Oral propranolol in the treatment of proliferating infantile haemangiomas: British Society for Paediatric Dermatology consensus guidelines.

BACKGROUND: Infantile 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. OBJECTIVES: To provide unified guidelines for the treatment of IH with propranolol. METHODS: This 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. RESULTS: The 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. CONCLUSIONS: These 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.

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.

Propranolol for infantile haemangiomas: a review.

Infantile haemangiomas are the most common benign tumour of infancy. However the majority are self-resolving and only a small minority of cases require treatment, with various different medications being used in the past. Over the last few years, propranolol, a non-selective ß-blocker, has become a popular and successful treatment for infantile haemangiomas. However, further research on its safety is needed if it is going to be used more frequently. This article summarises the current literature on propranolol for haemangioma treatment with emphasis on its toxicity and adverse event profile.

Review of modern techniques in detecting port-wine stain response to laser therapy.

BACKGROUND: Traditional mechanisms of assessing port-wine stain response to laser therapy have rested mainly on subjective determinations by physician and patient. However, the wide variation in treatment response poses a profound need for objective devices to measure treatment outcomes so that maximum effectiveness of therapy can be achieved without unnecessary repeat treatments. OBJECTIVE: The purpose of this paper will be to review noninvasive techniques to measure port-wine stain response to laser therapy. METHODS: This report is based on a review of medical and bioscience literature. RESULTS: Several techniques including laser Doppler, reflectance spectrophotometry, tristimulus colorimetry, and videomicroscopy have been developed to address the need for objective measurement devices. CONCLUSION: While many instruments are available, these techniques are limited by cost, small test size area, and/or inconclusive correlation with clinical response. A number of experimental techniques may circumvent many of the problems inherent in currently-available commercial technologies.

Epidermal Langerhans cell apoptosis is induced in vivo by nonanoic acid but not by sodium lauryl sulphate.

Exposure to irritants may cause chronic irritant contact dermatitis (ICD), characterized by irregular epidermal thickening and a predominantly dermal mononuclear cell infiltrate. The mechanisms involved, and why only certain individuals are affected, are not clearly understood. Different irritants may trigger different cellular and molecular interactions between resident skin cells and recruited inflammatory cells. In some individuals these interactions may become self-perpetuating resulting in persistent inflammation in the absence of continued exposure. This study examined Langerhans cell (LC) density in clinically normal skin of 46 patients with chronic ICD and 10 healthy individuals, and compared the action of the two irritants nonanoic acid (NA) and sodium lauryl sulphate (SLS) on the LCs and keratinocytes of clinically normal skin in patients with chronic ICD. There was a higher number of LCs/mm basement membrane in patients compared with controls, although there was no difference in the number of dendrites/LC nor in dendrite length. SLS induced keratinocyte proliferation after 48 h exposure, had no effect on LC number or distribution, and induced keratinocyte apoptosis after 24 and 48 h exposure. In contrast, NA decreased keratinocyte proliferation after 24 h exposure but this returned to basal levels after 48 h, and induced epidermal cell apoptosis after only 6 h exposure. NA dramatically decreased LC number after 24 and 48 h exposure, which was accompanied by basal redistribution and decreased dendrite length. Most significantly, NA induced apoptosis in over half of the LCs present after 24 and 48 h exposure.

Accumulation of p53 is associated with tumour progression in cutaneous lesions of renal allograft recipients.

Renal allograft recipients suffer from a markedly increased susceptibility to premalignant and malignant cutaneous lesions. Although various aetiological factors have been implicated, little is known of the associated genetic events. In this study we initially employed immunocytochemical techniques to investigate the prevalence and localisation of accumulated p53 in over 200 cutaneous biopsies (including 56 squamous cell carcinomas) from renal allograft recipients and immunocompetent controls. In renal allograft recipients accumulated p53 was present in 24% of uninvolved skin samples, 14% of viral warts, 41% of premalignant keratoses, 65% of intraepidermal carcinomas and 56% of squamous cell carcinomas [squamous cell carcinoma and intraepidermal carcinoma differed significantly from uninvolved skin (P < 0.005) and viral warts (P < 0.01)]. A similar trend was revealed in immunocompetent patients (an older, chronically sun-exposed population) but with lower prevalence of p53 immunoreactivity: 25% of uninvolved skin samples, 0% of viral warts, 25% of keratoses, 53% of intraepidermal carcinomas and 53% of squamous cell carcinomas. These differences were not statistically significant. Morphologically, p53 immunoreactivity strongly associated with areas of epidermal dysplasia and the abundance of staining correlated positively with the severity of dysplasia. These data suggest that p53 plays a role in skin carcinogenesis and is associated with progression towards the invasive state. No correlation was observed between accumulated p53 and the presence of human papillomavirus (HPV) DNA in any of the lesions. Single-strand conformational polymorphism analysis (exons 5-8) was used to determine the frequency of mutated p53 in 28 malignancies with varying degrees of immunopositivity. p53 mutations were found in 5/9 (56%) malignancies with p53 staining in > 50% of cells, reducing to 1/6 (17%) where 10-50% of cells were positively stained and none where < 10% of cells were stained. These data imply that factors other than p53 gene mutation play a part in accumulation of p53 in skin cancers.

Changing forms of juvenile pityriasis rubra pilaris--a case report.

Pityriasis rubra pilaris (PRP) is a rare disease affecting both males and females. The aetiology is unknown, but it has an ill-defined relationship with psoriasis. Within the spectrum of PRP certain disease patterns are recognized, and regarded by many as helpful prognostic indicators. Griffiths has suggested a clinically based classification based on a series of 98 patients seen at St John's Hospital, London between 1950 and 1972 (Table 1). Classical type 1 PRP is an erythematous squamous disorder typically showing follicular hyperkeratosis, perifollicular erythema and sharply demarcated islands of unaffected skin. The palms and soles become hyperkeratotic and often exhibit a characteristic orange hue. Type III PRP is the juvenile counterpart of classical type I PRP. The following case report describes a patient who presented with type III PRP but later went on to develop the type IV or circumscribed, juvenile onset PRP.

Intravascular histiocytosis.

The majority of cases of intravascular lymphomatosis are B-cell lymphomas with only the occasional case being of T-cell type. We report a case of intravascular lymphomatosis in which the proliferating cells were of histiocytic type; the tumour has recurred following treatment.

Prevalence of human papillomavirus DNA in cutaneous neoplasms from renal allograft recipients supports a possible viral role in tumour promotion.

It is well established that renal allograft recipients (RARs) have an increased incidence of viral warts and premalignant and malignant cutaneous lesions, and the risk of their development increases in proportion to duration of graft survival. It has been postulated that, in addition to the effects of prolonged immunosuppression and previous sun exposure, human papillomaviruses (HPV) may also contribute to the carcinogenic process. In this study, the prevalence of HPV DNA was examined in a range of premalignant and malignant cutaneous tumours from 50 immunosuppressed patients (47 renal allograft recipients plus three cardiac allograft recipients) and 56 immunocompetent patients using Southern hybridisation as a low-stringency screening method and type-specific polymerase chain reaction (PCR) assays for eight HPV types. The combined results for renal allograft recipients show that HPV DNA was detectable in 79% of viral warts, 42% of premalignant keratoses, 33% of intraepidermal carcinomas, 43% of invasive squamous cell carcinomas and 16% of uninvolved skin specimens (squamous cell carcinomas/renal allograft recipients significantly different at P < 0.05 from uninvolved skin specimens/renal allograft recipients). In immunocompetent patients the pattern of HPV DNA prevalence was 100% for viral warts; 25% for keratoses, 23% for intraepidermal carcinomas, 22% for squamous cell carcinomas and 8% for uninvolved skin. No single HPV type predominated in tumour specimens from either group. More tumours were found to contain HPV DNA by Southern hybridisation analysis than PCR, indicating the presence of HPV types other than HPV 1, 2, 5, 6, 8, 11, 16 and 18 in some tumours. However, 'low cancer risk' HPV types 1, 2 and 6 as well as 'high cancer risk' HPV types 5 and 16 were specifically detected by PCR in a small number of neoplasms. These data suggest that multiple HPV types may contribute to cutaneous neoplasia in RARs and that they appear to act early in the process of carcinogenesis, perhaps by functioning as tumour promoters via stimulation of cell proliferation.

Possible relationships between changes in body weight set-point and stress metabolism after treating rats chronically with D-fenfluramine. Effects of feeding rats acutely with fructose on the metabolism of corticosterone, glucose, fatty acids, glycerol and triacylglycerol.

Rats were maintained on a corn oil diet and treated with D-fenfluramine at doses of 2.5 mg/kg twice a day for 11 days or with 10 mg or 25 mg/kg once a day for 12 days. The lower dose of D-fenfluramine produced no marked changes in body weight and after 11 days of treatment the weights of the rats on average were only 2% lower than the controls. The food intake of these rats was only decreased on the first day. The two higher doses of D-fenfluramine decreased the food consumption for about 3 days but thereafter it was similar to that of the control rats. The body weight of these rats fell on the first day, but after about four days the gain in body weight paralleled rather than approached that of the control rats. Increasing the dose of D-fenfluramine progressively decreased the relative size of the epididymal fat pad. At the end of the treatment period the rats were fed acutely with fructose to increase the circulating concentrations of corticosterone and to stimulate triacylglycerol synthesis. All three doses of D-fenfluramine decreased the concentration of circulating triacylglycerol after fructose feeding. The 10 mg/kg dose also decreased the basal concentration of triacylglycerol. The two higher doses of fenfluramine decreased the rises in the circulating concentrations of corticosterone, glycerol and fatty acids that are produced by fructose feeding. The basal concentrations of these compounds in the absence of fructose feeding were not significantly affected by the 10 mg/kg dose of D-fenfluramine. The possible relationship between the effect of chronic treatment with D-fenfluramine in decreasing a metabolic stress response and lipolysis is discussed relative to its hypotriglyceridaemic action and its effect on body weight-set point. The results demonstrate that D-fenfluramine produced persistent changes in metabolism at a time when the treated rats were growing at the same rate as the control rats and when they were eating similar quantities of food.