Achy shoulders and a very high CRP Sarah Tansley Rheumatology, Clinical Fellow

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

PMR diagnosis  Core Inclusion criteria Age > 50 Age > 50 Bilateral shoulder or pelvic girdle aching or both Bilateral shoulder or pelvic girdle aching or both Morning stiffness >45 minutes Morning stiffness >45 minutes Evidence of acute phase response Evidence of acute phase response No active cancer, active infection or active GCA No active cancer, active infection or active GCA  No urgency to start steroids – can investigate first

Factors which Increase the likelihood of a non-PMR diagnosis  Age <60 years  Chronic Onset  Lack of shoulder involvement  Lack of inflammatory stiffness  Normal or very high CRP  Peripheral arthritis  Systemic symptoms, weight loss, neurological signs  Incomplete or non-response to steroids 15mg Prednisolone should result in >70% improvement within 1 week and normalisation of inflammatory markers within 4 weeks

Who to refer  BSR guidelines recommend specialist referral when Age <60 Age <60 Chronic onset >2 months Chronic onset >2 months Lack of shoulder involvement Lack of shoulder involvement Lack of inflammatory stiffness Lack of inflammatory stiffness Prominent systemic features; weight loss, night pain, neurological signs Prominent systemic features; weight loss, night pain, neurological signs Features of other rheumatic disease Features of other rheumatic disease Normal or extremely high acute phase response Normal or extremely high acute phase response Treatment dilemmas (inadequate response to steroids, inability to reduce steroids, contraindication to steroids etc) Treatment dilemmas (inadequate response to steroids, inability to reduce steroids, contraindication to steroids etc)

RA diagnosis  Aim for early diagnosis and treatment but lack of features of established disease can cause difficulty  Considerable variability in presenting symptoms and lab results  History Polyarticular involvement –may be small number of joints initially Polyarticular involvement –may be small number of joints initially Morning stiffness (>30 minutes) suggests inflammatory joint pain Morning stiffness (>30 minutes) suggests inflammatory joint pain Chronicity Chronicity  Examination Joint tenderness MCP, MTP, wrists Joint tenderness MCP, MTP, wrists RA nodules, not usually seen until later RA nodules, not usually seen until later Upper and lower extremity involvement Upper and lower extremity involvement

Synovitis

Rheumatoid Arthritis Investigations  No single diagnostic test  Serology RF RF 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 individualsPositive in 5-10% of healthy individuals Anti- CCP Abs Anti- CCP Abs As sensitiveAs sensitive Much more specificMuch more specific

Rheumatoid Arthritis Investigations  Inflammatory markers Non-specific Non-specific Useful for distinguishing inflammatory conditions from non-inflammatory Useful for distinguishing inflammatory conditions from non-inflammatory  Full blood count Anaemia of chronic disease, leucocytosis, thrombocytosis Anaemia of chronic disease, leucocytosis, thrombocytosis  Radiology Erosions of cartilage and bone Erosions of cartilage and bone Presence more useful diagnostically with increasing duration of disease Presence more useful diagnostically with increasing duration of disease

Radiology

ACR/EULAR classification criteria  Designed to classify patients as RA earlier for purpose of clinical trials – not diagnostic criteria  Still useful, several differences from 1987 criteria which aimed to classify people with established disease  Target population At least 1 joint with definite synovitis/swelling At least 1 joint with definite synovitis/swelling Synovitis not better explained by another disease Synovitis not better explained by another disease  Score >6 classified as RA Score Joint Involvement 1 large large small small 3 >10 joints 4 Serology Negative RF & anti-CCP Ab 0 Low positive RF or anti-CCP Ab 2 High positive RF or anti-CCP Ab 3 Acute Phase Reactants Normal CRP & ESR 0 Abnormal CRP or ESR 1 Duration of Symptoms < 6 weeks 0 >6 weeks 1

Polymyalgic onset RA  Bajocchi et al 2000 LO-RA vs YO-RA LO-RA vs YO-RA Polymyalgic symptoms more common in LO RAPolymyalgic symptoms more common in LO RA Higher frequency of shoulder involvement in LO RAHigher frequency of shoulder involvement in LO RA  Lopez-Hoyos et al 2004 Anti-CCP Abs in differential diagnosis of RA vs PMR Anti-CCP Abs in differential diagnosis of RA vs PMR 65% LO RA anti-CCP Ab +ve65% 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 RA  Gran, Mykebust 1999 Incidence and Characteristics of peripheral arthritis in PMR & TA Incidence and Characteristics of peripheral arthritis in PMR & TA 231 patients prospectively studied patients prospectively studied All ?PMR/TA in Norwegian county referred to rheumatology before treatmentAll ?PMR/TA in Norwegian county referred to rheumatology before treatment Followed throughout the disease courseFollowed throughout the disease course 187 ‘pure’ PMR 187 ‘pure’ PMR 38.5% developed peripheral arthritis 38.5% developed peripheral arthritis 11 developed RA (4.8% 6 female and 5 male) 11 developed RA (4.8% 6 female and 5 male)

Polymyalgic RA Mean duration of PMR at RA diagnosis was 63.2 months Mean duration of PMR at RA diagnosis was 63.2 months 5/8 patients had erosive x-ray changes 5/8 patients had erosive x-ray changes 6/11 patients had positive RF (all negative initially) 6/11 patients had positive RF (all negative initially) Mean CRP higher at diagnosis among those who developed arthritis (88.6 vs 59.7) Mean CRP higher at diagnosis among those who developed arthritis (88.6 vs 59.7)

Polymyalgic onset RA  Pease et al 2009 Prospective study of 147 patients presenting with PMR & 142 patients with LO-RA Prospective study of 147 patients presenting with PMR & 142 patients with LO-RA Reviewed accuracy of initial diagnosis Reviewed accuracy of initial diagnosis 23% PMR patients had peripheral synovitis23% PMR patients had peripheral synovitis In contrast to seronegative LO-RA, PMR patients younger, myalgia more frequent, PIP/MCP/wrist arthritis less frequentIn contrast to seronegative LO-RA, PMR patients younger, myalgia more frequent, PIP/MCP/wrist arthritis less frequent Combination of wrist + MCP and/or PIP highly suggestive of RACombination of wrist + MCP and/or PIP highly suggestive of RA

Polymyalgic onset RA  Pease et al patients with new onset LO-RA, PMR or TA >60 yrs 349 patients with new onset LO-RA, PMR or TA >60 yrs 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 expected for their stage of diseaseAll 9 dependant on higher steroid dose than typically expected for their stage of disease Initially synovitis suppressed by steroids but returned when dose loweredInitially synovitis suppressed by steroids but returned when dose lowered Initial plasma viscosity higher in this group (mean of 2.0 vs 1.86)Initial plasma viscosity higher in this group (mean of 2.0 vs 1.86) Difficulty to distinguish may lead to delay in correct diagnosis (average 13 months)Difficulty to distinguish may lead to delay in correct diagnosis (average 13 months)

Summary  Several challenges in diagnosing RA, particularly early in the disease course  Variety of possible presentations  Polymyalgic symptoms are common in elderly onset RA  May lead to diagnostic delay  No single diagnostic test; clinical history and examination important