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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 -
The American Journal of Tropical... May 2017AbstractDapsone is a bactericidal and bacteriostatic against , a causative agent of leprosy. Dapsone is also applied in a range of medical fields because of its... (Review)
Review
AbstractDapsone is a bactericidal and bacteriostatic against , a causative agent of leprosy. Dapsone is also applied in a range of medical fields because of its anti-inflammatory and immunomodulatory effects. Dapsone hypersensitivity syndrome (DHS) is a rare yet serious adverse drug reaction (ADR) caused by dapsone involving multiple organs. We performed a systematic review of published articles describing dapsone-induced hypersensitivity syndrome, including all Chinese articles and the latest literature available in online databases published between October 2009 and October 2015. We determined the prevalence, clinical characteristics, and mortality rate of DHS. Importantly, we also summarized the recent advances in genetic testing allowing prediction of ADRs. In an initial systematic electronic search, we retrieved 191 articles. Subsequently, these articles were further filtered and ultimately 84 articles (60 Chinese case reports, 21 non-Chinese articles, and three epidemiological studies) were selected, which included 877 patients. The prevalence of DHS among Chinese patients was 1.5% with a fatality rate of 9.6%. Early withdrawal of dapsone and appropriate treatment reduced the fatality rate. Most importantly, genetic screening for the HLA-B*13:01 allele among high-risk populations showed a significant utility as a useful genetic marker to DHS. In conclusion, this review discusses the epidemiological and clinical characteristics of DHS among Chinese patients, which may help physicians to understand this syndrome.
Topics: Adolescent; Adult; Aged; Alleles; Child; China; Dapsone; Drug Hypersensitivity; Drug Substitution; Female; Genetic Testing; HLA-B13 Antigen; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Prevalence; Primary Prevention; Survival Analysis; Syndrome
PubMed: 28167593
DOI: 10.4269/ajtmh.16-0628 -
Dermatologic Therapy Jul 2016Discoid lupus erythematosus (DLE) is a chronic cutaneous disease characterized by inflammatory plaques that, in the absence of prompt diagnosis and treatment, may lead... (Review)
Review
Discoid lupus erythematosus (DLE) is a chronic cutaneous disease characterized by inflammatory plaques that, in the absence of prompt diagnosis and treatment, may lead to disfiguring scarring and skin atrophy. However, there is limited evidence for which treatments are most effective. Currently, no medications have been approved specifically for the treatment of DLE. Many of the drugs described in the literature were developed for use in other immune disorders. This review will summarize current therapeutic options for DLE and their supporting evidence with discussion of prevention, topical measures, physical modalities, and systemic therapies, including newer potential therapies.
Topics: Adrenal Cortex Hormones; Calcineurin Inhibitors; Dapsone; Humans; Hydroxychloroquine; Laser Therapy; Lupus Erythematosus, Discoid; Methotrexate; Phototherapy; Retinoids; Smoking Cessation; Thalidomide
PubMed: 27073142
DOI: 10.1111/dth.12358 -
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 Dermatological Treatment Dec 2024There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities.
BACKGROUND
There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities.
METHODS
We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines.
RESULTS
Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria.
CONCLUSIONS
Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.
Topics: Humans; Female; Middle Aged; Male; Hydroxychloroquine; Pilot Projects; Chronic Disease; Chronic Urticaria; Urticaria; Omalizumab; Histamine H1 Antagonists; Cyclosporine; Dapsone; Anti-Allergic Agents; Acetates; Cyclopropanes; Quinolines; Sulfides
PubMed: 38508226
DOI: 10.1080/09546634.2024.2329784 -
JAMA Dermatology Jan 2019The first-line treatment for patients with chronic spontaneous urticaria (CSU), which is divided into idiopathic and autoimmune subtypes, consists of H1-antihistamines....
IMPORTANCE
The first-line treatment for patients with chronic spontaneous urticaria (CSU), which is divided into idiopathic and autoimmune subtypes, consists of H1-antihistamines. However, limited evidence guides the treatment of CSU after maximal therapy with antihistamines fails. Two randomized clinical trials suggest that dapsone may be a successful second-line therapy.
OBJECTIVE
To evaluate the efficacy and safety of dapsone therapy in patients with CSU.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective medical record review included 79 patients with CSU treated with dapsone who presented to the tertiary care academic medical center at the New York University School of Medicine, New York, New York, from January 1, 2005, through April 15, 2017. Follow-up was completed on February 28, 2018. Data were analyzed from March 1 through May 31, 2018.
EXPOSURES
Treatment with oral dapsone for CSU.
MAIN OUTCOMES AND MEASURES
Efficacy of dapsone therapy for CSU was evaluated as improvement, complete response, and remission.
RESULTS
Seventy-nine patients (65% women; mean [SD] age, 49.8 [16.1] years [range, 20-79 years]) were included in the analysis. Forty-five patients had chronic idiopathic urticaria and 34 had chronic autoimmune urticaria. Improvement in CSU was observed in 62 patients (78%) (36 [80%] with idiopathic and 26 [76%] with autoimmune disease) with dapsone. Mean (SD) time to improvement was 1.1 (1.0) months. A complete response was achieved in 29 (47%) of these 62 patients (16 [44%] with idiopathic and 13 [50%] with autoimmune disease). Mean (SD) time to complete response was 5.2 (5.2) months. Dapsone therapy was tapered in 21 patients after a mean (SD) of 2.4 (2.2) months and discontinued in 18. Ten patients experienced remission with no subsequent flares, even after dapsone therapy was discontinued with follow-up of 0.3 to 10.0 months. Sixteen patients experienced mild adverse effects. Two serious adverse effects were reported.
CONCLUSIONS AND RELEVANCE
Results of this study suggest that dapsone is a useful and well-tolerated second-line therapy for patients with CSU in whom antihistamines and other first-line agents have failed.
Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Chronic Disease; Dapsone; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Male; Middle Aged; Remission Induction; Retrospective Studies; Treatment Outcome; Urticaria; Young Adult
PubMed: 30476976
DOI: 10.1001/jamadermatol.2018.3715 -
Experimental Eye Research May 2021Uveitis is the inflammation of uveal tract comprising of iris, ciliary body and choroid. Blood ocular barriers maintaining the homeostasis of eye breach during uveitis,...
Uveitis is the inflammation of uveal tract comprising of iris, ciliary body and choroid. Blood ocular barriers maintaining the homeostasis of eye breach during uveitis, leads to high risk for sight-threatening complications. The purpose of this study was to compare the anti-inflammatory activity enabled by two diverse pharmacological agents (prednisolone and dapsone) using their effect on aqueous humor proteome. Wistar rats of either sex (150-200g) were used and randomly divided into various groups. Normal group was injected with 0.1ml normal saline (NS), endotoxin (LPS) (200 μg/0.1ml NS) was injected into endotoxin induced inflammatory groups followed by 0.1% dapsone and 1% prednisolone treatment in endotoxin induced uveitis (EIU) groups, respectively. Aqueocentesis was performed post 24 hour inflammation and samples were subjected for clinical parameter evaluation, cytokine analysis as well as global proteomic analysis using High-resolution mass spectrometer. Following which spectrum analysis, production spectra of peptides were matched against R. Norvegicus Protein Database (Uniport) using Proteome Discoverer (v2.2). Upon clinical evaluation, the anterior segment images post dapsone and prednisolone treatment have shown marked decrease in hyperaemia, miosis and iridial vessels vasodilation in rat eyes as compared to inflammation group. The result of cytokine analysis revealed 0.1% dapsone and prednisolone both significantly decreased the TNF-α levels. HRMS studies analysis expressed 140, 160, 158 and 141 proteins unique to normal, EIU, Dapsone and prednisolone group respectively. To conclude aqueous humor pharmacoproteomic revealed the anti-inflammatory activity of the dapsone comparable to the prednisolone treatment in endotoxin induced uveitis. The topical dapsone may be used as an alternative therapeutic option in treating uveitis without elevating intraocular pressure.
Topics: Administration, Topical; Animals; Anti-Infective Agents; Aqueous Humor; Dapsone; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Glucocorticoids; Male; Prednisolone; Proteomics; Rats; Rats, Wistar; Uveitis, Anterior
PubMed: 33722510
DOI: 10.1016/j.exer.2021.108534 -
European Journal of Internal Medicine Sep 2023
Topics: Humans; Dapsone; Pneumonia, Pneumocystis; Anemia, Hemolytic; Methemoglobinemia
PubMed: 37169635
DOI: 10.1016/j.ejim.2023.04.030 -
Chemical Research in Toxicology Mar 2023Drug-responsive T-cells are activated with the parent compound or metabolites, often via different pathways (pharmacological interaction and hapten). An obstacle to the...
Drug-responsive T-cells are activated with the parent compound or metabolites, often via different pathways (pharmacological interaction and hapten). An obstacle to the investigation of drug hypersensitivity is the scarcity of reactive metabolites for functional studies and the absence of coculture systems to generate metabolites in situ. Thus, the aim of this study was to utilize dapsone metabolite-responsive T-cells from hypersensitive patients, alongside primary human hepatocytes to drive metabolite formation, and subsequent drug-specific T-cell responses. Nitroso dapsone-responsive T-cell clones were generated from hypersensitive patients and characterized in terms of cross-reactivity and pathways of T-cell activation. Primary human hepatocytes, antigen-presenting cells, and T-cell cocultures were established in various formats with the liver and immune cells separated to avoid cell contact. Cultures were exposed to dapsone, and metabolite formation and T-cell activation were measured by LC-MS and proliferation assessment, respectively. Nitroso dapsone-responsive CD4+ T-cell clones from hypersensitive patients were found to proliferate and secrete cytokines in a dose-dependent manner when exposed to the drug metabolite. Clones were activated with nitroso dapsone-pulsed antigen-presenting cells, while fixation of antigen-presenting cells or omission of antigen-presenting cells from the assay abrogated the nitroso dapsone-specific T-cell response. Importantly, clones displayed no cross-reactivity with the parent drug. Nitroso dapsone glutathione conjugates were detected in the supernatant of hepatocyte immune cell cocultures, indicating that hepatocyte-derived metabolites are formed and transferred to the immune cell compartment. Similarly, nitroso dapsone-responsive clones were stimulated to proliferate with dapsone, when hepatocytes were added to the coculture system. Collectively, our study demonstrates the use of hepatocyte immune cell coculture systems to detect in situ metabolite formation and metabolite-specific T-cell responses. Similar systems should be used in future diagnostic and predictive assays to detect metabolite-specific T-cell responses when synthetic metabolites are not available.
Topics: Humans; Coculture Techniques; Drug Hypersensitivity; Dapsone; Liver; Hepatocytes; Lymphocyte Activation
PubMed: 36812109
DOI: 10.1021/acs.chemrestox.2c00343 -
Journal of Immunology (Baltimore, Md. :... Apr 2023Previous studies have shown that cysteine-reactive drug metabolites bind covalently with protein to activate patient T cells. However, the nature of the antigenic...
Previous studies have shown that cysteine-reactive drug metabolites bind covalently with protein to activate patient T cells. However, the nature of the antigenic determinants that interact with HLA and whether T cell stimulatory peptides contain the bound drug metabolite has not been defined. Because susceptibility to dapsone hypersensitivity is associated with the expression of HLA-B*13:01, we have designed and synthesized nitroso dapsone-modified, HLA-B*13:01 binding peptides and explored their immunogenicity using T cells from hypersensitive human patients. Cysteine-containing 9-mer peptides with high binding affinity to HLA-B*13:01 were designed (AQDCEAAAL [Pep1], AQDACEAAL [Pep2], and AQDAEACAL [Pep3]), and the cysteine residue was modified with nitroso dapsone. CD8+ T cell clones were generated and characterized in terms of phenotype, function, and cross-reactivity. Autologous APCs and C1R cells expressing HLA-B*13:01 were used to determine HLA restriction. Mass spectrometry confirmed that nitroso dapsone-peptides were modified at the appropriate site and were free of soluble dapsone and nitroso dapsone. APC HLA-B*13:01-restricted nitroso dapsone-modified Pep1- (n = 124) and Pep3-responsive (n = 48) CD8+ clones were generated. Clones proliferated and secreted effector molecules with graded concentrations of nitroso dapsone-modified Pep1 or Pep3. They also displayed reactivity against soluble nitroso dapsone, which forms adducts in situ, but not with the unmodified peptide or dapsone. Cross-reactivity was observed between nitroso dapsone-modified peptides with cysteine residues in different positions in the peptide sequence. These data characterize a drug metabolite hapten CD8+ T cell response in an HLA risk allele-restricted form of drug hypersensitivity and provide a framework for structural analysis of hapten HLA binding interactions.
Topics: Humans; Dapsone; Cysteine; CD8-Positive T-Lymphocytes; HLA-B Antigens; Drug Hypersensitivity; Peptides; Haptens
PubMed: 36881872
DOI: 10.4049/jimmunol.2200531