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.

[Urticaria in children]. / Urticaire de l'enfant.

The cumulative incidence of urticaria in children is close to 10%. Two forms are described: the superficial form and the deep form, or angioedema. In young children aged under 3 years, urticaria is commonly annular and ecchymotic, and is mistaken for erythema multiforme or acute hemorrhagic edema. Serum sickness-like reaction is a particular form of urticaria characterized by angioedema of the extremities, fever and arthralgia, and it is chiefly drug-induced (cephalosporins). With children, questioning and clinical examination are essential and, in most cases, reveal an etiology. The main causes of acute or recurrent urticaria are viral infections and/or drugs (non-specific histamine release), whereas chronic urticaria is mostly due to physical causes. In developed countries, parasitic infections are rarely the cause. Arguments in favor of a food allergy are as follows: a setting of atopy, onset within one hour of taking the suspect food, absence of fever or infection, a duration of less than 24 hours, possible association with other signs of anaphylaxis, and further recurrence with each new intake of the suspect food. First-line treatment of urticaria without signs of severity consists solely of non-sedating antihistamine (associated with removal of the cause where the latter has been determined). Nearly one-third of cases of urticaria in children progress over a prolonged period of more than 6 weeks, thus constituting chronic urticaria (most often a form of mild recurrent urticaria during episodes of infection and/or medication). Chronic urticaria is very rarely due to an underlying inflammatory disease or a genetic disease such as cryopyrinopathy, and first-line etiological assessment is usually limited to the following tests: CBC, sedimentation speed and/or CRP, and transaminases.

Allergic contact reaction to antiseptics in very young children.

BACKGROUND: Contact dermatitis from topical antiseptic use has been reported mostly in adults, but rare cases of chlorhexidine contact dermatitis have also been described in young children. OBJECTIVE: To evaluate contact allergic dermatitis to antiseptics in young children. METHODS: The children mostly referred for a misdiagnose (cellulitis) were patch tested with a selection of the European baseline series, an antiseptics series and the personal topical products used. RESULTS: Fourteen children (8 boys, 6 girls) received a diagnosis of contact dermatitis to antiseptics between May 2010 and December 2017. The mean age at diagnosis was 38 months (8 months to 8 years); three children only had a personal history of atopy. Chlorhexidine gluconate was positive in seven cases, and benzalkonium chloride in eight cases, and in four cases, both allergens were positive. CONCLUSION: These small case series confirm that both chlorhexidine and benzalkonium chloride are implicated in contact dermatitis from antiseptic use in the paediatric population. We emphasize the initial misdiagnose of these patients, the very young age of the children and the allergenic potential of common antiseptics in non-atopic children. We hypothesize that the systematic use of antiseptics for umbilical cord care could be responsible for the sensitization in newborns.

[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.

Pre- vs. post-pubertal onset of vitiligo: multivariate analysis indicates atopic diathesis association in pre-pubertal onset vitiligo.

BACKGROUND: Limited epidemiological data exist that compare clinical features of pre- and post-pubertal nonsegmental vitiligo. OBJECTIVES: To compare factors associated with pre- and post-pubertal onset vitiligo. PATIENTS AND METHODS: A prospective observational study was conducted of patients with vitiligo attending the clinic between 1 January 2006 and 1 July 2011. The Vitiligo European Task Force questionnaire was completed for each patient and thyroid function and antithyroid antibodies were screened. Other forms of vitiligo (segmental, focal, mucosal, not classifiable) were excluded. RESULTS: A total of 679 patients were included; 422 had post-pubertal and 257 pre-pubertal onset of vitiligo. Vitiligo universalis was seen only in post-pubertal onset. In univariate analysis, there was no significant statistical difference for sex, Koebner phenomenon or disease activity between both groups; thyroid disease or presence of thyroid antibodies was more frequent in post-pubertal onset [odds ratio (OR) 0·31, P < 0·003] whereas atopic dermatitis was more often associated with or preceding pre-pubertal onset (OR 2·42, P = 0·006). In multivariate analysis, halo naevi, family history of vitiligo, premature hair greying, atopic dermatitis and previous episode of spontaneous repigmentation were independently associated with pre-pubertal onset. In contrast, stress as onset factor, personal history of thyroid disease and acrofacial type were associated with post-pubertal onset. CONCLUSIONS: Pre-pubertal onset vitiligo is strongly associated with personal and family history of atopy, suggesting that the predisposing immune background in vitiligo is not limited to autoimmunity, as also noted in alopecia areata. This study also suggests reconsidering the epidemiological data on sex ratio in vitiligo.

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.