Andreu Fernández-Codina

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.

Good outcome of interstitial lung disease in patients with scleroderma associated to anti-PM/Scl antibody.

OBJECTIVE The objective of this article was to establish the clinical course of interstitial lung disease (ILD) in scleroderma related to the presence of anti-PM/Scl antibody compared with anti-Scl-70 in a Spanish cohort. Furthermore, no study has thoroughly investigated the outcome of pulmonary function test in the first group of patients. METHODS A total of 63 Spanish patients with scleroderma and ILD were selected in a retrospective observational study. Among them, 14 were positive for anti-PM/Scl antibodies and 49 for anti-Scl-70. Clinical assessments, including pulmonary function test, were collected. Variations equal or greater than 10% in forced vital capacity (FVC) were considered significant. Progression-free survival of disease was defined as the period of stable illness since pulmonary fibrosis diagnosis. RESULTS Anti-Scl-70 patients had a higher frequency of diffuse SSc subset, peripheral vasculopathy, and gastrointestinal involvement. Inflammatory myopathy was associated to anti-PM/Scl antibody. Anti-PM/Scl patients presented more improvement in FVC during follow-up, 30.8% compared to a 7.1% in Scl-70 group (P = 0.04), with less worsening of this parameter (15.4% vs 52.4% in Scl-70 patients, P = 0.01), and secondary less frequency of severe restrictive pattern (FVC < 50%) (7.7% compared to 42.9% in the other group, P = 0.02). Regarding treatment, more anticalcineurinics were used in anti-PM/Scl patients, while cyclophosphamide and mycophenolate were mainly used in anti-Scl-70 patients. The progression-free survival of disease was higher in anti-PM/Scl patients, with 76% at 10 years from diagnosis of ILD against a 29% in the Scl-70 group. CONCLUSIONS Several features and prognosis of ILD in SSc may be modified depending on the identified immunological profile.

Cardiac tamponade and severe pericardial effusion in systemic sclerosis: report of nine patients and review of the literature

To describe the clinical characteristics, treatment and outcome of patients with systemic sclerosis (SSc) developing severe pericardial effusion or cardiac tamponade.

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,

Lung transplantation in systemic sclerosis: A single center cohort study

OBJECTIVE Lung transplantation (LT) has been proposed as a treatment for advanced interstitial lung disease (ILD) and/or pulmonary hypertension (PH) associated to systemic sclerosis (SSc) but few studies have been reported. The aim of this study was to describe the clinical features, complications and survival of a single-center cohort of patients with SSc that underwent LT and to compare their survival with a group of non-SSc transplanted patients. METHODS Fifteen patients with SSc were transplanted between May 2005 and April 2015. Standard international criteria were used to determine eligibility for LT. The severity of gastroesophageal involvement was not considered as a major contraindication if symptoms were under control. RESULTS Eight (53.3%) patients had diffuse cutaneous SSc. Eleven (73%) underwent bilateral LT. The main indication for LT was ILD, with or associated PH in 4 cases. Acute cellular rejection and infections were the most frequent complications. Functional lung tests tended to keep stable after transplantation. Median survival was 2.4 years (Q1-Q3: 0.7-3.7 years). We did not find differences in survival between patients transplanted with SSc versus those transplanted due to non-SSc ILD or PH. SSc complications were scarce with no patient developing PH after LT. CONCLUSIONS LT was an effective treatment for advanced ILD and/or PH associated to SSc in our study. Gastroesophageal reflux was not a limitation for LT in SSc in this study. Complications and survival did not differ from non-SSc patients undergoing LT.

Mixed Connective Tissue Disease and Epitope Spreading: An Historical Cohort Study

Objectives Mixed connective tissue disease (MCTD) is characterized by the presence of anti-U1-snRNP autoantibodies and a variable set of associated clinical features. Some MCTD patients test positive over time to autoantibodies against Sm, proteins spatially related with U1-snRNP. This situation has been attributed to expanding of the autoimmune response by a phenomenon known as epitope spreading. Our aim was to study the frequency of this phenomenon in MCTD patients and the specific clinical features of those with epitope spreading. Methods All anti-U1-RNP-positive patients (2010–2015) were retrospectively reviewed, and those meeting the MCTD criteria were included in the study. Patients showing epitope spreading were compared with the remainder of the MCTD cohort. In addition, the clinical features of patients with epitope spreading were compared before and after the phenomenon occurred. Results Among 72 anti-U1-RNP-positive patients, 40 (37 women) were diagnosed with MCTD. Thirteen MCTD patients (43%) presented epitope spreading, mainly during the first 2 years after the diagnosis of the disease (median, 1.4 years). Patients with epitope spreading had a significantly lower prevalence of skin sclerosis (0% vs. 44%, P = 0.004) and a greater prevalence of interstitial lung disease (46% vs. 15%, P = 0.05) than those without. Arthritis (92% vs. 25%, P = 0.02) and muscle involvement (67% vs. 17%, P = 0.02) were less frequent after epitope spreading had occurred. Conclusion Epitope spreading is common in MCTD, occurring early after the diagnosis. The clinical manifestations in patients with this phenomenon differ from those without, and their clinical features change after the immunological phenomenon has occurred.

Atypical scleromyxedema with prominent nodular lesions associated with immune thrombocytopenia: An unusual presentation

To the Editor: Scleromyxedema (SM) is a rare cutaneous mucinosis that usually occurs with monoclonal gammopathy ([83.2%), predominantly an IgG lambda subtype. SM may show a great variety of extracutaneous manifestations ( gastrointestinal, musculoskeletal, neurologic, pulmonary, cardiac, and renal involvement) leading to significant morbidity and mortality. We report a case of SM with prominent scalp involvement, presence of nodular lesions, and immune thrombocytopenia. A 69-year-old woman presented with a 2-week history of facial edema and progressive eruption. The patient also reported severe scalp pruritus and increased hair loss. On physical examination, skin-colored firm papules, nodules, and edema of the face and both hands were observed. The papules were initially located on the scalp, neck, and back of the auricular area, then gradually involved upper aspect of the trunk and the surrounding skin showed scleroderma-like induration in these areas. Several nodules, 4 to 10 mm in size, were present on the scalp, forehead (Fig 1), and side portions of the chin. Pathological examination of biopsy specimens from a nodular scalp lesion and of a neck papule (Fig 2) revealed an increase in fibroblasts, collagen, and deposits of mucin in the papillary and midreticular dermis. Laboratory analysis showed a progressive low platelet count (60-10 10/ L, normal range 150-400 10/ L, platelet count within normal limits 6 months earlier), with a normal peripheral blood smear result and a normocellular bone marrow with trilineage hematopoiesis. Serum protein electrophoresis, immunofixation electrophoresis of serum and urine, and immunoglobulin free light chain assays did not show paraproteinemia. Other laboratory examination findings including thyroid function were within normal limits and autoantibody screening produced negative results. Computed tomographic scans of the chest, abdomen, and pelvis showed no relevant abnormalities. Electromyography detected signs consistent

Takayasu's arteritis relapse

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

Treatment Algorithms for Systemic Sclerosis According to Experts

There is a lack of agreement regarding treatment for many aspects of systemic sclerosis (SSc). We undertook this study to generate SSc treatment algorithms endorsed by a high percentage of SSc experts.