Anti-Oxidative Therapy with Oral Dapsone Improved HCV Antibody Positive Annular Elastolytic Giant Cell Granuloma

A 72-year-old fisherman who was positive for the HCV antibody developed an annular, erythematous, infiltrated lesions on sun-exposed areas. The lesions were diagnosed as annular elastolytic giant cell granuloma both clinically and histologically. Topical corticosteroid and cryotherapy with liquid nitrogen for several months failed to improve the lesions. We then started dapsone, a known anti-oxidant, at 50 mg/day. A month later, the margins of the erythematous lesions faded, and the infiltration gradually decreased. No recurrence has been observed for one year after the start of the therapy. Anti-oxidative therapy appears to be effective for annular elastolytic giant cell granuloma and could be an alternate therapy for refractory granulomatous disease.     

A controlled trial of dapsone versus pyrimethamine-sulfadoxine for primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmosis in patients with AIDS

Pneumocystis carinii pneumonia (PCP) is the most common opportunistic human immunodeficiency virus (HIV)-related infection, occurring in 85 % of HIV infected patients without prophylaxis. Preventive treatment is required when CD₄ cell count falls below 200 cells per cubic millimeter. Cotrimoxazole has been shown to be highly effective but alternative drug regimens are often necessary because of the frequent drug hypersensitivity exhibited by HIV infected patients. The aim of this prospective, open, randomized, one-site study, involving HIV-infected patients with a CD₄ cell count below 200/mm³, or a percentage under 20%, randomly assigned to receive either dapsone 50 mg daily or Fansidar^® one tablet weekly, was to compare the efficacy and safety of these drugs in the primary prophylaxis of PCP. Both dapsone and Fansidar^® appear to be safe and effective alternative agents for the prevention of PCP. Their role in Toxoplasma gondii prophylaxis requires further evaluation.     

Deliberate self-poisoning with dapsoneA case report and summary of relevant pharmacology and treatment

We report the case of a 14-year-old girl who deliberately ingested 8–9 g of dapsone and presented with severe methaemoglobinaemia and altered mental status. Prompt treatment with repeated doses of methylene blue and organ support brought about control of the methaemoglobinaemia and averted organ failure.     

Genetically determined N-acetylation and oxidation capacities in Japanese patients with non-occupational urinary bladder cancer

Summary Genetically determined polymorphisms of N-acetylation and oxidative capacity have been studied using dapsone and metoprolol in 51 Japanese patients with spontaneous bladder cancer and 203 healthy control subjects.The results for N-acetylation pharmacogenetics were against the initial expectation that there would be a preponderance of slow acetylators in the cancer group, as 3 such patients (5.9%) were found as compared to 13 (6.4%) in the healthy group. There was no poor metabolizer (PM) of metoprolol in the cancer group, whereas in the healthy group one (0.5%) was a PM. There were no significant differences between the groups in the frequency of slow acetylator and poor oxidiser phenotypes, or in the frequency distribution profiles of acetylation (monoacetyldapsone/dapsone) and oxidative metabolic ratio (log metoprolol/-hydroxymetoprolol).The results indicate that neither N-acetylation nor the debrisoquine/sparteine-type oxidative phenotype and/or capacity represent a genetic predisposition to spontaneous bladder carcinogenesis in Japanese patients. In the normal Japanese population there is a great predominance of rapid acetylators and extensive oxidisers.     

Severe methemoglobinemia due to topical dapsone misuse in a teenage girl

Dapsone gel is a topical treatment for facial acne in adolescents and adults, and while systemic dapsone therapy is known to be associated with methemoglobinemia, once-daily topical dapsone has been well tolerated with few side effects in large randomized controlled trials. We describe the first reported case of severe methemoglobinemia in a healthy adolescent using daily topical dapsone. Although the medication was prescribed for facial use only, the patient reported topical use over her back and chest as well. This case illustrates the potential for significant systemic dapsone absorption even with daily topical dosing and demonstrates the need for clear anticipatory guidance to prevent the potential morbidity and mortality associated with methemoglobinemia from improper topical dapsone use.     

Dapsone for chronic idiopathic thrombocytopenic purpura in children and adults--a report on 90 patients

Data on 90 patients (55 adults and 35 children) with chronic idiopathic thrombocytopenic purpura (ITP) and a platelet count of <50 x 10(9)/L treated with dapsone at a dose of 1-2 mg/kg/d are presented. A response was observed in 57 (63.3%) patients. The average time for response was 3.5 months (range 1-9) and the average duration of treatment with dapsone was 10.4 months (range 4-14). Overall response rates of 65.7% and 61.8% were observed in children and adults respectively. Side effects requiring discontinuation of therapy were observed in three (2%) patients. These results demonstrate that dapsone is an effective, inexpensive and well-tolerated treatment for chronic ITP, in both children and adults and could be considered for patients who fail steroid therapy.     

Treatment of antiviral‐resistant recurrent erythema multiforme with dapsone

Recurrent erythema multiforme (REM) is a chronic disease characterized by frequent episodes of target cutaneous lesions in an acral distribution. Conventional treatment includes systemic corticosteroids and antiviral therapy. The aim of this study was to evaluate dapsone as a potential steroid sparing‐agent for the treatment of REM after a failed trial of at least one antiviral therapy (acyclovir, famciclovir, or valacyclovir). A retrospective chart review was conducted on thirteen patients with a diagnosis of REM who underwent treatment with dapsone after failing at least one antiviral therapy. Out of 13 patients, 6 showed complete response (CR) and 5 showed partial response (PR). The underlying cause was identified in 5 patients with all showing at least PR. Adverse effects, observed in 4 patients, included fatigue, macrocytic anemia, anxiety, insomnia and involuntary movements, and drug‐induced lupus erythematosus. A continuous course of dapsone, titrated up from 25 mg/day to a dose at which clinical improvement is seen with acceptable patient tolerance, is a viable steroid sparing‐agent for REM treatment after a failed trial of antiviral therapy.     

Dapsone-induced cholestasis and impairment of bile salt output in the rat

To evaluate the effect of dapsone (4,4'-diaminodiphenylsulfone, DDS) on biliary bile salt secretion, we administered the drug to male and female Wistar rats at a dose of 30 mg/kg body wt, twice a day, for 4 days. DDS decreased basal bile flow by about 20% in both male and female rats. In addition, basal biliary bile salt secretion was decreased by the drug in animals from both sexes (about 30% decrease). Bile salt maximum secretory rate, as evaluated by infusing tauroursodeoxycholate at stepwise-increasing rates, was not affected by DDS in either male or female rats, suggesting that the density of canalicular bile salt transporters is preserved. The size of the bile salt pool and the rate of de novo synthesis of bile salts, measured in bile salt-depleted animals, were decreased by about 33 and 35%, respectively; there was no difference in response between males and females. The ability of the ileum to reabsorb bile salts, as estimated by analysis of the expression of the ileal apical sodium-dependent bile salt transporter and of sodium taurocholate transport activity in brush border membrane vesicles, was not affected by DDS in either males or females. Overall, our findings suggest that an impairment of de novo synthesis mediated by a direct inhibition of CYP3A metabolism, rather than a decreased intestinal reabsorption of bile salts, accounts for the decrease in bile salt pool size. The dissociation between alteration of bile secretory function and the oxidative stress induced by DDS, which is known to be relevant only in male rats, is discussed.