Combination therapy improves the recovery of the skin barrier function: an experimental model using a contact allergy patch test combined with TEWL measurements.

BACKGROUND: Nickel (Ni) allergic contact dermatitis (ACD) alters the skin barrier. OBJECTIVE: Our aim was to compare the efficacy of combination therapies on ACD, using a topical corticosteroid and a corneotherapy agent (barrier cream), with that of a single therapy with corticosteroids. METHODS: On day 1, 3 Ni test patches were applied on each forearm of 14 Ni-patch-test-positive females. Four contained 5% Ni and 2 physiological saline. Either topical corticosteroid or barrier cream were matched with the combination of both products on 3 of the 4 Ni ACD. The fourth was not treated. Clinical scoring, transepidermal water loss (TEWL) and stratum corneum (SC) capacitance were measured before (day 1) and after (days 4-8) ACD. RESULTS: The combination therapy showed a significant decrease in TEWL values and an increase in SC capacitance. CONCLUSION: Combining a topical corticosteroid with corneotherapy agents prevents the delay in the healing process of skin barrier disruption due to ACD.     

Evaluation of efficacy of a skin lipid mixture in patients with irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: a multicenter study

Disturbances of skin barrier function occur in several skin diseases, e.g., atopic dermatitis (AD), irritant/allergic contact dermatitis (ICD, ACD). Skin barrier damage triggers the production of cytokines that stimulate lipogenesis which may also cause inflammatory processes. The aim of this study was to evaluate the efficacy of a topical skin lipid mixture in the treatment of ICD, ACD and AD. 580 consecutive patients suffering from ICD, ACD or AD were treated with a skin lipid mixture containing ceramide-3 and patented nanoparticles. Patients received the lipid mixture alone or in combination with topical corticosteroids until clearance or for 8 weeks. Both treatment groups statistically improved all parameters considered at week 4 and 8 as compared to baseline. Between the 2 treatment groups, there was a statistically significant difference in favour of combined therapy for (ICD, ACD, AD, respectively): erythema, pruritus and overall disease severity; erythema and pruritus; erythema, pruritus, fissuring and overall disease severity. No statistically significant difference was found for (ICD, ACD, AD, respectively): dryness, scaling and fissuring; scaling, fissuring and overall disease severity; dryness and scaling. Between the 2 ACD treatment groups, there was a statistically significant difference in favour of the skin lipid mixture for dryness. In conclusion, the study shows that balanced lipid mixtures are effective in improving barrier properties and the clinical condition of the skin in contact dermatitis.     

Effect of a topical corticosteroid, a retinoid and a vitamin D3 derivative on sodium dodecyl sulphate induced skin irritation

Exposure of the skin to sodium dodecyl sulfate (SDS) leads to disruption of barrier and skin irritation. We used repetitive short exposure to a low molarity SDS solution as an in vivo model to mimic the development of irritant contact dermatitis. In this model, we studied clinical (erythema), functional (transepidermal water loss(TEWL)) and cell biological changes, 24 healthy volunteers were patch tested with SDS (0.2%) for 4 h a the day for 5 consecutive days. After removal of the patches, the exposed sites were treated 1 × daily either with a topical corticosteroid (triamcinolon acetoide cream 0.05%). a retinoid (tretinoin cream 0.025%). or a vitamin D₃ derivative (calcipotriol ointment 50 microgram/g). Irritant reactions were assessed by erythema scoring and measurement of barrier function with TEWL up to 14 days after the first challenge. Skin biopsies were taken for cell biological changes at day 4. Vehicle-treated sites served as controls. Repetitive exposure of human skin to SDS resulted in a gradual increase in erythema scoring and TEWL associated with the upregulation of proliferative cells as measured by the expression of Ki-67-antigen and of differentiation markers, visualized by increased expression of involucrin and epidermal-fatty-acid binding protein (E-FABP). Skin irritation as assessed by erythema scoring and TEWL was not significantly suppressed by triamcinolone cream. However, a significant reduction of the number of cycling keratinocytes and a decrease in involucrin positive cell layers was observed in this group. Neither treatment with calcipotriol ointment nor with tretinoin cream induced improvement of skin irritation as judged by visual scoring and TEWL. In contrast to steroid treatment no significant elf eel of calcipotriol ointment or tretinoin cream treatment was observed with regard to the number of cycling cells and differentiation markers. Further studies are needed to assess whether treatment with topical corticosteroids is an effective modality in skin irritation and irritant contact dermatitis.     

Barrier recovery and influence of irritant stimuli in skin treated with a moisturizing cream

Moisturizers are used daily by many people to alleviate symptoms of clinically and subjectively dry skin. Recent studies suggest that certain ingredients in creams may accelerate the recovery of a disrupted barrier and decrease the skin susceptibility to irritant stimuli. In the present single-blind study, a moisturizing cream was tested for its influence both on barrier recovery in surfuctant-damaged skin and on the susceptibility of normal skin to exposure to the irritant sodium lauryl sulphate (SLS). Parameters measured were transepidermal water loss (TEWL) and skin corneometer values, indicating degree of hydration. Treatment of surfactant-damaged skin with the test cream for 14 days promoted barrier recovery, as observed as a decrease in TEWL. Skin corneometer values also normalized more rapidly during the treatment. In normal skin, use or the test cream significantly reduced TFWL after 14 days of treatment, and irritant reactions to SLS were, significantly decreased. Skin corneometer values increased after only 1 application and remained elevated after 14 days. In conclusion, the accelerated rate of recovery of surfactant-damaged skin and the lower degree of SLS-induced irritation in normal skin treated with the test cream may be of clinical relevance in attempts to reduce contact dermatitis due to irritant stimuli.     

Occupational hand dermatitis in a tertiary referral dermatology clinic in Taipei

Occupational skin disease is one of the most common occupational diseases. The hand is the most frequent site of involvement in occupational skin disease. We interviewed and examined patients seen in the Contact Dermatitis Clinic of the National Taiwan University Medical Center, a tertiary referral center in Taipei City. For patients suspected of having allergic skin diseases, patch testing was carried out using the, European standard series and suspected allergens. Occupational hand dermatitis (OHD) WHS diagnosed according to medical history, work exposure, physical examination, and patch lest findings. 36% of patients seen were diagnosed as having OHD. Electronics, hairdressing. medical, chemical, and construction were the most important industries causing OHD. In the 16–1 patients with OHD. 58.5%. had irritant contact dermatitis (ICD) and 41.5% allergic contact dermatitis (ACD). Dorsal fingers, nail folds, and dorsal hands were most frequently involved in patients with ACD: dorsal fingers, volar fingers and fingertips were most frequently involved in those with ICQ Using logistic regression analysis, we were able to identify the most important clinical presentations that predicted the types of OHD. ACD versus ICD. Patients with atopic history and palm involvement were more likely to have ICD, and those with nail fold involvement more likely to have ACD. In patients with ACD, the most important allergens were dichromate. nickel, cobalt, fragrance mix, epoxy resin, thiuram mix, and p-phenylenediamine. In this study, we identified the important industries and causal agents for OHD. Future preventive measures focused on these industries and agents lo reduce OHD will be warranted.     

In vivo nickel allergic contact dermatitis: human model for topical therapeutics

Techniques to determine efficacy of topical agents on allergic contact dermatitis (ACD) may benefit from refinement. The aim of this study was to develop an in vivo human model system for the bioengineering and visual quantification of the effect of topical agents on nickel ACD, and to correlate ACD parameters. 14 nickel patch-test-positive subjects were included in a placebo-controlled, double-blind study after a pre-screening procedure with a standard diagnostic patch test with nickel sulfate in 54 healthy human volunteers. 5% nickel sulfate in petrolatum in a Finn Chamber was applied on forearm skin for 48 h to create a standardized dermatitis. Thereafter, the dermatitis was treated with a model topical agent and a placebo control while recording endpoint parameters daily for 10 days. Resolution was quantified with 4 parameters: visual scoring (VS), transepidermal water loss (TEWL) (Tewameter), skin blood flow volume (BFV) (laser Doppler flowmeter), and skin color (a* value) (Colorimeter). The model agent reduced cutaneous allergic reactions, especially on day 8 to 10, in comparison with the placebo control. A highly significant linear relationship exists among all parameters, except between a* and BFV. This model may provide robust biometrics for determining the efficacy of topical therapeutics on experimentally induced ACD.     

Efficacy of topical corticosteroids on irritant skin reactions

Topical corticosteroids are frequently used in the treatment of irritant contact dermatitis (ICD). The efficacy of this treatment has, however, not been thoroughly established, and experimental studies on the topic have provided conflicting results. The aim of the present study was to evaluate the effect of potent topical corticosteroids on experimentally-induced irritant skin reactions in a double-blind, vehicle-controlled study. 16 healthy volunteers had sodium lauryl sulfate patch tests symmetrically applied to the upper arms. After removal of patch tests, a potent topical cortico-steroid (betamethasone-17-valerate) was applied to the irritant skin reaction on one arm, while the corresponding vehicle was applied to the irritant skin reaction on the opposite arm 2 × daily for 7 days. Reactions were evaluated by measurement of transepidermal water loss (TEWL) and erythema. After 7 days, statistically significant lower values of TEWL and erythema were found in corticosteroid-treated, compared to the vehicle-treated, skin reactions. The results indicate that topical corticosteroids improve healing of ICD.     

Effect of different moisturizers on SLS-irritated human skin

Moisturizers are widely used to treat irritant contact dermatitis (ICD). Their use is, however, not well-documented and standardized models for testing skin care products are needed to acquire documentation of their efficacy. The present study was undertaken to evaluate the effect of 6 commonly-used moisturizers on the recovery of irritated human skin. No commercial interests were involved in the study. 36 healthy volunteers had patch tests with SLS 0.5% applied on their forearms/upper arms for 24 h. After irritation of the skin, all volunteers had a moisturizer applied on one forearm/upper arm, respectively, 3 x daily for the following 5 days. The other forearm/upper arm served as an untreated control. Each moisturizer was tested on 12 volunteers and each volunteer tested 2 moisturizers at the same time. Evaluation was done on days 1, 3 and 8 by transepidermal water loss, electrical capacitance, laser Doppler flowmetry, DermaSpectrometry and clinical scoring. All 6 moisturizers were found to accelerate regeneration of the skin barrier function when compared to irritated non-treated skin. The most lipid-rich moisturizers improved barrier restoration more rapidly than the less lipid-rich moisturizers. We suggest this experimental model for further moisturizer efficacy testing.     

Non-invasive evaluation of the kinetics of allergic and irritant contact dermatitis

Reflectance confocal microscopy (RCM) allows non-invasive visualization of human skin in vivo. It has been used to describe the histopathological features of acute contact dermatitis (CD). This work was designed to investigate the kinetics of both allergic and irritant CD (ACD and ICD) in vivo. Eighteen subjects with a prior diagnosis of ACD were patch tested with the specific allergen sodium lauryl sulfate as an irritant, and appropriate controls. RCM, transepidermal water loss (TEWL), and fluorescence excitation spectroscopy (FES) were performed at several time points within 2 wk after patch removal. After removal of the Finn chambers at 48 h, superficial epidermal changes, primarily involving the stratum corneum, and increased epidermal thickness were mainly present in ICD. ACD, on the other hand, showed microvesicle formation peaking at 96 h following patch removal. Both ACD and ICD showed exocytosis and similar degrees of spongiosis on RCM. TEWL and FES demonstrated a significant difference between ACD and ICD. RCM, TEWL, and FES are valuable non-invasive tools to quantitatively study the kinetics of the pathophysiology of acute CD reactions in vivo and monitor the changes at a cellular level.     

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

To examine the skin harrier 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 TCVV'L was observed in the patients with acute and with healed irritant contact dermatitis (ICD) as compared LO healthy volunteers ( P ≤ 0.01). TEWL values in both test areas were com parable and markedly correlated ( p ≤ 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 acme ICD was significantly higher ( P ≤ 0.01). than that of the group with healed ICD, but not for TCWL at the thigh suggesting that ICD may aggravate the barrier function of the adjacent involved skin. It is assumed, that increased basal TEWL in patients with ICD may relied 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.     

Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm)

Patients with atopic skin show a defective barrier function both in rough and in clinically normal skin, with an increasing risk of developing contact dermatitis. Moisturizing creams are often used in the treatment of dry skin. The purpose of this study was to investigate the influence of treatment with a urea-containing moisturizer on the barrier properties of atopic skin. Fifteen patients with atopic dermatitis treated one of their forearms twice daily for 20 days with a moisturizing cream. Skin capacitance and transepidermal water loss (TEWL) were measured at the start of the study and after 10 and 20 days. On day 21 the skin was exposed to sodium lauryl sulphate (SLS) and on day 22 the irritant reaction was measured non-invasively. Skin capacitance was significantly increased by the treatment, indicating increased skin hydration. The water barrier function, as reflected by TEWL values, tended to improve (P = 0.07), and the skin susceptibility to SLS was significantly reduced, as measured by TEWL and superficial skin blood flow (P < 0.05). Thus, it seems that certain moisturizers could improve skin barrier function in atopics and reduce skin susceptibility to irritants. The mechanism and the clinical relevance need further investigation.     

The effect of two moisturisers on skin barrier damage in allergic contact dermatitis

Nickel (Ni)-induced allergic contact dermatitis (ACD) was performed in human volunteers to study the role of moisturisers in preventing ACD-related skin barrier damage. 15 Ni-sensitive females (mean age: 29.5 years; range: 23-38) were included. On days 1, 21, 24 and 26, TEWL, stratum corneum (SC)-capacitance and clinical score were evaluated on four test sites on the right and left forearms. Both a highly and a poorly hydrating moisturising formulation were applied on two sites from days 1 to 21, after which Ni-ACD was induced on the 2 pre-treated sites and one non-treated area. On day 24, TEWL values were significantly increased on the site pre-treated with poorly hydrating product compared to the rich formulation pre-treated site. SC-hydration was significantly improved on the latter site on days 21, 23 and 26. Long-term use of inadequate moisturiser increases skin barrier damage due to Ni-ACD.     

Olopatadine hydrochloride accelerates the recovery of skin barrier function in mice

BACKGROUND: 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. OBJECTIVES: To investigate the effects of olopatadine and a steroid on the recovery of skin barrier function after barrier disruption in mice. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

The efficacy of different moisturizers on barrier recovery in hairless mice evaluated by non-invasive bioengineering methods

Moisturizers (emollients) are used frequently on normal and diseased skin. However, only few studies have examined their effects in dynamic situations and in more clinically relevant settings. We evaluated the effect of 4 commonly used products in a hairless mice model after acute skin barrier perturbation with acetone. The efficacy was evaluated by measurement of the transepidermal water loss (TEWL) and electrical conductance at various time intervals during barrier repair. The test products were compared with acetone-treated air-exposed controls allowed to recover otherwise normally and with a known irritant product, chlorhexidine cream 1%. Locobase® was the most effective product in correcting barrier function and significantly improved barrier function during early stages of barrier recovery (<6 h) with out interfering with late stages of barrier recovery (>6 h). The irritant control product, chlorhexidine cream 1%, delayed barrier recovery in the late stages. The model makes it possible to evaluate the combined effects of exogenous and endogenous components on barrier repair and to select the potentially most effective products before perforating more cumbersome and time-consuming field studies.     

Less skin irritation from alcohol-based disinfectant than from detergent used for hand disinfection

BACKGROUND: The benefit of alcohol-based disinfectant used on normal skin has been debated. OBJECTIVES: The objective of the present study was to compare the effects of repeated exposure to an alcohol-based disinfectant, a detergent and an alcohol-based disinfectant/detergent alternately for 10 days, including noninvasive measurements in the evaluation. Skin reactivity in irritated skin after a 4-week interval was also evaluated. MATERIALS AND METHODS: Detergent, disinfectant and alternate disinfectant and detergent were applied twice daily every 10 min for 1 h to the ventral upper arms and forearms of 17 healthy volunteers. A control area was included. After 4 weeks an SLS patch was applied to each area. Irritant reactions were quantified with a visual score recording and measurements of transepidermal water loss (TEWL) and skin colour were performed on days 1, 5, 11, 38 and 40. RESULTS: On day 5 the detergent caused a higher visual score than either disinfectant applied alone or alternate disinfectant and detergent, P < 0.05. On day 11 detergent and alternate disinfectant and detergent caused a higher score than disinfectant, P < 0.05. An increased irritant response for detergent compared with disinfectant alone and alternate disinfectant and detergent was confirmed by TEWL evaluations on days 5 and 11, P < 0.001, while no significant difference was found by colour measurement. After 4 weeks, when evaluated by colour measurement, significantly less response to the SLS patch was found on the disinfectant-treated area compared with the control area and detergent area, and a similar trend was found for TEWL, although it was not statistically significant. CONCLUSION: Alcohol-based disinfectant caused less visible skin irritation and less skin barrier disruption than the use of detergent. The alternate use of detergent and disinfectant caused less irritation than the use of detergent, and a possible interaction between the two irritants was not indicated. After 4 weeks there was a tendency for decreased skin reactivity in the skin areas which had 4 weeks previously been exposed to disinfectant.     

Repair of acetone- and sodium lauryl sulphate-damaged human skin barrier function using topically applied emulsions containing barrier lipids

BACKGROUND: It is generally acknowledged that well-formulated moisturizing skin care products can restore disturbed barrier function that can be assessed by transepidermal water loss (TEWL) measurements. When ceramides and/or other barrier lipids are incorporated, it is, however, not always clearly demonstrated which ingredients of the formulation exert the beneficial effects. OBJECTIVES: In this study the effects of topically applied ceramide-containing mixtures on the barrier repair of sodium lauryl sulphate (SLS)- and acetone-induced skin damage have been studied in human volunteers. TEWL and stratum corneum hydration measurements were carried out. The emulsions applied contained either a mixture of two types of ceramides, CerIII and CerIIIB (emulsion 1) or a complete mixture of ceramides III, IIIB and VI together with phytosphingosine, cholesterol and the free fatty acid linoleic acid (emulsion 2). RESULTS: After SLS damage, it was observed that barrier recovery was significantly accelerated by topical application (14 days, 2 x/d) of emulsion 2 compared with the results obtained with emulsion 1. Corneometrical results were not relevant due to the occurrence of scaly fissured skin, failing to provide a good skin/probe contact. Although no effect on TEWL could be observed, the improvement of skin hydration after acetone treatment and a single application of the emulsions, was significantly more positive for emulsion 2 than for emulsion 1. CONCLUSIONS: The investigative methods used in this study show that ceramides combined with other skin lipids can improve barrier repair after damage.     

Efficacy of topical corticosteroids in nickel-induced contact allergy

In this study we used the nickel contact allergy patch (CAP) test to investigate the effect of topical corticosteroids on allergic contact dermatitis (ACD). On day 1, three CAP tests were applied for 48 h on the forearms of 20 female volunteers with a known nickel ACD. CAP of the right forearm contained 5% nickel, and of the left forearm physiological saline. Clinical scoring, transepidermal water loss and skin hydration were measured on day 1 before CAP application, on day 4 (0, 2 and 6 h) after ACD and from days 5 to 8 (0 h). A topical corticosteroid and its vehicle were applied twice daily starting from day 4 on two ACD sites. Transepidermal water loss values were significantly decreased on the topical-corticosteroid-treated sites in the early phase of ACD (day 4, 6 h after the first application) while clinical efficacy showed significant improvement on days 7 and 8. The vehicle was found to improve skin hydration only on day 8. In conclusion the topical corticosteroid improved the skin barrier function in the early inflammatory phase of ACD (day 4, 6 h). The lack of improvement in transepidermal water loss in the later phase of ACD might be accounted for by the secondary effects of the corticosteroid on proliferation and differentiation of keratinocytes.     

Claim substantiation and efficiency of hydrating body lotions and protective creams

In the present work a practical claim substantiation study is shown by the example of 5 commercially available body lotions. Their efficacy with respect to effects on transepidermal water loss (TEWL) and stratum corneum (SC) hydration of ageing skin has been examined. Results were obtained after single and repeated application (14 days, 2 x a day). The best performing product was then selected and further tested for its potential effects on sodium lauryl sulfate (SLS)-damaged skin. This was done in a younger population and the recovery of the impaired barrier function was followed by TEWL measurements. The selected body lotion had a high efficacy, improving both the TEWL and SC hydration of ageing skin by more than 30%. When applied to SLS-damaged skin, the product was able to improve skin barrier repair in comparison with physiological barrier repair. The results of this study show that a combination of non-invasive objective measurements can be used to substantiate product claims. Claims can be made with respect to protective and preventive properties of products, but also as to effectiveness of topical skin treatment in the case of abnormal barrier function or barrier restoration.     

Instrumental evaluation of subclinical responses to 0.05% NiSO4 patch tests

Background/aims : The possibility of identifying allergic reactions while they are not clinically evident could prove extremely useful in studying the evolution of skin responses in experimentally-induced contact dermatitis. In drug research and in cosmetological research, the sensitizing properties of new molecules or haptens present in the product in a low concentration also need be clarified. The object of the present study was to validate noninvasive techniques and their use for the study of subclinical allergic reactions.
Methods : 70 nickel-sensitized subjects previously standard tested with 5% nickel sulphate in petrolatum were challenged with a 0.05% nickel sulfate solution on the volar aspect of the forearm, application for 24 h and measurement at 72 h. Colorimetry, evaporimetry (transepidermal water loss, TEWL) and high-frequency echography were used to characterize reactions.
Results : Colorimetry and TEWL did not show any significant differences between patch test areas and control areas. Skin thickness determination, conversely, evidenced a significant increase both with respect to baseline values and control areas.
Conclusion : Echographic evaluation is able to detect modification of skin thickness of subclinical allergic patch test reactions to nickel sulfate while colorimetry and TEWL failed to detected such minute changes.     

Thimerosal positivities: the rôle of SH groups and divalent ions

The clinical efficiency of mitigating contact dermatitis with a Ginkgo biloba extract and carboxyme-thyl-β-1,3-glucan formulation was investigated in a double-blind versus placebo study using 22 subjects (Caucasian women aged 22–55 years) with allergic contact dermatitis from various substances in the European standard series. The formulation was applied to intact skin 2× a day for 2 weeks ("in use" application) prior to a single application of a selected contact allergen under a Finn Chamber for 24 h. Readings were carried out in a blind study by a dermatologist 2 and 3 days after patch removal. Representative photographs were taken of treated, placebo and untreated test areas. 68.2% of the panelists showed significantly reduced skin reactivity ( p = 0.037*) on the treated site 2 days after patch removal, versus untreated and/or placebo sites. This finding indicates that the Ginkgo biloba /carboxymethyl-β-1,3-glucan formulation can mitigate against allergic contact dermatitis.