A. Maruani

Lack of Effect of Propranolol in the Treatment of Lymphangioma in Two Children

Abstract:u2002 Vascular lesions such as hemangiomas and lymphangiomas can cause significant mortality and morbidity, as well as amblyopia when located in the orbit. Oral propranolol can regress infantile hemangioma during infancy and up to 23u2003months of age, but its effect on lymphangioma has not been demonstrated. We present two cases of lymphatic malformations treated with oral propranolol. Patient 1 is a 2‐year‐old boy with macrocystic bilateral cervical lymphangioma extending to the pharynx and larynx and microcystic lymphangioma of the tongue. The patient was started on propranolol 2u2003mg/kg/day starting at 17u2003months of age, and after 3u2003months only a very slight decrease in tongue volume was noted. Patient 2 is a 3.5‐year‐old boy with magnetic resonance imaging evidence of right facial complex lymphangioma with venous malformation. The patient was placed on oral propranolol 2u2003mg/kg/day. After 3u2003months of treatment, no change in the lesion was noted except for a transient decrease in the size of the conjunctival telangiectasia. Propranolol 2u2003mg/kg/day was not effective in treating lymphatic malformations in two children, both older than 17u2003months at the time of treatment.

Efficiency of low-frequency ultrasound sonophoresis in skin penetration of histamine: a randomized study in humans.

Low-frequency ultrasound (US) applied to skin (sonophoresis) has been investigated to enhance the transdermal transport of various drugs. Histamine is usually used in allergy investigations. We aimed to investigate, in a randomized study, the transdermal penetration of histamine with sonophoresis. Ten subjects were included. Their right forearm was divided into three zones, which were randomly assigned a treatment: no US, US(1) (I(1)=2.72 W/cm(2)), US(2) (I(2)=3.50 W/cm(2)). The primary outcome was area of induced papule, which revealed histamine penetration. Secondary outcomes were echographic measurement of papule (skin thickness) and pruritus. Measurements were taken immediately after US application and after 30 min, 2 h and 24 h. Arm zones without US application showed no papules induced by histamine; 9/10 subjects receiving US showed papules. Their mean size increased with increased intensity of US but not significantly. The skin thickness increased with US. Pruritus occurred in 7/10 cases after US and histamine. The adverse events were skin erythema, pain and tinnitus. Though this study included a few number of patients, it confirms that sonophoresis enhances skin penetration of histamine. This technology could be used at therapeutic levels: histamine could be used with sonophoresis as a positive control in allergy testing instead of prick tests, which involve skin disruption with a lancet.

Molecular diagnosis of PIK3CA -related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing

Purpose:Postzygotic activating mutations of PIK3CA cause a wide range of mosaic disorders collectively referred to as PIK3CA-related overgrowth spectrum (PROS). We describe the diagnostic yield and characteristics of PIK3CA sequencing in PROS.Methods:We performed ultradeep next-generation sequencing (NGS) of PIK3CA in various tissues from 162 patients referred to our clinical laboratory and assessed diagnostic yield by phenotype and tissue tested.Results:We identified disease-causing mutations in 66.7% (108/162) of patients, with mutant allele levels as low as 1%. The diagnostic rate was higher (74%) in syndromic than in isolated cases (35.5%; P = 9.03u2009×u200910−5). We identified 40 different mutations and found strong oncogenic mutations more frequently in patients without brain overgrowth (50.6%) than in those with brain overgrowth (15.2%; P = 0.00055). Mutant allele levels were higher in skin and overgrown tissues than in blood and buccal samples (P = 3.9u2009×u200910−25), regardless of the phenotype.Conclusion:Our data demonstrate the value of ultradeep NGS for molecular diagnosis of PROS, highlight its substantial allelic heterogeneity, and confirm that optimal diagnosis requires fresh skin or surgical samples from affected regions. Our findings may be of value in guiding future recommendations for genetic testing in PROS and other mosaic conditions.Genet Med advance online publication 02 February 2017

High-resolution ultrasonography assists the differential diagnosis of blue naevi and cutaneous metastases of melanoma

Backgroundu2002 Metastases of cutaneous melanoma may simulate benign blue naevi clinically.

Low-frequency ultrasound sonophoresis to increase the efficiency of topical steroids: a pilot randomized study of humans.

Topical steroids are efficient in vasoconstriction potential, which is linked to their anti-inflammatory activity. Low-frequency ultrasound (US) applied on the skin (sonophoresis) may enhance the transdermal transport of various steroids. We aimed to assess, in a simple, blinded, randomized controlled pilot study, the clinical efficiency of sonophoresis in increasing vasoconstriction by enhancing the transdermal penetration of topical steroids in human skin. The study took place in the Clinical Investigation Center of the University Hospital of Tours and involved healthy volunteers. Three circular zones were delimited on each of the subjects forearms: zone 1 (right and left) received topical steroids with 1-h occlusion, zone 2 with 2-h occlusion, and zone 3 with massage. Forearms were randomized to first undergo US, using a 36 kHz probe, delivered in a pulsed mode (2s on/5s off), during 5 min, with a US intensity of 2.72 W/cm(2), or no US. We used betamethasone 17-valerate in cream form as the topical steroid. The primary outcome was difference between forearms in skin color (increased whiteness reflecting the intensity of vasoconstriction) measured by 2 scores: values obtained with a chromameter (the higher the value, the whiter the skin) and a clinical visual score. The measurements were taken by a dermatologist by blinded assessment. Fifteen subjects were included. Vasoconstriction was significantly higher with the topical steroid applied after US, especially in zone 2, than without US. Vasoconstriction was increased at 1, 2, 3, 4, and 6h (e.g., chromameter score 63.4 versus 65.2, p=0.017 at 4h) and disappeared at 24h. Moreover, 2-h occlusion gave higher vasoconstriction scores than did 1-h occlusion or massage alone, whether US was applied or not. The use of low-frequency US coupled with 2-h occlusion is a synergistic way to increase the efficiency of topical steroids by enhancing skin permeability.

Arterial blood flow in limbs with port-wine stains can predict length discrepancy

SIR, Port-wine stains (PWS) on a limb can be part of Klippel– Trenaunay syndrome (KTS). This vascular disorder consists of PWS, venous abnormalities and limb hypertrophy. Limb hypertrophy has been reported in about 60% of patients with KTS. The length discrepancy may result in disfigurement, gait disturbance, pelvic tilting, scoliosis or back pain. One single study was conducted to determine risk factors for limb length discrepancy (LLD) in congenital vascular malformations. The extent of the malformation was the single independent risk factor for LLD. In healthy adults, arterial blood flow (ABF) is not significantly different between left and right proximal leg arteries. Mean difference is estimated to be almost 10%. Two previous studies have suggested that, in patients with KTS, ABF is greater in the limb with PWS. The purpose of this work was to determine whether the ultrasonographic measurement of ABF in limbs can predict LLD in children with congenital PWS on a limb. This retrospective study included children (age £ 16 years) followed up in the Hospital Centre of Tours (France) between 1992 and 2006 who had PWS on a limb. Excluded were patients with arteriovenous malformations or patients who had already had surgical treatment on limbs. The limbs were measured by tape measure. We considered as clinically relevant an LLD ‡ 10 mm. Duplex ultrasonography was performed to establish ABF at the proximal part of the limb. Results were expressed as mL min. For each child, ABF was determined at the same time in both the affected limb and the normal limb. Unaffected limbs were thus used as the control. The difference in ABF between the affected and normal limbs was expressed as a percentage. We considered as relevant a difference in ABF of ‡ 50% between the two limbs. Children who had been followed up for at least 1 year were reviewed, to determine whether they had developed an LLD or, if they already had one, if it had increased. We considered as clinically significant an LLD of ‡ 10 mm. Thirty children with 31 PWS on a limb were included. One child had PWS on both an upper and the homolateral lower limb. There was a clinically measurable LLD in 10 cases and no significant discrepancy in 21 cases (Table 1). Mean ABF in limbs with PWS was significantly greater than in normal limbs (P = 0Æ006). Mean ± SD difference in ABF between the limbs with PWS and the normal limbs was 45 ± 85% (Table 1). Twenty-three children with 24 PWS had been followed up (Table 1). Children who either developed an LLD ‡ 10 mm or showed an increase of ‡ 10 mm in a previous LLD had shown a significantly greater difference in ABF between the two limbs at first examination (P = 0Æ002). There was a relation between an ABF difference of ‡ 50% between affected and contralateral limbs at first examination

Effect of physician dress style on patient confidence

Backgroundu2002 We lack data on how physicians can instill confidence in patients.

Treatment of early-onset Gorham syndrome with 8-year follow-up.

Abstract:u2002 A case of Gorham disease with several years of follow‐up is reported. At birth he had a mass in the thigh which was had pathology demonstrating a lymphangioma. By age 3 years, he had lymphedema of the ipsilateral foot and discrepant leg lengths. Radiography revealed heterogenous dystrophy of the bones and osteolysis of the hallux. At age 6, a spontaneous fracture of the right tibia was treated with surgery. Histopathology of a bone sample demonstrated bone remodelling, fibrous tissue, and large vascular lacunas within bone tissue, bordered by cells expressing the lymphaticmarker D2–40. At 8 years old, lymphedema of the right inferior leg had increased, leg lengths still differed, but other clinical signs were absent.

Extensive, erosive congenital self‐healing cell histiocytosis

Case 1 A newborn full-term male, with no family history of skin disease, presented multiple erosive lesions on 40% of the cutaneous surface, predominantly on the face and scalp. He showed discrete erosions in the oral and nasal mucosal membranes. The suspected diagnoses were congenital bullous epidermolysis, diffuse impetigo, staphylococcal scaled-skin syndrome or neonatal pemphigus. Histopathology examination revealed, underlying a slightly acanthosic epidermis, a massive infiltration of Langerhans histiocytosis cells (large cells with kidney-shaped nuclei) intermixed with infiltrates of eosinophils. Sporadic ulceration was observed, with a disruption of the basal membrane. Immunohistochemical staining of cells revealed positivity for S-100 and CD1a protein. Electron microscopy examination of a skin sample showed lobulated nuclei inside the histiocytes, with Birbeck granules. The skin erosions resolved spontaneously (Fig. 1). After 3 months, the crusted lesions had completely disappeared, leaving non-inflammatory scars with numerous small epidermal cysts (Fig. 2).

Kératoacanthome de la marge anale

Resume Nous rapportons un cas de keratoacanthome de la marge anale chez un homme de 34 ans. Apres des biopsies negatives, le diagnostic histologique etait obtenu par analyse histologique de la piece d’excision. Neuf cas de keratoacanthome de la marge anale ont ete publies dans la litterature. Notre observation se distingue par l’âge jeune du malade. Nous discutons le principal diagnostic differentiel du keratoacanthome anal, le carcinome epidermoide bien differencie.