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Chinese Medical Journal Jul 2023
Topics: Humans; Dapsone; Drug Hypersensitivity; Hypersensitivity; Syndrome
PubMed: 37057725
DOI: 10.1097/CM9.0000000000002492 -
Archives of Disease in Childhood.... Jun 2022A 3-year-old boy presented with a 5-day history of bullous skin lesions localised mainly in the upper and lower limbs and in the genital region (figure 1). Lesions were...
A 3-year-old boy presented with a 5-day history of bullous skin lesions localised mainly in the upper and lower limbs and in the genital region (figure 1). Lesions were not pruritic nor painful and showed a central crust. There was no family history of skin disorders or autoimmune diseases. The child never had fever and his physical examination was otherwise unremarkable.
Topics: Biopsy; Child; Child, Preschool; Dapsone; Exanthema; Humans; Immunoglobulin A; Male
PubMed: 33214238
DOI: 10.1136/archdischild-2020-319179 -
Indian Journal of Dental Research :... 2014Acute febrile neutrophilic dermatosis or Sweet's syndrome (SS) is characterized by painful, erythematous plaques of rapid onset accompanied by fever. The etiology of SS...
Acute febrile neutrophilic dermatosis or Sweet's syndrome (SS) is characterized by painful, erythematous plaques of rapid onset accompanied by fever. The etiology of SS is unknown and it may be associated with antecedent infections, malignancies, autoimmune diseases, drugs and vaccines, upper respiratory or gastrointestinal infection, pregnancy, inflammatory bowel disease as well as chemotherapy or idiopathic. The standard therapy for SS is systemic corticosteroids. We report a rare case of 19-year-old young male patient with complaint of severe ill-defined type of pain in both jaws associated with plaques and papules on extensor surfaces of upper and lower extremities with bodyache and myalgia. Histopathological examination suggested perivascular neutrophilic infiltration with scattered eosinophils. Sweet syndrome has rare oral manifestations secondary to hematological changes. It can also present as a paraneoplastic syndrome (malignancy-associated form of condition, which is most commonly related to acute myelogenous leukemia), which leads to poor prognosis and thus it requires careful examination, early diagnosis and long-term follow-up.
Topics: Acetaminophen; Adult; Cetirizine; Dapsone; Drug Therapy, Combination; Humans; Male; Prednisone; Sweet Syndrome; Young Adult
PubMed: 25099003
DOI: 10.4103/0970-9290.138358 -
European Journal of Medicinal Chemistry Dec 2023Perforin is a pore-forming protein whose normal function enables cytotoxic T and natural killer (NK) cells to kill virus-infected and transformed cells. Conversely,...
Perforin is a pore-forming protein whose normal function enables cytotoxic T and natural killer (NK) cells to kill virus-infected and transformed cells. Conversely, unwanted perforin activity can also result in auto-immune attack, graft rejection and aberrant responses to pathogens. Perforin is critical for the function of the granule exocytosis cell death pathway and is therefore a target for drug development. In this study, by screening a fragment library using NMR and surface plasmon resonance, we identified 4,4-diaminodiphenyl sulfone (dapsone) as a perforin ligand. We also found that dapsone has modest (mM) inhibitory activity of perforin lytic activity in a red blood cell lysis assay in vitro. Sequential modification of this lead fragment, guided by structural knowledge of the ligand binding site and binding pose, and supported by SPR and ligand-detected F NMR, enabled the design of nanomolar inhibitors of the cytolytic activity of intact NK cells against various tumour cell targets. Interestingly, the ligands we developed were largely inert with respect to direct perforin-mediated red blood cell lysis but were very potent in the context of perforin's action on delivering granzymes in the immune synapse, the context in which it functions physiologically. Our work indicates that a fragment-based, structure-guided drug discovery strategy can be used to identify novel ligands that bind perforin. Moreover, these molecules have superior physicochemical properties and solubility compared to previous generations of perforin ligands.
Topics: Perforin; Ligands; Killer Cells, Natural; Cell Death; Dapsone
PubMed: 37716187
DOI: 10.1016/j.ejmech.2023.115786 -
Journal of Postgraduate Medicine 2018
Topics: Adult; Biopsy; Clofazimine; Dapsone; Humans; Leprostatic Agents; Leprosy, Lepromatous; Male; Microscopy, Acoustic; Rifampin; Treatment Outcome
PubMed: 29386417
DOI: 10.4103/jpgm.JPGM_373_17 -
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 -
Experimental Lung Research 2020Multiple pharmacological interventions tested over the last decades have failed to reduce ARDS mortality. This short note recounts past data indicating that (i)...
Multiple pharmacological interventions tested over the last decades have failed to reduce ARDS mortality. This short note recounts past data indicating that (i) neutrophils home along an IL-8 gradient, (ii) in ARDS, massive neutrophil accumulation and degranulation in and along bronchoalveolar spaces contributes to damage and hypoxia, (iii) large increases in IL-8 are one of the chemotaxic signals drawing neutrophils to the ARDS lung, and (iv) old data from dermatology and glioblastoma research showed that the old drug against Hansen's disease, dapsone, inhibits neutrophils' chemotaxis to IL-8. Therefore dapsone might lower neutrophils' contributions to ARDS lung pathology. Dapsone can create methemoglobinemia that although rarely problematic it would be particularly undesirable in ARDS. The common antacid drug cimetidine lowers risk of dapsone related methemoglobinemia and should be given concomitantly.
Topics: Anti-Infective Agents; Cimetidine; Dapsone; Histamine H2 Antagonists; Humans; Methemoglobinemia; Neutrophils; Respiratory Distress Syndrome
PubMed: 32286085
DOI: 10.1080/01902148.2020.1753266 -
Anais Brasileiros de Dermatologia 2018
Topics: Dapsone; Dermatologic Agents; Humans; Male; Middle Aged; Treatment Outcome; Vasculitis, Leukocytoclastic, Cutaneous
PubMed: 30066783
DOI: 10.1590/abd1806-4841.20187470 -
International Journal of Molecular... Dec 2022Some physicians use dapsone as part of the standard treatment of severe COVID-19 patients entering the ICU, though some do not. To obtain an indication of whether...
Some physicians use dapsone as part of the standard treatment of severe COVID-19 patients entering the ICU, though some do not. To obtain an indication of whether dapsone is helping or not, we undertook a retrospective chart review of 29 consecutive ICU COVID-19 patients receiving dapsone and 30 not receiving dapsone. As we previously reported, of those given dapsone, 9/29 (30%) died, while of those not given dapsone, 18/30 (60%) died. We looked back on that data set to determine if there might be basic laboratory findings in these patients that might give an indication of a mechanism by which dapsone was acting. We found that the neutrophil-to-lymphocyte ratio decreased in 48% of those given dapsone and in 30% of those not given dapsone. We concluded that dapsone might be lowering that ratio. We then reviewed collected data on neutrophil related inflammation pathways on which dapsone might act as presented here. As this was not a controlled study, many variables prevent drawing any conclusions from this work; a formal, randomized controlled study of dapsone in severe COVID-19 is warranted.
Topics: Humans; COVID-19; Neutrophils; Dapsone; Retrospective Studies; Intensive Care Units; Lymphocytes
PubMed: 36555204
DOI: 10.3390/ijms232415563 -
The Journal of Allergy and Clinical... 2014Management of antihistamine refractory chronic idiopathic urticaria (CIU) has poorly defined therapeutic options. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Management of antihistamine refractory chronic idiopathic urticaria (CIU) has poorly defined therapeutic options.
OBJECTIVE
To evaluate the efficacy of dapsone (4,4'-diaminodiphenylsulfone) in antihistamine refractory CIU compared with placebo.
METHODS
Twenty-two patients with antihistamine refractory CIU were randomly assigned to 100 mg of dapsone daily or placebo for 6 weeks in a 14-week double-blind, placebo-controlled crossover trial. End points were measured from a daily diary that reflected the weekly hive score, the weekly itch score, and a visual analog scale (VAS) score. Secondary to a carryover effect, the first period results were analyzed as a parallel design that compared placebo with dapsone directly by using repeated-measures analysis.
RESULTS
After 6 weeks, the patients in the dapsone arm showed mean improvement over baseline in VAS (2.3 [95% CI, 0.6-4.1], P = .01), urticaria score (-3.5 [95% CI, -6.2 to -0.9], P = .01), and itch score (-4.8 [95% CI, -7.6 to -2.1], P = .001), whereas the placebo arm showed no improvement over baseline for VAS, urticaria, or itch scores. Dapsone showed greater improvement compared with placebo for itch (P = .047) and VAS (P = .04). Of the 22 patients, 3 showed complete resolution of hives and itch with dapsone, whereas 31% and 41% had ≥ 50% resolution of hives and itch, respectively. No serious adverse effects were observed with dapsone.
CONCLUSION
To our knowledge, this is the first double-blind, placebo controlled study of dapsone in CIU and indicates that dapsone has efficacy in patients with antihistamine refractory CIU.
Topics: Adult; Anti-Allergic Agents; Chronic Disease; Cross-Over Studies; Dapsone; Double-Blind Method; Drug Resistance; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Urticaria
PubMed: 25213055
DOI: 10.1016/j.jaip.2014.06.004