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OBJECTIVE: Clinical practice guidelines (CPG) worldwide help steer the management of early-onset neonatal sepsis (EONS). These documents typically discourage the use of risk assessment tools. However, prior work has shown that the Kaiser Permanente calculator (Early-Onset Sepsis Calculator [EOScalc]) could be a useful tool in EONS risk assessment. This study aimed to determine the agreement between the recommendations of the Colombian EONS CPG and those of the EOSCalc tool in a cohort of newborns in Bogotá, Colombia. STUDY DESIGN: Multicenter retrospective observational cohort study. We included newborns with a gestational age ≥ 34 weeks who were admitted to the neonatal care unit with a suspected diagnosis of EONS between 2017 and 2019. Agreement between the two tools was examined using Cohen's kappa under two scenarios (unequivocal and cautious). RESULTS: Of the 23.490 live births, 470 (1.71%) were admitted to the neonatal care unit with a presumptive diagnosis of EONS. This diagnosis was confirmed in seven patients by means of blood cultures, with group B streptococcus the most common organism (57%; 95% confidence interval [CI]: 18.4-90.1). A single death occurred among the patients with confirmed EONS (lethality: 14.3%). The overall incidence of EONS was 0.298 per 1,000 live births. After splitting the recommendations into two scenarios regarding antibiotic use, unequivocal and cautious, the agreement between EOSCalc and the CPG was below 15% (6 and 14%, respectively). CONCLUSION: Recommendations from the Colombian EONS CPG show poor agreement with the EOSCalc, with the latter detecting all newborns with EONS. Although the use of EOSCalc is clinically and administratively advantageous, further prospective studies are warranted to determine the safety of its implementation. KEY POINTS: · Colombian EONS CPGs recommend that an outsized number of newborns be given antibiotics.. · The KP EOSCalc risk assessment calculator shows poor agreement with CPG recommendations.. · The Colombian CPGs should be updated to include the use of risk assessment calculators..
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Introducción: la enfermedad trombótica venosa es una de las principales complicaciones mortales en pacientes internados y en pacientes operados. Tiene dos presentaciones: trombosis venosa profunda (TVP) y tromboembolia pulmonar (TEP). La TVP es una afección en la que se desarrolla un coágulo de sangre generalmente en las venas de las piernas. La incidencia del TVP en cirugía maxilofacial ha sido pobremente reportada y se considera poco común. Objetivo: describir caso de TVP en una paciente joven a quien se le realizó cirugía ortognática, con el fin de destacar el uso de anticonceptivos no orales como posible factor de riesgo para el desarrollo de esta inusual complicación posterior a una cirugía craneomaxilofacial. Caso clínico: paciente femenina de 24 años, con diagnóstico de anomalía dentofacial de clase II, sometida a cirugía ortognática bimaxilar + mentoplastia con antecedente de anticoncepción subcutánea con Etonogestrel 68 mg hace 3 años. El día 10 del postoperatorio asistió a la unidad de urgencias por dolor y edema en miembro inferior izquierdo; se sospecha TVP y se inicia anticoagulación con 1 mg/kg de heparina de bajo peso molecular subcutáneo (HBPM) cada 12 horas. El diagnóstico de TVP fue confirmado por medio de ecografía doppler de miembros inferiores. Posteriormente, a los 7 días del evento, medicina interna suspendió manejo con cumarínico y continuó anticoagulación con Rivaroxaban 20 mg VO cada 24 horas. Conclusión: el diagnóstico de TVP debe considerarse en mujeres a quienes se les practica cirugía ortognática y presentan antecedentes de tratamiento con anticonceptivos hormonales, incluidas las formas no orales.
Introduction: Venous thrombotic disease is one of the main fatal complications in hospitalized patients and in operated patients. It has two presentations: deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE). DVT is a condition in which a blood clot usually develops in the veins of the legs. The incidence of DVT in maxillofacial surgery has been poorly reported and is considered uncommon. Objective: To describe a case of DVT in a young female patient undergoing orthognathic surgery in order to highlight the use of non-oral contraceptives as a possible risk factor for the development of this unusual complication in craneomaxilofacial surgery. Clinical case: 24-year-old female patient, diagnosed with class II dentofacial anomaly, underwent bimaxillary orthognathic surgery + mentoplasty with a history of subcutaneous contraception with Etonogestrel 68 mg 3 years ago. On postoperative day 10 she attended the emergency department for pain and edema in the left lower limb, DVT was suspected, and anticoagulation was started with 1 mg/kg of subcutaneous low molecular weight heparin (LMWH) every 12 hours. The diagnosis of DVT was confirmed by lower limb Doppler ultrasound. Subsequently, 7 days after the event, Internal Medicine suspended management with coumarin and continued anticoagulation with Rivaroxaban 20 mg OV every 24 hours. Conclusion: Remember that the diagnosis of DVT should be considered in women with a history of recent orthognathic surgery in treatment with hormonal contraceptives, including non-oral forms.
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Humanos , Feminino , Adulto JovemRESUMO
Resumen Introducción: El comportamiento suicida hace referencia a las diversas conductas para dejar de vivir es un fenómeno multifactorial ampliamente estudiado en población urbana, sin embargo, la población campesina, especialmente agricultores y trabajadores agrícolas están entre los grupos de alto riesgo. Objetivo: Evaluar las relaciones entre el riesgo suicida y las estrategias de afrontamiento al estrés en una muestra de 76 campesinos entre los 18 y 79 años del municipio de El Santuario, Colombia, durante la emergencia sanitaria por Covid-19. Método: Para este estudio se utilizó un diseño descriptivo correlacional de corte transversal y se emplearon como instrumentos la Escala de Evaluación de Riesgo Suicida -ERS- y la Escala de Estilos y Estrategias de Afrontamiento (EEEAE). Resultados: Los resultados encontrados en la Escala ERS no indicaron niveles clínicos de riesgo suicida. Y respecto a la EEEAE casi siempre los participantes usaban las estrategias de Reevaluación positiva, Apoyo social, Desconexión cognitiva y Resolver el problema. Hubo correlaciones negativas entre todas las dimensiones de la escala ERS con EEEAE, menos entre las dimensiones Depresión/Desesperanza y Aislamiento/Soporte social (ERS) con la Desconexión cognitiva (EEEAE) y especialmente la estrategia de Reevaluación Positiva tuvo un peso significativo sobre riesgo suicida. Conclusiones: La Reevaluación Positiva es una estrategia de afrontamiento que puede proteger la salud mental ante situaciones de estrés asociados con el riesgo suicida de la población campesina, los agricultores y trabajadores agrícolas.
Abstract Introduction: Suicidal behavior refers to the various behaviors to stop living, it is a multifactorial phenomenon widely studied in the urban population, however, the rural population, especially farmers and agricultural workers, are among the high-risk groups. Objective: Evaluate the relationships between suicidal risk and stress coping strategies in a sample of 76 peasants between 18 and 79 years of age from the municipality of El Santuario, Colombia during the Covid-19 health emergency. Method: For this study, a cross-sectional correlational descriptive design was used. The Suicide Risk Assessment Scale -SRAS- and the Coping Styles and Strategies Scale were used as measurement instruments (CSSS). Results: The results found in the SRAS Scale did not indicate clinical levels of suicidal risk. And regarding the EEEAE, the participants almost always used the strategies of Positive Reappraisal, Social Support, Cognitive Disconnection and Problem-Solving skills. There were negative correlations between all the dimensions of the SRAS scale with CSSS, less between the dimensions Depression/Hopelessness and Isolation/social support (SRAS) with Cognitive Disconnection (CSSS) and especially the Positive Reappraisal had a significant weight on suicidal risk. Conclusions: Positive Reappraisal is a coping strategy that can protect mental health in situations of stress associated with suicidal risk of the rural population, farmers, and agricultural workers.
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BACKGROUND: A new variant of endemic pemphigus foliaceus (EPF) has been documented, El Bagre-EPF. We aimed to study antinuclear antibodies (ANAs) in these patients. METHODS: We performed a case-control study, testing 57 patients affected by this disease and 57 controls from the endemic area matched by work activity and demographics. The participants were evaluated clinically as well as by detection of ANAs utilizing HEp-2 cells. We utilized Triton-induced partial permeabilization of the cell membranes, allowing for the visualization of intracellular and intranuclear antigens. We also immunoadsorbed the ANAs using synthetic peptides to elucidate the nature of the ANA. RESULTS: We detected the presence of a new pattern of ANAs. The new pattern of ANAs was seen in 24% of the El Bagre-EPF patients, compared to our controls (P < 0.001). The new ANA pattern consisted of a thin nuclear and nucleolar rim, finely speckled nucleolar, nuclear membrane pores stains, and a positive intranuclear stain directed against small nuclear components, as well as cytoplasmic deposits of autoantibodies were also observed. The new ANAs pattern perfectly colocalized with commercial antibodies to miocardium-enriched zonula occlusans-1 associated protein (MIZAP), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), p0071 and desmoplakins I-II (all from Progen Biotechnik). Additionally in 14% of patients with El Bagre-EPF forme fruste and hyperpigmented clinical presentations, a classic homogeneous ANA pattern was observed with autoantibodies specific for Ro, La, Sm, and double-stranded DNA antigens. Immunoadsorption with peptide-based sequences from MIZAP, ARVCF, p0071 and desmoplakins I-II removed the new ANA pattern. CONCLUSIONS: We describe a new pattern of ANAs in El Bagre-EPF, colocalizing with autoantibodies directed against MIZAP, ARVCF, p0071, and desmoplakins I-II.
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Pênfigo , Humanos , Pênfigo/diagnóstico , Pênfigo/epidemiologia , Anticorpos Antinucleares , Desmoplaquinas/metabolismo , Estudos de Casos e Controles , Colômbia/epidemiologia , Pele/metabolismo , Doenças Endêmicas , Autoanticorpos , Antígenos , Fosfoproteínas/metabolismo , Moléculas de Adesão Celular/metabolismo , Proteínas do Domínio Armadillo/metabolismoRESUMO
BACKGROUND: A new variant of endemic pemphigus foliaceus is present in El Bagre, Colombia, and surrounding municipalities (El Bagre-EPF) that affects the skin and in some presentations affects other organs with autoantibodies directed against cell junctions. METHODS: We studied 200 El Bagre-EPF patient perilesional skin biopsies, as well as 200 skin biopsies from normal controls in the endemic area. RESULTS: We observed blister extrusions of sebaceous glands or entire pilosebaceous units via the isthmus in 23% of the patients and not in the controls. CONCLUSIONS: The extrusion of hair follicular unit contents is consistent with our previous pathologic findings of autoreactivity to these units, and their observed clinical decrease in patients affected by El Bagre-EPF.
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Pênfigo , Autoanticorpos , Vesícula/epidemiologia , Colômbia/epidemiologia , Doenças Endêmicas , Humanos , Pênfigo/patologia , América do SulRESUMO
BACKGROUND: El Bagre endemic pemphigus foliaceus (El Bagre-EPF) is a new variant of endemic pemphigus foliaceus present in the El Bagre area of Colombia, South America. Here, we investigate the presence of complement/C5-b9 in lesional skin of patients and matched controls from the endemic area. We also aim to compare the patient's autoantibody levels using indirect immunofluorescent titers (IIF) and correlate with the lesional presence of complement/C5b-9. METHODS: A case-control study was carried out by testing for the presence of complement/C5b-9 in lesional skin in 43 patients affected by El Bagre-EPF, as well as 43 matched, healthy controls from the endemic area. Skin biopsies were obtained and evaluated via hematoxylin and eosin staining, and immunohistochemistry. RESULTS: The presence of complement/C5b-9 was observed in all cases of the patients affected by El Bagre-EPF and was not observed in the controls from the endemic area (P < 0.001). The patients' autoantibody titers utilizing IIF for IgG and IgM showed correlation between higher autoantibody titers and stronger intensity of staining with complement/C5-b9 staining (P < 0.001). CONCLUSION: Patients affected by El Bagre-EPF have lesional deposition of complement/C5b, which correlates with disease severity and previously established serologies.
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Proteínas do Sistema Complemento/imunologia , Pênfigo/imunologia , Pênfigo/patologia , Autoanticorpos/imunologia , Biópsia , Estudos de Casos e Controles , Colômbia/epidemiologia , Feminino , Humanos , Imuno-Histoquímica/instrumentação , Masculino , Pênfigo/epidemiologia , Índice de Gravidade de Doença , Pele/patologia , Dermatopatias/epidemiologia , Dermatopatias/imunologia , Dermatopatias/patologiaRESUMO
BACKGROUND: The majority of the patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre EPF or pemphigus Abreu-Manu), have experienced vision problems; we have previously reported several ocular abnormalities. METHODS: Here, we aimed to investigate reactivity to optic nerves in these patients. We utilized bovine, rat and mouse optic nerves, and performed immunofluorescence and confocal microscopy to test for optical nerve autoreactivity. We tested 45 patients affected by this disease and 45 controls from the endemic area matched by age, sex and work activity. RESULTS: Overall, 37 of the 45 patient sera reacted to the optic nerve envelope that is composed of leptomeninges; the reactivity was polyclonal and present mostly at the cell junctions (P < 0.001). The immune response was directed against optic nerve sheath cell junctions and the vessels inside it, as well as other molecules inside the nerve. No control cases were positive. Of interest, all the patient autoantibodies co-localized with commercial antibodies to desmoplakins I-II, myocardium-enriched zonula occludens-1- associated protein (MYZAP), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), and plakophilin-4 (p0071) from Progen Biotechnik (P < 0.001). CONCLUSION: We conclude that the majority of the patients affected by pemphigus Abreu-Manu have autoantibodies to optic nerve sheath envelope cell junctions. These antibodies also co-localize with armadillo repeat gene deleted in velo-cardio-facial syndrome, p0071 and desmoplakins I-II. The clinical significance of our findings remains unknown.
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BACKGROUND: We previously showed that one-third of patients affected by endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF), display autoreactivity to the heart. OBJECTIVE: The purpose of this study was to investigate rhythm disturbances with the presence of autoantibodies and correlate them with ECG changes in these patients. METHODS: We performed a study comparing 30 patients and 30 controls from the endemic area, matched by demographics, including age, sex, weight, work activities, and comorbidities. ECG as well as direct and indirect immunofluorescence, immunohistochemistry, and confocal microscopic studies focusing on cardiac node abnormalities were performed. Autopsies of 7 patients also were reviewed. RESULTS: The main ECG abnormalities seen in the El Bagre-EPF patients were sinus bradycardia (in one-half), followed by left bundle branch block, left posterior fascicular block, and left anterior fascicular block compared with the controls. One-third of the patients displayed polyclonal autoantibodies against the sinoatrial and/or AV nodes and the His bundle correlating with rhythm anomalies and delays in the cardiac conduction system (P <.01). The patient antibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), and myocardium-enriched zonula occludens-1-associated protein (MYZAP; Progen Biotechnik) (P <.01). CONCLUSION: One-third of the patients affected by El Bagre-EPF have rhythm abnormalities that slow the conduction of impulses in cardiac nodes and the cardiac conduction system. These abnormalities likely occur as a result of deposition of autoantibodies, complement, and other inflammatory molecules. We show for the first time that MYZAP is present in cardiac nodes.
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Autoanticorpos/imunologia , Bradicardia/etiologia , Doenças Endêmicas , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/fisiologia , Pênfigo/complicações , Adulto , Biópsia , Bradicardia/epidemiologia , Bradicardia/fisiopatologia , Estudos de Casos e Controles , Colômbia/epidemiologia , Eletrocardiografia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Incidência , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Pênfigo/diagnóstico , Pênfigo/epidemiologia , Projetos Piloto , Pele/patologiaRESUMO
BACKGROUND: We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America (El Bagre-EPF, or pemphigus Abreu-Manu). El Bagre-EPF differs from other types of EPF clinically, epidemiologically, immunologically and in its target antigens. We reported the presence of patient autoantibodies colocalizing with armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), a catenin cell junction protein colocalizing with El Bagre-EPF autoantibodies in the heart and within pilosebaceous units along their neurovascular supply routes. Here we investigate the presence of ARVCF in skin and its possibility as a cutaneous El Bagre-EPF antigen. METHODS: We used a case-control study, testing sera of 45 patients and 45 controls via direct and indirect immunofluorescence (DIF/IIF), confocal microscopy, immunoelectron microscopy and immunoblotting for the presence of ARVCF and its relationship with El Bagre-EPF autoantibodies in the skin. We also immunoadsorbed samples with desmoglein 1 (Dsg1) ectodomain (El Bagre-EPF antigen) by incubating with the positive ARVCF samples from DIF and IIF. RESULTS: ARVCF was expressed in all the samples from the cases and controls. Immunoadsorption with Dsg1 on positive ARVCF immunofluorescence DIF/IIF cases showed that the immune response was present against non-desmoglein 1 antigen(s). Overall, 40/45 patients showed colocalization of their autoantibodies with ARVCF in the epidermis; no controls from the endemic area displayed colocalization. CONCLUSIONS: We demonstrate that ARVCF is expressed in many areas of human skin, and colocalizes with the majority of El Bagre-EPF autoantibodies as a putative antigen.
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El tratamiento con implantes convencionales no puede hacer parte de la rehabilitación implantosoportada en maxilares edéntulos totales en algunos pacientes, debido a la resorción ósea avanzada o por neumatización del seno maxilar, lo que conduce a cantidades inadecuadas de tejido óseo para el anclaje de los implantes. Durante más de tres décadas, técnicas quirúrgicas para colocación de injertos óseos antes o simultáneamente con la colocación del implante se ha convertido en la rutina en rehabilitación oral. Diversas técnicas de aumento óseo, como la elevación de seno maxilar o injerto óseo, se han descrito con el objetivo común de aumentar el volumen de hueso de soporte. Actualmente con el desarrollo de la técnica en implantes cigomáticos se pueden evitar estas técnicas de injertos óseos devolviendo a los pacientes mejor calidad de vida y estética adecuada con un trauma menor y facilitando el tratamiento y el pronóstico del mismo.
Treatment with conventional implants can not be part of the implant rehabilitation in edentulous jaws in some patients due to advanced bone resorption or sinus neumatization, which leads to inadequate amounts of bone to anchor the implants. For over three decades, surgical placement of bone prior to or simultaneously with implant placement grafting techniques has become routine in oral rehabilitation. Several bone augmentation techniques such as sinus lift or bone graft, have been reported with the common goal of increasing the volume of load bearing bone. Now with the development of technology in zygomatic implants can prevent these bone graft techniques returning patients better quality of life and appropriate aesthetics. With less trauma and facilitating the treatment and prognosis of it.
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Palmoplantar lichen planus is an uncommon dermatosis. We present a case of 38-year-old Caucasian male with a history of pruritic, scaly lesions on the right plantar foot. Physical examination revealed whitish plaques and numerous spiny hyperkeratotic papules and focal scaling. A biopsy demonstrated orthohyperkeratosis and acanthosis of the epidermis. Immunohistochemical staining revealed positivity within the epidermis and/or lichenoid infiltrate with CD3, CD8, CD45, CD68, myeloid histiod antigen, BCL2, p27, p53, HLA-DPDQDR, metallothionein and tissue inhibitor of metalloproteinases 1. The diagnosis of PPLP was thus confirmed; this case illustrates that PPLP should be considered in the differential diagnosis of uncommon foot dermatoses with a significant junctional inflammatory component.
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Dermatoses do Pé/patologia , Dermatoses da Mão/patologia , Líquen Plano/patologia , Adulto , Biópsia , Diagnóstico Diferencial , Epiderme/patologia , Humanos , Imuno-Histoquímica , MasculinoRESUMO
Palmoplantar lichen planus is an uncommon dermatosis. We present a case of 38-year-old Caucasian male with a history of pruritic, scaly lesions on the right plantar foot. Physical examination revealed whitish plaques and numerous spiny hyperkeratotic papules and focal scaling. A biopsy demonstrated orthohyperkeratosis and acanthosis of the epidermis. Immunohistochemical staining revealed positivity within the epidermis and/or lichenoid infiltrate with CD3, CD8, CD45, CD68, myeloid histiod antigen, BCL2, p27, p53, HLA-DPDQDR, metallothionein and tissue inhibitor of metalloproteinases 1. The diagnosis of PPLP was thus confirmed; this case illustrates that PPLP should be considered in the differential diagnosis of uncommon foot dermatoses with a significant junctional inflammatory component.
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Adulto , Humanos , Masculino , Dermatoses do Pé/patologia , Dermatoses da Mão/patologia , Líquen Plano/patologia , Biópsia , Diagnóstico Diferencial , Epiderme/patologia , Imuno-HistoquímicaRESUMO
En muchas enfermedades dermatológicas se presentan ampollas, pero no todas son de etiología autoinmune. Para el estudio de las enfermedades ampollosas se deben tener en cuenta las manifestaciones clínicas, la historia de cómo y cuándo empezaron las ampollas, las características epidemiológicas e histológicas (por ejemplo, el nivel de la piel en el que se producen las ampollas) y la presencia o no de infiltrados inflamatorios. Para corroborar la etiología autoinmune de la enfermedad ampollosa es importante contar con los resultados de pruebas como la inmunofluorescencia directa e indirecta, el inmunoblotting, el ensayo inmunoenzimático (ELISA), la inmunoprecipitación y la microscopía electrónica. La información sobre los títulos séricos de autoanticuerpos ayuda a orientar mejor el tratamiento inmunosupresor.
Blisters may appear in many dermatological diseases, but they are not necessarily of autoimmune etiology. For the study of blistering diseases, it is necessary to take into account the clinical aspects, the history of when and how blisters appeared, the epidemiological and histological information (for instance, the skin level at which blisters are located), and whether inflammatory infiltrates are present. In order to corroborate the autoimmune etiology of blisters, it is important to have the results of confirmatory tests such as direct and indirect immunofluorescence, immune blotting, enzyme-linked immune-assay (ELISA), immune precipitation, and electronic microscopy. Information on autoantibodies serum titers may help to conduct a more precise immunosuppressive therapy.
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Humanos , Doenças Autoimunes/etiologia , Dermatopatias Vesiculobolhosas/imunologia , Pênfigo/diagnóstico , Pênfigo/etiologiaRESUMO
Thermostable microbial lipases are potential candidates for industrial applications such as specialty organic syntheses as well as hydrolysis of fats and oils. In this work, basic biochemical engineering tools were applied to enhance the production of BTL2 lipase cloned in Escherichia coli BL321 under control of the strong temperature-inducible λP(L) promoter. Initially, surface response analysis was used to assess the influence of growth and induction temperatures on enzyme production, in flask experiments. The results showed that temperatures of 30 and 45°C were the most suitable for growth and induction, respectively, and led to an enzyme specific activity of 706,000 U/gDCW. The most promising induction conditions previously identified were validated in fed-batch cultivation, carried out in a 2L bioreactor. Specific enzyme activity reached 770,000 U/gDCW, corresponding to 13,000 U/L of culture medium and a lipase protein concentration of 10.8 g/L. This superior performance on enzyme production was a consequence of the improved response of λP(L) promoter triggered by the high induction temperature applied (45°C). These results point out to the importance of taking into account protein structure and stability to adequately design the recombinant protein production strategy for thermally induced promoters.
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Escherichia coli/genética , Temperatura Alta , Lipase/biossíntese , Proteínas de Bactérias , Reatores Biológicos , Clonagem Molecular , Estabilidade Enzimática , Escherichia coli/metabolismo , Lipase/genética , Lipase/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
BACKGROUND: Melanin and melanophages are commonly seen under the basement membrane zone of the skin in patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF). OBJECTIVE: Our study was conducted to determine the nature of these pigmentary alterations. METHODS: We utilized clinical, histopathologic and immunologic techniques including direct and indirect immunofluorescence, immunohistochemistry, Bielschowsky staining and immunoelectron microscopy studies. RESULTS: In the El Bagre-EPF patients, we detected dermal melanin in melanophages and antigen-presenting cells, in close proximity to neural and vascular markers. The melanophages consisted of a mixed population expressing CD68, myeloid/histoid antigen and S-100 protein. By immunoelectron microscopy, the presence of autoantibodies in proximity to melanin granules was confirmed within the melanocytes utilizing 10-nm gold particles. CONCLUSION: Dermal antigen-presenting cells, including melanophages, seem to contain a diverse combination of molecules, representative of an immunologic process where these cells are engulfing both autoantigens and/or cellular debris in El Bagre-EPF. Autoantibodies to discrete components of melanocytes were also identified; the clinical and immunologic significance of these findings remains unknown. Our work may provide a possible explanation of a darkened complexion in patients affected by endemic pemphigus foliaceus.
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Autoanticorpos/imunologia , Membrana Basal/imunologia , Membrana Basal/ultraestrutura , Melaninas/imunologia , Melanócitos/imunologia , Melanócitos/ultraestrutura , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/patologia , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Colômbia , Derme/imunologia , Derme/patologia , Doenças Endêmicas , Feminino , Humanos , Masculino , Pênfigo , Proteínas S100/imunologiaRESUMO
Several patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF) have experienced a sudden death syndrome, including persons below the age of 50. El Bagre-EPF patients share several autoantigens with paraneoplastic pemphigus patients, such as reactivity to plakins. Further, paraneoplastic pemphigus patients have autoantibodies to the heart. Therefore, we tested 15 El Bagre-EPF patients and 15 controls from the endemic area for autoreactivity to heart tissue using direct and indirect immunofluorescence, confocal microscopy, immunohistochemistry, immunoblotting, and immunoelectron microscopy utilizing heart extracts as antigens. We found that 7 of 15 El Bagre patients exhibited a polyclonal immune response to several cell junctions of the heart, often colocalizing with known markers. These colocalizing markers included those for the area composita of the heart, such as anti-desmoplakins I and II; markers for gap junctions, such as connexin 43; markers for tight junctions, such as ezrin and junctional adhesion molecule A; and adherens junctions, such pan-cadherin. We also detected colocalization of the patient antibodies within blood vessels, Purkinje fibers, and cardiac sarcomeres. We conclude that El Bagre-EPF patients display autoreactivity to multiple cardiac epitopes, that this disease may resemble what is found in patients with rheumatic carditis, and further, that the cardiac pathophysiology of this disorder warrants further evaluation.
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Autoanticorpos/metabolismo , Doenças Endêmicas , Miocárdio/metabolismo , Pênfigo/epidemiologia , Pênfigo/imunologia , Adulto , Animais , Complexo Antígeno-Anticorpo/metabolismo , Autoanticorpos/imunologia , Autoantígenos/imunologia , Autoantígenos/metabolismo , Caderinas/imunologia , Caderinas/metabolismo , Bovinos , Moléculas de Adesão Celular/imunologia , Moléculas de Adesão Celular/metabolismo , Colômbia , Conexina 43/imunologia , Conexina 43/metabolismo , Proteínas do Citoesqueleto/imunologia , Proteínas do Citoesqueleto/metabolismo , Morte Súbita Cardíaca , Desmoplaquinas/imunologia , Desmoplaquinas/metabolismo , Coração/fisiologia , Coração/fisiopatologia , Humanos , Imuno-Histoquímica , Junções Intercelulares/ultraestrutura , Camundongos , Microscopia Eletrônica , Pessoa de Meia-Idade , Miocárdio/imunologia , Miocárdio/ultraestrutura , Pênfigo/mortalidade , Pênfigo/fisiopatologia , Ratos , Receptores de Superfície Celular/imunologia , Receptores de Superfície Celular/metabolismo , Adulto JovemRESUMO
Senear Usher syndrome is a variant of pemphigus foliaceus, confined to seborrheic sites and considered to be a clinical overlap syndrome, with features of both pemphigus foliaceus and lupus erythematosus. We recently described autoantibodies to skin eyelid meibomian glands in patients with a new variant of endemic pemphigus foliaceus (El Bagre EPF) in South America. We tested for El Bagre EPF patient sera autoreactivity to pilosebaceous units utilizing direct and indirect immunofluorescence, confocal microscopy, immunohistochemistry and immunoelectron microscopy. Hematoxylin and eosin staining of skin biopsies revealed that one third of the patients affected by El Bagre-EPF demonstrated some histologic alteration of the pilosebaceous units. By immunohistochemistry, most El Bagre EPF biopsies demonstrated evidence of an autoimmune response along the neural and vascular supply routes of the pilosebaceous units. An active immune response was seen with antibodies such as anti-human mast cell tryptase, myeloid/histoid antigen, CD8, CD20, CD68, CD117/c-kit, ZAP-70 and vimentin. Immunoelectron microscopy demonstrated autoantibodies within the hair follicle and at the basement membrane area of the sebaceous glands. El Bagre-EPF patients have autoantibodies to pilosebaceous units and to their surrounding neurovascular packages. Our results warrant further characterization and may explain the loss of hair described in severe endemic pemphigus foliaceus before the therapeutic steroid era.
Assuntos
Autoanticorpos/análise , Autoimunidade/imunologia , Doenças Endêmicas , Glândulas Tarsais/metabolismo , Pênfigo/imunologia , Pele/metabolismo , Biópsia , Colômbia/epidemiologia , Desmoplaquinas/imunologia , Desmoplaquinas/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imuno-Histoquímica , Glândulas Tarsais/patologia , Microscopia Confocal , Pênfigo/epidemiologia , Pênfigo/patologia , Placofilinas/imunologia , Placofilinas/metabolismo , Pele/patologiaRESUMO
BACKGROUND: Endemic pemphigus foliaceus (EPF), is also known as "fogo selvagem" or "wild fire," reflecting the intense burning sensation of the skin reported by patients with this disease. Based on this finding, we tested for neural autoreactivity in patients affected by a new variant of EPF (El Bagre-EPF). METHODS: We tested 20 El Bagre-EPF patients, 20 normal controls from the endemic area, and 20 age- and sex-matched normal controls from outside the endemic area. We tested for autoreactivity to several immunoglobulins and complement. Both human skin and bovine tail were used as antigens. RESULTS: We detected autoreactivity to neural structures, mechanoreceptors, nerves, perineural cell layers of the arachnoid envelope around the optic nerve, brain structures, and to neuromuscular spindles; these structures colocalized with several neural markers. The patient antibodies also colocalized with desmoplakins 1 and 2, with the armadillo repeat protein deleted in velo-cardio-facial syndrome and with p0071 antibodies. Autoreactivity was also found associated with neurovascular bundles innervating the skin, and immunoelectron microscopy using protein A gold against patient antibodies was positive against the nerve axons. Paucicellularity of the intraepidermal nerve endings and defragmentation of the neural plexus were seen in 70% of the cases and not in the controls from the endemic area (p<0.005). Neuropsychological and/or behavioral symptoms were detected in individuals from the endemic area, including sensorimotor axonal neuropathy. CONCLUSIONS: Our findings may explain for the first time the "pose of pemphigus," representing a dorsiflexural posture seen in EPF patients vis-a-vis the weakness of the extensor nerves, and furthermore, the autoreactivity to nerves in EPF could explain the "burning sensation" encountered in EPF disease.
Assuntos
Antígenos/imunologia , Autoanticorpos/imunologia , Plexo Corióideo/imunologia , Desmoplaquinas/metabolismo , Doenças Endêmicas , Nervo Óptico/imunologia , Corpúsculos de Pacini/imunologia , Pênfigo , Pele/imunologia , Adulto , Animais , Antígenos/análise , Antígenos/metabolismo , Autoanticorpos/análise , Autoanticorpos/metabolismo , Axônios/imunologia , Axônios/patologia , Antígenos CD57/genética , Antígenos CD57/imunologia , Antígenos CD57/metabolismo , Estudos de Casos e Controles , Bovinos , Plexo Corióideo/efeitos dos fármacos , Plexo Corióideo/patologia , Colômbia/epidemiologia , Desmoplaquinas/genética , Feminino , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Imunoglobulinas/análise , Imunoglobulinas/imunologia , Imunoglobulinas/metabolismo , Imuno-Histoquímica , Masculino , Mercúrio/efeitos adversos , Microscopia Imunoeletrônica , Pessoa de Meia-Idade , Proteína Básica da Mielina/genética , Proteína Básica da Mielina/metabolismo , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/patologia , Corpúsculos de Pacini/efeitos dos fármacos , Corpúsculos de Pacini/patologia , Pênfigo/epidemiologia , Pênfigo/imunologia , Pênfigo/patologia , Pênfigo/fisiopatologia , Postura , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
BACKGROUND: Previously, we described a new variant of endemic pemphigus foliaceus (EPF) in Colombia, South America (El Bagre-EPF). OBJECTIVE: Continuing our characterization of this variant of EPF, we now focus on one of our previously reported clinical findings: the presence of ocular lesions. These ocular lesions are seen in patients having extensive skin involvement, as measured by the Lund and Browder scale, which is generally used for patients with skin burns. METHODS: We specifically searched for evidence of autoreactivity to various eyelid structures in these patients and correlated our immunologic data with the clinical findings. We performed indirect immunofluorescence studies using normal-appearing human eyelid skin from routine blepharoplasties as substrate tissue. We tested sera from 12 patients with El Bagre-EPF and ocular lesions, 5 patients with sporadic (nonendemic) pemphigus foliaceus, and 20 healthy control subjects (10 from the El Bagre-EPF endemic area and 10 from nonendemic areas). We used fluorescein isothiocyanate conjugated goat antiserum to human total IgG/IgA/IgM as a secondary antibody. In addition, we used fluorescein isothiocyanate conjugated antibodies to human fibrinogen, albumin, IgG, IgE, C1q, and C3, Texas Red (Rockland Immunochemicals, Inc, Gilbertsville, PA), Alexa Fluor 555, or Alexa Fluor 594 (Invitrogen, Carlsbad, CA). Ki-67 (a cell proliferation marker) was used to determine the cell proliferation rate, and nuclear counterstaining was performed with either 4', 6-diamidino-2-phenylindole or Topro III (Invitrogen, Carlsbad, CA). RESULTS: We observed autoreactivity to multiple eyelid structures, including meibomian glands and tarsal muscle bundles at different levels, and some areas of the epidermis and the dermis close to the isthmus of the eyelids. Tarsal plate autoreactivity was seen in 10 of 12 of the El Bagre-EPF sera and in one control with pemphigus erythematosus. Furthermore, immunoprecipitation using an eyelid sample as a substrate with 1 mmol/L of sodium orthovanodate showed autoreactivity to several antigens, including some of possible lipid origin. LIMITATIONS: The main limitation of this study is the fact that the antigen or antigens remain unknown. CONCLUSION: We identified for the first time to our knowledge autoantibodies to meibomian glands and tarsal muscle in El Bagre-EPF. Our findings suggest that the autoantibodies to the ocular structures cause the clinical and histopathological findings in the ocular lesions in El Bagre-EPF.
Assuntos
Autoanticorpos/análise , Oftalmopatias/imunologia , Pálpebras/imunologia , Músculos Faciais/imunologia , Glândulas Tarsais/imunologia , Pênfigo/imunologia , Feminino , Imunofluorescência , Humanos , MasculinoRESUMO
We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America (El Bagre-EPF). On physical examination, the palms and soles of El Bagre-EPF patients reveal an edematous texture and mild hyperkeratosis, in comparison with the non-glabrous skin of the patients where blisters, pustules or other lesions are commonly found. Based on the preceding observation, we tested the palms of 20 El Bagre-EPF cases and 20 controls from the endemic area for any pathological alterations in the samples by direct immunofluorescence (DIF). Our DIF demonstrated pathological deposits of fibrinogen and albumin, as well as IgG, IgA, IgM, IgD and C3c, at 1) the epidermal basement membrane zone; 2) around isolated areas in the epidermis, 3) within the dermal vessels and nerves, and 4) in areas surrounding dermal neurovascular structures and sweat glands. Specific markers for blood vessels, including 1) anti-intercellular adhesion molecule 1 (ICAM-1)/CD54, and 2) anti-junctional adhesion molecule (JAM-A); as well as specific markers for nerves, including 1) anti-glial fibrillary acidic protein (GFAP), and 2) anti-human neuron specific enolase (NSE) co-localized with the patients' autoantibodies. Although no blisters, ulcerations, pustules or erosions are clinically observed on the palms of El Bagre-EPF patients, our DIF detected distinct immunoreactivity in palm tissue. These alterations may contribute to the clinically edematous texture of the palms and the mild clinical hyperkeratosis found in most of these patients. We propose that normal glabrous skin and non-glabrous skin may be different with regard to the expression of selected molecules, which may vary in number, size or structural organization depending on their anatomical site. Our findings may also partially explain the hyperkeratotic palms that have been clinically well documented in the chronic phase of fogo selvagem i.e., endemic pemphigus foliaceus, in Brazil.