Faculty Bibliography

OBJECTIVES: To better categorize the epidemiologic profile, clinical features, and disease associations of loose anagen hair syndrome (LAHS) compared with other forms of childhood alopecia. DESIGN: Retrospective survey. SETTING: Academic pediatric dermatology practice. Patients Three hundred seventy-four patients with alopecia referred from July 1, 1997, to June 31, 2007. MAIN OUTCOME MEASURES: Epidemiologic data for all forms of alopecia were ascertained, such as sex, age at onset, age at the time of evaluation, and clinical diagnosis. Patients with LAHS were further studied by the recording of family history, disease associations, hair-pull test or biopsy results, hair color, laboratory test result abnormalities, initial treatment, and involvement of eyelashes, eyebrows, and nails. RESULTS: Approximately 10% of all children with alopecia had LAHS. The mean age (95% confidence interval) at onset differed between patients with LAHS (2.8 [1.2-4.3] years) vs patients without LAHS (7.1 [6.6-7.7] years) (P < .001), with 3 years being the most common age at onset for patients with LAHS. All but 1 of 37 patients with LAHS were female. The most common symptom reported was thin, sparse hair. Family histories were significant for LAHS (n = 1) and for alopecia areata (n = 3). In 32 of 33 patients, trichograms showed typical loose anagen hairs. Two children had underlying genetic syndromes. No associated laboratory test result abnormalities were noted among patients who underwent testing. CONCLUSIONS: Loose anagen hair syndrome is a common nonscarring alopecia in young girls with a history of sparse or fine hair. Before ordering extensive blood testing in young girls with diffusely thin hair, it is important to perform a hair-pull test, as a trichogram can be instrumental in the confirmation of a diagnosis of LAHS

Despite their rarity, diseases of premature aging, or 'progeroid' syndromes, have provided important insights into basic mechanisms that may underlie cancer and normal aging. In this review, we highlight these recent developments in Hutchinson-Gilford progeria syndrome (HGPS), Werner syndrome, Bloom syndrome, Cockayne syndrome, trichothiodystrophy, ataxia-telangiectasia, Rothmund-Thomson syndrome, and xeroderma pigmentosum. Though they are caused by different mutations in various genes and often result in quite disparate phenotypes, deciphering the molecular bases of these conditions has served to highlight their underlying basic similarities. Studies of progeroid syndromes, particularly HGPS, the most dramatic form of premature aging, have contributed to our knowledge of fundamental processes of importance to skin biology, including DNA transcription, replication, and repair, genome instability, cellular senescence, and stem-cell differentiation

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare disorder of keratinization involving the intraepidermal eccrine duct (acrosyringium). We detail two examples of this unique clinicopathological entity--one with a more typical clinical presentation and one with a solitary lesion and late adult onset. In addition, we discuss the distinctive histologic and immunohistochemical findings and review the literature

Most metastatic melanoma patients fail to respond to available therapy, underscoring the need to develop more effective treatments. We screened 2,000 compounds from the Spectrum Library in human melanoma cell lines to identify compounds that enhanced the cytotoxic effect of temozolomide, a drug used to treat metastatic melanoma. Screening was done with the temozolomide-resistant melanoma cell line SK-MEL-19, and six compounds were identified that had little or no inherent cytotoxicity but significantly enhanced growth-inhibition by temozolomide. These compounds were tested in five additional melanoma cell lines. Cell proliferation and death assays were used to compare the efficacy of single agent temozolomide versus combination treatments. Effects of combination treatment on levels of DNA double-strand breaks, the DNA repair protein O(6)-methylguanine-DNA-methyltransferase, apoptosis [measured by cleaved caspase-3 and poly(ADP-ribose) polymerase], and cell cycle were examined. Pyrimethamine, an antiparasitic, sensitized melanoma cells to temozolomide. Temozolomide combined with Pyrimethamine synergistically inhibited cell proliferation in melanoma cells with combination index values of 0.7 or less. In addition, combination treatment induced cell cycle arrest and increased both DNA damage and apoptosis. The increase in cell death due to combination treatment was rescued by leucovorin. Other folate antagonists were also effective enhancers of temozolomide-induced cytotoxicity, and the effects of antifolates were also evident in gliomas. Our screening approach led to the identification of Pyrimethamine, an orally available drug that efficiently crosses the blood-brain barrier, as a potent enhancer of the efficacy of temozolomide as an antineoplastic agent via inhibition of folate metabolism

BACKGROUND: The condition known as macrocephaly-cutis marmorata telangiectatica congenita syndrome (M-CMTC) is a rare congenital syndrome of unknown etiology characterized by macrocephaly and vascular lesions that have been described as either cutis marmorata or cutis marmorata telangiectatica congenita (CMTC). Most patients also exhibit facial and limb asymmetry; somatic overgrowth; developmental delay; capillary malformations of the nose, philtrum, and/or upper lip; neurologic abnormalities; syndactyly or polydactyly; craniofacial abnormalities; and joint laxity or soft skin. OBSERVATIONS: We describe 12 patients with this condition from tertiary care medical centers (8 cases) and accrued via an M-CMTC support group Web site (4 cases). All patients showed reticulated or confluent port-wine stains (PWS), not CMTC. Seven of the 12 patients also had centrofacial capillary malformations. In our comprehensive review of 100 previously reported cases, only 34 were accompanied by photographs that were sufficiently clear to review for diagnostic purposes. None had true CMTC, with most having reticulated PWS or persistent cutis marmorata. CONCLUSIONS: Reticulated or confluent PWS and persistent capillary malformations of the central face, rather than CMTC, are the most characteristic cutaneous vascular anomalies seen in so-called M-CMTC syndrome. The name macrocephaly-capillary malformations (M-CM) more accurately reflects the features of this syndrome