A. Mahr

Management of giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA)

PURPOSEnManagement of giant cell arteritis (GCA, Hortons disease) involves many uncertainties. This work was undertaken to establish French recommendations for GCA management.nnnMETHODSnRecommendations were developed by a multidisciplinary panel of 33 physicians, members of the French Study Group for Large Vessel Vasculitis (Groupe détude français des artérites des gros vaisseaux [GEFA]). The topics to be addressed, selected from proposals by group members, were assigned to subgroups to summarize the available literature and draft recommendations. Following an iterative consensus-seeking process that yielded consensus recommendations, the degree of agreement among panel members was evaluated with a 5-point Likert scale. A recommendation was approved when ≥ 80% of the voters agreed or strongly agreed.nnnRESULTSnThe 15 retained topics resulted in 31 consensus recommendations focusing on GCA nomenclature and classification, the role of temporal artery biopsy and medical imaging in the diagnosis, indications and search modalities for involvement of the aorta and its branches, the glucocorticoid regimen to prescribe, treatment of complicated GCA, indications for use of immunosuppressants or targeted biologic therapies, adjunctive treatment measures, and management of relapse and recurrence.nnnCONCLUSIONSnThe recommendations, which will be updated regularly, are intended to guide and harmonize the standards of GCA management.

Brief Report: Prevalence of Antineutrophil Cytoplasmic Antibodies in Infective Endocarditis

Infective endocarditis (IE) mimics primary systemic vasculitis, and there are sporadic reports of positivity for antineutrophil cytoplasmic antibodies (ANCAs) among patients with IE. Because the frequency of ANCAs in IE is unknown, this study was undertaken to assess the seroprevalence of ANCAs in a large number of patients with IE.

Épidémiologie et histoire naturelle de l’artérite à cellules géantes (Horton)

Knowledge of the natural history and epidemiology of giant cell arteritis (GCA) is growing. With the recent conceptual change, GCA is no longer considered a disease with mandatory cranial symptoms but, rather, a larger disease spectrum also including idiopathic aortitis in people older than 50 and polymyalgia rheumatica with large-vessel involvement. The incidence peak between age 70 and 80 years, greater frequency in females and greater occurrence in Nordic countries are well-established epidemiological characteristics. Conversely, the notion that the incidence of GCA is increasing is challenged by several recent population-based studies suggesting a trend reversal for about 15 to 20 years. The known link with the allele HLA-DRB1*04 was confirmed by a genome-wide association study that also found associations with two other genetic polymorphisms. Recent studies indicating a link with varicella zoster virus infection have invigorated the hypothesis of an infectious cause for GCA. Smoking is the most solidly recognized environmental risk factor, but other traditional cardiovascular risk factors do not seem to predispose to GCA. Evidence is mounting that overall mortality in GCA patients is at best slightly higher than expected in relation to general population mortality data, but GCA is associated with an increase in morbidity and mortality specifically related to aortic aneurysm or other cardiovascular causes. Further studies are needed to integrate the current knowledge into a single etiological model.

Unusual Pseudotumoral Right Atrial Involvement in Listeria monocytogenes Septicemia

A 44-year-old woman was referred to our cardiology department because of septicemia caused by Listeria monocytogenes and sick sinus syndrome. The patient had a history of paresthesia of the limbs 7 years earlier with multiple sclerosis–like lesions on brain magnetic resonance imaging and positive tests for antinuclear antibodies and anti-double-stranded DNA antibodies. Full recovery occurred after a short course of glucocorticoids and hydroxychloroquine, and the patient did not experience any relapse.nnTwo weeks before hospitalization, the patient was admitted to a nearby hospital with a history of 1 week of fatigue, high-grade fever, mild chest pain, and an otherwise unremarkable physical examination. Baseline laboratory tests disclosed a C-reactive protein level of 103 mg/L, hemoglobin of 11.0 g/dL, leukocytosis of 11 350/mm3, plasma fibrinogen of 8.1 g/L, mild hepatic cytolytic and cholestasic changes, a normal serum gamma globulin level, and negative hepatitis B virus, hepatitis C virus, and HIV serology. Blood cultures and urine analysis were negative. Antinuclear antibody levels were 1:1600 (<1:80), but no anti-double-stranded DNA or anti-extractable nuclear antigen antibodies were detectable. Thoracic and abdominal computed tomography scans, brain magnetic resonance imaging, and cerebrospinal fluid analysis were normal. Follow-up blood cultures grew L monocytogenes in …

Histiocytose à cellules de Langerhans de l’adulte

Langerhans cell histiocytosis (LCH) is a rare disease affecting both genders and can occur at any age. It often evolves through successive flares, and its severity varies from benign forms that dont require treatment to life threatening disease. Some patients have important functional impairment with psychological and social consequences and prolonged disability. LCH may affect only one organ, with uni- or multifocal involvement or be multisystem disease involving multiple organs. The organs most frequently involved are bones, lung, skin and the endocrinal system. Pulmonary LCH is strongly related to smoking. Some patients have mixed histocytosis combining LCH and other histiocytic disorders. The diagnosis relies on the histological study of tissues samples, and shows tissue infiltration with large cell with pale cytoplasm and reniform nucleus, staining for CD1a and Langerin (CD207) on immunohistochemistry. The BRAFV600E mutation is observed in tissue samples in approximately half of patients and the activation of the RAS-RAF-MEK-ERK pathway has been shown to be constantly activated in LCH lesions, regardless the BRAF status. These findings represent an important forward step in the understanding of the physiopathology of the disease. Treatment must be adapted to the severity of the disease and goes from conservative observation to systemic chemotherapy. Therapies targeting the RAS-RAF-MEK-ERK pathway are promising treatments for progressive disease.

Prise en charge de l’artérite à cellules géantes : recommandations du groupe d’études français de l’artérite à cellules géantes (GEFA)

Introduction Il y a de nombreuses incertitudes concernant la prise en charge pratique d’une arterite a cellules geantes (Horton, ACG), notamment du fait de la description de nouvelles approches diagnostiques et therapeutiques avec des resultats d’etudes parfois difficiles a interpreter voire discordantes. Cette situation peut conduire a des appreciations divergentes concernant la meilleure maniere de prendre en charge une ACG. L’objectif de ce travail etait d’etablir des recommandations d’experts pour la prise en charge d’une ACG. Materiels et methodes Un groupe de travail de 33xa0medecins emanant du groupe d’etude francais de l’ACG (GEFA) et representant diverses specialites (medecine interne, rhumatologie, radiologie, anatomopathologie et medecine nucleaire) a ete forme pour elaborer des recommandations. Les sujets a traiter ont ete selectionnes sur propositions des membres du groupe, suivies de discussions collectives en se concentrant sur des questions d’actualite et/ou sujettes a controverses. Les sujets etaient repartis a des sous-groupes de 3xa0a 4xa0participants qui avaient la responsabilite de faire une synthese des donnees de la litterature et une ebauche d’une ou plusieurs recommandations. Ces recommandations ont ete ensuite travaillees au cours d’un processus de concertation iteratif qui comportait notamment 2xa0reunions presentielles du groupe. Au terme du processus, chaque membre du groupe a cote son degre d’acceptation pour chaque recommandation sur une echelle a 5xa0niveaux (de «xa0pas du tout d’accordxa0» a «xa0completement d’accordxa0»)xa0; une recommandation a ete validee si au moins 80xa0% des participants etaient «xa0d’accordxa0» ou «xa0completement d’accordxa0» avec la formulation proposee. Resultats Quinze questions ayant trait a la terminologie (1xa0item), classification (1xa0item), le diagnostic (6xa0items) et traitement (7xa0items) de l’ACG ont ete retenues et fait l’objet de recommandations validees. Les recommandations formulees concernent le concept de classification de l’ACG, le positionnement de la biopsie d’artere temporale et de l’imagerie medicale dans le diagnostic d’une ACG, les indications et modalites de recherche d’une atteinte de l’aorte et de ses branches, la conduite de la corticotherapie, le traitement des formes d’ACG compliquees, les indications de traitements adjuvants par immunosuppresseurs/-modulateurs ou biotherapies ciblees, les indications de traitements associes de protection vasculaire et la prise en charge des rechutes et recidives. Ces recommandations prennent notamment position sur la place preponderante de la biopsie d’artere temporale pour diagnostiquer une ACG, le principe de traiter habituellement une ACG en 1re intention par une corticotherapie sans traitement adjuvant, et l’interet de depister et surveiller regulierement l’apparition de complications aortiques par tomodensitometrie. Conclusion Les 15xa0questions ayant fait l’objet de recommandations consensuelles permettent de guider et harmoniser les pratiques de prise en charge de l’ACG, notamment sur le plan diagnostique et therapeutique, en France et ailleurs.

Reply: To PMID 24497495.

is identical to the prevalence of PR3-ANCA in authentically inflammatory vasculitis. Bartonellae found in human endocarditis have a specific tropism for vascular endothelial cells and enhance vascular neoproliferation by either induction of endothelial cell proliferation, inhibition of endothelial cell apoptosis, or production of vascular endothelial growth factor by infected macrophages. Bartonella infection releases the chemoattractant interleukin-8, possibly resulting in the recruitment of circulating polymorphonuclear cells (PMNs) and monocyte/macrophages to the site of infection (4,5). Furthermore, B quintana lipopolysaccharide delayed the apoptotic behavior of isolated human neutrophils (5). We can hypothesize that, during delayed PMN apoptosis induced by bartonellae, PR3 remains in contact with the host immune system for a longer period of time, leading to production of anti-PR3 antibodies. Nevertheless, Bartonella-associated IE is completely cured with antibiotics and does not share any clinical or pathologic features with vasculitis, other than vascular skin purpura. In conclusion, in IE due to either gram-positive bacteria or Bartonella, ANCA seems to be more of a marker of chronic vascular inflammation than an effector of the disease.

Prevalence of anti-neutrophil cytoplasmic antibodies in infective endocarditis: An analysis of 109 cases

Introduction.– It has been suggested that ear, nose, and throat (ENT) involvement in ANCA-associated vasculitis (AAV) may carry the advantage of earlier recognition of the systemic vasculitis. Alternatively, differences in histological findings between patients with MPO-ANCA and PR3-ANCA might represent different routes in the pathogenesis of vasculitic disease in these subsets of patients. This study investigates whether ENT involvement in AAV is associated with better renal function and histopathology than AAV without ENT involvement. Methods.– Renal biopsies with 7 glomeruli were available from 152 newly diagnosed AAV patients from four international multicenter trials. Age, ENT involvement, ANCA type (PR3 or MPO), interstitial fibrosis and tubular atrophy (IFTA), tubulitis, interstitial infiltrates and the histopathologic classification of ANCA-associated glomerulonephritis (AAGN) were analyzed as candidate determinants of GFR at diagnosis (GFR0). The relation of GFR0, IFTA and the histopathological classification with ENT involvement was analyzed at the time of diagnosis. Results.– Sixty-four patients had ENT involvement at diagnosis, 88 patients had not. Multivariate analysis revealed that in combination with ENT involvement (r = 0.25, P = 0.000), age (r = 0.34, P = 0.000), IFTA (r = 0.16, P = 0.000), tubulitis (r = 0.16, P = 0.001), interstitial infiltrates (r = 0.20, P = 0.000) and the histopathologic classification of AAGN (r = 0.411, P = 0.000) were associated with GFR at diagnosis. Patients with ENT involvement had a higher GFR0 (60 mL/min versus 44 mL/min, P = 0.000), less IFTA (P = 0.001) and a histopathologic more favourable class (P = 0.000) than patients without ENT involvement. Increasing numbers of active BVAS ENT parameters (range: 0–6) showed a high correlation with increased renal function at time of diagnosis (P = 0.000). Conclusion.– ENT involvement in AAV with renal disease is associated with better renal function and less severe histological renal injury, probably due to diagnosis before the development of irreversible chronic lesions.

Signes inauguraux de la périartérite noueuse et de la polyangéite microscopique : étude rétrospective de 75 patients

Des 21 patients traitEs, 52 % tirent bEnEfice de la cortieothErapie. ,~ lissue du suivie, deux tiers restent sous corficofdes. Dans le groupe favorable, la dur~e moyenne de la corticothErapie est de 2,5 ans contre plus de 5 ans pour les autres, chez lesquels on nexclut pas un effet freinateur sur lEvolution pour la moitiE dentre eux. Quel que soit limmunosuppresseur, en dehors d un cas, ils n ont pas montrE de b~nEfice. Seule la moitiE des interventions chirurgicales effeetuEes reste fonetionnelle apr~s 44 mois de suivi moyen. 1Service de m~decine interne, t~pital ~douard-Herriot, 69347 Lyon cedex 03; eservice de rnddecine interne, h~pital Grenoble, 38700 La Tronche ; Sservice de m6decine interne, h<~pital Lyon sud, 69495 Pierre Bdnite ; 4service de mddecine interne, h~pital Nord, 42055 Seint-~tienne, France