Dapsone at a Glance
- Dapsone (4,4’-diaminodiphenylsulfone) is classified as sulfonamide but has unique pharmacologic properties.
- Diseases with consistent response to dapsone are dermatitis herpetiformis, erythema elevatum diutinum, linear immunoglobulin A dermatosis/chronic bullous disease of childhood and bullous eruption of systemic lupus erythematosus.
- Diseases with sporadic response to dapsone encompass a wide spectrum and are as diverse as collagen vascular/autoimmune diseases and acne. In these diseases, dapsone can be used as a corticosteroid sparing agent.
- A unifying feature of responsive diseases is neutrophilic and eosinophilic granulocytes.
- Dapsone is also effective in certain infections such as leprosy, actinomycetoma, or rhinosporidiosis.
- Adverse effects are hemolysis and methemoglobulinemia. Glucose-6-phosphate dehydrogenase (G6PD) level should be obtained before beginning dapsone treatment. Dapsone should only be given with great caution to patients with G6PD deficiency.
- Other adverse effects are neuropathy, a mononucleosis-like hypersensitivity syndrome termed the sulfone syndrome, and agranulocytosis.
Dapsone's interference with the folate biosynthetic pathway accounts for its antibiotic effect and it is still sometimes used as an antibiotic in pneumocystis pneumonia prophylaxis (PCP) and in combinations for treatment of leprosy and malaria. However, dapsone is used in dermatology for its anti-inflammatory effect, the mechanisms of which are still incompletely characterized. Dapsone inhibits migration of neutrophils to areas of inflammation by inhibiting neutrophil chemotaxis to the chemoattractant signals F-met-leu-phe1,2 and leukotriene B4 (LTB4).3–5 In addition to this effect on neutrophil migration, dapsone also inhibits the adherence of neutrophils to skin-localized IgA6 and endothelium.7 Additionally, dapsone has been shown to inhibit the release of inflammatory mediators including interleukin-8 (IL-8),8 PGD2, and tumor necrosis factor-α (TNF-α).9 Finally, dapsone has been shown to inhibit the myeloperoxidase H2O2-halide-mediated cytotoxic system,10–11 perhaps by inhibiting the calcium flux necessary for these events.12 Myeloperoxidase is the enzyme in the azurophilic granules of neutrophils and in the lysosomes of monocytes that catalyzes the conversion of hydrogen peroxide and chloride ions into hypochlorous acid, a potent oxidant that causes cell damage.
Figure 225-1 shows the chemical structure of dapsone [4,4′-diaminodiphenylsulfone].13,14 Although dapsone is classified as a sulfonamide, cross-reactions occur in only 7%–22% of sulfa-allergic patients. They are usually mild and do not necessitate stopping dapsone.15,16 If side effects are substantial, sulfapyridine may be tried. Sulfapyridine is thought to have similar mechanisms of action although with a reduced activity level and a lower incidence of toxicity. However, in the United States, it is available only on a compassionate-use basis from the manufacturer.
Chemical structure of dapsone and sulfapyridine.
Dapsone tablets are available in 25- and 100-mg sizes; therapeutic doses for various conditions range from 25 mg to approximately 400 mg. Dapsone is well absorbed from the gut with peak levels being reached ...