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PubMed1996

[Agranulocytosis induced by dapsone prescribed for dermatitis herpetiformis].

INTRODUCTION: Dapsone is a drug widely prescribed in dermatology. It can lead to undesirable side effects including hematologic disorders. CASE REPORT: A patient with dermatitis herpetiformis was treated with dapsone. Agranulocytosis developed 6 weeks later and was revealed by fever and pneumonia which resolved under antibiotics. The agranulocytosis regressed without specific treatment after drug withdrawal. Blood counts returned to normal 2 weeks later. DISCUSSION: Dapsone-induced agranulocytosis is in common (1/10,000 to 1/20,000). The drug is widely prescribed, particularly for leprosy. Nevertheless, when dapsone is prescribed for dermatitis herpetiformis, the risk of agranulocytosis increases 25-fold reaching 1/400. The indication for dapsone must always made carefully, with surveillance of the blood counts every 15 days during the first 3 months of treatment for dermatitis herpetiformis.

Agranulocytosis↗

PubMedDate not supplied

Comparison of trimethoprim-sulfamethoxazole, dapsone, and pentamidine in the prophylaxis of Pneumocystis carinii pneumonia.

STUDY OBJECTIVE: To compare the incidence of Pneumocystis carinii pneumonia (PCP) in patients infected with the human immunodeficiency virus (HIV) receiving one of three prophylactic agents. DESIGN: Retrospective chart review. SETTING: A university-affiliated Department of Veterans' Affairs medical center HIV clinic. PATIENTS: All 200 HIV-infected patients enrolled in the clinic who were prescribed a PCP prophylactic drug during 18 months. INTERVENTIONS: Patients were administered oral trimethoprim-sulfamethoxazole (TMP-SMX) DS, oral dapsone, or aerosolized pentamidine in a heirarchic fashion. A subset of 110 patients received only one of the prophylaxis regimens for at least 6 months; they were examined separately for the purpose of statistical analysis. MEASUREMENTS AND MAIN RESULTS: One case of PCP was diagnosed in 1110 patient-months of oral TMP-SMX DS therapy, 6 in 418 patient-months of oral dapsone therapy, and 3 in 164 patient-months of aerosolized pentamidine therapy. In the subset population, the documented incidence of PCP was 0% among 71 TMP-SMX DS-treated patients, 16% among 25 dapsone-treated patients (p < 0.004), and 14% among 14 aerosolized pentamidine-treated patients (p < 0.03). For patients receiving primary prophylaxis, the incidence of PCP was 0% for 58 receiving TMP-SMX, 15% for 20 receiving dapsone (p = 0.015), and 17% for 6 receiving pentamidine (p = 0.094). CONCLUSION: We believe TMP-SMX DS was more effective than oral dapsone or aerosolized pentamidine in preventing PCP in these HIV-infected patients.

AIDS-Related Opportunistic Infections↗

PubMed1997

[Vitamin E as protective agent against hemolysis in leprosy patients under dapsone treatment].

Dapsone (4,4'diaminodiphenyl-sulphone) commonly used in the treatment of patients who suffer from leprosy, is a strongly oxidative drug, producing damage to the red cell membrane. This study investigated whether Vitamin E would have a protective effect on the red cell membrane from oxidant damage caused by Dapsone in patients with leprosy. We have studied 16 patients for 4 months, divided into two groups. Group 1 (n = 7) dapsone (DDS): 100 mg/day; Group 2 (n = 9) dapsone: 100 mg/day in addition with Vitamin E: 800 U/day. We did not include patients with low levels of Glucose-6-Phosphate Dehydrogenase (G-6-PD) because of their sensibility to this drug. At the beginning of the treatment we determined the level of G-6-PD. All patients showed a normocytic normochromic anemia with a decrease in Haptoglobine levels (below 5 mg/dl). Statistical analyses showed that reticulocyte counts did not present significant differences between groups all through evolution. As for methemoglobin (Hi) we observed in Group 1 an increase between the first and the fourth month, which was not seen in group 2. Statistical analyses of the results suggest that oral Vitamin E confers partial protective effect and does not correct the hemolysis parameters produced by Dapsone treatment except for Hi levels which were more sensitive to the oxidant damage.

Adult↗

PubMed1998

Dapsone induced pulmonary eosinophilia without cutaneous allergic manifestations--an unusual encounter--a case report.

Dapsone is a drug of choice in the treatment of leprosy. In addition it is very useful in the treatment of many other dermatological conditions. The "dapsone-induced hypersensitivity" is not unknown. However, to the best of our knowledge, pulmonary eosinophilia induced by dapsone without any cutaneous allergic manifestation has not been reported in leprosy patients. Pulmonary eosinophilia (Loeffler's syndrome) induced by dapsone without cutaneous manifestation has been reported in a non leprosy patient by Janier et al. We report a case of pulmonary eosinophilia associated with dapsone therapy in a patient with lepromatous leprosy without allergic cutaneous manifestations and our experience in the management of this patient.

Dapsone↗

PubMed1996

Twice-weekly dapsone for primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infection: efficacy, safety and pharmacokinetic data.

OBJECTIVES: In this study we evaluated the pharmacokinetics, efficacy and safety of dapsone given 100 mg twice weekly as primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients with HIV-1 infection. METHODS: This was a prospective open trial, evaluating a total of 55 HIV-1-infected patients with CD4 cell counts below 200/mm3 and without previous episodes of PCP. Plasma concentrations of dapsone were determined with high-performance liquid chromatography (HPLC). After a mean follow-up of 471 days, the PCP rates per year of observation were 6.79%. Discontinuation of treatment as a result of severe side effects was required in four patients (7.5%). At steady state, mean plasma concentrations 24, 72, 96 and 144 h following the administration of dapsone were 1.46plus minus0.8, 0.28plus minus0.20, 0.30plus minus0.21 and 0.37plus minus0.27 mg/L, respectively. Dapsone plasma levels showed a high interpatient variability. The values for the pharmacokinetic parameters were comparable to those described for healthy volunteers. CONCLUSIONS: The administration of 100 mg twice weekly of dapsone seems appropriate to maintain effective plasma concentrations of the drug and to prevent PCP with good safety in patients with HIV-1-related immunodeficiency.

Journal Article↗

PubMed1992

Human liver microsomal N-hydroxylation of dapsone by cytochrome P-4503A4.

One of the major routes of elimination of dapsone (4,4'-diaminodiphenylsulfone) is by N-oxidation, to produce a hydroxylamine metabolite. The specific form of cytochrome P-450 (P-450) involved in this oxidation reaction was examined in human liver microsomal preparations previously characterized with respect to their content of several known P-450 enzymes. Among five preparations, the rank order of activity for dapsone hydroxylamine formation was most well correlated with the immunochemically determined level of P-4503A4 (r = 0.94, p less than 0.03). Moreover, inhibition of microsomal oxidation was observed with antibodies specific to P-4503A, with a maximum reduction of greater than 90%, but was not produced by antibodies specific to P-4501A2, P-4502CMP, or P-4502E1. Prior incubation of microsomes with gestodene (100 microM) or troleandomycin (20 microM), known selective mechanism-based inhibitors of P-4503A enzymes (in the presence of NADPH), led to 75% and 40% reductions in catalytic activity, respectively. In contrast, preincubation with increasing concentrations of alpha-naphthoflavone, a known activator of P-4503A4, increased dapsone N-hydroxylation in a concentration-dependent manner, with 5-fold activation being observed at 50 microM alpha-naphthoflavone. Finally, P-4503A4 isolated from human liver microsomes and cDNA-expressed P-4503A4 (in yeast) were both able to catalyze dapsone N-hydroxylation, with the latter preparation exhibiting a 3-fold activation in the presence of 100 microM alpha-naphthoflavone. Collectively, these findings demonstrate that N-oxidation of dapsone in human liver is predominantly mediated by P-4503A4, and they suggest that quantitative measurement of this metabolic pathway in vivo might serve as an index of the activity of this enzyme.

Antibodies↗

PubMed2005

Comparison of colchicine, dapsone, triamcinolone, and diphenhydramine therapy for the treatment of brown recluse spider envenomation: a double-blind, controlled study in a rabbit model.

OBJECTIVE: To compare the efficacy of dapsone, diphenhydramine, colchicine, and intralesional triamcinolone in the treatment of brown spider bites. We used a purified venom that reproducibly produces a large eschar. To mimic real-life circumstances, all agents were administered following a 2-hour delay after envenomation. The animals were evaluated for the presence of coagulopathy to determine if the incidence of systemic findings correlated with the type of treatment. DESIGN AND SETTING: In a research laboratory, 60 New Zealand white rabbits each received an intradermal injection of 20 microg of purified Loxosceles reclusa venom. The rabbits were divided into 5 groups of 12; a control group and 4 groups treated with a drug (either colchicine, triamcinolone, diphenhydramine, or dapsone). Measured end points included maximum eschar size as well as histologic grading of depth, inflammation, and thrombosis. INTERVENTIONS: Treatment with colchicine, triamcinolone, diphenhydramine, or dapsone. MAIN OUTCOME MEASURES: Maximum eschar size as well as histologic grading of depth, inflammation, and thrombosis. RESULTS: There was no significant difference with respect to eschar size (1-way analysis of variance, P = .003). There was no significant difference between any treatment with respect to presence or absence of ulcer, necrosis, large vessel vasculitis, or small vessel vasculitis. The only outcome of significance was that triamcinolone offered protection from thrombosis (chi2 likelihood ratio, P = .04). We also noted evidence of coagulopathy in all of the envenomated animals. The rabbits had grossly elevated activated partial thromboplastin time results, which were corrected with 1:1 mixing with normal rabbit plasma, suggesting an acquired factor deficiency. We did not detect an individual factor deficiency or a lupus anticoagulant. CONCLUSIONS: In a rabbit model, none of the agents tested (dapsone, diphenhydramine, colchicine, and intralesional triamcinolone) had an effect on eschar size. Triamcinolone appeared to offer some protection against histologic evidence of thrombosis, but this protection did not translate into a difference in clinical outcome. All animals developed evidence of coagulopathy, regardless of treatment. The coagulopathy could be corrected by fresh rabbit plasma, suggesting an acquired factor deficiency.

Animals↗

PubMed1977

Dapsone-induced peripheral neuropathy.

Peripheral neuropathy is a rare complication of dapsone therapy. This neuropathy appears primarily to be of the motor type, and recovery occurs on discontinuation of the drug therapy. The patient in this report developed a marked motor deficit as well as a selective marked loss of vibration sense shortly after the initiation of a relatively low dose of dapsone. Recovery was rapid on cessation of the therapy. This patient was found to be a slow acetylator of isoniazid, and therefore is probably a slow acetylator of dapsone. The possible mechanisms of the neurotoxicity of dapsone and the role of altered metabolism are discussed.

Acne Vulgaris↗

PubMed2002

Dapsone as an oral corticosteroid sparing agent for asthma.

BACKGROUND: Oral corticosteroids are used as a treatment for asthma, however they are often associated with serious side effects. Dapsone is a sulfone with anti-inflammatory properties, therefore it may have a beneficial effect in the treatment of asthma and act as a corticosteroid-sparing agent. OBJECTIVES: The objective of this review is to assess the safety and efficacy of adding dapsone to oral corticosteroids in adults with stable asthma who are dependent on oral corticosteroids with the intention of eventually minimizing or eliminating the use of these steroids. SEARCH STRATEGY: The Cochrane Airways group trials register and reference lists of potential articles were searched. SELECTION CRITERIA: Randomised controlled trials investigating the addition of dapsone compared to placebo in stable corticosteroid dependent asthmatics. DATA COLLECTION AND ANALYSIS: No trials were found that met the selection criteria. MAIN RESULTS: No meta-analyses could be performed. REVIEWER'S CONCLUSIONS: No randomised controlled trials have been published, so there is no reliable evidence to show whether dapsone is beneficial or otherwise in the management of steroid-dependent asthmatic patients. There is a need for well designed randomised controlled trials to be performed. These must be carried out double-blind, since oral corticosteroid reduction requires a judgement on the part of the physician, who may be open to bias if the treatment allocation is known.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1993

Dapsone for autoimmune thrombocytopenic purpura.

Twenty-one human immunodeficiency virus (HIV)-free and six HIV-infected adults with autoimmune thrombocytopenic purpura (AITP) were treated with dapsone (100 mg/day). A response was observed in 13 patients (median platelet count before 25 x 10(9)/L, range 3-49; after 109 x 10(9)/L, range 69-241). Thrombocytopenia recurred in four of the responders in whom dapsone was discontinued. No response was observed in 12 patients. Dapsone had to be withdrawn after two weeks of treatment in the remaining two patients and after six to eight weeks in three other patients due to intolerance. No serious hematological complications were observed. These results confirm that dapsone is a safe, inexpensive, and effective treatment of AITP.

Adult↗

PubMed2006

The sulfone syndrome secondary to dapsone prophylaxis in a patient undergoing unrelated hematopoietic stem cell transplantation.

Dapsone is commonly used for pneumocystis carinii pneumonia (PCP) prophylaxis in immunocompromised patients. It has been used as an alternative therapy in the hematopoietic stem cell transplant (HSCT) setting in patients who can't tolerate trimethoprim-sulfamethoxazole. The Sulfone syndrome is not a well-known sequela of dapsone therapy and occurs at various doses, ranging from 50-300 mg/d. In all cases the syndrome occurs within 2 months of initiating therapy. Its clinical manifestations include: fever, methemoglobinemia, hemolytic anemia, exfoliative dermatitis and transaminits. A 51-year old female underwent a matched unrelated hematopoiectic stem cell transplant for acute mylogenous leukemia. Dapsone therapy was initiated on day +28 at a dose of 100 mg/day for PCP prophylaxis secondary to the patient's history of a sulfonamide allergy. On day +59, one month after initiation of therapy she developed hepatitis, hemolytic anemia, fever and methemoglobinemia of 8%. She was transferred to the intensive care unit and subsequently developed an exfoliative dermatitis. We conclude that the clinical presentation of this patient after HSCT on dapsone therapy coincide with the sulfone syndrome not previously described in a patients after HSCT.

Anemia, Hemolytic↗

PubMed1977

High-speed liquid chromatographic analysis of dapsone and related compounds.

A nonaqueous solvent absorptive support system and an aqueous solvent reversed-phase support liquid chromatographic system for analysis of dapsone and related compounds were investigated. The absorptive support system was more suitable for analysis of dapsone in raw materials, formulations, and tissue residues. The suitability was judged by the relative selectivity, efficiency, precision, and sensitivity of the systems. The adsorptive support system was used for the analysis of trace amounts of raw material impurities and dapsone metabolites. Coupling fluorometric detection to the chromatographic system yielded a 10-pg on-column detection limit for dapsone; the UV detection limit was 250 pg.

Adsorption↗

PubMed1986

Sustained-release delivery systems, I: Phase diagram studies of dapsone and selected derivatives.

In order to develop slowly dissolving particles containing the antileprotic drug dapsone (4,4'-sulfonylbisbenzamine, that would be suitable for a sustained-release intramuscular injection, the dilauryl and monolauryl derivatives of dapsone, N,N'-didodecanoyl-4,4'-sulfonylbisbenzamine and N-dodecanoyl-4,4'-sulfonylbisbenzamine, respectively, were studied for their ability to form solid dispersions with the parent compound. The 1:2 binary phase diagram showed these two compounds were partially miscible in the liquid state, leading to the coexistence of a monotectic and a eutectic system in the phase diagram. The 1:3 phase diagram showed that these compounds were completely miscible in the liquid state and formed discontinuous solid solutions in the solid state. At a cooling rate of 2.5 degrees C min-1, eutectic mixtures lying on the dapsone side of the eutectic point formed glass solutions. Taken as a whole, the results demonstrate that the molecular interactions between 1 and 3 are stronger than those between 1 and 2. Accordingly, 3 would appear to be the better carrier for reducing the rate of dissolution of dapsone from a solid dispersion.

Calorimetry, Differential Scanning↗

PubMedDate not supplied

Management of dapsone poisoning complicated by methaemoglobinaemia.

The currently recommended dosage regimen for methylene blue (intermittent bolus dose) in the treatment of methaemoglobinaemia caused by dapsone is often inadequate. This is due to the long half-life of dapsone which provides a continuing oxidative stress that can cause a recurrence of clinically significant methaemoglobinaemia. Methylene blue infusion is effective, as demonstrated in an illustrative case report, and should be supported by repeated doses of activated charcoal to enhance dapsone elimination. The principles of treatment of methaemoglobinaemia due to dapsone can be applied to methaemoglobinaemia due to any agent producing prolonged oxidative stress.

Adult↗

PubMed1997

Dapsone hydroxylamine inhibits the LTB4-induced chemotaxis of polymorphonuclear leukocytes into human skin: results of a pilot study.

OBJECTIVE: Dapsone (4,4'diaminodiphenylsulfone) is effective in treating leprosy, chronic inflammatory conditions and opportunistic infections in HIV patients. By the oral route, the sulfone is metabolized to monoacetyldapsone (MADDS) and dapsone hydroxylamine (DDS-NOH). We have addressed the question as to whether these dapsone metabolites have anti-inflammatory properties of their own in vivo. TREATMENT AND METHODS: After two weeks topical pre-treatment with MADDS (1%), DDS-NOH (1%) and clobetasol proprionate (CP; 0.05%) dissolved in acetone, as a reference, 10 ng leukotriene B4 (LTB4) were applied on the upper arms of eight healthy volunteers. After 24 h, biopsies were taken and the polymorphonuclear leukocytes (PMN) were quantified fluorometrically using elastase as marker enzyme. RESULTS: MADDS did not show any inhibitory activity on trafficking of PMN compared to the corresponding control and nontreated area (untreated: 790 +/- 450 PMN/10 micrograms skin; p > 0.05, acetone: 840 +/- 578 PMN/10 micrograms skin; MADDS: 1099 +/- 556 PMN/10 micrograms skin), whereas DDS-NOH caused a statistically significant inhibition of PMN accumulation as did the reference CP (DDS-NOH: 128 +/- 143 PMN/10 micrograms skin; CP: 86 +/- 131 PMN/10 micrograms skin, p < 0.01). CONCLUSIONS: These results indicate that DDS-NOH has anti-inflammatory potential which might contribute to the effectiveness of dapsone therapy.

Adult↗

PubMed1991

Dapsone in low doses prevents Pneumocystis carinii pneumonia in the rat model.

Less toxic drugs are needed for the prophylaxis and treatment of Pneumocystis carinii pneumonia (PCP) in patients with AIDS. Rats immunosuppressed with cortisone were given dapsone, chlorproguanil (CPG) and chlorcycloguanil (CCG), alone or in combination, in the diet and the P. carinii attack rate was compared with that of untreated controls. Dapsone alone at doses of 25 and 5 mg/kg/day was 100% effective in preventing PCP. The efficacy of CPG and CCG, however, could not be properly assessed because of the lack of acceptance of the diet by the animals. Even so, as a result of the findings with dapsone in this study, and because of its pharmacokinetics and minimum inhibitory concentration for P. carinii in vitro, a clinical trial of reduced dosage of dapsone given prophylactically to human beings is suggested. Such a trial may show a decrease in the toxicity of the drug that usually accompanies its long-term administration but retention of its efficacy.

Administration, Oral↗

PubMed1994

Dapsone attenuates kainic acid-induced seizures in rats.

We tested the ability of dapsone (4,4'-diamino-diphenyl sulfone) to attenuate kainic acid-induced seizures. We observed that 9.375 and 12.5 mg/kg doses of dapsone administered 30 min before a single kainic acid (10 mg/kg) i.p. injection were able to decrease the time of electroencephalographic seizures by 52% and 82%, respectively, as compared with rats administered with 10 mg/kg kainic acid only. The 12.5 mg/kg dose of dapsone was also able to diminish both kainic acid-evoked body and head shakes (58%) and kainic acid-induced mortality (75%). These results suggest that dapsone could be used in clinical trials as anticonvulsant.

Animals↗

PubMedDate not supplied

Dapsone intoxication: two case reports.

Two patients with dapsone intoxication, an adult and a 16-month-old child, are reported. Both developed symptomatic methemoglobin concentrations, of 35% and 37%, respectively, and improved with intravenous methylene blue. Methemoglobin levels subsequently rose in both cases to 25% at 24 and 37 hours, respectively. The recurrence of elevated methemoglobin levels resulted from either continued absorption of dapsone or its toxic metabolite from the gastrointestinal tract. Both patients were begun on serial oral activated charcoal and the child received a second methylene blue treatment. During the intoxication, serum hemoglobin concentrations dropped 2 gm with an increase in the reticulocyte count. Review of 20 cases of dapsone overdose from the literature showed that the major toxic manifestations are methemoglobinemia and hemolysis. Delayed sulfhemoglobinemia, reported in only one case, resolved spontaneously. The treatment of dapsone intoxication is intravenous methylene blue for symptomatic methemoglobinemia, gastric decontamination, and early administration of serial oral activated charcoal. Hemolysis is mild but transfusions may be required for patients with a glucose-6-phosphate dehydrogenase deficiency.

Adolescent↗