RHEUMATOID ARTHRITIS

BPT701
MODULE-IV
SANHITA SENGUPTA
ASST. PROF, BWU, AHS.
RHEUMATOID ARTHRITIS
Definition: Rheumatoid arthritis (RA) is a systemic autoimmune
disease characterized by inflammatory arthritis and extra-articular
involvement. It is a chronic inflammatory disorder caused in many cases
by the interaction between genes and environmental factors, including
tobacco, that primarily involves synovial joints. Rheumatoid arthritis
(RA) is a chronic multi-system inflammatory autoimmune disease of
indefinite etiology. The disease primarily affects synovial joints
eventually progressing to ongoing inflammation, destruction of both
cartilaginous and bony elements of the joint, with resultant pain and
disability.
 Pathology

• Rheumatoid arthritis is a chronic progressive disease that affects joints and

systems. Due to the presence of autoantibodies (seropositivity) in rheumatoid
arthritis, which is an autoimmune disease, many symptoms have occurred, such
as joints and bone destruction and mortality. genetic and environmental factors
affect the development of the illness.
• T cells, B cells, and pro‐inflammatory cytokines (TNF, interleukin (IL)-1, and IL-6)
have a key role in the development of the disease. Autoreactive T cells and B
cells accumulate in the synovial tissues of patients with rheumatoid arthritis. T
cells are immunologically tolerant to autoantigens; however, when self-
tolerance is broken, autoreactive T cells are activated, and they stimulate B cells
to induce the production of autoantibodies. Autoantibodies form immune
complexes with antigens, which are deposited in tissues and activate
complements to cause histological damage (type III allergy).
• The presence of HLA‐DRB1, particularly HLA‐DRB1, is associated with disease
progression by affecting peptides.
 PATHOLOGY
• Genetic factors affecting the development of rheumatoid arthritis have
been associated with anti‐citrullinated protein antibody (ACPA) positive.
When ACPA is positive, the risk of developing rheumatoid arthritis is
increased. The presence of ACPA and RF was detected 10 years before
the diagnosis of rheumatoid arthritis, and it indicated that there is an
increase in ACPA, such as serum cytokine concentrations, especially
before the onset of joint involvement. Patients with RA with RF, ACPA, or
both are designated as having seropositive RA. Anti-cyclic citrullinated
peptide (anti-CCP) antibodies are highly disease specific, and bone or
cartilage destruction is more likely to progress in patients positive for
anti-CCP antibodies.
• Elevated Rheumatoid factor is present and no known cause have been
identified.
Diagnosis and special tests

 Diagnostic tests play an important role in the diagnosis of RA, but

diagnosis is based on clinical findings.
 RF is frequently used in the diagnosis and follow ‐up of rheumatoid
arthritis but is not a distinctive diagnostic parameter because it is also
detected in other rheumatic diseases.
 Anti‐cyclic citrullinated peptide/protein (anti ‐CCP) is especially used
for early diagnosis.
 The most widely used and most reliable test, anti ‐ccp2, was accepted
as the gold standard in anti‐citrullinated protein antibody ( ACPAs) in
2010. As a result of a joint study by American College of
Rheumatology (ACR) and European League Against Rheumatism
(EULAR) for rheumatoid arthritis diagnostic criteria, ACPA has been
included in the current 2010 rheumatoid arthritis diagnostic criteria.
The 2010 American College of Rheumatology/European League against rheumatism classification criteria for Score
rheumatoid arthritis
Target population (who should be tested?): patients who
1. Have at least 1 joint with definite clinical synovitis (swelling)
2. With the synovitis not better explained by another disease
Classification criteria for RA (score-based algorithm: add score of categories a–d;
A score of ≥6/10 is needed for classification of a patient as having definite RA)
A. Joint involvement
1 large joint 0
2–10 large joints 1
1–3 small joints (with or without involvement of large joints) 2
4–10 small joints (with or without involvement of large joints) 3
>10 joints (at least one small joint) 5
B. Serology (at least one test result is needed for classification)
Negative RF and negative ACPA 0
Low‐positive RF or low‐positive ACPA 2
High‐positive RF or high‐positive ACPA 3
C. Acute‐phase reactants (at least one test result is needed for classification)
Normal CRP and normal ESR 0
Abnormal CRP or abnormal ESR 1
D. Duration of symptoms
<6 weeks 0
≥6 weeks 1
 2010 ACR/EULAR Classification Criteria for RA
1. Number and size of involved joints
 2 to 10 large joints = 1 point (shoulders, elbows, hips, knees, and ankles)
 1 to 3 small joints = 2 points (metacarpophalangeal joints, proximal interphalangeal joints, second through
fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists)
 4 to 10 small joints = 3 points
 Greater than 10 joints (including at least 1 small joint) = 5 points
2. Serological testing for rheumatoid factor or anti-citrullinated peptide/protein antibody
 Low positive = 2 points
 High positive = 3 points
3. Elevated acute phase reactant (erythrocyte sedimentation rate [ESR] or C-reactive
protein [CRP]) = 1 point
4. Symptom duration of at least six weeks = 1 point.

A total score greater than or equal to 6 classifies the patient as having RA.
Stages of RA as Defined by the ACR

• Stage 1: No destructive changes on X-rays

• Stage 2: Presence of X-ray evidence of periarticular osteoporosis,
subchondral bone destruction but no joint deformity
• Stage 3: X-ray evidence of cartilage and bone destruction in addition
to joint deformity and periarticular osteoporosis
• Stage 4: Presence of bony or fibrous ankylosis along with stage 3
features
CLINICAL PRESENTATION
Joint pain is the universal characteristic in RA patients, but the long-standing
disease has several features, easily recognizable by a trained rheumatologist, but
often misdiagnosed by other specialists. The key to the recognition of the clinical
and physical findings of RA is the capability to recognize the outcome of the
synovial proliferation and inflammation. As was already stated before, RA can
affect any peripheral joints, with predilection on the small joints of the hands and
feet, followed by the elbow, shoulder, ankle or knee.
1. Hand and wrist

Hand and wrist involvement with secondary deformity is a typical feature of late RA. If in the early RA,
the physical findings are not extensive, in the late disease one can identify an entire panel of changes. The
late, irreversible and most prevalent changes in hands include “swan-neck” and “boutonnière”
deformities, along with metacarpophalangeal joints (MCP) swelling, subluxation and “ulnar drift,” or
ulnar deviation. Swelling of the MCP and wrists joints, together with atrophy of the intrinsic muscles of
the hand, leads to the aspect of the hand like “two-humped camel’s back,” while the ulnar deviation
makes it similar to the “mole’s paw.” Persistent inflammation adjacent to ulnar styloid, together with the
laxity of the radioulnar ligament leads to a movement of the styloid under the examiner’s pressure,
similar to the “piano key”.
Arrow A & C showing – boutonnière
deformity
Empty arrow B & C – Swan-neck
deformity
 Short Note on deformities
• The boutonnière deformity presumes the flexion of the proximal interphalangeal
(PIP) joint and extension of the distal interphalangeal (DIP) joint. The cause of the
boutonnière deformity is the lesion of the central slip of the extensor tendon, secondary
to tenosynovitis and PIP swelling, with the lateral and volar displacement and
conversion of the lateral bands of the extensor tendon, into flexors of the PIP joint. In
time, shortening of the tendon leads to hyperextension of the DIP joints. If the DIP
swelling is disrupting the extensor tendons, the joints will be forced to remain flexed
(due to the action of the only remaining tendons, the flexors).
• The swan-neck means hyperextension of the PIP and flexion of the DIP. Besides, if
the bulging of the PIP is volar, the lateral bands subluxate dorsally, generating
hyperextension in the PIP joint and the aspect of the swan-neck deformity.
• The involvement of the thumb results in severe functional impairment, due to the
loss of the grip between the index finger and the tip of the thumb. The most prevalent
pathological aspect of the thumb in RA is one of a “flails,” followed by the boutonnière
deformity, which is the same as described before, just one joint back proximally.
Elbow
• The elbow is often involved in both early and in longstanding rheumatoid
arthritis. Because of its unique role in maneuvering and positioning the
hand in space, the loss of normal motion and stability, or increased pain
with the use of this joint are all significant sources of impairment in
patients with RA. Synovitis of the elbow joint can be identified by
palpation between the olecranon and the epicondyles, especially the
lateral one. Olecranon bursitis is a common finding in patients with RA
but should be differentiated from the one appearing in polyarticular gout.
To mention, in RA it tends to be more frequently bilateral.
Shoulder involvement
• The shoulder joint is a complex joint and because of its deep location it is
difficult to confirm accurately the joint effusion, or the rotator cuff tears
only by physical examination, therefore shoulder lesions are often under
diagnosed. When involved, it might generate limitation of motion in all
planes, with suggestive secondary scapulothoracic movement, or
“shoulder pad” sign. The pain generated by joint effusion, subacromial
subdeltoid bursitis, or rotator cuff tendon tears is often referred into the
deltoid muscle. The fluid inside the biceps tendon sheet is not uncommon.
Knee joint involvement
• Knee joint synovitis is a frequent finding in patients with RA, anterior
swelling being easily detectable through clinical examination, by the
“bulge sign” or the ballottement of the patella with the index finger
downwards, into the fluid. The Baker cyst is a benign fluctuant swelling
of the gastrocnemius-semimembranosus bursa in the popliteal fossa at the
back of the knee, resulted after severe effusion at the level of the knee
joint. Hip joint involvement is associated with pain over the greater
trochanter, probably due to bursitis and pain elicited by Patrick’s test, or
Flexion-Abduction-External Rotation maneuver (FABER).
Other type of involvement
• Bilateral pain, tenderness, swelling and limitation of jaw movements
might be the result of temporomandibular joint involvement and due
to these symptoms, patients experience limitations in their daily
activities, such as eating, speaking and swallowing.
• The involvement of the cervical spine is the most serious skeletal
manifestation in patients with RA. Instabilities of the upper cervical
spine can lead to headache, neck pain, paresthesias, weakness, signs of
vertebrobasilar insufficiency or neurological complications such as
bowel and bladder sphincter impairment.
 Extra-articular features of RA
• Felty’s syndrome represents the association of RA with splenomegaly and
leukopenia (neutropenia) and usually occurs in seropositive patients with
longstanding, deforming disease with rheumatoid nodules present.
• Pulmonary nodules and pneumoconiosis appear in patients with RA and
extensive exposure to coal dust (Caplan’s syndrome), silica and asbestos.
• Pericarditis is the most common cardiac feature of heart involvement, usually
asymptomatic. Myocardial disease secondary to granulomatous lesions similar
to rheumatoid nodules can lead to arrhythmia.
• Other extraarticular manifestations of RA include neurological impairment,
secondary to mononeuritis multiplex, to nerve compression by synovial
proliferation (carpal tunnel syndrome) or to atlantoaxial subluxation; eye
involvement includes keratoconjunctivitis sicca, episcleritis or scleromalacia
perforans (secondary to a perforating rheumatoid nodule).
• Muscle atrophy is frequent, especially near affected joints.
 DIFFERENTIATION BETWEEN OA
AND RA
• Clinically, the diagnosis of RA can be differentiated from
osteoarthritis (OA) as the affected areas in RA are the proximal
interphalangeal (PIP) and metacarpophalangeal (MP) joints; OA
typically affects the distal interphalangeal (DIP) joint.
• OA is the most common type of arthritis and is caused by wear and
tear rather than an autoimmune condition. It has no effects on the
lungs, heart, or immune system.
• In addition, OA typically affects only one side of the body, as
opposed to the symmetrical nature of RA.
• Another differentiating factor is that RA patients suffer from
persistent morning stiffness for at least ≥1 h. Patients with OA may
have morning stiffness, but this typically resolves or decreases
within 20–30 min
 CLINICAL FEATURES
1. The characteristic symptoms of rheumatoid arthritis are morning stiffness and
polyarticular pain and swelling. Patients often complain of stiffness from the onset
of the disease and experience difficulty in moving fingers on awakening, which is
often described as having difficulty in forming a fist.
2. Arthralgia is often associated with swelling and limited mobility. These symptoms
are likely to appear in the joints of the fingers and toes (e.g., proximal
interphalangeal, metacarpophalangeal, and metatarsophalangeal joints), knees,
feet, hands, elbows, and cervical spine, among other areas. However, the distal
interphalangeal joints are rarely the site of initial onset.
3. Patients often complain of general symptoms such as malaise, fatigue, and fever.
4. Frequently accompanying symptoms include dry eyes associated with
keratoconjunctivitis, xerostomia due to sialadenitis, subcutaneous rheumatoid
nodules on the extensor surface of the forearm, numbness of the hands and feet
associated with compressive neuropathy, and shortness of breath on exertion or a
dry cough due to interstitial pneumonia.
 CLINICAL FEATURES
5. Visual inspection and palpation tend to reveal tenderness and
swelling of articular soft tissues and an accumulation of synovial fluid.
6. Affected joints are characterized by inflammatory findings such as
swelling, redness, and hot flashes.
7. In general, multiple joints usually tend to be bilateral, symmetrical,
and often mobile.
8. As joint destruction progresses, various patterns of joint
deformation are observed, such as the buttonhole deformity and swan-
neck deformity of the finger joints. In case of atlantoaxial subluxation,
occipital headache and numbness of the hands may occur. When
inflammation spreads to the tendons, patients develop carpal tunnel
syndrome due to the swelling of the trigger finger or wrist.
PT MANAGEMENT OF RA
• Cold/Hot Applications

Cold/hot modalities are the most commonly used physical agents in arthritis treatment. It is
well known that cold application is mostly used in acute stages whereas hot is used in chronic
stages of RA.

By using heat, analgesia is accomplished, muscle spasm relieved, and elasticity of periarticular
structures obtained. Heat can be used before exercise for maximum benefit. Thermotherapy
may be applied as a superficial hot-pack, infrared radiation, paraffin, fluidotherapy, or
hydrotherapy. Applications are recommended for 10–20 minutes once or twice a day. Caution
is necessary in patients with sensorial deficits and impaired vascular circulation in hands and
feet because of burn risk. Cold application is preferred in active joints where intra-articular
heat increase is undesired. Cold-pack, ice, nitrogen spray, and cryotherapy are different
methods of applying cold-therapy.
Cartilage-destroying enzymes are produced within the inflamed joints of patients with RA.
Levels of destructive enzymes such as collagenase, elastase, hyaluronidase, and protease are
affected by the temperature of local joints. With temperatures of 30° Celsius or lower, effects
of these enzymes are negligibly small. Normal intra-articular temperature is 33° Celsius,
whereas it may rise up to 36° Celsius in patients with RA. Increasing intra-articular
temperature is also related to an increase in collagenase activity and cartilage damage.
Despite the inhibition of cell proliferation and metabolic activation within the synovial fluid
at 41–42° Celsius, it cannot be used as a therapeutic method because of irreversible joint
damage.
Various studies have investigated the changes within joints upon application of heat. Intra-
articular temperature increased by superficial heat application. In the first 5 minutes, the
joint temperature decreased but subsequently, as expected, it began to rise. It has been
suggested that within the first few minutes, superficial vessels become dilated and
circulation moves away from the inflamed synovial tissue. The opposite of this occurs during
the cold application. Effects of heat application change between normal healthy subjects and
patients with inflamed joints. Accordingly, skin temperature rises with paraffin at the most
and intra-articular joint temperature with diathermy application. Temperature increase with
short-wave diathermy application continues for 40 minutes. However, it has been observed
that increased intra-articular temperature has no beneficial effect on clinical prognosis or
radiologic progression. Skin temperature decreases the most by cold air application, whereas
intra-articular temperature decreases the most by ice application. Increased intra-articular
temperature by cold-pack application may be explained by reactional temperature rise with
short-term application, which was previously mentioned.
• Electrical Stimulation
Electrostimulation is used in patients with RA to relieve pain.
Transcutaneous electrical nerve stimulation (TENS) therapy is the most commonly
used method.
Various studies have reported an increase in hand grip strength after daily application
of 15 minutes of TENS and a decrease in pain after using TENS once a week for 3
weeks. Levy and colleagues observed reduction of synovial fluid and inflammatory
exudate following TENS application in acute arthritis and suggested that pain relief
may be partially explained by this effect. It cannot be used in every painful joint
simultaneously, which is a disadvantage in patients with polyarticular involvement.
Interferential current can also be used for analgesia. Studies have shown its efficacy on
pain relief, swelling, and improvement in ROM.
Also, no difference was found between interferential current and TENS in the
magnitude of analgesia.
Joint Protection Strategies

• Joint protection strategies, such as rest and splinting, using compressive gloves, assistive devices, and adaptive
equipment, have beneficial effects in managing RA symptoms and deformities.

Rest and Splinting

• The joints should be put into rest during the acute stage of the disease.

• Bed rest relieves the pain in cases of extensive joint involvement. It is critical, at this stage, to put the joints into rest
at a functional position. Rest position should be as follows: shoulder joint in 45° abduction, both wrist joints in 20°
to 30° dorsal flexion, fingers slightly in flexion, hips at 45° abduction without any flexion, knees totally extended, and
feet in a neutral position.

• Splints may be used to give desired position at rest and functional positioning to the involved active joints. Increased
compliance can be gained by offering the patient splints made of soft materials. Orthosis and splinting are used for
the following objectives: to diminish pain and inflammation, to prevent development of deformities, to
prevent joint stress, to support joints, and to decrease joint stiffness.
• Various reports have shown benefits of wrist splints in controlling pain and inflammation and preventing the development of
deformities.

• Flexible wrist orthosis increases hand grip strength by 20% to 25%.

• Various ring orthoses have been developed to prevent finger deformities. Major factors determining patient compliance to the orthosis
are size of the orthosis, the heat generated at the skin by the orthosis, hardness of the parts in contact with the skin, and whether it
interferes with functions of the hand.

• Joint stress in the feet may be alleviated by medial arc supporting pad at the sole of the foot and by metatarsal pad. Viscoelastic soles
may decrease shock loading occurring at proximal tibia during the gait, by up to 40%.

• Philadelphia corset may be recommended if atlantoaxial involvement is present. Orthosis provides better immobilization and may be
used in the presence of cervical instability.

• Compression Gloves

• Patients using compression gloves have reported reduced joint swelling and increased well-being. Improvement may be provided by
using compression gloves for hour intervals or only at night in patients with inflammation in their hands or fingers. Gentle
compression is beneficial because of the containment of joint swelling and subsequent decrease of pain.
Assistive Devices and Adaptive Equipment

• Interventions such as assistive devices and adaptive equipments have beneficial effects on joint
protection and energy conservation in arthritic patients. Assistive devices are used in order to
reduce functional deficits, to diminish pain, and to keep patients' independence and self-efficiency.
Loading over the hip joint may be reduced by 50% by holding a cane. In fact, most of these
instruments are originally designed for patients with neurologic deficits; therefore, certain
adaptations may be needed for them to be used in patients with arthritis. Elevated toilet seats,
widened gripping handles, arrangements related with bathrooms, etc. might all facilitate the daily
life. The procedures needed to increase compliance of the patient with the environment and to
increase functional independence are mainly determined by the occupational therapist.

Massage Therapy

• Massage is a commonly used treatment tool that improves flexibility, enhances a feeling of
connection with other treatment modalities, improves general well being, and can help to diminish
swelling of inflamed joints. Massage is found to be effective on depression, anxiety, mood, and pain.
• THERAPEUTIC EXERCISE

• Prior to establishing an exercise program for patients with RA, the following characteristics should be considered:

• Whether the involvement of the joints is local or systemic, stage of the disease, age of the patient, and compliance of

the patient with the therapy. Duration and severity of the exercise are adjusted according to the patient. ROM

exercises, stretching, strengthening, aerobic conditioning exercises, and routine daily activities may be used as

components of exercise therapy.

• There should be no straining exercises during the acute arthritis. However, every joint should be moved in the ROM

at least once per day in order to prevent contracture. In the case of acutely inflamed joints, isometric exercises

provide adequate muscle tone without exacerbation of clinical disease activity. Moderate contractures should be

held for 6 seconds and repeated 5–10 times each day. It should be remembered that if isometric exercises are

performed in a magnitude of more than 40% of maximum voluntary contraction, they may lead to impairment in

blood circulation and fatigue after the exercise. If the disease activity is low, then isotonic exercises should be

performed by using very low weights. Low-intensity isokinetic knee exercises (by 50% of the maximum voluntary

contraction) were reported to be safe and effective in patients with RA.

• If pain persists more than 2 hours or too much fatigue, loss of
strength, or increase in joint swelling occurs after an exercise
program, then it should be revised.
• Also, walking does not lead to intra-articular pressure increase in
healthy subjects but does so in a knee with inflammation and
effusion. Thus, patients with active arthritis should particularly
avoid activities such as climbing stairs or weight lifting.
• Producing excessive stress over the tendons during the stretching
exercises should be avoided. In sudden stretches, tendons or joint
capsules may be damaged. Finally, in chronic stage, conditioning
exercises such as swimming, walking, and cycling with adequate
resting periods are recommended. They increase muscle
endurance and aerobic capacity and improve functions of the
patient in general, and they also make the patient feel better.
Patient Education

• In patients with RA, sociopsychological factors affecting the disease process such as
poor social relations, disturbance of communication with the environment, and
unhappiness and depression at work are commonly encountered. Scholten and
colleague have organized multidisciplinary education with the participation of
rheumatologists, orthopedicians, physiotherapists, psychologists, and social workers
for patients with arthritis. In this program, there is information about benefits and
adverse effects of drug therapy, importance of physiotherapy, use of orthosis,
psychological coping methods, self-relaxation, and various diets. In addition, patients
are taught how to perform the scheduled exercises and how to protect the joints
during routine daily life. Patients who have participated in this program have revealed
improvement in disability associated with the disease, psychosocial interaction, and
clinical prognosis. All clinics that deal with the treatment of rheumatic diseases should
provide education and information to their patients about their condition and the
various physical therapy and rehabilitative options that are available to improve their
quality of life.
QUESTIONS
• Identify the comorbid conditions associated with rheumatoid arthritis.
• Summarize the pathology of rheumatoid arthritis.
• Outline the use of rheumatoid factor and anti-citrullinated protein antibodies in
evaluating rheumatoid arthritis.
• Compare OA and RA.
• Summarize the clinical presentation of RA.
• Review the importance of physiotherapy management for those affected with
rheumatoid arthritis.
• Review the joint protection technique for a RA patient.
• Write a short note on any two deformities seen in RA: Boutonnier deformity,
swan-neck deformity, ulnar drift, zig-zag deformity of thumb.
• Describe the orthosis used in RA.
• What patient education is given to a patient with RA to resist further
Importance of ACPA and RF in identifying
RA
• Rheumatoid arthritis (RA) is a chronic and systemic inflammatory autoimmune disorder characterized
by synovial inflammation, progressive erosive arthritis and extra-articular involvements.
• The presence of anti-citrullinated protein autoantibodies (ACPA) represents a hallmark feature of RA.
Based on ACPA status, RA patients can be sub-grouped into two major subsets: ACPA-positive RA
(ACPA+ RA) and ACPA-negative RA (ACPA– RA).
• ACPA can be detected in circulation years before the onset of clinical overt symptoms, and the
presence of ACPA usually associates with more aggressive bone and joint destruction, suggesting the
citrulline-specific immune response is critical in disease initiation and evolution in ACPA + RA.
• In contrast, the etiology of ACPA– RA remains largely unknown. Genetic studies have implied that
ACPA+ RA and ACPA– RA are two distinct disease entities with differential underlying pathophysiology.
• There also lies some differences in clinical characteristics between the two subsets. It's showed that
ACPA– RA had more tender joints, more difficulty in clenching fists and shorter symptom duration at
the time of first presentation with arthralgia compared to ACPA + RA, but ACPA+ RA progressed to
arthritis more quickly thereafter.
• As for extra-articular manifestations, a lower probability was reported in ACPA – RA.
The presence, absence, titers, and isotypes of rheumatoid factors have
important implications for the diagnosis and prognosis of rheumatoid
arthritis. The seropositive patients (RF-positive) with RA may experience
more aggressive and erosive joint disease and extra-articular
manifestations such as rheumatoid nodules and vasculitis than those
who are seronegative (RF-negative). Similarly, the high titers of RF would
lead to a greater likelihood of a patient having RA and probably a poorer
prognosis. Also, patients with RA have different timing of appearance of
RF. Some patients actually develop RF preceding the symptomatic
disease. The earlier onset of RF in such patients has been associated with
more severe disease.