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Expert Opinion on Drug Safety Oct 2020The human leukocyte antigen (HLA)-B*13:01 was reported as an important risk factor for dapsone hypersensitivity syndrome (DHS) in Chinese and Thai populations. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The human leukocyte antigen (HLA)-B*13:01 was reported as an important risk factor for dapsone hypersensitivity syndrome (DHS) in Chinese and Thai populations.
RESEARCH DESIGN AND METHODS
From the Korean nationwide registry, seven subjects with previous DHS were included. Their HLA allele/phenotype frequencies were compared with 8 dapsone-tolerant subjects recruited from a single institution, and general population (n = 485) in Korea. The authors also performed a meta-analysis with these data using previous Chinese and Thai studies.
RESULTS
Among the seven DHS subjects, 85.7% presented with the HLA-B*13:01 allele. The HLA-C*03:04, HLA-DRB1*12:02 (both in linkage disequilibrium with HLA-B*13:01), and HLA-A*02:01 alleles were also presented in 85.7%, 71.4%, and 71.4%, respectively. Subjects with HLA-B*13:01 were susceptible to developing DHS compared to dapsone-tolerant controls (odds ratio [OR]: 73.667) and the Korean general population (OR: 139.500). HLA-C*03:04 (OR: 40.935), HLA-DRB*12:02 (OR: 36.613), and HLA-A*02:01 (OR: 5.862) showed similar results. In meta-analysis, HLA-B*13:01 was associated with dapsone-induced hypersensitivity (overall OR: 42.692), and subgroup analyses according to the control types demonstrated similar results (OR:43.694 and 41.866, respectively).
CONCLUSIONS
Similar to previous Asian population studies, HLA-B*13:01 is significantly associated with the risk of DHS in Korea. These associations may be useful for preventing DHS and improving drug safety.
Topics: Adult; Aged; Asian People; Child; Dapsone; Drug Hypersensitivity Syndrome; Female; Genotype; HLA-B13 Antigen; Humans; Leprostatic Agents; Male; Middle Aged; Registries; Republic of Korea; Risk Factors
PubMed: 32700588
DOI: 10.1080/14740338.2020.1796965 -
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 -
Archives of Medical Research Aug 2021Crohn's disease (CD), a type of inflammatory bowel disease (IBD), emerges with severe gastrointestinal (GI) tract inflammation, sometimes known as hostile abdomen....
BACKGROUND
Crohn's disease (CD), a type of inflammatory bowel disease (IBD), emerges with severe gastrointestinal (GI) tract inflammation, sometimes known as hostile abdomen. Conventional treatment of CD has several limitations such as insufficient response to treatment, and intolerable side effects of drugs. In addition, the high cost of biologic drugs prevents patients from continuing their treatment. Dapsone showed vigorous anti-inflammatory effects on the skin diseases, lung diseases and inflammatory diseases of the nervous system. Hence, we decided to investigate the effect of dapsone on animal model of CD.
METHODS
In this study, colitis was induced by instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) 100 mg/kg. Rats were treated with daily gavage of dapsone (10, 12.5 and 20 mg/kg). Seven days after induction of colitis, specimens were collected for pathological and molecular assessments.
RESULTS
Dapsone (12.5 and 20 mg/kg) preserved the histologic architecture of the colon and prevented crypts irregularity. Additionally, it decreased tissue edema and hindered inflammatory cells infiltration. Besides, all doses of dapsone decreased tissue concentration of tumor necrosis factor α (TNF-α) and interferon γ (INFγ). Western blot revealed that dapsone could attenuate inflammation via downregulation of toll-like receptor 4 (TLR4) and dephosphorylation of nuclear factor kB (NF-kB).
CONCLUSION
Based on these findings, dapsone attenuates inflammation and decreases TNF-α and INF-γ in animal model of CD. It acts through TLR4/NF-kB pathway to exert these effects.
Topics: Animals; Colitis; Colon; Dapsone; Disease Models, Animal; Humans; NF-kappa B; Rats; Signal Transduction; Toll-Like Receptor 4; Trinitrobenzenesulfonic Acid
PubMed: 33814208
DOI: 10.1016/j.arcmed.2021.03.005 -
Dermatology Online Journal Oct 2022A 4-year-old boy presented with blistering on his face and distal upper and lower extremities. Subepidermal blisters containing neutrophils and eosinophils visualized on...
A 4-year-old boy presented with blistering on his face and distal upper and lower extremities. Subepidermal blisters containing neutrophils and eosinophils visualized on histology supported the diagnosis of linear IgA bullous dermatosis of childhood (LABDC). The dermatosis presents with vesicles and tense blisters in an annular distribution, erythematous papules, and/or excoriated plaques. Histopathology shows subepidermal blisters with a neutrophilic infiltrate in the dermis, mainly concentrated at the tips of dermal papillae in the early stage of the disease, which can be mistaken for the pattern of neutrophilic infiltration as seen in dermatitis herpetiformis. Dapsone is the treatment of choice, which is started at a dosage of 0.5mg/kg/day. Linear IgA bullous dermatosis of childhood is a rare autoimmune disease that can be mistaken for other conditions with similar presentations but should always be considered in the differential diagnosis of children with blistering.
Topics: Male; Child; Humans; Child, Preschool; Linear IgA Bullous Dermatosis; Blister; Autoimmune Diseases; Dapsone; Neutrophils; Immunoglobulin A
PubMed: 36809139
DOI: 10.5070/D328559270 -
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 -
Immunopharmacology and Immunotoxicology Jun 2020Ischemia/reperfusion can cause injury to tissues and compromise functionality of organs due to inflammatory processes. Significantly, development of these effects in...
Ischemia/reperfusion can cause injury to tissues and compromise functionality of organs due to inflammatory processes. Significantly, development of these effects in kidney tissue has been a challenging issue that leads to acute renal injury. In this study, anti-inflammatory, anti-oxidative, and protective features of dapsone on kidney ischemia/reperfusion injury were investigated. Renal ischemia was induced in rats by bilateral renal arteries clamping for 45 min followed by 24 h reperfusion phase. The effects of different doses of dapsone (1, 3, 10 mg/kg) on ischemia/reperfusion injury in kidney tissue were investigated by targeting BUN, Creatinine, LDH, MDA, MPO, IL-1β, TNF-α, and NFκB. In addition histopathological examination was performed by H&E staining method. Comparing the findings of this study showed significant reduction in BUN and LDH in 10 mg/kg dapsone received groups, and Cr, MDA, and MPO in 3 mg/kg dapsone received groups. The serum level of TNF-α was significantly decreased with both doses of 3 and 10 mg/kg dapsone. The same results were observed in the serum level of IL-1β and NFκB. Besides, remarkable improvement in histological damages was also observed with dapsone treatment. These results support the hypothesis that the positive effects of dapsone on the renal ischemia/reperfusion injury are mediated by modulating inflammatory cascades.
Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Dapsone; Disease Models, Animal; Interleukin-1beta; Kidney; Lipid Peroxidation; Male; NF-kappa B; Oxidative Stress; Rats, Wistar; Reperfusion Injury; Tumor Necrosis Factor-alpha
PubMed: 32321337
DOI: 10.1080/08923973.2020.1755308 -
Cureus Mar 2023Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is an autoimmune condition with various triggers. Because of the lack of randomized controlled trials on LABD... (Review)
Review
Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is an autoimmune condition with various triggers. Because of the lack of randomized controlled trials on LABD treatment, management options are mostly anecdotal. This paper provides a comprehensive review of treatment options from a literature review of reported treatments to arm clinicians with a guideline for the management of LABD in both pediatric and adult patients as well as those recalcitrant to first-line therapy (dapsone and steroids). We additionally illustrate an algorithm to use for the management of LABD to aid clinicians when faced with unique patient circumstances.
PubMed: 37090290
DOI: 10.7759/cureus.36481 -
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