Nefropatía por enfermedad relacionada a IGG4 / Nephropathy due to IGG4-related disease

IgG4-related disease (ER-IgG4) is a group of systemic fibro-inflammatory diseases, whose renal involvement is rare and difficult to diagnose. Diagnosis is usually made by serological and histological studies. Treatment is based on systemic corticosteroids. The renal prognosis is determined by the patient's comorbidities and the degree of fibrosis in the renal biopsy. We present the case of an elderly patient with exacerbated chronic kidney disease, whose study showed nephropathy associated with ER-IgG4.

La enfermedad relacionada a IgG4 (ER-IgG4) es un grupo de enfermedades fibro-inflamatorias sistémicas, cuya afectación renal es poco frecuente y de difícil diagnóstico. Habitualmente el diagnóstico se realiza mediante estudios serológicos e histológicos. El tratamiento se basa en corticoides sistémicos. El pronóstico renal está determinado por las comorbilidades del paciente y el grado de fibrosis en la biopsia renal. Se presenta el caso de un paciente adulto mayor con enfermedad renal crónica reagudizada, cuyo estudio demostró nefropatía asociada a ER-IgG4.

Comparison of clinical features and outcomes of proliferative, fibrotic, and mixed subtypes of IgG4-related disease: A retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients' clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes.@*METHODS@#We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.@*RESULTS@#We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils ( P = 0.010), total IgE ( P = 0.006), high-sensitivity C-reactive protein ( P <0.001), erythrocyte sedimentation rate ( P <0.001), complement C4 ( P <0.001), IgG ( P = 0.001), IgG1 (P <0.001), IgG4 (P <0.001), and IgA ( P <0.001), at baseline were significantly different among three subtypes. Compared with proliferative and mixed subtypes, the fibrotic subtype showed the lowest rate of relapse (log-rank P = 0.014).@*CONCLUSIONS@#Our study revealed the differences in demographic characteristics, clinical manifestations, organ involvement, laboratory tests, treatment agents, and outcomes across proliferative, fibrotic, and mixed subtypes in the retrospective cohort study. Given significant differences in relapse-free survival among the three subtypes, treatment regimens, and follow-up frequency should be considered separately according to different subtypes.

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.

Una inusual causa de estrechez de la vía aérea laringotraqueal / An unusual cause of laryngotracheal airway narrowing

La enfermedad relacionada con inmunoglobulina (Ig) G4 es una enfermedad de reciente conocimiento que puede comprometer cualquier órgano teniendo preferencias por ciertas regiones del cuerpo, donde la región de cabeza y cuello es uno de sus principales puntos afectados, pudiendo comprometer tanto la órbita, glándulas salivales, glándulas lagrimales, glándula tiroides, cavidades paranasales, hueso temporal, faringe y laringe. Este último órgano es infrecuentemente comprometido, solo existiendo 12 casos registrados en la literatura antes de la publicación de este escrito. Presentamos un caso de una mujer de 49 años con historia de disnea frente a esfuerzo, diagnosticándose una estenosis subglótica la cual fue manejada quirúrgicamente con una reconstrucción laringotraqueal. En el estudio histopatológico se evidenció histología compatible con enfermedad relacionada con IgG4, por lo que se inició tratamiento médico con corticotera- pia oral por un lapso de 2 meses en conjunto con inmunología. Paciente luego de 4 años de seguimiento, no ha presentado recaídas, manteniendo un lumen subglótico adecuado.

Immunoglobulin (Ig) G4-related disease is a medical condition of recent knowledge that can compromise any organ, having preferences for certain regions of the body, where the head and neck region is one of the main affected points, being able to affect orbit, salivary glands, lacrimal glands, thyroid gland, paranasal cavities, temporal bone, pharynx and larynx. The latter is infrequently compromised, with only 12 cases registered in the literature before the publication of this writing. We present a case of a 49-year-old woman with a history of exertional dyspnea, diagnosed with a sub- glottic stenosis which was managed surgically with laryngotracheal reconstruction. The histopathological study revealed histology compatible with IgG4-related disease, so medical treatment with oral corticosteroid therapy was started for a period of 2 months in conjunction with immunology. After 4 years of follow-up, the patient has not presented relapses, maintaining an adequate subglottic lumen.

Pathological significance of plasma cell infiltration in diagnosing lymph node diseases / 中华病理学杂志

Objective: To investigate the value of plasma cells for diagnosing lymph node diseases. Methods: Common lymphadenopathy (except plasma cell neoplasms) diagnosed from September 2012 to August 2022 were selected from the pathological records of Changhai Hospital, Shanghai, China. Morphological and immunohistochemical features were analyzed to examine the infiltration pattern, clonality, and IgG and IgG4 expression of plasma cells in these lymphadenopathies, and to summarize the differential diagnoses of plasma cell infiltration in common lymphadenopathies. Results: A total of 236 cases of lymphadenopathies with various degrees of plasma cell infiltration were included in the study. There were 58 cases of Castleman's disease, 55 cases of IgG4-related lymphadenopathy, 14 cases of syphilitic lymphadenitis, 2 cases of rheumatoid lymphadenitis, 18 cases of Rosai-Dorfman disease, 23 cases of Kimura's disease, 13 cases of dermal lymphadenitis and 53 cases of angioimmunoblastic T-cell lymphoma (AITL). The main features of these lymphadenopathies were lymph node enlargement with various degrees of plasm cell infiltration. A panel of immunohistochemical antibodies were used to examine the distribution of plasma cells and the expression of IgG and IgG4. The presence of lymph node architecture could help determine benign and malignant lesions. The preliminary classification of these lymphadenopathies was based on the infiltration features of plasma cells. The evaluation of IgG and IgG4 as a routine means could exclude the lymph nodes involvement of IgG4-related dieases (IgG4-RD), and whether it was accompanied by autoimmune diseases or multiple-organ diseases, which were of critical evidence for the differential diagnosis. For common lesions of lymphadenopathies, such as Castleman's disease, Kimura's disease, Rosai-Dorfman's disease and dermal lymphadenitis, the expression ratio of IgG4/IgG (>40%) as detected using immunhistochemistry and serum IgG4 levels should be considered as a standard for the possibility of IgG4-RD. The differential diagnosis of multicentric Castleman's diseases and IgG4-RD should be also considered. Conclusions: Infiltration of plasma cells and IgG4-positive plasma cells may be detected in some types of lymphadenopathies and lymphomas in clinicopathological daily practice, but not all of them are related to IgG4-RD. It should be emphasized that the characteristics of plasma cell infiltration and the ratio of IgG4/IgG (>40%) should be considered for further differential diagnosis and avoiding misclassification of lymphadenopathies.

Medical visit status and clinical features in patients with IgG4 related disease / 北京大学学报(医学版)

OBJECTIVE@#To understand the medical treatment and clinical characteristics of patients with IgG4-related disease (IgG4-RD) with complex clinical manifestations and easy to be misdiagnosed and missed, and to improve the recognition of this disease among doctors from relevant medical departments.@*METHODS@#A retrospective analysis was conducted on the medical records of patients diagnosed with IgG4-RD who were hospitalized and discharged from Peking University Third Hospital from January 1, 2012 to December 31, 2022. The patient' s medical visit status, clinical manifestations, laboratory examinations, diagnosis, and treatment information were summarized.@*RESULTS@#A total of 116 patients diagnosed with IgG4-RD were included in this study, with a male to female ratio of 2. 52∶ 1 and an average age of (61.83±10.80) years. The departments for initial visits were gastroenterology, general surgery, and ophthalmology. While the departments responsible for definitive diagnosis were gastroenterology, rheumatology and immunology, and respiratory medicine. Twenty-one patients (18. 10%) required consultation and treatment from three or more departments before receiving a definitive diagnosis. The median time from symptom onset to the initial clinic visit was 2 (1, 7) months, and the median time from symptom onset to diagnosis was 1 (1, 12) month. Twenty-four patients (20.69%) underwent surgical resection of the affected sites before diagnosis. According to the classification criteria of IgG4-RD, sixty-eight (58.62%) cases were diagnosed definitively, eight (6.9%) cases were likely to be diagnosed, and 40 (34.48%) cases were suspected to be diagnosed. In the 68 definitively diagnosed patients, the most commonly affected organs were submandibular gland, the pancreas, biliary tract, parotid in sequence. The median serum IgG4 (IgG4, immunoglobulin G4) level was 6.16 (3. 61, 12. 30) g/L. Fifty-seven patients (83.82%) were treated with glucocorticoids, and 14 patients (20.59%) were treated with immunosuppressants. The use of immunosuppressants was mainly in the rheumatology and immunology department (78. 57%).@*CONCLUSION@#IgG4-RD is more common in elderly males, with submandibular gland, the pancreas, biliary tract, and parotid being most commonly affected. The distribution of initial visit departments in patients is wide. The proportion of definitive diagnosis based on pathology is relatively low. In terms of treatment, the main approach is steroid treatment, while the use of immunosuppres-sants is not widespread.

A case of duodenal ulcer as prominent manifestation of IgG4-related disease / 北京大学学报(医学版)

A case of IgG4-related disease presented with a duodenal ulcer to improve the understan-ding of IgG4-related diseases was reported. A 70-year-old male presented with cutaneous pruritus and abdominal pain for four years and blackened stools for two months. Four years ago, the patient went to hospital for cutaneous pruritus and abdominal pain. Serum IgG4 was 3.09 g/L (reference value 0-1.35 g/L), alanine aminotransferase 554 U/L (reference value 9-40 U/L), aspartate aminotransferase 288 U/L (reference value 5-40 U/L), total bilirubin 54.16 μmol/L (reference value 2-21 μmol/L), and direct bilirubin 29.64 μmol/L (reference value 1.7-8.1 μmol/L) were all elevated. The abdominal CT scan and magnetic resonance cholangiopancreatography indicated pancreatic swelling, common bile duct stenosis, and secondary obstructive dilation of the biliary system. The patient was diagnosed with IgG4-related disease and treated with prednisone at 40 mg daily. As jaundice and abdominal pain improved, prednisone was gradually reduced to medication discontinuation. Two months ago, the patient developed melena, whose blood routine test showed severe anemia, and gastrointestinal bleeding was diagnosed. The patient came to the emergency department of Beijing Hospital with no improvement after treatment in other hospitals. Gastroscopy revealed a 1.5 cm firm duodenal bulb ulcer. After treatment with omeprazole, the fecal occult blood was still positive. The PET-CT examination was performed, and it revealed no abnormality in the metabolic activity of the duodenal wall, and no neoplastic lesions were found. IgG4-related disease was considered, and the patient was admitted to the Department of Rheumatology and Immunology of Beijing Hospital for further diagnosis and treatment. The patient had a right submandibular gland mass resection history and diabetes mellitus. After the patient was admitted to the hospital, the blood test was reevaluated. The serum IgG4 was elevated at 5.44 g/L (reference value 0.03-2.01 g/L). Enhanced CT of the abdomen showed that the pancreas was mild swelling and was abnormally strengthened, with intrahepatic and extrahepatic bile duct dilation and soft tissue around the superior mesenteric vessels. We pathologically reevaluated and stained biopsy specimens of duodenal bulbs for IgG and IgG4. Immunohistochemical staining revealed remarkable infiltration of IgG4-positive plasma cells into duodenal tissue, the number of IgG4-positive cells was 20-30 cells per high-powered field, and the ratio of IgG4/IgG-positive plasma cells was more than 40%. The patient was treated with intravenous methylprednisolone at 40 mg daily dosage and cyclophosphamide, and then the duodenal ulcer was healed. IgG4 related disease is an immune-medicated rare disease characterized by chronic inflammation and fibrosis. It is a systemic disease that affects nearly every anatomic site of the body, usually involving multiple organs and diverse clinical manifestations. The digestive system manifestations of IgG4-related disease are mostly acute pancreatitis and cholangitis and rarely manifest as gastrointestinal ulcers. This case confirms that IgG4-related disease can present as a duodenal ulcer and is one of the rare causes of duodenal ulcers.

The similar characteristics of IgG4-related disease and allergic diseases / 中华预防医学杂志

IgG4-related disease (IgG4-RD) is a chronic inflammation with fibrosis. About 30% to 40% of patients with IgG4-RD are complicated with atopic manifestations as allergic rhinitis and asthma, usually with elevated serum total immunoglobulin E and peripheral blood eosinophils, which are also of some value for predicting disease activity and relapse. Similar to allergic diseases, activation of type 2 inflammation is also observed in the pathogenesis of IgG4-RD, and eosinophils, basophils, mast cells, thymic stromal lymphopoietin, IL-33, IL-4, IL-5, and IL-13 all participate in the pathogenesis of IgG4-RD. Studies of susceptible genes showed that IgG4-RD and allergic disease shared the same susceptible genes. Monoclonal antibodies targeting type 2 inflammation pathway may become a novel choice for IgG4-RD treatment.

The similar characteristics of IgG4-related disease and allergic diseases / 中华预防医学杂志

IgG4-related disease (IgG4-RD) is a chronic inflammation with fibrosis. About 30% to 40% of patients with IgG4-RD are complicated with atopic manifestations as allergic rhinitis and asthma, usually with elevated serum total immunoglobulin E and peripheral blood eosinophils, which are also of some value for predicting disease activity and relapse. Similar to allergic diseases, activation of type 2 inflammation is also observed in the pathogenesis of IgG4-RD, and eosinophils, basophils, mast cells, thymic stromal lymphopoietin, IL-33, IL-4, IL-5, and IL-13 all participate in the pathogenesis of IgG4-RD. Studies of susceptible genes showed that IgG4-RD and allergic disease shared the same susceptible genes. Monoclonal antibodies targeting type 2 inflammation pathway may become a novel choice for IgG4-RD treatment.

IgG4-related disease associated with immune thrombocytopenia: A clinical case report

Autoimmune pancreatitis is a characteristic manifestation of the spectrum of the disease related to IgG4, a rare autoimmune disorder that presents clinically with obstructive jaundice due to the infiltration of plasma cells and fibrosis in the pancreas. There may be other symptoms in case of involvement of other organs, and in very rare cases there is hematological involvement. We present the case of an adult man with signs of cholestasis secondary to type I autoimmune pancreatitis, with involvement of other organs and associated with thrombocytopenia that improved with systemic corticosteroid-based immunosuppressive treatment, after which the patient showed favorable clinical and analytical evolution over time.

La pancreatitis autoimmune es una manifestación característica del espectro de la enfermedad relacionada con IgG4, trastorno raro de tipo autoinmune que se presenta clínicamente con ictericia obstructiva debido a la infiltración de células plasmáticas y fibrosis en el páncreas; puede presentarse con otra sintomatología en caso de afectación de otros órganos y en muy raras ocasiones hay compromiso hematológico. Se presenta el caso de un hombre adulto con signos de colestasis secundaria a una pancreatitis autoinmune tipo i, con compromiso de otros órganos y asociada con trombocitopenia que mejoró con el tratamiento inmunosupresor a base de corticoide sistémico, luego del cual se observó una evolución favorable en cuanto a la clínica y analítica en el transcurso del tiempo.

Cervical lymph nodes in rheumatology: A diagnostic dilemma

The case is presented on a 52-year-old male patient, who was seen in the Rheumatology department. He had painless lymph nodes in the cervical, axillary, supraclavicular, and neck region. He also had a fever, and parotid and submaxillary gland enlargement. Complementary studies were performed, showing normocytic-normochromic anemia, thrombocytopenia and eosinophilia, impaired renal function with hypoalbuminaemia and hematuria, ANA 1/5120, Sm+, ACL+. Biopsies were also performed on the compromised tissues, reaching the diagnosis of Rosai-Dorfman Disease and IgG4-related Disease. Differential diagnoses of cervical, axillary and inguinal lymph nodes, with fever, renal and hematological compromise are discussed.

Se describe el caso de un paciente varón de 52 años que consulta al servicio de reumatología por presentar adenopatías indoloras en las regiones cervical, axilar, supraclaviculares y en la nuca, así como fiebre, aumento de tamaño de parótidas y submaxilares. Se realizan estudios complementarios que arrojan como resultado anemia normocítica-normocrómica, trombocitopenia y eosinofilia, alteración de la función renal con hipoalbuminemia y hematuria, FAN 1/5.120, Sm+, ACL+ y biopsia de los tejidos comprometidos, por lo que se arriba al diagnóstico de enfermedad de Rosai-Dorfman y enfermedad relacionada con IgG4. Se discuten diagnósticos diferenciales de adenopatías cervicales, axilares e inguinales, fiebre, compromiso renal y hematológico.

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.

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.

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.

Update on classification, diagnosis, and management of immunoglobulin G4-related disease / 中华医学杂志(英文版)

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized chronic fibro-inflammatory autoimmune disease, and its recognition has been constantly increasing worldwide over the last few years. A correct and timely recognition, as well as appropriate intervention, is crucial for the treatment of IgG4-RD. For certain subtypes of IgG4-RD, organ-specific criteria are formulated to make the diagnosis more accurate. New biomarkers have emerged in the recent years to aid the disease diagnosis, its prognosis prediction, as well as therapy response monitoring. Although recurrence is very common in IgG4-RD, glucocorticoid is still the first-line treatment for the majority of patients. The factors that affect the likelihood of disease relapse are multifaceted. The selection strategy of various steroid-sparing agents is still being explored. Besides, when patients have special sites involvement leading to severe clinical conditions, surgical operation or interventional therapy should also be considered. An update on classification, diagnosis, and management of IgG4-RD is provided in the current study to fully elucidate the recommended clinical practice of this mysterious disease.

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.

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.

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.

Clinical characteristics of central nervous system involvement in IgG4 related diseases / 北京大学学报(医学版)

OBJECTIVE@#To improve the understanding of the clinical characteristics of immunoglobulin G4-related disease (IgG4-RD) with central nervous system (CNS) involvement, so as to contribute to the early diagnosis and treatment.@*METHODS@#In this study, 10 patients with IgG4-RD with CNS involvement were selected. Clinical data including demographic features, clinical manifestations, organ involvement, laboratory findings, radiological results, pathology, treatments and outcomes were collected retrospectively.@*RESULTS@#Among the 10 IgG4-RD patients complicated with CNS involvement, 6 cases manifested as pituitary involvement and 4 cases manifested as dural involvement. Only 2 patients had nervous system involvement alone, while the left patients were complicated with other organ involvement besides nervous system. Half of the patients presented nervous system involvement as the initial manifestation, and the main symptoms of nervous system included polydipsia, polyuria, headache, decreased vision and so on. In the laboratory examination, the serum IgG4 level was increased in 9 cases (90.0%), and the total serum IgE was increased in 7 cases (87.5%). At the same time, their IgG, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were increased, while complement (C) 3 and C4 were decreased in some patients. Eight patients underwent tissue biopsies in different parts, the pathological examination showed a large number of lymphocyte and plasma cell infiltration, accompanied by fibrous tissue proliferation in part. All the patients were treated with glucocorticoids, and 8 cases (80%) were given immunosuppressants at the same time, and 3 cases were treated with rituximab when they expe-rienced disease relapse. As a result, 2 cases (20%) achieved complete remission (CR), and 8 cases (80%) achieved partial remission (PR). The median follow-up time was 13.5 months, and 4 cases relapsed.@*CONCLUSION@#Pituitary and dura are common affected organs of IgG4-RD with CNS involvement. Most IgG4-RD patients with CNS involvement are combined with other organ involvement, but half of them presented nervous system involvement as the initial manifestation, and the symptoms are not typical. In order to make an early diagnosis, laboratory, imaging examination and tissue biopsy should be taken into consideration in combination if necessary.