RA presentations can be highly variable

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The presentation of rheumatoid arthritis is highly variable so it is important to reassess if there is poor response to treatment after initial diagnosis


A 38-year-old male presents with pain in bilateral knees, right lateral epicondyle and bilateral thumb MCP joints.  He works full-time as a painter.  His job involves repetitive use of his right hand, squatting, kneeling and climbing ladders.  His symptoms have been present for three months and are starting to interfere with his ability to perform his job. There is morning stiffness of around 15 minutes and he worsens at the end of a work day.

How can I narrow a differential diagnosis in someone presenting with multifocal pain?

My considerations are:

Is the pain inflammatory in nature? Inflammatory joint pain typically has morning stiffness longer than 30 minutes, joint swelling and worsening with rest.   

Does the pain have a mechanical basis? Mechanical joint pain typically worsens with activity (especially repetitive activity) and is relieved by rest. Is he worse at the end of the work day? Does he improve over the weekend or on holidays?

What is the distribution of joint involvement – oligoarticular, polyarticular, symmetrical or asymmetrical?

Is there a past history (or family history) of psoriasis, suggestive of psoriatic arthritis?

Spondyloarthritis. Are there features of inflammatory back pain – morning pain and stiffness in the low back or buttock, waking him from sleep and improving with activity?

Are there features of enthesitis – Achilles tendinopathy, lateral epicondyle pain, trochanteric pain?  Enthesitis may suggest a spondyloarthritis.

Connective tissue disease – Raynaud’s phenomenon, rashes, photosensitivity, sicca symptoms (dry eyes and mouth), alopecia, mouth ulcers and unexplained fevers.

Recent travel or infective illnesses, suggestive a viral arthritis or reactive arthritis.

The distribution of joints in his case is not particularly revealing as both large and small joints are involved. Examination shows typical features of lateral epicondylitis, with point tenderness on the lateral epicondyle, increased pain with resisted wrist and finger extension and a slightly weak grip strength, even though this is his dominant hand. There is tenderness over the first MCP joint but no appreciable synovitis. There is anterior knee pain with squatting but no knee effusion. There is weakness of both gluteal muscles and quadriceps, demonstrated by poor control and medial tracking of the knee with single leg standing and squatting. 

Blood tests for C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are in the normal range.  Rheumatoid factor, CCP antibodies, ANA and HLA B27 are negative.  Ultrasound of the right elbow shows a swollen common extensor tendon with a heterogeneous appearance, consistent with lateral epicondylitis. Bilateral knee X-rays are normal.

On balance of the history, examination and laboratory work, I feel his pain is most likely to be mechanical and related to the demands of his job.

I prescribe analgesia with meloxicam 15mg daily and recommend physiotherapy for the lateral epicondylitis and a lower limb strengthening program to improve his biomechanics.

One month later, he reports the right lateral epicondyle pain is much better. His knee and thumb pain is worse and he is struggling to work. Examination now shows bilateral knee effusions, and synovitis of the thumb MCP joints. 

His symptoms are progressing and examination findings are different, so my original diagnosis has to be questioned. 

The presence of knee effusions and synovitis make me suspect an inflammatory arthritis.
I would like some supporting evidence to back up my clinical suspicions.

A right knee MRI scan (his most symptomatic knee) shows no osteoarthritis, a small medial meniscal tear, a moderate joint effusion and synovitis. The meniscal tear is small and doesn’t really explain his symptoms, so I regard it as an incidental finding.  The joint effusion is out of proportion to the other findings. 

I perform a joint aspirate which shows leucocytes 12,638 x106/L, 80% are neutrophils  Crystal analysis is negative and cultures are negative.  A leucocyte count greater than 2,000 x106/L is inflammatory.

This confirms that he has a seronegative inflammatory arthritis. The main differential in this setting is spondyloarthritis or rheumatoid arthritis.

Given the lack of other features of spondyloarthritis, I diagnose him with seronegative rheumatoid arthritis.

I start him on low dose prednisone (10mg daily) for immediate symptom control and then initiate methotrexate. My standard approach is to use methotrexate, 10mg weekly for two weeks and then increase to 20mg weekly, if there are no side-effects.

I use folic acid 5mg weekly, taken the day after methotrexate. Folic acid is used to reduce liver test abnormalities (transaminases) and also reduces gastrointestinal side-effects. Rheumatologists will have different schedules for titrating both methotrexate and folic acid. Methotrexate generally takes about two months to be effective.

Over the subsequent 18 months, his arthritis fluctuates. He eventually requires addition of sulfalsalazine as a second DMARD. His CRP increases and more joints become involved. 
I progress to using a biologic DMARD and he eventually improves with etanercept, a TNF inhibitor given as a weekly subcutaneous injection.  He is now working full-time as a painter and has only minor symptoms of rheumatoid arthritis.

The presentation of rheumatoid arthritis is highly variable. As you can see in this case, he presented with oligoarticular pain and it only became clearer with time that he had an inflammatory condition.

It is important to reassess if there is poor response to treatment after your initial diagnosis!

Dr Andrew Jordan is a rheumatologist based in Parramatta, Sydney, with a special interest in inflammatory arthritis, gout and osteoporosis 

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