About The Author

Dr Manoj R. kandoi is the founder president of “Institute of Arthritis Care & Prevention”

an NGO involved in the field of patient education regarding arthritis. Besides providing

literature to patient & conducting symposiums, the institute is also engaged in creating

patients “Self Help Group” at every district level. The institute also conducts a certificate

course for healthcare professionals & provide fellowship to experts in the field of

arthritis.

The author has many publications to his credit in various journals. He has also written a

book “ The Basics Of Arthritis” for healthcare professionals.

The author can be contacted at:

Dr manoj R. kandoi

C-202/203 Navare Arcade

Shiv Mandir Road, Opposite Dena Bank

Shiv mandir Road, Opposite Dena bank

Shivaji Chawk, Ambarnath(E) Dist: Thane Pin:421501

State: Maharashtra Ph: (0251)2602404 Country: India

Membership Application forms of the IACR for patients & healthcare professionals

can be obtained from.

Institute of Arthritis Care & Prevention

C/o Ashirwad Hospital

Almas mension, SVP Road, New Colony,

Ambarnath(W) Pin:421501 Dist: Thane

State: Maharashtra Country: India

Ph: (0251) 2681457 Fax: (0251)2680020

Mobile ;9822031683

Email: drkandoi@yahoo.co.in

Preface:

Studies have shown that people who are well informed & participate actively in

their own care experience less pain & make fewer visits to the doctor than do other

people with arthritis. Unfortunately in India & many third world countries we do not

have patient education & arthritis self management programs as well as support groups.

This is an attempt to give a brief account of various arthritis, their prevention & self

management methods which can serve as useful guide to the patients of arthritis.

It would be gratifying if the sufferers of the disease knew most of what is given in the

book.

Acknowledgement\

I am thankful to Dr (Mrs) Sangita Kandoi for her immense help in proofreading & for her

invaluable suggestions. The help rendered by Nisha Jaiswal is probably unrivalled.

Thanks also to vidya, Sheetal and parvati for their continous support throughout the

making of the book. The author is grateful to his family for the constant inspiration they

offered. The author alone is responsible for the shortcoming in this piece of work. He

welcomes suggestions for improvement from the readers.

RHEUMATOID ARTHRITIS:

Rheumatoid arthritis (RA) is an immuno – inflammatory disease that affects joints and

extra articular tissues.

Epidemiology:

The reported prevalence of RA in adults varies from 0.5% to 3.8% but is slightly

less in the tropics. varying from 0.2% to 1.2%.

The sex ratio is 4: 1 in favour of females.

The prevelence increases with age and sex differences diminish in the older age

group.

The onset is most frequent during the fourth and fifth decades of life, with 80% of

all patients developing the disease between the age of 35 -50.

Etiology:

The theoretical causes proposed are following.

A. Infectitious: Hemolytic and nonhemolytic types of streptococci has been isolated

from joints and regional lymph nodes.

B. Endocrine: This is suggested by clinical response to therapeutic steroids.

C. Allergic: The patients frequently exhibit various allergic menifestations.

Eosinophilia is frequent.

D. Metabolic

Pathogenesis:

Rheumatoid arthritis is an immunologically mediated event, although the original

initiating stimulus has not been characterized. It is believed that the inflammatory process

in the tissue is driven by the CD 4 + T cells infiltrating the synovium.

The tissue inflammation is reminiscent of delayed type hypersensitivity reaction

occurring in response to soluble antigens or microorganisms. It remains unclear whether

the persistent T-cell activity represent a response to a persistent exogenous antigen or to

altered auto antigens such as collagen immunglobulin or one of the heat shock proteins or

perhaps both. Alternatively it could represent persistent responsiveness to

activated autologous cells such as might occur as a result of Epstein Barr virus infection

or persistent response to a foreign antigen or superantigen in the synovial tissue. Finally

rheumatoid inflammation could reflect persistent stimulation of T-cells by synovial

derived antigens. Overriding the chronic inflammation in the synovial tissue is an acute

inflammatory process in the synovial fluid. The exudative synovial fluid contains more

polymorphonuclear cells than mononuclear cells. The precise mechanism by which bone

and cartilage destruction occurs has not been completely resolved, the majority of

destruction is in juxtaposition to the inflamed synovium or pannus, that spreads to cover

the articular cartilage. This vascular granulation tissue is composed of proliferating

fibroblasts, small blood vessels and a variable number of mononuclear cells. It produces a

large amount of degradation enzymes including collagenase and

stromelyin, that may facilitate tissue damage. The cytokines IL-I and TNF- play an

important role by stimulating the cells of the pannus to produce collagenase and other

neutral proteases.

Evidence of immune overactivity in RA:

1. The presence in the serum of an abnomal immunoglobin –rheumatoid factor

2. The infilteration of the synovial tissue by immunological competent cells,

lymphocytes, and plasma cells, which are reponsible for the local production of

immunoglobins including rheumatoid factor.

3. The presence of immune antigen-antibody complexes within leucocytes in

synovial fluid and peripheral blood

4. The finding of lowered complement levels in the synovial fluid

Postulated role of humoral and cellular immunity in pathogenesis of rheumatoid

arthritis:

Antigen (? Microbial)

in joint

Sensitisation of B cells Sensitisation of T cells

Release of lymphokines

Production of IgG antibodies

Autosensitisation Macrophage Fibroblast Osteoclast

to IgG Activation growth activating factor

Formation of rheumatoid Release of

Factor - Collagenase

- PGE2

IgG-anti IgG complex - Plasminogen activator

Bone

Resorption

Immune complex mediated

Joint injury

Destruction of bone, cartilage

Perpetuation of inflammation,

fibrosis

Histology of rheumatoid nodules:

It reveals distinct zones:

A central area of necrosis

A palisade of elongated, connective tissue cells arranged radially in a corona

about the necrotic zone.

Enveloping granulation tissue with chronic inflammation cells

Clinical features:

Rheumatoid arthritis is characterized by joint pain, stiffness and symmetrical swelling of

a number of peripheral joints. Initially, pain may be experienced only on movement of

joints but rest pain and prolonged early morning stiffness develop gradually.

Characteristically, RA is a chronic polyarthritis. In approximately two – thirds of patients

it begins with fatigue, anorexia. Generalized weakness and vague musculoskeletal

symptoms.

In the typical case the small joints of the fingers and toes are the first to be affected. As

the disease progresses, it tends to spread to involve the wrists, elbows, shoulders, knees,

ankles, subtalar and midtarsal joints. The hips becomes involved only in the more severly

affected, but neck pain and stiffness from cervical spine disease is common.

Clinically. synovial inflammation cause swelling. tenderness and limitation of motion.

Warmth is usually evident on examination. especially of large joints such as the knee

joints. Swelling results from accumulation of synovial fluid. hypertrophy of the synovium

and thickening of the joint capsule. Motion is limited by pain.

Joints affected in rheumatoid arthritis:

Common - Wrist knee, ankles and elbows

- MP joints of hand

- PI P joints of fingers

Less common - Hip joint

Uncommon - Atlanto-axial joint

- Cervical spine facet joints

Progression:

As the disease advances, muscle atrophy and tendon sheath and joint destruction result in

limitation of joint motion, joint instability and deformities. At first, deformities are

correctable, but later permanent contractures develop resulting in characteristic

deformities in feet, the knees, hips and elbow. Anterior subluxatin of the

metacarpophalangeal joints is common with ulnar deviation of the fingers. Other finger

deformities lead to greater loss of hand function. These include the "swan neck"

deformity, the boutonniere or button -hole deformity (fixed flexion of the proximal

interphalangeal joint and extension of the terminal

interphalangeal joint) and deformity of the thumb. Dorsal subluxation of the ulnar styloid

of the wrist is common and may contribute to rupture of the 4th and 5th extensor tendons

when these are already the site of

tenosynovitis.

In the forefoot, subluxation of the metatarsophalangeal joints is followed by clawing of

the toes and callosities over the exposed metatarsal heads, tenosynovitis and bursitis are

integral of RA, as tendon sheaths and bursae are also lined with synovium.

Stages of rheumatoid arthritis:

1. Potentially reversible soft tissue proliferations: In this Stage the disease is limited

to the synovium with associated hypertrophy and effusion.

2. Controllable but irreversible soft tissue destruction and early cartilage erosions:

X-rays shows a reduction in the joint space but the articular congruency is well

maintained.

3. Irreversible soft tissue and bony changes: There is erosion of subchondral bone,

subluxation or dislocation of joint or fibrous ankylosis.

Deformities in rheumatoid arthritis:

Hand - Drop fingers from rupture of extensor tendon

- Fingers: Swan neck deformity

Boutonniere deformity

- Ulnar drift of the hand

- Z- deformity of the thumbs

Elbow - Flexion deformity

Knee - Early: Flexion deformity

- Late: Triple deformities: flexion, posterior

Subluxation and lateral rotation

Foot - Hallux valgus, hammer toe, etc

Ankle - Equinus deformity

A. Minimum damage occurs at the site of maximum compression.

B. Fold of synovium over the cartilage is the site of maximum damage.

Extra articular manifesations:

Rheumatoid arthritis is a systemic disease, Anorexia, weight loss, lethargy, myalgia and

raynaud's phenomenon occur commonly throughout its course, Rheumatic nodules

develop in 20% to 30% of persons with RA. They are usually found on periarticular

structures, extensor surfaces or other areas subjected to mechanical pressure, but they can

develop else where including the pleura and meninges. Nodules vary in size and

consistency and are rarely symptomatic, but on occasion they break down as a result of

trauma or become infected. They are found almost invariably in individuals with

circulating rheumatoid factor.

The other extra articular features of the disease, are listed below:

Diagnosis:

Rheumatic fever: As a rule large joints are involved with associated fever, leukocytosis,

tonsillitis and cardiac. pulmonory and kidney inflammatorv lesions. Relatively younger

people are involved

Radiological features are absent and also titre is raised. It responds very well to

salicylates.

Systemic - Fever, weight loss, fatigue, susceptibility to infection

Musculoskeletal - Muscle wasting, tenosynovitis, bursitis, osteoporosis

Haematological - Anaemia, thrombocytosis, eosinophilia

Lymphatic - Splenomeagaly, felty’s syndrome

Ocular - Episcleritis, scleritis

Vasculitis - Digital arteritis, ulcers, pyoderma gangrenosum

Cardiac - Pericarditis, myocarditis, endocarditis, conduction defects

Pulmonary - Nodules, pleural effusions, bronchiolitis

Neurological - Cervical cord compression

- Compression neuropathies, peripheral neuropathy

Osteoarthritis: The older age group is affected, mainly involving DIP and large weight

bearing joints with osteophyte formation. Systemic symptoms are absent, subchondral

scierosis is seen on x-rays and ESR is not elevated.

Laboratory findings:

Rheumatoid factor: No tests are specific for diagnosing RA. However rheumatoid

factors are found in more than two thirds of adults with the disease. The presence of

rheumatoid factors is not specific for RA as it is found in 5% of healthy persons.

The presence of rheumatoid factor can be of prognostic significance because patients

with high titres tends to have more severe and progressive disease with extraarticular

manifestations.

Index

Occurance of rheumatoid factor in selected conditions

Rheumatic Disease

Adult rheumatoid arthritis

Sjogrens syndrome

Systemic lupus erythmatosus

Scleroderma

Mixed connective tissue disease

Polymyositis

Actual viral infections

Chronic Inflammatory disease

Tuberculosis

Syphilis

Infective endocarditis

Neoplasms

Miscellaneous

Elderly but otherwise healthy individuals

Sarcoidosis

Chronic hepatitis

After transfusions

After renal transplantations

Other laboratory findings:

Normochromic normocytic, anaemia is frequently present in active RA Eosinophilia

when present usually reflects severe systemic disease. The erythrocyte sedimentation rate

Methods of testing RA factor:

I. Latex screening

II. Latex test (Normal < 20)

III. Sheep cell agglutination test (Rose waaler) (SCAT) (normal < 32)

IV. Differential agglutination test (normal < 16)

(ESR) is useful for assessment of disease activity. It is increased in nearly all patients

with active RA. C-reactive protein (CRP) is a useful marker or acute phase reactant and

valuable in the management. High levels of CRP at the onset of disease correlates with

poor prognosis.

Special Investigation:

a. Synovial biopsy: Rheumatoid pattern (villus formation with thickening nf

synovial layer and infiltration with abnormal cells in rheumatoid arthritis (also in

SLE, stills disease).

b. Synovial fluid: May show positive Rose- Waaler test in joint fluid before it can

be detected in blood. Fluid may show polymorphonuclear or mononuclear

leucocytes containing cytoplasmic inclusion bodies.

c. Arthoscopy: In accute RA synovium is diffusely erythematous and friable. In

chronic presentation. It is usually polypoid and thickened.

Synovial fluid examination:

Radiographic evaluation:

The primary value of radiography is to determine the destruction and bone erosion

produced by the disease is monitoring the impact of theraphy with disease -modifying

drugs or surgical intervention.

The sequence of early radiological sign in RA are.

1. Soft tissue swelling due lo joint effusion

2. Perarticular symmetrical osteoporosis with reduction in the width of shaft cortices

and loss of normal trabecular pattern.

3. Periosteal reaction with new osteogenesis along the shaft near the capsular

attachment.

4. Subchondral cyst formation.

5. Subchondral erosions due to actual loss of bone substance by erosion along the

marginal areas of the joint.

Normal Osteoarthritis RA Infective Arthritis

Gross Examination

Viscocity High High Law Variable

Colour Colourless Straw yellow Yellow Variable

Clarity Transparent Transparent Translucent Opaque

Laboratory Findings:

WBC Count <200 200-2000 2000-7500 >10000

PMN Leucocytes <25% <25% >50% >75%

Culture - - - +

Mucin Clot Firm Firm Friable Friable

Glucose Level Equal to Nearly Equal < 25 mg % > 25 mg %

Blood to blood glucose of blood of blood

glucose glucose glucose

Revised criteria for the classification of Rheumatoid A

1. Guidelines for classification:

a. Four of seven criteria are required to classify a patient as having

rheumatoid arthritis (RA).

b. Patients with two or more clinical diagnosis are not excluded

2. Criteria:

a. Morning stiffness: Stiffness in and around the joints lasting 1 hr. before

maximal improvement.

b. Arthritis of three or more joint areas: At least three joint areas, observed

by a physician simultaneously, have soft tissue swelling or joint effusions,

not just bony over growth. The 14 possible joint areas involved are right or

left proximal interphalangeal metacarpophalangeal, wrist. Elbow, knee,

ankle and metatarsophalangeal joints.

c. Arthritis of hand joint. Arthritis of wrist, metacarpophalongeal joint or

proximal interphalangeal joint.

d. Symmetric arthritis: simultaneously involvement of the same joint areas

on both sides of the body.

e. Rheumatoid nodules. Subcutaneous nodules over bony prominences,

extensor surface or juxtarticular regions observed by a physician.

f. Serum rheumatoid factor: Demonstration of abnormal amounts of serum

rheumatoid factor by any method for which the result has been positive in

less than 5% of normal control subjects.

g. Radiographic changes: Typical changes of RA on posterroanterior hand

wrist radiographs which must include erosions or unequivocal bony

decalcification localized in or most marked adjacent to the involved joints.

Major differences between rheumatoid arthritis and spondyoarthropathies:

Stage Extent of disease Radiological appearance

1. Synovium Soft tissue shadowing

Marginal Erosions

2. Synovium and articular cartilage Joint space narrowing

3. Synovium, articular cartilage and Bony destruction and joint deformities

subchondral bone collapse

Rheumatoid arthritis Spondyloarthropathies

Peripheral Arthritis Symmetric Polyarticular Asymmetric Pauciarticular

Sacroilitis No Yes

Spondylitis No Yes

Enthesopathy No Yes

Rheumatoid factor Present (85%) Absent

Subcutaneous Yes Absent

nodules

HLA B27 No Yes

Clinical differentiation between RA and OA:

Laboratory Differentiation in rheumatoid arthritis:

Management of rheumatoid arthritis:

Principle:

Control of joint inflammation

Arrest and / or retard the disease process

Maintain joint function and prevent deformities

Goal: The goal of treatment is to control inflammation sufficiently to prevent or retard

joint damage with ultimate goal being to induce complete remission.

Treatment Methods:

Medication:

By NSAIDS (Non - Steroidulantiin flammamatory agents)

By corticosteroids and

By disease modifying antirheumatic drugs (DMARDs)

Simple analgesics: Paracetamol 500mg with or without dextropro poxyphene

hydrochloride 65mg three times a day is useful in pain management.

Rheumatoid Arthritis osteoarthritis

Age Commonly between Rare before 40 years

20 and 50

General Condition Usually anaemic, undernourished - Well nourished may be obese

And chronically ill, frequently -Anaemia usually absent

Slight fever - No fever

Joint Involvement - Polyarthalgia - Usually limited weight bearing joints

- Bilaterally symmetrical - DIP mere commonly involved

- PIP joint especially involved

Appearance of joint - Boggy synovitis - Synovitis not usually severe

- Ankylosis may occur - Never ankylosis

- Extreme deformity may occur - Uncommon to proceed into extreme

- limitation of joint motion +++ - Limitation of joint motion usually

Lesser

Morning stiffness -Usually ++ . -> 15 minutes < 15 minutes if present

Muscular atrophy More severe Less severe and not characteristic

Subcutaneous present in 15% to 20% not present

nodules of patient

reaboratory diffentiation in rheumatoid arthritis:

Rhe/lmatoid arthriti,s O,steoarthritis

,,'

RA test -RA test +ve in)30% of -never definitely i

ESR typical cases -' positive

C R proteins -ESR an~ CRPproterm; -normal

raised

Synovial biopsy -pannus formation and -absent

i nodules seen

x-rays

,'; osteoporosis ++ -absent ""

in;~, osteophytes absent -present

ankylosis ++ -absent

!

I

~ M~lnagement of rheum~lt()i<l ~Irthritis :

Pri/iciple :

~' .

.Control f joint inflammation

.Arrest a d / or retard the disease process

~ Maintain' joint function and prevent deformities

~(ial : The goal of treatment is to control inflammation sufficiently to

prevent or retard joint damage with ultimate goal being to il]duce complete

remission.

.13

\

"

--

Subcutaneous Present in 15% to 20% of patient Not present

nodules

Rheumatoid Arthritis osteoarthritis

RA Test -RA test +ve in 75% of typical cases - Never definitely positive

ESR C R proteins -ESR and CRP raised - Normal

Synovial Biopsy -Pannus formation and nodules seen - Absent

X-Rays Osteoporosis ++ - Absent

osteophytes absent - Present

ankylosis - Absent

NSAIDS: NSAIDS reduce joint and swelling and may improve, they do not alter disease

progression. Nevertheless predictable course of rheumatoid arthritis at presentation they

are used as initial treatment. If patients continue to experience persistent symptoms,

morning stiffness and fatigue for 2 -3 months, treatment with DMARDs is indicated.

Corticosteroids: Although corticosteroid usually produce immediate and dramatic

antinflammatory effects in RA, they do not alter progression of the disease. Further more,

clinical manifestations of the active disease reappear when the drug is discontinued.

DMARD: DMARDs are drugs, which modify the course of the disease. The aim of

resorting to DMARD in rheumatoid arthritis is to postpone or preclude the use of

corticosteroids, which have their well known side effects. These drug can reduce the

activity of rheumatoid arthritis including pain, stiffness and swelling. Most disease

modifying drugs take six to twelve weeks before a beneficial effects is noted.

Drugs of this type do not possess immediate anti -inflammatory effect but will improve

joint pain, stiffness, swelling and reduce systemic symptoms. Their main benefit is in

inducing, a symptomatic remmissin for 1 -2 years in 40 -60% of patients. They are

usually introduced in a pyramidal fashion. Starting with the safest determined by the

severity of the disease.

The current treatment startegy invloves the early use of DMARD to limit joint damage

and preserve function.

Indications for disease-modifying drugs:

Persistent symptoms and signs of inflammatory arthritis

Evidence of progressive radiological damage

Troublesome extra -.articular manifestations

Palindromic (returning / recurrent) rheumatoid arthritis.

Examples: Methodtrexate gold compounds, D -penicillamine, the antimalarials and

sulfasalazine.

Advantages of DMARDs:

Reduce disease progression

Improve functional disability

Decrease pain.

Interfere with inflammatory processes.

Retard development of joint erosion.

The new treatment paradigm with respect to DMARDs: Earlier concept was to use

DMARD for advanced cases and relatively later in rheumatoid arthritis. Recent data

shows that damage to the bones and synovial tissue begin during the first couple of years

of disease onset and aggressive

use of DMARDs during this phase helps in reduction of joint damage and subsequent

deformity and disabiltity.

Many experts are now recommending that patients with moderate or severe, RA should

start therapy with DMARDs as well as NSAID.

Staged therapy in rheumatoid arthritis:

Disease modifying antirheumatic drugs:

Antimalarials: The successful use of antimalarials dates back several decades.

Antimalarials used are chloroquine and its analogue hydroxychloroquine.

Meta -analysis of second line - therapy suggests that antimalarial drugs have a very

favourable risk: benefit ratio. Response generally occurs in 40 to 50% of patients. After

several decades of use, there is an impression that patients with milder disease have the

greatest potential for a positive response of therapy.

The usual dose of hydroxychloroquine is 200 - 400mg/day. Clinical benefit with

hydroxychloroquine is noted in about half the patients in 4 –12 weeks and the drug

should be discontinued if there is no effect within 6 months.

Sulfasalazine: Sulafasalazine is the only drug currently used that was specially developed

for the therapy of rheumatoid arthritis. The drug is useful as therapy of mild to moderate

rheumatoid arthritis. It generally takes 12 -20 weeks for response to occur. The usual

starting dose is 500mg/day for 1 week with dose escalations weekly until dose of 2 to

3g/day is achieved. Dose of 3g/day may be associated with greater toxicity. Side effects

of sulfasalazine include gastrointestinal toxicity, rash, headaches, dizziness, haematologic

toxicity (hemolytic anaemia, leukopenia) and fever. Routine monitoring of the blood

count is required. The drug is most commonly used inpatients with mild to moderate

disease and in combination with many other second line therapies including

methotrexate.

Methotraxate: Methotraxate works more quickly than other DMARDs with significant

improvement in symtoms in 4-6 weeks. It is currently a frequently used DMARD. Most

rheumatologists recommend use of methotrexate as the initial DMARD, especially in

individuals with aggressive RA. Maximal improvement is observed after 6 months of

therapy. Major toxicity includes gastrointestinal upset, oral ulceration and liver function

abnormalities that appears to be doses related and reversible. Full blood count and liver

function tests must be monitored regularly and care must be taken to avoid drug

interaction with sulphonamides. Liver biopsy is recommended for individuals with

persistent liver function abnormalities. Acute pulmonary toxicity is an unpredictable

problem in 5 -10% of patients. The salient development of progressive hepatic fibrosis

has been recorded and the drug should not be given to chronic alcoholic patients.

Stage Medical Surgical Physiotheraphy

Stage I DMARDS Synovectomy Joint Mobilization

NSAIDS

Stage II NSAIDS Soft- tissue repair Splints

DMARDS Arthroplasty

Stage III NSAIDS Arthroplasty Splints and

Arthrodesis Walking aids

Parenteral gold and D - pencillamine:

These are slow -acting suppressive antirheumatic drugs which have been shown to

decrease the progression of erosive changes as well as reduce the activity of the disease

in 50 -60% of patients. Due to a high incidence of toxic effects, treatment with these

agents should only be considered as

an addition to basic therapy when there are clear indications for the use of a disease

modifying drug and the patients has failed to respond to antimalarials or sulfasalazine.

Two parenteral gold preparations are available aurothioglucose and sodium thiomolaste.

The major difficulties with parenteral gold are its delayed action and side effect profile.

Adverse events occur in

approximately 40% of patients and include skin reactions, stomatitis, proteinuria and

nephrotic syndrome, thrombocytopenia, eosinophilia, agranulocytosis, aplastic anaemia,

pneumonitis, colitis, hepatitis and neurotoxcity, hypotension, dizziness, weakness, nausea

and vomiting. Auranofin is an orally absorbed gold preparation. Despite initial

enthusiasm for auranofin there has been a reduction in interest in this drug. This is most

likely due to the delayed onset of action and limited efficacy. The most common side

effects with auranofin are loose stools and diarrhea. Routine monitoring of the blood

count and urinalysis is required.

D-penicillamine has been demonstrated to be effective in randomized controlled trials.

However, it has a delayed onset of action and side effects occur frequently. It has a

similar toxicity profile to parenteral gold and additionally can cause rare autoimmune

reactions including myasthenia gravis and lupus. D -penicillamine is believe to be more

toxic than parenteral gold.

Cytotoxic and Immunosupressive agents:

A number of cytotoxic and immunosupressive agents have been found to have both

symptomic and slow acting disease modifying activity in rheumatoid arthritis. The effect

as mediated by their usefulness is limited by immediate and potential long term toxicity.

They include azathioprine, cyclophosphamide and cyclosprin A.

The indication for use of these agents at present are limited to:

Life -threatening extra -articular manifestations which have failed to respond.to

corticosteroids or second line agents.

Severe active symptomatic and progressive joint disease that has failed to respond

to all other forms of therapy.

Patients receiving unacceptably high doses of corticosteroids in whom dose

reduction has not been possible.

Azathioprine:

An antimetabolite, is generally reserved for patients who have failed conventional

therapy including methotrexate. The onset of action is generally after 12 to 24 weeks. A

return in disease activity occurs with drug discontinuation. Side effects include

gastrointestinal intolerance, nausea~norexia, vomiting, pancreatitis, hepatotoxicity,

leukopenia macrocytic anaemia and rarely infection. Concern has been expressed

regarding the potential for cancer with long term therapy routine and regular monitoring

of the complete blood count and periodic monitoring of liver function tests are required.

Cyclophoshamide:

Cyclophoshamide is a potent immunosuppressive drug that has been shown to be

efficacious in rheumatoid arthritis. Despite its efficacy profile there is limited use of this

drug due to long term toxicity concerns. With chronic administration. Carcinogenesis is a

major concern and generally

precludes its use in this chronic disease.

Cyclosporin A:

Cyclosporin A is generally reserved for patients with refractory rheumatoid arthritis who

have failed a trial with azathioprinc or methotrexate. Discontinuation of cyclosprin A is

associated with a flare of

disease activity. Side effects include gastrointestinal intolerance, headaches,

paraesthesias, flushing. gingival hypertrophy. tremors, hypertrichosis hypertension and

renal toxicity. Its use in many patients is limited due to cost.

Monitoring parameters on long term use:

Newer therapeutic approaches:

lnfliximab and etanercept have recently been approved for use in the treatment of

rheumatoid anthritis. Both drugs have shown to reduce disease activity they directly

target TNF -2. a proinflammatory cytokine, which plays a key role in the pathological

inflammatory process in rheumatoid arthritis. They have been associated with an

increased risk of upper respiratory tract infection and more rarely with cases of serious

infection. Their exact place in therapy of RA is not yet established and at present they are

very expensive.

American College of rheumatology (ACR) criteria for measuring improvement in

disease activity in patients with rheumatoid arthritis

Drug Monitoring Interval

Gold CBC, Urine Prior to each injection

D-Penicillamine CBC, Urine Every 15 days for months

then every 1-3 months

Chloroquine Visual Field Prior to start of therapy then

6 monthly

Sulfasalazine CBC Every 15 days for 3 months

LFT Every 2-3 months 6 monthly

Methotrexate CBC Every one month for 3 months

Then once in 3 months

LFT Once in 3 months after 6 months

6 monthly

Criteria Method of assessment

A reduction in

Number of swollen joints Assessment of >- 28 joints

Number of tender joints Assessment of >- 28 joints

Plus an involvement in >- 3 of the following

Role of leflunomide in RA:

Leflunomide has a unique mechanism of action. It acts by inhibiting denovo pyrimidine

synthesis thus preventing proliferation of activated T lymphocytes.

It is known to improve functional scores of patient and retard radiological evidence of

structural damage.

Dose schedule:

It is usually started for first 3 days as 100 mg/day (5 tables of 20 mg)

subsequently maintenance dose of20 mg/daily can be given up to 2 years.

Adverse reactions:

These include diarrhoea, elevated liver enzymes (ACT and AST), alopecia, rash,

sometimes acute skin reactions like toxic epidermal necrolysis and Stevens-Johnson

syndrome.

Toxic effects of immunosuppressive drugs:

Orthopaedic treatment:

1) Rest

2) Splintage

a. For relief of pain and inflammation

Patient’s assessment of pain 10 cm visual analogue scale

Patient’s assessment of disease status 10 cm visual analogue scale

Physician’s assessment of disease status 10 cm visual analogue scale

Patient’s assessment of disability Use of validated instrument (e.g. health

assessment questionarre)

Acute phase reactants ESR or CRP levels

A minimum clinical response is defined as a 20% improvement (ACR 20)

Azathi- Metho- Cyclophos- Chloram- Cyclos-

Oprine trexate Phamide bucil porin

GI Tract + ++ + + +

Bone Marrow ++ ++ ++ +++ +

Bladder 0 0 +++ 0 0

Kidneys 0 + 0 0 +++

Liver + +++ 0 0 ++

Lungs + +++ + + 0

Gonads 0 0 +++ +++ 0

Fetus -+

+++ +

- +

- +

-

Neoplasia ++ +/- ++ ++ +

b. Prevention of deformity

c. Correction of deformity

d. Postoperative.

3) Hydrocortisone injection: When one or two large joints are involved not responding to

systemic medication, intraarticular steroid injection can give dramatic relief.

Indication for use of local corticosteroid injection in rheumatoid arthritis

a. Intra-articular injection for the patients with one or two active joints.

b. For temperary relief in tendinitis and tendon nodules e.g. trigger finger.

c. Capsular or ligamentous involvement e.g. shoulder

d. As a palliative method in the treatment of carpal tunnel and other compression

syndomes.

Contraindications:

a. Uncertain diagnosis

b. Proven or possible infection

c. Severe joint damage

d. Severe local osteoperosis

e. A neurological deficit: as it may produce charcot type arthropathy.

4) Surgery: Surgical options are

a. Synoviectomy

b. Corrective surgeries including capsulotomies, tenotomy tendon transfer, bony

osteotomies & arthrodesis.

c. Joint replacement.

Synoviectomy

a. When not responding to medication.

b. Involving one or two joints.

c. Threatening impending rupture of tendon.

Types:

a. Open synoviectomy

b. Laser synoviectomy

c. Arthroscopic synoviectomy

d. Radioisotope synoviectomy

Selection of patients for knee synovectomy.

1. Those with persistent, painful synovitis with proliferative synovium not

responding to medical therapy over a period of 3 months.

2. There should be a useful range of movement (i.e. atleast 45° of flexion) without

any persistent flexion contracture.

3. The joint should be stable.

4. There should not be severe destruction of joint space or subchondral bone loss.

Osteotomy

When patient is relative younger > 55 years of age

Only partial involvement of joint.

Most commonly done at hip (intertrochanteric osteotomy and abduction

osteotomy)

Arthrodesis:

Provides long term relief

Usually reserved in peripheral joints where arthroplasty may not succeed or is not

feasible

Puts extra stress on large joints which may lead to secondary OA

Rheumatoid arthritis of upper extremity

- History

- Physical evaluation

- Functional evaluation

Tenosynovitis Wrist joint synovitis

Flexor Extensor Splintage

Steroid injection Splintage Rupture Medical control

No Response No response

Good Poor

response response

Tenosynovectomy Reconstructive

surgery

Continue Synoviectomy

Distruption of Joint destruction Good response

Supporting structure

Continue medication

Reconstructive surgery

Prognosis:

Various factors affecting the outcome in a rheumatoid case are as follows:

A. Natural history of the disease: Which may be fulminant in some or punctuated

with episodes of remissions and exacerbations.

B. Sex & age at onset: Women of child bearing age with mainly upper extremity

involvement has a progressively severe disease. Male with history of onset before

30 yrs. have a better prognosis.

C. Type of onset: Insidous - onset disease has been found to have a more protracted

course.

D. E.S.R & creative protein: High levels of ESR is associated with more erosive

arthritis.

E. Rheumatoid factor : Higher titre are associated with poor prognosis.

F. Anaemia: Anaemia is associated with progressive rheumatoid arthritis.

G. Radiological erosions: Occurance before 2 years of onset is a bad prognosis sign.

H. Histopathological changes: Excessive synovial proliferation with increased

number of synovial cells with DR antigen, carry bad prognosis.

Clinical manifestation -urgent clinical problems

Acute cricoarytenoid arthritis:

This is a life threatening disorder that produces sudden hoarsness, dyspnea, stridor and

tightness of the throat. On palpation, the cricoarytenoid joints are tender and examination

of indirect laryngoscopy

reveals marked erythema and swelling of the arytenoids and vocal cards. It usually

responds well to corticosteroid (including local injection and inhalation).

Synovial cyst: Fluid filled synovial cysts may enlarge and rupture into the surrounding

soft tissues. Sudden bending of the knee may precipitate rupture of a synovial cyst in the

popliteal fossa behind the knee (Baker's

cyst). Ruptured cyst usually respond quickly to aspiration and corticosteroid injection.

Surgery is rarely indicated.

Tendon Rupture: Rupture occur most often in the extensor tendon over the dorsum of the

hand leading to altered finger extension. It requires surgical intervention.

Septic Arthritis: It may occur in those patients treated with intraarticular steroids or

immunosupressive agents. Unexplained persistent or progressive inflammation in a single

joint may be an indication of joint

aspiration. Arthrocentesis confirms the diagnosis.

Uncommon Complication: Amyloidosis: It is found at post-martem in about 20% of

cases. However few patients show signs of amyloidosis. Proteinuria leading to nephrosis

is the usual presentation.