Effects of impermeable and semipermeable glove materials on resolution of inflammation and epidermal barrier impairment after experimental skin irritation

Semipermeable membranes might be suitable for glove liners or comfort gloves in individuals with irritant contact dermatitis (ICD).

contribute to development or worsening of ICD. 3 These findings are particularly important for professions in which long glove wearing times and exposure to detergents are common, such as healthcare workers, food handlers or cleaning staff. Therefore, the use of glove linersdefined as a separate glove-like hand covering-made of cotton (COT) underneath impermeable protective gloves is frequently recommended to counteract effects of glove occlusion and prevent hand dermatitis by trapping the moisture. [4][5][6][7][8] Beneficial effects of COT gloves on the skin barrier function have been shown in various studies. [9][10][11][12][13][14][15][16] However, when COT glove liners are worn for a longer period of time, the absorbed sweat causes a saturation effect. Thus, a regular change of COT glove liners is necessary, especially in individuals suffering from hyperhidrosis.
Glove liners made of semipermeable materials may serve as alternative to COT glove liners in reducing occlusion effects of impermeable protective gloves. 9,11,12,[17][18][19][20][21] Sympatex (SYM, Sympatex Technologies GmbH, Unterföhring, Germany) is a polyesterpolyether based semipermeable compact membrane which is selectively permeable, that is, water vapour of human sweat permeates along the diffusion gradient from the skin surface through the membrane, whereas liquids such as water are prevented from penetrating through the membrane from the outside. [22][23][24] When a semipermeable membrane is used as glove liner material, the moisture evaporating from the skin surface is considered to permeate through the membrane and remain in the gap between the glove liner and the impermeable protective glove or leak out via the cuff. 25 By reducing occlusion effects, semipermeable membranes may decrease skin irritation caused by wearing of impermeable protective gloves. 11,18,20,21 In addition, they may serve as a barrier against allergens released from the outer gloves (e.g., rubber accelerators). 26,27 Another application for gloves made of cotton or semipermeable membranes is their use as so-called 'comfort gloves' during the day or overnight by patients with hand dermatoses to cover the sensitive lesional skin, increase the efficacy of topical therapy, prevent smudges of ointments applied on the skin and as a protective barrier against scratching. [28][29][30][31][32] Previously, we demonstrated that gloves made of SYM are well accepted and tolerated as glove liners 12 or in combination with COT gloves as comfort gloves 33 in patients with hand dermatoses. Some preliminary studies suggest in addition that semipermeable membranes may enhance epidermal barrier regeneration after experimental skin irritation which seems to depend on the duration and frequency of application. 18,20,21,34 Therefore, we aimed to extent previous preliminary research by assessing the effect of semipermeable membranes made of SYM on resolution of inflammation and epidermal barrier impairment after experimental skin irritation when applied (i) alone to mimick the use as comfort gloves and (ii) in combination with occlusive glove material to mimick the use as glove liners. The results were compared with those of irritated skin covered with occlusive glove material alone, covered with a combination of COT and occlusive material, or uncovered irritated skin to assess the tolerability and effects of the different materials and to find out if SYM could serve as a good alternative to COT also glove liner material.

| Study population
Twenty-four healthy volunteers (5 males, 19 females) aged 20-60 years (mean: 31.4 years) without skin lesions on the hands and forearms were recruited for the study which took place in November and December 2016. Prior to study participation, a dermatologist checked for eligibility according to the inclusion and exclusion criteria (Table S1). Subjects were allowed to have contact to water (shower/bath) as usual but were instructed to avoid direct application of detergents, moisturizers, emollients or topical medications to their forearms 3 days before and during the study period and to avoid activities which induce strong sweating (e.g., sports) during the study period. All investigations were performed in accordance with the ethical principles for medical research involving human subjects documented in the World Medical Association Declaration of Helsinki. 35 All participants gave written informed consent. The study and the consent procedure were approved by the Ethics Committee of the Osnabrück University (reference 46/9).

| Test procedure
At baseline (T0), five test areas of 2.0 cm in diameter were marked in equal distance to each other on clinically normal skin of each volar forearm ensuring a 4 cm distance to the wrist and to the cubital fossa ( Figure 1). For skin irritation, 60 μL of a 1% sodium lauryl sulfate (SLS) solution (analytical grade, purity >99%, Co. Merck KGaA, Darmstadt, Germany) dissolved in deionized water was applied to nine of the test areas which were then covered with large Finn chambers (12.0 mm diameter, SmartPractice Europe GmbH, Greven, Germany). One area on each forearm was left untreated. After 24 h (T1), the chambers were removed and four of the irritated test areas on each forearm were covered in randomized order with square patches (4.0 Â 4.0 cm) of different materials/combination of materials (Table 1). One remaining irritated area was left uncovered and served as control (CON). The patches of OCC or SYM were fixed with medical adhesive tape

| Transepidermal water loss
In all test areas, the SLS irritation led to an impairment of the epider-  (Figure 2; Tables S2-S4).

| Skin humidity
In all test areas, the skin irritation caused a slight decrease of SH from baseline (T0) to T1 (n.s.) and a significant further decrease after three

| Erythema
The inflammation led to a significant increase of a* values from baseline to T1 ( p < 0.001) in all irritated test areas. Except from the areas covered with OCC, the a* values in all other areas decreased significantly from T2 to T3 indicating beginning resolution of inflammation.
There were no significant differences between the test areas at any time point with only one exception: At T3, there was significantly less erythema in areas covered with SYM/OCC than with OCC (p = 0.004) (Tables S2-S4).

F I G U R E 4
Boxplot to compare the skin humidity-kinetics (SH) of irritated skin areas on the forearms covered for 8 h with Sympatex (SYM), Sympatex/vinyl (SYM/OCC), vinyl (OCC), cotton/vinyl (COT/OCC) and uncovered irritated skin areas. The bars represent the differences from baseline SH at different time points (T1-T4). The horizontal line in the middle of the box, whose lower and upper boundary lines are defined by the 25% quantile and the 5% quantile of the measured values, respectively, represents the position of the median. Symbols (stars) indicate significant differences at *p < 0.05; **p < 0.01 and ***p < 0.001 in comparison of material covers throughout the examination process. The figure illustrates that the areas covered with SYM/OCC showed significantly higher values than those covered with OCC alone and uncovered areas at T2, while the areas covered with COT/OCC showed significantly higher values than areas covered with SYM/OCC. At T3, the areas covered with OCC alone showed significantly lower values than all other areas.

| Skin surface pH
There were no significant differences in pH values between the test areas at any time, but three coverings with OCC, SYM/OCC or COT/OCC led to a significant increase of pH values (T1 vs. T2; Tables S2-S4).

| Clinical score
The VS of all irritated test areas increased significantly from baseline (T0) to T1 ( p < 0.001) indicating skin inflammation. Afterward, the VS of all test areas decreased continuously.
Only the VS of uncovered areas ( p = 0.003) and areas covered with COT/OCC ( p = 0.008) decreased significantly from T1 to T2.
The VS of areas covered with OCC only was the highest at T2, T3 and

| General aspects
In general, measurements of TEWL and SH represent the most common bioengineering methods to assess the epidermal barrier function. 45,46 Measurements of the pH may have additional value. 42,47 Skin inflammation is mainly assessed by measuring erythema (a*). 39 The VS was used as an additional typical instrument to assess inflammation. 48 As expected, the standardized skin irritation with SLS 1% The effects of semipermeable membranes (among them SYM and/or Gore-Tex) on resolution of inflammation and skin barrier impairments after experimental skin irritation (usually SLS 0.5% or 1% for 24 h) has already been investigated in a few small studies using short-term coverings 20,21 as well as long-term coverings. 11,18,34,51 Two studies additionally investigated the effects of semipermeable membranes underneath occlusive material. 11