Morphoea presenting histopathologically as mycosis fungoides: an illustrative series of four cases.

AIMS: There have been exceptional reports of morphoea presenting with epidermal changes overlapping histopathologically with cutaneous T cell lymphoma of the mycosis fungoides type (MF). This phenomenon gives rise to an ambiguous clinicopathological scenario in which distinguishing these conditions may be challenging. The aim of this study is to characterise the clinical, histopathological and molecular findings of this phenomenon through a case series. METHODS AND RESULTS: Four patients with classical clinical presentation of morphoea but unusual histopathology displaying typical findings of morphoea, together with intra-epidermal CD8 positive lymphocytes indistinguishable from MF, were identified. The clinical phenotypes of morphoea were varied, and they all presented early in the active phase of the disease. They all exhibited intra-epidermal lymphocytes with tagging and cytological atypia. Pautrier-like microabscesses were also seen. Using molecular analysis, two cases showed clonal TCR gene rearrangement. Follow-up of all cases has been consistent with classical morphoea. CONCLUSION: Early morphoea can seldom present with atypical clonal intra-epidermal lymphocytes indistinguishable from MF. The fact that these changes can occur in several different clinical subtypes of morphoea raises the possibility that this could be a pattern of inflammation in early disease more common than currently appreciated.

In Vivo Evaluation of Laser-Induced Optical Breakdown (LIOBS) by 1064-nm Nd:YAG Fractional Picosecond Laser With Reflectance Confocal Microscopy and Precise Histopathologic Correlation.

OBJECTIVES: Picosecond lasers with a microlens array can cause laser-induced optical breakdown (LIOBS) and LIC (Intradermal laser-induced cavitation) within high-fluence areas. This study aimed to describe the clinical, reflectance confocal microscopy (RCM), histopathological findings, and the characteristics of vacuoles caused by LIOBS and LIC in individuals with skin types III and IV. MATERIALS AND METHODS: This study was performed on six Chilean healthy volunteers, males and females, aged 35-65 years old with Fitzpatrick skin phototypes III-IV. The laser was applied in the inner proximal area of the nondominant arm. RCM evaluation was performed 24 h later; 48 h later, skin biopsies were performed on the laser-treated areas. Clinical, histological, and RCM findings were recorded. RESULTS: Every individual developed a 10 mm2 area of clinical erythema in the treated area. Under RCM, all six volunteers had hyporeflective spherical structures at the level of the epidermis, consistent with intraepidermal vacuoles. Histopathological evaluation revealed different sizes of vacuoles in both the epidermis and dermis. CONCLUSION: The LIOBS and LIC processes and the secondary production of vacuoles could be highly valuable for effective dermal remodeling treatment and aid in promoting the production of new collagen, elastic fibers, and growth factors that could improve skin texture. These structures were visible under RCM and histopathological evaluation.

[Deterioration of vital signs as predictors of major medical emergencies in hospitalized patients]. / Alteración de signos vitales dentro de las 72 h previas a la activación de código azul en pacientes adultos hospitalizados de un hospital universitario.

BACKGROUND: Medical emergencies (ME) in hospitalized patients (cardiac and respiratory arrest, suffocation, asphyxia, seizures, unconsciousness) are associated with high morbidity and mortality. Most of these patients have signs of physiological deterioration prior to the appearance of the emergency. Early detection of warning signs by rapid response teams (RRT) may provide an opportunity for the prevention of major adverse events. AIM: To identify clinical signs predicting death, need for mechanical ventilation, or transfer to a more complex unit during the 72 hours prior to the activation of the ME code. To evaluate the association of each trigger with specific major adverse events. PATIENTS AND METHODS: Medical records of 184 hospitalized adult patients in whom the ME code was activated between 2009 and 2014 were reviewed. RESULTS: Seventy five percent patients who experienced a ME had predictive signs of poor clinical outcome. Polypnea and airway involvement were associated to mechanical ventilation. Hypotension and hypoxemia were associated with mortality. CONCLUSIONS: In the absence of RRT, special attention should be given to patients with polypnea, airway involvement, hypotension and desaturation, since these are associated with poor clinical outcomes.

Clinical characterization of Chilean patients with IgE-mediated food allergy. / Caracterización clínica de pacientes chilenos con alergia alimentaria mediada por IgE.

BACKGROUND: Food allergy (FA) is an entity of high and growing prevalence, which can be mediated by IgE or cellular immunity. It can have a wide range of symptoms and be triggered by multiple food antigens, which vary in different geographical areas. OBJECTIVES: To describe clinical characteristics of Chilean patients with IgE-mediated FA. PATIENTS AND METHOD: Retrospective review of patients with IgE-mediated FA treated at a tertiary healthcare center in Santiago, Chile, between 2006 and 2016. Demographic characteristics, clinical manifestations, and trigger foods were evaluated. RESULTS: A to tal of 282 patients diagnosed with IgE-mediated FA were included. 89% had FA onset before 18 years of age and most of these before one year of age (median of age: one year; range: one month-55 years). The most common clinical manifestations were hives, angioedema, dyspnea, and vomiting. 40% had symptoms compatible with anaphylaxis. The foods most frequently involved were egg, cow's milk, peanut, shellfish, walnut, tomato, wheat, avocado, fish, and legumes. Egg, cow's milk, and peanut allergies were the most frequent at pediatric age, while seafood allergy was the most frequent among adults. CONCLUSION: Foods causing IgE-mediated FA in Chile were similar to those described in other countries, although the frequency of tomato and avocado allergy, which are unusual in international series, stands out. Anaphylaxis incidence was high, emphasizing the need for epinephrine autoinjec tors in Chile.

Intra-amniotic Candida albicans Infection Treated With Liposomal Amphotericin B With a Successful Neonatal Outcome.

Intra-amniotic infection with Candida species is an uncommon but severe condition with high fetal morbimortality and no established clinical guidelines for its management. We report a Candida albicans intra-amniotic infection diagnosed in a 25-week pregnant woman, successfully treated with high-dose liposomal amphotericin B. Pregnancy was prolonged until 30 weeks, and despite persistently positive Candida cultures in amniotic fluid, a healthy newborn was delivered without evidence of systemic infection. Amphotericin concentration was determined at birth, revealing levels over 30 times higher in mother's and cord blood than in the amniotic fluid, probably explaining the clinical protection despite failure in obtaining fungal clearance.

Galectin-8 counteracts folic acid-induced acute kidney injury and prevents its transition to fibrosis.

Acute kidney injury (AKI), characterized by a sudden decline in kidney function involving tubular damage and epithelial cell death, can lead to progressive tissue fibrosis and chronic kidney disease due to interstitial fibroblast activation and tissue repair failures that lack direct treatments. After an AKI episode, surviving renal tubular cells undergo cycles of dedifferentiation, proliferation and redifferentiation while fibroblast activity increases and then declines to avoid an exaggerated extracellular matrix deposition. Appropriate tissue recovery versus pathogenic fibrotic progression depends on fine-tuning all these processes. Identifying endogenous factors able to affect any of them may offer new therapeutic opportunities to improve AKI outcomes. Galectin-8 (Gal-8) is an endogenous carbohydrate-binding protein that is secreted through an unconventional mechanism, binds to glycosylated proteins at the cell surface and modifies various cellular activities, including cell proliferation and survival against stress conditions. Here, using a mouse model of AKI induced by folic acid, we show that pre-treatment with Gal-8 protects against cell death, promotes epithelial cell redifferentiation and improves renal function. In addition, Gal-8 decreases fibroblast activation, resulting in less expression of fibrotic genes. Gal-8 added after AKI induction is also effective in maintaining renal function against damage, improving epithelial cell survival. The ability to protect kidneys from injury during both pre- and post-treatments, coupled with its anti-fibrotic effect, highlights Gal-8 as an endogenous factor to be considered in therapeutic strategies aimed at improving renal function and mitigating chronic pathogenic progression.

[Pediatric ANCA-associated vasculitis, a case series]. / Vasculitis asociadas a ANCA en pediatría, serie de casos clínicos.

INTRODUCTION: ANCA-associated vasculitis (AAV) is an infrequent disease in childhood. International literature about pediatric vasculitis is scarce, and it mainly refers to other systemic vasculitides with a higher incidence in childhood, such as IgA vasculitis and Kawasaki disease. OBJECTIVE: To describe the clini cal and laboratory characteristics of a series of pediatric cases with AAV. PATIENTS AND METHOD: Re trospective, descriptive study of patients with diagnosis of AAV treated at a tertiary health center from Santiago, Chile, between 2000 and 2020. Electronic medical records were reviewed collecting epidemiological, laboratory, images, and biopsies data. RESULTS: There were five cases of pediatric pa tients with AAV, with varying degrees of severity, and the age range at the onset was 5.5 to 13.5 years. We observed frequent renal involvement in microscopic polyangiitis (MPA) and eye involvement due to orbital pseudotumor in patients with granulomatosis with polyangiitis (GPA), an infrequent manifestation in the international pediatric literature. Patients were treated according to recommen dations extrapolated from clinical trials in adult populations, showing excellent clinical response to induction therapy with systemic corticosteroids and cyclophosphamide or rituximab. During main tenance therapy, most of the patients were stable on rituximab, azathioprine, or methotrexate. No patient developed organ damage and all cases achieved discontinuation of the corticosteroid therapy. CONCLUSION: This report describes the clinical characteristics of AAV in a series of pediatric patients. In this series, renal involvement was common in MPA and eye involvement due to orbital pseudotu mor in GPA. The clinical response with treatment according to recommendations extrapolated from the adult population was favorable.

Galectin-8 induces partial epithelial-mesenchymal transition with invasive tumorigenic capabilities involving a FAK/EGFR/proteasome pathway in Madin-Darby canine kidney cells.

Epithelial cells can acquire invasive and tumorigenic capabilities through epithelial-mesenchymal-transition (EMT). The glycan-binding protein galectin-8 (Gal-8) activates selective ß1-integrins involved in EMT and is overexpressed by certain carcinomas. Here we show that Gal-8 overexpression or exogenous addition promotes proliferation, migration, and invasion in nontumoral Madin-Darby canine kidney (MDCK) cells, involving focal-adhesion kinase (FAK)-mediated transactivation of the epidermal growth factor receptor (EGFR), likely triggered by α5ß1integrin binding. Under subconfluent conditions, Gal-8-overexpressing MDCK cells (MDCK-Gal-8H) display hallmarks of EMT, including decreased E-cadherin and up-regulated expression of vimentin, fibronectin, and Snail, as well as increased ß-catenin activity. Changes related to migration/invasion included higher expression of α5ß1 integrin, extracellular matrix-degrading MMP13 and urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) protease systems. Gal-8-stimulated FAK/EGFR pathway leads to proteasome overactivity characteristic of cancer cells. Yet MDCK-Gal-8H cells still develop apical/basolateral polarity reverting EMT markers and proteasome activity under confluence. This is due to the opposite segregation of Gal-8 secretion (apical) and ß1-integrins distribution (basolateral). Strikingly, MDCK-Gal-8H cells acquired tumorigenic potential, as reflected in anchorage-independent growth in soft agar and tumor generation in immunodeficient NSG mice. Therefore, Gal-8 can promote oncogenic-like transformation of epithelial cells through partial and reversible EMT, accompanied by higher proliferation, migration/invasion, and tumorigenic properties.

Meningitis tuberculosa: un desafío diagnóstico en pediatría / Tuberculous meningitis: diagnostic challenge in pediatrics

Resumen La meningitis por Mycobacterium tuberculosis es infrecuente en pediatría y su diagnóstico definitivo representa un desafío clínico. Presentamos el caso de un lactante de dos años, que presentó un cuadro de meningitis crónica. Se logró el diagnóstico tras la sospecha imagenológica y la confirmación tras la búsqueda seriada del complejo M. tuberculosis por RPC en LCR y en biopsia de tejido cerebral. A pesar de sus complicaciones, el paciente respondió favorablemente al tratamiento antituberculoso. En Chile, la tuberculosis es infrecuente en niños y los síntomas son generalmente inespecíficos. Los hallazgos en RM cerebral asociados a alteraciones del LCR permiten sospechar el compromiso meníngeo precozmente. Se recomienda iniciar el tratamiento antituberculoso empírico ante la sospecha, ya que mejora el pronóstico. A pesar de los avances diagnósticos y terapéuticos, la meningitis tuberculosa sigue teniendo una alta tasa de complicaciones y un pronóstico ominoso.

Abstract Mycobacterium tuberculosis meningitis is rare in the pediatric population and its definitive diagnosis represents a clinical challenge. We present the case of a 2-year-old infant with chronic meningitis. Diagnosis was accomplished by suggestive radiological findings and serial search for M. tuberculosis complex by real-time polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF) and in brain tissue. Despite the complications, the patient evolved favorably with the tuberculosis treatment. In Chile, tuberculosis is a rare disease in children and symptoms are generally nonspecific. Brain MRI findings associated with CSF alterations allow early suspicion of MTBC. Start of empirical antituberculosis treatment upon suspicion is recommended given it is associated with better prognosis. Despite diagnostic and therapeutic advances, MTBC continues to have a high complication rate and an ominous prognosis.

Síndrome hematofagocítico como manifestación inicial de linfoma de Hodgkin clásico / Hemophagocytic syndrome as the initial manifestation of Hodgkin lymphoma

Introducción: las histiocitosis son un grupo heterogéneo de enfermedades; una de ellas es el síndrome hematofagocítico (SHF). Sus causas pueden ser infecciosas, neoplásicas, autoinmunes o relacionadas a inmunodeficiencias adquiridas; el linfoma de Hodgkin clásico (LHc) es una causa poco frecuente. Se reporta el caso de un hombre inmunodeprimido de 35 años que ingresa al hospital febril y con insuficiencia respiratoria grave.Métodos: se recopiló información clínica pertinente y se revisó material de biopsia estudiado con tinción de hematoxilina ­ eosina, técnica inmunohistoquímica e hibridación in situ cromogénica. Resultados: estudios de laboratorio muestran pancitopenia, altera-ción de pruebas hepáticas, hipertrigliceridemia, hipoalbuminemia e hiperferritinemia. El estudio de médula ósea hematopoyética con mielograma y biopsia muestran hallazgos compatibles con LHc, signos de hemofagocitosis e infección por virus Epstein-Barr (VEB). Se diagnostica SHF como primera manifestación de LHc e infección por VEB. Conclusiones: a la fecha, se describen 74 pacientes re-portados con SHF como manifestación de LHc; en el 84% fue su primera manifestación. Si bien la presentación clínica presentada es infrecuente, se ha propuesto una asociación en hombres con inmunodeficiencia, SHF, LHc e infección por VEB; por lo que se sugiere una sospecha diagnóstica alta.

Introduction: histiocytosis are a heterogeneous group of diseases; one of them is the hemophagocytic syndrome (HS). Its causes can be infectious, neoplastic, autoimmune or related to acquired immunodeficiencies; classic Hodgkin lymphoma (cHL) is a rare cause.We present the case of an immunosuppressed 35-year-old male who was admitted with fever and acute respiratory failure. Methods:pertinent clinical reports and biopsy material were reviewed; including hematoxylin-eosin stained slides from formalin-fixed and pa-raffin-embedded tissue blocks and immunohistochemical and chromogenicin situhybridisation studies. Results:laboratory studies revealed pancytopenia, abnormal liver functions, hypertriglyceridemia, hypoalbuminemia e hyperferritinemia. Bone marrow aspiration smear and biopsy showed a malignant lymphoid neoplasm consistent with cHL, signs of hemophagocytosis, and Epstein-Barr virus (EBV) infection. HS, as an initial manifestation of cHL, was diagnosed.Conclusions:to our best knowledge, there are 74 reported cases of cHL with HS; in 84% it was the initial clinical manifestation. Though this is an unusual presentation, an association between immu-nodeficiency, HS, cHL, and EBV infection has been proposed; so a high diagnostic suspicion is suggested.

Caso de paraqueratosis pustulosa: entidad poco frecuente y síntoma de enfermedad inflamatoria del aparato ungueal en pacientes pediátricos / Case of pustular parakeratosis: a rare entity common and symptom of inflammatory disease of the nail apparatus in pediatric patients

La paraqueratosis pustulosa es una entidad poco descrita en la literatura y se define como un proceso inflamatorio cutáneo, ungueal y periungueal en el área distal de un dedo habitualmente pulgar o índice, frecuentemente en la infancia. Su evolución suele ser benigna y la respuesta a emolientes tópicos es favorable. A continuación, se presenta un caso de esta enfermedad con el objetivo de resaltar su consideración en patologías ungueales pediátricas.

Pustular parakeratosis is an entity scantly described in literature. It has been described as a skin, nail, and periungual inflammatory process in the distal area of a finger, usually the thumb or index finger, frequently in childhood. Its evolution is usually benign and management is favorable with topical emollients. A clinical case is presented, to raise awareness of this entity in pediatric nail pathologies.

Alteración de signos vitales dentro de las 72 h previas a la activación de código azul en pacientes adultos hospitalizados de un hospital universitario / Deterioration of vital signs as predictors of major medical emergencies in hospitalized patients

Background: Medical emergencies (ME) in hospitalized patients (cardiac and respiratory arrest, suffocation, asphyxia, seizures, unconsciousness) are associated with high morbidity and mortality. Most of these patients have signs of physiological deterioration prior to the appearance of the emergency. Early detection of warning signs by rapid response teams (RRT) may provide an opportunity for the prevention of major adverse events. Aim: To identify clinical signs predicting death, need for mechanical ventilation, or transfer to a more complex unit during the 72 hours prior to the activation of the ME code. To evaluate the association of each trigger with specific major adverse events. Patients and Methods: Medical records of 184 hospitalized adult patients in whom the ME code was activated between 2009 and 2014 were reviewed. Results: Seventy five percent patients who experienced a ME had predictive signs of poor clinical outcome. Polypnea and airway involvement were associated to mechanical ventilation. Hypotension and hypoxemia were associated with mortality. Conclusions: In the absence of RRT, special attention should be given to patients with polypnea, airway involvement, hypotension and desaturation, since these are associated with poor clinical outcomes.

Caracterización clínica de pacientes chilenos con alergia alimentaria mediada por IgE / Clinical characterization of Chilean patients with IgE-mediated food allergy

INTRODUCCIÓN: La alergia alimentaria (AA) es una entidad de elevada y creciente prevalencia, pudiendo ser mediada por IgE o inmunidad celular. Puede presentar amplia sintomatología y ser gatillada por múltiples antígenos alimentarios, lo que varía en diversas zonas geográficas. OBJETIVO: Describir las características clínicas de pacientes chilenos con AA IgE-mediada. PACIENTES Y MÉTODO: Revisión retrospectiva de pacientes con AA IgE-mediada atendidos en un centro terciario de salud de Santiago, Chile entre los años 2006 y 2016. Se evaluaron características demográficas, manifestaciones clínicas y alimentos gatillantes. RESULTADOS: Se incluyeron 282 pacientes con diagnóstico de AA IgE-mediada. El 89% debutó con AA antes de los 18 años de edad y de estos, la mayoría antes del año (mediana: 1 año; rango: 1 mes - 55 años). Las manifestaciones clínicas más frecuentes fueron urticaria, angioedema, disnea y vómitos. Un 40% tenía historia compatible con anafilaxia. Los alimentos más frecuentes fueron huevo, leche de vaca, maní, mariscos, nuez, tomate, trigo, palta, pescados y legumbres. Alergia a huevo, leche de vaca y maní fueron más frecuentes en edad pediátrica, mientras que en adultos fueron los mariscos. CONCLUSIONES: Los alimentos causantes de AA IgE-mediada en Chile fueron similares a los descritos en otros países, aunque destaca la elevada frecuencia de alergia a tomate y palta, poco habituales en series internacionales. La incidencia de anafilaxia fue alta, lo que instala la necesidad de contar con autoinyectores de adrenalina a nivel nacional.

BACKGROUND: Food allergy (FA) is an entity of high and growing prevalence, which can be mediated by IgE or cellular immunity. It can have a wide range of symptoms and be triggered by multiple food antigens, which vary in different geographical areas. OBJECTIVES: To describe clinical characteristics of Chilean patients with IgE-mediated FA. Patients and Method: Retrospective review of patients with IgE-mediated FA treated at a tertiary healthcare center in Santiago, Chile, between 2006 and 2016. Demographic characteristics, clinical manifestations, and trigger foods were evaluated. RESULTS: A to tal of 282 patients diagnosed with IgE-mediated FA were included. 89% had FA onset before 18 years of age and most of these before one year of age (median of age: one year; range: one month-55 years). The most common clinical manifestations were hives, angioedema, dyspnea, and vomiting. 40% had symptoms compatible with anaphylaxis. The foods most frequently involved were egg, cow's milk, peanut, shellfish, walnut, tomato, wheat, avocado, fish, and legumes. Egg, cow's milk, and peanut allergies were the most frequent at pediatric age, while seafood allergy was the most frequent among adults. CONCLUSION: Foods causing IgE-mediated FA in Chile were similar to those described in other countries, although the frequency of tomato and avocado allergy, which are unusual in international series, stands out. Anaphylaxis incidence was high, emphasizing the need for epinephrine autoinjec tors in Chile.