Advances in gut microbiomes and immunology of IgG4-related hepatobiliary and pancreatic diseases / 中华肝脏病杂志

IgG4-related disease (IgG4-RD) is an immune-mediated condition associated with chronic fibroinflammatory lesions that can affect nearly any organ. IgG4-related hepatobiliary and pancreatic diseases are IgG4-RD involving the hepatobiliary and pancreatic system, which is characterized with elevated serum IgG4 concentrations, large numbers of IgG4 positive lymphoplasma cells infiltration in affected organs, storiform fibrosis, and imaging changes of organ morphology. Due to the lack of reliable biomarkers, histopathology is still an important basis for diagnosis. The pathogenesis of IgG4-related hepatobiliary and pancreatic diseases has not been clarified. This review focuses on the recent advances in intestinal microecology-immunology, host genetics-immunity and recurrence monitoring of IgG4-related hepatobiliary and pancreatic diseases.

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, 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.

Computed Tomography Imaging Features of IgG4-related Nephropathy / 中国医学科学院学报

Objective To investigate the computed tomography(CT)imaging features of IgG4-related kidney disease(IgG4-RKD).Methods The clinicopathological and imaging data of 36 IgG4-RKD patients(including 26 cases of renal parenchyma,10 cases of renal pelvis,24 cases of double kidney or multiple lesions,and 12 cases of single focus)were retrospectively analyzed.Results IgG4-RKD had specific clinicopathological and imaging features.Although the kidney or renal pelvis was involved,there were no common clinical manifestations of malignant tumors such as hydronephrosis and hematuria.The boundary was clear and complete,and it had typical characteristics of continuous progressive enhancement.The peak value was mostly in the solid and excretory phase,and there were no imaging manifestations such as liquefaction,necrosis,cystic degeneration,and calcification.Even if the renal pelvis was obviously involved and the focus was large,there was no invasion of the peripheral renal parenchyma,the shape of the renal pelvis still existed,the wall was smooth,and there was no enlarged peripheral lymph nodes.Conclusions CT images of IgG4-RKD are similar to those of renal malignant tumors.Based on clinicopathological features,CT findings,and blood IgG4-related tests,a definite diagnosis can be made and unnecessary operation can be avoided.

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 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.