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Dermatology and Therapy Feb 2022Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent disease, usually presenting after puberty with inflammatory lesions that mainly affect the apocrine... (Review)
Review
INTRODUCTION
Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent disease, usually presenting after puberty with inflammatory lesions that mainly affect the apocrine gland-bearing areas of the body, most commonly the axillary, inguinal and anogenital regions. The treatment of HS is associated with certain challenges due to intrinsic resistance to various treatments and the presence of comorbidities and complications. The antibiotic dapsone is an established treatment for HS, but the current evidence base is limited. The aim of this review is to systematically review the literature on the efficacy of dapsone in the treatment of HS.
METHODS
The Cochrane, PubMed and CINAHL databases were searched for relevant articles to be included in the systematic review.
RESULTS
A total of seven studies, with a cumulative patient population of 135 patients, were included. Of these 135 patients, 62.2% demonstrated various degrees of improvement following treatment. However, as only three of the seven studies used dapsone monotherapy it is difficult to assess the effectiveness of dapsone because the benefits observed may be due to concurrently administered treatment.
CONCLUSION
Overall, the quality of evidence supporting the use of dapsone is weak. However, it is a well established treatment recommended in current, various national guidelines. There is a crucial need for well-designed randomized controlled trials to support its usage.
PubMed: 34997914
DOI: 10.1007/s13555-021-00674-x -
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 -
Indian Journal of Dermatology,... 2022Psoriasis is a common skin disease that affects 1-3% of the general population. The treatment depends on body surface area involved, quality of life impairment and... (Review)
Review
Psoriasis is a common skin disease that affects 1-3% of the general population. The treatment depends on body surface area involved, quality of life impairment and associated comorbidities. The treatment options include topical therapy, phototherapy, conventional systemic therapy (methotrexate, cyclosporine and acitretin), biologics and oral small molecules (apremilast and tofacitinib). Despite the availability of newer therapies such as biologics and oral small molecules, many a time, there is a paucity of treatment options due to the chronic nature of the disease, end-organ toxicity of the conventional drugs or high cost of newer drugs. In these scenarios, unconventional treatment options may be utilized as stand-alone or adjuvant therapy. In this review, we have discussed these uncommonly used treatment options in the management of psoriasis.
Topics: Anti-Bacterial Agents; Bariatric Surgery; Bevacizumab; Colchicine; Dapsone; Diet; Dipeptidyl-Peptidase IV Inhibitors; Fumarates; Glucagon-Like Peptide-1 Receptor; Humans; Immunologic Factors; Isotretinoin; Life Style; Probiotics; Psoriasis; Somatostatin; Sulfasalazine; Thiazolidinediones
PubMed: 34623042
DOI: 10.25259/IJDVL_22_2021 -
The Medical Letter on Drugs and... Nov 2020
Topics: Acne Vulgaris; Adolescent; Adult; Androgen Receptor Antagonists; Anti-Bacterial Agents; COVID-19; Child; Female; Humans; Keratolytic Agents; Male; Masks; Pandemics; Phototherapy; Young Adult
PubMed: 33443492
DOI: No ID Found -
Drug and Chemical Toxicology May 2021Drug-induced liver injury is an important cause of hepatotoxicity and poses a challenging clinical problem with respect to both diagnosis and management. Patients... (Review)
Review
Drug-induced liver injury is an important cause of hepatotoxicity and poses a challenging clinical problem with respect to both diagnosis and management. Patients susceptible to hepatotoxicity on exposure to dapsone is constantly on the rise. Dapsone (4,4'-diaminodiphenylsulfone) is clinically used alone or in combination with rifampicin for the treatment of a variety of dermatological disorders such as acne, dermatitis herpetiformis, psoriasis, infections, leprosy and pneumonia in AIDS patients. However, the clinical use of dapsone is limited because of dose-dependent adverse hematological reactions. The cholestatic injury caused by dapsone and its - hydroxylated metabolites hinders bile flow and causes oxidative stress and hepatic necrosis, further, leading to hemolysis responsible for hepatitis due to iron overload in the liver. Hence, clinicians' awareness of the hepatotoxic potential of dapsone is highly warranted.
Topics: Animals; Anti-Infective Agents; Chemical and Drug Induced Liver Injury; Dapsone; Dose-Response Relationship, Drug; Hemolysis; Humans; Iron Overload; Methemoglobinemia; Oxidative Stress
PubMed: 31631707
DOI: 10.1080/01480545.2019.1679829 -
Journal of Drugs in Dermatology : JDD Nov 2023Management of hidradenitis suppurativa (HS) is challenging since no single treatment provides consistently effective results, leaving patients with frequent relapses....
BACKGROUND
Management of hidradenitis suppurativa (HS) is challenging since no single treatment provides consistently effective results, leaving patients with frequent relapses. Dapsone combines anti-microbial and anti-inflammatory properties that address aspects of HS pathogenesis. Few studies have evaluated the efficacy of oral dapsone on HS, especially in severe disease.
OBJECTIVE
This study aims to evaluate the clinical outcomes of patients with moderate-to-severe HS treated with dapsone.
METHODS
This retrospective chart review evaluated HS patients treated with oral dapsone over the past 10 years at one center. Treatment outcomes were classified based on Hurley staging, physician exam, and symptom progression. Adverse effects and concomitant treatment with dapsone were reviewed.
RESULTS
Nineteen (19) patients with moderate-to-severe (Hurley Stage II-III) HS treated with oral dapsone were identified. Within 1-3 months, on dosages of dapsone varying from 25-100 mg/day, 3 patients (15.8%) had a clinically significant improvement in symptoms, 10 patients (52.6%) had a slight improvement, and 6 patients (31.6%) had no change in disease state; no patients deteriorated. The majority who improved were also on other medications, most commonly adalimumab. 4 patients experienced adverse effects, with nausea being most common; otherwise, dapsone was well-tolerated.
CONCLUSIONS
Dapsone may have some efficacy for moderate-to-severe HS and seems well-tolerated. J Drugs Dermatol. 2023;22(11):e12-e16 doi:10.36849/JDD.4936e.
Topics: Humans; Hidradenitis Suppurativa; Retrospective Studies; Adalimumab; Drug-Related Side Effects and Adverse Reactions; Dapsone
PubMed: 37943259
DOI: 10.36849/JDD.4936 -
Current Organic Synthesis 2020Sulfur-containing compounds represent an important class of chemical compounds due to their wide range of biological and pharmaceutical properties. Moreover,... (Review)
Review
BACKGROUND
Sulfur-containing compounds represent an important class of chemical compounds due to their wide range of biological and pharmaceutical properties. Moreover, sulfur-containing compounds may be applied in other fields, such as biological, organic, and materials chemistry. Several studies on the activities of sulfur compounds have already proven their anti-inflammatory properties and use to treat diseases, such as Alzheimer's, Parkinson's, and HIV. Moreover, examples of sulfur-containing compounds include dapsone, quetiapine, penicillin, probucol, and nelfinavir, which are important drugs with known activities.
OBJECTIVE
This review will focus on the synthesis and application of some sulfur-containing compounds used to treat several diseases, as well as promising new drug candidates.
CONCLUSION
Due to the variety of compounds containing C-S bonds, we have reviewed the different synthetic routes used toward the synthesis of sulfur-containing drugs and other compounds.
Topics: Animals; Heterocyclic Compounds; Humans; Sulfur Compounds
PubMed: 32091342
DOI: 10.2174/1570179417666200212113412 -
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 -
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 -
Turkiye Parazitolojii Dergisi Dec 2020causes rhinosporidiosis, which is manifested as tumor-like polyps developing primarily in the nostrils and conjunctiva in human and animals. This disease is... (Review)
Review
causes rhinosporidiosis, which is manifested as tumor-like polyps developing primarily in the nostrils and conjunctiva in human and animals. This disease is characterized by the presence of large, round-shaped mature stage and small endospores with resistance to culturing. was first reported in 1900 as a sporozoan parasite, but later classified as a lower fungi, although its morphological similarity with aquatic parasites were also noticed. According to 18S small-subunit ribosomal DNA sequencing, belongs to a group of fish parasite DRIP clade located between the animal and fungal divergence. Histological examination is thus necessary for the definitive diagnosis of rhinosporidiosis, and the first line of treatment is usually total surgical excision and electro-cauterization of the polyp base. Among the drug therapies attempted, remission has been reported in some patients who received only Dapson treatment. This disease is endemic across India, Pakistan and Sri Lanka and occurs sporadically in other parts of The World with a common history of patients bathing in stagnant water. An outbreak in Serbia during 1992-1995 and 5 rhinosporidiosis cases from Turkey have been reported until date. Considering that rhinosporidiosis is associated with exposure to water and the agent belongs to a branch of aquatic parasites, it has been proposed that aquatic animals are the natural hosts and that the mammalian hosts acquire infection by contacting contaminated water. Therefore, there is a need for the investigation of the infection in fish besides mammalian animals as reservoirs as well as to conduct screening of antiparasitic drugs with infected fish or infected cell lines with the nearest phylogenetic relatives of .
Topics: Animals; Antiparasitic Agents; Fishes; Humans; Life Cycle Stages; Phylogeny; Rhinosporidiosis; Rhinosporidium
PubMed: 33269573
DOI: 10.4274/tpd.galenos.2020.7221