Apcdd1 is a dual BMP/Wnt inhibitor in the developing nervous system and skin.

Animal development and homeostasis depend on precise temporal and spatial intercellular signaling. Components shared between signaling pathways, generally thought to decrease specificity, paradoxically can also provide a solution to pathway coordination. Here we show that the Bone Morphogenetic Protein (BMP) and Wnt signaling pathways share Apcdd1 as a common inhibitor and that Apcdd1 is a taxon-restricted gene with novel domains and signaling functions. Previously, we showed that Apcdd1 inhibits Wnt signaling (Shimomura et al., 2010), here we find that Apcdd1 potently inhibits BMP signaling in body axis formation and neural differentiation in chicken, frog, zebrafish. Furthermore, we find that Apcdd1 has an evolutionarily novel protein domain. Our results from experiments and modeling suggest that Apcdd1 may coordinate the outputs of two signaling pathways that are central to animal development and human disease.

Immune cell regulation of the hair cycle.

The ability to manipulate the mammalian hair cycle will lead to novel therapies and strategies to combat all forms of alopecia. Thus, in addition to the epithelial-mesenchymal interactions in the hair follicle, niche and microenvironmental signals that accompany the phases of growth, regression and rest need to be scrutinized. Immune cells are well described in skin homeostasis and wound healing and have recently been shown to play an important role in the mammalian hair cycle. In this review, we will summarize our current knowledge of the role of immune cells in hair cycle control and discuss their relevance to human hair cycling disorders. Increased attention to this aspect of the hair cycle will provide new avenues to manipulate hair regeneration in humans and provide better insight into developing better ex vivo models of hair growth.

Novel therapies for alopecia areata: The era of rational drug development.

Treatments for alopecia areata (AA) have evolved over the decades from broad and nonspecific therapies to those that are now more targeted and rationally selected. This was achieved by means of close cooperation and communication between clinicians and basic scientists, which resulted in the elucidation and understanding of the unique pathophysiology of AA. In this review we discuss this evolution and how novel therapies for AA have changed over the decades, what we have in our current arsenal of drugs for this potentially devastating disease, and what the future holds.

A rare combination of sebaceoma with carcinomatous change (sebaceous carcinoma), trichoblastoma, and poroma arising from a nevus sebaceus.

We report a case of a 48-year-old Malay female who presented with multiple tumors arising from a large nevus sebaceus on her right parieto-temporal scalp. Histologically, the tumors corresponded to a sebaceoma with carcinomatous change, a poroma and a trichoblastoma. Immunohistochemical staining of the sebaceous tumor with p53 showed strong within the areas of carcinomatous change, while there was negative to weak staining within the sebaceoma-like areas. A discussion on the potential secondary neoplasms from a nevus sebaceus ensues, with a review of this literature on multiple tumors from a nevus sebaceus.

Extramammary Paget disease: Immunohistochemistry is critical to distinguish potential mimickers.

Extra-mammary Paget disease (EMPD) is a rare intra-epithelial carcinoma that is usually found on the apocrine-rich skin of the perineum. We report 2 cases in which EMPD was initially misdiagnosed on the initial punch biopsy as melanoma-in-situ and Bowen disease respectively. Reasons for the misdiagnoses included a rare pigmented axillary variant of EMPD in the first case and atypical bowenoid features on H&E in the second. The cases are described with a critical review of the histopathological findings, along with a review of the current literature. This highlights the necessity of a comprehensive immunohistochemical panel for the assessment of intra-epithelial pagetoid atypical cells.

Expression of Staphylococcus aureus Virulence Factors in Atopic Dermatitis.

Atopic dermatitis (AD) is a skin inflammatory disease in which the opportunistic pathogen Staphylococcus aureus is prevalent and abundant. S. aureus harbors several secreted virulence factors that have well-studied functions in infection models, but it is unclear whether these extracellular microbial factors are relevant in the context of AD. To address this question, we designed a culture-independent method to detect and quantify S. aureus virulence factors expressed at the skin sites. We utilized RNase-H‒dependent multiplex PCR for preamplification of reverse-transcribed RNA extracted from tape strips of patients with AD sampled at skin sites with differing severity and assessed the expression of a panel of S. aureus virulence factors using qPCR. We observed an increase in viable S. aureus abundance on sites with increased severity of disease, and many virulence factors were expressed at the AD skin sites. Surprisingly, we did not observe any significant upregulation of the virulence factors at the lesional sites compared with those at the nonlesional control. Overall, we utilized a robust assay to directly detect and quantify viable S. aureus and its associated virulence factors at the site of AD skin lesions. This method can be extended to study the expression of skin microbial genes at the sites of various dermatological conditions.

Fas-ligand staining in non-drug- and drug-induced maculopapular rashes.

BACKGROUND: Morphologically and histopathologically, drug- and non-drug-induced maculopapular rashes can be almost indistinguishable. It has been postulated that Fas-ligand (Fas-L) is involved in the pathogenesis of drug rashes but not in the genesis of rashes, such as viral exanthems, that are not induced by medications. AIM: This study sought to determine if epidermal Fas-L is a distinguishing feature in the pathology of drug and non-drug maculopapular rashes. METHODS: Archived skin biopsies of patients with a confirmed diagnosis of drug or non-drug maculopapular rashes (n = 10 each) and positive and negative controls were retrieved for immunohistochemical staining for Fas-L. The proportion of Fas-L-positive skin biopsies were compared. The presence of tissue eosinophilia was also evaluated. RESULTS: Ten percent of non-drug-induced rashes were Fas-L positive compared to 50% of drug rashes (p = 0.05). Twenty percent of non-drug exanthems had moderate tissue eosinophilia, while 60% from drug rashes had moderate to dense tissue eosinophilia (p = 0.17). CONCLUSION: There is a trend toward Fas-L being more prevalent in the epidermis of drug maculopapular rashes, although this did not reach statistical significance. This is possibly because of the small sample size.

Telogen Effluvium - a review of the science and current obstacles.

Telogen effluvium (TE) is a common cause of diffuse non-scarring hair loss that is usually precipitated by physiological stress such as childbirth or sudden weight loss. Despite its high rate of remission, this phenomenon of sudden excessive hair loss can be very worrisome and upsetting for affected individuals and may significantly impact their quality of life. Due to the multifactorial causes and precipitants of TE, it is often challenging to diagnose and manage. Further, the mechanisms through which physiological stress influences the human hair cycle is unknown, and there are no targeted treatments for the management of TE. This review will describe the approach in making a diagnosis of TE, summarize the latest developments made in understanding the mechanisms of TE, outline the treatments tried, and recommend ways for advancing the study of this dermatological condition.

A Subset of TREM2+ Dermal Macrophages Secretes Oncostatin M to Maintain Hair Follicle Stem Cell Quiescence and Inhibit Hair Growth.

Hair growth can be induced from resting mouse hair follicles by topical application of JAK inhibitors, suggesting that JAK-STAT signaling is required for maintaining hair follicle stem cells (HFSCs) in a quiescent state. Here, we show that Oncostatin M (OSM), an IL-6 family cytokine, negatively regulates hair growth by signaling through JAK-STAT5 to maintain HFSC quiescence. Genetic deletion of the OSM receptor or STAT5 can induce premature HFSC activation, suggesting that the resting telogen stage is actively maintained by the hair follicle niche. Single-cell RNA sequencing revealed that the OSM source is not intrinsic to the hair follicle itself and is instead a subset of TREM2+ macrophages that is enriched within the resting follicle and deceases immediately prior to HFSC activation. In vivo inhibition of macrophage function was sufficient to induce HFSC proliferation and hair cycle induction. Together these results clarify how JAK-STAT signaling actively inhibits hair growth.

Acquired Diffuse Trichomalacia Associated With Prolonged Use of a Detangling Hairbrush.

This case series reports on cases of diffuse alopecia with trichomalacia after use of a detangling hairbrush.

Tissue engineering of human hair follicles using a biomimetic developmental approach.

Human skin constructs (HSCs) have the potential to provide an effective therapy for patients with significant skin injuries and to enable human-relevant drug screening for skin diseases; however, the incorporation of engineered skin appendages, such as hair follicles (HFs), into HSCs remains a major challenge. Here, we demonstrate a biomimetic approach for generation of human HFs within HSCs by recapitulating the physiological 3D organization of cells in the HF microenvironment using 3D-printed molds. Overexpression of Lef-1 in dermal papilla cells (DPC) restores the intact DPC transcriptional signature and significantly enhances the efficiency of HF differentiation in HSCs. Furthermore, vascularization of hair-bearing HSCs prior to engraftment allows for efficient human hair growth in immunodeficient mice. The ability to regenerate an entire HF from cultured human cells will have a transformative impact on the medical management of different types of alopecia, as well as chronic wounds, which represent major unmet medical needs.

The Changing Landscape of Alopecia Areata: The Translational Landscape.

Recent genetic and preclinical studies have increased our understanding of the immunopathogenesis of alopecia areata (AA). This has allowed expedited development of targeted therapies for the treatment of AA, and a paradigm shift in our approach and understanding of autoimmunity and the hair follicle. The synergy between preclinical studies, animal models, and translational studies has led to unprecedented advances in the treatment options for AA, ultimately benefiting patients who have had little recourse. In this review, we summarize the scientific field of contemporary AA research, and look forward to potential new technologies and developments.

JAK-STAT Signaling Jump Starts the Hair Cycle.

Legrand et al show that JAK/STAT5 signaling in the dermal papilla is required for anagen onset in the murine hair cycle. Interestingly, others have shown that JAK-inhibition is able to induce telogen-to-anagen transition in wild-type mice. This apparent contradiction highlights the complexity of interactions within the hair follicle, and encourages further discussion on the role of JAK-STAT signaling in the various stem cell niches of the hair follicle.

Single Treatment with 100-Microsecond Alexandrite Laser Clears Selected Acquired Melanocytic Nevi in Type IV Asian Facial Skin.

CONTEXT: Small common acquired melanocytic nevi (AMNs) are common on Asian facial skin. AIMS: To show that the 755 nm Alexandrite laser stacked at the 100-µs long-pulsed mode (µsAL) is an effective modality for the removal of selected AMNs. SETTINGS AND DESIGN: This was a retrospective case series, followed up with a telephone interview. MATERIALS AND METHODS: A retrospective analysis of all patients treated between January 2010 and April 2012 with the µsAL laser for small AMNs was conducted. Pre- and post-treatment facial photographs and photographs of the individual lesions were analyzed by two independent dermatological surgeons for degree of clearance and complications. A telephone interview was conducted with the patients to assess their satisfaction with the procedure. RESULTS: A total of 18 patients with 53 lesions were included. 7/18 (38.9%) of patients had 'excellent' results. No patients had 'mild' or 'poor' results. At 4 week post-treatment, 49/53 (92.5%) were totally cleared, with 14/53 (26.4%) reporting mild atrophy, and 11/53 (20.8%) reporting mild post-inflammatory hypopigmentation. The majority of lesions had negligible complications. 9/18 (50%) judged the procedure to be 'excellent', and all patients reported that they would recommend this procedure to a friend seeking removal of small facial AMNs. CONCLUSION: The µsAL is an effective modality for the removal of small facial AMNs.

Current treatment strategies in pediatric alopecia areata.

Alopecia areata (AA) is a non-scarring autoimmune disease of the hair follicle that can present at any age. Pediatric cases are commonly seen in a dermatology clinic, and management can potentially be challenging, with a small proportion of cases experiencing a chronic relapsing course marked by distressing hair loss that can bring about significant psychosocial morbidity. We review the established treatments for pediatric alopecia areata, alongside second and third line therapies that have shown to be efficacious. We also offer a treatment algorithm as a guide to the treatment of pediatric AA.

Is propionibacterium acnes associated with hair casts and alopecia?

We report a series of four patients who presented with complaints of diffuse non-scarring alopecia. They had similar clinical features of alopecia, hyperseborrhea, and distinct keratinaceous hair casts that encircled the hair shafts. Propionibacterium acnes was isolated from two of the patients' scalp, and Gram-positive, Giemsa-positive bacteria were seen in the hair follicles in the scalp biopsy of one of the patients. The patients' symptoms did not respond to standard treatment for seborrheic dermatitis, but responded to a course of systemic antibiotics targeting P. acnes. We propose a role for P. acnes colonization of the terminal hair follicles in the pathogenesis of hair casts, and possibly diffuse non-scarring alopecia. Possible mechanisms of pathogenesis are discussed with a literature review.