Frank Rippke

The Acidic Milieu of the Horny Layer

The acidic pH of the horny layer, measurable on the skin surface, has long been regarded as a result of exocrine secretion of the skin glands. The ‘acid mantle’ was thought to regulate the bacterial skin flora and to be sensitive primarily to skin cleansing procedures.In recent years, an increasing number of investigations have been published on the changes in, and constituents and functions of, the pH of the deeper layers of the stratum corneum, as well as on the influence of physiological and pathological factors. A central role for the acidic milieu as a regulating factor in stratum corneum homeostasis is now emerging. This has relevance to the integrity of the barrier function, from normal maturation of the stratum corneum lipids through to desquamation. Changes in the pH and the organic factors influencing it appear to play a role, not only in the pathogenesis, prevention and treatment of irritant contact dermatitis, but also of atopic dermatitis and ichthyosis and in wound healing.On the basis of these findings, a broader concept, exceeding the superficial ‘acid mantle’ theory, has been formulated.

Stratum Corneum pH in Atopic Dermatitis

AbstractRecent studies have provided new insights into the occurrence, causes, and pathogenetic consequences of changes in the skin pH in atopic dermatitis, particularly with respect to skin barrier function and colonization with Staphylococcus aureus. Growing evidence suggests an impaired release of proton donors, such as amino acids, urocanic acid, and lactic acid, to the stratum corneum in atopic dermatitis, as a result of reductions in filaggrin proteolysis and sweat secretion. In addition, an impaired formation of free fatty acids from sebaceous lipids and epidermal phospholipids seems to be involved. Because both lipid organization and lipid metabolism in the stratum corneum requires an acidic pH, these alterations might contribute to the disturbance of skin barrier function observed in atopic dermatitis. Furthermore, bacterial growth and virulence of S. aureus, as well as defensive host mechanisms, have increasingly been delineated as pH dependent, giving rise to a new understanding of the pathophysiology underlying increased skin colonization seen in atopic dermatitis.

Topical Use of Dexpanthenol in Skin Disorders

Pantothenic acid is essential to normal epithelial function. It is a component of coenzyme A, which serves as a cofactor for a variety of enzyme-catalyzed reactions that are important in the metabolism of carbohydrates, fatty acids, proteins, gluconeogenesis, sterols, steroid hormones, and porphyrins. The topical use of dexpanthenol, the stable alcoholic analog of pantothenic acid, is based on good skin penetration and high local concentrations of dexpanthenol when administered in an adequate vehicle, such as water-in-oil emulsions. Topical dexpanthenol acts like a moisturizer, improving stratum corneum hydration, reducing transepidermal water loss and maintaining skin softness and elasticity. Activation of fibroblast proliferation, which is of relevance in wound healing, has been observed both in vitro and in vivo with dexpanthenol. Accelerated re-epithelization in wound healing, monitored by means of the transepidermal water loss as an indicator of the intact epidermal barrier function, has also been seen. Dexpanthenol has been shown to have an anti-inflammatory effect on experimental ultraviolet-induced erythema.Beneficial effects of dexpanthenol have been observed in patients who have undergone skin transplantation or scar treatment, or therapy for burn injuries and different dermatoses. The stimulation of epithelization, granulation and mitigation of itching were the most prominent effects of formulations containing dexpanthenol. In double-blind placebo-controlled clinical trials, dexpanthenol was evaluated for its efficacy in improving wound healing. Epidermal wounds treated with dexpanthenol emulsion showed a reduction in erythema, and more elastic and solid tissue regeneration. Monitoring of transepidermal water loss showed a significant acceleration of epidermal regeneration as a result of dexpanthenol therapy, as compared with the vehicle. In an irritation model, pretreatment with dexpanthenol cream resulted in significantly less damage to the stratum corneum barrier, compared with no pretreatment. Adjuvant skin care with dexpanthenol considerably improved the symptoms of skin irritation, such as dryness of the skin, roughness, scaling, pruritus, erythema, erosion/fissures, over 3 to 4 weeks. Usually, the topical administration of dexpanthenol preparations is well tolerated, with minimal risk of skin irritancy or sensitization.

Efficacy of Urea Therapy in Children with Ichthyosis

Background: Ichthyoses are genetic disorders of keratinization which are uncomfortable due to their conspicuous scaling, itching and cosmetic problems. Especially in childhood, ichthyoses can lead to social discrimination and psychological problems. Efficient therapies are necessary which are safe and well tolerated. Objective: The aim of the study was to investigate the keratolytic and moisterurizing properties as well as the tolerance of a new urea lotion when applied to hyperkeratotic and ichthyotic skin in childhood. Methods: The study was conducted as a multicenter, randomized, placebo-controlled, double-blind, semilateral investigation. Sixty children between 1 and 16 years treated one side of the most affected extremity with Laceran 10% urea lotion for 8 weeks. On the other side the urea-free Laceran lotion base was given. On each side of the body a control area was left untreated. The investigators evaluated the global severity of ichthyotic symptoms with the help of a visual analogue scale. Results: The analysis of the global estimation of severity of ichthyosis showed improvements being stronger in the body areas treated with Laceran 10% urea lotion (from 4.8 to 2.0 points) than in the areas treated with the urea-free Laceran lotion base (from 4.8 to 2.5 points). The response rates were 65% after 4 weeks and 78% after 8 weeks for Laceran 10% urea lotion, 50% after 4 weeks and 72% after 8 weeks for the urea-free Laceran lotion base. Conclusion: It can be ascertained that Laceran 10% urea lotion has a strong positive effect on generalized ichthyotic keratinization disorders.

Effects of topically applied antioxidants in experimentally provoked polymorphous light eruption.

BACKGROUND Polymorphous light eruption (PLE) is the most common photodermatosis, with a prevalence of 10-20% in Western European countries and in the USA. Only few preventive measures for PLE exist, while its etiology and pathogenesis are still elusive. Recent theories on pathogenesis discuss the possible influence of oxidative stress. OBJECTIVE The presented randomized, placebo-controlled, double-blind study examines for the first time the protective effect of 3 different topically applied antioxidative preparations in experimentally photo-induced PLE. METHOD 30 patients with a history of PLE underwent photoprovocation after having had applied 3 different formulations with antioxidants and one formulation with the vehicle only to the extensor surface of their upper arms, representing the individual site of predilection, twice daily for 1 week prior to and during the consecutive week of photoprovocation. The antioxidants used were combinations of different concentrations of alpha-glycosylrutin, ferulic acid and tocopheryl acetate. RESULTS Evaluation after the 4th photoprovocation revealed that the development and severity of PLE and concomitant pruritus were significantly reduced by the application of distinct combinations of antioxidants. CONCLUSION The results offer a new insight into possible pathomechanisms of PLE and suggest a new approach for preventive and therapeutic measures.

Anti-Inflammatory Effect of Hamamelis Lotion in a UVB Erythema Test

Background: Although Hamamelis virginiana has long been used in the traditional treatment of skin diseases, there are few controlled clinical studies defining the extent of its anti-inflammatory action. Objective:The anti-inflammatory efficacy of pH5 Eucerin aftersun lotion with 10% hamamelis distillate, the vehicle and a prior aftersun formulation were tested in 30 healthy volunteers using a modified UVB erythema test as model of inflammation. Methods: Four UVB doses ranging from 1 to 2 MED were evaluated in each subject. Test fields on the back were treated occlusively for 48 h following irradiation. Chromametry and visual scoring were used to determine the degree of erythema in the treated fields and an untreated, irradiated control field 7, 24 and 48 h after irradiation. Results: Erythema suppression ranged from approximately 20% at 7 h to 27% at 48 h in the hamamelis fields. A suppression of 11–15% was recorded in the fields treated with the other lotions. Significant differences were noted between hamamelis and these lotions. Conclusion: These data provide evidence for an anti-inflammatory action of the aftersun lotion with 10% hamamelis and support the usefulness of the UVB erythema test with multiple UV doses for the testing of nonsteroidal anti-inflammatory agents.

Anti-inflammatory efficacy of topical preparations with 10% hamamelis distillate in a UV erythema test

In 40 volunteers the efficacy of three lotions with 10% hamamelis distillates from different suppliers, two vehicles, dimethindene maleate 0.1% gel, hydrocortisone 1% cream and hydrocortisone 0.25% lotion were investigated in a modified UV erythema test with three UV dosages (1.2, 1.4 and 1.7 MED). The test preparations were applied occlusively over a 48-hour period following irradiation. Chromametric measurement of redness and visual assessment were performed 24, 48 and 72 h after induction of erythema. The hydrocortisone formulations were most effective in erythema suppression. An anti- inflammatory effect was noted for all three hamamelis lotions as well as for the vehicles. A significantly greater suppression of erythema than seen with the vehicles was noted for one of the hamamelis lotions at 1.4 MED. The efficacy of the antihistamine dimethindene maleate did not surpass the hamamelis lotions or the vehicles. Even though the differences between the hamamelis lotions were slight, it was possible to make an objective selection of the best hamamelis distillate for aftersun purposes.

Prevention of Follicular Penetration: Barrier-Enhancing Formulations against the Penetration of Pollen Allergens into Hair Follicles

The hair follicles could be a reservoir for topically applied substances. They are not only surrounded by a close network of blood capillaries, which makes them interesting for drug delivery, but they are also the host of dendritic cells, which are important for immunomodulation. Previously, pollen allergens were shown to penetrate into the hair follicles. The application of barrier-enhancing formulations might represent an effective strategy to prevent pollen protein penetration into the hair follicle. In the present study, porcine skin areas were pretreated with 4 barrier-enhancing emulsions. One skin area served as control and remained without pretreatment. Afterwards, fluorescein-isothiocyanate-labeled grass pollen proteins were applied to the porcine skin samples, and their penetration was investigated via fluorescent laser scanning microscopy. It was shown that the barrier-enhancing formulations were able to significantly reduce the penetration of exogenous proteins into the hair follicles, the extent of such reduction depending on the formulation.

Efficacy and safety of Eucerin 10% Urea Lotion in the treatment of symptoms of aged skin

Two features of senescent skin are dryness and itching, which are caused by a reduced water-binding capacity of the stratum corneum. Urea, topically applied, is known to increase the water content of the stratum corneum and thereby improves the symptoms of dry and itching skin. The aim of the study was to compare the efficacy and safety of a lotion containing 10% urea (Eucerin® 10% Urea Lotion) with that of the urea-free lotion base in the treatment of the symptoms of aged skin. In a randomized double-blind vehicle-controlled study with a semilateral design, 60 elderly volunteers (mean age 64.1 years) with characteristic symptoms of aged but otherwise healthy skin were treated over a period of 4 weeks. The study protocol used surface moisture content of the forearm skin as determined by corneometry as the primary efficacy criterion and subjective symptoms (dryness, itching) as secondary efficacy criteria. Eucerin 10% Urea Lotion proved to be superior to its vehicle in increasing skin hydration, as shown b...

Modulation of atopy patch test reactions by topical treatment of human skin with a fatty acid-rich emollient

Measures directed at improving the skin barrier function are thought to be effective in preventing reexacerbation of atopic dermatitis, but direct proof of a prophylactic effect of emollients has been elusive. In the present study, the atopy patch test has been employed as a model for the initiation phase of atopic dermatitis in order to assess whether pretreatment of non-lesional skin with a fatty acid-rich emollient (Eucerin® Omega Creme) has a prophylactic effect in patients with atopic dermatitis. Pretreatment of test sites with Eucerin® Omega Creme either prevented or diminished the development of eczema, as compared with untreated control test sites in the same patients (n = 38). These studies indicate that the use of fatty acid-rich emollients prevents the development of atopic eczema. They also demonstrate that the atopy patch test can be used to assess the capacity of a given regimen to exert prophylactic effects in this disease.