What anti-tuberculosis (anti-TB) medication is likely causing a patient's symptoms of paresthesia (needles and pricks) after they stopped taking their prescribed pyridoxine (vitamin B6) supplements?

Isoniazid-Induced Peripheral Neuropathy: Cause and Management

Isoniazid is the anti-TB medication causing the patient's symptoms of paresthesia (needles and pricks) after discontinuing pyridoxine (vitamin B6) supplements. This peripheral neuropathy is a well-documented side effect of isoniazid that occurs due to its interference with pyridoxine metabolism 1, 2, 3.

Mechanism of Isoniazid-Induced Neuropathy

Isoniazid causes peripheral neuropathy through the following mechanisms:

• Competes with pyridoxal phosphate for the enzyme apotryptophanase 3
• Interferes with pyridoxine metabolism, leading to vitamin B6 deficiency 2
• Reduces glutamic-oxaloacetic transaminase (GOT) activity in the blood 4
• Affects both the coenzyme (pyridoxal phosphate) and apoenzyme components 4

Risk Factors for Developing Isoniazid-Induced Neuropathy

The following factors increase the risk of developing peripheral neuropathy:

• Slow acetylator status (genetic predisposition affecting approximately 50% of Blacks and Caucasians) 3
• Discontinuation of prescribed pyridoxine supplements 2, 4
• Higher doses of isoniazid 4, 5
• Comorbid conditions such as:
  • Diabetes
  • Alcoholism
  • Malnutrition
  • Chronic renal failure
  • HIV infection
  • Pregnancy or breastfeeding
  • Advanced age 2, 6

Clinical Presentation

Isoniazid-induced neuropathy typically presents as:

• Paresthesia (needles and pricks sensation) 7
• Burning feet sensation as an early manifestation 6
• Predominantly sensory symptoms initially, but can progress to motor involvement 7
• Distal to proximal progression of symptoms 6
• Loss of ankle and knee reflexes in severe cases 7

Management

1. Resume pyridoxine supplementation immediately:

   • Standard preventive dose: 25-50 mg daily 2
   • Treatment dose for established neuropathy: 100 mg daily 2

2. Continue isoniazid therapy (do not discontinue TB treatment) 7

3. Monitor for symptom improvement:

   • Symptoms typically improve within weeks to months of pyridoxine supplementation 7, 6
   • Motor symptoms generally resolve faster than sensory symptoms 7

4. Consider acetylator status testing if symptoms are severe or persistent 6

5. Dose adjustment of isoniazid may be necessary in slow acetylators (reduce to 3 mg/kg/day or less) 6

Prevention

To prevent recurrence of neuropathy:

• Ensure continuous pyridoxine supplementation throughout the entire course of anti-TB therapy 2
• Educate the patient about the importance of taking all prescribed medications, including supplements
• Monitor for early signs of neuropathy at follow-up visits
• Consider higher doses of pyridoxine (50 mg/day) for patients with additional risk factors 2

Important Considerations

• Peripheral neuropathy is more common in slow inactivators of isoniazid 4, 5
• Even low doses of pyridoxine (6 mg daily) have been shown to be effective in preventing isoniazid-induced neuropathy 5
• Some patients may experience mild residual sensory impairment even after treatment with pyridoxine 7
• HIV co-infection increases the risk of peripheral neuropathy, as it is also a common neurological complication of HIV infection 8

The correct answer is D. Isoniazid.