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Drugs May 2024Although several biological disease-modifying antirheumatic drugs (bDMARDs), including interleukin (IL)-17A inhibitors, are approved for psoriatic arthritis, the... (Review)
Review
Although several biological disease-modifying antirheumatic drugs (bDMARDs), including interleukin (IL)-17A inhibitors, are approved for psoriatic arthritis, the treatment of this disease remains suboptimal. Bimekizumab (Bimzelx), a dual IL-17A and IL-17F inhibitor, is approved in the EU, Great Britain and Japan for the treatment of psoriatic arthritis. In pivotal phase 3 clinical trials in patients who were bDMARD-naïve or previously had an inadequate response or intolerance to tumour necrosis factor (TNF) α inhibitors, bimekizumab improved the signs and symptoms of psoriatic arthritis across a range of joint, skin, radiographic and patient-reported outcomes compared with placebo, including the proportion of patients achieving a ≥ 50% response in the American College of Rheumatology criteria. Phase 2 clinical trial data have shown that responses are maintained up to 3 years. Bimekizumab was generally well tolerated in patients with psoriatic arthritis, with a safety profile consistent with that in other approved indications. The most common adverse events included nasopharyngitis, upper respiratory tract infection, oral candidiasis, headache and diarrhoea. In conclusion, bimekizumab extends the treatment options available to patients with psoriatic arthritis.
Topics: Humans; Arthritis, Psoriatic; Antibodies, Monoclonal, Humanized; Interleukin-17; Antirheumatic Agents
PubMed: 38703349
DOI: 10.1007/s40265-024-02026-3 -
Microbiology Spectrum Jun 2024Candidiasis places a significant burden on human health and can range from common superficial vulvovaginal and oral infections to invasive diseases with high mortality....
UNLABELLED
Candidiasis places a significant burden on human health and can range from common superficial vulvovaginal and oral infections to invasive diseases with high mortality. The most common species implicated in human disease is , but other species like are emerging. The use of azole antifungals for treatment is limited by increasing rates of resistance. This study explores repositioning bisphosphonates, which are traditionally used for osteoporosis, as antifungal synergists that can improve and revitalize the use of azoles. Risedronate, alendronate, and zoledronate (ZOL) were tested against isolates from six different species of , and ZOL produced moderate antifungal activity and strong synergy with azoles like fluconazole (FLC), particularly in . FLC:ZOL combinations had increased fungicidal and antibiofilm activity compared to either drug alone, and the combination prevented the development of antifungal resistance. Mechanistic investigations demonstrated that the synergy was mediated by the depletion of squalene, resulting in the inhibition of ergosterol biosynthesis and a compromised membrane structure. In , synergy compromised the function of membrane-bound multidrug transporters and caused an accumulation of reactive oxygen species, which may account for its acute sensitivity to FLC:ZOL. The efficacy of FLC:ZOL was confirmed in a infection model, where combinations improved the survival of larvae infected with and to a greater extent than monotherapy with FLC or ZOL, and at reduced dosages. These findings demonstrate that bisphosphonates and azoles are a promising new combination therapy for the treatment of topical candidiasis.
IMPORTANCE
is a common and often very serious opportunistic fungal pathogen. Invasive candidiasis is a prevalent cause of nosocomial infections with a high mortality rate, and mucocutaneous infections significantly impact the quality of life of millions of patients a year. These infections pose substantial clinical challenges, particularly as the currently available antifungal treatment options are limited in efficacy and often toxic. Azoles are a mainstay of antifungal therapy and work by targeting the biosynthesis of ergosterol. However, there are rising rates of acquired azole resistance in various species, and some species are considered intrinsically resistant to most azoles. Our research demonstrates the promising therapeutic potential of synergistically enhancing azoles with non-toxic, FDA-approved bisphosphonates. Repurposing bisphosphonates as antifungal synergists can bypass much of the drug development pipeline and accelerate the translation of azole-bisphosphonate combination therapy.
Topics: Antifungal Agents; Drug Synergism; Microbial Sensitivity Tests; Azoles; Humans; Diphosphonates; Candida; Animals; Drug Resistance, Fungal; Candidiasis; Fluconazole; Biofilms; Candida glabrata; Candida albicans
PubMed: 38695556
DOI: 10.1128/spectrum.00121-24 -
National Journal of Maxillofacial... 2024While fluconazole use is generally considered safe and well-tolerated, there has been an increasing number of reports regarding several adverse events. Therefore, the...
While fluconazole use is generally considered safe and well-tolerated, there has been an increasing number of reports regarding several adverse events. Therefore, the present study aimed to present a unique case in which photobiomodulation therapy (PBMT) was employed to manage bullous erythema multiforme lesions secondary to fluconazole intake. A 32-year-old female patient sought emergency dental care due to painful orofacial lesions that had developed two days after oral fluconazole use for recurrent vulvovaginal candidiasis. Given the acute clinical features, a diagnosis of bullous erythema multiforme secondary to fluconazole was established. Prednisone 20 mg was then prescribed for five days, and fluconazole intake was immediately discontinued. As the initial treatment strategies failed to show improvement in the clinical condition, three PBMT sessions were proposed every other day. Within seven days, almost complete wound healing was observed, and any pain complaints were no longer present. The resolution of orofacial lesions within a short period suggests that PBMT could be a promising tool for managing drug-induced bullous erythema multiforme. However, more studies are needed to confirm this statement.
PubMed: 38690232
DOI: 10.4103/njms.njms_128_22 -
Microbiology Spectrum Jun 2024Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the...
UNLABELLED
Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing data set characterizing the upper respiratory microenvironment during COVID-19 and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our previous study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection of species-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals. Using matched single-cell transcriptomic profiles of these individuals' respiratory mucosa, we identify epithelial immune signatures suggestive of IL17 stimulation and anti-fungal immunity. Further, we observe a significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggest that IL17 stimulation-in part driven by colonization-and blunted interferon signaling represent a common feature of severe COVID-19 infection.
IMPORTANCE
In this paper, we present an analysis suggesting that symptomatic and asymptomatic fungal coinfections can impact patient disease progression during COVID-19 hospitalization. By looking into the presence of other pathogens and their effect on the host immune response during COVID-19 hospitalizations, we aim to offer insight into an underestimated scenario, furthering our current knowledge of determinants of severity that could be considered for future diagnostic and intervention strategies.
Topics: Humans; Interleukin-17; COVID-19; Coinfection; Interferon Type I; Male; SARS-CoV-2; Middle Aged; Female; Epithelial Cells; Adult; Nasal Mucosa; Aged; Nasopharynx; Candidiasis; Mycoses
PubMed: 38687064
DOI: 10.1128/spectrum.03516-23 -
Nigerian Journal of Clinical Practice Apr 2024Tobacco smoking statistics are alarming and the oral mucosa is the first human part of the body that is exposed to the toxic substances of smoking. (Observational Study)
Observational Study
BACKGROUND
Tobacco smoking statistics are alarming and the oral mucosa is the first human part of the body that is exposed to the toxic substances of smoking.
AIMS
Considering the high prevalence rate of tobacco-associated problems in the oral cavity and few studies on the Iranian population regarding the effects of smoking on the oral cavity, this study aimed to evaluate the relationship between smoking and oral lesions in the Iranian population.
MATERIALS AND METHODS
Observational study. In this observational study, the oral cavities of 200 participants (smokers = 100 and non-smokers = 100) were examined by a trained dental student under the supervision of an oral and maxillofacial medicine expert, and the presence of coated tongue, leukoedema, leukoplakia, smoker's palate, smoker's melanosis, erythroplakia, frictional hyperkeratosis, acute pseudomembranous candidiasis, and erythematous candidiasis were recorded. Xerostomia was evaluated based on participants' self-reporting through a questionnaire. All data were analyzed using T-test, Chi-square test, odd ratio, 95% confidence interval, Fisher's exact test, and Spearman's rank correlation coefficient.
RESULTS
The results of this study showed smoking is significantly associated with an increased risk of coated tongue (OR: 1.80, 95% CI: 1.32-3.54, P = 0.005), smoker's melanosis (OR: 6.176, 95% CI: 3.28-11.62, P = 0.00002), and frictional hyperkeratosis (OR: 1.33, 95% CI: 0.68-2.60, P = 0.005). However, no significant association was observed between smoking and leukoedema (OR: 1, 95% CI: 0.51-1.94, P = 1). None of the participants presented smoker's palate, erythroplakia, and candidiasis.
CONCLUSIONS
This study's results showed that smokers exhibited a greater chance of developing oral lesions compared to non-smokers.
Topics: Humans; Iran; Male; Female; Mouth Mucosa; Adult; Middle Aged; Mouth Diseases; Smokers; Smoking; Non-Smokers; Prevalence; Young Adult; Xerostomia; Aged; Leukoplakia, Oral
PubMed: 38679769
DOI: 10.4103/njcp.njcp_702_23 -
AIDS Research and Therapy Apr 2024Bacillus Calmette-Guérin (BCG) reactions are the most common cause of immune reconstitution inflammatory syndrome (IRIS) in HIV-positive infants who initiate...
BACKGROUND
Bacillus Calmette-Guérin (BCG) reactions are the most common cause of immune reconstitution inflammatory syndrome (IRIS) in HIV-positive infants who initiate antiretroviral therapy (ART). There is limited evidence regarding the incidence of BCG-IRIS; however, reports from outpatient cohorts have estimated that 6-9% of infants who initiated ART developed some form of BCG-IRIS within the first 6 months. Various treatment approaches for infants with BCG-IRIS have been reported, but there is currently no widely accepted standard-of-care.
CASE PRESENTATION
A 5-month-old male HIV-exposed infant BCG vaccinated at birth was admitted for refractory oral candidiasis, moderate anemia, and moderate acute malnutrition. He had a HIV DNA-PCR collected at one month of age, but the family never received the results. He was diagnosed with HIV during hospitalization with a point-of-care nucleic acid test and had severe immune suppression with a CD4 of 955 cells/µL (15%) with clinical stage III disease. During pre-ART counseling, the mother was educated on the signs and symptoms of BCG-IRIS and the importance of seeking follow-up care and remaining adherent to ART if symptoms arose. Three weeks after ART initiation, he was readmitted with intermittent subjective fevers, right axillary lymphadenopathy, and an ulcerated papule over the right deltoid region. He was subsequently discharged home with a diagnosis of local BCG-IRIS lymphadenitis. At six weeks post-ART initiation, he returned with suppurative lymphadenitis of the right axillary region that had completely eviscerated through the skin without signs of disseminated BCG disease. He was then started on an outpatient regimen of topical isoniazid, silver nitrate, and oral prednisolone. Throughout this time, the mother maintained good ART adherence despite this complication. After 2.5 months of ART and one month of specific treatment for the lymphadenitis, he had marked mass reduction, improved adenopathy, increased CD4 count, correction of anemia, and resolution of his acute malnutrition. He completely recovered and was symptom free two months after initial treatment without surgical intervention.
CONCLUSIONS
This case details the successful management of severe suppurative BCG-IRIS with a non-surgical approach and underlines the importance of pre-ART counseling on BCG-IRIS for caregivers, particularly for infants who initiate ART with advanced HIV.
Topics: Humans; Male; Lymphadenitis; BCG Vaccine; Infant; HIV Infections; Immune Reconstitution Inflammatory Syndrome; Treatment Outcome
PubMed: 38678293
DOI: 10.1186/s12981-024-00614-7 -
Dentistry Journal Apr 2024Vitamins play a vital role in human health, particularly in the development and maintenance of oral health in children. These nutrients are broadly categorized into... (Review)
Review
Vitamins play a vital role in human health, particularly in the development and maintenance of oral health in children. These nutrients are broadly categorized into fat-soluble and water-soluble types, crucial for children's well-being. The objective of this study is to investigate the impact of vitamin deficiencies on the oral health of children, focusing on how these deficiencies contribute to various oral health issues and determining the relationship between specific vitamin shortages and oral diseases. Findings indicate that shortages in vitamins A and D lead to enamel issues and a higher susceptibility to dental diseases, vitamin E assists in treating oral mucositis, and vitamin K is essential for blood clotting in dental surgeries. Deficits in B-complex and vitamin C result in enamel hypomineralization and soft tissue ailments, including aphthous stomatitis and gingival petechiae. Additionally, a lack of vitamin B7 compromises the immune response, increasing oral candidiasis risk. Therefore, vitamin deficiencies markedly affect children's oral health, highlighting the need for joint efforts between dental professionals and caregivers for effective pediatric care. Addressing vitamin deficiencies through supplementation and tailored dental care emphasizes the significance of nutritional health in children's overall and dental well-being, advocating for a collaborative approach to achieve optimal health outcomes.
PubMed: 38668021
DOI: 10.3390/dj12040109 -
International Immunopharmacology May 2024Innate lymphoid cells (ILCs), as newly discovered antigen-independent innate immune cells, respond promptly to stimuli by secreting effector cytokines to exert effector... (Review)
Review
Innate lymphoid cells (ILCs), as newly discovered antigen-independent innate immune cells, respond promptly to stimuli by secreting effector cytokines to exert effector functions similar to those of T cells. ILCs predominantly reside at mucosal sites and play critical roles in defending against infections, maintaining mucosal homeostasis, regulating inflammatory and immune responses, and participating in tumorigenesis. Recently, there has been a growing interest in the role of ILCs in oral diseases. This review outlines the classifications and the major characteristics of ILCs, and then comprehensively expatiates the research on ILCs in oral cancer, primary Sjogren's syndrome, periodontal diseases, oral lichen planus, oral candidiasis, Behcet's disease, and pemphigus vulgaris, aiming at summarising the implications of ILCs in oral diseases and providing new ideas for further research.
Topics: Humans; Immunity, Innate; Mouth Diseases; Animals; Lymphocytes; Cytokines
PubMed: 38663313
DOI: 10.1016/j.intimp.2024.112122 -
Archives of Dermatological Research Apr 2024Bimekizumab is a humanized monoclonal IgG1 antibody with a unique mechanism of action, as it inhibits both IL17A and IL17F molecules. This dual inhibition is thought to... (Observational Study)
Observational Study
INTRODUCTION
Bimekizumab is a humanized monoclonal IgG1 antibody with a unique mechanism of action, as it inhibits both IL17A and IL17F molecules. This dual inhibition is thought to be responsible for its high efficacy in treating chronic plaque psoriasis with rapid onset of action in Randomized Controlled Trials (RCTs). Concerning safety, oral candidiasis was one of the most common drug-related adverse events, commonly mild-to-moderate in severity. Although data from RCTs supporting this efficacy and safety profile of bimekizumab is numerous, results from the real-world setting concerning short- and mid-term treatment effectiveness and safety profile are limited.
MATERIALS AND METHODS
An observational, retrospective, monocentric study was conducted at the Psoriasis Outpatient Unit of "A. Sygros" Hospital for Skin and Venereal Diseases, in Athens, Greece, which included 61 adult patients with moderate-to-severe skin psoriasis, who received at least one dosage of bimekizumab.
RESULTS
At week 4, 65.7% achieved PASI75, 45.7% PASI90, and 32.4% PASI100. After 16 weeks of treatment, 92.3/76.9/66.7% of the patients achieved PASI75/90/100, respectively. Increased BMI, previous treatment with another IL-17 inhibitor, or previous exposure to another biologic did not seem to influence the possibility of achieving PASI90 and PASI100 at week 16 of bimekizumab treatment in this cohort. Six (9.8%) cases of possibly drug-related AEs were reported, from which four incidences of oral candidiasis.
CONCLUSION
Our results confirm that this IL17A/F inhibitor is highly effective, with a tolerability profile similar to the one expected from RCTs.
Topics: Humans; Psoriasis; Male; Female; Antibodies, Monoclonal, Humanized; Middle Aged; Retrospective Studies; Adult; Interleukin-17; Treatment Outcome; Severity of Illness Index; Candidiasis, Oral; Aged; Dermatologic Agents
PubMed: 38662223
DOI: 10.1007/s00403-024-02868-7 -
The Journal of Dermatology Apr 2024Systemic treatments are important for patients with moderate-to-severe psoriasis; however, they may occasionally cause adverse infectious events. Although the risk of...
Systemic treatments are important for patients with moderate-to-severe psoriasis; however, they may occasionally cause adverse infectious events. Although the risk of severe infections with psoriatic treatments is well established, little is known about cutaneous infections. Therefore, we studied the frequency of cutaneous infections in patients with psoriasis who underwent biologic treatment. A total of 878 patients (237 females and 641 males) were analyzed in this follow-up survey conducted in 2020 and based on the Western Japan Psoriasis Registry. The observed skin phenotypes were psoriasis vulgaris (83.3%), pustular psoriasis (7.5%), and psoriatic arthritis (28.9%). The most frequently prescribed systemic drug was apremilast (11.3%), followed by ixekizumab (11.0%), risankizumab (10.9%), and secukinumab (10.4%). The incidence of cutaneous bacterial infections was 12 (1.37% of the total patients), with cellulitis being the most common (8/12, 67%). The incidence of viral infections was 11 (1.25%) including the most common, herpes zoster (9/11, 82%); and that of fungal infections was 45 (5.13%) including 33 (73%) and seven (16%) patients with trichophytosis and oral candidiasis, respectively. Multivariate analysis revealed that cutaneous bacterial infections were frequently observed in patients receiving tumor necrosis factor-α (odds raio [OR] 9.917, 95% confidence interval [CI] 2.069-47.572, p = 0.004) and interleukin (IL)-17 (OR 10.798, 95% CI 2.35-49.616, p = 0.002) inhibitor treatments. A history of otitis media and treatment with oral medications (OR 4.50, 95% CI 1.281-15.804, p = 0.019 and OR 3.80, 95% CI 1.141-12.679, p = 0.03 respectively) were associated with a higher ORs for cutaneous viral infections. Furthermore, age and use of IL-17 inhibitors were associated with elevated ORs for fungal infections. In conclusion, our study reveals that systemic therapies may increase the risk of cutaneous viral infections. Therefore, dermatologists should exercise caution in this regard.
PubMed: 38660962
DOI: 10.1111/1346-8138.17245