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Toxicology Reports Dec 2023The case report describes a case of a severe dapsone (more than 200 tablets dapsone 100 mg) and mild methotrexate intoxication (10 tablets methotrexate 10 mg) as an...
The case report describes a case of a severe dapsone (more than 200 tablets dapsone 100 mg) and mild methotrexate intoxication (10 tablets methotrexate 10 mg) as an attempt to commit suicide, resulting in severe cyanosis with elevation in methemoglobin concentration, treated with methylene blue, ascorbic acid, folinic acid, multidose activated charcoal and hemodialysis. Measurements of blood gases, dapsone and methotrexate levels were performed. Furthermore a hepatitis, pulmonary artery thrombus and a strange taste sensation were diagnosed, probably related to dapsone. The patient recovered and was discharged from hospital after five days. Acute intoxication from excessive dapsone intake is uncommon and clear treatment guidelines are lacking. We here report the treatment modalities as a result of a dapsone intoxication, including the effects on the overall condition of the patient.
PubMed: 37868805
DOI: 10.1016/j.toxrep.2023.10.006 -
Translational Medicine of Aging 2023COVID-19 is an immune-mediated disease whose pathophysiology uses SAMHD1 tetramerization and cGAS-STING signaling, toll-like receptor 4 (TLR4) cascade, spike protein-... (Review)
Review
COVID-19 is an immune-mediated disease whose pathophysiology uses SAMHD1 tetramerization and cGAS-STING signaling, toll-like receptor 4 (TLR4) cascade, spike protein- inflammasome activation, and neuropilin 1 (NRP1) signaling. Variants of concern, such as SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, BA.2.75.2, and other mutants, have emerged. The longitudinal memory T-cell response to SARS-CoV-2 persists for eight months after symptom onset. Therefore, we must achieve viral clearance to coordinate immune cell reactions. Aspirin, dapsone, and dexamethasone as anticatalysis medicines have been used to treat COVID-19. They are shown to work harmoniously with modulating ILCs. Therefore, it needs to prescribe this immune triad to alleviate the clinical pathologic course and block exacerbation mechanisms due to diverse SARS-CoV-2 variants.
PubMed: 37388715
DOI: 10.1016/j.tma.2023.06.005 -
Journal of Biomedical Science Aug 2022Severe cutaneous adverse drug reactions (SCARs) are a group of serious clinical conditions caused by immune reaction to certain drugs. The allelic variance of human...
BACKGROUND
Severe cutaneous adverse drug reactions (SCARs) are a group of serious clinical conditions caused by immune reaction to certain drugs. The allelic variance of human leukocyte antigens of HLA-B*13:01 has been strongly associated with hypersensitivities induced by dapsone (DDS). T-cell receptor mediated activation of cytotoxic T lymphocytes (CTLs) has also been suggested to play an essential role in pathogenesis of SCARs. However, HLA-B*13:01-DDS-TCR immune synapse that plays role in drug-induced hypersensitivity syndrome (DIHS) associated T cells activation remains uncharacterized.
METHODS
To investigate the molecular mechanisms for HLA-B*13:01 in the pathogenesis of Dapsone-induced drug hypersensitivity (DDS-DIHS), we performed crystallization and expanded drug-specific CTLs to analyze the pathological role of DDS-DIHS.
RESULTS
Results showed the crystal structure of HLA-B*13:01-beta-2-microglobulin (β2M) complex at 1.5 Å resolution and performed mutation assays demonstrating that I118 or I119, and R121 of HLA-B*13:01 were the key residues that mediate the binding of DDS. Subsequent single-cell TCR and RNA sequencing indicated that TCRs composed of paired TRAV12-3/TRBV28 clonotype with shared CDR3 region specifically recognize HLA-B*13:01-DDS complex to trigger inflammatory cytokines associated with DDS-DIHS.
CONCLUSION
Our study identified the novel p-i-HLA/TCR as the model of interaction between HLA-B*13:01, DDS and the clonotype-specific TCR in DDS-DIHS.
Topics: Cicatrix; Dapsone; Drug Hypersensitivity; HLA-B Antigens; Humans; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 35964029
DOI: 10.1186/s12929-022-00845-8 -
Case Reports in Dermatology 2017Subcorneal pustular dermatosis (SCPD, Sneddon-Wilkinson disease) is a rare chronic-relapsing skin disorder that typically manifests as flaccid sterile pustules without... (Review)
Review
Subcorneal pustular dermatosis (SCPD, Sneddon-Wilkinson disease) is a rare chronic-relapsing skin disorder that typically manifests as flaccid sterile pustules without systemic symptoms. Although the accumulation of neutrophils is acknowledged to be a hallmark of SCPD, its exact pathomechanism is still not known. Several chemotactic factors have been implicated in neutrophil recruitment and invasion, including the proinflammatory cytokine TNF-α. These findings correspond well with clinical reports of successful off-label use of TNF blocking agents in cases that were refractory to first-line therapy, mostly with dapsone. We report the case of a 29-year-old male with atypical and severe manifestation of SCPD that resolved after a single dose of infliximab. Consolidation was observed 1 day after treatment and regression of skin lesions occurred after a few days. Residual scarring and postlesional hyperpigmentation was seen at a 2-month follow-up appointment. The patient was initiated on a daily maintenance therapy with dapsone, which led to a drop in hemoglobin and had to be stopped. Upon development of small, scaly lesions, a maintenance therapy with infliximab was started and the patient has had no recurrence to date. Anti-TNF agents present a promising option for patients affected by severe SCPD. We review the reports of similar cases in the literature to date.
PubMed: 28559813
DOI: 10.1159/000468917 -
Allergy Aug 2019Research into drug hypersensitivity associated with the expression of specific HLA alleles has focussed on the interaction between parent drug and the HLA with no...
BACKGROUND
Research into drug hypersensitivity associated with the expression of specific HLA alleles has focussed on the interaction between parent drug and the HLA with no attention given to reactive metabolites. For this reason, we have studied HLA-B*13:01-linked dapsone hypersensitivity to (a) explore whether the parent drug and/or nitroso metabolite activate T cells and (b) determine whether HLA-B*13:01 is involved in the response.
METHODS
Peripheral blood mononuclear cells (PBMC) from six patients were cultured with dapsone and nitroso dapsone, and proliferative responses and IFN-γ release were measured. Dapsone- and nitroso dapsone-specific T-cell clones were generated and phenotype, function, HLA allele restriction, and cross-reactivity assessed. Dapsone intermediates were characterized by mass spectrometry.
RESULTS
Peripheral blood mononuclear cells from six patients and cloned T cells proliferated and secreted Th1/2/22 cytokines when stimulated with dapsone (clones: n = 395; 80% CD4 CXCR3 CCR4 , 20% CD8+CXCR3 CCR4 CCR6 CCR9 CCR10 ) and nitroso dapsone (clones: n = 399; 78% CD4+, 22% CD8 with same chemokine receptor profile). CD4 and CD8 clones were HLA class II and class I restricted, respectively, and displayed three patterns of reactivity: compound specific, weakly cross-reactive, and strongly cross-reactive. Nitroso dapsone formed dimers in culture and was reduced to dapsone, providing a rationale for the cross-reactivity. T-cell responses to nitroso dapsone were dependent on the formation of a cysteine-modified protein adduct, while dapsone interacted in a labile manner with antigen-presenting cells. CD8 clones displayed an HLA-B*13:01-restricted pattern of activation.
CONCLUSION
These studies describe the phenotype and function of dapsone- and nitroso dapsone-responsive CD4 and CD8 T cells from hypersensitive patients. Discovery of HLA-B*13:01-restricted CD8 T-cell responses indicates that drugs and their reactive metabolites participate in HLA allele-linked forms of hypersensitivity.
Topics: Adult; Cross Reactions; Dapsone; Female; Gene Expression; HLA-B Antigens; Humans; Hypersensitivity; Immunophenotyping; Lymphocyte Activation; Male; Middle Aged; Nitroso Compounds; Sensitivity and Specificity; T-Lymphocyte Subsets; T-Lymphocytes
PubMed: 30844087
DOI: 10.1111/all.13769 -
P & T : a Peer-reviewed Journal For... Apr 2016Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey) for combination HIV-1 therapy; dapsone gel, 7.5% (Aczone) for acne vulgaris; extended-release tofacitinib...
Emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey) for combination HIV-1 therapy; dapsone gel, 7.5% (Aczone) for acne vulgaris; extended-release tofacitinib (Xeljanz XR) for rheumatoid arthritis; and brivaracetam (Briviact) for epilepsy.
PubMed: 27069339
DOI: No ID Found -
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 -
The Journal of Biological Chemistry Dec 2023Positive heterotropic cooperativity, or "activation," results in an instantaneous increase in enzyme activity in the absence of an increase in protein expression. Thus,...
Positive heterotropic cooperativity, or "activation," results in an instantaneous increase in enzyme activity in the absence of an increase in protein expression. Thus, cytochrome P450 (CYP) enzyme activation presents as a potential drug-drug interaction mechanism. It has been demonstrated previously that dapsone activates the CYP2C9-catalyzed oxidation of a number of nonsteroidal anti-inflammatory drugs in vitro. Here, we conducted molecular dynamics simulations (MDS) together with enzyme kinetic investigations and site-directed mutagenesis to elucidate the molecular basis of the activation of CYP2C9-catalyzed S-flurbiprofen 4'-hydroxylation and S-naproxen O-demethylation by dapsone. Supplementation of incubations of recombinant CYP2C9 with dapsone increased the catalytic efficiency of flurbiprofen and naproxen oxidation by 2.3- and 16.5-fold, respectively. MDS demonstrated that activation arises predominantly from aromatic interactions between the substrate, dapsone, and the phenyl rings of Phe114 and Phe476 within a common binding domain of the CYP2C9 active site, rather than involvement of a distinct effector site. Mutagenesis of Phe114 and Phe476 abrogated flurbiprofen and naproxen oxidation, and MDS and kinetic studies with the CYP2C9 mutants further identified a pivotal role of Phe476 in dapsone activation. MDS additionally showed that aromatic stacking interactions between two molecules of naproxen are necessary for binding in a catalytically favorable orientation. In contrast to flurbiprofen and naproxen, dapsone did not activate the 4'-hydroxylation of diclofenac, suggesting that the CYP2C9 active site favors cooperative binding of nonsteroidal anti-inflammatory drugs with a planar or near-planar geometry. More generally, the work confirms the utility of MDS for investigating ligand binding in CYP enzymes.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Dapsone; Flurbiprofen; Kinetics; Naproxen; Humans
PubMed: 37866634
DOI: 10.1016/j.jbc.2023.105368 -
Pharmaceutics Dec 2020Leprosy disease remains an important public health issue as it is still endemic in several countries. , the causative agent of leprosy, presents tropism for cells of the... (Review)
Review
Leprosy disease remains an important public health issue as it is still endemic in several countries. , the causative agent of leprosy, presents tropism for cells of the reticuloendothelial and peripheral nervous system. Current multidrug therapy consists of clofazimine, dapsone and rifampicin. Despite significant improvements in leprosy treatment, in most programs, successful completion of the therapy is still sub-optimal. Drug resistance has emerged in some countries. This review discusses the status of leprosy disease worldwide, providing information regarding infectious agents, clinical manifestations, diagnosis, actual treatment and future perspectives and strategies on targets for an efficient targeted delivery therapy.
PubMed: 33322356
DOI: 10.3390/pharmaceutics12121202 -
Clinical Case Reports May 2021Dapsone therapy is associated with methemoglobinemia. Pulse oximetry is used to indicate adequate oxygen saturations, and co-oximetry is needed to diagnose low arterial...
Dapsone therapy is associated with methemoglobinemia. Pulse oximetry is used to indicate adequate oxygen saturations, and co-oximetry is needed to diagnose low arterial oxygen saturations. Clinicians should aware while prescribing dapsone.
PubMed: 34084488
DOI: 10.1002/ccr3.4054