BMJ 2016;352:i387 doi: 10.1136/bmj.

i387 (Published 23 March 2016)

Page 1 of 3

Practice

PRACTICE
EASILY MISSED?

Rheumatoid arthritis
1

Kate Harnden foundation year 1 doctor , Colin Pease consultant rheumatologist , Andrew Jackson
3
general practitioner
St James University Hospital, Leeds LS9 7TF, UK; 2Rheumatology, Chapel Allerton Hospital, Leeds LS7 4SA, UK; 3Bingley Medical Practice,
Canalside Health Care Centre, Bingley BD16 4RP, UK
1

A 43 year old woman with six weeks of bilateral wrist pain is

diagnosed with repetitive strain injury. Five weeks later, she
returns with worsening pain. On further questioning, she reports
increasing fatigue and two hours of morning stiffness in her
hands. Examination reveals bilateral wrist and
metacarpophalangeal joint swelling. She is referred to a
rheumatologist, who diagnoses rheumatoid arthritis and initiates
treatment.

What is rheumatoid arthritis?

Rheumatoid arthritis is an autoimmune, polyarticular arthritis

characterised by progressive joint destruction and deformity,
usually of peripheral joints (box 1). Its cause is unknown, and
extra-articular organ involvement such as interstitial lung disease
and Sjgrens syndrome may occur. Appropriate early therapy
improves symptoms, function, and mortality, and may reduce
comorbidities.

Why is it missed?
Observational studies in England, Europe, and the United States
all report delayed referral by general practitioners. A 2009
National Audit Office report found that patients in England with
undiagnosed rheumatoid arthritis visited their general
practitioner an average of four times before being referred; 18%
visited over eight times.4 Detecting early rheumatoid arthritis
is difficult as musculoskeletal problems are common in general
practice. Clinical signs may be subtle, inflammatory markers
such as erythrocyte sedimentation rate and C reactive protein
are often normal, and more specific markers are also often
negative (31% of patients are seronegative for rheumatoid factor
and 33% are negative for anti-CCP (cyclic citrullinated peptide)
antibodies).5

Why does it matter?

The disability created by rheumatoid arthritis causes 28% of
patients to give up their job within a year.6 There is a three
month therapeutic window of opportunity, from symptom
onset in which treatment can delay disease progression.7
Delaying treatment after this window has been shown to increase
radiographic damage and mortality.7 8 Furthermore, a treatment
delay of 3-6 months will make monotherapy less potent at
inducing drug free remission.9

How is it diagnosed?
Clinical features

The main symptoms are:

Joint pain, swelling, and stiffness, commonly affecting
wrists, proximal interphalangeal, metacarpophalangeal,
and metatarsophalangeal joints.
Early morning stiffness that lasts over 30 minutes
(sensitivity 74-77%, specificity 48-52%10)

Systemic symptoms such as weight loss, fatigue (84% of

patients at presentation in an observational study11) and
malaise.
Features on examination include:
Swelling of three or more joints (specificity of 73%12)
Tenderness largely along the joint line

Synovitis, producing a boggy or doughy swelling,

which may be subtle

A positive squeeze testpain on gently squeezing the

metacarpophalangeal or metatarsophalangeal joints together

Correspondence to: K Harnden kateharnden@doctors.org.uk

This is one of a series of occasional articles highlighting conditions that may be more common than many doctors realise or may be missed at first
presentation. The series advisers are Anthony Harnden, professor of primary care, Department of Primary Care Health Sciences, University of
Oxford, and Richard Lehman, general practitioner, Banbury. To suggest a topic for this series, please email us at practice@bmj.com.
For personal use only: See rights and reprints http://www.bmj.com/permissions

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BMJ 2016;352:i387 doi: 10.1136/bmj.i387 (Published 23 March 2016)

Page 2 of 3

PRACTICE

What you need to know

Consider rheumatoid arthritis in any patient presenting with joint pain, swelling, and morning stiffness of over 30 minutes
Refer within two weeks if symptoms affect small joints of the hands or feet, or more than one joint, or have been present for at least
three months
Starting treatment with combination disease-modifying antirheumatic drugs (including methotrexate), especially within three months
of symptom onset, can slow disease progression and improve symptoms, function, and quality of life
When rheumatoid arthritis is suspected, x ray symptomatic joints and measure rheumatoid factor, erythrocyte sedimentation rate, and
C reactive protein without delaying referral, as negative results do not exclude the diagnosis

Box 1: How common is rheumatoid arthritis?

In a 2010 systematic review, estimated prevalence in North America and Northern Europe was between 0.5% and 1.1%. Developing
countries have a lower prevalence (0.1-0.5%)1
Rheumatoid arthritis is more common in women (3:1 female:male ratio).1 It can present at any age, but in a retrospective cohort study
the mean age of onset was 55.6 years2
The number of new cases identified in the UK each year is around 20 000.3 An average UK general practitioner will therefore see one
new case every two years

(fig 1) (sensitivity 40-48% but specificity 84% for early

disease12).
Synovitis of the wrist of flexor tendons may also present with
carpal tunnel symptoms such as pain and paraesthesia along the
distribution of the median nerve.
Box 2 outlines the indications for referral.

Investigations
If rheumatoid arthritis is suspected, refer within two weeks to
rheumatology and request the following blood tests without
delaying referral: rheumatoid factor (69% sensitive and 85%
specific5), erythrocyte sedimentation rate, and C reactive protein.
If rheumatoid factor is negative, consider requesting a test for
anti-CCP antibodies, which has similar sensitivity to rheumatoid
factor (67%) but is more specific (95%).5 14
X ray the hands and feet if symptomatic without delaying
referral, as erosive damage may be present, despite other
investigations being normal. Ultrasound may be more sensitive
for early synovitis, but its availability is limited in the UK.13 15

How is it managed?
In the UK, early arthritis clinics have been set up to assess and
treat patients with suspected rheumatoid arthritis.
Initial treatment involves offering a combination of
disease-modifying antirheumatic drugs (methotrexate,
sulphasalazine, etc) as soon as possible to slow disease
progression and improve symptoms, function, and quality of
life.13 Glucocorticoids, given intra-articularly, intramuscularly,
or orally, provide quick, short term symptom relief and may
slow joint damage. However, referring general practitioners
should offer a glucocorticoid trial only if the patient is unlikely
to be seen promptly in secondary care, as the drugs can make
confirmatory diagnosis difficult. Annual review by general
practitioners should include checking for and managing
comorbidities such as cardiovascular disease, osteoporosis, and
depression.13

Contributors: KH had the original idea for the article and researched
the literature. All authors contributed towards planning and drafting the
article. KH is guarantor.

For personal use only: See rights and reprints http://www.bmj.com/permissions

Competing interests: We have read and understood the BMJ policy on

declaration of interests and declare the following interests: CP is
treasurer of the British Society for Rheumatology; AJ is employed within
a Federation owned community musculoskeletal service within sessions
that he is paid for and he is a shareholder in profits made. Employed
on an ad hoc basis as an RCGP musculoskeletal tutor.
Provenance and peer review: Not commissioned; externally peer
reviewed.
1
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15

Turesson C, OFallon WM, Crowson CS, Gabriel SE, Matteson EL. Extra-articular disease
manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years.
Ann Rheum Dis 2003;62:722-7. doi:10.1136/ard.62.8.722. pmid:12860726.
Myasoedova E, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. Is the incidence
of rheumatoid arthritis rising?: results from Olmsted County, Minnesota, 1955-2007.
Arthritis Rheum 2010;62:1576-82. doi:10.1002/art.27425. pmid:20191579.
Wiles N, Symmons DP, Harrison B, et al. Estimating the incidence of rheumatoid arthritis:
trying to hit a moving target?Arthritis Rheum 1999;42:1339-46. doi:10.1002/1529-0131(
199907)42:7<1339::AID-ANR6>3.0.CO;2-Y. pmid:10403260.
National Audit Office. Services for people with rheumatoid arthritis. Stationery Office,
2009. www.nao.org.uk/publications/0809/services_for_people_with_rheum.aspx.
Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic
citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern
Med 2007;146:797-808. doi:10.7326/0003-4819-146-11-200706050-00008. pmid:
17548411.
National Rheumatoid Arthritis Society. I want to work: National Rheumatoid Arthritis
Society survey 2007. NRAS, 2007. www.nras.org.uk/data/files/Publications/I%20want%
20to%20work%20survey%202007.pdf.
Bykerk V, Emery P. Delay in receiving rheumatology care leads to long-term harm. Arthritis
Rheum 2010;62:3519-21. doi:10.1002/art.27691. pmid:20722032.
Symmons DP, Jones MA, Scott DL, Prior P. Longterm mortality outcome in patients with
rheumatoid arthritis: early presenters continue to do well. J Rheumatol
1998;25:1072-7.pmid:9632066.
Mttnen T, Hannonen P, Korpela M, et al. FIN-RACo Trial Group. FINnish Rheumatoid
Arthritis Combination therapy. Delay to institution of therapy and induction of remission
using single-drug or combination-disease-modifying antirheumatic drug therapy in early
rheumatoid arthritis. Arthritis Rheum 2002;46:894-8. doi:10.1002/art.10135. pmid:
11953964.
van Nies JA, Alves C, Radix-Bloemen AL, et al. Reappraisal of the diagnostic and
prognostic value of morning stiffness in arthralgia and early arthritis: results from the
Groningen EARC, Leiden EARC, ESPOIR, Leiden EAC and REACH. Arthritis Res Ther
2015;17:108. doi:10.1186/s13075-015-0616-3. pmid:25904188.
Turkcapar N, Demir O, Atli T, et al. Late onset rheumatoid arthritis: clinical and laboratory
comparisons with younger onset patients. Arch Gerontol Geriatr 2006;42:225-31. doi:10.
1016/j.archger.2005.07.003. pmid:16191448.
Visser H. Early diagnosis of rheumatoid arthritis. Best Pract Res Clin Rheumatol
2005;19:55-72. doi:10.1016/j.berh.2004.08.005. pmid:15588971.
National Institute for Health and Care Excellence. Rheumatoid arthritis in adults:
management (Clinical guideline 79). 2009. www.nice.org.uk/guidance/CG79.
National Collaborating Centre for Chronic Conditions (UK). Rheumatoid arthritis: national
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21413195.
Nam JL, Hensor EM, Hunt L, Conaghan PG, Wakefield RJ, Emery P. Ultrasound findings
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BMJ 2016;352:i387 doi: 10.1136/bmj.i387 (Published 23 March 2016)

Page 3 of 3

PRACTICE

Box 2: When to refer (based on National Institute for Health and Care Excellence (NICE) guidance13)
Refer anyone with suspected persistent, unexplained synovitis to rheumatology
Refer within two weeks if:
Small joints of the hands or feet are affected
More than one joint is affected
At least three months have elapsed between symptom onset and presentation

How patients were involved in the creation of this article

We sought the opinion of a patient with rheumatoid arthritis, who described how her initial diagnostic process had been frustrating, with
multiple visits to her general practice. She stated how essential a diagnosis had been in helping her manage and come to terms with the
condition. Her comments about the importance of early diagnosis and appropriate management were taken into account when drafting the
article.

Figure

Fig 1 Squeeze test of (A) metacarpophalangeal and (B) metatarsophalangeal joints (adapted from Arthritis Research UK
www.arthritisresearchuk.org/arthritis-information/inflammatory-arthritis-pathway/step-one.aspx)

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