Keratolytic Agents Research Articles

Atomistic insights into salicylic acid treatment on human keratinized skin by XPS combined with argon gas cluster sputtering: A pilot study

Stratum corneum is the skin's outermost layer, whose main constituent is keratin. The treatment of dermatological diseases showing hyperkeratosis is a serious problem in dermatology and cosmetics seriously affecting the population showing increasing prevalence. One of the treatment is a peeling agent like salicylic acid (SA), categorized as a keratolytic agent, however its mode of action is not fully understood. X-ray photoelectron spectroscopy (XPS) is a method for monitoring the changes of surface composition at atomistic level in 5–10 nm depth. The development of argon cluster sputtering enabled the investigation of deeper regions (nanometric level) even for biomaterials. In this pilot study, the mode of action of SA has been studied at atomistic level for the first time. Different concentrations of SA (3, 5, 10 wt%) in different time frames (1 day, 1 week, 1 month) was applied on human keratinized skin. The carbon, nitrogen and oxygen peak have not shown changes during the treatment, not showing the suggested desmolytic mechanism of SA. However, significant changes were observed in the sulfur peak, with increasing time and concentration the rate of sulfonate and sulfate was increased compared to thiol group indicating the break of sulfide bonds between the polypeptide chains in keratin, indicating that keratolysis happens at nanometric level. Already a 1 week-10 wt% SA treatment resulted in higher rate of sulfate compared to sulfonate indicating further oxidation of the keratolytic product. However, 1 month-10 wt% treatment resulted in the same surface composition as 3 wt%-1-month treatment indicating that enough time with low concentration can exert the same effect as higher concentrations. These findings have relevance in the design of future SA-based dermatologic therapies.

Investigation of keratolytic impact of synthetic bolalipids on skin penetration of a model hydrophilic permeant

Synthetic single-chain bolalipids (SSCBs) are novel excipients in drug delivery, with potential as stabilizers or solubilizers. However, their impact on skin barrier function has not been comprehensively studied. Therefore, two SSCBs (PC-C24-PC and PC-C32-PC) were studied in aqueous systems for their impact on penetration of a model permeant into porcine skin. Concentrations of 0.05 – 5 % w/w were tested; PC-C24-PC formulations were low-viscosity liquids while PC-C32-PC formed viscous dispersions to gels at room temperature. Formulations were compared for their ability to enhance sodium fluorescein penetration (SF, 0.1 % w/w) into skin via tape stripping. Using NIR-densitometry, the effect of SSCB formulations on corneocyte cohesion was evaluated. Data were compared with phospholipid mixture Lipoid S-75, sodium dodecyl sulfate (SDS), and polyethylene glycol 12-hydroxystearate (PEG-HS), and distilled water as negative control. Contrary to the hypothesis, both SSCBs failed to increase SF penetration into the stratum corneum, but rather showed a significant decrease in penetration depth compared to water. Both SSCBs exhibited a keratolytic effect at 5 % w/w, leading to substantial removal of proteins from the skin surface. Consequently, SSCBs may not enhance penetration of hydrophilic drugs into skin, but could be used as keratolytic agents.

Vitamin D3 and the Molecular Pathway of Skin Aging

Many women pay attention to skin aging. Signs of aging such as lines, wrinkles, dry skin, hyperpigmentation, and loss of elasticity affect skin appearance and self-confidence. Age, lifestyle, and particularly UV irradiation stimulate reactive oxygen species (ROS) production. ROS induces the breakdown of collagen through matrix metalloproteinases (MMPs). Collagen and elastin play a pivotal role in skin aging. They maintain skin integrity, strength, and resiliency. Antioxidant and keratolytic agents are often used in anti-aging products, including several vitamins such as vitamin A, B, C and E. To date, several studies have been reported in the literature for the effects of vitamin D on collagen synthesis and MMPs inhibition. This review focuses on identifying and assessing the molecular pathways of vitamin D effects related to skin aging. The literature was collected from Google Scholar, Elsevier, Science Direct, PubMed, and Scopus databases and accessed between January 2019 and May 2022. The literature screening was conducted using keywords like “vitamin D3”, “collagen”, “matrix metalloproteinases”, “skin aging” and related to the study topic were included. The effect of vitamin D3 on MMPs inhibition (particularly on MMP-1, MMP-3, and MMP-9) has been widely published. Several studies have reported that vitamin D increases collagen synthesis and clinically improves skin elasticity. However, there have been controversial results regarding how vitamin D3 affects transforming growth factor-β (TGF-β) correlated with skin elasticity by the molecular pathway. Therefore, it can be concluded that vitamin D3 is a potential alternative agent in improving skin aging.

Exploring the Protective Efficacy of Topical Products for Actinic Keratosis Against Ultraviolet-Induced DNA and Protein Damage: An Experimental, Double-Blind Irradiation Study.

Introduction Numerous studies have delved into the clinical efficacy of different topical treatments for actinic keratosis (AK). However, our understanding remains limited regarding their capacity to prevent DNA and protein damage caused by ultraviolet radiation (UVR). Objectives The aim of this study was to analyze and compare the preventive capabilities of various AK-targeted products in countering DNA and protein alterations in human biopsies following exposure to experimental UVR. Methods Twelve healthy Caucasian volunteers (six men and six women) aged 18 years and above, with Fitzpatrick skin types II-III, participated in an experimental irradiation study. Six topical products, containing various ingredients (DNA repair enzymes, antioxidants, keratolytic agents, cyclooxygenase inhibitors, and/or sunscreens) were tested. The experimental sites were exposed to UVR at six times the minimal erythema dose for eight consecutive days. Each test product was applied 30 to 45 minutes before irradiation at a standard thickness of 2 mg/cm2. A control site was treated with the vehicle alone, serving as a negative control. The study focused on cyclobutane pyrimidine dimers (CPDs) and protein carbonylation (PC) as molecular markers of UVR-induced DNA and protein damage, respectively. Results The efficacy of different AK-targeted topical products showed substantial variation when applied to normal skin before experimental exposure to UVR. While sunscreens, predictably, played a crucial role, additional ingredients (i.e., DNA repair enzymes and antioxidants) also acted as vital protective agents for both the cellular genome and proteome, shielding them against UVR-induced damage. Conclusion In topical products specifically designed for AK, the strategic integration of DNA repair enzymes and antioxidants, in addition to sunscreens, establishes a critical defense mechanism against the detrimental effects of UVR on cellular DNA and proteins.

P28 Traumatic anserine folliculosis: a cause of facial follicular papules

Abstract Traumatic anserine folliculosis (TAF) is an infrequently reported condition, presenting with grouped follicular papules, usually on the face of young people, induced by repeated frictional trauma or pressure. A suggestive history may allow clinical differentiation of TAF from other folliculocentric keratotic disorders. We present three children diagnosed with TAF in our department: (i) A 12-year-old boy with asymmetry of the mental protuberance, presented with a 1-year history of scaly, lichenified erythema with monomorphic nonpigmented papules over the more prominent side; histology showed mild hyperkeratosis and some rudimentary hair follicles with keratin-filled follicular openings. (ii) A 7-year-old boy with a 1-year history of a hyperpigmented patch on the chin with multiple skin-coloured papules and a sandpaper feel; dermoscopy showed follicular papules with keratin plug; he had a habit of reading with his chin resting on his knee; the skin changes improved with topical retinoid and postural changes. (iii) A boy with follicular papules on one cheek since the age of 8 years, with history of persistent leaning his hand on his cheek while reading; the papules resolved with a change in posture, but similar changes arose at a new pressure area on his chin. The clinical features of grouped monomorphic skin-coloured follicular papules on an erythematous or hyperpigmented background, and a suggestive history, may allow the diagnosis of TAF. Described histological findings are hyperkeratosis, rudimentary follicles and dilated follicular openings filled with keratotic material. Management includes identifying and correcting postural habits; topical keratolytic agents and retinoids may also be beneficial.

PA14 Aquagenic palmar wrinkling in a 15-year-old swimmer

Abstract A 15-year-old girl presented with a 1-year history of recurrent palmar wrinkling on contact with water. This was associated with a burning sensation within minutes of water exposure and progressive persistent thickening of the palmar skin. She was otherwise well, with no family history of note, including cystic fibrosis (CF). She had no regular medication or newly introduced medications before the onset of wrinkling. Moderate improvement in hyperkeratosis was seen with twice-daily use of urea 10% and salicylic acid 10% creams; however, the discomfort experienced in water was negatively affecting her ability to continue competitive swimming. On examination, there was palmar hyperlinearity with focal hyperkeratosis over the thenar and hypothenar eminences. Immersion of the hands in lukewarm water resulted in wrinkling within 2 min and peaking at 3 min, at which point the patient reported a burning sensation. Wrinkling resolved within 30 min of drying her hands. Baseline laboratory investigations were normal. Biopsy of the palm in the wrinkled state showed subtle prominence and dilation of sweat gland ducts. A diagnosis of aquagenic syringeal keratoderma (ASK) was made. At the 3- and 6-month reviews, the patient reported spontaneous resolution of wrinkling on contact with water, which was confirmed clinically. Residual hyperkeratosis had similarly resolved, although subtle palmar hyperlinearity persisted. She was able to resume competitive swimming activities without symptoms. The ASK is a rare condition, classically affecting the palms of young women, in which palmar wrinkling occurs within minutes of immersion in water. It may be asymptomatic or associated with stinging, burning or paraesthesia. Palmar wrinkling typically resolves after drying of the hands without persisting signs. The mechanism for this phenomenon is unclear, with theories including acquired abnormalities in eccrine glands, an underlying primary keratoderma, or potential induction by cyclooxygenase. Aquagenic palmar wrinkling is also recognized in association with CF, both in individuals with the disease and carriers, with more rapid onset of wrinkling in the former. In this case, there was no suggestion of personal or family histories of CF, and hyperkeratosis persisted for months at a time until liberal regular use of keratolytic topical agents was introduced. Hereditary papulotranslucent acrokeratoderma, a differential diagnosis in this case, was considered; however, in this condition once papules and wrinkling appear, they typically remain and are further exacerbated by water exposure. For this patient, a diagnosis of atypical ASK was favoured due to the persisting sequelae, with probable mild atopic dermatitis reflected by palmar hyperlinearity. This case serves to highlight this rare dermatological phenomenon and its impact on a teenage swimmer.

Terra firma-forme dermatosis: a condition not to be forgotten (a case report)

Introduction: Terra firma-forme dermatosis is a benign condition and it can affect anyone, but it seems to be more common in children and young adults. It may appear as brownish or black spots that look like dirt. Typically, affected individuals are asymptomatic. Case description: A healthy 3-year-old girl, presented in our clinic with a 6-month history of brownish spots that looked like ‘dirt’, which were spread through the chest and flanks. After examination, we suspected that it was terra firma-forme dermatosis, so we rubbed the affected areas with gauze soaked in 70% isopropyl alcohol, thus removing these stains. After two months, the child presented with no injuries. Comment: Terra firma-forme dermatosis can be diagnosed and treated with the rubbing of gauze embedded in 70% isopropyl alcohol in the affected areas. It is important to prevent skin xerosis, by using smoothing cream with keratolytic agents like salicylic acid in order to accelerate the healing and complete resolution of the lesions. It is essential to make an early diagnosis to prevent unnecessary diagnostic and treatment procedures.

Nevoid Hyperkeratosis of the Nipple – A Case Report and Review of Literature

Nevoid hyperkeratosis of the nipple and areola (NHNA) is a rare, benign, idiopathic condition, which occurs predominantly in women of child-bearing age. It is characterized by asymptomatic, hyperkeratotic, verrucous plaques, and either unilateral or bilateral over the nipple and areola. It has to be differentiated from Darier disease, seborrheic keratosis, atopic dermatitis, Paget’s disease, frictional hyperkeratosis, and cutaneous T-cell lymphoma. Fused rete ridges, compact orthohyperkeratosis, and filiform papillomatosis are seen on histopathology. Dermoscopy shows keratotic structureless areas with brownish clods. There is no specific treatment, long-term use of calcipotriol and keratolytic agents for more than 6 months, and surgical therapy is recommended. This case is reported to highlight the use of dermoscopy in the diagnosis of NHNA.

A RARE CASE OF PAPILLON-LEFEVRE SYNDROME: A CASE REPORT

Papillon Lefevre syndrome is an extremely rare autosomal recessive disorder characterized by diffuse palmoplantar hyperkeratosis, rapidly progressive and devastating periodonitis, and pyodermas. The etiopathogenesis of the disorder is multifactorial, with genetic and immunological factors playing a major role. Consanguinity is a contributing factor. Genetic mutations of the gene 11q14- q21 encoding for cathepsin-c, a lysosomal protease that activates enzymes involved in a variety of inflammatory and immune processes. Management directed towards halting periodontal destruction using conventional periodontal treatment, systemic antibiotics, oral hygiene instructions, antiseptic mouth rinses. Palmoplantar hyperkeratosis usually treated with topical application of emollients, keratolytic agents, topical steriods and systemic retinoids.

Darier's follicular dyskeratosis

Darier's follicular dyskeratosis (synonym: Dariers disease, DarierWhites disease) is a rare genetic disease with an autosomal dominant type of inheritance, which belongs to the group of acantholytic dermatoses and is characterized by a violation of keratinization processes with lesions of the skin, nails, mucous membranes of the oral cavity and genitals. Dariers disease is caused by a mutation in the ATP2A2 gene. This disrupts the operation of the SERCA2 pump and leads to a violation of calcium homeostasis in keratinocytes and a decrease in intercellular adhesion. Dariers disease is manifested by brownish papules in seborrheic and intertriginal areas with a keratotic surface, which can merge into macerated plaques. Typical nail changes in Dariers disease include red and white longitudinal stripes ending in V-shaped notches on the free edge of the nail plates. Warty acrokeratosis, as well as bullous, hemorrhagic, comedonic and linear-segmental types are clinical variants of Dariers disease. Dariers disease is often associated with neuropsychiatric disorders. Exacerbation may be caused by superinfection with Staphylococcus aureus or by herpes simplex virus. Histology in Darieres disease is characterized by pronounced dyskeratosis. For local therapy, keratolytic agents are important, as well as antiseptic treatment to avoid superinfection. In addition, local corticosteroids are used. Among the systemic methods of treatment, the systemic retinoids are the most effective. Ablative methods of treatment (dermabrasion, CO2 laser, Er:YAG laser) are effective in limited areas.

Successful Treatment of an Adult with Atopic Dermatitis and Lamellar Ichthyosis Using Dupilumab

Lamellar ichthyosis (LI) is a rare autosomal cornification disorder, with most cases due to a mutation in the transglutaminase-1 (TGM1) gene on chromosome 14. Patients with LI usually present with a collodion membrane and mild erythroderma at birth, with the collodion membranes shedding within the first weeks of life and being replaced by a generalized scale. Typically, LI is managed with oral retinoids, emollients, and keratolytic agents, eg, lactic acid. We report an LI case associated with atopic dermatitis and asthma that showed a marked improvement with dupilumab treatment. This finding is highly significant as it may represent a breakthrough in the treatment of LI, thus more research is needed to investigate the potential benefits of dupilumab for the treatment of ichthyosis, such as the effects observed in our patient.

Cubosomal Betamethasone-Salicylic Acid Nano Drug Delivery System for Enhanced Management of Scalp Psoriasis.

IntroductionBetamethasone dipropionate (BD), a potent corticosteroid, and salicylic acid (SA), a keratolytic agent, have been used in combination to treat scalp psoriasis; however, undesirable side effects associated with their prolonged topical use are inevitable. In this study, BD and SA were loaded into cubosomes, a nanoparticulate system with outstanding biocompatibility, bio-adhesivity and penetration power.MethodsDesign of experiments (DOE) was utilized to prepare thirteen different cubosomal dispersions by emulsification technique using glycerol monoolein (GMO) as a lipid phase and Poloxamer 407 (P407) as a surfactant, sodium carboxymethyl cellulose (SCMC) was added to enhance the dispersions’ rheological properties. The thirteen dispersions were in-vitro characterized for their particle size, polydispersity index (PDI), zeta potential, BD and SA content and rheological behaviour. The desirability of an optimized formula (OF) was set to the smallest particle size, lowest zeta-potential and highest viscosity. The OF was in-vitro characterized for the same parameters in addition to transmission electron microscope imaging and in-vitro drug release. The OF’s anti-psoriatic activity was evaluated in-vivo using an imiquimod-induced psoriasis model.ResultsThe OF achieved a particle size of 197.4 ± 9.47 nm, a PDI of 0.443 ± 0.025, a zeta potential of −44.4 ± 0.141mv, BD content of 105.85 ± 2.290%, SA content of 88.855 ± 2.920% with shear-thinning rheological behaviour and completed in-vitro drug release within 2–3 hours. The in-vivo studies confirmed the cubosomes’ higher anti-psoriatic efficacy over the commercial product with lower changes in ear thickness, spleen to body weight ratio, psoriasis area severity index score and improved histopathological findings.ConclusionThe developed BD SA-loaded cubosomes exhibit promising anti-psoriatic activity attributed to its nano-size and unique lipid content, with enhanced skin penetration and modified rheological properties; increasing the formulation’s in-contact duration with the scalp resulting in lower application frequency and thus reduced BD and SA associated side effects.

Systematic Review and Meta-analysis on Synthetic Antifungal versus Keratolytic Agents for Topical Treatment of Pityriasis Versicolor

Background. Pityriasis versicolor is a common fungal infection of the superficial skin layer caused by Malasseziafurfur, a normal commensal in the skin. Keratolytic agents are popular, cheap, and readily available over-the-counter treatments for pityriasis versicolor. Conventional antifungal agents are more expensive, requiring prescription, and may induce resistant strains. However, evidence of their comparative safety and efficacy is still lacking.Objectives. To assess the efficacy and safety of synthetic antifungals compared to keratolytic agents in the topical treatment of pityriasis versicolor through a systematic review.Methods. We searched the following databases: MEDLINE (from 1966) through PubMed, CENTRAL (Issue 9 of12, September 2021), EMBASE (from 1974), LILACS (from 1987); Herdin (from 1970), www.clinicaltrials.gov, www.isrctn.com, www.trialregister.nl. We contacted researchers in the field, hand searched relevant conference abstracts, and the Journal of the Philippine Dermatological Society 1992-2019. We included all randomized controlled trials involving patients with diagnosed active pityriasis versicolor where topical antifungal was compared with a topical keratolytic for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias using the Cochrane collaboration tool, and extracted data from included studies. We used RevMan 5.3 to pool dichotomous outcomes using risk ratios (RR) and continuous outcomes using the mean difference (MD), using random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi² test and the I² test. We presented results using forest plots with 95% confidence intervals. We planned to create a funnel plot to determine publication bias but were unable to due to few studies. A Summary of Findings table was created using GRADE profile software for the primary outcomes. Results. We included 8 RCTs with a total of 617 participants that compared azole preparations (ketoconazole,bifonazole and econazole) versus keratolytic agents (selenium sulfide, adapalene, salicylic-benzoic acid). Pooled data showed that azoles did not significantly differ from keratolytic agents for clinical cure (RR 0.99, 0.88, 1.12; 4 RCTs, N=274, I2=55%; very low-quality evidence), and adverse events (0.59 [0.17, 2.06]; very low-quality evidence) based on 6 RCTs (N=536). There were two patients given a keratolytic agent (selenium sulfide shampoo) who had acute dermatitis and discontinued treatment. Conclusion. It is uncertain whether topical azoles are as effective as keratolytic agents in clinical clearance andoccurrence of adverse events in patients with pityriasis versicolor. A wider search of grey literature and local studies are warranted. Larger RCTs with low risk of bias are recommended.

Efficacy of a Retinoid, Keratolytic, Anti-Inflammatory and Antibacterial Gel and Spray Formulations in Mild Common Acne

Background and Objectives: For the treatment of mild/moderate acne, topical retinoids and antibacterial molecules are used in monotherapy or in combination. An exfoliating and anti-inflammatory action can increase the clinical efficacy of this therapeutic approach. A topical product in Gel and Spray Formulations (GF and SF) with retinoids (hydroxypinacolone retinoate and encapsulated retinol), with anti-inflammatory (niacinamide), antibacterial (biopep15) and keratolytic (glycolic and salicylic acids) activity has recently been developed. Topical retinoids have anti-inflammatory, anti-seborrheic and anticomedone-formation properties. Biopep15 is an oligopeptide with antibacterial action that can interfere with lipoteichoic acid, a component of the wall of Cutibacterium acnes. In addition, Biopep15 can perform also an antagonistic action against the Toll-Like-Receptor 2, involved in the pathogenesis of acne. Niacinamide has a well-known anti-inflammatory action. Salicylic and glycolic explain keratolytic and exfoliating activities. In this study the objective was to determine the efficacy and tolerability of GF and SF in mild/ moderate comedogenic acne. Methods: In a 4-week, open-label, prospective trial, 32 patients between the ages of 15 and 30 have been evaluated. All participants gave their written consent. Treatment with gel (for facial lesions) and spray (for lesions located on thorax, back and shoulder) applied twice daily were used. To assess clinical efficacy, a count of comedogenic lesions (open and closed comedones; non-inflammatory lesions: NIL) and inflammatory lesions (IL; papules, and pustules) was performed and the reduction in the number of lesions after 2 and 4 weeks of treatment was evaluated. An evaluation of Total lesions count (TL; NIL+IL) was also performed.The lesion count data were analysed with a paired Student's t test.We evaluated also the exfoliating/keratolytic activity and the effect on sebum production assessed at baseline, after 2 and 4 weeks of treatment. Finally, to evaluate Cutibacterium acnes (C. acnes) skin colonization, we performed a fluorescence detection of skin porphyrin content at baseline and at day 28, by mean of Visiopor PP 34 camera. Results: All patients completed the trial. At baseline the NIL, IL and TL count were 14.3, 8.7 and23, respectively. After 2 weeks of GF/SF treatment, NIL, IL and TL significantly decreased to 9.7 (-32%), 6.8 (-22%) and 16.5 (-29%), respectively. At the end of the treatment, a significant reduction in comparison with baseline was observed for NIL (-49%) IL (-63%) and TL (-54%). The exfoliating index evaluated in comparison with baseline value improved not significantly by 13% at day 14, and significantly (p=0.05) by 18% at day 24. The Cutibacterium acnes skin colonization area was significantly (p=0.02) reduced by 28% in comparison with baseline. Treatment was well tolerated, and local tolerability was assessed as optimal by all patients. Conclusion: This new anti-acne combination formula based on retinoids, antibacterial oligopeptide, keratolytic and anti-inflammatory agents have shown high clinical efficacy and good tolerability in patients with mild to moderate acne. The treatment shows also a keratolytic effect and a significant reduction of C. acnes skin colonization.

Portraying molecular modulation and therapeutic aspects of psoriasis: Retrospection and current status

• Psoriasis is an autoimmune disease of the skin with chronic inflammatory conditions. • Various signaling pathways are involved in its pathophysiology. • The basis of molecular modulation of psoriasis has been addressed. • Various strategies to counter this complex disease have been discussed in detail. • Recent development in the anti-psoriatic therapy has been discussed. Psoriasis is a hyperproliferative skin disorder which is associated with dysregulation of the immune system. In this genetically transmitted disease, the immune system is activated by various triggers such as genetic predisposition, stress, and pathogenic microbes which in turn stimulate various immunocytes such as keratinocytes, macrophages, monocytes, dendritic cells and T-cells to secrete various pro-inflammatory cytokines that ultimately accelerate inflammation and cause psoriatic plaques. These cytokines are also responsible for T-cell differentiation, keratinocyte hyperproliferation, and accumulation of neutrophils and lymphocytes in the skin. At the molecular level, several pathways have been proposed underlying the pathophysiology of psoriasis that directly or indirectly kindle various psoriatic factors. The most common pathways include PDE-4, ICAM-1, LFA-1 and JAK/STAT pathways. In order to target these pathways, various strategies have been developed that counter moderate to severe psoriasis. The most effective therapies include interleukin inhibitors, TNF-α inhibitors, JAK inhibitors, PDE-4 inhibitors and immunosuppressants such as methotrexate, cyclosporin, tazarotene, and acitretin. Apart from these inhibitors, phototherapy (UV-A and PUVA) and topical therapies (corticosteroids, vitamin D analogs, retinoids, emollients, and keratolytic agents) have also been employed for the treatment of mild to moderate psoriasis. This review provides the retrospective analysis of psoriasis and current therapeutic options which are under development for the amelioration of psoriatic diseases. The information provided in this report may be helpful for the research community engaged in the development of effective novel therapies against psoriasis.

Meibomian Gland Dysfunction: A Dermatological Perspective on Pathogenesis and Treatment Outlook.

Meibomian glands are modified oil-producing glands that produce meibum and can become dysfunctional and negatively affect the lipid layer in the tear film, resulting in ocular surface diseases such as evaporative dry eye. Abnormal keratin production and aggregation at the meibomian gland orifice has been implicated in the pathogenesis of meibomian gland dysfunction (MGD). Current treatments largely ignore the role of keratin proteins. This review paper synthesizes various publications on hyperkeratinization and its role in MGD pathogenesis and proposes a novel treatment strategy for MGD that involves the use of keratolytic agents commonly used in dermatological treatments.

Circle Hairs in a Patient with Multiple Myeloma

Circle hair is a rare body-hair disorder of unknown etiology, typically characterized by perfectly or nearly perfectly coiled hair located below the cornified layer of the skin. Its main histopathological features are dilated hair-follicle infundibula and entrapped hair shafts. After its first description in 1963, there have only been a small number of reported cases, and its pathophysiology remains unclear. Herein, we report a case of an 80-year-old woman with skin lesions and abnormal hairs on both legs. We also propose a possible mechanism of her circle hairs: it may have occurred as an effect of her acquired ichthyosis secondary to her underlying multiple myeloma. There is no specific treatment for circle hairs, and reassurance that it is a harmless condition is sufficient. We prescribed a topical humectant and keratolytic agent to moisten the skin and lessen the hair entrapment, which resulted in clinical improvement. As the pathogenesis of the disease is unknown, further studies are warranted.

Urea in Dermatology: A Review of its Emollient, Moisturizing, Keratolytic, Skin Barrier Enhancing and Antimicrobial Properties.

Urea is a hygroscopic molecule (capable of absorbing water) present in the epidermis as a component of the natural moisturizing factor (NMF) and is essential for the adequate hydration and integrity of the stratum corneum. Urea improves skin barrier function including antimicrobial defense by regulating gene expression in keratinocytes relevant for their differentiation and antimicrobial peptide production. It also plays a fundamental role in regulating keratinocyte proliferation. One of the first uses of urea in modern medicine was the topical treatment of wounds due to its proteolytic and antibacterial properties. At present, urea is widely used in dermatology to improve skin barrier function and as one of the most common moisturizers and keratolytic agents. Urea-containing formulations are available in diverse formulations and concentrations. Multiple clinical trials on the use of urea-containing formulations have shown significant clinical improvement in many of the dermatosis presenting with scaly and dry skin such as atopic dermatitis, ichthyosis, xerosis, seborrheic dermatitis and psoriasis, among others. Furthermore, urea can increase skin penetration and optimize the action of topical drugs. Urea-based products are well tolerated; their side effects are mild and are more frequent at high concentration. Here, we present a review of the use of urea in dermatology, discussing its mechanism of action, safety profile and frequent indications.

Common foot disorders

Up to 75% of Americans will experience foot health problems at some point in their lives. Women are 4 times more likely to experience foot problems than men. The most common disorders are corns or calluses; ingrown toenails or other nail afflictions; foot infections, including athlete's foot and warts; and foot injuries and structural problems. Corns are small, raised, sharply demarcated, hyperkeratotic lesions with a central core, usually caused by pressure from underlying bony prominences or joints. They usually present on the bulb of the great toe, the dorsum of the fourth or fifth toe, or tips of the middle toes. A callus has a broad base, with relatively even thickening of skin. They are generally raised, yellow, and found on the bottom of the foot in areas such as the heel, ball of the foot, and toes, and on the sides of the foot. Self-care options to treat corns and calluses include a daily footbath followed by application of an emollient foot cream to help retain moisture and pliability; keeping the feet warm; and instituting moderate exercise daily. Dead tissue should be removed gently with a callus file or pumice stone. Pads or shoe inserts may also reduce pressure on the affected areas. Salicylic acid, a keratolytic agent, is the only nonprescription preparation marketed for the removal of corns and calluses. Three dosage forms are available in various concentrations (6%–17% in a topical gel, 12%–40% in a plaster vehicle, and 12%–27.5% in a collodion-like vehicle). When used in a collodion-like medium, the product forms an adherent flexible or rigid film, prevents moisture evaporation, and aids the penetration of the active ingredient into the affected tissue. Stop treatment and consult an appropriate health care provider if swelling, reddening, or irritation of the skin develops, or if pain occurs immediately with product application. Nonpharmacologic options for corns and calluses include full-shoe inserts to provide cushioning and absorb shock, partial insoles when the patient needs cushioning or support in a certain portion of the shoe, and a heel cup or heel cushion, depending on the location and extent of the pain. Another foot issue that lends itself to self-care is ingrown toenails. Warm water soaks for 10 to 20 minutes several times a day and insertion of small cotton wisps or dental floss under the impinged nail edge are very beneficial nonpharmacologic options. The only over-the-counter pharmacologic option is sodium sulfide 1% gel. This is applied topically twice daily for up to 7 days and relieves pain by softening the nail or hardening the nail bed. Patients may also experience exercise-induced foot injuries, particularly those caused by running, jogging, or other high-impact physical activities. Appropriate footwear is critical. Patients will often ask about other issues that coincide with foot pain such as shin splints, blisters, and ankle sprains. Each of these ailments has self-care options focused on symptom relief while incorporating an element of preventive care. Ice or cold wraps can help relieve shin splint pain. Prevention is key when it comes to blisters, but if one develops it should be covered with moleskin for protection. Application of compound tincture of benzoin or a flexible collodion product before exercise can decrease pain and accelerate healing by promoting re-epithelialization. If blisters break, a first aid antibiotic can be applied to the broken skin to prevent secondary bacterial infection. Treatment of ankle sprains should be started as soon as possible with a compression bandage, ice, and elevation. For these conditions, NSAIDs can be used for pain and inflammation relief. Patients with diabetes or peripheral vascular disease should be referred to their primary care provider as these individuals commonly have factors contributing to a loss of pain/injury perception. Patients should clean and inspect their feet daily for any changes and have a yearly comprehensive foot evaluation assessing any changes in foot appearance or tactile sensation. Recommend patients wear proper-fitting, comfortable shoes; use caution when “breaking in” new shoes; use moisturizing lotion sparingly on the tops and bottoms of dry feet; and allow feet to completely dry before donning shoes to prevent excess moisture buildup. Foot disorders provide great opportunities for pharmacists to help improve patient comfort.

Oxidative stress in the skin: Impact and related protection.

Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness and wrinkles. Besides these, skin microbiota are also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well-known antioxidants, namely vitamin C, resveratrol and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress-induced skin pigmentation and aging.