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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Infantile hemangioma: treatment with short course systemic corticosteroid therapy as an alternative for propranolol.

Infantile hemangiomas (IHs) are increasingly being treated with propranolol or other beta-blockers, but before this therapeutic option was available, oral glucocorticosteroids (GCSs) were the criterion standard treatment and are still the alternative modality in problematic cases. Nevertheless, there is no standard treatment protocol for the dose and duration of GCSs. Long-term treatment with GCSs is associated with unwanted side effects such as growth suppression, behavioral changes, and reflux. Twenty-one children with troublesome IHs were treated according to an algorithm with 3 mg/kg/day of oral prednisolone divided three times per day with varying duration and number of GCS courses. Two blinded investigators independently interpreted therapy results using the Hemangioma Activity Score (HAS). Side effects were determined according to reports in patient charts and parental questionnaires. The median duration of a short course of GCSs was 2 weeks (range 1-6 weeks). The number of courses was 2 (range 1-5). The median cumulative dose was 91 mg/kg. Growth stabilized in all patients, with a good response (>50% reduction in HAS) in 62% and a favorable response (30-50% reduction is HAS) in 23%. Twelve of the 21 children (57%) had minor side effects. Persistent side effects did not occur. Intermittent short course, systemic, high-dose GCS therapy is an effective and safe treatment modality for IH, with a substantially lower cumulative dose of GCSs compared to prolonged therapy and no major side effects. This treatment is an alternative in cases in which propranolol fails or is contraindicated.

Wet-wrap treatment in children with atopic dermatitis: a practical guideline.

Treatment of children with severe atopic dermatitis (AD) can be especially challenging because several possible intervention treatments have (relative) contraindications in childhood. In recent years, wet-wrap treatment (WWT) has been advocated as a relatively safe and efficacious intervention in children with severe or refractory AD. The goal of this article is to provide a practical guideline as a starting point for clinicians who are interested in using WWT in their own clinical practice. We will address several practical issues surrounding the use of WWT by describing our own experiences, supplemented with data from the literature.

Evaluation of intra-lesional corticosteroids in the treatment of peri-ocular haemangioma of infancy: still an alternative besides propranolol.

PURPOSE: Haemangioma of infancy (HOI) is the most frequently occurring benign tumour of infancy. Alarming HOI require treatment. Current therapy is empirically based; corticosteroids are often administered but in recent publications propranolol was reported to be more effective. Peri-ocular HOI are highly sensitive to corticosteroids. Our goal was to evaluate the effectiveness of intra-lesional corticosteroids in the treatment of peri-ocular HOI. METHODS: We selected all patients with peri-ocular HOI who had only been treated with intra-lesional corticosteroids at our hospital from 1993 until 2009. Treatment was standardized according to a prospective protocol. RESULTS: A total of n = 34 patients were included. There were no complications at all after therapy. A second intra-lesional injection was necessary in five patients. At follow-up after 6 and 12 months after injection, 94 and 91% of the patients, respectively, had regression of the HOI. Astigmatism, Haemangioma Activity Score and global assessments all had improved after therapy. CONCLUSIONS: This study shows that intra-lesional therapy with corticosteroids is very safe in the treatment of peri-ocular HOI. It remains a good and safe alternative besides propranolol or when propranolol therapy is not possible (e.g. asthma, PHACE syndrome, and certain cardiac diseases).

Tumour necrosis factor (TNF)-blocking agents in juvenile psoriatic arthritis: are they effective?

OBJECTIVES: To evaluate the effectiveness of tumour necrosis factor (TNF) blockers in juvenile psoriatic arthritis (JPsA). METHODS: The study was a prospective ongoing multicentre, observational study of all Dutch juvenile idiopathic arthritis (JIA) patients using biologicals. The response of arthritis was assessed by American College of Rheumatology (ACR) paediatric response and Wallace inactive disease criteria. The response of psoriatic skin lesions was scored by a 5-point scale. RESULTS: Eighteen JPsA patients (72% female, median age onset 11.1 (range 3.3-14.6) years, 50% psoriatic skin lesions, 39% nail pitting, 22% dactylitis) were studied. The median follow-up time since starting anti-TNFα was 26 (range 3-62) months. Seventeen patients started on etanercept and one started on adalimumab. After 3 months of treatment 83% of the patients achieved ACR30 response, increasing to 100% after 15 months. Inactive disease reached in 67% after 39 months. There was no discontinuation because of inefficacy. Six patients discontinued treatment after a good clinical response. However, five patients flared and restarted treatment, all with a good response. During treatment four patients (two JPsA and two JIA patients with other subtypes) developed de novo psoriasis. In four of the nine patients the pre-existing psoriatic skin lesions improved. CONCLUSION: Anti-TNFα therapy in JPsA seems effective in treating arthritis. However, in most patients the arthritis flared up after treatment discontinuation, emphasising the need to investigate optimal therapy duration. The psoriatic skin lesions did not respond well and four patients developed de novo psoriasis.

Rhabdoid tumor mimicking hemangioma.

We report a young boy with a malignant tumor, which remained unrecognized for 8 months because it was assumed to be a hemangioma. The presentation of a rhabdoid tumor mimicking hemangioma is very rare. It was reported only on two earlier occasions. Rhabdoid tumors are one of the most aggressive types of malignancies encountered in pediatric oncology. It is important to recognize that a fast growing vascular lesion in a child will often be a hemangioma, but could also be an aggressive tumor.

Imatinib mesylate for children with dermatofibrosarcoma protuberans (DFSP).

Dermatofibrosarcoma protuberans (DFSP) is a rare malignant soft tissue tumor in children. DFSP is characterized by a specific fusion of the platelet-derived growth factor beta (PDGFbeta) with the collagen type 1alpha1 (COL1alpha1) gene which renders these tumors responsive to targeted therapy with tyrosine kinase inhibitors, such as imatinib mesylate, as is reported in adults. In the current report, we describe the first small pediatric DFSP series, in which response to imatinib mesylate contributed to successful treatment outcome.

Efficacy and safety of fluticasone propionate 0.005% ointment in the long-term maintenance treatment of children with atopic dermatitis: differences between boys and girls?

Treatment of atopic dermatitis (AD) in children tends to stabilize the condition in the short term. 'Maintenance' treatment options in children are limited. To assess the efficacy and safety of twice daily treatment with fluticasone propionate 0.005% (FP) ointment during 4 wk and the efficacy and safety of twice weekly maintenance treatment with FP in preventing exacerbations or remissions of AD during a 16 wk follow-up period. Ninety children (aged 4-10 yr) with moderate to severe AD were included in a randomized, multi-centre study and received FP ointment twice daily during the acute phase. Children whose AD was in remission after 4 wk of treatment, entered the maintenance phase. In addition to twice daily emollient, children were randomly allocated to receive FP or placebo ointment twice weekly on consecutive days. Efficacy was assessed by the objective SCORAD. Eighty-seven (97%) completed the 4-wk acute study period. Extensive remission was achieved in 78 (87%) children, and 75 children entered the maintenance phase. Intermittent treatment with FP resulted in less severe AD and significantly reduced risk of further relapse as compared with placebo. The risk of an exacerbation of AD was more than twice as high in the placebo group as in the FP group (hazard ratio 2.182, 95% CI). AD in girls was better controlled than in boys. This long-term study shows that the addition of twice weekly FP to standard maintenance therapy significantly reduces the risk of relapse in children with moderate severe AD.