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1.  The Clinical Relevance of Maintaining the Functional Integrity of the Stratum Corneum in both Healthy and Disease-affected Skin 
It has been recognized for approximately 50 years that the stratum corneum exhibits biological properties that contribute directly to maintaining and sustaining healthy skin. Continued basic science and clinical research coupled with keen clinical observation has led to more recent recognition and general acceptance that the stratum corneum completes many vital “barrier” tasks, including but not limited to regulating epidermal water content and the magnitude of water loss; mitigating exogenous oxidants that can damage components of skin via an innate antioxidant system; preventing or limiting cutaneous infection via multiple antimicrobial peptides; responding via innate immune mechanisms to “cutaneous invaders” of many origins, including microbes, true allergens, and other antigens; and protecting its neighboring cutaneous cells and structures that lie beneath from damaging effects of ultraviolet radiation. Additionally, specific abnormalities of the stratum corneum are associated with the clinical expression of certain disease states. This article provides a thorough “primer” for the clinician, reviewing the multiple normal homeostatic functions of the stratum corneum and the cutaneous challenges that arise when individual functions of this thin yet very active epidermal layer are compromised by exogenous and/or endogenous factors.
PMCID: PMC3175800  PMID: 21938268
2.  Use of Oral Isotretinoin in the Management of Rosacea 
Rosacea is a chronic inflammatory disease affecting roughly 16 million Americans. Topical and oral antibiotic/anti-inflammatory agents are currently the mainstay of therapy and are often used in combination. In this article, the authors discuss the use of oral isotretinoin in the management of rosacea, exploring dosage, comparable efficacy, safety, and cost.
PMCID: PMC3175801  PMID: 21938271
3.  Oral Apremilast for the Treatment of Plaque Psoriasis 
This article provides an update on the use of oral apremilast, a phosphodiesterase-4 (PDE4) inhibitor, for the treatment of plaque psoriasis. Emphasis is placed on safety evaluations, although efficacy considerations are also addressed. Both two-year and three -year data analyses support the favorable safety profile reported in pivotal trials with this agent. Although effective in many study subjects despite baseline characteristics, higher response rates were noted in those with a baseline psoriasis area and severity index (PASI) score <20 and in subjects not previously treated with systemic therapy for psoriasis. Gastrointestinal (GI) side effects are the most common adverse events (AEs) reported, especially during the first few weeks of use; recommendations on management of GI AEs are discussed. Psychological AEs appear to be rare, including with prolonged durations of use, and are not clearly associated with the drug itself as depression and suicidal behaviors are common in individuals with psoriasis. Data reported through up to 182 weeks of exposure to apremilast do not support an association with cardiac AEs, emergence of malignancies, enhanced predilection to develop significant opportunistic infections, or reactivation of occult infection, such as tuberculosis.
PMCID: PMC5110328  PMID: 27878061
4.  Application of Nail Polish During Topical Management of Onychomycosis 
Topical antifungal management of toenail onychomycosis has been fraught with several therapeutic challenges including difficulty gaining access to the site of infection and the need for prolonged durations of therapy. In addition, there has been a marked lack of information on the impact of toenail polish application on drug penetration after application. This article reviews available data from studies evaluating the effect of nail polish on antifungal drag penetration using ex vivo laboratory models with cadaver fingernail plates with both tavaborole 5% solution and efinaconazole 10% solution. In addition, changes in nail polish appearance and color transfer to applicators are also discussed, with changes noted with topical efinaconazole. Importantly, there are no data on whether or not nail polish application alters the efficacy of these topical agents.
PMCID: PMC5022994  PMID: 27672416
5.  Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society 
In this third article of the three-part series, management of skin and soft tissue infections is reviewed with emphasis on new information on methicillin-resistant Staphylococcus aureus. Due to changes in the evolution of methicillin-resistant Staphylococcus aureus clones, previous distinctions between healthcare-acquired methicillin-resistant Staphylococcus aureus and community-acquired methicillin-resistant Staphylococcus aureus are currently much less clinically relevant. Many nosocomial cases of methicillin-resistant Staphylococcus aureus infection are now caused by community-acquired methicillin-resistant Staphylococcus aureus, with changing patterns of antibiotic susceptibility and resistance. Also reviewed are clinical scenarios where antibiotics may not be needed and suggestions for optimal use of antibiotic therapy for dermatologie conditions, including recommendations on perioperative antibiotic use.
PMCID: PMC4928452  PMID: 27386047
6.  Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society 
In this second part of a three-part series addressing several issues related to antibiotic use in dermatology, potential effects of antibiotic use on the human microbiota and microbiome are reviewed. Data from available literature on the microbiologic effects of specific therapeutic agents commonly used in dermatology, including oral isotretinoin, tetracycline agents, and sub-antimicrobial (sub-antibiotic) dose doxycycline, are also discussed.
PMCID: PMC4928475
7.  Use of Polypodium leucotomas Extract in Clinical Practice 
Polypodium leucotomas extract is a natural product derived from a tropical fern that is available as an over-the-counter product in the United States and several other countries. A designated brand of oral Polypodium leucotomas extract has been shown in several research studies to exhibit a variety of antioxidant and photoprotective properties. Clinical research with this same formulation of Polypodium leucotomas extract has demonstrated multiple potential therapeutic applications. This article provides a thorough overview of research completed with Polypodium leucotomas extract and outlines suggested approaches for clinical use.
PMCID: PMC4928478  PMID: 27386044
8.  Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society 
Oral and topical antibiotics are commonly prescribed in dermatologie practice, often for noninfectious disorders, such as acne vulgaris and rosacea. Concerns related to antibiotic exposure from both medical and nonmedical sources require that clinicians consider in each case why and how antibiotics are being used and to make appropriate adjustments to limit antibiotic exposure whenever possible. This first article of a three-part series discusses prescribing patterns in dermatology, provides an overview of sources of antibiotic exposure, reviews the relative correlations between the magnitude of antibiotic consumption and emergence of antibiotic resistance patterns, evaluates the impact of alterations in antibiotic prescribing, and discusses the potential relevance and clinical sequelae of antibiotic use, with emphasis on how antibiotics are used in dermatology.
PMCID: PMC4898580  PMID: 27462384
9.  Activity of Dapsone versus Community and Hospital Pathogens from the CANWARD Study 
Background: Topical dapsone gel is a sulfone antibiotic approved for acne treatment. No microbiology studies were conducted during dapsone gel clinical trials and it is unclear whether 1) dapsone has antimicrobial activity that may be of clinical relevance in dermatology and 2) dapsone could affect the normal microbiome of facial skin where it is most commonly applied. This study assessed the in vitro activity of dapsone versus Gram-positive and Gram-negative bacterial pathogens obtained from patients with infections. Methods: CANWARD is a national, annual, and ongoing surveillance system to assess the patterns of antibiotic-resistant pathogens in Canada. In 2014, 15 tertiary care medical centers collected 3,511 isolates from blood, respiratory tract, urine, and wounds. Antimicrobial susceptibility was assessed using CLSI broth microdilution method. Results: Dapsone demonstrated relatively poor activity versus Gram-negative bacilli with most MIC50, MIC90 in the range of 512μg/mL and >512μg/mL, respectively. In contrast, dapsone demonstrated activity versus Gram-positive cocci, such as Staphylococcus (including methicillin-resistant S. aureus [MRSA], methicillin-sensitive S. aureus [MSSA]), Streptococcus, and Enterococcus—several strains of S. epidermidis had MICs of 32 and 64μg/mL; there were strains of E. faecalis with MICs of 8, 16, 32, and 64μg/mL; and several strains of S. agalactiae and S. pyogenes demonstrated dapsone MICs of 4, 8, 16, 32, and 64μg/mL. Conclusion: Dapsone has demonstrated antimicrobial activity in vitro. Whether this activity is part of the mechanism of action of topical dapsone in acne remains unknown. There are limited cutaneous pharmacokinetic data with topical dapsone including skin concentrations achieved with topical dapsone therapy; however, topical dapsone as a 2% nanoemulsion has shown very high (1196-3837.34μg/cm2) local skin concentrations. At these high concentrations, topical dapsone would be expected to affect the skin flora of patients with acne (especially Gram-positive cocci, such as Staphylococcus and Streptococcus). These concentrations are multiple times higher (20x-1000x) than the dapsone MICs found for many MSSA, MRSA, S. epidermidis, S. agalactiae, and S. pyogenes, any of which may be present on the skin of acne patients. Whether this results in resistance to dapsone or more importantly results in resistance to chemically unrelated antimicrobials is currently unknown.
PMCID: PMC4896821  PMID: 27354888
10.  Onychomycosis of Toenails and Post-hoc Analyses with Efinaconazole 10% Solution Once-daily Treatment 
Topical treatment for toenail onychomycosis has been fraught with a long-standing reputation of poor efficaey, primarily due to physical properties of the nail unit that impede drug penetration. Newer topical agents have been formulated as Solution, which appear to provide better therapeutic response in properly selected patients. It is important to recognize the impact the effects that mitigating and concomitant factors can have on efficaey. These factors include disease severity, gender, presence of tinea pedis, and diabetes. This article reviews results achieved in Phase 3 pivotal studies with topical efinaconazole 10% Solution applied once daily for 48 weeks with a focus on how the aforementioned factors influenced therapeutic outcomes. It is important for clinicians treating patients for onychomycosis to evaluate severity, treat concomitant tinea pedis, address control of diabetes if present by encouraging involvement of the patient’s primary care physician, and consider longer treatment courses when clinically relevant.
PMCID: PMC4771389  PMID: 27047631
11.  Clindamycin Phosphate 1.2%/Tretinoin 0.025% Gel for the Treatment of Acne Vulgaris: Which Patients are Most Likely to Benefit the Most? 
Clindamycin phosphate 1.2%/tretinoin 0.025% gel is a topical combination formulation used once daily for the treatment of acne vulgaris, with approval in the United States for patients >12 years of age. Three 12-week, randomized, vehicle-controlled, pivotal trials included > 1,800 actively treated subjects. In addition, an open-label, 52-week study was also completed with 442 subjects enrolled. The skin tolerability, safety, and efficacy of clindamycin phosphate 1.2%/tretinoin 0.025% gel applied once daily is well-established based on data from pivotal studies and analyses in other subsequent publications including from pooled analysis of results from 4,550 subjects. This article discusses results from the pivotal 12-week, Phase 3 studies of clindamycin phosphate 1.2%/tretinoin 0.025% gel applied once daily in 845 subjects with mild, moderate, or severe facial acne vulgaris and differentiates patterns of therapeutic response using study endpoint successes defined as clear, almost clear, or at least a 2-grade improvement in the AV severity rating.
PMCID: PMC4479365  PMID: 26155323
12.  Oral Doxycycline in the Management of Acne Vulgaris: Current Perspectives on Clinical Use and Recent Findings with a New Double-scored Small Tablet Formulation 
Oral antibiotics have been used for the treatment of acne vulgaris for six decades. Among dermatologists, tetracyclines represent at least three-fourths of the oral antibiotics prescribed in clinical practice. Unlike other specialties, antibiotic use in dermatology is predominantly for the treatment of noninfectious disorders, such as acne vulgaris and rosacea, which usually involves prolonged therapy over several weeks to months as compared to short courses used to treat cutaneous infections. At the present time, doxycycline and minocycline are the most commonly prescribed tetracyclines in dermatology, used primarily for treatment of acne vulgaris with a long overall favorable track record of effectiveness and safety. Although both are commonly used, doxycycline may be chosen by clinicians more readily as there is a lower risk of rare yet potentially serious adverse reactions, although doxycycline does warrant preventative measures to reduce the risks of esophagitis and phototoxicity reactions. This article reviews data with a new double-scored small 150mg tablet of doxycycline hyclate that has proven functional scoring, exhibits bioavailability similar to enteric-coated doxycycline, and has been shown to be associated with a low potential for gastrointestinal adverse reactions very comparable to what is achieved with enteric-coated tablets.
PMCID: PMC4445892  PMID: 26029331
14.  The Role of Topical Antifungal Therapy for Onychomycosis and the Emergence of Newer Agents 
Onychomycosis is a common infection of the nail unit that is usually caused by a dermatophyte (tinea unguium) and most frequently affects toenails in adults. In most cases, onychomycosis is associated with limited treatment options that are effective in achieving complete clearance in many cases. In addition, recurrence rates are high in the subset of treated patients who have been effectively cleared, usually with an oral antifungal agent. There has been a conspicuous absence of medical therapies approved in the United States since the introduction of topical ciclopirox (8% nail lacquer), with no new effective agents introduced for more than 10 years. Fortunately, newer agents and formulations have been under formal development. While patients might prefer a topical therapy, efficacy with ciclopirox 8% nail lacquer, the only available agent until the very recent approval of efinaconazole 10% solution, has been disappointing. The poor therapeutic outcomes achieved with ciclopirox 8% nail lacquer were not unexpected as the cure rates achieved in the clinical trials were unimpressive, despite concomitant nail debridement, which was an integral part of the pivotal trials with ciclopirox 8% nail lacquer. Efinaconazole 10% solution and tavaborole 5% solution are new topical antifungals specifically developed for the treatment of dermatophyte onychomycosis. In Phase 3 clinical trials, both newer agents were applied once daily for 48 weeks without concomitant nail debridement. Mycologic cure rates with efinaconazole 10% solution are markedly superior to what was achieved with ciclopirox 8% nail lacquer. To add, they appear to be nearly comparable to those achieved with oral itraconazole in pivotal clinical trials. However, it is important to remember that direct comparisons between different studies are not conclusive, are not generally considered to be scientifically sound, and may not be entirely accurate due to differences in study design and other factors. Well-designed and properly powered head-to-head studies are needed in order to draw definitive conclusions about efficacy comparisons between therapies, at least based on academic and regulatory standards. Although tavaborole 5% solution is in an earlier phase of development for onychomycosis, treatment success rates reported thus far for both efinaconazole 10% solution and tavaborole 5% solution are superior to ciclopirox 8% nail lacquer. As a result, a new era of onychomycosis appears to be upon us that incorporates topical therapy more effectively than in the past. Not only may these newer topical agents provide viable monotherapy alternatives to oral therapy for onychomycosis, topical therapy for onychomycosis that is effective, well tolerated, and easy to use may also find a role in combination therapy, and/or as continued therapy after initial clearance to reduce recurrence or re-infection.
PMCID: PMC4106353  PMID: 25053979
15.  Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel 
Excess cathelicidin and kallikrein 5 (KLK5) have been hypothesized to play a role in the pathophysiology of rosacea.
We sought to evaluate the effects of azelaic acid (AzA) on these elements of the innate immune system.
Gene expression and protease activity were measured in laboratory models and patients with rosacea during a 16-week multicenter, prospective, open-label study of 15% AzA gel.
AzA directly inhibited KLK5 in cultured keratinocytes and gene expression of KLK5, Toll-like receptor-2, and cathelicidin in mouse skin. Patients with rosacea showed reduction in cathelicidin and KLK5 messenger RNA after treatment with AzA gel. Subjects without rosacea had lower serine protease activity (SPA) than patients with rosacea. Distinct subsets of patients with rosacea who had high and low baseline SPA were identified, and patients with high baseline exhibited a statistically significant reduction of SPA with 15% AzA gel treatment.
Study size was insufficient to predict clinical efficacy based on the innate immune response to AzA.
These results show that cathelicidin and KLK5 decrease in association with AZA exposure. Our observations suggest a new mechanism of action for AzA and that SPA may be a useful biomarker for disease activity.
PMCID: PMC3910251  PMID: 23871720
antimicrobial peptides; azelaic acid; cathelicidin; kallikrein 5; LL-37; rosacea; serine protease
16.  From the Test Tube to the Treatment Room 
The development of new drug classes and novel molecules that are brought to the marketplace has been a formidable challenge, especially for dermatologic drugs. The relative absence of new classes of antimicrobial agents is also readily apparent. Several barriers account for slow drug development, including regulatory changes, added study requirements, commercial pressures to bring drugs to market quickly by developing new generations of established compounds, and the greater potential for failure and higher financial risk when researching new drug classes. In addition, the return on investment is usually much lower with dermatologic drugs as compared to the potential revenue from “blockbuster” drugs for cardiovascular or gastrointestinal disease, hypercholesterolemia, and mood disorders. Nevertheless, some researchers are investigating new therapeutic platforms, one of which is boron-containing compounds. Boron-containing compounds offer a wide variety of potential applications in dermatology due to their unique physical and chemical properties, with several in formal phases of development. Tavaborole, a benzoxaborole compound, has been submitted to the United States Food and Drug Administration for approval for treatment of onychomycosis. This article provides a thorough overview of the history of boron-based compounds in medicine, their scientific rationale, physiochemical and pharmacologic properties, and modes of actions including therapeutic targets. A section dedicated to boron-based compounds in development for treatment of various skin disorders is also included.
PMCID: PMC3935647  PMID: 24578778
17.  Incorporation of a Barrier Protection Cream in the Management of Chronic Hand Dermatitis 
A commonly encountered skin disorder in outpatient dermatology practice is hand dermatitis. In a considerable subset of patients, hand dermatitis can be a major source of prolonged distress when a pattern of chronicity develops due to repeated exposure to a variety of potential etiological factors. Most of the etiological factors are exogenous in nature. Hand dermatitis is an equal opportunity disease that affects both genders and occurs in individuals from all ethnic and cultural backgrounds. It is important to note that the term hand dermatitis does not refer to one specific diagnostic entity. Rather, hand dermatitis refers to multiple patterns of clinical disease that can be induced by a variety of exogenous sources. Occupational exposures with inadequate hand protection may be an important cause of epidermal barrier disruption, and in some cases contact allergy may be the primary cause or contribute to chronic hand dermatitis. In certain individuals, endogenous sources, such as atopic skin, cutaneous allergy (eczematous pattern), or skin hypersensitivity (urticarial pattern), may innately create predisposition to the development of hand dermatitis. Hand dermatitis can become a chronic problem that is often difficult to manage effectively. As consistency with hand protection and avoidance of irritant and allergenic contactants are integral to the effective treatment of chronic hand dermatitis, there is a high dependence on consistent patient adherence. Regardless of the etiological factors causing chronic hand dermatitis, lack of consistent hand protection is often a major reason why therapeutic results are suboptimal in some cases as exposure to the causes of the hand dermatitis are not adequately prevented. Regular wearing of protective gloves is not always feasible depending on the occupation, and although topically applied skin barrier protectants may be helpful in some cases, scientific data are generally limited with many products. This article provides an overview of hand dermatitis, reviews data supporting the therapeutic benefit of a specific barrier protection hand cream, and discusses ingredient modifications to the original formulation. The newer formulation does not alter the skin barrier protection components; however, the new ingredients were selected to add barrier repair properties to the original product, which was designed only as a skin barrier protectant.
PMCID: PMC3935650  PMID: 24578780
19.  Kallikrein 5-Mediated Inflammation in Rosacea 
Rosacea is a chronic inflammatory condition of facial skin estimated to affect more than 16 million Americans. Although the pathogenesis of rosacea is not fully understood, recent evidence in vitro as well as in vivo has supported the role of increased levels of the trypsin-like serine protease, kallikrein 5, in initiating an augmented inflammatory response in rosacea. The increase in the quantity and magnitude of biological activity of kallikrein 5 leads to production of greater quantities of cathelicidin (LL-37), an antimicrobial peptide associated with increases in innate cutaneous inflammation, vasodilation, and vascular proliferation, all of which are characteristic features of rosacea. In this article, the authors review the literature supporting the role of kallikrein 5 in the pathophysiology of rosacea, including how therapeutic interventions modulate the effects of kallikrein 5, thus providing further support for this pathophysiological model that at least partially explains many of the clinical features of cutaneous rosacea.
PMCID: PMC3930536  PMID: 24563692
20.  What’s New in the Medicine Cabinet? 
This article is the first in a periodic series of therapeutic topics with short reviews gleaned from major dermatology meetings, especially Scientific Poster Sessions, and is designed to provide information that may assist the readers in adapting information from the literature to their clinical practice. The topics covered in this issue are discussions of the clinical relevance of newer information about acne pathophysiology, acne in adult women, and topical corticosteroid spray formulations for chronic plaque psoriasis.
PMCID: PMC3930537  PMID: 24563693
21.  The Role of Skin Care as an Integral Component in the Management of Acne Vulgaris: Part 1: The Importance of Cleanser and Moisturizer Ingredients, Design, and Product Selection 
Acne vulgaris is a very common facial skin disorder accounting for approximately 10 percent of all visits to ambulatory dermatology practices across the United States annually. Over time, greater attention has been directed to the roles of multiple epidermal barrier functions in various dermatological disorders, especially the stratum corneum permeability barrier and antimicrobial barrier. As a result, it has become readily apparent that professional direction of skin care is very important in the overall management of acne vulgaris. This article discusses several reasons that support the importance of incorporating specified skin care recommendations and instructions into the overall management plan for acne vulgaris. In addition, the article reviews formulation characteristics and some of the scientific data on two commercially available products that are recommended for use as a skin care regimen in patients with acne-prone and acne-affected skin, a foam wash and a moisturizer with a sun protection factor 30 broad spectrum photoprotection rating. The rationale for inclusion of specific ingredients are discussed along with an overview of research results including use in patients with acne vulgaris.
PMCID: PMC3997205  PMID: 24765221
22.  The Role of Skin Care as an Integral Component in the Management of Acne Vulgaris: Part 2: Tolerability and Performance of a Designated Skin Care Regimen Using a Foam Wash and Moisturizer SPF 30 in Patients with Acne Vulgaris Undergoing Active Treatment 
Proper skin care is considered to be an important component of the total management plan for patients with acne vulgaris. A 28-day, open-label study provided both practical and scientific information on a designated skin care regimen in subjects with acne vulgaris. The cutaneous tolerability overall performance, and assessment of objective parameters evaluating the epidermal permeability barrier were documented with use of a specific foaming skin cleanser and a moisturizer with an SPF 30 broad spectrum rating in actively treated subjects with acne vulgaris. The results were favorable overall with the regimen shown to be nonirritating based on investigator and subject assessments, with high subject satisfaction and cosmetic acceptability ratings reported for both the foaming skin cleanser and the moisturizer with an SPF 30 broad spectrum rating. Objective instrumental testing of transepidermal water loss and epidermal hydration support that this skin care regimen assists in correcting epidermal permeability barrier dysfunctions that are innately present in acne vulgaris, worsened during a flare, and are known to be associated with many medications used to treat acne vulgaris. The recommendation of a specified skin care regimen incorporated into the overall management of acne vulgaris simplifies and standardizes the program for the patient, demonstrates a high level of interest by the clinician, and reduces the risk of the patient self-acquiring facial skin care products that may increase skin irritation.
PMCID: PMC3997206  PMID: 24765222
23.  Atopic Dermatitis and the Stratum Corneum: Part 3: The Immune System in Atopic Dermatitis 
Part 3 of this three-part review of atopic dermatitis and the stratum corneum barrier discerns how immune dysregulation, including upregulation of a TH2 inflammation pattern, augmented allergic sensitization, sustained wound healing inflammation, and impaired innate immunity, plays an integral role in the pathogenesis of atopic dermatitis. An increased understanding of the interdependence, polymorphisms, and dysregulations of epidermal barrier functions, including the stratum corneum permeability barrier, immune defense, and antimicrobial barriers, should provide further knowledge about the pathophysiological mechanisms that are clinically relevant and that contribute to the development of atopic dermatitis. Further understanding of these mechanisms should lead to newer therapies that target specific pathogenic components of atopic dermatitis.
PMCID: PMC3997207  PMID: 24765223
24.  Topical Corticosteroid Application and the Structural and Functional Integrity of the Epidermal Barrier 
Topical corticosteroids are a very important part of the treatment of many skin disorders, especially eczematous dermatoses. When utilized properly and judiciously these agents often achieve excellent results in clearing or markedly improving many dermatological disorders. As some studies have shown, topical corticosteroids, despite their ability to decrease inflammation through several mechanisms, induce abnormalities in lipid synthesis and intercellular bilayer structure in the stratum corneum, which appear to prolong epidermal barrier recovery. These adverse effects may contribute to eariier eczematous flaring if measures to provide barrier repair are not undertaken. In addition, although topical corticosteroids are applied only to sites affected by the skin eruption, the incorporation of “barrier friendly” excipients into the vehicle that improve stratum corneum permeability barrier function and integrity is very rational.
PMCID: PMC3848648  PMID: 24307921
25.  Atopic Dermatitis and the Stratum Corneum: Part 2: Other Structural and Functional Characteristics of the Stratum Corneum Barrier in Atopic Skin 
This three-part review presents what is currently known about the involvement and interdependency of the epidermal barrier and immune response in the etiopathogenesis of atopic dermatitis. Part 1 of this review depicted the role of filaggrin in atopic dermatitis while this article, Part 2, evaluates the role of serine proteases and specific lipids in the structural and functional integrity of the stratum corneum and its multiple barrier functions in atopic dermatitis. Upregulation of serine protease activity causes adverse structural changes of the stratum corneum due to degradation of certain stratum corneum proteins that are integral to epidermal structure and functions, interference with the formation of the stratum corneum intercellular lipid membrane, which normally regulates epidermal water flux and gradient, and induction of a TH2 pattern of inflammation, which is the hallmark profile of atopic skin. Alteration in lipid ratios and changes in lipid-directed enzymes may play a role in the impairment of barrier functions that are associated with atopic dermatitis. In Part 3, immune dysregulation, including upregulation of a TH2 inflammation pattern, augmented allergic sensitization, sustained wound healing inflammation, and impaired innate immunity are discussed. The roles of the stratum corneum permeability barrier, the immune defense barrier, and antimicrobial barrier in AD pathogenesis are explained in detail. With this explanation, the interdependence of the multitude of polymorphisms and dysregulations seen in AD skin will become clear. The condensing of these impaired and/or dysregulated functions and how they interact should provide further knowledge about the pathogenic mechanisms that cause atopic dermatitis, how they are clinically relevant, and how they may assist in developing more specific therapies directed at the pathogenesis of atopic dermatitis.
PMCID: PMC3848653  PMID: 24307926

Results 1-25 (65)