, such as Ayurveda, from India, acupressure, acupuncture and Chinese herbal medicine from China, known collectively as Traditional Chinese Medicine (TCM), and Western Herbal Medicine (from Europe). Homeopathy from Germany osteopathy from USA, aromatherapy (from France),Bach flower remedies (from England).Biofeedback (from the USA). Until about the mid-1970s alternative therapies were collective known as fringe and labeled unconventional or unorthodox practices. Alternative, however, embraces all practices that are not orthodox and it is the word used to describe therapies that are not part of conventional medical practice in USA.

Australia

Rheumatoid Arthritis and Its Management About half the total population of Australia is reckoned to use at least one nonmedically prescribed remedy each year and one-quarter of the total population consult and alternative therapy. It is not permitted to treat certain diseases, such as cancer, by any alternative therapy. The three most popular therapies are probably massage, naturopathy, Chinese and Western herbal, medicine. New Zeeland Chiropractors and osteopaths in New Zeeland are registered as medical auxiliaries. South Africa An act in 1982 in South Africa incorporated all alternative practitioners into a register supervised by the Associated Health Service Professional Board. It has the same status as the orthodox practitioners register. United Kingdom In the UK chiropractic and osteopathy are registered therapies and members of the registering boards are allowed to practice. Practitioners of almost any therapy have the right to practice under common law as except they cannot be involved with dentistry, midwifery, veterinary surgery or treat venereal, disease. No treatment or remedies for cancer can be advertised but anyone is allowed to treat the disease. In 1995 a consumers Association survey showed healing, osteopathy, chiropractic, homeopathy, aromatherapy and acupuncture to be the most popular alternative therapies, while aromatherapy is the fastest growing. In the USA each of the 50 states decides its own policy regarding alternative medicine. In most states alternative techniques are described. Chiropractic, the most popular alternative therapy, is registered by all states and doctors refer to and receive referrals chiropractors. While herbal medicine is banned in many states. New York State however recognizes all therapies and supports freedom of choice in health. Ayurveda, chiropractic and TCM are very popular therapies, aromatherapy and homoeopathy less so.

Health is perceived to be not merely the absence of disease but a positive quality of living. 5

Patients demand to be more actively involved knowledgeable about, their own health. There is a fear of conventional drug treatment and surgery. Patients are becoming aware of the limitations of orthodox medicine. Patients want more communication with, and more information from, their doctors than they receive.

CHAPTER - 2
2.1 INTRODUCTION TO RHEUMATIOD ARTHRITIS: 6

Rheumatoid Arthritis and Its Management Definition: Rheumatoid arthritis is a chronic symmetrical polyarthritis of unknown cause and is characterized by chronic inflammatory synovitis of mainly peripheral joints along with systemic disturbances and extra-articular features. Course of disease is prolonged with exacerbations and remission. Characterized by: Symmetrical inflammatory polyarthritis Extra-articular involment e.g. in lungs and many other organs Progressive joint damage causing severe disability

General consideration: Rheumatoid Arthritis (RA) is a chronic, systemic inflammatory disorder that may effect many tissues and organs, but principally attacks flexible (sensorial) joints. The process produces an inflammatory response of the capsule around the joints (synovium) secondary to swelling (hyperplasia) of synovial cells, excess synovial fluid, and the development of fibrous tissue (pannus) in the synovium.The pathology of the disease process often leads to the destruction of articular cartilage and ankylosis of the joints. Rheumatoid arthritis can also produce diffuse inflammation in the lungs, membrane around the heart (pericardium), the membranes of the lung (pleura), and white of the eye (sclera), and also nodular lesions, most common in subcutaneous tissue. Although the cause of rheumatoid arthritis is unknown, autoimmunity plays a pivotal role in both its chronicity and progression, and RA is considered a systemic autoimmune disease. About 1% of the worlds population is afflicted by rheumatoid arthritis, women three times more often than men. Onset is most frequent between the ages of 40 and 50, but people of any age can be affected.

It can be a disabling and painful condition, which can lead to substantial loss of functioning and mobility if not adequately treated. It is a clinical diagnosis made on the basis of symptoms, physical exam, radiographs (X-rays) and labs, although the American College 7

of Rheumatology (ACR) and the European league Against Rheumatism (EULAR) publish classification criteria for the purpose of research. Diagnosis and long-term management are typically performed by a rheumatologist, an expert in joint, muscle and bone diseases. Various treatments are available. Non-pharmacological includes physical, orthoses, occupational therapy and nutritional but these do not stop the progression of joint destruction. Analgesia (painkillers) and anti-inflammatory drugs, including steroids are used to suppress the symptoms, while disease-modifying antirheumatic drugs (DMARDs) are required to inhibit or halt the underlying immune process and prevent long-term damage. In recent times, the newer group of biologics has increased treatment options. The name is based on the term rheumatic fever, an illness which includes joint pain is derived from the Greek word pebua-rheuma (nom.),pebuaro - rheumatos (gen.) ( flow, current).The suffix-oid ( resembling) gives the translation as joint inflammation that resembles rheumatic fever. The first recognized description of rheumatoid arthritis was made in 1800 by Dr.Augustin Jacob Landre-Beauvais (1772-1840) of Paris. Signs and symptoms While rheumatoid arthritis primarily affects joints, problems involving other of the body are known to occur. Extra-articular (outside the joints) manifestations other than anemia (which is very common) are clinically evident in about 15-25% of individuals with rheumatoid arthritis. It can be difficult to determine whether diseases manifestation are directly caused by the rheumatoid process itself, or from side effects of the medications commonly used to treat it for example, lung fibrosis from methotrexate or osteoporosis from corticosteroids.

CHAPTER - 3
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Rheumatoid Arthritis and Its Management 3.1 Signs and Symptoms of Rheumatoid arthritis The types and severity of symptoms of rheumatoid arthritis varies between individuals. At the onset of the disease, the symptoms of rheumatoid arthritis can be vague and develop slowly. They may not include the classic symptom of joint pain that people often associate with arthritis. These indistinct, early symptoms may include fatigue, loss of appetite, and weakness. Other early symptoms include muscle achiness throughout the body and stiffness that lasts more than one hour after rising in the morning. Ultimately, joint pain develops and can be accompanied by inflammation and swelling in the joints. Joint pain generally affects wrists, fingers, knees, feet, and ankles on both sides of the body. Joint destruction may develop within 1-2 years after the onset of the disease. Other symptoms may include problems with the eyes, deformities in the hands and feet, fever, paleness, anemia, nodules under the skin, swollen glands, and redness and inflammation of the skin. Because of the generalized inflammatory nature of rheumatoid arthritis, it can affect almost any organ in the body and lead to life threatening complications. These include rheumatoid vasculitis, a type of inflammation of the blood vessels, which can lead to atherosclerosis, stroke, heart attack and other cardiac conditions. Skin ulcerations and infections, bleeding stomach ulcers, and nerve problems that cause pain, numbness, or tingling may also occur. The eyes can also be affected and the neck bones can become instable The list of signs and symptoms mentioned in various sources for Rheumatoid arthritis includes the 29 symptoms listed below: Joint pain Joint swelling Joint stiffness Morning joint stiffness Joint stiffness after inactivity Joint tenderness Warm joints Ankle arthritis Foot arthritis Finger arthritis Wrist arthritis

Symmetrical joint pattern - both sides of the body afflicted. Morning stiffness Weight loss 9

 3.2

Fatigue Decreased appetite Occasional fever Bouts of mild fever Malaise Episodic flares with remissions Variable symptoms - different people experience different effects Skin bumps (rheumatoid nodules) - about 25% of cases get these Anemia Neck pain Dry eyes Dry mouth Tiredness Afternoon fatigue Afternoon malaise Joints The arthritis of joints known as synovitis is inflammation of the synovial membrane that

lines joints and tendon sheaths. Joints become swollen, tender and warm, and stiffness limits their movement. With time RA nearly affects multiple joints (it is a polyarthritis), most commonly small Joints of the hands, feet and cervical spine, but larger joints like the shoulder and knee can also be involved. Synovitis can lead to tethering of tissue with loss of movement and erosion of the joint surface causing deformity and loss of function. Rheumatoid arthritis typically manifests with signs of inflammation, with the affected joints being swollen, warm, painful and stiff, particularly early in the morning on waking or following prolonged inactivity. Increased stiffness early in the morning is often a prominent feature of the disease and typically lasts for more than an hour. Gentle movement may relieve symptoms in early stages of the disease.

These signs help distinguish rheumatoid from non-inflammatory problems of the joints, often referred to as osteoarthritis wear-and tear arthritis. In arthritis of non-inflammatory

10

Rheumatoid Arthritis and Its Management causes, signs of inflammation and early morning stuffiness are less prominent with stiffness typically less than 1 hour, and movements induce pain caused by mechanical arthritis. In RA, the joints are often affected in a fairly symmetrical fashion, although this is not specific, and the initial presentation may be asymmetrical. As the pathology progresses the inflammatory activity leads to tendon tethering and erosion and destruction of the joint surface, which impairs range of movement and leads to deformity. The fingers may surfer from almost any deformity depending on which joints are most involved. Although any joint may be affected in RA,the proximal interphalangeal and metacarpophalangeal joints of fingers as well as the wrist, knee ankles and toes are most often involved. Distal interphalangeal joints are characteristically spared. 3.3 Deformities As the disease advances (after months or year) pain, muscle spasm and joints destruction results in limitation of joint movement, joint instability,subluxation(partially dislocation) and deformities. 3.3.1 Hands and wrists
Spindling of fingers:

In early stages, swelling of metacarpophalangeal joints produces

spindling of fingers
Anterior subluxation

of the metacarpophalangeal joints along with ulnar deviation of fingers Characterized by hypertension at the proximal interphalangeal joints Characterized by fixed flexion of the proximal interphalangeal joint

develops due to weakening of joint capsule and muscle wasting.

Swan neck deformity:

and fixed flexion at the distal interphalangeal joints

Button hole deformity:

and extension of the distal interphalangeal joint

11

Z deformity of thumb :

Characterized by hypertension of the first interphalangeal joint and Tenosynovitis at the wrist can entrap the median nerve and

flexion of the first metacarpophalangeal joint with consequent loss of thumb mobility
Carpal tunnel syndrome:

produce carpal tunnel syndrome Extra-articular features in hands may be palmer erythema and vasculitic lesions in nail beds, nail folds, and digital pulp. 3.3.2 Feet and ankles Lateral deviation of the toes and subluxation (partially dislocation) of the metacarpophalangeal joints, so that the heads of the metatarsals become palpable in the soles of the feet and patient often describes as sensation of walking on pebbles. Ankle develops valgus deformity. 3.3.3 Knee Synovial effusions and quadriceps wasting are early features: Later on flexion, valgus (bent outwards) or varus (bent inwards) deformity appear with joint instability. Synovial effusion (demonstrated with patellar tap by fixing the knee fingers and thumb of left hand, then sharply tapping the patella downwards produces a dip when effusion is present. Bakers Cyst: It is an extension of inflamed synovium into the popliteal space, causing pain and swelling. High pressure generated by flexion of knee can cause rupture of cyst into calf, manifesting as calf swelling, tenderness and pitting edema. 3.3.4 Cervical Spine Synovitis of upper cervical spines leads to bone destruction, damage of ligaments that causes atlantoaxial subluxation which may damage the spinal cord.

3.4 Skin 12

Rheumatoid Arthritis and Its Management The rheumatoid nodule, which is often subcutaneous, is the coetaneous feature most characteristic of rheumatoid arthritis. It is a type of inflammatory reaction known to pathologists as a necrotizing glaucoma. The initial pathologic process in nodule formation is unknown but may be essentially the same as the synovitis, since similar structural features occur in both. The nodule has a central area of fibrinoid necrosis that may be fissured and which corresponds to the fibrin-rich necrotic material found in and around an affected synovial space. Surrounding the necrosis is a layer of palisading macrophages and fibroblasts, corresponding to the intimal layer in synovium and a cuff of connectives tissue containing clusters of lymphocytes and plasma cells, corresponding to the suboptimal zone in synovitis. The typical rheumatoid nodule may be a few millimeters to a few centimeters in diameter and is usually found over bony prominences, such as the colcannon, the calcaneal tuberosity.the metacarpophalangeal joints, or other areas that sustain repeated mechanical stress. Nodule is associated with a positive RF (rheumatoid factor) titer and severe erosive arthritis. Rarely, these can occur in internal organs or at diverse sites on the body. Several forms of vasculitis occur in rheumatoid arthritis. A benign form occurs as micro infarcts around the manifolds. More severe forms include livedo reticular is, which is a network (reticulum) of erythematous to purplish discoloration of the skin caused by the presence of an obliterative coetaneous capillaropathy. Other, rather rare, skin associated symptoms include: Pyoderma dermatosis. Sweets syndrome, a neutrophilic dermatosis usually associated with myeloproliferative disorders. gangrenosum, a necrotizing,ulcerative,noninfectious neutrophilic

Drug reactions. 13

Erythematic nodoseum Lobular panniculitis Atrophy of digital skin Palmar erythema Diffuse thinning (rice paper skin),and skin fragility (often worsened by corticosteroid use).

3.5 Lungs. Fibrosis of the lungs is a recognized response to rheumatoid disease. It is also a rare but well recognized consequence of therapy (for example with methotrexated and leflunomide) Caplan,s syndrome describes lung nodules in individuals with rheumatoid arthritis and additional exposure to coal dust. Pleural effusions are also associated with rheumatoid arthritis. Another complication of RA is Rheumatoid lung Disease. It is estimated that about one quarter of Americans with develops Rheumatoid Lung Disease. 3.6 KIDNEYS Renal amyloidosis can occur as a consequence of chronic inflammation. Rheumatoid arthritis may affect the kidney glomerulus's directly through a vasculopathy or a mesangial infiltrate but this is less well documented (though this is not surprising, considering immune complex-mediated hypersensitivities are known for pathogenic deposition of immune complexes in organs where blood is filtered at high pressure to form other fluids, such as urine and synovial fluid) Treatment with Penicillamine and gold salts are recognized causes of membranous nephropathy.

3.7 HEART AND BLOOD VESSELS. 14

Rheumatoid Arthritis and Its Management People with rheumatoid arthritis are more prone to atherosclerosis, and risk myocardial infarction (heart attack) and stroke is markedly increased. Other possible complications that may arise include: pericarditis, endocarditic, left ventricular failure, valaulitis and fibrosis. Many people with rheumatoid arthritis do not experience the same chest pain that others feel when they have angina or myocardial infarction. To reduce cardiovascular risk, it is crucial to maintain optimal control of the inflammation caused by rheumatoid arthritis (which may be involved in causing the cardiovascular risk factors such as blood lipids and blood pressure. Doctors who treat rheumatoid arthritis patients should be sensitive to cardiovascular risk when prescribing antiinflammatory medications, and may want to consider prescribing routine use of low doses of aspirin if the gastrointestinal effects are tolerable 3.8 OTHER 3.8.1 Musculoskeletal Subcutaneous nodules (In 20%): Usually seen at sites of pressure or friction such as the exterior surfaces of the forearms below the elbow,scalp,sacrum,scapula.A chilles tendon, as well as on the fingers and toes.
Bursitis:The

olecranon and other bursae may become swollen. Particularly affecting the flexor tendons in the palm of the hand and may around affected joints especially in the hands.

Tenosynovitis:

contribute to flexion deformities.

Muscle wasting:

3.8.2 Ocular The eye is directly affected in the form of episcleritis which when severe can very rarely progress to perforating scleromalacia.Rather more common is the indirect effect of keratoconjunctivitis sicca, which is a dryness of eyes and mouth caused by lymphocyte infiltration of lacrimal and salivary glands. When severe, dryness of the cornea can lead to keratitis and loss of vision. Preventive treatment of severe dryness with measures such as nasolacrimal duct occlusion is important.

3.8.3 Hepatic 15

Cytokine production in joints and /or hepatic Kupfer cells leads to increased activity of hepatocytes with increased production of acute-phase proteins, such as C-reactive protein, and increased release of enzymes such as alkaline phosphates into the blood. In Fealtys syndrome, Kuppfer cell activation is so marked that the resulting increase in hepatocyte activity is associated with nodular hyperplasia of the liver, which may be palpably enlarged. Although Kupffer cells are within the hepatic parenchyma, they are separate from hepatocytes.As a result there is little or no microscopic evidence of hepatitis (immuremediated destruction of hepatoctes).Hepatic involvement in RA is essentially asymptomatic. 3.8.4 Hematological. Anemia is by far the most common abnormality of the blood cells. Rheumatoid arthritis may cause a warm autoimmune hemolytic anemia.The red cells are of normal size and colour (normocytic and normochromic).A low white blood cell count (Neutrogena) usually only occurs in patients with Fehys syndrome with an enlarged liver and spleen.The mechanism of neutropenia is complex.An increased platelet count (thrombocytosis)occurs when inflammation is uncontrolled,asdoes the anemia.Iron deficiency may also be present due to GIT blood loss from analgesic ingestion. 3.8.5 Neurological Peripheral neuropathy mononeuritis multiplex may occur. The most common problem is carpal tunnel syndrome caused by compression of the median nerve by swelling around the wrist.Atlanto axial subluxation can occur, owing to erosion of the odontoid process and or transverse ligaments in the cervical spines connection to the skull. Such an erosion (>3mm) can give rise to vertebrae slipping over one another and compressing the spinal cord. Clumsiness is initially experienced, but without due care this can progress to quadriplegia.

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Rheumatoid Arthritis and Its Management 3.8.6 Constitutional symptoms Constitutional symptoms including fatigue, low grade fever, malaise, and morning stiffiness, loss of appetite and loss of weight are common systemic manifestations seen in patients with active rheumatoid arthritis. 3.8.7 Osteoporosis Local osteoporosis occurs in RA around inflamed joints.It is postulated to be partially caused by inflammatory cytokines.More general osteoporosis is probably contribution to by immobility, systemic cytokine effects, local cytokine release in bone marrow and corticosteroid therapy. 3.8.8 Lymphoma The incidence of lymphoma is increased in RA, although it is still uncommon.

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CHATER - 4
4.1 Diagnosis: Diagnosis of RA is based on history, examination, X-Ray findings and serology (RA factor).Rheumatoid arthritis presents initially with non specific symptoms but assume its characteristic features with in 1-2 years of onset. The following features support diagnosis of rheumatoid arthritis. 1 Bilateral symmetrical inflammatory polyarthritis involving small and large joints both the upper and lower extremities with sparing of axial skeleton except cervical spine suggest diagnosis 2 3 Systemic features indicative of inflammatory nature of disease such as morning stiffness support the diagnosis Presence of subcutaneous nodules is helpful diagnostic feature.

4.4.1 Physical Examination:

Joint involvement is the characteristic feature of rheumatoid arthritis. In general, the small joints of the hands and feet are affected in a relatively symmetric distribution. In decreasing frequency, the MCP, wrist, PIP, knee, MTP, shoulder, ankle, cervical spine, hip, elbow, and temporomandibular joints are most commonly affected. Affected joints show inflammation with swelling, tenderness, warmth, and decreased range of motion (ROM). Atrophy of the interosseous muscles of the hands is a typical early finding. Joint and tendon destruction may lead to deformities such as ulnar deviation, boutonniere and swan-neck deformities, hammer toes, and, occasionally, joint ankylosis. Other commonly observed musculoskeletal manifestations include tenosynovitis (defined as inflammation of the tendon and its enveloping tendon sheath ) and associated tendon rupture due to tendon and ligament involvement, most commonly involving the fourth and fifth digital extensor tendons at the wrist; periarticular osteoporosis due to localized inflammation; generalized osteoporosis due to systemic chronic inflammation, immobilization-related changes, or corticosteroid therapy; and carpal tunnel syndrome. Most patients with RA have muscle atrophy from disuse, which is often secondary to joint inflammation. Fingers: The boutonniere deformity, demonstrated in the image Fig N0.6 , describes nonreducible flexion at the PIP joint along with hyperextension of the distal interphalangeal (DIP) joint of the finger. This deformity occurs as a result of synovitis stretching or rupturing the PIP joint through the central extensor tendon, with concomitant volar displacement of the lateral bands. When the lateral bands have 18

Rheumatoid Arthritis and Its Management subluxed far enough to pass the transverse axis of the joint, they become flexors of the PIP joint. Hyperextension of the DIP joint occurs as the tendons shorten with time. A compensatory and reducible hyperextension may occur at the MCP joint. Consequences of boutonniere deformity are loss of thumb mobility and pincher grasp. Swan-neck deformity of the finger describes hyperextension at the PIP joint with flexion of the DIP joint (see the image Fig NO.7). The deformity may be initiated by (1) disruption of the extensor tendon at the DIP joint with secondary shortening of the central extensor tendon and hyperextension of the PIP joint, or (2) volar herniation of the PIP joint capsule due to weakening from chronic synovitis with subsequent tightening of the lateral bands and central extensor tendon. The lateral bands may become shortened over time and lie dorsally, limiting PIP flexion and ineffectively extending the DIP joint. Tightness of intrinsic muscles (eg, interossei, lumbricals) may cause major declines in mobility of the fingers. This characteristic is ascertained on examination when the PIP joint cannot be flexed while the MCP joint is fully extended, but it can be flexed if the MCP is in flexion (Bunnell test); primary PIP joint pathology would be evident with the MCP joint in either position. To assess this accurately, the phalanx must be aligned with the metacarpal, as the intrinsic muscles on the ulnar side are slack when ulnar deviation at the MCP joint exists, thus allowing more motion. Flexor tenosynovitis of the fingers is common and suggests a poor prognosis. "Triggering" of the finger occurs when thickening or nodule formation of the tendon interacts with the concomitant tenosynovial proliferation, trapping the tendon in a flexed position (stenosing tenosynovitis). Tendon rupture may occur due to infiltrative synovitis in the digit or bony erosion of the tendon at the wrist (especially the flexor pollicis longus). Arthritis mutilans (sometimes called opera glass hands) results if destruction is severe and extensive, with dissolution of bone. In the small joints of the hands, the phalanges may shorten and the joints may become grossly unstable. Pulling on the fingers during examination may lengthen the digit much like opening opera glasses, or the joint may bend in unusual directions merely under the pull of gravity. Aso see the image Fig NO.13 for hand deformities. Metacarpophalangeal joints: As seen in the image Fig NO.8 , 2 typical deformities that alter the alignment of the palmar skeletal arches and the stability of the fingers may occur at the MCP joints: volar subluxation and ulnar deviation. Most cases of ulnar deviation are accompanied by counterpoised radial deviation of the wrist, roughly proportional to the degree of ulnar deviation of the fingers. The volar plate is firmer and more substantial than other portions of the MCP joint capsule and, therefore, effectively limits extension and dorsal movement at the joint. The greater strength of the flexor muscles relative to the extensor muscles causes volar migration of the proximal

19

phalanx after synovial-based inflammation has weakened ligament and tendon insertions about the MCP joint capsule. Ulnar deviation occurs after synovitis has led to stretching and attenuation of the volar plate and collateral ligaments, allowing dislocation of the flexor tendon volarward and ulnarward. The supporting structures of the extensor tendons also may become attenuated or destroyed by synovial distention and invasion, loosening the tendons so that they no longer ride centrally and dorsally over the metacarpal head but move into the cleft between the MCP joints. If the extensor tendon subluxation is beyond the transverse axis of the MCP joint, the tendon becomes a flexor at that joint, further limiting the active extension of the fingers. Wrists: Multiple deformities may occur in the wrist. Disruption of the radioulnar joint with dorsal subluxation of the ulna (caput ulna), as well as rotation of the carpus on the distal radius with an ulnarly translocated lunate, is common. The combination of an ulnar drift of the fingers and carpal rotation is known as a zigzag deformity. Shortening of the carpal height (noted on radiographs), due in part to cartilage loss, is seen with rotational deformities. Dorsal subluxation of the ulna often allows the ulnar styloid to be depressed volarly on examination, much like depressing a piano key. Subluxation may lead to rupture of the extensor tendons of the little, ring, and long fingers, because the end of the distal ulna is roughened secondary to erosion of bone and may abrade the tendons as they move back and forth during normal hand function, much like a rope being frayed while rubbing over a sharp rock. This process is especially likely to lead to tendon rupture if there is associated tenosynovitis. (See the image Fig No.9) . Entrapment neuropathy may result from synovitis about the flexor tendons. Entrapment of the median nerve as it passes through the carpal tunnel leads to decreased sensation on the palmar aspect of the thumb, index finger, and long finger and on the radial aspect of the ring finger; weakness and atrophy of the muscles in the thenar eminence also occurs. The less frequent entrapment of the ulnar nerve at the wrist causes decreased sensation over the little finger and the ulnar aspect of the ring finger and decreased interosseous muscle strength and mass. Elbow: Elbow involvement is often detected by palpable synovial proliferation at the radiohumeral joint and is commonly accompanied by a flexion deformity, such as in contractures. Olecranon bursal involvement is common, as are rheumatoid nodules in the bursa and along the extensor surface of the ulna. Nodules are clearly seen in the image Fig NO.26. .

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Rheumatoid Arthritis and Its Management Shoulders: Rheumatoid arthritis commonly involves the shoulders and is manifested by tenderness, nocturnal pain, and limited motion. Initially, swelling occurs anteriorly, but it may be difficult to detect and is present on examination in a minority of patients at any point in time. Rotator cuff degeneration secondary to synovitis may limit abduction and rotation. Superolateral migration of the humerus occurs with complete tears. Glenohumeral damage leads to pain with motion and at rest and typically leads to severely restricted motion or "frozen shoulder syndrome." Acromioclavicular arthritis is not as frequent or as disabling as the other manifestations of this disease. Feet and ankles: The ankle joint itself is rarely involved without midfoot or MTP involvement. The ankle does not often deform, as it is a mortise joint. Major structural changes occur in the midfoot and foot due to the combination of chronic synovitis and weight bearing. Posterior tibialis tendon involvement or rupture may lead to subtalar subluxation, which results in eversion and migration of the talus laterally. Midfoot disease leads to loss of normal arch contour with flattening of the feet. The MTP joints are inflamed in most patients and, due to the heavy loads they bear, commonly become deformed over time. The great toe typically develops hallux valgus (a bunion); subluxation of the phalanx at the MTP joint of the other toes predominantly occurs dorsally. The toes may exhibit compensatory flexion due to a fixed length of the flexor tendons, thus resulting in hammer toes (thought to look like piano hammers). The second and third metatarsal heads commonly protrude and may become the primary weight-bearing surface at the MTP joints. Calluses and pain upon weight bearing result. Knees: Rheumatoid arthritic knees may develop large effusions and abundant accumulation of synovium. Knee effusions and synovial thickening are common and are easily detected during the early course of the disease. Persistent effusions may lead to inhibition of quadriceps function by spinal reflexes, resulting in subsequent atrophy. Instability may develop after progressive loss of cartilage and weakening of ligaments; deformity may include genu valgus or varus and flexion deformities. The energy expenditure to stand or walk significantly increases if there are flexion deformities of the knees. Hips: The hips are commonly involved in rheumatoid arthritis; however, because of their deep location, their involvement is not always readily apparent early on during the course of the disease. Hips are difficult to examine by direct inspection or 21

palpation. Limited motion or pain on motion and weight bearing are the hallmarks of hip involvement. The Patrick maneuver (flexion, external rotation, and abduction) is abnormal in this situation. A flexion deformity may be demonstrable by conducting a Thomas test, which is performed by flexing one hip (with the patient supine) while restricting pelvic motion by keeping the other hip in the neutral position on the examination table. If the hip cannot be maintained in the neutral position, a contracture is present. Cervical spine: Neck pain on motion and occipital headache are common manifestations of cervical spine involvement (see the image Fig NO.10). Most patients with cervical spine involvement have a history of the disease for more than 10 years. Clinical manifestations of early cervical spine disease consist primarily of neck stiffness that is perceived throughout the entire arc of motion. The atlantoaxial joint is a synovial-lined joint and is susceptible to the same proliferative synovitis and subsequent instability seen in the peripheral joints. Patients with severe destruction in the hands (arthritis mutilans) are very likely to have symptomatic cervical spine abnormalities, as are those patients taking significant amounts of corticosteroids for control of rheumatoid arthritis. . Neurologic involvement ranges from radicular pain to a variety of spinal cord lesions that may result in weakness (including quadriparesis), sphincter dysfunction, sensory deficits, and pathologic reflexes. Transient ischemic attacks (TIAs) and cerebellar signs may reflect vertebral artery impingement from cervical subluxation or basilar artery impingement from upward migration of the dens. Tenosynovitis of the transverse ligament of C1 may lead to C1-C2 instability. Myelopathy secondary to rupture of the transverse ligament may lead to neurologic deficits. Radiculopathy is most common at the C2 root, although symptomatic subluxations may occur at any level. Symptoms of cervical myelopathy are gradual in onset and are often unrelated to either the development of or accentuation in neck pain. When neck pain does occur, it frequently radiates over the occiput region in the distribution of the C1-3 nerve roots. The Lhermitte sign, in which tingling paresthesia that descends through the thoracolumbar spine occurs as the cervical spine is flexed, is typically observed. During the physical examination, it is important to assess the following signs and symptoms: Stiffness Tenderness Pain on motion Swelling Deformity Limitation of motion

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Rheumatoid Arthritis and Its Management Extra-articular manifestations Rheumatoid nodules

Genetic and environmental factors play a role in pathogenesis. Although laboratory testing and imaging studies can help confirm the diagnosis and track disease progress, rheumatoid arthritis primarily is a clinical diagnosis and no single laboratory test is diagnostic. Complications of rheumatoid arthritis may begin to develop within months of presentation; therefore, early referral to or consultation with a rheumatologist for initiation of treatment with disease-modifying antirheumatic drugs is recommended. Several promising new disease-modifying drugs recently have become available, including leflunomide, tumor necrosis factor inhibitors, and anakinra. Nonsteroidal anti-inflammatory drugs, corticosteroids, and nonpharmacologic modalities also are useful. Patients who do not respond well to a single disease-modifying drug may be candidates for combination therapy. Rheumatoid arthritis is a lifelong disease, although patients can go into remission. Physicians must be aware of common comorbidities. Progression of rheumatoid arthritis is monitored according to American College of Rheumatology criteria based on changes in specific symptoms and laboratory findings. Predictors of poor outcomes in early stages of rheumatoid arthritis include low functional score early in the disease, lower socioeconomic status, early involvement of many joints, high erythrocyte sedimentation rate or Creactive protein level at disease onset, positive rheumatoid factor, and early radiologic changes. Rheumatoid arthritis is characterized by persistent joint synovial tissue inflammation. Over time, bone erosion, destruction of cartilage, and complete loss of joint integrity can occur. Eventually, multiple organ systems may be affected. 4.1.2 Imaging: X-rays of the hands and feet are generally performed in people with a polyarthritis. In rheumatoid arthritis, there may be no changes in the early stages of the disease, or the Xray may demonstrate juxta-articular osteopenia, soft tissue swelling and loss of joint space. As the disease advances, there may be bony erosion and subluxation X-rays of other joints may be taken if symptoms of pain swelling occur in those joints. Other medical imaging techniques such as magnetic resonance imaging (MRI) and ultrasound are also used in rheumatoid arthritis.

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There have been technical advances in ultrasonography.High sfrequency transducers(10MHz or higher) have improved the spatial resolution of ultrasound images, these images can depict 20% more erosions than conventional radiography.Also, colour Doppler and power Doppler ultrasound,which show vascular signals of active synovitis depending on the drgree of inflammation,are useful in assessing synovial inflsmmstion. This is important, since in the early stages of rheumatoid arthritis, the synovium is primarily affected, and synovitis seems to be the best predictive marker of future joint damage. 4.1.3 BLOOD TESTS When RA is clinically suspected, immunological studies are required, such as testing for the presence of rheumatoid factor (RF,a non-specific antibody).A negative RF does not rule out RA; rather, the arthritis is called seronegative. This is the case in about 15% of patients.During the first year of illness, rheumatoid factor is more likely to be negative with some individuals converting to seropositive status over time.RF is also seen in other illnesses, for example Sjogrens syndrome, Hepatitis C,chronic infections and in approximately 10% of the healthy population and therefore the test is not very specific. Because of this low specificity, new serological tests have been developed,which test for the presence of anticitrullinated protein antibodies (ACPAs) or anti-CCP.Like Rf, these tests are positive in only a proportion (67%) of all R A cases, but are rarely positive if RA is not present, giving it a specificity of around 95%.As with RF, there is evidence for ACP as being present in many cases even before onset of clinical disease.

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Rheumatoid Arthritis and Its Management The most common tests for ACP As are the anti-CCP (cyciccitrullinated peptide) test and the Anti-MCV assay (antibodies against mutated citrullinated Vimentin).Recently a serological point-of-care test (POCT) for theearly detection of RA has been developed. This assay combines the detection of rheumatoid factor and anti-MCV for diagnosis of rheumatoid arthritis and shows a sensitivity of 72% and specificity of 99.7%. Also, several other blood tests are usually done to allow for other causes of arthritis, such as lupus erythematosus. The erythrocyte (te sedimentation rate (ESR), C-reactive protein, full blood count, renal function, liver enzymes and other immunological tests (e.g.,antinuclear antibody/ANA) are all performed at this stage.Elevated ferritin levels can reveal hemochromatosis, a mimic RA, or be assign of Stills disease a seronegative,usually juvenile, variant of rheumatoid.

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Laboratory and Imaging Findings Associated with Rheumatoid Arthritis

Creactive protein*

Typically increased to >0.7 picograms per mL; may be used to monitor disease course. Erythrocyte Often increased to >30 mm per hour; may be used to monitor disease sedimentation rate* course. Hemoglobin/hematocrit* Slightly decreased; hemoglobin averages around 10 g per dL (100 g per L); normochromic anemia, also may be normocytic or microcytic. Liver function* Normal or slightly elevated alkaline phosphatase Platelets* Usually increased Radiographic findings of May be normal or show osteopenia or erosions near joint spaces in early involved joints* disease; wrist and ankle films are useful as baselines for comparison with future studies. Rheumatoid factor* Negative in 30 percent of patients early in illness; if initially negative, can repeat six to 12 months after disease onset; can be positive in numerous other processes (e.g., lupus; scleroderma; Sjgrens syndrome; neoplastic disease; sarcoidosis; various viral, parasitic, or bacterial infections); not an accurate measure of disease progression. White blood count* May be increased Anticyclic citrullinated Tends to correlate well with disease progression; increases sensitivity when peptide antibody used in combination with rheumatoid factor; more specific than rheumatoid factor (90 versus 80 percent); not readily available in many laboratories. Antinuclear antibody Limited value as a screening study for rheumatoid arthritis Complement levels Normal or elevated Immunoglobulins Elevated alpha-1 and alpha-2 globulins possible. Joint fluid evaluation Consider if an affected joint can be tapped and diagnosis is uncertain; straw-colored fluid with fibrin flecks often seen; fluid may clot at room temperature; 5,000 to 25,000 white blood cells per mm3 (5 to 25 109 per L) with 85 percent polymorphonuclear leukocytes a common finding; in rheumatoid arthritis, cultures are negative, there are no crystals, and fluid glucose level typically is low. Urinalysis Microscopic hematuria or proteinuria may be present in many connective tissue diseases. *Recommended for initial evaluation for rheumatoid arthritis. note: Renal function, although not as likely to change as a direct effect of disease, should be followed to assess renal effects of drug therapy.

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Rheumatoid Arthritis and Its Management CHAPTER- 5 5.1 RHEUMATIOD ARTHRITIS CLASSIFICATION CRITERIA: In 2010 the 2010 ACR/EULAR Rheumatoid Arthritis Classification Criteria were introduced. These new classification criteria overruled the old ACR criteria of 1987 and are adapted for early RA diagnosis . The newclassification criteria jointly published by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR)establish a point vvalue between 0 and 10.every patient with a point total of 6 or higher is unequivocally classified as an RA patient, provided he has synovitis in at least one joint and given that there is no other diagnosis better explaining the synovitis.Four areas are covered in the diagnosis. Joint involvement, designating the metacarpophalangeal joints,proximal interphalangeal joints,the interphalangeal joint of the thumb, second through third metatarsophalangeal joint and wrist as small joints, and elbows, hip joints and knees as large joints; Involvement of 2-10 large joints gives 1point Involvement of 1-3 small joints (with or without involvement of large joints) gives points Involvement of 4-10 small joints (with or without involvement of large joints) gives points Involvement of more than 10 joints (with involvement of at least 1 small joint) gives 5 points. Serological Parameters-including the rheumatoid factor as well as ACPA- ACPAstand for anti-citrullinated protein antibody Negative RF and negative ACPA gives 0 points Low-positive RF or low-positive ACPA gives 2 points High-positive RF or high-positive ACPA gives 3 points Acute phase reactants:1 point for elevated erythrocyte sedimentation rate,ESR,or CRP value (c-reactive protient). Duration of arthritis: 1 point for symptoms lasting six weeks or longer. The new criteria accommodate to the growing understanding of rheumatoid arthritis and the improvement in diagnosing RA and disease treatment. In the new criteria serology 27

and autoimmune diagnostics carries major weight, as ACPA detection is appropriate to diagnose the disease in an early state, before joints destructions occur. Destruction of the joints viewed in radiological images was a significant point of the ACR criteria from 1987. This criterion no longer is regarded to be relevant, as this is just the type of damage that treatment is meant to avoid. The criteria are not intended for the diagnoseis for routine clinical care; they were primarily intended to categorize research (classification criteria).In clinical practice,the following criteria apply: Two or more swollen joints Morning stiffness lasting more than one hour for at least six weeks The detection of rheumatoid factors or autoantibodies against ACPA such as autoantibodies to mutated citrullinated vimentin can confirm the suspicion of rheumatoid arthritis.A negative autoanibody result does not exclude a diagnosis of RA.

Revised American Rheumatism Association Criteria for Classification of Rheumatoid Arthritis

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Rheumatoid Arthritis and Its Management

Percentage with rheumatoid arthritis if sign or symptom is*: Sign or symptom Morning stiffness

Definition Stiffness in or around the affected

LR+ 1.9

LR0.5

Present 39

Absent 14

joints for at least one hour after initiating movement Arthritis of three Three or more of the following joints or more joint noted to be fluid-filled or have soft tissue areas swelling: wrist, PIP, MCP, elbow, knee, ankle, MTP Hand joint Wrist, MCP, or PIP joints among the involvement symptomatic joints observed Symmetric Right and left joints involved for one or arthritis more of following: wrist, PIP, MCP, elbow, knee, ankle, MTP Rheumatoid Subcutaneous nodules in regions nodules surrounding joints, extensor surfaces, or bony prominences Serum Positive result using any laboratory test rheumatoid that has a positive predictive value of 95 factor positive percent or more (i.e., is positive in no more than 5 percent of patients without rheumatoid arthritis) Radiographic Hand and wrist films show typical changes changes of erosions or loss of density adjacent to affected joints

1.4

0.5

32

13

1.5 1.2 3.0 8.4

0.4 0.6 0.98 0.4

33 29 50 74

12 17 25 13

11

0.8

79

21

*Assumes overall probability of rheumatoid arthritis of 30 percent. PIP, MCP, and MTP joints need not be absolutely symmetrical. LR+ = positive likelihood ratio; LR-= negative likelihood ratio; PIP= proximal interphalangeal; MCP= metacarpophalangeal; MTP= metatarsophalangeal.

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5.2

Types Of Rheumatoid Arthritis: Rheumatoid arthritis is an autoimmune, progressive disease in which the immunity of our body is confused and starts attacking our own healthy tissues. The disease mainly affects joints. But it can also affect ligaments, tendons, and other systemic organs. There are various types of rheumatoid arthritis.Juvenile Rheumatoid Arthritis is the RA occurring in children below the age of 16. In this too, there are three types, viz. polyarticular, pauciarticular and systemic juvenile rheumatoid arthritis. In polyarticular JRA, five or more joints are affected. It is one of the most dangerous types of rheumatoid arthritis and needs to be controlled as soon as possible by aggressive treatment. Pauciarticular JRA or oligoarthritis attacks four or less joints and occurs more in girls than in boys. Systemic JRA or Stills disease is the type which starts with high fever and rashes which occur and go suddenly and involve the internal organs too. In all types of JRA, pain, stiffness and swelling of joints are the common symptoms and it is good to detect and treat JRA early so that the child wont suffer more in future.Another type of rheumatoid arthritis is ankylosing spondylitis. It involves intense back pain and inflammation of spine and larger joints. The joints like elbows and knees are mostly affected in this type. The occurrence of this RA is thrice in men than in women.Polymyalgia rheumatica is a type which shows symptoms like aching and stiffness. This type of RA affects ligaments, muscles, tendons and tissues around the joints.One of the types of rheumatoid arthritis is hip rheumatoid arthritis, which affects normally the smaller joints and tendons and usually occurs at a later stage of life. Another is knee rheumatoid arthritis in which joints of knees become tender, swollen, stiff and obviously painful. Cervical spondylosis is one more type of rheumatoid arthritis which is more commonly can be referred to as age-related wear and tear. It mainly affects joints in the neck. One more type of rheumatoid arthritis is lupus. In medical terminology it is called systemic lupus erythematosus. It is a chronic inflammatory disease. Joint pain and inflammation occur in this, along with symptoms in other body organs too. Kidney disorder, lung and heart impairment, neurological symptoms, lesions and rashes are some of the symptoms. It is strange that the patients suffering from this type of RA generally dont have to face any joint destruction. However, in the long run, bone deformities occur without erosion. This is also an autoimmune disorder.

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Rheumatoid Arthritis and Its Management Whichever is the type of rheumatoid arthritis, barring a few exceptions, joint pain, inflammation, swelling and tenderness are its common symptoms. It is a complicated disease in terms of diagnosis. No decisive test is available to ensure its presence. Therefore, you should know all the types and their symptoms in detail. So that when some of the symptoms occur in yourself or anybody you know, you can get the diagnosis done and start the treatment in time. Typically, this disease occurs anywhere between the age of 30 and 70 or more. But children too suffer from this disease and if they are left untreated, they can suffer much in future. Therefore you should know all types of rheumatoid arthritis thoroughly, so as to remain careful about yourself and your dear ones. 5.3 Juvenile Rheumatoid Arthritis: Juvenile rheumatoid arthritis is the most prevalent form of arthritis occurring in children. It can occur between the age of 6 months and 16 years. The exact cause of the disease is not known. Research tells us that it is an autoimmune disease. Autoimmune disease occurs when the white blood cells fail to identify the difference between a foreign intruder like bacteria and virus and bodys own healthy tissue and produce chemicals to kill them, which causes pain and inflammation. It is very important to diagnose the disease in its initial stage and treat it before it becomes uncontrollable. There are three types of juvenile RA and in all of them, joints are the common sites of inflammation. More than one joint can be inflamed and the more the number of affected joints, the more severe is the disease. In that case, the symptoms rarely go in remission. The first type of juvenile RA is oligoarticular JRA, which occurs in four or fewer joints. Its symptoms are pain, swelling or stiffness in the joints. Commonest joints which are inflamed are of wrist and knee. Sometimes, joint symptoms are not seen, but inflammation of iris, i.e. the colored portion of the eye, occurs, which is called iridocyclitis, uveitis, or iritis. Early detection of this can be done by an ophthalmologist. In another form of juvenile RA, called polyarticular JRA, five or more joints are affected. This is more common in girls than boys. Small joints, like that in hands and weightbearing joints, like that in hips, knees, ankles, neck and feet are affected more. Lowgrade fever and bumps or nodules may also be associated. The nodules appear on the spots where more pressure is applied while leaning or sitting. Third type is systemic juvenile rheumatoid arthritis. This affects whole body. Its symptoms include high fever which increases often in the evenings and may suddenly come to normal. When the fever starts, the child looks pale, feels very ill or develops rashes. The rash may come and go suddenly. Sometimes spleen and lymph nodes get enlarged. Consequently, several of the joints get swollen, painful and stiffened. 31

An initial sign of juvenile RA is limping fingers, wrists or knees. Sudden swelling may occur in the joints, which can persist. Neck, hips and other joints too can become stiffened. Suddenly appearing and disappearing rashes may also occur in one after another area. Major symptom is the high fever appearing in the evening and suddenly dropping to normal. The treatment of juvenile RA often includes medication, physiotherapy and exercise, but in some specific situations, the child has to take injections of corticosteroids into the joints or even surgery. It is the job of the general physician, rheumatologist and the physiotherapist to develop the best treatment plan for the child. Treatment is mainly focused on symptom relief, i.e. relief from pain and inflammation, and slow down or stop the further damage to the joints and remove the limitations on the mobility as far as possible. The medicines primarily contain non-steroidal anti-inflammatory drugs (NSAIDs), like ibuprofen. They are for restricting the harmful chemicals released from the white blood cells and thus reducing pain and inflammation. If they cannot control the pain and inflammation, the doctor may start other medicines, like methotrexate. 5.4 Palindromic Rheumatoid Arthritis: Palindromic rheumatoid arthritis has much similarity in symptoms and appearance with rheumatoid arthritis, but is different in that, it hardly causes permanent joint damage. Recurring attacks of pain and swelling in the joints of knees, fingers and large joints are the main characteristics of the disease. Nodules, quite same as those produced in RA, are produced on the affected joints, which usually a rheumatologist can identify and does further testing to confirm the presence of palindromic RA. The patient may or may not suffer from weakness and fever, during the repeated flares which make the joints swollen and painful and are, therefore, often confusing the disease with rheumatoid arthritis. It occurs equally in men and women, unlike RA, which occurs more prominently in women. Also, it can occur at any age between 20 and 70; however, the disease as such is rare. Though in 40% patients of palindromic arthritis, the attacks become more frequent, x-rays of the affected joints do not generally show any narrowing of joints, which occurs in RA. A very less percentage of sufferers develops a full-scale rheumatoid arthritis from palindromic arthritis and may test positive also for the rheumatoid factor. The patients of palindromic arthritis may show high sedimentation rates during blood tests and also may show high levels of C-Reactive Protein in the blood. Some studies have inferred the connection of anti-malarial drugs, like Plaquenil, to high risk of developing palindromic arthritis, which later develops into full-scale rheumatoid arthritis.

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Rheumatoid Arthritis and Its Management Diagnosis of palindromic rheumatoid arthritis is difficult and may take time. It is usually based on elimination of other conditions and finally concluding about the occurrence of the disease. This is because there is no specific test for the diagnosis of this disease. Also it becomes more difficult with the possibility of presence of other auto-immune diseases. However, it is interesting to note that presence of rheumatoid factor indicates high chances of developing rheumatoid arthritis in future. The flares of palindromic rheumatism may last from a few hours to a few days and then suddenly subside and may not show for a long time. They form a pattern with the symptom-free periods. More commonly 2 to 3 joints are involved and the soft tissue surrounding the joints may also be involved with swelling at particular spots. Particularly finger pads and heel pads are affected. This is a disease caused by unknown factor. An opinion says that it is an abortive form of RA, indicated by the raised levels of antikeratin antibodies (AKA) and anti-cyclic citrullinated peptide antibodies (anti-CCP), which is the characteristic of rheumatoid arthritis. Initial treatment includes pain-killers and anti-inflammatory drugs. The physician may also start an anti-depressant. As the attacks are highly unpredictable, the treatment is quite difficult. If the attacks are very frequent, long-term treatment with the disease-modifying anti-rheumatoid drugs (DMARDs), which is administered in rheumatoid arthritis patients, may have to be started. To adopt a diet, free of pain-causing prostaglandins and arachidonic acid, may help quite a lot. It includes lots of vegetables, fruits, cold water fish, nuts and soy products. It is a must to keep away from weight-gaining foods and oils containing omega-6 fatty acids, namely, sesame oil, sunflower oil, corn oil, wheat germ oil and soybean oil. Palindromic rheumatoid arthritis is thus a disease which rarely causes any harm and you have to manage the pain attacks, by which it is characterized. 5.5 Pannus Rheumatoid Arthritis: Pannus in rheumatoid arthritis is defined as thickened synovial tissue which covers articular cartilage, i.e. the cartilage present in joints. Synovial tissue is the tissue of synovium i.e. the lining of the joints. With the thickening and proliferation of synovium, the joint is filled by the thickened tissue and the tissue thus abnormally proliferated, spreads across the articular cartilage and subsequently causes erosions. There is also a risk of the pannus to penetrate into the bone and bone marrow and harm the surrounding parts such as joint capsule and tendons. In patients of rheumatoid arthritis, pannus formation is an unavoidable situation in the long run. Pannus triggers destruction of bone and cartilage. Continuous progression of 33

the disease normally coincides with the process of pannus formation. Pannus is generally a membrane of vasuclarised granulated tissue and is formed of mesenchyme and bone marrow derived cells. It is rich in fibroblasts, macrophages and lymphocytes, received from synovial tissue. It overgrows the bearing surface of the arthritic joint and is connected to the breakdown of the articular surface Pannus formation also triggers macrophges to discharge IL-2, prostaglandins, plateletderived growth factor, and substance P. All these, in turn, stimulate destruction of cartilage and bone erosion. Rheumatoid arthritis is an autoimmune, inflammatory, systemic, progressive disease. Though its principal site of occurrence is joints, it may become systemic too, meaning other organs of the body too may be involved. The ways of joint destruction caused in rheumatoid arthritis vary more than in case of osteoarthritis. Being an autoimmune disease, the rheumatoid arthritis is characterized by impaired immune system which eats up bodys own healthy tissues, the process of which takes place in three phases of inflammation. First is inflammation of synovial lining, second is spread of pannus membrane into the joint and third is release of certain enzymes by the inflamed cells which start digesting cartilage and bone, thereby joint destruction takes place. Studies, done regarding similarities and differences between the progression of these three processes, and especially, formation of pannus in rheumatoid arthritis and osteoarthritis, show that there is much similarity in the pannus formation of both the conditions. But the osteoarthritis pannus, after invading the cartilage does not give rise to marginal erosions, which happens in rheumatoid arthritis. MMPs (matrix metalloproteases) are some enzymes belonging to a large proteolytic enzyme group. They degrade the extracellular matrix. In the early stages of RA, MMPs increase in pannus and partake in the invasion of cartilage. They do that by destroying extracellular matrix and by stimulating other proteinases. Some of these stimulated proteinases may either directly degrade the cartilage, thereby causing joint destruction or they may degrade extracellular matrix and thus helps pannus invasion. The proteinases can be released by synovial fibroblast and cells resembling macrophages and are capable to digest the contents of the cartilage matrix and the destruction process takes place mainly in areas near inflamed pannus tissue. Panuus also occurs in the cornea of the eye from the conjunctiva as a response to inflammation and the condition is called chronic superficial keratitis. Pannus in rheumatoid arthritis is a quite dangerous condition and if left untreated, may even lead to sudden death and therefore needs immediate attention .

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Rheumatoid Arthritis and Its Management 5.6 Seronegative Rheumatoid Arthritis: Seronegative rheumatoid arthritis is the rheumatoid arthritis in which the blood doesnt contain Rheumatoid Factor (RF or RhF). While diagnosing RA, doctors get a range of laboratory tests done and also evaluate the physical symptoms. Testing of blood for rheumatoid factor is the most common way to help determine the presence of disease. But some patients, though they show all the arthritic symptoms, are negative for rheumatoid factor. Despite a negative rheumatoid factor test result, various other tests, to detect the presence of rheumatoid arthritis, can be done, such as, the erythrocyte sedimentation rate (ESR), X-rays, complete blood count (CBC), C-reactive protein (CRP) and antinuclear antibodies. Rheumatoid arthritis is a disease which cannot be diagnosed easily. Therefore, performing a series of tests is usual to reach its diagnosis. This type of rheumatoid arthritis is more common in men. Common symptoms of seronegative RA are same as those of seropositive RA and they are swollen, painful and tender joints, flu-like symptoms, stiffness in the morning, muscle pain and limitations on movements. Other symptoms are fatigue, weakness and general stiffness of the body. The disease has a tendency to flare up in the mornings after long time of rest. During this time, pain and limited movement of joints, especially in wrists, ankles and back, are often seen. It is difficult to monitor the progress of seronegative rheumatoid arthritis. When the rheumatoid factor is present in the blood, doctors can know how far and intense the disease has developed. The severity of the disease is easy to identify which is indicated by increased number of rheumatoid factor. This becomes impossible in the seronegative RA patients because of the absence of rheumatoid factor. A remedy for this is suggested to these patients by the doctor and it is observing and documenting the ongoing of the flares. This is very essential for these patients. It is best to keep a calendar of flares. It will help the doctor by providing necessary information about the condition that takes place between the periods of remission. Evaluating the severity and frequency of flare-ups will help the doctor to determine whether the condition is getting more serious, because s/he cannot successfully perform a rheumatoid factor test. Just like seropositive rheumatoid arthritis, treatment of seronegative rheumatoid arthritis too focuses on relief from pain, inflammation and slowing down the destruction of joints. The most common medicine is NSAID, i.e. non-steroidal anti-inflammatory drugs, analgesic drugs, DMARDs, i.e. disease modifying antirheumatic drugs and biologic response modifiers. A major (and relieving) difference which medical studies have observed is that patients with seronegative RA have comparably less joint erosion and destruction than patients 35

having seropositive RA. Also the tendency for developing rheumatoid nodules under the skin is less in this disease than the positive population. Moreover, though the other symptoms are same as in the positive group, their severity is less, which too is a bit relieving. 5.7 Seropositive Rheumatoid Arthritis: Seropositive rheumatoid arthritis is nothing but the same rheumatoid arthritis, the blood test done for which shows presence of rheumatoid factor, or RF, in it. Rheumatoid arthritis stealthily enters the body, when our immune system goes haywire and attacks its own healthy tissues, considering them to be foreign invaders, major amongst them being the joints. During this process of attack of immune system on healthy tissues, rheumatoid factor is produced. It is not necessary that individuals who do not show rheumatoid factor in their blood test, i.e. they are seronegative, do not have rheumatoid arthritis. They too may have the disease, but it is somewhat milder. Whether you are seropositive or seronegative, does not make much difference in the situation that you have caught the disease and you will have to live with it. The disease mainly attacks the joints, though it affects other parts of the body too. It is an autoimmune disease, and occurs when the immune system is disturbed. It can occur at any age between 20 and 70. It is more prevalent in women. It is not definite that you will suffer from flares of pain and stiffness continuously or at particular time intervals. Different patients show wide variety in this. In some patients, the disease is continuously disturbing, while in some other patients flares may last for only a short period, after which there is a long period of remission. In any case, you will have to observe certain care so as not to let the pain and inflammation worsen. There is no definite cure for this disease and the treatment is mainly based on symptom relief. In seropositive rheumatoid arthritis, it can only be said that the patient definitely has the disease, which is not certain with the seronegative counterpart. And in that case, you will have to take the necessary medicines, take proper diet and exercise, take plentiful rest and try to minimize the symptoms, mainly pain and joint stiffness. You should remain active as far as possible. But it should not be done at the cost of increased pain. In most people, morning stiffness is experienced. You should find out what gives you relief from the pain and stiffness. And for that you have to educate yourself well about the disease. During a fight, if you know whom you are fighting with, you can win the fight. So get more and more knowledge and information about the disease. You can do this by regularly discussing with your health care provider, monitoring your symptoms and symptom relief, telling it to the doctor, reading about the disease and also, discussing with other patients suffering from same disease.

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Rheumatoid Arthritis and Its Management

In this disease, nothing can be said definitely and everything is based on trial and error, to which medicines too are not exceptions. Regarding medicine you have to depend on your doctor, who knows better than you which medicine acts well for you. But there are certain things that you can monitor and manage on your own. You can observe carefully, which activity increases the flare, which food and medicine brings about relief, which time of the day, month or year the flare is worst, and so on. Based on these observations, you can learn more and more how to live with your seropositive rheumatoid arthritis happily.

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CHAPTER 6
6.1 DIFFERENIAL DIAGNOSES. Several other medical conditions can resemble RA, and usually need to be distinguished from it at the time of diagnosis. Crystal induced arthritis(gout, and pseudo gout) usually involves particular joints (knee,MTPI,heels) and can be distinguished with aspiration of joint fluid if in doubt. Redness (RAdoesn't have redness at the joints), asymmetric distribution of affected joints, pain occurs at night and the starting pain is less than an hour with gout. Osteoarthritis- distinguished with X-rays of the affected joints and blood tests, age (mostly older patients), Starting pain less than an hour, a-symmetric distribution of affected joints and pain worsens when using joint for longer periods. Systemic lupus erythematosus (SLE)- distinguished by specific clinical symptoms and blood tests (antibodies against double-stranded DNA).s One of the several types of psoriatic arthritis resembles RA- nail changes and skin symptoms distinguish between them. Lyme disease causes erosive arthritis and may closely resemble RA- it may be distinguished by blood test in endemic areas. Reactive arthritis (previously Reiter's disease) - asymmetrically involves heel, sacroiliac joints, and large joints of the leg. It is usually associated with arthritis, conjunctivitis, iritis, painless buccal ulcers, and keratoderma blennorrhagica. Ankylosing spondlitis- this involves the spine, although a RA like symmetrical small-joint polyarthritis may occur in the context of this condition. Hepatitis C- RA- Like symmetrical small-joint polyarthritis may occur in the context of this codition.Hepatitis C may also induce Rheumatoid Factor auto-antibodies. 38

Rheumatoid Arthritis and Its Management Rarer causes that usually behave differently but may cause joint pains: Sarcoidosis, amyloidosis,and Whipples disease can also resemble RA. Hemochromatosis may cause hand joint arthritis. Acute rheumatic fever can be differentiated from RA by a migratory pattern of joint involvement and evidence of antecedent streptococcal infection. Bacterial arthritis (such as streptococcus) is usually asymmetric, while RA usually involves both sides of the body. Gonococcal arthritis (another bacterial arthritis) is also initially migratory and involves tendons around the wrists and ankles. Differential Diagnosis of Rheumatoid Arthritis Diagnosis Connective tissue diseases Fibromyalgia Hemochromatosis Infectious endocarditis Polyarticular gout Polymyalgia rheumatica Sarcoidosis Seronegative spondyloarthropathies, reactive arthritis Stills disease Thyroid disease Viral arthritis Comments Such as scleroderma and lupus Evaluate for trigger points. Iron studies and skin coloration changes may guide diagnosis. Rule out murmurs, high fever, and history of intravenous drug use. Joints often erythematous; podagra commonly found; gout and rheumatoid arthritis rarely coexist, but calcium pyrophosphate deposition disease can accompany rheumatoid arthritis. Rheumatoid arthritis, unlike polymyalgia rheumatica, rarely presents with pain in the proximal joints of the extremities only. Granulomas likely, as are hypercalcemia and chest film findings. Tend to be more asymmetric than rheumatoid arthritis. More commonly involve the joints of the spine. Evaluate for history of psoriasis, Reiters comorbidities, inflammatory bowel disease. Reactive arthritis can be postinfective, sexually acquired, or related to gastrointestinal disorders. Tends to present with fever, leukocytosis with left shift, sore throat, splenomegaly, liver dysfunction, and/or rash. Consider thyroid-stimulating hormone level depending on symptoms. Consider parvovirus, hepatitis B.

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6.2

Diseases with Symptoms Similar to Rheumatoid Arthritis Diseases with Symptoms Similar to Rheumatoid Arthritis Disease Osteoarthritis Infectious Arthritis Lyme disease, septic arthritis, bacterial endocarditis, mycobacterial and fungal arthritis, viral arthritis Reiter syndrome (a disorder characterized by arthritis and inflammation in the eye and urinary tract), rheumatic fever, inflammatory bowel disease Gout and pseudogout Specific Subtypes

Postinfectious or Reactive Arthritis

Crystal Induced Arthritis Other Rheumatic Autoimmune Diseases Other Diseases

Systemic vasculitis, systemic lupus erythematosus, scleroderma, Still's Disease (also called juvenile rheumatoid arthritis), Behcet's disease Chronic fatigue syndrome, hepatitis C, familial Mediterranean fever, cancers, AIDS, leukemia, Whipple's disease, dermatomyositis, Henoch-Schonlein purpura, Kawasaki's disease, erythema nodosum, erythema multiforme, pyoderma gangrenosum, psoriatic arthritis

6.3

MONITORING PROGRESSION; The progression of rheumatoid arthritis can be followed using scores such as Disease

Activity Score of 28 joints (DAS 28). It is widely used as an indicator of RA disease activity and response to treatment, but is not always a reliable indicator of treatment effect. The joints included in DAS28 are (bilaterally): proximal interphalangeal joints (10 joints), metacarpophalangeal joints (10), wrists (2), elbows (2), shoulders (2) and knees(2). When looking at these joints both the number of joints with tenderness upon touching (TEN 28) and swelling (SW 28) are counted. In addition, the erythrocyte sedimentation rate (ESR) is measure.

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Rheumatoid Arthritis and Its Management Also, the patient makes a subjective assessment (SA) of disease activity during the preceding 7 days on a scale between 0 and 100, where 0 is no activity and 100 is highest activity possible. With these parameters, DAS 28 is calculated as:

DAS28 = 0.56 X TEN28 + 0.28 X SW28 + 0.70 X In (ESR) 0.014 X SA From this, the disease activity of the patient can be classified as follows : 3.2 Current DAS28 Inactive DAS 28 difference from initial value >1.2 >0.6 but 1.2 0.6 Good Moderate No improvement improvement Moderate improvement Moderate improvement improvement Moderate improvement No improvement No improvement No improvement

>3.2 but 5.1 > 5.1

Moderate Very active

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CHAPTER 7
7.1 PATHOPHYSIOLOGY AND CAUSES Rheumatoid arthritis is a form of autoimmunity, the causes of which are still incompletely known. It is a systemic (whole body) disorder principally affecting synovial tissues. The key pieces of evidence relating to pathogenesis are: A genetic link with HLA-DR4 and related all types of MHC Class II and the T cellassociated protein PTPN 22. An undeniable link with cigarette smoking and the pathogenesis of rheumatoid vasculitis,a typical feature of this condition. A remarkable deceleration of disease progression in many cases by blockade of the cytokine TNF (alpha). A similar dramatic response in many cases to depletion of B lymphocytes, but no comparable response to depletion of T lymphocytes. A more or less random pattern of whether and when individuals predisposed are affected. the presence of auto antibodies to 1gGFc, known as rheumatoid factors (RF), and antibodies to citrullinated peptides (ACPA) These data suggest that the disease inv loves abnormal B cellT cell interaction, with presentation of antigens by B cells to T cells via HLA-DR eliciting TCell help and consequent production of RF and ACZPA. Inflammation is then driven either by B cell or T cell products stimulating release of TNF and other cytokines. The process may be facilitated by an effect of smoking on citrullination but the stochastic (random)epidemiology suggest that the rate limiting step in genesis of disease in predisposed individuals may be can inherent stochastic process within the immune response such as immunoglobulin or T cell receptor gene recombination and mutation.(See entry under autoimmunity for general mechanisms.)

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Rheumatoid Arthritis and Its Management If TNF release is stimulated by B cell products in the form of RF or ACPAcontaining immune complexes, through activation of immunoglobulin Fc receptors then RA can be seen as a form of Type III hypersensitivity. If TNF release is stimulated by T cell products such as inerleukin-17 it might be considered closer to type IV hypersensitivity although this terminology may be getting some what dated and unhelpful. The debate on the relative roles of immune complexes and T cell products in inflammation in RA has continued for 30 years. There is little doubt that both B and T cells are essential to the disease. However, there is good evidence for neither cell being necessary at the site of inflammation. This tends to favor immune complexes (based on antibody synthesized elsewhere) as the initiators, even if not the sole perpetuators of inflammation,. Moreover, work by Thurlings and others in Paul-Peter Takes group and also by Arthur Kavanaghs group suggest that if any immune cells are relevant locally they are the plasma cells, which derive from B cells and produce in bulk the antibodies selected at the B cell stage. Although TNF appears to be the dominant, other cytokines (chemical mediators) are likely to be involved in inflammation in RA .Blockade of TNF does not benefit all or all tissue (lung disease and nodule may get worse).Blockade of II, 1. IL- 15 and IL-6 also have, beneficial effects and II-17 may be important.Constitutional symptoms such as fever, malaise, loss of appetite and weight loss are also caused by cytokines released in to the blood stream. As with most autoimmune diseases, it is important to distinguish between the causes (S) that trigger the process, and those that may permit it to persist and progress. 7.2 POSSIBLE INFECTOUS TRIGGERS. It has long been suspected that certain infections could be triggers for this disease. The mistaken identity theory suggests that an infection triggers an immune response, leaving behind antibodies that should be specific to that organism. The antibodies are not sufficiently specific, though, and set off an immune attack against part of the host. Because the normal host molecule Looks 43

like a molecule on the offending organism that triggered the initial immune reaction this phenol neon is called molecular mimicry. Some infections organism suspected of triggering rheumatoid arthritis include Mycoplasma, Erysipelothrix, parvovirus B19 and rubella, but these associations have never been supported in epidemiological studies. Nor has convincing evidence been presented for other types triggers such as food allergies. Epidemiological studies have confirmed a potential association between RA and two herpes virus infections: Epstein-Bar virus (EBV) and Human Herpes Virus 6 (HHV-6). Individuals with RA are more likely to exhibit an abnormal immune esponse to the Epstein Barr virus. The allele HLA DRB1 x0404 is associated with low frequencies of T cells specific for the EBV glycoprotein 110 and predisposes one to develop RA. 7.3 PSYCHOLOGICAL FACTORS: There is no evidence that physical and emotional effects or stress could be a trigger for the disease. The many negative findings suggest that either the trigger varies, or that it might in fact be a chance event inherent with the immune response, as suggested by Edwards et al. 7.4 CONTINUED ABNORMAL IMMUNE RESPONSE: The factors that allow an abnormal immune response, once initiated, to become permanent and chronic, are becoming more clearly understood. The genetic association with HLA-DR4,as well as the newly discovered associations with the gene PIPN22 and two additional genes, all implicate altered thresholds in regulation of the adaptive immune response. It has also become clear from recent studies that that these genetic factors may interact with the most clearly defined environmental risk factor for rheumatoid arthritis, namely cigarette smoking . Other environmental factors also appear to modulate the risk of acquiring RA, and hormonal factors in the individual may explain some features of the disease, such as the higher occurrence in women, the not infrequent consent after child-birth, and the (slight) modulation of disease risk by hormonal medications. Exactly how altered regulatory threshold allow the triggering of a

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Rheumatoid Arthritis and Its Management specific autoimmune response remains uncertain. However, one possibility is that negative feedback mechanisms that normally maintain tolerance of self are overtaken by aberrant positive feedback mechanisms for certain antigens such as 1gG Fc (bound by RF) and cirtrullinated fibrinogen (bound by ACPA)(see entry on autoimmunity). Once the abnormal immune response has become established (which may take Several years before any symptoms occur), plasma cells derived from lymphocytes produce rheumatoid factors and ACPA of the 1gG and 1gM classes in large quantities. These are not deposited in the way that they are in systemiclupus. Rather, they appear to activate macrophages through Fc receptor and perhaps complement binding. This can contribute to inflammation of the synovium,in terms of edema, vasodilation and infiltration by activated T-cells (mainly CD4 in nodular aggregates and DC8 in diffuse infiltrates).Synovial macrophages and dendritic cells further function as antigen presenting cells by expressing MHC class II molecules, leading to an established local immune reaction in the tissue. The disease progresses in concert with formation of granulation tissue at the edges of the synovial lining (pannus) with extensive angiogenesis and production of enzymesthat cause tissue damage.Modern pharmacological treatment of RA target these mediators. Once the inflammatory reaction is established, the synovium thickens,the cartilage and the underlying bone begins to disintegrate and evidence of joint destruction accrues 7.5 ROLE OF VITAMIN D: The discovery of the vitamin D receptor (VDR) in the cells of the immune system and the fact that activated dendrites cells produce the vitamin D hormone suggested that vitamin D could have immunoregulatory properties. VDR, a member of the nuclear hormone receptor super family, was identified in mononuclear cells,dendritic cells, antigen presenting cells, and activated T-B lymphocytes. In synthesis, the most evident effects of the D-hormone on the immune system seem to be in the down regulation of the Th1-driven autoimmunity. Low serum levels of vitamin D3 might be partially related, among other factors, to prolonged daily darkness (reduced activation of the pre vitamin D by the ultra violet 45

B sunlight), different genetic background (i.e vitamin D receptor polymorphism) and nutritional factors, and explain the latitude-related prevalence of autoimmune diseases such as rheumatoid arthritis ( RA), by co considering the potential immunosuppressive roles of vitamin D.25(OH)D3 plasma levels have been found inversely correlated at least with the RA disease activity showing a circannual rhythm (more severe in winter). Recently, greater intake of vitamin D was associated with a lower risk of RA, as well as a significant clinical improvement was strongly correlated with the immunomodulating potential vitamin D-treated RA patients. In patients with rheumatoid arthritis measuring vitamin D is a level seems particularly pertinent as deficiency is highly prevalent in the group. Vitamin D is already known to be important in preventing osteoporosis and fracture falls, which are also common in RA.It is too early to tell whether administering vitamin D directly affects disease activity.

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Rheumatoid Arthritis and Its Management

CHAPTER - 8
8.1 Complications of Untreated Rheumatoid Arthritis :

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Complication Comments Anemia Cancer Correlates with erythrocyte sedimentation rate and disease activity; three fourths of patients have anemia of chronic disease; one fourth of patients respond to iron therapy. May be secondary to treatments; lymphomas and leukemias two to three times more common in patients with rheumatoid arthritis; increased risk for various solid tumors; genitourinary cancer risk is reduced in rheumatoid arthritis, perhaps because of nonsteroidal anti-inflammatory drugs. Pericarditisone third of patients may have asymptomatic pericardial effusion at diagnosis; atrioventricular blockrare; myocarditisdiffuse inflammation can occur, may or may not be symptomatic. Tenosynovitis of transverse ligament can lead to instability of atlas on axis. Caution must be used during endotracheal intubation; may see loss of lordosis of the neck and decreased range of motion; C4-C5 and C5-C6 subluxations are possible; may see joint space narrowing on lateral cervical spine films; avoid flexion films until odontoid fracture ruled out if injury is suspected; myelopathy can occur, with gradual onset of upper extremity weakness and paresthesias. Episcleritis rarely occurs. Cutaneous sinuses form near affected joints, connecting bursa to the skin. More likely to be an effect of rheumatoid arthritis treatment. Ulnar deviation at metacarpophalangeal joints; boutonniere deformityflexed PIP and hyperextended DIP; swan neck deformitythe reverse of boutonniere, with flexed DIP and hyperextended PIP; thumb hyperextension; increased risk of tendon rupture Frozen shoulder may develop; popliteal cysts can arise; carpal and tarsal tunnel syndromes common. Lung nodules can coexist with cancers and form cavitary lesions; cricoarytenoid joint inflammation can arise, with hoarseness and laryngeal pain; pleuritis present in 20 percent at onset of disease; not usually associated with pleuritic pain; interstitial fibrosisrales may be noted on lung examination. Often have necrotic tissue in their centers; found in 20 to 35 percent of patients with rheumatoid arthritis; usually found on extensor surfaces of the limbs or other pressure points; may form nearly anywhere, including on the sclera, vocal cords, sacrum, or Vertebral bodies. Forms include distal arteritis, pericarditis, peripheral neuropathy, cutaneous lesions, arteritis of viscera, and coronary arteritis; increased risk of developing if male sex, high rheumatoid factor titers, treatment with steroids, number of disease-modifying antirheumatic drugs prescribed; associated with increased risk of myocardial infarction.

Cardiac complications Cervical spine disease

Eye problems Fistula formation Increased infections Hand joint deformities Other joint deformities Respiratory complications Rheumatoid nodules

Vasculitis

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Rheumatoid Arthritis and Its Management

CHAPTER - 9 9.1 RHEUMATOID ARTHRITIS AND PREGNANCY

Pregnancy alters the immune state, possibly contributing to change in the course of rheumatoid arthritis. For decades, the ameliorating effects of pregnancy on disease activity in women with RA have been observed. No specific guidelines address obstetric monitoring in patients with RA.Because little available data suggest a significant risk for preterm birth, preeclampsia, or fetal growth restriction in pregnant patients with this disease, no special obstetric monitoring is indicated beyond what is performed for usual obstetric care.

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It is important to counsel patients about the teratogenicity adverse effects of the medications used to treat rheumatoid arthritis before starting therapy, patients may need a reminder about the importance of using contraception during DMARD therapy and that some of these medications may need to be discontinued several months before conception is planned. In addition to discontinuation, some patients who take DMARDs may require treatment with other medications to enhance their clearance. Patients with rheumatoid arthritis must be monitored closely following delivery, because they the potential to have arthritis flare-ups during the postpartum period. 9.2 Rheumatoid Arthritis Makes It Difficult to Conceive

A study done in Denmark on about 68,120 women who became pregnant between 1996 and 2002 has come to the conclusion that presence of Rheumatoid Arthritis makes it difficult for the women to conceive. Women with Rheumatoid Arthritis Find It Hard To Get Pregnant According to the study, published in the journal Arthritis and Rheumatism, it was found that almost 25% women suffering from RA tried unsuccessfully for a year to conceive before finally getting pregnant as compared to 16% women who did not have RA. 10% of women with RA were treated for infertility as compared to 8% women without RA. 41% of women with RA got pregnant within 2 months of trying as compared to 48% women who did not suffer from RA. Thus it was concluded that rheumatoid arthritis makes it difficult for the women to conceive. Though the disease does not affect the fertility rate, it seems to increase the time to pregnancy. It is difficult to say whether the time to pregnancy increases because of the rheumatoid arthritis or because of the various medicines taken to counter RA. There is no evidence till date to suggest that RA hinders pregnancy. However, the patients of RA trying to conceive are asked to stop their medications beforehand as these may have deleterious effect on the fetus. Medicines like methotrexate are known to roduce birth defects whereas newer disease modifying anti-rheumatic drugs (DMARDs) like etanercept and infliximab have not been studied enough for their effect on the developing embryo. It has been hypothesized that this sudden stoppage of treatment for RA results in the flaring up of the disease which may somehow be related to difficulty in conceiving. Rheumatoid Arthritis has different effects on the different stages of pregnancy Rheumatoid Arthritis is an autoimmune disease commonly affecting the women, wherein the bodys immune system fails to recognize its own tissue and starts damaging the joints resulting in pain, inflammation and subsequent destruction of the joints. Women suffering from RA may take longer to conceive because of inconsistent ovulation; and fatigue and pain leading to a decrease in sex drive. Before trying to conceive, it is better to consult the doctor so that any harmful medication is tapered off or is replaced by some other safe alternative. Different medications for RA take different time to be completely washed away from the system. RA has different

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Rheumatoid Arthritis and Its Management effects on the different stages of pregnancy. During the first trimester of pregnancy, women suffering from RA tend to get more fatigued. Almost 70 to 80% women report an improvement in their symptoms during the second trimester of pregnancy. This is especially true in women who are negative for the rheumatoid factor and anti CCP autoantibody. The fatigue worsens once again with the onset of the third trimester though now it is more related to the growing weight of the baby. RA increases the chances of an early labor and delivery of a premature baby. The likelihood of undergoing a cesarean s to deliver the baby is also more. This is because of the involvement of the hip joint by the arthritis. RA tends to flare up in the post partum period. Getting back with the old medication that the patient was taking before pregnancy should be discussed with the doctor in view of breast feeding. Though women with RA take slightly longer to conceive, the delay is not very significant. It is advisable for such women not to put their plans of having a baby on hold as it will be more difficult to conceive in the late reproductive years.

CHAPTER 10 10.1 Management of Rheumatoid Arthritis under various therapies:

There is no known cure for rheumatoid arthritis, but many different types of treatment can alleviate symptoms and or modify the disease process. Recommendations of the American College of Rheumatology (ACR), published in 2008, followed a trend in 51

supporting earlier, more aggressive treatment of RA, and reflected heightened expectations of treatment effectiveness, including remission or substantial alleviation of symptoms for a rising percentage of patients. The goal of treatment is twofold: alleviating the current symptoms, and preventing the future destruction of the joints with the resulting handicap if the disease is left unchecked.These two goals may not always coincide:while pain relievers may achieve the first goal, they do not have any impact on the long term consequences. For these reasons,the ACR recommends that RA should generally be treated with at least one specific anti-rheumatic medication, also named DMARD(see below), to which other medications may be added depending on how long a person has had RA, how active the disease is, and prognostic factors (such as X-ray evidence of bone erosion; elevation of blood factors such as rheumatoid factor, anti-cyclic citrullinated peptide, C-reactive protein, and erythrocyte sedimentation rate; age and gender; physical functioning; and smoking, for example).Cortisone therapy has offered relief in the past, but its long-term effects have been deemed undesirable. However, cortisone injections can be valuable adjuncts to a long-term treatment plan, and using low dosages of daily cortisone (e.g,prednisone or prednisolone,5-7.5 mg daily)can also have an important benefit if added to a proper specific anti-rheumatic treatment.

The management of Rheumatoid Arthritis includes: A-Pharmacological Treatment B-Non-Pharmacological Treatment Pharmacological Treatment Medical management of RA involves three general approaches: Disease Modifying Anti-Rheumatic Drugs(DMARs) Biological Agents/Immunosuppressive drugs Non Steroidal anti-inflammatory drugs(NSAIDs)

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Rheumatoid Arthritis and Its Management 10.2 Low dose corticosteroids DISEASE MODIFYING ANTI-RHEUMATIC DRUGS (DMARDs) The term Disease-modifying anti-rheumatic drug (DMARD) originally meant a drug that affects biological measures such as ESR and haemoglobin and autoantibody levels, but is now usually used to mean a drug that reduces the rate of damage to bone and cartilage.DMARDs have been found both to produce durable symptomatdelay or halt progression.This is important as such damage is usually irreversible. Anti-inflammatories and analgesics improve pain and stiffness but do not prevent joint damage or slow the disease progression.There is an increasing recognition among rheumatologists that permanent damage to the joints occurs at a very early stage in the disease. In the past it was common to start with just an anti-inflammatory drug, and assess progression clinically and using X-rays.If there was evidence that joint damage was starting to occur then a more potent DMARD would be prescribed.Ultrasound and MRI are more sensitive methods of imaging the joints and have demonstrated that joint damage occurs much earlier and in more sufferers than was previously thought.People with normal X-rays will often have erosions detectable by ultrasound that X-rays could not demonstrate. The aim now is to treat before damage occurs.

There may be other reasons why starting DMARDs early is beneficial as well as prevention of structural joint damage. From the earliest stages of the disease, as well as prevention of the immune system that signal to one another in ways that may involve a variety of positive feedback loops (it has long been observed that a single corticosteroid injection may abort synovitis in a particular joint for long periods).Interrupting this process as possible with an effective DMARD (such as methotrexate) appears to improve the outcome from the Ra for years afterwards. Delaying therapy for as little as a few months after the onset of symptoms can result in worse outcomes in the long term. There is therefore considerable interest in

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establishing the most effective therapy with early arthritis, when they are most responsive to therapy and have the most to gain. Disease-modifying anti-rheumatic drugs have been used in the treatment of rheumatic arthritis for a long time now. Over 90% of rheumatologists now use combitination therapy of multiple disease modifying drugs for rheumatoid arthritis as it has become apparent that using combination of these drugs does not increase their relative toxicity profiles. Common combinations of DMARDs include methotrexatehydroxychloroquine,methrexate-sulfasalazine,sulfasalazine-hydroxychloroquine, methotrxate- hydroxychloroquine sulfasalazine. In order to be effective, disease modifying anti-rheumatic drugs must be administered before the deformaities appear or the erosive disease occurs.Usually,Rheumatologists do not wait for the fulfillment of the criteria for classification of RA as published by the American College of Rheumatology (ACR) and start treatment with this type of drugs if the pain and synovitis persist and the function is compromised. 10.3 TRADITIONAL SMALL MOLECUAR MASS DRUGS. Chemically synthesized DMARDs: Azathioprine Ciclosporin (cyclosporine A) D-penicillamine Gold salts Hydroxychloroquine Leflunomide Methotrexate (MTX) Minocycline Sulfasalazine (SSZ) Cytotoxic drugs:Cyclophosphamide and

The most important and most common adverse events relate to liver and bone marrow toxicity (MTX,SSZ, leflunomide, azathioprine,gold compounds, D-penicillamine ), renal

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Rheumatoid Arthritis and Its Management toxicity (cyclosporine A, parenteral gold salts, D-penicillamine),peneumonitis (MTX),allergic skin reactions (gold compounds,SSZ),autoimmunity (D-penicillamine,SSZ,minocyciline) and infections (azathioprine,cyclosporine A). Hydroxychloroquine may cause ocular toxicity, although this is rare, and because hydroxchloroquine does not affect the bone marrow or liver it is often considered to the DMARD with the least toxicity. Unfortunately hydroxychloroquine is not very potent, and is usually insufficient to control symptoms on its own. Methotrexate is considered by many rheumatologists to be the Most important and useful DMARD, largely because of lower drop-out rates for reasons of toxicity. Nevertheless, methotrexate is often considered as a very toxicdrug.This reputation is not entirely justified, and at times can result in people being denied the most effective treatment for their arthritis. Although methotrexate does have the potential to suppress bone marrow or cause hepatitis, these effects can be monitored using regular blood tests, and the drug withdrawn at an early stage if the tests are bnormal before any serious harm is done(typically the blood tests return to normal after stopping the drug).In clinical trials, where one of a range of different DMARDs were used, people who were prescribed methotrexate stayed on their medication the longest (the others stopped because of either side-effects or failure of the drug to control the arthritis). Methotrexate is often preferred by rheumatologists because if it does not control arthritis on its own then it works well in combination with many other drugs, especially the biological agents. Other DMARDs may not be as effective or as safe in combination with biological agents. Sulphasalazine: Although it appears to be a highly efficient drug in the treatment of rheumatoid arthritis, sulphasalazine may cause side effects that can range in severity from mild to serious.Mild side effects that may arise from treatment with sulphasalazine include nausea and skin rash. Generally, nausea that appears as a result of treatment with this DMARD occurs in the first days of treatment and then it tends to diminish to disappearance. To avoid nausea, specialists recommend starting with low doses and then gradually increasing them until the usual dosage is achieved. Skin rash has been reported in nearly 5% of the patients and it may present pruritues.Rare side effects include Stevens-Johnson syndrome and reduced fertility due to reversible oligospermia. Severe side effects that can 55

appear from therapy with sulphasalzine, through rare, aplastic anemia and neutropenia which may result in the death of the patient. The latter is estimated to have occurred in approximately 2% of the patients but death and further complications were avoided by removing the drug from the patients therapy.Also according to WHO, there have been approximately 700 of patients in whom this medicine caused blood dyscrasis,Leukopenia has also been reported therapies with sulphasalazine, but in very rare cases. Anti-malarials such as chloroquine and hydropchloroquine have been used to treat rheumatoid arthritis.It has been pointed out, through clinical studies, that chloroquine has a higher toxicity compared to hydroxychloroquine.Although hydroxyxhloroquine appears to be more efficient in treating rheumatoid arthritis than placebo, it is also inferior to sulphasalazine, especially in what may also produce side effects.Mild side effects from hydroxychloroquine include nausea and skin rash. More serous, bone marrow suppression may occur, though rare.Also, aplastic anemia and agranulocytosis can develop as a result of anti-malarial therapy and may potentially cause the death of the patient.A much more worrisome side effect from treatment with antimalarials is the damage that these drugs seem to be causing to the cornea and retina. Recent studies have however shown that if the dosage of hydroxychloroquine given to the patients dose not exceed 6.5 mg/kg, the risks of developing ocular complications are minimal.

Gold compounds are also options in treating this type of disease. Specialists agree that injectable gold is much more effective in the treatment of rheumatoid arthriris than auranofin.Yet,this type of drug has been shown to be more efficient than placebo and even though its level of toxicity is quite low , auranofin seems to be causing more side effects than any other type of DMARD.Auranofinent is therefore not considered efficient in the treatment of rheumatoid arthritis because of its poor resultsand because it is intolerable for most patients.Sodium aurothiomalate (Myocrisin)on the other hand is another type of gold compound that is injected and which appears to be as efficient as sulphasalazine,dpenicillamine and methotrexate.

56

Rheumatoid Arthritis and Its Management Given that there is not enough proof that gold compounds are indeed efficient in preventing the progression of erosions and the high toxicity of these drugs, they are usually not included in the treatment plan for rheumatoid arthritis. A Cochrane systematic review has determined that Abatacept was an effective treatment for rheumatoid arthritis. Against placebo, it was found to increase monbility and make patients twice as likely to achieve a 50% improvement in symptoms. However Cochrane has called for more studies to be conducted, given the lack of evidence to distinguish between the biologics available rheumatoid arthritis. 10.4 BIOLOGICAL AGENTS. Biological agents (biologics ) include: Tumor necrosis factor alpha (TNFa) blockers-etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira),certolzumab pegol (Cimzia),golimumab (simponi) Interleukin 1 (1L-1 ) blockers- anakina (Kineret) Monoclonal antibodies against B cells- rituximab (Rituxan) T cell costimulation blocker abataacept (Orencia) Interleukin 6 (1L-6) blockers tocilizumab (an anti-1L-6 receptor antibody) (RoActemra Actemra).

10.5

DMARDs for Treatment of Rheumatoid Arthritis Time to benefit

DMARD Adalimumab (Humira)

Dosage 40 mg SC every two weeks

Adverse effects

Monitoring Monitor for TB, histoplasmosis, and other infections; CBC and ALT at

Comments Monoclonal antibody to TNF-3; shown to reduce disease activity 57

A few days Infusion reactions; to four increased infection months risk, including TB reactivation Rare: demyelinating

DMARD

Dosage

Time to benefit

Adverse effects disorders

Monitoring baseline and monthly until dose is stable; may continue every two to three months thereafter. CBC at baseline, monthly for three months, then every three months

Comments with acceptable safety.

Anakinra (Kineret)

100 to 150 mg Within 12 SCper day weeks; lasting effects by 24 weeks

Infections and decreased neutrophil counts; headaches, dizziness; nausea Rare: hypersensitivity

Auranofin (Ridaura)

3 mg orally twice per day or 6 mg orally per day 50 to 150 mg orally per day

Four to six Diarrhea Rare: months leukopenia

Azathioprine (Imuran)

Two to three months

CBC and urine protein (by dipstick) every one to three months Nausea Rare: CBC every one leukopenia; sepsis; to two weeks lymphoma until dose is stable, then every one to three months Nausea; paresthesias,

Interleukin-1 receptor antagonist; used when treatment with another DMARD has failed. Has modest effects compared with other DMARDs. Has greater toxicity and is used less commonly than other DMARDs.

Cyclosporine (Gengraf, Neoral, generic)

2.5 to 5 mg per Two to kgorally per four day months

Creatinine every Significant clinical benefit two weeks until

tremor; headaches; dose is stable, up to one year; gingival then monthly; adverse effects hypertrophy; consider CBC, limit use. hypertrichosis Rare: LFTs, and hypertension; renal potassium level disease; sepsis tests

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Rheumatoid Arthritis and Its Management

DMARD

Dosage

Time to benefit

Adverse effects

Monitoring

Comments

D250 to 750 mg Three to Nausea; loss of Penicillamine orally per day six months taste; rash; (Cuprimine) reversible platelet decrease Rare: proteinuria; late autoimmune disease Etanercept (Enbrel) 25 mg SC A few days Contraindicated in twice per week to 12 infection; mild or 50 mg SC weeks injection site per week reactions Rare: demyelination

CBC and urinary Used less protein by commonly than dipstick every other DMARDs. two weeks until dose is stable, then every one to three months CBC and ALT at baseline and monthly until dose is stable; may continue every two to three months thereafter. Combination of TNF receptor and portion of IgG1; inhibits TNF-3; slows joint damage.

Hydroxychloro 200 to 400 mg Two to six Nausea; headaches Eye quine orally per day months Rare: abdominal examinations (Plaquenil) pain; myopathy; every 12 months retinal toxicity in patients older than 40 years and those with previous eye disease

Can be used when diagnosis uncertain; moderate effect but relatively low toxicity.

Gold sodium thiomalate (Myochrysine ) Aurothiogluc ose (Solganal) Infliximab

25 to 50 mg IM Six to every two to eight four weeks weeks

Mouth ulcers; rash; vasomotor symptoms after injection Rare: leukopenia; thrombocytopenia; proteinuria; colitis 3 mg per kg IV A few days Infusion reactions;

CBC and urinary protein by dipstick every two weeks until dose is stable, then with each injection Monitor for TB,

Has significant withdrawal rate in trials because of toxicity. Monoclonal 59

DMARD (Remicade)

Dosage

Time to benefit

Adverse effects increased infection risk, including TB reactivation Rare: demyelinating disorders

Monitoring

Comments

at weeks zero, to four 2, and 6, then months every eight weeks

Leflunomide (Arava)

100 mg orally per day for three days, then 10 to 20 mg orally per day

histoplasmosis, antibody to and other TNF-3; reduces infections; CBC disease activity and ALT at with acceptable baseline and safety. monthly until dose is stable; may continue every two to three months thereafter. Four to 12 Nausea, diarrhea; Hepatitis B and C Inhibits weeks rash; alopecia; serology in high- pyrimidine (tending highly teratogenic, risk patients; synthesis and toward even after CBC, creatinine, may suppress four) discontinuation and LFTs T-cell Rare: leukopenia; monthly for six activation; hepatitis; months, then improves thrombocytopenia every one to two multiple clinical months; repeat outcomes and AST or ALT in delays two to four weeks radiographic if initially changes; can elevated, and be eliminated adjust dose as from system needed. with cholestyramine in patients wishing to conceive. One to two Nausea, diarrhea; months fatigue; mouth ulcers; rash, alopecia; abnormal LFTs Rare: low WBC and platelets; pneumonitis; sepsis; liver disease; EpsteinBarr virusrelated CBC, creatinine, Rapid onset and LFTs (six to 10 monthly for six weeks); tends months, then to produce every one to two more sustained months; repeat results over AST or ALT in time than other two to four weeks DMARDs and if initially lowers allelevated, and cause mortality;

Methotrexate

12 to 25 mg orally, IM, or SC per week

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Rheumatoid Arthritis and Its Management

DMARD

Dosage

Time to benefit

Adverse effects lymphoma; nodulosis

Monitoring adjust dose as needed; liver biopsy if no resolution on discontinuation.

Comments

Minocycline (Minocin)

100 mg orally twice per day

One to three months

Staphylococca l protein A immunoadsor ption (Prosorba column) Sulfasalazine (Azulfidine)

Extracorporeal; Three weekly for 12 months weeks

2 to 3 g orally per day in divided doses

One to three months

can be used when cause of polyarthritis uncertain; often combined with newer DMARDs. Dizziness; skin None needed Effective in pigmentation combination with prednisone for management of new-onset rheumatoid arthritis. Hypotension and Follow CBC Used only in anemia during refractory procedure; catheter patients when site infection, joint many other pain, fatigue treatments have failed. Nausea, diarrhea; CBC every two to Rapid onset headache; mouth four weeks for (eight to 13 ulcers; rash, three months, weeks); enteric, alopecia; contact then every three coated forms lens staining; months available; can reversible be used when oligospermia; diagnosis abnormal LFTs uncertain; Rare: leukopenia modest effects compared with other medications.

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10.6

ANTI-INFLAMMATORY AGENTS AND ANALGESICS. Anti-inflammatory agents include: Glucocorticoids Non-steroidal anti-inflammatory drug (NSAIDs, most also act as analgesics) Analgesics include: Paracetamol (acetaminophen in US and Canada) Opiates Diproqualone Lidocaine topical

Historic treatments for RA have also included: rest, ice, compression and elevation, apple diet, nutmeg, some light exercise every now and then nettles, bee venom, copper bracelets, rhubarb diet, extractions of teeth, fasting, honey, vitamins, insulin, maggents, and electroconvulsive therapy (ECT). Most of these have either had no effect at all, or their effects have been modest and transient, while not being generalizable. NSAIDs used in the treatment of RA include: Aspirin - though not recommended for children due to side effects and the risk of Reye's syndrome. Salicylate medications Buffered aspirin Ibuprofen (Advil, Motrin IB) Ketoprofen (Orudis) Naproxen (Naprosyn) NSAID COX-2 inhibitors Celecoxib (Celebrex) Rofecoxib (Vioxx) Disease-modifying antirheumatic drugs (DMARDs) Gold salts (Myochrysine, Ridaura) - oral or injected Antimalarials Hydroxychloroquine (Plaquenil) Penicillamine (Cuprimine, Depen) Sulfasalazine (Azulfidine) 62

Rheumatoid Arthritis and Its Management Arava (leflunomide) Immunosuppresssive medications Methotrexate (Rheumatrex) Azathioprine (Imuran) Cyclosporine (Sandimmune, Neoral) Lefluomide (Arava) Corticosteroids (glucocorticoids) Prednisone (Deltasone, Orasone) Methylprednisolone (Medrol) Biologic Response Modifiers Etanercept (Enbrel) Kineret (anakinra) - an IL-1 blocker Remicade (infliximab) - in combination with methotrexate. Antibody blood filtering - for severe rheumatoid arthritis. Prosorba Column (apheresis) ibuprofen, naproxam, etodolac nabumetone, sulindac, tolementin, choline magnesim salicylate, diclofenac,difiusinal,indometticin, ketoprofen, oxaprozin, and piroxoicam. Cortisone therapy become a controversial medical solution become even through it can provide great relief; there are some questions as to the usefulness of the procedure over a long period of time. Corticosreroids Corticosteroids usually produce an immediate and dramatic anti-inflammatory affect in RA.They can be used on short term basis for the following indication: Severe exacerbation which are not remitting with NSAIDs and DMARs. Severe extra-articular manifestation e.g. pericarditis,perforating eye lesion. Active and progressive disease that management. When there is contraindication to or therapeutic failure of methotrexate or other DMARs. When other measures fail to control persistently disabling symptoms in breadwinners,young mothers who have to return to work. *Low dose(< 7.5 mg/day) prednisolone is effective to achieve desired clinical effect. *Recent evidence suggests that low dose corticosteroid therapy retard the progression of bone erosion. does not respond favorably to conservative

63

*Intra-articular corticosteroid may be helpful if one or two joints are the chief source of difficulty.Injection Triamcinolone 10-20 mg depending on size of the joint may be given for symptoms relief,but not more than 4-times/year. 10.7 SURGERY. In early phases of the disease, an arthroscopic or open synovectomy may be performed. It consists of the removal of the inflamed synovia and prevents a quick destruction of the affected joins. In older patients, the strum synovectomy may be performed. It is successful in approximately half of patients. The surgery is mostly done on knee, elbow, shoulder, ankle or tarsal joints.Ithas to be performed before the destruction of the cartilage. Severely affected joints may require joint replacement surgery, such as knee replacement. Postoperatively, physiotherapy is always necessary. 108 Non-Pharmacological Treatment: Lifestyle treatments Rest Exercise Adequate nutrition Joint care Joint splinting Avoid alcohol - may interact with some RA medications. Rehabilitation treatments Splinting - of the hands Physiotherapy Occupational therapy Mobility aids Stress relief Relaxation therapy Biofeedback Support groups Weight loss Regular exercise is important for marinating joint mobility and making the joint muscles stronger. A Cochrane Review of studies determined that exercise programs

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Rheumatoid Arthritis and Its Management designed to improve strength and stamina were safe and led to moderate benefits for RA sufferers. 10.9 OTHER THERAPIES Other therapies are weight loss, orthoses, occupational therapy, podiatry, physiotherapy, immunoadsorption therapy, joint injections, and special tools to improve hand movements (e.g. special tin-openers). Ayurvedas, mostly in southern India, is another source of treatment, and while it is popular in India there are no studies to show that it benefits patients with RA.One survey in the United Kingdom between 1998and 2002 found that arthritis, in its various forms, was among the five most common reasons for the medicinal use of cannabis. The Prosorba column blood filtering device (removing 1gG) was approved by the FDA in 1999 for treatment of RA.However it was discontinued at the end of 2006. The effectiveness of treating RA with acupuncture is inconclusive, and more rigorous research seems to be warranted according to one study. One study of 873 patients with RA found that those who drank some alcohol (none drank more than 10 units of alcohol a week) had reduced severity of symptoms compared to those who drank no alcohol. However a spokeswoman for the Arthritis Research UK (who co-funded the study) warned that some RA treatments, like methotexate, could damage the liver when taken with large amounts of alcohol. Experimental chemicals capable to lower secretion of inflammatory cytokines linded to arthritis include Dimethyl sulphoxide and dimethyl sulphone (Kloesch et al,.Life Seiences Volume 89 ,Issues 13-14).However, it is important to safeguard liver against potential toxicity (Brayton,Cornell Vet.,76-61.

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10.9.1 Homeopathic Treatment of Rheumatoid Arthritis: Homoeopathy The word homoeopathy is derived from the Greek homeos meaning like and pathos meaning suffering. Principal of Homoeopathy Homoeo therapy is based on thee principals. Like Cures Like

That is, a substance that produces the symptoms of a disease may also cure it. This is known as law of similar that which makes sick shall heal. Minimum Dose

It is believed that more a substance is diluted, the more potent it becomes. Uniquencess of the Remedy

Which is regarded as specifies to a particular patient at a particular time. Mechanism of Action Stimulate the body immune system and strengnthens it against illness Stimulate the body own vital force(hemostasis),the mechanism that generate self healing and helps to achieve equilibrium Several other mechanisms are under investigation.

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Rheumatoid Arthritis and Its Management

Repertory Is an index to the symptoms of diseases and their remedies, in which thy are arranged in an orderly manner so that they can be found easily Remedy Is something as a medicine that cures or relieves a disease or bodily disorder Types of Remedy Classical Remedy: That is named after the single remedy product it contains Indicated or Combined Remedy: That is usually a combination of three or four remedies that are suitable for treating a particular problem Clinical Uses Chronic Conditions:Arthritis,Allergies,Autoimmune Diseases Non life Threatening Conditions : Viral infections, Minor Trauma Recurrent Conditions:Otitis media Dynamic Conditions:Hydrocele,FibriodUterus,Benign enlargement of prostate

Currently FDA considers these medicines as non prescription products. WHO state that Homoeopathy is the second most used medical system internationally Non physician may practice Homoeopathy within the scope of practice of their specific profession. Homeopathy offers a wider range of options than Conventional medicine. Constitutional Homeopathic treatment with the management of an experienced and professional Homeopath is an excellent choice for Rheumatoid Arthritis. The 67

Constitutional approach of Homeopathy, which considers mind and body together as one, bestows a lot of significance to emotions, and believes that emotional factors are vital in the development of most of the diseases, including Rheumatoid Arthritis. It can even be the cause of Rheumatoid Arthritis. Heredity plays an important role in Rheumatoid Arthritis. However, a study conducted at the Stanford University School of Medicine, suggested that emotions can overcome genetics. The study showed that even those who are genetically predisposed to Rheumatoid Arthritis can avoid the disease by staying emotionally healthy. If you are at risk for Rheumatoid Arthritis, you can avoid getting the disease if you stay in good condition psychologically. In conclusion, for every patient suffering from Rheumatoid Arthritis Classical Homeopathy treatment must be given a serious consideration for long term and lasting relief. Homeopathy is often helpful for relieving pain and stiffness. A constitutional remedy, with the guidance of an experienced homeopath, is often the best approach for dealing with chronic conditions. Following are the Drugs available for Rheumatoid Arthritis. Arnica Chronic arthritis with a feeling of bruising and soreness may be helped by this remedy. The painful parts feel worse from being moved or touched. (Herbal Arnica gels and ointments may also help to soothe arthritic pain when applied externally to areas of inflammation and soreness.) Aurum metallicum Wandering pains in the muscles and joints that are better from motion and warmth, and worse at night, suggest a need for this remedy. Deep pain may be felt in the limbs when the person tries to sleep, or discomfort may wake the person up. People who need this remedy are often serious and focused on work or career, with a tendency to feel depressed. Bryonia This remedy can be helpful for stiffness and inflammation with tearing or throbbing pain, made worse by even the smallest motion. The condition may have developed gradually, and is worse in cold dry weather. Discomfort is aggravated by being touched or bumped, or from any movement. Pressure brings relief (if it stabilizes the area) and improvement also comes from rest. The person may want to stay completely still and not be interfered with.

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Rheumatoid Arthritis and Its Management

Calcarea carbonica This remedy may be useful for deeply aching arthritis involving node formation around the joints. Inflammation and soreness are worse from cold and dampness, and problems may be focused on the knees and hands. Weakness in the muscles, easy fatigue from exertion, and a feeling of chilliness or sluggishness are common. A person who needs Calcarea is often solid and responsible, but tends to become extremely anxious and overwhelmed when ill or overworked. Causticum This remedy may be indicated when deformities develop in the joints, in a person with a tendency toward tendon problems, muscle weakness, and contractures. The hands and fingers may be most affected, although other joints can also be involved. Stiffness and pain are worse from being cold, and relief may come with warmth. A person who needs this remedy often feels best in rainy weather and worse when the days are clear and dry. Calcarea fluorica This remedy is often indicated when arthritic pains improve with heat and motion. Joints become enlarged and hard, and nodes or deformities develop. Arthritis after chronic injury to joints also responds to Calcarea fluorica. Dulcamara If arthritis flares up during cold damp weather, or after the person gets chilled and wet, this remedy may be indicated. People needing Dulcamara are often stout, with a tendency toward back pain, chronic stiffness in the muscles, and allergies. Kali bichromicum When this remedy is indicated, arthritic pains may alternate with asthma or stomach symptoms. Pains may suddenly come and go, or shift around. Discomfort and inflammation are aggravated by heat, and worse when the weather is warm. Kali carbonicum Arthritis with great stiffness and stitching pains, worse in the early morning hours and worse from cold and dampness, may respond to this remedy-especially if joints are becoming thickened or deformed. People who need this remedy often have a rigid moral code, and tend to feel anxiety in the stomach.

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Kalmia latiflora Intense arthritic pain that flares up suddenly may responds to this remedy-especially when problems start in higher joints and extend to lower ones. Pain and inflammation may begin in the elbows, spreading downward to the wrists and hands. Discomfort is worse from motion and often worse at night. Ledum palustre Arthritis that starts in lower joints and extends to higher ones may respond to this remedy. Pain and inflammation often begin in the toes and spread upward to the ankles and knees. The joints may also make cracking sounds. Ledum is strongly indicated when swelling is significant and relieved by cold applications. Pulsatilla If rheumatoid arthritis pain is changeable in quality or the flare-ups move from place to place, this remedy may be useful. The symptoms (and the person) feel worse from warmth, and better from fresh air and cold applications. People who need this remedy usually are emotional and affectionate, sometimes having teary moods. Rhododendron This remedy is strongly indicated if swelling and soreness flare up before a storm, continuing until the weather clears. Cold and dampness aggravate the symptoms. Discomfort is often worse toward early morning, or after staying still too long. The person feels better from warmth and gentle motion, and also after eating. Rhus toxicodendron Rheumatoid arthritis, with pain and stiffness that is worse in the morning and worse on first motion, but better from continued movement, may be helped with this remedy. Hot baths or showers, and warm applications improve the stiffness and relieve the pain. The condition is worse in cold, wet weather. The person may feel extremely restless, unable to find a comfortable position, and need to keep moving constantly. Continued motion also helps to relieve anxiety. Ruta graveolens Arthritis with a feeling of great stiffness and lameness, worse from cold and damp and worse from exertion, may be helped with this remedy. Tendons and capsules of the joints

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Rheumatoid Arthritis and Its Management can be deeply affected or damaged. The arthritis may have developed after overuse, from repeated wear and tear.

Dosage Homeopathy Dosage Directions Select the remedy that most closely matches the symptoms. In conditions where selftreatment is appropriate, unless otherwise directed by a physician, a lower potency (6X, 6C, 12X, 12C, 30X, or 30C) should be used. In addition, instructions for use are usually printed on the label. Many homeopathic physicians suggest that remedies be used as follows: Take one dose and wait for a response. If improvement is seen, continue to wait and let the remedy work. If improvement lags significantly or has clearly stopped, another dose may be taken. The frequency of dosage varies with the condition and the individual. Sometimes a dose may be required several times an hour; other times a dose may be indicated several times a day; and in some situations, one dose per day (or less) can be sufficient.If no response is seen within a reasonable amount of time, select a different remedy.

10.9.2

Acupuncture for Rheumatoid Arthritis

Rheumatoid arthritis and Osteoarthritis, also known as degenerative joint disease, is commonly referred to as the wear and tear disease. Fortunately today, there are many safe and effective alternatives to ease the pain and suffering. Acupuncture doctors decrease pain by increasing the release of endorphins (morphine-like chemicals) that block pain especially during times of stress or pain.

How does it work

Acupuncture is routinely used to relieve pain such as low back, knee, arthritis, sciatica, headaches, tennis elbow, facial and chronic pain where the underlying cause has yet to be discovered. Chinese Medicine considers pain to be a stagnation of energy, blood or body fluids. By inserting very fine needles along the energy pathways called meridians, acupuncture harmonizes and enhances the bodies own natural restorative powers. And, it works well with other alternative healing therapies. People are typically void of exercise which maintains the flow of our bodily fluids and keeps our muscles and joints limber. Acupuncture is very effective for the treatment of arthritic pain and the results are usually felt immediately.

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 A general guide for the treatment of rheumatoid arthritis

When applying acupuncture treatment for example, there are main points and secondary points. Because there are different causes for Rheumatoid Arthritis, the following acupuncture points will vary according to the symptom.

Mainly caused by pathogenic wind: Fengmen (B12), Kanshu (BL 18), Leshu ( BL 17) Mainly caused by pathogenic cold: Dazhui (GV 14), Guanyuan (CV 4) Mainly caused by pathogenic dampness: Pishu (BL 20), Chungwan (CV 12), Yinlingquan (SP 9) Mainly caused by heat transformed by exogenous pathogen: Quchi (LI 11), Hoku (LI 4)

Treatment for Rheumatoid Athritis using acupuncture prevents and cures this condition by stimulating the human body through the role of meridians and acupuncture points. Joints have a complex structure and rely on the surrounding muscles, ligaments, bursa and other structures so that joints are vulnerable to aute and chronic injury due to the invasion of exogenous pathogens. Meridians become blocked by exogenous pathogens resulting in blood stasis which leads to pain. Acupuncture treatment of Rheumatiod arthritis works to expel cold-dampness and promote blood circulation. Once the Qi flow and blood are flowing smoothly, rheumatoid symptoms will disappear accordingly.

Clinical Trials for Rhematoid Arthritis

1. A recent study from China shows that both traditional acupuncture and electroacupuncture a type in which pulsating electrical currents are sent through the needles to stimulate target areas may reduce tenderness. All 36 participants had a standardized treatment, whether they received traditional acupuncture or electroacupuncture. During a total of 20 sessions throughout a 10-week period, needles were placed at a depth of about 10 to 20 millimeters and left in place for 30 minutes. 2. In a German study, 304,674 people with knee osteoarthritis who received 15 sessions of acupuncture combined with their usual medical care had less pain and stiffness, improved function and better quality of life than their counterparts who had routine care alone. The improvements occurred immediately after completing a three-month course of acupuncture and lasted for at least another three months, indicating osteoarthritis is among conditions treated with acupuncture.

CONCLUSION:
Acupuncture is both a viable and popular alternative to effectively help you with your rheumatoid arthritis or osteoarthritis without side effects. 10.9.3 Ayurveda Treatment of Rheumatoid Arthritis. 72

Rheumatoid Arthritis and Its Management

Ayureda is a comprehensive andinterative health science origination in India.Ayureda, commonly translated as the knowledge of life is part of the Vedas an ancient Hindu text written in the Sanskrit language. Ayurvedic medicine has been practiced continuously for more than 5,000 years and is respected world wide as a safe, effective and holistic approach to lifelong health.Ayurveda has particular application to those suffering with the chronic pain and inflammation of arthritis, a condition known as amavata in Ayurvedic medicine. Ama is the toxin that builds up in the body usually as a result of improper digestion. These toxins circulate throughout the body and typically deposit in weaker area such as the joints. This leads to the arthritis symptoms of pain and inflammation. The vata, as identified in Ayurveda medicine, is one of three basic energetic forces that vitalize the body. Aynrveda distinguishes three categories of arthritis, corresponding to the three energetic forces vata, pitta and kapha. Principle of ayurdic healing. The Ayurvedie approach to healing first takes into account the unique circumstances of the individual seeking relied.Ayurvedie treatment depends upon an individual's basic energy and body type and the external environment in which they live.Ayurveda identifies three basic energetic forces, called doshas,or body humors, that underlie all bodily proceses. The relative balance of energy of these doshas is a determining factor in the overall health of an individual and in her susceptibility to illness and degenerative disease. The three doshas of Ayurvedic Medicine are: Vata:- This vital energy regulates blood circulation, breath, heartbeat, and even the blinking of the eyes. Pitta:This vital energy regulates the metabolic systems including body temperature, digestion, and absorption of nutrients. Kapha;- This vital energy is responsible for physical growth, maintaining the immune system, and providing body parts with the necessary moisture. Ayurveda treatment of arthritis.

It is important to engage the services of a qualified Ayurveda practitioner who can provide an accurate assessment of one's individual condition and of the specific dosha imbalance and type of arthritis that may be causing the distress.A qualified Ayurveda practitioner can identify specific treatments appropriate for one's unique needs and characteristics. Ayurveda treatment for arthritis may include a combination of the following:-

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Dietary and lifestyle adjustments Specific Yoga asanas, or exereises, including the Sun Salute Breathing techniques to alleviate stress and anxiety Oil massage and heat therapy Short periods of fasting to help eliminate toxiety Panchkarma, a specific detoxifying regime in Ayurveda Detoxifying and nutritive herbs or herbal combinations Enemas and colonies Ingesting fresh juices, such as carrot, beet, cucumber, grapes, apples, oranges and papaya, and castor oil.

Successful treatment of arthritis with Ayurveda may require that one reduce or eliminate use of certain aggravating dietary substances such as nicotine, caffeine, white sugar, and alcohol. In addition, one may be required to minimize dietary intake of certain gas producing foods such as potatoes, broccoli and cabbage, and maintain an environment sheltered from cold winds and damp conditions. Ayurveda approach for the treatment of Rheumatoid Arthritis. Some of the more frequently used berbs and herbal combinations for Ayurvedic treatment of arthritis include many plants native to India. Most are available for purchase through your local Ayurvedic practitioner or health food supplier. Western scientific research has confirmed the effectiveness of many herbs used in Ayurvedic medicine in the of ostco-and rheumatoid arthritis. Asafetida (Ferula Assafoetida)- Known in Ayurveda medicine as Hing,this herb can be combined with coconut oil or ginger paste to provide relief from inflammation. Garlic (Allium Sativium)-Known in Ayurveda medicine as Lehsun,this herb helps to strengthen the immune system and cleanse toxins,or ama, from the system. Ginger root (Zingiber officinale)-Known as Sunthi in Ayurveda, this herb relives pain and inflammation of arthritis. Guggul (Commiphora mukul)-a resin from the guggul tree, native to India.This substance helps eleeanse and rejuvenate the body,especially the blood vessels and the joints.

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Rheumatoid Arthritis and Its Management Licorite (Glycyrrhiza Glabra)- Known in Ayurveda medicine as Yashimadhu, acts effectively as an anti-inflammatory to reduce arthritis pain in the joints. Turmeric (Circuma Longa ) Known in Ayurveda medicine as Haldi, this pungent herbis an anti-inflammatory agent and alleviates pain,particularly in osteoarthritis,response modififying agents such as anti-TNF antibody therapy, may present with serious infections and /or malignancies. Additionally, adverse events from RA medications may include liver toxicity, renal toxicity, bone narrow depression, lung inflammation, and skin manifestations. Patients taking anti-TNF agents must avoid live-virus vaccines. Reflexology.

10.9.4

Reflexology, or zone therapy, is an alternative medicine involving the physical act of applying pressure to the feet, hands, or ears with specific thumb, finger, and hand techniques without the use of oil or lotion. It is based on what reflxologists claim to be a system of Zones and reflex areas that say an image of the body on the feet and hands, with premise that such work effects a physical change to the body. A 2009 systematic review of randomized condomised controlled trials concludes that The best evidence available to date dose not demonstrate convincingly that reflexology is an effective treatment for any medical condition. There is no consensusnreflexologists on how reflexology is supposed to work: a unifying theme is the idea that areas on the food correspond to areas of the body, and that by manipulation these one can improve health trough ones.Reflexologists divide the body into ten equal vertical zones, five on the right and five on the left. Concerns have been raised by medical professional that treating potentially serious illnesses with reflexology, which has no proven efficacy, could delay the seeking of appropriates medical treatmenent Mechanism The Reflexology Association of Canada defines reflexology as; A natural healing art based on the principle that there are reflexes in the feet, hands and ears and their referral areas within zone related areas. Which correspond to every past, gland and organ of the body. Through application of pressure on these reflexes without the use of tools, crimes or lotions, improves circulation and helps promote the natural function of the related areas of the body. Reflexologies posit that the blockage of an energy filed, invisible life force, or Oi can prevent healing. Another tenet of reflexology is the belief that practitioners can relieve stress and pain in other parts of the body through the manipulation of the feet. One claimed explanation is that the pressure received in the feet that balance the nervous system or release chemicals such endorphins that reduce stress and pain. These hypotheses are 75

rejected by general medical community who cite a lack of scientific evidence and the well tested germ theory of diseas. Common criticisms of reflexology are the lack of evidence for its claimed effects, or of a scientific or demonstrated basis for its theories, of central regulation, acereditation and licensing or of medical training provided to reflexologists, and the short duration of training programmes.As with other pseudosciences without any proven effect beyond placebo, if patients rely on them and delay or even reject effective medical treatment there can be significant health risks. Reflexologys claim to manipulate energy (Qi) has been high controversial, as there is no scientific for the existence of life energy (Qi) energy balance.

Use by population. An example of a reflexology chart of the Hand, demonstrating the areas of hand that practitioners believe correspond with organs in the zones of the body. Reflexology is one of the most used alternative therapies in Denmarks national survey from 2005 showed that 21.4 % of the Danish population had used reflexology, at some point in the life and 6.1% had used reflexology within the previous year. A study from Norway showed that 5.6 % the Norwegian population in 2007had used reflexology with the last 12 months. Regulation In the United Kingdom,refexology is coordinated on a voluntary basis by the Complementary and Natural Healthcare Council (CNHC) Registrants are required to meet Standards of Proficiency outland by profession Specific Bosrds,as CNHC is voluntary any one practicing can describe themselves as reflexologies. When the CNHC began admitting efflexologists, a sceptic search for and found 14 of them claiming efficacy on illnesses. Once pointed out. The CNHC had the claims retracted as it conflicted with their Adverting stadtising Standards Authority. History Reflexology was introduced to the United States in 1913 by William II .Fitzgerald.M.D (1872-1942), ear nose, and throat specialist, and Dr.Edwin Bowers.Fitzerald claimed that applying pressure had an anesthetic effect on other areas of the body. Reflexology was modified in the 1930s and 1940s by Eunice D.Ingham (18891974), nurse and physiotherapist. Ingham claimed that the feed and hands especially sensitive, and mapped the entire body into reflexes on the feed renaming zone therapy to refexology.Inghams theories are in the United States and United Kingdom, Although modern methods also exist. Reflexology has had several clinical trials dedicated to it over the years with mixed results. One systematic review found, The best evidence available to date not demonstrates convincing that reflexology is effective treatment for any medical

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Rheumatoid Arthritis and Its Management 10.9.5 Yoga Treatment of Rheumatoid Arthritis. Continuing research shows the therapeutic benefits that yoga has on rheumatoid arthritis. As long as you take gentle approach, yoga can provide relief for body and soul. By Dennis Thompson Jan Medically reviewed by pat F bass iii MD, MPH. The practices of yoga might seem daunting to a person with rheumatoid arthritis (RA). The thought of bending stretching into and then holding pretzel-like poses while your joints are inflamed may sound impossible. However research has shown that gentle yoga can be of great benefit as rheumatoid arthritis treatment. Yoga movements can help the body by increasing strength and flexibility while meditative parts of the practice help mind allowing you to sleep better and feel more energetic and happy RA patients also report reduced pain as a result of regular yoga practice. Some patients may have trouble doing all the things in yoga, but anything that keeps range of motoring in the joints will keep the joints flexible says Scott Zashin MD clinical assistant professor of internal medicine in the rhemutolog division at University of taxes Southwestern medical School at Dallas and a rhematiogist at Presbyterian Hospitals of dalais and Plano. Yoga Benefits for RA symptoms. Scientific in major medical journals have found that yoga can help arthritis patients by; Building muscle strength Increasing flexibility Promoting better balance Reducing body aches and pains Creating a better sense of well-being Reducing feelings of anxiety and depression

These findings continue to be supported by new research. According to a study presented at a recent annual meeting of the American College Rheumatology, 30 sedentary adults with rheumatoid arthritis reported reduced joint pain and swelling after participating in an eight, week yoga program modified to accommodate their reduced flexibility and other symptoms. The results of a study appearing in the Indian journal of Rheumatology found that the 26 RA patients who followed an eight week yoga program experienced considerable improvement in their arthritis symptoms and some were able to stop taking arthritis medications they had been presented. 77

In another study published in Alternative therapies, the benefits for a group of 16 women with rheumatoid arthritis who participated in three yoga classes a week over 10 week arthritis. According to research in the journal Psychosomatic Medicine, a study of 50 healthy women found that those who were expert yoga practitioners had a reduced inflammatory response to stressful conditions compared with yoga novices.

The Safe Approach to Yoga. People interested in pursuing yoga as a rheumatoid arthritis treatment should follow some basic guideline basic guidelines to make sure that practice will provide relief without any exercise injury. Get the go -ahead. Before starting yoga, ask your doctor about any specific limitations or restrictions you should observe given your specific arthritic condition. Choose an appropriate class. Find a gentle or beginners yoga class that will accommodate any limitations in your range of motion flexibility. Many gyms and yoga studios offer classes specially designed for people with arthritis. Make sure your teacher is certified. React to any pain. physically, if theres a type of movement or stretch that causes pain or if you hart more, the day after you do yoga, then its either not the right activity for you or you need to modify it Zashin says.

Be mindful of your neck. If someone with rheumatoid arthritis has neck involvement, [Yoga] might not be the best therapy, Zashin says. With yoga, you can sometimes put the neck into strange positions. You want to avoid positions that would aggravate neck issues. Practicing yoga that suits your bodys abilities may bring welcome relief; a gentle of this ancient therapy can not only help with your rheumatoid arthritis pains, but should relax you and enable you to better enjoy daily activities.

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CHAPTER 11
11.1 Prognosis:

Rheumatoid arthritis prognosis is compromised if there is a delay in the diagnosis and proper treatment. The prognosis is either exacerbation or remission. It varies highly from person to person. However, it is generally observed that nearly 40% patients with rheumatoid arthritis are disabled after 10 years. Some patients show a comparatively self-limited disease, while others show a chronic progressive disease. An unfavourable prognosis is correlated with signs like high serum titer of autoantibodies, such as, RF and anti-cyclic citrullinated peptide (CCP), an increased number of affected joints, extra-articular manifestations, female sex, age younger than 30 and systemic symptoms. This unfavourable prognosis is in terms of joint damage and disability. One more unfavourable sign is insidious onset. Much worsened prognosis of rheumatoid arthritis is seen in patients with positive RF (Rheumatoid Factor) results. However, the absence of RF does not always indicate a good prognosis. Other laboratory test findings indicating a poor prognosis are early radiological evidence of bone injury, high levels of C1q component of complement, persistent anemia of chronic disease and the presence of anti-CCP antibodies. If the disease remains persistent for more than 1 year, it is likely to cause joint deformities and disability. Whereas if the symptoms last for a few weeks or months, followed by remission, better prognosis is indicated. General mortality rate in RA patients is 2.5 times more than that in common population. Much of this increased mortality results from infection, poor nutrition and vasculitis. RA is also related to cardiovascular risk factors.

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Rheumatoid arthritis prognosis, along with other factors, is based more importantly on how prominent the disease is currently, i.e. if it is in a flare, a remission or can it be managed well with treatment. Nearly 10 to 20% of the patients show sudden onset of the disease, which is followed by a long period of no symptoms. This is called a prolonged remission. Some patients of RA show coming and going symptoms, occurring between flares, which can last for months and are referred to as intermittent symptoms of rheumatoid arthritis. Majority of the patients have chronic, progressive type of RA and need long-term medical treatment. Factors that affect the prognosis so as to make the patients more vulnerable to a progressive and bad form of rheumatoid arthritis are intense flares lasting for a long time, disease diagnosed at young age and being active for years and presence of rheumatoid nodules. It is better to assess and reassess all the influencing factors and get the tests, like xrays and other laboratory tests, done and see if physical results have improved. If it is evident from the tests that the disease is very active, the doctor may need to change the course of treatment for a more aggressive one so as to slow down or stop the disease progression. Biologic, combined with traditional, DMARDs have been proven to be very effective in the management of rheumatoid arthritis. Rheumatoid arthritis prognosis regarding the daily activities can be monitored by taking HAQ, i.e. Health Assessment Questionnaire, periodically, which helps you to determine whether your functions are improving or deteriorating and if they are deteriorating, your doctor needs to change to better About 15% of all RA patients will have symptoms for a short period of time and will ultimately get better, leaving them with no long-term problems. A number of factors are considered to suggest the likelihood of a worse prognosis. These include: race and gender (female and Caucasian). more than 20 joints involved. extremely high erythrocyte sedimentation rate. extremely high levels of rheumatoid factor. consistent, lasting inflammation. evidence of erosion of bone, joint, or cartilage on x rays. poverty. older age at diagnosis. rheumatoid nodules. other coexisting diseases. certain genetic characteristics, diagnosable through testing. Patients with RA have a shorter life span, averaging a decrease of three to seven years of life. Patients sometimes die when very severe disease, infection, and gastrointestinal

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Rheumatoid Arthritis and Its Management bleeding occur. Complications due to the side effects of some of the more potent drugs used to treat RA are also factors in these deaths.

11.1.2

PROGNOSTIC FACTORS: Poor prognostic factors include persistent synovitis, early erosive disease,extra-articular findings(including subcutaneous rheumatoid nodules),positive serum RF findings, positive serum anti-CCP auto antibodies, carrier ship of HLA-DR4 Shared Epitope alleles, family history of RA, poor functional status, socioeconomic factors, elevated acute phase response (erythrocyte sedimentation rate [ESR], Creactive protein [CRPL], and increased clinical severity. High titers of rheumatoid factor Insidious onset of disease More than a year of active disease without remission Early development of nodules or erosion Extra-articular manifestation Severe functional impairment MORTALITY. Estimates of the life shortening effect of RA vary; most sources cite a lifespan reduction of 5 to 10 years. According to the UKs National Rheumatoid Arthritis Society, Young age onset, long disease duration, the concurrent presence of other health problems (called co-morbidity), and characteristics of severe RA ---such as poor functional ability or overall health status, a lot of joint damage on x-rays, the need for hospitalization or involvement of organs other than the joints ---have been shown to associate with higher mortality. Positive response to treatment may indicate a better prognosis. A 2005 study by the Mayo clinic noted that RA suffers suffer a doubled risk of 81

11.1.3

heart disease, independent of other risk factors such as diabetes, alcohol abuse, and elevated cholesterol, blood pressure and body mass index. The mechanism by which RA causes this increased risk remains unknown; the presence of chronic inflammation has been proposed as a contributing factor.

CAHPTER -12
12. EPIDEMIOLOGY. The incidence of RA is in the region of 3 cases per 10,000 populations per annum. Onset is uncommon under the age of 15 and from then on the incidence rises with age until the age of 80. The prevalence rate is 1 %, with women affected three to five times as often as men. It is up to three times more common in smokers than nonsmokers, particularly in men, heavy smokers, and those who are rheumatoid factor positive. A study in 2010 found that those who drank modest amounts of alcohol regularly were four times less likely to get rheumatoid arthritis than those who never drank. Some Native American groups have higher prevalence rates (5-6%) and people from the Caribbean region have lower prevalence rates. First degree relatives prevalence rate is 2-3% and disease genetic concordance in monozygotic is approximately 15-20%.It is strongly associated with the inherited tissue type Major histocompatibility complex (MHC) antigen HLA-DR4 (most specifically DR0401 and 0404)- hence family history is an important risk factor. The risk of first developing the disease (the disease incidence) appears to be greatest for women between 40 and 50 years of age, and for men somewhat later. A is a chronic disease, and although rarely, a spontaneous remission may occur, the natural course is almost invariably one of persistent symptoms, waning intensity, and a progressive deterioration of is joint structures leading to deformations and disability.

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CHAPTER - 13
13. HISTO.RY The first known traces of arthritis date back at least as far as 4500BC.A text dated 123 AD first describes symptoms very similar to rheumatoid arthritis. It was noted in skeletal remains of Native Americans found in Tennessee. In the Old World the disease is ravishingly rare before the 1600s, and on this basis investigators believe it spread across the Atlantic during the Age of Exploration. In 1859 the disease acquired its current name. An anomaly has been noticed from investigation of Pre-Columbian bones. The bones from the Tennessee site show no signs of tuberculosis even though it was prevalent at the time throughout the Americas. Jim Mobley, at Pfizer, has discovered a historical pattern of epidemics of tuberculosis followed by a surge in the number of rheumatoid arthritis cases a few generations later.Mobley attributes the spikes in arthritis to selective pressure caused by tuberculosiss hyper vigilant immune system is protective against tuberculosis at the cost of an increased risk of autoimmune disease. The art of peter Paul Rubens may possibly depict the rheumatoid arthritis. In his later paintings, his rendered hands show, in the opinion of some physicians, increasing deformity consistent with the symptoms of disease. Rheumatoid arthritis appears to some to have been depicted in 16 th century paintings. However, it is generally recognized in art historical circles that the painting of hands in the sixteenth and seventeenth century followed certain stylisedconventions, most clearly seen in the Mannerist. It was conventional, for instance to show the up help right hand of Christ in

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what now appears adeformed posture.These conventions are easily misinterpreted as portrayals of disease. They are much too widespread for this to be plausible. The fist recognized description of rheumatoid arthritis was in 1800 by French physician Dr Augustin Jacob Landre-Beauvais (1772-1440) who was based in the famed Salpetriere Hospital in Paris.The name rheumatoid arthritisitself was coined in 1859 by British rheumatologist Dr.Alfred Baring Garrod.

CHAPTER 14 PHOTOGRAPHS

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Fig- 1 HUMAN SKELETON ANTERIOR VIEW

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Fig 2 HUMAN SKELETON POSTERIOR VIEW

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Fig 3 CROSS SECTION VIEW OF BONE

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Fig 4 PANNUS FORMATION

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Fig 5 BOUTONNIERE DEFORMITY.

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Fig -6

RHEUMATOID CHANGES IN THE HAND

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Fig 7 SUBLUXATION IN THE METACARPOPHALANGEAL JOINTS, WITH ULNAR DEVIATION, IN A PATIENT WITH RHEUMATOID ARTHRITIS OF THE HANDS.

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Fig - 9 Fig-8 CORONAL, T1-WEIGHTED MAGNETIC RESONANCE IMAGING SCAN SHOWS CHARACTERISTIC PANNUS AND EROSIVE CHANGES IN THE WRIST IN A PATIENT WITH ACTIVE RHEUMATOID ARTHRITIS.

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Fig -9 LATERAL VIEW OF THE CERVICAL SPINE IN A PATIENT WITH RHEUMATOID ARTHRITIS SHOWS EROSION OF THE ODONTOID PROCESS

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Fig -10 A COMMON FEATURE IN RA IN THE FEET IS PROMINENCE Of THE METATARSAL HEADS DUE TO METATARSOPHALANGEAL SUBLUXATION

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Fig 11 RHEUMATOID ARTHRITIS HANDS DEFORMITIES

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Fig-12

IMAGE OF HAND SHOWING LATE STAGE OF RA, WITH BOUTONNIERE DEFORMITY, ULNAR DEVIATION OF METACARPOPHALANGEAL JOINTS AND SWANNECK DEFORMITY OF FINGERS.

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Fig -13 PSORIATIC ARTHRITIS OF FOURTH TOE

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Fig -14 RHEUMATOID ARTHRITIS HAND DEFORMITY

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Fig-15

Photos show examples of RA with inflammation in the joints and surrounding tissue.

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Fig -16 Bilateral ulnar deviation of hands

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Fig-17

RHEUMATOID VASCULITIS

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Fig -18

KNEE NODULE IN RA

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Fig -19 CORONAL, T1-WEIGHTED MAGNETIC RESONANCE IMAGING SCAN SHOWS CHARACTERISTIC PANNUS AND EROSIVE CHANGES IN THE WRIST IN A PATIENT WITH ACTIVE RHEUMATOID ARTHRITIS.

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Fig - 20 SOFT-TISSUE SWELLING AND EARLY EROSIONS IN THE PROXIMAL INTERPHALANGEAL JOINTS IN A PATIENT WITH RHEUMATOID ARTHRITIS OF THE HANDS.

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Fig -21 SAGITTAL FAT-SATURATED T2-WEIGHTED MAGNETIC RESONANCE IMAGE (MRI) SCAN OF THE RING FINGER SHOWS FLUID WITH HIGH SIGNAL INTENSITY AROUND THE FLEXOR TENDONS RESULTING FROM TENOSYNOVITIS IN A PATIENT WITH RHEUMATOID ARTHRITIS OF THE HANDS

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. Fig 22 SAGITTAL T1-WEIGHTED MRI SHOWS EROSIVE CHANGES IN THE LUNATE, CAPITATE, AND METACARPAL BASES IN A PATIENT WITH RHEUMATOID ARTHRITIS OF THE HANDS.

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Fig-23

POWER DOPPLER IMAGE SHOWS HYPEREMIC BLOOD FLOW IN THE FLEXOR TENDON SHEATH IN A EUMATOID ARTHRITIS OF THE HANDS.

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Fig -24 RHEUMATOID NODULES AT THE ELBOW.

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Fig -25 A 78-YEAR-OLD MAN HAD RHEUMATOID ARTHRITIS DIAGNOSED 4 YEARS AGO. RHEUMATOID NODULES WERE EVIDENT ON BOTH ELBOWS. THERE WAS SWELLING OF THE METACARPALPHALANGEAL AND PROXIMAL-INTERPHALANGEAL JOINTS OF BOTH HANDS AS WELL AS WASTING OF THE SMALL MUSCLES AND CONTRACTURE OF THE PALMAR APONEUROSIS .

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Fig -26

SUBLUXATION IN THE METACARPOPHALANGEAL JOINTS, WITH ULNAR DEVIATION, IN A PATIENT WITH RHEUMATOID ARTHRITIS OF THE HANDS.

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Fig-27

NEEDLES BEING INSERTED INTO A PATIENT'S SKIN

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Fig-28

LATERAL VIEW OF THE CERVICAL SPINE IN A PATIENT WITH RHEUMATOID ARTHRITIS SHOWS EROSION OF THE ODONTOID PROCESS

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Fig 29 RHEUMATOID CHANGES IN THE HAND..

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39. 40.

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