Isoniazid induced palmoplantar hyperhidrosis

Case report

A 15-year-old boy developed a headache for a week with a right focal seizure, associated with five episodes of non-projectile vomiting. Clinical and fundal examination was normal at that time. A contrast-enhanced magnetic resonance imaging of the brain revealed a left frontal tuberculoma with perilesional oedema, for which he was started on four-drug antitubercular therapy (ATT), along with oral dexamethasone and levetiracetam by a local practitioner.

Five months after starting ATT, the boy presented to our centre with paraesthesia burning sensations and pricking pain initially in both feet, which later involved his legs and eventually his hands over the next three weeks. This was associated with excessive sweating over both palms and soles. The hyperhidrosis occurred throughout the day but worsened during exams or whenever he felt anxious. It caused him difficulty in writing assignments and holding objects and led to public embarrassment on several occasions. No other area of his body was similarly affected. He had no other associated symptoms like pungent body odour, fever, heat intolerance, change in body weight or altered bowel habits. He had no other medical condition and was not receiving any medication other than those prescribed to him.

Clinical examination revealed areflexia in both lower limbs, with decreased vibration sensation, but other sensations preserved. There was profuse sweating of both palms and soles (Figure 1). Muscle bulk, tone and power were unremarkable in all limbs. Nerve conduction studies showed sensory axonal polyneuropathy affecting both lower and upper limbs. While sympathetic skin response showed an abnormal response, including reduced amplitude in both palms, cardiac autonomic function testing was normal. Endocrinal evaluation, including thyroid function testing and repeat neuroimaging, showed no new abnormality. OPEN IN VIEWER

After starting oral pyridoxine supplementation at 40 mg/day, the boy showed gradual improvement in symptoms over the next two months. On the last follow-up after four months of starting pyridoxine, the paresthesia and hyperhidrosis had reduced to a minimum. We thus established a final diagnosis of sensory-autonomic neuropathy due to pyridoxine deficiency caused by isoniazid treatment.

Discussion

While primary focal hyperhidrosis is usually idiopathic, with onset around puberty, predominantly affecting the axillary region and seen in 3% of otherwise healthy persons, the hands, feet and other areas are also sometimes affected. ¹

Isoniazid, an essential constituent of first-line ATT, interferes with pyridoxine metabolism.^2,3 This is dose-related and usually appears some months after starting medication. ⁴ Usually, the initial symptoms are numbness, tingling, pricking pains and burning sensations in the feet and later on involving the legs and eventually hands in a length-dependent manner. ⁵ Neurological examination commonly reveals areflexia or hyporeflexia, decreased distal sensation and mild distal weakness, more prominent in the lower limbs. ⁶ Later, a motor-sensory polyneuropathy may develop, but symptoms of autonomic dysfunction such as anhydrosis or hyperhidrosis are extremely rare.^7,8 Most often, hyperhidrosis is seen at the onset of polyneuropathy, which later disappears as nerve damage progresses and ultimately leads to anhydrosis.

Instead of embarking on antiperspirant use, simple pyridoxine supplementation can lead to the reversal of symptoms in such cases.