K Dani, R Ramachandran, H A Capell, R Madhok
Centre For Rheumatic Diseases, University Medical Unit, Glasgow Royal Infirmary
Correspondence to : R Madhok, Centre For Rheumatic Diseases, University Medical Unit, Glasgow Royal Infirmary Email: gcl103@clinmed.gla.ac.uk
SMJ 2005 50(3): 125-126
Abstract
Rheumatoid Arthritis (RA) is a common inflammatory arthritis1 with pain and loss of function among its most disabling symptoms. These are mostly secondary to inflammation or mechanical damage to the joints. However it is also important to consider disease complications as a cause of symptoms, especially when the response to treatment is suboptimal. We report an RA patient whose symptoms were resistant to standard therapy, and were actually due to peripheral neuropathy.
Case report
A 63-year-old lady with a six year history of seropositive RA presented with symptoms initially suggestive of a flare of synovitis affecting upper and lower limbs. She reported that recent proximal interphalangeal joint injections with corticosteroid to the left hand had not led to an improvement. On further enquiry she reported decreased power and heaviness in her hands extending from her finger tips to her elbow. She denied paraesthesiae or tingling. She had never manifest any extraarticular complications of RA. Drugs included a combination of Methotrexate, Sulphasalazine and Hydroxychloroquine for the past year, and nabumetone. Alcohol intake was limited to social occasions and she smoked 15 cigarettes daily.
On examination there was active synovitis of both wrists, left knee and left ankle. Neurological examination was hindered by pain and deformity. Tone, power, reflexes, co-ordination and proprioception were normal in all four limbs and her plantar response was ‘flexor’ bilaterally. There was, however, loss of sensation to pin-prick and light touch in the upper limbs in a glove distribution. Examination of the cranial nerves did not reveal any abnormality. There was no evidence of vasculitis, rheumatoid nodules or any other features of extra-articular disease.
Investigations showed an elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at 65mm/hr and 32mg/dl respectively, with thrombocytosis. She was normoglycaemic and had normal thyroid function. Electrolytes, immunoglobulins, ANCA, B12 and folate levels and myeloma screen were unremarkable. Chest X-ray was normal. Cervical spine x-rays showed only minor degenerative changes. Nerve conduction studies demonstrated a mixed sensory-motor axonal neuropathy involving all four limbs distally. Treatment with Gabapentin provided a moderate improvement in symptoms. The dose of Sulphasalazine was also increased to treat her synovitis.
Discussion
Recent advances in RA treatment have focussed on controlling synovitis, and thus disease related complications may be easily overlooked. Neuropathy, which can also cause pain, weakness and muscle wasting is one of the more common extra-articular manifestations of RA and occurs in about 10% of RA patients but subclinical evidence of neuropathy can be found in up to 50%.2 When reviewing an RA patient who presents with distal limb pain, the following features may suggest an underlying neuropathy;
• Pain resistant to conventional analgesics, antiinflammatory agents and local measures
• Positive neurological symptoms such as paraesthesiae and tingling
• Sensory loss, either well circumscribed or patchy
When a neuropathy is considered, it is important to be aware of other potential mechanisms. Entrapment neuropathy, the most common of which is carpal tunnel syndrome, occurs in up to fifty percent of patients.3 The classical feature of acroparaesthesia affecting the median digits in carpal tunnel syndrome is not always present and many present with less well defined impairment because of cross innervation between the median and ulnar nerve. Cervical spine instability occurs in up to 60% of patients with long standing RA.4 This may result in a radiculopathy or myelopathy which can mimic peripheral neuropathy. Myelopathy in particular can cause sensory symptoms which are difficult to localise and differentiate from those of articular disease. Magnetic Resonance Imaging (MRI) may be necessary for diagnosis.
A distal sensory neuropathy similar to that in our patient can also occur. It is slowly progressive and is associated with mild motor symptoms. Nerve biopsy studies reveal mild proliferative endarteritis and segmental demyelination with areas of axonal degeneration.5 Up to 75% of patients recover partially or completely.6 A detailed drug history is essential. Although classically seen with gold therapy, peripheral neuropathy has also been rarely implicated with cyclosporin, sulphasalazine, and hydroxychloroquine.. Recently, leflunamide has also been linked to a reversible form of neuropathy.7
Small fibre neuropathy is also common. This should be considered in patients with prominent symptoms but subtle signs. Nerve conduction studies are generally normal in such patients and a definite diagnosis can only be obtained by skin biopsy and specific electrophysiological measurements.8 The underlying aetiology is rarely discovered but it has been linked to Sjogren’s Syndrome and amyloidosis, two conditions closely associated with RA. It is also important to exclude causes unrelated to RA. Myeloma and paraneoplastic-related neuropathies need to be considered in the older patient with a high ESR. Diabetes, thyroid related disorders and vitamin B12 deficiency should be excluded.
In summary, our patient had ‘arthritis-like’ symptoms unresponsive to local and systemic measures. A detailed clinical evaluation suggested an underlying peripheral neuropathy, confirmed on nerve conduction studies. This case illustrates the fallacy of attributing all causes of pain and weakness in RA to active joint disease and treating them with escalating doses of conventional analgesia and disease modifying agents. Clearly it is important that the presence of peripheral neuropathy is promptly recognised. Nevertheless, tight control of synovitis is vital.
Key message
Peripheral neuropathy frequently presents as pain and weakness and needs to be excluded in RA patients unresponsive to conventional treatment
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