Definition RA is a non-suppurative, systemic inflammatory disease of unknown cause characterized by a symmetrical poly-arthritis affecting peripheral joints & extra articular structures. It is a chronic inflammatory disease affecting the synovium & leading to joint damage & absorption of adjacent bone. The course of disease is variable but tend to be chronic & characterized by exacerbations & remissions.
INTRODUCTION Chronic systemic inflammatory disease of unknown etiology Affects the synovial membranes of multiple joints Prevalence 1-2% of the population 0.7% in rural area Indians Female : Male ratio 3:1 Usual age of onset 20-40 years though individuals of any age group may be affected
Hypothesized causes1. Initiating factor therapy: An initiating factors causes joint inflammation It does not switch off after acute episode2. Infectious theory: Infection from diphtheroids & mycoplasms or from the viruses – rubella, harpes zoster3. Genetic predisposition: Relative of people with RA are more prone to develop the disease than rest of population.
Genetics of RA Genetic factors gives prevalence of 2%–12% in first-degree relatives of RA sufferers – i.e. approx ten times that of other population. The human leukocyte antigen (HLA) component accounts for around 30% of the genetic risk.
1987 AMERICAN COLLEGE OFRHEUMATOLOGY CRITERIA FOR RA Patients must have 4 of the 7 criteria: 1. Morning stiffness lasting at least 1 hour* 2. Swelling in three or more joints* 3. Swelling in hand joints* 4. Symmetric joint swelling* 5. Erosions or decalcification on x-ray of hand 6. Rheumatoid nodules 7. Abnormal serum rheumatoid factor. [*Must be present at least six weeks]
American Rheumatology AssociationRemission Criteria for RA (Eberhardt a Fex 1998) 4 or more of the following criteria must be fulfilled for at least 2 consecutive months: 1. Duration of morning stiffness not exceeding 15 min 2. No fatigue 3. No joint pain (by history) 4. No joint tenderness or pain on motion 5. No soft tissue swelling in joints or tendonsheaths 6. ESR<30mm after 1 hour for a female or <20mm after 1 hour for a male
Pathology RA is generalized disorder of connective tissue affecting – Articular structure & Extra articular structures
Progressive changes in joints Stage I: Inflammation of the synovial membrane spreads to articular cartilage & other soft tissues. Limitation of joint movt with pain & muscle spasm
Stage II: Granulation tissue formation within synovial membrane & spread to periarticular tissue. Cartilage disintegration & joint filled with granulation Thickening of joint capsule, tendon (with sheaths) & impaired joint movt permanently.
Stage III: Granulation tissue converted into fibrous tissue with adhesion formation between tendon, joint capsule & articular surface. Articular surface cover partly by cartilage & partly by fibrous tissue.
Stage IV: Permanent joint damage and deformity disability
Extra articular changes Nodule formation: In the pressure area & may be subcutaneous or intracutaneous. They may present in organs such as lung & heart. Vascular changes: It constitute inflammation of all size arteries. The lumen of small vessels can become obliteration.
Clinical feature Articular features Pain Loss of function Tenderness Stiffness Swelling Deformity Warmth over the joint Muscle wasting Erythema Decreased ROM
Common Extra Articular Feature of RA Nodules, Anaemia, Lymphadenopathy,Systemic Amyloidosis, Vasculitis, Felty’s SyndromeOcular Keratoconjunctivitis, Scleritis & EpiscleritisBone Osteoporosis Peripheral nerve entrapment, PeripheralNeurology neuropathy, Cervical spine instability, Cervical cord compression, nerve root compression Pleuritis, Pleural effusion, Pulmonary alveolitisPulmonary and fibrosis Pericarditis & myocarditis, Pericardial effusion,Cardiovascular Conduction defect, Atherosclerosis
CLINICAL FEATURE Swelling is confined to the area of the joint capsule Synovial thickening feels like a firm sponge Prominent ulnar deviation in the right hand MCP and PIP swelling in both hands Synovitis of wrist
Referral for Specialist Treatment Refer for specialist opinion with any person suspected persistent synovitis of undetermined cause. Refer urgently if any of the following apply: 1. The small joints of the hands or feet are affected 2. More than one joint is affected 3. There has been a delay of 3 months or longer between onset of symptoms and seeking medical advice.
Do not avoid referring urgently any person with suspected persistent synovitis of undetermined cause whose blood tests show a normal acute- phase response or negative Rh factor.
Investigation There is no single diagnostic test for RA Investigations are used to support the clinical diagnosis and negative results do not exclude the diagnosis of RA No of test are available with rheumatologist to rule out the different remarks of the disease Acute phase reactants, Autoantibodies, Synovial fluid examination, radiography, newer markers of inflammation etc
Acute phase reactant These are the proteins produce by hepatocytes Synthesis is effected by the proinflammatory cytokines IL-6, IL-1 &TNF-alfa The concentration of these protein may- Increase (+ve APRs) Decrease (-ve APRs)
Positive acute phase reactant Ceruloplasmin Mild elevation Complement C3 Complement C4 Alfa1-acid glycoprotein Alfa1-proteinase inhibitor Moderate elevation Haptoglobin Fibrinogen (causing elevate ESR) C reactive protein Marked elevation Serum amyloid A proteinNegetive acute phase reactants Albumin Transferrin
Erythrocyte sedimentation rate (ESR) ESR has been using as a reliable indicator of inflammation & still clinically useful Rises >24 hours after inflammation onset and symptoms Gradually returns to normal 4 weeks after resolution It is a measure of rouleaux formation which is dependent on the concentration of – Fibrinogen, Immunoglobulin & Some other plasma protein Normal ESR is – 0–20mm in females, 0–15 in male
In rheumatology - Elevated ESR increases the probability of inflammatory arthritis, whereas a normal ESR increases the probability of non-inflammatory condition like mech. pain Moderately elevated ESR can help to asses the disease activities in RA
C-reactive protein It raises 24 hr after the onset of inflammation. Short half life of 5-7 hours Rapidly declines after condition resolves Can raises up to 1,000 fold It is a sensitive & early indicator of inflammation The normal concentration is less then 0.6 mg/dl In rheumatic conditions The level range between 1-10 mg/dl except in systemic vascuities (500 mg/dl)
Rheumatoid Factor Rheumatoid factor (RF) is a term used to describe a group of autoantibodies The RF test is considered the basic screen and hallmark for the autoimmune disorder RA The three subclasses of RF include IgM, IgA and IgG autoantibodies. Most tests for RF measure each of these subtypes
The simultaneous presence of all 3 types is usually only seen in RA In patients with RA, IgM RF predominates & the other subtypes are usually present in lower amounts It is found in the sera of 80% of pts with RA Extra-articular features of RA are common in pts with high concentrations of rheumatoid factor But it is a poor guide to the severity of joint disease & to the success or otherwise of Rx
Antinuclear antibody (ANA) The test is to exclude the systemic lupus erythromatus when the test is negative Presence of ANA increases the likelihood of an autoimmune disease It checks blood levels of antibodies that are often present in connective tissue diseases or other autoimmune disorders, such as lupus There are also tests for individual types of ANA’s that may be more specific to people with certain autoimmune disorders ANA’s are also sometimes found in healthy people Therefore, having ANA’s in the blood does not necessarily mean that a person has a disease
Urea & electrolytes (U&E) Mild elevation of alkaline phosphatase and gamma-GT in rheumatic conditions
Uric acid/ Synovial fluid analysis It is a simple test & provides valuable information specially in mono arthritis patient Joint aspiration is done to obtain a sample of synovial fluid The test provides important diagnostic information whether Crystals (found in pts with gout or other types of crystal- induced arthritis) Bacteria or viruses (found in pts with infectious arthritis) are present in the joint.
Classification of Synovial fluid finding Non inflammatory Inflammatory Normal Septic (OA) (RA)Colour Colourless Straw to yellow Yellow VariableClarity Transparent transparent Translution OpaqueViscosity High High Low VariableMucin clot Firm Firm Friable FriableCell count/ul <200 200 - 2,000 2,000 - 75,000 > 10,000Polymorphs < 25% < 25 % > 50 % > 75 %Culture Sterile Sterile Sterile Positive
Urinalysis In this test, a urine sample is studied for protein, RBC, WBC or casts These abnormalities indicate kidney disease, which may be seen in several rheumatic diseases such as lupus or vasculitis Some medications used in the Rx of arthritis can also cause abnormal findings on urinalysis
Complete blood count (CBC) CBC determines the number of WBC, RBC & platelets present in a sample of blood Some rheumatic conditions or drugs used to treat arthritis are associated with a low WBC (leukopenia), low RBC (anemia), or low platelet count (thrombocytopenia) When doctors prescribe medications that affect the CBC, they periodically test the patient’s blood
White blood cell count (WBC) This test determines the number of WBC present in a sample of blood The number may increase as a result of infection or decrease in response to certain medications, or with certain diseases, such as lupus Low numbers of WBC increase a person’s risk of infections
Hematocrit (PCV, packed cell volume) This test and the test for hemoglobin measure the number of RBC present in a sample of blood A decrease in the number of RBC (anemia) is common in people with inflammatory arthritis and rheumatic diseases.
Liver function Tests for liver function may give abnormal results in patients with RA Serum concentrations of transaminases & alkaline phosphatase may be moderately elevated when the disease is active
Thyroid function (TSH, T3, T4) It was found that the mean T4 levels in the RA patients were significantly higher T3 levels were more than 2 SD above controls T4 levels were higher in 27 patients TSH levels were more than 2SD above Thyroid hormonal defects are related with the disease duration & not with the disease activity
Bone marrow examination There is mounting evidence that osteoclasts are involved in the pathogenesis of a component of the focal bone erosions in RA
Muscle enzyme (CPK) Patients with RA usually have low Creatine Kinase (CK) values Even mild rise in CK levels may suggest presence of polymyositis, which may be confirmed on muscle biopsy High incidence of vasculitis in biopsied muscle suggests that it may be the primary event in the pathogenesis of myositis in RA
Labs (ARA recommended, butdo not exclude diagnosis) Initial Labs Complete Blood Count with differential Rheumatoid Factor (Initially positive in 70%) Sedimentation Rate (ESR) or C-Reactive Protein (C-RP) Additional labs in preparation for rheumatic agents Liver Function Tests Renal Function tests Markers of disease course C-Reactive Protein (C-RP) Erythrocyte Sedimentation Rate Wrist X-Ray or Ankle X-Ray Anticyclic citrullinated peptide antibody
Laboratory findings in RA Anaemia: normochromic or hypochromic, normocytic (if microcytic consider iron deficiency) Thrombocytosis Raised erythrocyte sedimentation rate Raised C reactive protein concentration Raised ferritin concentration as acute phase protein Low serum iron concentration Low total iron binding capacity Raised serum globulin concentrations Raised serum alkaline phosphatase activity Presence of rheumatoid factor
Other causes of positive test forrheumatoid factor Other connective tissue diseases Viral infections Leprosy Leishmaniasis Subacute bacterial endocarditis Tuberculosis Liver diseases Sarcoidosis Mixed essential cryoglobulinaemia
Differential diagnosis of RA Psoriatic arthritis--always seronegative Primary nodal osteoarthritis Other connective tissue diseases – SLE Calcium pyrophosphate deposition disease Polyarticular gout Fibromyalgia Medical conditions presenting with arthropathy – thyroid disease
Principles of Treatment Early initiation of treatment Multidisciplinary team approach Patient education Assessment of response to treatment Hospital admission Complication (cost) of untreated disease
Early initiation of Treatment Goals of early treatment Symptom control Reduction of joint damage & disability Maintenance or improvement of quality of life
Multidisciplinary team approach GP Rheumatologist Physical therapist Occupational therapist Nurse specialist Dietitian Podiatrist Pharmacist Social worker
Patient education Should be adopted by all members of multidisciplinary team in both 1ry & 2ndry care. Should be provided with an information on booklet & if possible one to one education.
Assessment of response to Rx Quantification of disease activity & outcome is important in assessing, comparing & standardizing treatment of RA.
Clinical measures of response to Rx includes – Patient opinion Physician opinion Extend of synovitis (no of swollen or tender or both) Duration/ severity of stiffness after inactivity Functional ability Laboratory measures of response to Rx includes – Acute phase response (ESR, CRP) Anaemia Radiological progression
Hospital admission Multiple joint involved acute phase patient may required hospitalization. Selective patient may benefit from more intensive hospital based Rx from multidisciplinary team. It is essential to maintained specialist IP facilities for selected RA patients.
Complication/ Cost of untreateddisease Personal costs – Lost work opportunities Decreased leisure activities Stress on relationships Costs to society – Loss of working skills of RA individuals Loss of contributions to the home The burden of economic cost for care
Management Pharmacological management Analgesics – Simple analgesics should be used in place of NSAIDs Paracetamol, Codeine Or Compound Analgesics DMARDs should be introduced to suppress disease activity. Cyclo-oxygenase-2 (COX-2) Inhibitors.
Diet and complementary therapies Inform people with RA that there is no strong evidence that their arthritis will benefit with diet. However, they could be encouraged for the principles of a Mediterranean diet Mediterranean Diet: More Bread, Fruit, Vegetables & Fish Less Meat & Replace Butter & Cheese With Products Based On Vegetable And Plant Oils. Fasting has shown to be benefit in some patient.
Diet and complementary therapies Complementary therapies that although some may provide short-term symptomatic benefit, there is little or no evidence for their long-term efficacy. If a person with RA decides to try complementary therapies, advise them: These approaches should not replace conventional Rx This should not prejudice the attitudes of members of the multidisciplinary team, or affect the care offered.
Approach to PT Assessment Note the time of day you make assessment; this could be very important for reassessment as many patients have variation in symptoms throughout the day. For example, if you carried out your initial assessment early in the morning, then reassessed at midday, you could get very different responses because ........??? By noon her morning stiffness would have eased.
How long does her morning stiffness last? Does she have any systemic symptoms that might impact upon your ideas for management? e.g. has the RA affected her heart or does she fatigue easily? Has she had any physiotherapy before and how has she responded?
Problem list Pain in all joints affected especially hips & knees Reduced range of movement in all affected joints Reduced muscle strength Reduced mobility both in bed & during locomotion (no longer able to get around with walking frame) Reduced function.
Aims of Physiotherapy Rx To reduce pain & stiffness To maintain or increase ROM in affected joints To maintain or increase muscle strength in affected groups To prevent deformities To maximise function, independence and quality of life
An Approach to Physiotherapy Rx Despite pharmacological advances in Rx of RA many patients still present with functional deficits who need physiotherapy. According to World Confederation of Physical Therapists (WCPT) Physiotherapy is ‘concerned with identifying & maximizing movement potential, within the spheres of promotion, prevention, treatment and rehabilitation’.
WCPT components ofphysiotherapy interventions Thermotherapy – hot/cold packs, paraffin/wax baths and infrared. Ice application – It provides cooling to skin temp which is raise by inflammation. Cooling will diminish the rate of swelling & production of irritants. It also helps in alleviate some of pain. Ice can be applied regularly @ 2/day
Heat application – Acute conditions – Heat application to the inflamed joint is not recommended. Chronic conditions – Thermotherapy, especially paraffin baths combined with ex, should included as an intervention to improve ROM & decrease pain & stiffness.
Therapeutic ultrasound Therapeutic US without additional therapeutic interventions is effective for reducing joint tenderness caused by RA. Continuous US is more effective for patients with chronic RA. Mechanical effect of both pulsed & continuous US increases skin permeability, thus decreasing inflammatory response, reducing pain & facilitating the soft tissue healing process.
Both pulsed and continuous US reduce nerve conduction velocity of pain nerve fibres. Continuous US, however, has thermal effects that reduce muscle spasms and pain. The thermal effects also cause vasodilatation, which enhances the excretion of chronic inflammatory cells.
Pulse electromagnetic energy There is minimal literature of PEME in RA But in some studies it has shown to be effective
Interferential therapy Helps in minimizing pain in RA The electrodes needs to place carefully in pts with high dose steroid Used of such modalities may addicted to the patient & when experiencing multiple joint pain it would be impractical. Dosage – 90 – 100 Hz – reduce nerve accommodation 50 – 100 Hz – improve healing, blood supply & membrane permeability
TENS It has been proven to be effective in managing chronic pain. Different dosage may be used with disease activity levels Many patient tend to substitute medication with TENS.
Hydrotherapy Hydrotherapy produces physiological, functional and psychological benefits. Long-term hydrotherapy reduces the rate of hospital admissions and does not increase joint destruction. However, it is not suitable for all RA patients due to contra-indications and the cost of hydrotherapy reduces its widespread availability.
Joint Protection & Provision ofWalking & Disability Aids / Splinting Provision of sticks or crutches Reduce lower limb loading Helps in pain relieve & improving mobility in RA. However, redistribution of load to the small joints of the upper limbs requires especially designed walking aids, e.g. gutter frames Splinting It can reduce pain & improve function. Splinting is usually applied by occupational therapists (OTs), but a trained Therapist may supply splints.
Characteristics of an ideal splint The splint should be – Inexpensive Easy & quick to make Comfortable Light & neat Strong Functionally accurate Fitting optimal Cosmetically accepted
Advantage of splinting Correct deformities Provide support & rest Easy application & removal Prevent dynamic instability Offer functional efficiency Reduce the impact of unwanted force on body Provide means of strengthening, re-educative & assistive aids.
Disadvantage of splint Possibility of muscular weakness & wasting Loss of mobility Tendency to fixed in one position of splint Fabrication, trial & application are painful.
Exercise therapy On land & Aquatic physiotherapy includes – Aerobic activities, Flexibility Strengthening ex, Core stability ex, Balance rehabilitation, Promotion of lifestyle physical activity.
Manual therapy Manual therapy– includes – Mobilisation Manipulation Myofascial release Trigger point therapy Acupuncture and Massage.
Course & Prognosis of RA The course of disease is variable & unpredictable Prognosis in term of function is reasonably good: 25 % - Remains fit for all-round activities 40 % - Moderate impairment of function 25 % - Badly disable 10 % - Wheelchair dependent
Prognosis is poor if – RH-f is high Erosion of the joint surface appear early Nodules Systemic manifestations
Reducing the risk of RA Health promotion Smoking cessation
Reference PK Pispati. Manual of Rhrumatology Michael L Snaith. ABC of rheumatology; London; BMJ publishing group; 1996 Hillary chappel et al. management of early rheumatoid arthritis. Scottish Intercollegiate Guideline; 2000; 13-14 Elaine Moore. Rheumatoid factor diagnosing rheumatoid arthritis and related disorders; Mar 19, 2006 Vinita Agrawal et al. Muscle involvement in rheumatoid arthritis: clinical & histological characteristics and review of literature, J Indian Rheumatol Assoc, 2003 : 11 : 98 - 103