A 55-year-old nurse was started on multidrug therapy 3 weeks ago to treat pulmonary tuberculosis contracted from a former patient. He comes to his primary care provider due to fatigue and low-grade fever for several days. He also has had muscle aches and severe joint pain in his elbows, wrists, and knees. The patient says, "I don't think it's the flu; I had the vaccine months ago." He has no current respiratory symptoms apart from pleuritic chest pain. The patient has no other significant past medical or family history. His examination is unremarkable. Laboratory results are as follows: An abnormality in which of the following metabolic processes most likely underlies this patient's current condition?

Question

A 55-year-old nurse was started on multidrug therapy 3 weeks ago to treat pulmonary tuberculosis contracted from a former patient.  He comes to his primary care provider due to fatigue and low-grade fever for several days.  He also has had muscle aches and severe joint pain in his elbows, wrists, and knees.  The patient says, "I don't think it's the flu; I had the vaccine months ago."  He has no current respiratory symptoms apart from pleuritic chest pain.  The patient has no other significant past medical or family history.  His examination is unremarkable. Laboratory results are as follows:  An abnormality in which of the following metabolic processes most likely underlies this patient's current condition?

Quizplus · Accepted Answer

11ec160b_3c81_e5f2_9249_f32e25e52864_MD0001_00 This patient's clinical findings (constitutional symptoms, arthralgias, and pleuritic chest pain), anti-histone antibodies, and recent isoniazid use support the diagnosis of drug-induced lupus erythematosus (DILE). Unlike classic lupus, DILE typically lacks the usual cutaneous manifestations (eg, malar rash) and is rarely associated with neurologic or renal complications. Clinical improvement is rapid on discontinuation of the causative agent. Procainamide, hydralazine, and isoniazid are metabolized via phase II acetylation in the liver. Hepatic expression of N-acetyltransferase is genetically determined, and patients with a slow acetylator phenotype are at greater risk of developing DILE. Patients who are slow acetylators are also predisposed to isoniazid-induced peripheral neuropathy due to increased drug concentrations. (Choice B) Liver hydrolysis is a phase I reaction in which a compound is cleaved by adding water (eg, esterase or amidase enzymes). Phase I metabolism usually precedes phase II conjugation metabolism. (Choice C) Liver hydroxylation is a phase I oxidation transformation catalyzed by the cytochrome P450 monooxygenase system. Addition of a hydroxyl group reduces lipid solubility and facilitates excretion. (Choice D) Liver sulfate conjugation is a phase II metabolic pathway that biotransforms drugs into more polar compounds that are more water soluble and easily excreted. (Choice E) Certain drugs are hydrolyzed by plasma esterases, which rapidly cleave ester linkages after the drug enters the circulation. This rapid inactivation allows for the short duration of action of these medications. Many drugs used in anesthesia (eg, succinylcholine, tetracaine, remifentanil) are metabolized by plasma hydrolysis. (Choice F) A few drugs are not metabolized in the body. They are excreted in the urine mostly unchanged and are still pharmacologically active. Educational objective: Drug-induced lupus erythematosus (DILE) is characterized by abrupt onset of lupus symptoms (eg, fever, arthralgias, pleuritis) with positive anti-histone antibodies. It has been linked to drugs metabolized by N-acetylation in the liver (eg, procainamide, hydralazine, isoniazid). Genetically predisposed individuals who are slow acetylators are at greater risk for developing DILE.

A 55-Year-Old Nurse Was Started on Multidrug Therapy 3 Weeks