Comorbidities & burden of disease in atopic dermatitis.

BACKGROUND: Atopic dermatitis is associated with an increased frequency of other atopic & allergic manifestations, including asthma in 10% to 30% of cases depending on age, allergic rhinitis, food allergies, eosinophilic diseases, and allergic conjunctivitis. The comorbidities outside the atopic march are overall less frequent than in psoriasis. OBJECTIVE: This review aims to demonstrate the intense, broad burden of this disease, comorbidities and its multidimensional involvement as a complex, heterogeneous disease. METHODS: Methods: The present narrative review summarizes the findings from the world's largest epidemiological studies and smaller, AD-specific studies on the comorbidities and burdens of this disease. RESULTS: Results: The risk of asthma, specifically, and other atopic manifestations and skin infections, generally, is clearly increased among patients with AD. Of the other skin diseases, there is an undeniable risk of alopecia areata, vitiligo, and contact eczema and a lower risk of developing other autoimmune diseases. While comorbidities exist, their frequency seems to be modified by lifestyle, particularly by smoking. There is a link with overweight, obesity, and metabolic syndrome, especially in severe AD. This is also the case for cardiovascular diseases; however, with OR/HRs below 1.5. There is no link to type II diabetes but, rather, to type I in children. In all other areas, the data are often inconsistent, and any increase in risk is low. Eye diseases seem to be the only exception. AD also has psychiatric consequences, including attention-hyperactivity disorder, anxiety, depression, and sometimes suicidality, especially when severe. CONCLUSIONS: Conclusions: The recently published work largely confirms our existing understanding of AD.

[Guidelines on atopic dermatitis for Mexico (GUIDAMEX): using the ADAPTE methodology]. / Guía de dermatitis atópica para México (GUIDAMEX): lineamientos usando metodología ADAPTE.

With the advancement of knowledge in relation to the physiopathogenesis of atopic dermatitis (AD), several new therapeutic forms have been developed. There are also new guidelines for self-care. On the other hand, there is still an underdiagnosis of AD in Mexico. Thus, the need was seen to develop a national guide, with a broad base among the different medical groups that care for patients with AD. The Atopic Dermatitis Guidelines for Mexico (GUIDAMEX) was developed with the ADAPTE methodology, with the endorsement and participation of ten national medical societies, from physicians in Primary Healthcare to allergists and dermatologists. Throughout the manuscript, key clinical questions are answered that lead to recommendations and suggestions for the diagnosis of AD (including differential diagnosis with immunodeficiency syndromes), the recognition of comorbidities and complications, non-pharmacological treatment including therapeutic education, treatment of flares and maintenance therapy. The latter encompasses general measures to avoid triggering factors, first-line treatment focussed on repair of the skin barrier, second-line treatment (topical proactive therapy), and third-line phototherapy or systemic treatment, including dupilumab and JAK inhibitors.

Con el avance de los conocimientos en relación con la fisiopatogenia de la dermatitis atópica (DA) se han desarrollado varias formas terapéuticas nuevas. Asimismo, existen nuevos lineamientos para el autocuidado. Por otro lado, aún existe un subdiagnóstico de la DA en México. Así, se vio la necesidad de desarrollar una guía nacional, con base amplia entre las diferentes agrupaciones médicos que atienden pacientes con DA. Se desarrolló la Guía de DA para México (GUIDAMEX) con la metodología ADAPTE, con el aval y la participación de diez sociedades médicas nacionales, desde médicos del primer contacto hasta alergólogos y dermatólogos. A lo largo del escrito se contestan preguntas clínicas clave que llevan a recomendaciones y sugerencias para el diagnóstico de la DA (incluyendo diagnóstico diferencial con síndromes de inmunodeficiencia), el reconocer de las comorbilidades y complicaciones, las medidas generales (tratamiento no farmacológico) incluyendo la educación terapéutica, el tratamiento de los brotes y el tratamiento de mantenimiento. Este último abarca las medidas generales de evitar agravantes, el tratamiento de primera línea reparador de la barrera cutánea, de segunda línea (manejo proactivo tópico), hasta la fototerapia y el tratamiento sistémico de la tercera línea, incluyendo dupilumab y los inhibidores de la cinasa de Jano.

Dermatoscopic Patterns in Vitiligo.

Vitiligo is a chronic, acquired autoimmune pigmentary skin disease, most times it can be diagnosed clinically. Dermoscopy can confirm vitiligo in a non-invasive way. It is a diagnostic technique that visualizes sub-macroscopic morphological structures which correspond with specific histological structures. It detects subtle changes in the pigment pattern, evaluates vitiligo activity, attempts of re-pigmentation, leucotrichia, and differentiates it from other hypo pigmentary disorders. Most dermatoscopic clues used to assess vitiligo activity are found at the perifollicular level in the center and edge of the lesion. Perifollicular pigmentation is present in both active lesions and treated pigmented lesions with treatment. However, perifollicular depigmentation represents poor response, in treated lesions, and poor prognosis in untreated ones. The center of the lesion has reduced and/or absent pigment network, in active and stable lesions. If on dermoscopy the center of the lesion shows islands of pigment, erythema, or telangiectasias, re-pigmentation is suggested. At the periphery of the lesion, unstable vitiligo usually shows up as a diffuse border, trichrome pattern, micro-Koebner/comet tail phenomenon, satellite lesions, or a tapioca sago pattern. In stable lesions it is more frequent to find well defined or trichromic border. Pigmented lesions commonly present sharp borders and marginal or perilesional hyperpigmentation.

Acné en el recién nacido / Acne in the newborn

Resumen El acné neonatal es una dermatosis transitoria que ocurre entre la segunda y la cuarta semanas de vida en uno de cada cinco niños. Es más frecuente en los varones, con una relación de sexo masculino-femenino de 4.5:1. Las manifestaciones clínicas incluyen comedones abiertos y cerrados que pueden progresar a lesiones inflamatorias como pápulas, pústulas eritematosas y, en casos raros, nódulos y quistes. Las zonas afectadas incluyen la frente, las mejillas, el mentón y los párpados, y en algunas ocasiones puede extenderse a la piel cabelluda, el cuello y el tronco. Ocurre por la mayor producción de andrógenos placentarios y neonatales (de origen suprarrenal en ambos sexos y de origen testicular en los varones), que provoca hipertrofia de las glándulas sebáceas y mayor producción de sebo. La mayoría de los casos son leves y autolimitados. Cuando el acné neonatal es grave y prolongado, se debe considerar la posibilidad de hiperandrogenismo, cuyas causas más frecuentes en esta edad son la hiperplasia suprarrenal congénita y los tumores, adrenales o gonadales, productores de andrógenos. El diagnóstico del acné neonatal es clínico: se debe distinguir de la pustulosis cefálica neonatal, otras dermatosis neonatales vesiculopustulares, enfermedades infecciosas y reacciones acneiformes. Habitualmente, un dermolimpiador suave y agua resultan suficientes para su manejo. Las lesiones obstructivas (comedones abiertos y cerrados) pueden requerir retinoides tópicos o ácido azelaico al 20%, y las lesiones inflamatorias, algunos antibióticos tópicos.

Abstract Neonatal acne (NA) is a transitory dermatosis that occurs between the second and fourth weeks of life in 20% of children. This condition is more frequent in males, with a male-female ratio of 4.5:1. Present primary skin lesions are open and closed comedones which can evolve into papules, erythematous pustules and, in rare cases, nodules and cysts. NA topography includes the forehead, cheeks, chin, and eyelids, but occasionally it spreads to the scalp, neck, and trunk. NA occurs due to an elevated production of placental and neonatal androgens (of adrenal origin in both sexes and of testicular origin in males) which cause enlargement of the sebaceous glands and increases the production of sebum. Most cases are mild and transient, but if NA is severe and long-lasting, clinical and paraclinical examination will be necessary to find congenital adrenal hyperplasia or a virilizing tumor of adrenal or gonadal origin. The diagnosis of NA is clinical; its main differential Ádiagnoses are neonatal cephalic pustulosis, other neonatal vesiculopustular dermatoses, infectious diseases, and acneiform reactions. The resolution of NA is spontaneous. In most cases, the use of a mild dermal cleanser and water will be sufficient. For comedogenic lesions (open and closed comedones), topical retinoids or 20% azelaic acid may be used, as well as some topical antibiotics for inflammatory lesions.

Phakomatosis pigmentovascularis II A and II B: clinical findings in 24 patients.

Nearly 200 cases of phakomatosis pigmentovascularis (PPV) have been reported worldwide, most of them of Japanese origin. There are 5 types and 10 subtypes of PPV. Its etiology might be explained by the twin spotting phenomenon. The relative frequency of PPV at the National Institute of Pediatrics was 5.8 per 100,000 pediatric patients and 0.634 per 100,000 dermatological patients. We report 24 cases of PPV with an average follow up of 5 years and the following findings: PPV type II A in 4 male and 2 female patients with melanosis bulbi in 3 and glaucoma in 1. PPV type II B in 7 male and 11 female patients, with melanosis bulbi in 9, glaucoma in 9, iris mammillations in 2, Sturge Weber syndrome in 6 female patients, and Klippel-Trenaunay syndrome in 2 males, hemifacial, hemicorporal, or limb hypertrophy without venous insufficiency in 6 female and 4 male patients. During the follow-up time of 60 months, progressive fading of melanotic and vascular macules were observed in 7 patients. No other types of PPV were found. Systemic involvement in PPV was related to the body surface area affected by the vascular macules. Ectodermal and mesodermal migration disorders might be involved in the pathogenesis of PPV.

Two distinct types of speckled lentiginous nevi characterized by macular versus papular speckles.

BACKGROUND: Speckled lentiginous nevus (SLN; synonym: nevus spilus) is a darkly spotted light-brown macule that mostly occurs as an isolated lesion of rather limited dimensions but sometimes may involve large areas of the body. So far, this skin disorder has been considered to represent one clinical entity. OBJECTIVE: Because SLN is occasionally associated with complex birth defects such as phacomatosis pigmentovascularis, phacomatosis pigmentokeratotica, or SLN syndrome, we tested our idea that two different types of SLN may exist, each one associated with a particular syndrome. METHODS: A review of case reports on SLN published during the years 1970-2004 was performed. RESULTS: This evaluation of cases provided evidence that two different types of SLN exist, in the form of macular versus papular SLN, each one being related to a specific syndrome. Macular SLN is characterized by a tannish-brown background with darker flat speckles. The distribution of speckles is rather even and resembles a polka-dot pattern. Histopathologically, this type of SLN is characterized by what has been called a 'jentigo' pattern in the darker speckles and by some nests of melanocytes at the dermoepidermal junction at the tips of the papillae, whereas the background pigmentation shows the microscopical features of a lentigo. Papular SLN is characterized by a light-brown macule superimposed by multiple melanocytic nevi in the form of papules or nodules that show a more uneven distribution reminiscent of a star map. Small dark macules may likewise be present. Histopathologically, the papular component consists of dermal or compound melanocytic nevi. A separation of the two types of SLN is important because our analysis showed that macular SLN is a hallmark of a particular type of phacomatosis pigmentovascularis, whereas papular SLN is typically present in phacomatosis pigmentokeratotica as well as in SLN syndrome. CONCLUSIONS: Macular SLN and papular SLN appear to be two distinct cutaneous entities. This dichotomy may turn out to be important when such nevi will be analyzed at the molecular level.

Indeterminate cell histiocytosis. Clinical and pathologic study in a pediatric patient.

Indeterminate cell histiocytosis is a rare disorder involving altered homing mechanisms of the cutaneous histiocytic/dendritic system. It has been described predominantly in adults, with less than a dozen cases in children. A 13-year-old adolescent girl presented with a 4-year history of asymptomatic erythematous nodules and plaques, measuring from 1 to 5 cm in diameter, that were located mainly on the trunk and proximal portions of her limbs. A skin biopsy showed dermal diffuse infiltration of histiocytic cells. Most of the histiocytic cells were strongly positive for S100 protein. No Birbeck granules were found. Treatment with topical steroid was ineffective. After 6 months of pure coal tar and 5% 5-fluorouracil cream, an almost total clearing of lesions was observed. An accurate diagnosis of this condition is mandatory in order to avoid unnecessary treatments. Conservative management is also discussed.

Epidermal nevus syndromes: clinical findings in 35 patients.

Of the patients with epidermal nevi, 10-18% may have disorders of the eye, nervous, and musculoskeletal systems. A predisposition to malignant neoplasms in ectodermal and mesodermal structures may also be found. There are six different epidermal nevus syndromes described so far: Proteus, congenital hemidysplasia with ichthyosiform nevus and limb defect syndrome, phakomatosis pigmentokeratotica, sebaceous nevus, Becker nevus, and nevus comedonicus. Thirty-five patients with epidermal nevus syndrome seen at the National Institute of Pediatrics in Mexico City during a 31-year period are described. This syndrome represented 7.9% of 443 patients with epidermal nevi; its relative frequency was 1 case per 11,928 pediatric patients and 1 case per 1080 dermatologic patients. Nine epidermal nevus syndrome patients (26%) had Proteus syndrome. Sebaceous nevus syndrome was found in six patients (17%), while the nevus comedonicus syndrome was found in three (8%). Two patients were diagnosed with phakomatosis pigmentokeratotica and one patient with congenital hemidysplasia with ichthyosiform nevus and limb defect syndrome. This is the first report of phakomatosis pigmentokeratotica and congenital hemidysplasia with ichthyosiform nevus and limb defect syndrome in Mexican patients. One patient had an inflammatory linear verrucous epidermal nevus with systemic involvement. Thirteen patients (37%) had keratinocytic nevi with systemic involvement. We propose the keratinocytic nevus syndrome to be defined as the association of a keratinocytic nevus with neuronal migration and/or musculoskeletal disorders in addition to a higher risk for mesodermal neoplasms.

Gonadoblastoma y disgenesia gonadal mixta / Gonadoblastoma and mixed gonadal dysgenesis

Introducción. El gonadoblastoma se describió por primera vez en 1953 por Scully, se sabe que ocurre casi exclusivamente en gónadas disgenéticas y primordialmente en las primeras 2 décadas de la vida, se asocia a la presencia de material genético del cromosoma Y. Aproximadamente el 30 por ciento de los pacientes con disgenesia gonadal desarrollan gonadoblastoma, 40 por ciento bilateral, por si mismo se podría considerar una neoplasia in situ; sin embargo, del 25 al 30 por ciento se asocia a germinomas que se deben tratar de manera específica. Caso clínico. Se presenta el caso de una paciente educada en el rol femenino de 15 años de edad con ambigüedad de genitales y cariotipo 45XO/46XY. Se le realizó genitoplastia en 2 tiempos con laparotomía exploradora y extirpación de la gónadas disgenéticas, en ambas presentó gonadoblastoma y en una de ellas un germinoma; recibió quimioterapia con cisplatino y ciclosfosfamida por 6 ciclos y durante su seguimiento no hubo evidencia de metástasis o tumor residual. conclusión. El gonadoblastoma es el tumor germinal más frecuente en los pacientes con disgenesia gonadal mixta; por si mismo tiene un comportamiento neoplásico, pero no se han reportado metástasis. Sin embargo, predispone a la presentación de otros tumores germinales como: germinoma, coriocarcinoma, tumor de senos endodérmicos, etc. Por lo tanto, se recomienda extirpación temprana de las gónadas disgéneticas y el manejo específico de la neoplasia germinal de encontrarse otro tumor además del gonadoblastoma