Fernando Martínez-Valle

IgG4-Related Disease: Results From a Multicenter Spanish Registry.

AbstractIgG4-related disease (IgG4-RD) is a rare entity consisting of inflammation and fibrosis that has been described in multiple organs. Concrete diagnostic criteria have been established recently and there is a lack of large series of patients.To describe the clinical presentation, histopathological characteristics, treatment and evolution of a series of IgG4-RD Spanish patients.A retrospective multicenter study was performed. Twelve hospitals across Spain included patients meeting the current 2012 consensus criteria on IgG4-RD diagnosis.Fifty-five patients were included in the study, 38 of whom (69.1%) were male. Median age at diagnosis was 53 years. Thirty (54.5%) patients were included in the Histologically Highly Suggestive IgG4-RD group and 25 (45.5%) in the probable IgG4-RD group. Twenty-six (47.3%) patients had more than 1 organ affected at presentation. The most frequently affected organs were: retroperitoneum, orbital pseudotumor, pancreas, salivary and lachrymal glands, and maxillary sinuses.Corticosteroids were the mainstay of treatment (46 patients, 83.6%). Eighteen patients (32.7%) required additional immunosuppressive agents. Twenty-four (43.6%) patients achieved a complete response and 26 (43.7%) presented a partial response (<50% of regression) after 22 months of follow-up. No deaths were attributed directly to IgG4-RD and malignancy was infrequent.This is the largest IgG4-RD series reported in Europe. Patients were middle-aged males, with histologically probable IgG4-RD. The systemic form of the disease was frequent, involving mainly sites of the head and abdomen. Corticosteroids were an effective first line treatment, sometimes combined with immunosuppressive agents. Neither fatalities nor malignancies were attributed to IgG4-RD.

IgG4-related disease: Evidence from six recent cohorts.

IgG4-related disease (IgG4-RD) is a rare autoimmune fibrosing disorder. In this review we aim to describe and compare the characteristics of the six largest IgG4-RD cohorts, since the new 2012 consensus diagnostic criteria were released. These observational studies were published between 2012 and 2015. Patients were included using the comprehensive diagnostic criteria or the 2012 consensus criteria. Results were reviewed and summarized. Most patients were middle aged men. Fibro-inflammatory masses developed in virtually all organs except the brain, with an unexplained preference for salivary glands, lymph nodes and pancreas. Corticosteroids were the treatment of choice but up to 40% of patients relapsed within the first year. Standardized response assessment tools, biomarkers and the validation of new treatments are still in development. In conclusion, the features of IgG4-RD are similar across the globe. At the moment, corticosteroids are the only validated treatment but rituximab seems to be promising.

Churg–Strauss Syndrome: An evolving paradigm

The Churg-Strauss Syndrome is an ANCA-associated vasculitis, an inflammatory multisystem disease with preference to the respiratory tract. Peripheral and tissue eosinophilia are the pathological hallmarks of this condition. The etiopathogenesis is unknown but some cytokines appear to play a central role and could be targets for new therapies.

Assessment of amyloid deposits by 18F-florbetapir positron emission tomography

A 76-year-old female consulted for tongue enlargement over the previous 10 months. She reported sore mouth, progressive difficulty swallowing and weight loss. The study of monoclonal gammopathy showed a monoclonal peak at serum with a monoclonal component IgG kappa in the immunofixation. A bone marrow biopsy showed 20 % of plasmatic cells with a kappa chain restriction, suggestive of multiple myeloma. Finally, a fine needle puncture of the tongue was performed, which was indicative of amyloidosis due to light chain deposit. In view of the information revealed by the work of Dorbala et at. [1], the patient underwent F]-florbetapir (Amyvid) positron emission tomography (PET) imaging 40 min after intravenous injection of 370 MBq, in order to assess the extension of amyloid deposits. F]Florbetapir is a beta amyloid radiotracer used in the diagnosis of Alzheimer’s disease [2, 3]. In this patient, the florbetapir PET scan revealed strong radiotracer amyloid uptake in the tongue, without other whole-body abnormal tracer accumulation (C), compared to sagittal views of F]-florbetapir PET images of a patient with mild cognitive impairment without brain amyloid tracer uptake (A) and a patient with Alzheimer’s disease with positive brain amyloid tracer uptake (B). To our knowledge, this is the first reported case of the use of F]-florbetapir (AmyvidTM) PET for evaluation of extracardiac deposits in amyloid disease. The florbetapir PET is a reliable technique that can improve the diagnosis and management of patients with amyloidosis.

Idiopathic retroperitoneal fibrosis: IgG4 infiltration in a cohort of Spanish patients

Sections were stained with haematoxylin and eosin as well as for Masson’s trichrome. Immunostaining for IgG4 was performed on 4-μm-thick paraffin-embedded human surgical biopsy sections using as the primary antibody a mouse anti-human IgG4 monoclonal antibody (clone MC011, the Binding Site, Birmingham, UK). Sections were also immunostained for anti-CD4 (clone 4B12, Master Diagnostica, Granada, Spain; commercial pre-concentrated dilution 1:2) and anti-CD8 (clone C8/144B, Dako Cytomation, Glostrup, Denmark; dilution 1:50) antibodies using an autostainer (Bond-Max Leica, Wetzlar, Germany). Immunohistochemistry slides were evaluated by two independent pathologists; discordant cases were re-evaluated. IgG4-positive plasmacytes were counted in 3 different high-power fields (hPF) at 400× for each specimen in the most prominently inflamed areas, and the results were compared. the stained cell recount was performed using Soft Imagin System Cell-B (Olympus, Spain). Nineteen patients were male. All patients were of Caucasian race/ethnicity except a North African subject. Mean ± standard deviation age at diagnosis was 51.8 ± 16.4 years. Mean time elapsed from onset of symptoms to diagnosis was 5.2 ± 5.13 months. histopathological features of the studied patients are shown in table 1 and Fig. 1. thirteen surgical biopsies were recovered. All patients presented 2 or more of the characteristic pathological features proposed by Deshpande et al. [4] (lymphoplasmacytic infiltrate, storiform fibrosis and obliterative phlebitis). IgG4-positive immunostaining was found in 8 individuals (61.5 %), but only 3 patients presented >30 IgG4 plasma cells/hPF × 400 (mean 45.4; range 37.2–65.5). the other 10 subjects showed <30 IgG4 plasma cells/hPF × 400 (mean 3.8; range 0–29.8). Only three patients fulfilled the requests for histological highly Sir,

A 72-year-old man with dyspnea, circumferential aortic thickening, and weight loss.

History of the present illness One month before admission, the patient was studied by a general practitioner as a result of a 15-kg weight loss during the previous 3 months, as well as hyporexia and asthenia. He reported occasional fever, mainly in the evenings. For this reason, tumor markers and abdominal echography were performed, without pathologic findings, and a gastroesophageal endoscopy only manifested a hiatal hernia. In addition, he experienced slow but progressive worsening of his New York Heart Association functional class during the last 2 months. He had required an emergency department admission with congestive heart failure. A bilateral pleural effusion was documented, and he was admitted under treatment with diuretics and angiotensinconverting enzyme inhibitors.

Seudotumor pancreático de etiología tuberculosa

Fundamento Revisar las caracteristicas clinicas de la tuberculosis pancreatica y su diagnostico diferencial con las tumoraciones pancreaticas. Pacientes y metodo Descripcion de tres casos de tuberculosis pancreatica diagnosticados du-rante un periodo de 2 anos en un hospital universitario de 850 camas. Resultados En los tres casos, las tecnicas de imagen realizadas demostraron afeccion del pan-creas, en forma de desestructuracion, agrandamiento e imagenes hipodensas e hipoecoicas. Uno de los pacientes fue diagnosticado inicialmente de forma erronea de una neoplasia pan-creatica. Se establecio el diagnostico de tuberculosis pancreatica por puncion de absceso sub-cutaneo en un caso, por sospecha clinica en otro y por laparoscopia exploradora en el tercero. Solo un paciente presentaba una inmunodepresion de base. Los tres pacientes se curaron contratamiento antituberculoso triple habitual. Conclusiones La tuberculosis pancreatica se debe considerar en todo paciente que se presentacon una masa pancreatica.

Takayasu's arteritis relapse

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 18 mars 2017

Treatment and outcomes in patients with IgG4-related disease using the IgG4 responder index

BACKGROUND IgG4-related disease (IgG4-RD) is an autoimmune disease triggering an inflammatory cascade that leads to fibrosis. Outcome measures are limited and treatment options remain underexplored. OBJECTIVES To assess the variation of the IgG4 responder index (IgG4-RI) in a cohort of IgG4-RD patients and to explore their treatments and outcomes. METHODS We studied the clinical phenotype, severity of the disease and response to treatment in an ambispective multicenter cohort study including 14 different hospitals in Spain. All patients met the 2012 international consensus on pathology criteria for diagnosis. RESULTS Sixty-eight patients were included, with a mean age of 53.4 years and predominance of male sex. The most commonly involved tissues were: retroperitoneum (33%), orbital pseudotumor (28%) and maxillary and paranasal sinuses (24%). IgG4-RI values were higher in patients with multiorgan disease and before treatment. After being treated, IgG4-RI values were lower, in accordance with the high rates of treatment response. Most patients received: glucocorticoids (GC), surgery, azathioprine (AZA), mofetil mycophenolate or rituximab. GC alone, GC plus surgery and GC plus AZA were given in the most of the IgG4-RD disease activity episodes. All treatments had high response rates but relapses and flares were common. CONCLUSIONS IgG4-RI is a promising outcome measure in IgG4-RD, but still in development. Treatment algorithms are ill defined. GC and rituximab are the drugs with more evidence available. Disease modifying anti-rheumatic drugs may have a role in IgG4-RD and warrant more prospective studies.

Utility of the 18F-Florbetapir positron emission tomography in systemic amyloidosis

Abstract Amyloidosis comprises a group of heterogeneous conditions. To ascertain the burden of disease is important because it can determine the treatment as well as the evolution of the disease. Recent reports have shown good results in diagnosing cardiac amyloidosis using 18F-florbetapir. We hypothesize that combining whole body PET/CT with 18F-Florbetapir can be useful to characterize the burden of the disease. We included 25 patients, 13 of them with different types of amyloidosis, and 12 with Alzheimer’s disease as controls. Target-to-background ratio was computed for multiple organ using maximum standardized uptake values. Organ involvement was described (standardized techniques versus PET) according to different kinds of amyloidosis showing promising results in AA and AL types. Heart involvement showed poorer results when compared to tongue, lung or thyroid gland. Multiple organ involvement in patients previously labelled as having negative organ affectation could be identified. This is the first study to evaluate the utility of 18F-florbetapir in the assessment of the global extension of disease. Our results show that this technique is useful for its diagnosis.