Skin Barrier Function In Patients Research Articles

Changes of filaggrin and its gene in patients with ichthyosis vulgaris

Objective To detect mutations in the filaggrin (FLG) gene and expressions of FLG and loricrin in patients with ichthyosis vulgaris (Ⅳ),and to investigate their clinical significance.Methods Tissue specimens were resected from the skin lesions of 10 patients with Ⅳ and normal skin of 14 healthy human controls,and immunohistochemical SP method was used to detect the expressions of filaggrin and loricrin.The expression intensity was determined by the Image-Pro Plus (IPP) software,and expressed as positive units (PU).Blood samples were collected from 10 patients of Han nationality with Ⅳ and 100 healthy human controls followed by DNA extraction.PCR and DNA sequencing were performed to detect the presence of 13 mutations (3321delA,441delA,1249insG,E1795X,S3296X,R501X,2282de14,R2447X,S2889X,7945delA,3702delG,Q2417X,R4307X) in the FLG gene.Results FLG was mainly expressed in the cytoplasm of keratinocytes in the stratum corneum,granular layer,prickle layer and basal layer,and loricrin was observed in the cytoplasm and nuclei of keratinocytes in the granular layer,prickle layer and basal layer,in both the lesional and normal skin.Compared with the normal skin,the lesional skin showed significantly weaker expressions of FLG (0.208 2 ± 0.008 0 vs.0.230 0 ± 0.0228,t =3.30,P ＜ 0.01) and loricrin (0.137 0 ± 0.011 2 vs.0.149 3 ± 0.007 3,t =3.07,P ＜ 0.01).Sequencing analysis identified two mutations,including 3321delA in 7 patients and 441delA in 2 patients.No mutations were detected in the healthy controls.Conclusions The 3321delA and 441delA mutations in the FLG gene may represent the most frequent genetic cause of Ⅳ in patients of Han nationality.The low expressions of FLG and loricrin may be associated with the impairment of skin barrier function in patients with Ⅳ. Key words: Ichthyosis vulgaris; Mutation; Filaggrin; Loricrin

Physiometry of facial skin in patients with acne and healthy individuals

Objective To approch acne characteristics and to facilitate its treatment by comparing the skin physiology function of patients with acne and healthy individuals.Methods Forty patients with acne and 40 healthy controls were included into this study.Cutometer,Sebumeter,Corneometer,Tewameter,and Mexameter were used,respectively,to measure the skin elasticity,sebum,water,t rans-epidermis water loss and red pigment index in the following facial areas:forehead,lateral canthus,right and left cheek,right and left U-zone.Results A significant increase was observed in the level of sebum in the forehead,right and left cheek of patients as compared with controls (P＜ 0.05).A significant decrease was observed in the level of water in the right and left cheek and U-zone of patients compared with controls (P＜0.05).A significant decrease was observed in the level of trans-epidermis water loss in the right and left cheek and forehead of patients compared with controls (P＜0.05).A significant increase was observed in the level of red pigment index in the right and left cheek,forehead,right and left U-zone of patients compared with controls (P＜0.05).However,the level of skin elasticity was of no significant difference between the patients and controls (P＞0.05).Conclusions Compared with the controls facial sebum secretion is increased with reduced skin barrier function in patients with acne. Key words: Acne; Skin; Elasticity; Sebum; Water; Red pigment

Human β-defensin-2 as a marker for disease severity and skin barrier properties in atopic dermatitis

Skin infections related to disrupted antimicrobial defence are a common problem in atopic dermatitis (AD). Altered levels of antimicrobial peptides, including human β-defensin (hBD)-2, have been reported in AD skin, and a link to impaired barrier function has been suggested. To study hBD-2 in relation to skin barrier function in patients with AD and controls, and to study hBD-2 in relation to disease severity. Twenty-five patients with AD and 11 controls were enrolled. hBD-2 peptide concentration was determined in stratum corneum samples collected by a minimally invasive tape-stripping method. Disease severity was assessed by SCORing Atopic Dermatitis (SCORAD), and skin barrier function was evaluated by measurement of transepidermal water loss (TEWL) and skin pH. Patients with AD were characterized according to filaggrin mutations. hBD-2 concentrations in the stratum corneum were found to differ between lesional and nonlesional AD skin and controls, with the highest values in lesional skin (P < 0·001). SCORAD and TEWL were significantly increased in participants with measureable hBD-2 (P < 0·018 and P < 0·007, respectively). Significant correlations between hBD-2 in lesional skin, and TEWL and SCORAD were observed (R = 0·55 and R = 0·44, respectively). No correlations with skin pH were found. hBD-2 was not found to relate to filaggrin mutations. A significant correlation was found between hBD-2, disturbed skin barrier function and disease severity. The minimally invasive skin sample technique enables evaluation of the stratum corneum and its proteins over time and provides the possibility of relating these findings to treatment, infections and physiological variations.

Evaluation of skin barrier function in patients with facial acne, eczema, melasma and solar dermatitis and its clinical significance.

Objective To compare skin barrier function among patients with facial acne,subacute eczema,melasma and solar dermatitis.Methods Three hundred patients,including 80 patients with facial acne,60 subacute facial eczema,80 facial melasma and 60 facial solar dermatitis,as well as 60 healthy controls were recruited in this study.Skin sebum content and transepidermal water loss (TEWL) were measured by a sebmeter and Tewameter TM 210 (Courage and Khazaka,Germany),respectively.Stratum comeum hydration was measured with a Scalar Moisture Checker (Scalar Corporation,Japan).Statistical analysis was carried out using analysis of variance and t test.Results Compared with the healthy controls,patients with facial acne showed increased skin sebum content and TEWL value but decreased stratum corneum hydration (all P ＜ 0.01),and patients with subacute eczema,solar dermatitis and melasma displayed lower sebum content and stratum corneum hydration but higher TEWL value (all P ＜ 0.01).Skin sebum content was significantly higher in patients with facial acne than in patients with subacute eczema,solar dermatitis and melasma ((184.65 ± 83.07) vs.(21.86 ± 18.94),(25.10 ±14.22) and (36.05 ± 32.84) μg/cm2,all P ＜ 0.01),but was similar between the patients with subacute eczema,solar dermatitis and melasma (P ＞ 0.05).In terms of stratum corneum hydration,patients with subacute eczema and solar dermatitis were statistically lower than those with acne and melasma (18.66％ ± 7.85％ and 20.91％ ± 8.05％ vs.24.32％ ± 8.16％ and 28.02％ ± 4.67％,all P ＜ 0.01),patients with facial subacute eczema were similar to those with solar dermatitis (P ＞ 0.05),and patients with facial acne were statistically lower than those with melasma (P ＜0.01).TEWL value was significantly higher in patients with melasma than in patients with acne,solar dermatitis and subacute eczema ((13.80 ± 4.t 3) vs.(20.86 ± 8.78),(22.85 ± 9.84) and (22.48 ± 10.37) μg/m2 h,all P ＜ 0.01),but similar between patients with acne,solar dermatitis and subacute eczema (P ＞ 0.05).Conclusions Skin barrier function is somewhat impaired in patients with facial acne,subacute eczema,melasma and solar dermatitis.Therefore,to recover skin barrier function may facilitate the treatment of these diseases. Key words: Facial dermatoses; Skin physiometry; Skin, barrier

Netherton Syndrome with Multiple Non-melanoma Skin Cancers

textabstractNetherton syndrome (NS) is a rare autosomal recessive genodermatosis caused by SPINK-5 mutations. The SPINK-5 gene encodes the serine protease inhibitor LEKTI and is located on chromosome 5q32. Unopposed degradation of corneodesmosomes is the basis for a severely impaired skin barrier function in patients with NS. Effective treatments for patients with NS are limited. Some success has been achieved with local application of corticosteroids or tacrolimus/pimecrolimus (1). Retinoids, acitretin as well as isotretinoin, have been used systemically, with variable benefits, whilst higher doses mostly worsen the disease, probably because of deteriorating effects on the skin barrier (2). Cyclosporine and oral corticosteroids are also prescribed to patients with NS (3, 4). There is one report of the successful use of intravenous immunoglobulins (IVIG), but this therapy has some clear limitations (5). Recently, Maatouk et al. (6) reported clinical improvement in Netherton syndrome with narrowband ultraviolet (UV) B phototherapy. A similar response was observed by Kaminska et al. (7), while clinical improvement induced by UVA1 therapy has been reported by Capezzera et al. (8). Because of these positive results, it may be tempting to use UV therapy readily in patients with NS. However, long-term use of UV is associated with an increased risk of developing skin cancer. Non-melanoma skin cancer is, unfrequently observed in patients with NS. Natsuga et al. (9) only found 3 cases in the literature, out of a total of approximately 150 cases of NS reported (9-13). However, most articles deal with this syndrome in childhood.

Improvement of skin barrier function in atopic dermatitis patients with a new moisturizer containing a ceramide precursor

Background: Atopic dermatitis (AD) is characterized by barrier abnormalities, including insufficient ceramides in the stratum corneum (SC). Objective: To measure the effects of a new moisturizer (CRM) containing a ceramide precursor in improving skin barrier function in patients with controlled atopic dermatitis. Methods: In this randomized, intra-individual comparison, investigator-blinded study, CRM was applied to the test area of one lower leg for 27 days (the other leg remained as untreated control). Evaluations at baseline and day 28 included transepidermal water loss (TEWL), skin hydration by corneometry, dryness severity, Raman spectroscopy, and collection of adverse events. Results: After 4 weeks of treatment, results showed a significantly greater reduction of TEWL and clinical dryness scores, and increased skin hydration (all p < 01) in the CRM-treated than untreated area. A significantly higher level of ceramide (p < 05) and a trend toward increased water content was observed with Raman in the SC for CRM than for the control. There were no related AEs. Conclusion: Skin barrier function and hydration were significantly improved after CRM treatment.

Noninvasive bioengineering assessment of the skin barrier function in patients with chronic venous insufficiency

Chronic venous insufficiency (CVI) comprises all symptoms caused by permanent venous and capillary hypertension. While the clinical manifestations of the disease have been well characterized, there is little knowledge on the skin barrier function in the affected patients. The aim of the study was to assess noninvasively the barrier function in patients with CVI stage C2 and stage C4 according to the CEAP classification in comparison with healthy controls (stage C0). Thirty patients with CVI without concomitant diseases and 15 healthy, aged-matched controls were recruited for the study. The skin barrier function was assessed by measuring transepidermal water loss (TEWL), capacitance and skin colour symmetrically on the calf, medial and lateral malleolus, posterior arch (arcus venosus) and volar forearm. Compared with the forearm, there was a tendency for increased TEWL and significant reduction of capacitance on all measurement sites on the lower limb. Compared with the control group, the patients with CVI had significantly higher TEWL values on all measurement sites on the lower extremities while no difference in capacitance between patients and controls was observed. Changes in the epidermal barrier function in patients with CVI are readily detectable by bioengineering methods as early as stage C2 and are manifested by significantly increased TEWL. Our results suggest that the reduced stratum corneum hydration in patients with CVI is due to anatomical differences rather than venous disease. These findings may help better understand the factors contributing to disease progression and its complications.

Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis

Background Two types of atopic dermatitis (AD) have been proposed, with different pathophysiological mechanisms underlying this seemingly heterogeneous disorder. The extrinsic type shows high IgE levels presumably as a consequence of skin barrier damage and feasible allergen permeation, whereas the intrinsic type exhibits normal IgE levels and is not mediated by allergen-specific IgE. Objectives To investigate the relationship between pruritus perception threshold and skin barrier function of patients with AD in a comparison between the extrinsic and intrinsic types. Methods Enrolled in this study were 32 patients with extrinsic AD, 17 with intrinsic AD and 24 healthy individuals. The barrier function of the stratum corneum was assessed by skin surface hydration and transepidermal water loss (TEWL), and pruritus perception was evaluated by the electric current perception threshold (CPT) of sensory nerves upon neuroselective transcutaneous electric stimulation. Results Skin surface hydration was significantly lower and TEWL was significantly higher in extrinsic AD than intrinsic AD or normal controls. Although there was no statistically significant difference in CPT among extrinsic AD, intrinsic AD and normal controls, CPT was significantly correlated with skin surface hydration and inversely with TEWL in intrinsic AD and normal controls, but not extrinsic AD. Finally, CPT was correlated with the visual analogue scale of itch in the nonlesional skin of patients with extrinsic but not intrinsic AD. Conclusions Patients with extrinsic AD have an impaired barrier, which increases the pre-existing pruritus but rather decreases sensitivity to external stimuli. In contrast, patients with intrinsic AD retain a normal barrier function and sensory reactivity to external pruritic stimuli.

Atopic dermatitis: Therapeutic concepts evolving from new pathophysiologic insights

Recent insights into the relevance of the epidermal barrier function and its interaction with components of the innate and adaptive immune responses in patients with atopic dermatitis (AD) give rise to a number of novel potential treatment options. In particular, the identification of loss-of-function mutations in the barrier protein filaggrin and of a diminished expression of certain antimicrobial peptides in AD skin stimulates new concepts to think beyond the T(H)1/T(H)2 paradigm. This review will focus on these most recent discoveries and will discuss new and corresponding proof-of-concept trials in patients with AD. It will further speculate on novel ways to restore the homeostasis among the 3 major components in AD skin suspected to be clinically relevant.

Olopatadine hydrochloride accelerates the recovery of skin barrier function in mice

The skin barrier function in patients with atopic dermatitis is disrupted and prolonged topical steroid therapy produces epidermal barrier disturbance. Olopatadine hydrochloride (olopatadine; Allelock; Kyowa Hakko Kogyo Co., Ltd, Shizuoka, Japan) is an antiallergic drug with histamine H(1) receptor antagonistic action. This drug alleviates skin inflammation and decreases the number of scratching episodes in a murine model of chronic contact dermatitis. To investigate the effects of olopatadine and a steroid on the recovery of skin barrier function after barrier disruption in mice. The skin barrier of the ears of mice was disrupted by tape stripping. The recovery of skin barrier function was monitored by measurement of transepidermal water loss (TEWL) after barrier disruption. Epidermal hyperplasia was induced by repeated tape stripping for 7 days. Olopatadine was administered orally once daily from 3 days before the first barrier disruption. Betamethasone 17-valerate (betamethasone) was applied topically once daily from 3 days before barrier disruption. Tape stripping led to a significant increase in TEWL. TEWL decreased with time after tape stripping and the skin barrier function recovered by over 60% within 9 h after tape stripping. The recovery of skin barrier in olopatadine-treated mice was significantly accelerated, compared with that in vehicle-treated mice. In contrast, the skin barrier recovery in mice treated with topical betamethasone was significantly delayed, compared with that in vehicle-treated mice. Combined treatment with olopatadine and betamethasone ameliorated the delay in barrier recovery induced by topical treatment with betamethasone. In addition, olopatadine significantly prevented the increase in epidermal thickness induced by prolonged barrier disruption. These results suggest that systemic administration of olopatadine accelerates the recovery of skin barrier function and ameliorates the adverse effects of topical steroids on skin barrier recovery.

Skin barrier function in patients with completely healed atopic dermatitis

Although it has been well established that the dry skin often seen in patients with atopic dermatitis shows a deranged barrier function, there is no unanimity of opinion as to whether the barrier in normal-appearing skin of patients with the disease is deranged or not. Hence, it remains unclear whether individuals with atopic dermatitis constitution have an intrinsic derangement of skin barrier function or not. To settle this problem, in the present study we examined transepidermal water loss and stratum corneum water content in normal appearing skin of the upper back of 16 patients with completely healed atopic dermatitis who had been free from skin symptoms for 5 years or more, 30 patients with active atopic dermatitis, and 39 healthy subjects. The transepidermal water loss values and the stratum corneum water content values in normal-appearing skin of the completely healed patients were not different from the values in normal controls. These findings indicate that skin barrier function is not disturbed in patients with completely healed atopic dermatitis.

Baseline transepidermal water loss in patients with acute and healed irritant contact dermatitis

To examine the skin barrier function of patients with acute and healed irritant contact dermatitis (n = 80) baseline transepidermal water loss (TEWL) was quantitatively measured using an evaporimeter. Healthy subjects served as controls (n = 40). Test areas were the forearm and the thigh. A significant increase in TEWL was observed in the patients with acute and with healed irritant contact dermatitis (ICD) as compared to healthy volunteers (P < or = 0.01). TEWL values in both test areas were comparable and markedly correlated (P < or = 0.01) with each other in every group. Thus, it is possible that basal TEWL depends more on the intrinsic skin barrier function of the subjects rather than the 2 anatomical regions examined. TEWL at the forearm with acute ICD was significantly higher (P < or = 0.01) than that of the group with healed ICD, but not for TEWL at the thigh suggesting that ICD may aggravate the barrier function of the adjacent uninvolved skin. It is assumed, that increased basal TEWL in patients with ICD may reflect a constitutional deviation of epidermal barrier function. This event seems to be comparable with the well-known symptom of atopic individuals. Using a detailed atopic scoring system in such a study may clarify the question of whether a proportion of patients with hand ICD may indeed be atopic individuals.