Randomized, double-blind, active-controlled, multicentre, phase III clinical trial with two stages to assess the safety and efficacy of letibotulinum toxin a vs. onabotulinum toxin a for subjects with moderate to severe crow's feet.

BACKGROUND: Letibotulinum toxin A (LeBA) was approved by the Ministry of Food and Drug Safety (known as the Korea Food & Drug Administration) for cosmetic indications in 2012. However, the efficacy and safety of this newly introduced LeBA have not been investigated in crow's feet lines (CFL) treatment and standardization before its universal use. OBJECTIVE: The aim of this multicentre, double-blind, randomized, parallel, active-controlled Phase III clinical trial with two stages (ClinicalTrials.gov identifier: NCT03408236) was to investigate the non-inferiority of LeBA vs. the existing onabotulinum toxin A (OnBA) for the treatment of CFL. METHODS: A total of 240 subjects were randomized to either the test (LeBA) or control (OnBA) group. At the baseline and at weeks 4 while maximum smiling (primary efficacy assessment), 8, 12 and 16, investigator's on-site evaluation, independent evaluator, evaluation by the subjects, subjects' satisfaction assessment and safety assessment were performed. RESULTS: At week 4, the response rate of primary efficacy assessment was 69.75% and 68.33% in the test (LeBA) and control (OnBA) groups, respectively, without a significant difference. Other minor secondary evaluation results showed significant differences suggesting that LeBA offered better improvement than OnBA, but the overall results did not show significant differences between the two groups. CONCLUSION: This study showed that LeBA was as effective and safe as OnBA for the treatment of CFL at the same doses.

Topically applied treatments for external genital warts in nonimmunocompromised patients: a systematic review and network meta-analysis.

Selecting a topical treatment from among the numerous topical agents for external genital warts remains challenging without clear evidence. Our aim was to evaluate comparatively the efficacy and safety of topical agents for external genital warts using a network meta-analysis. We included all randomized controlled trials that evaluated any topically applied treatment for external genital warts. Using the R package netmeta, network meta-analyses were performed with a frequentist approach. We identified 41 relevant studies comprising 6371 patients. Among conventional agents, podophyllotoxin 0·5% solution (odds ratio 1·94, 95% confidence interval 1·02-3·71) was significantly more efficacious than imiquimod 5% cream for lesion clearance; however, it was associated with a higher overall adverse event rate. Sinecatechins 15% ointment (odds ratio 0·21, 95% confidence interval 0·12-0·34) was significantly less efficacious than imiquimod 5% cream. Idoxuridine, polyhexamethylene biguanide, cidofovir and SB206 showed comparable therapeutic efficacies with conventional therapies. None of the treatments were significantly different from each other with respect to recurrence, patients with severe adverse events, or patients who withdrew because of treatment-related adverse events. Conventional modalities were efficacious and well tolerated, although each of them had their advantages and disadvantages. Additional efficacy and safety studies are warranted for unconventional agents.

Efficacy and safety of PAC-14028 cream - a novel, topical, nonsteroidal, selective TRPV1 antagonist in patients with mild-to-moderate atopic dermatitis: a phase IIb randomized trial.

BACKGROUND: Transient receptor potential vanilloid subfamily, member 1 (TRPV1) may play an important role in pruritus and inflammation induction in atopic dermatitis (AD). The treatment effect of TRPV1 antagonist via topical application in patients with AD remains unknown. OBJECTIVES: To assess the clinical efficacy and safety of PAC-14028, a TRPV1 antagonist, via topical application in patients with AD. METHODS: In this 8-week, phase IIb, randomized, double-blind, multicentre, vehicle-controlled study, patients with mild-to-moderate AD were randomized to receive PAC-14028 cream 0·1%, 0·3%, 1·0% or vehicle cream twice daily. The primary efficacy end point was the Investigator's Global Assessment (IGA) success rate defined as the percentage of patients with an IGA score of 0 or 1 at week 8. The secondary efficacy end points included the severity Scoring of Atopic Dermatitis (SCORAD) index and Eczema Area and Severity Index (EASI) 75/90. RESULTS: A total of 194 patients were enrolled. IGA success rates at week 8 were 14·58% for vehicle cream, 42·55% for PAC-14028 cream 0·1% (P = 0·0025 vs. vehicle), 38·30% for PAC-14028 cream 0·3% (P = 0·0087 vs. vehicle) and 57·45% for PAC-14028 cream 1·0% (P < 0·001 vs. vehicle). In particular, statistically significant differences were found between the vehicle and treatment groups in the IGA success rates with two-grade improvement. The SCORAD index, EASI 75/90, sleep disturbance score and pruritus visual analogue scale showed a trend towards improvement. No significant safety issues were reported. CONCLUSIONS: PAC-14028 cream may be an effective and safe treatment modality for the treatment of patients with mild-to-moderate AD.

Neutrophilic urticarial dermatosis and Sweet-like neutrophilic dermatosis: under-recognized neutrophilic dermatoses in lupus erythematosus.

Background/Objectives Neutrophilic dermatoses can be associated with autoimmune connective tissue diseases such as systemic lupus erythematosus (SLE). We analyzed clinical and histological features of neutrophilic urticarial dermatosis (NUD) and Sweet-like neutrophilic dermatosis (SLND)-the most recently delineated entities of the neutrophilic dermatoses. Methods We retrieved database medical records of patients with SLE whose skin biopsy demonstrated a neutrophilic-predominant infiltrate of the skin, and included those whose biopsies revealed findings of SLND or NUD. Results SLND skin lesions lasted longer than those of NUD and were localized to sun-exposed areas. All NUD cases resolved within one week either spontaneously or with treatment such as antihistamines, but SLND skin lesions lasted longer than one week; prednisone was used in four of these five patients. All NUD cases were found in existing SLE patients and were not associated with systemic signs of flare-up of SLE. However, 80% of SLND cases experienced flare-up of SLE; and in 60%, SLND developed concomitantly with SLE as a presenting sign. Conclusion Different clinical courses and relationships with SLE suggest that NUD and SLND have different pathogeneses for neutrophilic inflammatory reactions.

Expression of programmed death-1 in cutaneous extranodal natural killer/T-cell lymphoma and its effect on clinical findings and biological behaviour.

BACKGROUND: Recent studies have evaluated the expression of programmed death-1 (PD-1) and its prognostic value in malignant T-cell lymphomas. OBJECTIVES: This study investigated whether the positivity of PD-1 was associated with the clinical characteristics of cutaneous extranodal NK/T-cell lymphoma (ENKTL) and evaluated its effects on survival outcomes. METHODS: Forty-one patients with cutaneous ENKTL were included. Clinical features and survival outcomes were analysed according to the positivity of PD-1. RESULTS: There was no significant difference between primary cutaneous ENKTL and secondary cutaneous ENKTL in the expression of PD-1. The degree of disease dissemination was not affected by the positivity of PD-1. Higher positivity for PD-1 was associated with lesions presenting erythematous to purpuric patches that are mainly composed of small tumour cells. Cutaneous ENKTL presenting nodular lesions had a significantly lower number of PD-1-positive infiltrating cells than those with other clinical morphologies. There was no significant effect of PD-1 expression on outcomes such as overall and progression-free survival. LIMITATIONS: This study used a retrospective design and had a small sample size. CONCLUSION: Higher PD-1 positivity is associated with small-cell-predominant cutaneous ENKTL. However, PD-1 expression has no prognostic value in cutaneous ENKTL.

Secondary cutaneous lymphoma: comparative clinical features and survival outcome analysis of 106 cases according to lymphoma cell lineage.

BACKGROUND: The relative frequency, clinical features and survival outcomes of secondary cutaneous lymphoma remain poorly understood. OBJECTIVES: To determine the clinical characteristics and survival outcomes of secondary cutaneous lymphoma. MATERIALS AND METHODS: The present retrospective cohort study included all 106 patients who presented with secondary cutaneous lymphoma. Patient medical records were reviewed to determine the clinical features, survival outcomes and prognostic factors. Survival outcomes were analysed by using the Kaplan-Meier method and comparisons between lymphoma cell lineages [T or natural killer (T-/NK)-cell vs. B-cell lymphoma] were performed using the log-rank test. RESULTS: Secondary cutaneous lymphomas consisted of mature T-/NK-cell lymphomas (56%), mature B-cell lymphomas (35%), immature haematopoietic malignancies (8%) and Hodgkin lymphoma (1%). The T-/NK-cell lineage lymphoma cases were more likely to have multiple and disseminated skin lesions than the B-cell lineage lymphoma cases. The lymphoma cell lineage did not significantly influence survival outcomes. Patients who showed cutaneous involvement within 6 months of the initial diagnosis of primary disease had a poorer overall survival (OS) outcome than patients who developed cutaneous dissemination 6 or more months after the initial diagnosis (P < 0.001). Patients with disseminated skin lesions had a poorer OS than patients with localized skin lesions (P = 0.028). The two lymphoma cell lineages differed in terms of prognostic factors that influenced survival. CONCLUSIONS: Skin lesion characteristics such as time point of appearance and extent affect the survival outcomes of secondary cutaneous lymphoma. Cell lineage did not influence survival outcomes but the two lineages are associated with different prognostic factors.

Efficacy and safety of injection with poly-L-lactic acid compared with hyaluronic acid for correction of nasolabial fold: a randomized, evaluator-blinded, comparative study.

BACKGROUND: Hyaluronic acid (HA) fillers and poly-L-lactic acid (PLA) fillers are frequently used to correct facial wrinkles. AIM: To compare the efficacy and safety of a novel injectable poly-L-lactic acid (PLA) filler and a well-studied biphasic HA filler for the treatment of moderate to severe nasolabial folds. METHODS: In this multicentre, randomized, evaluator-blinded, comparative study, subjects were randomized for injections with PLA or HA into both nasolabial folds. Efficacy was determined by calculating the change in Wrinkle Severity Rating Scale (WSRS) relative to baseline. Local safety was assessed by reported adverse events. RESULTS: At week 24, mean improvement in WSRS from baseline was 2.09 ± 0.68 for the PLA side and 1.54 ± 0.65 for the HA side. Both injections were well tolerated, and the adverse reactions were mild and transient in most cases. CONCLUSIONS: PLA provides noninferior efficacy compared with HA 6 months after being used to treat moderate to severe nasolabial folds.

Facial and extrafacial eosinophilic pustular folliculitis: a clinical and histopathological comparative study.

BACKGROUND: Although more than 300 cases of eosinophilic pustular folliculitis (EPF) have been reported to date, differences in clinicohistopathological findings among affected sites have not yet been evaluated. OBJECTIVES: To evaluate differences in the clinical and histopathological features of facial and extrafacial EPF. METHODS: Forty-six patients diagnosed with EPF were classified into those with facial and extrafacial disease according to the affected site. Clinical and histopathological characteristics were retrospectively compared, using all data available in the patient medical records. RESULTS: There were no significant between-group differences in subject ages at presentation, but a male predominance was observed in the extrafacial group. In addition, immunosuppression-associated type EPF was more common in the extrafacial group. Eruptions of plaques with an annular appearance were more common in the facial group. Histologically, perifollicular infiltration of eosinophils occurred more frequently in the facial group, whereas perivascular patterns occurred more frequently in the extrafacial group. Follicular mucinosis and exocytosis of inflammatory cells in the hair follicles were strongly associated with facial EPF. CONCLUSIONS: The clinical and histopathological characteristics of patients with facial and extrafacial EPF differ, suggesting the involvement of different pathogenic processes in the development of EPF at different sites.

Paediatric cutaneous lymphoma in Korea: a retrospective study at a single institution.

BACKGROUND: The clinical features and incidences of cutaneous lymphoma (CL) differ by ethnicity and age. However, there is to our knowledge no study to show characteristics and distribution of paediatric CL in Asian population. OBJECTIVE: The aim of this study was to investigate distinctive clinicopathological features of CL in paediatric population, particularly in Korea. METHODS: We conducted a clinicopathological review of 41 paediatric cases with CL, diagnosed at Asan Medical Center from January 1990 to December 2012. The clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from paediatric patients with CL were analyzed. In addition, the results in this present paediatric group were compared with previously reported studies in the Korean all-ages group and Western paediatric group. RESULTS: Lymphomatoid papulosis was more common in the present paediatric group than in the all-ages group (34.5% vs. 9.4%) and Western paediatric group (34.5% vs. 17.7%). Mycosis fungoides, the most common cutaneous lymphoma in the all-ages group and Western paediatric group, is the second most common subtype in this study. Three of nine paediatric mycosis fungoides patients (33%) have the follicular variant. Compared with all-ages group, B-lmphoblastic lymphoma was relatively higher incidence (10.3% vs. 1%) and NK-/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma was relatively in lower proportions in the paediatric group. CONCLUSION: The clinical features and distribution of paediatric CL in our study suggest that CL of Asian childhood is quite different from that of adulthood and Western childhood.

RimabotulinumtoxinB vs. onabotulinumtoxinA for the treatment of forehead lines: an evaluator-blind, randomized, pilot study.

BACKGROUND: Optimum dose ratios of rimabotulinumtoxinB (BTX-B) and onabotulinumtoxinA (BTX-A) have not been determined for forehead wrinkles. OBJECTIVE: To compare the efficacy and safety of BTX-B and BTX-A for the treatment of forehead lines. METHODS: Twenty-two women (mean age, 40 years) with symmetrical moderate to severe forehead lines were randomized to receive single intramuscular injections of BTX-A and BTX-B on either side of the forehead, at a potency ratio of 1 : 70 or 1 : 100. Subjects were followed-up for 16 weeks. Four physicians evaluated patients' photographs according to the 4-point Facial Wrinkling Grade (FWG). Clinical Improvement Scale (CIS) was calculated by subtracting FWG score at each visit from that at baseline. Patient satisfaction scores and adverse events were also recorded. RESULTS: Both BTX-A and BTX-B were effective for the treatment of forehead lines. At both potency ratios, BTX-A had a longer duration of action than BTX-B, while BTX-B led to faster improvement than BTX-A. There was no significant difference in CIS between 700 U and 1000 U BTX-B treatments. Adverse effects were mild and transient. CONCLUSION: Both BTX-A and BTX-B were effective and well tolerated for the treatment of forehead wrinkles at potency ratios of 1 : 70 and 1 : 100.

Clinical analysis of deep cutaneous mycoses: a 12-year experience at a single institution.

Deep cutaneous mycoses can cause significant morbidity and mortality, especially in immunocompromised patients. There have been few studies focusing on deep cutaneous mycoses and there are no data from Asian countries. This study aimed to investigate clinical characteristics, underlying predisposing factors, aetiological organisms and outcomes in patients with deep cutaneous mycoses. A retrospective medical record review of patients with deep cutaneous mycoses treated at a tertiary referral centre in Korea from 1999 to 2010. Forty-one cases of deep cutaneous mycosis were identified (median age: 49). Most patients (32/41) had impaired immunological status, and seven of the remaining nine had a history of physical trauma. Neutropenia and long-term use of antibiotics were detected in 13 and 12 patients respectively. Nodular skin lesions were the most common type (17/41) and the morphology of the lesions varied. Fungal organisms were identified by culture and histopathology of skin specimens. Candida (16/41) was the most common organism, followed by Aspergillus, Alternaria, Fusarium (4/41 each). Systemic antifungal treatment was successful in 28 patients, while nine patients died from the fungal infection. Our study may lead to improved insights into deep cutaneous mycoses as their incidence is increasing and they vary in different clinical settings.

Synchronous infection with Mycobacterium chelonae and Paecilomyces in a heart transplant patient.

A 41-year-old male who was 3 years status post heart transplant presented with a 3-month history of painful erythematous nodules and ulcers on his lower legs and right hand. First, Mycobacterium chelonae infection was revealed through several biopsies with molecular sequence analysis, and combination treatment, including clarithromycin, was started. During the treatment, lesions of the legs showed an improvement, but a fluctuant erythematous nodule on the thumb did not respond. Repetitive biopsy from the thumb ultimately identified Paecilomyces species and the patient was treated with itraconazole and terbinafine sequentially. Our case is the first report, to our knowledge, of synchronous infection with non-tuberculous mycobacteria (NTM) and Paecilomyces in a solid organ transplant recipient. Our findings highlight the importance of recognizing cutaneous NTM infections or deep mycoses, as well as the importance of choosing an appropriate treatment.

Eruptive pseudo-angiomatosis lesions are associated with intravascular neutrophils and do not harbour Epstein-Barr virus.

BACKGROUND: Eruptive pseudo-angiomatosis (EPA) is a rare, relatively newly described cutaneous disorder characterized by the sudden onset of several bright red, angioma-like papules surrounded by blanched halo. Its aetiology is unknown; however, viral infection or mosquito bites have been speculated as possible causes. OBJECTIVE: This study aims to determine the clinical and histopathological features of EPA, and whether it is associated with Epstein-Barr virus (EBV) infection. METHODS: We conducted a retrospective chart review of 25 EPA cases from 2006 to 2008. In order to determine latent EBV infection, EBV-encoded small RNA (EBER) in situ hybridization was performed in 18 subjects. To determine EPA's distinguishing histological characteristics, we compared the cases with 22 control cases of perivascular lymphocytic infiltration for haematoxylin and eosin, CD3, CD4, CD8, CD31 and c-kit staining patterns. RESULTS: The patient sample's female-to-male ratio was 2.1 : 1, and the patients' age ranged from 5 to 79 years (average 46 years). The lesions appeared during the months of July to September in all but 3 patients. Skin biopsies demonstrated capillary ectasia with perivascular mononuclear cellular infiltrates in the upper dermis. Most patients were otherwise healthy, and routine laboratory results were all normal except in one patient who had diabetes. The skin lesions faded without any treatment in 1-2 weeks. Results of EBER in situ hybridization were all negative. The only histological distinguishing feature of EPA was the presence of intravascular neutrophils, which was found to be present in 19 of the 20 EPA cases (95%), in contrast to only 3 of the 22 control subjects (14%) (P < 0.0001). CONCLUSION: The sudden onset of lesions during the summer months among our patients supports the 'paraviral eruption' concept of this probably underdiagnosed condition. The significant presence of intravascular neutrophils may be a diagnostic clue of EPA in South Korea.

Breast Tumor Malignancy Classification using Smartphone Compression-induced Sensing System and Deformation Index Ratio.

Smartphone-based compression-induced sensing system uses the light diffusion pattern to characterize the early-stage breast tumor noninvasively. The system is built on a smartphone and cloud platform to capture, transfer, and interface with the user. The compressed tissue's deforming pattern creates distinctive tactile images due to the size and hardness of the tumor. From the compression-induced images, we estimate the size of the tumor using projection analysis and the tumor's malignancy using the tissue deformation index ratio. Deformation index ratio is based on the changes of a healthy region over the tumorous region. By using the projection analysis, the human patient tumor size estimation resulted in 52.3% of the average error. For a small number (seven) of the feasibility test, the tumor's malignancy was classified based on the deformation index ratio with 67.0% of sensitivity and 100% specificity.

High-dose squalene ingestion increases type I procollagen and decreases ultraviolet-induced DNA damage in human skin in vivo but is associated with transient adverse effects.

BACKGROUND: Evidence for beneficial effects of squalene on ultraviolet (UV)-induced photoageing of the skin is lacking. AIM: To investigate whether squalene supplementation improves signs and molecular markers of photoageing in human skin in vivo. METHODS: In total, 40 female volunteers aged > 50 years received two different doses [13.5 g/day (low-dose group) and 27 g/day (high-dose group)] of squalene for 90 days. At baseline and at the completion of the study, facial wrinkles were measured using skin replicas. Skin samples were taken to compare type I procollagen and matrix metalloproteinase 1 mRNA levels by real-time reverse-transcriptase PCR, and for type I procollagen immunostaining. Skin samples were also taken 24 h after 2 x minimal erythema dose (MED) of UV irradiation before and after squalene intake to assess UV-induced thymine dimer formation and keratinocytic apoptosis. RESULTS: In total, 37 subjects completed the trial. Transient loose stool was experienced by 35% of volunteers in the low-dose group and 55% in the high-dose group. Facial wrinkles decreased significantly (P < 0.05) in the high-dose group, while procollagen type I mRNA levels and MED increased significantly in the low-dose group. Procollagen immunostaining tended to increase in both groups. Facial erythema decreased and pigmentation increased significantly in both groups. UV-induced keratinocytic apoptosis and thymine dimer staining were substantially reduced in both groups. CONCLUSIONS: Daily ingestion of 13.5 or 27 g of squalene per day resulted in antiageing effects in photoaged skin. However, in view of the frequent incidence of loose stool experienced by the subjects, the risk-benefit ratio of high-dose squalene supplementation is too high to recommend it for treating skin ageing.

Tumor size and elasticity estimation using Smartphone-based Compression-Induced scope.

A simple-to-use, noninvasive, and risk-free system, which will provide accurate identification of potentially life threatening malignant tumors using tactile pressure, is developed. The Smartphone-based Compression-Induced (SCI) Scope will allow physicians to quickly capture the mechanical properties of a benign or malignant tumor with the convenience of a smartphone platform. The size and elasticity property is described using estimating methods from the pressure-induced images of SCI Scope. The device is based on the Apple iPhone 6. The image will be captured through a waveguide. The image information in combination with the force sensor value will be transmitted wirelessly to a computer for processing. The size and elasticity estimation experiments with SCI Scope showed that the size estimation error of 2.31% and estimated relative elastic modulus error of 23.9%.