Is Acne Associated With Eczema Like Epidermal Barrier Dysfunction?
Acne Vulgaris and the Epidermal Barrier
Is Acne Vulgaris Associated with Inherent Epidermal Abnormalities that Cause Impairment of Barrier Functions? Do Any Topical Acne Therapies Alter the Structural and/or Functional Integrity of the Epidermal Barrier?
Unlike in atopic dermatitis (eczema), epidermal barrier dysfunction is not what generally enters your mind when one is asked to explain or note cutaneous problems associated with acne vulgaris (AV). Although even more studies are required, there is a body of literature that supports the principle that AV is associated with intrinsic problems in epidermal barrier functions.
In addition, some therapies used to treat AV can cause changes within the epidermis that can lead to changes that interrupt a few of the typical physiological functions of the epidermis, including the stratum corneum (SC). When it come to AV, one needs to likewise consider the follicular epithelial barrier, which is directly involved with changes that occur during both comedogenesis, and in stages of swelling, especially with follicular rupture.
Changes in follicular keratinization are essential parts of the pathogenesis of AV and take place in the subclinical stages of acne lesion development (microcomedo formation). Filaggrin is a crucial protein in epidermal differentiation and contributes to the structural and practical stability of the SC. Within acne lesions, there is a boost in filaggrin expression in keratinocytes lining the follicle wall.
In addition, Propionibacterium acnes has been shown to enhance filaggrin expression in cultured keratinocytes as well as in explants of human skin. Importantly, it is not known if the changes in filaggrin expression noted in AV are primary or secondary events. An interesting hypothesis was raised by the outcomes of a research analyzing filaggrin mutations in patients with xerosis.
Study subjects were queried for a history of skin conditions and signs and symptoms of dry skin. Whole blood samples were acquired with DNA extracted and evaluated for null mutations in filaggrin. The odds ratio of having AV was 0.3 in the subjects carrying one copy of the null mutation. Although this was not statistically significant, and a history of AV was self-reported, the authors assumed that a null mutation in the filaggrin gene could be safety against AV.
Another research study checked this hypothesis in a cohort of Singaporean Chinese clients presenting with AV where they assessed and performed screening for 22 types of filaggrin null mutations in 287 clients with AV and in more than 400 control subjects. A comparative analysis failed to identify a statistically substantial adverse association between AV and filaggrin mutations in this population. The idea that a decreased ability to express filaggrin due to genetic mutation associates directly with a lower ability to form acne lesions is interesting; however, research studies to date do not provide cogent evidence to plainly support this hypothesis.
In AV, the barrier functions of both the epidermis of the exposed skin surface and the follicular epithelial lining are to think about. Both might be involved in pathophysiological mechanisms associated with AV or with impaired physiological properties of the SC, such as regulation of water flux and/or epidermal hydration.
Surface skin. The facial skin of patients with AV varies from regular skin of people without AV in a number of methods. Although exceptions might exist, sebum production is higher and the size of sebaceous glands are bigger in people with acne-prone facial skin who are currently known to have AV as compared to the facial skin of people without AV. In addition, the normal-appearing facial skin of clients with AV can show specific perifollicular and follicular patterns of inflammatory cellular seepage and inflammatory marker expression that are really much like the patterns observed in early acne papules provide for within 6 hours.
These findings and the observations of others recommend that subclinical inflammation exists early in the introduction of acne lesion development even in the absence of follicular hyperkeratinization.
As even more attention is now being given to the role of various barrier functions of the epidermis (especially the SC) in various disease states, it is important to know if there are any inherent structural or practical epidermal barrier aberrations in AV that could be essential to attend to therapeutically, particularly as particular medications used to deal with AV can change some epidermal properties.
Yamamato et al1 examined sebum secretion, SC lipids, transepidermal water loss (TEWL), and conductance within the SC of male clients with mild-to-moderate AV (n=36), age variety 14 to 26 years, and age-matched male control subjects (n=29). They discovered that the patients with AV exhibited significantly higher sebum secretion and higher TEWL and considerably minimized SC conductance (corneometry screening). The combined findings of higher TEWL and lower SC hydration (decreased conductance) kept in mind in the clients with AV compared with controls supports SC permeability barrier disability associated with AV.
In addition, acne patients had significantly reduced free sphingosine and total ceramides in their SC, which is indicative of a lacking intercellular lipid membrane and correlates with disability of the SC permeability barrier. The increase in TEWL and decrease in SC hydration (conductance) were of greater magnitude in patients with AV of moderate extent as as compared to those with mild acne seriousness and as compared to normal control subjects. These latter findings suggest that the degree of SC permeability barrier problems associates directly with the severity of AV.
Follicular skins (epithelium). In addition to the exposed skin of the integumentary surface, the follicular epithelium likewise contributes to cutaneous barrier functions. Loss of physical obstacle integrity often takes place when the intensity of swelling minimizes the strength of the follicular wall. In AV, the proliferation of P. acnes within the follicle starts numerous inflammatory cascades associated with innate, acquired, and humoral immunological feedbacks; direct inflammatory effects of enzymes (i.e., lipases, matrix metalloproteases); and inflammation caused by catalytic breakdown products.
When intrafollicular and perifollicular inflammatory processes considerably magnify, attenuation of the follicular wall can cause numerous degrees of rupture with subsequent leakage of sebum, keratin, bacteria, and cellular debris into the dermis. The presence of these substances, which are foreign to the dermis, provokes more inflammation that is deeper, eventuating in the emergence of a nodular or nodulocystic acne lesion.
It is very important to differentiate the lipids and other elements of the intercellular lipid membrane of the SC, the core structural component of the epidermal permeability barrier, from the lipids and other elements of sebum that reside in the pilosebaceous hair follicle.
Lipids in sebum are distinct from the SC lipids. Also, the content of sebum in clients with AV might be different from people without AV. In a small study of males, age range 15 to 25 years, with AV (n=9) and without AV (n=9), the sebum content differed in between the two groups. In the males with AV, the sebum amount was 59-percent higher, squalene was enhanced roughly two-fold, and free fatty acids were decreased. A relative crucial fatty acid insufficiency has likewise been gone over connected to pilosebaceous contents. In AV, increased sebum flow downregulates linoleic acid leading to a relative deficiency which may play a role in comedogenesis.
How Do Some Topical Acne Therapies Alter Epidermal Barrier Functions?
Some topical medications, systemic medications, and physical procedures used to deal with AV and/or acne scarring can result in changes in SC permeability barrier function based on enhanced TEWL and in many cases visible indications of xerosis. Increases in TEWL have been reported with benzoyl peroxide, tretinoin, tazarotene, and isotretinoin, which portrays findings in acne-treated skin that can be connected to epidermal barrier functions. Different efforts have been made to reduce disabilities of the SC permeability barrier induced by acne therapies.
Benzoyl peroxide. Benzoyl peroxide (BP) has been used extensively for the treatment of AV for more than 6 decades, offering the capability to noticeably lower counts and reduce the proliferation of P. acnes, including restraint of the emergence of antibiotic-resistant pressures of the organism.
It is renowneded that BP can trigger cutaneous inflammation in some patients, which appears to be depending on concentration, carrier solution, type of adjunctive skin care, other concomitant acne medications, and the intrinsic skin level of sensitivity of the individual. Allergic contact dermatitis from BP is much less usual than irritant dermatitis. Despite the prevalent use of BP over many years for AV in both prescription and non-prescription formulas, there is a paucity of data on what epidermal effects BP may induce, although it has been revealed to show some "keratolytic" activity.
In one study, investigators attempted to balance out the 1.8-fold increase in TEWL from application of BP 10 % by topical administration of alpha-tocotrienol, an isomer of vitamin E. The changes induced by BP show that this agent causes damage to the SC lipid bilayer, which results in a boost in TEWL as well as produces some impairment of the epidermal antioxidant barrier by reducing levels of vitamin E. Application of alpha-tocotrienol did mitigate BP-induced peroxidation of SC lipids, but did not balance out the increase in TEWL.
A study on sebum from acne lesions reported in Dermatoendocrinology. 2009 May-Jun; 1(3): 157– 161 shows that sebum of acne patients contains 2.2-fold more squalene, 1.84-fold more triglycerides, 1.59-fold more sebum, 1.49-fold more sapienic acid, 1.33-fold more wax esters and lowered free fatty acid levels (0.79-fold) than the sebum of control subjects without acne.
In this study the sebum of people influenced and not influenced by acne was studied. They picked a young male population to ensure adequate levels of sebum and to avoid possible effects of the menstrual cycle on sebum output.
As anticipated, the subjects with acne secreted larger quantities of sebum than the control (59 %). The only class of lipids that was reduced in the acne subjects was free fatty acids. In contrast, wax/cholesterol esters and triglycerides were enhanced in the acne group. The specific lipid that varied the most between the two groups was squalene, 2.2-fold, which also stood for a considerably greater proportion of the overall sebaceous lipids in acne subjects compared to controls (20 % versus 15 % respectively).
Squalene is a precursor of cholesterol. Most mammalian cells manufacture cholesterol, which consists of a crucial molecule for membrane fluidity and bilayer structure. Squalene as a long unsaturated hydrocarbon does not accumulate in high levels in the majority of the tissues where it is swiftly converted to lanosterol and finally to cholesterol. The uniqueness in human sebum is that this non-polar hydrocarbon accumulates in unusually high levels (12– 15 %) as compared to the levels of any other tissue or organ. On the other hand cholesterol accounts for less than 2 % of the total sebaceous lipids.
Squalene, as a long and highly unsaturated hydrocarbon in nature, is a lube and has high penetration effectiveness suggesting its prospective duties in addition to cholesterol synthesis. Previous reports showed possible duties of squalene oxidation products in UV defense. Nevertheless it is not known if squalene's capability to scavenge free radicals is of a benefit or rather the opposite, given that metabolites of this oxidation process can likewise cause irritability.
These squalene oxidation products, together with unsaturated free fatty acids, have been reported to be comedogenic in study models. Furthermore a recent research reported that peroxidated squalene causes the production of inflammatory mediators in HaCaT keratinocytes, which could support the involvement of lipid peroxides in establishing the inflammatory process in acne.
Squalene could possibly alter the rheological properties of sebum, as it is the most non-polar molecule in sebum, however the most unsaturated also. This particle could serve as a lipid pen for acne susceptible skin, as it is much more upregulated than the remainder of the lipids and the overall sebum level. In contrast the sapienic acid, the significant sebaceous fatty acid, is a measure of the respective complete amount of sebum. It is noteworthy to point out that uncompromised males had comparable levels of squalene regardless of age. However people with acne had 1.6-fold higher sebum but likewise 2.2-folds higher amount of squalene.
The reearchers performed a comparative analysis of lipids in young males with and without acne. They determined squalene to be considerably enhanced in acne clients, therefore standing for a lipid marker associated with acne. It would be of interest to perform a blind analysis of this in larger groups. It could retrospectively determine acne susceptible individuals in relationship with differential squalene secretion.
Better analytical techniques would help to increase our understanding of squalene, its metabolites and their role in the induction or the upkeep of the acne lessions. The field of "sebum-omics" is open for lots of new discoveries and is regularly boosted by advances in analytical methods. This will eventually clarify intriguing skin-related conditions such as acne. In conclusion, the study documented both quantitative and qualitative differences in sebum of unaffected and acne influenced individuals.
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