Acute irritant threshold correlates with barrier function, skin hydration and contact hypersensitivity in atopic dermatitis and rosacea

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Errata

This article is corrected by:

  1. Errata: Corrigendum Volume 23, Issue 1, 78, Article first published online: 30 December 2013

Abstract

The aim of the study was to disclose interactions between epidermal barrier, skin irritation and sensitization in healthy and diseased skin. Transepidermal water loss (TEWL) and stratum corneum hydration (SCH) were assessed in adult patients with atopic dermatitis (AD), rosacea and healthy controls. A 4-h patch test with seven concentrations of sodium lauryl sulphate was performed to determine the irritant threshold (IT). Contact sensitization pattern was revealed by patch testing with European baseline series. Subjects with a lower IT had higher TEWL values and lower SCH. Subjects with positive allergic reactions had significantly lower IT. In AD, epidermal barrier deterioration was detected on both volar forearm and nasolabial fold, while in rosacea, impeded skin physiology parameters were observed on the facial skin only, suggesting that barrier impediment is restricted to the face in rosacea, in contrast with AD where the abnormal skin physiology is generalized.

Background

Epidermal barrier impairment observed in certain dermatoses hinders the protective skin function against irritants and allergens [1]. Loss of function mutations in the gene encoding for filaggrin in atopic dermatitis (AD) patients results in impaired permeability barrier [2]. Filaggrin mutations have been linked to increased susceptibility to chronic irritant dermatitis [3] and contact allergy to haptens such as nickel [4]. Irritancy plays an important role in the development of contact cutaneous hypersensitivity. A ‘danger’ hypothesis was proposed, according to which allergen-contact will sensitize only in the presence of a danger signal – typically irritant stimulus or minor trauma [5, 6]. Impaired barrier function was observed in dermatoses previously not linked to a barrier defect. This abnormality could result from increased stratum corneum tryptic enzyme activity, for example in rosacea patients [7, 8].

Questions

We assessed epidermal barrier function and SCH in relation to skin irritation threshold to different concentrations of sodium lauryl sulphate (SLS), and the contact sensitization in subjects with AD, rosacea and healthy individuals. We hypothesize that there is a link between barrier impairment and the susceptibility to contact sensitization, which can be established via testing the acute irritant threshold (IT) to SLS. We were further interested in analysing whether this would be a local or generalized phenomenon.

Design

Thirty-one subjects with active mild-to-moderate AD, 28 age-matched subject with erythema-telangiectatic rosacea and 32 age- and sex-matched healthy subjects with no history of present or past skin and systemic disease were recruited.

Basal epidermal barrier functions as TEWL and SCH were assessed by non-invasive biophysical measurements at two anatomical sites – volar forearm and nasolabial fold. The measurement sites were free of disease lesions.

Twenty microliters of SLS in distilled water (20%, 10%, 5%, 2.5%, 1%, 0.5% and 0.1%). was pipetted on filter paper disc in a Finn chamber (diameter 8 mm) for each concentration. The chambers were attached to the upper inner arm for 4 h. The IT was assessed as the lowest concentration of SLS to which the subjects reacts with a homogenous erythema 24 h after application. Patch testing was performed with European baseline series according to the protocols of the International Contact Dermatitis Research Group [9].

Results

Baseline TEWL and SCH values are presented in Figs 1 and 2. TEWL was significantly higher on the volar forearm in AD in comparison with both rosacea (P < 0.001) and healthy subjects (P < 0.001). TEWL values from the nasolabial fold were higher in AD compared with healthy (P < 0.001). TEWL was higher in rosacea than healthy (P = 0.127) and lower in comparison with AD (P = 0.070) without reaching statistical significance.

Figure 1.

Epidermal permeability barrier function under basal conditions. At nasolabial fold, atopics show significantly higher values in comparison with healthy subjects. At volar forearm, the atopic dermatitis group shows significantly higher values versus rosacea and healthy subjects. Transepidermal water loss values are expressed in g/m².h as mean ± SEM. ***P < 0.001.

Figure 2.

Stratum corneum (SC) hydration under basal conditions. At nasolabial fold, atopic dermatitis and rosacea patients show significantly lower values as healthy subjects. On the volar forearm, atopic dermatitis patients show significantly lower values than rosacea patients and healthy subjects. The corneometric values are expressed in arbitrary units (A.U.) as mean ± SEM. ***P < 0.001.

Stratum corneum hydration was lower on the forearm in AD than in rosacea (P < 0.001) and healthy subjects (P < 0.001). In the nasolabial fold, lower corneometric values were observed in AD (P < 0.001) and rosacea individuals (P < 0.001) compared with healthy. Age and skin phototype had no influence on the skin barrier parameters (P > 0.05; data not shown). Gender only mildly influenced TEWL values on the forearm, because males (23.6 ± 1.8 g/m2 h) had slightly higher TEWL values than females (19.4 ± 0.9) on the nasolabial fold (P = 0.02).

Negative correlation was detectable between IT values and TEWL at both, volar forearm (ρ = −0.343; P = 0.001) and nasolabial fold (ρ = −0.340; P = 0.001), which means higher TEWL values correlated with a lower IT. SCH was positively correlated with IT at the volar forearm (= 0.266; P = 0.01) but not to the values obtained from nasolabial fold (= −0.074; P = 0.483). Age, gender and skin phototype did not influence the IT (all P > 0.05; data not shown). Lower IT was observed in patients with AD (P < 0.05) compared with healthy subjects. No difference was observed between rosacea patients and healthy individuals (P = 0.277).

Contact sensitization pattern is depicted in Table S1. No difference between the three groups in the number of positive subjects could be found (P > 0.05). However, the total number of positive reactions was two times higher in AD than in healthy and three times higher than in rosacea. Gender and skin phototype did not differ between patch positive and negative subjects, while the mean age of patch positive subjects (32.3 ± 8.9) was lower than the one of the patch negative subjects (41.4 ± 13.1), (P = 0.04). Patch test positive subjects had significantly lower IT than the patch negative patients (P = 0.021). Table S2 summarizes the patch test results and IT values.

The presence of active dermatitis provokes barrier impediment at sites of uninvolved skin distant from the lesions in AD [10-12]. These observations were confirmed by this study (Fig. 1). We showed enhanced susceptibility to SLS (lower IT) and exceeding number of positive allergic patch test reactions (nickel being the most common allergen) in AD patients in comparison with rosacea and healthy subjects. The impaired barrier function facilitates the penetration of allergens and together with irritant ‘danger’ stimuli contributes to the development of contact hypersensitivity. Deteriorated barrier function and decreased SCH were evidenced in subjects with rosacea. In contrast to AD patients, these discrepancies were only notable on the nasolabial fold but not on the forearm. The biophysical abnormalities were observed only in close proximity to the diseased site indicating that rosacea as an inflammatory disease is not generally related to an impaired barrier function unlike AD. No generalized skin hyper-reactivity could be shown for rosacea as witnessed by the similar IT pattern to one of the healthy subjects (P = 0.277). Therefore, one can assume that skin physiology deteriorations are a consequence of the inflammation in rosacea. A certain limitation of our study is that it is inconclusive whether the local increased skin dryness and barrier impairment are the proceeding or are already existent when the inflammation in rosacea begins. Rosacea patients showed no statistical differences in IT and sensitization patterns in comparison with healthy individuals, suggesting the locally restricted skin hyper-reactivity to the face. In our model, the IT test was able to distinguish between the localized (facial) and generalized (AD) skin hyper-reactivity.

Acknowledgements

Razvigor Darlenski performed the research, designed the research study, contributed essential reagents or tools, analysed the data and wrote the manuscript. Jana Kazandjieva and Nikolai Tsankov performed the research, designed the research study and contributed essential reagents or tools. Joachim W. Fluhr designed the research study, contributed essential reagents or tools, anlalysed the data and wrote the manuscript.

Conflict of interests

The authors have declared no conflicting interests.

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