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.

Integrative Transcriptome Analyses Empower the Anti-COVID-19 Drug Arsenal.

The beginning of the 21st century has been marked by three distinct waves of zoonotic coronavirus outbreaks into the human population. The COVID-19 (coronavirus disease 2019) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emerged as a global threat endangering the livelihoods of millions worldwide. Currently, and despite collaborative efforts, diverse therapeutic strategies from ongoing clinical trials are still debated. To address the need for such an immediate call of action, we leveraged the largest dataset of drug-induced transcriptomic perturbations, public SARS-CoV-2 transcriptomic datasets, and expression profiles from normal lung transcriptomes. Most importantly, our unbiased systems biology approach prioritized more than 50 repurposable drug candidates (e.g., corticosteroids, Janus kinase and Bruton kinase inhibitors). Further clinical investigation of these FDA-approved candidates as monotherapy or in combination with an antiviral regimen (e.g., remdesivir) could lead to promising outcomes in patients with COVID-19.

Loss of ferrochelatase is protective against colon cancer cells: ferrochelatase a possible regulator of the long noncoding RNA H19.

BACKGROUND: Ferrochelatase (FECH) is the last enzyme of the heme biosynthesis pathway. Deficiency in FECH was associated with many diseases, including protoporphyria. Correlation studies showed that variations of FECH expression was detected in human carcinomas and more specifically in colon cancer. Nevertheless, the potential role of FECH in colon cancer carcinogenesis in vitro was not depicted yet. METHODS: A small interfering RNA (siRNA) was used to knockdown FECH in human Caco-2 colon cancer cells. The effect of FECH down-regulation on the cellular proliferation, the migration and the expression of target genes was assessed in cancer cells and compared to human normal fibroblasts. RESULTS: Following FECH down-regulation, our results demonstrated that the proliferation of Caco-2 cells was not affected. Furthermore, the migration of cancer and normal cells was affected, only when an additional stress factor (H2O2) was applied to the medium. The expression of twist, snail, hypoxia induced factor (HIF-1α) and vascular endothelial growth factor (VEGF) was reduced in Caco-2 cells. Conversely, VEGF and HIF-1α expression were upregulated by up to 2 folds in control fibroblasts. Interestingly, the pro-carcinogenic long noncoding RNA (LncRNA) H19 was 70% down-regulated in Caco-2 cells upon FECH down regulation whereas no effect was observed in normal fibroblasts. CONCLUSIONS: In conclusion, we showed that loss of FECH is protective against colon cancer tumorigenesis in vitro and this effect could possibly be mediated through inhibition of H19.

Use of Topical Glycolic Acid Plus a Lovastatin-Cholesterol Combination Cream for the Treatment of Autosomal Recessive Congenital Ichthyoses.

Importance: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders caused by defects in signaling pathways involved in epidermal proliferation and differentiation, leading to a wide range of skin manifestations. Therapeutic options are limited and often unsatisfactory. Topical cholesterol and statin as a combined formulation has proven successful in the treatment of patients with CHILD syndrome (congenital hemidysplasia ichthyosis and limb defects). Objective: To assess change in disease severity score after a 3-month therapeutic regimen consisting of a glycolic acid, 10% to 20%, cream and a combination cream of lovastatin, 2%, with cholesterol, 2%, in the treatment of ARCI. Design, Setting, and Participants: This case series of 15 patients with ARCI was conducted at the American University of Beirut, a referral center in the Middle East region for genodermatoses, between May 2017 and January 2018. No age groups were excluded; all patients were from the Middle East area; and all were initially not responsive to treatment with hydrating creams in combination with urea creams, 30% to 40%, or glycolic acid, 10% to 20%. Excluded were patients who had been taking systemic retinoids within 3 months before the start of the study. Interventions: A 3-month therapeutic regimen of glycolic acid, 10% to 20%, cream and a combination of lovastatin, 2%, with cholesterol, 2%, cream. Main Outcomes and Measures: Percentage change in disease severity scores following 2 and 3 months of study treatment. Results: Of the 15 patients included in the study, 10 were male (mean age, 11.2 years; age range, 2-38 years). The average percentage reduction in the disease severity score was 33.7% at 2 months (from 60.8 to 40.2) and 57.5% at 3 months (from 60.8 to 21.9). Adverse effects were mild and consisted mainly of irritation and burning. Conclusions and Relevance: These findings suggest a benefit from a treatment regimen consisting of glycolic acid, 10% to 20%, and a combination of lovastatin, 2%, with cholesterol, 2%, in the treatment of ARCI. This combination of creams might also prove to be beneficial in other types of ichthyoses and other dermatological diseases with a defective skin barrier.

CHILD syndrome: A modified pathogenesis-targeted therapeutic approach.

Congenital Hemidysplasia with Ichthyosiform nevus and Limb Defects (CHILD syndrome) is a rare X-linked dominant genodermatosis caused by mutations in the NAD(P) dependent steroid dehydrogenase-like protein gene. Its defect leads to accumulation of toxic metabolic intermediates upstream from the pathway block and to the deficiency of bulk cholesterol, probably leading to altered keratinocyte membrane function, resulting in the phenotype seen in CHILD syndrome. Symptomatic treatment using emollients and retinoids to reduce scaling has long been used until recently, whereby new therapeutic means based on the pathogenesis-targeted therapy have been developed. We subsequently chose to use the same pathogenesis-based therapy using a 2% cholesterol and 2% lovastatin cream with or without glycolic acid in two of our patients. Improvement in CHILD skin lesions was seen as early as 4 weeks after initiation. The addition of glycolic acid helped improve the penetrance of the cholesterol and lovastatin cream into the thick waxy scales. Our study confirms the efficacy of the pathogenesis-targeted therapy and introduces the possibility of modifying its formula by adding glycolic acid in order to improve the treatment.

A review of Parry-Romberg syndrome.

Parry-Romberg syndrome, also known as progressive hemifacial atrophy, is a rare disorder characterized by unilateral facial atrophy affecting the skin, subcutaneous tissue, muscles, and sometimes extending to the osteocartilaginous structures. It has been associated with various systemic manifestations, particularly neurologic, ophthalmologic and maxillofacial. In this article, we review Parry-Romberg syndrome with its associated findings (neurologic, ophthalmologic, cardiac, rheumatologic, endocrinologic, infectious, orthodontic and maxillofacial, and autoimmune), underlying cause, differential diagnoses (en coup de sabre, scleroderma, and Rasmussen encephalitis), and therapeutic options.

Sweet's syndrome: retrospective study of clinical and histologic features of 44 cases from a tertiary care center.

BACKGROUND: Sweet's syndrome (SS) is an uncommon disorder characterized by the abrupt onset of erythematous papules and plaques that histologically exhibit diffuse dermal neutrophilic infiltrate and edema. There are usually associated constitutional symptoms such as fever, neutrophilia, elevated serum inflammatory markers, and associated disorders. The aim of this study was to assess the clinical and histologic features of all patients diagnosed with SS at our institution between 1971 and 2008 and to compare their findings with those published in the literature. METHODS: Retrospective review of 44 cases of SS diagnosed at the American University of Beirut - Medical Center between 1971 and 2008. Data collected included clinical (age, gender, morphology and distribution of lesions, associated symptoms and disorders, therapy) and histologic features, as well as laboratory abnormalities. RESULTS: Most of our patients showed the typical clinical, histologic, and laboratory abnormalities characteristic of SS. Of our 44 patients, 33 (75%) had classic SS while 11 (25%) had an underlying malignant disorder. Of all patients, 7 (16%) were in the pediatric age group, five (11%) had the neutrophilic dermatosis of the dorsal hands variant of SS and two (5%) had subcutaneous SS. Most patients were treated with a tapering dose of systemic corticosteroids with a good response. CONCLUSION: The clinical and histologic findings of the 44 SS patients in our study are generally comparable to those published in the literature, with some differences.

Treatment of pachydermoperiostosis pachydermia with botulinum toxin type A.

BACKGROUND: Pachydermoperiostosis (PDP) is a rare hereditary disorder characterized by digital clubbing, periostosis, and pachydermia. Pachydermia results in leonine facies, a major cause of cosmetic and functional morbidity in these patients. Its treatment is usually surgical. So far, no medical treatment has been suggested to alleviate this morbidity. OBJECTIVE: We sought to assess the role of botulinum toxin type A (BTX-A) in improving the cosmetic appearance of pachydermia in patients with PDP. METHODS: Three patients with PDP were treated with BTX-A for their leonine facies. A total of 70 to 80 U were used to treat the upper third of the face. Photographs were taken at baseline and at 2 and 6 weeks after the injections. The patients were followed up periodically for at least 6 months. Wrinkle severity was assessed at relaxation using the 4-point facial wrinkle scale at baseline, week 6, and month 6. In addition, a subjective assessment of the improvement of the extent and depth of the facial rhytides/furrows over the upper third of the face was performed by the same investigator at week 6 and month 6. RESULTS: Using the subjective assessment of the improvement of wrinkles, all 3 patients exhibited a fair to excellent response at week 6 that started manifesting 1 week after the BTX-A treatment. All patients demonstrated a residual effect 6 months after the treatment. One patient exhibited a mild exacerbation of his ptosis. LIMITATIONS: Major limitations were the small number of patients and the administration of BTX-A injections and assessment of their response by a single unblinded physician. CONCLUSION: BTX-A is a simple procedure that may be of value in temporarily improving the cosmetic appearance of pachydermia in patients with PDP.

Streptococcus sp. and Staphylococcus aureus isolates from patients with psoriasis possess genes that code for toxins (superantigens): clinical and therapeutic implications.

Superantigens are powerful T lymphocyte-stimulating agents that are believed to contribute to the pathogenesis of certain diseases such as psoriasis. Toxins produced by Streptococcus pyogenes and Staphylococcus aureus are superantigens. The aim of this study was to detect genes that code for superantigens in Streptococcus and Staphylococcus aureus isolates from psoriatic patients. Primers to amplify streptococcal pyrogenic exotoxin A, B, and C and streptolysin O genes and staphylococcal enterotoxin A, B, C, and D genes were used. Streptococcal exotoxin B was detected in five streptococcal isolates. Staphyloccocus aureus enterotoxin A and/or C genes were detected in nine S. aureus isolates. Isolates from 13 of 22 patients possesed gene(s) that code for toxin(s) (superantigens). These results might support the role of superantigens in the exacerbation of psoriasis.

Risk factors for the development of striae gravidarum.

OBJECTIVE: The purpose of this study was to identify risk factors associated with striae gravidarum (SG). STUDY DESIGN: A cross-sectional study of 112 primiparous women delivering at a private teaching hospital was conducted. Participants were assessed during the immediate postpartum period for evidence of SG. Presence and severity of SG were compared to characteristics of women using t tests and Chi-square tests. RESULTS: Sixty percent of the study participants had developed SG. Women who developed SG were significantly younger (26.5 +/- 4.5 vs 30.5 +/- 4.6; P < .001) and had gained significantly more weight during pregnancy (15.6 +/- 3.9 vs 38.4 kg +/- 2.7; P < .001). Birthweight (BW), gestational age at delivery, and family history of SG were associated with moderate/severe SG. CONCLUSION: Maternal age and weight gain during pregnancy are associated with SG. BW, family history of SG, and gestational age at delivery are associated with moderate/severe SG.

Dermatologic manifestations of parathyroid-related disorders.

Dermatologic manifestations of parathyroid-related disorders, although rare in sporadic cases, are not uncommon in familial syndromes. Patients with familial hyperparathyroidism have several types of skin lesions. In multiple endocrine neoplasia 1, patients commonly have angiofibromas (85%) and collagenomas (70%), lesions that show loss of one 11q13 allele, the molecular abnormality in multiple endocrine neoplasia 1. They can also present with lipomas or café-au-lait spots. Cutaneous amyloidosis, an entity that can occur sporadically, has been described in multiple endocrine neoplasia 2a and is usually localized to the interscapular area. Metastatic calcification is an entity commonly encountered in patients with hyperparathyroidism and renal failure. It can be complicated by infections and necrosis. It is best treated by controlling hypercalcemia, hyperphosphatemia, hyperparathyroidism, antibiotics, and analgesia. Parathyroidectomy is reserved for refractory cases. Hypoparathyroidism presenting in the context of polyglandular failure type 1 is characterized by mucocutaneous candidiasis. Pseudohypoparathyroidism, an inherited disorder with end-organ unresponsiveness to parathyroid hormone, is characterized by Albright hereditary osteodystrophy. Patients present with short stature, round facies, brachydactyly, and short fourth or fifth metacarpals.

Physiological and biological skin changes in pregnancy.

Pregnancy affects all organ systems in the body, including the skin. Some skin changes are physiological, whereas others such as the dermatoses of pregnancy are pathological. Dermatologists regularly encounter pregnant patients, and the identification of normal skin changes and their differentiation from disease states are essential to insure the well-being of both mother and fetus. This review discusses the physiological skin changes in pregnancy, including alterations in pigmentation, hair, nail, and connective tissue, as well as vascular and hematologic changes and modulation of glandular function.