The antifungal agent itraconazole is considered safe in patients with diabetes (1,2) but has been associated with acute painful neuropathy in patients taking vincristine (3–5). We describe a patient with diabetic neuropathy who developed acute painful neuropathy with itraconazole therapy.
A 37-year-old man with poorly controlled type 1 diabetes of 19 years’ duration presented with an excematous rash affecting his lower abdomen. Skin scrapings grew C. albicans. Itraconazole (200 mg/day) was prescribed, but on the 4th day of treatment he developed acute bilateral leg weakness with stabbing pain in the hips and legs and difficulty walking. He was taking no other medication apart from insulin. He was known beforehand to have peripheral neuropathy with absent ankle reflexes and mild postural hypotension.
On examination, his BMI was 24 kg/m2, his calf muscles were tender, and he had moderate proximal leg weakness. His muscle tone was normal and knee reflexes preserved. There was no change in postural hypotension or sensory abnormalities. Itraconazole was stopped after 7 days. Over the next 6 months his pain improved, although he lost 6 kg in weight. The power in his legs recovered, but the knee reflexes were lost. Over the next year his pain improved and he became asymptomatic.
At the onset of his symptoms, blood count, erythrocyte sedimentation rate, renal function, and serum creatine kinase were normal. On repeated follow-up, these blood tests and his HbA1c remained unchanged. The vibration perception threshold at the medial malleolus rapidly declined over the next year. Nerve conduction studies of the upper and proximal lower limbs were normal, but conduction velocities were slow in the distal lower limbs. Over the next year, the distal lower limb compound muscle action potential amplitudes reduced, sug-gesting loss of these nerve fibers. Electromyography (EMG) was normal at presentation, but after 6 months showed signs of lower-limb muscle denervation. There were no features to support lumbar plexopathy. As the abnormalities were most marked in the distal muscles, this suggests axonal degeneration, which tends to affect the longest nerve fibers first.
There are a number of diagnostic possibilities. Acute painful neuropathy generally occurs within days of rapid improvements in glycemic control, which was not the case in our subject. Diabetic amyotrophy often presents with severe anterior thigh muscle pain and weight loss; however, EMG typically shows evidence of lumbosacral plexopathy (6). Acute diabetic radiculopathy can cause acute pain and weakness, but the symptoms are usually in a single nerve root distribution. Diabetic cachexia can be associated with profound weight loss, symmetrical peripheral neuropathy, and autonomic dysfunction but is generally associated with painful dysesthesias without weakness (7).
In this man with preexisting diabetic neuropathy, the sudden onset of neurological symptoms with itraconazole ther-apy, axonal degeneration on electrophysiological testing, and stabilization after stopping itraconazole suggest that a drug-induced polyneuropathy is the most likely diagnosis. Drug-induced neuropathy is associated with axonal degeneration, lasting weeks or months (8). Discontinuing the administration of the drug does not always lead to improvement, as the damage to neuronal structures or function can be permanent.
