Rheumatoid Arthritis
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Transcript of Rheumatoid Arthritis
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: [email protected]
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.