Effect of a lipid-rich emollient containing ceramide 3 in experimentally induced skin barrier dysfunction

In the present study we compared the effect of a ceramide 3-containing emollient (Locobase(R) Repair) with a control emollient (vaselinum album/cremor lanette ana) and untreated damaged skin using clinical, bioengineering and immunohistochemical methods in two different models of experimentally induced skin barrier dysfunction. In model A (n = 13) skin barrier dysfunction was inflicted at three investigation sites by tape stripping. In model B (n = 13) the volunteers were patch tested at three investigation sites with sodium dodecyl sulphate (0.2%) for 4 h a day for 4 consecutive days. The investigation sites were treated once a day with the above-mentioned agents. Irritant reaction was assessed daily by erythema scoring and measurements of transepidermal water loss (TEWL). After 5D, punch biopsies were taken from all sites. Immunohistochemical assessment was carried out with respect to epidermal proliferation, epidermal differentiation and Langerhans cells. Tape stripping resulted in an erythematous reaction and an increase of TEWL associated with up-regulation of cycling cells, involucrin and expression of cytokeratin 16. At day 4, ceramide 3-containing emollient significantly decreased (p < 0.03) the erythema score, TEWL and cycling cells in comparison with the untreated site. Repetitive exposure to SDS induced a variable degree of erythema, gradual increase of TEWL, an increase of cycling cells, and up-regulation of involucrin, E-FABP and SKALP. The treatment with the control emollient significantly prevented erythema, increase of TEWL and cycling cells at day 4 compared to the untreated site. In summary, the present study demonstrated that both tested emollients improve skin barrier in different conditions compared to the untreated skin. There is some indication that formulations containing skin-related lipids might be of benefit in barrier disruption following tape stripping. Different models and clinical trials are needed to establish the usefulness in specific conditions of emollients containing skin-related lipids.     

Emollients in a propanol-based hand rub can significantly decrease irritant contact dermatitis

The objective of this study is to determine the effect of emollients in a propanol-based hand rub on skin dryness and erythema. In this prospective, randomized, controlled, double-blind trial, 35 subjects participated; of them approximately half were atopic (modified Erlanger atopy score > or =8). 2 propanol-based formulations were tested in a repeated open application test, 1 contained a mixture of emollients (0.81%, w/w). 2 aliquots of 0.7 ml of each formulation were applied twice per day over 2 weeks to the cubital fossa of each subject after random assignment of the preparations. Treatment areas were assessed before each application and 3 days postfinal application by visual inspection for erythema and dryness according to a standard scale. The sum score over all assessment time-points served as primary parameter. The mean sum score for erythema and dryness was significantly lower for the hand rub with emollients (0.8 +/- 2.4) in comparison with that for the hand rub without emollients (1.5 +/- 3.5; P = 0.022; Wilcoxon signed rank test). A comparison of the atopic and non-atopic subjects revealed no significant difference for any of the products (P > 0.05; Mann-Whitney U-test). It is concluded that the addition of emollients to a propanol-based hand rub can significantly decrease irritant contact dermatitis under frequent-use conditions.     

Novel treatment of chronic severe hand dermatitis with bexarotene gel

BACKGROUND: Hand dermatitis is an eczematous inflammation of the hands that is related to occupation or to routine activities. It often becomes chronic, and in some patients may become severe and disabling. Topical corticosteroids are effective treatment, particularly for milder forms, but they often lose effectiveness with time and can produce skin atrophy. OBJECTIVES: To evaluate bexarotene gel topical therapy for safety, tolerability and efficacy in patients with chronic hand dermatitis. METHODS: A phase I-II open-label randomized clinical study of bexarotene gel, alone and in combination with a low- and a mid-potency steroid, was conducted in 55 patients with chronic severe hand dermatitis at two academic clinics. RESULTS: Patients using bexarotene gel monotherapy reached a 79% response rate for > or = 50% clinical improvement and a 39% response rate for > or = 90% clearance of hands. Adverse events possibly related to treatment in all patients were stinging or burning (15%), flare of dermatitis (16%) and irritation (29%). Thirteen patients (24%) withdrew early, including two for related adverse events and five for inadequate response. CONCLUSIONS: Bexarotene gel appears to be safe, tolerated by most patients, with useful therapeutic activity in chronic severe hand 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.     

Sites of dermatitis in a patch test population: hand dermatitis is associated with polysensitization

Background  Sites of dermatitis in larger series of contact allergic patients are rarely reported. Increased risk of polysensitization has been linked only to stasis dermatitis and leg ulcers. However, a large proportion of polysensitized individuals may have dermatitis in other skin areas.
Objectives  To examine the site of dermatitis at time of first appearance in contact allergic individuals with special focus on the distribution of dermatitis in polysensitized individuals and to examine if widespread dermatitis is more frequent in polysensitized than in single/double-sensitized patients.
Methods  A matched case–control study was carried out including 394 polysensitized and 726 single/double-sensitized patients who responded to a postal questionnaire. All subjects were recruited from a hospital patch test population.
Results  The hands were the most frequent and the anogenital region was the least frequent skin area affected with dermatitis. Dermatitis on the hands/wrists [odds ratio (OR) 1·58], in the armpits (OR 1·56) and on the back (OR 1·91) was positively associated with polysensitization. The hands were the only skin area with dermatitis which maintained the association to polysensitization in two subpopulations consisting of, respectively, individuals with and without atopic eczema. Dermatitis on the scalp was negatively associated with polysensitization (OR 0·66) primarily for individuals without atopic eczema. The dermatitis did not seem to be more widespread in polysensitized compared with single/double-sensitized patients.
Conclusions  Special awareness in patients with hand dermatitis seems justified either to prevent development of multiple contact allergies or to document polysensitization as an aetiological factor.     

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.     

Efficacy of a barrier cream and its vehicle as protective measures against occupational irritant contact dermatitis

The actual advantage of barrier creams over bland emollients for skin protection is still hotly debated. In a randomized, double-blinded study, a newly-introduced barrier cream and its moisturizing vehicle were compared regarding their skin compatibility, efficacy and resulting acceptance. Thus, 2 panels of 25 hospital nurses with mild signs of skin irritation were asked to use 1 of the test products provided (verum or vehicle) over a period of 4 weeks. Effects of both types of preparations were studied weekly by clinical examination and the instrumental assessment of bioengineering parameters. Results showed no significant differences between barrier cream and vehicle. In both groups, clinical skin status improved and stratum corneum hydration increased significantly during the study period. Both preparations were tolerated and accepted well, thus showing both skin protection and skin care. These results contribute to the debate as to whether a strict distinction between "skin care" and "skin protection" products is justified. The vehicle alone is capable of positively influencing skin status. Emphasis must be laid on regular, frequent, and correct application of a product for it to be effective.     

Tacrolimus ointment in the treatment of occupationally induced chronic hand dermatitis

Background:  Occupational hand dermatitis (OHD) is a common and often chronic condition. Usage of topical corticosteroids is limited in long-term therapy because of potential side-effects. New treatment options are highly appreciated.
Objective:  To study efficacy and safety of tacrolimus in patients suffering from OHD.
Patients and Methods:  In a prospective, open, multicentre study, 29 patients with OHD of predominantly mild-to-moderate severity were treated with tacrolimus ointment (Protopic^® 0.1%) during a 4-week active treatment period with twice daily application followed by a 2-month optional treatment period. Efficacy was evaluated by the use of a standardized hand eczema score and by clinical severity rating, conducted on all study visits (screening, baseline and weeks 2, 4, 6, and 12). Adverse events were recorded for safety evaluation.
Results:  The hand eczema score declined significantly after 2 weeks of treatment compared with baseline and further declined until the end of the study. Finally, 12 (44%) patients were clear of hand eczema. Worsening of the dermatitis occurred in 2 patients (7%). Clinical grading indicated improvement too. Overall tolerability was good.
Conclusion:  Topical tacrolimus might be an efficacious treatment option for chronic OHD. Blinded and randomized controlled studies are necessary to confirm the results of this pilot study.     

Effect of dupilumab on hand eczema in patients with atopic dermatitis: An observational study

Systemic treatment options for chronic hand eczema are limited. Dupilumab is used in atopic dermatitis (AD) but is not licensed for (isolated) hand eczema. In this observational prospective study we aimed to determine the response of hand eczema to dupilumab in patients with AD. Adult patients with hand eczema and AD received dupilumab s.c. at a 600 mg loading dose, followed by 300 mg every 2 weeks. Primary outcome was a minimum improvement of 75% on the Hand Eczema Severity Index after 16 weeks (HECSI‐75). Secondary outcomes were severity, measured using the Photographic guide; quality of life improvement as patient‐reported outcome, measured using the Dermatology Life Quality Index (DLQI); and AD severity, measured using the Eczema Area and Severity Index (EASI). Forty‐seven patients were included (32 males; mean age, 45 years). HECSI‐75 was achieved by 28 (60%). Mean HECSI score reduction was 49.2 points (range, 0–164; 95% within‐subject confidence interval, 46.4–52.0), which was already significantly decreased after 4 weeks (P < 0.001). DLQI score mean improvement was 8.8 points (standard deviation [SD], 6.0) or 70.0% decrease (SD, 26.4) (P < 0.001). Eighteen patients (38%) were classified as responders on the Photographic guide. There was no difference in response between chronic fissured and recurrent vesicular clinical subtypes. Similar percentages of patients achieving EASI‐75 and HECSI‐75 were seen after 16 weeks. In conclusion, this study shows a favorable response of hand eczema to dupilumab in patients with AD. This raises the question whether a response will also be seen in isolated hand eczema.     

Ascertainment of hand dermatitis using a symptom-based questionnaire; applicability in an industrial population

In this study, the applicability of a symptom-based questionnaire on hand dermatitis was assessed in a population of rubber workers. The questionnaire was previously validated in a study among nurses. 224 subjects employed in 9 different companies completed a questionnaire on skin complaints. Subsequently, 202 workers attended the physical examination of the skin by a dermatologist. The ascertainment of skin complaints according to the questionnaire was compared to the medical evaluation. The 2 different diagnostic tools used for assessing dermatitis resulted in dissimilar estimates of the prevalence of active hand dermatitis, ranging from 6.9% to 38.1% of all workers. Using the medical evaluation as 'gold standard' we observed a moderate sensitivity and specificity (respectively 71.4%; 95% CI: 47.7-95.1 and 76.1%; 95% CI: 70.0-82.2), a low positive predictive value (18.2%; 95% CI: 8.0-28.4) and a high negative predictive value (97.3%; 95% CI: 94.7-99.9) for the classification based on the self-administered questionnaire. When evaluated against 'first symptoms of dermatitis' the sensitivity decreased, while the specificity remained almost the same. The deviant findings between the present and the original validation study of the same questionnaire among nurses hamper its applicability in populations with different occupations. Therefore, if questionnaires are to be used, validity studies have to be carried out to evaluate differences in perception of skin diseases between different (occupational) populations.     

Superiority of a vitamin B12‐barrier cream compared with standard glycerol‐petrolatum‐based emollient cream in the treatment of atopic dermatitis: A randomized,left‐to‐right comparative trial

Atopic dermatitis (AD) is a result of complex genetic, epigenetic, environmental, and immunological interactions with an overlapping epidermal barrier defect. The study evaluates the efficacy and tolerability of topical Vitamin B12‐barrier cream (MB12) compared with standard glycerol‐petrolatum‐based emollient cream (GPC) used three times a day for mild AD. The study was conducted as a on one hemi‐body randomized, controlled, single‐blind, intra‐patient left‐to‐right comparative trial by patients with clinical diagnosis of mild AD measured with total SCORAD index over 4 months. MB12 was compared on one hemi‐body treated (GPC). The comparisons of score values were performed primarily by using non‐parametric procedures: Mann–Whitney‐U test (for independent samples) and Wilcoxon test (for dependent samples). All 22 patients were randomized (left or right side treated with MB12 or GPC). At week 12 a reduction from baseline in SCORAD index was assessed in both body sites with 77.6% SCORAD index reduction in the MB12 treated body sites versus 33.5% in the GPC treated body sites. These results suggest that MB12 could represent a new option in the treatment of mild AD.     

A UVB phototherapy protocol with very low dose increments as a treatment of atopic dermatitis

From 1991 to 1992, 15 patients with atopic dermatitis were treated with a new UVB treatment regimen guided by skin reflectance measurements. The new treatment was characterized by very low dose increments from start to end of therapy. The median cumulative dose increment during therapy was only 20%. The severity of the disease, the efficacy of the treatment, the occurence of adverse effects and the cumulative UVB dose were obtained from the case records. This data were compared in an open study with the data obtained from 17 patients with atopic dermatitis who were treated from 1988 to 1991 at the department with a standard UVB treatment regimen with stepwise dose increments. There was no difference in the severity of the disease at the beginning of the therapy between the two groups. The skin reflectance-guided low-dose UVB therapy was not significantly faster (3.5 weeks) than the regimen with stepwise dose increments (4.5 weeks). The cumulative UV exposure was four times lower with the new treatment regimen (34 standard erythema doses) compared with the old regimen (161 standard erythema doses), P <0.001. The healing score was significantly higher with the new treatment regimen compared with the old, P <0.05. This study indicates that skin reflectance-guided UVB phototherapy may enable the dermatologist to lower the cumulative UVB exposure significantly without losing effect.     

Reduction of relapses of atopic dermatitis with methylprednisolone aceponate cream twice weekly in addition to maintenance treatment with emollient: a multicentre, randomized, double-blind, controlled study

Background The relapsing nature of atopic dermatitis (AD) presents a challenge for its long‐term treatment. Efficacy and safety of corticosteroids have been proven in the acute treatment of active AD, but their long‐term efficacy and potential to reduce or prevent relapses have only partially been addressed. Objectives To investigate long‐term management (16 weeks) of AD with methylprednisolone aceponate (MPA) 0·1% cream twice weekly in addition to an emollient (Advabase^®) after stabilization of an acute severe or very severe flare of AD with MPA cream. Methods Patients ≥ 12 years of age with a ≥ 2‐year history of moderate to severe AD were eligible for this multicentre, randomized, double‐blind, controlled study if they presented with an acute flare of severe or very severe AD [Investigator’s Global Assessment (IGA) score ≥ 4]. After successful treatment of the flare in an acute phase (AP), patients received either MPA twice weekly plus emollient or emollient alone over a 16‐week maintenance phase (MP). The primary study endpoint was time to relapse of AD. Secondary endpoints included relapse rate and disease status, the patient’s assessment of intensity of itch, the Eczema Area and Severity Index, the IGA score, affected body surface area, Dermatology Life Quality Index (DLQI) and children’s DLQI (CDLQI), patient’s and investigator’s global assessment of response and patient’s assessment of quality of sleep. Results Two hundred and forty‐nine patients entered the AP and 221 continued into the MP. Time to relapse was longer in the MPA group than in the emollient group. The probability of remaining free from relapse after 16 weeks was 87·1% in the MPA group compared with 65·8% for the emollient. Patients treated with MPA twice weekly had a 3·5‐fold lower risk of experiencing a relapse than patients treated with emollient alone (hazard ratio 3·5, 95% confidence interval 1·9–6·4; P < 0·0001). MPA was also superior to emollient for all other efficacy endpoints. Therapy with both treatments was well tolerated. Conclusions MPA twice weekly plus an emollient provides an effective maintenance treatment regimen to control AD. Once stabilized, treatment with MPA significantly reduces the risk of relapse and the intensity of itching, and improves the overall patient status.     

Treatment with a barrier-strengthening moisturizing cream delays relapse of atopic dermatitis: a prospective and randomized controlled clinical trial

Background  Standard treatment of atopic dermatitis (AD) is based on topical glucocorticosteroids or calcineurin inhibitors to treat flares combined with moisturizer treatment to alleviate dry skin symptoms. Patients with AD have an abnormal skin barrier function, and strategies for reducing the risks for eczema would be to repair the barrier or prevent barrier dysfunction.
Objectives  The objective of this study was to explore the time to relapse of eczema during a 26-week maintenance treatment with a urea containing moisturizer compared to no treatment (neither medical nor non-medicated preparations) after successful clearing of atopic lesions. The moisturizer has previously been shown to improve skin barrier function.
Methods  Patients applied betamethasone valerate (0.1%) on eczematous lesions during a 3-week period. Those with cleared eczema entered a 26-week maintenance phase, applying the moisturizer or left the previously affected area untreated. Upon eczema relapse, patients were instructed to contact the clinic and to have the relapse confirmed by the investigator.
Results  Fifty-five patients entered the study and 44 patients were included in the maintenance phase (22 using moisturizer twice daily and 22 using no treatment). Median time to relapse for patients treated with moisturizer was > 180 days (duration of the study) compared with 30 days for the no-treatment group. Sixty-eight per cent of the patients treated with the moisturizer and 32% of the untreated patients remained free from eczema during the observation period.
Conclusions  Maintenance treatment with a barrier-improving urea moisturizer on previous eczematous areas reduced the risk of relapse to approximately one third of that of no treatment.     

The improvement of infantile atopic dermatitis during the maintenance period: A multicenter,randomized, parallel controlled clinical study of emollients in Prinsepia utilis Royle

In order to investigate the effect of daily emollient treatment on infantile atopic dermatitis (AD) during the maintenance period, a total of 309 children younger than 2 years with moderate AD (155 and 154 in the treatment and control groups, respectively) were enrolled in this multicenter, randomized, parallel controlled clinical trial. Subjects were topically treated with desonide cream and emollients in Prinsepia utilis Royle for 2–4 weeks before entering the maintenance period and then differentially treated with either emollients for treatment or none for control. The cumulative maintenance rate, time to flare and improvement of eczema area and severity index (EASI) and infant's dermatitis quality of life index (IDQOL) were evaluated. Results showed that the cumulative maintenance rate of the treatment group (60.5%, 95% CI 50.0–69.4%) was significantly higher than that of the control group (23.5%, 95% CI 15.2–33.0%) (p < .001). The median time to flare in the treatment group was 90 days (interquartile range, IQR 28–90), which was significantly longer than that in the control group (28 days [IQR 18–67]) (p < .001). At Week 4 in the maintenance period, the EASI and IDQOL scores of the treatment group were lower than those of the control group. In conclusion, the application of emollients during the maintenance period of infantile AD can significantly reduce the risk of AD flares, prolong the time to flare and improve the clinical symptoms.