Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune, chronic,

inflammatory, systemic disease primarily affecting the
synovial lining of joints as well as other connective tissue.
It is characterized by a fluctuating course, with periods of
active disease and remission. The onset and progression
vary from mild joint symptoms with aching and stiffness to
abrupt swelling, stiffness, and progressive deformity.

Pathophysiology
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory
disease with unknown origin that is primarily localised in the
peripheral joints. In addition, the structures around the joints are
often affected, such as tendons, bursae and muscle attachment
sites. Because RA is a systemic condition, organs such as the skin,
heart and
lungs can also be involved in the disease process. In rarer cases,
there may be general symptoms such as fever, malaise and weight
loss.
Inflammation of the synovial tissue is also characteristic of RA. The
synovium forms the covering layer in parts of the joint that are
not covered with cartilage and supplies avascular structures with
nutrients. Synovial tissue is also found in the tendons and the
bursae. The synovial tissue is greatly thickened and inflamed in RA
patients. This hypertrophied synovium is called pannus. Where this
inflamed tissue becomes locally ingrown in the transition between
the synovium and the cartilage damage to the cartilage and bone
develops, a bone destruction that ultimately results in erosions of
the bone.
In addition to localised damage, diffuse breakdown of the cartilage
occurs. This breakdown is the result of the enzymes produced by
the inflamed synovium. Disrupted cartilage production also occurs.
Combined, all of this results in a thinner layer of cartilage.
Periarticular symptoms that can occur as a result of the thickened
or inflamed synovial tissue are bursitis, tendinitis or

tendovaginitis.

A.2.2 Risk factors for disease development

RA is generally considered to be an immune-mediated disease
with unknown origin. Supposedly, the immune system becomes
disrupted due to a combination of genetic predisposition and
environmental factors, such as smoking or an infection. In both
cases, inflammatory proteins are released that cause other inflammation
in the joints.

Clinical presentation
Inflammation of the joints (arthritis) is the main symptom of RA.
Characteristic for the onset of RA is a chronic, symmetrical arthritis
 yof primarily the joints of the hands and fingers (metacarpophalangeal
[MCP] and proximal interphalangeal [PIP] joints) and feet
(metatarsophalangeal [MTP] joints). All other peripheral joints, the
jaw (temporomandibular joints) and the atlanto-axial joint (C1-C2)
in the neck (cervical spine) can be involved in the disease process.
Extra-articular synovial structures, such as ligaments, bursae and
tendons, can also be involved in the disease process, such as the
bursae around the elbow and the shoulder, the trochanter major
of the femur or the Achilles tendon and the flexor and extensor
tendons of the hand.
Inflammation of the synovium causes localised pain, swelling and
stiffness, which lead to limited range of motion of the affected
joints. Joint inflammation can damage the bone and cartilage
and the periarticular structures, which in time becomes visible
on X-ray as erosive abnormalities or loss of cartilage. In part due
to the damage to the collagen structures such as ligaments and
tendons (e.g. ruptures), joint instability and/or joint deformation
may occur. Due to treatment with medication, the characteristic RA
deformities of the fingers and wrist are occurring less and less: in
the fingers, the ulnar deviation of the MCP joints, the ‘swan neck’
deformity (hyperextension of the PIP joint with flexion of the distal
interphalangeal [DIP] joint) or the ‘boutonnière’ deformity (flexion
of the PIP joint and hyperextension of the DIP joint), and in the
wrist, a misalignment caused by radial sliding of the carpus relative
to the radius. One current rare complication is the destruction of
the dens and the transverse ligament, whereby subluxation of the
first relative to the second cervical vertebra can cause compression
of the spinal cord, which can lead to a (sometimes serious) neurological
deficit.
In addition to localised pain and stiffness, general symptoms
often occur, such as generalised morning stiffness and fatigue. The
muscle strength, muscle endurance and aerobic (cardiorespiratory)
capacity are generally reduced in RA patients.
Relatively frequently RA is paired with Sjögren’s syndrome, which is
characterised by decreased function of the mucous membranes (dry
mouth) and tear ducts (dry eyes). Involvement of the organs, in the
form of pericarditis, pleuritis or rheumatoid nodules in the skin,
lungs or heart, is relatively rare. The same applies to inflammation
of the blood cells (vasculitis) which, depending on the location
and extent of the inflammation, can lead to various abnormalities,
such as renal impairment, neuropathies and skin disorders (ulcers).
Comorbidity occurs relatively frequently with RA. This can occur as a
result of (complications of) the disease and/or medication use and/
or can occur independently of RA. Patients with RA have an increased
chance of certain lymphomas and infections and – in part
related to the inflammatory nature of the disease – an increased
cardiovascular risk. In addition, RA patients also have other disorders,
just as in the general population. Cross-section research has
shown that depression, malignancies, asthma, chronic obstructive
pulmonary disease (COPD), osteoporosis, diabetes mellitus and
secondary osteoarthritis are frequent co-morbidities (either related
to RA or not).

Diagnosis
The RA diagnosis is made by the rheumatologist based on the
medical history taking and a physical exam, supplemented by
laboratory and radiological tests. In 80-90% of RA patients blood
tests show an acute phase response (presence of acute inflammatory
protein), characterised by increased C-reactive protein (CRP),
increased blood sedimentation, thrombocytosis and anaemia.
Rheumatoid factors are found in about 80% of RA patients. There
are three types of rheumatoid factors: IgA, IgG and IgM, with the
latter being the most frequent. Antibodies against cyclic citrullinated
peptides (CCPs) are also found – virtually exclusively in patients
with RA. These can be demonstrated with the help of an anti-CCP
test. Laboratory testing of synovial fluid is primarily done to rule
out other disorders, such as crystal arthritis or septic arthritis.
Some time after disease onset, characteristic radiological abnormalities
(periarticular decalcification, cartilage loss and erosive
abnormalities of the bone) can be demonstrated on X-rays. These
characteristic radiological abnormalities are often first seen in the
joints of the hands (MCP joints) and the feet (MTP joints). Inflammatory
symptoms in the joints (hydrops and capsule swelling)
and of the structures around the joints (bursae and tendons) can
be shown with the help of echography and magnetic resonance
imaging (MRI).
Classification criteria for RA were developed in order to classify the
illness, thereby enabling scientific research. These criteria are not
suitable for early treatment of patients with RA in daily practice.
When a patient presents with joint inflammation that does not
(yet) meet the classification criteria, an assessment is made as to
whether this is a case of developing RA or another form of arthritis
(such as viral arthritis, reactive arthritis or crystal arthritis [or gout],
Lyme arthritis or septic arthritis)

Classifi cation criteria for RA according to the American College of Rheumatology (ACR).
The diagnosis of RA is made if patients
meet at least 4 of the 7 criteria, with criteria 1 to 4 having been met for at least 6 weeks.
Criterion Defi nition
1 morning stiffness - stiffness of the joints that does not disappear completely within one
hour
2 arthritis in three or more joints - swelling or hydrops Identifi ed by a doctor
3 arthritis in the joints of the hand - swelling or hydrops in the wrist, metacarpophalangeal or
proximal interphalangeal joints
4 symmetric arthritis - simultaneous infl ammation of identical joints on both sides of the
body
5 nodules - subcutaneous or periosteal nodules identifi ed by a doctor
6 rheumatoid factors - presence of antibodies against IgG in the serum, as shown by an
agglutination test
7 radiographic changes - presence of erosions on radiographs of the hands and wrists
Determination of the disease activity
Remission: DAS28 < 2.6
Low disease activity: DAS28 = 2.6-3.2
Moderate disease activity: DAS28 = 3.2-5.1
High disease activity: DAS28 > 5.1

Principles of Management—Active
Inflammatory Period of RA
Management guidelines are summarized in Box 11.2.
Joint protection. Because periods of active disease may
last several months to more than a year, education in the
overall treatment plan, safe activity, and joint protection
(Box 11.3) begins as soon as possible.34 It is imperative
to involve the patient in the management so he or she
learns how to conserve energy and avoid potential
deforming stresses during activities and when exercising.

Principles of Joint Protection30,49

• Monitor activities and stop when discomfort or fatigue
begins to develop.
• Use frequent but short episodes of exercise (three to five
sessions per day) rather than one long session.
• Alternate activities to avoid fatigue.
• Decrease level of activities or omit provoking activities if
joint pain develops and persists for more than 1 hour
after activity.
• Maintain a functional level of joint ROM and muscular
strength and endurance.
• Balance work and rest to avoid muscular and total body
fatigue.
• Increase rest during flares of the disease.
• Avoid deforming positions.
• Avoid prolonged static positioning; change positions during
the day every 20 to 30 minutes.
• Use stronger and larger muscles and joints during activities
whenever possible.
• Use appropriate adaptive equipment.

Energy conservation. It is important that the patient

learns to respect fatigue and, when tired, rests to minimize
undue stress to all the body systems. Because
inflamed joints are easily damaged and rest is encouraged
to protect the joints, the patient is taught how to
rest the joints in nondeforming positions and to intersperse
rest with ROM.
Joint mobility. Gentle grade I and II distraction and
oscillation techniques are used to inhibit pain and minimize
fluid stasis. Stretching techniques are not performed
when joints are swollen.
Exercise. The type and intensity of exercise varies
depending on the symptoms. The patient is encouraged
to do active exercises through as much range of motion
(ROM) as possible (not stretching). If active exercises
are not tolerated owing to pain and swelling, passive
ROM is used. Once symptoms of pain and signs of
swelling are controlled with medication, exercises can
progress as if subacute.

Functional training. Activities of daily living (ADL)

may need to be modified in order to protect the joints. If
necessary, splints and assistive devices should be used to
provide protection.

Principles of Management—Subacute
and Chronic Stages of RA
As the intensity of pain, joint swelling, morning stiffness,
and systemic effects diminish, the disease is considered
subacute. Often medications can decrease the acute symptoms
so the patient can function as if in the subacute stage.
The chronic stage occurs between exacerbations. This may
be very short in duration, or it may last many years.
The treatment approach is the same as with any subacute
and chronic musculoskeletal disorder, except appropriate
precautions must be taken because the pathological
changes from the disease process make the parts more susceptible
to damage.
To improve function, exercise should be aimed at
improving flexibility, muscle performance, and cardiopulmonary
endurance.13
Nonimpact or low-impact conditioning exercises such
as swimming and bicycling, performed within the tolerance
of the individual with RA, improve aerobic capacity
and physical activity and decrease depression and
anxiety.6,39,77 Group activities such as water aerobics also
provide social support in conjunction with the activity.
P R E C A U T I O N S : The joint capsule, ligaments, and
tendons may be structurally weakened by the rheumatic
process (also as a result of using steroids), so the dosage
of stretching and joint mobilization techniques used to
counter any contractures or adhesions must be carefully
graded.
C O N T R A I N D I C A T I O N S : Vigorous stretching or
manipulative techniques.

Dutch physical activity guidelines

• Exercise is good; more exercise is better.
• Do at least 150 minutes per week of moderately intensive
exercise, such as walking or biking, spread out over several
days. Longer, more frequent and/or more intensive exercise
has an additional health benefit.
• Perform muscle and bone strengthening activities at least
twice per week, combined with balance exercises in the
case of elderly patients.
• Avoid sitting still too much

B.5 Contraindications for exercise therapy

[Explanation: see Note 8]
There are absolute contraindications for exercise therapy in the
following RA-related medical situations:
• fever; and/or
• a spinal column fracture; and/or
• arthrogenic instability of the cervical spine; and/or
• a recent tendon rupture (especially for exercise therapy in the
area where the rupture occurred).
B.6 Yellow and red flags
[Explanation: see Note 8]
The therapist might indicate yellow and/or red flags. Yellow flags
are indications of psychosocial or behavioural risk factors for maintaining
and/or exacerbating the health problems related to RA. Red
flags are patterns of symptoms (warning signals) which could point
to severe pathology and which may warrant additional medical
diagnosis. The therapist can point out these yellow and red flags
during the screening – based on direct access (without a referral
for physical therapy or exercise therapy) – but yellow and red flags
can also occur over the course of the treatment.
During treatment, the therapist must take yellow flags into
account; but yellow flags can also be a reason to consider - in
consultation with the GP - involving another healthcare provider.
The pattern of symptoms for RA is specific. The therapist must know
this pattern in order to indicate red flags that do not fit this
pattern.

The recommended measurement instrumentsc for supporting the diagnostic process and
evaluating the treatment
in RA patients are:
• a Numeric Rating Scale (NRS) for fatigue;[2]
• a Numeric Pain Rating Scale (NPRS);[2]
• the Borg Rating of Perceived Exertion Scale (Borg RPE scale 6-20);[3,4]
• the Dutch Consensus Health Assessment Questionnaire Disability Index (HAQ-DI);[5,6]
• the Patient-Specific Complaints (PSC); [7]
• the Six Minute Walking Test (6MINWT).[8-10]
When assessing the various aspects of physical functioning, preference is given to a
combined application of a
self-reported questionnaire and a performance-based test.

Optional measurement instruments can be chosen based on clinical reasons for supporting the
diagnostic
process and for evaluation.
Optional measurement instruments are:
Functions and anatomical characteristics
• The Hand Held Dynamometer (HHD). This measurement instrument can be used to
measure grip strength
as a gauge for the general muscle strength.[11]
• A submaximal strength test. This test should be used to determine the training intensity if a
weight lifting
machine is used during the muscle strength measurement.[12-14] For example, a submaximal
1RM test,
where 1RM can be estimated with the help of the Holten diagram.[25]
Activities
• The Quick DASH can be used to determine the degree of limitations in the entire upper
extremities if there
are complaints of the shoulder and/or arm and/or hand.[15,16]
• The accelerometer or pedometer can be used to evaluate physical activity during the day or
week. The accelerometer
is suitable for supporting the facilitation of an active lifestyle, for example in order to comply
with the exercise guidelines.[17]
• The MET method shows the metabolic load of various motor activities and can be used to
estimate the
patient’s exercise capacity.[18]
Participation
• The Work Productivity and Activity Impairment questionnaire [WPAI]). This questionnaire
can be used if
you want to know the extent to which health problems resulting from RA impede specific
aspects of work
performance.[19]
Personal factors
• The Rheumatoid Arthritis Quality of Life (RAQoL). This questionnaire can be used to get
an idea of the
quality of life and to what extent quality of life is influenced by the treatment. The RAQoL is
suitable for
the ‘quality of life improvement’ goal.[20]
• The International Physical Activity Questionnaire - Short Form (IPAQ-SF) is the shortened
version of the
IPAQ. The IPAQ-SF can be used to estimate the activity level.[21,22]
• Compliance with the exercise guidelines. An evaluation can be performed to see whether
someone meets
the ‘Dutch physical activity guidelines’.[23]
Table 7.1 offers an interpretation, per measurement instrument, of the outcome and the
clinically relevant
difference as a gauge for monitoring the progress of the treatment. The clinically relevant
difference is based
on the minimal clinically important difference (MCID) for RA patients. If the MCID with RA
is unknown, the MCID
for another patient population is given or – based on the literature – the MCID is 30%.[24]

KNGF guideline Rheumatoid arthritis Practice guideline

Overview of relevant questions when taking the history of patients with RA*
General
• What is the patient’s need for assistance? (Patient-Specific Complaints; PSC)
• What are the expectations regarding physical or exercise therapy?
• What are the expectations regarding the progression of the symptoms?
Functions and anatomical characteristics
Is there:
• pain in one or more joints? (Numeric Pain Rating Scale [NPRS]) What is de location of the
pain (which joints)? Is the pain related to
exertion? What is the progression of the pain in the morning, afternoon, evening or night
time?
• inexplicable, persistent severe pain and/or inflammatory symptoms in one or more joints?
(Potential red flag)
• morning stiffness and/or start-up stiffness? If so, for how long?
• swelling of one or more joints? If so, which joints?
• limited range of motion and/or stiffness in one or more joints? If so, which joints?
• fatigue? (Numeric Rating Scale for fatigue; NRS fatigue)
• reduced muscle strength? If so, where and during which activities?
• decreased endurance?
• skin problems (ulcers) or nail fold infarcts that may be associated with RA?
• problems when chewing or swallowing?
• dry mouth and/or dry eyes, for example as a result of Sjögren’s syndrome
• high blood pressure? (cardiovascular risk factor)
• high cholesterol? (cardiovascular risk factor)
• neck pain and/or pain in the back of the head, in combination with paraesthesia and/or
dysesthesia, motor deficit, ‘twitching’
legs, and/or a sandy feeling in the hands? (neurological symptoms that could indicate a red
flag)
• sensory disorders? (potential red flags)
• balance problems? (potential red flags)
• sleep problems?
• sudden increase of symptoms or an acute RA flare-up? (potential red flag)
• severe back pain, possibly after a fall? (potential red flag with osteoporosis and [long-term]
corticosteroid use)
• signs of infection somewhere other than in the joints, possibly accompanied by fever and/or
general malaise? (potential red flag
with the use of biologicals)
The text box below contains examples of relevant questions when taking a patient’s history.
The questions can be adapted to suit the
therapist’s communication style and the patient’s communication level.
V-20/2018 5
KNGF guideline Rheumatoid arthritis Practice guideline
Activities (PSC)
• Are there limitations to performing activities of daily living and/or functions such as:
- changing posture (for example, turning around in bed, getting up from bed, sitting down);
- self-care, such as getting dressed and undressed, showering, combing the hair (optional
measurement instrument for arm and
hand function; Quick-DASH);
- walking (at home or outside), climbing stairs;
- picking up items from the ground;
- writing or other fine motor activities;
- eating and/or drinking;
- cycling, driving a car or using public transportation;
- sexual activities.
• Does the patient meet the ‘Dutch physical activity guidelines’? (see section A.5.2)
- If so, with which activities and for how many minutes per week?
- If not, what is the most important impeding factor? Which degree of physical activity is
achieved? With which activities and for
how many minutes per week? (optional measurement instrument: accelerometer/pedometer
or the MET method).
Participation
• What is the family situation? (in order to assess the daily exertion compared to the capacity)
Are there limitations resulting from the symptoms in:
• relationships and/or social contacts?
• paid or volunteer work? (optional measurement instrument: Work Productivity and Activity
Impairment questionnaire [WPAI])
• free time, e.g. when playing sports or engaging in hobbies?
• quality of life (optional measurement instrument: RA Quality of Life Questionnaire
[RAQol])
External factors
• Is there a family history of RA?
• Is there a family history of cardiovascular disease?
• How do the people surrounding the patient (partner, family, friends, co-workers) respond to
the symptoms?
• What is the patient’s living situation? Are there stairs in the house and how does the patient
do climbing these stairs?
• Does the patient use medication? If so, which ones? What is the effect of the medication?
Are there side effects? If so, which ones?
• Has the patient previously undergone physical or exercise therapy for RA? If so, what was
the result?
• Other than the rheumatologist, is there another medical specialist or other healthcare
provider involved with the patient for
treating the RA or related comorbidity?
• Does the patient use modifications, aids or facilities for activities of daily living or
household tasks? How about at work or during
sport or leisure activities?
• Does the patient use a walking aid? If so, what is the effect?
• Does the patient use an aid to perform activities? (standing support, stand-up chair, wheeled
stool, knee support)? If so, what is
the effect?
• Has any surgery been performed in the past (for example, joint replacement surgery or
tendon surgery)? If so, how long ago did this
take place and how did the recovery progress?
Personal factors
• What are the patient’s views regarding exercise?
• How does the patient handle the complaints in his/her daily life? Among other things,
measures the patient has undertaken to
influence his/her complaints, such as resting/exercise, and are these helping?
Is there:
• comorbidity? If so, which ones? Does this influence the patient’s functional movement
and/or exercise capacity?
• overweight? (cardiovascular risk factor)
• smoking? If so, how much does the patient smoke? (cardiovascular risk factor)
• facilitating or inhibiting factors towards exercise? If so, which ones?
• a need for information about RA and the treatment?
• fear, for example of falling?
* Possible contraindications, yellow and red flags, risk factors, prognostic factors and
measurement instruments are listed in
parentheses.
V-20/2018 6
B.2 Physical examination
[Explanation: see Note 6]
The physical examination of the RA patient consists of evaluating
(the quality of) physical activity in relation to the limitations in
activities. As with the history taking, this is done using the ICF Core
Set for rheumatoid arthritis. The physical examination provides
information about the presence of risk factors for an unfavourable
progression (section A.5), contraindications for exercise therapy
(section B.5) and yellow and red flags (section B.6), based on
which the treatable quantities can be determined. An overview
of relevant points of attention for the physical examination of
patients with RA is provided in the text box below.
Relevant points of attention during the physical examination of patients with RA
Functions and anatomical characteristics
Inspection
• Where is the pain reported (which joints)? During which movement(s) does the pain occur
in the respective joints?
• Is there any swelling of the respective joints? If so, which joint(s) and to which degree
(slight, moderate or severe). Is the swelling
diffuse or localised?
• Are there changes in position or deformities of the joint(s), in particular the hands, wrists or
feet? (see section A.3).
Palpation
• Is there any swelling of the joints or surrounding structures (e.g. tendons, bursae)?
• Is there any temperature increase of the joint(s)?
• Is palpation painful?
Functional examination
• Active movement examination:
- determination of the range of motion of all joints of the upper and lower extremities and of
the cervical spine in all directions;
- assessment of the combined shoulder and elbow function by having the patient perform
several combined movements (for
example, the hair combing movement).
• Passive movement examination of the joints with limited range of motion that was
determined during the active movement
examination
Assessment of:
• the muscle weakness and muscle endurance of the upper and lower extremities;
• the active and passive stability, muscle length and proprioception;
• the static and dynamic balance;
• the sensitivity of primarily the upper extremities (potential red flag);
• the hand function (movement examination), but also coordination, gripping function and the
functioning of the flexor and
extensor tendons in the hand (including tendon gliding);
• the physical functioning (Six Minute Walking Test (6MINWT)) is a supporting functional
test to estimate the physical functioning and
to use as a baseline measurement for the treatment);
• the aerobic capacity (for example, with the help of the Borg scale (6-20) or the heart rate).
Activities
Inspection
Assessment of:
• the gait pattern; such as heel strike, ankle function, knee function (is there a flexion
contracture, for example?) and hip function
(is there a Trendelenburg, for example?), trunk rotation and arm function;
• the quality of movement during functional activities, such as standing, getting up and sitting
down, bending, transfers, getting
(un)dressed, walking up/down stairs, reaching and gripping, picking something up from the
floor and writing;
• specific activities that are restricted during work, sports or other leisure activities;
• use of aids;
• performance of other specific activities where symptoms are reported