Current and future treatments of alopecia areata and trichotillomania in children.

INTRODUCTION: Treatment options for hair disorders are generally very limited. These options are even more limited in children due to the lack of trials and clinical research. Moreover, physicians are sometimes scared to treat children with drugs without safety data, especially because most hair disorders are benign. AREAS COVERED: The objective of this paper is to review current and future treatments for alopecia areata and trichotillomania, two disorders that are sometimes encountered in differential diagnosis or even occur together and probably affect the mental condition of the patient involved more than others. EXPERT OPINION: Hair disorders are very stressful in paediatric population. Both physicians and families are often unsatisfied leading to non-compliance. New drugs with less side- effects are needed to increase the percentage of cure. It is also crucial to refine genetic studies on alopecia areata in order to identify new potential drugs worth studying. Moreover, studies on trichotillomania should not be evaluated only by psychiatrics, but also by dermatologists.

Mastocytosis: a comprehensive insight.

Mastocytosis refers to a heterogeneous group of clinical disorders characterized by an abnormal accumulation of mast cells (MCs) in various tissues. The skin is the organ most frequently involved, but all organs may be affected. The clinical signs and symptoms are produced by the functional effects of mast cell-derived mediators and the anatomical distribution of the mast cells. The 2008 WHO-classification defines 7 categories of mastocytosis. Skin disease, with or without systemic involvement, is by far the most common form of childhood mastocytosis. Measurement of serum tryptase is important in the diagnostic algorithm of pediatric mastocytosis. In children with tryptase <20 ng/mL, the diagnosis of cutaneous mastocytosis (CM) may be decided upon without bone marrow examination (BME), unless other signs of SM are present. If the baseline tryptase level exceeds 100 ng/mL, a BME should be considered regardless of age. If the serum tryptase is 20-100 ng/mL in children without other signs of SM, the provisional diagnosis "mastocytosis in the skin" (MIS) can be established and monitored until puberty. If MIS remains present after puberty, a BME should be performed. In adult-onset mastocytosis a complete staging and application of the systemic mastocytosis criteria should always be performed. Treatment is mainly directed at alleviation of symptoms. As c-kit mutations prove to be very important in the pathogenesis of mastocytosis, targeted therapies using kit inhibitors may evolve as important future therapeutic options.

EAACI position paper for practical patch testing in allergic contact dermatitis in children.

INTRODUCTION: Allergic contact dermatitis (ACD) in children appears to be on the increase, and contact sensitization may already begin in infancy. The diagnosis of contact dermatitis requires a careful evaluation of a patient's clinical history, physical examination, and skin testing. Patch testing is the gold standard diagnostic test. METHODS: Based on consensus, the EAACI Task Force on Allergic Contact Dermatitis in Children produced this document to provide details on clinical aspects, the standardization of patch test methodology, and suggestions for future research in the field. RESULTS: We provide a baseline list of test allergens to be tested in children with suspected ACD. Additional tests should be performed only on specific indications.

Scoring the therapeutic effects of oral propranolol for infantile hemangioma: A prospective study comparing the Hemangioma Activity Score (HAS) with the Hemangioma Severity Scale (HSS).

BACKGROUND: Validated and reliable instruments to measure disease severity are needed to substantiate the benefit of therapies for infantile hemangioma. Two purpose-made systems have been described: the Hemangioma Activity Score (HAS) and the Hemangioma Severity Scale (HSS). OBJECTIVE: We sought to compare the HAS with the HSS in terms of ease of use, accuracy, and outcome in infants treated with oral propranolol. METHODS: A prospective study of 54 infants with infantile hemangioma was conducted from October 2009 to December 2012. Propranolol was initiated at 0.5 mg/kg/d and increased to 2 mg/kg/d on day 3. The HAS and the HSS were applied independently by 2 observers. RESULTS: Intraclass correlation coefficients of the HAS and HSS between the observers was comparable but HSS scores often remained the same upon improvement of the infantile hemangioma and therefore did not reflect disease severity. HAS decreased over time, with a dramatic drop in the first week reflecting an immediate therapeutic response. LIMITATIONS: This is a single-institution study and there may have been some selection bias in the patients who were referred for treatment. CONCLUSIONS: This study suggests that the HAS is preferable to the HSS in evaluating infantile hemangioma response to treatment.

Treatment of infantile haemangiomas: recommendations of a European expert group.

UNLABELLED: With a prevalence of 2.6-4.5 %, infantile haemangiomas (IH) represent the most common tumour of infancy. While the majority of IH does not require therapy and regresses spontaneously, about 10 % of IH exhibit complications such as obstruction, ulceration or disfigurement. With the advent of oral propranolol, many conventional treatment options have become obsolete. This paper summarizes current recommendations for management of complicated IH. These recommendations have been written by an expert group after a consensus process including bibliographic review, several drafts of synthesis, meetings with quantitative voting system and redaction of an approved final manuscript. CONCLUSION: Oral propranolol is the first-line agent for the treatment of complicated IH. WHAT IS KNOWN: • Infantile haemangiomas (IH) are the most common tumours of infancy. Within a very short period after its discovery and long before the publication of randomized controlled trials, propranolol has become the number one agent for the treatment of complicated IH. What is New: • We report IH treatment recommendations of an international, interdisciplinary team of experts, based on an up-to-date review of the literature.

Recent developments in the management of common childhood skin infections.

A literature review and clinical commentary on diagnosis and treatment of common childhood bacterial, fungal and viral skin infections is presented including impetigo, folliculitis, staphylococcal scalded skin syndrome, tinea capitis, warts and molluscum contagiosum.

Correlation between Objective SCORAD and Three-Item Severity Score used by physicians and Objective PO-SCORAD used by parents/patients in children with atopic dermatitis.

BACKGROUND: A self-assessment rating scale (SAS) is a good tool to assess the fluctuating disease severity and quality of life (QoL) in children with atopic dermatitis (AD). The European Task Force on Atopic Dermatitis created an SAS based on the Scoring Atopic Dermatitis (SCORAD) index, called the Patient-Oriented SCORAD (PO-SCORAD). OBJECTIVE: The aim of our study was to measure the correlation between alternative systems such as the OBJECTIVE SCORAD, the Three-Item Severity (TIS) score and the OBJECTIVE PO-SCORAD. We also investigated the correlations between the objective severity assessments and QoL. METHODS: In a specialized outpatient clinic, an observational prospective study was performed with children ≤16 years with AD. RESULTS: Seventy-five children were included. A good and significant correlation was shown between OBJECTIVE SCORAD and OBJECTIVE PO-SCORAD: Spearman's ρ correlation (rs) = 0.63 (p < 0.001). The correlation with QoL was moderate, but still significant (rs = 0.41-0.61, p < 0.001). CONCLUSION: The OBJECTIVE PO-SCORAD can be used for the evaluation of fluctuating AD and correlates significantly with the OBJECTIVE SCORAD and the less time-consuming TIS score.

Pimecrolimus in atopic dermatitis: consensus on safety and the need to allow use in infants.

Atopic dermatitis (AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long-term management with anti-inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti-inflammatory treatment of AD. Pimecrolimus 1% is approved for second-line use in children (≥2 yr old) and adults with mild-to-moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long-term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short- and long-term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long-term intermittent use. Unlike topical corticosteroids, long-term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post-marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered.

Trichotillomania in Children.

BACKGROUND: Trichotillomania is an often underdiagnosed condition. Little is known about trichotillomania in childhood. We aimed to analyze the characteristics of children with trichotillomania to increase information on this condition. METHODS: A retrospective study of an electronic database was performed in a tertiary children's hospital. Information from patients with trichotillomania was systematically classified under the categories 'who', 'what', 'when', 'where', 'why', and 'how'. RESULTS: A total of 33 patients had a diagnosis of trichotillomania (28 females, 5 males; peak age between 3 and 4 years). Scalp involvement was most common and nail biting was observed in 5 patients. Only 51.5% of patients had parents who noticed their child's hairpulling. Hair on or under the bed was the most common clue suggesting that hairpulling occurred. Triggering factors identified in 16 children included physical appearance, family-related issues, school-related issues, and concurrent illness. The noninvasive hair pull test was negative in all children. There was a high non-follow-up rate, and treatment outcomes varied. CONCLUSION: A set of 6 specific questions, based on the '5Ws and 1H' principle, facilitates the gathering of important information on children with unexplained nonscarring hair loss and helps clinicians be cognizant of possible outcomes of trichotillomania. This will be especially useful to clinicians who are not familiar with this elusive condition.

Educational paper: Pathogenesis of infantile haemangioma, an update 2014 (part I).

UNLABELLED: Infantile haemangioma (IH) is the most frequent childhood tumour. Although it is benign and self-limiting, severe complications can arise due to localisation and fast tumour growth. Management and therapy of IH has changed greatly after 2008 with propranolol. However, the pathogenesis remains elusive. This update provides an overview of all possible mechanisms currently considered. We discuss the possibility that several mechanisms act together, although local hypoxia seems to be important. Clinically, in about half of the cases, an IH is preceded by an anaemic macula (local ischaemia) or a so-called precursor lesion. Laboratory findings indicate stabilisation and an increased transcription activity of hypoxia-inducible factor 1 alpha (HIF1α), leading to up-regulation of its downstream target genes (such as vascular endothelial growth factor (VEGF)), which normally occurs in cases of hypoxia. CONCLUSION: Three main hypotheses have been proposed, namely (1) the theory of tissue hypoxia, (2) the theory of embolization of placental endothelial cells and (3) the theory of increased angiogenic and vasculogenic activity.

Educational paper: therapy of infantile haemangioma--history and current state (part II).

UNLABELLED: Infantile haemangioma (IH) is the most frequent tumour of infancy. Although it is benign and self-limiting, severe complications can arise due to localisation and fast tumour growth. Also, IHs leave scars after regression in more than half of the cases. Management and therapy of IH have changed greatly after 2008. This update provides an overview of the older therapy options before 2008, which mainly consisted of the administration of corticosteroids, and discusses the modern management with new therapy options such as ß-blockers (both systemically and topically). CONCLUSION: ß-blockers are promising and are currently preferred above corticosteroids, but ß-blockers still do not give a definitive treatment.

A statistical model to predict the reduction of lichenification in atopic dermatitis.

Acute symptoms of atopic dermatitis (AD), such as erythema, oedema/papulations and excoriations, respond quickly to topical corticosteroid treatment. Conversely, lichenification is regarded as a troublesome non-acute symptom of chronic AD which can take months of treatment before any improvement is seen. However, very little data actually support this opinion. Here, we analyse lichenification scores in 3 multicentre, short-term studies of nearly similar design. Two of these studies were active comparator dosage trials administered with either fluticasone propionate cream or ointment once or twice daily, the third study was a placebo control. In each of these 4-weeks studies lichenification was measured weekly. For the evaluation of the lichenification score over time a random-coefficients regression model was used. In all active treatments lichenification significantly improved (p < 0.005) within one week. Improvement continued afterwards, with > 80% of patients scoring no, very mild or mild lichenification after 4 weeks. We developed a model in which the lichenification score drops off linearly with the square root of time. The resulting convexly shaped downward time trend of lichenification was significant during all treatments and was significantly stronger during active treatment than with placebo. Fluticasone propionate can improve moderate to severe lichenification in a relative short period of time.

The effectiveness of finasteride and dutasteride used for 3 years in women with androgenetic alopecia.

BACKGROUND: The effectiveness of finasteride and dutasteride in women with androgenetic alopecia has been the subject of debate. AIM: To evaluate the effectiveness of finasteride and dutasteride on hair loss in women with androgenetic alopecia over a period of 3 years. METHODS: From a database containing systematically retrieved data on 3500 women treated for androgenetic alopecia between 2002 and 2012 with finasteride 1.25 mg or dutasteride 0.15 mg, a random sample stratified for age and type of medication was taken to yield 30 women in two age categories: below and above 50 years, and for both medications. Hair thickness of the three thinnest hairs was measured from standardized microscopic images at three sites of the scalp at the start of the treatment and after 3 years of continuous medication intake. The macroscopic images were evaluated independently by three European dermatologists/hair experts. The diagnostic task was to identify the image displaying superior density of the hair. RESULTS: Both age categories showed a statistically significant increase in hair thickness from baseline over the 3-year period for finasteride and dutasteride (signed rank test, P=0.02). Hair thickness increase was observed in 49 (81.7%) women in the finasteride group and in 50 (83.3%) women in the dutasteride group. On average, the number of post-treatment images rated as displaying superior density was 124 (68.9%) in the finasteride group, and 118 (65.6%) in the dutasteride group. Dutasteride performed statistically significantly better than finasteride in the age category below 50 years at the central and vertex sites of the scalp. CONCLUSIONS: Finasteride 1.25 mg and dutasteride 0.15 mg given daily for 3 years effectively increased hair thickness and arrested further deterioration in women with androgenetic alopecia.

Evidence - based pharmacological treatment of atopic dermatitis: an expert opinion and new expectations.

Atopic dermatitis (AD) is one of the most common skin diseases with a complex multifactorial background. The clinical presentation, the aggravating factors and the complications vary according to the age of the patients. Most cases, approximately 60-80%, present for the 1(st) time before the age of 12 months. Adult-onset AD has been observed as a special variant. Pruritus is the worst sign of AD, which also often indicates an exacerbation and is considered to be the most annoying symptom of AD. Treatment is preferably started based on the severity of AD. In only 10% of the cases, AD is so severe that systemic treatment is necessary. Systemic treatment including topical wet-wrap treatment is indicated in the worst and recalcitrant cases of AD. Systemic treatment of AD is discussed with regards to the evidence-based efficacy and safety aspects. I prefer wet-wraps as a crisis intervention in severe childhood cases, whereas UV and systemic treatments are the choices in patients older than 10 years. Probiotics are not useful in the treatment. If they have any effect at all it may only be in food-allergic children with AD. Finally, anti-histamines are not effective against pruritus in AD. They are only effective against urticarial flares and in cases with food-allergy. This article consists of an expert opinion on evidence-based pharmacological treatment of AD, but it is not a systemic review.

The proactive wet-wrap method with diluted corticosteroids versus emollients in children with atopic dermatitis: a prospective, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Wet-wrap treatment (WWT) has been advocated as a relatively effective treatment in children with severe atopic dermatitis (AD). WWT often serves as crisis intervention for AD. OBJECTIVES: We sought to evaluate the use of WWT with diluted corticosteroids in comparison with emollient in children with severe AD during 4 weeks in a proactive schedule during which the frequency of corticosteroid applications was tapered. METHODS: A randomized, double-blind, placebo-controlled study was performed in children aged 6 months to 10 years with severe AD (objective SCORAD at least 40 ± 5), comparing WWT with diluted corticosteroids (1:3 mometasone furoate 0.1% ointment and for the face 1:19 mometasone furoate 0.1% ointment under a mask) with emollient (petrolatum 20% in cetomacrogol cream). The primary outcome was improvement of the objective SCORAD; secondary outcomes included Patient-Oriented Eczema Measure and quality-of-life index. RESULTS: WWT with diluted corticosteroids acted faster and was more efficacious than WWT with emollients. Best results were obtained in age groups 6 to 9 years and 0 to 3 years. The difference in efficacy evaluated by objective SCORAD was significant at all measuring points. This also applied to the quality-of-life index. LIMITATIONS: The study group was relatively small. CONCLUSIONS: WWT for severe AD is an effective therapy option for at least a period of 4 weeks.

Minoxidil 5% solution for topical treatment of loose anagen hair syndrome.

A 2-year-old girl with a diagnosis of loose anagen hair syndrome was treated with a tapering regime of minoxidil 5% solution over 28 months, resulting in quick, significant clinical improvement with no adverse effects.

Educational paper: neonatal skin lesions.

Although most skin lesions in neonates are transient or benign, they may also be the presenting symptom of a life-threatening disease such as herpes neonatorum. In the present review, we present a short overview of neonatal skin lesions and a practical table to guide the general paediatrician in the diagnosis and management of neonatal skin lesions. Recent reviews are cited for further reading.

Educational paper: parenting a child with a disfiguring condition-how (well) do parents adapt?

UNLABELLED: Studies indicate serious levels of stress among parents of children with a medical condition. Moreover, adaptation seems to be a specific challenge for parents of children with a disfiguring condition because of the visible nature of the condition. In the present overview, we performed a literature search in PubMed, Embase, and PsycINFO to identify both qualitative and quantitative studies concerning psychological distress among parents of children with a disfiguring condition. Two of the authors critically appraised the retrieved citations. A total of 1,459 publications were identified, of which 21 qualitative and 22 quantitative studies met our inclusion criteria. Most qualitative studies infer that the birth of a child with a disfiguring condition starts an adaptation process in which parents experience a range of negative emotions and have concerns related to the visible nature of the condition. The results of quantitative studies are mixed and contradictory, and together suggest that some, but not all parents of a child with a disfiguring condition experience stress. Methodological limitations of the quantitative studies and potential stressors are discussed, and recommendations for future research are made. CONCLUSION: The present overview neither shows that the existing literature is conclusive about the perceived strain among the parents of children with a disfiguring condition nor does it provide evidence for a relationship between visibility and parental strain.

Allergic contact dermatitis in children: which factors are relevant? (review of the literature).

Allergic contact dermatitis (ACD) in children is increasing. Sensitization to contact allergens can start in early infancy. The epidermal barrier is crucial for the development of sensitization and elicitation of ACD. Factors that may influence the onset of sensitization in children are atopic dermatitis, skin barrier defects and intense or repetitive contact with allergens. Topical treatment of ACD is associated with cutaneous sensitization, although the prevalence is not high. ACD because of haptens in shoes or shin guards should be considered in cases of persistent foot eruptions or sharply defined dermatitis on the lower legs. Clinical polymorphism of contact dermatitis to clothing may cause difficulties in diagnosing textile dermatitis. Toys are another potentially source of hapten exposure in children, especially from toy-cosmetic products such as perfumes, lipstick and eye shadow. The most frequent contact allergens in children are metals, fragrances, preservatives, neomycin, rubber chemicals and more recently also colourings. It is very important to remember that ACD in young children is not rare, and should always be considered when children with recalcitrant eczema are encountered. Children should be patch-tested with a selection of allergens having the highest proportion of positive, relevant patch test reactions. The allergen exposure pattern differs between age groups and adolescents may also be exposed to occupational allergens. The purpose of this review is to alert the paediatrician and dermatologist of the frequency of ACD in young children and of the importance of performing patch tests in every case of chronic recurrent or therapy-resistant eczema in children.