Update on the role of plasmacytoid dendritic cells in inflammatory/autoimmune skin diseases.

Plasmacytoid dendritic cells (pDCs) represent a specialized dendritic cell population that exhibit plasma cell morphology, express CD4, CD123, blood-derived dendritic cell antigen-2 (BDCA-2) and Toll-like receptor (TLR)7 and TLR9 within endosomal compartments. When activated, pDCs are capable of producing large quantities of type I IFNs (mainly IFN-α/ß), which provide antiviral resistance and link the innate and adaptive immunity. While generally lacking from normal skin, pDCs infiltrate the skin and appear to be involved in the pathogenesis of several inflammatory, infectious (especially viral) and neoplastic entities. In recent years, pDC role in inflammatory/autoimmune skin conditions has been extensively studied. Unlike type I IFN-mediated protective immunity that pDCs provide at the level of the skin by regulated sensing of microbial or self-nucleic acids upon skin damage, excessive sensing may elicit IFN-driven inflammatory/autoimmune diseases. In this review, focus will be on the role of pDCs in cutaneous inflammatory/autoimmune dermatoses.

A case of bilateral Parry-Romberg syndrome successfully treated with hyaluronic acid filler augmentation.

Parry-Romberg syndrome is a rare acquired neurocutaneous disorder typically characterized by hemifacial atrophy. Few cases of bilateral facial involvement have been reported. We report a case of a 60-year-old female with a 20-year history of progressive bilateral facial atrophy. Although an initial diagnosis of acquired partial lipodystrophy was considered, a diagnosis of bilateral Parry-Romberg was favored for three main reasons: (a) lipoatrophy was confined to the face (b) imaging findings of enophthalmos and underlying white matter changes (c) laboratories showing absence of C3 nephritic factor and normal complement levels. The patient was treated with hyaluronic acid fillers with dramatic improvement in cosmetic appearance.

Ocular Rosacea Causing Corneal Melt in an African American Patient and a Hispanic Patient.

PURPOSE: To discuss two rare presentations of ocular rosacea in a Hispanic patient and an African American patient with unusual ocular manifestations. CASE REPORT: Case 1: a 43-year-old Hispanic woman presented with right eye corneal perforation. Her prior medical history was significant for rosacea only, diagnosed clinically by a dermatologist. Her eye exam showed signs of bilateral ocular rosacea. An emergent full thickness tectonic corneal patch graft was done. The patient's bilateral eye symptoms improved one month after initiating rosacea treatment. Case 2: a 51-year-old African American man with long standing history of untreated rosacea presented with bilateral peripheral corneal thinning with neovascularization that led to right eye corneal perforation. Glue and bandage contact lens were applied. The patient did well 4 weeks after starting antibacterial, oral steroids, and rosacea treatment. DISCUSSION: Ocular rosacea can present in Hispanic and African American patients with severe manifestations such as corneal perforation.

Plasmacytoid dendritic cell role in cutaneous malignancies.

Plasmacytoid dendritic cells (pDCs) correspond to a specialized dendritic cell population that exhibit plasma cell morphology, express CD4, CD123, HLA-DR, blood-derived dendritic cell antigen-2 (BDCA-2), and Toll-like receptor (TLR)7 and TLR9 within endosomal compartments. Through their production of type I interferons (IFNs) and other pro-inflammatory cytokines, pDCs provide anti-viral resistance and link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer (NK) cells. While lacking from normal skin, pDCs are usually recruited to the skin in several cutaneous pathologies where they appear to be involved in the pathogenesis of several infectious, inflammatory/autoimmune, and neoplastic entities. Among the latter group, pDCs have the potential to induce anti-tumour immunity; however, the complex interaction of pDCs with tumor cells and their micro-environment appears to contribute to immunologic tolerance. In this review, we aim at highlighting the role played by pDCs in cutaneous malignancies with special emphasis on the underlying mechanisms.

Identification of several mutations in ATP2C1 in Lebanese families: insight into the pathogenesis of Hailey-Hailey disease.

BACKGROUND: Hailey-Hailey disease (HHD) is an inherited blistering dermatosis characterized by recurrent erosions and erythematous plaques that generally manifest in intertriginous areas. Genetically, HHD is an autosomal dominant disease, resulting from heterozygous mutations in ATP2C1, which encodes a Ca2+/Mn2+ATPase. In this study, we aimed at identifying and analyzing mutations in five patients from unrelated families diagnosed with HHD and study the underlying molecular pathogenesis. OBJECTIVES: To genetically study Lebanese families with HHD, and the underlying molecular pathogenesis of the disease. METHODS: We performed DNA sequencing for the coding sequence and exon-intron boundaries of ATP2C1. Heat shock experiments were done on several cell types. This was followed by real-time and western blotting for ATP2C1, caspase 3, and PARP proteins to examine any possible role of apoptosis in HHD. This was followed by TUNEL staining to confirm the western blotting results. We then performed heat shock experiments on neonatal rat primary cardiomyocytes. RESULTS: Four mutations were detected, three of which were novel and one recurrent mutation in two families. In order for HHD to manifest, it requires both the genetic alteration and the environmental stress, therefore we performed heat shock experiments on fibroblasts (HH and normal) and HaCaT cells, mimicking the environmental factor seen in HHD. It was found that stress stimuli, represented here as temperature stress, leads to an increase in the mRNA and protein levels of ATP2C1 in heat-shocked cells as compared to non-heat shocked ones. However, the increase in ATP2C1 and heat shock protein hsp90 is significantly lower in HH fibroblasts in comparison to normal fibroblasts and HaCaT cells. We did not find a role for apoptosis in the pathogenesis of HHD. A similar approach (heat shock experiments) done on rat cardiomyocytes, led to a significant variation in ATP2C1 transcript and protein levels. CONCLUSION: This is the first genetic report of HHD from Lebanon in which we identified three novel mutations in ATP2C1 and shed light on the molecular mechanisms and pathogenesis of HHD by linking stress signals like heat shock to the observed phenotypes. This link was also found in cultured cardiomyocytes suggesting thus a yet uncharacterized cardiac phenotype in HHD patients masked by its in-expressivity in normal health conditions.