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Results in Clinical, Cosmetic and Investigational Dermatology: 1,248

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Crystal Zhou, Abhinav Vempati, Curtis Tam, Jeffrey Khong, Ruslan Vasilev, Kevin Tam, Sanam Hazany, Salar Hazany
Clinical, Cosmetic and Investigational Dermatology, pp 731-738;

Post-acne scarring is a common consequence of acne vulgaris with no universal cure. Although there have been many recent advances to address acne scars physically, there is still a lack of research that investigates their psychosocial impacts. Our comprehensive PubMed search presents an overview of existing information to highlight known sources of mental distress caused by post-acne scarring, both related to and independent of the psychosocial detriments caused early on by active acne. The literature indicates that acne scarring is a distinct condition from acne vulgaris and therefore requires a comprehensive clinical approach unique from those available for active acne.
Hee Kyung Kim, Hyun-Jo Kim, Jae Yun Kim, , Jiwon Son, Yongsung Hwang,
Clinical, Cosmetic and Investigational Dermatology, pp 721-729;

Background: Single to multiple pulse packs of bipolar, alternating current radiofrequency (RF) oscillations have been used for various medical purposes using invasive microneedle electrodes. This study was designed to evaluate the effects of pulse widths and cycles of RF pulse packs on immediate and delayed thermal tissue reactions in in vivo rat skin. Methods: RF energy at the frequency of 1 MHz and power of 70 W was delivered at each experimental setting into in vivo rat skin at 1.5-mm microneedle penetration, and then, tissue samples were obtained after 1 h and 3, 7, 14, and 21 days and histologically analyzed. Results: A single-pulse-pack RF treatment generated coagulative necrosis zones in the dermal peri-electrode area and zones of non-necrotic thermal reactions in the dermal inter-electrode area. Multiple pulse-pack, RF-treated rat skin specimens revealed that the number and size of peri-electrode coagulative necrosis were markedly decreased by increasing the number of pulse packs and accordingly decreasing the conduction time of each pulse pack. The microscopic changes in RF-induced non-necrotic thermal reaction in the inter-electrode area were more remarkable in specimens treated with RF of 7 or 10 pulse packs than in specimens treated with RF of 1– 4 pulse packs. Conclusion: The gated delivery of multiple RF pulse packs using a bipolar, alternating current, 1-MHz RF system using insulated microneedle electrodes efficiently generates non-necrotic thermal tissue reactions over the upper, mid, and deep dermis and subcutaneous fat in the inter-electrode areas.
Weikang Shi, Yuwen Lu, Fangyan Zhou, Huiyi He, Jicong Jiang, Ximao Xue
Clinical, Cosmetic and Investigational Dermatology, pp 717-720;

Eosinophilic pustular folliculitis (EPF) is a rare, chronic, itchy, aseptic disease. Although most cases of infantile EPF (I-EPF) are detected in infants, we found that a 7-year-old child with I-EPF, who received treatment with oral azithromycin in combination with topical narrow bound Ultra Violet B light (NB-UVB) irradiation, with no recurrence at follow-up. Our experience with the successful treatment of this patient can provide a reference for more pediatric patients.
Ana Lucia Gonzaga da Cunha, Rossana Vasconcelos, David Di Sessa, Gabriel Sampaio, Pitila Ramalhoto, Bruno F Zampieri, Bárbara S Deus, Suyan Vasconcelos, Talitha Bellote, Juiano Carvalho, et al.
Clinical, Cosmetic and Investigational Dermatology, pp 697-704;

Background: There is substantial interpersonal variation in the patterns of muscular contraction that substantiates the use of personalized points of application and dosages in clinical practice to achieve optimal results. Nevertheless, there has been no real-life therapeutic series with botulinum toxin for aesthetic treatment of the face in which the subjects were systematically followed to assess its long-term benefit. Purpose: To assess the performance and length of the treatment of glabellar and forehead lines with IncobotulinumtoxinA in a real-life setting. Patients and Methods: We enrolled 20 adults with indications for the treatment of upper facial dynamic lines (glabella and forehead) with botulinum toxin. The protocols of injection points were personalized by the injectors. The participants were photographed under maximum facial contraction before the application (D0) and after 15, 90, 120, and 180 days. The photos were randomly assessed by two blinded experienced raters to consensually grade the dynamic lines according to the Merz Aesthetics Scales (MAS). Efficacy was defined as the reduction in the MAS score. Results: At D15, 18 (90%; 95% CI: 80%– 100%) participants reached the zero score, or a 2-point reduction on the MAS score from the forehead and 16 (80%; 95% CI: 65– 90%) reached that reduction for the glabella. These values from D90 were 14 (70%; 95% CI: 55– 85%) for both sites. At D120, these values were 11 (55%; 95% CI: 35– 75%) and 8 (40%; 95% CI: 25– 55%) for the forehead and glabella. At D180, 10 (50%; 95% CI: 30– 70%) participants presented a MAS score for forehead or glabella dynamic lines lower than the score assessed at D0. Conclusion: As much as 70% of the patients sustained a reduction of scores after 120 days of the treatment for dynamic glabellar and forehead lines. Half of the patients evidenced prolonged benefit at 180 days.
, Moemena Maher Fathi Khalil, , Naglaa Sameh Zaki, Aya Fahim
Clinical, Cosmetic and Investigational Dermatology, pp 705-715;

Background: Acanthosis nigricans (AN) is a common chronic skin disorder clinically presents by velvety hyperpigmented lesions mainly at the flexural areas. Fractional photothermolysis has been reported to improve both pigmentary and textural changes by removing thin layers of skin with minimal thermal damage. Other options are the Q-switched (Qs) Nd:YAG (1064 nm) and Qs KTP (532 nm) lasers. Both can induce collagen remodeling by dermal photo-mechanical microdamage. Aim of the Work: The aim of this study was to assess the clinical efficacy and the safety of fractional CO2 laser versus Qs Nd:YAG and KTP lasers in the treatment of acanthosis nigricans. Methods: This randomized-controlled split neck study was conducted on 23 patients suffering from AN. For each patient, one side of the neck was randomly assigned to fractional CO2 laser and the other side to Qs Nd:YAG and KTP lasers every four weeks for four months followed by 4 monthly follow-up assessment. Acanthosis Nigricans Area and Severity Index (ANASI) score, melanin and erythema indices as well as Patient Satisfaction Scale (PSS) were used to assess improvement on each side separately. Results: There was no statistically significant difference regarding the clinical improvement between the side treated with Fractional CO2 laser and the side treated with Qs Nd:YAG and KTP lasers (P value > 0.05). In most patients, both sides showed improvement during different sessions of therapy, as regards ANASI scores, melanin indices, patient satisfaction scores, and side effects. Conclusion: In this study, we concluded that both fractional CO2 and Q-switched lasers proved to be a safe and effective line of treatment of acanthosis nigricans.
Yuanzhi Liu, Yongjun Chen
Clinical, Cosmetic and Investigational Dermatology, pp 687-692;

Background: Facial injection has become popular in aesthetic dermatology. Although injections of these tissue fillers are considered a low-risk procedure, they are not without potentially significant drawbacks. Case Presentation: We would like to report a case about cutaneous Mycobacterium abscessus infection after facial injection of hyaluronic acid in China, which obtained satisfactory clinical efficacy by drainage and surgical excision. Conclusion: Biological techniques are useful in the diagnosis of cutaneous M. abscessus infection. Surgical excision of skin lesion is effective for cutaneous M. abscessus infection.
Yu-Tong Wu, Dong-Qing Ye, Cui-Hong Lian
Clinical, Cosmetic and Investigational Dermatology, pp 693-696;

Giant condylomata acuminata (a sexually transmitted disease caused by HPV infection) currently is treated in many methods. Surgery, the mainstay treatment of giant condylomata acuminata, may cause a high cost or scar formation. It is important to explore effective and safe treatment options. Although the external treatment of traditional Chinese medicine treatment of condyloma acuminatum has not been widely used, in our case, the use of traditional Chinese medicine successfully treated a perianal giant condyloma acuminatum patient who also suffered from mixed hemorrhoid and IgA nephropathy meanwhile. The treatment process was simple and the effect obvious. There was no recurrence more than 10 months after treatment finished, and the patients felt safe, comfortable and highly coordinated. The outcome of this case suggests that the traditional Chinese medicine might be considered as a mild and effective option for the treatment of giant condyloma acuminatum.
Sandrine Bergera-Virassamynaïk, Nathalie Ardiet, Michèle Michèle Sayag NAOS Group
Clinical, Cosmetic and Investigational Dermatology, pp 677-686;

Purpose: Atopic dermatitis (AD) is a chronic relapsing, inflammatory disease which causes eczematous lesions. Itching and symptoms visibility can have a significant impact on quality of life. This is the case when eyelids are affected. Therefore, we evaluated a dermo-cosmetic product designed to care AD on eyelids. Subjects and Methods: An initial analysis of the product included 20 healthy women with no AD signs. A clinical evaluation of the effect of the product on AD sign severity was performed on 33 subjects presenting AD symptoms on eyelids. We also analyzed the product’s capacity to prevent relapses in a parallel group clinical evaluation performed on 66 subjects. Results: First, on the forearm skin of healthy subjects, the product reduces erythema and decreases transepidermal water loss when used for 28 days. Second, when clinically evaluated on subjects with eyelid symptoms undergoing a corticoid treatment, the product leads to reduced AD signs scored by a dermatologist, better self-evaluation of symptoms by subjects, and improved quality of life. Besides, upon assessment in a randomized controlled clinical evaluation with subjects prone to AD relapses but without symptoms, the product also drastically reduces relapse frequency. If erythema reduction is the only sign identified by a dermatologist, the product greatly and rapidly improves the quality of life of subjects. Conclusion: These effects can be explained by the known actions of the product’s ingredients. Rich in hydrating compounds, fatty acids and anti-inflammatory compounds, it aims at maintaining and restoring the epidermis structure and function to preserve it from irritants. It effectively shows that a daily care and hygiene routine with a dermo-cosmetic product designed according to an ecobiological approach leads to objective improvement of AD and subjective perception of quality of life.
Hend M Alotaibi
Clinical, Cosmetic and Investigational Dermatology, pp 545-552;

Hidradenitis suppurativa, a chronic inflammatory disease of the skin, affects a patient’s quality of life to a greater extent. While the disease burden, including its incidence and prevalence, has been extensively studied in the western population, there is a paucity of data from developing countries on the epidemiology of Hidradenitis suppurativa. Therefore, a general literature review was conducted to shed light on the epidemiology of Hidradenitis suppurativa across the globe. We reviewed the most recently available information on epidemiology, including incidence, prevalence, risk factors, prognosis and quality of life, complications, and associated comorbid among patients with Hidradenitis suppurativa. The estimated global prevalence of Hidradenitis suppurativa is found to be 0.00033– 4.1%, with a relatively higher prevalence of 0.7– 1.2% in European and US populations. Both genetic and environmental factors are associated with Hidradenitis suppurativa. Patients with Hidradenitis suppurativa have associated comorbid such as cardiovascular disease, type II diabetes mellitus, mental health issues, and sleep and sexual dysfunctions. These patients spend poor quality of life and tend to be less productive. Future studies are needed to assess the burden of Hidradenitis suppurativa in developing countries. Since the disease tends to be underdiagnosed, future studies should rely on clinical diagnosis rather than self-reporting to avoid the potential of recall bias. Attention needs to be diverted to developing countries with less amount of data on Hidradenitis suppurativa.
Su Su Wang, Juan Bai, Jianjun Qiao Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of ChinaCorrespondence: Jianjun Qiao, Email Juan Bai, Jianjun Qiao
Clinical, Cosmetic and Investigational Dermatology, pp 673-676;

Acute generalized exanthematous pustulosis (AGEP), an uncommon severe cutaneous adverse reaction, is believed to be a T cell-mediated hypersensitivity reaction, of which the most common cause is medication. However, infections have also been reported to be associated with AGEP. Here, we present a case of AGEP possibly related with Staphylococcus pettenkoferi.
Shuo Li, Yiding Xiao, Yang Wang, Ming Bai, Fengzhou Du, Hailin Zhang
Clinical, Cosmetic and Investigational Dermatology, pp 615-616;

Corrigendum for the article Exploration of Influencing Factors for Postoperative Recurrence in Patients with Madelung’s Disease on the Basis of Multivariate Stepwise Cox Regression Analysis
Ratih Rinendyaputri
Clinical, Cosmetic and Investigational Dermatology, pp 613-614;

Letter for the article A Comparative Study on Adipose-Derived Mesenchymal Stem Cells Secretome Delivery Using Microneedling and Fractional CO2 Laser for Facial Skin Rejuvenation
Mingzhu Jin, Xiao Xu
Clinical, Cosmetic and Investigational Dermatology, pp 565-580;

Introduction: Secondary to war wounds, trauma, etc., hypertrophic scar formation is the cause of an excessive proliferation of fibroblasts and accumulation of collagen fibers, which might affect cosmetic appearance, and could cause malignant transformation. miRNAs play an important role in disease regulation via inhibiting post-transcriptional protein translation by targeting and binding to the 3’ UTR region of mRNA. Here we explore the mechanism and interventions of scar formation from the perspective of miRNA. Methods: Hypertrophic scar-associated differential miRNAs were screened by analyzing sequencing data of normal skin and hypertrophic scar, and verified by RT-qPCR. Signaling pathways that may be influenced by differentially miRNAs were analyzed using KEGG and GO. miRNA mimics were used to explore the effects of miRNAs on SMAD signaling pathway proteins. Dual-luciferase assays were used to explore the targeted binding of miRNAs. The mimics of the miRNA were used to explore the impact of miRNAs on the proliferation, migration, apoptosis and collagen synthesis levels of hypertrophic scar fibroblasts. The scar model of rabbit ear was used to verify the influence of miRNA on wound healing and scar formation in vivo. Results: Expression of miR-182-5p was found to be considerably decreased in hypertrophic scars and fibroblasts. miR-182-5p was found to act mainly by targeting the 3’UTR region of SMAD4, but not SMAD1 or SMAD3. miR-182-5p overexpression may drastically suppress the proliferation and migration of fibroblasts, accompanied by enhanced apoptosis and reduced collagen fiber synthesis. The overexpression of miR-182-5p in in vivo experiments could effectively inhibit hypertrophic scar formation without affecting the speed and quality of wound healing. Conclusion: miR-182-5p inhibits hypertrophic scar formation by decreasing the proliferation and migration of fibroblasts via SMAD4 pathway, and is expected to become a novel hypertrophic scar therapeutic target.
Chaofan Wang, Yimei Du, Lingbo Bi, Xuewen Lin, Min Zhao, Weixin Fan
Clinical, Cosmetic and Investigational Dermatology, pp 603-612;

Introduction: Androgenetic alopecia (AGA) has negative impacts on both men and women in terms of appearance and mental stress. Spironolactone is a synthetic aldosterone receptor antagonist known to stimulate hair growth and has been widely used by dermatologists to treat AGA. Objective: To conduct a systematic review evaluating the efficacy and safety of topical and oral spironolactone in AGA treatment. Methods: We searched PubMed, Embase, the Cochrane Library, and the Web of Science until October 23rd, 2022, for human studies evaluating the efficacy of spironolactone for the treatment of AGA, regardless of doses and routes. Results: We retrieved 784 papers and ultimately 7 articles matched our inclusion criteria and comprised 618 AGA patients (65 men, 553 women), 414 of them received spironolactone treatment. Oral spironolactone doses ranged from 25mg to 200mg daily, with the vast majority between 80mg and 110 mg. Dosage forms for topical spironolactone use include gels of 1% and solutions of 5% twice daily. Both oral and topical spironolactone have been shown efficacy for alopecia recovery, but topical use has significantly fewer side effects and is suitable for any gender. It showed better efficacy in combination with other therapies such as oral or topical minoxidil compared with monotherapy. Conclusion: Spironolactone is an effective and safe treatment of androgenic alopecia which can enhance the efficacy when combined with other conventional treatments such as minoxidil. Topical spironolactone is safer than oral administration and is suitable for both male and female patients, and is expected to become a common drug for those who do not have a good response to minoxidil. Furthermore, more high-quality clinical randomized controlled studies should be performed.
David Canty, Catherine Rhéaume, Birgitte Sondergaard, Celina Niño, Ron S Broide, Amy D Brideau-Andersen
Clinical, Cosmetic and Investigational Dermatology, pp 581-591;

Objective: The goal of this study was to compare the unit-to-unit biological activity of the vacuum-dried formulation of prabotulinumtoxinA (prabotA) and onabotulinumtoxinA (onabotA) in preclinical assays. Methods: Reconstituted 100 U vials of prabotA and onabotA were tested in 3 distinct assays: plate-capture light chain activity (PC-LCA), measuringlight chain enzymatic activity after recovery of toxin from reconstituted product using a proprietary toxin capture step; cell-based potency assay (CBPA), measuring the intoxication steps of binding, translocation, and light chain activity (synaptosomal-associated protein 25 [SNAP25] cleavage); and mouse Digit Abduction Score (DAS), evaluating muscle paresis. Each assay tested 3 separate prabotA and onabotA lots on several independent test dates. Results: Multiple orthogonal assays established that when assessed on a unit-to-unit basis, the biological activity of prabotA is lower than that of onabotA. In the PC-LCA and CBPA assays, onabotA displayed 1.51 ± 0.14–fold higher (mean ± SD) and 1.33 ± 0.07–fold higher (mean of pooled lots ± SEM) activity than prabotA, respectively. Similarly, the mouse DAS data showed that onabotA had 1.4 ± 0.1–fold higher (mean ± SEM) potency than prabotA. Results of all 3 assays demonstrated differences in potency, efficacy, and duration of action between onabotA and prabotA on a unit-to-unit basis. Conclusion: Preclinical assays established differences in the biological activity of onabotA and prabotA, supporting that the units of biological activity are not interchangeable.
Meng Liu, Xinyi Liu, Yuqian Wang, Ziyang Wang, Huihui Tuo, Yiguo Feng, Yan Zheng
Clinical, Cosmetic and Investigational Dermatology, pp 593-601;

Background: Epidermal cysts are common benign epithelial tumors. They are known to result from penetrating-type injuries or infection of human papillomavirus. The differential diagnosis commonly includes multiplex steatocystoma, lipoma, and neurofibroma. Pathological examination is essential for diagnosis, and surgical excision is the recommended treatment. Objective: We report a case in a man who presented with a cystic lesion on the scalp over 22 years to provide clinical evidence for mechanism of epidermal cysts. We conducted epidemiological analysis of 3949 patients with epidermal cysts to clarify the epidemiological characteristics and clinical features of epidermal cysts. Patients and Methods: A total of 3949 individuals with confirmed epidermal cysts were collected for analysis. Data were expressed as mean ± SEM and analyzed using Student’s t-test. Results: Our data showed that the mean age of diagnosis of males was statistically earlier than that of females (P< 0.001), but no significant difference in sex predilection was observed (P=0.55). The high incidence age of males and females was in the young and middle stage. Lesion locations were a bit different among age groups, but the face was the most common site of epidermal cyst at all age stages. Conclusion: Our case offers clinical evidence to the theory which refers trauma as one of the main causes of epidermal cysts in hair-bearing area. According to analysis of large number of samples, we can further support the idea that epidermal cyst has equal sex predilection and mainly occurs on the young and middle-aged adults. It is usually solitary and most likely to be found on face and trunk.
Shannaz Nadia Yusharyahya, Valdi Ven Japranata, , , , Lis Surachmiati Suseno,
Clinical, Cosmetic and Investigational Dermatology, pp 671-672;

Response to Letter in regards to A Comparative Study on Adipose-Derived Mesenchymal Stem Cells Secretome Delivery Using Microneedling and Fractional CO2 Laser for Facial Skin Rejuvenation [Letter]
Astrid Teresa
Clinical, Cosmetic and Investigational Dermatology, pp 617-633;

Laser procedures for skin care is becoming increasingly popular and used by the global community and affect many aspects of human life. However, there is very little research on the role of men in women’s decision to follow this dermatological procedure. This study aimed to identify the role of men in motivating women to choose laser-based procedure. A systematic literature review research design was applied in this study. A total of 27 papers were obtained by searching PubMed Central for the 2013– 2022 editions. The extraction of samples and the motivation of patients or research respondents in choosing laser procedures for cosmetic treatments were conducted to obtain clues about the role of men in making these decisions. Only six studies explicitly reveal the role of men as motivators of women to perform laser-based dermatological procedures. Four of these six studies were conducted in Asia in countries with a high degree of collectivism. The remaining two studies reveal a minor role for men in women’s motivation to choose dermatological procedures. Other studies only indirectly implicate the role of men through intrasexual competition, increased self-esteem, and the needs of the world of work. Limitations of the study lies in the non-specificity of the study sample in the female population, laser-based treatments, and the role of men in motivating women. The role of men in motivating women to perform laser-based skin care procedures is stated explicitly in collectivist cultures while only implicitly in individualist cultures. These findings indicate that the strategy of utilizing the added value of men to laser treatment procedures should be directed at the relationship between men and women in real terms in collective cultured countries.
Xinxin Li, Yifang Sun, Juan Du, Fang Wang, Xiaolan Ding
Clinical, Cosmetic and Investigational Dermatology, pp 635-638;

Vitiligo is an acquired autoimmune skin disorder, clinically characterized by distinct white macules and patches resulting from progressive melanocyte destruction. JAK-STAT pathway plays an important role in the loss of epidermal melanocytes. Baricitinib can block the JAK-STAT pathway and the downstream chemokines as a new JAK1/2 inhibitor. In this report, we describe the successful treatment of 2 patients with oral baricitinib combined with NB-UVB phototherapy, which provides a good alternative and supplementary to treat refractory vitiligo.
Ling Zhou, Juanjuan Wang, Hui Hou, Jiao Li, Juan Li, Jiannan Liang, Junqin Li, Xuping Niu, Ruixia Hou,
Clinical, Cosmetic and Investigational Dermatology, pp 659-669;

Objective: Autophagy, an intracellular process of self-digestion, has been shown to modulate inflammatory responses. In the present study, we determined the effects of autophagy on inflammatory response induced by M5 cytokines. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with M5 cytokines to induce inflammation. Expression levels of mRNA for inflammatory cytokines and BIRC2 were compared in HUVECs with vs without induction of autophagy with rapamycin (RAPA) by PCR, while cell apoptosis was assessed by flow cytometry and caspase-3 activity assay kit. Expression levels of LC3, p62, p-p38 MAPK (Thr180/Tyr182), p-mTOR (Ser2445) and p-ULK1 (Ser555) proteins were measured by Western blotting. The nitric oxide (NO) content, NO synthase (NOS) activity and cell angiogenesis were also evaluated. Results: Induction of autophagy with RAPA decreased expression levels of IL6, IL8 and CCL20, in addition to reduction in inflammation-induced apoptosis in HUVECs. Moreover, RAPA increased LC3II, while decreasing p62 expression. Likewise, expression levels of p-p38 MAPK and p-mTOR proteins were markedly decreased by the treatment with RAPA. Finally, RAPA treatment increased the NO content and the NOS activity, and inhibited angiogenesis. Conclusion: Induced autophagy can improve the function of endothelial cells in psoriasis, suggesting approaches to induce autophagy can be used to ameliorate psoriasis.
Chan Dai, Huoying Chen, Mengya Jiao, Na Zhang, Xuhuan Tang, Anqi Fan, Shiwang Liu, Zhigang Qian, Chenchen Wang, Yong Xu, et al.
Clinical, Cosmetic and Investigational Dermatology, pp 639-650;

Purpose: IL-33 is constitutively expressed in skin tissues. Alopecia, a T cells-driven disorder of the hair follicles (HFs), is a common complication in the development of psoriasis. However, the role of IL-33 in psoriatic alopecia remains uncovered. Here, we investigated the roles of IL-33 in inducing pathological changes of hair follicles in psoriasis. Patients and Methods: Clinical samples and imiquimod (IMQ)-induced psoriatic mice samples were used to investigate the pathological changes and T-cell infiltration of HFs. By using immunohistochemistry staining, the distribution and expression alteration of IL-33 in HFs were determined. Next, by using IL-33 and ST2 knockout mice, we investigated the role of IL-33/ST2 axis in the pathological changes of HFs in psoriasis. Meanwhile, recombinant IL-33 protein was subcutaneous injected to confirm its effect. Finally, RNA sequencing was used to clarify the genes and signaling pathways that involved in this process. Differentially expressed genes were further verified by RT-PCR in cultured HFs in vitro. Results: We found that the pathological changes of HFs and T cells infiltration in imiquimod-induced psoriatic mice were similar to that in psoriasis patients. The IL-33 positive keratinocytes in the outer root sheath of HFs were increased in both psoriasis patients and psoriatic model mice compared with the controls. By using gene knockout mice, we found that the pathological changes and T cell infiltration were attenuated in IL-33−/− and ST2−/− psoriatic model mice. In addition, subcutaneous injection of recombinant IL-33 exacerbated the pathological changes of HFs and T cell infiltration. RNA sequencing and RT-RCR revealed that IL-33 upregulated the transcription of genes related to keratinocytes proliferation and T lymphocytes chemotaxis. Conclusion: Our study identifies that IL-33 promotes the pathological changes of HFs in psoriasis, which contributes to psoriatic alopecia. Inhibition of IL-33 may be a potential therapeutic approach for psoriatic alopecia.
Tianyi Wang, Wang You, Linna Zhao, Bingxin Zhang, Hongmei Wang
Clinical, Cosmetic and Investigational Dermatology, pp 651-658;

Aim: The application of network analysis algorithms promoted the development of network pharmacology. This study aimed to combine network pharmacology and signed random walk with restart (SRWR) to reveal the mechanism by which Lithospermum erythrorhizon Sieb (LES) exerts effects on atopic dermatitis (AD). Methods: The compounds and targets of LES were retrieved from Traditional Chinese Medicine Integrated Database (TCMID) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and important compounds and targets were identified by intersection analysis and protein–protein interaction (PPI) network. Results: We found that active LES-derived compounds such as caffeic acid, Isovaleric acid, Arnebinol, and Alannan may inhibit PTGS2, HSP90AA1 and MAPK14, which are key mediators involved in PI3K-Akt pathway, vascular endothelial growth factor signaling pathway, Fc epsilon RI signaling pathway, and calcium signaling pathway. Conclusion: The application of SRWR could identify potential targets of LES with a low false-positive rate and help elucidate the mechanism of action of traditional Chinese medicine.
Chunhui Tian, Weipin Xie, Lifang Chen, Xuebao Liu, Zhongping Zhongping Hao Department of Otorhinolaryngology Head and Neck Surgery
Clinical, Cosmetic and Investigational Dermatology, pp 537-543;

Objective: To introduce a novel method of modified through and through suture with collagen sutures in conjunction with anterior chondrectomy of auricular pseudocyst and assess its therapeutic efficacy. Subjects and Methods: The study comprised 87 patients with unilateral auricular pseudocyst, treated in our department from December 2019 to November 2021. Following anterior chondrectomy of the cyst, modified through and through suture was performed using collagen sutures. Evaluation of successful resolution of the problem, assessment of complications, recurrence, and ultimate ear cosmesis was undertaken with a minimum of 6 months follow-up. Results: There were 83 males and 4 females, ages ranged from 26– 78 years old, with a median age of 41 years. The right and left ears were affected in, 52 and 35 patients, respectively. Local skin color deepening was found in 15 patients within 3 months, which returned to normal within 5 months. During the follow-up, such complications as anaphylaxis, hematocele in the surgical cavity, incision infection, and deformity were not observed in any patients. All patients were cured with a single operation without relapse. Conclusion: The modified through and through suture with collagen sutures in conjunction with anterior chondrectomy of an auricular pseudocyst is characterized by a straightforward, single-stage operation, with no relapses, few complications, restoration of normal ear cosmesis, and high patient acceptance.
Gabriella Fabbrocicni, Sara Cacciapuoti, , Lucia Gallo, Matteo Megna
Clinical, Cosmetic and Investigational Dermatology, pp 529-536;

Background: Tildrakizumab, an anti-IL-23, showed promising efficacy and safety profiles in two randomized clinical-trials (reSURFACE-1 and reSURFACE-2), comparing tildrakizumab superiority to placebo and etanercept. Due to its recent availability in clinical-practice, real-life data are still limited. Objective: To assess the efficacy and safety of tildrakizumab in a real-world-practice in patients suffering from moderate-to-severe psoriasis. Methods: A 52-week observational retrospective study enrolled patients suffering from moderate-to-severe plaque-psoriasis, starting tildrakizumab treatment. Results: A total of 42 patients were included in the study. Mean PASI showed a significant reduction at each follow-up (p< 0.001), reducing from 13.5± 5.9 at baseline, 2.8± 3.8 at week-28, resulting stable up to week-52. High rates of patients reached both PASI90 and PASI100 responses at both week 16 (PASI90: 52.4%, PASI100: 33.3%) and week 28 (PASI90: 76.1%, PASI100: 61.9%), maintaining these up to week 52 (PASI90: 73.8%, PASI100: 59.5%). The impact of treatment on patient’s quality of life has been evaluated with DLQI, which showed a significant reduction during follow-ups. Conclusion: Our data confirm tildrakizumab as an effective and generally safe treatment for the management of moderate-to-severe psoriasis, with high rates of both PASI90 and PASI100 responses, and very few reported adverse events, up to 52 weeks of follow-up.
Jie Dong, Yuntao Duan, Kunning Zhang, Xiuying Zhang
Clinical, Cosmetic and Investigational Dermatology, pp 505-514;

Cutaneous lymphadenoma (CL) is an uncommon epithelioid tumor that is usually present on the head and face. It was first described by Santa Cruz and Barr in 1987, as a lymphoepithelial tumor, and was renamed as CL in 1991. Although CL is considered as a benign tumor, there are cases of recurrence after shave excision and metastasis to regional lymph nodes. Correct diagnosis and complete resection are of great importance. Here, we report a typical case of CL and make a comprehensive review of this rare skin tumor.
Clinical, Cosmetic and Investigational Dermatology, pp 515-527;

Acne Vulgaris is a chronic inflammatory skin disease, and one of the most prevalent inflammatory dermatoses among teenagers, affecting more than > 95% of boys and 85% of girls. Adult female acne (AFA) is a subtype of acne, pragmatically defined as affecting women over the age of 25. The clinical presentation of AFA may be distinguished from adolescent acne according to some key clinical and psychosocial characteristics. The etiopathogenic factors and the chronic clinical course that are implicated in AFA make management complex and challenging. A frequent tendency to relapse makes the requirement for maintenance therapy highly likely. Therefore, AFA typically requires a specific, tailored therapeutic approach. This paper presents six challenging case studies that demonstrate the efficacy of azelaic acid gel (AZA) in adult female acne. The six cases use AZA as monotherapy, as part of a combination regimen at treatment initiation, or as maintenance treatment (which is frequently required in this adult population). The positive outcomes achieved in this case series demonstrate that AZA can be efficacious, result in excellent patient satisfaction in mild to moderate adult female acne, and can be effective as a maintenance therapy.
Guanming Li, Airun Zhang, Silan Yang, Niyang Lin, Xiaoyi Fang
Clinical, Cosmetic and Investigational Dermatology, pp 499-504;

Aplasia cutis congenita (ACC) is a rare disease with an unclear pathogenic mechanism. ACC has been suggested to result from the disrupted development or degeneration of skin in the uterus. This study describes two cases that may have underlying pathogenic cause that have not been previously reported. Two neonates who were admitted to the neonatal intensive care unit due to “skin lesions on the limbs” without other deformities or complications were diagnosed with type VII ACC by dermatologist. The mothers showed positivity for hepatitis B virus (HBV) surface antigen and elevated level of HBV DNA copies, which may be related to ACC. But this association could be a coincidence. Both neonates were treated with antibacterial dressings and achieved satisfactory healing.
Jiachen Sun, Hongqing Zhao, Lin Fu, Jing Cui,
Clinical, Cosmetic and Investigational Dermatology, pp 479-498;

Background: Based on photochemical reactions through the combined use of light and photosensitizers, photodynamic therapy (PDT) is gaining popularity for the treatment of skin cancer. Various photosensitizers and treatment regimens are continuously being developed for enhancing the efficacy of PDT on skin cancer. Reviewing the development history of PDT on skin cancer, and summarizing its development direction and research status, is conducive to the further research. Methods: To evaluate the research trends and map knowledge structure, all publications covering PDT on skin cancer were retrieved and extracted from Web of Science database. We applied VOSviewer and CiteSpace softwares to evaluate and visualize the countries, institutes, authors, keywords and research trends. Literature review was performed for the analysis of the research status of PDT on skin cancer. Results: A total of 2662 publications were identified. The elements, mechanism, pros and cons, representative molecular photosensitizers, current challenges and research progress of PDT on skin cancer were reviewed and summarized. Conclusion: This study provides a comprehensive display of the field of PDT on skin cancer, which will help researchers further explore the mechanism and application of PDT more effectively and intuitively.
Yanqiu Zhang, Yaling Li, Hongwei Yan
Clinical, Cosmetic and Investigational Dermatology, pp 463-477;

Background: Melanoma is a highly malignant skin tumor with a poor prognosis. Identification of novel biomarkers might potentially reveal the underlying mechanisms of melanoma progression. Methods: We demonstrated the relationship between pan-cancer CLEC2B expression and melanoma samples in The Cancer Genome Atlas (TCGA) database. Next, the Kaplan-Meier plot and Cox regression analysis determined the prognostic value of CLEC2B in melanoma. Biological pathway enrichment was screened by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), enabling the correlation analysis between the immune infiltration level and CLEC2B expression in melanoma. Our final claim was validated using qPCR, immunohistochemistry, Western blot, cell colony formation assays, ethynyldeoxyuridine (Edu) analysis, and cell Invasion assays. Results: Our study revealed that the high CLEC2B expression correlates with poor overall survival of melanoma patients. Moreover, a low expression of CLEC2B was found in the A375 cell line. In addition, CLEC2B has significant prognostic value in melanoma diagnosis, with an AUC of 0.896. Prognostic analysis showed the low expression of CLEC2B to be independently associated with melanoma patients. Moreover, the expression of CLEC2B was significantly correlated with B cells, eosinophils, macrophages, neutrophils, NK cells, T helper cells, Tregs, Th1 cells, Th17 cells, and Th2 cells. PCR and immunohistochemistry indicated CLEC2B to be significantly downregulated in melanoma. The cell colony formation assay showed CLEC2B knockout increased the proliferation of A375 cells. Conclusion: Our study established low levels of CLEC2B to be poor prognostic markers, enabling immunosuppressive cell infiltration in melanoma.
Li Zhang, Zhongxiao Wu
Clinical, Cosmetic and Investigational Dermatology, pp 457-461;

Sintilimab is a recombinant fully human anti-programmed cell death protein 1 (PD-1) monoclonal antibody that blocks the interaction of PD-1 with its ligand. It was approved to use in patients with gastric malignancy. Toxic epidermal necrolysis (TEN) is a rare, life-threatening cutaneous drug reaction. Here, we report a 70-year-old female patient with gastric malignancy who developed severe TEN 10 days after initiation of sintilimab. The patient did not respond to the systemic corticosteroids and intravenous immunoglobulin therapies but improved after the subcutaneous injection of adalimumab (40 mg) that is a monoclonal antibody directed against antitumor necrosis factor-α. Her rashes rapidly resolved within 24 hr. By the seventh day, the bullae had scabbed and most skin lesions had subsided. The patient showed no sign of organ dysfunction. This is the first reported case of immune checkpoint inhibitor-induced TEN successfully treated with adalimumab.
Huijing Wang, Ying Wang, Zhancai Zheng, Yong Cui
Clinical, Cosmetic and Investigational Dermatology, pp 453-456;

Granuloma annulare (GA) is an uncommon disease in dermatology. Here, we report a case of generalized GA combined with Sjogren’s syndrome (SS) in a 65-year-old woman. To our knowledge, generalized GA combined with SS has not been reported before.
Jing Yang, Kun Hu, Xingyu Li, JingJin Hu, Minjia Tan, Mi Zhang, Junchen Chen, Yehong Kuang
Clinical, Cosmetic and Investigational Dermatology, pp 443-451;

Background: The Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI) are important evaluation tools for assessing psoriasis severity and guiding treatment options. However, the scores of PASI and DLQI are often inconsistent. Objective: This study aimed to identify the factors affecting the consistency between PASI and DLQI. Methods: The retrospective study was based on 4125 patients. We collected the PASI, DLQI, demographic and clinical characteristics data. Results: DLQI has a weak correlation with PASI (r=0.37; P< 0.001). For the DLQI > 10 groups, DLQI has almost no correlation with PASI (r=0.16; P< 0.001). There are 43.60% of mild-to-moderate patients (PASI< 10) in the DLQI> 10 groups. Our adjusted model showed that foot (OR=2.109; 95% CI:1.581– 2.815) involvement led to the greatest impairment of QoL except for PASI≥ 10 (OR=5.547; 95% CI:3.477– 8.845). Furthermore, DLQI impairment was associated with female (OR=1.336; 95% CI:1.071– 1.667); the age of 20– 39 subgroup (OR=1.795; 95% CI:1.100– 2.930); psoriatic arthritis (OR=1.718; 95% CI:1.208– 2.443); higher income (OR = 1.408; 95% CI: 1.067– 1.858); family history of psoriasis (OR=1.460; 95% CI:1.131– 1.885). Moreover, the influence of exposed lesions (such as scalp; face; neck; nails; and hands) were positively associated with severely impaired QoL. Conclusion: Dermatologists should recognize the underestimated disease burden of psoriasis patients and actively identify and treat mild-to-moderate patients with high burden. In particular, the foot was a significant contributor to the burden.
Minjia Tan, Yan Luo, JingJin Hu, Kun Hu, Xingyu Li, Jing Yang, Junchen Chen, , Yehong Kuang
Clinical, Cosmetic and Investigational Dermatology, pp 397-405;

Purpose: Psoriasis patients often suffers from anxiety and depression. Inflammation, anxiety, and depression have been associated with each other, but the relationship has not been examined in subjects with psoriasis. The primary objective was to investigate the relationship between the C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) and depression among patients with psoriasis. Methods: In this case-control, cross-sectional study, 239 individuals with psoriasis and 142 with healthy controls (HCs) were recruited. Psychological as well as clinical, and laboratory data were collected. Results: 50.2% of subjects with psoriasis reported depressive symptoms, compared with 26.8% of HCs. 39.7% and 17.6% observed anxiety symptoms in psoriasis patients and HCs. The odds of anxiety (AOR= 3.123; 95% CI = 1.851– 5.269) and depression (AOR= 2.698; 95% CI = 1.690– 4.306) were higher in psoriasis patients relative to HCs. Furthermore, the elevated CRP (AOR =2.139; 95% CI = 1.249– 3.663) and ESR (AOR =1.827; 95% CI = 1.078– 3.096) were the risk factors of depression in patients with psoriasis. The threshold for distinguish psoriasis patients in depression was 3.24 (area under the curve [AUC], 0.605; sensitivity, 0.57; specificity, 0.64) for CRP and 26.5 (AUC, 0.632; sensitivity, 0.52; specificity, 0.73) for ESR. Conclusion: A substantial prevalence of anxiety and depression symptoms was observed in Chinese psoriasis subjects, and the odds were much higher in psoriasis patients relative to HCs. The elevated CRP and ESR level was significantly associated with depression in psoriasis patients. Besides, the discrimination capability of CPR and ESR on depression further indicates the extra value of inflammatory biomarkers in the management of psoriasis patients.
Xiaofeng Chen, Qiyan Deng, Xiaolong Li, Li Xian, Dehai Xian, Jianqiao Zhong
Clinical, Cosmetic and Investigational Dermatology, pp 407-417;

Psoriasis, a chronic immune-mediated inflammatory skin disease, influences approximately 2– 3% of the world’s population. At present, the etiology of psoriasis remains unclear and there is still no causal treatment available. Recent studies indicate that oxidative stress (OS) and T cells dysregulation may participate in the pathogenesis of psoriasis, among which M1-dominant macrophage polarization is a crucial contributor. Macrophages mainly polarize into two different subsets, ie, classically activated macrophage (M1) and alternatively activated macrophage (M2). M1 polarization tends to exacerbate psoriasis via producing substantial reactive oxygen species (ROS) and inflammatory mediators, to encourage OS invasion and T cells dysregulation. Thus, targeting M1 polarization can be a possible therapeutic alternative for psoriasis. Loganin, belonging to iridoid glycosides, is a pharmaceutically active ingredient originated from Cornus officinalis, exerting multiple biological activities, eg, immunomodulation, antioxidation, anti-inflammation, etc. More importantly, it could effectively suppress M1 polarization, thereby arresting OS aggression and T cells’ dysregulation. Numerous studies have confirmed that loganin is quite reliable for diseases treatment via suppressing M1 polarization. Nevertheless, reports about loganin treating psoriasis have seldom appeared so far. Accordingly, we hold a hypothesis that loganin would availably manage psoriasis through preventing M1 polarization. Data from previous studies guarantee the potential of loganin in control of psoriasis.
Wei Liu, Qin Chen,
Clinical, Cosmetic and Investigational Dermatology, pp 429-442;

Melasma is a common acquired disorder of pigmentation that negatively impacts quality of life. Present treatments show poor therapeutic effect with frequent recurrence. This in large part is due to the currently limited understanding of the disease’s etiology. It is urgent to elucidate the pathogenesis of melasma to further the discovery of new therapeutic strategies. Recent studies show that melasma is triggered or aggravated by a variety of factors, including genetic susceptibility, ultraviolet radiation, and sex hormone dysregulation. Ultraviolet B radiation upregulates the expression of several melanocyte-specific genes and stimulates the release of key factors that participate in the synthesis of melanin. There is a significant increase in melanin in both the epidermal and dermal layers of affected skin, possibly due to abnormalities in crosstalk between the melanocytes and other cells. Melanogenesis is regulated through various signaling networks including the Wnt/β-catenin, PI3K/Akt, cAMP/PKA, and SCF/c-kit-mediated signaling pathways. In addition, inflammatory mediators, oxidative stress, neuroactive molecules, sebocytes, etc, have also been proved to be related to the pathogenesis of melasma. This review provides a comprehensive update on the current understanding of the pathogenesis of melasma.
Yifan Wu, Yun Hui, Fang Liu, Huan Chen, Kehan Liu, Qiying Chen, Yifan He, Nan Hong, Wenliang Yan, Qingtao Kong, et al.
Clinical, Cosmetic and Investigational Dermatology, pp 419-427;

Background: The frequent coexistence of obesity and metabolic syndrome in patients with Androgenetic alopecia (AGA), may indicate a common pathogenetic pathway with adipokines being a possible implicating cytokine. Objective: This study was conducted to investigate the changes in serum levels of adipokines, insulin resistance, vitamin D status and their relationship with AGA, and the relationship between serum levels of adipokines and insulin resistance. Methods: 80 male patients with AGA were selected as the experimental group and 60 healthy males served as the control group. Both the AGA group and healthy control group were divided into 2 groups according to the presence or absence of insulin resistance (IR): the IR group and the NIR group. Serum levels of leptin, adiponectin, resistin, visfatin, insulin and 25(OH)D were evaluated in all subjects. Results: Compared with the control group, AGA patients showed higher serum levels of leptin and lower adiponectin/leptin (Adpn/Lep) ratio (P< 0.05), and both were positively correlated with the severity of the disease. Compared with the AGA NIR group, serum leptin levels were increased in the AGA IR group (P< 0.05). AGA IR group and AGA NIR group possessed lower Adpn/Lep ratio when compared with the healthy IR group and healthy NIR group respectively (P< 0.05). The multi-factor logistic regression analysis results showed decreased Adpn/Lep level and increased leptin level as risk factors for AGA. AGA Patients had lower vitamin D levels than healthy controls (P< 0.05). Conclusion: Patients with AGA show an imbalance between pro- and anti-inflammatory adipokines, and probably be involved in AGA pathogenesis. Insulin resistance may influence levels of adipokines, but the present findings cannot indicate insulin resistance plays a role in the onset of AGA. The insufficiency and deficiency of vitamin D are common health concern in our subjects and may be involved in the dysfunction of adipocytes and the development of AGA.
Shannaz Nadia Yusharyahya, Valdi Ven Japranata, , , , Lis Surachmiati Suseno,
Clinical, Cosmetic and Investigational Dermatology, pp 387-395;

Background: The efficacy of adipose-derived mesenchymal stem cells (ADMSCs) secretome for skin aging has been established, yet no studies hitherto directly investigated the best administration method for such purpose. Purpose: We aimed to compare microneedling (MN) versus fractional CO2 laser (FL) as methods of delivery for ADMSCs secretome in the treatment of aging skin. Patients and Methods: A single-blind, randomized split-face clinical trial was conducted on 30 Indonesian women (aged 35– 59 years old) with signs of facial cutaneous senescence. Their initial aging status was assessed by dermoscopy photoaging scale (DPAS) and Janus-III measurement system. In the second and fourth weeks, all participants were treated with both MN and FL, followed by the application of a four-fold concentrated ADMSC secretome. The assignment of which side of the face received MN or FL was done by computer-based randomization. Skin parameters were reevaluated on the fourth and sixth weeks, along with patient satisfaction, level of comfort, preference for administration techniques, and also adverse events experienced during the study. Appropriate statistical analyses were subsequently performed at a significance level of 0.05. Results: Significant improvements in total DPAS and wrinkles were found in the MN and FL groups at the end of the trial. In contrast, no statistical differences in all parameters were observed between groups in the fourth and sixth weeks. FL scored higher than MN for satisfaction and preference, but lower in terms of comfort. Pain, burning sensation, and itch were the side effects experienced by subjects upon treatment. Two patients had prolonged reddish skin succeeding FL treatment, which relieved with moisturizer application. Conclusion: Both MN and FL yielded comparable results for improving several skin aging features. However, subjective preference for ADMSCs secretome administration method may differ when considering satisfaction, comfort, and possible adverse events.
Camila Valpaços, Stéphanie Leclerc-Mercier, Luana Lopes, Diego Svoboda, Daniele Miranda, Priscila Correia, José Junior, Erika Fernandes, Veronique Francois-Newton, Madiiha Bibi Mandary, et al.
Clinical, Cosmetic and Investigational Dermatology, pp 375-385;

Purpose: Tretinoin is a topical gold standard for photoaging treatment. However, patient adherence can be impaired by local tolerability in the first 1– 2 weeks of treatment. Mineral 89 Probiotic Fractions® (M89PF) containing Vichy volcanic mineralizing water®, probiotic fractions, hyaluronic acid, niacinamide and tocopherol was developed to fulfill the need for adjunctive products that can reinforce skin barrier and manage retinoid induced irritation. Patients and Methods: The study included 38 women, aged 44– 60 years, phototype II–VI, applying 0.025% tretinoin gel once nightly for 84 days. For 28 days, one hemi face was treated with M89PF and sunscreen SPF 50+ while other hemi face received sunscreen only. Then, M89PF application was changed to full face. Evaluations were performed at days 0, 7, 28 and 84. Erythema, dryness, fine lines, skin tone, radiance and pore appearance were assessed by a dermatologist. Tolerability was evaluated through self-assessment questionnaire. Skin hydration levels, inflammatory and oxidative stress biomarkers were analyzed by immunological assay: Interleukin(IL)-8, IL1-alpha, IL1-Receptor Antagonist (IL-1Ra), Prostaglandin E2 (PGE2), Catalase and Superoxide Dismutase (SOD). Results: Hemiface analysis showed that erythema, fine lines, skin tone, radiance, pore appearance, hydration, tightness, dryness, burning, itching and stinging sensations were improved (p< 0.05) on the M89PF side. At full face analysis on D84, erythema, fine lines, skin tone, radiance and pore appearance were improved compared to D0 (p< 0.001). Tightness, dryness, burning, itching and stinging were reduced when compared to D7 (p< 0.05). Dermatology Life Quality Index (DLQI) and Skindex 16 showed improvement in quality of life (p< 0.05). IL-1RA increased at D28 (p=0.003) and PGE2 decreased at D28 and D84 compared to D0 (p< 0.01). Conclusion: M89PF reduced retinoid induced irritation with a good tolerability profile and, used as an adjunct to topical tretinoin, significantly improved skin hydration, erythema, fine lines, skin tone, radiance and pore appearance.
Xinyi Shao, Hao Li, Tingqiao Chen, Yangmei Chen, Xue Qin, Lin Liu, Xiaoyan Luo, Jin Chen
Clinical, Cosmetic and Investigational Dermatology, pp 359-367;

Objective: To illustrate the association of monocyte to high-density lipoprotein cholesterol ratio (MHR) and other serum indicators with the pathogenesis and prognosis of immunoglobulin A vasculitis (IgAV) patients in different subgroups. Methods: A total of 158 adult patients and 113 healthy controls were enrolled, and the clinical presentation and laboratory indexes were comprehensively assessed. Results: IgAV patients show significantly elevated levels of inflammatory parameters and lipid profiles compared to healthy controls (P < 0.05). Higher levels of the MHR and other normal inflammatory indicators were found in patients with Gastrointestinal (GI) involvement compared to other subgroups. And in group with GI involvement, significantly higher white blood cell (WBC), neutrophil, complement 4 (C4), NLR (neutrophil-to-lymphocyte ratio) and PLR (platelet-to-lymphocyte ratio) levels and lower levels of apolipoprotein-a (Apo-a) were observed. Their correlation analysis demonstrated positive results between MHR level and white blood cell (WBC) count (r = 0.416, P = 0.034), D-Dimer (r = 0.464, P = 0.026) and monocyte (r = 0.947, P < 0.001). And the time until first remission of skin purpura was shown positively correlated with their age (r = 0.456, P = 0.043), C-reactive protein (CRP) level (r = 0.641, P = 0.018), D-Dimer level (r = 0.502, P = 0.040) while negatively correlated with albumin (Alb) level (r=− 0.626, P = 0.003) and low-density lipoprotein (LDL) level (r=− 0.478, P = 0.033). Conclusion: Our study suggests that those biomarkers represented for inflammatory responses, lipid profile and immunological functions have significant differences in the subgroups of adult IgAV patients. In addition, we also found that MHR level may serve as a potential biomarker for the pathogenesis and prognosis of IgAV patients with GI involvement.
, Ilaria Piscitelli, Gabriella Fabbrocini, , , Matteo Megna
Clinical, Cosmetic and Investigational Dermatology, pp 369-373;

The introduction of biologic drugs revolutionized the management of moderate-to-severe forms of psoriasis. However, safety concerns still remain, particularly on patient affected by opportunistic infections. In this scenario, the safety of biologic drugs in patient with HBV infection is debated. Globally, screening for hepatitis before starting biological treatment is mandatory as well as a referral to an infectivologist and eventual prophylactic management should be evaluated case by case, also considering risk factors. On the one hand, the use of anti-Tumor Necrosis Factor seems to increase the risk of HBV reactivation, conversely, the use of recently approved classes of biologics [anti-interleukin (IL) 17 and anti-IL23] seems to have a lower risk of HBV reactivation. However, the evidence on the safety of anti-IL23 drugs in patients affected by HBV is scant, particularly for patients undergoing treatment with tildrakizumab. Herein, we report the first case of a female patient affected by moderate-to-severe psoriasis and with chronic HBV infection undergoing prophylaxis, successfully treated with tildrakizumab without reporting hepatitis reactivation. Even if limited, our case seems to confirm available evidence about the safety of anti-IL23, particularly tildrakizumab, on patients with chronic HBV infection undergoing prophylaxis.
Qinqin Tang, Yanjun Zhou, Yujuan Chen, Jie Chen, Xincai Xiong
Clinical, Cosmetic and Investigational Dermatology, pp 339-343;

Sporotrichosis is a deep fungus infection caused by the Sporothrix. In China, the most common species is Sporothrix globosa which is difficult to treat with most antifungal drugs. Atypical clinical forms of sporotrichosis can be a hinder to clinicians for an early diagnosis and treatment. We report a case of fixed cutaneous sporotrichosis of the face caused by S. globosa in a healthy adult that was initially misdiagnosed as rosacea due to its unusual clinical features. We made an effort to dermoscopically track changes in skin lesions both before and after treatment, confirming that itraconazole was effective in the treatment of sporotrichosis.
Mei Wang, Leran Zhao, Kun Wang, , Jingji Jin, Dong Wang, Huimin Yan,
Clinical, Cosmetic and Investigational Dermatology, pp 345-357;

Purpose: Omalizumab is a humanized anti-immunoglobulin (Ig) E monoclonal antibody that is effective in treating some patients with chronic spontaneous urticaria (CSU) who do not respond to antihistamines. Gut microbiome plays a role in the pathogenesis of allergies and autoimmune diseases. Here, we investigated differences in the gut microbiome of adolescent CSU patients before and after omalizumab treatment, which has not been previously reported. Patients and Methods: Ten adolescent CSU patients were given 300 mg omalizumab subcutaneously in three treatments at 4-week intervals. Urticaria Activity Score (UAS7) was applied to evaluate the efficacy of each omalizumab treatment during follow-up. Fecal samples were collected before and 12 weeks after the first treatment. Total DNA of the gut microbiota in all fecal samples were extracted. The 16S rRNA gene-targeted sequencing technology was used for the analysis of the diversity and distribution of gut microbiome, followed by bioinformatics analysis. Results: UAS7 scores decreased significantly after each treatment compared with the baseline (all P < 0.0001). There were five well-controlled responders and five non-responders after three treatment sessions of omalizumab. The dominant bacteria phyla in all fecal samples were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Alpha diversity analysis showed no significant difference before and after treatment (P > 0.05), whereas beta diversity analysis revealed a significant difference in the bacterial abundance before and after treatment (P < 0.01). The relative abundance of Alphaproteobacteria and Betaproteobacteria at the class level and Burkholderia, Rhodococcus, and Sphingomonas at the genus level decreased significantly after treatment (linear discriminant analysis > 4, P < 0.05). The functional prediction results showed that the dioxin and xylene degradation pathways were more abundant before treatment. Conclusion: Omalizumab is effective in treating CSU and the abundance of Alphaproteobacteria and Betaproteobacteria was reduced after treatment, which may help improve the treatment outcomes in adolescent CSU patients.
, Nicole Terpak, Sebastien Massard, Amber Schwartz,
Clinical, Cosmetic and Investigational Dermatology, pp 317-324;

Introduction: Retinol is known to have positive benefits on the skin including enhancements in barrier function, increased epidermal thickness, reductions in fine lines and wrinkles and reductions in hyperpigmentation. Improved methods to enhance the penetration of retinol are desirable. Methods: A study was conducted to examine if addition of natural jojoba (Simmondsia chinensis) oil might help passively enhance the penetration of retinol through the skin’s lipid barrier. The model used to examine the passive penetration of the retinol is the skin parallel artificial membrane permeation assay (Skin-PAMPA). In this study, three formulations were examined. The formulations included two control blends: a moisturizing emulsion without retinol and the same product containing 1.0% retinol without jojoba oil. The remaining formulation contained similar concentrations of retinol with 10% jojoba oil. The studies were conducted by applying the products to the Skin-PAMPA models at 37°C/5% CO2 for 16 hours and then extraction of the acceptor reservoir with cyclohexane (ratio 1:5 acceptor fluid to cyclohexane). The resulting acceptor reservoir cyclohexane solutions were analyzed for retinol by High Performance Liquid Chromatography (HPLC). Results: The formulations without retinol showed no indications of retinol penetration by HPLC. The control formulation with 1.0% retinol demonstrated that retinol had permeated the membrane in the 16-hour timeframe with a measured Area Under the Curve (AUC) of 7 units. Analysis of the formulation containing 1.0% retinol and 10% jojoba oil indicated retinol had permeated with a AUC of 285 units, a nearly 40-fold increase in active retinol permeation. Discussion: The ability for jojoba oil to directly act to help skin permeation of a key skin care active like retinol has not been previously demonstrated. This potential for jojoba oil to enhance passive skin penetration of critical skin actives, like retinol, can help to improve the performance of skin care products employing active topical ingredients.
Laiji Ma, Yujie Niu, Chunying Yuan, Tianming Bai, Suzhen Yang, Man Wang, Yan Li, Li Shao
Clinical, Cosmetic and Investigational Dermatology, pp 325-337;

Purpose: Everyone pursues perfect skin, but there exist significant differences between cultures, and no commonly accepted standards have been established. Therefore, our study attempted to define the “ideal skin” of oriental women and analyze the relationship between different skin physiological parameters and microbiomes. Patients and Methods: Based on our customized grading standard, the VISIA CR photos of 111 young women aged from 18 to 25 in Shanghai were collected and scored by the severity of pores, acne, spots, and wrinkles. The volunteers were then divided into “ideal skin” (W1), “normal skin” (W2), and “undesirable skin” (W3) groups. The physiological parameters of facial skin were measured by non-invasive instrumental methods, and the skin microbiome was analyzed by 16S rRNA and ITS high-throughput sequencing. Results: From “ideal skin” to “undesirable skin”, the skin physiological parameters, α-diversity, and composition of the facial microbiome showed noticeable regular changes. Compared with the “normal skin” (W2) and “undesirable skin” (W3), the “ideal skin” (W1) group had lower sebum content, TEWL, melanin, hemoglobin, and roughness but higher hydration content and skin pH value. Furthermore, the Shannon index of skin bacteria was significantly increased in W1 (P = 0.004), suggesting that the ideal skin had higher species diversity. From W1 to W3, the species composition was changed significantly. The abundance of Actinobacteria was increased, while Proteobacteria and Bacteroidetes were decreased. Correspondingly, the abundances of lipophilic Propionibacterium and Malassezia were increased, while the abundances of Stenotrophomonas, Pseudomonas, Ralstonia, and Streptococcus, were significantly decreased. Additionally, Spearman correlation analysis revealed strong correlations between the physiological parameters and the microbiota. Notably, the Shannon index of skin bacteria was significantly positively correlated with skin hydration (P = 0.03) but negatively correlated with the abundance of Cutibacterium (P = 0.000), hemoglobin content (P = 0.025), and sebum content (P = 0.5). Therefore, the skin hydration content and the abundance of Cutibacterium played an important role in maintaining the α-diversity and skin homeostasis. Conclusion: Ideal skin had better water-oil balance and barrier function, higher microbial diversity, and more reasonable species distribution. Therefore, daily skincare needs to control skin oil and maintain skin microecological balance to achieve ideal skin conditions for young women aged 18– 25 years old.
Sadan Mohammed Al Harbi, Nada Jomaan Al Ghamdi, Tarek Mohamed Elsharkawy, , Sultan Bajawi
Clinical, Cosmetic and Investigational Dermatology, pp 309-316;

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a lymphoproliferative disorder in which the majority of cells are reactive T cells with only a minor population of neoplastic large B cells. THRLBCL is a very rare lymphoma, and most cases are nodal THRLBCL; an extranodal case of THRLBCL presenting primarily on the skin is an extremely rare occurrence with only a few cases reported in the literature. Here, we report a case of a primary cutaneous THRLBCL in a 41-year-old Saudi male who presented unusually with multiple skin lesions. He was successfully treated with electron beam radiotherapy and had a complete resolution with no recurrence as of his 24-month follow-up.
Fitria Salim, , Oki Suwarsa, Endang Sutedja
Clinical, Cosmetic and Investigational Dermatology, pp 301-307;

Background: Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease that can be triggered by various precipitating factors, including colonization by Staphylococcus aureus (S. aureus). The toll-like receptor (TLR), which belongs to the family of pattern recognition receptors (PRR), can recognize components of S. aureus, such as staphylococcal enterotoxin B (SEB). This receptor is known to be expressed on monocytes. However, the understanding of the role of SEB in the pathogenesis of AD through the TLR pathway, especially TLR2 and TLR6, is not widely known. Purpose: To investigate the expression of TLR2 and TLR6 on peripheral blood monocytes induced by SEB during AD exacerbations. Patients and Methods: Twenty AD patients and 20 healthy subjects as a control group were selected. A 5 mL blood sample from each subject was taken for monocyte culture, which was induced by SEB for three days, and the outcomes were assessed by flow cytometry to evaluate TLR2 and TLR6 expression. Results: The expression of TLR2 on peripheral blood monocytes in AD patients was increased compared to healthy controls (p = 0.000), but not for the expression of TLR6 (p = 0.304). In the AD group, TLR2 and TLR6 expression on peripheral blood monocytes after being induced by SEB was significantly increased compared to before induction (p = 0.025 and p = 0.023, respectively), but not in the control group (p = 0.737 and p = 0.100, respectively). Conclusion: There is significantly increased expression of TLR2 and TLR6 on peripheral blood monocytes induced by SEB during exacerbation in AD patients.
Ephrem Ashenafi, Teferra Abula, , Mahlet Arayaselassie, Moti Sori
Clinical, Cosmetic and Investigational Dermatology, pp 279-299;

Background: The leaves of Vernonia auriculifera (Asteraceae) have traditionally been used to treat wounds in several regions of Ethiopia. The purpose of this study was to assess the wound healing properties of the leaf extract and solvent fractions of V. auriculifera in mice. The leaf extract and solvent fractions of V. auriculifera have also been evaluated for their anti-oxidant properties because of their impact on the wound healing process. Material and Methods: Air-dried leaves were extracted using 80% methanol. They were also successively fractionated with n-hexane, ethyl acetate, and methanol. The residue was then macerated in water for 72 hr. Simple ointment bases were formulated according to British Pharmacopoeia. Thereafter, two types of ointment formulations, 2.5% w/w and 5% w/w, were formulated. Wound healing and acute dermal toxicity studies were performed on mice. To assess free radical scavenging activity, a 2,2-diphenyl-2-picrylhydrazyl free radical (DPPH) assay was performed. Results: In both models, wounds treated with 2.5% and 5% (w/w) of the ME, the aqueous fraction (AQF), methanol fraction (MEF), and ethyl acetate fraction (EAF) ointments demonstrated significant wound healing activity, as shown by enhanced wound contraction, a shortened epithelialization time, increased hydroxyproline content, and enhanced tissue breaking strength. The extract and solvent fractions displayed free radical scavenging activity with IC50 values of 1.2 mg/mL, 1.46 mg/mL, 1.5 mg/mL, and 2.83 mg/mL for ME, AQF, MEF, and EAF, respectively, as compared to 1.42 mg/mL for ascorbic acid. Conclusion: The result of this study indicates that 80% of methanol extract and solvent fractions are endowed with wound healing activity. Additionally, this study has also revealed that ME, AQF, MEF, and EAF have the capacity to scavenge free radicals. The study indicated that the wound healing effect could be attributed to the anti-inflammatory and antioxidant activities.
Pierre Bourgeois, Mirela Mariana Roman, Justine Schweicher, Pauline Lavoisier, Philippe Maquet, Clarence Karler, Mateusz Lizewski, Alessandro Fouarge, Nicolas Cuylits, Véronique del Marmol, et al.
Clinical, Cosmetic and Investigational Dermatology, pp 257-265;

Background: The number of people within the European population having at least one tattoo has increased notably and with it the number of tattoo-associated clinical complications. The injected inks are known to be removed by the lymphatic vessels and can be found in the draining lymph nodes. Aim of the Study: To report our observations on the lymphatic drainages seen under tattoos using near infrared fluorescence imaging of these lymphatic vessels after the injection of indocyanine green. Material and Methods: Indocyanine green was injected intradermally at the basis of the 20 tattooed area(s) in 19 subjects (nine women and ten men; mean age = 28.6). Ten subjects had only black tattoos (six upper limbs and four lower limbs), five (two upper limbs and three lower limbs) black and white tattoos and five multi-colored tattooed limbs (four lower limbs and one upper limb). Results: The imaging exams revealed alterations in eight individuals, seven of whom had tattoos on their lower limbs. Furthermore, the imaging results showed that the abnormalities might be related to the tattooed limb, the tattoo extent and colour. Conclusion: Alterations of the cutaneous lymphatic channels are frequently observed under tattooed territories. Their causal factors should be more precisely studied in future works and these lymphatic alterations should be considered in tattooed patients when using similar imaging techniques for therapeutic and surgical assessments.
Fei Wang, Jitao Liu, Quan An, Yiming Wang, Yang Yang, Tong Huo, Simin Yang, Ruijun Ju, Qianghua Quan
Clinical, Cosmetic and Investigational Dermatology, pp 267-278;

Introduction: Inflammation generally refers to the body’s defensive response to stimuli, and skin inflammation is still one of the major problems that affect human physical and mental health. While current pharmacological treatments are reported to have cytotoxicity and various side effects, herbal medicines with few side effects and low cytotoxicity are considered as alternative therapeutic approaches. Methods: In order to investigate anti-inflammatory effects and mechanisms of ALOE, the potential cytotoxicity of A. vera extracts (ALOE) was determined in vitro at first. The production of the pro-inflammatory proteins (ie, IL-6, TNF-α) in lipopolysaccharides (LPS) and ultraviolet A (UVA)-stimulated HaCaT and RAW264.7 cells were then treated with ALOE to test its inhibitory effects using enzyme-linked immunosorbent assay (ELISA). To further explore the anti-inflammatory mechanisms of ALOE, quantitative Polymerase Chain Reaction (qPCR) was used to analyze the mRNA expression of inflammatory genes iNOS, COX-2 and NO production. For NF-κB and MAPK signaling pathways analysis, Western blotting and nuclear fluorescence staining were used to evaluate the expression of key factors. Results: ALOE did not exhibit obvious cytotoxicity (0– 3 mg/mL) in vitro. ALOE was able to inhibit the expression of pro-inflammatory cytokines IL-6, TNF-α and functioned more prominently in LPS-induced model. ALOE could also suppress the mRNA expression of LPS-induced iNOS and COX-2 and further down-regulate NO level. Furthermore, ALOE reduced the protein expression of P65 in NF-κB signaling pathway and suppressed LPS-induced activation of ERK and JNK, instead of p38 MAPK pathway. Conclusion: Taken together, these results demonstrated that ALOE is a potential treatment in suppressing LPS-stimulated inflammation reactions targeting NF-κB, JNK and ERK signaling pathways. The anti-inflammatory effects of ALOE indicated that it has the potential to become an effective cosmetic ingredient.
Yuan Li, Xiaole Zhen, Xiaojuan Yao, Jiejie Lu
Clinical, Cosmetic and Investigational Dermatology, pp 253-256;

Minocycline is a tetracycline derivative antibiotic commonly used to treat acne, rosacea, and other inflammatory skin conditions. Taking minocycline risks inducing skin pigmentation. If minocycline-induced hyperpigmentation is not treated, it may take months to years for the symptoms to subside after discontinuation of the drug, or the hyperpigmentation may never disappear completely, which can lead to cosmetic anxiety and affect people’s quality of life. Previous treatment options for hyperpigmentation were mainly q-switched nd: YAG, ruby, and alexandrite lasers. This article reports a case of facial hyperpigmentation caused by minocycline using a combination of chemical peel and intense pulsed light in a patient with eosinophilic cellulitis (Wells syndrome) who was taking oral minocycline. This case suggests combining chemical peel and intense pulsed light is an effective treatment option for minocycline-induced hyperpigmentation.
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