Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey.

BACKGROUND: Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. OBJECTIVES: The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. METHODS: Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. RESULTS: The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg(-1) per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg(-1) vs. 2 mg kg(-1) vs. > 2 mg kg(-1) , the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33-1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04-5·46, P = 0·04, Ptrend < 0·001. CONCLUSIONS: The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.

Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity.

BACKGROUND: Filaggrin, coded by FLG, is the main source of several major components of natural moisturizing factor (NMF) in the stratum corneum (SC), including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA). Loss-offunction mutations in FLG lead to reduced levels of filaggrin degradation products in the SC. It has recently been suggested that expression of filaggrin may additionally be influenced by the atopic inflammatory response. In this study, we investigated the levels of several breakdown products of filaggrin in the SC in healthy controls (CTRL) and patients with atopic dermatitis (AD) in relation to FLG null allele status. We examined the relationship between NMF (defined here as the sum of PCA and UCA) and AD severity. METHODS: The SC levels of filaggrin degradation products including PCA, UCA, histidine (HIS) and tyrosine were determined in 24 CTRL and 96 patients with moderate-to-severe AD. All subjects were screened for 11 FLG mutations relevant for the study population. RESULTS: The levels of PCA, UCA and HIS correlated with FLG genotype. Furthermore, these levels were higher in the CTRL when compared to AD patients with no FLG mutations. Multiple regression analysis showed that NMF levels were independently associated with FLG genotype and severity of disease. CONCLUSION: Decreased NMF is a global feature of moderate-to-severe AD; within AD, FLG genotype is the major determinant of NMF, with disease severity as a secondary modifier. NMF components are reliably determined by a noninvasive and relatively inexpensive tape stripping technique.

The role of filaggrin in the atopic diathesis.

Atopic dermatitis (AD) is an inflammatory disease characterized by pruritic skin lesions, immunodysregulation, disrupted epidermal barrier function and IgE-mediated sensitization to food and environmental allergens. Identification of the aetiology of AD has become increasingly a priority, as it is clear that the disease burden exceeds AD alone, with many children suffering severe, multi-system and occasionally life-threatening allergic disease. Previous approaches to understanding AD have centred on mechanisms in the adaptive immune system, often with an emphasis on the Th1-Th2 paradigm. Recently, the conceptual focus has increasingly shifted to include a primary defect in the epithelial barrier as a threshold event in moderate-to-severe AD. Familial aggregation of the disease is well established through many family studies of AD, asthma and allergic rhinitis, suggesting a significant heritable component. The identification of loss-of-function mutations in the filaggrin (FLG) gene, whose product is a key structural protein in the outermost layer of the epidermis in up to 50% of patients with AD, provides a significant insight into explaining disease initiation and points to a complex secondary interplay of environmental and immunological sequelae once barrier disruption is established. The elucidation of the environmental, genetic and immunobiological modifiers of this structural molecule may also direct our understanding of the pathomechanisms and endotypes central to the atopic diathesis. The recent identification of a murine model for FLG-AD, with the detection of a homozygous frame-shift mutation in the Flg gene in flaky-tail (ft/ft) mice, stands to rapidly accelerate our understanding of mechanisms and therapeutic intervention points in AD. Refining the molecular understanding of AD and its subtypes will allow for specific diagnostic, treatment and ultimately, preventative algorithms, and has opened an exciting new world of investigative challenges and collaborations.

Juvenile folliculotropic and ichthyosiform mycosis fungoides.

Ichthyosiform mycosis fungoides (MF) is a recently recognized clinical variant of MF, which appears as dry scaling patches and plaques, or as a generalized eruption. Acquired ichthyosis is well recognized as a paraneoplastic cutaneous presentation of malignancy, especially in lymphoproliferative disorders. In contrast, the ichthyosiform eruption in ichthyotic MF is attributable to infiltration of the skin by tumour cells. We report the case of a 15-year-old boy who presented with a 5-year history of enlarging pruritic plaques on the forehead and back, patchy alopecia and generalized ichthyosis. Histology of the forehead and back showed a dense, lymphocytic, folliculocentric and perivascular infiltrate of predominantly CD4-positive T cells consistent with folliculotropic MF. Histological examination of biopsies from ichthyotic skin found similar features. Our patient had a histological diagnosis at the age of 15 years, making him the youngest reported patient with either folliculotropic MF or ichthyotic MF.

Sweet's syndrome in association with common variable immunodeficiency.

Sweet's syndrome (SS), a rare reactive neutrophilic dermatosis, has been reported to occur in association with a variety of systemic disorders, categorized by von den Diesch into idiopathic, paraneoplastic, pregnancy and parainflammatory subgroups. The parainflammatory group has been well defined, and includes a wide spectrum of infectious triggers and disorders of immune dysregulation. To date, however, no cases of SS have been described in the context of common variable immunodeficiency (CVID). We report a case of paediatric-onset SS, previously reported as idiopathic, with a subsequent diagnosis of CVID.

Juvenile localised scleroderma: a retrospective review of response to systemic treatment.

BACKGROUND: Juvenile localised scleroderma (JLS) is a rare connective tissue disorder in childhood. Most lesions are benign and self-limiting, but some progress to cause functional disabilities and cosmetic disfigurement. These lesions require systemic treatment, the mainstay of which is corticosteroids and methotrexate. AIM: To report the experience of the use of systemic treatment in children with JLS in our department. METHODS: We performed a retrospective chart review looking at the patients who received systemic treatment over 14 years and recorded their outcomes. RESULTS: Ten children with aggressive JLS were treated with systemic immunosuppressive therapy. There was an 80% response to treatment. Three of the responders relapsed off treatment, but responded to a further course of therapy. Mean disease duration at diagnosis was 8 months. Treatment was generally well tolerated with few side effects. CONCLUSION: Early recognition of aggressive localised scleroderma and appropriate referral is imperative for a good outcome.

Management of vascular birthmarks: review of a multidisciplinary clinic.

Vascular birthmarks comprise a diverse group of congenital lesions and represent a significant cosmetic and functional burden for patients. They remain a diagnostic and management challenge for physicians due to their extremely variable clinical presentation and often complex anatomical associations. As each type of vascular lesion has a treatment program individual to it, optimal functional and cosmetic outcomes require accurate diagnosis. Primary physicians readily diagnose and manage uncomplicated lesions, such as isolated haemangiomas and innocuous capillary malformations. However, given the complexity and relative rarity of many other vascular birthmarks, specialised multidisciplinary clinics are central to their management. In this review, we present our experience regarding the diagnostic range of vascular anomalies, associated symptomatology, and management of patients with vascular birthmarks attending the multidisciplinary Joint Vascular Birthmark Clinic at Our Lady's Children's Hospital, Crumlin. Vascular tumours represented 57% of cases reviewed, malformations accounting for 43%. Of patients not previously seen at the JVBC or by any of the individual consultants, the initial or referring diagnosis was incorrect in 42%. Significantly, 62% of vascular malformations were assigned an incorrect diagnosis, highlighting the need for a specialised clinic.

'Peeling paint' dermatitis as a presenting sign of cystic fibrosis.

Presentation of cystic fibrosis with a rash is rare, with only 19 previously reported cases. This unusual presentation is associated with false negative sweat tests, delays in diagnosis and considerable mortality. Multiple nutritional deficiencies, the aberrant production of prostaglandins and free-radical mediated damage have been implicated in the pathogenesis of this kwashiorkor-like dermatitis. In spite of the rarity of this presentation, recognition of the rash is important, not only to expedite the diagnosis, but also to gain insight into the disease. We present a further case to highlight this unusual presentation and discuss potential pathophysiological mechanisms.

Construction of an ordered overlapping library of bacteriophage P1 DNA in phage vector lambda D69.

A library of bacteriophage P1 DNA was constructed in the phage vector lambda D69. The DNA of some 150 randomly chosen lambda-P1 hybrid phages containing P1 DNA fragments 5-10 kb in size was analyzed by restriction endonuclease digestion using enzymes EcoRI, BglII, and BamHI that cleave P1 DNA at known positions on the physical map of P1. Approximately one third of the phages contained P1 DNA inserts having two or more restriction sites for any one of these enzymes, thus allowing the location of the insert to be determined with respect to the physical map. Genetic tests allowed detection of lambda-P1 hybrid phages possessing inserts with functional P1 ban and CmR genes. A subset of 18 phages was analyzed in more detail; their P1 DNA inserts comprise an ordered collection of overlapping P1 DNA fragments that cover almost 98% of the P1 genome.