A 54-year-old woman comes to the office as a new patient. She immigrated to the United States 3 weeks ago for political asylum. The patient has a history of hypertension and type 2 diabetes mellitus. She was also diagnosed with active pulmonary tuberculosis 4 months ago. She completed 2 months of intensive antituberculosis therapy with 4 drugs and now is on isoniazid and rifampin alone. Repeat sputum testings for acid-fast bacillus are negative. The patient feels well overall but does have tingling and numbness of the bilateral hands and feet that started a few weeks ago; she has no cough, fever, chills, or night sweats. She does not use tobacco, alcohol, or illicit drugs. Temperature is 37 C (98.6 F), blood pressure is 126/84 mm Hg, and pulse is 84/min. Lung auscultation reveals fine crackles in the left upper lung field. Heart sounds are normal and regular. Neurologic examination shows normal motor strength but decreased touch and pain sensation in the bilateral upper and lower extremities. Romberg sign is positive. Skin examination shows no abnormalities. Hemoglobin A1C level is 7%. Chest x-ray reveals fibrotic changes in the left upper lung. Which of the following is the most likely cause of this patient's current symptoms?
Active tuberculosis is typically treated with 2 months of isoniazid (INH), rifampin, ethambutol, and pyrazinamide. Most patients then transition to several months of INH and rifampin alone. Drug side effects are common with treatment, most notably INH-induced hepatotoxicity and peripheral neuropathy.
INH-induced peripheral neuropathy is caused by pyridoxine (vitamin B6) deficiency. INH binds the active form of pyridoxine, resulting in renal excretion. Most patients have large enough stores of pyridoxine to tolerate increased excretion; however, those with malnourishment, pregnancy, or certain comorbid illnesses (eg, diabetes mellitus) may develop a deficiency. Because pyridoxine serves as a crucial cofactor in the synthesis of neurotransmitters, deficiencies typically manifest with neurologic symptoms. Most commonly, patients develop numbness and tingling in a "stocking-glove" distribution. Physical examination usually reveals deficits in proprioception and vibration; over time, touch, pain, and temperature sensation may be affected.
Those at high risk for pyridoxine deficiency (such as this patient with diabetes mellitus) should be given prophylactic pyridoxine supplementation while on INH.
(Choice A) Vitamin B12 deficiency affects the dorsal/lateral spinal columns, resulting in paresthesias, ataxia, and loss of vibratory sensation/proprioception. This patient with diabetes mellitus on INH is at high risk for pyridoxine deficiency and most likely has INH-induced peripheral neuropathy.
(Choice B) Guillain-Barré syndrome causes acute inflammatory demyelinating polyneuropathy that usually manifests with paresthesias of the toes and fingertips followed by ascending motor weakness. This patient has had numbness and tingling for a few weeks without motor weakness; INH-induced peripheral neuropathy is far more likely.
(Choice C) Amyotrophic lateral sclerosis is a progressive, neurodegenerative disorder that causes motor neuron loss. Patients usually have significant muscle weakness or incoordination. This patient with sensory changes and no motor weakness is unlikely to have this diagnosis.
(Choices E and F) Neuropathy caused by diabetes mellitus (microvascular nerve injury) or monoclonal plasma cell disorders (paraprotein neuropathy) usually begins in the feet with alterations in proprioception/vibratory sensation. Paraprotein neuropathy may progress to motor weakness. This patient is at high risk for INH-induced pyridoxine deficiency due to diabetes mellitus; with a few weeks of sensory symptoms in both the hands and feet with no motor symptoms, INH-induced peripheral neuropathy is more likely.
Educational objective:
Patients with malnutrition, pregnancy, or certain comorbid conditions (eg, diabetes mellitus) should be started on pyridoxine supplementation when treated for latent or active tuberculosis with isoniazid (INH). This helps prevent INH-induced peripheral neuropathy, which is due to INH-mediated pyridoxine deficiency.