Compromiso oftálmico en enfermedad relacionada con IgG4 / Ophthalmic involvement in IgG4-related disease

Resumen Introducción: la enfermedad oftálmica relacionada con IgG4 (EOR-IgG4) presenta una frecuencia del 11-59%. Pocos estudios describen las disparidades con los pacientes con ER-IgG4 extraoftálmica (NO EOR-IgG4). Objetivos: describir las características clínicas, imagenológicas, anatomopatológicas, resultados de laboratorio y tratamiento de la EOR-IgG4, y compararlas con las de los pacientes NO EOR-IgG4. Materiales y métodos: se realizó un estudio descriptivo sobre una cohorte de 54 pacientes con ER-IgG4. Se reclutaron 16 pacientes con EOR-IgG4 y 38 con NO EOR-IgG4. Se compararon ambos grupos. Resultados: la EOR-IgG4 predominó en mujeres. El 75% presentó afectación oftálmica bilateral. El antecedente de asma se asoció al grupo NO EOR-IgG4 (p=0,018). Los pacientes con EOR-IgG4 presentaron niveles séricos menores de IgE e IgG total, y la glándula lagrimal fue la estructura más afectada. Predominó el infiltrado linfoplasmocitario y eosinofílico, siendo la fibrosis estoriforme más frecuente que la no estoriforme en el grupo EOR-IgG4. Conclusiones: si bien los resultados fueron similares a lo reportado previamente, en discordancia con otras series, encontramos asociación negativa entre el asma y los niveles de IgG total sérica en los pacientes EOR-IgG4.

Abstract Introduction: IgG4-related ophthalmic disease (IgG4-ROD) presents a frequency of 11-58.8%. Few studies describe the disparities with patients with extraophthalmic IgG4-related disease (NOT IgG4-ROD). Objectives: describe the clinical, imaging, pathological characteristics, laboratory results, and treatment of IgG4-ROD characteristics; and compare them with those of the NOT IgG4-ROD patients. Materials and methods: a descriptive study was carried out on a cohort of 54 patients with ER-IgG4. 16 patients with IgG4-ROD and 38 with NOT IgG4-ROD were recruited. The data was analyzed with the SPSS Statistics 19 software. Results: IgG4-ROD predominated in women. 75% presented bilateral ophthalmic involvement. A history of asthma was associated with the NOT IgG4-ROD group (p=0,018). Patients with IgG4-ROD presented lower serum levels of IgE and total IgG, and the lacrimal gland was the most affected structure. Lymphoplasmacytic and eosinophilic infiltrates predominated, with storiform fibrosis being more frequent than non-storiform in the IgG4-ROD group. Conclusions: although the results were similar to those previously reported, in disagreement with other series, we found a negative association between asthma and serum total IgG levels with EOR-IgG4 patients.

Enfermedad relacionada a IgG4. Serie clínica de pacientes chilenos / IGG4-related disease. Report of 52 patients

BACKGROUND: IgG4-related disease (IgG4 RD) is an immune-mediated fibro-inflammatory disorder, with tissue infiltration of IgG4+ plasma cells. It causes pseudotumors, tumors, and a wide spectrum of clinical manifestations. AIM: To report the clinical, laboratory, histopathological and treatment characteristics of a group of Chilean patients with IgG4 RD. MATERIAL AND METHODS: Review of medical records of 52 patients aged 18 to 76 years with IgG4 RD seen at six medical centers. RESULTS: Elevated IgG4 serum levels (> 135 mg/dl) were found in 18 of 44 (41%) patients. There was histological confirmation of the disease in 46 patients. The most common sites of involvement were lungs, eyes and kidneys. Eighteen (35%) patients had only one organ involved, 34 (65%) patients had two organs and 13 (25%) patients had three or more organs. The involvement of two organs was significantly more common in men (p < 0.05). In patients with only one organ involvement, the most frequent location was orbital and meningeal. All patients with kidney or lung disease had multiorgan involvement. All patients received corticosteroid therapy, 67% synthetic immunosuppressants, and 16% rituximab. CONCLUSIONS: ER-IgG4 can affect any tissue. Multiorgan involvement was more common in this series, with preference for lungs, eyes and kidneys. An excellent response to steroids is characteristic of the disease, but with a high relapse rate that requires additional immunosuppression.

Sialoadenitis esclerosante asociada a enfermedad por IgG4: reporte de un caso / Sclerosing sialadenitis associated with IgG4 disease: case report

Las enfermedades relacionadas con IgG4 (ER-IgG4) son entidades fibroinflamatorias e inmunomediadas, caracterizadas por la afección multiorgánica, con la formación de pseudotumores que provocan lesión tisular y daño orgánico subsecuente. Se describe el caso de un paciente de 43 años que presentó sialoadenitis esclerosante y cumplió todos los criterios diagnósticos de enfermedad relacionada con IgG4.

IgG4-related diseases (IgG4-RD) are fibroinflammatory immune-mediated entities characterized by multiorgan involvement with the development of pseudotumors that cause tissue injury and subsequent organ damage. We describe the case of a 43-year-old man who presented sclerosing sialadenitis and fulfilled the diagnostic criteria for IgG4-related disease.

Pacientes con compromiso orbitario y renal: Diagnósticos diferenciales poco frecuentes / Patients with orbitary and kidney commitment: Rare differential diagnoses

Se comunica una serie de tres casos clínicos que consultaron al servicio de Reumatología por compromiso orbitario y renal. Uno de ellos presentó pseudotumor orbitario con proteinuria en rango nefrótico; se realizó biopsia y se encontró infiltrado linfoplasmocitario denso y fibrosis estoriforme con inmunohistoquímica: 15 células IgG4+ por campo de alto poder y relación IgG/IgG4 ≤40%, concluyendo diagnóstico de enfermedad relacionada por IgG4. El segundo y tercer caso presentaron compromiso ocular con "ojos de mapache" y lesiones amarillentas en párpados, ambos con proteinuria >500 mg/24 h, con biopsia de piel rojo Congo positiva y birrefringencia verde manzana con luz polarizada. Se discuten distintos diagnósticos diferenciales poco frecuentes a tener en cuenta en estos pacientes.

A series of three cases that consulted the rheumatology service due to orbital and renal involvement is reported. One of them presented orbital pseudotumor with proteinuria in the nephrotic range, a biopsy was performed, finding dense lymphoplasmacytic infiltrate and storiform fibrosis with immunohistochemistry: 15 IgG4 positive cells per HPF and IgG/IgG4 ratio ≤40%, concluding diagnosis of IgG4 related disease. The second and third cases presented ocular involvement with raccoon eyes and yellowish lesions on the eyelids, both with proteinuria greater than 500 mg/24 h, with apple-green birefringence of amyloid on congo red staining. Different rare differential diagnoses to take into account in these patients are discussed.

Enfermedad relacionada con IgG4: reporte de un caso y revisión de la literatura / IgG4-related disease: a case report and literature review

Immunoglobulin G4 (IgG4-RD) -related disease is a regional or systemic fibroinflammatory disease of unknown etiology. It has a characteristic histopathological appearance of dense lymphoplasmacytic infiltrates with abundant IgG4 positive plasma cells, storiform fibrosis and obliterative phlebitis with the appearance of inflammatory swelling or swollen lesions. This entity frequently affects the pancreas, salivary glands, and lymph nodes, but it can compromise almost any structure in the human anatomy. This new disease entity includes a wide variety of diseases such as Mikulicz disease, autoimmune pancreatitis, Riedel's thyroiditis, interstitial nephritis, and retroperitoneal fibrosis. Glucocorticoid therapy can resolve clinical and pathologic abnormalities and impaired organ function. IgG4-RD was internationally recognized in 2011, and new evidence has accumulated on its pathogenesis, clinical characteristics, and treatment. However, much is still unknown about the behavior of IgG4 in vivo, the participation of this molecule in disease, and whether its role in IgG4-related disease is primary or secondary. The text below is based on a brief review of the most recent literature on this entity in relation to a clinical case.

Enfermedad relacionada con IgG4, según criterios ACR/EULAR 2019 sin evidencia de IgG4 en sangre / IgG4-related disease according to ACR/EULAR 2019 criteria without evidence of IgG4 in blood

INTRODUCCIÓN. La enfermedad relacionada con IgG4 es una patología fibroinflamatoria multiorgánica, de origen desconocido, que simula trastornos malignos, infecciosos e inflamatorios. Los criterios del American College of Rheumatology y la European League against Rheumatism 2019, son útiles para el diagnóstico diferencial de ésta enfermedad cuando se no se cuenta con evidencia de inmunoglobulina G4 en sangre. CASO CLÍNICO. Paciente hombre de 45 años de edad, nacido en Ambato-Ecuador, con ingreso en noviembre del 2017, en emergencias del Hospital de Especialidades Carlos Andrade Marín, con presencia de tos con hemoptisis leve, febrícula, astenia, pérdida de peso e hiporexia de dos semanas de evolución. Se realizó múltiples exámenes, tras observar infiltrados pulmonares intersticiales, con elevación de inmunoglobulina G en suero, negativas para malignidad; se sospechó de enfermedad relacionada a inmunoglobulina G4. Se ampliaron los estudios para descartar otras patologías más prevalentes y cuyo diferencial es primordial. Se inició tratamiento con prednisona y micofenolato con buena respuesta clínica; durante dos años. DISCUSIÓN. La evidencia científica registró que el hallazgo más importante en la enfermedad relacionada con inmunoglobulina G4 fue un aumento de sus niveles séricos. La recurrencia de la enfermedad en un órgano afectado o la aparición de un nuevo órgano involucrado pudo conducir al diagnóstico en el caso presentado. CONCLUSIÓN. La enfermedad relacionada con inmunoglobulina G4 al ser una patología heterogénea, inmunomediada, al simular otras afecciones puede retrasar el diagnóstico; se debe tener una alta sospecha clínica, si al excluir otros procesos infecciosos, autoinmunes y/o eoplásicos, hay evidencia de patología fibroesclerosante multiorgánica sin causa establecida.

INTRODUCTION. IgG4-related disease is a multiorgan fibroinflammatory pathology of unknown origin that mimics malignant, infectious, and inflammatory disorders. The criteria of the American College of Rheumatology and the European League against Rheumatism 2019 are useful for the differential diagnosis of this disease when there is no evidence of immunoglobulin G4 in blood. CLINICAL CASE. 45-year-old male patient, born in Ambato-Ecuador, with admission in November 2017, in the emergency room of the Hospital de Especialidades Carlos Andrade Marín, with the presence of cough with mild hemoptysis, fever, asthenia, weight loss and hyporexia of two weeks of evolution. Multiple tests were performed, after observing interstitial pulmonary infiltrates, with elevated serum immunoglobulin G, negative for malignancy; immunoglobulin G4-related disease was suspected. Studies were extended to rule out other more prevalent pathologies whose differential is paramount. Treatment with prednisone and mycophenolate was started with good clinical response; for two years. DISCUSSION. The scientific evidence recorded that the most important finding in immunoglobulin G4-related disease was an increase in its serum levels. Recurrence of the disease in an affected organ or the appearance of a new involved organ could have led to the diagnosis in the presented case. CONCLUSION. Immunoglobulin G4-related disease, being a heterogeneous, immune-mediated pathology, by simulating other conditions may delay diagnosis; a high clinical suspicion should be maintained if, when other infectious, autoimmune and/or neoplastic processes are excluded, there is evidence of multiorgan fibrosclerosing pathology without established cause.

IgG4-related Disease: a diagnostic challenge

Immunoglobulin IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition with a characteristic histopathological appearance that can affect almost any organ. The clinical features result from a focal or diffuse appearance of a tumor-like swelling of the affected organs, identified by physical and/or imaging examination. Herein, we report the case of a 38-year-old male complaining of a worsening chronic right lumbar pain associated with legs and scrotum edema. He also had itchy and erythematous cutaneous lesions on the abdominal wall over the last 8 months, and complained of a diffuse and mild to moderate abdominal discomfort. On examination, the liver was firmly enlarged and tender. His legs had 2+ symmetrical pitting edema extending from his feet to just above the knees. An abdominal computed tomography scan showed a large mass (10 x 8 x 4cm) involving the abdominal infrarenal aorta and the iliac arteries, and compressing the inferior vena cava, with dilated iliac veins, raising the possibility of lymphoproliferative disease. During the initial investigation, the laboratory workup revealed anemia, without other marked changes. A laparoscopic-guided biopsy of the peri-aortic mass was undertaken. The histological report associated with IgG4 immunoglobulin measurement rendered the diagnosis of IgG4-RD. The patient had a favorable outcome after the use of glucocorticoids with the abdominal mass remission.

El ojo: Un rompecabezas diagnóstico: Estudio observacional descriptivo y revisión / The Eye: A Diagnostic Puzzle: Descriptive observational study and review

Se comunica una serie de casos, multicéntricos de la cual participaron cinco instituciones. La muestra fue de 17 pacientes, de los cuales 11 pertenecían al Hospital Dr. J.M. Cullen. Todos consultaron por compromiso orbitario y/o periorbitario. El compromiso en hombres fue de 23.4% y un 76.6% en mujeres. La edad media en años fue de 45.4 (17-69 años). Dentro de los diagnósticos encontrados, cinco casos fueron Enfermedad Relacionada con IgG4 (ER-IgG4), dos casos de Enfermedad de Erdheim Chester (EEC), dos Xantogranuloma, dos xantelasmas, un caso de metástasis de cáncer de mama, un caso de orbitopatía tiroidea, un caso de Amiloidosis con mieloma múltiple, y tres sin diagnóstico. Se revisan los diagnósticos diferenciales encontrados.

A series of multicentric cases is reported, of which five institutions participated. The sample was of 17 patients, of which 11 belonged to our Hospital, the Dr. J.M. Cullen Hospital. All consulted for orbital and/or periorbital commitment. The commitment in men was 23.4% and 76.6% in women. The average age in years was 45.4 (17-69 years). Among the diagnoses found, five cases were IgG4-Related Disease, two cases of Erdheim Chester Disease, two Xantogranuloma, two xanthelasmas, a case of breast cancer metastases, a case of thyroid orbitopathy, a case of Amyloidosis with multiple myeloma, and three without diagnosis. Differential diagnoses found are reviewed.

Type 1 autoimmune pancreatitis: relapse with liver abscess / Pancreatite autoimune tipo 1: recidiva com abscesso hepático

ABSTRACT: Type 1 autoimmune pancreatitis is a cause of chronic pancreatitis related to the systemic disease known as IgG4-related Sclerosing Disease. Case report: We report the case of a 64-year-old male patient who presented recurrentepigastric pain radiating to the back, associated with jaundice, xerostomia, nausea, and vomiting, since 2014, diagnosed two years later with an unresectable pancreatic adenocarcinoma. The diagnosis was questioned after a few follow-up months without clinical deterioration when it was suggested the possibility of type 1 autoimmune pancreatitis in its pseudotumoral form. The patient was then treated with glucocorticoids, obtaining significantclinical improvement. After two years of follow-up, he returned asymptomatic with images suggestive of sclerosingcholangitis and a large liver abscess. Importance of the issue: The present case denotes the difficulty found in this diagnosis due to clinical and radiological resemblances with pancreatic adenocarcinoma. Besides that, it presents a seldom described disease complication, the liver abscess. (AU)

RESUMO: A pancreatite autoimune tipo 1 é uma causa de pancreatite crônica relacionada à doença sistêmica conhecida como Doença Esclerosante relacionada à IgG4. Relato do caso: Relatamos o caso de um paciente do sexo masculino,64 anos, que apresentou quadros recorrentes de dor epigástrica com irradiação para as costas, associada com icterícia, xerostomia, náuseas e vômitos desde 2014, diagnosticado após 2 anos com adenocarcinoma pancreático irressecável. O diagnóstico foi questionado após alguns meses de acompanhamento sem deterioração clínica, quando aventaram a possibilidade de forma pseudotumoral da pancreatite autoimune tipo 1. Realizou tratamento com glicocorticoides, obtendo melhora clínica importante. Após dois anos de acompanhamento, retorna assintomático com imagens sugestivas de colangite esclerosante e volumoso abscesso hepático. Importância do problema: O presente caso denota uma dificuldade encontrada no diagnóstico dessa entidade devido a semelhanças clínico-radiológicas com o adenocarcinoma pancreático. Além disso, apresenta uma complicação pouco descrita da doença, o abscesso hepático. (AU)

Paquimeningitis relacionada con IgG4 y la visión. Reporte de caso / Ophthalmological manifestations of IgG4-related pachymeningitis. A case repor

Introducción: la inmunoglobulina G4 es un subtipo de inmunoglobulina G que corresponde a menos del 5% del total de inmunoglo-bulinas. Niveles elevados de esta molécula se han asociado con el desarrollo de diferentes patologías. Método: presentación de caso clínico. Resultados: se presenta el caso de una mujer de 51 años que consultó por disminución de agudeza visual, escotoma central en ojo izquierdo y edema de papila bilateral. Se encontraron signos compatibles con paquimeningitis en la resonancia nuclear magnética. También presentó aumento de presión de apertura en la punción lumbar. En el estudio de laboratorio se observó un aumento en los niveles plasmáticos de IgG4, lo cual llevó al diagnóstico de paquimeningitis relacionada con IgG4. La paciente fue tratada con corticoides y azatioprina, con excelente evolución posterior al normalizar agudeza visual y campos visuales. Conclusión: en este artículo se describen tres elementos importantes a considerar en estos pacientes: pérdida de visión, edema de discos ópticos y cambios en campo visual.

Introduction: G4 immunoglobulin is 5% of total immunoglobulins in plasma. Elevated levels of this protein are associated with several diseases. Methods: clinical case report. Results: we report a case of a 51-year-old woman who presented with loss of vision, a central scotoma over her left eye and bilateral optic disc edema. She had findings compatible with pachymeningitis based on magnetic resonance imaging. She also exhibited an increased opening pressure in lumbar puncture. In the laboratory workup, we found a two-fold increase in IgG4 levels, which led to a diagnosis of pachymeningitis related to IgG4. The patient was treated accordingly with corticosteroids and azathioprine. The patient experienced excellent progression with complete recovery of her visual acuity and normalization of the visual fields. Conclusion: there is three elements to consider in these patients: vision loss, optic disc edema and visual field changes.

Policondritis recidivante asociada a enfermedad por IgG4 / Relapsing polychondritis associated with IgG4-related disease

La policondritis recidivante (RP) es un trastorno autoinmune sistémico poco frecuente que se caracteriza por episodio y deterioro progresivo de la inflamación del cartílago. Aproximadamente el 30% de los pacientes con RP tienen enfermedad concurrente. Sin embargo, hay tres casos previos reportados de RP relacionado con enfermedad relacionada con la inmunoglobulina G4 (IgG4-RD). Nosotros presentamos otro caso de una mujer de 37 años que desarrolló RP aproximadamente 1 año antes del diagnóstico de IgG4-RD. La asociación entre ER-IgG4 y RP sigue sin estar clara.

Relapsing polychondritis (RP) is a rare systemic autoimmune disorder characterized by the episodic and progressive deterioration of cartilage inflammation. Approximately 30% patients with RP have concurrent disease. However, there are three cases reports of RP complicated by immunoglobulin G4-related disease (IgG4-RD). Here we report another case of a 37-year-old female who developed RP approximately 1 years before IgG4-RD diagnosis. The association between IgG4-RD and RP remains unclear.

Tumor retroperitoneal en el espectro de enfermedades asociadas a igg4 / Retroperitoneal tumor in the clinical spectrum of igg4 related disease

Presentamos el caso de una mujer de 55 años sin antecedentes, que acude por dolor abdominal, se realiza una tomografía abdominopélvica evidenciando un tumor retroperitoneal de aspecto quístico en la periferia de la aorta abdominal, que afecta el riñón izquierdo. Se le realizó una laparotomía exploratoria, nefrectomía izquierda, tumorectomía retroperitoneal y una resección de un fragmento de la aorta abdominal con reporte histopatológico, corroborado por una prueba inmunohistoquímica de fibrosis retroperitoneal y aortitis por IgG4. El espectro de enfermedades relacionadas con IgG4 es de origen inmunológico con la capacidad de involucrar casi cualquier órgano. La epidemiología no es precisa, aunque se observa mayor predilección por la raza asiática, siendo más común durante la séptima década de vida. El diagnóstico radica en la coexistencia de varios parámetros clínicos, laboratoriales e histopatológicos, sin ser ninguno de estos patognomónicos. El objetivo del presente artículo es exponer el reporte de un caso con manifestación inusual de fibrosis retroperitoneal y dar a conocer que la importancia del diagnóstico radica en la decisión terapéutica, ya que cursa con buena respuesta al tratamiento inmunosupresor.

We present the case of a 55-year-old woman, with noclinical pathological history, who presented with abdominal pain, abdominopelvic tomography showing retroperitoneal tumoral in the periphery of the abdominal aorta, which affects the left kidney producing hydronephrosis. Exploratory laparotomy, left radical nephrectomy, retroperitoneal tumorectomy and resection of a fragment of abdominal aorta were performed, with histopathological report, corroborated by immunohistochemistry of retroperitoneal fibrosis and IgG4 aortitis. The spectrum of diseases related to IgG4, are of immunological origin that can involve almost any organ. The epidemiology is not precise, although a greater predilection for the Asian race is observed, being more common in the seventh decade of life, it should be suspected in patients with unexplained pain in one or more organs.The diagnosis lies in the coexistence of several clinical, laboratorial and histopathological parameters, without being any of these pathognomonic. We present a case with unusual presentation of retroperitoneal fibrosis and the importance of the diagnosis lies in the therapeutic decision, since it responds well to immunosuppressive treatment, without requiring surgical management.

Policondritis recidivante asociada a enfermedad por IgG4 / Recurrent Polychondritis Associated with IgG4 Disease

La policondritis recidivante (RP) es un trastorno autoinmune sistémico poco frecuente que se caracteriza por episodio y deterioro progresivo de la inflamación del cartílago. Aproximadamente el 30% de los pacientes con RP tienen enfermedad concurrente. Sin embargo, hay tres casos previos reportados de RP relacionado con enfermedad relacionada con la inmunoglobulina G4 (IgG4-RD). Nosotros presentamos otro caso de una mujer de 37 años que desarrolló RP aproximadamente 1 año antes del diagnóstico de IgG4-RD. La asociación entre ER- IgG4 y RP sigue sin estar clara.

Relapsing polychondritis (RP) is a rare systemic autoimmune disorder characterized by the episodic and progressive deterioration of cartilage inflammation. Approximately 30% patients with RP have concurrent disease. However, there are three cases reports of RP complicated by immunoglobulin G4-related disease (IgG4-RD). Here we report another case of a 37-year-old female who developed RP approximately 1 years before IgG4-RD diagnosis. The association between IgG4-RD and RP remains unclear

Pseudotumor retroperitoneal como apresentação de doença relacionada à IgG 4: relato de caso / Retroperitoneal pseudotumor as a presentation of IgG4-related disease: a case report

Apresentamos um caso de doença relacionada à IgG4 devido às suas várias formas de apresentação clínica e dificuldades diagnósticas, objetivando acrescentar à literatura científica essa apresentação atípica. Trata-se de um homem de 65 anos com dor abdominal, febre e sintomas urinários. Exames laboratoriais inocentes para processo infeccioso agudo. Em tomografia computadorizada de abdome, evidenciou-se pseudotumor em região retroperitoneal, envolvendo ureter, veia e artéria ilíacas. Foi submetido à ressecção cirúrgica, tendo sido confirmado o diagnóstico de doença relacionada à IgG4 pela imuno-histoquímica. Iniciou tratamento com glicocorticoide com melhora clínica importante, seguindo em acompanhamento ambulatorial.

This is a case report of IgG4-related disease because of its wide variety of clinical presentations and difficulties in diagnosis, aiming at adding this atypical presentation to scientific literature. It is a case of a 65-year-old man with abdominal pain, fever and urinary symptoms. Laboratory tests were naive for acute infectious processes. In a computed tomography of the abdomen, retroperitoneal pseudotumor involving ureter, and iliac vein and artery was found. The patient underwent surgical resection, and the diagnosis of IgG4-related disease was confirmed by immunohistochemistry. The treatment was begun with glucocorticoids, with important clinical improvement. He was followed in outpatient settings.

Anticuerpos IgG4 específicos anti Aedes aegypti como factor protector en niños con dengue grave / Aedes aegypti-specifc IgG4 Antibodies as a Protection Factor in Children with Severe Dengue / Anticorpos IgG4 específicos anti-aedes aegypti como fator de proteção em crianças com dengue grave

Resumen: Introducción: La infección por el virus del dengue es un problema de salud pública mundial. El virus es transmitido por la picadura de mosquitos del género Aedes. Las proteínas de la saliva del vector Aedes aegypti inducen anticuerpos IgE e IgG4 específicos, cuya relación con la gravedad del dengue aún es desconocida. Objetivo: Evaluar la asociación entre anticuerpos IgE e IgG4 específicos anti A. aegypti con la gravedad de la infección por dengue. Método: Se realizó un estudio transversal en el que se incluyeron 16 niños con dengue grave (DG), 15 niños con dengue con signos de alarma (DCSA) y 26 niños sanos, todos menores de 15 años. Se determinaron niveles séricos de IgE e IgG4 específicas de A. aegypti; también se cuantificó VEGF, SST2 y VEGFRI por ELISA. Para las variables cualitativas se calcularon proporciones y odds ratio (OR); en las variables cuantitativas se hallaron medianas, rango intercuartílico y se utilizó la prueba U Mann Whitney. Resultados: La oportunidad de los niños de tener dg con niveles séricos de IgG4 específica mayores de 0,5 OD es 78 % menor [OR=0,22] (IC de 95 % de 0,06-0,77), comparado con la oportunidad de tener dg con niveles séricos de IgG4 específica menores de 0,5 OD. Plaquetas (p=0,0002) y VEFG (p=0,003) más elevado en los pacientes con DCSA y SST2 fue más alto en el DG (p=0,004). Conclusión: Niveles de anticuerpos de IgG4 anti A. aegypti se relacionan con menor gravedad clínica del dengue.

Abstract: Introduction: Dengue virus infection is a global public health problem. The bite of Aedes mosquitoes transmits the virus. The proteins in the saliva of the Aedes aegypti vector induce specific IgE and IgG4 antibodies, whose relationship with the severity of dengue is still unknown. Aim: To evaluate the association between A. aegypti-specific IgE and IgG4 antibodies and the severity of dengue infection. Method: A cross-sectional study was carried out involving 16 children with severe dengue (DG), 15 children with dengue and warning signs (DCSA), and 26 healthy children, all of them under 15 years of age. Serum levels of A. aegypti-specific IgE and IgG4 were determined; VEGF, SST2, and VEGFRI were also quantified by ELISA. For the qualitative variables, proportions and odds ratios (OR) were calculated; as to the quantitative variables, medians and interquartile range were found and the U Mann Whitney test was used. Results: Children's chance of having DG with specific IgG4 serum levels greater than 0.5 DO is 78 % lower [OR = 0.22] (95% CI, 0.06-0.77), compared to the possibility of having dg with specific IgG4 serum levels less than 0.5 DO. Platelets (p = 0.0002) and VEFG (p = 0.003) that are higher in patients with DCSA and SST2 were higher in DG (p = 0.004). Conclusion: A. aegypti-specific IgG4 antibody levels are related to lower clinical severity of dengue.

Resumo: Introdução: A infecção pelo vírus da dengue é um problema mundial de saúde pública. O vírus é transmitido pela picada de mosquitos do gênero Aedes. As proteínas na saliva do vetor Aedes aegypti induzem anticorpos IgE e IgG4 específicos, cuja relação com a gravidade da dengue ainda é desconhecida. Objetivo: Avaliar a associação entre anticorpos IgE e IgG4 específicos Anti-Aedes ae-gypti com a gravidade da infecção por dengue. Método: Foi realizado um estudo transversal no qual foram incluídas 16 crianças com dengue grave (DG), 15 crianças com dengue com sinais de alarme (DCSA) e 26 crianças saudáveis, todas com menos de 15 anos de idade. Os níveis séricos de IgE e IgG4 específicos para Aedes aegypti foram determinados. VEGF, SST2 e VEGFR1 também foram quantificados por ELISA. Para as variáveis qualitativas, foram calculadas proporções e odds ratio (OR). Nas variáveis quantitativas foram encontradas medianas, intervalo interquartil e utilizado o teste U de Mann Whitney. Resultados: A chance de as crianças terem dg com níveis séricos de IgG4 específica maiores que 0,5 od é 78% menor [OR=0,22] (IC 95% 0,06-0,77), em comparação com a chance delas terem dg com níveis séricos de IgG4 específica menor que 0,5 od. As plaquetas (p=0,0002) e VEFG (p=0,003) foram maiores nos pacientes com DCSA e o SST2 foi maior no DG (p=0,004). Conclusão: Os níveis de anticorpos IgG4 Anti-Aedes aegypti estão relacionados à menor gravidade clínica da dengue.

Gastropatía hipertrófica por IgG4: reporte del primer caso en Chile / IgG4 related hypertrophic gastropathy: report of one case

IgG4 related disease is a systemic autoimmune disease, which can affect different organs. The most common digestive manifestation is autoimmune pancreatitis (AIP), followed by involvement of bile ducts and the major papilla. The stomach is only rarely involved. We report a 71-year-old diabetic woman consulting for jaundice and weight loss. Abdominal CAT scan, cholangio resonance imaging, endosonography and a serum IgG4 of five times the normal value, lead to the diagnosis of an autoimmune pancreatitis. An upper gastrointestinal endoscopy showed a diffuse thickening of gastric folds. The pathological study confirmed the presence of IgG4 positive plasma cells. The patient was successfully treated with steroids.

Enfermedad por IgG4 multisistémica: a propósito de un caso: revisión de la literatura / Multisystemic IgG4 disease: a case report: literature review

We report a 63-year-old male patient who consulted for a 4-month history of xerophthalmia, xerostomia and cervicalgia, associated with jaundice, choluria, low weight and night sweats. Exams show an obstructive pattern and abdominal ultrasound describes a possible mass in the pancreatic head with secondary dilation of the bile duct. Colangio-MRI (magnetic resonance imaging) confirms a focal pancreatic head lesion that determines intrapancreatic bile duct stenosis, proximal dilation of the bile duct and stenosis of the main pancreatic duct. Pancreatic neoplasia versus autoimmune pancreatitis (PAI) is proposed, complementing a study with a count of IgG subclasses where IgG4 stands out at 1050 mg/dl (normal range: 3.9-86) and computed tomography (CT) of the thorax, abdomen and pelvis, that in addition to the biliary-pancreatic alterations, shows thickening of the vesicular wall, multiple bilateral lesions in the renal parenchyma and peri-aortic soft tissue. Salivary gland biopsy reports lymphoplasmacytic infiltrate characteristic of IgG4 disease. A disease related to IgG4 (ER-IgG4) is diagnosed with pancreatic, renal, biliary, vascular, lymphatic, salivary and lacrimal glands involvement. It is treated with corticoidal therapy, evolving favorably with resolution of the symptomatology and regression of imaging alterations.

Se reporta caso de paciente de sexo masculino de 63 años que consulta por cuadro de 4 meses de xeroftalmia, xerostomía y cervicalgia, asociado a ictericia, coluria, baja de peso y sudoración nocturna. En exámenes destaca pruebas hepáticas con un patrón obstructivo y ecografía abdominal que muestra una posible masa en la cabeza pancreática con dilatación secundaria de la vía biliar. Colangio-resonancia (resonancia magnética-RM) confirma una lesión focal en la cabeza pancreática que determina estenosis del colédoco intrapancreático, dilatación proximal de la vía biliar y estenosis del conducto pancreático principal. Se plantea neoplasia de páncreas versus pancreatitis autoinmune (PAI), complementando estudio con recuento de subclases de IgG donde destaca IgG4 de 1.050 mg/dl (rango normal: 3,9-86) y tomografía computada (TC) de tórax, abdomen y pelvis, que además de las alteraciones bilio-pancreáticas, demuestra engrosamiento de la pared vesicular, lesiones múltiples bilaterales en el parénquima renal y tejido de partes blandas peri-aórtico. Biopsia de las glándulas salivales informa sialoadenitis crónica e inespecífica. Se diagnostica una enfermedad relacionada a IgG4 (ER-IgG4) con compromiso pancreático, renal, biliar, vascular, linfático, de glándulas salivales y lagrimales. Se trata con terapia corticoidal, evolucionando favorablemente con resolución de la sintomatología y regresión de las alteraciones imagenológicas.

Enfermedad pulmonar intersticial por IgG4 / IgG4-related interstitial lung disease

Las enfermedades relacionadas con inmunoglobulina G4 (IgG4) son un grupo heterogéneo de cuadros clínicos que pueden afectar un solo órgano o tener compromiso sistémico. Se presenta el caso de una mujer de 55 años, internada por un cuadro de tos seca, fiebre, disnea progresiva e insuficiencia respiratoria. La tomografía de tórax evidenció áreas de vidrio esmerilado difusas, patrón reticular y consolidación alveolar. Recibió tratamiento habitual para neumonía de la comunidad y corticoides sistémicos, presentando buena evolución y otorgándose el alta. Al mes se reinterna por estenosis subglótica, progresión de infiltrados pulmonares y aumento del volumen palpebral y de las glándulas submaxilares. Se realizaron biopsias transbronquial y de glándulas salivales que mostraron infiltración por IgG4. También se detectó aumento de los niveles de IgG4 en plasma. Recibió tratamiento con inmunosupresores evolucionando con buena respuesta.

IgG4-related disease is a heterogeneous group of diseases that can affect a single organ or manifest as a systemic disease. We present the case of a 55-year-old female, admitted for dry cough, fever, progressive dyspnea and respiratory failure. Chest CT showed areas of diffuse ground glass, reticular pattern and alveolar consolidation. She received treatment for community acquired pneumonia and systemic corticosteroids with good response. One month later, she was admitted again due to subglottic stenosis, progression of pulmonary infiltrates, and increased palpebral and submaxillary glands volume. Transbronchial and salivary gland biopsies showed infiltration by IgG4. Increased levels of plasma IgG4 were also detected. Immunosuppressive therapy was given with good response.

Hipofisitis linfoplasmocitaria y fibrosis retroperitoneal asociadas a un síndrome poliglandular autoinmune: enfermedades relacionadas con IgG4. Caso clínico / Hypophysitis and retroperitoneal fibrosis associated with autoimmune polyglandular syndrome and IgG4-related disease: report of one case

We report a 23 year old woman presenting with a nephrotic syndrome due to minimal change disease, central diabetes insipidus, primary hypothyroidism, vitiligo and universal alopecia. Eleven years later, she presented secondary amenorrhea due to hypogonadotropic hypogonadism, with mild hyperprolactinemia and central adrenal insufficiency. A magnetic resonance imaging of the sella turcica showed a pituitary mass with suprasellar extension that was resected using a transsphenoidal approach. Pathology confirmed the presence of a lymphoplasmacytic hypophysitis. She needed a second surgical resection due to mass growth and neuro-ophthalmologic impairment. One year later, systemic lupus erythematosus, arterial hypertension and type 2 diabetes mellitus were diagnosed. Two years later, due to back pain, constipation and renal failure, retroperitoneal fibrosis was found, satisfactorily treated with glucocorticoids and colchicine. Hence, this clinical vignette shows the coexistence of autoimmune polyglandular syndrome with retroperitoneal fibrosis and lymphoplasmacytic hypophysitis. Tissue analysis showed the presence of IgG4 producing plasma cells in the pituitary and retroperitoneum, which constitute a basis for the diagnosis of IgG4 related disease.

Apresentação periorbitária de doença relacionada ao IgG4 / Periorbital presentation of IgG4 related disease

Resumo A doença relacionada ao IgG4 é uma condição imunomediada caracterizada pela presença de lesões com reação inflamatória associada à fibrose e à infiltração linfoplasmocitária rica em plasmócitos tissulares IgG4 positivos, compondo um espectro de doenças fibroproliferativas. A patogênese da DRIgG4 ainda é pouco compreendida e o tratamento é empírico. Relatamos o caso de um homem de 50 anos com lesões amareladas palpebrais associadas a edema local, diagnosticadas previamente como processo alérgico, até que biópsia com estudo imuno-histoquímico e dosagem de IgG4 sérico aventaram a hipótese de doença relacionada ao IgG4. Foi iniciado tratamento com corticoide e rituximabe, observando-se estabilização do quadro e sem apresentação de outras formas clínicas da doença.

Abstract IgG4-Related Disease is an immunomediated condition that is characterized by the presence of inflammatory lesions associated with fibrosis and lymphoplasmacytic infiltration rich in positive IgG4 tissue plasmocytes, forming a spectrum of fibroproliferative diseases. The pathogenesis of IgG4-RD is still poorly understood and the treatment is empirical. We report the case of a 50-year-old man with yellow eyelid lesions associated with local edema, previously diagnosed as an allergic process, until biopsy with immunohistochemical study and serum IgG4 dosage revealed the hypothesis of IgG4 related disease. Treatment with corticoid and rituximab was initiated, showing stabilization of the condition, without presenting other clinical forms of the disease.