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Why is a woman's osteoarthritis still not responding despite years of treatment? That's what Navin Kumar Devaraj, MD, of Universiti Putra Malaysia, was trying to determine in a patient's case he reported in the about a 71-year-old woman who presented to a primary care clinic for a routine checkup.

She had long-standing hypertension and diabetes mellitus, and told Devaraj, whom she had seen at her previous visit, that for the previous 5 years she had continuing pain in both knees, and that it affected her mobility.

History and Assessment

Her history included being diagnosed by other primary care providers with bilateral knee osteoarthritis, and receiving treatment with analgesics, as well as glucosamine and physiotherapy. This regimen, however, had not relieved her pain, which was causing her serious difficulty with walking.

On assessment, she rated her pain as 6-8 on a 10-point scale, noting that the pain was most intense early in the day and then lessening slightly over the course of the day. She said both her knees were quite stiff at times, but there was no sign of swelling.

Physical examination showed that her vital signs were stable. Her knees showed a normal range of motion, although there was some tenderness at the joint line. Clinicians detected no evidence of effusion, and tests revealed normal stability in her tendons and ligaments.

Based on the persistent pain and minimal improvement, clinicians x-rayed both her knees, and tested her connective tissue using a screening profile that included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide (anti-CCP), anti-neutrophil cytoplasmic antibody plus anti-double stranded DNA antibody, and rheumatoid factor (RF). She was asked to return in 2 weeks.

At that follow up, her lab results showed elevated RF (67 IU/mL), ESR (78 mm/hr), and anti-CCP (47 u/ml). Knee x-rays showed features characteristic of rheumatoid arthritis (RA): joint space narrowing, soft tissue swelling, and peri-articular erosions. Results of other investigations were normal.

Diagnosis and Treatment

The medical team arrived at a diagnosis of RA and the patient was started on low-dose prednisolone concurrently with methotrexate, taking into account that her liver function was normal.

At her next follow-up appointment, she reported having much less pain; her pain score had improved significantly -- down to 1-3 on the 10-point scale. Clinicians continued treatment with methotrexate but discontinued the prednisone. She was advised to return for liver function monitoring every 3 months, given that liver toxicity and fibrosis are known side effects of methotrexate.

Discussion

In reporting this case of a woman who had a 5-year delay in diagnosis of RA, Devaraj noted that the diagnosis of a rheumatologic problem can be difficult, especially if not all the diagnostic criteria or typical clinical features are seen.

He stressed that early detection of RA is important because a "delay in diagnosis may worsen prognosis, which may lead to further damage to the joints and organs such as the lungs and the heart, and even to death."

The author noted that in the 2010 American College of Rheumatology -- European League Against Rheumatism (ACR-EULAR) – which includes aspects such as disease duration, whether large or small joints are involved, and serological evidence of elevation in inflammatory markers such as anti-CCP, RF, ESR, and CRP. A score of 6 or more is generally considered to define rheumatoid arthritis, while lower scores suggest a lower likelihood that the condition is RA.

Using these criteria, the patient in this case would have a score of only 4, which for a diagnosis of RA would need to be associated with other features such as classical x-ray findings -- which were indeed seen in this patient, Devaraj said. This can present diagnostic challenges, especially when scores of less than 6 are obtained on the gold standard ACR-EULAR classification, he added.

This perspective was echoed in a recent on the diagnosis and management of RA by Peter Taylor, MD, PhD, of the University of Oxford in England, who observed that the disease often begins insidiously, with signs and symptoms developing slowly over a period of weeks.

Devaraj concluded that disease-modifying antirheumatic drugs such as methotrexate or azathioprine should be started as soon as possible to prevent further harm to the joints and organs, and that early diagnosis and subsequent initiation of treatment will help improve the prognosis.