Faculty Bibliography

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in humans worldwide. Studies suggest that BCCs exhibit immunoprotection, similar to other keratinocyte carcinomas, although the mechanisms of defence have not been defined. OBJECTIVES: To examine if indoleamine 2,3-dioxygenase (IDO), an immune privilege-associated enzyme, would be expressed in BCC, regulated in part by CXCR3. METHODS: We analysed the expression and function of IDO in human BCC (hBCC) tissues using nonlesional skin epithelial (NL) tissues as a control. RESULTS: Quantitative real-time reverse transcription-polymerase chain reaction (qPCR) revealed significant upregulation of IDO1 and IDO2 (12.5- and 19.14-fold change, respectively) in nodular hBCCs as compared with NL tissues. Immunohistochemistry showed that IDO colocalized with keratin 17, a BCC keratinocyte marker, in hBCC tissues. Western blot identified a full-length IDO (42 kDa) product and a splice variant ( approximately 30 kDa) in BCC tissues. Kynurenine assays and qPCR were conducted to determine IDO enzymatic activity in hBCCs in vitro with CXCL11 supplementation, which has previously been shown to be required for the tumour cell growth. Addition of CXCL11 upregulated IDO2 and increased l-kynurenine concentration in a dose-dependent manner in hBCCs while normal primary keratinocytes exhibited no response. Conclusions: The expression of IDO at both mRNA and protein levels in hBCC tissues, the upregulation of IDO2 and the IDO-mediated l-kynurenine production in hBCCs with CXCL11 treatment suggest that functional IDO is synthesized by hBCC tumours and may be used as a method of immunoprotection during tumorigenesis. Also, IDO enzymatic activity may be modulated by CXCR3/CXCL11 signalling in BCCs.

BACKGROUND: We report on a first case of lichen planopilaris (LPP) mimicking androgenetic alopecia (AGA) in an individual who has been break-dancing on his head for many years. LPP is an autoimmune inflammatory scalp condition that when left untreated can result in scarring and irreversible hair loss. The etiology of LPP is unknown. Different treatment modalities are used for LPP and AGA. OBJECTIVE: To increase the awareness of physicians to the possibility of scarring hair loss (LPP) presenting like AGA. RESULTS: Scalp examination showed scarring patches of hair loss. A scalp biopsy confirmed the diagnosis of LPP. CONCLUSION: Chronic scalp trauma due to break dancing may be a trigger for LPP. A meticulous scalp examination should be performed before making a diagnosis of nonscarring conditions of hair loss such as AGA. Early recognition of LPP and appropriate treatment are important before scarring and irreversible hair loss ensue.

BACKGROUND: Although central scalp hair loss is a common problem in African American women, data on etiology or incidence are limited. OBJECTIVE: We sought to determine the frequency of various patterns and degree of central scalp hair loss in African American women and to correlate this with information on hair care practices, family history of hair loss, and medical history. METHODS: Five hundred twenty-nine subjects at six different workshops held at four different sites in the central and/or southeast United States participated in this study. The subjects' patterns and degree of central scalp hair loss were independently assessed by both subject and investigator using a standardized photographic scale. Subjects also completed a detailed questionnaire and had standardized photographs taken. Statistical analysis was performed evaluating answers to the questionnaire relative to pattern of central hair loss. RESULTS: Extensive central scalp hair loss was seen in 5.6% of subjects. There was no obvious association of extensive hair loss with relaxer or hot comb use, history of seborrheic dermatitis or reaction to a hair care product, bacterial infection, or male pattern hair loss in fathers of subjects; however, there was an association with a history of tinea capitis. LIMITATIONS: There was no scalp biopsy correlation with clinical pattern of hair loss and further information on specifics of hair care practices is needed. CONCLUSIONS: This central scalp photographic scale and questionnaire provide a valid template by which to further explore potential etiologic factors and relationships to central scalp hair loss in African American women

Basal cell carcinoma (BCC) is the most common skin malignancy encountered worldwide. We hypothesized that CXC chemokines, small cytokines involved in inducing directed leukocyte chemotaxis, could play a key role in the modulation of BCC growth. In this study, quantitative RT-PCR revealed that the chemokines CXCL9, 10, 11, and their receptor CXCR3 were significantly upregulated by an average 22.6-fold, 9.2-fold, 26.6-fold, and 4.9-fold, respectively in BCC tissue samples as compared with nonlesional skin epithelium. Immunohistochemistry analysis revealed that CXCR3, CXCL10, and CXCL11, but not CXCL9, colocalized with cytokeratin 17 (K17) in BCC keratinocytes. In addition, CXCR3 and its ligands were expressed in cells of the surrounding BCC stroma. The chemokines and K17 were also expressed in cultured human immortalized HaCaT keratinocytes. Exposure of HaCaT cells or primary BCC-derived cells to CXCL11 peptides in vitro significantly increased cell proliferation. In primary BCC-derived cell cultures, addition of CXCL11 progressively selected for K17+/CXCR3+ co-expressing cells over time. The expression of CXCR3 and its ligands in human BCC keratinocytes, the enhancement of keratinocyte cell proliferation by CXCL11, and the homogeneity of K17+ BCC cells in human BCC-isolated cell population supported by CXCR3/CXCL11 signaling all suggest that CXCR3 and its ligands may be important autocrine and/or paracrine signaling mediators in the tumorigenesis of BCC.

Various therapeutic agents have been described for the treatment of alopecia areata (AA), but none are curative or preventive. The aim of AA treatment is to suppress the activity of the disease. The high rate of spontaneous remission and the paucity of randomized, double-blind, placebo-controlled studies make the evidence-based assessment of these therapies difficult. The second part of this two-part series on AA discusses treatment options in detail and suggests treatment plans according to specific disease presentation. It also reviews recently reported experimental treatment options and potential directions for future disease management. LEARNING OBJECTIVES: After completing this learning activity, participants should be able to compare the efficacy and safety of various treatment options, formulate a treatment plan tailored to individual patients, and recognize recently described treatments and potential therapeutic approaches

Alopecia areata (AA) is an autoimmune disease that presents as nonscarring hair loss, although the exact pathogenesis of the disease remains to be clarified. Disease prevalence rates from 0.1% to 0.2% have been estimated for the United States. AA can affect any hair-bearing area. It often presents as well demarcated patches of nonscarring alopecia on skin of overtly normal appearance. Recently, newer clinical variants have been described. The presence of AA is associated with a higher frequency of other autoimmune diseases. Controversially, there may also be increased psychiatric morbidity in patients with AA. Although some AA features are known poor prognostic signs, the course of the disease is unpredictable and the response to treatment can be variable. Part one of this two-part series on AA describes the clinical presentation and the associated histopathologic picture. It also proposes a hypothesis for AA development based on the most recent knowledge of disease pathogenesis. LEARNING OBJECTIVES: After completing this learning activity, participants should be familiar with the most recent advances in AA pathogenesis, recognize the rare and recently described variants of AA, and be able to distinguish between different histopathologic stages of AA

BACKGROUND: Lichen planopilaris (LPP) and pseudopelade of Brocq (PPB) are two scarring alopecia diagnoses that exhibit similar clinical features. Some suggest LPP and PPB are not distinct diseases, but rather different clinical presentations in a spectrum derived from the same underlying pathogenic mechanism. OBJECTIVE: We explored the degree of similarity between LPP and PPB gene expression patterns and the potential for common and unique gene pathway and gene activity in LPP and PPB using microarrays. METHODS: Microarray analysis, using a 21K cDNA set, was performed on pairs of biopsies obtained from affected and unaffected scalp of untreated patients. Diagnosis was confirmed by histopathology. Significantly differentially expressed genes were identified by analysis of microarray results in various datasets and screened for signaling pathway involvement. Selected genes were validated by quantitative PCR and immunohistology. RESULTS: The global gene expression profiles in LPP and PPB versus comparative intra-control scalp tissue were distinguishable by significance analysis of microarrays (SAM). There was limited commonality in the gene expression profiles between LPP and PPB. Specific genes, such as MMP11, TNFSF13B, and APOL2, were identified with significantly differential expression in association with LPP versus PPB. CONCLUSIONS: Our findings may have important implications for understanding the pathogenesis of LPP and PPB at the molecular level. Results suggest LPP and PPB involve different mechanisms of disease development and should be regarded as biologically distinct cicatricial alopecia diagnoses. Genes that we have identified may be useful as markers of the respective diagnoses and may be potential therapeutic targets