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.

[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.

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.

Halo naevi and leukotrichia are strong predictors of the passage to mixed vitiligo in a subgroup of segmental vitiligo.

BACKGROUND: Until now, segmental vitiligo has been considered as a stable entity and mixed vitiligo, the association of segmental and nonsegmental vitiligo, has been reported rarely. OBJECTIVES: The aim of this study was to search for factors associated with the generalization of vitiligo in patients with segmental vitiligo. PATIENTS AND METHODS: This was a prospective observational study conducted in the vitiligo clinic of the Department of Dermatology of Bordeaux, France. The Vitiligo European Task Force questionnaire was completed for each patient attending the clinic with a confirmed diagnosis of segmental vitiligo after exclusion of other forms of vitiligo (focal, mucosal, not classifiable.) Thyroid function and antithyroid antibodies were screened if not obtained in the previous year. RESULTS: One hundred and twenty-seven patients were recruited: 101 had segmental vitiligo and 26 had segmental vitiligo that evolved into mixed vitiligo; 56 were male and 71 were female. Most patients had onset of segmental vitiligo before the age of 18. When conducting multivariate analysis, we found the following to be independent factors associated with the evolution of patients' disease from segmental vitiligo to mixed vitiligo: initial percentage of body surface involvement of the segment >1% [odds ratio (OR) 15·14, P=0·002], the presence of halo naevi (OR 24·82, P=0·0001) and leukotrichia (OR 25·73, P=0·0009). CONCLUSIONS: Halo naevi association and leukotrichia at first consultation in segmental vitiligo are risk factors for the progression of segmental vitiligo to mixed vitiligo. In addition, this progression of segmental vitiligo to mixed vitiligo carries a stronger link if initial segmental involvement is situated on the trunk.

[Metronidazole: alternative treatment for ocular and cutaneous rosacea in the pediatric population]. / Le métronidazole, alternative thérapeutique des rosacées oculaires et cutanées de l'enfant.

OBJECTIVE: To assess the effectiveness and tolerance of systemic metronidazole in the treatment of childhood ocular and cutaneous rosacea. METHOD: Single-center multidisciplinary retrospective study. PATIENTS: Children aged between 1 and 15, with ocular and/or cutaneous rosacea, treated in the pediatric ophthalmology and dermatology department of Bordeaux, France, from January 1996 to September 2009. RESULTS: Eleven patients out of 20 had ocular and cutaneous rosacea, three had ocular symptoms only, and six had cutaneous symptoms only. In 11 patients (55%), the ocular symptoms preceded the skin disease. Meibomian cyst and phlyctenular conjunctivitis were the main symptoms. Keratitis was seen in four patients and lower corneal ulcer in two cases. The papulopustular form was the most frequent dermatologic form. All patients with ocular involvement received first-line treatment of eyelid hygiene. No topical ophthalmic treatment such as corticosteroid or cyclosporine 0.5% or 2% was used. Thirteen patients who showed no improvement despite eyelid treatment, the association of ocular and cutaneous rosacea, severe ocular involvement with keratitis, and severe recurrent cutaneous rosacea were treated orally. Two patients, aged between 12 and 14 years, received treatment with an anti-inflammatory dose of doxycycline for 2 to 3 months and achieved complete remission. One 22-month-old patient received oral treatment with erythromycin at a dose of 250 mg three times daily for 4 months. Ten patients, aged 12 to 64 months, were treated with systemic Metronidazole. Treatment lasting at least 3 months at a dose between 20 and 30 mg/kg per day was necessary to obtain complete and lasting remission. An early cessation of treatment, before 3 months, seems associated with partial remission of the disease and early recurrence. In cases complicated by ocular keratitis and corneal ulcer, prolonged treatment lasting 6 months led to clinical remission. The short courses (3-6 months) were preferred to long-term administration to prevent neurological toxicity. Maintenance therapy was based on eyelid hygiene. No recurrences and no toxic effects were observed at a median of 48 ± 6 months. CONCLUSION: Childhood ocular rosacea is not rare, but is often misdiagnosed. It often precedes skin symptoms but it can remain isolated. Metronidazole could be alternative treatment for ocular and cutaneous rosacea in the pediatric population.

Infantile haemangioma: part I. Pathophysiology, epidemiology, clinical features, life cycle and associated structural abnormalities.

Infantile haemangioma (IH) is the most common tumour of infancy. Its typical natural history is characterized by an early rapid growth following birth and a slow spontaneous regression phase within a period of 3 to 7 years. The exact aetiopathogeny underlying IH is still to be fully understood, but the role of fetal hypoxic stress is strongly suggested as a triggering signal in epidemiological studies. IH are composed of a complex mixture of cells including multipotent stem cells, a majority of immature endothelial cells, pericytes, dendritic cells and in the late stage, adipocytes. Most of IH are nodular and are not associated with malformations. However, in some cases, IH referred to as segmental may be associated with developmental abnormalities such as PHACES and PELVIS/SACRAL syndromes.

Infantile haemangioma: part II. Risks, complications and treatment.

Because of their spontaneous involution, most infantile haemangiomas (IH) do not require therapeutic intervention. However, in 10 to 15% of cases such as segmental and multifocal IH, locations in the periocular, airway and perineal areas, or complications of ulceration, treatment is necessary. Moreover, the risk of permanent scarring and disfigurement associated with IH, even if involution is complete, has been increasingly recognized as a rationale for treatment. Treatments for IH currently include topical, intralesional, systemic therapies, laser and surgical modalities depending on the clinical scenario. However, clinicians must carefully weigh the risks and benefits for each treatment. Recently, the efficacy of propranolol, a non-cardioselective beta-blocker, was reported and has been revolutionary in the management of IH.

Epicutaneous aeroallergen sensitization in atopic dermatitis infants - determining the role of epidermal barrier impairment.

BACKGROUND: Sensitization to atopens is an early phenomenon that overlaps with the onset of atopic dermatitis (AD) in infancy. Early epidermal barrier impairment may facilitate the epicutaneous penetration of atopens. OBJECTIVE: To correlate transepidermal water loss (TEWL) and aeroallergen sensitization in infants with AD. METHODS: In this cross-sectional study we enrolled 59 AD children and 30 controls aged 3-12 months. Transepidermal water loss in uninvolved skin, specific immunoglobulin E, atopy patch test (APT) and skin prick tests were performed with respect to seven aeroallergens, i.e., Dermatophagoides pteronyssinus, D. farinae, cat, dog, birch pollen, ambrosia, and cockroach. Environmental conditions were assessed by a questionnaire, and the house dust mite (HDM) concentration was determined in dust samples. RESULTS: Eighty-nine percent of AD infants had a positive APT vs one out of eleven controls. AD infants had a significantly higher mean TEWL than controls (27.4 vs 11.1 g/m(2)/h, P < 0001). Children with two or more positive APT had higher TEWL than the others (31.1 vs 19.0 g/m(2)/h, P < 0.025). No correlation was found between indoor APT results and exposure to HDM, cats, and dogs at home. CONCLUSIONS: This study confirms the high prevalence of delayed sensitization to indoor and outdoor aeroallergens in AD infants, and shows that the higher the TEWL, the higher the prevalence of sensitization to aeroallergens. These data are in favor of a major role of a constitutive epidermal barrier impairment in determining early atopen sensitization in infants with AD.