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Authors = Aditya K. Gupta

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24 pages, 1548 KiB  
Review
Onychomycosis in Diabetics: A Common Infection with Potentially Serious Complications
by Aditya K. Gupta, Amanda Liddy, Lee Magal, Avner Shemer, Elizabeth A. Cooper, Ditte Marie L. Saunte and Tong Wang
Life 2025, 15(8), 1285; https://doi.org/10.3390/life15081285 - 13 Aug 2025
Abstract
Onychomycosis is a prevalent and clinically relevant complication among individuals with diabetes. It is associated with an elevated risk of secondary fungal and bacterial infections, foot ulceration, and, in advanced cases, amputation. Factors contributing to the increased prevalence of onychomycosis in this population [...] Read more.
Onychomycosis is a prevalent and clinically relevant complication among individuals with diabetes. It is associated with an elevated risk of secondary fungal and bacterial infections, foot ulceration, and, in advanced cases, amputation. Factors contributing to the increased prevalence of onychomycosis in this population include age, peripheral vascular disease, poor glycemic control, neuropathy, suboptimal foot hygiene, and nail trauma. While dermatophytes are the most common pathogens, diabetic patients are more prone to mixed infections involving Candida species with varying antifungal susceptibility profiles, necessitating accurate identification to guide therapy. Prompt diagnosis and early intervention are important to prevent complications. Systemic antifungals such as terbinafine and itraconazole are considered first-line therapies, particularly for moderate to severe onychomycosis. However, drug interactions, renal, hepatic, and metabolic comorbidities may necessitate individualized treatment plans. For patients with mild to moderate disease, or contraindications to oral therapy, topical agents such as efinaconazole or tavaborole offer viable alternatives. Adjunctive measures, including education on foot hygiene, prompt treatment of tinea pedis, and environmental sanitization, are important in preventing recurrence and reinfection. This review summarizes the epidemiology, diagnosis, and treatment considerations for onychomycosis in diabetic patients, emphasizing the need for individualized care to improve outcomes in this high-risk population. Full article
(This article belongs to the Section Medical Research)
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14 pages, 670 KiB  
Review
Hygiene Practices Against Dermatophytic Fungi: A Review of Strategies to Combat Antifungal Resistance
by Aditya K. Gupta, Daniel Taylor, Tong Wang, Elizabeth A. Cooper and Ditte Marie L. Saunte
Biology 2025, 14(8), 1016; https://doi.org/10.3390/biology14081016 - 7 Aug 2025
Viewed by 223
Abstract
Superficial fungal infections of the feet, such as tinea pedis and onychomycosis, are highly prevalent and frequently recurrent, often due to persistent contamination of footwear, textiles, and foot care instruments. Despite growing concern over antifungal resistance, environmental sources of reinfection remain under-recognized in [...] Read more.
Superficial fungal infections of the feet, such as tinea pedis and onychomycosis, are highly prevalent and frequently recurrent, often due to persistent contamination of footwear, textiles, and foot care instruments. Despite growing concern over antifungal resistance, environmental sources of reinfection remain under-recognized in clinical practice. This review critically examines historical and contemporary methods used to sanitize shoes, socks, podiatric tools, and related materials. Evidence from peer-reviewed studies published between 1938 and 2025 was analyzed across multiple disinfection categories, including chemical agents, thermal methods, laundering, ultraviolet- and ozone-based technologies, antimicrobial textiles, and sterilization protocols. Findings reveal a range of efficacies, limitations, and practical considerations across methods, with steam sterilization emerging as the most reliable for reusable instruments. A multifaceted approach combining pharmacologic treatment with consistent environmental hygiene is essential for breaking reinfection cycles and reducing antifungal resistance. This review highlights the need for clinical education and research into scalable, effective disinfection strategies. Full article
(This article belongs to the Section Microbiology)
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18 pages, 2273 KiB  
Review
Terbinafine Resistance in Trichophyton rubrum and Trichophyton indotineae: A Literature Review
by Aditya K. Gupta, Susmita, Hien C. Nguyen, Amanda Liddy, Vasiliki Economopoulos and Tong Wang
Antibiotics 2025, 14(5), 472; https://doi.org/10.3390/antibiotics14050472 - 7 May 2025
Cited by 2 | Viewed by 3482
Abstract
Background/Objectives: Terbinafine has been the gold standard for the management of superficial fungal infections. The etiological agent generally is Trichophyton rubrum (T. rubrum); however, there has been increased reporting of a new terbinafine-resistant strain of the T. mentagrophytes complex (T. [...] Read more.
Background/Objectives: Terbinafine has been the gold standard for the management of superficial fungal infections. The etiological agent generally is Trichophyton rubrum (T. rubrum); however, there has been increased reporting of a new terbinafine-resistant strain of the T. mentagrophytes complex (T. mentagrophytes ITS genotype VIII otherwise known as T. indotineae). Here, we review the epidemiology, clinical features, diagnosis, and treatment of T. rubrum and T. indotineae infections. Methods: We conducted a systematic literature search using PubMed, Embase (Ovid), and Web of Science, resulting in 83 qualified studies with data summarized for clinical features, antifungal susceptibility, and terbinafine resistance mechanisms and mutations. Results: Dermatophytosis is most commonly caused by T. rubrum; however, in certain parts of the world, especially in the Indian subcontinent, T. indotineae infections have been reported more frequently. The majority of T. rubrum isolates remain susceptible to terbinafine (over 60% of isolates show MIC50 and MIC90 < 0.5 µg/mL). In contrast, for T. indotineae, 30% of isolates exhibit MIC50 ≥ 0.5 µg/mL and 80% exhibit MIC90 ≥ 0.5 µg/mL. Frequently detected squalene epoxidase (SQLE) mutations in T. rubrum are Phe397Leu/Ile (41.6%) and Leu393Phe (20.8%); in T. indotineae, these include Phe397Leu (33.0%) and Ala448Thr (24.5%). Other potential terbinafine resistance mechanisms in T. rubrum and T. indotineae are discussed. Conclusions: T. rubrum generally remain susceptible in vitro to terbinafine in contrast to T. indotineae. The essential components of an effective antifungal stewardship emphasize accurate clinical and laboratory diagnosis, susceptibility testing, and appropriate antifungal therapy selection with a multidisciplinary approach. Full article
(This article belongs to the Special Issue The Worldwide Problem of Antifungal Resistance: From Basic to Clinic)
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24 pages, 2063 KiB  
Systematic Review
Global Dermatophyte Infections Linked to Human and Animal Health: A Scoping Review
by Aditya K. Gupta, Tong Wang, Susmita, Mesbah Talukder and Wayne L. Bakotic
Microorganisms 2025, 13(3), 575; https://doi.org/10.3390/microorganisms13030575 - 3 Mar 2025
Cited by 3 | Viewed by 3267
Abstract
Dermatophytes are commonly encountered pathogens in clinical practice causing superficial infections of the skin, hair, and nails. These pathogens are often found on animals such as livestock (e.g., cattle, rabbits) and pets (e.g., cats, hedgehogs) that can lead to spillover infections in human [...] Read more.
Dermatophytes are commonly encountered pathogens in clinical practice causing superficial infections of the skin, hair, and nails. These pathogens are often found on animals such as livestock (e.g., cattle, rabbits) and pets (e.g., cats, hedgehogs) that can lead to spillover infections in human populations. Here, we reviewed published reports (2009–2024) of dermatophyte infections in animals and in humans with a history of animal contact. A literature search was completed in October 2024 using PubMed, Embase (Ovid), and Web of Science (Core Collection), which identified 250 articles. Generally, dermatophytes tend to infect younger animals with long hair and exhibit a species-specific host range. Microsporum canis was the most commonly reported species—linked to cats—that can cause tinea capitis, especially concerning the development of kerion in children. Trichophyton verrucosum is strongly associated with cattle. The Trichophyton mentagrophytes complex shows a diverse range of animal hosts, with rabbits being most frequently reported; however, T. mentagrophytes var. erinacei is almost exclusively isolated from hedgehogs, and T. mentagrophytes var. benhamiae is more commonly found on rodents (e.g., guinea pigs). Lastly, the geophilic Nannizia gypsea has been isolated from both dogs and cats. Managing dermatophyte zoonoses is an ongoing challenge, as healthcare providers may empirically treat with corticosteroids or antibacterial agents due to its atypical inflammatory appearance. Evidence of in vitro resistance against griseofulvin and fluconazole has been documented in multiple zoonotic dermatophyte species. Resistance development against terbinafine and itraconazole is also a possibility, although the number of reports is scarce. Under the principles of the One Health approach, research on human fungal diseases should take animal and environmental factors into account. A renewed call for increased testing efforts is warranted. Full article
(This article belongs to the Special Issue Current Pattern in Epidemiology and Antifungal Resistance)
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15 pages, 1150 KiB  
Article
Interdigital and Plantar Foot Infections: A Retrospective Analysis of Molecularly Diagnosed Specimens in the United States and a Literature Review
by Aditya K. Gupta, Tong Wang, Sara A. Lincoln and Wayne L. Bakotic
Microorganisms 2025, 13(1), 184; https://doi.org/10.3390/microorganisms13010184 - 16 Jan 2025
Cited by 2 | Viewed by 1178
Abstract
Up to one-quarter of the United States population is affected by tinea pedis (athlete’s foot). Tinea pedis of the web space (interdigital tinea pedis) is a common clinical presentation causing skin macerations and fissures. A “dermatophytosis complex” (i.e., concomitant bacterial colonization) further complicates [...] Read more.
Up to one-quarter of the United States population is affected by tinea pedis (athlete’s foot). Tinea pedis of the web space (interdigital tinea pedis) is a common clinical presentation causing skin macerations and fissures. A “dermatophytosis complex” (i.e., concomitant bacterial colonization) further complicates treatment. Here, we examined records of 14,429 skin specimens taken from the feet of dermatology and podiatry outpatients over a 4.6-year period; all specimens were subjected to multiplex qPCR diagnosis for the detection of dermatophytes, Candida, Corynebacterium minutissimum, Pseudomonas and Staphylococcus aureus. A literature search was conducted to review the reported prevalence of fungal and bacterial agents. In both interdigital and plantar foot specimens, dermatophytes (33.3–33.8%) and S. aureus (24.3–25%) were found to be the predominate pathogens. In the interdigital space, a higher prevalence of C. minutissimum (15.7% vs. 7.9%) and Pseudomonas (23.5% vs. 9.6%) was found. The detection of Pseudomonas was more likely to be observed in the presence of Candida, reflecting a higher risk of mixed infection. In dermatophyte-positive specimens, the “dermatophytosis complex” variant was observed at 45.5% (SD: 2.3). An analysis of patient characteristics showed male patients exhibiting higher likelihoods for dermatophyte, C. minutissimum, Pseudomonas and S. aureus detections. The elderly were disproportionately infected with Candida. In children, an S. aureus detection was more common, which could be attributed to impetigo. The recent literature lacks reporting on concomitant bacterial colonization in tinea pedis patients, likely due to the reliance on fungal culture supplemented with antibiotics. Geographical variation has been identified in the detection of the Trichophyton mentagrophytes complex. In conclusion, PCR diagnosis serves as a valuable tool for the management of tinea pedis. An accurate and timely detection of fungal pathogens and concomitant bacterial colonization can better inform healthcare providers of appropriate treatment selection. Full article
(This article belongs to the Special Issue Human Skin Microbiota, 2nd Edition)
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12 pages, 1091 KiB  
Article
Safety and Efficacy of a 48-Month Efinaconazole 10% Solution Treatment/Maintenance Regimen: 24-Month Daily Use Followed by 24-Month Intermittent Use
by Aditya K. Gupta and Elizabeth A. Cooper
Infect. Dis. Rep. 2025, 17(1), 7; https://doi.org/10.3390/idr17010007 - 13 Jan 2025
Cited by 1 | Viewed by 2016
Abstract
Background/Objectives: In an 18- to 24-month Treatment Phase with once-daily efinaconazole 10% solution, subjects with onychomycosis showed an increased rate of cure at Month 24 versus the phase III trials. In order to further improve efficacy, we initiated an extended intermittent efinaconazole Maintenance [...] Read more.
Background/Objectives: In an 18- to 24-month Treatment Phase with once-daily efinaconazole 10% solution, subjects with onychomycosis showed an increased rate of cure at Month 24 versus the phase III trials. In order to further improve efficacy, we initiated an extended intermittent efinaconazole Maintenance Phase with use 2–3 times weekly for an additional 24 months from Month 24 to Month 48. These are the first data presented for a 48-month efinaconazole use period. Methods: For patients completing 18–24 months of once-daily efinaconazole, the target great toenail from the Treatment Phase was graded as ‘Clinical Cure’ (≤10% affected area) or ‘No Clinical Cure’ (>10% affected area) at Month 24. Mycological and clinical outcomes were assessed every 4 months from Month 24 to Month 48. There were 35 patients who enrolled in the extension and continued intermittent efinaconazole use to Month 48. Patients with ‘Clinical Cure’ at M24 were reviewed for sustained cure at M48; patients with ‘No Clinical Cure’ were reviewed for development of ‘Cure’ at M48. All patients were reviewed at all visits for adverse events that may be related to efinaconazole use. Results: ‘Clinical Cure’ was found in 6 of 35 enrolled patients at Month 24, and clinical cure status was sustained to Month 48 with intermittent efinaconazole maintenance use. For 29 patients with ‘No Clinical Cure’, 3/29 achieved ‘Clinical Cure’ status at Month 48 with intermittent efinaconazole. Effective Cure and Complete Cure rates improved over the maintenance period to Month 48 in subjects without clinical cure at Month 24. Younger patients showed higher cure rates over the maintenance period, but age group cure differences did not reach statistical significance in this dataset, and 49% of the ≥70-year population had at least a 20% reduction in nail area with maintenance therapy to Month 48. There was only 1 case of possible efinaconazole application site reaction in the Intermittent Maintenance Period to Month 48; prolonged efinaconazole use to Month 48 does not appear to increase the risk of reaction. Efinaconazole use periods are associated with very low positive culture rates in this dataset, including typical contaminant organisms, suggesting efinaconazole presence in the nail plate is providing prophylactic therapy. Conclusions: Intermittent efinaconazole may provide suitable prophylaxis of onychomycosis relapse. Prolonged efinaconazole therapy to Month 48 appears to be safe for all ages and can continue to provide prophylaxis of onychomycosis with Intermittent Maintenance use beyond Month 24 to Month 48. Full article
(This article belongs to the Section Fungal Infections)
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1 pages, 143 KiB  
Reply
Reply to Cosio et al. Glycation of Nail Proteins as a Risk Factor for Onychomycosis. Comment on “Gupta et al. Diabetic Foot and Fungal Infections: Etiology and Management from a Dermatologic Perspective. J. Fungi 2024, 10, 577”
by Aditya K. Gupta, Avner Shemer, Vasiliki Economopoulos and Mesbah Talukder
J. Fungi 2025, 11(1), 47; https://doi.org/10.3390/jof11010047 - 8 Jan 2025
Viewed by 618
Abstract
We find the comment on the article titled “Diabetic Foot and Fungal Infections: Etiology and Management from a Dermatologic Perspective” informative and wish to thank the authors for their added insight on this complex topic [...] Full article
9 pages, 797 KiB  
Article
Molecular Identification of Etiological Agents in Fungal and Bacterial Skin Infections: United States, 2020–2024
by Aditya K. Gupta, Tong Wang, Sara A. Lincoln, Hui-Chen Foreman and Wayne L. Bakotic
Infect. Dis. Rep. 2024, 16(6), 1075-1083; https://doi.org/10.3390/idr16060087 - 18 Nov 2024
Viewed by 1451
Abstract
Background/Objectives: Cutaneous infections of fungal and bacterial origins are common. An accurate diagnosis—especially concerning pathogens that are difficult to isolate on culture—can be achieved using molecular methods (PCR) with a short turnaround time. Methods: We reviewed records of skin specimens (superficial [...] Read more.
Background/Objectives: Cutaneous infections of fungal and bacterial origins are common. An accurate diagnosis—especially concerning pathogens that are difficult to isolate on culture—can be achieved using molecular methods (PCR) with a short turnaround time. Methods: We reviewed records of skin specimens (superficial scrapings) submitted by dermatologists across the United States with a clinically suspected dermatitis. As per physician’s order, specimens were tested for infections either fungal (N = 4262) or bacterial (N = 1707) in origin. All unique specimens (one per patient) were subjected to real-time PCR assays where cases suspected of a fungal etiology were tested for dermatophytes, Malassezia and Candida, and cases suspected of a bacterial etiology were tested for Streptococcus pyogenes, Staphylococcus aureus, and the mecA gene potentially conferring β-lactam resistance. Results: Fungal agents were detected in 32.8% (SD: 4.5) of the submitted specimens, with most attributed to dermatophytes (19.3% (SD: 4.9)), followed by Malassezia (8.7% (SD: 2.8)) and Candida (2.9% (SD: 1.0)). Dermatophyte detection was more common in the elderly (≥65 years) compared to young adults (18–44 years) (OR: 1.8 (95% CI: 1.5, 2.2)), whereas Malassezia was more commonly detected in younger age groups (12.1–13.6%) than the elderly (5.6%). Candida was more frequently observed in females while dermatophytes and Malassezia were more frequently observed in males. Approximately one quarter of the submitted skin specimens tested positive for S. aureus (23.6% (SD: 3.4)), of which 34.4% (SD: 9.8) exhibited concurrent detection of the mecA gene. An S. aureus detection was more frequently observed in males (OR: 1.5 (95% CI: 1.2, 1.9)) and in children (OR: 1.7 (95% CI: 1.2, 2.5)). Streptococcus pyogenes was rarely detected. Among specimens positive for dermatophytes, 12.0% (20/166) showed co-detection of S. aureus and mecA, which is in contrast to 6.8% (70/1023) detected in samples without a fungal co-detection and 6.2% (8/130) in samples positive for Malassezia. Conclusions: PCR testing, when available, can be valuable as a part of routine care for diagnosing patients with clinically suspected skin infections. Further studies are warranted to survey the prevalence of resistant S. aureus isolates in dermatology outpatients, in particular with regard to the association with dermatophyte infections. Full article
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13 pages, 2888 KiB  
Article
Epidemiology of Onychomycosis in the United States Characterized Using Molecular Methods, 2015–2024
by Aditya K. Gupta, Tong Wang, Shruthi Polla Ravi, Avantika Mann, Sara A. Lincoln, Hui-Chen Foreman and Wayne L. Bakotic
J. Fungi 2024, 10(9), 633; https://doi.org/10.3390/jof10090633 - 5 Sep 2024
Cited by 3 | Viewed by 2011
Abstract
Onychomycosis is a recalcitrant fungal infection of the nail unit that can lead to secondary infections and foot complications. Accurate pathogen identification by confirmatory testing is recommended to improve treatment outcomes. In this study, we reviewed the records of 710,541 patients whose nail [...] Read more.
Onychomycosis is a recalcitrant fungal infection of the nail unit that can lead to secondary infections and foot complications. Accurate pathogen identification by confirmatory testing is recommended to improve treatment outcomes. In this study, we reviewed the records of 710,541 patients whose nail specimens were sent to a single molecular diagnostic laboratory between 2015 and 2024. PCR testing revealed a more comprehensive spectrum of pathogens than previously reported, which was corroborated by the demonstration of fungal invasion on histopathology. Consistent with our current understanding, the T. rubrum complex (54.3%) are among the most common pathogens; however, a significant portion of mycology-confirmed diagnoses were caused by the T. mentagrophytes complex (6.5%), Aspergillus (7.0%) and Fusarium (4.5%). Females were significantly more likely to be infected with non-dermatophytes molds (NDMs; OR: 2.0), including Aspergillus (OR: 3.3) and Fusarium (OR: 2.0), and yeasts (OR: 1.5), including Candida albicans (OR: 2.0) and C. parapsilosis (OR 1.6), than males. The T. mentagrophytes complex became more prevalent with age, and conversely the T. rubrum complex became less prevalent with age. Patients aged ≥65 years also demonstrated a higher likelihood of contracting onychomycosis caused by NDMs (OR: 1.6), including Aspergillus (OR: 2.2), Acremonium (OR: 3.5), Scopulariopsis (OR: 2.9), Neoscytalidium (OR: 3.8), and yeasts (OR: 1.8), including C. albicans (OR: 1.9) and C. parapsilosis (OR: 1.7), than young adults. NDMs (e.g., Aspergillus and Fusarium) and yeasts were, overall, more likely to cause superficial onychomycosis and less likely to cause dystrophic onychomycosis than dermatophytes. With regards to subungual onychomycosis, Aspergillus, Scopulariopsis and Neoscytalidium had a similar likelihood as dermatophytes. The advent of molecular diagnostics enabling a timely and accurate pathogen identification can better inform healthcare providers of appropriate treatment selections and develop evidence-based recommendations. Full article
(This article belongs to the Special Issue Personalized Mycology)
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12 pages, 2117 KiB  
Article
Extended Use of Topical Efinaconazole Remains Safe and Can Provide Continuing Benefits for Dermatophyte Toenail Onychomycosis
by Aditya K. Gupta and Elizabeth A. Cooper
J. Fungi 2024, 10(9), 620; https://doi.org/10.3390/jof10090620 - 30 Aug 2024
Cited by 2 | Viewed by 2308
Abstract
Introduction: Efinaconazole 10% topical solution labeling for onychomycosis describes phase III trials of 12 months of treatment; the slow growth of onychomycotic nails suggests a longer treatment period may increase efficacy. We present here the first evaluation of extended use of efinaconazole 10% [...] Read more.
Introduction: Efinaconazole 10% topical solution labeling for onychomycosis describes phase III trials of 12 months of treatment; the slow growth of onychomycotic nails suggests a longer treatment period may increase efficacy. We present here the first evaluation of extended use of efinaconazole 10% topical solution for up to 24 months. Materials and Methods: Enrolled patients (n = 101) had one target great toenail with mild to moderate distal lateral subungual onychomycosis and applied efinaconazole 10% topical solution to all affected toenails once daily for 18 months (EFN18) or 24 months (EFN24). Efficacy and safety were evaluated at each visit by visual review and mycology sampling. Results: Regarding the target toenail for patients treated for 24 months (EFN24), mycological cure (negative microscopy and culture) was 66.0% at Month 12, increasing to 71.7% at Month 24; effective cure (mycological cure and ≤10% affected nail) was 13.2% at Month 12, rising to 22.6% at Month 24. Mild to moderate application site reactions (symptoms of erythema/scaling) were the only efinaconazole-related reactions, in eight patients (7.9%). No systemic efinaconazole events or drug interactions were found. Patients aged 70 years or more had similar efficacy to younger patients at all time periods and did not show any increased treatment risks. Thinner nails exhibited better clearance versus thicker nails. A higher proportion of patients with Trichophyton mentagrophytes complex infection experienced application site reactions (35.7%), and a higher effective cure was found at Month 24 versus T. rubrum patients. Conclusion: There is a trend of increasing mycological cure and effective cure beyond Month 12 to Month 24, without an increased safety risk. The enrolled population in this trial was significantly older than in the phase III trials, with a greater degree of onychomycosis severity; however, increased age did not appear to reduce the chance of efficacy to Month 24 in this study. Our data suggest that lack of ability to clear nail dystrophy remains a significant problem for patients, rather than any lack of efinaconazole action over long-term treatment periods. Full article
(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections, Second Edition)
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15 pages, 2102 KiB  
Review
Diabetic Foot and Fungal Infections: Etiology and Management from a Dermatologic Perspective
by Aditya K. Gupta, Avner Shemer, Vasiliki Economopoulos and Mesbah Talukder
J. Fungi 2024, 10(8), 577; https://doi.org/10.3390/jof10080577 - 15 Aug 2024
Cited by 11 | Viewed by 4991
Abstract
Diabetes Mellitus (DM) is a significant global concern. Many diabetic patients will experience complications due to angiopathy, neuropathy, and immune dysfunction, namely diabetic foot ulcers (DFU) and diabetic foot infections (DFI), which can result in lower limb amputation and potentially death. The prevalence [...] Read more.
Diabetes Mellitus (DM) is a significant global concern. Many diabetic patients will experience complications due to angiopathy, neuropathy, and immune dysfunction, namely diabetic foot ulcers (DFU) and diabetic foot infections (DFI), which can result in lower limb amputation and potentially death. The prevalence of common superficial fungal infections, such as tinea pedis and onychomycosis, can directly increase a diabetic patient’s risk of developing both DFU and DFI. In this review article, we discuss the etiology of diabetic foot complications as well as considerations for both screening and management. We also discuss the role of the dermatologist within a multidisciplinary care team in prescribing and managing treatments for tinea pedis and onychomycosis infections within this patient population. We believe that reducing the burden of these fungal infections in the context of the diabetic foot will help reduce DFU and DFI complications and their associated morbidity and mortality. Full article
(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections, Second Edition)
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13 pages, 3080 KiB  
Article
Clinical Diagnosis and Laboratory Testing of Abnormal Appearing Toenails: A Retrospective Assessment of Confirmatory Testing for Onychomycosis in the United States, 2022–2023
by Aditya K. Gupta, Tong Wang, Elizabeth A. Cooper, Sara A. Lincoln, Hui-Chen Foreman, William P. Scherer and Wayne L. Bakotic
J. Fungi 2024, 10(2), 149; https://doi.org/10.3390/jof10020149 - 13 Feb 2024
Cited by 13 | Viewed by 4220
Abstract
Onychomycosis is an under-recognized healthcare burden. Despite the risk of misdiagnosis, confirmatory laboratory testing is under-utilized. Histopathologic examination with polymerase chain reaction (PCR) is currently the most effective diagnostic method; it offers direct detection and identification of a fungal invasion. In this retrospective [...] Read more.
Onychomycosis is an under-recognized healthcare burden. Despite the risk of misdiagnosis, confirmatory laboratory testing is under-utilized. Histopathologic examination with polymerase chain reaction (PCR) is currently the most effective diagnostic method; it offers direct detection and identification of a fungal invasion. In this retrospective cohort study, we assessed confirmatory testing results, with matching clinical diagnoses, in 96,293 nail specimens submitted during a 9-month period from 2022 to 2023. Toenail specimens were examined using fungal culture, histopathology and/or PCR. Clinical diagnoses were identified using the International Classification of Diseases 10th Revision codes. For clinically diagnosed onychomycosis patients, the overall positivity rate was 59.4%; a similar positivity rate (59.5%) was found in patients with clinically diagnosed non-fungal nail dystrophy. Performing a histopathologic examination with PCR was more likely to provide pathogen identification results than using fungal culture. Male patients had a higher rate of onychomycosis overall; however, female patients had more non-dermatophyte mold onychomycosis caused by Aspergillus. Clinically diagnosed onychomycosis patients with a co-diagnosis of tinea pedis were more likely to test positive for onychomycosis by PCR (odds ratio [OR]: 4.2; 95% confidence interval [CI]: 2.7–6.4), histopathology (OR: 2.5; 95% CI: 2.0–3.1) and fungal culture (OR: 3.2; 95% CI: 1.5–6.6). Our results support the use of confirmatory laboratory testing when there is a clinical diagnosis of onychomycosis. Full article
(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections, Second Edition)
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12 pages, 2043 KiB  
Article
Single-Point Nail Sampling to Diagnose Onychomycosis Caused by Non-Dermatophyte Molds: Utility of Polymerase Chain Reaction (PCR) and Histopathology
by Aditya K. Gupta, Elizabeth A. Cooper, Tong Wang, Sara A. Lincoln and Wayne L. Bakotic
J. Fungi 2023, 9(6), 671; https://doi.org/10.3390/jof9060671 - 14 Jun 2023
Cited by 17 | Viewed by 3047
Abstract
The three most commonly used methods for diagnosing non-dermatophyte mold (NDM) onychomycosis are culture, polymerase chain reaction (PCR), and histopathology. Toenail samples from 512 patients (1 sample/patient) with suspected onychomycosis were examined using all three diagnostic tests. A statistically significant association was found [...] Read more.
The three most commonly used methods for diagnosing non-dermatophyte mold (NDM) onychomycosis are culture, polymerase chain reaction (PCR), and histopathology. Toenail samples from 512 patients (1 sample/patient) with suspected onychomycosis were examined using all three diagnostic tests. A statistically significant association was found between PCR and histopathology results, as well as between fungal culture and histopathology results. All PCR-positive and culture-positive dermatophyte samples were confirmed by histopathology. However, 15/116 (12.9%) of culture-positive NDM samples had negative histopathology results, while all PCR-positive NDM samples were confirmed by histopathology. The overall rate of dermatophyte detection was higher using PCR compared to culture (38.9% vs. 11.7%); the lower rate of NDM detection by PCR (11.7% vs. 38.9%) could be attributed to the restriction of the assay design to seven pre-selected targets. When repeat sampling in the clinic is not possible, a combination of NDM detection by PCR and positive histopathology of hyphae may be a proxy for NDM infection, particularly where the NDM occurs without a concomitant dermatophyte. There was a high degree of correlation between negative PCR and negative histopathology. A negative PCR result with negative histopathology findings may be a reliable proxy for the diagnosis of non-fungal dystrophy. Full article
(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections)
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10 pages, 464 KiB  
Review
Dermatophytomas: Clinical Overview and Treatment
by Aditya K. Gupta, Tong Wang and Elizabeth A. Cooper
J. Fungi 2022, 8(7), 742; https://doi.org/10.3390/jof8070742 - 19 Jul 2022
Cited by 17 | Viewed by 5313
Abstract
Dermatophytomas are characterized as a hyperkeratotic fungal mass in the subungual space, showing as dense white or yellow, typically in longitudinal streaks or patches. Masses can be visualized by traditional microscopy or histology. Newer technologies such as dermoscopy and optical coherence tomography also [...] Read more.
Dermatophytomas are characterized as a hyperkeratotic fungal mass in the subungual space, showing as dense white or yellow, typically in longitudinal streaks or patches. Masses can be visualized by traditional microscopy or histology. Newer technologies such as dermoscopy and optical coherence tomography also provide visual features for dermatophytoma diagnosis. The density of fungal mass, and lack of adherence to the nail structures, as well as possible biofilm development, may play a role in the reduction in drug penetration and subsequent lack of efficacy with traditional oral therapies such as terbinafine and itraconazole. A combination of drug treatment with mechanical or chemical debridement/avulsion has been recommended to increase efficacy. The topical antifungal solutions such as tavaborole, efinaconazole, and luliconazole may reach the dermatophytoma by both the transungual and subungual routes, due to low affinity for keratin and low surface tension. Current data indicates these topicals may provide efficacy for dermatophytoma treatment without debridement/avulsion. Similarly, fosravuconazole (F-RVCZ) has an improved pharmacological profile versus ravuconazole and may be an improved treatment option versus traditional oral therapies. The availability of improved treatments for dermatophytomas is crucial, as resistance to traditional therapies is on the increase. Full article
(This article belongs to the Special Issue Onychomycosis Emerging Investigators)
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39 pages, 6776 KiB  
Review
Cardiovascular Risk Stratification in Diabetic Retinopathy via Atherosclerotic Pathway in COVID-19/Non-COVID-19 Frameworks Using Artificial Intelligence Paradigm: A Narrative Review
by Smiksha Munjral, Mahesh Maindarkar, Puneet Ahluwalia, Anudeep Puvvula, Ankush Jamthikar, Tanay Jujaray, Neha Suri, Sudip Paul, Rajesh Pathak, Luca Saba, Renoh Johnson Chalakkal, Suneet Gupta, Gavino Faa, Inder M. Singh, Paramjit S. Chadha, Monika Turk, Amer M. Johri, Narendra N. Khanna, Klaudija Viskovic, Sophie Mavrogeni, John R. Laird, Gyan Pareek, Martin Miner, David W. Sobel, Antonella Balestrieri, Petros P. Sfikakis, George Tsoulfas, Athanasios Protogerou, Durga Prasanna Misra, Vikas Agarwal, George D. Kitas, Raghu Kolluri, Jagjit Teji, Mustafa Al-Maini, Surinder K. Dhanjil, Meyypan Sockalingam, Ajit Saxena, Aditya Sharma, Vijay Rathore, Mostafa Fatemi, Azra Alizad, Vijay Viswanathan, Padukode R. Krishnan, Tomaz Omerzu, Subbaram Naidu, Andrew Nicolaides, Mostafa M. Fouda and Jasjit S. Suriadd Show full author list remove Hide full author list
Diagnostics 2022, 12(5), 1234; https://doi.org/10.3390/diagnostics12051234 - 14 May 2022
Cited by 24 | Viewed by 8028
Abstract
Diabetes is one of the main causes of the rising cases of blindness in adults. This microvascular complication of diabetes is termed diabetic retinopathy (DR) and is associated with an expanding risk of cardiovascular events in diabetes patients. DR, in its various forms, [...] Read more.
Diabetes is one of the main causes of the rising cases of blindness in adults. This microvascular complication of diabetes is termed diabetic retinopathy (DR) and is associated with an expanding risk of cardiovascular events in diabetes patients. DR, in its various forms, is seen to be a powerful indicator of atherosclerosis. Further, the macrovascular complication of diabetes leads to coronary artery disease (CAD). Thus, the timely identification of cardiovascular disease (CVD) complications in DR patients is of utmost importance. Since CAD risk assessment is expensive for low-income countries, it is important to look for surrogate biomarkers for risk stratification of CVD in DR patients. Due to the common genetic makeup between the coronary and carotid arteries, low-cost, high-resolution imaging such as carotid B-mode ultrasound (US) can be used for arterial tissue characterization and risk stratification in DR patients. The advent of artificial intelligence (AI) techniques has facilitated the handling of large cohorts in a big data framework to identify atherosclerotic plaque features in arterial ultrasound. This enables timely CVD risk assessment and risk stratification of patients with DR. Thus, this review focuses on understanding the pathophysiology of DR, retinal and CAD imaging, the role of surrogate markers for CVD, and finally, the CVD risk stratification of DR patients. The review shows a step-by-step cyclic activity of how diabetes and atherosclerotic disease cause DR, leading to the worsening of CVD. We propose a solution to how AI can help in the identification of CVD risk. Lastly, we analyze the role of DR/CVD in the COVID-19 framework. Full article
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