Segmental facial infantile haemangiomas in the era of propranolol: evaluation at 6 years of age.

BACKGROUND: The long-term evolution of children with segmental facial infantile haemangioma (SFIH) treated with propranolol remains unstudied. OBJECTIVES: The objective of this study was to evaluate the neurodevelopmental features of children with SFIH treated with propranolol at 6 years of age. METHODS: This retrospective case series study was conducted from January 2008 to June 2020 using data from medical files, patient examinations and appointments spanning 6 years. To be included, patients should present SFIH and have previously received propranolol. A complete physical examination, magnetic resonance imaging (MRI) of the head, echocardiography and ophthalmologic examination should have been performed. Neurodevelopmental features were divided into cognition, audition, vision, orality, motor skills and the occurrence of new symptoms. RESULTS: Thirty children with SFIH were included. Of these, 11 presented criteria of PHACES. Evaluation of neurodevelopmental features of the children at 6 years of age showed learning difficulties in one case but grade skipping in three cases. There were six cases of unilateral hearing loss that had not been diagnosed at birth, two of oral difficulties and one of minor hypotonia. Early headache was primarily reported as the main new outcome. All children were treated with propranolol, with three following oral steroid therapy. No severe adverse effects were reported. The median length of treatment with propranolol was 16 months, and the median age at treatment cessation was 21 months. Analysis based on segment implication showed the median length of treatment to vary from 12 months (if S3 was spared) to 25 months (if at least S3 was involved). Vascular laser therapy was used in 16 patients (53.3%) and surgery in four. CONCLUSION: In this case series, children with SFIH, including patients with PHACES criteria, presented a good tolerance of propranolol, as well as encouraged neurodevelopmental data. Segmental implication appears to have a significant impact on treatment duration and associated complications.

[Clinical and evolutionary characteristics of a child with aquagenic keratoderma: A retrospective study of 12 patients]. / Caractéristiques cliniques et évolutives de la kératodermie aquagénique de l'enfant : étude rétrospective de 12 cas.

INTRODUCTION: Aquagenic keratoderma (AK) is a rare condition characterized by wrinkled and edematous appearance of the skin of the hands occurring within minutes of immersion in water. Other than in a setting of cystic fibrosis, AK has rarely been reported in children, with only 13 clinical cases on record. Many clinicians are unfamiliar with AK and have fears relating to the association with cystic fibrosis The aim of this study is to describe the characteristics and to discuss management of the disease. METHODS: Retrospective, multicentre study, including children aged under 16 years presenting AK. RESULTS: 12 children were included. KA started at a mean age of 9.25 years (range: 20 months to 15 years). Clinical appearance and mode of onset were classical, with the palms being more severely affected than the soles. Pruritus or pain were reported in six cases. The median impact on daily life was 1.5/10. Some of the children underwent investigations: two had a negative sweat test, three had molecular analysis of the gene CFTR: one was negative and two had a heterozygote mutation. The course of the disease was variable: eight stabilizations, two exacerbations, one cure and one improvement. DISCUSSION: This is the first series on childhood KA. Clinical characteristics were similar to those seen in adults. Impact was moderate and the disease course was variable. Systematic medical check-up for cystic fibrosis does not appear warranted in children since to date, cystic fibrosis has not been diagnosed in any patients presenting AK alone. CONCLUSION: AK is rare in children and should not cause erroneous concern, and improvement can occur.

Percutaneous cryoablation of symptomatic venous malformations as a second-line therapeutic option: a five-year single institution experience.

PURPOSE: To report the mid-term outcomes of percutaneous cryoablation (PCA) performed as second-line therapeutic option of venous malformations (VM). MATERIAL AND METHODS: From 2011 to 2015, PCA was offered in 24 patients (mean age: 31 years, range: 12-64) as second-line treatment for recurrence of symptoms after sclerotherapy and when resection was not possible (due to lesion location or previous failure) or refused by the patient. Adverse effects were recorded, disease-free survival (DFS) and local tissue control (LTC) rates were calculated based on symptoms and volume evolution. RESULTS: Mean follow-up was 18.7 months (6-48). Nine (37.5%, 9/24) adverse effects occurred and three (12.5%, 3/24) were severe. Mean pain assessed by visual analog scale (VAS) was 41.7 mm (0-80) before treatment and 20.3 mm (0-80) (p=0.01) after. Mean volume decreased significantly after treatment from 22.4 cm3 (0.9-146) to 8.35 cm3 (0-81.3) (p<0.001). Pain recurred in nine patients and size of one lesion increased. The DFS and LTC rates were 54% [95%CI: 22.94-77.27] and 93.33% [61.26-99.03] at 24 months, respectively. Only VM volume >10 cm3 was associated with a higher risk of local recurrence (p=0.05). CONCLUSION: PCA as second-line treatment appears to be safe and effective for local control of VM according to mid-term results. KEY POINTS: • Percutaneous cryoablation of venous malformations appeared well tolerated. • Size of venous malformations decreased significantly after percutaneous cryoablation (p<0.001). • Pain decreased significantly after percutaneous cryoablation of venous malformations (p=0.01).

Percutaneous Image-Guided Cryoablation as Second-Line Therapy of Soft-Tissue Venous Vascular Malformations of Extremities: A Prospective Study of Safety and 6-Month Efficacy.

PURPOSE: To report the safety and short-term efficacy of percutaneous image-guided cryoablation performed as second-line therapy of venous vascular malformations (VVM) of extremities. MATERIALS AND METHODS: In this non-blinded, no-randomized trial, cryoablation was proposed in 14 patients presenting with symptomatic VVM for recurrences after treatment. Eligibility criteria were: cryoablation feasible, localization at least 5 mm from skin and nerves, absence of contra-indication for anesthesia. Safety was evaluated by the common terminology criteria for adverse events (AE). Clinical response was assessed by evaluating pain at day 7, month 2 and 6 using visual analog scale; quality of life before cryoablation and at 2 and 6 months after using questionnaire. Evolution of volume was evaluated by MRI at 6 months. Comparison was performed using the Wilcoxon test. RESULTS: A technical success was observed in all cases. While 11 patients (78.6%) presented AE (13 grade 1-2 and 3 grade 3), only two severe AE (grade 3) related to cryoablation occurred in two patients (14.3%) during the 6-month follow-up: one immediate sciatic paralysis and one delayed paresthesia. A clinical response was observed in 12 patients (85.7%) at 6 months. Pain decreased significantly from 42.5 ± 14.2 mm before the intervention to 11.8 ± 17.9 mm at 6 months (P = 0.002). A significant decrease in the mean volume from 12.8 ± 14.3 to 3 ± 2.7 cm3 was observed at 6 months (P = 0.002). CONCLUSION: Percutaneous cryoablation is a promising alternative treatment for sclerotherapy-resistant venous malformations. However, to improve safety, careful patient selection and treatment planning will be mandatory.

[What's new in pediatric dermatology?] / Quoi de neuf en dermatologie pédiatrique ?

The association of a birth defect and a segmental hemangioma is well established, a consensus concerning evaluation and monitoring of infants with PHACE or LUMBAR syndromes has been published. The efficacy of propranolol in infantile hemangioma is proven; however there were still unresolved issues concerning the safety in children; after 8 years of use on thousands of children safety data collection did not show any unexpected side effects. Topical treatment of infantile hemangiomas with beta-blockers, such as timolol, is very popular, but recent publications revealed a significant systemic absorption that could be responsible for severe side effects, such as bradycardia, in low birthweight infants. As a consequence, this therapeutic option should be considered with caution. In the last 2 years mTOR inhibitors have been tested in low-flow vascular malformations with varying success, but progress remains to be done in the treatment of vascular abnormalities. Today, genetics has led to advances in the understanding of the pathophysiology and in the future targeted therapies could probably be feasible. Skin barrier deficiency is responsible for the development of allergic phenomena in atopic patients, since it has been shown that sensibilisation, even to food, could probably be induced by skin contact. Unfortunately, the topical treatment with crisaborole, a phosphodiesterase 4 inhibitor, does not look like a revolution in children atopic dermatitis, its efficacy seems equivalent to emollient application. In the field of infectious diseases, changes in viral outbreaks are the most reported. Furthermore epidemic Zika virus, enteroviruses are responsible for expanded dermatological manifestations and also severe meningoencephalitis. Paraviral character of various eruptions, such as gloves and socks syndrome or eruptive pseudoangiomatosis is challenged.

[Propranolol in infantile hemangiomas]. / Traitement par propranolol des hémangiomes infantiles.

Propranolol has been recently approved by health authorities to treat infantile haemangiomas (IH). Propranolol is indicated in infants less than 5months of age with an IH requiring systemic therapy: IH at life-threatening and/or functional risk, painful ulcerated IH and IH that may cause permanent disfigurement. Propranolol should be initiated by physicians who have expertise in the diagnosis, treatment and management of IH. In addition, the first intake and every escalation should be administrated in a controlled clinical setting where adequate facilities for handling of adverse reactions, including those requiring urgent measures, are available. Then a monthly monitoring with dose adjustment weight is mandatory by the family doctor. Parents should be informed of the risk of hypoglycaemia and bronchoconstriction, especially during respiratory infectious outbreaks. The recommended duration of treatment is 6months without tapering. Relapses are possible necessitating a second course of 3 to 6months of treatment.

Stay in NICU and infantile haemangioma development.

BACKGROUND: Infantile haemangiomas (IHs) are more frequent in low birth weight babies, especially premature. OBJECTIVE: To compare the characteristics of infants with IHs who stayed in neonatal intensive care unit (NICU) vs. those with IHs who did not. METHODS: Prospective observational multicentric study. Consecutive infants consulting for IHs in two departments of paediatric dermatology were included and a questionnaire specifically designed was filled for each patient. To identify factors associated with hospitalization in NICU vs. no hospitalization in NICU, we conducted univariate logistic regression analyses. RESULTS: A total of 210 infants with 323 IHs were included (56 boys, 154 girls, F/M sex ratio 2.75/1); 27 stayed in NICU, whereas 183 did not. Limbs involvement and multiple IHs were more frequent in NICU infants. Similarly, infants who had stayed in NICU had an earlier onset of their IH. Multiple IH was more frequent in infants with a history of congenital onset of IH. CONCLUSION: Infants staying in NICU and those with congenital lesion are at risk for specific type and involvement of their IH and should be early addressed to a dermatologist in case of suspicion of IH to provide them an early diagnosis and to start a treatment if necessary as soon as possible.

Aplasia cutis congenita with dystrophic epidermolysis bullosa: clinical and mutational study.

BACKGROUND: Aplasia cutis congenita (ACC) has been associated with all clinical forms of inherited epidermolysis bullosa (EB), including dominant and recessive dystrophic EB (DDEB and RDEB). To date, only a few patients with DEB specifically combined with ACC have been described and genotyped and almost all cases represent dominant forms of the condition. OBJECTIVES: The aim of this study was to describe new mutations of COL7A1 in patients with DEB and ACC and investigate possible genotype-phenotype correlations. METHODS: Twenty-two patients with DEB and ACC were included among the 123 patients with DEB whose COL7A1 mutations have been identified in the Reference Centre in Nice. RESULTS: Seven patients presented a severe generalized RDEB phenotype (RDEB-sev-gen), while the other 15 suffered from milder phenotypes. We identified 28 mutations in COL7A1, of which nine are novel. Patients with severe phenotypes have mostly mutations leading to premature termination codon (PTC) and/or splice-site or missense mutations. Patients with the milder phenotypes have mostly glycine or arginine substitutions associated or not with other types of mutations. All amino acid substitutions fell within the carboxyl portion of the triple helix domain (THD) of collagen VII, close to the THD interruptions. CONCLUSIONS: Our findings suggest that ACC is a frequent manifestation in patients with DEB irrespective of the severity of the disease, and is due to leg rubbing in utero. In children with a moderate form of DEB with no or moderate skin fragility, a glycine substitution near the THD interruption domain of the collagen VII leading to thermolabile protein could explain this phenomenon.

Factors associated with the relapse of infantile haemangiomas in children treated with oral propranolol.

BACKGROUND: Although propranolol has become the first-line therapy for infantile haemangiomas (IHs), no study has yet investigated factors associated with the risk of relapse in children with IH treated with propranolol after cessation of treatment. OBJECTIVES: To compare factors associated with the risk of relapse in children with IH treated with oral propranolol. METHODS: We conducted a single-centre retrospective observational study. All files and photographs of patients with IH aged 5 months or less at the time of treatment initiation, and who were seen between 1 June 2008 and 31 December 2011 at the National Reference Center for rare skin diseases of Bordeaux, were retrospectively reviewed. RESULTS: In total 158 children were included, of whom 118 had not relapsed and 40 had relapsed. Fifty-two patients were boys and 106 were girls (male : female ratio 1 : 2), and 19 had a segmental IH (12%). When conducting multivariate analysis, only IHs with a deep component and those with segmental distribution were independently associated with relapse. CONCLUSIONS: Our study shows that segmental IHs, as well as haemangiomas with a deeper component, are more at risk of relapse and should thus indicate closer follow-up after treatment interruption, and/or longer treatment.

[Infantile hemangioma: update and treatment]. / Hémangiomes infantiles : actualités dans le traitement.

Infantile hemangioma (IH) is not strictly speaking a tumor, but the result of anarchic postnatal vasculogenesis. Hypoxia seems to play an important role as a predisposing factor. IHs can present three clinical morphologies: superficial, deep, or mixed. Localized IHs are oval or round, circumscribed lesions, whereas segmental IHs extend across a large anatomic area with a geographic shape. Localized IHs are often benign, except when they are located near a noble structure such as the airways or the orbital area. Segmental IH may be associated with birth defects (PHACES syndrome and SACRAL syndrome). Clinical follow-up of infants with IH should be very careful in the first weeks of life since 80% of all IHs have reached their final size at 5 months of age. The main indications for treatment of IHs are: life-threatening conditions (heart failure, respiratory distress), functional risks (amblyopia, swallowing disorders, etc.), aesthetic risks (especially IH of the face localized on the nose, lips, etc.), and painful ulcerated IH. Beta-blockers, namely propranolol, have quickly become the first-line therapy of complicated IH. The treatment should be given as soon as possible to avoid sequelae.

Autoimmune thyroid disease in vitiligo: multivariate analysis indicates intricate pathomechanisms.

BACKGROUND: Vitiligo/nonsegmental vitiligo (NSV) is often associated with thyroid dysimmunity although very few reports have studied this association using multivariate logistic regression. OBJECTIVE: To identify weighted factors associated with the presence of autoimmune thyroid disease (AITD) in a large cohort of patients with vitiligo/NSV. METHODS: This was a prospective observational study in 626 patients with a confirmed diagnosis of vitiligo/NSV attending the vitiligo clinic of the University Hospital Department of Dermatology, Bordeaux, France, from 1 January 2006 to 1 May 2012. The Vitiligo European Task Force (VETF) questionnaire was completed for each consecutive patient. AITD was defined as the presence of significant levels of serum antithyroperoxidase antibodies or evidence of autoimmune thyroiditis. Univariate and multivariate logistic regression procedures were conducted to identify factors associated with AITD in this cohort of patients with vitiligo/NSV. RESULTS: A total of 626 patients with vitiligo/NSV were included, of whom 131 had AITD (AITD-vitiligo). Stress as an onset factor, familial history of AITD, body surface involvement and duration of the disease were positively associated with AITD-vitiligo using univariate analysis, whereas female sex, age at onset of vitiligo, personal history of autoimmune disease and localization on the trunk were found to be independently associated with AITD-vitiligo. CONCLUSION: Vitiligo associated with AITD has clinical features distinct from vitiligo without AITD. In particular, female patients, and patients with longer duration of disease and greater body surface involvement are more likely to present with AITD and should thus be monitored for thyroid function and antithyroid antibodies on a regular basis.

Efficacy of systemic propranolol for severe infantile haemangioma of the orbit and eyelid: a case study of eight patients.

AIM: To assess the efficacy of systemic propranolol for severe capillary haemangiomas involving eyelid and orbit. METHOD: This was a longitudinal retrospective study that began in November 2007, involving eight children with disfiguring orbit and eyelid capillary haemangioma who received oral propranolol therapy. Three patients with life-threatening haemangiomas spreading to the orbit were first treated with systemic corticosteroids and beta-adrenergenic blocking agents. The remaining five patients with functional visual impairment received propranolol only. All children were given propranolol at a dose of 2 mg/kg body weight per day. The treatment was initiated between 2 and 36 months of age, with a follow-up period ranging from 6 to 30 months. Beta-blocking agents were used for 3-10 months. RESULTS: We observed a successful 100% regression: that is, clinical regression by flattening 24 h after the start of treatment, regression on colour Doppler ultrasound imaging with an increase in resistance index of blood vessels, or regression seen on MRI. No re-growth was observed after the trial ended. CONCLUSION: Despite their self-limiting course, infantile orbital and eyelid haemangiomas can cause visual impairment or disfigurement. Corticosteroids are used as first-line therapeutic agents for problematic infantile haemangiomas. Other options include interferon-α and vincristine, which present problematic side effects. In our series, propranolol was shown to inhibit haemangioma tumour growth with a better benefit/risk ratio. In the absence of any randomised study comparing the effects of systemic corticosteroids and propranolol, we propose that beta-blockers could be used as first-line therapy for severe periocular haemangiomas.