Sequelae following infantile haemangiomas treated with propranolol.

BACKGROUND: Oral propranolol accelerates the involution of infantile haemangiomas (IHs). However, it is not clear whether IHs treated with oral propranolol are associated with fewer sequelae than when left untreated. OBJECTIVES: To quantify and describe sequelae associated with IHs treated with oral propranolol, and to explore whether treated IHs are associated with fewer sequelae than untreated IHs. MATERIALS & METHODS: This multicentre, retrospective, cohort study included patients with IH treated with oral propranolol ≥2 mg/kg for at least six months, with photographic images available at baseline and at age 4-5 years. A historical comparison cohort comprised 185 patients with untreated IHs. Main outcomes/measures were: IH features, treatment characteristics and type/degree of sequelae. RESULTS: Oral propranolol, most commonly at 2 mg/kg/day (mean duration: nine months), was initiated in 171 patients (mean age: 6.02 months). After treatment, 125 of 171 (73.1%) IHs were associated with no/minimal sequelae. The most common sequelae were telangiectasia (78%), fibrofatty tissue (37%) and anetodermic skin (28%). Deep IHs were associated with significantly fewer sequelae than other subtypes. Ulceration appeared to increase the likelihood of severe sequelae. IHs with a stepped border was associated with more severe sequelae than those with a progressive border (44% versus 27%, p < 0.05). Treated IHs resolved without sequelae or were associated with a sequela that did not need correction in 27.7% more cases than untreated IHs (RR: 1.61; p < 0.001). CONCLUSION: Among IHs treated with oral propranolol, 73% resolved without, or were associated with minimal sequelae. Deep IHs were associated fewer sequelae than other subtypes. Oral propranolol decreased the likelihood of IH sequelae requiring correction.

Novel CYP4F22 mutations associated with autosomal recessive congenital ichthyosis (ARCI). Study of the CYP4F22 c.1303C>T founder mutation.

Mutations in CYP4F22 cause autosomal recessive congenital ichthyosis (ARCI). However, less than 10% of all ARCI patients carry a mutation in CYP4F22. In order to identify the molecular basis of ARCI among our patients (a cohort of ninety-two Spanish individuals) we performed a mutational analysis using direct Sanger sequencing in combination with a multigene targeted NGS panel. From these, eight ARCI families (three of them with Moroccan origin) were found to carry five different CYP4F22 mutations, of which two were novel. Computational analysis showed that the mutations found were present in highly conserved residues of the protein and may affect its structure and function. Seven of the eight families were carriers of a highly recurrent CYP4F22 variant, c.1303C>T; p.(His435Tyr). A 12Mb haplotype was reconstructed in all c.1303C>T carriers by genotyping ten microsatellite markers flanking the CYP4F22 gene. A prevalent 2.52Mb haplotype was observed among Spanish carrier patients suggesting a recent common ancestor. A smaller core haplotype of 1.2Mb was shared by Spanish and Moroccan families. Different approaches were applied to estimate the time to the most recent common ancestor (TMRCA) of carrier patients with Spanish origin. The age of the mutation was calculated by using DMLE and BDMC2. The algorithms estimated that the c.1303C>T variant arose approximately 2925 to 4925 years ago, while Spanish carrier families derived from a common ancestor who lived in the XIII century. The present study reports five CYP4F22 mutations, two of them novel, increasing the number of CYP4F22 mutations currently listed. Additionally, our results suggest that the recurrent c.1303C>T change has a founder effect in Spanish population and c.1303C>T carrier families originated from a single ancestor with probable African ancestry.

Efficacy of Propranolol Between 6 and 12 Months of Age in High-Risk Infantile Hemangioma.

BACKGROUND AND OBJECTIVES: There is no consensus on optimal treatment duration for propranolol in infantile hemangioma (IH). We evaluated the efficacy and safety of oral propranolol solution administered for a minimum of 6 months up to a maximum of 12 months of age in high-risk IH. METHODS: This single-arm, open-label, phase 3 study was conducted in patients aged 35 to 150 days with high-risk IH in 10 hospitals between 2015 and 2017. The study comprised a 6-month initial treatment period (ITP) plus continuation up to 12 months of age if complete success was not achieved, a follow-up, and a retreatment period. Patients received oral propranolol twice daily (3 mg/kg per day). The primary end point was the success rate at the end of the ITP. Furthermore, the persistence of IH response and efficacy of retreatment was evaluated. RESULTS: The success rate after 6 months of treatment was 47%, increasing to 76% at the end of the ITP. Of the patients who achieved success, 68% sustained success for 3 months without treatment, and 24% required retreatment. Of the 8 patients who were retreated, 7 achieved success. Adverse events, reported by 80% of patients, were mild, which were expected in this population or known propranolol side effects. CONCLUSIONS: Oral propranolol administered beyond 6 months and up to 12 months of age meaningfully increases the success rate in high-risk IH. Success was sustained in most patients up to 3 months after stopping treatment. Retreatment was efficacious, and the safety profile satisfactory.

Demodicosis in two patients with a previous history of Langerhans cell histiocytosis.

Demodex mites are commensal organisms rarely found in healthy children. Human demodicosis can be classified as a primary or a secondary form. The secondary form in children usually affects severely immunodepressed children. To our knowledge, this is the first report of human demodicosis associated with Langerhans cell histiocytosis. These cases show that this skin disorder can occur months after completing chemotherapy, without recurrence of the systemic disease.

Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK Signaling.

BACKGROUND: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified RASA1 mutations in 50% of patients with CM-AVM. Herein we studied non-RASA1 patients to further elucidate the pathogenicity of CMs and AVMs. METHODS: We conducted a genome-wide linkage study on a CM-AVM family. Whole-exome sequencing was also performed on 9 unrelated CM-AVM families. We identified a candidate gene and screened it in a large series of patients. The influence of several missense variants on protein function was also studied in vitro. RESULTS: We found evidence for linkage in 2 loci. Whole-exome sequencing data unraveled 4 distinct damaging variants in EPHB4 in 5 families that cosegregated with CM-AVM. Overall, screening of EPHB4 detected 47 distinct mutations in 54 index patients: 27 led to a premature stop codon or splice-site alteration, suggesting loss of function. The other 20 are nonsynonymous variants that result in amino acid substitutions. In vitro expression of several mutations confirmed loss of function of EPHB4. The clinical features included multifocal CMs, telangiectasias, and AVMs. CONCLUSIONS: We found EPHB4 mutations in patients with multifocal CMs associated with AVMs. The phenotype, CM-AVM2, mimics RASA1-related CM-AVM1 and also hereditary hemorrhagic telangiectasia. RASA1-encoded p120RASGAP is a direct effector of EPHB4. Our data highlight the pathogenetic importance of this interaction and indicts EPHB4-RAS-ERK signaling pathway as a major cause for AVMs.

Cutaneous Mucinosis of Infancy: A Rare Congenital Case with Coexisting Progressive, Eruptive, and Spontaneously Involuting Lesions.

Cutaneous mucinosis in infancy is rare. We report an infant with multiple congenital papules distributed over the trunk, neck, and extremities. These papules were mainly dispersed, but they also coalesced into plaques. Histopathologic findings showed features of cutaneous mucinosis of infancy (CMI). Over 2 years of follow-up, we observed that the preexisting lesions on the lower back and left trunk progressively increased in size, and a few new scattered papules continued to appear, mainly on the trunk; several lesions spontaneously resolved with no further complications. CMI is considered to be a persistent cutaneous disorder, even though spontaneously regressing cases have rarely been reported. This case demonstrates the broad clinical spectrum of CMI, with progressive, eruptive, and spontaneously involuting lesions all present in the same patient. This condition should be considered in the differential diagnosis of congenital or infantile-onset papules and plaques, especially those yellowish in color.

Esclerodèrmia localitzada infantil / Esclerodermia infantile localizada / Juvenile localized scleroderm

L'esclerodèrmia localitzada infantil és una malaltia rara que pot tenir diferents formes de presentació i graus d'afectació. El seu diagnòstic és eminentment clínic i in-clou la història clínica, l'anàlisi de l'aspecte de les lesions i la seva evolució. En cas de dubte es pot fer una biòpsia cutània que confirma la sospita diagnòstica. El tractament més acceptat i amb més bons resultats en l'actualitat és la corticoteràpia endovenosa en combinació amb el meto-trexat. L'objectiu del tractament és tant aturar la progressió de la lesió com reduir les seqüeles, per exemple les con-tractures articulars o les alteracions estètiques. A més del tractament farmacològic també s'aconsella un tractament rehabilitador, especialment en les lesions extenses

La esclerodermia localizada infantil es una enfermedad rara que puede tener diferentes formas de presentación y grados de afectación. Su diagnóstico es clínico e incluye la historia clínica, el análisis del aspecto de las lesiones y su evolución. En caso de duda se puede hacer una biopsia cutánea que confirma la sospecha diagnóstica. El tratamiento más aceptado y con mejores resultados en la actualidad es la corticoterapia endovenosa en combinación con el metotrexato. El objetivo del tratamiento es tanto detener la progresión de la lesión como reducir las secuelas, por ejemplo las contracturas articulares o las alteraciones estéticas. Además del tratamiento farmacológico también se aconseja un tratamiento rehabilitador, especialmente en las lesiones extensas (AU)

Juvenile Localized Scleroderma is a rare disease that can present in various different forms and degrees of involvement. The diagnosis is eminently clinical and medical history includes analysis of the appearance of the lesions and their evolution. If there is any doubt you can do a skin biopsy to confirm the suspected diagnosis. Nowadays the most accepted and successful treatment is intravenous steroids in combination with methotrexate. The treatment goal is to stop the progression of the injury and also reduce the consequences, for example joint contractures o aesthetic alterations. Besides pharmacological treatment, rehabilitation is also advisable, especially in extensive lesions (AU)

Dermatomiositis juvenil / Dermatomiositis juvenil / Juvenile dermatomyositis

La dermatomiositis juvenil, la miopatia inflamatòria més freqüent en pediatria, és una vasculopatia sistèmica que afecta habitualment la pell i el teixit musculoesquelètic, però que també pot afectar el tracte gastrointestinal i altres òrgans. El diagnòstic es basa en els criteris de Bohan i Peter i l'objectiu del tractament inclou el control dels símp-tomes i la prevenció de les complicacions. Un tractament escalonat precoç disminueix l'activitat de la malaltia i mi-llora el pronòstic a llarg termini

La dermatomiositis juvenil, la miopatía inflamatoria más frecuente en pediatría, es una vasculopatía sistémica que afecta habitualmente la piel y el tejido musculoesquelético, pero que también puede afectar el tracto gastrointestinal y otros órganos. El diagnóstico se basa en los criterios de Bohan y Peter y el objetivo del tratamiento incluye el control de los síntomas y la prevención de las complicaciones. Un tratamiento escalonado precoz disminuye la actividad de la enfermedad y mejora el pronóstico a largo plazo (AU)

Juvenile dermatomyositis, the most common inflammatory myopathy in children, is a systemic vasculopathy that usually affects skin and musculoskeletal tissue, but can also affect the gastrointestinal tract and other organs. Diagnosis is based on the criteria of Bohan and Peter and the treatment goal includes controlling symptoms and preventing complications. Staggered early treatment reduces disease activity and improves long-term prognosis (AU)

Epidermal Choristoma of the Tongue Mimicking a Congenital Melanotic Macule.

We report the fifth case of epidermal choristoma of the oral cavity in a Caucasian newborn with a congenital melanotic macule on the dorsum of the tongue. Epidermal choristoma is an exceedingly rare and benign condition probably caused by a developmental abnormality. It is identified according to the presence of normal skin in an abnormal location. Histologically it is identified according to areas of stratified epithelium and hyperpigmentation of the basal layer along with cutaneous adnexal structures (hair follicles, sebaceous or sweat glands). The clinical presentation is variable, but most of the cases described presented with a congenital lingual pigmented macule. These lesions should be included within the differential diagnosis of congenital lingual macules and distinguished from other entities such as congenital lingual melanotic macules and melanocytic lesions. Surgical excision is the treatment of choice. Epidermal choristoma is a benign condition that probably is underdiagnosed because it is a new and rare entity, and dermatologists should be aware of it.

RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation.

Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n = 100), common CM(s) (port-wine stain; n = 100), Sturge-Weber syndrome (n = 37), or isolated AVM(s) (n = 24). Fifty-eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM-AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the "second-hit" hypothesis as a pathophysiological mechanism for CM-AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild-type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up.

Unknown: a congenital nodule on the scapula.

We present a new case of a cutaneous bronchogenic cyst on the scapular area in a 2-year-old boy. The asymptomatic nodule over his right scapula had been detected at birth and had been gradually growing. Cutaneous bronchogenic cysts located near the scapula are extremely rare. The proposed mechanism is that the accessory buds from the tracheobronchial tree/primitive foregut migrated from the thorax in an aberrant manner to lie in a periscapular position. Cutaneous bronchogenic cysts are poorly recognized by clinicians because they lack pathognomonic clinical symptoms. The diagnosis is based on the histopathological findings in the majority of cases. Complete excision and histological examination are indicated to confirm the diagnosis, to relieve symptoms, and to prevent complications, such as infection or malignancy.

Neonatal erythroderma as a first manifestation of Menkes disease.

Menkes disease is an X-linked recessive lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration, connective tissue disturbances, and peculiar kinky hair are the main manifestations. The low serum copper and ceruloplasmin suggests the diagnosis, which is confirmed by mutation analysis of the ATP7A gene. We report an exceptional presentation of classic Menkes disease with neonatal erythroderma. Genetic study revealed a deletion in exons 8 to 12 in the ATP7A gene. This study could allow pediatricians and pediatric dermatologists to diagnose the disorder as early as possible to establish prompt treatment with parenteral copper-histidine supplementation to improve prognosis.

Prevalence of autosomal recessive congenital ichthyosis: a population-based study using the capture-recapture method in Spain.

BACKGROUND: Previous reports on the prevalence of autosomal recessive congenital ichthyosis (ARCI) were based on single source data, such as lists of members in a patient association. These sources are likely to be incomplete. OBJECTIVES: We sought to describe the prevalence of ARCI. METHODS: We obtained data from 3 incomplete sources (dermatology departments, a genetic testing laboratory, and the Spanish ichthyosis association) and combined them using the capture-recapture method. RESULTS: We identified 144 living patients with ARCI. Of these, 62.5% had classic lamellar ichthyosis and 30.6% had congenital ichthyosiform erythroderma. The age distribution included fewer elderly patients than expected. The prevalence of ARCI in patients younger than 10 years, the best estimate as less subject to bias, was 16.2 cases per million inhabitants (95% confidence interval 13.3-23.0). According to the capture-recapture model, 71% of the patients were not being followed up in reference units, 92% did not have a genetic diagnosis, and 78% were not members of the ichthyosis association. LIMITATIONS: The prevalence of ARCI in Spain and findings related to the Spanish health care system might not be generalizable to other countries. CONCLUSIONS: The prevalence of ARCI is higher than previously reported. Many patients are not being followed up in reference units, do not have a genetic diagnosis, and are not members of a patient association, indicating room for improvement in their care. Data suggesting a reduced number of older patients might imply a shorter life expectancy and this requires further study.

Dermatitis del pañal, prevención y tratamiento. Papel del Aloe vera / Preventing and treating nappy rash: the role of Aloe vera

La dermatitis del pañal (DP) es un cuadro clínico frecuente en la infancia, quepuede ser más o menos grave. La causa más frecuente es la irritativa, seguidade la candidiasis. En alguna ocasión puede ser una manifestación más de unaenfermedad cutánea o sistémica. El mejor tratamiento de la DP es la prevención,mediante cambios frecuentes del pañal, limpieza de la zona con agua yjabón suave después de las deposiciones, y aplicación de alguna crema barrera.El Aloe vera es una sustancia natural que tiene unas propiedades antiinflamatorias,antipruriginosas, cicatrizantes y, en determinadas concentraciones,se ha demostrado que tiene efecto bactericida, fungicida y viricida.Pensamos que puede ser útil junto con el óxido de cinc como adyuvante añadidoa un preparado tópico preventivo o terapéutico de la DP (AU)

Nappy rash is a common symptom in infancy which can be more or lessserious. The most frequent cause is irritation, followed by candidiasis. Onoccasions it may be a symptom of a cutaneous or systemic disorder. Themain treatment for nappy rash is prevention by means of frequent nappychanging, cleaning of the area with mild soap and water after depositionsand application of a barrier cream. Aloe vera is a natural substance whichpossesses anti-inflammatory, antipruriginous and healing properties, andat some concentrations it has been proven to have bactericidal, fungicidaland virucidal effects. The authors believe that it may be useful together withzinc oxide as an adjuvant added to a preventive or therapeutic skin preparationfor nappy rash (AU)

Herpes zoster in healthy infants and toddlers after perinatal exposure to varicella-zoster virus: a case series and review of the literature.

Exposure to varicella-zoster virus in utero or during the first months of life is the main risk factor for the development of herpes zoster (HZ) in healthy children. We report a case series of 16 infants and toddlers who presented with HZ after early exposure to varicella-zoster virus. Two patients had recurrences. Despite the severity of the rash in some cases, the benign course and the long-term good prognosis of HZ in healthy children is noteworthy.