Clinical and molecular change induced by repeated low-dose visible light exposure in both light-skinned and dark-skinned individuals.

BACKGROUND: Visible light (VL) is known to induce pigmentation in dark-skinned individuals and immediate erythema in light-skinned individuals. However, the effects of accumulated low-dose VL exposure across skin types are not well established. METHODS: Thirty-one healthy subjects with light (Fitzpatrick skin types [FST] I-II, n = 13) and dark (FST V-VI, n = 18) skin types were enrolled. Subjects' buttocks were exposed daily to VL, wavelength 400-700 nm, with a dose of 120 J/cm2 at 50 mW/cm2 , for four consecutive days. Microarray using Affymetrix GeneChip (49,395 genes) was performed followed by qRT-PCR on skin samples. RESULTS: Repeated low-dose VL irradiation induced immediate pigment darkening and delayed tanning in dark-skinned individuals while no discernable pigmentation and erythema were observed in light-skinned individuals. Top ten upregulated genes by repeated VL exposure in microarray included melanogenic genes such as tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1), dopachrome tautomerase (DCT), premelanosome protein (PMEL), melan-A (MLANA), and solute carrier family 24, member 5 (SLC24A5) and genes involved in inflammation/matrix remodeling/cell signaling including chemokine (C-C motif) ligand 18 (CCL18), BCL2-related protein A1 (BCL2A1), and cartilage oligomeric matrix protein (COMP). In qRT-PCR CCL18 was upregulated in light skin with a greater extent (mean fold change ± SD; 4.03 ± 3.28, p = .04) than in dark-skinned individuals (1.91 ± 1.32, p = .07) while TYR was not significantly upregulated in both skin types. CONCLUSION: This study highlights the genes upregulated by cumulative VL exposure involved in pigmentation, immune response, oxidation/reduction, and matrix remodeling across skin types providing relevant information on daily solar exposure.

The association of photo-induced collagen degeneration and the development of telangiectasias in rosacea.

Rosacea is a chronic, often progressive disorder characterized by facial erythema, telangiectasias, papules, pustules, and/or rhinophyma. In this study, we investigated the tissue structure in rosacea compared to controls. We performed a case-control study between five patients with mild-to-moderate erythematotelangiectatic rosacea (ETR) and five matched controls. Facial biopsy samples from rosacea patients and controls were stained with picrosirius red for collagen and CD31 for microvessel identification. Mean collagen content was significantly greater in control samples (19.603% ±8.821%) compared to rosacea samples (16.812% ± 7.787%, p = 0.030). In contrast, mean microvessel density was significantly higher in rosacea patients (4.775 E-5 ± 1.493 E-5 µm-3 ) compared to controls (2.559 E-5 ± 8.732 E-6 µm-3 , p = 0.004). Mean microvessel lumen area was also significantly higher in rosacea patients (491.710 ± 610.188 µm2 ) compared to controls (347.879 ± 539.624 µm2 , p = 0.003). We identified a correlation between decreased collagen content and increased microvessel size and density in rosacea patients that was not observed in controls. These structural changes to the dermal matrix may contribute to the characteristic vessel growth and dilation in rosacea.

Comparison of the skin microbiota in acne and rosacea.

Acne and rosacea, despite their similar clinical presentations, follow distinct clinical courses, suggesting that fundamental differences exist in their pathophysiology. We performed a case-control study profiling the skin microbiota in rosacea and acne patients compared to matched controls. Nineteen rosacea and eight acne patients were matched to controls by age ± 5 years, sex and race. DNA was extracted from facial skin swabs. The V3V4 region of the bacterial 16S rRNA gene was sequenced using Illumina MiSeq and analysed using QIIME/Metastats 2.0 software. The mean relative abundance of Cutibacterium acnes in rosacea with inflammatory papules and pustules (20.454% ±16.943%) was more similar to that of acne (19.055% ±15.469%) than that of rosacea without inflammatory papules and pustules (30.419% ±21.862%). C acnes (P = .048) and Serratia marcescens (P = .038) were significantly enriched in individuals with rosacea compared to acne. Investigating the differences between the skin microbiota in acne and rosacea can provide important clues towards understanding the disease progression in each condition.

Periocular infantile hemangiomas: Characteristics, ocular sequelae, and outcomes.

OBJECTIVES: To identify clinical factors associated with complications of periocular infantile hemangioma (IH) and monitor improvement in complication rates post-treatment. METHODS: Retrospective cohort study. Eighty-nine patients diagnosed with periocular IH at a pediatric dermatology clinic of a tertiary care center between 2001 and 2013 were included with parental approval. Parents were interviewed by telephone between July and September of 2015, then again in January 2018 to inquire about ophthalmologic follow-up. Electronic medical records were reviewed from January 2001 through January 2018. RESULTS: Sixty percent of patients demonstrated ocular sequelae, including astigmatism (33%), visual axis obstruction (29%), nasolacrimal duct obstruction (7%), ptosis (4%), amblyopia (3%), and strabismus (1%). Compared with superficial IH, deep and mixed IH had higher odds, 3.4 (P = 0.025) and 3.8 (P = 0.034), respectively, of developing ocular sequelae. All patients with astigmatism prior to involution of IH received systemic therapy, with a significant post-treatment decrease in the proportion of patients with astigmatism (40% to 18%, P = 0.027). Three-quarters of patients experienced complete IH involution by time of enrollment in kindergarten. Fifty-one (57.3%) patients received formal ophthalmologic evaluation confirmed through chart review or phone interview, with average follow-up duration of 51.2 months (range: 1.9, 99.3). CONCLUSION: Deep and mixed IH were more likely to demonstrate ocular complications than superficial IH. Rate of astigmatism decreased with systemic therapy. Our study suggests that patients with periocular IH have a lower rate of amblyopia now compared with the prepropranolol era and emphasizes the importance of early treatment of periocular IH to prevent permanent visual sequelae.

Chronological Aging in African-American Skin: A Reliable Photonumeric Scale Demonstrates Age and Body Mass Index as Contributing Factors.

BACKGROUND: Increased photoprotection by natural melanin allows for African-Americans to be less impacted by photoaging than Caucasians. However, less is known about chronological aging in this population. OBJECTIVE: To create a photonumeric scale for African-Americans to evaluate chronological skin aging and to explore contributing elements to intrinsic aging. METHODS: Standardized photographs of the upper inner arm were taken from 75 African-American participants. Five participants were chosen as standards to create a 9-point photonumeric scale (0 = none, 8 = most severe). The scale was utilized by three blinded dermatologists to independently rate participants' photographs. RESULTS: The interrater agreements were 0.768 (95% CI: 0.671-0.834) for trial 1 and 0.725 (0.608-0.794) for trial 2. The intrarater agreements were 0.757 (0.596-0.875), 0.850 (0.771-0.903), and 0.790 (0.686-0.855) for the three raters. Averaged chronological aging scores were correlated with participants' survey responses, which revealed age as a significant predictor (r = 0.72, p < 0.001). LIMITATION: Our study was limited by the sample size, although the number of study participants was similar on a investigation in Caucasians. CONCLUSION: This study created the first reliable photonumeric scale for chronologic skin aging in African-Americans and found increased age and greater BMI as contributors to intrinsic skin aging phenotype in this population.

Effect of Age, Gender, and Sun Exposure on Ethnic Skin Photoaging: Evidence Gathered Using a New Photonumeric Scale.

BACKGROUND: African-Americans are less affected by photoaging than lighter skin individuals. Although scales for photoaging have been developed for Caucasians and Asians, no scale exists for African-Americans. AIM: To develop a photonumeric scale for photoaging and to determine factors that contribute to photoaging in African-Americans. METHODS: Five participants' photographs were selected as standards to create a 9-point photonumeric scale (0 = none, 8 = most severe). Three blinded dermatologists used the scale to grade the remaining participants' photographs. RESULTS: Interrater reliabilities were 0.775 (95% CI: 0.635, 0.880) for trial 1 and 0.832 (0.747, 0.883) for trial 2. Intrarater reliabilities, assessed over a 1 week interval, were 0.863 (0.727, 0.940), 0.928 (0.890, 0.954), and 0.866 (0.739, 0.935) for the three graders, indicating strong agreement. Photoaging scores were then correlated with participants' survey on lifestyle factors, which yielded age as a significant predictor (r = 0.91, p < 0.001). Furthermore, multiple regression model to predict facial photoaging (adjusted R2 = 0.849) selected age (b1 = 0.111, p < 0.001), sun exposure (b2 = 0.206, p = 0.014), and gender (b2 = -0.388, p = 0.063) as the most important variables. CONCLUSIONS: A reliable photonumeric scale for photoaging in African Americans was developed. Age, sun exposure, and male gender were found to be contributory factors to photoaging.

Retrospective Study of Nasal Infantile Hemangiomas: Characteristics, Complications, and Outcomes.

BACKGROUND/OBJECTIVES: Nasal infantile hemangiomas (IHs) pose serious medical complications and psychosocial stress if tumor involution is incomplete or prolonged. The objective was to determine which IH characteristics are associated with complications and are predictive of outcome, assessed as the presence of IHs or residual skin changes upon kindergarten entry, to better manage these lesions and counsel families. METHODS: A retrospective chart review of all patients seen in the Division of Pediatric Dermatology at Johns Hopkins Medicine between 2001 and 2014 for nasal IHs (N = 89) was performed. A follow-up telephone interview with parents was conducted in June and July 2014. RESULTS: Complications were observed in 39% of patients. Segmental and indeterminate IHs were more likely to have complications than focal IHs (p = 0.01). Mixed IHs were more likely to ulcerate than deep or superficial IHs (p = 0.01). Eighty percent of patients had treatment and 19% had surgery. Although IHs regressed by kindergarten entry in 70% of patients, 78% of these patients had residual skin changes. Mixed and superficial IHs left more residua than deep IHs (p = 0.04). A statistical comparison of treatments with respect to outcome at kindergarten entry could not be made because subgroups were too small and heterogeneous. CONCLUSION: Nasal IHs had higher rates of complications and treatment than previous reports of IHs at all body sites. Lesions of segmental and indeterminate type and mixed depth should be identified as high risk and treated accordingly. Parents may be counseled that most nasal IHs involute by kindergarten but leave residua and that early referral for treatment may be important for the best outcome.

Rosacea is associated with chronic systemic diseases in a skin severity-dependent manner: results of a case-control study.

BACKGROUND: Rosacea is a common chronic inflammatory dermatosis of unclear origin. It has been associated with systemic comorbidities, but methodical studies addressing this association are lacking. OBJECTIVE: We evaluated: (1) the association between rosacea and systemic comorbidities; and (2) if the severity of rosacea is impacted by comorbidities. METHODS: This was a case-control study: patients with rosacea were matched (1:1) to rosacea-free control subjects by age, sex, and race. Relative risk estimates were calculated using logistic regression as odds ratios with 95% confidence intervals. RESULTS: Among 130 participants (65 patients/65 control subjects), we observed a significant association between rosacea and allergies (airborne, food), respiratory diseases, gastroesophageal reflux disease, other gastrointestinal diseases, hypertension, metabolic and urogenital diseases, and female hormone imbalance. Compared with mild rosacea, moderate to severe rosacea was significantly associated with hyperlipidemia, hypertension, metabolic diseases, cardiovascular diseases, and gastroesophageal reflux disease. LIMITATIONS: This was a case-control study with moderate sample size. Associated medical conditions were self-reported and could not always be confirmed by medication use and medical records. CONCLUSIONS: Rosacea is associated with numerous systemic comorbid diseases in a skin severity-dependent manner. Physicians should be aware of these associations to provide comprehensive care to patients with rosacea, especially to those with more severe disease.

Molluscum contagiosum: to treat or not to treat? Experience with 170 children in an outpatient clinic setting in the northeastern United States.

Despite the high prevalence of molluscum contagiosum (MC) in children, epidemiologic data on this common self-limited viral infection is limited. In this report we review our experience with the demographic characteristics, clinical characteristics, management, and time to resolution of MC in 170 children. A retrospective medical chart review and telephone survey were conducted on children younger than 16 years of age evaluated for MC in the Division of Pediatric Dermatology at the Johns Hopkins Children's Center, Baltimore, Maryland, from January 1, 2008, to December 31, 2011. Of 170 children with MC, 51.8% were female and 77.1% were Caucasian. The median age at diagnosis was 5 years and 46.5% had a history of atopic dermatitis (AD). Children with AD had significantly more MC lesions than those without (p < 0.05); 72.9% of children did not receive any treatment. MC lesions completely cleared within 12 months in 45.6% of treated and 48.4% of untreated children and within 18 months in 69.5% of treated and 72.6% of untreated children. Treatment (if any), sex, race, diagnosing physician, number of lesions at diagnosis, number of anatomic locations, or history of AD did not predict time to resolution of MC lesions. MC lesions completely resolved in approximately 50% of children within 12 months and in 70% within 18 months. Treatment did not shorten the time to resolution.

Children with Warts: A Retrospective Study in an Outpatient Setting.

BACKGROUND: The purpose is to investigate the demographics and course of common warts in children in an outpatient setting. METHODS: A retrospective medical chart review and telephone survey study were completed on an outpatient cohort of children (0-17 yrs) with a clinical diagnosis of warts at a single-center, university-based pediatric dermatology practice. The main outcome measures included management, time to resolution, and associated factors of warts in children. RESULTS: Of the 254 patients we contacted, 214 agreed to participate in the survey. The most commonly involved sites were the hands and the head and neck area. Most children received some form of therapy, but it is unclear that any form of treatment altered the course. However, children with a medical history of childhood infections or more than one anatomic site had significantly greater risk of having a longer time to resolution. CONCLUSION: Warts resolved in 65% of children by 2 years and in 80% within 4 years, regardless of treatment. With the exception of a history of childhood infections and having more than one anatomic site, time to resolution was not altered by wart or patient characteristics. Thus counseling without aggressive destructive treatment is a reasonable approach to managing warts in most children. Our findings will provide guidance in the process of shared decision making with parents and children.

Minocycline and Its Impact on Microbial Dysbiosis in the Skin and Gastrointestinal Tract of Acne Patients.

BACKGROUND: Associations between acne and gastrointestinal comorbidities suggest that microbial dysbiosis and intestinal permeability may promote inflammatory acne, a condition often managed with oral antibiotics. OBJECTIVE: We performed a case-control study to investigate the skin and gut microbiota in 8 acne patients before and after receiving oral minocycline compared to controls matched by age ±5 years, sex, and race. METHODS: DNA was extracted from stool samples and facial skin swabs. Sequencing of the V3V4 region of the bacterial 16S rRNA gene was performed using Illumina MiSeq and analyzed using QIIME/MetaStats 2.0 software. RESULTS: Acne patients included 7 female and 1 male, ages 20~32. Shannon diversity was not significantly different between the skin (p=0.153) or gut (p<0.999) microbiota of acne patients before and after antibiotics. The gut microbiota in pre-antibiotic acne patients compared to acne-free controls was depleted in probiotics Lactobacillus iners (p=0.001), Lactobacillus zeae (p=0.001), and Bifidobacterium animalis (p=0.026). After antibiotics, the gut microbiota of acne patients was depleted in Lactobacillus salivarius (p=0.001), Bifidobacterium adolescentis (p=0.002), Bifidobacterium pseudolongum (p=0.010), and Bifidobacterium breve (p=0.042), while the skin microbiota was enriched in probiotics Bifidobacterium longum (p=0.028) and Leuconostoc mesenteroides (p=0.029) and depleted in Staphylococcus epidermidis (p=0.009) and Prevotella nigrescens (p=0.028). At the phylum level, significant enrichment of Bacteroidetes in stool of acne patients following antibiotic treatment (p=0.033) led to a decreased Firmicutes to Bacteroidetes ratio. CONCLUSION: Minocycline produces significant derangements in the microbiota of the skin and gut, including many probiotic species, highlighting the potential for more targeted antimicrobial treatments for acne.

Characterization and Analysis of the Skin Microbiota in Rosacea: A Case-Control Study.

BACKGROUND: The efficacy of antibiotics in rosacea treatment suggests a role for microorganisms in its pathophysiology. Growing concern over the adverse effects of antibiotic use presents a need for targeted antimicrobial treatment in rosacea. OBJECTIVE: We performed a case-control study to investigate the skin microbiota in patients with rosacea compared to controls matched by age, sex, and race. METHODS: Nineteen participants with rosacea, erythematotelangiectatic, papulopustular, or both, were matched to 19 rosacea-free controls. DNA was extracted from skin swabs of the nose and bilateral cheeks of participants. Sequencing of the V3V4 region of the bacterial 16S ribosomal RNA gene was performed using Illumina MiSeq and analyzed using QIIME/MetaStats 2.0 software. RESULTS: Compared with controls, skin microbiota in erythematotelangiectatic rosacea was depleted in Roseomonas mucosa (p = 0.004). Papulopustular rosacea was enriched in Campylobacter ureolyticus (p = 0.001), Corynebacterium kroppenstedtii (p = 0.008), and the oral flora Prevotella intermedia (p = 0.001). The highest relative abundance of C. kroppenstedtii was observed in patients with both erythematotelangiectatic and papulopustular rosacea (19.2%), followed by papulopustular (5.06%) and erythematotelangiectatic (1.21%) rosacea. C. kroppenstedtii was also associated with more extensive disease, with the highest relative abundance in rosacea affecting both the cheeks and nose (2.82%), followed by rosacea sparing the nose (1.93%), and controls (0.19%). CONCLUSIONS: The skin microbiota in individuals with rosacea displays changes from that of healthy skin, suggesting that further studies examining a potential role for the skin microbiota in the pathophysiology of rosacea may be warranted.

Body mass index may predict the response to ipilimumab in metastatic melanoma: An observational multi-centre study.

INTRODUCTION: Immunotherapy is a well-established treatment option in patients with metastatic melanoma. However, biomarkers that can be used to predict a response in these patients have not yet been found, putting patients at risk of severe side effects. METHODS: In this retrospective analysis, we investigated the association between the body mass index and ipilimumab treatment response in patients with metastatic melanoma. Patients with metastatic melanoma who received a monotherapy of up to 4 doses of ipilimumab (3 mg/kg) every 3 weeks from 2011 to 2014 in three major hospitals in Austria were included. Patients were classified into two groups: normal group (BMI<25) and overweight group (BMI≥25). RESULTS: 40 patients had a normal BMI, and 36 had a BMI above normal. Patients with a BMI that was above normal showed significantly higher response rates (p = 0.024, χ2), and lower likelihood of brain metastases (p = 0.012, χ2). No differences were found between both groups with respect to gender (p = 0.324, χ2), T-stage (p = 0.197, χ2), or the occurrence of side effects (p = 0.646, χ2). Patients with a BMI above normal showed a trend towards longer overall survival (p = 0.056, Log-Rank), but no difference was found regarding progression-free survival (p = 0.924, Log-Rank). CONCLUSIONS: The BMI correlated with the response to ipilimumab treatment in a cohort of metastatic melanoma patients.

Rosacea: Epidemiology, pathogenesis, and treatment.

Rosacea is a chronic relapsing inflammatory skin disease with a high prevalence among adults of Northern European heritage with fair skin. Symptoms present in various combinations and severity, often fluctuating between periods of exacerbation and remission. Based on morphological characteristics, rosacea is generally classified into four major subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Diverse environmental and endogenous factors have been shown to stimulate an augmented innate immune response and neurovascular dysregulation; however, rosacea's exact pathogenesis is still unclear. An evidence-based approach is essential in delineating differences between the many available treatments. Because of the diverse presentations of rosacea, approaches to treatment must be individualized based on the disease severity, quality-of-life implications, comorbidities, trigger factors, and the patient's commitment to therapy.