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Blood Jun 2012
Topics: Aged; Anti-Infective Agents; Dapsone; Erythrocytes; Female; Hemolysis; Humans; Lichen Planus
PubMed: 22855947
DOI: 10.1182/blood-2011-07-365544 -
British Medical Journal Sep 1963
Topics: Chromium Isotopes; Dapsone; Dermatitis Herpetiformis; Hemolysis; Humans; Sulfones; Toxicology
PubMed: 14044869
DOI: 10.1136/bmj.2.5358.662 -
The New England Journal of Medicine Oct 2013Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%,...
BACKGROUND
Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome.
METHODS
We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls.
RESULTS
Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans.
CONCLUSIONS
HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).
Topics: Adult; Dapsone; Drug Hypersensitivity; Drug Therapy, Combination; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; HLA-B Antigens; Humans; Leprostatic Agents; Leprosy; Male; Polymorphism, Single Nucleotide; Risk Factors; Sequence Analysis, DNA
PubMed: 24152261
DOI: 10.1056/NEJMoa1213096 -
Current Opinion in Rheumatology May 2020Cutaneous lupus erythematosus (CLE) is a highly heterogeneous autoimmune disease. No specific Federal Drug Administration-approved therapies for CLE-alone are available,... (Review)
Review
PURPOSE OF REVIEW
Cutaneous lupus erythematosus (CLE) is a highly heterogeneous autoimmune disease. No specific Federal Drug Administration-approved therapies for CLE-alone are available, and resistance to conventional treatments is common. This review will summarize current treatment approaches and pending treatment strategies.
RECENT FINDINGS
Research into the pathogenesis of CLE is accelerating. A skewed type I interferon production and response contribute to CLE lesions. The pathophysiology of lesions may be similar among the lesional subtypes, and patients with a more TLR9-driven disease mechanism may have more benefit from hydroxychloroquine. Case reports continue to support the use of dapsone for CLE, especially bullous lupus erythematosus. Rituximab and Belimumab have efficacy in patients with systemic lupus erythematosus and severe active CLE. The significant role for type I interferons in CLE and encouraging clinical data suggest anifrolumab as a very promising agent for CLE. Dapirolizumab, BIIB059, Ustekinumab and Janus kinase inhibitors also have supportive early data as promising new strategies for CLE treatment.
SUMMARY
Continued research to understand the mechanisms driving CLE will facilitate the development and approval of new targets. The pipeline for new treatments is rich.
Topics: Antibodies, Monoclonal; Dapsone; Humans; Hydroxychloroquine; Interferon Type I; Lupus Erythematosus, Cutaneous; Rituximab; Ustekinumab
PubMed: 32141953
DOI: 10.1097/BOR.0000000000000704 -
The Journal of the Royal College of... Nov 1970
Topics: Dapsone; Diagnosis, Differential; Humans; Leprosy; Skin Diseases
PubMed: 5492616
DOI: No ID Found -
British Medical Journal Sep 1968
Topics: Acute Disease; Dapsone; Diagnosis, Differential; Humans; Leprosy; Peripheral Nervous System Diseases; Skin Manifestations
PubMed: 4299854
DOI: 10.1136/bmj.3.5620.725 -
International Journal of Molecular... Dec 2022Dapsone (DDS) therapy can frequently lead to hematological side effects, such as methemoglobinemia and DNA damage. In this study, we aim to evaluate the protective...
Dapsone (DDS) therapy can frequently lead to hematological side effects, such as methemoglobinemia and DNA damage. In this study, we aim to evaluate the protective effect of racemic alpha lipoic acid (ALA) and its enantiomers on methemoglobin induction. The pre- and post-treatment of erythrocytes with ALA, ALA isomers, or MB (methylene blue), and treatment with DDS-NOH (apsone hydroxylamine) was performed to assess the protective and inhibiting effect on methemoglobin (MetHb) formation. Methemoglobin percentage and DNA damage caused by dapsone and its metabolites were also determined by the comet assay. We also evaluated oxidative parameters such as SOD, GSH, TEAC (Trolox equivalent antioxidant capacity) and MDA (malondialdehyde). In pretreatment, ALA showed the best protector effect in 2.5 µg/mL of DDS-NOH. ALA (1000 µM) was able to inhibit the induced MetHb formation even at the highest concentrations of DDS-NOH. All ALA tested concentrations (100 and 1000 µM) were able to inhibit ROS and CAT activity, and induced increases in GSH production. ALA also showed an effect on DNA damage induced by DDS-NOH (2.5 µg/mL). Both isomers were able to inhibit MetHb formation and the S-ALA was able to elevate GSH levels by stimulating the production of this antioxidant. In post-treatment with the R-ALA, this enantiomer inhibited MetHb formation and increased GSH levels. The pretreatment with R-ALA or S-ALA prevented the increase in SOD and decrease in TEAC, while R-ALA decreased the levels of MDA; and this pretreatment with R-ALA or S-ALA showed the effect of ALA enantiomers on DNA damage. These data show that ALA can be used in future therapies in patients who use dapsone chronically, including leprosy patients.
Topics: Methemoglobin; Antioxidants; Thioctic Acid; Dapsone; Superoxide Dismutase; DNA Damage
PubMed: 36613503
DOI: 10.3390/ijms24010057 -
BMJ Case Reports Aug 2020Methaemoglobinaemia is a rare disease that is typically caused by a medication or other exogenous agent, with dapsone being the most common. It occurs when the...
Methaemoglobinaemia is a rare disease that is typically caused by a medication or other exogenous agent, with dapsone being the most common. It occurs when the concentration of methaemoglobin rises via ferrous haeme irons becoming oxidised to the ferric state, which shifts the oxygen dissociation curve to the left. The net result of an elevated methaemoglobin concentration is functional anaemia and impaired oxygen delivery to tissues. At lower blood levels, this can cause symptoms such as cyanosis, lethargy, headache and fatigue, whereas at higher levels it can be fatal. Here we discuss a subtle case of dapsone-induced methaemoglobinaemia presenting as subacute mental status changes and apparent hypoxia, thus highlighting the association between methaemoglobinaemia and dapsone. This case demonstrates the importance of thorough medication reconciliation and maintaining a broad differential diagnosis, while also recognising the significance of conflicting data and their implications for the workup.
Topics: Aged; Anti-Infective Agents; Confusion; Dapsone; Female; Humans; Memory Disorders; Methemoglobin; Methemoglobinemia; Oxygen
PubMed: 32843412
DOI: 10.1136/bcr-2020-235403 -
Journal of Global Antimicrobial... Sep 2022Dapsone is one of the important drugs in the treatment of leprosy. The present study aims to evaluate the resistance of Mycobacterium leprae isolates to dapsone, in turn... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Dapsone is one of the important drugs in the treatment of leprosy. The present study aims to evaluate the resistance of Mycobacterium leprae isolates to dapsone, in turn assisting in implementing better control strategies for leprosy elimination.
METHODS
A systematic literature search was conducted in PubMed, Embase, Medline, and Web of Science. Two independent reviewers selected the literature according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), extracted data, and evaluated the risk of bias. Drug resistance data were pooled using the random-effects model. Subgroup analysis was performed based on across sampling time, region, study population (treatment status, relapses status), and sample size.
RESULTS
A total of 30 studies were included. The results of meta-analysis showed that the dapsone resistance rate of leprosy patients after treatment was 8% (95% confidence interval [CI], 6%-10%). Compared to the rates of primary resistance of new cases without treatment therapy (pooled incidence, 4% [95% CI, 2%-5%]), treatment cases (13% [95% CI 9%-16%]) had secondary resistance, and relapse cases (26% [95% CI, 18%-33%]) had drug resistance. In addition, the drug resistance rate of monotherapy was significantly increased than that of relapsed patients treated with diamino-diphenylsulfone monotherapy. Subgroup analysis showed that the patients in the Western Pacific have the highest dapsone resistance, and the resistance to dapsone was slightly lower after 2005. For sample size, the rate in the group under 100 samples was significantly higher than in the other.
CONCLUSION
Dapsone resistance is closely related to leprosy relapse and long-term drug use. Dapsone monotherapy is one of important reasons for drug resistance in relapsed cases. Drug resistance varies among different populations and regions of the world.
Topics: Dapsone; Humans; Leprosy; Mycobacterium leprae; Recurrence; Risk Factors
PubMed: 35643395
DOI: 10.1016/j.jgar.2022.05.015 -
Antimicrobial Agents and Chemotherapy Jul 1994The safety and pharmacokinetics of weekly dapsone and weekly dapsone plus pyrimethamine were examined in adult patients with human immunodeficiency virus infection who... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The safety and pharmacokinetics of weekly dapsone and weekly dapsone plus pyrimethamine were examined in adult patients with human immunodeficiency virus infection who were at risk for pneumocystis pneumonia because of a prior episode or a CD4+ T-cell count less than 250 cells per mm3. Groups of patients received 100, 200, and 300 mg of dapsone as a single weekly dose. The maximum tolerated dose of weekly dapsone was established as 200 mg per week in patients receiving at least 500 mg of zidovudine concomitantly. This dose of dapsone was then found to be well tolerated when combined with pyrimethamine at 25 mg. Further patients were randomized to dapsone at 200 mg or dapsone at 200 mg plus pyrimethamine at 25 mg once weekly. Twenty-six patients each were followed for a median of 33 weeks on dapsone alone and 45 weeks on the combination. Seven patients in each group withdrew because of toxicity. Five patients receiving dapsone developed documented pneumocystis pneumonia, while four and two patients receiving dapsone plus pyrimethamine developed documented and presumptive pneumocystis pneumonia, respectively. To evaluate the tolerability of a higher dose of pyrimethamine, 11 patients had their regimen changed to dapsone at 200 mg plus pyrimethamine at 75 mg, which was well tolerated by 10 of the patients for a median period of 11 weeks. The pharmacokinetics of dapsone and pyrimethamine were examined by using a population pharmacokinetic model. Decreases in the apparent volume of the peripheral compartment were observed when multiple-dose regimens of dapsone were compared with single-dose dapsone and when multiple-dose regimens of dapsone with pyrimethamine were compared with multiple-dose dapsone alone. When administered weekly, dapsone at 200 mg and dapsone at 200 mg with pyrimethamine at 25 mg are both well-tolerated regimens. This preliminary study suggests that the efficacy of these regimens in preventing pneumocystis pneumonia, however, may be less than that of trimethoprim-sulfamethoxazole.
Topics: AIDS-Related Opportunistic Infections; Adult; Biological Availability; Chromatography, High Pressure Liquid; Dapsone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Pyrimethamine
PubMed: 7979291
DOI: 10.1128/AAC.38.7.1580