Inter- and intra-observer variability in the selection of therapy for infantile hemangiomas among pediatric dermatologists in Spain.

BACKGROUND: Guidelines and expert recommendations on infantile hemangiomas (IH) are aimed at increasing homogeneity in clinical decisions based on the risk of sequelae. OBJECTIVE: The objective was to analyze the inter- and intra-observer agreement among pediatric dermatologists in the choice of treatment for IH. METHODS: We performed a cross-sectional inter-rater and intra-rater agreement study within the Spanish infantile hemangioma registry. Twenty-seven pediatric dermatologists were invited to participate in a survey with 50 clinical vignettes randomly selected within the registry. Each vignette contained a picture of an infantile hemangioma with a clinical description. Raters chose therapy among observation, topical timolol, or oral propranolol. The same survey reordered was completed 1 month later to assess intra-rater agreement. Vignettes were stratified into hemangioma risk categories following the Spanish consensus on IH. The agreement was measured using kappa statistics appropriate for the type of data (Gwet's AC1 coefficient and Gwet's paired t test). RESULTS: Twenty-four dermatologists completed the survey. Vignettes represented 7.8% of the Spanish hemangioma registry. The inter-rater agreement on the treatment decision was fair (AC1  = 0.39, 95% confidence interval [CI]: 0.30-0.47). When stratified by risk category, good agreement was reached for high-risk hemangiomas (AC1  = 0.77, 95% CI: 0.51-1.00), whereas for intermediate- and low-risk categories, the agreement was only fair (AC1 0.31, 95% CI: 0.16-0.46 and AC1  = 0.38, 95% CI: 0.27-0.48, respectively). Propranolol was the main option for high-risk hemangiomas (86.4%), timolol for intermediate-risk (36.8%), and observation for low-risk ones (55.9%). The intra-rater agreement was good. The inter-rater agreement between pediatric dermatologists on the treatment of IH is only fair. Variability was most significant with intermediate- and low-risk hemangiomas.

Incidence of Melanoma in Catalonia, Spain, Is Rapidly Increasing in the Elderly Population. A Multicentric Cohort Study.

The incidence of melanoma has been increasing worldwide during recent decades. The objective of the study was to analyse the trends in incidence for in situ and invasive melanoma in the Spanish region of Catalonia during the period of 2008-2017. We designed a cross-sectional study with an age-period-cohort analysis of melanoma patient data from the Network of Melanoma Centres in Catalonia. Our database covered a population of over seven million and included a total of 8626 patients with incident melanoma. The main outcome measures were crude and age-standardised incidence rates to the European 2013 standard population. Joinpoint regression models were used to evaluate the population trends. We observed an increase in the age-standardised incidence rate (per 100,000 population) of all melanoma subtypes from 11.56 in 2008 to 13.78 in 2017 with an average annual percent change (AAPC) of 3.5%. This incidence increase was seen exclusively in the older population. Moreover, the stratified analysis showed a statistically significant increase in the age-standardised incidence rate for invasive (AAPC 2.1%) and in situ melanoma (AAPC 6.5%). In conclusion, the incidence of melanoma has continued to increase in the elderly population over recent decades, with a rapidly increasing trend of in situ melanomas and the lentigo maligna subtype.

Increasing incidence of lentigo maligna and lentigo maligna melanoma in Catalonia.

BACKGROUND: Recent epidemiological studies suggest that past data where superficial spreading melanoma was by far the most common subtype of melanoma may not reflect current patterns of sun exposure or other risk factors more involved in other subtypes of melanoma as lentigo maligna (LM) or lentigo maligna melanoma (LMM). METHODS: In order to measure the current situation in our country, all cases of LM and LMM diagnosed in 23 hospitals in Catalonia, from 2000 to 2007, were recorded. RESULTS: Although for the global period LM/LMM represented only 8.4% of cases, an increasing trend in this percentage was observed throughout the study period (from 6.9% [27 cases] in 2000 to 13.1% [94 cases] in 2007). Also, an increasing incidence of LM/LMM was observed, especially in chronically sun-exposed areas (85.5% involving the head and neck region). During the 8 years of the registry, the mean Breslow thickness of LMM remained stable. However, the increase in the number of LM (in situ) cases was significantly higher than the increase of the invasive ones. CONCLUSIONS: An important observation from this data is that aging of population and current sun exposure patterns could keep increasing the incidence of LM/LMM, which may become an important public healthcare problem, over the other histological subtypes. In order to establish primary or secondary preventive measures to the LM/LMM risk-population, it is imperative to highlight the importance of chronic sun damage as a melanoma risk factor, and not only sunburn, most commonly addressed in melanoma prevention campaigns.

Linear Unilateral Basaloid Follicular Hamartoma Following Blaschko's Lines: Two Case Reports and Review of the Literature.

Basaloid follicular hamartoma (BFH) is a rare follicular malformation characterized by variable clinical presentations and identical histopathologic features. We present the cases of a 3-month-old boy and an 8-year-old boy with linear unilateral BFH. To the best of our knowledge, only 14 cases of linear unilateral BFH have been described in the English-language literature.

Hypofractionated high-dose-rate plesiotherapy in nonmelanoma skin cancer treatment.

PURPOSE: Nonmelanoma skin cancer (NMSC) is the commonest cancer in humans. NMSC treatment currently includes surgery, radiation therapy, and topical approaches. The objective was to analyze and compare the outcomes, toxicity, and cosmesis of NMSC treated by two hypofractionated high-dose-rate (HDR) plesiotherapy techniques. METHODS AND MATERIALS: A retrospective institutional clinical study of 134 basal cell or squamous cell skin carcinomas treated at Radiation Oncology Department. Lesions were treated from November 2006 to December 2011 with a moderate hypofractionated HDR plesiotherapy using a fixed applicator or a customized mold. RESULTS: After a median follow-up of 33 months, overall disease-free survival at 3 and 5 years was 95.12% and 93.36%, respectively. For Leipzig applicator, disease-free survival at 3 years was 94.9% and 94.9% at 5 years, for customized mold was 93.1% at 3 years and 88% at 5 years. Complete regression was achieved in 98% of lesions. Two lesions persisted after treatment; both had been treated by a Leipzig applicator. Six lesions suffered local recurrence (five Leipzig applicators and three molds, p = 0.404). Grade <2 acute toxicity noted in 57.3% of patients. Only 2.2% of lesions had Grade 4 acute toxicity. Borderline significant increase of toxicity was associated with customized molds (p = 0.067). Larger tumors were associated with higher acute skin toxicity. The cosmesis outcomes were excellent or good in 82% of patients, fair in 13%, and not available in 5%. CONCLUSIONS: Hypofractionated HDR plesiotherapy is an effective and well-tolerated treatment for NMSC with different toxicity levels depending on the plesiotherapy technique used.

Melanoma incidence increases in the elderly of Catalonia but not in the younger population: effect of prevention or consequence of immigration?

All cases of MM diagnosed in 23 hospitals in Catalonia, from 2000 to 2007 were recorded and melanoma incidence calculated and adjusted for the European standard population via the direct method. The age standardised rate/100,000 inhabitants varied from 6.74 in 2000 to 8.64 in 2007 for all melanomas and from 4.79 to 5.80 for invasive MMs; the Breslow thickness was stable during the period. The increase in invasive melanoma incidence in the elderly was remarkable, the crude rate/100,000 inhabitants increasing from 11.04 (2000) to 15.49 (2007) in the 60-64 year population, while remaining more stable in the 30-34 year range, from 3.97 in 2000 to 4.55 in 2007, and with a tendency to decrease from 5.1 in 2000 to 2.5 in 2007 for the age range of 25-29 years. These lower age ranges are much more affected by immigration. Despite the large immigrant population (nearly one million immigrants arrived in Catalonia during the study period from countries with a low melanoma incidence), melanoma incidence in our region has risen considerably and this trend is likely to persist in the near future.

A new KRT16 mutation associated with a phenotype of pachyonychia congenita.

Pachyonychia congenita is a rare, autosomal dominant genetic disease characterized by painful palmoplantar keratoderma and hypertrophic nail dystrophy. This disorder is caused by mutations in any one of five cytoskeletal keratin proteins, K6a, K6b, K6c, K16 and K17. Here, we describe a new p.Leu421Pro (c.1262T>C) mutation in the highly conserved helix termination motif of K16 in a large Spanish family. Bioinformatic analyses as well as previous descriptions in the literature of homologous mutations in other keratin-coding genes show that this mutation is probably causative of the disease.

Liquen estriado en un lactante de 5 meses / Lichen striatus on a 5-month-old infant

Introducción. El liquen estriado es una dermatosis benigna que afecta a niños en un rango etario amplio, con un pico de incidencia en la edad preescolar y predilección por el sexo femenino. Afecta principalmente los miembros y típicamente en forma unilateral. Su rasgo clínico distintivo es su distribución, que sigue las líneas de Blaschko. Las características clínicas permiten su diagnóstico sin necesidad de recurrir a exámenes complementarios. Caso clínico. Se presenta un lactante varón de 5 meses de vida, refiriendo sus padres una erupción en la piel de tres semanas de evolución que afectaba antebrazo y tórax derecho. Previo a la consulta, se instauró tratamiento con crema hidratante sin mejoría del exantema. Su morfología y su distribución sugirieron el diagnóstico presuntivo. Comentarios. El liquen estriado es una patología dermatológica de características clínicas y evolutivas distintivas, que afecta principalmente a niños entre los 3 meses y los 15 años de edad. Dada su evolución autolimitada y sin complicaciones, sólo requiere un seguimiento clínico evolutivo hasta su resolución entre 3 a 24 meses. Dichas peculiaridades hacen del pediatra el referente para su diagnóstico y seguimiento evolutivo, transmitiendo a los padres el carácter benigno de la erupción, sin necesidad de dar un tratamiento específico (AU)

Background. Lichen striatus is a benign dermatosis that affects children in a wide age range, with a peak incidence in preschool and predilection for females. It mainly affects the limbs and typically unilaterally. Its distinctive clinical feature is its distribution along the Blaschko lines. Its clinical features enable the diagnosis without need for additional tests. Case report. We report a 5-month-old male infant, whose parents described a rash of 3 weeks duration that affected right forearm and chest. Prior to the consultation he was treated with moisturizer without improvement of the rash. Its morphology and distribution suggested the presumptive diagnosis. Comments. Lichen striatus is a dermatological pathology with distinctive evolutionary and clinical features, that mainly affects children between 3 months and 15 years of age. Given its self-limited and uncomplicated course, it only requires clinical follow-up until resolution from 3 to 24 months. These peculiarities make the pediatrician the referent doctor for diagnosis and follow-up, explaining its benign self-limited evolution without a specific treatment to parents (AU)

Revertant mosaicism due to a second-site mutation in COL7A1 in a patient with recessive dystrophic epidermolysis bullosa.

Despite the high incidence of revertant mosaicism (35%) in patients with the genetic skin disease epidermolysis bullosa (EB) due to correcting mutations in the genes COL17A1 and LAMB3, revertant mosaicism has not been described for COL7A1 until recently. Mutations in COL7A1 are responsible for the most devastating form of EB in adults, which is characterized by cocooned "mitten" deformities of the hands. This report shows in vivo reversion of an inherited COL7A1 mutation in a patient with recessive dystrophic EB who was homozygous for the frameshift mutation COL7A1:c.6527insC,p.2176FsX337. The patient exhibited a patch of clinically healthy revertant skin on her left forearm. The second-site mutation c.6528delT, which is present in revertant keratinocytes, resulted in correction of the reading frame. As the new CCC codon codes for the same amino acid proline as the wild-type codon CCT, the revertant cells expressed wild-type type VII collagen polypeptide, leading to restoration of skin function. We hypothesize that, on careful examination, revertant mosaicism might be found to be more common in patients with type VII collagen-deficient EB. Furthermore, the revertant keratinocytes might offer the possibility to explore cell-based therapeutic strategies, by culturing in vitro and subsequently grafting as part of bioengineered dermo-epidermal substitutes on affected skin.

Role of the CDKN2A locus in patients with multiple primary melanomas.

PURPOSE: We have studied a consecutive case series of patients with multiple primary melanoma (MPM) for the involvement of the melanoma susceptibility loci CDKN2A and CDK4. PATIENTS AND METHODS: One hundred four MPM patients (81 patients with two primary melanomas, 14 with three, five with four, one with five, two with six, and one with seven) were included. RESULTS: Seven different CDKN2A germline mutations were identified in 17 patients (16.3%). In total, we identified 15 CDKN2A exon 2, one exon 1alpha missense mutation, and one exon 1beta frameshift mutation. The age of onset was significantly lower and the number of primary melanomas higher in patients with mutations. CDKN2A mutations were more frequent in patients with familial history of melanoma (35.5%) compared with patients without (8.2%), with a relative risk (RR) of 4.32 (95% CI, 1.76 to 10.64; P = .001), and in patients with more than two melanomas (39.1%) compared with patients with only two melanomas (10%) with an RR of 3.29 (95% CI, 1.7 to 6.3; P = .002). The A148T polymorphism was more frequent in patients with MPMs than in the control population (P = .05). A variant of uncertain significance, A127S, was also detected in one patient. No CDK4 mutations were identified, suggesting that it has a low impact in susceptibility to MPM. CONCLUSION: MPM patients are good candidates for CDKN2A mutational screening. These patients and some of their siblings should be included in a program of specific follow-up with total body photography and digital dermoscopy, which will result in the early detection of melanoma in this subset of high-risk patients and improve phenotypic characterization.

The ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC): report of five cases.

We report five patients from two different pedigrees with the ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC). All had features of ectodermal dysplasia, but only three had limb ectrodactyly and orofacial clefting. The present patients illustrate the great phenotypic variability in the EEC syndrome. As no single feature, including any of the three cardinal signs, is mandatory for syndrome diagnosis, a meticulous examination of all family members is needed.