A 69-year-old woman with rheumatoid arthritis presented with swollen ankles. She was diagnosed as having rheumatoid arthritis over 18 years ago and had been relatively well controlled on non-steroidal antiinflammatory drugs until six months ago, when her joint pains and swelling required the addition of penicillamine to control her symptoms. The patient had a past history of hypertension, for which she took bendroflumethiazide. On examination she had symmetrical joint deformities consistent with rheumatoid arthritis. The heart rate was 90 beats/min and irregular. Her blood pressure measured 140/90 mmHg. The JVP was not raised. Both
heart sounds were normal and the chest was clear. Abdominal examination was normal. Inspection of the lower limbs revealed pitting oedema. Investigations are shown.
Hb 11 g/dl WCC 5 109/l Platelets 190 109/l Sodium 134 mmol/l Potassium 4.5 mmol/l Urea 6 mmol/l Creatinine 70 mol/l Bilirubin 11mol/l Alkaline phosphatase 100 iu/l Albumin 26 g/l Urinalysis Protein
What is the management?
a. Stop penicillamine.
b. Start prednisolone.
c. Start ACE inhibitor therapy.
d. Arrange renal biopsy.
e. Arrange IVU
a. Stop penicillamine.
The patient has heavy proteinuria and gives a relatively recent history of onset of swollen ankles shortly after starting penicillamine. The most likely diagnosis is penicillamine-induced membranous nephropathy, which usually occurs within 6–12 months of the initiation of drug therapy. Proteinuria resolves in virtually all cases after stopping the drug but this may take several months. Other causes of heavy proteinuria secondary to membranous nephropathy in rheumatoid arthritis include gold therapy. Renal amyloidosis is a recognized cause of heavy proteinuria complicating chronic rheumatoid arthritis. While it is possible that the patient may have renal amyloidosis, the relationship of the proteinuria to the
initiation of penicillamine points to a drug-induced membranous nephropathy. Other causes of renal disease in rheumatoid arthritis include analgesic nephropathy, focal segmental glomerulonephritis and rheumatoid vasculitis. All are characterized by blood in the urine. Analgesic nephropathy is usually secondary to non-steroidal antiinflammatory drugs and paracetamol. The proteinuria is rarely severe enough to cause nephrotic syndrome. Focal segmental glomerulonephritis is rare and is excluded by the absence of red cells in the urine. Rheumatoid vasculitis has a predilection for skin and the peripheral nervous system but in very rare circumstances may affect the kidneys. It is more likely in patients with severe disease, nodule formation, high titres of rheumatoid factor and hypocomplementaemia