Achy shoulders and a Achy shoulders and a very high CRPvery high CRP

Sarah TansleySarah Tansley

Rheumatology, Clinical FellowRheumatology, Clinical Fellow

Case discussion

A case of polymyalgic onset rheumatoid arthritis was discussed – details removed for confidentiality purposes.

PMR diagnosisPMR diagnosis

Core Inclusion criteriaCore Inclusion criteria Age > 50Age > 50 Bilateral shoulder or pelvic girdle aching or bothBilateral shoulder or pelvic girdle aching or both Morning stiffness >45 minutesMorning stiffness >45 minutes Evidence of acute phase responseEvidence of acute phase response No active cancer, active infection or active GCANo active cancer, active infection or active GCA

No urgency to start steroidsNo urgency to start steroids – can investigate – can investigate firstfirst

Factors which Increase the likelihood of a Factors which Increase the likelihood of a non-PMR diagnosisnon-PMR diagnosis

Age <60 yearsAge <60 years Chronic OnsetChronic Onset Lack of shoulder involvementLack of shoulder involvement Lack of inflammatory stiffnessLack of inflammatory stiffness Normal or very high CRPNormal or very high CRP Peripheral arthritisPeripheral arthritis Systemic symptoms, weight loss, neurological signsSystemic symptoms, weight loss, neurological signs Incomplete or non-response to steroidsIncomplete or non-response to steroids

15mg Prednisolone should result in >70% improvement 15mg Prednisolone should result in >70% improvement within 1 week and normalisation of inflammatory markers within 1 week and normalisation of inflammatory markers within 4 weekswithin 4 weeks

Who to referWho to refer

BSR guidelines recommend specialist referral whenBSR guidelines recommend specialist referral when Age <60Age <60 Chronic onset >2 monthsChronic onset >2 months Lack of shoulder involvementLack of shoulder involvement Lack of inflammatory stiffnessLack of inflammatory stiffness Prominent systemic features; weight loss, night pain, Prominent systemic features; weight loss, night pain,

neurological signsneurological signs Features of other rheumatic diseaseFeatures of other rheumatic disease Normal or extremely high acute phase responseNormal or extremely high acute phase response Treatment dilemmas (inadequate response to steroids, inability Treatment dilemmas (inadequate response to steroids, inability

to reduce steroids, contraindication to steroids etc)to reduce steroids, contraindication to steroids etc)

RA diagnosisRA diagnosis Aim for early diagnosis and treatment but lack of Aim for early diagnosis and treatment but lack of

features of established disease can cause difficultyfeatures of established disease can cause difficulty Considerable variability in presenting symptoms and lab Considerable variability in presenting symptoms and lab

resultsresults HistoryHistory

Polyarticular involvement –may be small number of joints initiallyPolyarticular involvement –may be small number of joints initially Morning stiffness (>30 minutes) suggests inflammatory joint painMorning stiffness (>30 minutes) suggests inflammatory joint pain ChronicityChronicity

ExaminationExamination Joint tenderness MCP, MTP, wristsJoint tenderness MCP, MTP, wrists RA nodules, not usually seen until laterRA nodules, not usually seen until later Upper and lower extremity involvementUpper and lower extremity involvement

SynovitisSynovitis

Rheumatoid Arthritis InvestigationsRheumatoid Arthritis Investigations No single diagnostic testNo single diagnostic test SerologySerology

RFRF• Positive in 70-80% of patients with RAPositive in 70-80% of patients with RA• May be negative, especially earlyMay be negative, especially early• Also seen in other conditions eg Sjogrens SyndromeAlso seen in other conditions eg Sjogrens Syndrome• Positive in 5-10% of healthy individuals Positive in 5-10% of healthy individuals

Anti- CCP AbsAnti- CCP Abs• As sensitiveAs sensitive• Much more specificMuch more specific

Rheumatoid Arthritis InvestigationsRheumatoid Arthritis Investigations

Inflammatory markersInflammatory markers Non-specificNon-specific Useful for distinguishing inflammatory conditions from Useful for distinguishing inflammatory conditions from

non-inflammatorynon-inflammatory Full blood countFull blood count

Anaemia of chronic disease, leucocytosis, Anaemia of chronic disease, leucocytosis, thrombocytosisthrombocytosis

RadiologyRadiology Erosions of cartilage and boneErosions of cartilage and bone Presence more useful diagnostically with increasing Presence more useful diagnostically with increasing

duration of diseaseduration of disease

RadiologyRadiology

ACR/EULAR classification criteriaACR/EULAR classification criteria

Designed to classify patients Designed to classify patients as RA earlier for purpose of as RA earlier for purpose of clinical trials – not diagnostic clinical trials – not diagnostic criteriacriteria

Still useful, several differences Still useful, several differences from 1987 criteria which aimed from 1987 criteria which aimed to classify people with to classify people with established diseaseestablished disease

Target populationTarget population At least 1 joint with definite At least 1 joint with definite

synovitis/swellingsynovitis/swelling Synovitis not better explained Synovitis not better explained

by another diseaseby another disease Score >6 classified as RAScore >6 classified as RA

ScoreScore

Joint InvolvementJoint Involvement

1 large1 large 00

2-10 large2-10 large 11

1-3 small1-3 small 22

4-10 small4-10 small 33

>10 joints>10 joints 44

SerologySerology

Negative RF Negative RF && anti-CCP Ab anti-CCP Ab 00

Low positive RF Low positive RF oror anti-CCP Ab anti-CCP Ab 22

High positive RF High positive RF oror anti-CCP Ab anti-CCP Ab 33

Acute Phase ReactantsAcute Phase Reactants

Normal CRP Normal CRP && ESR ESR 00

Abnormal CRP Abnormal CRP or or ESRESR 11

Duration of SymptomsDuration of Symptoms

< 6 weeks< 6 weeks 00

>6 weeks>6 weeks 11

Polymyalgic onset RAPolymyalgic onset RA

Bajocchi et al 2000Bajocchi et al 2000 LO-RA vs YO-RALO-RA vs YO-RA

• Polymyalgic symptoms more common in LO RA Polymyalgic symptoms more common in LO RA • Higher frequency of shoulder involvement in LO Higher frequency of shoulder involvement in LO

RA RA Lopez-Hoyos et al 2004Lopez-Hoyos et al 2004

Anti-CCP Abs in differential diagnosis of RA Anti-CCP Abs in differential diagnosis of RA vs PMRvs PMR• 65% LO RA anti-CCP Ab +ve 65% LO RA anti-CCP Ab +ve • No PMR patients anti-CCP Ab +veNo PMR patients anti-CCP Ab +ve• Polymyalgic onset RA 2/10 anti-CCP +vePolymyalgic onset RA 2/10 anti-CCP +ve

Polymyalgic onset RAPolymyalgic onset RA

Gran, Mykebust 1999Gran, Mykebust 1999 Incidence and Characteristics of peripheral Incidence and Characteristics of peripheral

arthritis in PMR & TAarthritis in PMR & TA• 231 patients prospectively studied 1987-1993231 patients prospectively studied 1987-1993• All ?PMR/TA in Norwegian county referred to All ?PMR/TA in Norwegian county referred to

rheumatology before treatmentrheumatology before treatment• Followed throughout the disease courseFollowed throughout the disease course

187 ‘pure’ PMR187 ‘pure’ PMR 38.5% developed peripheral arthritis38.5% developed peripheral arthritis 11 developed RA (4.8% 6 female and 5 male)11 developed RA (4.8% 6 female and 5 male)

Polymyalgic RAPolymyalgic RA

Mean duration of PMR at RA diagnosis Mean duration of PMR at RA diagnosis was 63.2 monthswas 63.2 months

5/8 patients had erosive x-ray changes5/8 patients had erosive x-ray changes 6/11 patients had positive RF (all 6/11 patients had positive RF (all

negative initially)negative initially) Mean CRP higher at diagnosis among Mean CRP higher at diagnosis among

those who developed arthritis (88.6 vs those who developed arthritis (88.6 vs 59.7)59.7)

Polymyalgic onset RAPolymyalgic onset RA

Pease et al 2009Pease et al 2009 Prospective study of 147 patients presenting Prospective study of 147 patients presenting

with PMR & 142 patients with LO-RAwith PMR & 142 patients with LO-RA Reviewed accuracy of initial diagnosisReviewed accuracy of initial diagnosis

• 23% PMR patients had peripheral synovitis 23% PMR patients had peripheral synovitis • In contrast to seronegative LO-RA, PMR In contrast to seronegative LO-RA, PMR

patients younger, myalgia more frequent, patients younger, myalgia more frequent, PIP/MCP/wrist arthritis less frequent PIP/MCP/wrist arthritis less frequent

• Combination of wrist + MCP and/or PIP Combination of wrist + MCP and/or PIP highly suggestive of RAhighly suggestive of RA

Polymyalgic onset RAPolymyalgic onset RA Pease et al 2005Pease et al 2005

349 patients with new onset LO-RA, PMR or TA >60 349 patients with new onset LO-RA, PMR or TA >60 yrsyrs• 9/171 initially diagnosed PMR changed to LO-RA9/171 initially diagnosed PMR changed to LO-RA• All 9 dependant on higher steroid dose than typically All 9 dependant on higher steroid dose than typically

expected for their stage of diseaseexpected for their stage of disease

• Initially synovitis suppressed by steroidsInitially synovitis suppressed by steroids but returned but returned when dose loweredwhen dose lowered

• Initial plasma viscosity higher in this group (mean of 2.0 Initial plasma viscosity higher in this group (mean of 2.0 vs 1.86)vs 1.86)

• Difficulty to distinguish may lead to delay in correct Difficulty to distinguish may lead to delay in correct diagnosis (average 13 months)diagnosis (average 13 months)

SummarySummary

Several challenges in diagnosing RA, Several challenges in diagnosing RA, particularly early in the disease courseparticularly early in the disease course

Variety of possible presentationsVariety of possible presentations Polymyalgic symptoms are common in Polymyalgic symptoms are common in

elderly onset RA elderly onset RA May lead to diagnostic delayMay lead to diagnostic delay No single diagnostic test; clinical history No single diagnostic test; clinical history

and examination importantand examination important