Pellagra Caused by Isoniazid

Abstract

Pellagra developed in a woman who was receiving isoniazid for disseminated sclerosis. Her intake of food was poor. The dermatitis appeared during a particularly sunny summer. Isoniazid was stopped. During the next three weeks her symptoms persisted. She continued to take the same inadequate diet. The burning sensations in both hands and feet were so severe that they caused her great distress. She was unable to sleep at night with her limbs covered. These latter symptoms were quickly relieved when nicotinamide was given. The dermatitis cleared completely in just over two weeks. As the symptoms of pellagra came while isoniazid was taken, there seemed to be a causal relationship. Other clinical observations are mentioned which point to isoniazid being a contributory factor in producing pellagra if the patient is in a pre-pellagrous condition. These clinical findings suggest a possible metabolic antagonism between isoniazid and nicotinamide. Isoniazid bears an undoubted structural similarity to nicotinamide, which is an integral component of an essential oxidation-reduction co-enzyme—that is, D.P.N. Experimental work has shown that it is possible by enzyme action to cause an exchange of isoniazid for the nicotinamide portion of D.P.N., which points to a mechanism whereby isoniazid might produce nicotinamide deficiency but in experiments on the whole animal this has not yet been demonstrated. The biological antagonism between isoniazid and pyridoxal is due to a purely chemical reaction. The suggestion that the pellagra-producing effect of isoniazid depends on the patient's initial level of nicotinamide being low would cover the facts observed in our case. The interest of these observations is not so much the causation of pellagra as the demonstration of an apparent relationship between isoniazid and a condition which is caused specifically by a nicotinamide deficiency ; this would therefore point to an interference by isoniazid in nicotinamide metabolism ; as an integral component of D.P.N., nicotinamide has its most important known metabolic function. The question remains whether these observations are a reflection in the human of the mechanism whereby the tubercle bacillus is inhibited by isoniazid. © 1956, British Medical Journal Publishing Group. All rights reserved.