The effect of damaged skin barrier induced by subclinical irritation on the sequential irritant contact dermatitis

Skin damage caused by a single specific stimulus has been extensively studied. However, many additional mild skin irritants are experienced every day before obvious irritant contact dermatitis (ICD) appears. The effect that these previously experienced mild irritations have on the incidence and severity of sequential ICD remains undefined. The purpose of this work was to explore whether the effects of skin barrier damage induced by either the open patch test with 1% sodium lauryl sulfate (SLS), tape stripping test (TAP) (10×), or irradiation with 0.75 median erythemal dose UVB (MED) will affect the severity of sequential irritant dermatitis induced by a 0.5% SLS occlusive patch test (PT). Nine treatments were applied to nine different locations of the ventral forearm of each subject at random. The nine treatment types were as follows: open patch test with 1% SLS; 10× TAP; UVB irradiation with 0.75 MED; open patch test with 1% SLS + PT with 0.5% SLS (SLSPT); 10× TAP + PT with 0.5% SLS (TAPPT); UVB irradiation with 0.75 MED + PT with 0.5% SLS (UVPT); PT with distilled water (DISPT); PT with 0.5% SLS (PT); and the CONTROL (no treatment). After 5 days of subclinical irritation, the PT was applied on day 6. Transepidermal water loss (TEWL), capacitance (CAP), and skin color (a*) were measured at baseline and on days 6, 7, and 8. After the PT, indices of irritancy of PT, UVPT, SLSPT, and TAPPT were 60, 80, 87 and 100%, respectively. The index of irritancy of TAPPT and SLSPT were significantly higher than that of PT (p < 0.05). Clinical scores of SLSPT and TAPPT were also significantly higher than PT (p < 0.05). After 5 days of irritation, TEWL of SLS, TAP, SLSPT, and TAPPT were increased significantly compared to that of baseline. After the PT, D-value of TEWL between day 8 and day 6 ((≥6-8)TEWL) of SLSPT and TAPPT were greater than that of PT, and D-value of TEWL between day 8 and day 7 ((≥7-8)TEWL) of SLSPT and TAPPT were less than that of PT values. After the PT, a* values of SLSPT, TAPPT and PT all increased. The D-value of a* between day 8 and day 6 ((≥6-8)a*) of SLSPT and TAPPT were significantly greater than that of PT. After the PT, D-value of CAP between day 8 and day 6 ((≥6-8)CAP) of SLSPT was significantly different as compared to PT. The open patch test with 1% SLS and 10× TAP destroys the skin barrier and is able to significantly increase the irritancy and severity of sequential ICD by 0.5% SLS PT, and therefore influences the recovery speed of inflammation. The open patch test with 1% SLS, 10× TAP, and UVB irradiation with 0.75 MED affects the skin barrier to different degrees. TEWL is a sensitive biophysical parameter that can reflect mild damage to the skin barrier induced by subclinical irritation.     

Comparison of tissue sources for the skin integrity function test (SIFT).

One of the in vitro models involved in an ECVAM-sponsored prevalidation study for acute skin irritation is the skin integrity function test (SIFT), which utilises full-thickness mouse skin. We have evaluated nine different skin types in order to identify the most useful model for assessing skin barrier function using transepidermal water loss (TEWL), electrical resistance (ER) and tritiated water flux (TWF) and sodium lauryl sulphate (SLS) as a standard skin irritant. Tissues were: human skin (epidermis and whole), reconstituted human epidermis (RHE), pig (dermatomed and whole), rabbit (whole), rat (epidermis and whole) and mouse (whole). Barrier function was measured following sodium lauryl sulphate (SLS) exposure and expressed as a damage ratio. Human epidermis gave good responses at high doses of SLS only. RHE had abnormally high permeability to water and therefore had little or no response to SLS. Pig skin gave low TEWL ratios and rabbit skin was a poor responder to SLS. Mouse whole skin performed best in this study, giving consistent high damage ratios to TEWL, ER and TWF following SLS treatment. Rat whole skin also performed well but was generally less responsive. We conclude that mouse skin is the best and most practical in vitro model for the SIFT approach for skin irritation prediction.     

Effect of saline iontophoresis on skin barrier function and cutaneous irritation in four ethnic groups.

The effect of saline iontophoresis on skin barrier function and irritation was investigated in four ethnic groups (Caucasians, Hispanics, Blacks and Asians). Forty healthy human volunteers were recruited according to specific entry criteria. Ten subjects, five males and five females, were assigned to each ethnic group. Skin barrier function was examined after 4 hours of saline iontophoresis at a current density of 0.2 mA/cm(2) on a 6.5 cm(2) area in terms of the measured responses: transepidermal water loss (TEWL), skin capacitance, skin temperature and visual scores. There were significant differences in TEWL among the ethnic groups prior to patch application. TEWL at baseline in ethnic groups was in the rank order: Caucasian>Asian>Hispanic>Black. Iontophoresis was generally well tolerated, and skin barrier function was not irreversibly affected by iontophoresis in any group. There was no significant skin temperature change, compared to baseline, in any ethnic groups at any observation point. Edema was not observed. At patch removal, the erythema score was elevated in comparison to baseline in all ethnic groups; erythema resolved within 24 hours. Thus, saline iontophoresis produced reversible changes in skin barrier function and irritation in healthy human subjects.     

Unexpected skin barrier influence from nonionic emulsifiers

Skin disorders are often treated with creams containing various active substances. The creams also contain emulsifiers, which are surface-active ingredients used to stabilize the emulsion. Emulsifiers are potential irritants and in the present study the influence of stearic acid, glyceryl stearate, PEG-2, -9, -40, and -100 stearate, steareth-2, -10 and -21 on normal as well as on irritated skin have been evaluated with non-invasive measurements. Test emulsions were created by incorporating 5% emulsifiers in a water/mineral oil mixture (50:50). The emulsions and their vehicle were then applied to normal skin for 48 h and to sodium lauryl sulfate (SLS) damaged skin for 17 h in aluminum chambers. Twenty-four hours after removal of the chambers the test sites were evaluated for degree of irritation. In normal skin, the emulsifiers induced significant differences in TEWL but not in skin blood flow. Five of the emulsifiers increased TEWL. In SLS-damaged skin an aggravation of the irritation was expected. However, no differences regarding skin blood flow was noted from the emulsifiers. Furthermore, three emulsifiers unexpectedly decreased TEWL. These results highlight the possibility of absorption of these emulsifiers into the lipid bilayer, which increase TEWL in normal skin and decrease TEWL in damaged skin.     

Comparative analysis between nasolabial and island pedicle flaps in the ala nose reconstruction. Prospective study

The goals of reconstructing deformities of the face secondary to skin cancer include reconstructing the area with similar tissue. The comparison between different types of local flaps for reconstruction of nasal ala is presented in a prospective, randomized study. The objective of this study was to compare the functional and esthetic outcomes between the nasolabial and island flaps. A total of 60 patients with skin cancer of the nose underwent ala reconstruction: 30 cases by nasolabial flap (group A) and 30 by island flap (group B). The two groups were homogeneous for sex, age, and anatomical area. Complications, scarring according to the scale of Vancouver, cosmetic appearance, and disorders of sensations were analyzed and statistical analysis was performed. In group A, early complications were more common than in group B. The scars of group B patients were more like those of undamaged skin. A total of 10% patients of group A evaluated the cosmetic appearance of their nose as very good, while in group B, 30% patients gave such an evaluation. Local flaps provide better reconstruction and the island flap appears to have more efficacy when compared with nasolabial flap for nasal ala reconstruction.     

Seasonal effects on the nasolabial skin condition

In the present work, nasolabial skin condition and the influence of seasonal changes during autumn and winter were studied in 16 healthy female volunteers. Apart from visual scoring of erythema and skin scaliness, transepidermal water loss (TEWL), skin hydration, apparent skin pH, skin colour and skin desquamation were biophysically measured. The study results showed that nasolabial TEWL was significantly higher during wintertime than in autumn. Also skin colour measurements and squamometry scorings revealed higher values, indicating a more reddish and scaly nasolabial skin during winter compared to autumn. Results from tape stripping and skin surface lipid analysis by high-performance thin-layer chromatography demonstrated significant differences for triglycerides and cholesterol esters, indicating a functionally inferior hydrolipidic layer during the winter season.     

Regional variations in skin barrier function and cutaneous irritation due to iontophoresis in human subjects.

The effect of saline iontophoresis on skin barrier function and irritation was investigated on three body sites (abdomen, chest and upper arm) in order to select an appropriate site for iontophoretic delivery of drugs. Thirty healthy human volunteers were recruited according to specific entry criteria. Ten subjects, five males and five females, were assigned to each body site group. Skin barrier function and irritation was examined after 4 h of saline iontophoresis at a current density of 0.2 mA/cm(2) on a 6.5 cm(2) area in terms of the measured responses: transepidermal water loss (TEWL), skin capacitance, skin temperature and visual scores. Alterations in TEWL due to iontophoresis were not observed in the upper arm and chest; however, changes in TEWL at the abdomen were observed and returned to baseline 2 h after patch removal. Similarly, changes in capacitance due to iontophoresis returned to baseline (P>0.05) at the three body sites 2 h after patch removal except under the anode at the abdomen (P<0.05). There was a significant increase in skin temperature due to iontophoresis at the anode and the cathode (P<0.05) at the upper arm. Edema was not observed. At patch removal, the erythema score was significantly (P<0.001) elevated in comparison to baseline at the three body sites. Erythema resolved within 24 h except at the chest under the anode, where the erythema score was still higher (P<0.01) than the baseline. Papules appeared in five subjects at the active anode site on the chest. In three of the subjects, these papules did not resolve until 24 h post patch removal. Thus, there was regional variation in the function of the skin and irritation due to iontophoresis. Irritation was greater at the chest than at the abdomen or upper arm.     

O/W emulsions compromise the stratum corneum barrier and improve drug penetration

BACKGROUND: W/O emulsions improve the stratum corneum barrier, while microemulsions tend to compromise it. We, therefore, were interested to explore the effects of O/W emulsions on the stratum corneum barrier. METHODS: Aqueous Cream BP 2001, Clioquinol Cream BP 1999 without clioquinol, Nonionic Hydrophilic Cream DAB 2001 without glycerol, Hydrophilic Skin Emulsion Base NRF S. 25., point of time 2001, without glycerol, and Base Cream DAC were tested versus untreated controls in 29 healthy volunteers for 7 days. Outcome measures included transepidermal water loss (TEWL), skin redness (chromametry a*-value) and erythrocyte circulation in the subpapillary vessels (laser Doppler). Barrier compromise was subsequently explored by performing the hydrocortisone blanching test using Hydrocortisone Cream 0.5% NRF 11.36. (outcome measure: a*-value) in 15 subjects and the sodium lauryl sulfate (SLS) irritation test (outcome measures: TEWL, a*-value, laser Doppler) in 14 subjects. RESULTS: Pretreatment with the test emulsions produced increases in TEWL (statistically significant for all test emulsions), a*-value (statistically significant for Aqueous Cream BP 2001 and Base Cream DAC), and laser Doppler value (statistically significant for all emulsions except Base Cream DAC). Hydrocortisone penetration was statistically significantly increased with all test emulsions versus untreated contols. SLS irritation was mostly statistically significantly increased versus untreated controls when analyzing the study endpoint-baseline difference. CONCLUSIONS: O/W emulsions may compromise the stratum corneum barrier and improve drug penetration.     

Enhancement of the results of neck liposuction with the FAMI technique

Submental liposuction is an excellent procedure for improving the aging neck by reducing the cervicomental angle and increasing the definition of the mandibular border. However, it does not address the loss of volume of the chin and perioral areas caused by atrophy of hard and soft tissues. In this study, thirty patients underwent concomitant submental tumescent liposuction and fat augmentation with the FAMI (fat autograft muscle injection) technique in order to assess short-term results and complications associated with these two relatively noninvasive procedures. All patients had improvement in the cervicomental border, a smoother mandibular border, and a more proportioned chin following 3-5 days of swelling. Patients followed for 6 months to one year had long term retention of fat. There were no significant complications. In this preliminary series, submental tumescent liposuction with FAMI provided enhanced aesthetic results with little downtime and minimal complications.     

Dermal toxicity and microscopic alterations by JP-8 jet fuel components in vivo in rabbit

In this study, we investigated the skin irritation, macroscopic and microscopic barrier alteration in vivo in rabbits from aliphatic and aromatic components of jet propellant-8 (JP-8) jet fuel. Macroscopic barrier properties were evaluated by measuring transepidermal water loss (TEWL), skin capacitance, and skin temperature; microscopic changes were observed by light microscopy. Draize visual scoring system was used to measure skin irritation. We found significant (P<0.05) increase in temperature at the site of all chemically saturated patches immediately after patch removal in comparison to the control site. Tridecane (TRI) produced a greater increase in temperature and capacitance at all time points than all the other components of JP-8. Both the aliphatic and aromatic components increased the TEWL at all time points. Tridecane produced greater increase in TEWL followed by naphthalene (NAP), 1-methylnaphthalene (1-MN), 2-metylnaphthalene (2-MN), tetradecane (TET), and dodecane (DOD). All of the above components of JP-8 caused moderate to severe erythema and edema, which were not resolved to the baseline even after 24 h of patch removal. Light microscopy revealed an increase in epidermal thickness (ET), and decrease in length and thickness of collagen fibers’ bundle by the above components of JP-8. These results suggest potential dermatotoxicity from the JP-8 components.     

用鼻唇沟皮瓣修复鼻部分缺损

目的探讨鼻唇沟皮瓣修复各类鼻部分缺损的方法。方法本组共11例。其中肿瘤切除术后致鼻部分缺损7例,鼻部皮内痣感染1例,鼻外伤致鼻部分缺损3例。均采用鼻唇沟皮瓣修复。其中1例鼻外伤后致鼻小柱、鼻尖及双侧鼻翼缺损,以双侧鼻唇沟皮瓣修复,其余均以单侧鼻唇沟皮瓣修复。结果本组8例同期修复,肿瘤切除后缺损直径为1.5～2.5cm术后一期愈合。3例外伤性鼻部分缺损同期修复1例,一期愈合;2例二期修复后延迟愈合。结论单侧鼻唇沟皮瓣能满足直径在2.5cm左右缺损修复的需要,对直径大于3cm面积的缺损,可考虑双侧鼻唇沟皮瓣。     

Assessment of skin absorption and irritation potential of arachidonic acid and glyceryl arachidonate using in vitro diffusion cell techniques.

Arachidonic acid (AA), a precursor of pro-inflammatory mediators, and its glycerin ester, glyceryl arachidonate (GA), are reportedly used in cosmetic products. In vitro skin penetration of AA and GA and GA's ester hydrolysis was determined in flow-through diffusion cells. AA penetration with human and rat skin was 19.5% and 52.3% of the applied dose respectively, a substantial amount of which remained in the skin at 24h. Similar penetration results were obtained with GA in human skin. However, GA penetration through cultured skin (EpiDerm) was 51% of the applied dose, almost all of which appeared in the receptor fluid. At least 27.8% of GA penetrating skin was hydrolyzed to AA. In vitro methods were used to assess skin irritation in diffusion cells. Skin irritation of AA, sodium lauryl sulfate (SLS), and Tween 80 was determined by changes in transepidermal water loss (TEWL), skin viability (3-(4,5-dimethylthiaxol-2-yl)-2,5-diphenyltetrazolium bromide, MTT, formation), and cytokine release (IL-1alpha). SLS irritation was much less pronounced in an emulsion versus an aqueous vehicle. No significant irritation was observed in vitro from AA in an emulsion. This work predicts that AA would penetrate human skin in vivo and that it could be formed in skin from topically applied GA.     

Regional and Individual Differences in Cutaneous Sensitivity to Chemical Irritants: Capsaicin and Menthol

Abstract

Regional and individual differences in sensory irritation produced by capsaicin and l-menthol were assessed in two experiments. Thresholds for irritation were measured on the forearm and cheek using a psychophysical method that combines a bilateral, forced-choice detection task with an intensity scaling task. Experiment 1 showed that thresholds on the cheek were higher than on the forearm for both chemicals; on average, thresholds were much lower for capsaicin than for menthol; there were large individual differences in thresholds for both chemicals on both sites; and capsaicin and menthol produced different qualities of sensation. In contrast to earlier findings, capsaicin failed to produce itching on either site. Experiment 2 showed that itching could be evoked on the forearm, but not the face, when capsaicin was applied in a single dose rather than in an ascending concentrations series, as it had been in experiment 1. It was hypothesized that the absence of itching in experiment 1 was due to a more rapid desensitization for itching compared to burning and stinging, and that the lack of itching on the cheek may reflect different chemosensory innervation on facial and forearm skin. Overall, the results demonstrate that psychophysical measurements can provide information about regional and individual differences in the susceptibility to sensory irritation from contact with environmental chemicals.     

Perioral dermatitis -- the role of nasal steroids

We present two patients with allergic rhinitis who developed perioral dermatitis (PD) after initiating intranasal steroid spray. Both patients had been previously misdiagnosed as having contact or seborrheic dermatitis, and therefore inappropriately and unsuccessfully treated with topical steroids. Physicians should be aware of this potential side effect of intranasal steroids to avoid incorrect therapeutic measures. In the setting of nasal steroids use, PD probably is an under-reported and commonly misdiagnosed condition that should be thought when a patient treated with nasal steroids present with small erythematous papules, papulovesicles, and papulopustules occurring against a background of redness, beginning in the nasolabial areas and spreading rapidly to the perioral zone.     

Subclinical, non-erythematous irritation with an open assay model (washing): sodium lauryl sulfate (SLS) versus sodium laureth sulfate (SLES).

Compared to exaggerated hand washing procedures, an open non-exaggerated assay better approximates consumer surfactant use. Our goal was to observe skin surface modifications induced by an open test with regard to discriminating between surfactant solutions. This human in vivo assay provided information about the effect of only three washes at the laboratory and a week of at-home use. Dorsal hand and volar forearm were compared. The results demonstrated that this clinical model permits exploration of subclinical surfactant-induced irritation. Both the volar forearm and the dorsal hand are capable of discriminating between the effects of sodium lauryl sulfate (SLS) and sodium laureth sulfate (SLES). Squamometry proved to be a sensitive assessment technique for detecting surfactant-induced subclinical skin surface alterations and for differentiating surfactant effects in this open application assay, in as few as three washes.     

Use of AbobotulinumtoxinA for Cosmetic Treatments in the Neck,and Middle and Lower Areas of the Face: A Systematic Review

AbobotulinumtoxinA (aboBoNT-A) has been used for various cosmetic purposes, including minimization of moderate to severe lines, or other cosmetic indications, in the face and neck. We carried out a systematic review to identify all relevant evidence on the treatment approaches and outcomes of aboBoNT-A as a cosmetic treatment of the middle and lower areas of the face, and the neck. Embase, MEDLINE, Cochrane Library, congress proceedings and review bibliographies were searched for relevant studies. Identified articles were screened against pre-specified eligibility criteria. Of 560 unique articles identified, 10 were included for data extraction (three observational studies, 1 randomized controlled trial [with two articles] and five non-randomized trials). The articles provided data on gummy/asymmetric smile (2), marionette lines (5), masseter muscle volume (2), nasal wrinkles (2), perioral wrinkles (3) and the platysma muscle (4). All articles reporting on efficacy of aboBoNT-A demonstrated positive results, including reduction of wrinkles (5), reduction of masseter muscle (2) and degree of gummy smile (1) compared with before treatment. No serious adverse events were reported and patient satisfaction was high. In conclusion, positive findings support further research of aboBoNT-A for the middle and lower areas of the face, and in the neck, which are largely unapproved indications.     

皮瓣移植修复耳鼻部皮肤缺损

目的探讨皮瓣移植修复耳鼻部皮肤缺损的作用。方法采用鼻唇沟皮瓣、额正中皮瓣、耳廓复合组织瓣、耳后皮片及颈部皮片重建耳鼻部皮肤缺损16例。结果16例皮瓣全部存活。结论皮瓣应用于耳鼻部皮肤缺损的修复，成功率高，效果良好。     

Percutaneous absorption of capsaicin,nonivamide and sodium nonivamide acetate from gel and ointment bases: In vitro formulation evaluations in pigs and in vivo bioengineering methods in humans

Nonivamide (NVA) and non-pungent sodium nonivamide acetate (SNA) are synthetic derivatives of capsaicin. In this study, in vitro formulation evaluations in pigs and in vivo bioengineering methods in humans were performed to obtain the information on percutaneous absorption for capsaicin, NVA and SNA. After the consideration of penetration capacity, skin irritation and physicochemical properties of the formulations in vitro, 0.6% Carbopol 940® gel form for capsaicin and NVA as well as 3.8% isopropyl myristate-added hydrophilic o/w ointment for SNA were utilized to study the following in vivo test in humans. In the study of in vivo surface recovery techniques, SNA showed an equivalent therapeutic capability to that of NVA after calculation of the antinociceptive index. After the quantification of skin erythema by laser Doppler flowmetry (LDF), capsaicin caused more severe irritation than NVA in humans. In addition, SNA showed no skin irritation, toxicity and pungent sensation. The transepidermal water loss (TEWL) values were determined using an evaporimeter. A comparison of the gel form showed there was significantly higher TEWL AUC values in capsaicin and NVA than in the control group. The AUC value of the hydrophilic ointment control group was significantly higher than that of the gel control group. The reason was that isopropyl myristate and sodium laurylsulfate, two additives incorporated in the hydrophilic base, could cause slight skin irritation resulting in the increase of TEWL. The results of this study suggest that SNA possesses potent antinociceptive activities after transdermal application. Furthermore, SNA can be used extensively in clinical therapy because it avoids any pungent skin sensation and burning pain to improve patients' compliance.     

Novel transdermal delivery of Timolol maleate using sugar esters: Preclinical and clinical studies

The feasibility of matrix controlled transdermal patch based on sugar fatty acid ester (SE) as penetration and absorption enhancer containing Timolol maleate (TM) was investigated. The influence of fatty acid type, chain length and hydrophile-lipophile balance (HLB) on the in vitro drug release as well as its permeation across hairless rat skin were studied and compared aiming to select a patch formula for clinical performance. Skin irritation induced by SE patch was evaluated by visual scoring, color reflectance measurements and non-invasive transepidermal water loss (TEWL) technique. The results indicated that among different SEs tried, laurate SE with shorter fatty acid chain length and higher HLB value significantly increased the amount of TM liberated from the patch (99 ± 2.1%) and its permeation across rat skin (86 ± 4.3%). The total drug permeation and flux values were approximately 5-fold greater compared to SE free patch. The extent of absorption of TM-SE patch expressed by AUC was 64% larger as compared to the oral solution with steady plasma concentration over 18 h and relative bioavailability (F_rel) of 163%. The developed patch was well tolerated by all the subjects with only moderate skin irritation, which was recovered in 24 h after patch removal. The results are very encouraging and offer an alternative approach to maintain higher, prolonged and controlled blood level profile of the drug over 18-24 h.     

Solid lipid nanoparticles-loaded topical gel containing combination drugs: an approach to offset psoriasis

Aim: The primary aim of present work was to develop effective combination drug therapy for topical treatment of psoriasis.

Methods: Betamethasone dipropionate and calcipotriol loaded solid lipid nanoparticles (CT-BD-SLNs) were prepared by hot melt high shear homogenization technique, which were then incorporated in Carbopol gel matrix. The anti-psoriatic potential was tested by sequential in vitro (skin permeation and dermal distribution, anti-proliferative effect in HaCaT cells) and in vivo (Draize patch irritation, transepidermal water loss (TEWL) and anti-psoriatic mouse tail studies) experiments.

Results: A negligible amount in receptor compartment, yet confined distribution of drugs to epidermal and dermal region of skin was observed in case of SLNs, which is essential for safe and effective anti-psoriatic therapy. Draize patch test and TEWL demonstrated negligible skin irritation and better skin tolerability of SLNs. The in vitro HaCaT cell line study demonstrated that SLNs delayed the abrupt growth of keratinocytes, while in vivo mouse tail model showed that SLNs gel significantly decreased the epidermal thickness and increased melanocyte count in comparison to commercial Daivobet® ointment.

Conclusions: The developed SLNs gel is expected to be potential strategies for treatment of psoriasis and other topical diseases.