Number of Affected Nails Is the Primary Determinant of Efinaconazole 10% Solution Usage for Onychomycosis.

Good adherence to treatment is necessary for the successful treatment of onychomycosis and requires that an appropriate amount of medication be prescribed. Most prescriptions for efinaconazole 10% solution, a topical azole antifungal, are for 4 mL per month but there are no data on patient factors or disease characteristics that impact how much medication is needed. Data from two phase 3 studies of efinaconazole 10% solution for the treatment of toenail onychomycosis were pooled and analyzed to determine monthly medication usage based on the number of affected toenails, percent involvement of the target toenail, body mass index (BMI), and sex. Participants with two or more affected nails required, on average, >4 mL of efinaconazole per month, with increasing amounts needed based on the number of nails with onychomycosis (mean: 4.39 mL for 2 nails; 6.36 mL for 6 nails). In contrast, usage was not greatly impacted by target toenail involvement, BMI, or sex. Together, these data indicate that the number of affected nails should be the major consideration when determining the monthly efinaconazole quantity to prescribe. J Drugs Dermatol. 2024;23(2):110-112.    doi:10.36849/JDD.7676.

Blistering Disorders of the Foot.

ABSTRACT: Multiple pathophysiologic and biomolecular processes lead to bullae, including disruption of adhesion molecules, accumulation of cell injury, and traumatic injury. Blistering disorders of the foot can cause symptoms such as pruritus, pain, and drainage and significantly impact quality of life. Microbiologic and histopathologic examination of tissue specimens should be considered for concerns regarding atypical etiology.This retrospective case series describes patients seen in a community hospital outpatient wound center in southeastern Wisconsin between January 2021 and June 2023 for atypical blistering disorders of the foot. The cases herein describe the history, clinical presentation, and treatment of three atypical blistering disorders of the foot. An 86-year-old man presented complaining of intensely pruritic blistering lesions to both feet. Histopathologic findings indicated eosinophilic infiltrate, and the patient was treated for an eosinophilic drug reaction. A 65-year-old man presented complaining of multiple painful blisters to the plantar aspect of both feet. Histopathologic examination of unroofed blister indicated bullous tinea. Finally, a 44-year-old man with long-standing type 1 diabetes presented complaining of a several-week history of a single blister to his anterior right foot of unknown etiology. The patient was diagnosed with bullosis diabeticorum.Blistering disorders of the foot are diagnostic challenges; diagnostic clarity is assisted by thorough history, clinical presentation, treatment response, microbial analysis, and histopathologic findings.

Comparing the Efficacy for Pulse Versus Continuous Dose Terbinafine Therapy in Patients With Onychomycosis.

Recently, treatment outcomes in patients with toenail onychomycosis have improved considerably due to more effective oral antifungal medications such as terbinafine and itraconazole. These medications can either be used continuously for several weeks at a lower dose or intermittently (pulsed) at a higher dose. Previous literature comparing pulse and continuous therapy has generated mixed results.  Our study aims to compare the efficacy, in terms of clinical cure rate, of continuous vs pulse dose terbinafine regimens for toenail onychomycosis. Sixty patients with onychomycosis of Fitzpatrick skin types IV to VI, between 15 and 65 years of age, were divided into a continuous treatment group receiving 250 mg terbinafine once daily for 12 weeks and a pulse treatment group receiving 250 mg twice daily terbinafine for 1 week repeated every 4 weeks for 12 weeks. Each patient was followed up at weeks 4, 8, and 12.  Efficacy of the continuous treatment group was significantly greater at 76.67% compared with 26.67% in the pulse treatment group. Thus, we conclude that the clinical cure rate of a continuous dose regimen of terbinafine is a superior treatment option for toenail onychomycosis. However, we also suggest further studies including combinations of multiple agents and hybrid regimen models for the optimal onychomycosis treatment.   J Drugs Dermatol. 2023;22(10):     doi:10.36849/JDD.7323R1.

A rare case of papular-purpuric "gloves and socks" syndrome associated with influenza.

Papular-purpuric "gloves and socks" syndrome (PPGSS) is a unique, self-limited dermatosis characterized by edema, erythema, and pruritic petechiae and papules in a distinct "gloves and socks" distribution. This is often accompanied by systemic symptoms, including fever, lymphadenopathy, asthenia, myalgia, and arthralgias. PPGSS has also been described as a manifestation of an underlying immunological mechanism that can be triggered by viral or drug-related antigens. A 32-year-old male developed a painful eruption on the bilateral hands and feet after being diagnosed with influenza B. On examination, scattered papular purpura with occasional overlying scale was noted on the bilateral hands, fingers, feet, toes, volar wrists, and ankles. Histopathologic sections showed a mixed pattern of inflammation with interface and spongiotic changes. A parakeratotic scale with overlying basket-weave orthokeratosis was also seen. Within the epidermis, there was intraepidermal vesicles and Langerhans cell microabscess formation with scattered apoptotic keratinocytes. The underlying dermis showed a superficial perivascular lymphocytic infiltrate with mild edematous changes, and extravasation of red blood cells. Clinicopathologic correlation strongly supported a diagnosis of popular-purpuric gloves and socks syndrome. The influenza virus has never been reported in association with PPGSS; thus, this case outlines an important new variant that clinicians should be familiar with.

Cutaneous larva migrans: an unusual souvenir from a Scottish holiday.

Cutaneous larva migrans acquired in western Scotland. A reminder that with a warming climate, conditions conventionally restricted to the tropics may be contracted in the British Isles in the absence of foreign travel.

Clinical characteristics, quality of life and risk factors for severity in palmoplantar pustulosis: a cross-sectional, multicentre study of 263 patients.

BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, chronic, inflammatory skin disease characterized by sterile pustules on palmar or plantar areas. Data on PPP are scarce. AIM: To investigate the clinical characteristics and risk factors for disease severity in a large cohort of Turkish patients with PPP. METHODS: We conducted a cross-sectional, multicentre study of patients with PPP recruited from 21 tertiary centres across Turkey. RESULTS: In total, 263 patients (165 women, 98 men) were evaluated. Most patients (75.6%) were former or current smokers. The mean Palmoplantar Pustulosis Area and Severity Index (PPPASI) was 8.70 ± 8.06 and the mean Dermatology Life Quality Index (DLQI) score was 6.87 ± 6.08, and these scores were significantly correlated (r = 0.52, P < 0.001). Regression analysis showed that current smoking was significantly associated with increased PPPASI (P = 0.03). Coexisting psoriasis vulgaris (PsV) was reported by 70 (26.6%) patients. Male sex prevalence, PPP onset incidence, disease duration, DLQI, and prevalence of nail involvement and psoriatic arthritis (PsA) were significantly increased among patients with PPP with PsV. Of the 263 patients, 18 (6.8%) had paradoxical PPP induced by biologic therapy, and these patients had significantly increased mean DLQI and prevalence of PsA (r = 0.03, P = 0.001). CONCLUSION: Our data suggest that smoking is a risk factor for both PPP development and disease severity. Patients with PPP with PsV present distinct clinical features and patients with biologic therapy-induced paradoxical PPP have reduced quality of life and are more likely to have PsA.

Patient characteristics in tardive COVID-19 pseudoperniosis: a case series of 16 patients.

BACKGROUND: Acute pseudoperniosis (PP) has a recognized association with COVID-19 and tends to occur without cold precipitation in young, healthy patients, often without a clear history of COVID-19. These lesions usually resolve within 2 weeks and without long-term sequelae. In the early months of 2021, patients with delayed and protracted PP began to emerge. We have called this presentation 'tardive COVID-19 PP (TCPP)'. AIM: To consolidate and expand knowledge on TCPP, we describe the clinical characteristics, treatments and outcomes of 16 patients with TCPP who were reviewed by our outpatient dermatology service. RESULTS: The initial clinical manifestations were erythema, swelling and PP of the fingers in 56.2%, and of the toes in 31.2%, desquamation in 56.2% and acrocyanosis in 12.5%. Ten patients had eventual involvement of all acral sites. The median duration of symptoms was 191 days. Six patients reported close contact with a confirmed or suspected case of COVID-19, but only two had positive COVID-19 tests. Four patients experienced complete or almost complete resolution of symptoms, while the rest remain under active treatment. CONCLUSION: Unlike acute PP, TCPP has a protracted and delayed presentation that is typically associated with profound acrocyanosis. Patients with TCPP represent a new phenomenon that is part of the post-COVID-19 syndrome, with risk factors and pathophysiology that are not yet fully understood. Our data indicate that likely predisposing factors for developing TCPP include young age, a preceding history of cold intolerance and an arachnodactyloid phenotype. Anorexia, connective tissue disorders or sickle cell trait may also predispose to TCPP. In addition, low titre antinuclear antibody positivity, the presence of cryoglobulins, or low complement levels may represent further risk factors. Finally, prolonged low temperatures are also likely to be contributing to the symptoms.

Therapeutic Recommendations for the Treatment of Toenail Onychomycosis in the US.

BACKGROUND: Onychomycosis affects around 14% of individuals in North America and Europe and is undertreated. Treatment is challenging as toenail growth can take 12–18 months, the nail plate may prevent drug penetration, and disease recurrence is common. National guidelines/consensus documents on onychomycosis diagnosis and treatment were last published more than 5 years ago and updated medical guidance is needed. METHODS: This document aims to provide recommendations for the diagnosis and pharmaceutical treatment of toenail onychomycosis following a roundtable discussion with a panel of dermatologists, podiatrists, and a microbiologist specializing in nail disease. RESULTS: There was a general consensus on several topics regarding onychomycosis diagnosis, confirmatory laboratory testing, and medications. Onychomycosis should be assessed clinically and confirmed with microscopy, histology, and/or culture. Terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical treatment. Efinaconazole can also be considered for off-label use for maintenance to prevent recurrences. For optimal outcomes, patients should be counseled regarding treatment expectations as well as follow-up care and maintenance post-treatment. CONCLUSIONS: This article provides important updates to previous guidelines/consensus documents to assist dermatologists and podiatrists in the diagnosis and treatment of toenail onychomycosis. J Drugs Dermatol. 2021;20(10):1076-1084. doi:10.36849/JDD.6291.

Management of chronic hand and foot eczema. An Australia/New Zealand Clinical narrative.

Chronic hand/foot eczemas are common, but treatment is often challenging, with widespread dissatisfaction over current available options. Detailed history is important, particularly with regard to potential exposure to irritants and allergens. Patch testing should be regarded as a standard investigation. Individual treatment outcomes and targets, including systemic therapy, should be discussed early with patients, restoring function being the primary goal, with clearing the skin a secondary outcome. Each new treatment, where appropriate, should be considered additive or overlapping to any previous therapy. Management extends beyond mere pharmacological or physical treatment, and requires an encompassing approach including removal or avoidance of causative factors, behavioural changes and social support. To date, there is little evidence to guide sequences or combinations of therapies. Moderately symptomatic patients (e.g. DLQI ≥ 10) should be started on a potent/super-potent topical corticosteroid applied once or twice per day for 4 weeks, with tapering to twice weekly application. If response is inadequate, consider phototherapy, and then a 12-week trial of a retinoid (alitretinoin or acitretin). Second line systemic treatments include methotrexate, ciclosporin and azathioprine. For patients presenting with severe symptomatic disease (DLQI ≥ 15), consider predniso(lo)ne 0.5-1.0 mg/kg/day (or ciclosporin 3 - 5 mg/kg/day) for 4-6 weeks with tapering, and then treating as for moderate disease as above. In non-responders, botulinum toxin and/or iontophoresis, if associated with hyperhidrosis, may sometimes help. Some patients only respond to long-term systemic corticosteroids. The data on sequencing of newer agents, such as dupilumab or JAK inhibitors, are immature.

Actinomycetoma Caused by Actinomadura mexicana, A Neglected Entity in the Caribbean.

Mycetoma is a chronic infection that is slow to develop and heal. It can be caused by fungi (eumycetoma) or bacteria (actinomycetoma). We describe a case of actinomycetoma caused by Actinomadura mexicana in the Caribbean region.

PAS stain based histological classification and severity grading of toenail onychomycosis.

Onychomycosis is a common world-wide health issue. Accurate detection is essential for treatment. Multiple studies have shown that PAS-stain based histological visualization of fungal elements is superior to either direct microscopy with 20% potassium hydroxide, or fungal culture. However, PAS stain based histological classification and severity grading of onychomycosis are lacking in the literature. Here we reported a fungal detection rate of 47.87% based on an analysis of 13,805 toenails processed for H&E and PAS stains over a three year period. Based on the analysis of fungal density, distribution and infiltrating depth level in 858 PAS-positive toenails, we created a novel PAS stain based histological classification system to classify onychomycosis as occult onychomycosis (OO), focal or diffuse subungual onychomycosis (FSO or DSO), focal or diffuse plate onychomycosis (FPO or DPO), focal or diffuse subungual and plate onychomycosis (FSPO or DSPO) and superficial onychomycosis (SO). The severities of OO, FSO and FPO were graded as mild, DSO and DPO as moderate, FSPO and DSPO as severe infections, which revealed that more than 75% PAS positive toenails were severe infections. Evaluation of 97 paired toenails biopsied pre- and post-treatment from 47 patients demonstrated that the severity of infection was significantly reduced from severe to mild and moderate levels. These data indicate that the current histological classification evaluates not only the severity of the fungal infection but also the response to treatment. We further propose a guideline for treatment of onychomycosis based on the histological classification and severity.

Labeled use of efinaconazole topical solution 10% in treating onychomycosis in children and a review of the management of pediatric onychomycosis.

Onychomycosis is a difficult to treat condition whose prevalence is increasing. Until recently, there was no FDA approved antifungal agent for the treatment of onychomycosis in children. Although systemic antifungal agents are effective, their use is restricted by the potential adverse events and drug-drug interactions. There is evidence regarding the safety and efficacy of topical antifungal agents for pediatric onychomycosis. We have summarized the results of a recently published study using efinaconazole topical solution 10% to treat onychomycosis in children and discuss management of pediatric onychomycosis. In a multicenter, open-label phase 4 study, efinaconazole 10% solution was applied topically once daily in children aged 6 to 16 years with mild to severe, culture positive, distal and lateral subungual onychomycosis. Treatment was for 48 weeks with a follow-up at week 52. Pharmacokinetics was performed in a subset of patients. There were 62 patients enrolled in the study. At week 52, the efficacy was mycological cure rate 65% and complete cure rate 40%. All treatment-emergent adverse events (TEAE) were mild to moderate in severity with none resulting in study discontinuation. The only treatment-related TEAE was ingrown toenail. Efinaconazole was detected at low levels in plasma. Efinaconazole topical solution 10% is effective and safe in treating onychomycosis in children age 6 to 16 years and was recently FDA-approved for this indication. The on-label use of other topical agents, tavaborole solution 5% and ciclopirox nail lacquer solution 8% is reviewed. We also briefly discuss the use of oral agents, terbinafine, itraconazole, and fluconazole in pediatric onychomycosis.

Safety, Pharmacokinetics, and Efficacy of Efinaconazole 10% Topical Solution for Onychomycosis Treatment in Pediatric Patients.

BACKGROUND: Pediatric onychomycosis management is challenging as there are limited treatment options. The objective of this study was to evaluate efinaconazole 10% topical solution in children with onychomycosis. METHODS: This phase 4, multicenter, open-label study (NCT02812771) evaluated safety, pharmacokinetics (PK), and efficacy of efinaconazole 10% topical solution in pediatric participants (6-16 years). Efinaconazole was administered once daily for 48 weeks, with a 4-week posttreatment follow up. Participants had culture-positive, mild-to-severe distal lateral subungual onychomycosis affecting at least 20% of at least 1 great toenail. The PK subset included participants 12-16 years with moderate-to-severe onychomycosis affecting at least 50% of each great toenail and onychomycosis in at least 4 additional toenails. RESULTS: Of 62 enrolled participants, 60 were included in the safety population and 17 in the PK population. Efinaconazole 10% topical solution was well tolerated. The concentration-time profiles for efinaconazole and its major metabolite were relatively stable, with only minor fluctuations during the 24-hour dosing interval. Systemic exposure to efinaconazole was low. By week 52, 65.0% of participants achieved mycologic cure, with a 36.7% mycologic cure rate observed as early as week 12. A total of 40.0% of participants achieved complete cure, 50.0% achieved clinical efficacy, and 88.3% achieved fungal cure by week 52. CONCLUSION: Efinaconazole was safe and efficacious in pediatric participants with mild-to-severe onychomycosis, with improved mycologic cure and complete cure rates compared with adults from two 52-week studies. J Drugs Dermatol. 2020;19(9):867-872. doi:10.36849/JDD.2020.5401.

A unique variant of juvenile papular-purpuric gloves and socks syndrome.

Parvovirus B19 is the most common causative agent of papular-purpuric gloves and socks syndrome (PPGSS), an often-underreported condition in the pediatric population. Classically, PPGSS presents with a papular-purpuric and at times petechial eruption of the hands and feet. (Dermatology. 1994;188:85; Int J Dermatol. 1996;35:626) We report a unique variant of juvenile PPGSS with prominent involvement of the flexural and extensor elbows, wrists, and knees.

[Occupational aspects of palmoplantar pustulosis : Discussion based on the evaluation of retrospective data]. / Berufsdermatologische Aspekte der Pustulosis palmoplantaris : Diskussionsbeitrag anhand einer retrospektiven Datenauswertung.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease. Its classification as a variant of psoriasis is controversial. Exogenous factors may affect PPP. OBJECTIVES: Occupational aspects of PPP based on a retrospective evaluation of patient data are discussed. METHODS: Data from 1518 patients who took part in a tertiary prevention program (TIP) for occupational skin diseases in our department between January 2015 and June 2019 were evaluated. RESULTS: PPP was diagnosed in 30 patients (1.98%). The hands were affected in all of them, while concomitant feet involvement was found in 83.3%. The majority was female (70.0%) and reported tobacco smoking (83.3%). Systemic treatment was continued or initiated in one third of patients. In only 8 patients (26.7%) was PPP considered to be work-related. CONCLUSIONS: PPP is an endogenous disease which is influenced by nonoccupational factors (e.g., tobacco smoking). Therefore, a thorough investigation is mandatory when assessing whether occupational factors are legally essential and exceed aggravation by everyday life. For this purpose, a well-documented course of the disease and a critical appraisal of occupational and nonoccupational factors are crucial. Only if occupational causality is probable can preventive measures be provided by the statutory accident insurance and PPP can be legally recognized as an occupational disease.

[Painful nodules on the soles in a pediatric patient: A diagnostic challenge]. / Nodulos plantares dolorosos tras ejercicio intenso en paciente pediátrica: Un reto diagnóstico.

INTRODUCTION: Idiopathic Palmoplantar Eccrine Hidradenitis (IPPH) is a rare neutrophilic derma tosis, with painful erythematous nodules of sudden onset in the plantar or palmoplantar region, in children without other underlying diseases. OBJECTIVE: To present a case that shows the main clinical and histological characteristics of this entity. CLINICAL CASE: 11-year-old girl with a 48-hours history of painful erythematous-violaceous nodules on the right foot plant associated with fever of up to 38.2 °C, with no history of interest except hyperhidrosis and intense exercising on previous days. Given the clinical suspicion of IPPH, a skin biopsy was performed, which showed inflammatory neutrophil infiltration around eccrine sweat glands and neutrophilic abscesses, confirming the diagnosis. Oral NSAIDs and rest were prescribed, with resolution of the lesions in 7 days. CONCLUSIONS: This case demonstrates the most important aspects of this entity, in many cases underdiagnosed, since it can be confused with other pathologies that occur with painful acral nodules, but have different pathogenic and therapeutic implications. To properly identify the IPPH allows preventing an unnecessary alarm, both patients and their parents, as in dermatologists and pediatricians themselves.

Infrared spectroscopy as a novel tool to diagnose onychomycosis.

BACKGROUND: The determination of causative organisms of onychomycosis is still not optimal. There remains a need for a cheap, fast and easy-to-perform diagnostic tool with a high capacity to distinguish between organisms. OBJECTIVES: To determine whether attenuated total-reflectance Fourier transform infrared (ATR-FTIR) spectroscopy can detect and differentiate causative agents in culture-based, ex vivo nail and in vivo nail models. METHODS: A methodological study was conducted. Both the ex vivo nail model and in vivo pilot study were carried out in an academic university hospital. RESULTS: Analysis of cultured fungi revealed spectral differences for dermatophytes (1692-1606 and 1044-1004 cm-1 ) and nondermatophytes and yeasts (973-937 cm-1 ), confirmed by dendrograms showing an excellent separation between samples from different genera or species. Exploration of dermatophytes, nondermatophytes and yeasts growing on ex vivo nails exposed prominent differences from 1200 to 900 cm-1 . Prediction models resulted in a 96·9% accurate classification of uninfected nails and nails infected with dermatophytes, nondermatophytes and yeasts. Overall correct classification rates of 91·0%, 97·7% and 98·6% were obtained for discrimination between dermatophyte, nondermatophyte and yeast genera or species, respectively. Spectra of in vivo infected and uninfected nails also revealed distinct spectral differences (3000-2811 cm-1 , 1043-950 cm-1 and 1676-1553 cm-1 ), illustrated by two main clusters (uninfected vs. infected) on a dendrogram. CONCLUSIONS: Our data suggest that ATR-FTIR spectroscopy may be a promising, fast and accurate method to determine onychomycosis, including identification of the causative organism, bypassing the need for lengthy fungal cultures.

Onychomycosis: Clinical overview and diagnosis.

Onychomycosis is a fungal nail infection caused by dermatophytes, nondermatophytes, and yeast, and is the most common nail disorder seen in clinical practice. It is an important problem because it may cause local pain, paresthesias, difficulties performing activities of daily life, and impair social interactions. In this continuing medical education series we review the epidemiology, risk factors, and clinical presentation of onychomycosis and demonstrate current and emerging diagnostic strategies.

Intralesional vitamin D3 versus Candida antigen immunotherapy in the treatment of multiple recalcitrant plantar warts: A comparative case-control study.

Intralesional immunotherapy is one of the therapeutic tools of warts. Intralesional Candida antigen was reported as successful treatment of warts. Topical and intralesional vitamin D have been used recently for wart treatment. We aim to evaluate the efficacy and safety of intralesional injection of vitamin D3 in treatment of multiple recalcitrant plantar warts in comparison with intralesional Candida antigen. Sixty patients were divided into three groups: Group I received intralesional vitamin D3, Group II intralesional Candida antigen, and Group III intralesional saline (control group). Injection was done every 3 weeks until clearance of warts or a maximum of three treatments. There was a statistically significant more reduction of warts numbers after treatment in Group I than in the other groups (p < .05). Group I showed better clinical response than Group II (p = .021). In both Groups I and II, clinical response was less favorable in patients with longer disease duration (p = .026). There was also limitation as it is a small study population. Intralesional vitamin D3 injection in multiple recalcitrant plantar warts is a simple, safe, cost effective treatment modality with minimal side effects, and superior results compared with intralesional injection of Candida antigen.

Characteristics, Associated Diseases, and Management of Gram-negative Toe-web Infection: A French Experience.

Gram-negative toe-web infection can cause pain and disability, be complicated by a long healing time, management failure, and cellulitis, and recur due to persistent predisposing factors. To describe the clinical features and management of Gram-negative toe-web infection and evaluate predisposing factors and associated diseases, their management, and the effect of controlling them on the rate of recurrence, we conducted a retrospective real-life study of patients with Gram-negative toe-web infection. Among the 62 patients (sex ratio 9:1), 31 experienced more than one episode of Gram-negative toe-web infection. Pseudomonas aeruginosa was the most prominent bacteria. Predisposing factors/associated diseases were eczema (66%), suspected Tinea pedis (58%), humidity (42%), hyperhidrosis (16%), psoriasis (11%), and vascular disorders (40%). Patients in whom associated diseases, such as eczema or psoriasis, were controlled did not relapse, suggesting the benefit of management of such conditions. We suggest that management of Gram-negative toe-web infection be standardised, with a focus on diagnosis and treatment of associated diseases.