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Eden Axler, Shari R Lipner Weill Cornell Medicine, Department of Dermatology, New York, NY, 10021, USACorrespondence: Shari R Lipner, Weill Cornell Medicine, Department of Dermatology, 1305 York Avenue, New York, NY, 10021, USA, Tel +1 646-962-3376, Fax +1 646-962-0033, Email shl9032@med.cornell.eduAbstract: Onychomycosis, a common fungal nail infection, affects > 20% of adults over age 60 and > 50% of people over age 70. Onychomycosis may cause pain, psychosocial problems, and secondary infections, therefore meriting treatment. This review describes the range of treatment modalities, including FDA-approved systemic drugs and topical therapies. Additionally, new and emerging oral and topical therapies are discussed. We emphasize the importance of tailoring onychomycosis therapy to individual patient characteristics, comorbidities, preferences, extent of nail involvement, and fungal species, such that physicians may optimize treatment outcomes, patient satisfaction, and safety.Keywords: dermatophyte, nail infection, topical therapy, systemic treatment, fungal susceptibility, treatment guidelines

Anne F Klassen,1 Charlene Rae,1 Maureen O’Malley,2 Trisia Breitkopf,1 Leah Algu,1 Jasmine Mansouri,3 Claire R Brown,4 Yi Wang,5 Shari R Lipner4 1Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; 2Division of Dermatology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada; 3Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; 4Department of Dermatology, Weill Cornell Medicine, New York City, NY, USA; 5Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, CanadaCorrespondence: Anne F Klassen, McMaster University, 3N27, 1200 Main Street W, Hamilton, ON, L8N 3Z5, Canada, Email aklass@mcmaster.caBackground: Patient-reported outcome measures (PROMs) are needed to measure outcomes that matter to people with nail conditions, from their perspective.Objective: To design a comprehensive new PROM (NAIL-Q) to measure outcomes important in toenail and fingernail conditions.Methods: A mixed methods iterative approach was used. Phase 1 involved concept elicitation interviews that were audio-recorded, transcribed, and coded line-by-line. Concepts were developed into scales and refined through cognitive debriefing interviews with patients and expert input. Data was then collected from an international sample using a crowdsource platform. Eligible participants were aged ≥ 18 years with a nail condition for at least 3 months. Rasch Measurement Theory (RMT) analysis was used to examine item and scale performance. Other psychometric tests included test–retest reliability, and convergent and construct validity.Results: Phase 1 interviews involved 23 patients with 10 nail conditions and input from 11 dermatologists. The analysis led to the development of 84 items for field-testing. In Phase 2, 555 participants completed the survey. Toenail conditions (n = 441) were more common than fingernail conditions (n = 186). The RMT analysis reduced the number of items tested to 45 in 7 scales measuring nail appearance, health-related quality of life concerns, and treatment outcomes. All items had ordered thresholds and nonsignificant chi-square p values. Reliability statistics with and without extremes for the Person Separation Index were ≥ 0.79 and Cronbach’s alpha were ≥ 0.83, and for intraclass correlation coefficients were ≥ 0.81. Construct validity was further supported in that most participants agreed that the NAIL-Q was easy to understand, asked relevant and important questions in a respectful way, and that it should be used to inform clinical care.Conclusion: The NAIL-Q is a rigorously designed and tested PROM that measures nail appearance, health-related quality of life and treatment outcomes. This PROM can be used in clinical practice to inform patient care and to include the patient perspective in research.Keywords: validity, reliability, psychometrics, health-related quality of life

Julianne M Falotico,1 Shari R Lipner2 1Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA; 2Weill Cornell Medicine, Department of Dermatology, New York, NY, USACorrespondence: Shari R Lipner, Weill Cornell Medicine, Department of Dermatology, 1305 York Avenue, NY, NY, 10021, USA, Tel +1 646-962-3376, Fax +1 646-962-0033, Email shl9032@med.cornell.eduAbstract: Onychomycosis is the most common nail disease encountered in clinical practice and can cause pain, difficulty with ambulation, and psycho-social problems. A thorough history and physical examination, including dermoscopy, should be performed for each patient presenting with nail findings suggestive of onychomycosis. Several approaches are available for definitive diagnostic testing, including potassium hydroxide and microscopy, fungal culture, histopathology, polymerase chain reaction, or a combination of techniques. Confirmatory testing should be performed for each patient prior to initiating any antifungal therapies. There are several different therapeutic options available, including oral and topical medications as well as device-based treatments. Oral antifungals are generally recommended for moderate to severe onychomycosis and have higher cure rates, while topical antifungals are recommended for mild to moderate disease and have more favorable safety profiles. Oral terbinafine, itraconazole, and griseofulvin and topical ciclopirox 8% nail lacquer, efinaconazole 10% solution, and tavaborole 5% solution are approved by the Food and Drug Administration for treatment of onychomycosis in the United States and amorolfine 5% nail lacquer is approved in Europe. Laser treatment is approved in the United States for temporary increases in clear nail, but clinical results are suboptimal. Oral fluconazole is not approved in the United States for onychomycosis treatment, but is frequently used off-label with good efficacy. Several novel oral, topical, and over-the-counter therapies are currently under investigation. Physicians should consider the disease severity, infecting pathogen, medication safety, efficacy and cost, and patient age, comorbidities, medication history, and likelihood of compliance when determining management plans. Onychomycosis is a chronic disease with high recurrence rates and patients should be counseled on an appropriate plan to minimize recurrence risk following effective antifungal therapy.Keywords: onychomycosis, nail disease, fungal nail infection, diagnosis, management, treatment, recurrence

Shari R Lipner, Richard K Scher Department of Dermatology, Weill Cornell Medical College, New York, NY, USA Abstract: Efinaconazole 10% topical solution is a new triazole recently approved for the treatment of onychomycosis. It inhibits fungal lanosterol 14α-demethylase in the ergosterol biosynthesis pathway, has potent antifungal activity against dermatophytes, as well as activity against Candida spp. and non-dermatophyte molds, and showed promising results in clinical trials. This review summarizes the mechanism of action, in vitro and in vivo data, clinical trials, safety, and quality-of-life data of efinaconazole as it applies to the treatment of onychomycosis. Keywords: efinaconazole, Jublia, onychomycosis, fungal infection, nail infection

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a distinctive lymphocyte rich vasoformative proliferation comprising epithelioid-appearing endothelial cells with partially canalized capillary vessels in a lymphohistiocytic and eosinophil rich environment. ALHE presents clinically as single or multiple pink-brown dome-shaped papules or nodules, most commonly on the ear and peri-auricular area, followed by the face, and scalp. ALHE involving the subungual unit is rare with only 5 previously reported cases and all involved the underlying bone. The authors describe a case of a painful subungual nodule of the left 1st fingernail in a 48-year-old woman. An excisional biopsy was performed confirming a diagnosis of ALHE. There was no bone involvement and immediately following excision of the tumor, there was complete resolution of her symptoms. Our patient’s presentation expands upon the clinical and histopathological spectrum of subungual ALHE.

The incidence and prevalence of melanoma are increasing globally, presenting a significant public health concern. The main genetic drivers of melanoma include BRAF, NRAS, KIT and triple wild-type (TWT) mutations. Little is known about the effects of these mutations on outcomes in terms of demographics and patient characteristics. We examined differences in melanoma mortality risk and mutation count across mutation type and patient disease profile. We extrapolated primary melanoma patient data from 14 studies via the cBioportal database. Patients were divided into demographic groups and classified according to BRAF, NRAS, KIT and TWT mutation status. Analyses included two-sample Student t -test and two-way analysis of variance tests analysis with Tukey's post hoc test. Survival outcomes were compared via Kaplan-Meier curve and Cox regression. NRAS-mutated patients exhibited decreased overall survival compared to BRAF-mutated patients. Male patients had higher mutation counts across all gene groups than females, with the fewest TWT mutations in comparison to BRAF, NRAS and KIT mutations. Males also exhibited increased mortality risk for NRAS, KIT and TWT mutations compared to BRAF mutations. An unknown primary melanoma was associated with increased mortality risk across all gene groups. NRAS-mutated acral melanoma patients had an increased mortality risk compared to NRAS-mutated cutaneous melanoma patients. Older patients had a higher mortality risk than younger patients. Patients with heavier versus lower weights had lower mortality risk, which was more pronounced for BRAF-mutated patients. These relationships highlight the importance of demographic and pathologic relationships to aid in risk assessment and personalize treatment plans., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Conflicts of interest Dr Shari Lipner declares no conflicts of interest.

Competing Interests: Conflicts of interest Dr Lipner has served as a consultant for Eli Lilly, Ortho-Dermatologics, Moberg Pharmaceuticals, and Belletorus Corporation.

Background: Molluscum contagiosum (MC) is a poxvirus that manifests as firm, smooth, dome-shaped, umbilicated, flesh-colored papules. In adults, MC is commonly spread by sexual contact, and is self-limited in patients with intact immune systems but more widely distributed and difficult to treat in immunocompromised persons. We analyzed cases of adult MC for associations with immunosuppression, lifestyle risk factors, and sexually transmitted infections (STIs)., Methods: Using the All of Us Research Program database, adults with MC were identified and matched with controls 1:10 based on demographic factors. Comorbidities, lifestyle risk factors, and medication exposures were analyzed. Odds ratios were calculated using logistic regression., Results: Our analysis included 146 cases of adults with MC and 1460 demographic-matched controls. Patients with MC were 48 years old on average, 59% female, and majority White (82.5%). Controls were similar for all demographic features. Adults with MC were more likely to have syphilis (odds ratio (OR) 16; 95% confidence interval (CI) 2.57-99.5), human immunodeficiency virus (HIV) (OR 9.54; 95% CI 3.95-23.0), chlamydia (OR 6.24; 95% CI 2.38-16.4), condyloma acuminata (OR 13.9; 95% CI 7.36-26.2), genital herpes (OR 4.13; 95% CI 1.87-9.15), or atopic dermatitis (AD) (OR 2.85; 95% CI 1.5-5.4) (all p < .01). There were no differences in prevalence of other comorbidities, lifestyle risk factors, nor medication exposures (all p > .05)., Conclusions: We showed that adult MC is associated with AD and STIs, including HIV, chlamydia, condyloma acuminata, genital herpes, and syphilis. Sexually active adolescents and adults and those diagnosed with AD may be screened for MC and counseled on their potentially increased risk., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ms. Hill, Ms. Parikh, and Dr. Lipner have no conflicts of interest.

In a commercial claims database analysis, <0.5% of patients with inflammatory bowel disease or rheumatoid arthritis developed an IFI within one year of initiating TNF-alpha therapy. Histoplasmosis was the most common IFI type. Overall IFI incidence varied based on region, underlying conditions, and use of certain immunosuppressive medications., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: Most primary cutaneous melanomas have pathogenesis driven by ultraviolet exposure and genetic mutations, whereas acral lentiginous melanoma (ALM) and metastatic melanoma are much less, if at all, linked with the former. Thus, we evaluated both ultraviolet related and non-ultraviolet related melanomas. Mutations in the MUC16 and TTN genes commonly occur concurrently in these melanoma patients, but their combined prognostic significance stratified by gender and cancer subtype remains unclear., Methods: The cBioPortal database was queried for melanoma studies and returned 16 independent studies. Data from 2447 melanoma patients were utilized including those with ALM, cutaneous melanoma (CM), and melanoma of unknown primary (MUP). Patients were grouped based on the presence or absence of MUC16 and TTN mutations. Univariate Cox regression and Student's t-tests were used to analyze hazard ratios and total mutation count comparisons, respectively., Results: TTN mutations, either alone or concurrently with MUC16 mutations, significantly correlated with worse prognosis overall, in both genders, and in CM patients. ALM patients with both mutations had better prognoses than CM patients, while ALM patients with neither mutation had worse prognosis than CM patients. For MUP patients, only MUC16 mutations correlated with worse prognosis. ALM patients with neither MUC16 nor TTN mutations had significantly more total mutations than MUP patients, followed by CM patients., Conclusion: TTN mutations are a potential marker of poor prognosis in melanoma, which is amplified in the presence of concurrent MUC16 mutations. ALM patients with neither gene mutations had worse prognosis, suggesting a protective effect of having both MUC16 and TTN mutations. Only MUC16 mutations conferred a worse prognosis for MUP patients. Comprehensive genetic profiling in melanoma patients may facilitate personalized treatment strategies to optimize patient outcomes., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Nail diseases are often associated with significant physical and psychosocial burden, but diagnosis is challenging due to nonspecific clinical and histological findings. Nailfold capillaroscopy has been studied for the diagnosis of systemic diseases, but studies on nail diseases are lacking., Objective: The objectives of our study were to characterize and compare capillary changes in a set of nail conditions versus controls, between nail groups, and based on demographic/clinical criteria., Methods: This was a prospective cross-sectional study of patients with nail psoriasis, onychomycosis, idiopathic onycholysis, brittle nail syndrome, nail lichen planus, retronychia, other nail conditions, and no nail findings (controls) undergoing capillaroscopy imaging/analysis., Results: Nail psoriasis versus control patients demonstrated decreased capillary length/density and increased abnormal capillaries, with higher frequency in older, male patients. Onychomycosis was associated with increased meandering capillaries compared with controls, nail psoriasis, and nail lichen planus. Retronychia is associated with increased disorganized polymorphic capillaries compared with controls and onychomycosis., Limitations: Limitations include a small sample size for certain nail conditions and small numbers of nail psoriasis patients with psoriatic arthritis., Conclusion: Our findings highlight nailfold capillaroscopy as a potentially quick, cost-effective, and noninvasive imaging modality, as an adjunct for diagnosis and treatment initiation for patients with onychodystrophies., Competing Interests: Conflicts of interest Dr Lipner has served as a consultant for Eli Lilly, Ortho-Dermatologics, BelleTorus Corporation, and Moberg Pharmaceuticals. Drs Hwang and Miller have no conflicts of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Competing Interests: Conflicts of interest Dr Lipner has served as a consultant for Ortho-Dermatologics, Eli Lilly, Moberg Pharmaceuticals, and BelleTorus Corporation.

Competing Interests: Conflicts of interest None disclosed.

Longitudinal erythronychia (LE) is defined as a longitudinal red band of the nail(s) and is classified as localized (involvement of 1 nail) or polydactylous (involvement of more than 1 nail). The differential diagnosis is distinct for these classifications. The etiologies of localized longitudinal erythronychia are most frequently benign subungual neoplasms and less often malignancies. Polydactylous longitudinal erythronychia is typically secondary to regional or systemic diseases, including lichen planus and Darier disease. LE is a common but underrecognized clinical finding. Increased dermatologist awareness of the clinical characteristics and differential diagnosis for LE is necessary given the possibility for malignancy and associated systemic disease. In this clinical review, the clinical features, differential diagnosis, evaluation, and management of LE are described., Competing Interests: Conflicts of interest Dr Rubin has served as a consultant for Castle Biosciences. Dr Tosti has served as a consultant for DS Laboratories, Almirall, Tirthy Madison, Eli Lilly, P&G, Pfizer, Myovant, Bristol Myers, Squibb, Ortho Dermatologics, and Concert. Dr Lipner has served as a consultant for Ortho-Dermatologics, Eli Lilly, BelleTorus Corporation, and Moberg Pharmaceuticals. Author Curtis, Author Ho, and Dr Jellinek have no conflicts of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest Dr Lipner has served as a consultant for Ortho-Dermatologics, Moberg Pharmaceuticals, Eli Lilly, and BelleTorus Corporation. Authors Zarzeka, Benedict, and McCloskey, Drs Lockhart and Gold have no conflicts of interest to declare.

Competing Interests: Conflicts of interest Dr Lipner has served as a consultant for Ortho-Dermatologics, Eli Lilly, Moberg Pharmaceuticals, and BelleTorus Corporation. Drs Axler, Lu, Darrell, and Vielemeyer have no conflicts of interest to declare.

Competing Interests: Conflicts of interest Dr Lipner has served as a consultant for Ortho-Dermatologics, Eli Lilly, Moberg Pharmaceuticals, and BelleTorus Corporation. Drs Axler, Katsiaunis, Charla, and Gold have no conflicts of interest to declare.

Competing Interests: Conflicts of interest Drs Axler, Malik, Lu, Hong, Desai, Malik, and Lipner have no conflicts of interest to declare. Financial Disclosure: Dr Lipner has served as a consultant for Ortho Dermatologics, Eli Lilly, Moberg Pharmaceuticals, and BelleTorus Corporation.

Competing Interests: Dr Lipner has served as a consultant for Ortho Dermatologics, Eli Lilly, BelleTorus Corporation, and Moberg Pharmaceuticals. Dr Ricardo and author Curtis have no conflicts of interest to declare.

Competing Interests: The authors have no conflicts of interest regarding this article.

Background: Pityriasis versicolor (PV), a cutaneous fungal infection, most commonly affects adolescents and young adults and is associated with hyperhidrosis and humid weather. Understanding other factors associated with PV might help improve diagnostic and treatment practices., Objectives: PV's associations with patient demographics, comorbidities and medication exposures were assessed using the All of Us Database, a large, diverse, national database from the United States., Methods: A case-control study with multivariable analysis was performed., Results: We identified 456 PV case-patients and 1368 control-patients. PV case-patients (vs. control-patients) were younger (median age [years] (standard deviation): 48.7 (15.4) vs. 61.9 (15.5); OR: 0.95, CI: 0.94-0.96) and more likely to be men versus women (42.8% vs. 33.9%, OR: 1.45, CI: 1.16-1.79) and Black (19.5% vs. 15.8%, OR: 1.35, 95% CI: 1.02-1.80) or Asian (4.6% vs. 2.7%, OR: 1.86, CI: 1.07-3.24) versus White. PV case-patients more frequently had acne (5.3% vs. ≤1.5%, OR: 5.37, CI: 2.76-10.48) and less frequently had type 2 diabetes mellitus (T2DM) (14.7% vs. 24.7%, OR: 0.52, CI: 0.39-0.70) and hypothyroidism (OR: 10.3% vs. 16.4%, OR: 0.59, CI: 0.42-0.82). In multivariable analysis, PV odds were significantly higher in those with acne and lower in those with T2DM, older age and female sex., Conclusions: Our results may be used as a basis for future studies evaluating whether acne treatment may decrease PV risk. Physicians could educate patients with acne about PV, including strategies to control modifiable PV risk factors, such as avoidance of hot and humid environments and avoidance of use of topical skin oils., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

As the world's population of adults greater than 60 years old continues to increase, it is important to manage nail disorders that may impact their daily lives. Nail disorders may have significant impact on quality of life due to decreased functionality, extreme pain, or social embarrassment. In this review, we discuss nail disorders affecting older patients, including physiologic, traumatic, drug-induced, infectious, environmental, inflammatory, and neoplastic conditions. Diagnosis of these conditions involves a detailed history, physical examination of all 20 nails, and depending on the condition, a nail clipping or biopsy and/or diagnostic imaging. Nails grow even more slowly in older adults compared to younger individuals, and therefore it is important for accurate diagnosis, and avoidance of inappropriate management and delay of treatment. Increased awareness of nail pathologies may help recognition and management of nail conditions in older adults.

Competing Interests: Conflicts of interest Dr Lipner has served as a consultant for Ortho-Dermatologics, Eli Lilly, BelleTorus Corporation, and Moberg Pharmaceuticals. Ms Curtis, Ms Schwartz, and Ms Evans have no conflicts of interest to declare.