Review Question - QID 217600

This patient presenting with a subacute cough, hemoptysis, fatigue, night sweats, unintentional weight loss, fever, and lung crackles in the setting of a positive acid-fast bacilli smear most likely has reactivation pulmonary tuberculosis. The standard treatment for this condition includes pyrazinamide, which can cause hyperuricemia and precipitate a gout flare (acutely painful great toe).

Pulmonary tuberculosis should be strongly considered in patients presenting with cough, hemoptysis, and constitutional symptoms (malaise, unintentional weight loss), especially if they are from an endemic region (Southeast Asia, Africa, Latin America). The gold standard for diagnosis is a sputum mycobacterial culture. In practice, sputum acid-fast smears and/or nucleic acid amplification tests are commonly used. Chest imaging usually shows opacities in the lower or middle lung lobes in primary tuberculosis and in the upper lobes in reactivation tuberculosis. The standard induction therapy for pulmonary tuberculosis consists of RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) therapy. One side effect of pyrazinamide is hyperuricemia due to decreased renal excretion, which can precipitate gout flares. Gout typically presents with severe pain in a monoarticular pattern (most commonly in the hallux joints). On physical exam, erythema, swelling, warmth, and stiffness and pain with range of motion of the affected joint will be appreciated. In chronic cases, subcutaneous deposits of uric acid known as tophi may also be appreciated.

Pham et al. describe the pathophysiology of pyrazinamide-induced urate retention. They discuss that pyrazinamide reduces the renal clearance of urate significantly. They recommend adequate hydration and monitoring of uric acid levels to minimize the risk of this complication.

Incorrect Answers:
Answer 1: Ethambutol is an inhibitor of arabinosyl transferase, which is responsible for mycobacterial cell wall synthesis. It is used in standard induction therapy for tuberculosis and can cause optic neuropathy as a side effect, presenting as diminished visual acuity and/or color vision disturbances.

Answer 2: Hydrochlorothiazide is a diuretic that is commonly used in the first-line treatment of primary hypertension. It also causes hyperuricemia which can precipitate a gouty flare, but is a less likely etiology in this patient who has been on this medication for a long time. Rather, the acute precipitating factor is likely starting ethambutol.

Answer 3: Isoniazid is an inhibitor of mycolic acid synthesis and is used in standard induction therapy for tuberculosis. It can cause peripheral neuropathy as a side effect due to its depletion of pyridoxine (B6), presenting as sensory paresthesia in the distal extremities. This can be prevented by the co-administration of B6 with isoniazid.

Answer 5: Rifampin is an inhibitor of bacterial DNA-dependent RNA polymerase and is used in standard induction therapy for tuberculosis. It can cause reddish-orange discoloration of bodily fluids (saliva, sweat, tears) as a side effect.

Bullet Summary:
Pyrazinamide is an anti-mycobacterial agent used in standard induction therapy for active tuberculosis and can cause hyperuricemia, which can precipitate a gouty attack.