How Clinically Relevant is Dapsone-related Peripheral Neuropathy?: An Overview of Available Data with Emphasis on Clinical Recognition.

19 19 QUESTIONS • CHALLENGES • CONTROVERSIES Dapsone, first developed in 1908, was initially intended for oral treatment of infectious diseases; however, dapsone was later shown to have potent anti-inflammatory properties. The anti-inflammatory mechanisms of dapsone appear to be separate from its antibacterial properties. Oral dapsone has been shown to be efficacious for dermatoses with neutrophilic infiltration, which is believed to be related to stabilization of neutrophil lysosomes and disruption of adherence properties of neutrophils. Several dermatological conditions are treated with dapsone, including leprosy, acne conglobata, dermatitis herpetiformis (as first-line treatment), pemphigoid, pemphigus, erythema elevatum diutinum, polychondritis, leucocytoclastic vasculitis, and Behcet’s disease. Dapsone is a second-line treatment for Pneumocystis jiroveci pneumonia. Oral dapsone therapy is associated with a constellation of hematological adverse reactions. The most common of these include hemolytic anemia (usually secondary to glucose-6-phosphate dehydrogenase [G6PD] deficiency), methemoglobinemia, and agranulocytosis. These more common side effects typically appear during the early phase of treatment and are dose related. Due to the heavy emphasis on monitoring for hematological side effects associated with oral dapsone use, neurological adverse reactions are likely to remain unrexognized, especially early in the course of their emergence. Neurological side effects of oral dapsone include ocular adverse effects, such as optic atrophy, and sensory and motor neuropathies. Dapsone-related peripheral neuropathy, although an uncommon side effect of oral treatment, is clinically significant due to its frequent subtle onset (especially with motor neuropathy) and the high potential for longterm persistence, including after cessation of dapsone intake. The onset of peripheral neuropathy after initiation of oral dapsone therapy is variable. Guidelines for monitoring the hematologic adverse effects of oral dapsone are in place, but are lacking for neurological side effects, such as peripheral neuropathy. Little direction for monitoring the neurological side effects of oral dapsone is provided in the literature. This article discusses various reports of neuropathies and the subtle initial symptoms that clinicians need to be cognizant of during treatment.