Topical statins as antifungals: a review.

Cutaneous fungal infections affect millions around the world. However, severe, multi-resistant fungal infections are increasingly being reported over the past years. As a result of the high rate of resistance which urged for drug repurposing, statins were studied and found to have multiple pleiotropic effects, especially when combined with other already-existing drugs. An example of this is the synergism found between several typical antifungals and statins, such as antifungals Imidazole and Triazole with a wide range of statins shown in this review. The main mechanisms in which they exert an antifungal effect are ergosterol inhibition, protein prenylation, mitochondrial disruption, and morphogenesis/mating inhibition. This article discusses multiple in vitro studies that have proven the antifungal effect of systemic statins against many fungal species, whether used alone or in combination with other typical antifungals. However, as a result of the high rate of drug-drug interactions and the well-known side effects of systemic statins, topical statins have become of increasing interest. Furthermore, patients with dyslipidemia treated with systemic statins who have a new topical fungal infection could benefit from the antifungal effect of their statin. However, it is still not indicated to initiate systemic statins in patients with topical mycotic infections if they do not have another indication for statin use, which raises the interest in using topical statins for fungal infections. This article also tackles the different formulations that have been studied to enhance topical statins' efficacy, as well as the effect of different topical statins on distinct dermatologic fungal diseases.

Ketogenic Diet and the Skin.

In dermatology, the role of dietary modifications as a means to manage or prevent skin disorders has recently gained special attention among patients and physicians. This is especially true for the currently popular ketogenic diet (KD), which comprises low carbohydrate, high fat, and adequate amount of protein. Recent evidence from basic science research, small clinical trials, population studies, and reports has presented promising potential role of KD as a supplementary or adjuvant treatment in different cutaneous disorders mainly due to its anti-inflammatory properties. This review is directed at raising awareness among dermatologists on the potential uses of KD in managing skin disorders, such as acne, psoriasis, and hidradenitis suppurativa, among others. In addition, cutaneous adverse reactions, such as prurigo pigmentosa and nutritional deficiencies, which have been associated with KD, are also discussed in this review.

Dermatological manifestations associated with COVID-19 and COVID-19 vaccination: results from the Lebanese COVID registry.

BACKGROUND: A number of cutaneous manifestations and adverse cutaneous reactions have been associated with COVID-19 infection and vaccine. OBJECTIVES: A Lebanese national registry was established to characterize the dermatologic manifestations and adverse cutaneous reactions associated with COVID-19 infection and vaccination in a sample of the Lebanese population. METHODS: An observational cross-sectional study was conducted via a web-based clinical form distributed to physicians wishing to report their cases from May 2021 till May 2022. RESULTS: In total, 142 patients were entered in the registry, of which 133 were adults and nine were pediatric patients. The main dermatological manifestations reported with COVID-19 infection in the adult group were urticaria (32.9%), telogen effluvium (21.4%), morbilliform (10%), and papulosquamous (8.6%) eruptions. Urticaria was the most common adverse cutaneous reaction to the vaccine (33%). Interestingly, herpes zoster was triggered in 12 patients post vaccination in our series with this finding more frequently seen in patients above the age of 41 (P = 0.013). In the pediatric group, the most reported dermatological findings associated with COVID-19 infection were malar erythema (25%) and telogen effluvium (25%). One 16-year-old patient developed lichen planus after one dose of a COVID-19 vaccine. No deaths were reported in both age groups. CONCLUSION: This Lebanese registry adds more robust evidence that clinical manifestations of the COVID-19 virus and vaccine are diverse. More studies are necessary to establish the pathophysiology of these dermatological findings in the context of COVID-19 infection and vaccination.

A X-linked nonsense APOO/MIC26 variant causes a lethal mitochondrial disease with progeria-like phenotypes.

APOO/MIC26 is a subunit of the MICOS complex required for mitochondrial cristae morphology and function. Here, we report a novel variant of the APOO/MIC26 gene that causes a severe mitochondrial disease with overall progeria-like phenotypes in two patients. Both patients developed partial agenesis of the corpus callosum, bilateral congenital cataract, hypothyroidism, and severe immune deficiencies. The patients died at an early age of 12 or 18 months. Exome sequencing revealed a mutation (NM_024122.5): c.532G>T (p.E178*) in the APOO/MIC26 gene that causes a nonsense mutation leading to the loss of 20 C-terminal amino acids. This mutation resulted in a highly unstable and degradation prone MIC26 protein, yet the remaining minute amounts of mutant MIC26 correctly localized to mitochondria and interacted physically with other MICOS subunits. MIC26 KO cells expressing MIC26 harboring the respective APOO/MIC26 mutation showed mitochondria with perturbed cristae architecture and fragmented morphology resembling MIC26 KO cells. We conclude that the novel mutation found in the APOO/MIC26 gene is a loss-of-function mutation impairing mitochondrial morphology and cristae morphogenesis.

Autoinflammatory diseases: what is behind them and what is new?

Autoinflammatory diseases are characterized by bouts of systemic or localized inflammation in the absence of an infection. While some autoinflammatory diseases are caused by a single gene mutation, others have been shown to be multifactorial, involving a large array of genes coupled with environmental factors. Previous studies briefly elucidated the molecular mechanisms behind the many autoinflammatory diseases, focusing on the dysregulation of interleukin (IL)-1ß or IL-18, nuclear factor- κB activation, and Interferons secretion. In this review, we precisely highlight the autoinflammatory disease-specific signalosomes, and we aim to provide a scaffold of the link between the various affected pathways.

Prevalence of Human Papillomavirus (HPV)-16 in Different Dental Infections in the Lebanese Population.

BACKGROUND: Dental infections, which are the main cause of tooth loss, are known to be caused by bacteria. However, recent research suggests that other organisms, such as viruses, may also play a role. In this study, we aim to detect the presence of human papillomavirus (HPV)-16 and assess its prevalence in tissues infected with various dental infections, including aggressive and chronic periodontitis, pericoronitis, and periapical infection, as well as healthy gingival tissues, saliva, and gingival crevicular fluid, for comparison. METHODS: A cross-sectional study including 124 adult healthy patients presenting with dental infections requiring dental extractions were conducted to assess the prevalence of HPV-16 in saliva, infected, and healthy tissues using quantitative polymerase chain reaction (PCR) tests. Samples were collected and a categorical scale was used for the prevalence. Statistical analyses were performed using Chi-square for the prevalence of HPV-16. RESULTS: Among the HPV-16-positive PCR cases, the prevalence of HPV-16 was highest in periapical infection tissues as compared to chronic periodontitis, aggressive periodontitis, pericoronitis, and control tissues. CONCLUSION: The prevalence of HPV-16 in periapical infection samples was the highest among the studied dental infection samples. Thus, a primary conclusion can be drawn about the presence of an association between HPV-16 and the occurrence of periapical infection.

Annular Lichenoid Dermatitis of Youth: Its Pathogenesis, Diagnosis, and Management.

Annular lichenoid dermatitis of youth (ALDY) is a newly described controversial benign lichenoid inflammatory cutaneous disorder often characterized by annular patches with hypopigmented center and surrounding erythematous border. Primarily, it affects the trunk and groin of young patients. Since its first description in 2003, additional patients have been reported, leading to better characterization of the entity; nevertheless, the pathogenesis is still unclear, and several hypotheses have been provided about possible triggering or causative factors. It tends to follow a chronic course, with some lesions spontaneously remitting, while others may be persistent or recur post-treatment. No standard validated treatment has been indicated so far for this disorder. Commonly prescribed topical treatment includes corticosteroids and calcineurin inhibitors with variable response.

A Portable Non-Invasive Electromagnetic Lesion-Optimized Sensing Device for the Diagnosis of Skin Cancer (SkanMD).

The article presented herein proposes an alternative skin cancer screening method that delivers non-invasive diagnosis and monitoring of skin lesions by leveraging electromagnetic waves with radio frequency technology and circuits. The proposed handheld device, named SkanMD, comprises a sensitive electromagnetic sensor, customized radio frequency wave analyzer circuits, and machine learning algorithms. The device is used in clinical studies that are performed on a total of 46 individuals that are composed of 18 patients with pre-diagnosed skin cancer, 10 individuals with benign nevi, 7 patients with arbitrary diseases, and 11 healthy individuals. These studies included the measurement of the reflection coefficient, S11, on multiple skin regions and recording the obtained complex values to build a Support Vector Machine (SVM)-based classification model. Due to the lesion-optimized sensor and the unified cross-patient classifier, our results differentiate between cancerous and non-cancerous skin lesions with a sensitivity that exceeds 92% and a specificity that exceeds 81.4%. These reported results are based on a limited population size study. They also demonstrate that SkanMD is a promising solution that could augment conventional diagnosis methods to greatly improve patient comfort and enable instantaneous and accurate diagnosis.

Erosive Pustular Dermatosis of the Scalp.

Erosive pustular dermatosis (EPD) is a rare entity, but it is generally overlooked or missed, rather than rarely encountered. It presents with erosions and shallow ulcers, accompanied by delayed healing and associated with cutaneous atrophy, rather than pustules. It exhibits predominance for women, with a predilection for a chronically sun-damaged scalp and, less commonly, the extremities, particularly the legs, as well as the face and mucosal surfaces. The role of infection, actinic damage, trauma, hormones, autoimmune disease, cutaneous atrophy, and genetics in the pathogenesis of EPD has been described in literature. Increased awareness and a high index of suspicion permit prompt treatment with topical corticosteroids, with or without oral zinc, followed by maintenance therapy with topical calcineurin inhibitors. Prevention, prior recognition, and prompt treatment are required for addressing this complex condition. (SKINmed. 2023;21:12-19).

Prevalence of Cosmetic Procedures among Lebanese Women.

Lebanese women have been portrayed as conceited and obsessed with physical appearance and its beautification through cosmetic procedures. Despite the pervasiveness of this notion, no formal studies have been conducted to assess the true prevalence of cosmetic procedures among Lebanese women. Additionally, no data exist to elucidate trends in popularity of cosmetic procedures over time. A cross-sectional study was conducted across Lebanese universities where surveys were distributed to women aged 18-31 years to estimate the prevalence of surgical, noninvasive, and dental cosmetic procedures in young Lebanese women. The collected survey data were analyzed using the Statistical Package for the Social Sciences (SPSS). In a sample of 877 women, 44% reported having undergone at least one cosmetic procedure in their lifetime. The most popular procedures performed were laser hair removal (32%), teeth whitening (14%), and rhinoplasty (9.3%). The obtained results revealed an increasing prevalence of cosmetic procedures, mirroring global trends. A variety of factors have contributed to the increasing popularity of cosmetic procedures, namely, higher availability, better affordability, and wider social acceptance over time. (SKINmed. 2022;20:422-427).

Treatments for Non-Syndromic Inherited Ichthyosis, Including Emergent Pathogenesis-Related Therapy.

The term 'inherited ichthyosis' refers to a heterogeneous group of mendelian disorders of cornification that involve the integument with varying degrees of scaling. The management of ichthyosis poses a challenge for most physicians. Treatment options proposed in the literature include moisturizers, topical keratolytics, topical and systemic vitamin D analogues, and topical and systemic retinoids; however, some of these modalities are less reliable than others. Despite the therapeutic impasse imposed by the options above, the emergence of pathogenesis-based treatments along with novel gene therapies appear promising and hold the potential to halt or even revert disorders that arise from single genetic mutations, although research is still quite lacking in this domain. Hence, this review aims to highlight the various treatment modalities available for the management of the cutaneous manifestations of non-syndromic inherited ichthyosis, with an added emphasis on pathogenesis-targeted therapies.

A Novel Pathogenic CDH3 Variant underlying Heredity Hypotrichosis Simplex detected by Whole-Exome Sequencing (WES)-A Case Report.

BACKGROUND: Heredity Hypotrichosis Simplex (HHS) is a rare non-syndromic disease form of Hypotrichosis Simplex (HS) characterized by progressive hair follicle (HF) miniaturization. It is usually inherited in an autosomal dominant manner. The differential diagnosis of HHS and the treatments remain challenging despite recent advancement. In this report, we describe a 19-year old female affected with HHS alongside most of her family members. METHODS: Whole Exome Sequencing (WES) was performed for some of the family members to unravel the culprit gene involved in HHS phenotype and ascertain the dermatological examination that was done to classify the phenotypes of the disease. RESULTS: A novel pathogenic variant in the CDH3 gene (p.Ser223GlyfsTer4) was identified as a plausible disease-causing variant for HHS. CONCLUSION: This is the first report to associate CDH3 variants with a HHS phenotype without macular degeneration using WES. WES is an important tool for genotype-phenotype correlation, precision in diagnosis, and in-depth understanding of the disease mechanisms, leading to possible novel therapeutic targets treatment and better patient's outcomes.

A Piez-o the jigsaw: the Piezo1 channel in skin biology.

The skin is the largest organ covering the entirety of the body. Its role as a physical barrier to the outside world as well as its endocrinological and immunological functions subject it to continuous internal and external mechanical forces. Thus, mechanotransduction is of the utmost importance for the skin in order to process and leverage mechanical input for its various functions. Piezo1 is a mechanosensitive ion channel that is a primary mediator of mechanotransduction and is highly expressed in the skin. The discovery of Piezo1 earned a Nobel Prize, and has had a profound impact on our understanding of physiology and pathology including paramount contributions in cutaneous biology. This review provides insight into the roles of Piezo1 in the development, physiology and pathology of the skin with a special emphasis on the molecular pathways through which it instigates these various roles. In epidermal homeostasis, Piezo1 mediates cell extrusion in conditions of overcrowding and division in conditions of low cellular density. Piezo1 also aids in orchestrating mechanosensation, DNA protection from mechanical stress and the various components of wound healing. Conversely, Piezo1 is pathologically implicated in melanoma progression, wound healing delay, cutaneous scarring and hair loss. By shedding light on these functions, we aim to unravel the potential diagnostic and therapeutic value Piezo1 might hold in the field of Dermatology.

Red scrotum syndrome: An update on clinicopathologic features, pathogenesis, diagnosis, and management.

The genital skin may be affected by a variety of dermatoses, be it inflammatory, infectious, malignant, idiopathic, or others. The red scrotum syndrome is characterized by persistent erythema of the scrotum associated with a burning sensation, hyperalgesia, and itching. Its cause is unknown, but proposed mechanisms include rebound vasodilation after prolonged topical corticosteroid use and localized erythromelalgia. The condition is chronic, and treatment is often difficult. Here we review the etiology, the physical and histopathologic findings, and the management of this condition. We also describe related conditions such as red scalp syndrome, red ear syndrome, and red vulva syndrome. Finally, we summarize the different cases reported in the literature and discuss the features that help in the differentiation of red scrotum syndrome from its mimickers.

Eosinophilic ulcer of the oral mucosa: An update on clinicopathologic features, pathogenesis, and management.

Eosinophilic ulcer of the oral mucosa is a benign, reactive, self-limited lesion. Its pathogenesis is unclear, and it clinically manifests as a punched-out ulcer with surrounding indurated border, raising suspicion for a possible malignancy. On histology, an acute and chronic dense inflammatory infiltrate can be appreciated, which can extend to the deep underlying tissue (including skeletal muscle). Eosinophils are especially conspicuous on hematoxylin and eosin staining and might play an important role in the development of the ulcer. Removal of possible triggers followed by monitoring and possible biopsy are among the initial recommendations. Most lesions heal spontaneously without the need for intervention. This review aims at assisting dermatologists to easily recognize this entity, avoiding unnecessary interventions and apprehension.

Malar rash in a young child with neurodevelopmental delay: a quiz.

-A 14-month-old boy born to consanguineous parents presented to our Dermatology Department with a 6-month history of a malar eczematous rash that worsens with sun exposure. He had butterfly-shaped, hyperpigmented exfoliating plaques, preceded by blister formation (figure 1). He was also noticed to have enophthalmos, a pinched nose, microcephaly and a cachectic physique. His height and weight were below the first percentile for his age. In addition, the patient was noticed to have motor and psychosocial delay; he does not respond to simple spoken requests, cannot get into sitting position without help or stand/walk with help of furniture. The eye examination was completely normal including the absence of retinal and corneal changes. Complete blood count, liver function tests and a karyotype did not show any abnormal findings. Imaging studies were not done.edpract;107/1/28/F1F1F1Figure 1Clinical image. A hyperpigmented exfoliating plaque distributed over the malar area associated with enophthalmos and a pinched nose. WHAT'S YOUR DIAGNOSIS?: Bloom syndrome.Rothmund Thomson syndrome.Cockayne syndrome.Xeroderma pigmentosum.Trichothiodystrophy. Answers can be found on page 02.