Clinical and radiological improvement in Gorham-Stout disease after sirolimus treatment.

BACKGROUND: Gorham-Stout disease (GSD) is a rare syndrome characterized by lymphatic malformations, mainly in bone structures, causing progressive osteolysis. Lymphatic endothelial cell proliferation depends on several growth factors that use the phosphoinositide-3 kinase (PI3K)/Akt pathway and converge on the mammalian target molecule of the rapamycin (mTOR) pathway. These findings have allowed treating GSD with mTOR pathway inhibitors such as sirolimus or everolimus. CASE REPORT: We present the case of a one-year-old female patient referred to our institution after a right femur fracture and progressive limb volume increase, disproportionately to the trauma. After several episodes of soft tissue infections, imaging studies showed pseudarthrosis, lytic lesions, and progressive loss of the right femur that ended in total absence. A femur biopsy showed lymphatic structures positive with D2-40 staining, diagnosing GSD. After six months of non-response to traditional treatments, the limb was disarticulated at the hip level, and oral sirolimus treatment was initiated, showing clinical and radiological improvement with minor lytic lesions and evidence of ossification after 20 months of treatment. CONCLUSIONS: Oral sirolimus treatment for GSD inhibits angiogenesis and osteoclastic activity, stimulating bone anabolism and leading to arrested osteolysis progression and improved ossification, quality of life, and patient prognosis. Therefore, sirolimus should be considered a therapeutic option for this rare disease.

INTRODUCCIÓN: La enfermedad de Gorham-Stout es un trastorno poco frecuente caracterizado por malformaciones linfáticas localizadas sobre estructuras óseas que causan osteólisis progresiva. La proliferación de células endoteliales linfáticas depende de factores de crecimiento que utilizan la vía de la fosfoinositida-3 cinasa (PI3K)/Akt y convergen en la vía de la molécula diana de rapamicina de los mamíferos (mTOR). Este conocimiento ha permitido el tratamiento de esta enfermedad con inhibidores de esta vía como sirolimus o everolimus. CASO CLÍNICO: Se presenta el caso de una paciente de sexo femenino de un año referida a nuestra institución tras presentar fractura de fémur derecho y aumento de volumen de dicha extremidad posterior a un traumatismo. Después de diversos episodios de infecciones de tejidos blandos se realizaron estudios de imagen que mostraron pseudoartrosis, lesiones líticas y ausencia total del fémur derecho, así como una biopsia de fémur que mostró estructuras vasculares positivas con tinción D2-40, diagnosticándose enfermedad de Gorham-Stout. Durante su abordaje, se realizó la desarticulación de la extremidad a nivel de la cadera y se inició tratamiento con sirolimus oral, presentando una mejoría clínica y radiológica con menores lesiones líticas y evidencia de osificación posterior a 20 meses de tratamiento. CONCLUSIONES: El tratamiento con sirolimus oral para la enfermedad de Gorham-Stout inhibe la actividad osteoclástica y la angiogénesis, estimulando el anabolismo óseo que resulta en la detención de la progresión de la osteólisis y una mejoría en la osificación, la calidad de vida y el pronóstico del paciente. Por tal motivo, el sirolimus debe considerarse como una opción terapéutica para esta enfermedad.

Clinical and radiological improvement in Gorham-Stout disease after sirolimus treatment / Mejoría clínica y radiológica en la enfermedad de Gorham-Stout después del tratamiento con sirolimus

Abstract Background: Gorham-Stout disease (GSD) is a rare syndrome characterized by lymphatic malformations, mainly in bone structures, causing progressive osteolysis. Lymphatic endothelial cell proliferation depends on several growth factors that use the phosphoinositide-3 kinase (PI3K)/Akt pathway and converge on the mammalian target molecule of the rapamycin (mTOR) pathway. These findings have allowed treating GSD with mTOR pathway inhibitors such as sirolimus or everolimus. Case report: We present the case of a one-year-old female patient referred to our institution after a right femur fracture and progressive limb volume increase, disproportionately to the trauma. After several episodes of soft tissue infections, imaging studies showed pseudarthrosis, lytic lesions, and progressive loss of the right femur that ended in total absence. A femur biopsy showed lymphatic structures positive with D2-40 staining, diagnosing GSD. After six months of non-response to traditional treatments, the limb was disarticulated at the hip level, and oral sirolimus treatment was initiated, showing clinical and radiological improvement with minor lytic lesions and evidence of ossification after 20 months of treatment. Conclusions: Oral sirolimus treatment for GSD inhibits angiogenesis and osteoclastic activity, stimulating bone anabolism and leading to arrested osteolysis progression and improved ossification, quality of life, and patient prognosis. Therefore, sirolimus should be considered a therapeutic option for this rare disease.

Resumen Introducción: La enfermedad de Gorham-Stout es un trastorno poco frecuente caracterizado por malformaciones linfáticas localizadas sobre estructuras óseas que causan osteólisis progresiva. La proliferación de células endoteliales linfáticas depende de factores de crecimiento que utilizan la vía de la fosfoinositida-3 cinasa (PI3K)/Akt y convergen en la vía de la molécula diana de rapamicina de los mamíferos (mTOR). Este conocimiento ha permitido el tratamiento de esta enfermedad con inhibidores de esta vía como sirolimus o everolimus. Caso clínico: Se presenta el caso de una paciente de sexo femenino de un año referida a nuestra institución tras presentar fractura de fémur derecho y aumento de volumen de dicha extremidad posterior a un traumatismo. Después de diversos episodios de infecciones de tejidos blandos se realizaron estudios de imagen que mostraron pseudoartrosis, lesiones líticas y ausencia total del fémur derecho, así como una biopsia de fémur que mostró estructuras vasculares positivas con tinción D2-40, diagnosticándose enfermedad de Gorham-Stout. Durante su abordaje, se realizó la desarticulación de la extremidad a nivel de la cadera y se inició tratamiento con sirolimus oral, presentando una mejoría clínica y radiológica con menores lesiones líticas y evidencia de osificación posterior a 20 meses de tratamiento. Conclusiones: El tratamiento con sirolimus oral para la enfermedad de Gorham-Stout inhibe la actividad osteoclástica y la angiogénesis, estimulando el anabolismo óseo que resulta en la detención de la progresión de la osteólisis y una mejoría en la osificación, la calidad de vida y el pronóstico del paciente. Por tal motivo, el sirolimus debe considerarse como una opción terapéutica para esta enfermedad.

On-person adaptive evolution of Staphylococcus aureus during treatment for atopic dermatitis.

The opportunistic pathogen Staphylococcus aureus frequently colonizes the inflamed skin of people with atopic dermatitis (AD) and worsens disease severity by promoting skin damage. Here, we show, by longitudinally tracking 23 children treated for AD, that S. aureus adapts via de novo mutations during colonization. Each patient's S. aureus population is dominated by a single lineage, with infrequent invasion by distant lineages. Mutations emerge within each lineage at rates similar to those of S. aureus in other contexts. Some variants spread across the body within months, with signatures of adaptive evolution. Most strikingly, mutations in capsule synthesis gene capD underwent parallel evolution in one patient and across-body sweeps in two patients. We confirm that capD negativity is more common in AD than in other contexts, via reanalysis of S. aureus genomes from 276 people. Together, these findings highlight the importance of the mutation level when dissecting the role of microbes in complex disease.

Concordance between referral and final diagnoses of pediatric patients with vascular malformations.

BACKGROUND: Vascular malformations (VaM) are a heterogeneous group of disorders resulting from the dysmorphogenesis of blood vessels. Although correct classification is relevant to providing adequate treatment according to evidence-based medicine, diagnostic terminology may be misused or need clarification. METHODS: We conducted a retrospective study to measure agreement and concordance between referral and final confirmed diagnoses of 435 pediatric patients with VaM newly referred to the multidisciplinary Vascular Anomalies Clinic (VAC) using Fleiss kappa (κ) concordance analysis. RESULTS: We found fair concordance between referral and confirmed diagnoses of VaM (κ 0.306, p < 0.001). Lymphatic malformations (LM) and VaM associated with other anomalies showed moderate diagnostic concordance (κ 0.593, p < 0.001 and κ 0.469, p < 0.001, respectively). CONCLUSIONS: Continuing medical education strategies are required to improve physician knowledge and diagnostic accuracy in patients with VaM.

INTRODUCCIÓN: Las malformaciones vasculares (MVa) son un grupo heterogéneo de trastornos resultantes de la dismorfogénesis de los vasos sanguíneos. A pesar de que la correcta clasificación es relevante para brindar un adecuado tratamiento de acuerdo con la medicina basada en la evidencia, la terminología diagnóstica podría resultar confusa o utilizarse de manera inapropiada. MÉTODOS: En este estudio retrospectivo se midieron el acuerdo y la concordancia entre los diagnósticos de referencia (o derivación) y los diagnósticos finales confirmados de 435 pacientes pediátricos con MVa recién remitidos a la Clínica de anomalías vasculares (CAV) multidisciplinaria, mediante el análisis de concordancia kappa de Fleiss (κ). RESULTADOS: Se encontró una buena concordancia entre los diagnósticos de referencia (o derivación) y los diagnósticos confirmados de MVa (κ 0.306, p < 0.001). Las malformaciones linfáticas (LM) y las MVa asociadas con otras anomalías presentaron concordancias diagnósticas moderadas (κ 0.593, p < 0.001 y κ 0.469, p < 0.001, respectivamente). CONCLUSIONES: Se requiere de estrategias de educación médica continua para mejorar el conocimiento de los médicos y la precisión diagnóstica de los pacientes con MVa.

Nail involvement in patients with epidermolysis bullosa: A systematic review.

Background: Nail changes in patients with congenital epidermolysis bullosa (EB) are caused by abnormalities of the nail matrix and bed secondary to pathogenic alterations of the dermoepidermal junction. Even though ungual alterations are extremely frequent in these patients, there are scarce studies about their frequency and/or association with subtypes or clinical course of EB. Objectives: To systematically review nail abnormalities in patients with EB reported in the literature. Methods: We searched all published articles in electronic databases until June 2020 reporting patients with EB with detailed descriptions of malformed/diseased nails using specific terms and inclusion/exclusion criteria. Clinical data were extracted by two independent authors. Descriptive statistics were used. Results: We included 36 articles reporting 74 individual patients with a mean age of 28.23 years: 29 (39.2%) had dominant dystrophic EB, 27 (36.4%) had junctional EB, 8 (10.8%) had EB simplex, 6 (8.1%) had Kindler syndrome and 4 (5.4%) had recessive dystrophic EB. The most common abnormalities were dystrophic nails (48.6%), anonychia (43.2%) and pachyonychia (40.5%). Anonychia was considered the most severe abnormality and was reported more frequently in patients with junctional (62.9%) and recessive dystrophic EB (50%). Multiple organ involvement was present in 52.7% of patients. Patients with severe junctional epidermolysis bullosa and recessive dominant epidermolysis bullosa presented anonychia since birth. Conclusions: In this summary of nail abnormalities in patients with EB, anonychia was more frequent in patients with severe EB subtypes and multiple organ involvement. Further prospective studies are required to understand the associations between nail abnormalities in specific EB subtypes and/or patient outcomes.

Concordance between referral and final diagnoses of pediatric patients with vascular malformations / Concordancia entre el diagnostico de referencia y final de pacientes pediátricos con malformaciones vasculares

Abstract Background: Vascular malformations (VaM) are a heterogeneous group of disorders resulting from the dysmorphogenesis of blood vessels. Although correct classification is relevant to providing adequate treatment according to evidence-based medicine, diagnostic terminology may be misused or need clarification. Methods: We conducted a retrospective study to measure agreement and concordance between referral and final confirmed diagnoses of 435 pediatric patients with VaM newly referred to the multidisciplinary Vascular Anomalies Clinic (VAC) using Fleiss kappa (κ) concordance analysis. Results: We found fair concordance between referral and confirmed diagnoses of VaM (κ 0.306, p < 0.001). Lymphatic malformations (LM) and VaM associated with other anomalies showed moderate diagnostic concordance (κ 0.593, p < 0.001 and κ 0.469, p < 0.001, respectively). Conclusions: Continuing medical education strategies are required to improve physician knowledge and diagnostic accuracy in patients with VaM.

Resumen Introducción: Las malformaciones vasculares (MVa) son un grupo heterogéneo de trastornos resultantes de la dismorfogénesis de los vasos sanguíneos. A pesar de que la correcta clasificación es relevante para brindar un adecuado tratamiento de acuerdo con la medicina basada en la evidencia, la terminología diagnóstica podría resultar confusa o utilizarse de manera inapropiada. Métodos: En este estudio retrospectivo se midieron el acuerdo y la concordancia entre los diagnósticos de referencia (o derivación) y los diagnósticos finales confirmados de 435 pacientes pediátricos con MVa recién remitidos a la Clínica de anomalías vasculares (CAV) multidisciplinaria, mediante el análisis de concordancia kappa de Fleiss (κ). Resultados: Se encontró una buena concordancia entre los diagnósticos de referencia (o derivación) y los diagnósticos confirmados de MVa (κ 0.306, p < 0.001). Las malformaciones linfáticas (LM) y las MVa asociadas con otras anomalías presentaron concordancias diagnósticas moderadas (κ 0.593, p < 0.001 y κ 0.469, p < 0.001, respectivamente). Conclusiones: Se requiere de estrategias de educación médica continua para mejorar el conocimiento de los médicos y la precisión diagnóstica de los pacientes con MVa.

Systemic treatment for severe atopic dermatitis in children: a case series / Tratamiento sistémico para dermatitis atópica grave en niños: una serie de casos

Abstract Background: Atopic dermatitis (AD) is children's most frequent chronic inflammatory skin disease. In most patients, this condition is controlled with topical treatments; however, some patients with severe AD do not respond to these treatments, requiring systemic therapy. There is insufficient information about the ideal dose, time of use, clinical response, and safety of systemic therapy in children with severe AD. This study described the clinical characteristics of patients with severe AD who required systemic treatment, drugs used, their clinical course, adverse effects, and associated complications. Methods: We conducted a retrospective review of the records of pediatric patients with severe AD treated in the Dermatology Clinic, Instituto Nacional de Pediatría (2000 to 2018), who required systemic treatment for more than 3 months. Results: We included 21 patients. The mean age at disease onset was 3.31 years. The drugs used were methotrexate (57.1%), thalidomide (38%), prednisone (42.8%), azathioprine (19%), mycophenolate mofetil (9.5%), cyclosporine (4.7%), and systemic steroids as bridging therapy (42.8%). Adverse effects were mild and were observed in two patients (9.5%) treated with methotrexate and mycophenolate mofetil. Conclusions: Methotrexate was the most frequently used drug in > 50% of the patients, and most patients attained remission. Cyclosporine, azathioprine, and mycophenolate mofetil were also effective. Side effects were mild and infrequent. Comparative studies of systemic treatments for severe AD in the pediatric population are necessary.

Resumen Introducción: La dermatitis atópica (DA) es la enfermedad inflamatoria crónica de la piel más común en niños. En la mayoría de los pacientes la enfermedad se controla con tratamientos tópicos; sin embargo, algunos pacientes con DA grave no responden a estos tratamientos, por lo que requieren de terapia sistémica. Existe poca información acerca de la dosis ideal, tiempo de uso, respuesta clínica y seguridad del tratamiento sistémico en niños con DA grave. Se realizó este estudio para describir las características clínicas de pacientes con DA grave que requirieron un tratamiento sistémico, los medicamentos utilizados, la evolución clínica, los efectos secundarios y las complicaciones asociadas. Métodos: Se llevó a cabo una revisión retrospectiva de los expedientes de pacientes pediátricos con DA grave atendidos en el Servicio de Dermatología, Instituto Nacional de Pediatría (2000 a 2018), que hayan requerido tratamiento sistémico por más de 3 meses. Resultados: Se incluyeron 21 pacientes. La media de edad de inicio de la enfermedad fue de 3.31 años. Los fármacos utilizados fueron metotrexato (57.1%), talidomida (38%), prednisona (42.8%), azatioprina (19%), mofetil micofenolato (9.5%), ciclosporina (4.7%) y esteroides sistémicos como terapia puente (42.8%). Se observaron efectos secundarios leves en dos pacientes (9.5%) tratados con metotrexato y mofetil micofenolato. Conclusiones: El metotrexato fue el medicamento utilizado en más del 50% de los pacientes con remisión en la mayoría de ellos. La ciclosporina, azatioprina y mofetil micofenolato también fueron efectivos. Los efectos secundarios fueron leves y poco frecuentes. Es necesario realizar estudios comparativos de tratamientos sistémicos para DA grave en la población pediátrica.

Nutritional status of pediatric patients with epidermolysisbullosa. A cross-sectional study / Estado nutricional de pacientes pediátricos con epidermólisis ampollosa. Un estudio transversal

Epidermolysis bullosa (EB) is a genetic disorder with con-tinuous formation of blisters and erosions in the skin and mu-cous membranes as well as multi-systemic involvement.Patients are at high-risk of malnutrition due to decreased foodintake and increased nutrient demand. This cross-sectionalretrospective study evaluated the daily caloric intake and nu-tritional status of pediatric patients with EB at a specializedclinic through anthropometric measurements and estimationof the daily intake by 24-hour dietary recall. We used the Waterlow and World Health Organization (WHO) malnutritionclassification schemes. Descriptive statistics were used. Weincluded 17 patients with a mean age of 8.4 years (SD 4.6),82.3% had malnutrition. Those with more severe subtypes,junctional and recessive dystrophic EB, had acute superim-posed on chronic malnutrition (100% and 63.4% respec-tively), wasting (100% and 72.6%), and stunting (0% and54.4%) more frequently. Most patients required supplemen-tation (caloric 76.4% and vitamin/mineral 100%). We concluded that there is a high frequency of malnutritionin our EB patients. Although their energy requirements is cal-culated to be increased in 100-150% of the estimate, our pa-tients only reach 73.1% of that, thus requiring supplementa-tion. Patients with more severe subtypes of EB had chronicmalnutrition more frequently. Even though malnutrition isclosely linked to wound healing and adequate growth and de-velopment of patients, there are few studies about nutritionin EB worldwide. We believe evaluating the nutritional status of these patients is the first step to identifying deficiencies, of-fering adequate comprehensive medical care and establishingnutritional interventions in a timely manner.(AU)

The Skin Microbiome of Patients With Atopic Dermatitis Normalizes Gradually During Treatment.

Background: Atopic dermatitis (AD) is characterized by an altered skin microbiome dominantly colonized by S. aureus. Standard treatment includes emollients, anti-inflammatory medications and antiseptics. Objectives: To characterize changes in the skin microbiome during treatment for AD. Methods: The skin microbiomes of children with moderate-to-severe AD and healthy children were investigated in a longitudinal prospective study. Patients with AD were randomized to receive either standard treatment with emollients and topical corticosteroids or standard treatment with the addition of dilute bleach baths (DBB) and sampled at four visits over a three-month period. At each visit, severity of AD was measured, swabs were taken from four body sites and the composition of the microbiome at those sites was assessed using 16S rRNA amplification. Results: We included 14 healthy controls and 28 patients. We found high relative abundances of S. aureus in patients, which correlated with AD severity and reduced apparent alpha diversity. As disease severity improved with treatment, the abundance of S. aureus decreased, gradually becoming more similar to the microbiomes of healthy controls. After treatment, patients who received DBB had a significantly lower abundance of S. aureus than those who received only standard treatment. Conclusions: There are clear differences in the skin microbiome of healthy controls and AD patients that diminish with treatment. After three months, the addition of DBB to standard treatment had significantly decreased the S. aureus burden, supporting its use as a therapeutic option. Further study in double-blinded trials is needed.

Incontinentia pigmenti: multisistemic genodermatosis.

Incontinentia pigmenti is an X-linked genodermatosis generally lethal in males; thus, it presents almost exclusively in females. It is caused by a loss-of-function mutation in the IKBKG (inhibitor of kappa polypeptide gene enhancer in B cells, kinase gamma) gene that prevents the NFÐºß (nuclear factor kappa-light-chain-enhancer of activated B cells) protein from migrating to the nucleus to begin the transcription of factors that amplify the immune response and prevent apoptosis. Consequently, mutant cells become vulnerable to apoptosis when exposed to cytokines and, in turn, lead to vaso-occlusion and ischemia of tissues, such as the skin, the central nervous system and the retina. Dermatological lesions are characteristic and occur in 100% of patients; they are distributed along Blaschko lines, which follow the pattern of migration of skin cells in embryogenesis. The cutaneous manifestations follow a sequence of four phases since birth: vesicular, verrucous, hyperpigmented and hypopigmented. These lesions are relevant for the disease because they guide the clinician towards the diagnosis. Additionally, they are accompanied by neurological abnormalities, such as seizures, and multiple ophthalmological manifestations, such as retinal detachment. Incontinentia pigmenti patients with no clinically significant ophthalmic or neurological compromise have a good prognosis and a normal life expectancy. The abnormalities present are permanent, which can be a cause of concern for the patients.

La incontinentia pigmenti es una genodermatosis ligada al cromosoma X, generalmente letal en los hombres. Está causada por una mutación con pérdida de función en el gen IKBKG (inhibitor of kappa polypeptide gene enhancer in B cells kinase gamma), que impide que la proteína NFÐºß (nuclear factor kappa-light-chain-enhancer of activated B cells) migre al núcleo y comience la transcripción de factores que amplifican la respuesta inmunitaria y previenen la apoptosis. Por tanto, las células mutantes se vuelven vulnerables a la apoptosis cuando son expuestas a citocinas y provocan vaso-oclusión e isquemia de tejidos como la piel, el sistema nervioso central y la retina. Las lesiones dermatológicas son características; se distribuyen a lo largo de las líneas de Blaschko, las cuales siguen el patrón de migración de las células de la piel en la embriogénesis, y ocurren en el 100% de los pacientes. Las manifestaciones cutáneas aparecen en una secuencia de cuatro fases que inicia desde el nacimiento: vesicular, verrucosa, hiperpigmentada e hipopigmentada. Estas lesiones son relevantes, puesto que orientan al clínico hacia el diagnóstico. Además, se acompañan de anomalías neurológicas, como crisis convulsivas, y múltiples manifestaciones oftalmológicas, como el desprendimiento de la retina. Los pacientes con incontinentia pigmenti, pero sin compromiso oftalmológico o neurológico clínicamente significativo, tienen un pronóstico bueno y una esperanza de vida normal. Las anomalías que se presentan son permanentes, lo que puede generar preocupación en los pacientes.

Incontinentia pigmenti: genodermatosis multisistémica / Incontinentia pigmenti: multisistemic genodermatosis

Resumen La incontinentia pigmenti es una genodermatosis ligada al cromosoma X, generalmente letal en los hombres. Está causada por una mutación con pérdida de función en el gen IKBKG (inhibitor of kappa polypeptide gene enhancer in B cells kinase gamma), que impide que la proteína NFкβ (nuclear factor kappa-light-chain-enhancer of activated B cells) migre al núcleo y comience la transcripción de factores que amplifican la respuesta inmunitaria y previenen la apoptosis. Por tanto, las células mutantes se vuelven vulnerables a la apoptosis cuando son expuestas a citocinas y provocan vaso-oclusión e isquemia de tejidos como la piel, el sistema nervioso central y la retina. Las lesiones dermatológicas son características; se distribuyen a lo largo de las líneas de Blaschko, las cuales siguen el patrón de migración de las células de la piel en la embriogénesis, y ocurren en el 100% de los pacientes. Las manifestaciones cutáneas aparecen en una secuencia de cuatro fases que inicia desde el nacimiento: vesicular, verrucosa, hiperpigmentada e hipopigmentada. Estas lesiones son relevantes, puesto que orientan al clínico hacia el diagnóstico. Además, se acompañan de anomalías neurológicas, como crisis convulsivas, y múltiples manifestaciones oftalmológicas, como el desprendimiento de la retina. Los pacientes con incontinentia pigmenti, pero sin compromiso oftalmológico o neurológico clínicamente significativo, tienen un pronóstico bueno y una esperanza de vida normal. Las anomalías que se presentan son permanentes, lo que puede generar preocupación en los pacientes.

Abstract Incontinentia pigmenti is an X-linked genodermatosis generally lethal in males; thus, it presents almost exclusively in females. It is caused by a loss-of-function mutation in the IKBKG (inhibitor of kappa polypeptide gene enhancer in B cells, kinase gamma) gene that prevents the NFкβ (nuclear factor kappa-light-chain-enhancer of activated B cells) protein from migrating to the nucleus to begin the transcription of factors that amplify the immune response and prevent apoptosis. Consequently, mutant cells become vulnerable to apoptosis when exposed to cytokines and, in turn, lead to vaso-occlusion and ischemia of tissues, such as the skin, the central nervous system and the retina. Dermatological lesions are characteristic and occur in 100% of patients; they are distributed along Blaschko lines, which follow the pattern of migration of skin cells in embryogenesis. The cutaneous manifestations follow a sequence of four phases since birth: vesicular, verrucous, hyperpigmented and hypopigmented. These lesions are relevant for the disease because they guide the clinician towards the diagnosis. Additionally, they are accompanied by neurological abnormalities, such as seizures, and multiple ophthalmological manifestations, such as retinal detachment. Incontinentia pigmenti patients with no clinically significant ophthalmic or neurological compromise have a good prognosis and a normal life expectancy. The abnormalities present are permanent, which can be a cause of concern for the patients.

Diagnosis and management of linear scleroderma in children.

PURPOSE OF REVIEW: Linear scleroderma is the most common subtype of localized scleroderma (LoS) in children. It can be associated with extracutaneous manifestations and long-term sequelae. Thus, appropriate diagnosis and management are key to improve the prognosis. In this review, we summarize the most relevant recent publications for the diagnosis, evaluation of disease activity and adequate management of patients with linear scleroderma. RECENT FINDINGS: There are specific clinical features that indicate activity in LoS; dermoscopy and Wood's lamp may be useful. Summarizing, scoring methods seem to provide the most adequate assessment of LoS; but several biomarkers that correlate with activity have been studied: E-selectin and IL-2 receptor, CD34+ dermal dendritic cells and Th/Th1 immunophenotype with decreased T helper (Th2), T regulatory (Tregs), B and natural killer (NK) cells. Recent studies propose hydroxychloroquine monotherapy and tocilizumab as potential therapeutic options. SUMMARY: Clinical evaluation, both physical exam and history, is the most important aspect in diagnosing and assessing activity of linear scleroderma. Clinical scoring methods may be most useful for evaluation of activity; eventually, other biomarkers could be relevant in clinical practice. For most patients with linear scleroderma, the first choice of treatment is methotrexate, but physical therapy, plastic surgery and/or orthopedic management are key to improve residual limitations and quality of life. VIDEO ABSTRACT: http://links.lww.com/MOP/A35.

The role of local temperature and other clinical characteristics of localized scleroderma as markers of disease activity.

BACKGROUND: Determining the activity of localized scleroderma (LS) remains crucial for decision making, and reliable clinical indicators of activity are lacking. Our objective in this study was to analyze the utility of infrared thermography (IRT) in assessing the activity of LS according to existing clinical scales. A secondary objective was to study whether clinical characteristics of patients and/or IRT have any role in predicting the activity of LS. METHODS: In this cross-sectional study, the activity of LS was determined using a visual analog scale (VAS), a dyspigmentation-induration-erythema-telangiectasias (DIET) scale, and a localized scleroderma skin severity index (LoSSI). Local temperature was measured by IRT. RESULTS: We studied 56 patients with a median age of 14.2 years. The mean difference in temperature between the affected and unaffected skin was 0.29°C. The comparison of patients with active versus inactive LS (using a 50% composite score cutoff) according to differences in temperature was not significant. An exploratory regression analysis showed an insignificant association of difference in temperature and other clinical characteristics for activity of LS. Our relatively small sample size consisted primarily of patients with low to moderate activity, and the lack of a standard definition of activity of LS was another limitation. CONCLUSIONS: There is a possible role for temperature and other clinical characteristics as predictors of activity of LS. More studies and better definitions of activity in LS are needed.

Synbiotics for Prevention and Treatment of Atopic Dermatitis: A Meta-analysis of Randomized Clinical Trials.

IMPORTANCE: Atopic dermatitis (AD) is a highly prevalent condition that may be associated with an altered gastrointestinal microbiota that promotes an immune environment more susceptible to allergic disease. Synbiotics, a mixture of prebiotics and probiotics, have been used for the prevention and treatment of AD. OBJECTIVE: To investigate the efficacy of synbiotics for primary prevention and treatment of AD. DATA SOURCES: PubMed/MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the CAB Abstracts Archive searchable database were searched from the inception of all databases to October 15, 2015, with no language restrictions. STUDY SELECTION: We included all published randomized clinical trials of synbiotics for prevention and/or treatment of AD. To be included, a publication needed to clearly define the intervention as oral administration of synbiotics (combination of probiotics and prebiotics) and must have included an assessment of AD disease severity, such as the Severity Scoring of Atopic Dermatitis (SCORAD) index, or the incidence of AD as an outcome measure. Only 8 of 257 initially identified studies (3%) met selection criteria. DATA EXTRACTION AND SYNTHESIS: Data extraction was independently done by multiple observers and cross-checked to avoid errors. The quality of the selected studies was critically examined following the Cochrane guidelines. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES: The primary outcomes were the SCORAD index (treatment studies) and the relative risk of AD (prevention studies). The hypothesis was formulated before data collection. RESULTS: A total of 257 abstracts were screened to identify 6 treatment studies (369 children enrolled; aged 0 months to 14 years) and 2 prevention studies (1320 children enrolled; up to age 6 months in one study and term neonates aged <3 days in the other). From the 6 treatment studies included for random-effects meta-analysis, the overall pooled change in SCORAD index in those treated with synbiotics at 8 weeks of treatment was -6.56 (95% CI, -11.43 to -1.68; P = .008). Heterogeneity was significant (I(2) = 77.1%; P = .001). Subgroup analysis showed that the beneficial effect was significant only when using mixed strains of bacteria (weighted mean difference, -7.32; 95% CI, -13.98 to -0.66; P = .03) and when used in children aged 1 year or older (weighted mean difference, -7.37; 95% CI, -14.66 to -0.07; P = .048). From the 2 prevention studies included, the pooled relative risk ratio of AD in those treated with synbiotics compared with placebo was 0.44 (95% CI, 0.11 to 1.83; P = .26). CONCLUSIONS AND RELEVANCE: This meta-analysis shows evidence that supports the use of synbiotics for the treatment of AD, particularly synbiotics with mixed strains of bacteria and for children aged 1 year or older. Further studies are needed to evaluate the effectiveness of synbiotics for primary prevention of AD.

Using behavioral economics to promote healthy behavior toward sun exposure in adolescents and young adults.

Skin cancer represents an important public health problem, and it is associated with ultraviolet radiation exposure, particularly at early ages. Unhealthy sun exposure and intentional tanning continue to be the trend among young people. Multiple interventions to raise awareness of the risks of sun exposure have been implemented, without necessarily translating into decreased unhealthy behaviors or skin cancer incidence rates. Behavioral economics adds a set of concepts and tools to potentially boost the efficacy of existing approaches to decrease unhealthy sun exposure. This paper reviews public health interventions that have been based in behavioral economics concepts and their results, and provides examples of new and creative ways physicians and health professionals can actively apply insights from behavioral economics to counsel teenagers and young adults about skin cancer prevention.

New insights into genes, immunity, and the occurrence of dermatophytosis.

Fungal infections in humans are among the most prevalent diseases globally. Superficial invasion by dermatophytes leads to skin, hair, and nail infection. Even though they have usually been associated with extrinsic conditions such as immunosuppression, environmental factors, and contaminated individuals, objects, or surfaces; people are not equally susceptible to dermatophyte infection, even when they have the same risk factors. This commentary summarizes findings that provide evidence of familial or genetic predisposition to fungal infection, mediated by innate and/or adaptive immunity.