Non-invasive intradermal imaging of cystine crystals in cystinosis.

IMPORTANCE: Development of noninvasive methodology to reproducibly measure tissue cystine crystal load to assess disease status and guide clinical care in cystinosis, an inherited lysosomal storage disorder characterized by widespread cystine crystal accumulation. OBJECTIVE: To develop an unbiased and semi-automated imaging methodology to quantify dermal cystine crystal accumulation in patients to correlate with disease status. DESIGN, SETTING AND PARTICIPANTS: 101 participants, 70 patients and 31 healthy controls, were enrolled at the University of California, San Diego, Cystinosis Clinics, Rady Children's Hospital, San Diego and at the annual Cystinosis Research Foundation family conference for an ongoing prospective longitudinal cohort study of cystinosis patients with potential yearly follow-up. EXPOSURES: Intradermal reflectance confocal microscopy (RCM) imaging, blood collection via standard venipuncture, medical record collection, and occasional skin punch biopsies. MAIN OUTCOMES AND MEASURES: The primary outcome was to establish an automated measure of normalized confocal crystal volume (nCCV) for each subject. Secondary analysis examined the association of nCCV with various clinical indicators to assess nCCV's possible predictive potential. RESULTS: Over 2 years, 57 patients diagnosed with cystinosis (median [range] age: 15.1 yrs [0.8, 54]; 41.4% female) were intradermally assessed by RCM to produce 84 image stacks. 27 healthy individuals (38.7 yrs [10, 85]; 53.1% female) were also imaged providing 37 control image stacks. Automated 2D crystal area quantification revealed that patients had significantly elevated crystal accumulation within the superficial dermis. 3D volumetric analysis of this region was significantly higher in patients compared to healthy controls (mean [SD]: 1934.0 µm3 [1169.1] for patients vs. 363.1 µm3 [194.3] for controls, P<0.001). Medical outcome data was collected from 43 patients with infantile cystinosis (media [range] age: 11 yrs [0.8, 54]; 51% female). nCCV was positively associated with hypothyroidism (OR = 19.68, 95% CI: [1.60, 242.46], P = 0.02) and stage of chronic kidney disease (slope estimate = 0.53, 95%CI: [0.05, 1.00], P = 0.03). CONCLUSIONS AND RELEVANCE: This study used non-invasive RCM imaging to develop an intradermal cystine crystal quantification method. Results showed that cystinosis patients had increased nCCV compared to healthy controls. Level of patient nCCV correlated with several clinical outcomes suggesting nCCV may be used as a potential new biomarker for cystinosis to monitor long-term disease control and medication compliance.

Idiopathic facial aseptic granuloma-A diagnostic challenge in pediatric dermatology.

Idiopathic facial aseptic granuloma is a distinct, benign lesion that presents in very young children and is characterized by a painless facial nodule that usually appears on the cheek. It is typically characterized by a prolonged course but heals spontaneously or in response to antibiotic treatment. The challenge is to diagnose this entity correctly, ideally based on clinical acumen, to avoid surgical intervention with facial sutures and the resultant scarring and unnecessary treatment interventions. In this article, we discuss three cases of idiopathic facial aseptic granuloma to raise awareness and highlight the diagnostic challenges and possible link to childhood rosacea.

Efficacy, Safety, and Tolerability of 4% 5-Fluorouracil Cream in a Novel Patented Aqueous Cream Containing Peanut Oil Once Daily Compared With 5% 5-Fluorouracil Cream Twice Daily: Meeting the Challenge in the Treatment of Actinic Keratosis.

BACKGROUND: Actinic keratosis (AK) is a neoplastic keratosis and a precursor of squamous cell carcinoma (SCC). OBJECTIVE: We are presenting data on a novel formulation of 4% 5-Fluorouracil (5-FU) in an aqueous vehicle cream containing peanut oil (Tolak) with once daily application versus treatment with 5% 5-FU twice daily for 4 weeks. METHODS: 1) A dose ranging study of 4% 5-FU cream once or twice daily for 2 or 4 weeks and its vehicle, compared to 5% 5-FU cream twice daily for 4 weeks in 121 subjects. 2) A double-blinded multicenter study involving 841 subjects for non-inferiority and safety of 4% 5-FU cream once daily vs 5% 5-FU cream twice daily over 4 weeks with 100% and 75% clinical clearance of AK's. RESULTS: 4% 5-FU qd q4wks achieved 100% clearance in 80% and 75% clearance in 100% of subjects vs 75% and 95% respectively with 5% 5-FU bid q4wks. 4% 5-FU qd2wks achieved 100% clearance in 60% and 75% clearance in 85% of subjects. 4% 5-FU qd q4wks recorded 65 adverse events and 30% application site skin irritation versus 71 events and 60% with 5% 5-FU bid q4wks. 4% 5-FU exceeded non-inferiority by 1.32% with sub-analysis for higher percentage of severely affected patients. 4% 5-FU showed 75% clearance of AK's in 80.5% vs 80.2% for 5% 5-FU with superior tolerability. CONCLUSIONS: 4% 5-FU cream is a novel, efficacious, superior tolerated once daily topical treatment for better compliance and treatment outcome. The peanut oil component is safe even in peanut-allergic patients.

J Drugs Dermatol. 2016;15(10):1218-1224.

The Harmonising Outcome Measures for Eczema (HOME) statement to assess clinical signs of atopic eczema in trials.

The lack of core outcome sets for atopic eczema (AE) is a major obstacle for advancing evidence-based treatment. The global Harmonising Outcome Measures for Eczema (HOME) initiative has already defined clinical signs, symptoms, quality of life, and long-term control of flares as core outcome domains for AE trials. This article deals with the standardization of measurement instruments to assess clinical signs of AE. To resolve the current lack of standardization of the assessment of clinical signs of AE, we followed a structured process of systematic reviews and international consensus sessions to identify 1 core outcome measurement instrument for assessment of clinical signs in all future AE trials. Systematic reviews indicated that from 16 different instruments identified to assess clinical signs of AE, only the Eczema Area and Severity Index (EASI) and the objective Scoring Atopic Dermatitis (SCORAD) index were identified as extensively validated. The EASI has adequate validity, responsiveness, internal consistency, and intraobserver reliability. The objective SCORAD index has adequate validity, responsiveness, and interobserver reliability but unclear intraobserver reliability to measure clinical signs of AE. In an international consensus study, patients, physicians, nurses, methodologists, and pharmaceutical industry representatives agreed that the EASI is the preferred core instrument to measure clinical signs in all future AE trials. All stakeholders involved in designing, reporting, and using clinical trials on AE are asked to comply with this consensus to enable better evidence-based decision making, clearer scientific communication, and improved patient care.

Natural ingredients in atopic dermatitis and other inflammatory skin disease.

Active naturals in dermatology have been experiencing a renaissance. Many of the naturals that have been known for centuries to be effective for various skin conditions have now been scientifically validated with the unraveling of the pathophysiology behind their medicinal mechanism. This article seeks to present data on the clinical use of key dermatological active naturals such as oatmeal, feverfew, chamomile, aloe vera, licorice, and dexpanthenol, as well as on recent multicenter and international clinical studies that support their efficacy and safety profile for a variety of inflammatory skin conditions.

Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting.

The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence-based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence-based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long-term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research.

Multiples in dermatology: markers for special considerations in diagnosis, therapy, and prognosis.

Multiples of certain cutaneous lesions should alert the clinician to a wider differential diagnosis and possible systemic associations although the individual skin lesion is often benign in nature and banal in appearance. This article focuses on such findings in selected multiple cutaneous lesions that may be classified according to the primary cutaneous feature as vascular, pigmentary, nevoid hamartomas, and tumors/neoplastic conditions. The clinical presentation of each entity and its significance, appropriate diagnostic evaluation, therapeutic and prognostic considerations and pertinent differential diagnoses will be reviewed.

Effective monitoring of isotretinoin safety in a pediatric dermatology population: a novel "patient symptom survey" approach.

BACKGROUND: Assessment of adverse effects in pediatric patients on oral isotretinoin has not been standardized and the exact incidence is unknown. OBJECTIVE: Our goal was to determine the usefulness of an isotretinoin symptom survey as a screening tool for assessment and quantification of adverse effects, including psychiatric symptoms, during isotretinoin treatment in a pediatric population of different age groups. METHODS: We performed a retrospective chart review on a random sample of patients treated with isotretinoin at a tertiary pediatric dermatology clinic where patients completed an isotretinoin symptom survey at each visit. Responses were stratified by age group and psychiatric history. RESULTS: The charts of 102 patients, representing 123 courses of isotretinoin and 760 treatment-months, were reviewed. A total of 722 (95.0%) symptom surveys were complete and 38 (5.0%) were incomplete/missing. Recorded side effects were similar to published adult data; dry lips/dry skin were reported in 94.25% and 72.13% of treatment-months of isotretinoin, respectively. Psychiatric symptoms were reported in 1.65%, with no statistical difference between patients with or without a mental health history. Patients aged 11 to 15 years had similar side-effect profiles to those aged 16 to 21 years. Impaired night vision, nosebleeds, and dry/bloodshot eyes were more common in the older age group. LIMITATIONS: This was a retrospective chart review, with known limitations. The study was performed at a tertiary referral center for pediatric dermatology, possibly allowing patient selection bias. CONCLUSIONS: The isotretinoin symptom survey appears to be an effective screening tool to standardize monitoring of isotretinoin side effects in the pediatric population.

Oral propranolol therapy for infantile hemangiomas beyond the proliferation phase: a multicenter retrospective study.

Pharmacological therapies for infantile hemangiomas were considered effective only during the proliferative phases. Recently reported beneficial effects of propranolol may extend beyond the proliferative phase of infantile hemangiomas. The purpose of the study was to assess the effect of oral propranolol therapy for infantile hemangiomas beyond the proliferative phase of these lesions. Members of the Society for Pediatric Dermatology were invited to participate in a multicenter retrospective study. Only children with infantile hemangiomas with documented cessation of lesions' growth or those older than 12 months of age were eligible for the study. Clinical and demographic information and digital photographs before, at the start, and following the treatment were collected. Scaled panels of photographs were distributed among preselected experienced pediatric dermatologists. Visual analog scale was used to assess photographs for each case. Paired t-test was used for statistical analyses. Data on 49 eligible patients from eight pediatric dermatology centers was collected. Seven cases were excluded because of insufficient photographic documentation. The age of the patients at the start of propranolol therapy ranged 7 to 120 months (mean 28 mos, median 22 mos). The duration of propranolol therapy ranged 1 to 8 months (mean 3.6 mos). The mean visual analog scale score before the treatment was 6.8 ± 2.15, and mean reduction in the visual analog scale score at the assessment was 2.6 ± 1.74 (p < 0.001). The rate of visual analog scale reduction was 0.4 per month before the start of the therapy, while this rate was accelerated to 0.9 per months following the therapy (p < 0.001). No significant side effects were reported. We conclude that propranolol is effective in infantile hemangiomas, including post-proliferative phase, and should be considered as the first-line therapy in that setting.

Calcineurin inhibitors in pediatric atopic dermatitis: a review of current evidence.

Atopic dermatitis (AD) is a common, chronic inflammatory dermatosis with a prevalence of 7-21% in school-aged children. Childhood AD has a profound impact on the social, personal, emotional, and financial perspectives of families. For the last half-century, topical corticosteroids of different potencies have been the mainstay of topical therapy. In recent years, two topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, have become available for the treatment of AD. Both tacrolimus and pimecrolimus have been extensively evaluated in the management of pediatric AD. Trials comparing them with placebo, topical corticosteroids, and each other have shown them to be effective and safe for continuous short-term use, and for noncontinuous use for up to 4 years. Long-term safety of TCIs is not known as they have been in clinical use for less than a decade.

Mechanism of action and clinical benefits of colloidal oatmeal for dermatologic practice.

Colloidal oatmeal has a long history of beneficial use in dermatology. It is a natural product that has an excellent safety record and has demonstrated efficacy for the treatment of atopic dermatitis, psoriasis, drug-induced rash and other conditions. In recent years, in vitro and in vivo studies have begun to elucidate the multiple mechanisms of action of naturally derived colloidal oatmeal. Evidence now describes its molecular mechanisms of anti-inflammatory and antihistaminic activity. The avenanthramides, a recently described component of whole oat grain, are responsible for many of these effects. Studies have demonstrated that avenanthramides can inhibit the activity of nuclear factor kappaB and the release of proinflammatory cytokines and histamine, well known key mechanisms in the pathophysiology of inflammatory dermatoses. Topical formulations of natural colloidal oatmeal should be considered an important component of therapy for atopic dermatitis and other conditions and may allow for reduced use of corticosteroids and calcineurin inhibitors.

A symptom scoring tool for identifying pediatric patients with eosinophilic esophagitis and correlating symptoms with inflammation.

BACKGROUND: Eosinophilic esophagitis (EE) is an increasingly recognized allergic disease entity that is difficult to distinguish clinically from other causes of esophagitis, especially gastroesophageal reflux disease (GERD). To our knowledge, there are no prospectively analyzed or validated symptom scoring tools for pediatric patients with EE and no prospective evaluation correlating symptoms with tissue inflammation. OBJECTIVES: To prospectively analyze a symptom scoring tool's ability to distinguish pediatric patients with EE from those with GERD and from control patients with and without allergies and to correlate symptoms with tissue inflammation. METHODS: A prospective study of a symptom scoring tool given to patients with EE (n = 35 not receiving EE targeted therapy), patients with GERD (n = 27 not undergoing acid suppression), allergic control patients (n = 24), and nonallergic control patients (n = 14) at an academic pediatric hospital. Histology and endoscopy scores were correlated with symptom complaints. RESULTS: The total symptom score was higher among patients with EE (mean, 6.51; 95% confidence interval [CI], 5.50-7.53) and GERD (mean, 5.44; 95% CI, 4.64-6.25) than in allergic (mean, 0.92; 95% CI, 0.28-1.55) and nonallergic (mean, 1.00; 95% CI, 0.40-1.60) patients (P < .001). Patients with EE and GERD complained of more nausea/vomiting, abdominal pain, heartburn/regurgitation, and nocturnal awakening than control groups (P < .001). Only dysphagia (mean, 0.9 [95% CI, 0.7-1.2] in EE patients vs 0.4 [95% CI, 0.2-0.7] in GERD patients) and anorexia/early satiety (mean, 1.4 [95% CI, 1.2-1.6] in EE patients vs 0.8 [95% CI, 0.5-1.1] in GERD patients) discriminate EE from GERD (P < .01). These symptoms also correlated with the severity of histologic and endoscopic findings (P < .05). CONCLUSION: Dysphagia and anorexia/early satiety identify pediatric patients with EE and correlate symptoms with tissue inflammation.

Fluocinolone acetonide 0.01% in peanut oil: safety and efficacy data in the treatment of childhood atopic dermatitis in infants as young as 3 months of age.

Fluocinolone acetonide 0.01% in a blend of refined peanut and mineral oils has been established as effective and safe treatment for atopic dermatitis in patients 2 years and older, including those with peanut sensitivity, for several years. We sought to study the safety of fluocinolone acetonide 0.01% oil and its potential for adrenal axis suppression in infants as young as 3 months of age. A controlled, open-label study was performed in children aged 3 months to 2 years with moderate to severe atopic dermatitis at two academic pediatric dermatology centers. Patients received topical fluocinolone acetonide 0.01% oil twice daily to affected areas involving a minimum of 20% body surface ratio for 4 weeks. Cortisol stimulation testing was performed at baseline and at the end of the treatment phase. Patients were monitored for medication use and adverse events. Efficacy was assessed using the Investigator Global Severity and Response scales. Thirty-two patients with moderate to severe atopic dermatitis were recruited into the study and 30 were evaluated with the Physician's Global Improvement Assessment tool. The mean body surface ratio treated for all age groups was 48%. Eighty-three percent of patients had marked or better improvement scores by week 2 and 96% by week 4, with 40% completely cleared. No adrenal suppression occurred in the 24 patients that met inclusion criteria for hypothalamus-pituitary axis (HPA) axis analysis. No relevant adverse events occurred. Results of this study support the safety and efficacy of fluocinolone acetonide 0.01% in refined peanut oil vehicle, for infants as young as 3 months of age with atopic dermatitis. No evidence of adrenal suppression or adverse local effects was demonstrated after 4 weeks of twice daily treatment.

Management of atopic dermatitis in the pediatric population.

Atopic dermatitis, one of the most common skin disorders in young children, has a prevalence of 10% to 20% in the first decade of life. It is a chronic illness that requires a multifaceted treatment strategy in the setting of limited therapeutic options. Balancing safety concerns with efficacious treatment is of particular importance in the pediatric population. Parents of patients with atopic dermatitis turn to their primary caregivers for guidance regarding this physically demanding and psychologically stressful condition. In addition to serving as a review of atopic dermatitis, this article delves into the state-of-the-art therapeutic options and includes a detailed review of the differences between topical corticosteroids and topical calcineurin inhibitors. We also discuss new treatment strategies that are being used by atopic dermatitis specialists, such as comprehensive "education-as-intervention" models, wet wraps, bleach baths, and systemic immunomodulatory therapies.

Topical therapy in pediatric atopic dermatitis.

With a prevalence of 10% to 20% in the first decade of life, atopic dermatitis (AD) is one of the most common skin disorders in young children. It is a chronic illness with limited therapeutic options. Topical anti-inflammatory agents remain at the core of medical management; however, their efficacy must be balanced with safety concerns, especially as they relate to the pediatric population. This article discusses the principles of topical AD therapy with a detailed review of the differences between topical corticosteroids and topical calcineurin inhibitors. It also includes specialized topical treatment strategies for AD, such as wet wraps and diluted bleach baths, and highlights the most common challenges to patient compliance in atopic dermatitis.

Safety of dermatologic drugs used in pregnant patients with psoriasis and other inflammatory skin diseases.

In patients with psoriasis, there is an increased availability of drugs for treatment. However, there are important questions about drug safety for mothers with psoriasis and their fetuses. Currently, there are limited safety data for many of the medications used. In this article, we review current pregnancy risk information for medications commonly used in the treatment of psoriasis. In addition, a list of teratology information resources is included to help practicing clinicians find up-to-date information regarding the safety of the medications they prescribe.