recommendation based on the EULAR standardized operating procedures for EULAR-endorsed recommendations (11, 12). Category Evidence from LEVELS OF EVIDENCE 1A Meta-analysis of randomized controlled trials 1B At least one randomized controlled trial 2A At least one controlled study without randomization 2B At least one type of quasi-experimental study 3 Descriptive studies, such as comparative studies, correlation studies, or case-control studies 4 Expert committee reports or opinions and/or clinical experience of respected authorities Grade Directly based on STRENGTH OF RECOMMENDATION A Category 1 evidence B Category 2 evidence or extrapolated recommendation from category 2 evidence C Category 3 evidence or extrapolated recommendation from category 1 or 2 evidence D Category 4 evidence or extrapolated recommendation from category 2 or 3 evidence the number of attacks (20). Since then, colchicine has become the basis of FMF treatment, and later on, several clinical trials definitively established its efficacy in preventing attacks and developing amyloidosis (21-23). Colchicine was officially approved in 2009 by the US Food and Drug Administration (FDA) for the acute flares of gout and FMF, as a single-ingredient oral formulation (Colcrys R) (24). Nowadays, according to 2016 EULAR recommendations for the management of FMF, colchicine represents the first-line treatment in FMF, with a level of evidence 1B and grade of recommendation A (13). Among other biological functions, colchicine has antiinflammatory properties based on the inhibition of leukocyte chemotaxis, which is caused by its interaction with tubulin and the resulting dysfunction of microtubules. Microtubules, composed by α-and β-tubulin heterodimers, are involved in cell division, signal transduction, migration, secretion, and regulation of gene expression (25). Colchicine has the ability to bind in a poorly reversible manner to soluble non-polymerized tubulin in the cells, with the formation of a tubulin-colchicine complex (26, 27), and the subsequent movement inhibition of intracellular granules (28). The predominant effect of colchicine on leukocytes, and more specific on granulocytes, has been correlated with the high concentrations of the drug in neutrophils compared to lymphocytes and monocytes. In this regard, defects in the efflux pumps with low activity of the P-glycoprotein 1 (PGY-1) efflux pump of granulocytes might explain the accumulation of colchicine in their cytoplasm (29, 30). Other anti-inflammatory effects of colchicine include the reduction of TNF-α production by macrophages and TNF-α

Giant cell arteritis (GCA) and Takayasu’s arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus.

No abstract

Primary pulmonary B-cell lymphomas (PP-BCLs) comprise a group of extranodal non-Hodgkin lymphomas of B-cell origin, which primarily affect the lung without evidence of extrapulmonary disease at the time of diagnosis and up to 3 months afterwards. Primary lymphoid proliferations of the lung are most often of B-cell lineage, and include three major entities with different clinical, morphological, and molecular features: primary pulmonary marginal zone lymphoma of mucosa-associated lymphoid tissue (PP-MZL, or MALT lymphoma), primary pulmonary diffuse large B cell lymphoma (PP-DLBCL), and lymphomatoid granulomatosis (LYG). Less common entities include primary effusion B-cell lymphoma (PEL) and intravascular large B cell lymphoma (IVLBCL). A proper workup requires a multidisciplinary approach, including radiologists, pneumologists, thoracic surgeons, pathologists, hemato-oncologists, and radiation oncologists, in order to achieve a correct diagnosis and risk assessment. Aim of this review is to analyze and outline the clinical and pathological features of the most frequent PP-BCLs, and to critically analyze the major issues in their diagnosis and management.