Insulin amyloidosis: A case report

Insulin amyloidosis is a rare form of localized amyloidosis due to insulin aggregation into subcutaneous amyloid fibrils. We describe the case of a 55 years old male with insulin-requiring type 1 diabetes presenting with two non-inflammatory intra-dermal nodules associated with local lymph node enlargement. Diagnosis was confirmed by Congo red coloration of the amyloid deposit and insulin protein identification on mass spectrometry. Insulin amyloidosis is a potential complication of repeated subcutaneous insulin injections. The main risk factor is the intrinsic characteristic of the insulin used. Insulin amyloidosis leads to systemic metabolic consequences such as chronic hyperglycemia or unpredictable hypoglycemia, as well as unesthetic cutaneous lumps or abscesses. Standard-of-care is yet to be defined but mainly rely on therapeutical education of insulin injections, while surgical excision is reported to improve glycemic control in some patients

INFILTRAT LYMPHOCYTAIRE PORTAL DANS LA MALADIE ALCOOLIQUE DU FOIE (FREQUENCE ET SIGNIFICATION)

AMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Maladie pulomonaire des dépôts de chaînes légères (étude anatomo-clinique, approche des mécanismes moléculaires et hypothèses pathogéniques sur la formation des kystes)

La maladie des dépôts de chaînes légères (LCDD) se caractérise par des dépôts tissulaires non organisés de chaînes légères d immunoglobulines (Ig) monoclonales produites par un clone plasmocytaire médullaire. C est une maladie systémique touchant exceptionnellement les poumons. Le but de ce travail est de décrire à partir de 5 observations une nouvelle entité : la LCDD pulmonaire kystique. Tout d abord, nous rapportons 4 patients présentant un syndrome obstructif et de nombreux kystes distribués dans les deux poumons. L évolution vers une insuffisance respiratoire terminale a nécessité le recours à la transplantation pulmonaire (TP) laquelle a été bilatérale chez tous les patients. Histologiquement, il existait une infiltration des cloisons alvéolaires, des petites voies aériennes et des vaisseaux par des dépôts non amyloïdes de chaînes légères . Les kystes correspondaient à une dilatation des alvéoles et des bronchioles. L examen de la moelle osseuse ne montrait pas d excès de plasmocytes et le rapport / était normal. Du fait de la normalisation du rapport / de chaînes légères libres sériques après TP et de l absence de récidive de la maladie après TP, nous avons émis l hypothèse que le clone B était intrapulmonaire. Par PCR, nous avons identifié un clone B majoritaire dans le tissu pulmonaire mais absent du sang périphérique. De plus, les clones B des différents patients partageaient le même récepteur VH4-34/VK1 non muté. Associés aux données cliniques et biologiques, ces résultats suggèrent que la LCDD pulmonaire kystique correspond à une nouvelle entité primitivement pulmonaire possiblement liée à une stimulation antigénique particulière. Parallèlement, nous rapportons 1 cas de LCDD pulmonaire kystique avec infiltration bronchique diffuse prédominante. Enfin, nous montrons que la formation des kystes est liée à une importante dégradation du réseau élastique pulmonaire qui pourrait être due à l activité des métalloprotéinases (MMP) en particulier MMP-9 et -2.Light chain deposition disease (LCDD) is characterized by intratissular deposits of non-organized monoclonal immunoglobulin (Ig) light chain subunits produced by a clonal bone marrow plasma cell population. It is a systemic disorder that particularly uncommonly affects the lung. The aim of this study is to describe from 5 cases a new entity: cystic lung LCDD. First, we report 4 patients with an obstructive pulmonary dyspnea and numerous cysts distributed in both lungs. The progression to end-stage respiratory failure required lung transplantation (LT) which was bilateral in all patients. Histologically, we observed non-amyloid light chain deposits in the wall of alveoli, small airways and vessels. Cysts resulted from the dilatation of alveolar spaces and bronchioles. Bone marrow examination did not disclose an excess of plasma cells and the / ratio was normal. The normalization of the serum free light chains / ratio after LT in one patient and the absence of relapse of the disease after LT suggested that the B-cell clone was located within the lung. Using PCR, we identified a dominant B-cell clone in the lung without peripheral blood involvement. Furthermore, we show that the different clonal expansions shared an unmutated VH4-34/VK1 receptor. Combined with clinical and biological observations, our data highly argue for a new antigen-driven primary pulmonary lymphoproliferative disorder. We also report 1 case of cystic lung LCDD with a predominant diffuse airway thickening. At last, we demonstrate that cyst formation is in relationship with an extensive degradation of the pulmonary elastic network that may be due to metalloproteinase (MMP) activity, especially MMP-9 and -2.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Dramatic beneficial effect of interleukin-1 inhibitor treatment in patients with familial Mediterranean fever complicated with amyloidosis and renal failure

Background. Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder, for which systemic AA amyloidosis is the major complication revealed most of the time by renal abnormalities. Current treatment is daily colchicine that prevents both recurrent inflammatory attacks and amyloidosis deposition in most patients. However, some patients still develop amyloidosis and renal failure. Functional studies suggest that interleukin (IL)-1 is implicated in the inflammatory reaction in FMF and therefore, IL-1 inhibitors could be a new approach to treat FMF. The aim of this series study was to evaluate anakinra in patients with FMF complicated with amyloidosis and renal failure

Release of metal particles from needles used for transbronchial needle aspiration

Background: Although mediastinoscopy is still the gold standard for diagnosis of mediastinal lymphadenopathy, minimally invasive procedures have been developed: transbronchial needle aspiration (TBNA) using a flexible bronchoscope (conventional TBNA) or linear echoendoscope (endobronchial ultrasound [EBUS]) allowing real-time guided lymph node aspiration. The observation of contamination of samples by foreign particles led us to determine the frequency and the nature of this material and to identify its origin. Methods: From June 2007 to November 2008, 141 consecutive patients underwent conventional TBNA (n = 84) or EBUS-guided TBNA (EBUS-TBNA) (n = 57). All cytologic samples were reviewed in blinded fashion, and contamination was assessed semiquantitatively. Mineral analysis using a transmission electron microscope equipped with an energy dispersive x-ray spectrometer was performed on the solution obtained after rinsing unused needles and on four samples of calf thymuses punctured with EBUS needles. Results: Foreign material, different from anthracosis, was identified in samples obtained with five different batches of needles, only from EBUS-TBNA(P<.0001). The contamination score was correlated to the number of passes(P =.035). Mineral analyses of the rinsing solutions from conventional TBNA needles were negative, whereas metal alloys of iron, titanium, nickel, and chromium were released with EBUS needles. The same contamination was identified in three of the four punctured calf thymuses. Conclusions: Dedicated EBUS-TBNA needles are able to release metal particles, probably by friction between the stylet and the needle, with a potential risk to inject particles into nodes. The long-term consequences are unknown, but the need for safety measures should be evaluated. © 2011 American College of Chest Physicians.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Do anti‐IL‐6R blockers have a beneficial effect in the treatment of antibody‐mediated rejection resistant to standard therapy after kidney transplantation?

International audienceAntibody‐mediated rejection (AMR) that resists to standard of care (SOC) therapy remains a major challenge after kidney transplantation and leads to graft failure in a majority of cases. The use of anti‐IL6 receptor antibodies was suggested to treat chronic antibody‐mediated rejection (cAMR) after failure of classical treatments. We treated nine patients with AMR resistant to apheresis, rituximab, and intravenous immunoglobulins, with a monthly infusion of tocilizumab and compared them with a historical cohort of 37 patients with similar clinical, immunological, and histological characteristics. The 1‐year graft survival and the decline in renal function did not differ between patients who received tocilizumab and those who did not. Histological follow‐up showed that despite a decrease in inflammation and tubulitis scores after tocilizumab, the course of antibody‐mediated lesions and chronic glomerulopathy were similar in both groups. In our study, the addition of monthly infusions of tocilizumab did not alter the course of AMR that resist to SOC therapy. Large randomized studies are urgently needed to assess the effect of tocilizumab in this context

Proteomic evidence of specific IGKV1-8 association with cystic lung light chain deposition disease

International audienc

Administration of the High-Density Lipoprotein Mimetic CER-001 for Inherited Lecithin–Cholesterol Acyltransferase Deficiency

International audienc