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Cureus Jan 2024Acquired methemoglobinemia is a treatable condition that is often clinically subtle and can be missed on routine clinical assessment. We present a 73-year-old male who...
Acquired methemoglobinemia is a treatable condition that is often clinically subtle and can be missed on routine clinical assessment. We present a 73-year-old male who was evaluated in the emergency department with worsening respiratory symptoms requiring oxygen. He tested COVID-19 positive and had new pulmonary emboli evident on his CT chest. The patient was on dapsone therapy as a treatment for bullous pemphigoid. The discrepancy between his oxygen levels on the pulse oximeter and blood gas was noted and was treated with 3% methylene blue for dapsone-induced methemoglobinemia. The patient received treatment for COVID-19 pneumonia and pulmonary emboli. Our case demonstrates that dapsone-induced methemoglobinemia can present concomitantly with other more common causes of acute hypoxic respiratory failure. It is noteworthy for physicians to maintain a high index of suspicion for oxygen level discrepancy in hypoxic patients and consider the possibility of acquired methemoglobinemia. Hence, earlier detection and treatment of the etiology of tissue hypoxia.
PubMed: 38327942
DOI: 10.7759/cureus.51830 -
The Medical Letter on Drugs and... Feb 2024
Topics: Humans; Acne Vulgaris
PubMed: 38294764
DOI: 10.58347/tml.2024.1695a -
Biochimica Et Biophysica Acta.... Mar 2024L-Ser supply in the central nervous system of mammals mostly relies on its endogenous biosynthesis by the phosphorylated pathway (PP). Defects in any of the three...
L-Ser supply in the central nervous system of mammals mostly relies on its endogenous biosynthesis by the phosphorylated pathway (PP). Defects in any of the three enzymes operating in the pathway result in a group of neurometabolic diseases collectively known as serine deficiency disorders (SDDs). Phosphoserine phosphatase (PSP) catalyzes the last, irreversible step of the PP. Here we investigated in detail the role of physiological modulators of human PSP activity and the properties of three natural PSP variants (A35T, D32N and M52T) associated with SDDs. Our results, partially contradicting previous reports, indicate that: i. PSP is almost fully saturated with Mg under physiological conditions and fluctuations in Mg and Ca concentrations are unlikely to play a modulatory role on PSP activity; ii. Inhibition by L-Ser, albeit at play on the isolated PSP, does not exert any effect on the flux through the PP unless the enzyme activity is severely impaired by inactivating substitutions; iii. The so-far poorly investigated A35T substitution was the most detrimental, with a 50-fold reduction in catalytic efficiency, and a reduction in thermal stability (as well as an increase in the IC for L-Ser). The M52T substitution had similar, but milder effects, while the D32N variant behaved like the wild-type enzyme. iv. Predictions of the structural effects of the A35T and M52T substitutions with ColabFold suggest that they might affect the structure of the flexible helix-loop region.
Topics: Animals; Humans; Serine; Magnesium; Ions; Mammals; Dapsone; Phosphoric Monoester Hydrolases
PubMed: 38278334
DOI: 10.1016/j.bbadis.2024.167034 -
PLoS Neglected Tropical Diseases Jan 2024The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of...
BACKGROUND
The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT.
METHODOLOGY
This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC).
RESULTS
A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs.
CONCLUSION
We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.
Topics: Adult; Humans; Female; Dapsone; Leprostatic Agents; Rifampin; Drug Therapy, Combination; Case-Control Studies; Clofazimine; Brazil; Leprosy; Drug-Related Side Effects and Adverse Reactions; World Health Organization
PubMed: 38271456
DOI: 10.1371/journal.pntd.0011901 -
Acta Dermato-venereologica Jan 2024Epidermolysis bullosa acquisita (EBA) rarely develops in childhood. This study retrospectively recruited paediatric patients with EBA (age ≤ 16 years), diagnosed by...
Epidermolysis bullosa acquisita (EBA) rarely develops in childhood. This study retrospectively recruited paediatric patients with EBA (age ≤ 16 years), diagnosed by clinical and histopathological features and results of immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA), and reviews their clinical manifestations, histopathology, immunological features, and responses to various treatments. All 7 included patients presented with inflammatory EBA. Among them, 3 had a bullous pemphigoid-like phenotype. Pathologically, in addition to dermal-epidermal blistering, in all patients, the distribution of neutrophils was superficial perivascular or interstitial, or in the dermal papilla. Mixed neutrophils and eosinophils were detected in 2 of the 3 patients with bullous pemphigoid-like phenotypes. In addition to treatment with glucocorticoids, dapsone was administered in 4 patients, while thalidomide and sulfasalazine were administered in 1 patient. All patients responded to the these therapies. Relapse was mainly due to reduction and cessation of glucocorticoids. In conclusion, EBA in childhood may be unique, and thus distinct from its adult counterpart. Specific treatment and follow-up protocols are required for therapy of this rare autoimmune skin disease in children.
Topics: Adult; Humans; Child; Adolescent; Epidermolysis Bullosa Acquisita; Pemphigoid, Bullous; Retrospective Studies; Autoimmune Diseases; Dapsone; Glucocorticoids
PubMed: 38270257
DOI: 10.2340/actadv.v104.11917 -
The American Journal of Tropical... Mar 2024Leprosy is a global health issue, causing long-term functional morbidity and stigma. Rapid diagnosis and appropriate treatment are important; however, early diagnosis is...
Leprosy is a global health issue, causing long-term functional morbidity and stigma. Rapid diagnosis and appropriate treatment are important; however, early diagnosis is often challenging, especially in nonendemic areas. Here, we report a case of borderline lepromatous leprosy accompanied by dapsone-induced (neutropenia, anemia, and methemoglobinemia) and clofazimine-induced (skin discoloration and ichthyosis) side effects and type 1 leprosy reactions during administration of the multidrug therapy. The patient completely recovered without developing any deformities or visual impairment. To ensure early diagnosis and a favorable outcome, clinicians should be aware of the diminished sensation of skin lesions as a key physical finding and manage the drug toxicities and leprosy reactions appropriately in patients on multidrug therapy.
Topics: Humans; Clofazimine; Dapsone; Drug Therapy, Combination; Leprostatic Agents; Leprosy; Leprosy, Borderline; Skin Diseases, Bacterial; Hypersensitivity; Peripheral Nervous System Diseases; Leprosy, Multibacillary; Leprosy, Lepromatous
PubMed: 38266303
DOI: 10.4269/ajtmh.22-0637 -
Journal Der Deutschen Dermatologischen... Mar 2024Non-biologic immunosuppressive drugs, such as azathioprine, dapsone or methotrexate are fundamental treatment options for a wide range of autoimmune and chronic...
Non-biologic immunosuppressive drugs, such as azathioprine, dapsone or methotrexate are fundamental treatment options for a wide range of autoimmune and chronic inflammatory skin diseases. Some of these drugs were initially used for malignancies (e.g., azathioprine or methotrexate) or infectious diseases (e.g., hydroxychloroquine or dapsone) but are nowadays mostly used for their immunosuppressive/immunomodulating action. Although dermatologists have years of clinical experience with these drugs, some of the mechanisms of action are not fully understood and are the subject of research. Although these drugs are commonly used, lack of experience or knowledge regarding their safety profiles and management leads to skepticism among physicians. Here, we summarize the mechanism of action and detailed management of adverse effects of the most commonly used immunosuppressive drugs for skin diseases. Furthermore, we discuss the management of these drugs during pregnancy and breastfeeding, as well as their interaction and handling during vaccination.
Topics: Pregnancy; Female; Humans; Azathioprine; Methotrexate; Immunosuppressive Agents; Skin Diseases; Dapsone; Autoimmune Diseases
PubMed: 38259085
DOI: 10.1111/ddg.15270 -
Journal of Biomolecular Structure &... Jan 2024Six drugs (dapsone, diltiazem, timolol, rosiglitazone, mesalazine, and milnacipran) that were predicted by network-based polypharmacology approaches as potential...
Six drugs (dapsone, diltiazem, timolol, rosiglitazone, mesalazine, and milnacipran) that were predicted by network-based polypharmacology approaches as potential anti-Alzheimer's drugs, have been subjected in this study for and evaluation to check their potential against protein fibrillation, which is a causative factor for multiple diseases such as Alzheimer's disease, Parkinson's disease, Huntington disease, cardiac myopathy, type-II diabetes mellitus and many others. Molecular docking and thereafter molecular dynamics (MD) simulations revealed that diltiazem, rosiglitazone, and milnacipran interact with the binding residues such as Asp52, Glu35, Trp62, and Asp101, which lie within the fibrillating region of HEWL. The MM-GBSA analysis revealed -7.86, -5.05, and -10.29 kcal/mol as the binding energy of diltiazem, rosiglitazone, and milnacipran. The RMSD and RMSF calculations revealed significant stabilities of these ligands within the binding pocket of HEWL. While compared with two reported ligands inhibiting HEWL fibrillation, milnacipran depicted almost similar binding potential with one of the known ligands (Ligand binding affinity -10.66 kcal/mol) of HEWL. Furthermore, secondary structure analyses revealed notable inhibition of the secondary structural changes with our candidate ligand; especially regarding retention of the 3/10 α-helix both by DSSP simulation, Circular dichroism, and FESEM-based microscopic image analyses. Taking further into experimental validation, all three ligands inhibited fibrillation in HEWL in simulated conditions as revealed by blue shift in Congo red assay and later expressing percentage inhibition in ThioflavinT assay as well. However, dose-dependent kinetics revealed that the antifibrillatory effects of drugs are more pronounced at low protein concentrations.Communicated by Ramaswamy H. Sarma.
PubMed: 38239069
DOI: 10.1080/07391102.2024.2305697