Peripheral neuropathy is a feared, but infrequent complication of isoniazid-based tuberculosis treatment which is thought to be attributable to acquired pyridoxine (B6) deficiency and resultant axonal degeneration. High serum isoniazid concentrations and drug-induced liver injury have been reported in patients with “slow acetylator” N-Acetyltransferase-2 (NAT2) enzyme genotypes in European and Asian populations. We present a case of painful distal, polyneuropathy in the setting of isoniazid administration despite B6 supplementation, in a patient later found to be a “slow acetylator”.

CASE PRESENTATION:
A 27-year-old surgical nurse was diagnosed with latent tuberculosis three years ago, after volunteering with an outreach clinic. She began standard 12-week isoniazid, rifapentine, and vitamin B6 100mg regimen. After the third dose, and worse with each subsequent dose, she developed “burning”, allodynia, hypesthesia, and “electrical current” lancinating pains in both hands and feet, interrupting her sleep and daily function. Pyridoxine levels were normal. B6 supplementation was increased, but her symptoms continued, prompting evaluation. Neurologic examination revealed touch, pinprick, and temperature loss in distal upper and lower limbs. Quantitative sensory testing (QST) revealed elevated vibratory threshold and hyperalgesia to heat-pain. EMG/NCS, autonomic testing, and other comprehensive laboratory testing were unrevealing. NAT2-genotype analysis demonstrated 5B/5B haplotype status (i.e. “slow acetylator”). Isoniazid was stopped, and the patient’s pain was managed with duloxetine, gabapentin, and topical amitriptyline-ketamine cream.

This case highlights the potential implications of NAT2 pharmacogenomics testing prior to treatment of latent tuberculosis within the US. Prior knowledge of this patient’s genotype preceding and during therapy may have led to drug-level monitoring and prevention of her painful polyneuropathy. Others have demonstrated elevated risk of organ damage in “slow acetylator” NAT2 genotypes, including polyneuropathy, in other populations where tuberculosis is more common. The prevalence of the “slow” acetylator genotype within the US has not been studied on a large scale.