Sterol Intermediates of Cholesterol Biosynthesis Inhibit Hair Growth and Trigger an Innate Immune Response in Cicatricial Alopecia

Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders

Sentinel Node Biopsy in Young Patients with Atypical Melanocytic Tumors of the Head and Neck

Objective To examine the diagnostic value of the sentinel lymph node biopsy in pediatric through young adult head and neck melanocytic tumors of unknown malignant potential. Study Design Retrospective case series. Setting Single academic institution. Subjects and Methods Demographics, histology, and outcomes were examined in 14 patients aged 4 to 24 years with head and neck melanocytic tumors of unknown malignant potential. Information on age at diagnosis, primary lesion characteristics, and sentinel lymph node biopsy were compared. Results Of 14 patients meeting criteria for head and neck melanocytic tumors of unknown malignant potential, 8 patients underwent sentinel lymph node biopsy (57%). Of those, 4 biopsies (50%) had positive sentinel nodes. All patients undergoing sentinel lymph node biopsy had primary lesions greater than 1 mm depth or mitotic rate of at least 1 mitosis per mm 2 . No patients had recurrence of their primary lesion at time of follow-up. Conclusion Our data show a high rate of node-positive sentinel lymph node biopsy for pediatric and young adult head and neck patients with melanocytic tumors of unknown malignant potential, supporting the value of sentinel lymph node biopsy in this population