Efficacy and safety of a thermal fractional skin rejuvenation system (Tixel) for the treatment of facial and/or scalp actinic keratoses.

Actinic keratoses are common cutaneous lesions with a potential to progress to invasive squamous cell carcinoma. Therefore, treatment is crucial. The Tixel® is a noninvasive thermomechanical device designed to transfer heat to the upper dermis in a controlled manner according to a predetermined setting. This study aimed to evaluate the safety and efficacy of a thermomechanical fractional skin resurfacing technology for the treatment of facial and scalp actinic keratoses. A prospective, open-label, before-after study was conducted in a tertiary medical centre from May 2020 to April 2021. Patients presenting with facial/scalp actinic keratoses of mild-to-moderate thickness underwent 2 or 3 Tixel treatments (depending on clinical improvement), 3-4 weeks apart. The reduction in lesion count and overall improvement in appearance were assessed by clinical examination and digital photography. Findings were compared between baseline and follow-up at 3 months after the last treatment session. Patient satisfaction was evaluated by questionnaire, and adverse effects were documented. A total of 20 patients participated in the study. All completed 2-3 treatments and follow-up visits. Assessment of digital photographs was performed by 2 assessors blinded to the timepoint at which each photo was taken (before or after treatment). The average number of lesions at baseline was 9.8 (± 4.8) and the mean reduction in lesion count was 7.9 (± 4.4) (80.6%). Complete clearance was observed in 31.6% of patients. No adverse effects were noted during treatment and follow-up. Most patients reported being "very satisfied" or "satisfied" with the treatment results (85%) and experience (95%). Treating facial and scalp actinic keratoses with the Tixel device was found to be effective and safe.

Hidradenitis suppurativa and atopic dermatitis: A 2-way association.

BACKGROUND: The coexistence of hidradenitis suppurativa (HS) and atopic dermatitis (AD) had been reported but, to our knowledge, was not investigated in controlled studies. OBJECTIVE: To evaluate the bidirectional association between HS and AD. METHODS: A population-based retrospective cohort study was conducted to compare the incidence rate of AD among patients with HS (n = 6779) and age-, sex-, and ethnicity-matched control individuals (n = 33,260). Adjusted hazard ratios (HRs) and adjusted odds ratios were estimated. RESULTS: The incidence of AD was 2.51 (95% confidence interval [CI], 2.07-3.02) and 1.24 (95% CI, 1.10-1.40) per 1000 person-years among patients with HS and control individuals, respectively. Patients with HS were twice as likely to develop AD as control individuals (HR, 2.06; 95% CI, 1.64-2.58). Furthermore, the prevalence of pre-existing AD was higher in patients with HS than in control individuals (2.5% vs 1.8%, respectively; P < .001). A history of AD was associated with a 40% increase in the odds of HS (odds ratio, 1.41; 95% CI, 1.19-1.67). Relative to patients with isolated HS, those with a dual diagnosis of HS and AD were younger and had a female predominance, lower prevalence of smoking, and lower body mass index. LIMITATIONS: Retrospective data collection. CONCLUSIONS: A bidirectional association between HS and AD was observed. Dermatologists should be aware of this association.

Dermoscopic features of basal cell carcinoma and its subtypes: A systematic review.

BACKGROUND: Multiple studies have reported on dermoscopic structures in basal cell carcinoma (BCC) and its subtypes, with varying results. OBJECTIVE: To systematically review the prevalence of dermoscopic structures in BCC and its subtypes. METHODS: Databases and reference lists were searched for relevant trials according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were assessed for the relative proportion of BCC dermoscopic features. Random-effects models were used to estimate summary effect sizes. RESULTS: Included were 31 studies consisting of 5950 BCCs. The most common dermoscopic features seen in BCC were arborizing vessels (59%), shiny white structures (49%), and large blue-grey ovoid nests (34%). Arborizing vessels, ulceration, and blue-grey ovoid nests and globules were most common in nodular BCC; short-fine telangiectasia, multiple small erosions, and leaf-like, spoke wheel and concentric structures in superficial BCC; porcelain white areas and arborizing vessels in morpheaform BCC; and arborizing vessels and ulceration in infiltrative BCC. LIMITATIONS: Studies had significant heterogeneity. Studies reporting BCC histopathologic subtypes did not provide clinical data on pigmentation of lesions. CONCLUSION: In addition to arborizing vessels, shiny white structures are a common feature of BCC. A constellation of dermoscopic features may aid in differentiating between BCC histopathologic subtypes.

The trichoscopic features of hair shaft anomalies induced by epidermal growth factor receptor inhibitors: A case series.

BACKGROUND: Although the clinical hair changes that occur under treatment with epidermal growth factor receptor inhibitors (EGFRIs) are documented, their trichoscopic features have not been reported. OBJECTIVE: To evaluate the trichoscopic findings in scalp and facial hair, induced by EGFRI treatment. METHODS: Patients treated with EGFRIs at a tertiary oncodermatology clinic in 2015 through 2017 were evaluated for macroscopic and trichoscopic changes. RESULTS: The cohort included 23 patients (13 women; median age, 68 years) treated with EGFRIs for an average of 13 months (range, 2-40 months). Macroscopically, 18 patients (78%) had dry, lusterless, coarse, kinky, brittle scalp hair, and 17 (74%) had trichomegaly of the eyebrows/eyelashes. Trichoscopic findings were of hair shaft anomalies including pili torti, affecting scalp hair in 20 patients (87%), eyebrows in 6 (26%), and eyelashes in 8 (50%), and asymmetric hyperpigmented fusiform widening of hair scalp in 3 (13%), eyebrows in 10 (43%), and eyelashes in 4 (25%). Dermoscopic findings of the peri- and interfollicular skin were scale, whitish erythematous structureless areas, and branching vessels. LIMITATIONS: Lack of trichoscopic-histologic correlation, lack of baseline examination. CONCLUSION: The trichoscopic correlates of the macroscopic hair changes under EFGRI treatment include pili torti, and asymmetric hyperpigmented fusiform widening, with dermoscopic cutaneous manifestations of scale, whitish erythematous structureless areas, and branching vessels.

Prophylactic Topical Treatment for EGFR Inhibitor-Induced Papulopustular Rash: A Randomized Clinical Trial.

BACKGROUND: The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%. OBJECTIVE: To investigate prophylactic topical treatment for EGFRI-induced rash. METHODS: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions. RESULTS: The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA. CONCLUSIONS: Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash.

Self-administered daylight-activated photodynamic therapy for the treatment of hand eczema: A prospective proof-of-concept study.

Photodynamic therapy (PDT), traditionally used in patients with nonmelanoma skin cancer, has been found to be effective for various inflammatory skin conditions. Daylight-activated PDT (DL-PDT), in which the sun serves as the light source, is substantially less painful than conventional PDT. This study aimed to determine the safety and efficacy of DL-PDT in a series of patients with chronic hand eczema (CHE). A proof-of-concept prospective design was used. Eight patients diagnosed with CHE at a tertiary dermatology clinic underwent DL-PDT. The first treatment was administered at the clinic and subsequent treatments (up to four total) were self-administered at home at 2-week intervals. Outcome was evaluated with the Investigator Global Assessment (IGA; score 0-4), Dermatology Life Quality Index (DLQI; score 0-24), and blinded review of clinical photographs (graded on a quartile scale by percent improvement). There were six male and two female patients of mean age 35 years. All underwent at least three treatments. The IGA score improved by 2.5 points at 1 month, 2.7 at 3 months, and 2.2 at 6 months post-treatment, and the DLQI score improved by 7.9, 6.6, and 6.1 points, respectively. Clinical photograph grades improved by 2.9 points at 3 months. Side effects were mild and transient. All patients had some degree of recurrence after 6 months of treatment. The self-administered DL-PDT is easy to perform, moderately effective, and safe to use in patients with CHE. Repeated treatments might be required to maintain remission.

The diagnostic accuracy of dermoscopy for basal cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Dermoscopy is a noninvasive technique for the diagnosis of skin lesions. Its accuracy for basal cell carcinoma (BCC) has not been systematically studied. OBJECTIVE: We sought to systematically investigate the accuracy of dermoscopy for the diagnosis of BCC compared with examination with the naked eye. METHODS: A systematic review of studies reporting the accuracy of naked eye examination and dermoscopy for the diagnosis of BCC was conducted. A meta-analysis for sensitivity and specificity was performed using a bivariate mixed-effects logistic regression modeling framework. RESULTS: Seventeen studies were identified. The pooled sensitivity and specificity of dermoscopy for the diagnosis of BCC were 91.2% and 95%, respectively. In studies comparing test performance, adding dermoscopy to naked eye examination improved sensitivity from 66.9% to 85% (P = .0001) and specificity from 97.2% to 98.2% (P = .006). The sensitivity and specificity of dermoscopy were higher for pigmented than nonpigmented BCC. Sensitivity increased when dermoscopy was performed by experts and when the diagnosis was based on in-person dermoscopy as opposed to dermoscopic photographs. LIMITATIONS: Significant heterogeneity among studies with a medium-to-high risk of bias. CONCLUSION: Dermoscopy is a sensitive and specific add-on tool for the diagnosis of BCC. It is especially valuable for pigmented BCC.

Acne and obesity: A nationwide study of 600,404 adolescents.

BACKGROUND: The association between body mass index (BMI) and acne is unclear. OBJECTIVE: To determine the association between BMI and acne in youths. METHODS: A nationwide, population-based, cross-sectional study was conducted in 2002-2015 by using medical data on 600,404 youths during compulsory military service. BMI was measured at age 17 years. Acne was diagnosed by dermatologists. Unadjusted and adjusted odds ratios (aORs) of acne in relation to BMI (stratified into 8 groups) were calculated, with the low-normal group (18.5≤ BMI ≤21.99 kg/m2) serving as the reference. RESULTS: The study included 299,163 males (49.9%) and 301,241 females (50.1%) with a mean age of 18.9 years (standard deviation, 0.6) and 18.7 years (standard deviation, 0.5), respectively, at recruitment. Acne was diagnosed in 55,842 males (18.7%) and 48,969 females (16.3%). The proportion of participants with acne decreased gradually from the underweight to the severely obese group (males, from 19.9% to 13.9%; females, from 16.9% to 11.3%). The findings on multivariable analysis were similar to the unadjusted analysis results, showing the lowest odds of acne in severely obese participants (aOR for males, 0.53; 95% confidence interval, 0.42-0.64; aOR for females, 0.5; 95% confidence interval, 0.37-0.62). The findings persisted in the sensitivity analyses. LIMITATIONS: Information was lacking on potential confounders and acne severity. CONCLUSION: In youths, overweight and obesity are inversely associated with acne in a dose-dependent manner.

Venous thromboembolism in patients with pemphigus: A cohort study.

BACKGROUND: Venous thromboembolism (VTE) has been reported to be a significant cause of death in patients with pemphigus. OBJECTIVE: We sought to assess the incidence and characteristics of VTE in patients with pemphigus. METHODS: A retrospective study following a cohort of 172 patients with newly diagnosed pemphigus for the development of VTE was conducted. RESULTS: Over a mean follow-up time of 4 years, 10 patients (6%) had development of VTE at a median of 4 months from pemphigus diagnosis. The highest risk was found in the first year, at 5 VTE events per 100 patient-years or a 5% VTE risk for that first year. Five patients had deep vein thromboses, 4 had pulmonary embolisms, and 1 had both. Age and gender were not related to the VTE risk. Most patients had VTE risk factors, either hereditary or acquired as the result of pemphigus treatments and their complications, including hospitalization, immobilization, and infections. LIMITATIONS: The use of existing health records limited the assessment of asymptomatic VTE and VTE risk factors; a matched control population was not studied. CONCLUSIONS: VTEs are not rare in patients with pemphigus, more so in the first year after diagnosis. VTE risk must be assessed in all patients, especially when hospitalized, and thrombo-prophylaxis should be initiated in qualifying cases.

Association of bullous pemphigoid with malignancy: A systematic review and meta-analysis.

BACKGROUND: Studies evaluating whether malignancy rate is increased in patients with bullous pemphigoid (BP) have reached conflicting results. OBJECTIVE: We sought to determine whether BP is associated with malignancy. METHOD: Medline, EMBASE, the Cochrane library, and reference lists of included studies were searched for comparative studies that evaluated the relationship between BP and malignancy. Data were analyzed on the basis of study design: cross-sectional, case control, and cohort. A meta-analysis was performed by using a random effects model to estimate pooled odds ratio. RESULTS: The review included 8 studies. No association between BP and overall cancer was found for any of the study designs. Although a single cohort study reported an association with lymphoid leukemia and kidney and larynx cancer, a pooled analysis of case-control studies did not. A pooled analysis of cross-sectional studies found a significant association between BP and hematologic malignancies. LIMITATIONS: The paucity of well-designed studies hindered the possibility of proving or disproving the BP-cancer association. CONCLUSION: We did not find an association of BP with overall malignancy, but a possible association with hematologic malignancy was observed.

The Effects of Common Over-the-Counter Moisturizers on Skin Barrier Function: A Randomized, Observer-Blind, Within-Patient, Controlled Study.

BACKGROUND: Moisturizers possibly improve atopic dermatitis (AD) by restoration of skin barrier, although some have detrimental effects. OBJECTIVE: The aim of the study was to estimate the effects of several routine moisturizers on barrier functions. METHODS: This is a randomized, forearm-controlled, observer-blind study. Patients older than 12 years with clear to moderate AD were randomized to 1 of 4 moisturizers (Cetaphil Cream, Aveeno Eczema Therapy Moisturizing Cream, CeraVe Moisturizing Cream, Vaseline) applied to nonlesional skin of 1 forearm and no moisturizer to the opposite forearm for 4 weeks. Transepidermal water loss (TEWL), capacitance, pH, and TEWL after tape stripping were evaluated at weeks 0 and 4. In addition, participants without AD underwent baseline measurements only. RESULTS: Twenty patients with AD completed the study. Baseline measurements between the AD group and 10 non-AD controls were similar. After the intervention (AD group), mean TEWL improved in the treated forearm and worsened in the untreated one, but the difference was not significant. There was no significant change in pH or in TEWL after tape stripping. Capacitance significantly improved in the moisturizer forearm. The study was underpowered as recruitment fell short. CONCLUSIONS: The effects of moisturizers on nonlesional AD skin were small and need to be addressed when powering future studies. Broadening investigations beyond the classic barrier properties might be useful in future studies.

Dupilumab-induced ocular surface disease (DIOSD) in patients with atopic dermatitis: clinical presentation, risk factors for development and outcomes of treatment with tacrolimus ointment.

AIM: To identify risk factors for the development of dupilumab-induced ocular surface disease (DIOSD) in adult patients with atopic dermatitis (AD) and describe outcomes of treatment. METHODS: A retrospective institutional cohort study performed at the Rabin Medical Center, Petach Tikva, Israel. Adult patients with AD who received dupilumab from March 2018 to June 2019 were included. Demographics, AD severity scores, blood IgE levels, previous atopic keratoconjunctivitis (AKC), dermatological response to dupilumab, ophthalmological evaluation and treatment were noted. Univariate and multivariate analyses were used to identify risk factors for DIOSD. RESULTS: Sixteen of 37 patients who were included in the study (43%) had new or exacerbated symptoms of ocular surface disease starting at 2 weeks following the first treatment. Three patients reported transient dry eye sensation which lasted 2 weeks; nine patients reported chronic dry eye sensation, and four patients (25%) had marked blepharoconjunctivitis. The presence of severe AD was the strongest predictor of DIOSD. Not a single patient with moderate AD had DIOSD. In multivariate analysis, prior AKC was a risk factor for DIOSD (R2=15.78, OR=23.28, p=0.005) while a family history of atopy was protective of DIOSD (R2=6.22, OR=0.13, p=0.05). All four patients with blepharoconjunctivitis had resolution of signs, and symptoms within days of starting periocular 0.03%-0.1% tacrolimus ointment. CONCLUSIONS: DIOSD is common in patients with AD receiving dupilumab. While most cases are mild, some patients can develop blepharoconjunctivitis which responds well to tacrolimus ointment. AD severity, and previous AKC are risk factors for DIOSD.

Are Biologics Efficacious in Atopic Dermatitis? A Systematic Review and Meta-Analysis.

BACKGROUND: Current systemic treatments for atopic dermatitis (AD) offer limited efficacy and are often restricted by safety concerns. Biologics may address the unmet need for improved AD therapeutics. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of biologic agents in AD. METHODS: A systematic review and meta-analysis of studies evaluating AD patients treated with biologics was performed. The primary outcome was the Eczema Area and Severity Index (EASI)-75 response, while secondary outcomes were SCOring Atopic Dermatitis (SCORAD)-75, EASI-50, SCORAD-50, Investigator Global Assessment 0/1 responses, change in responses from baseline, and adverse events. RESULTS: We included 13 randomized controlled trials (RCTs) and 10 observational studies evaluating nine biologics. High-quality evidence was available for dupilumab, nemolizumab and ustekinumab. Pooling five studies, at weeks 12-16 dupilumab 300 mg every week to every 2 weeks achieved EASI-75 responses of 55%, superior to placebo [relative risk (RR) 3.3, 95% confidence interval (CI) 2.9-3.6]. Nemolizumab had similar EASI-75 responses as placebo, but significantly improved pruritus. In online reports, lebrikizumab demonstrated superior EASI-50 responses versus placebo (RR 1.3, 95% CI 1.04-1.7), while tralokinumab had superior SCORAD-50 responses versus placebo, with borderline significance (RR 1.7, 95% CI 0.97-3.1). In two RCTs each, omalizumab and ustekinumab were comparable with placebo, while antithymic stromal lymphopoietin receptor, infliximab, and rituximab lacked adequate evidence of efficacy. All medications had a comparable safety profile to placebo. LIMITATIONS: Lack of RCTs and the use of variable outcome measures limited conclusions. CONCLUSION: Dupilumab is currently the only biologic with robust evidence of efficacy in AD. Nemolizumab, lebrikizumab, and tralokinumab show promise but further data are needed. Longer follow-up and larger studies will establish their safety profile.

Determining the Incidence of Pneumocystis Pneumonia in Patients With Autoimmune Blistering Diseases Not Receiving Routine Prophylaxis.

Importance: Pneumocystis pneumonia (PCP) is a potentially lethal opportunistic infection that primary prophylaxis can help prevent. The risk of prophylactic therapy must be weighed against the incidence of PCP in the patient population. Prophylaxis most frequently involves trimethoprim-sulfamethoxazole, with second-line therapies, including atovaquone, dapsone, and pentamide. The indication for prophylaxis in immunocompromised patients without HIV is less well defined. Previously, an incidence of at least 3.5% has been proposed as a cutoff to justify prophylaxis. Objective: To assess the incidence of PCP in patients with autoimmune blistering diseases receiving no routine prophylaxis. Design, Setting, and Participants: This was a retrospective analysis of patient medical records to determine the incidence of PCP infections. The multicenter study was performed at tertiary care centers that provide care for patients with autoimmune blistering disease in Germany, Italy, Singapore, Israel, and the Netherlands. Patients had a confirmed diagnosis of pemphigus vulgaris/foliaceus, bullous pemphigoid, epidermolysis bullosa acquisita, mucous membrane pemphigoid/cicatricial pemphigoid, or anti-p200 pemphigoid. Main Outcomes and Measures: To determine the incidence of PCP defined as patients with the International Classification of Diseases, Ninth Revision (ICD-9), code 136.3, for PCP, or free text documentation of PCP occurring based on characteristic radiographic findings with elevated lactate dehydrogenase, or hospitalization for pneumonia with bronchioalveolar lavage demonstrating Pneumocystis jiroveci on confirmatory stains. Results: A total of 801 patients with autoimmune blistering diseases were included in this study; their mean (SD) age was 66.5 (17.6) years, and a total of 465 (58%) were female. Only 1 patient developed PCP, resulting in an incidence rate of 0.1%. This incidence significantly fell below the recommended threshold of 3.5% (0.1% vs 3.5%, χ21 = 27.0; P < .001). This incidence was significantly lower than the previously reported incidence of PCP in all immunosuppressed dermatologic patients (0.1% vs 1.3%; χ21 = 8.2; P = .004). Conclusions and Relevance: Routine Pneumocystis prophylaxis for patients with autoimmune blistering diseases does not seem to be warranted. Patients with autoimmune blistering disease seem to have a lower risk of PCP than the general population of immunosuppressed dermatology patients. Risks of routine prophylaxis include hyperkalemia, hypoglycemia, photosensitivity, thrombocytopenia, and more rare adverse reactions.