Tofacitinib for the treatment of erythematotelangiectatic and papulopustular rosacea: A retrospective case series.

Rosacea is a chronic inflammatory skin disease characterized by facial erythema, papules, pustules, telangiectasia, and flushing. The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway appears to play a role in the pathogenesis of rosacea. Our study preliminarily explored the efficacy of JAK inhibitor tofacitinib in the treatment of rosacea. We retrospectively reviewed the cases of 21 patients with rosacea who were treated with oral tofacitinib. Patients received oral tofacitinib 5 mg as either monotherapy or adjunctive therapy. We have observed that 15 out of 21 patients (71.4%) patients experienced significant regression of erythema on the face (IGA ≤ 1), and a mean change of -2.24 in the Investigator's Global Assessment (IGA) score was significant improvement from baseline. Treatment with oral tofacitinib might be a potentially effective treatment to ameliorate the symptoms of rosacea.

Mesenchymal stem cells in cancer progression and anticancer therapeutic resistance.

Increasing evidence indicates that the tumor microenvironment appears to play an increasingly important role in cancer progression and therapeutic resistance. Several types of cells within the tumor stroma had distinct impacts on cancer progression, either promoting or inhibiting cancer cell growth. Mesenchymal stem cells (MSCs) are a distinct type of cells that is linked to tumor development. MSCs are recognized for homing to tumor locations and promoting or inhibiting cancer cell proliferation, angiogenesis and metastasis. Moreover, emerging studies suggests that MSCs are also involved in therapeutic resistance. In this review, we analyzed the existing researches and elaborate on the functions of MSCs in cancer progression and anticancer therapeutic resistance, demonstrating that MSCs may be a viable cancer therapeutic target.

Efficacy of noninvasive multisource radiofrequency treatment on periorbital rhytids using an imaging device.

OBJECTIVE: To evaluate the efficacy of the multisource radiofrequency in periorbital wrinkles treatment using a VISIA imager. METHODS: This is a prospective cohort study involving 30 sites in 15 patients. INCLUSION CRITERIA: healthy subjects with periorbital wrinkles. Patients underwent five treatment sessions for each site using multisource radiofrequency. VISIA imager was used before and after each treatment, and in 12-week follow-up. The wrinkle scores were calculated and compared between baseline and 12-week follow-up. Changing in periorbital wrinkles were evaluated by blinded dermatologist using a scale of 0-3. After the study, patients rated their satisfaction using a scale of 0-3. The study protocol was approved by our institutional human research review committee, according to the ethics guideline of Helsinki (1975). RESULTS: The effect of treatment on subjects on follow-up compared to baseline showed a highly significant difference with P-values <0.05. Only two patients had no improvement according to blind dermatologist assessment of photographs. Thirteen patients reported satisfaction scale between 1 and 3. CONCLUSIONS: The multisource radiofrequency is safe and effective in reducing periorbital rhytids, and with the help of VISIA imager we can get more objective data to evaluate the efficacy of radiofrequency treatment on the periorbital areas. Lasers Surg. Med. 51:251-255, 2019. © 2018 Wiley Periodicals, Inc.

The Polysaccharide Extracted from Umbilicaria esculenta Inhibits Proliferation of Melanoma Cells through ROS-Activated Mitochondrial Apoptosis Pathway.

Melanoma is one of the most aggressive skin cancers with an increasing rate of morbidity. Umbilicaria esculenta is an edible lichen and its main component of extracts-polysaccharide (PUE) has shown significant antitumor effects in a variety of cancer types such as stomach adenocarcinoma. However, whether it has an anti-melanoma effect and the underlying mechanism has not been revealed. In this article, we showed that PUE extracted from Umbilicaria esculenta could inhibit the growth of A875 and A375 melanoma cells but without obvious toxicity to normal vascular endothelial cells. The generation of reactive oxygen species (ROS) in A875 cells was significantly elevated when treated with PUE for 24h. In addition, the expression of caspase-3 and -9 also increased as compared to the controlled group which resulted in the apoptosis of A875 melanoma cells. In the meantime, when pre-treated with N-acetylcysteine (NAC), the ROS scavenger, PUE induced apoptosis and cell death could be reversed via suppression of elevated generation of ROS and ROS-mediated caspase-9 expression. In summary, our study demonstrated that PUE extracts from Umbilicaria esculenta have a potent anti-melanoma effect through the induction of ROS and caspases-3 and -9. It could provide a promising strategy of melanoma therapy with the components from the extracts of natural and edible plants such as lichen Umbilicaria esculenta.

Generalized multinucleate cell angiohistiocytoma: case report and literature review.

BACKGROUND: Multinucleate cell angiohistiocytoma (MCAH) is an uncommon benign fibrohistiocytic and vascular proliferation, which usually occurs as slow-growing grouped reddish-brown to purple papules and nodules on the distal extremities or face. Patients with generalized MCAH are extremely rare and to our knowledge, there are no more than 11 cases reported previously in the medical literature. OBJECTIVE: To describe the clinical, histopathologic features and immunohistochemical characteristics of all reported cases of generalized MCAH and investigate any potential clinicopathological correlations. METHODS: A systematic review of the literature was done with information collected and organized in a table. A new case report is also described in a 42-year-old female with generalized MCAH. Histopathologic and immunohistochemical features of multiple biopsies were analyzed. RESULTS: Men and women are equally affected. It is crucial to take multiple biopsies preferably from newly formed lesions to reach the correct diagnosis. The divergent results in immunohistochemistry staining for CD68 and estrogen receptor (ER) alpha necessitate further studies to reach a precise etiology and pathogenesis and secure it with certainty. CONCLUSION: Awareness of the clinicopathological hallmarks is important to avoid underdiagnosis of MCAH and the immunohistochemical features may contribute to understanding the pathogenesis of this rare disease.

Papular acantholytic dyskeratosis of the anogenital and genitocrural area: case series and review of the literature.

BACKGROUND: Papular acantholytic dyskeratosis (PAD) of the anogenital/genitocrural area is described as a rare distinct clinicopathological entity known to dermatopathologists, although its characteristic histopathologic pattern resembles both Hailey-Hailey disease and Darier disease. The objective of this study is to describe the clinical characteristics, histopathologic features and response to treatment of PAD. METHODS: We report in detail six cases of PAD. A literature search of the keyword 'papular acantholytic dyskeratosis' was performed on Google scholar and PubMed, 21 cases of this entity were found. A total of 27 patients including our six cases are reviewed in this study. RESULTS: The mean age at diagnosis was 38.8 years with a male to female ratio of 0.8 : 1. Clinically, papular lesions (55.6%) are the typical manifestation of PAD, and the anogenital area (63%) is the most commonly involved site. Lesions were resistant to topical steroids, subcutaneous interferon and antibiotics while one case showed complete resolution of the lesions after retinoid therapy. Laser therapy showed good results in one case. None of the patients had spontaneous remission. CONCLUSION: Awareness of the clinicopathological hallmarks herein may be important to avoid underdiagnosis of PAD and may contribute to understanding the pathogenesis of this rare disease.

Intravascular NK/T-cell lymphoma: a report of five cases with cutaneous manifestation from China.

BACKGROUND: Intravascular lymphoma is a rare type of lymphoma that frequently affects the skin and is usually of B-cell origin. This lymphoma type is very rare and not recognized as a separate entity in the 2008 World Health Organization classification of hematopoietic and lymphoid tissue tumors. METHODS: We reported five cases of intravascular NK/T cell lymphoma with cutaneous manifestation and reviewed 12 published cases involving Chinese patients with similar characteristics. RESULTS: All five patients were adults who exhibited red or brown patches or plaques on the lower extremities or trunk; four cases were associated with B symptoms; one case developed subsequent to a lymphoma on the face (possibly extranodal NK/T cell lymphoma, nasal type). Histopathologically, all patients exhibited abnormal, medium-sized intravascular lymphocytes in the dermis and subcutaneous tissues. All patients were positive for CD2, CD3ϵ, CD56 and cytotoxic proteins. All cases were Epstein-Barr virus (EBV) positive. Four of FIVE patients died of lymphoma within a few months of diagnosis. CONCLUSIONS: Intravascular NK/T-cell lymphoma is a rare highly aggressive and EBV-associated lymphoma that is prone to develop in Chinese patients. The relationship between intravascular NK/T-cell lymphoma and extranodal NK/T-cell lymphoma, nasal type, requires clarification.

Eccrine Angiomatous Hamartoma: A Clinicopathological Study of 26 Cases.

BACKGROUND: Eccrine angiomatous hamartoma (EAH) is a rare benign cutaneous tumor characterized by the proliferation of eccrine glands and capillaries. OBJECTIVE: The aim of this study was to summarize the clinicopathological characteristics of EAH. METHODS: A retrospective chart review was performed on all patients diagnosed with EAH from 1977 to 2012 in the Union Hospital, Wuhan, P.R. China, and the clinicopathological features were compared with the cases reported in the literature. RESULTS: A total of 26 patients with EAH were identified. The male:female ratio was 1.2:1. EAH most commonly presents as a solitary (80.8%) plaque (50.0%) on the lower extremities (61.5%). Most patients presented with hyperhidrosis localizing to the lesion. Although most patients did not have major pain or anatomic deformity, one patient had severe pain as well as difficulty walking and moving, necessitating leg amputation. The histopathological findings showed typical features of EAH. CONCLUSION: EAH is a rare but characteristically benign skin hamartomatous condition. In rare occasions it can be associated with severe structural and functional impairment.

Hybrid eccrine gland and hair follicle hamartoma: a new entity of adnexal nevus.

Eccrine nevus shows increase in number or size of eccrine glands, whereas hair follicle nevus is composed of densely packed normal vellus hairs, and eccrine-pilar angiomatous nevus reveals increase of eccrine, pilar, and angiomatous structures. No case with increased number of both eccrine glands and hair follicles only in the dermis has been previously reported. A 10-month-old girl presented with cutaneous hamartoma with overlying skin hyperpigmentation on her left hypochondrium since 3 months of age, in whom the lesion was completely excised. Histopathology demonstrated evidently increased number of both eccrine glands and hair follicles in the dermis with reactive hyperplasia of collagen fibers. No recurrence occurred after the tumor was completely excised. A term "hybrid eccrine gland and hair follicle hamartoma" is proposed for this unique lesion.

IL-22-Induced Ubiquitin-Specific Protease 15 Promotes Proliferation and Inflammation of Keratinocytes through Stabilization of Squamous Cell Carcinoma Antigen 2.

Ubiquitin-specific protease 15 (USP15) plays a significant role in regulating various biological processes in several autoimmune diseases and cancers. However, its role in psoriatic keratinocytes (KCs) has not been extensively studied. In this study, we described that USP15 promotes proliferation and inflammation in KCs by stabilizing squamous cell carcinoma antigen 2. We discovered that the expression of USP15 and squamous cell carcinoma antigen 2 was elevated in lesions from patients with clinical psoriasis and an imiquimod-induced psoriatic dermatitis mouse model. USP15 was able to bind, deubiquitinate, and stabilize squamous cell carcinoma antigen 2. Knocking down USP15 resulted in reduced KC inflammation and impaired KC viability and clonogenicity. Topically applying USP15 small interfering RNA significantly ameliorated imiquimod-induced psoriatic dermatitis and reduced the infiltration of T cells and neutrophils. In addition, we determined that IL-22 was a key cytokine that upregulated the expression of USP15. These findings provide insights regarding the mechanisms involved in the proliferation and inflammation of KCs mediated by IL-22, suggesting a potential IL-22-USP15-squamous cell carcinoma antigen 2 axis in the pathogenesis of psoriatic KCs.