Source: GUIPCAR Group. Clinical practice guideline for the management of rheumatoid arthritis. Quick
Reference Guide. Madrid: Spanish Society of Rheumatology; 2001. 19 p.
CLINICAL PRACTICE GUIDELINE FOR THE
MANAGEMENT OF RHEUMATOID
QUICK REFERENCE GUIDE
DIAGNOSING RHEUMATOID ARTHRITIS
CLASSIFYING RHEUMATOID ARTHRITIS
MEDICAL TREATMENT OF RHEUMATOID ARTHRITIS
CRITERIA FOR RESPONSE TO TREATMENT
EXTRA-ARTICULAR COMPLICATIONS OF RHEUMATOID ARTHRITIS
In 1998 the Spanish Society of Rheumatology (SER) decided to develop a Clinical Practice Guideline
(CPG) to help physicians make decisions about the diagnosis and treatment of patients with
rheumatoid arthritis (RA). This initiative of the SER was in response to a phenomenon frequently seen
in clinical practice: the large variability in the use of diagnostic, therapeutic and rehabilitative
procedures. The enormous amount of information produced as a result of a growing number of studies,
their variable methodological quality, and the complexity of comparing the results of different studies
constitute a major obstacle for clinicians in keeping up to date on important knowledge in their field.
This situation prompted the idea of producing a CPG for the management of RA (GUIPCAR), which
was undertaken by the Health Services Research Unit (UISS) of the Carlos III Health Institute. This
project took 2 years to complete. During this time, the UISS became a private company with the name
of Advanced Research Techniques in the Health Services (TAISS).
RA is a systemic disease, of unknown etiology, which is characterized by chronic inflammation of the
diarthrodial joints and is usually associated with severe morbidity. It is estimated to affect some
200,000 persons in Spain, with 20,000 new cases occurring each year. The quality of life is reduced in
most patients, who usually experience changes in functional capacity, with work disability and
RA also produces an enormous social cost. It has been estimated that the annual cost of this disease
in Spain exceeds 200 billion pesetas (US$1.04 million), of which 65 billion pesetas ($338.5 million) are
devoted to health expenditures.
There is evidence of large variability in the management of RA in Spain; this variability depends not
only on patient or disease characteristics, but also on characteristics of the hospital, department, or
physician providing patient care. For example, the mean number of patient visits in one center may be
double that of another, after adjusting for disease severity and functional class. Even more variability
has been seen in other areas, such as the use of diagnostic tests or management of treatment. These
facts may suggest that some diagnostic or therapeutic procedures are of uncertain value while other,
appropriate procedures may be underused.
The main objective of this guideline is to develop high quality criteria for the treatment of RA and to
reduce the variability that is not dependent on patient characteristics.
Contents and Methodology
This guideline describes the diagnostic and management strategies that an expert panel considered
appropriate for the evaluation and treatment of patients with RA. It focuses on RA in adults (excluding
juvenile RA) and includes diagnosis, evaluation, prognosis, and treatments such as drugs,
rehabilitation, and surgery. It does not cover other treatments such as acupuncture, and only briefly
treats extra-articular complications of RA such as amyloidosis, anemia, or Sjögren’s syndrome.
The guideline recommendations can be applied in both the hospital and outpatient setting except for
some, such as the guidelines for surgery, which obviously can only be performed in specialized
centers. This guideline is intended for rheumatologists and recommends that the diagnosis, monitoring,
and treatment of RA be carried out by physicians who are trained to identify patients in the early
phases of disease, to evaluate the disease stage, to suggest appropriate treatment for each stage in
the evolution of the disease, and to measure the response to treatment.
The recommendations for treatment with disease-modifying anti-rheumatic drugs (DMARDs) in this
guideline are based on a synthesis of the best available scientific evidence after making a systematic
review of the literature. The rest of the recommendations or considerations are based on scientific
evidence obtained without a systematic literature review, or on the opinions of the expert panel.
Using the Quick Reference Guide
This quick reference guide describes the most important recommendations contained in the guideline.
The recommendations are presented in this summary in an abbreviated form. Readers should refer to
the text of the guideline to see the complete recommendation, discussion, levels of evidence, and
bibliographic references. This quick reference guide includes a
. The algorithms
included at the end of the guideline allow the user to follow a logical decision-making process in
managing the patient.
DIAGNOSING RHEUMATOID ARTHRITIS
RA should be suspected in patients over 16 years of age who have joint inflammation or
effusion of more than 6 weeks duration in three or more joints, preferably of the hands and feet.
To date, the only universally accepted and used diagnostic criteria for RA are those proposed
by the American College of Rheumatology (ACR) for classification of the disease.
According to the ACR, the diagnosis of RA requires confirmation of at least four of the following criteria:
1. Morning stiffness lasting at least one hour before maximal improvement, for at least 6
2. Soft tissue swelling or effusion, observed by a physician, in at least three of the following joint
areas (right or left): proximal interphalangeal (PIP), metacarpophalangeal (MCP), wrist, elbow,
knee, ankle, or metatarsophalangeal (MTP) joints, for at least 6 consecutive weeks.
3. Swelling or effusion, observed by a physician, in the proximal interphalangeal,
metacarpophalangeal, or wrist joints, for at least 6 consecutive weeks.
4. Symmetrical (right and left sides) swelling or fluid in the joints mentioned in point 2, observed
by a physician, for at least 6 consecutive weeks.
5. Subcutaneous nodules over bony prominences or extensor surfaces, or in juxta-articular
regions, observed by a physician.
6. Demonstration of serum rheumatoid factor (RF) detected by any method that has been positive
in less than 5% of control subjects.
7. Radiographic evidence in the hands or wrists of articular erosions or osteopenia in or around
the affected joints.
Patients with RA should be evaluated and treated by physicians who are familiar with the
clinical management and treatment of the disease.
The initial evaluation of a patient with RA should include a clinical history and physical
clinical history should include background information that is important for RA diagnosis and
treatment, including previous diseases, life style, gynecological history, and occupation. If the patient
has been diagnosed with RA, the history should describe the clinical characteristics of the disease
obtained by patient interview and by reviewing reports and other documents provided by the patient
such as radiographs and laboratory tests. An understanding of how RA has evolved requires
knowledge of all types of previous and concurrent treatments, especially with analgesics, NSAIDs,
corticosteroids, and DMARDs, including the dosage, duration, reasons for withdrawal, tolerance, and
physical examination, note should be taken of the presence of pain, joint inflammation,
deformities, and subcutaneous nodules.
The evaluation and monitoring of RA should be based on a systematic evaluation of a minimum
set of parameters including joint pain and inflammation, the patient’s global assessment of
pain, global assessment of disease, functional disability, acute phase reactants, and radiologic
evidence of damage.
Validated methods should be used to assess the number of painful joints and the number of
swollen joints. Although the clinician will consider different factors in the choice of which index to use,
this guideline recommends the ACR count.
The articular indices assess the degree of pain and swelling by counting the number of painful joints
and the number of swollen joints. Different methods have been described, varying in the number of
joints evaluated, although only four are in widespread use: the ACR count, Ritchie index, 44-joint index,
and 28-joint index.
ACR count. The ACR count is considered to be the most complete index and is the US standard. It
includes an evaluation of tenderness in 68 joints and swelling in 66 joints (excluding both hips). The
following joints are assessed: distal interphalangeal, proximal interphalangeal, metacarpophalangeal,
wrist, elbow, shoulder, acromioclavicular, sternoclavicular, temporomandibular, hip (only for pain),
knee, ankle, subtalar, metatarsophalangeal, and proximal interphalangeal joints.
The subjective experience of pain should be assessed by the patient. It is recommended that
pain be measured using a horizontal visual analog scale, 10 cm in length, divided by vertical
marks into ten equal 1-cm segments. The measurements should be accompanied by numeric
descriptors from 0 to 10, with indicators at each end showing no pain (0) and worst pain (10).
A global assessment of disease should be made from the medical point of view and another
one from the patient’s point of view. For this measurement, the use of a 10 cm horizontal visual
analog scale is recommended, with vertical marks dividing it into 10 equal 1-cm segments. The
measurements should be accompanied by numeric descriptors from 0 to 10, indicating at each
end "very good" (0) and "very poor" (10).
Global disease assessments by both the physician and the patient are useful because their evaluations
may be quite different. The global assessment is very sensitive to clinical changes.
Self-perceived functional disability attributed to the disease should be evaluated using specific,
previously validated questionnaires such as the Health Assessment Questionnaire (HAQ).
There are various ways to estimate functional capacity based on joint mobility or the ability to perform
certain tasks as evaluated by an observer. The most widespread methods currently used consist of
specific questionnaires for rheumatic disease such as the HAQ or its abbreviated form, the Modified
Health Assessment Questionnaire (MHAQ), or the Arthritis Impact Measurement Scale (AIMS). They
are based on the patient’s own opinion about his or her disease. These questionnaires are
standardized instruments of proven validity and reliability. They evaluate those health dimensions that
are most affected by RA, particularly disability, especially in relation to physical function, and pain.
This guideline recommends the use of the HAQ, a 19-item self-administered questionnaire that
evaluates self-perceived physical disability to perform different activities of daily living grouped into
eight areas: dressing and grooming, rising, eating, walking, hygiene, reaching, gripping, and other
Laboratory tests should include the acute phase reactants (APRs) erythrocyte sedimentation
rate (ESR) and C-reactive protein (CRP). These two APRs are good indicators of the
inflammatory activity of the disease.
Laboratory tests should consist of a complete blood count, acute phase reactants (ESR, CRP),
rheumatoid factor (RF), liver function (GOT, GPT, GGT, alkaline phosphate, albumin), kidney function
(creatinine), calcium, and urinalysis. The presence of hepatitis B and C virus should be evaluated (in
relation to the hepatotoxicity of some of the drugs used in treatment).
These basic tests will facilitate RA monitoring and early detection of disease complications and side
effects of treatment. Whether to include other, complementary tests is left to the judgment of the
Radiographs of the hands, feet, and chest are recommended at the initial evaluation.
Radiographs of the feet and hands should be repeated annually for the first 3 years of disease
evolution, and thereafter as deemed appropriate.
The radiographs should be examined for the presence of bony erosions, which are more frequent at
disease onset. About 70% of patients have erosions of the hands or feet by the end of the first 2 or 3
years. Their presence and the speed of onset are associated with poorer outcome. Radiographs of
both hands and feet are justified by the fact that asymmetrical erosions (right or left) may appear, and
by the observation that in the first 2-3 years of the disease, erosions appear only on the feet, without
clinical symptoms, in up to 23-36% of patients.
A chest X-ray is recommended for initial evaluation and to identify the appearance of possible problems
during the course of the disease and its treatment.
The use of a composite index of disease activity, summarizing various parameters in a single
indicator, is a useful and valid procedure in assessing disease activity. As calculating such an
index can be time consuming, this guideline leaves its use to the judgment of the individual
rheumatologist. If one of these indices is used, however, this guideline recommends the
Disease Activity Score (DAS), in any of its versions.
These indices differ in the number of parameters included as well as in the methods used for their
calculation. Their advantages in comparison to conventional evaluation using single parameters are
that they avoid duplicate measurements and are more sensitive to change. Their disadvantages are a
certain degree of complexity in the calculations, difficulty of interpretation, and some problems related
with how they are constructed.
The DAS includes the Ritchie index (see description in the guideline), the number of swollen joints out
of 44 joints (NSJ44), ESR, and the patient’s global assessment of disease (PGA) on a visual analog
scale (0 cm "very good" - 10 cm "very poor"). The DAS is calculated using the following formula: