RHEUMATOID ARTHRITIS
Clinical features of
rheumatoid arthritis
Malvika Gulati
Ziad Farah
Maria Mouyis
Abstract
Rheumatoid arthritis (RA) is a multiorgan chronic inflammatory condi-
tion that affects 0.84% of the UK population. The cardinal clinical
feature is a symmetrical polyarthritis that predominantly affects the
small joints. RA can affect other components of the musculoskeletal
system (bursitis, tendinopathy, muscle atrophy, osteoporosis) and
almost every organ in the body. Extra-articular manifestations of RA
can be cutaneous, haematological, neurological, pulmonary, cardiac,
renal and ocular. A better understanding of the varied clinical aspects
of RA is vital to instigating appropriate management. This review pro-
vides a detailed description of the clinical manifestations of RA, both
musculoskeletal and extra-articular.
Keywords Atherosclerosis; chronic disease; inflammation; interstitial
lung disease; MRCP; rheumatoid arthritis; synovitis; tenosynovitis
Introduction
Rheumatoid arthritis (RA) is a multisystemic chronic inflamma-
tory disease, classically defined as a symmetrical deforming
polyarthritis.
Prevalence in the UK is estimated at 0.84% of adults aged >16
years.1 Onset can be at any age, with a peak incidence of 40e60
years. Women are three times more likely to develop RA,
noticeably in the postpartum period. Family history, cigarette
smoking and obesity are other recognized risk factors. Poorly
treated RA can lead to bony erosions, deformity and loss of
function. This article explores the articular and extra-articular
features of RA (summarized in Figure 1).
How do patients with rheumatoid arthritis present?
Individuals present with pain, swelling and stiffness in a sym-
metrical pattern, predominantly affecting the smaller joints of the
hands and feet. In some cases, the disease can develop from an
Malvika Gulati MB BS BSc is an ST6 Specialist Registrar in
Rheumatology and General Medicine, London, UK. Competing
interests: none declared.
Ziad Farah MB BS BSc (Hons) MRCP PG Cert Med Ed is a Year 4 Specialist
Registrar in Rheumatology and General Internal Medicine. He is
currently working for the London Deanery at the Royal London
Hospital, UK. Competing interests: none declared.
Maria Mouyis MB BCh DMH MRCP with SCE is a Consultant Physician
and Rheumatologist based at Northwick Park Hospital, London, UK.
Her research interests are varied and include ultrasound as well as
maternal medicine. Competing interests: none declared.
MEDICINE --:-
Please cite this article in press as: Gulati M, et al., Clinical features of rheumatoid arthritis, Medicine (2018), https://doi.org/10.1016/
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Key points
C Rheumatoid arthritis (RA) is a chronic multisystem inflamma-
tory condition
C Arthritis in RA is typically symmetrical and polyarticular, but in
some cases is asymmetrical, oligo- or mono-articular
C RA can affect other structures in the musculoskeletal system,
including tendons, bursae, muscles and bones
C Extra-articular manifestations of RA can be cutaneous,
vascular, neurological, haematological, pulmonary, cardiac,
renal, gastrointestinal or ocular
asymmetrical oligo- or polyarthritis onset, and rarely from a
monoarthritis. Palindromic RA is well recognized, with variable
episodes of polyarthritis lasting a few hours to days with com-
plete resolution of symptoms in the interim.
The diagnosis is largely clinical, supported by blood tests
(anti-cyclic citrullinated peptide, rheumatoid factor, inflamma-
tory markers), radiographs (erosions, periarticular osteopenia,
swelling) and ultrasonography. Clinical assessment should
include a focus on a thorough systemic enquiry to exclude other
diagnoses (e.g. polymyalgia rheumatica, infection, vasculitis,
autoimmune rheumatic disease, paraneoplastic disease) and in
particular seronegative spondyloarthropathy (psoriasis, inflam-
matory back pain, enteropathic features, dactylitis, uveitis).
Early referral and diagnosis are essential as there is a ‘window
of opportunity’ when early intervention may alter longer-term
outcomes.
Musculoskeletal features
Joints:
Upper limbs e clinical examination starts at the hands,
inspecting for swelling and deformity, palpating for tender and
swollen joints and assessing range of movement. The proximal
interphalangeal joints (PIPJs), metacarpophalangeal joints
(MCPJs), wrists, elbows and shoulders are individually exam-
ined. Classically, the distal interphalangeal joints (DIPJs) are
spared in RA; consider osteoarthritis, psoriatic arthritis and gout
as differential diagnoses if the DIPJs are involved. Tenderness
volar to the ulnar styloid can suggest involvement of extensor
carpi ulnaris e a common feature in early RA.
Deformity is not expected in the early stage unless the diag-
nosis has been delayed. When deformities are present, it is
important to determine whether these are reversible (i.e. Jac-
coud’s-type arthropathy, consider autoimmune rheumatic dis-
eases such as systemic lupus erythematosus) or irreversible.
Classic RA deformities involving the digits are the boutonni
ere
(irreversible flexion at the PIPJs and hyperextension at the
DIPJs), swan neck (irreversible hyperextension at the PIPJs and
flexion at the DIPJs) and Z-thumb (flexion at the MCPJs and
hyperextension at the interphalangeal joints to 90 ) deformities.
These changes result from damage to the tendons and joint
capsule.
1 Ó 2018 Published by Elsevier Ltd.
 RHEUMATOID ARTHRITIS

Summary diagram of the clinical manifestations of RA

Ocular Vascular
• Keratoconjunctivitis sicca • Rheumatoid vasculitis
• Episcleritis • Raynaud’s
• Scleritis • Atherosclerosis
• Scleromalacia perforans
Cardiac
Pulmonary • Coronary artery disease
• Parenchymal lung disease • Pericarditis
• Pleural disease
• Airways disease
• Complications of DMARDs Renal
• Tubulo-interstitial nephritis
• AA amyloid
Skin • Membranous
• Rheumatoid nodules glomerulonephritis
• Vascular lesions
Musculoskeletal
Gastrointestinal • Joint
• Oesophagitis, gastritis and • Tendon
peptic ulcer disease • Bursa
• Hepatotoxicity from DMARDs • Muscle
• Bone
Neurological
• Entrapment neuropathy Haematological
• Cervical myelopathy • Anaemia
• Peripheral neuropathy • Thrombocytosis
• Mononeuritis multiplex • Felty’s syndrome

DMARD, disease-modifying antirheumatic drug.

Figure 1

Flexor tenosynovitis can result in pain and ‘triggering’ of the
fingers. Tenderness, thickening and nodule formation are
palpable along the tendon.
Established RA changes at the MCPJs cause volar subluxation
and ulnar deviation. These are a consequence of damage to the
volar plate, tendons and supporting ligaments caused by syno-
vial inflammation.
Ulnar deviation at the MCPJs is associated with radial devia-
tion at the wrist. Dorsal subluxation of the ulna results in a
‘piano key’ movement allowing the ulna to be depressed. This
bony movement can cause damage to extensor tendons and
rupture.
Synovitis at the wrist and deformity can result in entrapment
neuropathies e carpal tunnel syndrome and, less commonly,
ulnar neuropathy.
Tenderness, synovitis, effusion and flexion deformity may be
seen at the elbow.
Swelling at the shoulder is difficult to elicit. RA commonly
involves the shoulder joint, causing rotator cuff tendinopathy,
tendon rupture, synovitis and bursitis. Patients can report pain,
stiffness and limited range of movement.
Lower limbs e the feet should be inspected for swelling and
deformity, and in particular for loss of the longitudinal arch. The
MTPJs are at risk of deformity because of synovitis and high
load-bearing. Hallux valgus can develop, with subluxation of the
other phalanges and claw toe formation resulting from flexor
tendon involvement. This alters biomechanics such that the
second and third MTPJs predominantly bear the load, with
resultant pain, underlying callosities and deformity.
The posterior tibialis tendon and the subtalar and talona-
vicular joints are frequently involved in RA, causing pain, ero-
sions and subtalar dislocation with loss of the arch of the foot.
Active synovitis at the knee results in pain and effusion.
Secondary degenerative changes are common. Posterior knee
pain can result from an enlarged Baker’s cyst.
The hip is less commonly involved in RA; synovitis is difficult
to elicit because of the deep-seated location.
Cervical spine e involvement of the cervical spine is less
common with modern therapies, and is usually seen in in-
dividuals with advanced disease. Patients report neck and oc-
cipital pain; neurological features can be present as a result of
compression of the nerve roots or spinal cord.
The atlas (C1) has a strong transverse ligament that maintains
the odontoid process (also known as the dens or peg) of the axis
(C2) against the posterior surface of the atlas (Figure 2). There is
a synovial articulation between the transverse ligament and the

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j.mpmed.2018.01.008
 RHEUMATOID ARTHRITIS
Atlas (C1)
Odontoid peg
Transverse
ligament
Spinal cord
Anterior
Figure 2 A diagrammatic representation of atlanto-axial subluxation viewed axially, caused by rupture of the transverse ligament secondary to
localized pannus formation, and migration of the atlas towards the cervical spinal cord, resulting in cervical myelopathy. Left: healthy state; right,
atlanto-axial subluxation.
posterior aspect of the odontoid process. Synovitis at this site can
result in odontoid erosion, instability of the transverse ligament
and rupture, placing the spinal cord at risk. The extended neck
position increases the risk of subluxation. Rarely, vertical
movement of the odontoid process into the foramen magnum
occurs e this can be fatal.
Other joints e temporomandibular joint (synovitis can
restrict mouth opening, and in children can result in micro-
gnathia). Involvement of the cricoarytenoid joint causes a change
in voice.
Tendons: trigger finger is seen in hand flexor tenosynovitis,
where the pathology results from a thickened tendon and ste-
nosis of the tendon sheath. Clinically, a thickened tendon with a
painful nodule is palpable.
Extensor tenosynovitis is evident as swelling on the dorsum of
the hand, accentuated by asking the patient to extend their fin-
gers. Rupture of the extensor tendons is more common than that
of the flexor tendons.
Bursae: bursitis can develop at a number of sites e olecranon,
subacromial subdeltoid and trochanteric bursitis.
Muscles: sarcopenia is common and results from deconditioning
caused by pain, corticosteroid use and neuropathy. Atrophy of
the intrinsic muscles of the hand can be marked in advanced RA.
Bones: although active synovitis can cause erosions at articular
sites, RA is associated with low bone density. This occurs as a
result of corticosteroid use and immobility.
Extra-articular manifestations of rheumatoid arthritis
Skin: rheumatoid nodules are the most common skin manifes-
tation of RA. These are typically observed in seropositive patients
and located subcutaneously at pressure areas (e.g. olecranon,
occiput, Achilles). They are firm and rubbery without being
tender. There can be a discrepancy between the severity of
articular inflammation and the degree of rheumatoid nodulosis.
Other skin manifestations of RA relate to vascular aetiology,
for example vasculitis, purpura and ulceration, including pyo-
derma gangrenosum.
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Anterior
Vascular:
Atherosclerosis e this is the most common vascular compli-
cation of RA. The risk of atherosclerosis correlates with the de-
gree of inflammation; reducing inflammation may reduce
cardiovascular risk.
Rheumatoid vasculitis e rheumatoid vasculitis typically
presents as petechiae, purpura or ulceration caused by inflam-
mation of the larger arterioles or arteries. This is a relatively rare
complication that can also be associated with peripheral neu-
ropathy or involvement of the internal organs. When present,
vasculitis often indicates severe disease and requires
immunosuppression.
Raynaud’s e Raynaud’s phenomenon rarely affects patients
with RA. Pathophysiology and management are similar to those
of patients with Raynaud’s secondary to other connective tissue
diseases.
Neurological: entrapment neuropathy and cervical myelopathy
were discussed above. RA can cause a length-dependent pe-
ripheral neuropathy in a glove-and-stocking distribution, typi-
cally presenting as tingling and paraesthesia. Less common is
mononeuritis multiplex, presenting as a sensorimotor
neuropathy.
Haematological:
Anaemia e the most common haematological manifestation
of RA is anaemia of chronic disease, manifesting as normocytic
anaemia. This correlates with disease activity and acute-phase
response. Patients can develop iron deficiency anaemia second-
ary to gastrointestinal blood loss from chronic non-steroidal anti-
inflammatory drug (NSAID) and glucocorticoid use. Vitamin B12
and folate deficiency can be a cause of anaemia in RA, especially
with methotrexate.
Thrombocytosis e this is part of the acute-phase response.
Felty’s syndrome e this is a triad of RA, splenomegaly and
neutropenia. Thrombocytopenia can be observed. This may not
correlate with the articular disease but is managed by optimizing
disease-modifying therapy.2
Pulmonary disease: in patients with RA, pulmonary disease can
be caused by the disease or by infections in an
 RHEUMATOID ARTHRITIS
immunocompromised host, or be an adverse consequence of
immune-modulatory therapy.3
Parenchymal lung disease e this includes RA interstitial lung
disease (RA-ILD) and, less commonly, pulmonary rheumatoid
nodulosis. Although RA-ILD is considered a late complication, it
is increasingly recognized that a proportion of asymptomatic RA
patients have undiagnosed RA-ILD early in the disease. Risk
factors for RA-ILD include male sex, older age, smoking history
and seropositivity.
The most common high-resolution computed tomography
(HRCT) pattern is usual interstitial pneumonitis, typified by
bilateral subpleural basal disease with honeycombing. The next
most common pattern is non-specific interstitial pneumonitis,
which is typically associated with other connective tissue dis-
eases and is characterized by ground-glass changes and mosai-
cism. Some patients develop an organizing pneumonia with
patches of consolidation.4
Pulmonary rheumatoid nodulosis is less common and has a
wide differential diagnosis that includes infection and malig-
nancy. In the context of pneumoconiosis, calcified pulmonary
nodules are known as Caplan’s lungs.
Pleural disease e pleuritis and pleurisy can be associated
with exudative pleural effusion. Rarely, recurrent pleuritis can
lead to pleural fibrosis. In some cases, bronchopleural fistula and
pneumothorax can result from a ruptured subpleural rheumatoid
nodule.
Airways disease e RA can involve small and large airways.
Bronchiectasis from recurrent infection can be identified on
HRCT. Rarely, patients can present with smaller airways disease
such as bronchiolitis and bronchiolitis obliterans that require
prompt immunosuppression.
Complications of disease-modifying antirheumatic drugs
(DMARDs) e a common adverse complication of synthetic and
biologic DMARD treatment is upper and lower respiratory tract
infections. Opportunistic infections can occur in this immuno-
compromised population. Drugs including methotrexate and
tumour necrosis factor inhibitors can cause interstitial pneumo-
nitis. Management involves discontinuation of the drug, supportive
measures and, in severe cases, intravenous corticosteroids.
Cardiac disease:
Coronary artery disease e atherosclerosis in RA has been
discussed above.
Pericarditis e as with pleural disease, the pericardium can
become inflamed, resulting in chest pain and rarely pericardial
effusion. Myocardial and endocardial inflammation can be pre-
sent. Severity of pericardial involvement often correlates with
articular disease and is controlled with DMARD therapy.
Renal disease: the kidney is rarely affected directly by RA.
Tubulo-interstitial nephritis can occur secondary to chronic
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NSAID use or nephropathy secondary to DMARD therapy, typi-
cally with older generation drugs such as penicillamine and gold
(which are now rarely used), and caused by chronic inflamma-
tion. This presents with proteinuria and can progress to
nephrotic syndrome. This complication is uncommon with
modern therapies that allow tighter control of disease activity.
Gastrointestinal manifestations: RA does not directly affect the
gastrointestinal tract. Chronic NSAID and corticosteroid use are
associated with oesophagitis, gastritis and peptic ulcer disease.
Hepatic toxicity may be seen with DMARD therapy.
Ocular manifestations:
Keratoconjunctivitis sicca e this can present on its own or in
the context of secondary Sjo €gren’s syndrome. The severity of
symptoms correlates with the patient’s age and the duration of
RA, but not with the severity of peripheral arthritis.5
Episcleritis e this is inflammation of the superficial layer of
the sclera, presenting as acute-onset red injection in one or both
eyes, causing pain and photophobia.
Scleritis e this is an ocular emergency. Anterior scleritis is
characterized by a red eye that sometimes has a characteristic
violet hue. Pain is often described as a boring pain. Scleral
dilatation can be sight-threatening. Posterior scleritis presents
with severe retro-orbital pain. Fundoscopy may reveal retinal
vasculitis, optic nerve oedema and retinal detachment. Scleritis is
often associated with long-standing RA and is more common in
patients with other extra-articular manifestations. If suspected, it
requires urgent review by an ophthalmologist.
Scleromalacia perforans e this is a very rare complication
that causes thinning of the sclera with a darkish blue tinge from
the appearance of the underlying black choroid layer. Scle-
romalacia is a late presentation with a relatively poor
prognosis. A
KEY REFERENCES
1 Arthritis Research UK. State of musculoskeletal health. 2017,
http://www.arthritisresearchuk.org/arthritis-information/data-and-
statistics/state-of-musculoskeletal-health.aspx (accessed 3 Sep
2017).
2 Rozin AP, Hoffman R, Hayek T, Balbir-Gurman A. Felty’s syndrome
without rheumatoid arthritis? Clin Rheumatol 2013; 32: 70e4.
3 European League Against Rheumatism. EULAR online course on
rheumatic disease. https://www.eular.org/edu_online_course.cfm
(accessed 10 Sep 2017).
4 Kim EJ, Collard HR, King TE. Rheumatoid arthritis-associated
interstitial lung disease: the relevance of histopathologic and
radiographic pattern. Chest 2009; 136: 1397e405.
5 Almaliotis D, Zakalka M, Gerofotis A, et al. Ocular manifestations in
rheumatoid arthritis. Open J Ophthalmol 2016; 6: 170.
4 Ó 2018 Published by Elsevier Ltd.
 RHEUMATOID ARTHRITIS

TEST YOURSELF
To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the
end of the issue or online here.

Question 1 What is the most likely radiological pattern?

A. Bibasal subpleural honeycombing
A 58-year-old woman presented with a 1-month history of pain
B. Calcific pulmonary nodulosis
and swelling involving the small joints of her hands bilaterally.
C. Cavitating apical lung lesions
D. Ground-glass changes with mosaicism
Which findings on clinical examination would best support a
E. Patches of consolidation
diagnosis of rheumatoid arthritis?
A. Bony swelling of the distal and proximal interphalangeal Question 3
joints
B. Distal interphalangeal joint tenderness and scaly rash A 42-year-old woman presented with sudden-onset, unilateral
C. Reversible joint deformity deep orbital pain that lasted for 10 hours. It had woken her up
D. Squaring of the thumb with tenderness the previous night, and she had been unable to return to sleep.
E. Tenderness near the ulnar styloid Ten years previously, she had been found to have rheumatoid
arthritis.
Eye examination revealed a red eye with some reduction in vi-
Question 2 sual acuity. The pupils were normal and reactive to light.
What is the most likely diagnosis?
A 63-year-old man presented with a 2-month history of pro-
A. Anterior uveitis
gressive shortness of breath on exertion, associated with a dry
B. Episcleritis
cough but no haemoptysis. He had previously been found to
C. Keratoconjunctivitis sicca
have seropositive rheumatoid arthritis, and had been taking
D. Scleritis
methotrexate for 8 years with good control. A high-resolution
E. Scleromalacia perforans
computed tomography scan of the chest was performed.

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Please cite this article in press as: Gulati M, et al., Clinical features of rheumatoid arthritis, Medicine (2018), https://doi.org/10.1016/
j.mpmed.2018.01.008