Feature: ATOPIC DERMATITIS Update - Ellen Meyer, Senior Editor, and Larisa Hubbs, Executive Editor Highlights of recent news and trends. Data Review Finds No Difference In Safety Profiles Among Currently Available Topical Therapies A recent British Journal of Dermatology review article based on systematic reviews of safety data supports the continued use of all currently available topical therapies for AD — including topical calcineurin inhibitors (TCIs), for which this report specifically accessed the most recent (at the time, September 2005) FDA studies, reports and meetings. The article (Girardi M, et al. A systematic review of the safety of topical therapies for atopic dermatitis. BJD. 2000;156:203–221.) focused on the following topical therapies: coal tar, doxepin, antibiotics/antiseptics, corticosteroids, as well as calcineurin inhibitors, and a list of questions, including the following: What are the local side effects of topical therapies for AD? What are the systemic exposures of topical therapies for AD and their effect on growth, the hypothalamic-pituitary-adrenal (HPA) axis and other physiological processes? What are the systemic side effects (infection and neoplasia) of topical therapies for AD? Method To answer the questions posed, investigators conducted a search of databases, links, studies, reports, meetings, and articles to determine the safety of topical therapies for AD. In addition to articles, investigators were also referred to a list of links recent at the time to recent FDA studies, reports and meetings regarding the topical calcineurin inhibitors. Qualitative review of the abstracted data was performed and reviewed at a meeting of all of the content and evidence-based medicine experts. Findings In this systematic review of published clinical trials and other sources of information, investigators stressed difference between what is known and what remains unknown in presenting their findings and drawing their conclusions, placing particular emphasis on any evidence of a link to cancer, presumably due to the FDA black box warning on TCIs, which was based on animal studies suggesting such a link. Local Side Effects Issues examined in the local side effects category included cutaneous malignancy, secondary infection, skin atrophy, striae, burning, itching, folliculitis, acne-like eruptions, allergic contact dermatitis, and even cataracts. In general, authors surmised that infections are infrequent and usually mild and that local adverse events of topical AD therapy are predominantly local cutaneous effects such as stinging, itching and erythema, which were difficult to quantify. They also found no reliable existing data indicating an increased risk of cutaneous neoplasia with any topical therapy for AD, including TCIs, for which a trend toward virally mediated skin infections was statistically insignificant. Systemic Exposures and Physiological Effects Authors noted all therapies for AD can result in some systemic exposure to the compound and thus all topical therapies for AD have the potential for systemic-related side effects or toxicity. The greatest systemic exposure to a topical therapy used for AD, they noted, occurs with use of coal tar and topical steroids (TS). The best-documented physiological effects of systemic exposure to TS are glucocorticoid related, with effects on the HPA axis and clinical manifestations including adrenal suppression and insufficiency, Cushing’s syndrome and growth retardation. Systemic Side Effects Authors found no data indicating an increased risk of systemic side effects or complications such as systemic infections or cancers related to the use of the various topical medications in the treatment of AD. (See Table above.) While they noted that systemic side effects have occasionally been attributed to TS but not TCIs, the length of many of the studies evaluating these treatments was not long enough to make any definite conclusions. Conclusion Based on the data they reviewed, the authors deemed the overall safety of all currently available AD therapies to be acceptable, noting that the only documented systemic side effects of such therapy being those occasionally seen with use of topical corticosteroids. Given that their data did not at this time support the use of one therapy over another based on any current evidence of difference in safety profiles, they recommended that individualized tolerability and efficacy should remain the most important factors in choice of treatment for AD. Maternal Diet During Pregnancy Associated with Childhood Allergy For better and for worse, what a mother eats during her last 4 weeks of pregnancy may affect fetal immune responses associated with childhood allergy. According to a study reported in the February issue of the American Journal of Clinical Nutrition, eczema in children at 2 years of age is positively associated with high maternal intake of margarine and vegetable oils and negatively associated with high maternal intake of fish during pregnancy. GATHERING THE DATA Findings were based on a semi-quantitative food-frequency questionnaire administered shortly after childbirth to evaluate maternal diet during the last 4 weeks of pregnancy. Using a German prospective birth cohort study (LISA), the investigators analyzed data from 2,641 children at 2 years of age. Other findings related to maternal food intakes and childhood allergy at age 2. Food allergen sensitization was associated with high maternal intake of celery and citrus and inhalant allergen sensitization was associated with high maternal intake of deep-frying vegetable fat, raw sweet pepper, and citrus fruit. Maternal Diet In Late Pregnancy Affects Children’s Risk for Eczema Medscape Medical News. Accessed April 12, 2007, http://www.medscape.com/viewarticle/552404. Arecent study found that repetitive stimuli using intense heat and cold, as well as scratching, inhibited itch and did not require direct physical interaction with the area of the skin from which the itch originated. The study, which examined patients suffering from chronic pruritus to determine how the sensory perception of itch was affected by the use of such stimuli, found innocuous heat and cold ineffective. Going Hot and Cold to Scratch an Itch METHOD AND PATIENTS Itch was induced with histamine iontophoresis in 21 healthy young participants. Then patients were subjected to stimuli, including innocuous warmth, innocuous cooling, noxious cold and noxious heat as well as scratching, which were applied 3 cm distal to the area of histamine iontophoresis. Subjects then rated their perceived intensity of this histamine-induced itch with a computerized visual analog scale. RESULTS Itch intensity ratings were significantly reduced during each period of scratching and repeated noxious heat and cold. Innocuous cooling and warming did not significantly alter itch intensity ratings. Inter-individual differences in histamine-induced itch sensitivity were unrelated to inter-individual differences in pain sensitivity. CONCLUSIONS This psychophysical study demonstrated that repetitive noxious thermal and scratching stimuli inhibited itch and did not require direct physical interaction with the area of the skin from which itch originated. Yosipovitch G, Duque MI, Fast K, Dawn AG, Coghill RC. Scratching and noxious heat stimuli inhibit itch in humans: a psychophysical study. BJD. 2007;156:629–634.) Topical Vehicle Type Tied to Adherence and Treatment Success An ongoing clinical investigation presented as a poster at the winter American Academy of Dermatology meeting in Washington, D.C., clandestinely used adherence monitors in an effort to connect the dots between patient compliance, topical atopic dermatitis medication vehicle and treatment success. METHOD The poster reviewed results compiled from the 14 atopic dermatitis patients who had completed the study at the time. Subjects were randomized to use one of three topical hydrocortisone 17-butyrate 0.1% preparations: ointment, cream or Lipocream. Without patients’ knowledge, each original tube was outfitted with a microprocessor to measure and record each time the tube was opened. Subjects were told to apply the given product to their AD lesions twice daily for 2 weeks and to maintain a treatment log that would be used to measure compliance. The patients were not informed prior to their follow-up visit that the adherence monitors’ microprocessors measure and record each time the tube is opened. RESULTS At the end of 2 weeks, there were considerable improvement in the severity of the disease. Eight of the 14 patients (57.1%) proved to be adherent and among them, 62.5% achieved treatment success. Results also indicated that 6 of 14 (42.9%) were non-adherent. Among the six patients who were non-adherent (42.9%), only two (33.3%) achieved treatment success. Based on the patients’ treatment logs, the treatment vehicle associated with the highest level of adherence was Lipocream, compared to cream and ointment. OFFERING DIFFERENT TREATMENTS Investigators from the Departments of Dermatology, Pathology and Public Health Sciences — all at Wake Forest University School of Medicine in Winston-Salem, N.C. — found that initial findings indicated a strong relationship between adherence and successful treatment outcomes and that patients’ preferences for different vehicles were a factor in improved compliance. With this in mind, they concluded that offering patients multiple vehicles from which to choose may help tailor treatment to individual patients and help improve patients’ adherence. Clobetasol Propionate Emollient Foam, 0.05%, Found Superior to Vehicle Foam for AD Two separate Phase III clinical trials of clobetasol propionate emollient foam, 0.05%, (Olux E) found clobetasol EF Foam — in a formulation specifically designed for use on the body — to be superior to vehicle foam for treatment of moderate to severe atopic dermatitis (AD) as well as for mild to moderate plaque-type psoriasis. ATOPIC DERMATITIS STUDY Method Clinical trials were conducted in people with moderate to severe atopic dermatitis. During the studies, 251 people were treated twice daily for 2 weeks with Olux-E Foam and 126 subjects were treated with vehicle foam. Results At the end of treatment, 131 of 251 subjects (52%) treated with Olux-E Foam compared with 18 of 126 (14%) treated with vehicle foam achieved treatment success, with treatment success define as an Investigator’s Static Global Assessment (ISGA) score of clear (0) or almost clear (1) with at least 2 grades of improvement from baseline, and scores of absent or minimal (0 or 1) for erythema and induration/papulation. Clobetasol EF Foam was found to be superior to vehicle foam for the composite primary efficacy endpoint in the proportion of subjects who attained treatment success. What’s more, each component of this composite primary efficacy endpoint also showed clobetasol EF foam to be superior to vehicle foam for each measure. CONCLUSION Clobetasol propionate emollient foam, 0.05%, is a super-high-potency topical corticosteroid in a novel formulation indicated for the treatment of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients over 12 years old. It was developed by the makers of Olux, and it also comes in a unique vehicle — hydroethanolic foam — expressly designed for the scalp. Significantly, the proportion of study participants who attained treatment success was four times higher in the clobetasol EF foam group compared to the vehicle foam group in patients with moderate to severe AD and mild to moderate plaque-type psoriasis. It should be noted that while the control vehicle was essentially approved with clear or almost clear data, Olux-E was held to four and five point composite endpoints, meaning a patient would need to hit all four and all five endpoints to be deemed a treatment success. No Clear Connection Shown Between Early Allergen Exposure and Atopic Dermatitis While many studies have explored the effect of allergen exposure in early life — even to include the 4 weeks prior to birth — this study conducted exposure-response analysis of allergen exposure and eczema outcomes up to age 8 years and investigated the role of other genetic and environmental determinants. METHODS The study followed a total of 593 children from birth to age 8 years. Concentrations of house dust mite and cat allergens were measured in dust samples collected from the home 8 weeks after birth. The risk of subsequent eczema, as defined by the U.K. diagnostic criteria, was determined according to different levels (quintiles) of allergen exposure at birth. RESULTS By age 8 years, 150 (25.3%) children had met the diagnostic criteria for eczema at least once. Visible flexural dermatitis was recorded at least once for 129 (28%). As in other studies, parental allergic history was positively associated with most eczema outcomes, as were higher maternal education and less crowded homes. No clear linear associations between early exposure to house dust mite or cat allergens were found, regardless of the definition of eczema used. The risk of eczema appeared to increase for the three lowest quintiles of house dust mite allergen exposure (odds ratio 1.37 for third quintile compared with first), and then to fall for the two highest quintiles (odds ratio 0.66 and 0.1) even after controlling for confounding factors. REDUCING DUST MITES COULD INCREASE ECZEMA The lack of any clear exposure–disease relationship between allergens in early life and subsequent eczema argues against allergen exposure being a major factor causing eczema. What’s more, authors concluded that if the lower levels of eczema at higher levels of house dust mites are confirmed, interventions aimed at reducing house dust mites in early infancy could paradoxically increase the risk of subsequent eczema. J.M. Harris, H.C. Williams, C. White, S. Moffat, P. Mills, A.J. Newman Taylor, P. Cullinan Early allergen exposure and atopic eczema. BJD. 2007; 156:698–704. Clothing as Part of the Therapeutic Treatment of Sensitive Skin By Zoe Diana Draelos, M.D. What is the role of clothing in the treatment of chronic skin conditions, particularly those involving sensitive skin? A recent study comparing pajamas and undershirts using new garment technology to similar garments made of 100% cotton found that an overwhelming majority of patients with sensitive skin preferred the study garment, which they claimed reduced itch and was generally more comfortable than its cotton counterpart. BACKGROUND The traditional therapies for sensitive skin due to psoriasis, eczema, and atopic dermatitis are aimed at the reduction of inflammation and itch control. Topical and/or oral medications may be prescribed along with recommendations for skincare products. While clothing typically is not considered part of the therapeutic armamentarium, it can have a profound impact on skin conditions, as in the case of itching precipitated by wool fabric, which is one of the minor criteria for the diagnosis of atopic dermatitis. For this reason, traditional dermatologic recommendations for clothing selection in sensitive skin patients specify loose-fitting 100% cotton garments. STUDY GARMENT The unique fabric (from Milliken & Company) studied in this research was made from silver-impregnated, long-fiber polyester yarn chosen for exceptional fabric softness and smoothness with a very low skin friction coefficient. Thus, the fabric reduced the chance of clothing triggering the itch/scratch cycle. Wearing friction was also reduced by the garment construction. Typical mass-produced clothing has raw seams on the inside with the stitching elevated above the fabric. Seams create areas of garment/skin friction. The study garments were specially constructed with non-irritating flat seams, soft sewing thread and covered elastic waistbands in the pants to further eliminate wearing friction. Efforts made to improve upon the comparator fabric, 100% cotton, considered sweat absorption. Cotton absorbs sweat readily, but holds the moisture within the fiber for an extended period. The study garments, on the other hand, were made from a 100% microfiber polyester yarn. Polyester wicks, but does not hold, perspiration from the skin surface. This makes the garment cooler to wear and eliminates skin maceration problems. The study garment yarn was also treated with silver, an antibacterial used in bandages and high endurance clothing. The silver prevents the development of body odor and decreases the ability of clothing to support bacterial growth. This may be important in atopic dermatitis and psoriasis where bacteria may be an inciting factor for disease initiation. The silver remains on the yarn through washing, decreasing the ability of the garment to support the growth of Staphylococcus epidermidis, Staphylococcus aureus, and streptococcal organisms, and others. STUDY DESIGN This study was a single-blind crossover design comparing a new garment technology with that existing in the current marketplace. The study enrolled 61 female or male subjects between the ages of 1 to 80 years of age with visible skin symptoms of atopic dermatitis, eczema, or psoriasis. Subjects were randomized to wear either the study garments (DermaSmart, Hill Dermaceuticals) or the commercially marketed 100% cotton garments (Adults: Fruit of the Loom T-shirts and JCPenney pajamas. Children: Fruit of the Loom T-shirts, Basic Brilliance pajamas) for the first 2 weeks of the study with a crossover for the last 2 weeks of the study. The study garments consisted of a T-shirt undergarment and pajamas. It was required that the T-shirts were worn at least 4 hours daily and the pajamas worn at all times while sleeping. Subjects were allowed to continue on all medications unchanged during the study, except that visible photographable skin disease was necessary for enrollment. Subjects were asked to keep all other aspects of their skin care routine unchanged. They returned to the research center at the end of weeks 2 and 4. The blinded dermatologist investigator performed skin evaluations and photographs at the end of weeks 2 and 4. An ordinal scale was used to rate dermatitis, erythema, desquamation, excoriation, lichenification, stinging/burning, itching, and overall assessment. The ordinal scale used was: 0=none, 1=slight, 2=mild, 3=moderate, 4=severe. In addition, a subject questionnaire was administered comparing the two different garments to capture the subject’s perception of skin itching. The subjects were asked to rate the garment on an ordinal scale in terms of overall impression, fabric softness, perspiration removal, fabric sensation, and itching reduction. The ordinal scale rating consisted of: - 2=disliked a lot, -1=disliked a little, 0=did not like or dislike, 1=liked a little, 2=liked a lot. RESULTS Results were based on the 59 participants who completed the study. The investigator comparison assessment showed a statistically significant (p<0.001) preference for the novel study garments over the currently marketed cotton garments. The study garment was judged statistically superior to the cotton garments in all areas assessed, including the following: dermatitis, erythema, desquamation, excoriation, lichenification, stinging/burning, and itching. The subject comparison data demonstrated a statistically significant preference for the novel study garment in terms of overall evaluation (p=0.001) and all other factors evaluated, including fabric softness, perspiration removal, fabric sensation, and itch reduction. FINDINGS Both the blinded investigator and the study subjects demonstrated a statistically significant preference for the study garments over 100% cotton garments after 2 weeks of wearing. The most significant finding was the itch reduction reported by the subjects. Itch is an extremely difficult symptom to control in both adults and children. Wearing an itch-reducing T-shirt under traditional clothing during the day and pajama pants and shirts at night provided around-the-clock skin friction reduction, which minimized clothing-induced itching. Itch may be further reduced by the ability of the fabric to wick sweat, which is critical to keeping the skin surface dry and cool. KEEPING ITCH UNDER WRAPS This study demonstrated that specially designed T-shirts and pajamas made from silver impregnated long filament 100% microfiber polyester may be beneficial as an adjunct to the treatment of sensitive skin. The Challenge of Treating Sensitive Skin Photo Courtesy of Dr. James Q. Del Rosso The Challenge of Treating Sensitive Skin -Zoe Diana Draelos, M.D. Treating sensitive skin can indeed present a challenge to the physician, since formulations that are typically not problematic for the general population cause intense stinging, burning, and redness in individuals with sensitive skin. PRESENTATION Patients with sensitive skin can either present with skin that appears normal to the eye or has overt skin disease. Visible sensitive skin is the easiest condition to diagnose, since the outward manifestations of erythema, desquamation, lichenification, and inflammation identify the presence of a severe barrier defect. However, any patient with a barrier defect will possess the signs and symptoms of sensitive skin until complete healing occurs. BARRIER DEFECT-INDUCED SENSITIVE SKIN The three most common causes of barrier defect-induced sensitive skin are eczema, atopic dermatitis, and psoriasis. These three diseases nicely illustrate the three components of sensitive skin, which include barrier disruption, immune hyper-reactivity, and heightened neurosensory response. Eczema and psoriasis are characterized by barrier disruption, which is the most common cause of sensitive skin. The barrier can be disrupted chemically with cleansers and cosmetics that remove intercellular lipids or physically by using abrasive substances that induce stratum corneum exfoliation. In eczema, the barrier may be defective either due to insufficient sebum production, inadequate intercellular lipids, or abnormal keratinocyte organization. In psoriasis, the barrier is defective due to the rapid production of poor-quality, abnormal skin. With both disease states, the end result is the induction of the inflammatory cascade accompanied by erythema, desquamation, itching, stinging, burning, and possibly pain. The immediate goal of treatment is to stop the inflammation through the use of topical, oral, or injectable corticosteroids, depending on the severity of the eczema and the percent of body surface area involved. Topical corticosteroids are the most frequently employed treatment, sometimes accompanied by the calcineurin inhibitors, pimecrolimus and tacrolimus. However, the resolution of the inflammation is not sufficient for the treatment of eczema. Proper skin care must also be instituted to minimize the return of the conditions that led to the onset of eczema. This includes the selection of maintenance skincare products, such as cleansers and moisturizers. In addition, it may be useful to wear specially designed clothing to reduce or soothe skin irritation, which is the subject of this study. Thus, the care of sensitive skin involves not only the treatment of the acute skin disease, but also the prevention of recurrence through proper skincare maintenance and clothing selection. Sensitive skin due to eczema is predicated only on physical barrier disruption, while the sensitive skin associated with atopic dermatitis is predicated both on a barrier defect and an immune hyper-reactivity, as manifested by the association of asthma and hay fever. Patients with atopic dermatitis not only have sensitive skin on the exterior of the body, but also sensitive mucosa lining the eyes, nose, and lungs. There is also a prominent link between the worsening of hay fever and the onset of skin symptoms, requiring broader treatment considerations. Recommended Reading Elsner P, Hatch K, Wigger-Alberti W. Textiles and the Skin, Karger Press, 2003. Hatch KL. Textile Science, West Publishing Company, 1993.             Skin & Aging - ISSN: 1096-0120 - Volume 15 - Issue 5 - May 2007 - Pages: 42 - 49