Performance of the 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease in a Latin American Cohort.

BACKGROUND/OBJECTIVE: The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria (2019 AECC) for IgG4-related disease (IgG4-RD) is considered a significant advancement in the study of this condition. Most studies evaluating their performance have focused on White and Asian patients, leaving a knowledge gap regarding Latin American populations. Therefore, this study aimed to assess the performance of the 2019 AECC for IgG4-RD in a cohort of Latin American patients. METHODS: A multicenter medical records review study was conducted, involving centers from Argentina, Chile, Mexico, Peru, and Uruguay. Data on IgG4-RD patients and mimicker conditions were collected through a standardized online form. The criterion standard for diagnosing IgG4-RD was based on the fulfillment of the Comprehensive Diagnostic Criteria for IgG4-RD and/or the Consensus Statement on Pathology. The 2019 AECC was retrospectively applied. RESULTS: We included 300 patients, with 180 (60%) having IgG4-RD and 120 (40%) having mimicker conditions. The 2019 AECC had a sensitivity of 66.7% and a specificity of 100%. Sensitivity increased to 73.3% when disease-specific autoantibody items were removed, without affecting specificity. The true-positive cases had more involved organs, a higher availability of biopsy results, and were more likely to belong to the Mikulicz/systemic and proliferative phenotypes. CONCLUSIONS: The use of the 2019 AECC for IgG4-RD in a Latin American population confirms its high specificity in excluding those without the disease. The presence of concomitant autoimmune diseases and clinically nonsignificant disease-specific autoantibodies excludes a significant number of patients from fulfilling the criteria.

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.

Immunoglobulin G4-Associated Rosai-Dorfman Disease: Report of 3 Cases.

Rosai-Dorfman disease is characterized by dilated lymph node sinuses filled with lymphocytes, plasma cells, and histiocytes. Many of these histiocytes classically exhibit emperipolesis of lymphocytes and plasma cells. Abundant immunoglobulin G4+ plasma cells occur in some cases, and a potential relationship with immunoglobulin G4-related disease has been suggested. Here, we report 3 cases of immunoglobulin G4-associated Rosai-Dorfman disease. Immunoglobulin G4-related disease was suspected based on immunoglobulin G4+ plasma cell infiltration, but the final diagnosis was immunoglobulin G4-associated Rosai-Dorfman disease. At present, the evidence does not support a link between immunoglobulin G4-associated Rosai-Dorfman disease and immunoglobulin G4-related disease, and one condition should not be considered part of the spectrum of the other. We believe it is of paramount importance to increase the awareness of immunoglobulin G4-associated Rosai-Dorfman disease for pathologists who interpret the biopsies and clinicians who integrate the diagnosis and treat such patients to not overdiagnose immunoglobulin G4-related disease.

Enfermedad relacionada con IgG4, enfermedad de Erdheim Chester y compromiso aórtico y/o sus ramas. Diagnóstico diferencial con otras vasculitis de grandes vasos / IgG4 related disease, Erdheim Chester disease and aortic involvement and/or its branches. Differential diagnosis with other large vessel vasculitis

La afección cardiovascular en entidades como Erdheim-Chester (EEC), una rara histiocitosis de células no Langerhans, y la enfermedad relacionada con IgG4 (ER-IgG4), una afección fibrinoinflamatoria inmunomediada, es muy variada y habitualmente asintomática hasta su progresión a daños irreversibles cuando no es sospechada. Ante la dificultad de realizar biopsias por el sitio anatómico, es fundamental valerse de características clínicas, demográficas o imagenológicas que puedan diferenciarlas de otras entidades, como las arteritis de grandes vasos. La población masculina, los mayores de 60 años con compromiso a nivel de la aorta abdominal infrarrenal o aneurismas a nivel de la aorta ascendente con o sin compromiso de otros órganos, son orientativos de ER-IgG4. En la EEC es característico el tejido blando concéntrico que recubre la aorta (aorta recubierta) y sobre todo ante la presencia de fibrosis retroperitoneal, compromiso de huesos largos, hidronefrosis, lesión renal aguda posrrenal e hipertensión arterial, existencia de tejido fibrótico perirrenal, engrosamiento de la fascia renal y tejido adiposo perirrenal (signo del riñón peludo).

Cardiovascular disease in entities such as Erdheim-Chester (ECD), a rare non-Langerhans cell histiocytosis, and IgG4-related disease (ER-IgG4), an immunemediated fibrinoinflammatory disease, is highly varied and usually asymptomatic until it progresses to irreversible damage if they are not taken into account. Given the difficulty of performing biopsies by the anatomical site, it is essential to use clinical, demographic or imaging characteristics that can differentiate them from other entities such as large vessel arteritis. Male population, over 60 years of age with involvement of the infrarenal abdominal aorta or aneurysms at the level of the ascending aorta with or without involvement of other organs, are indicative of ER-IgG4. In ECD, the concentric soft tissue covering the aorta (covered aorta) is characteristic, and especially in the presence of retroperitoneal fibrosis, involvement of long bones, hydronephrosis, post-renal acute kidney injury and arterial hypertension, the presence of perirenal fibrotic tissue, thickening of the renal fascia, perirenal adipose tissue (hairy kidney sign).

El secreto que revelan los ojos. Compromiso ocular como manifestación de enfermedades sistémicas no infecciosas / The secret revealed by the eyes. Ocular involvement as a manifestation of non-infectious systemic diseases

La coroides es el tejido ocular más comúnmente afectado por la enfermedad metastásica debido a su abundante vascularización y, en ocasiones, la primera manifestación (44-70% según las series) de cáncer de pulmón en hombres o de cáncer de mama en mujeres (3%). Síntomas oculares de inicio abrupto en pacientes jóvenes y signos al examen oftalmológico como engrosamiento de la pared posterior o lumpy-bumpy surface, entre otros, son orientativos. La uveítis anterior granulomatosa, la uveítis intermedia bilateral, la panuveitis bilateral o las lesiones granulomatosas a nivel coroideo o del nervio óptico se consideran indicativas de sarcoidosis en presencia de un cuadro radiológico compatible. Estas pueden preceder a los signos sistémicos en un 30% de los casos. Se presentan tres pacientes con signos y síntomas oftalmológicos que precedieron al diagnóstico de enfermedades sistémicas no infecciosas.

The choroid is the ocular tissue most commonly affected by metastatic disease due to its abundant vascularization and is sometimes the first manifestation (44-70% depending on the series) of lung cancer in men or breast cancer in women (3%). Abrupt-onset ocular symptoms in young patients and signs on ophthalmological examination such as thickening of the posterior wall, "lumpy-bumpy surface", among others, are indicative. Granulomatous anterior uveitis, bilateral intermediate uveitis, bilateral panuveitis or granulomatous lesions at the choroidal or optic nerve level are considered indicative of sarcoidosis in the presence of a compatible radiological picture. These may precede systemic signs in 30% of cases. We present 3 patients with ophthalmological signs and symptoms that preceded the diagnosis of non-infectious systemic diseases.

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.

Hallazgos histológicos de glándulas salivales mayores y menores en pacientes con enfermedad relacionada a IgG4 / Histological findings of major and minor salivary glands in patients with IgG4 related disease

Introducción: la enfermedad relacionada con IgG4 (ER-IgG4) es una afección inmunomediada, asociada con lesiones fibroinflamatorias que pueden ocurrir en casi cualquier órgano. Ante su sospecha clínica es fundamental realizar el examen histopatológico para excluir malignidad y otras enfermedades. El objetivo principal de este estudio fue describir los hallazgos histológicos de la biopsia de glándulas salivales labiales (GSL) en pacientes con diagnóstico de ER-IgG4 y, posteriormente, comparar estos hallazgos con la histología e inmunohistoquímica de la glándula salival mayor (GSM). Materiales y métodos: estudio retrospectivo, observacional y descriptivo sobre una cohorte de 40 pacientes con diagnóstico de ER-IgG4. Se incluyeron 26 pacientes con diagnóstico de ER-IgG4 que presentaron biopsias de GSL. Resultados: el 73% de la muestra tuvo un infiltrado linfoplasmocitario y el 11%, fibrosis con patrón no estoriforme. En ningún caso se halló arteritis obliterativa ni ninguna forma de flebitis. Al realizar la comparación con los hallazgos de las biopsias de GSM, no hubo significancia estadística. El 65% de los pacientes manifestó compromiso extraglandular y fueron los sistemas pancreato hepato biliar y las adenopatías los más afectados. Conclusiones: la biopsia incisional de glándula submandibular sería más útil y apropiada que la biopsia de GSL para un diagnóstico definitivo de ER-IgG4.

Introduction: IgG4-related disease (IgG4-RD) is an immune-mediated condition associated with fibroinflammatory lesions that can occur in almost any anatomical site. Histopathological examination is essential when suspected to diagnose it to exclude malignancy and other diseases. The objective of this study was to describe the histological findings of the minor salivary gland biopsy (GSL) in patients diagnosed with IgG4-RD, and subsequently to correlate these findings with the histology and immunohistochemistry of the major salivary gland (GSM). Materials and methods: retrospective, observational and descriptive study on a cohort of 40 patients diagnosed with RD-IgG4. Twenty-six patients diagnosed with IgG4-RD who presented SLG biopsies were included. Results: the 73% of the samples presented a lymphoplasmacytic infiltrate and 11% of them fibrosis with a non-storiform pattern. In no case was obliterative arteritis or any form of phlebitis found. When comparing the findings of the GSM biopsies, there was no statistical significance. Sixty-five percent of the patients presented extraglandular involvement; the pancreato-hepato-biliary system and the adenopathies were the most affected. Conclusions: incisional biopsy of the submandibular gland would be more useful and appropriate than LSG for a definitive diagnosis of IgG4-RD.

Clinical and Serological Features in Latin American IgG4-Related Disease Patients Differ According to Sex, Ethnicity, and Clinical Phenotype.

BACKGROUND/OBJECTIVE: Data on IgG4-related disease (IgG4-RD) come almost exclusively from cohorts from Asia, Europe, and North America. We conducted this study to describe the clinical presentation, phenotype distribution, and association with sex, ethnicity, and serological markers in a large cohort of Latin American patients with IgG4-RD. METHODS: We performed a multicenter medical records review study including 184 Latin American IgG4-RD patients. We assigned patients to clinical phenotypes: group 1 (pancreato-hepato-biliary), group 2 (retroperitoneal/aortic), group 3 (head and neck-limited), group 4 (Mikulicz/systemic), and group 5 (undefined). We focused the analysis on how sex, ethnicity, and clinical phenotype may influence the clinical and serological presentation. RESULTS: The mean age was 50.8 ± 15 years. Men and women were equally affected (52.2% vs 48.8%). Fifty-four patients (29.3%) were assigned to group 1, 21 (11.4%) to group 2, 57 (30.9%) to group 3, 32 (17.4%) to group 4, and 20 (10.8%) to group 5. Male sex was associated with biliary tract (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.36-8.26), kidney (OR, 3.4; 95% CI, 1.28-9.25), and retroperitoneal involvement (OR, 5.3; 95% CI, 1.45-20). Amerindian patients presented more frequently with atopy history and gallbladder involvement. Group 3 had a female predominance. CONCLUSIONS: Latin American patients with IgG4-RD were younger, and men and women were equally affected compared with White and Asian cohorts. They belonged more commonly to group 1 and group 3. Retroperitoneal and aortic involvement was infrequent. Clinical and serological features differed according to sex, ethnicity, and clinical phenotype.

Diffuse alveolar haemorrhage in systemic lupus erythematosus patients.

INTRODUCTION: Pulmonary haemorrhage (PH) in systemic lupus erythematosus (SLE) is a rare but potentially fatal complication due to its high mortality. Early treatment benefits the outcome. Reports on predictive factors of PH in SLE patients are scarce. OBJECTIVE: To describe a case series of PH in SLE patients that were attended in the Rheumatology Section of the J. M. Cullen Hospital and to compare this data with published results. METHODS: Patients with SLE (1982-1997 ACR criteria) and PH diagnosed by clinical criteria (cough, dyspnoea, haemoptysis), haemoglobin below 12 g/dL or drop greater than 2 points, new radiological infiltrate and bronchioalveolar lavage, monitored between June 1987 and December 2019 were studied. Demographic, clinical, laboratory, treatment and prognosis data related to PH were analysed. RESULTS: From a database of 306 SLE patients, 25 (8.2%) developed 29 episodes of PH. PH was the first manifestation of SLE in 8 patients. Renal involvement was the most frequent manifestation prior to the development of PH. SLE activity (measured by SLEDAI) was high during the episodes (mean: 16.8). Renal failure (p = .027) and mechanical respiratory support (p = .006) were related to mortality (40.7%) with statistical significance. Patients with SLEDAI higher to 10 at SLE onset showed more likelihood of developing PH. The OR was 2.68 (p = .046). CONCLUSIONS: Although treatment in SLE has progressed in recent years, PH continues to be a rare and severe complication of this disease. When a PH is suspected, studies to confirm it must be done rapidly, since early diagnosis and aggressive treatment have been shown to improve survival. We observed that patients with renal involvement and mechanical respiratory support had higher mortality than SLE patients without them.

Hemorragia alveolar difusa en pacientes con lupus eritematoso sistémico / Diffuse Alveolar Haemorrhage in Systemic Lupus Erythematosus Patients

Introducción: La hemorragia alveolar difusa (HAD) es una complicación infrecuente pero grave en pacientes con Lupus eritematoso sistémico (LES). Su tratamiento debe ser precoz, lo cual mejora la supervivencia. Las comunicaciones de factores predictores de HAD en pacientes con LES son escasas. Objetivo: Describir una serie de casos de HAD en pacientes con LES, del Servicio de Reumatología del Hospital J.M. Cullen, de Santa Fe, y compararlos con un grupo control de pacientes con LES del mismo Servicio y con los datos de la literatura. Material y métodos: Se incluyeron pacientes con LES (Criterios ACR 1982-1997) y HAD definida por parámetros clínicos (tos, disnea, hemoptisis), analíticos (caída de la hemoglobina por debajo de 12 g/dL o mayor a dos puntos respecto del basal en pacientes ya conocidos), imagenológicos (infiltrado radiológico y/o tomográfico bilateral o difuso) y lavado bronquioalveolar (BAL) (retorno sanguinolento en el lavado, más de 20% de siderófagos, sin evidencia de lesiones sangrantes), quienes concurrieron al servicio entre junio de 1987 y diciembre de 2019. Se analizaron datos demográficos, clínicos, de laboratorio, tratamientos y pronóstico de los pacientes. Resultados: Se trabajó con una base de datos de 306 pacientes con diagnóstico de LES, evaluándose 25 de ellos (8,2%) que presentaron 29 episodios de HAD (ocho de ellos como forma de inicio de la enfermedad). El compromiso renal fue el más frecuentemente asociado a la HAD (previo o concomitantemente). La actividad de la enfermedad medida por SLEDAI fue alta durante el episodio, y su media fue de 16,8 puntos. En todos los casos se constató sangrado pulmonar por BAL o tubo endotraqueal. Se halló significación estadística al relacionar la mortalidad (40,7%) con requerimiento de asistencia respiratoria mecánica (ARM) (p = 0,006) y falla renal (p = 0,027). Los pacientes con SLEDAI mayor a 10 al inicio de la enfermedad presentaron más posibilidades de desarrollar HAD (OR = 2,68, p = 0,046).(AU)

Introduction: Pulmonary haemorrhage (PH) in systemic lupus erythematosus (SLE) is a rare but potentially fatal complication due to its high mortality. Early treatment benefits the outcome. Reports on predictive factors of PH in SLE patients are scarce. Objective: To describe a case series of PH in SLE patients that were attended in the Rheumatology Section of the J. M. Cullen Hospital and to compare this data with published results. Methods: Patients with SLE (1982-1997 ACR criteria) and PH diagnosed by clinical criteria (cough, dyspnoea, haemoptysis), haemoglobin below 12 g/dL or drop greater than 2 points, new radiological infiltrate and bronchioalveolar lavage, monitored between June 1987 and December 2019 were studied. Demographic, clinical, laboratory, treatment and prognosis data related to PH were analysed. Results: From a database of 306 SLE patients, 25 (8.2%) developed 29 episodes of PH. PH was the first manifestation of SLE in 8 patients. Renal involvement was the most frequent manifestation prior to the development of PH. SLE activity (measured by SLEDAI) was high during the episodes (mean: 16.8). Renal failure (p = 0.027) and mechanical respiratory support (p = 0.006) were related to mortality (40.7%) with statistical significance. Patients with SLEDAI higher to 10 at SLE onset showed more likelihood of developing PH. The OR was 2.68 (p = 0.046). Conclusions: Although treatment in SLE has progressed in recent years, PH continues to be a rare and severe complication of this disease. When a PH is suspected, studies to confirm it must be done rapidly, since early diagnosis and aggressive treatment have been shown to improve survival. We observed that patients with renal involvement and mechanical respiratory support had higher mortality than SLE patients without them.(AU)

Relapsing polychondritis or relapsing polychondritis-like symptoms associated with IgG4-RD. Case reports and review of the literature.

Relapsing polychondritis (RP) is a rare systemic disorder characterised by recurrent, widespread chondritis of the auricular, nasal, and tracheal cartilages. Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated disease characterised by the infiltration of IgG4-bearing plasma cells into systemic organs. However, 25-35% of patients with RP have a concurrent autoimmune disease. The coexistence of RP and IgG4 is rare considering that, to the best of our knowledge, there are only four previous reports of RP or RP-like symptoms associated with IgG4-RD. We herein report two cases which could be RP or RP-like symptoms associated with IgG4-RD.

IgG4-Related Disease: Mimickers and Diagnostic Pitfalls.

BACKGROUND: The tendency of IgG4-related disease (IgG4-RD) to form pseudotumors, as well as its multisystemic nature, makes it the perfect mimicker of many conditions. Moreover, some clinical, serological, radiological, or histological features of the disease might be shared with some mimickers.Recently, 4 clinical phenotypes have been identified, and patients grouped in each phenotype have distinctive demographic, clinical, and serological features and outcomes, and, as expected, for each phenotype, a set of differential diagnoses should be considered. SUMMARY OF THE LITERATURE: The main differential diagnoses for the pancreato-hepato-biliary phenotype are pancreatic adenocarcinoma and cholangiocarcinoma. Other differential diagnoses include type 2 autoimmune pancreatitis and primary sclerosing cholangitis. In patients with retroperitoneal/aortic phenotype, inflammatory conditions such as idiopathic retroperitoneal fibrosis and large vessel vasculitides should be ruled out, and most of the time, a biopsy will be needed to exclude malignancies. In head and neck limited phenotype, autoimmune conditions (eg, granulomatosis with polyangiitis, Graves orbitopathy, sarcoidosis), malignancies, and histiocytosis should be ruled out, whereas the main differential diagnoses of the Mikulicz/systemic phenotype are Sjögren syndrome, granulomatosis with polyangiitis, and multicentric Castleman disease. CONCLUSIONS: Approaching a patient with probable IgG4-RD through a clinical phenotype framework will ease the diagnostic algorithm and facilitate the prompt recognition of the disease. There are certain clinical, serological, radiological, and histological features in each clinical phenotype that, if present, increase the likelihood that a patient may have IgG4-RD instead of the mimicker condition. Those clues that point toward IgG4-RD diagnosis should be actively sought in the workup of patients.

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.

Calcifilaxis de la arteria temporal simulando arteritis temporal / Calciphylaxis of the temporal artery simulating temporal arteritis

La calcifilaxis se caracteriza por una intensa deposición de calcio en pequeños vasos sanguíneos, piel y otros órganos, descripta principalmente en pacientes con insuficiencia renal crónica, trasplante renal o disfunción paratiroidea. Hasta la fecha, solo hay siete casos descriptos en la literatura de calcifilaxis que imita arteritis de células gigantes (ACG). En esta revisión presentamos el octavo caso documentado patológicamente.

Calciphylaxis is characterized by intense deposition of calcium in small blood vessels, skin, and other organs, described mainly in patients with chronic renal insufficiency, renal transplant of parathyroid dysfunction. To date, there are only seven cases described in literature of calciphylaxis mimicking giant cell arteritis (GCA). In this review, we present the eighth case pathologically documented.

En Reumatología, ¿generamos los maestros que el siglo XXI necesita? / In Rheumatology, do we generate the teachers that the 21st century needs?

¿Quiénes deberían ser maestros de la Reumatología Argentina? Uno pensaría los mejores. ¿Son los mejores? ¿Cuál debería ser el criterio de selección para tan honroso y destacado sitio? Nuestra Sociedad exige: "Todos aquellos que hayan cumplido 65 años y que con su actividad académica mediante, formaron jóvenes reumatólogos". ¿Cómo los formaron? ¿Sabemos? ¿Técnicos o humanistas? La formación de un discípulo, en este caso en Reumatología, debe ser integral. No solo lo técnico, sino también de igual importancia en lo humano. Un maestro dialoga, mantiene un ideal, renuncia al enriquecimiento y muestras sus llagas.

Who should be the great educators and masters of Argentinian Rheumatology? One would think they should be the best ones! But are they the best ones? What ought to be the selection criteria for such a distinguished and honourable position? Our society demands: "All of those who have turned 65 years old and who, thanks to their academic work, have trained young rheumatologists". How the latter were trained? Do we know? As mere technicians or as humane professionals? The academic training of a pupil of Rheumatology, as in this case, must be comprehensive. Not only the technical but also the human aspect is of the utmost importance. An educator converses, is true to an ideal, gives up/sacrifices enrichment and reveals their weak points.

Sobrevida, eficacia y seguridad de Golimumab en pacientes con Artritis Reumatoidea y Espondiloartritis: Datos de una cohorte argentina / Survival, efficacy and safety of Golimumab in patients with Rheumatoid Arthritis and Spondyloarthritis: Data from an Argentine cohort

Objetivos: Golimumab ha sido aprobado para el tratamiento de pacientes con artritis reumatoidea (AR), artritis psoriásica (APs) y espondiloartritis axial. Sin embargo, los datos provenientes de nuestra región son escasos. El objetivo de este estudio fue evaluar la eficacia, seguridad y sobrevida acumulada de golimumab en pacientes de la vida real con AR, APs y espondilitis anquilosante (EA) de diferentes centros de Argentina. Material y métodos: Se llevó a cabo un estudio longitudinal, en el que se incluyeron pacientes consecutivos mayores de 18 años con diagnóstico de AR (criterios ACR/EULAR 2010), APs (criterios CASPAR) y Espax (criterios ASAS 2009), que hayan iniciado tratamiento con golimumab de acuerdo a la indicación médica. Se obtuvieron los datos por revisión de historias clínicas. Se consignaron características sociodemográficas, clínicas, comorbilidades y tratamientos previos. Con respecto al golimumab, se registraron fecha de inicio, vía de administración y tratamientos concomitantes. Se determinó la actividad de la enfermedad mediante DAS28 en el caso de la AR, por DAPSA y MDA para APs y por BASDAI en el caso de Espax. Se consignó la presencia de eventos adversos (EA). En el caso de suspensión del tratamiento, se identificaron la fecha y motivo del mismo. Los pacientes fueron seguidos hasta la suspensión del golimumab, pérdida de seguimiento, muerte, o finalización del estudio (30 de noviembre de 2020). Resultados: Se incluyeron 182 pacientes, 116 con diagnóstico de AR, 30 con APs y 36 con Espax. La mayoría de ellos (70.9%) eran mujeres con una edad mediana (m) de 55 años (RIC 43.8-64) y una duración de la enfermedad m de 7 años (RIC 4-12.7) al inicio del tratamiento. El 34.6% de los mismos habían recibido al menos una droga modificadora de la enfermedad (DME) biológica (-b) o sintética dirigida (-sd) previamente. El seguimiento total fue de 318.1 pacientes/año. El tratamiento con golimumab mostró mejoría clínica en los tres grupos de pacientes. La incidencia de eventos adversos fue de 6.6 por 100 pacientes/año, siendo las infecciones las más frecuentes. Durante el seguimiento, 50 pacientes (27.5%) suspendieron golimumab, la causa más frecuente fue el fracaso del tratamiento (68%), seguida de la falta de cobertura (16%) y el desarrollo de eventos adversos (10%). La persistencia de golimumab fue del 76% y 68% a los 12 y 24 meses, respectivamente. Se registró una sobrevida de 50.2 meses (IC 95% 44.4-55.9). Los pacientes que habían recibido tratamiento previo con DME-b y/o -sd mostraron una menor sobrevida (HR 2.4, IC 95% 1.3-4.4). Conclusiones: El tratamiento con golimumab en pacientes de la vida real en Argentina ha demostrado una buena eficacia y seguridad. La sobrevida del fármaco fue de más de 4 años y casi el 80% seguía usando golimumab después de un año. El tratamiento previo con otros DME-b o -sd se asoció con una menor sobrevida al tratamiento.

Objectives: Golimumab is approved for patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis. However, data from our region are scarce. The aim of this study was to evaluate the efficacy, safety, and cumulative survival of golimumab in real-life patients with RA, PsA and axial spondyloarthritis (axSpa) from different rheumatology centers in Argentina. Material and methods: We performed a longitudinal study of consecutive adults with RA (ACR/EULAR 2010 criteria), PsA (CASPAR criteria) and axSpa (ASAS 2009 criteria), who have started treatment with golimumab according to medical indication. Data was obtained by review of medical records. Sociodemographic and clinical data, musculoskeletal manifestations, comorbidities and previous treatments were recorded. In reference to golimumab treatment, start date, route of administration and concomitant treatments were identified. Disease activity was assessed using DAS28 for RA patients, DAPSA and MDA for PsA and BASDAI for axSpa. The presence of adverse events was recorded. If golimumab was stopped, date and cause was documented. Patients were followed up until golimumab discontinuation, loss of follow-up, death, or study completion (November 30, 2020). Results: In total 182 patients were included, 116 with a diagnosis of RA, 30 with PsA and 36 with axSpa. Most of them (70.9%) were female with a median (m) age of 55 years (IQR 43.8-64) and m disease duration of 7 years (IQR 4-12.7) at treatment initiation. Al least one prior biological (-b) and/or targeted synthetic (-ts) disease modifying antirheumatic drug (DMARD) was received by 63 patients (34.6%). Total follow-up was 318.1 patients/year. Golimumab treatment showed clinical improvement in all three groups of patients. The incidence of AE was 6.6 per 100 patients/year, being infections the most frequents ones. During follow-up, 50 patients (27.5%) discontinued golimumab, the most frequent cause was treatment failure (68%), followed by lack of health insurance (16%) and adverse events (10%). Golimumab persistence was 76% and 68% at 12 and 24 months, respectively. Treatment survival was 50.2 months (95% CI 44.4-55.9). Patients who had received prior treatment with b- or ts-DMARDs showed lower survival (HR 2.41, 95% CI 1.3-4.4). Conclusions: Golimumab treatment in real life patients in Argentina has shown good efficacy and safety. Drug survival was over 4 years and almost 80% were still using golimumab after one year. Prior treatment with other b- or ts-DMARDs was associated with lower treatment survival.

Differential diagnosis between pancreatic involvement in IgG4-related disease and pancreatic cancer. / Diagnóstico diferencial entre compromiso pancreático en enfermedad relacionada con IgG4 y cáncer de páncreas.

IgG4-related disease is a systemic disorder characterised by diffuse or tumoural inflammatory lesions. It can mimic pancreatic cancer, leading to errors in diagnosis and treatment increasing rates of morbidity and mortality in patients. The aim of this review is to take a differential diagnostic approach to these two entities using epidemiology, clinical and laboratory findings, imaging and histopathology.

Rheumatic manifestations associated with cocaine addiction / Manifestaciones reumatológicas asociadas al consumo de cocaína

ABSTRACT Cocaine use is associated with several rheumatic syndromes. A series of cases is presented of 10 patients (7 male and 3 female), age at onset: 19-38 years-old. They consulted due to a variety of symptoms: fever, arthritis, swollen hands, stroke, fetal losses, arterial hypertension, alveolar hemorrhage, leucocytoclastic vasculitis, genital bleeding, among others. Half of them showed positive ANA and Ro antibodies, lymphopenia and positive P-ANCA. Treatments with steroids in bolus, cyclophosphamide and rituximab were used, with a good response. This series highlights clinical manifestations at onset that can mimic primary rheumatic diseases. Rheumatologists should consider cocaine use in the differential diagnoses of vasculitis and pseudovasculitis syndromes.

RESUMEN El uso de cocaína se asocia con varios síndromes reumáticos. Se trata de 10 pacientes (7 varones y 3 mujeres) con una edad al inicio del cuadro entre 19-38 anos, quienes consultaron por una variedad de síntomas: fiebre, artritis, tumefacción de manos, accidente isquémico transitorio, pérdidas fetales, hipertensión arterial, hemorragia alveolar, vasculitis leucoci-toclástica y hemorragia genital, entre otros. La mitad de estos pacientes presentaron ANA y anticuerpo anti-Ro positivos, linfopenia y p-ANCA positivo. Fueron tratados con corticoides intravenosos en bolo, ciclofosfamida y rituximab, con buena respuesta. Esta serie resalta las manifestaciones clínicas que, al inicio del cuadro, pueden imitar una enfermedad reumática primaria. Los reumatólogos debieran considerar a la cocaína en el diagnóstico diferencial de las vasculitis y los síndromes seudovasculíticos.

Diffuse Alveolar Haemorrhage in Systemic Lupus Erythematosus Patients. / Hemorragia alveolar difusa en pacientes con lupus eritematoso sistémico.

INTRODUCTION: Pulmonary haemorrhage (PH) in systemic lupus erythematosus (SLE) is a rare but potentially fatal complication due to its high mortality. Early treatment benefits the outcome. Reports on predictive factors of PH in SLE patients are scarce. OBJECTIVE: To describe a case series of PH in SLE patients that were attended in the Rheumatology Section of the J. M. Cullen Hospital and to compare this data with published results. METHODS: Patients with SLE (1982-1997 ACR criteria) and PH diagnosed by clinical criteria (cough, dyspnoea, haemoptysis), haemoglobin below 12 g/dL or drop greater than 2 points, new radiological infiltrate and bronchioalveolar lavage, monitored between June 1987 and December 2019 were studied. Demographic, clinical, laboratory, treatment and prognosis data related to PH were analysed. RESULTS: From a database of 306 SLE patients, 25 (8.2%) developed 29 episodes of PH. PH was the first manifestation of SLE in 8 patients. Renal involvement was the most frequent manifestation prior to the development of PH. SLE activity (measured by SLEDAI) was high during the episodes (mean: 16.8). Renal failure (p = 0.027) and mechanical respiratory support (p = 0.006) were related to mortality (40.7%) with statistical significance. Patients with SLEDAI higher to 10 at SLE onset showed more likelihood of developing PH. The OR was 2.68 (p = 0.046). CONCLUSIONS: Although treatment in SLE has progressed in recent years, PH continues to be a rare and severe complication of this disease. When a PH is suspected, studies to confirm it must be done rapidly, since early diagnosis and aggressive treatment have been shown to improve survival. We observed that patients with renal involvement and mechanical respiratory support had higher mortality than SLE patients without them.

Comparación de pacientes con lupus eritematoso sistémico tratados en centros públicos versus centros privados de salud / Comparison of systemic lupus erythematosus patients treated in the public system of health versus private centers

Estudios recientes sobre lupus eritematoso sistémico (LES) han comunicado desenlaces más favorables gracias al mejor conocimiento de la enfermedad, al manejo más experto del mismo y al uso racional de los tratamientos. En este estudio se identificaron 301 pacientes con lupus eritematoso sistémico (LES), vistos entre 1988 y 2019. Doscientos veintiocho fueron tratados en el sistema público de salud y 73 en el sistema privado. Ambos grupos fueron comparados, observando que los primeros tenían menor edad al momento de la primera consulta y al inicio del LES y menor tiempo de evolución hasta la primera consulta que los pacientes atendidos en el sistema privado de salud de manera estadísticamente significativa. También mostraron mayor frecuencia de leucopenia, con presencia de anticuerpo Sm y compromiso renal en la primera consulta, como así también mayor uso de corticoides EV. Los pacientes hospitalarios presentaron mayor daño acumulado en los primeros 10 años de evolución, pero el desenlace muerte fue similar en ambos grupos. Ambos grupos de pacientes (tanto los del sistema público como los del sector privado) fueron atendidos por especialistas, realizando un cuidadoso seguimiento de estos pacientes.

Recent studies on systemic lupus erythematosus (SLE) have reported more favorable outcomes thanks to better knowledge of the disease, more expert management of it, and rational use of treatments. In this study we identified 301 SLE patients, seen between 1988 and 2019. Two hundred and twenty eight patients were treated in the public health system and 73 in private practice. In comparing both groups, we discovered that patients in the public health system were younger at first consultation and at SLE onset and that the mean duration of their disease prior to first consultation was shorter in a statistically significant way. Also, they showed more frequence of leucopenia, Sm antibody, renal involvement and received I.V. corticosteroids. Patients treated in the public system of health showed more accrual damage over the 10 first years of the disease than patients seen in the private system of health, but death in both groups was similar. Patients from both public and private groups were attended by medical specialist practices who made close follow-ups.