Diagnosis and management of allergic contact dermatitis in children: common allergens that can be easily missed.

PURPOSE OF REVIEW: Contact dermatitis is an economically burdensome pediatric disease, and it is important to know the top allergens that have remained as top offenders for over the last decade. RECENT FINDINGS: A comparative analysis of the 20-allergen screen was done against the current top 40 pediatric allergens, and it revealed that the 20-allergen screening series would have theoretically only captured 47.5% of the relevant contact allergens (52.5% failure to detect rate). In addition, the T.R.U.E. Test (SmartPractice, Phoenix, Arizona, USA) would have revealed 60% of the top 40 allergens (40% failure to detect rate). SUMMARY: Patch testing in children has become a more common practice, and management requires the identification and avoidance of the offending allergen from the sensitized person's environment.

Fluorouracil Enhances Photodynamic Therapy of Squamous Cell Carcinoma via a p53-Independent Mechanism that Increases Protoporphyrin IX levels and Tumor Cell Death.

Photodynamic therapy (PDT), using 5-aminolevulinic acid (ALA) to drive synthesis of protoporphryin IX (PpIX) is a promising, scar-free alternative to surgery for skin cancers, including squamous cell carcinoma (SCC) and SCC precursors called actinic keratoses. In the United States, PDT is only FDA approved for treatment of actinic keratoses; this narrow range of indications could be broadened if PDT efficacy were improved. Toward that goal, we developed a mechanism-based combination approach using 5-fluorouracil (5-FU) as a neoadjuvant for ALA-based PDT. In mouse models of SCC (orthotopic UV-induced lesions, and subcutaneous A431 and 4T1 tumors), pretreatment with 5-FU for 3 days followed by ALA for 4 hours led to large, tumor-selective increases in PpIX levels, and enhanced cell death upon illumination. Several mechanisms were identified that might explain the relatively improved therapeutic response. First, the expression of key enzymes in the heme synthesis pathway was altered, including upregulated coproporphyrinogen oxidase and downregulated ferrochelatase. Second, a 3- to 6-fold induction of p53 in 5-FU-pretreated tumors was noted. The fact that A431 contains a mutant form p53 did not prevent the development of a neoadjuvantal 5-FU effect. Furthermore, 5-FU pretreatment of 4T1 tumors (cells that completely lack p53), still led to significant beneficial inductions, that is, 2.5-fold for both PpIX and PDT-induced cell death. Thus, neoadjuvantal 5-FU combined with PDT represents a new therapeutic approach that appears useful even for p53-mutant and p53-null tumors. Mol Cancer Ther; 16(6); 1092-101. ©2017 AACR.

Pigmented basal cell carcinoma: increased melanin or increased melanocytes?

BACKGROUND: Studies on the precise cause of increased melanization in pigmented basal cell carcinomas (BCC) are limited. We aimed to determine whether the cause of melanization is from increased number of melanocytes or increased melanin pigment, and if there is a difference in the number of melanocytes on different sun-exposed locations. METHODS: A retrospective review of 45 skin biopsies from January 2011 to February 2011 was performed; 30 were diagnosed as pigmented BCC and 15 as non-pigmented BCC. Immunohistochemistry for MART-1 (melanoma-associated antigen recognized by T-cell 1)/Melan-A (clone M2-7610 + M2-9E3; Leica Microsystems Inc. Buffalo Grove, IL, USA) from Biocare Medical (Concord, CA, USA) was performed on all biopsies. Associations between histopathologic features, number of melanocytes, location, and specific diagnoses were analyzed by Mann-Whitney U test. RESULTS: The mean melanocyte count per high powered field in pigmented BCCs from sun-exposed skin was 101.9 and from intermittently sun-exposed skin was 122.5, as compared to the controls (nodular non-pigmented BCC) of 27.4 (p = 0.002) and 34.9 (p = 0.002), respectively. CONCLUSIONS: Pigmented BCCs have a higher mean melanocyte count as compared to non-pigmented BCCs irrespective of location. Therefore, the pigment is not only due to increased melanin, but also due to increased melanocytes.

Association of lichen planopilaris with thyroid disease: a retrospective case-control study.

BACKGROUND: Studies on the precise causes and comorbidities seen with lichen planopilaris (LPP) are limited. OBJECTIVE: We sought to determine the prevalence of thyroid diseases in patients with LPP. METHODS: Medical records of 166 patients with LPP and 81 age- and gender-matched control subjects seen in the Department of Dermatology at the Cleveland Clinic Foundation in Ohio between 2000 and 2013 were reviewed. RESULTS: A diagnosis of thyroid disease was present in 34% (n = 57) of the 166 patients with LPP, and in 11% (n = 9) of the control subjects (P = .0001). When confined to hypothyroidism only, this disease was found in 29% (n = 48) of the patients with LPP and 9% (n = 7) of the control subjects (P = .0003). LIMITATIONS: This study was limited by being retrospective. CONCLUSION: In our patients, LPP was associated with thyroid disease, especially hypothyroidism.

Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer.

Breast cancer remains a major cause of death in the United States as well as the rest of the world. In view of the limited treatment options for patients with advanced breast cancer, preventive and novel therapeutic approaches play an important role in combating this disease. The plant-derived triterpenoids, commonly used for medicinal purposes in many Asian countries, posses various pharmacological properties. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells as well as anticancer efficacy in preclinical animal models. Numerous triterpenoids have been synthesized by structural modification of natural compounds. Some of these analogs are considered to be the most potent antiinflammatory and anticarcinogenic triterpenoids known. This review examines the potential role of natural triterpenoids and their derivatives in the chemoprevention and treatment of mammary tumors. Both in vitro and in vivo effects of these agents and related molecular mechanisms are presented. Potential challenges and future directions involved in the advancement of these promising compounds in the prevention and therapy of human breast cancer are also identified.