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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 -
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 -
Spine Oct 2021Prospective longitudinal experimental study.
STUDY DESIGN
Prospective longitudinal experimental study.
OBJECTIVE
We evaluate the effect of dapsone on tactile allodynia and mechanical hyperalgesia and to determine its anti-oxidant effect in a spinal cord injury (SC) model in rats.
SUMMARY OF BACKGROUND DATA
Neuropathic pain (NP) as result of traumatic spinal cord injury is a deleterious medical condition with temporal or permanent time-course. Painful stimuli trigger a cascade of events that activate the N-methyl-D-aspartate (NMDA) receptor, inducing an increase in oxidative stress. Since there is no effective treatment for this condition, dapsone (4,4'diaminodiphenylsulfone) is proposed as potential treatment for NP. Its anti-oxidant, neuroprotective, and anti-inflammatory properties have been documented, however, there is no evidence regarding its use for treatment of NP induced by SCI.
METHODS
In this study, we evaluated the anti-allodynic and anti-hyperalgesic effect of dapsone as preventive or acute treatment after NP was already established. Furthermore, participation of oxidative stress was evaluated by measuring lipid peroxidation (LP) and glutathione concentration (GSH) in rats with SCI.
RESULTS
Acute treatment with dapsone (3.1-25 mg/kg, i.p.) decreased nociceptive behaviors in a dose-dependent manner, decreased LP, and increased GSH in the injured tissue 15 days after the injury was produced. On the other hand, preventive treatment (3 h post-injury, once daily for 3 days) with dapsone (3.1-25 mg/kg, i.p.) yielded similar results.
CONCLUSION
The findings suggest that the anti-nociceptive effect of dapsone is regulated through the decrease of oxidative stress and the excitotoxicity is associated with the activation of NMDA receptors.Level of Evidence: N/A.
Topics: Animals; Dapsone; Disease Models, Animal; Hyperalgesia; Neuralgia; Oxidative Stress; Prospective Studies; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries
PubMed: 34517396
DOI: 10.1097/BRS.0000000000004015 -
Dermatology (Basel, Switzerland) 2022Necrobiosis lipoidica (NL) is a rare granulomatous disorder of unknown aetiology. Randomized controlled studies are not available due to it being an orphan disease.
BACKGROUND
Necrobiosis lipoidica (NL) is a rare granulomatous disorder of unknown aetiology. Randomized controlled studies are not available due to it being an orphan disease.
OBJECTIVES
We evaluated patients in 2 dermatological centres to cluster data about epidemiology, the therapeutic approaches for NL, and their efficacy.
MATERIALS AND METHODS
Comorbidity and the efficacy of the applied treatment was assessed for 98 patients.
RESULTS
We identified 54% of patients with concomitant diabetes and 19% with thyroidal disorders. Topical steroids (85.7%) were predominantly used followed by calcineurin inhibitors (31%) and phototherapy (41.8%). Systemically, fumaric acid esters were more frequently applied (26.8%) than steroids (24.4%) and dapsone (24.4%). Steroids, compression therapy, calcineurin inhibitors, phototherapy, fumaric acid esters, and dapsone showed remarkable efficacy.
CONCLUSION
Therapeutic options were chosen individually in accordance with the severity of NL and presence of ulceration. Topical calcineurin inhibitors, systemic application of fumaric acid esters, and dapsone represent effective alternatives to the use of steroids.
Topics: Adolescent; Adult; Calcineurin Inhibitors; Cluster Analysis; Comorbidity; Dapsone; Diabetes Mellitus; Female; Fumarates; Humans; Male; Necrobiosis Lipoidica; Retrospective Studies; Steroids; Thyroid Diseases; Young Adult
PubMed: 33827092
DOI: 10.1159/000514687 -
The Journal of Infection Apr 2023The World Health Organization (WHO) recommends multidrug therapy (MDT) with rifampicin, dapsone, and clofazimine for treating leprosy, which is based on very low-quality... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The World Health Organization (WHO) recommends multidrug therapy (MDT) with rifampicin, dapsone, and clofazimine for treating leprosy, which is based on very low-quality evidence. Here, we performed a network meta-analysis (NMA) to produce quantitative evidence to strengthen current WHO recommendations.
METHOD
All studies were obtained from Embase and PubMed from the date of establishment to October 9, 2021. Data were synthesized with frequentist random-effects network meta-analyses. Outcomes were assessed using odds ratios (ORs), 95% confidence intervals (95% CIs), and P score.
RESULTS
Sixty controlled clinical trials and 9256 patients were included. MDT was effective (range of OR: 1.06-1255584.25) for treating leprosy and multibacillary leprosy. Six treatments (Range of OR: 1.199-4.50) were more effective than MDT. Clofazimine (P score=0.9141) and dapsone+rifampicin (P score=0.8785) were effective for treating type 2 leprosy reaction. There were no significant differences in the safety of any of the tested drug regimens.
CONCLUSIONS
The WHO MDT is effective for treating leprosy and multibacillary leprosy, but it may not be effective enough. Pefloxacin and ofloxacin may be good adjunct drugs for increasing MDT efficacy. Clofazimine and dapsone+rifampicin can be used in the treatment of a type 2 leprosy reaction. Single-drug regimens are not efficient enough to treat leprosy, multibacillary leprosy, or a type 2 leprosy reaction.
AVAILABILITY OF DATA AND MATERIALS
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
Topics: Humans; Leprostatic Agents; Rifampin; Clofazimine; Network Meta-Analysis; Drug Therapy, Combination; Leprosy; Dapsone; Leprosy, Multibacillary
PubMed: 36796681
DOI: 10.1016/j.jinf.2023.02.019 -
Chemical Research in Toxicology Dec 2017Dapsone (DDS) causes hypersensitivity reactions in 0.5-3.6% of patients. Although clinical diagnosis is indicative of a hypersensitivity reaction, studies have not been...
Dapsone (DDS) causes hypersensitivity reactions in 0.5-3.6% of patients. Although clinical diagnosis is indicative of a hypersensitivity reaction, studies have not been performed to define whether dapsone or a metabolite activates specific T-cells. Thus, the aims of this study were to explore the immunogenicity DDS and nitroso DDS (DDS-NO) using peripheral blood mononuclear cells from healthy donors and splenocytes from mice and generate human T-cell clones to characterize mechanisms of T-cell activation. DDS-NO was synthesized from DDS-hydroxylamine and shown to bind to the thiol group of glutathione and human and mouse albumin through sulfonamide and N-hydroxyl sulphonamide adducts. Naïve T-cell priming to DDS and DDS-NO was successful in three human donors. DDS-specific CD4+ T-cell clones were stimulated to proliferate in response to drug via a MHC class II restricted direct binding interaction. Cross reactivity with DDS-NO, DDS-analogues, and sulfonamides was not observed. DDS-NO clones were CD4+ and CD8+, MHC class II and I restricted, respectively, and activated via a pathway dependent on covalent binding and antigen processing. DDS and DDS-NO-specific clones secreted a mixture of Th1 and Th2 cytokines, but not granzyme-B. Splenocytes from mice immunized with DDS-NO were stimulated to proliferate in vitro with the nitroso metabolite, but not DDS. In contrast, immunization with DDS did not activate T-cells. These data show that DDS- and DDS-NO-specific T-cell responses are readily detectable.
Topics: Animals; Cell Proliferation; Cells, Cultured; Chromatography, High Pressure Liquid; Dapsone; Healthy Volunteers; Humans; Lymphocyte Activation; Mass Spectrometry; Mice; Molecular Structure; Nitroso Compounds; Serum Albumin; Spleen; T-Lymphocytes
PubMed: 29045131
DOI: 10.1021/acs.chemrestox.7b00263 -
American Journal of Clinical Dermatology Dec 2016Subcorneal pustular dermatosis (SPD), also known as Sneddon-Wilkinson disease, is a rare, benign yet relapsing pustular dermatosis. Its incidence and prevalence have not... (Review)
Review
Subcorneal pustular dermatosis (SPD), also known as Sneddon-Wilkinson disease, is a rare, benign yet relapsing pustular dermatosis. Its incidence and prevalence have not been well studied. It characteristically presents as hypopyon pustules on the trunk and intertriginous areas of the body. SPD is similar to two other disease entities. Both SPD-type immunoglobulin (Ig)-A pemphigus and annular pustular psoriasis clinically and histologically present similarly to SPD. Immunologic studies separate SPD-type IgA pemphigus from SPD and pustular psoriasis. However, there is still an unclear designation as to whether SPD is its own entity distinct from pustular psoriasis, as the once thought characteristic histologic picture of psoriasis does not hold true for pustular psoriasis. SPD has been reported to occur in association with several neoplastic, immunologic, and inflammatory conditions. Dapsone remains the first-line treatment for SPD, although dapsone-resistant cases have been increasingly reported. Other therapies have been used singly or as adjunctive therapy with success, such as corticosteroids, immunosuppressive agents, tumor necrosis factor inhibitors, and ultraviolet light therapy. This article provides a review of the last 30 years of available literature, with a focus on successful treatment options and a suggestion for reappraisal of the classification of SPD.
Topics: Connective Tissue Diseases; Dapsone; Diagnosis, Differential; Glucocorticoids; Hematologic Diseases; Humans; Immunosuppressive Agents; Pemphigus; Phototherapy; Psoriasis; Rare Diseases; Recurrence; Skin Diseases, Vesiculobullous
PubMed: 27349653
DOI: 10.1007/s40257-016-0202-8 -
Clinical Medicine (London, England) Sep 2020Methaemoglobinaemia is an uncommon but potentially serious condition. It can be caused by congenital or acquired cause. Drug-induced methaemoglobinaemia is the commonest...
Methaemoglobinaemia is an uncommon but potentially serious condition. It can be caused by congenital or acquired cause. Drug-induced methaemoglobinaemia is the commonest cause of acquired methaemoglobinaemia. The clinical signs and symptoms of methaemoglobinaemia include dyspnoea, desaturation, presence of saturation gap, headache, nausea and seizures depending on level of serum methaemoglobinaemia. We illustrate a case of dapsone-induced methaemoglobinaemia and its successful treatment by intravenous methylene blue.
Topics: Dapsone; Humans; Methemoglobinemia; Methylene Blue
PubMed: 32934050
DOI: 10.7861/clinmed.2020-0364 -
International Journal of Dermatology Oct 2020Histoid leprosy is a rare variant of leprosy with a unique clinical presentation and bacilli rich histology. These patients are large reservoirs for disease and vectors... (Review)
Review
Histoid leprosy is a rare variant of leprosy with a unique clinical presentation and bacilli rich histology. These patients are large reservoirs for disease and vectors for spread, making prompt diagnosis and treatment crucial. To date, no consensus on treatment and duration exists. This paper aims to investigate the efficacy, safety, and duration of varying treatment regimens in patients with histoid leprosy. A systematic PubMed review of all articles published before January 2020 containing the key words histoid leprosy. All patients included must have completed their prescribed treatments with comment on outcomes and treatment duration. The review generated 165 articles containing 62 cases that met inclusion criteria. A majority of cases reported excellent clinical outcomes with limited adverse events. Regimens included variations of rifampicin, dapsone, clofazimine, minocycline, ofloxacin, and sulforthormadine with most treatment duration lasting 12 or 24 months. Existing literature is limited to case reports or case series and may be subject to publication bias of successful cases. Many reports lack quantifiable data regarding outcomes and rely on clinical judgment. Continued observation for complete clearance or relapse was limited. The findings demonstrate that multibacillary-multidrug therapy is an efficacious and safe treatment for histoid leprosy. No significant differences were observed between 12 and 24 months of treatment. There remains no consensus on treatment duration for histoid leprosy.
Topics: Clofazimine; Consensus; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy
PubMed: 32544270
DOI: 10.1111/ijd.14962 -
Current Topics in Medicinal Chemistry 2022Leprosy (Hansen's disease) is a neglected tropical disease affecting millions of people globally. The combined formulations of dapsone, rifampicin and clofazimine...
BACKGROUND
Leprosy (Hansen's disease) is a neglected tropical disease affecting millions of people globally. The combined formulations of dapsone, rifampicin and clofazimine (multidrug therapy, MDT) is only supportive in the early stage of detection, while "reemergence" is a significant problem. Thus, there is still a need to develop newer antileprosy molecules either of natural or semi-synthetic origin.
OBJECTIVES
The review intends to present the latest developments in the disease prevalence, available therapeutic interventions and the possibility of identifying new molecules from phytoextracts.
METHODS
Literature on the use of plant extracts and their active components to treat leprosy was searched. Selected phytoconstituents were subjected to molecular docking study on both wild and mutant types of the Mycobacterium leprae. Since the M. leprae dihydropteroate synthase (DHPS) is not available in the protein data bank (PDB), it was modelled by the homology model method and validated with the Ramachandran plot along with other bioinformatics approaches. Two mutations were introduced at codons 53 (Thr to Ile) and 55 (Pro to Leu) for docking against twenty-five selected phytoconstituents reported from eight plants that recorded effective anti-leprosy activity. The chemical structure of phytochemicals and the standard dapsone structure were retrieved from the PubChem database and prepared accordingly for docking study with the virtual-screening platform of PyRx-AutoDock 4.1.
RESULTS
Based on the docking score (kcal/mol), most of the phytochemicals exhibited a higher docking score than dapsone. Asiaticoside, an active saponin (-11.3, -11.2 and -11.2 kcal/mol), was proved to be the lead phytochemical against both wild and mutant types DHPS. Some other useful phytoconstituents include echinocystic acid (-9.6, -9.5 and -9.5 kcal/mol), neobavaisoflavone (-9.2, -9.0 and -9.0 kcal/mol), boswellic acid (-8.90, -8.90 and -8.90 kcal/mol), asiatic acid (-8.9, -8.8 and -8.9 kcal/mol), corylifol A (-8.8, 8.0, and -8.0), etc. Overall, the computational predictions support the previously reported active phytoextracts of Centella asiatica (L.) Urban, Albizia amara (Roxb.) Boivin, Boswellia serrata Roxb. and Psoralea corylifolia L. to be effective against leprosy.
CONCLUSION
A very small percentage of well-known plants have been evaluated scientifically for antileprosy activity. Further in vivo experiments are essential to confirm anti-leprosy properties of such useful phytochemicals.
Topics: Cost of Illness; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Molecular Docking Simulation; Mycobacterium leprae; Phytochemicals
PubMed: 34503409
DOI: 10.2174/1568026621666210909162435