Showing papers in "Revue de Médecine Interne in 2017"

Role of B cells in the pathogenesis of systemic sclerosis.

Abstract: Systemic sclerosis (SSc) is an orphan disease characterized by progressive fibrosis of the skin and internal organs. Aside from vasculopathy and fibrotic processes, its pathogenesis involves an aberrant activation of immune cells, among which B cells seem to play a significant role. Indeed, B cell homeostasis is disturbed during SSc: the memory subset is activated and displays an increased susceptibility to apoptosis, which is responsible for their decreased number. This chronic loss of B cells enhances bone marrow production of the naive subset that accounts for their increased number in peripheral blood. This permanent activation state can be explained mainly by two mechanisms: a dysregulation of B cell receptor (BCR) signaling, and an overproduction of B cell survival signals, B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). These disturbances of B cell homeostasis induce several functional anomalies that participate in the inflammatory and fibrotic events observed during SSc: autoantibody production (some being directly pathogenic); secretion of pro-inflammatory and pro-fibrotic cytokines (interleukin-6); direct cooperation with other SSc-involved cells [fibroblasts, through transforming growth factor-β (TGF-β) signaling, and T cells]. These data justify the evaluation of anti-B cell strategies as therapeutic options for SSc, such as B cell depletion or blockage of B cell survival signaling.

Opportunistic autoimmunity secondary to cancer immunotherapy (OASI): An emerging challenge

Abstract: With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists. Within irAEs, we propose to individualize the induced autoimmunity by the term "Opportunistic Autoimmunity Secondary to Cancer Immunotherapy" (OASI). The aims of this article are (1) to present the different available checkpoint inhibitors and the OASIs reported with these treatments and (2) to propose practical recommendations for diagnosis, pre-therapeutic assessment and management of OASIs. The need for predictive biomarkers of OASIs occurrence will also be discussed.

Sarcoidosis post-anti-PD-1 therapy, mimicking relapse of metastatic melanoma in a patient undergoing complete remission

Abstract: Novel treatments of metastatic melanoma include the usage of checkpoint inhibitors such as anti-cytotoxic-T-lymphocyte-associated antigen (CTLA-4) or anti-programmed death-1 (PD-1) antibodies, which are immunomodulatory antibodies that enhance the immune response against tumors. While they have substantially improved the prognosis for patients, these therapies are associated with a large spectrum of immune-related adverse effects (irAEs). We report a patient developing pulmonary and cutaneous sarcoidosis after pembrolizumab therapy while complete regression of stage IV melanoma was perceived. Coincident development of sarcoidosis and metastatic melanoma as illustrated by this case report poses a diagnostic challenge because, in contrast to other irAEs, both diseases share common features such as pulmonary lesions, hilar adenopathies and skin nodules. Considering sarcoidosis as a potential side-effect of pembrolizumab treatment is crucial to avoid misdiagnosis with malignant lesions, hence careful description and reporting of such cases is primordial for patient care and may also provide us with insightful knowledge on the pathogenesis of immune-related diseases.

High oxygen affinity hemoglobins

Abstract: High oxygen affinity hemoglobins are responsible for rare and heterogeneous autosomic dominant genetic diseases. They cause pure erythrocytosis, sometimes accountable for hyperviscosity and thrombosis, or hemolysis. Differential diagnoses must be first ruled out. The diagnosis is based on the identification of a decreased P50, and their possible characterization by cation exchange-high performance liquid chromatography and capillary electrophoresis. Finally, genetic studies of the responsible globin chain gene will confirm the mutation. The prognosis mainly relies on the P50 decrease rate and on the hemoglobin cooperativity impairment. Disease management should be personalized, and it should primarily depend on smoking cessation and physical activity. Phlebotomy and platelet aggregation inhibitors' prescriptions can be discussed. There is no contraindication to flights, high-altitude conditions, or pregnancy. Nevertheless, blood donation must be prohibited.

Les lymphœdèmes : du diagnostic au traitement

Abstract: Lymphedema results from impaired lymphatic transport with increased limb volume. Lymphedema are divided in primary and secondary forms. Upper-limb lymphedema secondary to breast cancer treatment is the most frequent in France. Primary lymphedema is sporadic, rarely familial or associated with complex malformative or genetic disorders. Diagnosis of lymphedema is mainly clinical and lymphoscintigraphy is useful in primary form to assess precisely the lymphatic function of the two limbs. Erysipelas (cellulitis) is the main complication, but psychological or functional discomfort may occur throughout the course of lymphedema. Lipedema is the main differential diagnosis, defined as an abnormal accumulation of fat from hip to ankle. Lymphedema management is based on complete decongestive physiotherapy (multilayer low-stretch bandage, manual lymph drainage, skin care, exercises). The first phase of treatment leads to a reduction of lymphedema volume and the second phase stabilizes the volume. Multilayer low-stretch bandage and elastic compression is the cornerstone of the complete decongestive physiotherapy. Patient-education programs, including self-management, aim to improve patient autonomy.

Lupus érythémateux systémique et lymphopénie : aspects cliniques et physiopathologiques

Abstract: Resume La lymphopenie est tres frequente au cours du lupus erythemateux systemique (LES), et profonde ( 3 ) dans 10 % des cas. Elle touche principalement les lymphocytes T, notamment CD4 + . Les mecanismes physiopathologiques sont complexes, faisant intervenir des anticorps lymphocytotoxiques, un exces d’apoptose, une sensibilite accrue a la lyse par le complement, de meme qu’une repression de la lymphopoiese et des phenomenes de sequestration lymphocytaire. La lymphopenie dans le LES est independante des autres cytopenies et des immunosuppresseurs recus. Elle est associee a l’activite de la maladie, au risque de poussee lupique et aux sequelles viscerales. Le risque infectieux est principalement bacterien, et une lymphopenie 3 ), qui constituent tres probablement un sous-groupe de LES avec deficit immunitaire primitif associe et necessitant une prise en charge specifique.

[Multiple facets of ADA2 deficiency: Vasculitis, auto-inflammatory disease and immunodeficiency: A literature review of 135 cases from literature].

Abstract: Deficiency of adenosine deaminase 2 (DADA2) is a recently described auto-inflammatory disorder. It is an autosomal recessive inherited disease, caused by mutations in the ADA2 gene (formerly known as CECR1) encoding ADA2 enzyme. Besides its role in the purine metabolism, it has been postulated that ADA2 may act as a growth factor for endothelial cells and in the differenciation of monocytes. Thus, deficiency of ADA2 would lead to endothelial damage and a skewing of monocytes into M1 pro-inflammatory macrophage, causing DADA2 manifestations. Three core clinical features have been described: inflammatory-vascular signs, hematologic abnormalities and immunodeficiency. Clinically, patients display intermittent fever, cutaneous vascular manifestations, such as livedo, ischemic strokes, arthralgia and abdominal pain crisis. Corticosteroids and immunosuppressive agents (i.e. cyclophosphamide, azathioprine, ciclosporin, methotrexate) appear to be poorly effective. Although the mechanism has not been elucidated, anti-TNF agents have been proven efficient in DADA2 and should therefore be used as first line therapy for vasculitis. Role of anti-platelet and anticoagulant therapies in stroke-prophylaxis remains to be discussed, as those patients display a high risk of intracranial bleeding.

Mésusage et dépendance aux opioïdes de prescription : prévention, repérage et prise en charge

Abstract: Since the 1990s, the use of prescription opioids has largely spread, which has brought a real progress in the treatment of pain. The long-term use of prescription opioid is sometimes required, and may lead to pharmacological tolerance and withdrawal symptoms, i.e. pharmacological dependence on prescription opioids. Occasionally, this may also lead to misuse of prescription opioids (MPO). MPO preferentially occurs in vulnerable individuals, i.e., those with a young age, history of other addictive or psychiatric disorders, especially anxious and depressive disorders. MPO is associated with numerous complications, including an increased risk of fatal overdose. Prevention of MPO begins before the opioid prescription, with the identification of potential vulnerability factors. A planned and personalized monitoring should be systematically implemented. In vulnerable patients, contractualizing the prescription is warranted. During follow-up, the relevance of the prescription should be regularly reconsidered, according to the benefit observed on pain and the potential underlying signs of MPO. Patients with suspected MPO should be referred early to pain or addiction centers. The treatment of MPO should be based on multidisciplinary strategies, involving both the addiction and pain aspects: progressive opioid withdrawal, non-pharmacological measures against pain, or switching to medication-assisted treatment of addiction (i.e., buprenorphine or methadone).

L’ischémie mésentérique à l’ère des structures d’urgences vasculaires intestinales

Abstract: Mesenteric ischemia is a gut and life-threatening, medical and surgical, digestive and vascular emergency. Mesenteric ischemia is the result of an arterial or venous occlusion, a vasospasm secondary to low-flow states in intensive care patients, aortic clamping during vascular surgery or intestinal transplantation. Progression towards mesenteric infarction and its complications is unpredictable and correlates with high rates of mortality or a high risk of short bowel syndrome in case of survival. Thus, mesenteric ischemia should be diagnosed and treated at an early stage, when gut injury is still reversible. Diagnostic workup lacks sensitive and specific clinical and biological marker. Consequently, diagnosis and effective therapy can be achieved by a high clinical suspicion and a specific multimodal management: the gut and lifesaving strategy. Based on the model of ischemic stroke centers, the need for a multidisciplinary and expert 24/24 emergency care has led, in 2016, to the inauguration of the first Intestinal Stroke Center (Structure d'urgences vasculaires intestinales [SURVI]) in France. This review highlights the pathophysiological features of chronic and acute mesenteric ischemia, as well as the diagnosis workup and the therapeutic management developed in this Intestinal Stroke Center.

Les atteintes neurologiques au cours de la sarcoïdose : diagnostic et traitement

Abstract: Neurological localizations of sarcoidosis are heterogeneous and may affect virtually every part of the central or peripheral nervous system. They are often the inaugural manifestation of sarcoidosis. The diagnosis may be difficult due to the lack of extra-neurological localization. Diagnosis may be discussed in the presence of an inflammatory neurological disease, in particular in case of suggestive radiological or biological pattern. Cerebrospinal fluid analysis shows lymphocytic pleiocytosis, often with low glucose level. The diagnosis relies on a clinical, biological and radiological presentation consistent with neurosarcoidosis, the presence of non-caseating granuloma and exclusion of differential diagnoses. Screening for other localizations of sarcoidosis, in particular cardiac disease may be obtained during neurosarcoidosis. The treatment of neurosarcoidosis relies on corticosteroids although immunosuppressive drugs are usually added because of the chronic course of this condition and to limit the side effects of steroids. Treatments and follow-up may be prolonged because of the high rate of relapses.

Déficit en sphingomyélinase acide (maladie de Niemann-Pick B) : une étude rétrospective multicentrique de 28 patients adultes

Abstract: Resume Introduction Le deficit en sphingomyelinase acide est une maladie de surcharge lysosomale autosomique recessive allant d’une forme neuro-viscerale severe de l’enfant, la maladie de Niemann-Pick A, a une forme chronique viscerale evoluant jusqu’a l’âge adulte, la maladie de Niemann-Pick B (NP-B). Methodes Etude retrospective multicentrique francaise de patients adultes suivis entre 1985 et mars 2015 pour une maladie de NP-B. Recueil des donnees cliniques et paracliniques a partir des dossiers medicaux. Resultats Vingt-huit patients (19 hommes, 9 femmes) ont ete analyses. Seize patients ont ete diagnostiques avant l’âge de 10 ans. Les principaux symptomes au diagnostic etaient l’hepatosplenomegalie et l’atteinte pulmonaire interstitielle. Une thrombopenie etait notee dans 24 des 28 cas (plaquettes Conclusion La maladie de NP-B associe une hepatosplenomegalie et une atteinte pulmonaire interstitielle. Un diagnostic precoce permet de reduire les complications et d’eviter les procedures inappropriees (par exemple splenectomie). A l’heure actuelle, la prise en charge repose principalement sur un traitement symptomatique, mais un essai de phase 2/3 de traitement enzymatique substitutif est en cours.

Lithiase rénale de l’adulte : des mécanismes au traitement médical préventif

Abstract: Nephrolithiasis is a very common (prevalence around 10 to 12% in France) and recurrent disorder. Nephrolithiasis is associated to chronic kidney disease and is responsible for 2 to 3% of cases of end-stage renal disease, mainly if it is associated to nephrocalcinosis or to a monogenic disorder (1.6% of nephrolithiasis in adults, among them 1% of cystinuria). To understand the underlying pathophysiological processes, stone analysis (morphology and using infrared spectrophotometry) as well as minimal biological assessment including urine crystal research are required. The calcic nephrolithiasis is the more frequent subtype (>80%). Its medical treatment relies on simple dietary rules: non-alkaline hyperdiuresis>2 liters/day, calcium intake normalization (1 gram per day divided between the three principal meals), normalization of sodium (6 to 7 grams per day) and protein intake (1g/kg of theoretical body weight/day), and eviction of foods rich in oxalate. In case of persistent hypercalciuria (>0.1mmol/kg of theoretical body weight/day on free diet), a thiazide diuretic can be started while being aware to correct iatrogenic decrease in plasma potassium and urine citrate excretion. Measurement of bone mineral density must systematically be performed in patients with high 24 h-urinary calcium excretion. The medical treatment of uric acid nephrolithiasis relies on alkaline hyperdiuresis (goal of urine pH: 6.2 to 6.8). The use of allopurinol is justified only if urine uric acid is over 4mmol/day. Thanks to a well-managed preventive medical treatment, one can expect to stop the activity of nephrolithiasis in more than 80% of cases, making it one of the most accessible renal pathologies to preventive medical treatment.

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

Abstract: 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.

Thromboses sous agonistes du récepteur de la thrombopoïétine au cours du purpura thrombopénique immunologique. Étude rétrospective multicentrique en France

Abstract: Resume Introduction Le risque de thrombose sous agonistes du recepteur de la thrombopoietine (romiplostim, eltrombopag) chez des patients traites pour un purpura thrombopenique immunologique est mal apprecie en vie reelle de meme que les circonstances de survenue d’un evenement thrombotique et sa prise en charge. Les objectifs de cette etude etaient de preciser les facteurs de risque, les circonstances de survenue et la prise en charge des thromboses survenant sous agonistes au cours du purpura thrombopenique immunologique. Methode Etude multicentrique retrospective nationale francaise, incluant les cas signales aux centres regionaux de pharmacovigilance. Resultats Quarante et un cas de thromboses (13 arterielles) chez 36 patients (14 hommes et 22 femmes, âge median : 59 ans) ont ete inclus sur une periode de janvier 2009 a octobre 2015. Vingt patients etaient traites par romiplostim, 15 par eltrombopag et 1 patient recevait les deux medicaments. Trente-trois patients (92 %) avaient un autre facteur de risque de thrombose. Dix (28 %) avaient un antecedent de thrombose et 13 (36 %) avaient recu une perfusion d’immunoglobulines dans le mois precedent l’evenement thrombotique. Le taux plaquettaire median etait de 172 G/L (1 a 1049 G/l) ; 3 patients avaient des anticorps anti-phospholipides et 4 thrombophilies constitutionnelles de faible impact (mutation heterozygote du facteur V Leiden, elevation du facteur VIII, mutation heterozygote du gene MTHFR ) etaient notees ; 18 patients (50 %) etaient splenectomises. L’evolution de la thrombose etait favorable dans 22 cas (56 %) apres traitement par anticoagulants ou antiagregants avec un suivi moyen de 13 mois. Des manifestations hemorragiques sous traitement antiagregant ou anticoagulant ont ete observees chez 14 % des patients, dont 5 % etaient severes (1 deces d’hemorragie intracrânienne, 1 deces de choc hemorragique). Conclusion Une evaluation rigoureuse du risque thrombotique doit preceder l’instauration d’un traitement par agoniste du recepteur de la thrombopoietine. Le role des anticorps antiphospholipides ou d’une thrombophilie constitutionnelle reste a definir. Cette prescription doit etre evitee en cas d’antecedent thrombotique. L’evolution defavorable etait principalement secondaire a des sequelles ischemiques.

Prise en charge des symptômes médicalement inexpliqués en médecine interne : un paradigme de la relation médecin-malade en situation d’incertitude

Abstract: Medically unexplained symptoms (MUS) are extremely common in general practice as in all medical specialties, but their designation is not unambiguous and the approaches to take care of the patients differ from conventional therapeutic approaches. The difficulty is not to confirm the diagnosis, which is rapidly obvious with some experience, but to establish a genuinely human therapeutic relationship, without any technical help, which pushes the doctor to the edge of his empathy and communication skills. The discomfort or even distress regularly encountered by physicians in front of a patient with MUS shows that the foundations of the doctor-patient relationship under uncertainty are poorly mastered. Patients with MUS are regularly abused by the doctors, who unwittingly participate in the maintenance of their symptoms and even freeze them, leading to disastrous psychosocial and economic consequences. Yet the doctor-patient relationship is the key to their recovery or, at least, their improvement. The means of a successful patient-centered relationship are not always intuitive but can be learned. It is therefore essential to include SMI in medical school curricula and post-graduate medical education. Finally, if the management of early MUS mainly concerns the family medicine, that of severe MUS, including some fibromyalgia and chronic fatigue syndromes, falls within the scope of the internist doctor, who should be able to deliver a comprehensive care in partnership with the general practitioner and possibly a psychiatrist.

Épidémiologie et pharmacoépidémiologie du purpura thrombopénique immunologique

Abstract: During the last decade, the development of large clinical and population-based cohorts led to new findings in the epidemiology and the pharmacoepidemiology of immune thrombocytopenia (ITP). The incidence is estimated to 3-4 for 105 inhabitants/year, with a slight female predominance and peaks in children and patients after 60 years. The incidence rate is 9 for 105 inhabitants/year in males after 75 years. Variations across ethnic groups are discussed. In France, there is a North-South gradient and a peak of incidence during winter suggesting the role of viruses in ITP pathophysiology. Myelodysplastic syndromes are an emergent cause of secondary ITP. The incidence of intracranial bleeding is about 1% by year and the risk increases with aging. Exposure to splenectomy decreases while rituximab and thrombopoietin receptor agonists (TPO-RA) are the most used second-line drugs for persistent ITP. Mortality is slightly increased in primary ITP as compared with the general population. ITP patients have an increased risk of infection, thrombosis and hemorrhage. Aging, lung diseases, splenectomy, corticosteroids and rituximab are risk factors for infection while influenza and pneumococcal vaccines are associated with a 50% decrease of infection risk. Aging, cardiovascular risk factors, lupus anticoagulant and splenectomy are risk factors for thrombosis. The risk of thrombosis associated with corticosteroids and TPO-RAs must be further investigated.

Prise en charge diagnostique des uvéites : recommandations d’un groupe d’experts

Abstract: Introduction. – La demarche diagnostique au cours des uveites n’est pas standardisee. Elle doit prendre en compte l’epidemiologie des uveites, cibler les affections les plus severes et/ou les plus frequentes, et/ou susceptibles de beneficier d’un traitement specifique. Ce travail a ete realise afin de proposer des recommandations pour le diagnostic des uveites. Methodes. – Les recommandations ont ete etablies par un groupe de 15 experts, internistes, ophtalmo- logistes et rhumatologues, a partir d’une revue de la litterature et de l’etude ULISSE qui est la premiere etude prospective a avoir evalue une strategie diagnostique pour les uveites. Sont exclues de ces recom- mandations les uveites de l’enfant, de l’immunodeprime, les vascularites retiniennes severes et les entites purement ophtalmologiques. Resultats. – Le bilan paraclinique doit en premier lieu etre oriente par les elements de l’interrogatoire et les signes cliniques. La serologie syphilitique est la seule serologie systematique. Les serologies toxoplasmose et herpes virus seront realisees en cas de suspicion diagnostique et avant tout prelevement oculaire. En l’absence de cause identifiee, nous proposons un bilan paraclinique oriente par les caracteristiques de l’uveite. Il comporte un typage HLA B27 (uveite anterieure aigue unilaterale non granulomateuse), un dosage de l’enzyme de conversion de l’angiotensine, un test IFN-μ release assay (IGRA) et un scanner thoracique (uveite chronique), une IRM cerebrale associee a une ponction de chambre anterieure avec dosage de l’interleukine 10 (uveite intermediaire ou posterieure apres 40 ans). La rentabilite d’examens complementaires non orientes est tres faible.

Nocardiose : analyse rétrospective d’une série de 19 cas

Abstract: Resume Introduction Les nocardioses sont rares, de diagnostic clinique et microbiologique difficile, avec une morbi-mortalite importante, et surviennent souvent sur terrain debilite. Peu de donnees existent en France. Methodes Etude retrospective monocentrique de 2002 a 2014 incluant tous les patients avec au moins un prelevement microbiologique positif a Nocardia. Resultats Dix-neuf patients, dont 15 hommes, ont ete inclus, d’âge moyen 58 ans (25–85). Dix-sept presentaient un terrain a risque (pathologies pulmonaires 13, corticotherapie 12, tumeurs 2, infection par le VIH 2, diabete 3, greffe renale 2, lymphopenie 1). On denombre 12 infections pulmonaires, 3 infections cerebrales, 2 infections cutanees, 1 infection ganglionnaire, et 1 infection corneenne. La croissance souvent lente du germe conduit a un delai median de resultat de 35 jours (3–95). Neuf especes ont ete retrouvees. Quinze patients (79 %) ont recu une ou plusieurs lignes antibiotiques comprenant entre autres : cotrimoxazole (n = 9), amoxicilline (n = 7) cefotaxime/ceftriaxone (n = 7), imipeneme (n = 3) ou amikacine (n = 3). La duree moyenne de l’antibiotherapie etait de 207 jours. Quatre patients n’ont pas recu d’antibiotiques a cause d’un resultat tardif ou d’une co-infection bacterienne masquant la nocardiose. On deplore 5 deces (26 %) dont 2 imputables a une atteinte cerebrale. Six patients ont gueri, 4 ont rechute, l’evolution est inconnue pour 4, et 1 est encore en cours de traitement. Conclusion La prise en charge des nocardioses est compliquee. Une meilleure connaissance de celles-ci par une etude clinico-microbiologique nationale semble necessaire.

Manifestations ophtalmologiques de la sarcoïdose : que doit savoir l’interniste ?

Abstract: Sarcoidosis is one of the leading causes of inflammatory eye disease. Any part of the eye and its adnexal tissues can be involved. Uveitis and optic neuropathy are the main manifestations, which the internists face. This review reports the state of knowledge for these two ocular involvements and proposes an assessment-algorithm for sarcoidosis in patients with suspected sarcoid uveitis. Two groups of patients with sarcoid uveitis can be distinguished: one young and multiethnic group in which ophthalmological findings are various and another group of elderly Caucasian women with mostly chronic posterior uveitis. Clinically isolated uveitis revealing sarcoidosis remains a strictly ocular condition in a large majority of cases. Although it could be a serious condition involving functional prognosis, an early recognition in addition to a growing therapeutic arsenal including intravitreal implant seems to have improved visual prognosis of the disease in the last years. Systemic corticosteroids are indicated when uveitis does not respond to topical corticosteroids or when there is bilateral posterior involvement, especially macular edema and occlusive vasculitis. In up to 25% of cases that require an unacceptable dosage of corticosteroids to maintain remission, additional immunosuppression is used, including methotrexate, azathioprine, and mycophenolate mofetil. Regarding systemic sarcoidosis, infliximab and adalimumab have been successfully used for the treatment of refractory or sight-threatening disease. Optic neuropathy often affects women of African and Caribbean origin. Some authors recommend that patients be treated with high-dose corticosteroids and concurrent immunosuppression from the onset for this manifestation, which may be associated with a poorer outcome.

Les vascularites urticariennes hypocomplémentémiques

Abstract: Hypocomplementemic urticarial vasculitis (HUV), called anti-C1q vasculitis in the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides, is a rare systemic vasculitis of unknown etiology, affecting small vessels. HUV is characterized by urticarial lesions, hypocomplementemia and systemic manifestations, mostly musculoskeletal and ocular, but also gastrointestinal, pulmonary and kidney involvement. Anti-C1q antibodies are detected in only half of the patients, and low C1q seems to represent a more sensitive marker. Published data on the therapeutic management are scarce in the literature. Hydroxychloroquine and colchicine seem to represent effective first-line therapies. In patient with relapsing or refractory disease, response rates appeared slightly higher for corticosteroids together with conventional immunosuppressive agents, in particular azathioprine, mycophenolate mofetil, or cyclophosphamide, while a rituximab-based regimen tended to have higher efficacy. The best strategy for treating HUV has yet to be defined.

Dépistage de l’hypertension artérielle pulmonaire au cours de la sclérodermie systémique : comparaison de l’algorithme DETECT à une discussion pluridisciplinaire en centre de compétence

Abstract: Resume Introduction L’hypertension arterielle pulmonaire (HTAP) est une complication grave de la sclerodermie systemique (SSc), importante a depister L’etude DETECT a propose en 2013 un algorithme de depistage Nous avons compare les indications au catheterisme cardiaque droit posees par cet algorithme, a celles retenues par une reunion de concertation pluridisciplinaire en centre de competences Patients et methodes Etude prospective monocentrique non interventionnelle ayant inclus les patients suivis pour SSc, pour qui les donnees etaient suffisantes pour appliquer l’algorithme DETECT Nous avons calcule l’algorithme et compare ses indications a la realisation d’un catheterisme cardiaque droit avec celles retenues dans notre centre suite a une reunion de concertation pluridisciplinaire Resultats Au total, 117 patients ont ete inclus En appliquant l’algorithme a l’ensemble de la population, l’indication du catheterisme etait retenue pour 70 d’entre eux ; la reunion de concertation pluridisciplinaire avait egalement retenu cette indication pour 15 d’entre eux dont 7 avaient finalement une HTAP En appliquant l’algorithme aux patients ayant une DLCO Conclusion L’application de l’algorithme DETECT a permis de depister toutes les HTAP diagnostiquees suite a la reunion de concertation pluridisciplinaire Cependant, il multiplie par trois le nombre de catheterisme cardiaque droit a realiser

[Prevalence and risk factors of vitamin D deficiency in healthy adults aged 18-65 years in northern France].

Abstract: Resume Introduction Le depistage et le traitement de l’insuffisance en vitamine D sont l’objet de nombreux travaux. Beaucoup de facteurs de risque ont ete mis en evidence et des populations a risque ont ete identifiees. La population des adultes sains, exposee aux memes facteurs de risque, n’a ete que rarement etudiee. L’objectif principal etait d’evaluer la prevalence de l’insuffisance en vitamine D aux seuils de 30, 20 et 10 ng/mL. L’objectif secondaire etait d’identifier des facteurs de risque d’insuffisance en vitamine D au seuil de 20 ng/mL. Methodes Il s’agit d’une etude epidemiologique descriptive, prospective et monocentrique. Deux cent quatre-vingt-dix-sept sujets ont ete inclus et etudies entre janvier et fevrier 2015. La prevalence de l’insuffisance en vitamine D a ete evaluee aux seuils de 10, 20 et 30 ng/mL ainsi que les facteurs de risque associes au seuil de 20 ng/mL a partir d’un questionnaire. Resultats Au total, 92,3 % des sujets presentaient un taux de 25(OH) vitamine D strictement inferieur a 30 ng/mL, 75,1 % strictement inferieur a 20 ng/mL et 27,9 % strictement inferieur a 10 ng/mL. Le sexe masculin (p = 0,0001), l’âge (p = 0,012), l’absence de vacances en region ensoleillee (p = 0,03) et l’absence de prise de complements vitaminiques sur ordonnance (p = 0,002) ressortent comme des facteurs de risques independants au seuil de 20 ng/mL. Conclusion Dans notre population, l’insuffisance en vitamine D chez l’adulte sain est frequente et tres souvent severe. Une strategie de depistage et de supplementation systematique permettrait de limiter la survenue et les complications de nombreuses pathologies tout en assurant un equilibre nutritionnel.

Prévalence et facteurs de risque de la rétinopathie drépanocytaire dans un centre de suivi drépanocytaire d’Afrique subsaharienne

Abstract: Resume Introduction La retinopathie est une complication chronique a risque fonctionnel important chez le drepanocytaire, dont l’incidence est mal connue en Afrique subsaharienne, faute de depistage. Ce travail decrit les resultats d’un depistage systematique de la retinopathie drepanocytaire dans un centre de suivi des drepanocytaires au Mali. Methodes Tous les drepanocytaires âges de 10 ans et plus, suivis au centre, ont ete depistes entre 2010 et 2012 par un examen du fond d’œil complete si besoin par une angiographie. Les caracteristiques des patients porteurs d’une retinopathie ont ete comparees a celles de drepanocytaires sans retinopathie recrutes durant la meme periode et selectionnes au hasard. Resultats La retinopathie avait une prevalence globale de 8,8 % chez les 1604 drepanocytaires âges de 10 ans et plus et concernait 91/731 (12,4 %) drepanocytaires SC, 38/734 (5,2 %) SS, 5/53 (9,4 %) Sβ 0 thalassemiques et 8/86 (9,3 %) Sβ + thalassemiques. La forme proliferante de la retinopathie etait plus frequente chez les SC ( p 0 thalassemiques. Conclusion La retinopathie touche pres d’un patient drepanocytaire sur dix et sa prevalence est negativement associee au taux d’hemoglobine fœtale. L’efficience d’un depistage systematique de la retinopathie drepanocytaire doit etre etudiee en Afrique, ainsi que l’interet de la phlebotomie et de l’hydroxycarbamide en traitement preventif.

L’observance dans la maladie de Wilson : intérêt d’un suivi rapproché au long cours

Abstract: Resume Introduction L’observance dans la maladie de Wilson, pathologie genetique rare, est cruciale. Il existe des traitements efficaces si prescrits precocement et pris a vie. Sinon, les consequences sont gravissimes : handicap ou deces. Ce travail vise a determiner le taux et les facteurs de non-observance. Methodes Etude prospective au Centre national de reference de la maladie de Wilson (Paris et Lyon) sur 8 mois. L’observance a ete evaluee a l’inclusion et au 8e mois par un questionnaire quantifiant le nombre de prises manquees, un autoquestionnaire precisant les causes de non-observance et des echelles analogiques evaluant la relation medecin–malade et le rapport au traitement. Au meme moment, un entretien avec la psychologue etait realise et la gravite des symptomes depressifs evaluee par l’inventaire de depression de Beck. Tous les deux mois, une psychologue realisait un entretien telephonique evaluant l’observance et le ressenti des patients. Resultats Trente-neuf patients ont ete inclus, d’un âge moyen de 34 ans (± 9,9). A M0, 84,6 % etaient mal-observants. Ils ne differaient pas pour ce qui est de l’âge, du type de traitement ou de la qualite de la relation au medecin, mais avaient ete diagnostiques plus recemment (p = 0,049) et presentaient plus frequemment des signes neurologiques (p = 0,007). Des symptomes depressifs etaient presents chez 38,5 % d’entre-eux. A M8, la proportion de patients mal-observants etait egale a 56,8 % et 21,6 % presentaient des symptomes de depression. Conclusion Les patients atteints de maladie de Wilson ont des difficultes d’observance, sans etre forcement depressifs. Un suivi multidisciplinaire rapproche semble pouvoir ameliorer l’observance, en particulier pour les patients atteints de troubles neurologiques.

[Aspirin: Indications and use during pregnancy].

Abstract: Aspirin (acetylsalicylic acid) has been used ever since the Antiquity for its painkilling and anti-inflammatory effects. Its antiplatelet properties have then extended its indications to the field of coronaropathy and vascular cerebral disease, and finally to vascular placental disease. Aspirin has been widely prescribed since the 1980's to prevent pre-eclampsia, intra-uterine growth retardation and fetal death of vascular origin. It has also been proposed to prevent unexplained recurrent miscarriages. Its use during pregnancy is considered as safe, provided the daily doses do not exceed 100mg. Aspirin has been proven efficient to prevent pre-eclampsia and fetal growth restriction in high-risk patients. The benefits of prescribing aspirin have been demonstrated neither for vascular placental disease prevention in low risk patients, nor in cases of unexplained recurrent miscarriages.

Sarcoïdose cardiaque : avancées diagnostiques et thérapeutiques

Abstract: Sarcoidosis is a granulomatous disorder of unknown cause characterized by non-caseating granuloma in young adults. Cardiac involvement is rare and range from 2 to 75% depending on diagnostic criteria. Cardiac involvement in sarcoidosis may be asymptomatic or may manifest as rhythm/conduction troubles or congestive heart failure. The diagnosis and treatment of cardiac sarcoidosis may be challenging. However, advances have come in recent years from the use of cardiac MRI and 18FDG-TEP scanner, as well as from the stratification of the risk of ventricular tachycardia/fibrillation. Due to the rarity of the disease, there is no reliable prospective large study to guide therapeutic strategy for cardiac sarcoidosis. Corticosteroids are probably efficacious, in particular in case of atrio-ventricular block or moderate heart failure. Immunosuppressive drugs have not been largely studied but methotrexate could be helpful. In refractory forms, TNF-α antagonists have been used with success.

Abcès de la rate : du diagnostic au traitement

Abstract: Splenic abscess is septic collection which occurs after haematogenous spread or local dissemination. Splenic abscess is an uncommon and rare condition, more frequently affecting male and immunocompromised patients. There are no guidelines regarding its diagnosis and management. Computed tomography (CT) scan is highly sensitive and specific (95% and 92%, respectively) in the diagnosis of splenic abscess. Diagnosis is based on blood cultures which are positive in 24 to 80% of cases. Bacterial growth culture of abscess after drainage is more efficient (50-80%) and can be performed after surgery or percutaneous drainage under imaging, including CT scan. Microorganisms involved are frequently enterobacteriaceae, gram-positive cocci and anaerobes. This particular ecology leads to an empiric broad-spectrum antibiotic therapy, with a variable duration, from 10days to more than one month. Management remains very close to the one applied in case of liver abscesses. The role of splenectomy in the prevention of recurrence remains controversial. We reviewed the literature regarding splenic abscesses, from diagnosis to therapy.

Principales parasitoses cutanées : mise au point

Abstract: Resume Les parasitoses cutanees sont frequentes en pathologie humaine. Elles sont cosmopolites mais leur distribution mondiale est irreguliere. Les donnees epidemiologiques fiables sur la prevalence et/ou l’incidence de ces parasitoses sont rares mais la prevalence est surtout elevee dans les pays subtropicaux et tropicaux. Les parasitoses cutanees sont principalement dues aux arthropodes (acariens et insectes) qui parasitent le tegument ou les phaneres. De nombreuses especes de parasites sont en cause, expliquant la grande diversite de leurs manifestations cutanees. Les plus frequentes sont dues aux ectoparasites comme la gale ou les pediculoses (du cuir chevelu, corporelle ou pubienne). Les signes cliniques peuvent etre lies a la penetration du parasite sous la peau, a son developpement, aux venins inocules ou aux manifestations allergiques qu’il entraine. Le diagnostic peut etre aise en cas de signes cliniques pathognomoniques (i.e. sillons des espaces interdigitaux pour la gale) ou parfois plus difficile. Certaines caracteristiques epidemiologiques (piqure diurne ou nocturne, saisonnalite) ou semiologiques (piqures uniques ou multiples, lineaires ou en bouquet) peuvent etre d’une aide precieuse. La place des outils d’imagerie non invasive moderne (dermoscopie ou microscopie confocale in vivo) sera a determiner a l’avenir mais l’œil et l’experience du specialiste (dermatologue, infectiologue, parasitologue, entomologiste) reste pour l’instant indispensable pour orienter ou etablir un diagnostic de certitude. Pour la plupart des parasitoses cutanees, les propositions therapeutiques reposent rarement sur des etudes de fort niveau de preuve ou d’essais randomises mais plutot sur des recommandations d’expert ou sur l’experience personnelle.

Les uvéites au cours de la maladie de Behçet

Abstract: Introduction L’uveite est l’atteinte oculaire la plus frequente au cours de la maladie de Behcet (MB). Elle peut etre severe et met en jeu le pronostic visuel. Patients et methodes Nous avons etudie retrospectivement les dossiers de 403 patients atteints d’une MB (criteres du groupe international d’etude de la MB), suivis entre 2000 a 2012. Nous avons inclus 153 patients presentant une uveite. Ils ont ete exclus de l’analyse les dossiers des patients dont nous ne disposons pas des details de l’atteinte oculaire. Resultats Cent-trente-huit patients etaient etudies ; 101 hommes et 37 femmes. L’âge moyen au debut de la maladie etait de 27 ± 9,4 ans et l’âge moyen au moment du diagnostic 31,88 ± 9,5 ans. Le delai moyen entre le premier signe de la maladie et le diagnostic de l’uveite etait de 3,37 ± 3 ans. L’uveite etait revelatrice de la MB dans 96 cas (23,8 % de tous les patients). Quatre patients etaient asymptomatiques. Une baisse de l’acuite visuelle etait notee chez 55 patients avec une cecite chez huit. Un flou visuel etait signale par 63 patients et une rougeur oculaire etait decrite chez 74 patients. Le type d’uveite le plus frequent etait une panuviete (n = 55). Une uveite posterieure etait notee chez 25 patients. Une uveite intermediaire ou anterieure etait retrouvee a l’examen initial chez respectivement 42 et 16 patients. L’uveite etait bilaterale dans 88 des cas. Elle etait associee a une vascularite retinienne dans 83 cas. Une corticotherapie etait prescrite chez 128 patients (0,5 mg/kg/j dans 50 % cas sinon 1 mg/kg/jour). Les immunosuppresseurs etaient indiques chez 118 patients. En traitement d’attaque : cyclophosphamide IV (n = 77) ou azathioprine (n = 40) ou methotrexate (n = 1) et en entretien : azathioprine (n = 89) et methotrexate (n = 5). Les uveites anterieures isolees ont ete traitees par collyre. Apres traitement, 48 patients n’ont fait aucune nouvelle poussee, 48 autres ont eu une ou deux poussees et 23 patients ont presente plus que deux poussees d’uveite. L’evolution finale etait a type de remission sans sequelle (n = 45), remission avec sequelle (n = 68), amelioration (n = 4) et aggravation (n = 5). Une cecite definitive etait notee chez 25 patients. Une cataracte etait objectivee chez 40 patients. Le suivi moyen etait de 66 ± 48,8 mois. Conclusion La MB est une cause frequente de cecite chez les sujets jeunes. Un diagnostic precoce et un traitement adequat permet de prevenir les sequelles oculaires et la cecite.

Syndrome de Lemierre : diagnostic, exploration, traitement

Abstract: Lemierre's syndrome is a rare and severe sepsis that can rapidly lead to a life-threatening condition in the absence of early management. This syndrome described at the beginning of the 20th century combines oropharyngeal infection complicated with septic thrombosis of the internal jugular vein and septic emboli predominantly pulmonary. Fusobacterium necrophorum, anaerobic germ, Gram negative bacillus is the main germ in this "necrobacillosis". The diagnosis is should be confirmed precociously with cervicothoracic CT-scan, reference exam, and bacteriological examinations (especially in atypical forms). Its management consists of an emergency antibiotic treatment, combining a third-generation cephalosporin or a betalactam with metronidazole, anticoagulant therapy to be reserved for high-risk situations related to thrombosis. Surgical treatment may be required.