婴幼儿血管瘤(IH)是婴儿常见的胎记,由扩张的血管组成。这些胎记也称为草莓痣。大多数草莓痣会生长几个月,然后在几个月或几年间自发地逐渐缩小。但是,在大约15%的病例中,它们会累及眼、耳、口、鼻和肛周等部位,造成严重的功能障碍。此外,它们有时能够消退,但造成毁容。2008年,有报告称,β‐受体阻滞药普萘洛尔经口服用(口服),能够非常有效地使这些胎记迅速缩小。本文旨在就如何最好地对IH儿童患者使用普萘洛尔为医生提供指南。制定指导涉及多个阶段:对八个欧洲国家/地区的现行实践开展国际性调查;系统性文献综述;从19个中心收集当地现行指南生成70项声明。然后由来自相关专科(皮肤科、儿科、儿科心脏病学和儿科ENT外科)的19名专家仔细审查这70项声明。使用既定的研究方案,经由这些专家就涵盖八个类别的47项声明达成一致。这些类别包括:开始服用普萘洛尔的适应症(即应在哪些情况下服用);禁忌症(即不应在哪些情况下服用);所需的治疗前测试;开始治疗;治疗期间的监控以及何时停止治疗。这些声明还涵盖了出现其他并发症的儿童的治疗。虽然这些指南在英国实施,但是作者希望对欧洲的其他国家/地区同样有用。

Introduction Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare autosomal recessive disorder that results from homozygous germline mutations in one of the mismatch repair genes MLH1, MSH2, MSH6 and PMS. CMMRD syndrome results in a predisposition to childhood malignancy, with an increased risk of developing central nervous system (CNS), haematological and gastro-intestinal (GI) tract cancers. Colorectal polyps and cutaneous manifestations resembling neurofibromatosis type 1 are common. We present the case of a patient with CMMRD syndrome and bronchiectasis, an association not previously documented in the literature. Case report A 13-year-old boy of Pakistani origin born to consanguineous parents was referred to the paediatric outpatient clinic with anaemia. Both parents had a diagnosis of Lynch syndrome and elder brother a diagnosis of CMMRD syndrome with a previous history of CNS primary neuro-ectodermal tumour and basal cell carcinoma. Consultation revealed a history of chronic productive cough and recurrent lower respiratory tract infections with evidence of finger clubbing on examination. Cutaneous manifestations included a large scalp congenital melanocytic naevus, multiple CALMs, hypopigmented lesions and axillary and inguinal freckling. Persistent left lower lobe changes were noted on chest X-ray. Bronchoscopy demonstrated normal airway anatomy with increased secretions noted from left lower lobe bronchus. CT chest confirmed a diagnosis of bronchiectasis. Sweat test and ciliary biopsy were normal. Immunoglobulin A was low at <0.7 g/L while lymphocyte subset analysis was unremarkable. Baseline pulmonary function testing demonstrated a moderate restrictive defect with no evidence of obstruction. Genetic screening was performed in light of family history which identified a familial homozygous MSH6 sequence variant, c.3175del p.(Val1059fs), consistent with a diagnosis of CMMRD syndrome. Bowel screening was undertaken and colonoscopy identified a large colorectal villous adenoma with focal high-grade dysplasia. The patient subsequently developed focal seizures and was diagnosed with a right fronto-parietal brain tumour with three metastatic lesions. Biopsy, although not conclusive, was felt to be representative of a high-grade glial or embryonal tumour. Conclusion CMMRD syndrome is associated with a complex array of clinical manifestations and a wide tumour spectrum. Bronchiectasis has not been previously documented in the literature and should be considered where a history of chronic respiratory symptoms exists.

BackgroundInfantile haemangiomas (IH) are the most common vascular tumours of infancy. Despite their frequency and potential complications, there are currently no unified U.K. guidelines for the treatment of IH with propranolol. There are still uncertainties and diverse opinions regarding indications, pretreatment investigations, its use in PHACES (posterior fossa malformations-haemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe) syndrome and cessation of treatment. ObjectivesTo provide unified guidelines for the treatment of IH with propranolol. MethodsThis study used a modified Delphi technique, which involved an international treatment survey, a systematic evidence review of the literature, a face-to-face multidisciplinary panel meeting and anonymous voting. ResultsThe expert panel achieved consensus on 47 statements in eight categories, including indications and contraindications for starting propranolol, pretreatment investigations, starting and target dose, monitoring of adverse effects, the use of propranolol in PHACES syndrome and how to stop treatment. ConclusionsThese consensus guidelines will help to standardize and simplify the treatment of IH with oral propranolol across the U.K. and assist in clinical decision-making.

Infantile haemangiomas (IH) are common birthmarks in babies consisting of dilated blood vessels. They are also known as strawberry naevi. Most of them grow for a few months, then gradually shrink spontaneously over a period of months or years. However, in about 15% of cases they can cause serious functional problems when they involve important structures such as the eye, ear, mouth, nose and the peri-anal area. In addition they can sometimes resolve, but leaving significant disfigurement. In 2008 it was reported that the beta-blocker drug propranolol, given orally (by mouth), was very effective in causing these birthmarks to shrink rapidly. This paper is designed to provide guidance to doctors on how best to administer propranolol to children with IH. Developing the guidelines involved several stages: an international survey of current practice in eight European countries; a systematic review of the literature; collecting current local guidelines from 19 centres leading to the generation of 70 statements. These 70 statements were then scrutinised by 19 experts from relevant specialities (Dermatology, Paediatrics, Paediatric Cardiology and Paediatric ENT surgery). Using an established research protocol, agreement was reached by these experts on 47 statements covering eight categories. These categories include: indications for starting propranolol (i.e. it which situations it should be used); contraindications (i.e. in which situations it should not be used); pre-treatment tests needed; initiation of treatment; monitoring during treatment and when to stop treatment. They also cover treatment of children with additional medical complications.Although these guidelines are UK-based, the authors hope that they will be useful in other European countries also.

Linked Article: van Geel, et al. Br J Dermatol 2016; 174: 152–57 .

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.

Whole-body ultraviolet (UV)A1 (340-400 nm) phototherapy was first introduced 30 years ago, but is currently available in the UK in only three dermatology departments. A workshop to discuss UVA1 was held by the British Photodermatology Group in May 2009, the aim of which was to provide an overview of UVA1 phototherapy and its role in practice, and to identify areas in which further studies are required. The conclusions were that UVA1 phototherapy is an effective treatment in several inflammatory skin diseases, including localized scleroderma and atopic eczema (AE); however, deficiencies and limitations exist in the published evidence base. For most diseases, such as AE, other treatments also exist, which are generally more effective than UVA1. However, for some diseases, particularly morphoea, the evidence of efficacy is stronger for UVA1 than for other treatments. Acute adverse effects of UVA1 are minimal. The risk of long-term adverse effects, particularly skin cancer, is unknown. Medium to high doses of UVA1 are needed for efficacy in most situations, but the equipment to deliver such doses is large, expensive and difficult to install. UVA1 is currently underprovided, and the recommendation of the workshop is that more tertiary centres should have access to UVA1 phototherapy in the UK.

BACKGROUND:Allergic contact dermatitis (ACD) in childhood was considered rare until recently. However, reports are increasing, which may reflect an increased incidence and/or more frequent patch testing of children. It is also likely that allergen exposure in children has changed with time.AIMS:To determine the most common contact allergens and the rate of positive patch-test reactions among children with suspected contact allergy.METHODS:We carried out a retrospective case study of 114 children (66 girls and 48 boys) aged from 3 to 15 years (median 11.5) patch tested over a 3-year period. Indications for patch testing included uncontrolled or deteriorating atopic dermatitis, localized dermatitis or a history of reacting to a specific allergen.RESULTS:Of 110 children for whom we had notes, 83 (75%) had a history of atopy. Positive reactions that were of current, past or possible relevance were seen in 61 children (54%); in 58 (52%) of 111 tested with the standard series (SS) and in 6 (10%) of 60 tested with the medicament series. None of the children patch tested to the corticosteroid (n = 47), shoe (n = 15), fragrance (n = 12), cosmetic (n = 10) or rubber (n = 5) series had a positive reaction. However, 11 (10%) reacted to rubber allergens within the SS and one of five to their own shoes. The lowest rate of relevant positive reactions was among those with deteriorating atopic dermatitis (22%) and facial (33%) or perioral dermatitis (40%), and the highest rate amongst those with eyelid (86%) or hand (71%) dermatitis. Nickel was the most common allergen (20%) in line with previous reports (82% female), followed by rubber chemicals (10%), fragrance (7.2%), cobalt (5.4%) and lanolin (wool alcohol) (4.5%).CONCLUSIONS:The reported incidence of ACD among children, in particular nickel and rubber allergy, appears to be increasing, which may relate to changing fashions and hobbies. Contact allergy should be considered in all children with dermatitis, particularly with eyelid or hand dermatitis, and patch testing carried out more frequently.

The primary cause of collagen degeneration in necrobiosis lipoidica (NL) is proposed to be immunologically mediated vascular disease. Ultraviolet (UV)A1 has been used successfully to treat scleroderma in which both vascular damage and collagen dysregulation also occur. We treated six patients with NL [(five women; mean age of 32 years (range 22-70) and mean disease duration of 2.9 years (range 6 months to 5 years)] with a high-output ultraviolet (UV)A1 2-kW filtered metal halide source (Dr Hönle; Dermalight ultrA 1) having an emission spectrum of 340-440 nm. All patients had NL on the shins, which had been unresponsive to potent topical corticosteroid therapy (n = 6) and had responded minimally or not at all to TL-01 UVB (n = 2), topical psoralen plus UVA (PUVA) soaking (n = 2) or oral PUVA (n = 1) therapy. Patients received a variable number of total exposures (15-51), given 3-5 times weekly. NL resolved completely in one patient; this patient had minimal improvement after the first course of 16 exposures, but after a further 13 exposures, resolution occurred 6 months later. Two subjects obtained moderate improvement in their overall disease severity after 15 and 24 exposures, while two had only minimal improvement after 15 and 51 exposures. The remaining patient had no improvement after 16 treatments. Patients with the shortest disease duration had the greatest response. UVA1 therapy may be of benefit for the treatment of NL as an adjuvant therapy to topical corticosteroids or as a second-line alternative to other phototherapies, and may have a superior outcome in a proportion of patients.

Background. Lichen sclerosus (LS) is characterized histologically by an inflammatory T-cell infiltrate, sclerosis and thickening of the dermis, and epidermal atrophy. Ultraviolet (UV) A1 therapy has been shown to be effective in the management of morphea and scleroderma, diseases that have some histological and clinical similarities with LS, and more recently in extragenital LS.Aim. To determine the effectiveness of UVA1 therapy for genital LS.Methods. Seven women with severe genital LS uncontrolled by ultrapotent topical corticosteroids, with a median age of 62 years (range 48-78) and disease duration of 6-47 years, were treated with UVA1 therapy from a high output source. After completion of UVA1 therapy, a clinician and the patient graded the overall response of symptoms and physical signs.Results. Five patients improved with therapy. Three obtained moderate improvement in overall disease severity and two had minimal improvement. Of these five, one relapsed within 3 months and another after a year. Both had a further course of UVA1 therapy, resulting in minimal improvement in one and moderate improvement in the other. In the remaining three, disease severity had improved to a point where intermittent use of topical corticosteroids resulted in acceptable control.Discussion. UVA1 therapy may be of benefit in the management of vulval LS, a disease that is often poorly responsive to standard therapies. The therapy is well tolerated and could provide an acceptable therapeutic option for patients with severe disease.

BACKGROUND:Chronic disease can have physical and psychological effects which affect social functioning. These effects can be better understood from the perspective of parent and child by the use of health-related quality of life (HRQL) measures. Various HRQL measures are now available, of which generic health measures have been the most widely used. These permit comparison between different diseases and also the normal population.OBJECTIVES:To cross-validate a new generic HRQL proxy measure for children, the Children's Life Quality Index (CLQI), with an established speciality-specific dermatological questionnaire, the Children's Dermatology Life Quality Index (CDLQI), in a group of children with chronic skin diseases. The impairment of HRQL in the same group of children with skin disease was then compared with that associated with other common chronic childhood diseases using the CLQI.METHODS:The CDLQI was completed by 379 children aged 5-16 years with skin disease of more than 6 months' duration. Their parents (n=379) and parents of 161 children aged 5-16 years with other chronic diseases were also asked to complete a proxy measure, the CLQI.RESULTS:Using linear regression analysis, the CLQI and the CDLQI scores showed a strong linear association (rs=0.72, P<0.001) and on a Bland-Altman plot, reasonably good agreement (expressing scores out of 100, the 95% limits of agreement were from -25.5/100 to 26.7/100). In the child's opinion psoriasis and atopic dermatitis (AD) caused the greatest impairment (CDLQI scores of 30.6% and 30.5%), followed by urticaria (20%) and acne (18%). Using the generic CLQI (scored 0-36), from the parental perspective the highest score was for AD (33%), followed by urticaria (28%), psoriasis (27%) and alopecia (19%). Comparing this with children with other chronic diseases, those with cerebral palsy had the highest score (38%), followed in descending order by those with generalized AD (33%), renal disease (33%), cystic fibrosis (32%), urticaria (28%), asthma (28%) and psoriasis (27%). Diseases such as epilepsy (24%) and enuresis (24%) scored higher than diabetes (19%), localized eczema (19%), alopecia (19%) and acne (16%).CONCLUSIONS:Using the CLQI we have shown that HRQL impairment in children with chronic skin disease is at least equal to that experienced by children with many other chronic diseases of childhood, with AD and psoriasis having the greatest impact on HRQL among chronic skin disorders and only cerebral palsy scoring higher than AD. Cross-validation of the CLQI with the CDLQI in the group of children with skin disease demonstrates a strong linear association and good agreement between the two.

As phototoxic skin reactions caused by psoralen are induced by wavelengths within the UVA1 spectrum, we assessed the potential of the small amount of psoralen in a normal diet to provoke phototoxicity in volunteers with skin types I and II. Threshold erythema was unaffected by ingestion of a 200-g portion of parsnip.

BACKGROUND:Atopic dermatitis (AD) accounts for 10-20% of referrals to secondary care dermatology, often requiring multiple visits and occupying much valuable time and resources.OBJECTIVES:We audited the usefulness (ease of use, reliability and sensitivity to change) of two simple and easy to use quality of life (QoL) measures, the Infants' Dermatitis Quality of Life Index (IDQOL) and Dermatitis Family Impact (DFI), for assessing the impact on QoL of AD in infants and their families in a routine clinical setting. We also examined the impact of an initial consultation with a dermatology team on AD severity and QoL impairment from the parent's perspective.METHODS:The parents of 203 infants (mean age 19.8 months) with AD attending paediatric dermatology clinics completed the DFI and IDQOL. The parents of 50 of these infants completed both questionnaires before first and second consultations.RESULTS:In the 203 children the mean of both the IDQOL and DFI scores was 8.47 (median 8 and 7 and SD 5.8 and 6.5, respectively). The IDQOL and DFI correlated well (r(s) = 0.776, P < 0.0001). The parent's assessment of the global severity of AD correlated well with the IDQOL score (r(s) = 0.636, P < 0.0001) but less well with the DFI (r(s) = 0.394, P < 0.001). The highest-scoring IDQOL items were itching and scratching, problems at bathtime and time taken to fall asleep. The highest-scoring DFI items were tiredness/exhaustion, sleep loss and emotional distress. In both measures these domains also correlated most strongly with eczema severity. After dermatology consultation the median global severity score, rated by 50 parents, fell from 2 (SD 0.83) to 1 (SD 0.8; 95% confidence interval, CI 0.5-1), the median IDQOL score fell from 8 (SD 5.92) to 5.5 (SD 5.92; 95% CI 2-5.5) and the median DFI score fell from 9 (SD 6.45) to 3 (SD 6.56; 95% CI 2-5.5). In 50 infants the median IDQOL scores for those infants with global AD severity scores of 1, 2 and 3 were 5 (SD 5.65), 8 (SD 4.27) and 14 (SD 5.67), respectively and improved by 10%, 38% and 64%, respectively while the median DFI scores improved by 54%, 56% and 79%, respectively. The most improved IDQOL items were the time taken to get to sleep and difficulty at mealtimes and the most improved DFI domains were tiredness/exhaustion and emotional distress in the parents.CONCLUSIONS:We have provided further important information on the effects of AD on infants and their families using the IDQOL and DFI QoL measures. We demonstrate the usefulness of these measures in routine clinical management of AD and show the beneficial effect for both infants and parents of the initial consultation by a dermatology team in a secondary care setting.