- Email: [email protected]
A pilot study of the efficacy and safety of pimecrolimus 1% cream in the treatment of Netherton syndrome: Interim results
P2325 Measuring adherence to topical 5-fluorouracil in a clinic population Mandeep Kaur, MD, Wake Forest University Health Sciences, Winston-Salem, NC, United States; Steven Feldman, MD, PhD, Wake Forest University Health Sciences, NC, United States; Alan Fleischer, MD, Wake Forest University Health Sciences, Winston-Salem, NC, United States; Mark Tusa, MD, Wake Forest University Health Sciences, Winston-Salem, NC, United States Background: Actinic keratosis is a very common premalignant condition most commonly treated with medications and destructive methods, like cryosurgery. Lack of adherence to a medication regimen could be the underlying source of treatment failure. Objectives: To determine the adherence to topical 5-fluorouracil in patients who actually use it, and to determine how common treatment failure is due to poor adherence. Methods: We plan to explore adherence to topical treatment through an investigator-blinded, open trial of adherence in approximately 20 patients, aged 50 or greater, with actinic keratosis treated with topical 5-fluorouracil cream, utilizing electronic monitors to quantitatively assess adherence. All subjects will be assigned to treatment with topical 0.5% fluorouracil to the face and anterior scalp daily for 4 weeks. Subjects will be instructed to apply the smallest amount of study medication possible that is just sufficient to cover all of the affected areas. Subjects will return at week 8 for a final lesion count. Throughout the study, subjects’ medication usage will be monitored by the Medical Events Monitoring System (MEMS). Subjects will be informed that adherence rates are being collected, but will not be informed of the MEMS caps. Results: The findings of this study will be discussed; we anticipate an improvement in actinic keratosis lesion in subjects who adhered to 5- fluorouracil. Discussion: Implications of this study will be discussed.
Benjamin Wiegand, PhD, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, Canada; Nikoforos Kollias, PhD, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States Skin barrier function begins its development in utero and is believed to reach complete maturity by week 34 of gestational age. Clinically, there is interest in understanding the prevalence of conditions such as irritant contact dermatitis that impact infants distinctly from adults. In this study, we challenge the hypothesis that cutaneous barrier function is fully complete in full-term infants. Skin barrier properties were evaluated among 124 infants (3-months to 4 years-of-age) and 104 adults (14-73 years) using a combination of traditional and novel methods such as in vivo Raman confocal micro-spectroscopy applied to infant skin. Hydration values are found to be elevated during the first year of life compared to adults. Transepidermal water loss values follow a similar pattern. Water concentration profiles demonstrate a higher mass concentration of water within the stratum corneum of infant skin as well as a steeper water gradient compared to adults. The absorption and desorption rates and the distribution of exogenously applied water into the skin are significantly higher for infants. In adult skin, water desorption follows a single process with a single rate constant, whereas in infants it includes two processes with two distinct rate constants. Natural moisturizing factors were found to be in lesser abundance within infant skin as measured by Raman confocal, indicating one potential mechanism for the higher water flux seen in infants. The results of this study demonstrate that not only does the barrier function of infant skin continue to develop postpartum, but surprisingly it appears to continue to develop at least through the first year of life. The data also reaffirm that infant skin is different from adult skin and remains so for an extended period of time. In conclusion, this study demonstrates that the distribution and transport of water through the superficial layers of the skin are distinctly different between infants and adults suggesting the need for greater protection of infant skin. 100% Funded By Johnson & Johnson Consumer and Personal Products Worldwide.
This study was supported by a grant from Sanofi-Aventis.
P2326 The association of asymmetric skin cancers with time spent in an automobile Susan Butler, MD, Saint Louis University, Saint Louis, MO, United States; Scott Fosko, MD, Saint Louis University, Saint Louis, MO, United States; Christopher Kling, MD, Saint Louis University, Saint Louis, MO, United States; Elizabeth Duvall, Saint Louis University, Saint Louis, MO, United States Background: It is well-known that UV exposure increases the risk for skin cancer. Automobile drivers get more UV exposure on the left side of the body than the right, particularly on the hands, arms, and face. Previous literature has shown an association between this unilateral exposure to UV light and an asymmetric distribution of photodamage, solar purpura and AKs. It would be expected that skin cancers would also be more prevalent on the left side of the body in automobile drivers. Objectives: To evaluate whether more skin cancers develop on the left side of the body and to determine the association of asymmetric skin cancers with time spent in an automobile. Methods: A retrospective chart review was performed of all the patients with skin cancer treated with Mohs in 2004. Type of skin cancer, location, and gender were evaluated to determine if a predominance of left-sided skin cancers existed in our patient population. To directly correlate the presence of asymmetric skin cancer with UV exposure from automobile driving, a questionnaire evaluating driving habits was given to SLU dermatology Mohs surgical patients. Results: A total of 1,047 patients (898 non-midline cancers) were included in the retrospective chart review. There were 608 BCCs, 178 SCCs, 23 MM, 25 MMIS, and 64 miscellaneous cancers. Fifty-three percent of all types of cancer occurred on the left, and 47% on the right (p = 0.059). Both sexes developed more skin cancers on the left side, but more asymmetry was found in males (p = 0.08) than in females (p = 7.86). When comparing those cancers occurring only in the areas most often exposed in automobiles (head, neck, arms, and hands), there are significantly more cancers on the left in males (p = 0.039), but not in females. Conclusions: There was significantly higher prevalence of skin cancer on the left head, neck, arms, and hands seen only in males, which supports the hypothesis that this may be due to UV exposure while driving. This gender difference may be attributed to the practice of males riding on the left side of the car more frequently. The results of the questionnaire correlating asymmetrical skin cancers with driving habits will help directly measure this influence. The data collected from the questionnaires was not available at the time of publication, but will likely show patients with left-sided skin cancers have spent more time driving an automobile than those with right-sided skin cancers. Commercial support: None identified.
PEDIATRIC DERMATOLOGY P2400 Infant skin barrier maturation in the first year of life Janeta Nikolovski, PhD, Johnson & Johnson Consumer Products Worldwide, Skillman, NJ, United States; Georgios Stamatas, PhD, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States;
FEBRUARY 2007
P2401 A pilot study of the efficacy and safety of pimecrolimus 1% cream in the treatment of Netherton syndrome: Interim results Albert Yan, MD, Children’s Hospital of Philadelphia, Philadelphia, PA, United States; Kara Shah, MD, PhD, Children’s Hospital of Philadelphia, Philadelphia, PA, United States; Christina Kubrak, Children’s Hospital of Philadelphia, Philadelphia, PA, United States; Anne Parneix-Spake, MD, Novartis, East Hanover, NJ, United States Netherton syndrome is a rare, autosomal recessive genodermatosis associated with mutations in the SPINK5 (serine protease inhibitor LEKTI) gene. Characterized by neonatal erythroderma, a chronic eczematous dermatitis, trichorrhexis invaginata, and ichthyosis linearis circumflexa, patients with Netherton syndrome also exhibit a reduction in cutaneous barrier function. Prior reports have documented improvement of the cutaneous manifestations of Netherton syndrome in patients using the topical calcineurin inhibitor, tacrolimus 0.1% ointment. These benefits were, however, limited by significant percutaneous absorption, resulting in high systemic levels of tacrolimus. In this pilot study, identical 12-year-old twin siblings with Netherton syndrome were treated with twice daily applications of topical 1% pimecrolimus cream to 50% of the total body surface area. Both patients were assessed at baseline, 1 wk, 2 wks, 4 wks, 8 wks, 12 wks, and 24 wks. Screening of complete blood counts and serum chemistries revealed transient self-limited elevations in transaminase levels, while pimecrolimus blood concentrations remained consistently low. In this study, the highest value observed in blood pimecrolimus levels in patients with Netherton syndrome was 1.26 ng/mL. The highest previously observed in children with atopic dermatitis using topical pimecrolimus was 2.6 ng/mL. Meanwhile, clinical improvement was also evident using a variety of clinical outcome measures. Key: [Patient 1 value, Patient 2 value] *Baseline Eczema and Severity Index (EASI) scores decreased from baseline values of [20, 21] to a nadir of [5.6, 9.9] at 4 wks, indicating a drop of [72%, 53%] in EASI scores. *Similarly, Netherton Area and Severity Assessment (NASA) scores decreased from baseline values of [21.9, 24.2] to a nadir of [7.6, 12] at 4 wks. This represents an improvement of [65%, 50%], respectively. *Pruritus scores dropped from baseline values for both patients of 8.5/10 to 2/10 at 12 wks. *Investigator Global Evaluation of Disease improved by ;50% from baseline values of [12/16, 11/16] tp [6, 5] at 12 wks. *Child Dermatology Quality of Life Index (CDLQI) measurements at 24 wks [5,4] also improved, decreasing from baseline values of [15, 9]. Maximum scores of 30 are possible. Assessment of transepidermal water loss (TEWL) was accomplished using the portable, handheld Vapometer (Delfin Technologies). Paradoxically, measurements of TEWL appeared to increase as clinical outcome measures improved. Pimecrolimus 1% cream may represent a safe and effective option for treating the cutaneous features of Netherton syndrome. Longer-term studies with additional patients will be necessary to confirm these preliminary findings. References: 1. Allen A, Siegfried E, Silverman R, Williams ML, Elias PM, et al. Arch Dermatol 2001;137(6):747-50. 2. Oji V, Beljian G, Beier K, Traupe H, et al. Br J Dermatol 2005;153(5):1067-8. Printing costs were provided by Novartis Pharmaceuticals.
J AM ACAD DERMATOL
AB153
Benjamin Wiegand, PhD, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, Canada; Nikoforos Kollias, PhD, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States Skin barrier function begins its development in utero and is believed to reach complete maturity by week 34 of gestational age. Clinically, there is interest in understanding the prevalence of conditions such as irritant contact dermatitis that impact infants distinctly from adults. In this study, we challenge the hypothesis that cutaneous barrier function is fully complete in full-term infants. Skin barrier properties were evaluated among 124 infants (3-months to 4 years-of-age) and 104 adults (14-73 years) using a combination of traditional and novel methods such as in vivo Raman confocal micro-spectroscopy applied to infant skin. Hydration values are found to be elevated during the first year of life compared to adults. Transepidermal water loss values follow a similar pattern. Water concentration profiles demonstrate a higher mass concentration of water within the stratum corneum of infant skin as well as a steeper water gradient compared to adults. The absorption and desorption rates and the distribution of exogenously applied water into the skin are significantly higher for infants. In adult skin, water desorption follows a single process with a single rate constant, whereas in infants it includes two processes with two distinct rate constants. Natural moisturizing factors were found to be in lesser abundance within infant skin as measured by Raman confocal, indicating one potential mechanism for the higher water flux seen in infants. The results of this study demonstrate that not only does the barrier function of infant skin continue to develop postpartum, but surprisingly it appears to continue to develop at least through the first year of life. The data also reaffirm that infant skin is different from adult skin and remains so for an extended period of time. In conclusion, this study demonstrates that the distribution and transport of water through the superficial layers of the skin are distinctly different between infants and adults suggesting the need for greater protection of infant skin. 100% Funded By Johnson & Johnson Consumer and Personal Products Worldwide.
This study was supported by a grant from Sanofi-Aventis.
P2326 The association of asymmetric skin cancers with time spent in an automobile Susan Butler, MD, Saint Louis University, Saint Louis, MO, United States; Scott Fosko, MD, Saint Louis University, Saint Louis, MO, United States; Christopher Kling, MD, Saint Louis University, Saint Louis, MO, United States; Elizabeth Duvall, Saint Louis University, Saint Louis, MO, United States Background: It is well-known that UV exposure increases the risk for skin cancer. Automobile drivers get more UV exposure on the left side of the body than the right, particularly on the hands, arms, and face. Previous literature has shown an association between this unilateral exposure to UV light and an asymmetric distribution of photodamage, solar purpura and AKs. It would be expected that skin cancers would also be more prevalent on the left side of the body in automobile drivers. Objectives: To evaluate whether more skin cancers develop on the left side of the body and to determine the association of asymmetric skin cancers with time spent in an automobile. Methods: A retrospective chart review was performed of all the patients with skin cancer treated with Mohs in 2004. Type of skin cancer, location, and gender were evaluated to determine if a predominance of left-sided skin cancers existed in our patient population. To directly correlate the presence of asymmetric skin cancer with UV exposure from automobile driving, a questionnaire evaluating driving habits was given to SLU dermatology Mohs surgical patients. Results: A total of 1,047 patients (898 non-midline cancers) were included in the retrospective chart review. There were 608 BCCs, 178 SCCs, 23 MM, 25 MMIS, and 64 miscellaneous cancers. Fifty-three percent of all types of cancer occurred on the left, and 47% on the right (p = 0.059). Both sexes developed more skin cancers on the left side, but more asymmetry was found in males (p = 0.08) than in females (p = 7.86). When comparing those cancers occurring only in the areas most often exposed in automobiles (head, neck, arms, and hands), there are significantly more cancers on the left in males (p = 0.039), but not in females. Conclusions: There was significantly higher prevalence of skin cancer on the left head, neck, arms, and hands seen only in males, which supports the hypothesis that this may be due to UV exposure while driving. This gender difference may be attributed to the practice of males riding on the left side of the car more frequently. The results of the questionnaire correlating asymmetrical skin cancers with driving habits will help directly measure this influence. The data collected from the questionnaires was not available at the time of publication, but will likely show patients with left-sided skin cancers have spent more time driving an automobile than those with right-sided skin cancers. Commercial support: None identified.
PEDIATRIC DERMATOLOGY P2400 Infant skin barrier maturation in the first year of life Janeta Nikolovski, PhD, Johnson & Johnson Consumer Products Worldwide, Skillman, NJ, United States; Georgios Stamatas, PhD, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States;
FEBRUARY 2007
P2401 A pilot study of the efficacy and safety of pimecrolimus 1% cream in the treatment of Netherton syndrome: Interim results Albert Yan, MD, Children’s Hospital of Philadelphia, Philadelphia, PA, United States; Kara Shah, MD, PhD, Children’s Hospital of Philadelphia, Philadelphia, PA, United States; Christina Kubrak, Children’s Hospital of Philadelphia, Philadelphia, PA, United States; Anne Parneix-Spake, MD, Novartis, East Hanover, NJ, United States Netherton syndrome is a rare, autosomal recessive genodermatosis associated with mutations in the SPINK5 (serine protease inhibitor LEKTI) gene. Characterized by neonatal erythroderma, a chronic eczematous dermatitis, trichorrhexis invaginata, and ichthyosis linearis circumflexa, patients with Netherton syndrome also exhibit a reduction in cutaneous barrier function. Prior reports have documented improvement of the cutaneous manifestations of Netherton syndrome in patients using the topical calcineurin inhibitor, tacrolimus 0.1% ointment. These benefits were, however, limited by significant percutaneous absorption, resulting in high systemic levels of tacrolimus. In this pilot study, identical 12-year-old twin siblings with Netherton syndrome were treated with twice daily applications of topical 1% pimecrolimus cream to 50% of the total body surface area. Both patients were assessed at baseline, 1 wk, 2 wks, 4 wks, 8 wks, 12 wks, and 24 wks. Screening of complete blood counts and serum chemistries revealed transient self-limited elevations in transaminase levels, while pimecrolimus blood concentrations remained consistently low. In this study, the highest value observed in blood pimecrolimus levels in patients with Netherton syndrome was 1.26 ng/mL. The highest previously observed in children with atopic dermatitis using topical pimecrolimus was 2.6 ng/mL. Meanwhile, clinical improvement was also evident using a variety of clinical outcome measures. Key: [Patient 1 value, Patient 2 value] *Baseline Eczema and Severity Index (EASI) scores decreased from baseline values of [20, 21] to a nadir of [5.6, 9.9] at 4 wks, indicating a drop of [72%, 53%] in EASI scores. *Similarly, Netherton Area and Severity Assessment (NASA) scores decreased from baseline values of [21.9, 24.2] to a nadir of [7.6, 12] at 4 wks. This represents an improvement of [65%, 50%], respectively. *Pruritus scores dropped from baseline values for both patients of 8.5/10 to 2/10 at 12 wks. *Investigator Global Evaluation of Disease improved by ;50% from baseline values of [12/16, 11/16] tp [6, 5] at 12 wks. *Child Dermatology Quality of Life Index (CDLQI) measurements at 24 wks [5,4] also improved, decreasing from baseline values of [15, 9]. Maximum scores of 30 are possible. Assessment of transepidermal water loss (TEWL) was accomplished using the portable, handheld Vapometer (Delfin Technologies). Paradoxically, measurements of TEWL appeared to increase as clinical outcome measures improved. Pimecrolimus 1% cream may represent a safe and effective option for treating the cutaneous features of Netherton syndrome. Longer-term studies with additional patients will be necessary to confirm these preliminary findings. References: 1. Allen A, Siegfried E, Silverman R, Williams ML, Elias PM, et al. Arch Dermatol 2001;137(6):747-50. 2. Oji V, Beljian G, Beier K, Traupe H, et al. Br J Dermatol 2005;153(5):1067-8. Printing costs were provided by Novartis Pharmaceuticals.
J AM ACAD DERMATOL
AB153