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• RA has an annual incidence of approximately 0.4 per
1000 in females and 0.2 per 1000 in males.
• A prevalence of 0.4% to 1% is reported in diverse
• Twin and family studies demonstrate a heritability of
60%; approximately 30% of genetic risk is attributed
to the shared epitope encoded on the human
leukocyte antigen molecules.
• Hormonal and reproductive factors contribute to the
female excess and parity, breast feeding, and
exogenous hormones are modifiers of risk.
• Smoking is the strongest known environmental risk
factor for RA; other lifestyle factors and exposures
such as alcohol, antioxidant intake, and traffic
pollution may also play a role.
THE 1987 ACR CRITERIA
- Morning stiffness in and
around the joints,
- Lasting at least 1 hour
2.Arthritis in three or more
• Soft tissue swelling or fluid (not
bony overgrowth) observed by a
physician presenting simultaneously
for at least 6 weeks.
• Possible areas: right or left
3.Arthritis of hand joints
• Swelling of :
- wrist and
- metacarpophalangeal or
- proximal interphalangeal joints
for at least 6 weeks.
• Simultaneous involvement of the same joint areas
(defined in 2) on both sides of the body (bilateral
involvement of proximal interphalangeal, metacarpophalangeal, or
metatarsophalangeal joints is acceptable without absolute symmetry) for
at least 6 weeks.
• Subcutaneous nodules
- bony prominences,
- extensor surfaces, or
- in juxta-articular regions,
observed by a physician.
• Detected by a method that is positive in fewer than
5% of normal controls.
• Typical of RA on posteroanterior hand and wrist
• they must include:
- erosions or
- unequivocal bony decalcification localized in or most
marked adjacent to the involved joints (OA changes
alone do not qualify).
A) AR 8 meses. Erosiones en todas MTF
B) AR 5 años. Desorganización articular.
OA: Joint space loss tends to be
assymetrical. Subchondral sclerosis,
geodes and osteophytes become more
prominent with time.
Please note that a marginal osteophytes
can simulate an erosion immediately
above or below.
Knee X-rays in advanced inflammatory
arthritis. Note that joint space loss is
homogeneous and symmetrical. There is
subchondral osteopenia (as opposed to
sclerosis) and erosions can be present .
At least four criteria must be fulfilled for
classification of RA;
patients with two clinical diagnoses are not excluded.
(mean duration of symptoms, 7.7 years)
Morning stiffness in and around the joints, lasting at least 1 hour before
2.Arthritis in three or more joint areas
Soft tissue swelling or fluid (not bony overgrowth) observed by a physician
presenting simultaneously for at least 6 weeks
3.Arthritis of hand joints
Swelling of wrist and metacarpophalangeal or proximal interphalangeal joints
for at least 6 weeks
Simultaneous involvement of the same joint areas (defined in 2, above) on
both sides of the body (bilateral involvement of proximal interphalangeal,
metacarpophalangeal, or metatarsophalangeal joints is acceptable without
absolute symmetry) for at least 6 weeks
Subcutaneous nodules over bony prominences, extensor surfaces, or in juxta-articular
regions, observed by a physician
6.Rheumatoid factor Detected by a method that is positive in fewer than 5% of normal controls
Typical of RA on posteroanterior hand and wrist radiographs; they must
include erosions or unequivocal bony decalcification localized in or most
marked adjacent to the involved joints (OA changes alone do not qualify)
Impact on classification of antibodies to
citrullinated peptides (ACPA)
• ACPA may be involved in the pathogenesis of the
disease, and have been shown to be a more specific
marker for RA than RF, particularly for subjects with
• In early RA, the specificity of ACPA ranges from 94% to
100% compared with RF, in which the specificity ranges
from 23% to 96%; the sensitivity of RF and ACPA are
equivalent in both early and long-duration RA.
Impact on classification of antibodies to
citrullinated peptides (ACPA)
• The impact of the addition of ACPA to the existing
1987 ACR criteria to classify early RA, in which 4 of 8
rather than 4 of 7 criteria are required, results in an
increase in the sensitivity for detecting early RA.
Morning stiffness in and around the joints, lasting at least 1 hour
before maximal improvement
2.Arthritis in three or more joint areas
Soft tissue swelling or fluid (not bony overgrowth) observed by a
physician presenting simultaneously for at least 6 weeks
3.Arthritis of hand joints
Swelling of wrist and metacarpophalangeal or proximal
interphalangeal joints for at least 6 weeks
Simultaneous involvement of the same joint areas (defined in 2,
above) on both sides of the body (bilateral involvement of
proximal interphalangeal, metacarpophalangeal, or
metatarsophalangeal joints is acceptable without absolute
symmetry) for at least 6 weeks
Subcutaneous nodules over bony prominences, extensor
surfaces, or in juxta-articular regions, observed by a physician
Detected by a method that is positive in fewer than 5% of
Typical of RA on posteroanterior hand and wrist radiographs;
they must include erosions or unequivocal bony decalcification
localized in or most marked adjacent to the involved joints (OA
changes alone do not qualify)
Clinical features of rheumatoid
Morning stiffness and
symmetric swelling in
joints are the typical
• Early diagnosis of RA is critical, but many cases of
“early arthritis” are not RA.
• Anti-citrullinated peptide antibodies (ACPAs) occur
earlier than rheumatoid factor and are more specific
The hallmark of RA is
-tenderness of multiple
particularly the small
joints of the hands and feet.
• Most patients experience joint stiffness or gelling for
more than an hour in the morning.
• The blood of approximately 80% of RA patients
contains RF, an immunoglobulin binding the Fc region
of the IgG molecule.
• Rheumatoid nodules are seen in about 20% of
80% of RA patients contains RF
• Prognosis and outcome are improved when DMARD
therapy is started within a few weeks or months of
DMARDs results in
than when DMARD
delayed for even
It is well established
that erosive damage
on radiographs of the
hands and feet
develops early in the
course of RA.
• Typical sites of osseous erosion of a rheumatoid wrist shown here include triquetrum, pisiform, scaphoid, and radius. There also are erosions at
the ulnar aspect of the distal radius and the distal ulnar styloid process secondary to involvement of the inferior radioulnar compartment. Diffuse
cartilage loss also is evident in the radiocarpal compartment. (Courtesy of Dr. Barbara Weissman.)
Progression of radiographic damage occurs to a lesser
degree in patients receiving early therapy than in those
for whom therapy is delayed.
•Correlation between radiographic damage and
disability over time.
• Patients have a greater likelihood of attaining
remission with early treatment.
• The diagnosis of rheumatoid arthritis be made as
soon as possible so that DMARD treatment can be
started without delay.
In osteoarthritis (A.) joint space loss is usually focal or asymmetrical
while in inflammatory arthritis (B.) it tends to be uniform and diffuse
Clinical case “Pain in the hands (III)”. Please note that although inspection suggests joint swelling, this can only be proved by palpation.
In rheumatoid arthritis
(A.) periarticular osteopenia is an early radiological feature.
• In osteoarthritis (B.) subchondral bone sclerosis is a typical finding. Also notice the
loss of joint space in both conditions.
Nodal osteoarthritis of the hands. Discrete bony nodules around PIP
(Bouchard nodes) and DIP joints (Heberden nodes).
Nodular deformity of the finger, with deviations of one phalanx over the other in nodal
Fusiform swelling around the 2nd and 3rd proximal interphalangeal joints
AR DEFORMIDAD ARTICULAR/DESORGANIZACIÓN
• Commonly, patients will
polyarthritis (≥ 5) of the
small joints of the hands,
involvement can occur
• RF and ACPAs have been
found in up to half of
patients with RA up to 5
years before their
development of clinical
• Stiffness or gelling in the joints is present on arising,
often taking several hours to abate.
• Patients will typically report soft tissue swelling over
the knuckles and describe markedly reduced grip
• Discomfort in the feet is generally most prominent in
the metatarsal area.
Profound fatigue often accompanies the joint complaints,
and anorexia and mild weight loss may occur.
Typically, patients with RA do not present with rash, fever,
headache, visual disturbance, or pleuropericardial
• The pattern of joint involvement
in RA is typical in most cases.
- proximal interphalangeal (PIPs),
- metacarpophalangeal (MCPs),
- ankles, and
- metatarsophalangeal (MTP) joints.
Examination and clinical features
of specific joints
• Ability to recognize the manifestations of synovial
• Unlike the normal synovial lining, which is only one
or two cell layers thick, the RA synovium proliferates
out of control (pannus).
• AIJ. Leg length discrepancy due to chronic arthritis of the left
• This proliferating synovium has a “doughy” or
“squishy” feel on palpation. This finding is often
referred to as “synovitis”; however, the classic
inflammatory signs of heat and redness are usually
• Rheumatoid nodules are quite specific for RA and
occur in about 20% of patients, generally those with
more severe disease and high-titer RF.
• They occur over extensor surfaces and joints, at sites
of chronic mechanical irritation (elbow, toe, and
heel), and in the subcutaneous tissues of the fingers
• A. Rheumatoid nodules. usually
small with a regular surface.
• B. Irregular nodules with white
deposits – gouty tophy.
• Synovial cyst of the wrist. The swelling is soft on palpation.
The hand in early RA. View of the right hand, showing
swelling of the MCP and PIP joints. Swelling of the PIP
joints is typical of RA and associated with morning
stiffness, difficulty making a fist, reduced grip strength,
and tenderness of the affected joints
Palpation of the dorsal and volar aspects of the MCP and PIP
joints to detect synovial proliferation.
“Four-point” technique for palpating the small joints of the hands.
Flexor tenosynovitis is
common and may lead
to a “trigger finger.”
The flexor tendons for
the fingers pass
through a pulley near
the palmar surface of
the MCP joint.
Signs of late
subluxation at the
MCPs with “ulnar
atrophy of the
intrinsic muscles of
A, Swan neck deformity. This common deformity leads to hyperextension of the proximal interphalangeal joints and flexion of the distal interphalangeal joints.
B, Boutonnière deformity. This deformity, which is the opposite of swan neck deformity, is marked by flexion of the proximal interphalangeal joints and extension of the distal
interphalangeal joints. (Courtesy of Iain McInnes, MD.)
• Boutonnière and swan-neck deformities. The boutonnière deformity—PIP flexion and DIP hyperextension—results from
relaxation of the central slip, with “buttonholing” of the PIP joint between the lateral bands. The swan-neck deformity—
MCP flexion, PIP hyperextension, and DIP flexion—may be mobile, snapping, or fixed. Its pathogenesis may be related
primarily to PIP or MCP involvement. Combinations of MCP and PIP involvement are less frequent
A: patient with early rheumatoid arthritis. There are no joint deformities,
but the soft tissue synovial swelling around the third and fifth proximal
interphalangeal (PIP) joints is easily seen.
B: patient with advanced rheumatoid arthritis with severe joint deformities
including subluxation at the metacarpophalangeal joints and swan-neck
deformities (hyperextension at the PIP joints).
• Progressive destruction of a metacarpophalangeal joint by rheumatoid
arthritis. Shown are sequential radiographs of the same second
metacarpophalangeal joint. A: The joint is normal 1 year prior to the
development of rheumatoid arthritis. B: Six months following the onset of
rheumatoid arthritis, there is a bony erosion adjacent to the joint and
joint space narrowing. C: After 3 years of disease, diffuse loss of articular
cartilage has led to marked joint space narrowing.
• The thumb can be affected by several deformities.
Arguably the most common has been described as the
flail interphalangeal (IP) joint, in which case the
patient loses the ability to flex that joint.
• This results in significant functional impairment due
to loss of pinch strength, whereby the patient pinches
the index finger against the proximal phalanx.
• At the wrist, synovial proliferation around the ulnar
styloid occurs; and as the disease progresses, laxity of
the radioulnar ligament gives rise to the “piano key”
sign, as the ulnar styloid moves up and down in
response to dorsal pressure from the examiner's
• Carpal tunnel syndrome from compression of the
median nerve is quite common and often responds
to treatment of the disease.
• Subluxation of the wrist can result in severe disease.
• Extensor tenosynovitis of the extensor carpi ulnaris
and extensor digitorum communis sheaths in the
dorsal wrist produces a characteristic pattern that is
virtually unique to RA
Tenosynovial swelling from tenosynovitis —the “tuck” sign. Tenosynovial swelling overlies the metacarpals of the right hand.
Bulging becomes accentuated with full extension of all the fingers of the hand. Persistent tenosynovitis over the dorsal wrist may
lead to extensor tendon erosion and rupture, particularly of the tendons of the fourth and fifth fingers.
• The tubular swelling of the common extensor tendon
sheath ends abruptly just distal to the wrist joint. This often obscures swelling at the
dorsal wrist (radiocarpal) joint itself. Damage from the chronic
tensosynovial inflammation and friction where the
extensor tendons of the third, fourth, and fifth fingers cross the jagged and
eroded ulnar styloid can lead to tendon rupture with inability
to actively extend those fingers.
Subluxation of the wrist in severe disease, associated with extensor tenosynovitis
and extensor tendon rupture.
• Three characteristic
findings occur at the
- Synovitis may be
palpated between the
lateral epicondyle and
- The radiohumeral joint
is just distal to the
Swelling of the olecranon
bursa often occurs in more
severe disease and tends
to be bilateral.
In fact, bilateral olecranon
bursal swelling occurs only
in RA, gout, and
The olecranon and
extensor surface of the
proximal ulna are very
common sites for
Shoulder involvement typically produces significant
limitation of motion in all planes.
A visible effusion of the glenohumeral joint is unusual
but can produce a “shoulder pad” sign.
On examination, the
patient will elevate the
scapula to improve
range of motion for
Shoulder pain is often
referred to the
Evidence of impingement of the
supraspinatus and biceps tendons is
Owing to ongoing
(either partial or
complete) of the
rotator cuff group
of muscles may
swelling may also
be seen at the
Abnormalities of the
shoulder in rheumatoid
arthritis. The Grashey
posterior oblique view
of a shoulder shows
joint space narrowing
with a marginal erosion
and cystic change of
the humeral head
adjacent to the greater
arrow). Elevation of
the humeral head with
respect to the glenoid
rotator cuff tear. There
also is tapering of the
distal end of the
clavicle and widening
(Courtesy of Dr.
• Spine involvement in RA is mostly limited to the
cervical spine, particularly the upper portion.
• On examination, one notices decreased range of
motion in all planes.
• The most critical involvement occurs at the
atlantoaxial joint, where the ring of C1 pivots on the
odontoid peg of C2. The transverse ligament of the
axis courses around the posterior portion of the
odontoid, preventing subluxation of C1 on C2
• Tenosynovitis here can decrease the space available
for the upper cervical cord, as it passes through the
bony spinal canal posterior to the odontoid. This can
also lead to laxity of the transverse ligament or
erosion of the odontoid.
This radiograph of the rheumatoid cervical spine
in flexion demonstrates atlantoaxial subluxation as
the arch of C1 slides forward (arrows).
Laxity of the transverse
ligament or erosion of the
odontoid, in which case the
ring of C1 can move forward
on neck flexion (atlantoaxial
subluxation), reducing the
diameter of the spinal canal
and compressing the upper
of the cranium on
the spinal column,
movement of the
odontoid into the
Cranial settling occurs when the cranium migrates caudally onto the odontoid, which impinges on the
brain stem above the foramen magnum. The odontoid should not extend much above a line drawn
between the white and black arrows.
occur as a
Rheumatoid arthritis of the
cervical spine. T2-weighted sagittal
image shows low signal
periodontoid pannus (P). Odontoid
process appears irregular
secondary to erosions (arrow).
The atlantodental distance shows
mild widening (solid line). There
also is vertical subluxation without
signs of cord compression.
Anterior subarachnoid space is
compromised by disk protrusions
at multiple levels. Erosions
(arrowheads) are seen at the
vertebral end plates at the C6-C7
level. (Courtesy of Dr. Barbara
• Rheumatoid arthritis of the cervical spine. A, Lateral radiograph in flexion shows severe
anterior atlantoaxial subluxation with a wide anterior atlantodental interval (asterisks)
and decreased posterior atlantodental interval (arrow). B, Almost complete reduction of
subluxation is noted on the lateral view in extension. There also is subaxial subluxation
at the level of C4-C5 (arrowheads) with erosive changes in various facet joints. O,
odontoid. (Courtesy of Dr. Barbara Weissman.)
• Cervical spine involvement/clinical manifestations:
- neck pain,
- sensation that the head might fall off,
- transient ischemic attack,
- bowel and bladder sphincter impairment.
• The development of any of these symptoms in a
patient with severe RA calls for immediate neurologic
• The hip is frequently affected in RA, and progressive
disease can lead to severe secondary osteoarthritis
requiring total joint replacement. Pain from the hip
joint itself is experienced in the groin and medial
thigh, sometimes radiating to the buttock.
• Pain over the greater trochanter, which most patients
refer to as the “hip,” is more likely due to bursitis.
Patrick's test (also
known by the acronym
FABER for flexion-abduction-
rotation) puts the hip
through passive motion
in all major planes and
produces groin pain in
the presence of true hip
Sudden development of hip pain suggests avascular
necrosis or fracture in patients taking long-term
• Rheumatoid involvement of the knee joints is easy to
detect by physical examination and is often a good
indicator of disease activity.
Swelling of the left knee: loss of bone contours
and suprapatellar swelling. Patients usually
keep the knee in flexion
• Distention of
of the knee
cyst in the
Baker's cyst in the popliteal region.
• Baker's cyst in the popliteal region. Rupture of such a
popliteal cyst can produce swelling, heat, and pain in
the posterior calf, resembling a deep venous
thrombosis. A hemorrhagic “crescent” sign below
the malleoli may result.
Acute synovial rupture. A 51-year-old man with RA of 3 years’ duration developed a
right knee effusion after an evening of square dancing. Two days later he noted
progressive pain and swelling of the right calf. (a) Six days later there was bluish
discoloration of both sides of the ankle. (b) A few weeks later, after more dancing, he
noted posterior thigh pain and swelling that soon became associated with purple
discoloration of his right posterior thigh.
• Progressive synovitis can lead to loss of articular
cartilage, secondary osteoarthritis, and the need for
total knee arthroplasty.
can be very
In chronic disease, quadriceps atrophy and flexion
contracture are common.
Muscle atrophy of the right
thigh in association with
ipsilateral knee arthritis.
The ankle: the
capsule of the
effacing the normal
contour of the
The joint line itself can be
palpated between that
tendon and the medial
malleolus, where synovial
proliferation can be
Progressive joint damage to the
tibiotalar, subtalar, and talonavicular
joints can result in ankle and midfoot
pronation and loss of the transverse
arch, producing mechanical symptoms
that can be quite challenging to
Rheumatoid arthritis of the ankle. There is diffuse loss
of cartilage space with erosions of the fibula (arrows).
The scalloping along the medial border of the distal
fibula is designated the fibular notch sign and is a
characteristic finding in rheumatoid arthritis. The
hindfoot is in valgus alignment
• Tendinitis of the posterior tibialis develops posterior
and medial to the medial malleolus. In the same
area, the posterior tibial nerve can be compressed in
the tarsal tunnel, leading to paresthesias on the sole
of the foot.
• Fig. 1. Bilateral swelling of the
ankle joints, retrocalcaneal bursae,
and in the area of the synovial
sheaths of the posterior tibialis,
flexor hallucis longus, and peroneal
longus and brevis tendons and in
the area of extensor tendons in an
HLA-B27 10-year-old boy having
neither axial symptoms nor
radiographic sacroliitis, (A)
posterior view and (B) lateral view.
Reprinted from Burgos-Vargas R,
Pacheco-Tena C, Vázquez-Mellado
spondyloarthropathies. Rheum Dis
Clin North Am 1997;23:569–98;
• The forefoot: tenderness to palpation of the
individual MTP joint or to squeezing the forefoot.
• Swelling can be seen in the dorsum of the foot just
proximal to the toes.
• As disease progresses, the metatarsals sublux on the
plantar aspect of the proximal phalanges, displacing
the soft tissue fat pads that normally underlie the
• Furthermore, the forefoot broadens and the
transverse arch of forefoot disappears, so that
the patient's metatarsal heads are now
directly bearing the weight of the entire body.
and in advanced
cases of RA,
ulcerations occur at
on the flexor
tendons from the
Cabeza de los
• Rheumatoid arthritis is a clinical diagnosis for which
there is no one single physical finding or laboratory
test that is pathognomonic.
• As a practical matter, a patient older than the age of
18 who has symmetric joint pain and swelling in the
hands and feet and morning stiffness is likely to have
RA, especially if the RF and/or the ACPA findings are
• Some data suggest that definitive treatment should
be administered within 3 months of the onset of
• Therein lies the advantage for the 2010 ACR/EULAR
Survival of patients with extra-articular manifestations of rheumatoid arthritis
Fig. 83.2 Gross anatomic specimen of a rheumatoid nodule. The yellow tissue is
caused by fibrinoid necrosis
Rheumatoid nodules in a patient with
long-standing rheumatoid arthritis treated
with low-dose weekly methotrexate
Fig. 83.6 Pleural effusion and rheumatoid nodule in rheumatoid arthritis. Changes
associated with diffuse interstitial fibrosis are also present.
• The most common radiographic finding is bilateral
basilar interstitial abnormalities, which are often
asymmetric. Initially, these may appear as patchy
alveolar infiltrates; with progressive disease a more
reticulonodular pattern is seen.
• High-resolution computed tomography (CT) and
open lung biopsy are considered the gold standard
methods for diagnosing interstitial lung disease.
• Systemic vasculitis in RA is uncommon and often occurs in
rheumatoid patients who have long-standing disease of more
than 10 years.
• Rheumatoid synovitis may not be active when the features of
the systemic vasculitis are present.
• Small vessel vasculitis commonly involves the skin and causes
nailfold infarcts, digital gangrene, and leg ulcers.
Nailfold infarcts in a patient
with rheumatoid arthritis
Digital tip and proximal infarcts in a patient
with rheumatoid vasculitis.