Cost-Effectiveness Analysis of Abrocitinib Compared with Other Systemic Treatments for Severe Atopic Dermatitis in Spain.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by itchy, painful, and dry skin. Despite the great number of available therapies, economic evaluations are still needed to provide evidence on their cost efficiency. This research aimed to evaluate the cost effectiveness of the Janus kinase (JAK) inhibitor abrocitinib (200 mg) compared with dupilumab (300 mg), tralokinumab (300 mg), baricitinib (2 and 4 mg), and upadacitinib (15 and 30 mg) for the treatment of patients with severe AD from the Spanish National Health System (NHS) perspective. METHODS: A hybrid model consisting of a decision tree linked to a Markov model was developed to estimate costs, quality-adjusted life-years (QALYs), total years in response and incremental cost-per-QALY gained (willingness-to-pay [WTP] threshold: €25,000/QALY). Adults with severe AD entered the decision tree and response (75% reduction in baseline Eczema Area and Severity Index score, EASI-75) was considered at 16 and 52 weeks. After this time, patients entered the Markov model (remainder of the 10-year time horizon), which consisted of three health states: maintenance with active therapy, subsequent treatment, or death. All costs were presented in 2022 euros (€). Additionally, cost per number-needed-to-treat (NNT) was calculated for abrocitinib and dupilumab based on a head-to-head post-hoc analysis. RESULTS: Abrocitinib 200 mg was dominant (i.e., lower incremental costs and higher incremental benefit) compared with all studied alternatives (dupilumab 300 mg, tralokinumab 300 mg, baricitinib 2 and 4 mg, upadacitinib 15 and 30 mg) with a QALYs gain of 0.49, 0.60, 0.64, 0.43, 0.45, and 0.08, respectively, and per-person costs savings of €22,097, €24,140, €14,825, €7,116, €12,805, and €45,189, respectively. Considering the WTP threshold, abrocitinib was dominant or cost effective compared with all alternatives for most simulations. Additionally, abrocitinib was dominant compared with all alternatives when evaluating the cost effectiveness over a 5-year time horizon. NNT showed that abrocitinib was dominant versus dupilumab. CONCLUSIONS: The results of the study show that abrocitinib is a cost-effective therapy compared with other JAK inhibitors and biological therapies from the Spanish NHS perspective.

A novel pathogenic variation of DOCK6 gene: the genotype-phenotype correlation in Adams-Oliver syndrome.

BACKGROUND: Adams-Oliver syndrome (AOS) (#614,219) is a multiple malformation disorder characterized by the presence of aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). METHODS AND RESULTS: We describe a confirmed case of AOS with a novel pathogenic variation in Dedicator Of Cytokinesis 6 (DOCK6) gene, with neurological abnormalities, characterized by the presence of a multiple malformation entity with extensive cardiological and neurological abnormalities. CONCLUSIONS: In AOS, genotype-phenotype correlations have been described. DOCK6 mutations appear to be related with congenital cardiac and central nervous system malformations associated with intellectual disability, as illustrated in the present case.

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.

Juvenile Xanthogranuloma as Differential Diagnosis of a Vulvar Mass: A Case Report.

Vulvar masses in children are an unusual finding but their differential diagnosis is extensive. In case of solid masses, rhabdomyosarcoma (RMS) must always be considered due to the fact that it is the most common tumor in external genitals during childhood. However, RMS has a radiological appearance very similar to juvenile xanthogranuloma (JXG). We present a 16-month-old girl with a 2 cm solid mass on her left labia majora, with four overlying cutaneous papules. After imaging tests, an excisional biopsy was programmed due to high malignancy suspicion. Histopathology of the mass and one of the papules was diagnostic for JXG. After a 12-month follow-up, the patient shows no signs of relapse or complication. Deep JXG is an uncommon entity in childhood and exceptional in the genital area. Therefore, it must be included in the differential diagnosis of a solid vulvar mass, especially if accompanying yellowish xanthomatous cutaneous lesions are present.

KRAS mutation identified in a patient with melorheostosis and extended lymphangiomatosis treated with sirolimus and trametinib.

Detection of KRAS mutation in skin biopsy in a patient with melorheostosis, lymphantiomatosis and vascular stenosis. She was successfully treated with trametinib.

Ectodermal dysplasia with congenital adermatoglyphia (Basan syndrome): Report of two cases presenting with extensive congenital milia.

Basan syndrome is a rare autosomal dominant genodermatosis, characterized by rapidly healing congenital acral bullae, congenital milia and adermatoglyphia (lack of finger and toeprints). This type of ectodermal dysplasia has been infrequently reported in the literature. A pathogenic mutation in the SMARCAD1 gene has been demonstrated to cause this rare disorder.

Pigmented Dermatofibrosarcoma Protuberans: Description of a pediatric case. / Dermatofibrosarcoma protuberans pigmentado: Descripción de un caso pediátrico.

INTRODUCTION: Bednar tumor is a rare low-grade sarcoma considered the pigmented variant of dermatofibrosarco ma protuberans (DFSP). OBJECTIVE: To describe the clinical and histopathological characteristics, treatment and evolution of this rare neoplasm. CLINICAL CASE: A 9-year old female presented with a 2-year history of an indurated, asymptomatic papule on the back of her fourth left toe. The incisio nal biopsy was compatible with pigmented DFSP. The immunohistochemical study showed intense positivity for CD34 throughout the lesion, with negative factor XIIIa. We complemented the study with molecular cytogenetics (FISH) for PDGFB gene (22q13.1) which showed an abnormal pattern in tumor cells, but not in the melanocytes or the peritumoral skin. Delayed Mohs surgery and skin substitute dressing were performed without neoplastic recurrence at 5 years of follow up. Conclu sion: Pigmented DFSP is a low-grade sarcoma that is very rare in pediatric patients. The classical and pigmented variants should be suspected in the presence of a single papulonodular lesion of slow and progressive growth, with presence of spindle cells with storiform pattern in the biopsy and positive immunohistochemical study for CD34. It is an entity with good prognosis, with little risk of recurren ce and metastasis, if complete excision is achieved.

Dermatofibrosarcoma protuberans pigmentado: descripción de un caso pediátrico / Pigmented Dermatofibrosarcoma Protuberans: description of a pediatric case

Resumen: Introducción: El tumor de Bednar es un sarcoma de bajo grado, infrecuente, considerado como la variante pigmen tada del dermatofibrosarcoma protuberans (DFSP). Objetivo: describir las características clínicas, histopatológicas, el tratamiento y la evolución de un caso pediátrico de esta infrecuente neoplasia. Caso Clínico: escolar de 9 años que consultó por una pápula indurada asintomática, de dos años de evolución en el dorso del cuarto dedo del pie izquierdo. La biopsia incisional de la lesión fue com patibles con un DFSP pigmentado. El estudio inmunohistoquímico mostró positividad intensa para CD34 en toda la lesión, con factor XIIIa negativo. Se complementó el estudio de la pieza histológica con citogenética molecular FISH para el gen PDGFB (22q13.1) el cual reflejó un patrón anómalo en las células tumorales, no así en los melanocitos ni en la piel peritumoral. Se realizó cirugía micrográfica de Mohs diferida con cobertura mediante sustituto dérmico, sin recidiva ni recurrencia tumoral a los 5 años de seguimiento. Conclusiones: El DFSP pigmentado es un sarcoma de bajo grado, que muy infrecuentemente se presenta en pacientes pediátricos. Las variantes clásica y pigmentada deben ser sospechadas ante una lesión papulonodular única, de crecimiento lento y progresivo, con presencia de células fusiformes con patrón estoriforme en la biopsia y con estudio inmunohistoquímico positi vo para CD34. Es una entidad con buen pronóstico, con escaso riesgo de recurrencia y metástasis, si se logra la realización de una extirpación completa.

Abstract: Introduction: Bednar tumor is a rare low-grade sarcoma considered the pigmented variant of dermatofibrosarco ma protuberans (DFSP). Objective: To describe the clinical and histopathological characteristics, treatment and evolution of this rare neoplasm. Clinical Case: A 9-year old female presented with a 2-year history of an indurated, asymptomatic papule on the back of her fourth left toe. The incisio nal biopsy was compatible with pigmented DFSP. The immunohistochemical study showed intense positivity for CD34 throughout the lesion, with negative factor XIIIa. We complemented the study with molecular cytogenetics (FISH) for PDGFB gene (22q13.1) which showed an abnormal pattern in tumor cells, but not in the melanocytes or the peritumoral skin. Delayed Mohs surgery and skin substitute dressing were performed without neoplastic recurrence at 5 years of follow up. Conclu sion: Pigmented DFSP is a low-grade sarcoma that is very rare in pediatric patients. The classical and pigmented variants should be suspected in the presence of a single papulonodular lesion of slow and progressive growth, with presence of spindle cells with storiform pattern in the biopsy and positive immunohistochemical study for CD34. It is an entity with good prognosis, with little risk of recurren ce and metastasis, if complete excision is achieved.

Lesiones cutáneas aisladas en un neonato: un caso de histiocitosis de Langerhans congénita / Isolated skin lesions in a neonate: A case of congenital Langerhans cell histiocytosis

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Immune dysregulation and Th2 polarization are associated with atopic dermatitis in heart-transplant children: A delicate balance between risk of rejection or atopic symptoms.

Atopic dermatitis (AD) has a high incidence in heart-transplant children, and the reason why there is more AD after transplantation is still unknown. We conducted a cross-sectional study comparing 11 AD and 11 non-AD age-matched heart-transplant children, to assess which immune alterations are related to AD in these patients. AD patients had been transplanted at a younger age compared to non-AD, indicating that age at transplant may be determinant in the onset of AD. The earlier thymectomy in AD heart-transplant children favored the presence of more differentiated phenotypes in the T cell compartment. We observed a clear reduction in the T-helper 1/T-helper 2 (Th1/Th2) ratio in AD children. This Th2 polarization was related to eosinophilia and high immunoglobulin E levels, but also to an impaired regulatory T cell (Treg) suppression, which could be secondary to an exhaustion of the Treg compartment. Interestingly, AD patients were free of rejection episodes (0/11) in comparison to non-AD children (4/11). We propose that a predominant Th2 phenotype may prevent the emergence of Th1 responses associated with graft rejection. A more differentiated Treg phenotype could also play a role in preventing acute rejection in the first year posttransplant. Our findings provide useful insights and knowledge for the better understanding of atopic disorders in transplanted children.

Congenital tufted angioma: A multicenter retrospective study of 30 cases.

BACKGROUND: Recent reports indicate that tufted angioma is a rare vascular neoplasm that manifests more frequently at birth than previously thought. Few studies specifically address congenital presentation. OBJECTIVES: We analyzed the clinicopathological characteristics, clinical course, and treatment of congenital tufted angioma (cTA) and evaluated variables that were indicative of problematic lesions. METHODS: We performed an observational retrospective study of 30 patients with cTA in 9 Spanish hospitals over a 14-year period. Histopathology and immunohistochemistry studies were performed. RESULTS: Congenital tufted angioma mainly affected the limbs (56.67%), followed by the face and/or neck (23.33%). Almost three-quarters of facial cTA were located over the mandibular area. Immunohistochemically, proliferating cells expressed markers of endothelial cells, with some clusters of cells, especially at the periphery of the aggregates, showing positivity for podoplanin. As no associated complications were observed in 66.67% of cases, no treatment was started. LIMITATIONS: Data were collected retrospectively. CONCLUSIONS: Our findings emphasize the clinical features and course of cTA. The possibility of cTA should be considered when a poorly defined congenital infiltrative vascular tumor with(out) overlying hirsutism appears over the mandibular area. Location on the face and/or neck requires a more comprehensive workup, since potentially severe complications often appear early.