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Background To estimate patient acceptable symptom state (PASS) and minimal clinically important difference (MCID) for patient-reported outcomes in systemic sclerosis (SSc). Methods We conducted a secondary analysis of the SCLEREDUC trial, a 12-month randomized controlled trial comparing the efficacy of physical therapy to usual care in 220 SSc patients followed-up from September 2005 to October 2010. Self-rated state and change in patient health at 12 months were assessed by using 2 external anchors extracted from the Medical Outcomes Study 36-Item Short-Form. Patients who self-rated their health as “excellent”, “very good” or “good” were the PASS group and those who self-rated their health change as “somewhat better” were the MCID group. Main outcomes were the estimates of PASS by using the 75th percentile method and of MCID by using the mean change in scores method for pain and activity limitation. Results PASS (95% confidence interval) and mean (SD) MCID estimates at 12 months were 53.75 (34.00 to 68.00) and −6.74 (32.02) for the joint-pain visual analog scale (range 0–100), 1.41 (1.13 to 1.63) and −0.21 (0.48) for the Health Assessment Questionnaire (HAQ, range 0–3), 1.27 (1.07 to 1.62) and −0.13 (0.45) for the scleroderma HAQ (range 0–3), 26.00 (17.00 to 37.00) and -3.38 (9.87) for the Cochin Hand Function Scale (range 0–90), and 19.40 (17.20 to 21.90) and −5.69 (6.79) for the McMaster-Toronto Arthritis Patient Preference Disability Questionnaire (range 0–30), respectively. Conclusions We provide, for the first time, the PASS and MCID estimates for pain and activity limitation in SSc. Trial registration ClinicalTrials.gov Identifier: NCT00318188. First Posted: April 26, 2006.

Resume Introduction La maladie de Gaucher (MG) est une maladie genetique lysosomale, due a un deficit d’activite de la beta-glucocerebrosidase, caracterisee par des atteintes hematologiques, viscerales et osseuses. L’objectif principal de notre etude etait de decrire le parcours diagnostique de patients atteints de MG de type 1 et le role du medecin interniste. Methodes Etude retrospective multicentrique incluant des patients atteints de MG de type 1, menee au sein de 16 centres, entre 2009 et 2011. Resultats Cinquante-cinq patients atteints d’une MG de type 1 ont ete inclus, suivis par un interniste ou un hematologue. Ils etaient initialement hospitalises dans 8 services de specialite differents. Le diagnostic a ete etabli par un myelogramme chez 22 patients (40 %), par un dosage enzymatique de la glucocerebrosidase chez 15 patients (27 %), par une biopsie medullaire chez 9 patients (16 %). Le recours au dosage enzymatique etait plus frequent apres 1990. Le delai entre la date de premiere hospitalisation pour symptomes en lien avec la MG et le diagnostic definitif etait inferieur a 1 an pour 38 patients (81 %). Les suspicions de MG etaient majoritairement adressees a un medecin interniste. Conclusion La maladie semble mieux reconnue et diagnostiquee plus rapidement depuis 1990 malgre la multiplicite des parcours, dans lesquels le role du medecin interniste parait important.

Resume Introduction Le syndrome d’hyperemese cannabique (SHC) est caracterise par des episodes repetes de nausees et vomissements survenant chez des adultes jeunes, consommateurs chronique de cannabis. Le signe marquant de ce syndrome est la prise repetee et compulsive de douches chaudes. Nous en rapportons six cas. Observations Trois femmes et 3 hommes, consommateurs chroniques de cannabis, presentaient un tableau typique du SHC, mais non diagnostique jusqu’alors : nausees, vomissements, douleur abdominale a predominance matinale et amaigrissement survenant chez des adultes de moins de 50 ans. Les symptomes etaient calmes par la prise repetee de douches chaudes. Le bilan paraclinique etait negatif. Apres prise en charge addictologique et sevrage, les symptomes digestifs disparaissaient. Conclusion Le SHC est de diagnostic clinique. Sa meconnaissance conduit a une errance medicale et entraine la realisation repetee d’examens couteux, parfois invasifs. La physiopathologie est mal connue. Le traitement repose sur le sevrage definitif en cannabis.

Objective.Clara cell secretory protein (CC16) is a sensitive marker of bronchial epithelial cell damage. The CC16 serum level is elevated in patients with pulmonary fibrosis, but its predictive value on lung disease progression has not yet been studied. We aimed to assess the value of serum CC16 concentration in predicting lung disease deterioration in patients with systemic sclerosis (SSc).Methods.We prospectively analyzed and followed 106 patients with SSc during a 4-year period for the risk of developing combined deleterious event, defined as a 10% decrease in total lung capacity or forced vital capacity from baseline, or death, according to serum CC16 at inclusion. Receiver-operating characteristic (ROC) curve analysis was performed for prediction of events during the first 2 years after inclusion. Cumulative risks of combined events were computed by Kaplan-Meier analysis.Results.The best cutoff level of serum CC16 for prediction of a combined event was 33 ng/ml, with 76% sensitivity and 65% specificity (area under the ROC curve: 0.71, 95% CI 0.61–0.81, p < 0.0001). Progression of lung disease evaluated by a mean time-to-event differed between patients with high baseline serum CC16 (42.8 mos, 36.3–49.3) and those with low serum CC16 (56.3 mos, 50.9–61.7; log-rank test, p < 0.001). After adjustment for age, duration of disease, clinical and lung function measures, the risk of combined event occurrence in patients with high serum CC16 was significantly higher than in those with low CC16 (HR 2.9, 1.2–6.75, p < 0.05).Conclusion.High baseline serum CC16 predicts lung disease worsening in patients with SSc.

BACKGROUND: In France, primary-care physicians referring patients for admission can choose between public and private hospitals. The factors that govern their choices are unknown. METHODS: Among all patient admissions reported from 1997 to 2011 by primary-care physicians participating in the Sentinels(®) network, we identified those due to orthopaedic conditions or trauma. We then identified the factors associated with referral to a private hospital rather than to a public hospital. RESULTS: Of 45,960 admissions reported to Sentinels(®) in 1997-2011, 2794 (6.1%) were for orthopaedic/trauma care. The main reasons for admission were hip fractures (27.5%), elective orthopaedic surgery (15.5%), fractures of the humerus (5.9%), wrist fractures (5.4%), soft-tissue lesions of the forearm or hand (5.0%), and spinal injuries (4.5%). Private hospitals were chosen more often for orthopaedic/trauma patients than for patients with other conditions (40% vs. 21.6% of cases, P

Resume Introduction En France, pour le recours a l’hospitalisation, les medecins generalistes ont le choix entre des etablissements publics et des etablissements prives. Les facteurs motivant ce choix ne sont pas connus. Methodologie Toutes les declarations de recours a l’hospitalisation rapportees entre 1997 et 2011 par les medecins participant au reseau Sentinelles® ont ete incluses dans cette etude. Les motifs de recours pour pathologies orthopediques et traumatiques ont ete extraits de ces declarations. Les facteurs influencant le choix de recours vers une hospitalisation privee plutot que vers une hospitalisation publique ont ete analyses. Resultats Au cours de la periode d’etude, 45 960 declarations de recours a l’hospitalisation ont ete effectuees par les medecins Sentinelles®. Parmi ces recours, 2794 (6,1 %) concernaient des motifs orthopediques/traumatiques. Il s’agissait principalement de fractures du femur proximal (27,5 %), d’interventions chirurgicales programmees (15,5 %), de fractures de l’humerus (5,9 %), de fractures du poignet (5,4 %), de lesions des parties molles de la main et de l’avant-bras (5,0 %) et de traumatismes rachidiens (4,5 %). L’orientation se faisait plus frequemment vers une structure privee pour les pathologies orthopediques/traumatiques (40 % des cas) que pour les autres pathologies (21,6 % des cas) (p Conclusion Le choix d’un secteur d’hospitalisation public ou prive par les medecins generalistes ne semble pas etre aleatoire en ce qui concerne les pathologies orthopediques/traumatiques. A l’heure de la convergence tarifaire, des analyses complementaires semblent necessaires. Niveau de preuve IV.

A sub-clinical inflammatory aortitis is very frequent in patients with giant cell arteritis, and can be the only localization of the disease. In most patients, this aortitis is asymptomatic and is of no consequence on the patient's survival. The relative risk of developing an aortic dissection or aneurysm is 17.3. Evolution towards an aneurysm or an aortic dissection is unpredictable and rare; and seems independent of the disease activity and the associated vascular risk factors. Isolated aortitis treatment is not consensual, but often similar to the treatment of giant cell arteritis and adapted to clinical and biological markers of disease activity. Screening for sub-clinical aortitis with FDG-PET should not be prescribed in patients with typical presentation of giant cell arteritis. A systematic screening of aortic complications in giant cell arteritis patients could be done with a chest X-ray and an abdominal ultrasound possibly completed with an aortic CT-scan at time of diagnosis, in order to look for aneurysms with possible surgical indication.

International audience; In a pilot ProtoArray analysis, we identified 6 proteins out of 9483 recognized by autoantibodies (AAb) from patients with systemic sclerosis (SSc). We further investigated the 6 candidates by ELISA on hundreds of controls and patients, including patients with Systemic Lupus Erythematosus (SLE), known for high sera reactivity and overlapping AAb with SSc. Only 2 of the 6 candidates, Ephrin type-B receptor 2 (EphB2) and Three prime Histone mRNA EXonuclease 1 (THEX1), remained significantly recognized by sera samples from SSc compared to controls (healthy or with rheumatic diseases) with, respectively, 34% versus 14% (P = 2.10(-4)) and 60% versus 28% (P = 3.10(-8)). Above all, EphB2 and THEX1 revealed to be mainly recognized by SLE sera samples with respectively 56%, (P = 2.10(-10)) and 82% (P = 5.10(-13)). As anti-EphB2 and anti-THEX1 AAb were found in both diseases, an epitope mapping was realized on each protein to refine SSc and SLE diagnosis. A 15-mer peptide from EphB2 allowed to identify 35% of SLE sera samples (N = 48) versus only 5% of any other sera samples (N = 157), including SSc sera samples. AAb titers were significantly higher in SLE sera (P< 0.0001) and correlated with disease activity (p< 0.02). We could not find an epitope on EphB2 protein for SSc neither on THEX1 for SSc or SLE. We showed that patients with SSc or SLE have AAb against EphB2, a protein involved in angiogenesis, and THEX1, a 3'-5' exoribonuclease involved in histone mRNA degradation. We have further identified a peptide from EphB2 as a specific and sensitive tool for SLE diagnosis.

Resume Propos Les facteurs associes a l’adherence a une corticotherapie orale prolongee sont mal connus. En particulier, on ne sait pas si le ressenti des patients concernant ce traitement influence leur niveau d’adherence rapportee. Patients et methodes Etude transversale menee dans deux services de medecine interne durant une periode de six mois. Les patients consultants traites au long cours par corticotherapie orale etaient sollicites pour remplir un questionnaire estimant notamment leur ressenti vis-a-vis de la corticotherapie (estime grâce au questionnaire Beliefs about Medicines Questionnaire [BMQ]) et leur adherence au traitement (estimee grâce a l’echelle de Morisky). Les facteurs associes au niveau d’adherence rapportee etaient estimes par regression logistique. Resultats Cent quatre-vingt-un questionnaires etaient analyses (femmes : 79 %, âge median [IQR] : 47 [33–61] ans, duree mediane de la corticotherapie : 18 [7–72] mois, posologie quotidienne mediane d’equivalent prednisone : 10 [6–20] mg). Quatre-vingt-trois (46 %) des 181 patients consideraient le traitement comme plus « inquietant » que « necessaire ». Une adherence non optimale a la corticotherapie etait rapportee par 19 % des patients. Par rapport aux patients declarant une adherence optimale, ces patients etaient significativement plus jeunes (OR : 0,96 [0,93–0,98] pour chaque annee d’âge supplementaire, p = 0,002) et ressentaient plus frequemment le traitement comme inquietant plutot que necessaire (OR : 3,08 [1,27–7,46], p = 0,01). Conclusion Une bonne information des patients concernant la necessite de la corticotherapie et une prise en compte adaptee de parametres tels que les effets indesirables ou le sentiment de dependance vis-a-vis du traitement, pourraient permettre d’ameliorer l’adherence a la corticotherapie.

Among adults, liver involvement is relatively frequent in Langerhans' cell histiocytosis (LCH), even though it is often overlooked. In fact, the liver involvement may be missed in apparently localized LCH or when it is the sole site of involvement. We present 23 cases of liver involvement in LCH out of a cohort study of 85 adult patients included in the French Histiocytosis Study Group Registry. The most frequent clinical setting was multiorgan involvement (87% of our cases). The main histological pattern in liver LCH was sclerosing cholangitis (56% of the cases). The symptoms included hepatomegaly (48%) and/or liver biochemistry abnormalities (61%, including cholestasis associated with increased transaminases levels in 35% of cases, cholestasis only in 22% and increased transaminases levels only in 4% of the cases). Particularly suggestive of the diagnosis was the observation of biliary tree abnormalities through magnetic resonance imaging (MRI). The natural history of liver LCH fits into two stages: early infiltration by histiocytes and late sclerosis of the biliary tree. We found that liver involvement had a significant impact on survival. Thus we suggest that clinical and biological liver evaluation must be performed regularly onwards to screen every LCH adult patient from the time of the initial diagnosis. MRI and liver biopsy should be considered as soon as the data point to a possible liver localization. If this diagnosis is confirmed, we suggest a treatment with ursodesoxycholic acid, as in other cholestatic diseases, together with treatments specifically directed towards LCH. However, the ideal treatment of liver LCH remains to be found, and in advanced cases transplantation is the sole option.

Pregnancy in women diagnosed with systemic sclerosis is an infrequent situation with a generally favourable outcome according to the most recent studies. Women with systemic sclerosis who wish to become pregnant should obtain preconception counselling in order to withdraw teratogenic drugs and to carefully assess the disease activity. Severe organ impairment, early diffuse systemic sclerosis and pulmonary hypertension ought to discourage patients from pregnancy, as these situations are at high risk of complications for both mother and fetus during pregnancy and puerperium. During pregnancy, the most frequent maternal complication is worsening of gastroesophageal reflux, and the most severe complications are renal crisis and flaring arterial pulmonary hypertension. Angiotensin converting enzyme inhibitors are indicated at any stage of the pregnancy if renal crisis is suspected. Adverse obstetric outcomes are dominated by prematurity which may be the consequence of intra-uterine growth restriction or preeclampsia. Those complications might account for systemic sclerosis-associated vasculopathy, or for the presence of antiphospholipid antibodies. Patients with a previous history of placental insufficiency might benefit from treatment with aspirin, low dose anticoagulants or even nitric oxide donors. During the pregnancy, abnormal bilateral uterine artery Doppler is a predictor of vascular insufficiency and might guide initiation of further preventive treatments. Multicentric prospective cohort studies are warranted to identify more precisely the predictors of pregnancy-related complications and to define the best management of these patients.

Objective.To study the frequency and characteristics of patients with Wegener’s granulomatosis (WG) strictly and persistently localized to one organ.Methods.Retrospective analysis of the French Vasculitis Study Group (FVSG) WG cohort.Results.Sixteen patients (3.2% of the cohort) were identified who had isolated lung nodules, ear-nose-throat, or ocular involvement that did not progress to systemic disease (median followup, 58 mo) over the period of observation. Ten received first-line therapy with cyclophosphamide, which was effective in 4. Cotrimoxazole alone achieved remission in one, combined with corticosteroids in 3. Eight required subsequent treatments because of first-line failure or relapse.Conclusion.Strictly and persistently localized WG is uncommon. Optimal treatment remains to be determined.

Over the past several decades, the use of intravenous human normal immunoglobulin (IVIg) products in a diverse range of immunodeficiency, inflammatory and infectious disorders has increased significantly. Newer manufacturing processes have increased the yield of intact IVIg molecules and have also improved the tolerability and safety of these products, including reducing the transmission risk of blood-borne diseases. While there are no appreciable differences between the numerous commercially available IVIg products in terms of efficacy, different manufacturing processes and the final composition of IVIg products have resulted in different safety and tolerability profiles. The tolerability profile of different IVIg products may be idiosyncratic for individual patients and may not be predictable, based on product characteristics. Consequently, patients receiving an IVIg product should be carefully monitored at initial exposure, and switching of products should be avoided. To achieve the best outcomes in patients requiring IVIg therapy, treatment should be tailored to the patient's needs. The risk/benefit profile of an IVIg in relation to patient risk factors and the underlying immune deficiency, or autoimmune or inflammatory disorder should be considered when deciding on the most appropriate therapy.

Introduction/Background We aimed to determine patient acceptable symptom state (PASS) and minimally clinically important improvement (MCII) estimates for patient-reported outcomes (PROs) in systemic sclerosis (SSc). Material and method Two hundred and twenty patients participated in the SCLEREDUC trial, a 12-month, randomised controlled study comparing the efficacy on disability assessed by the HAQ-DI at 12-months of physical therapy compared to usual care in patients with SSc. Self-rated state and change in patient health at 12 months post-randomization were assessed by using 2 external anchoring questions from the Medical Outcomes Study 36-Item Short Form. Patients who self-rated their health as “excellent”, “very good” or “good” were considered as having an acceptable symptom state and those who self-rated their health change at 12 months as “somewhat better” were considered as minimally improved. PASS estimates were obtained using the 75th percentile method and the MCII estimates by using the mean change in scores method. Results Answers to both anchoring questions at 12 months were available for 151/220 (68.6%) participants. PASS (95% CI) and mean (SD) MCII estimates at 12 months were respectively: 53.75 (34.00 to 68.00) and −6.74 (32.02) for the joint-pain visual analog scale (range 0–100), 1.41 (1.13 to 1.63) and −0.21 (0.48) for the Health Assessment Questionnaire Disability Index (HAQ-DI, range 0–3), 1.27 (1.07 to 1.62) and −0.13 (0.45) for the scleroderma HAQ (sHAQ, range 0–3), 26.00 (17.00 to 37.00) and −3.38 (9.87) for the Cochin Hand Function Scale (range 0–90), and 19.40 (17.20 to 21.90) and −5.69 (6.79) for the McMaster-Toronto Arthritis Patient Preference Disability Questionnaire (range 0–30). For all PROs, higher scores indicate higher symptoms levels. Conclusion The present study provides PASS and MCII estimates for commonly used PROs in SSc. These estimates are useful in interpreting the clinical relevance of outcomes used in patients’ care and in clinical trials. ClinicalTrials.gov identifier: NCT00318188 .

Resume Introduction Le hoquet chronique, defini par des secousses repetitives durant plus de 48 heures, est une condition pathologique mal connue pour laquelle des donnees cliniques suggeraient une origine gastro-œsophagienne. Methodes Nous avons prospectivement etudie 184 patients adresses pour hoquet chronique rebelle avec endoscopie digestive superieure et d’autres investigations adaptees dans trois centres cliniques de 1995 a 2009. Nous avons teste une regle therapeutique selon laquelle toute anomalie digestive decouverte etait a priori la cause la plus probable du hoquet. Si son traitement prioritaire echouait ou si le bilan digestif etait negatif, une origine neurologique ou autre etait recherchee et traitee. Resultats Nous avons decouvert plus de 80 % d’anomalies digestives auxquels le hoquet etait imputable, et l’evolution a ete : remission complete chez 48 patients, partielle chez 116 patients, 20 echecs essentiellement dus a la persistance d’une maladie causale incurable, comme une tumeur inoperable du tronc cerebral. La regle therapeutique a ete suivie avec succes chez 123 patients (66 %) ; chez 38 patients, l’evolution a ete favorable sous traitement empirique, ne suivant pas la regle proposee ; chez 23 patients, l’evolution a ete defavorable. Conclusion Le hoquet chronique est bien le plus souvent une maladie œsophagienne.

OBJECTIVE To describe features of reactive haemophagocytic syndrome (RHS) in HIV-1-infected adult patients. To compare characteristics of patients with malignancy-associated RHS and infection-associated RHS. DESIGN AND SETTING Retrospective study in three departments of Infectious Diseases/Internal Medicine at three French tertiary centres. PATIENTS AND METHODS Medical charts of HIV-1-infected adult patients and RHS seen between January 2006 and December 2007 were reviewed. Demographic, clinical and laboratory data obtained at the time of RHS episode were compared between patients with malignancy-associated RHS and infection-associated RHS using non-parametric tests. The overall survival was assessed using the Kaplan-Meier method. RESULTS Fifty-eight HIV-1-infected patients were diagnosed with RHS [certain RHS n = 43, possible RHS n = 15, median (range) age 42 (23-85) years, men 76%]. At time of RHS, the median duration of HIV infection was 4 (0-22) years and 57% received HAART. The median CD4 lymphocyte count was 91 (2-387)/microl and 35% of patients had a plasma HIV-1 RNA less than 50 copies/ml. Underlying haemopathy/malignancy (Hodgkin lymphoma n = 10) or infection (tuberculosis n = 9, cytomegalovirus infection n = 5) were evidenced for 31 and 23 patients, respectively. Patients with haemopathy/malignancy-associated RHS presented more frequently with splenomegaly (97 vs. 70%, P < 0.01), lower aspartate aminotransferase (36 vs. 84 UI/l, P < 0.01) and lactate dehydrogenase (530 vs. 911 UI/l, P < 0.01) levels and CD8 cell count (234 vs. 588/microl, P < 0.01). Eighteen (31%) patients died. The overall survival was not statistically different between the two groups (P = 0.68). CONCLUSION In the HAART era, RHS is frequently associated with underlying haemopathy/malignancy, especially Hodgkin lymphoma. The prognosis remains poor but seems, however, better than in the pre-HAART era.

Summary Background Factors influencing adherence to long-term (i.e. ≥ 3 months) systemic glucocorticoid therapy are poorly understood. Objective To evaluate the relationship between glucocorticoid-induced adverse events and therapeutic adherence in patients on long-term glucocorticoid treatment. Methods A cross-sectional survey was conducted in three departments of dermatology/internal medicine between April and September 2008. Patients were asked to provide data regarding symptoms they attributed to glucocorticoids, and adherence to treatment was measured using the four-item Morisky–Green adherence scale. Logistic regression analyses were used to assess the association between reported adverse events and adherence to glucocorticoids. Results A total of 255 questionnaires were completed and analysed [women 78%; median age 48 years (interquartile range (IQR) 34–65); connective tissue diseases 59%; median duration of treatment 24 months (IQR 8–72); median daily dose 10 mg (IQR 6–20)]. Among these 255 patients, 199 (78%) reported themselves as ‘good adherents’ and 56 (22%) as ‘poor adherents’ to treatment. Poor adherence was associated with younger age [odds ratio (OR) 0·97, 95% confidence interval (CI) 0·95–0·99, per increasing year; P

Objective.Identification of an association between IRF5 rs2004640 and systemic sclerosis (SSc) has highlighted a key role for type 1 interferon (IFN). Additional functional IRF5 variants have been identified as autoimmune susceptibility factors. Our aim was to investigate whether IRF5 haplotypes confer susceptibility to SSc, and to perform genotype haplotype-phenotype correlation analyses.Methods.We genotyped IRF5 rs377385, rs2004640, and rs10954213 in 1623 individuals of French European Caucasian origin. SSc patient subphenotypes were analyzed according to cutaneous subsets and for SSc-related pulmonary fibrosis.Results.Case-control studies of single markers revealed an association between IRF5 rs3757385, rs2004640, and rs10954213 variants and SSc. We identified an IRF5 risk haplotype “R” (padj = 0.024, OR 1.23, 95% CI 1.07–1.40) and a mirrored protective haplotype “P” (padj = 8.8 × 10−3, OR 0.78, 95% CI 0.68–0.90) for SSc susceptibility. Genotype-phenotype correlation analyses failed to detect any association with a single marker. By contrast, phenotype-haplotype correlation analysis was able to detect intra-cohort association and to discriminate SSc patients with from those without the following clinical traits: “R” and/or “P” haplotypes identified diffuse cutaneous SSc (p = 0.0081) and fibrosing alveolitis (p = 0.018).Conclusion.IRF5 haplotypes are more informative than single markers, suggesting that they could be helpful for risk stratification of SSc patients. Our study provides further evidence of a key role of IRF5 in SSc severity.

Resume Introduction On ne sait pas si la prescription d’un regime pauvre en sodium permet de limiter l’augmentation des chiffres tensionnels chez les patients recevant une corticotherapie systemique. Methodes Etude monocentrique, croisee, la premiere periode de regime sode ( 6 g/j) etant tiree au sort, proposee a des patients debutant une corticotherapie systemique et ayant une pression arterielle avant traitement inferieure ou egale a 159/99 mmHg. Des donnees demographiques et cliniques etaient relevees a l’inclusion, puis chaque periode de regime sode durait trois semaines. La pression arterielle de chaque patient etait relevee au terme de chacune de ces periodes. Par ailleurs, il etait demande aux patients de remplir durant une semaine de chaque periode un semainier alimentaire. Ces semainiers etaient analyses par une dieteticienne qui calculait les apports sodes et caloriques moyens de chaque patient au cours de chaque periode. La relation entre apports sodes et variation des chiffres de pression arterielle etait evaluee grâce a des modeles mixtes. Resultats Entre juin 2006 et juin 2008, 49 patients ont ete inclus, 24 dans le groupe 1 (periode 1 = sel 6 g/j ; femmes : 56 % ; âge moyen : 60 ± 19 ans ; posologie initiale moyenne de prednisone : 56 ± 16 mg/j). Les apports sodes moyens des deux groupes etaient respectivement de 2,5 ± 1,8 et 9,3 ± 1,9 g/j pour la periode 1 et de 7,8 ± 3,2 et 3,8 ± 2,9 g/j pour la periode 2. Les variations des chiffres de pression arterielle n’etaient pas significativement associees aux apports sodes ou au groupe de randomisation. Il n’y avait pas d’effet ordre. Cinq patients (2 patients du groupe 1 et 3 patients du groupe 2) avaient une pression arterielle systolique superieure d’au moins 20 mmHg par rapport a leur pression arterielle systolique initiale apres six semaines de traitement. Conclusion A court terme, les apports sodes ne semblent pas influencer les variations des chiffres de pression arterielle des patients debutant une corticotherapie systemique.

Objective An algorithm for the detection of pulmonary arterial hypertension (PAH), based on the presence of dyspnea and the findings of Doppler echocardiographic evaluation of the velocity of tricuspid regurgitation (VTR) and right-sided heart catheterization (RHC), which was applied in a large multicenter systemic sclerosis (SSc) population, estimated the prevalence of PAH to be 7.85%. The aim of this observational study was to investigate the incidence of PAH and pulmonary hypertension (PH) during a 3-year followup of patients from the same cohort (the ItinerAIR-Sclerodermie Study). Methods Patients with SSc and without evidence of PAH underwent evaluation for dyspnea and VTR at study entry and during subsequent visits. Patients in whom PAH was suspected because of a VTR of 2.8–3.0 meters/second and unexplained dyspnea or a VTR of >3.0 meters/second underwent RHC to confirm the diagnosis. Results A total of 384 patients were followed up for a mean ± SD of 41.03 ± 5.66 months (median 40.92 months). At baseline, 86.7% of the patients were women, and the mean ± SD age of the patients was 53.1 ± 12.0 years. The mean ± SD duration of SSc at study entry was 8.7 ± 7.6 years. After RHC, PAH was diagnosed in 8 patients, postcapillary PH in 8 patients, and PH associated with severe pulmonary fibrosis in 2 patients. The incidence of PAH was estimated to be 0.61 cases per 100 patient-years. Two patients who exhibited a mean pulmonary artery pressure of 20–25 mm Hg at baseline subsequently developed PAH. Conclusion The estimated incidence of PAH among patients with SSc was 0.61 cases per 100 patient-years. The high incidence of postcapillary PH highlights the value of RHC in investigating suspected PAH.

Nitric oxide metabolites (NOx) in serum, and alveolar concentration of NO (CA(NO)), are markers of inflammation and alveolitis, respectively, in systemic sclerosis (SSc). We prospectively evaluated the usefulness of both NOx and CA(NO) to assess lung involvement and skin fibrosis in SSc. Serum NOx, and CA(NO) measured by two different methods, namely the two-compartment (2CM) and the "trumpet" models (TM), were concomitantly assessed in 65 patients with SSc and 17 healthy controls. Whilst serum NOx remained comparable between groups, CA(NO) were significantly higher in SSc patients (n=65, 6.7ppb; 4.8-9.7 and 5.9ppb; 3.9-8.9) as compared with controls (n=17, 3.0ppb; 2.0-3.8 and 1.8ppb; 1.1-2.9, p

Background General practitioners’ perception of the discomfort their patients experience because of corticosteroid-induced adverse events is unknown. Methods An observational epidemiological study was conducted in September 2007. Eight hundred and sixty general practitioners belonging to the reseau Sentinelles® were asked to complete an electronical questionnaire. The questionnaire aimed to assess their perception of discomfort induced by adverse events induced by a long-term (i.e., ≥ 3 months) corticosteroid therapy among their patients. Results were compared with the declaration made by 115 long-term corticosteroid treated patients followed in an internal medicine department. Results Two hundred and ninety-three general practitioners responded to the questionnaire (response rate: 34%). They were predominantly male (87%). Forty-eight percent of them reported 400 to 600 monthly visits. The mean length of corticosteroid therapy for patients was 44 ± 38 months and the mean daily dosage was 15 ± 14 mg. They suffered mainly from lupus erythematosus (33%) or giant cell arteritis (15%). The adverse events considered to be the most disturbing by patients were lipodystrophy (25%), followed by weight gain (18%) and neuropsychiatric complaints (16%). Physicians widely overestimated the discomfort caused by weight gain cited as the most disturbing adverse event by 59% of them and underestimated that induced by mood disorders cited as the most disturbing by only 3% of them. Conclusion The discomfort caused by corticosteroid-induced neuropsychiatric adverse events are underestimated by general practitioners.

Resume Introduction Les internistes sont frequemment prescripteurs de corticotherapies systemiques prolongees, mais on ne sait pas si la perception qu’ils ont de la frequence et de la gene induite par les effets indesirables de ces traitements est correcte. Methodes L’enquete a ete menee a l’aide d’un questionnaire electronique compose de questions a choix simple ou a choix multiples et adresse par courriel aux 813 medecins internistes, membres de la Societe nationale francaise de medecine interne, disposant d’une adresse electronique. Dans ce questionnaire, il etait demande aux praticiens d’estimer la frequence et la gene induite par les effets indesirables d’une corticotherapie systemique prolongee (c’est-a-dire, prescrite durant au moins trois mois). A titre indicatif, les resultats obtenus etaient compares aux donnees fournies par des patients traites au long cours par corticoides, vus en consultation d’un service de medecine interne et qui rapportaient leur vecu du traitement en termes de frequence des effets indesirables et de gene induite. Resultats Quarante et un pour cent des internistes ont repondu au questionnaire. Il s’agissait essentiellement d’hommes (71 %) travaillant en centre hospitalo-universitaire (53 %). Chez les 115 patients dont les reponses etaient analysables, la duree moyenne de corticotherapie etait de 44 ± 38 mois, prescrite a la posologie moyenne de 15 ± 14 mg par jour, le plus souvent pour un lupus (33 %) ou une maladie de Horton (15 %). La lipodystrophie, les troubles trophiques cutanes, les troubles neuropsychiatriques et l’insomnie etaient rapportes par plus de la moitie des patients. La frequence estimee par les praticiens des manifestations neuropsychiatriques, des troubles cutanes et de la lipodystrophie etait nettement inferieure a la frequence rapportee par les patients. Si les modifications morphologiques (prise de poids et lipodystrophie) etaient citees par les praticiens comme les effets indesirables les plus genants, en accord avec l’avis des patients, les medecins sous-estimaient la gene induite par les troubles neuropsychiatriques et l’insomnie. Conclusion La frequence et la gene induite par les troubles neuropsychiatriques cortico-induits semblent sous-estimees par les medecins internistes.

Objectives. Male microchimerism (Mc) persisting from pregnancy has been found at greater frequencies and/or higher quantities in women with scleroderma (SSc) compared with controls, suggesting a possible role in disease development. Moreover, women with an HLA-compatible child have a higher risk to develop SSc. We tested the hypothesis, on our French SSc cohort, that women with lcSSc and dcSSc, two distinct clinical subsets, have a different profile in terms of Mc and HLA compatibility in families. Methods. We studied 98 women (52 lcSSc and 46 dcSSc) for male Mc, by real-time PCR, in their whole blood and/or peripheral blood mononuclear cells (PBMC). Similarly, 91 matched healthy women were analysed. Complete HLA-DRB1 typing was obtained for 58 SSc and 68 control families (proband/children). Results. Women with lcSSc (N ¼ 50) had male Mc more often in their whole blood than women with dcSSc (N ¼ 40, 20 vs 5%, P ¼ 0.038), but not significantly more than controls. By contrast, women with dcSSc (N ¼ 36) hold Mc more often in PBMC (25 vs 9%), but not significantly and have greater quantities than controls (N ¼ 82, P ¼ 0.048). This contrast is also visible in feto-maternal HLA-DRB1 compatibility, which was increased only among women with lcSSc (N ¼ 33) compared with controls (N ¼ 68, P ¼ 0.003). Conclusion. For the first time, we showed that women with lcSSc and dcSSc hold male Mc in different blood compartments. Furthermore, a distinct pattern between the two SSc subtypes is observed for feto-maternal HLA-DRB1 compatibility. These results suggest a different mechanism behind each type of disease.

Resume Introduction A l’exception des mesures concernant la prevention de l’osteoporose, il n’existe pas de recommandations consensuelles quant aux mesures adjuvantes a prescrire lors d’une corticotherapie systemique prolongee. Nous avons cherche a savoir si les pratiques des internistes concernant ces mesures adjuvantes etaient homogenes ou pas. Methodes L’enquete a ete menee a l’aide d’un questionnaire electronique adresse, en septembre 2007, par courriel aux 813 medecins internistes membres de la Societe nationale francaise de medecine interne disposant d’une adresse electronique. Ce questionnaire concernait la frequence de prescription des mesures associees a une corticotherapie systemique prolongee et pour lesquelles il n’existait pas de recommandations consensuelles (regime alimentaire, mesures d’entretien musculaire, supplementation potassique, protection gastrique, vaccination antigrippale, relais par hydrocortisone). Resultats Trois cents trente-six des 813 medecins sollicites ont repondu au questionnaire (taux de reponse : 41 %). Ces repondeurs etaient majoritairement des hommes (71 %) et travaillaient principalement en centre hospitalo-universitaire (53 %). En ce qui concernait les mesures dietetiques preconisees, seul le regime hyposode etait prescrit de facon relativement homogene par les praticiens (69 % des praticiens le prescrivaient chez plus de 80 % de leurs patients). Un regime hypocalorique, pauvre en glucides et riche en proteines, etait ou non preconise par les praticiens. Une kinesitherapie d’entretien musculaire n’etait pas frequemment proposee (74 % des praticiens la prescrivaient chez moins de 20 % de leurs patients). En revanche, il n’existait aucun consensus concernant la recommandation ou non d’un exercice physique regulier. La supplementation potassique, la protection gastrique, la vaccination antigrippale et le relais hydrocortisone ne faisaient egalement l’objet d’aucun consensus au sein de la communaute interniste. Conclusion Les principales mesures adjuvantes a une corticotherapie systemique prolongee ne font l’objet d’aucun consensus au sein de la communaute interniste francaise.

Digital ulcers are a frequent event in systemic scleroderma. Despite their frequency, there is currently no consensus about their management. Curative treatment is based on local care and vasodilatating agents, together with the prevention of superinfection. Preventive measures require the elimination of risk factors and reeducation. For multiple recurrent ulcers, endothelin receptor inhibitors or prostacyclin derivatives are also prescribed. Surgery is useful in the case of substantial retraction or bothersome calcifications. In all cases, calcium channel blockers are continued.

Objectives: To describe presentation and outcome of patients with scleroderma renal crisis (SRC). Methods: SRC was defined as rapidly progressive oliguric renal insufficiency and/or rapidly progressive arterial hypertension occurring during the course of systemic sclerosis (SSc). Chronic dialysis-free survival was analysed using multivariate Cox proportional hazards regression models. The risk for developing SRC associated with corticosteroid (CS) exposure during the preceding 1- or 3-month periods was analysed according to a case–crossover design. Results: A total of 50 SSc patients aged 53.3 (14.5) (mean (SD)) years were included in the study. SRC occurred between 1979 and 2003, after a mean (SD) disease duration of 27.7 (49.1) months. A total of 43 (86%) patients had diffuse SSc, 5 (10%) had limited cutaneous SSc and 2 (4%) had SSc sine scleroderma. At the time of SRC, 10 (20%) patients were taking angiotensin converting enzyme inhibitors, and mean creatininaemia was 468 (293) μmol/l. A total of 28 (56%) patients required haemodialysis. In all, 11 patients underwent a renal biopsy, all of them had specific vascular lesions of SRC. Multivariate analyses retained age >53 years and normal blood pressure as independent predictors of decreased dialysis-free survival. Exposure to CS prior to SRC was identified in 30 (60%) patients. The odds ratios for developing SRC associated with CS exposure during the preceding 1- or 3-month periods were 24.1 (95% CI 3.0–193.8) and 17.4 (95% CI 2.1–144.0), respectively. Conclusion: SRC remains associated with severe morbidity and mortality. CS might increase the risk of developing SRC. Further studies are needed to confirm these results.

Resume Propos Il n'existe aucune donnee dans la litterature concernant : 1) l'observance des patients traites par corticoides aux recommandations dietetiques qui leurs sont preconisees ; 2) le lien entre alimentation et apparition d'une lipodystrophie cortico-induite (LCI). Methodes Etude de cohorte bicentrique effectuee entre juin 2003 et mai 2005. Tous les patients debutant une corticotherapie systemique etaient invites a participer. Ils recevaient des conseils dietetiques par une dieteticienne puis notaient sur un semainier tous leurs apports alimentaires au cours d'une semaine par mois durant le premier et le troisieme mois de traitement. Les questionnaires etaient analyses en aveugle par deux dieteticiennes qui calculaient la moyenne quotidienne des apports calorique, protidoglucidolipidique, sode et en alcool. Par ailleurs, trois evaluateurs se prononcaient a la fin du suivi sur la presence ou l'absence d'une LCI en analysant les photographies des patients prises au depart et apres trois mois de traitement. Une regression logistique etait effectuee pour mettre en evidence d'eventuels facteurs de risque alimentaires a l'apparition d'une LCI. Resultats Quatre-vingt-huit patients ont ete inclus et 80 ont ete suivis au moins trois mois (femmes : 76 %, âge moyen : 59,1 ± 18,7 ans). La plupart de ces patients (65 %) souffraient de maladie de Horton ou de connectivite. La posologie initiale moyenne de prednisone etait de 54 ± 17 mg/j et celle du troisieme mois de 31 ± 15 mg. Les recommandations dietetiques etaient globalement bien suivies en debut de corticotherapie hormis en ce qui concerne les apports protidiques qui demeuraient insuffisants. La restriction sodee etait plus strictement suivie par les femmes que par les hommes. En analyse multivariee, des apports caloriques quotidiens eleves (> 30 kcal/kg par jour) etaient significativement associes au risque de developper une LCI. En revanche, nous ne mettions pas en evidence de lien entre apports glucidiques, lipidiques, protidiques ou sodes et apparition d'une LCI. Conclusion Les recommandations dietetiques preconisees aux patients debutant une corticotherapie sont globalement bien suivies en debut du traitement. Un regime controle en calories pourrait permettre de limiter le risque de LCI.

The alveolar concentration of exhaled nitric oxide (CA,(NO)) is increased in patients with systemic sclerosis (SSc), but whether this increase is related to the severity of interstitial lung disease (ILD) in SSc has not yet been investigated. In total, 58 SSc patients prospectively underwent pulmonary function tests (PFTs), echocardiogram and fibrosis scoring on pulmonary computed tomography (CT). Patients were divided into two groups according to the presence (or not) of ILD. Measurements of CA,(NO) were assessed in all SSc patients and compared with those obtained in 19 healthy volunteers. Relationships were sought between CA,(NO) PFTs and CT scan fibrosis scores. Overall, CA,(NO) was significantly increased in SSc patients (median (range) 6.2 (3.8-9.9) ppb) as compared with controls (2.0 (1.2-3.0) ppb). Among SSc patients, CA,(NO) was significantly higher in patients with ILD compared with patients without ILD (n = 33, 7.5 (5.2-11.9) ppb versus n = 25, 4.9 (3.1-7.0) ppb, respectively). CA,(NO) was inversely related to total lung capacity (r = -0.34) and the diffusing capacity of the lung for carbon monoxide (r = -0.37) and was directly related to CT scan fibrosis scores (r = 0.36). An increased alveolar concentration of exhaled nitric oxide could, at least in part, either reflect or contribute to the severity of lung disease and could be used to noninvasively assess the extent of interstitial lung disease in systemic sclerosis.

Objective To assess the construct validity of the Cochin Hand Function Scale (CHFS) and the relevance of using aggregate scores for the scleroderma Health Assessment Questionnaire (sHAQ) and Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) in systemic sclerosis (SSc). Methods We evaluated 50 patients with SSc (mean ± SD age and disease duration 54 ± 12 years and 9 ± 8 years, respectively), of which 26 had limited cutaneous SSc (lcSSc) and 23 diffuse SSc (dSSc). Quality of life was assessed by the SF-36, global disability by the Health Assessment Questionnaire (HAQ) and sHAQ, and hand disability by the CHFS. Construct validity was assessed by convergent and divergent validity (Spearman's rank correlation coefficient) and factor analysis. Results The CHFS had good construct validity and its total score explained 75% of the variance of the HAQ. The HAQ had better construct validity than the aggregate sHAQ and their scores correlated well (r = 0.88). The aggregate sHAQ was no better than the HAQ in discriminating between lcSSc and dSSc. SF-36 physical and mental components had acceptable convergent and divergent validity. Factor analysis of the 8 subscales extracted 3 factors explaining 72% of the variance, which differed from the a priori stratification with physical and mental subscales extracted in the same factor. Conclusion In patients with SSc, the CHFS has good construct validity, the HAQ should be preferred over the aggregate sHAQ for assessing physical functioning, and use of SF-36 physical and mental components aggregate scores is questionable.

Summary Objective To describe the main features of severe strongyloidiasis in corticosteroid-treated patients Methods We report on 3 cases of corticosteroid-treated patients with severe strongyloidiasis and review cases of severe strongyloidiasis in corticosteroid-treated patients reported in the literature. Results One hundred and fifty-one cases of severe strongyloidiasis complicated a therapy with corticosteroids were evaluated. The mean age of the patients was 48 ± 17 years and 71% were men. Corticosteroids were given for hematological malignancies in 34 (23%), systemic lupus erythematosus or vasculitis in 27 (18%), and nephropathy or renal transplantation in 32 (21%). At time of infection, the mean daily dosage of prednisone-equivalent was 52 ± 42 mg (median: 40 mg) and 84% of patients had received a cumulative dosage of prednisone-equivalent higher than 1000 mg. The total duration of treatment ranged from 4 days to 20 years (6 months or less: 69%). Non-specific gastro-intestinal symptoms were reported in 91% of these patients associated or not with pulmonary complaints. Low-grade fever was present in 54% of patients. Fifty-nine patients (39%) experienced severe bacterial or yeast infection during the course of severe strongyloidiasis. Peripheral eosinophilia was detected at presentation in 32% of patients. Strongyloidiasis was usually confirmed by repeated stool examinations. Thiabendazole was the treatment the more widely used. Eighty-nine patients (59%) deceased during the course of the disease. Conclusions Severe strongyloidiasis is a risk in every corticosteroid-treated patient who has traveled to a soil-infested country, even if the contact was 30 years prior. This diagnosis should be suspected in patients who either experience unusual gastro-intestinal or pulmonary symptoms or suffer from unexplained Gram-negative bacilli sepsis.

Points essentiels La classification des sclerodermies est difficile mais indispensable car elle permet de decrire les differentes formes cliniques et d’estimer leur pronostic. La classification de base oppose les formes localisees et systemiques. Les premieres sont circonscrites, respectent en regle les mains et ne s’accompagnent ni de phenomene de Raynaud ni d’atteintes viscerales sauf de voisinage immediat. Elles posent des problemes essentiellement esthetiques, mais parfois fonctionnels. Les secondes sont symetriques, touchent prioritairement les mains, avec un Raynaud severe. Elles peuvent etre tres invalidantes et posent parfois des problemes vitaux, notamment par l’atteinte des visceres (poumons, cœur, reins, tube digestif, vaisseaux pulmonaires, systeme locomoteur). Il existe une sous-classification en fonction de l’atteinte cutanee. Les sclerodermies systemiques touchant le tronc sont classees “sclerodermies systemiques cutanees diffuses”. L’association de Raynaud, d’anomalies capillaroscopiques et d’autoanticorps specifiques permet de definir les “sclerodermies systemiques limitees” au sein desquelles les patients ayant une sclerose cutanee distale sont classes “sclerodermies systemiques cutanees limitees”. Le terme “Crest” tend a etre abandonne pour cette classification plus precise, mais qui peut encore evoluer.

Resume Propos. – Le cyclophosphamide en bolus mensuels est utilise pour traiter les sclerodermies systemiques avec atteinte pulmonaire. Depuis 1996 l'intensification therapeutique par cyclophosphamide suivie d'autogreffe de cellules souches hematopoietiques peripheriques a permis (etudes de phase I–II) d'ameliorer significativement l'atteinte cutanee et les scores fonctionnels au cours des sclerodermies systemique graves. Cependant, la toxicite cardiaque du cyclophosphamide intraveineux reste discutee chez ces patients. Methodes. – Afin d'analyser la toxicite cardiopulmonaire potentielle de ce traitement, nous avons etudie retrospectivement tous les patients atteints de sclerodermie systemique grave traites par cyclophosphamide intraveineux lors d'une intensification therapeutique suivie d'autogreffe (groupe A) ou en bolus mensuels (groupe B), recrutes dans sept centres francais. Les parametres evaluant les fonctions cardiaques et pulmonaires au debut du traitement puis lors du dernier suivi entre six et 12 mois apres le debut du traitement ont ete compares (moyennes ± deviation standard) avec le test de Mann-Whitney. Resultats. – Les deux groupes (A = 14, B = 13) etaient comparables au debut du traitement. Les doses moyennes (/m2) de cyclophosphamide recues dans le groupe A etaient superieures (p = 0,02) a celles recues dans le groupe B. Apres un suivi moyen comparable de dix mois, la cardiotoxicite (grades OMS) immediate du cyclophosphamide (n = 3 groupe A, n = 2 groupe B), et l'evolution des fonctions cardiaque et pulmonaire ne sont pas differentes entre les deux groupes. Conclusion. – Malgre des doses de cyclophosphamide superieures lors de l'autogreffe, la cardiotoxicite precoce ne semble pas augmentee comparee aux bolus mensuels. L'essai prospectif europeen ASTIS, en cours, permettra de comparer les benefices respectifs de ces deux formes de traitement par cyclophosphamide dans la sclerodermie systemique severe.

Objective To analyze hematopoietic and immune reconstitution after autologous hematopoietic stem cell transplantation (HSCT) in 7 patients with systemic sclerosis (SSc). Methods Two groups of patients were retrospectively constituted according to whether they had a favorable clinical response (group A; n = 4) or no response or a relapse of disease (group B; n = 3) after HSCT. Immune reconstitution was analyzed every 3 months using lymphocyte immunophenotyping, α/β T cell receptor (TCR) diversity analysis, and ex vivo thymic function analysis by quantification of TCR rearrangement excision circles (TRECs). Results Patients had similar characteristics at study entry, except for a lower modified Rodnan skin thickness score (P = 0.03) and a lower Health Assessment Questionnaire score (P = 0.05) in group A than in group B. The number of reinjected cells and the time to hematopoietic reconstitution were similar in both groups. The absolute numbers of CD19+ and CD20+ B cells were lower in group A than in normal controls (P < 0.05) and within the normal range in group B. Absolute numbers of T and natural killer lymphocytes were normal before HSCT. Numbers of CD3+ cells remained low thereafter. Numbers of CD8+ cells were back to normal 3 months after HSCT in both groups. B cell counts were low until 6 months after HSCT in group A and stayed in the normal range in group B. The CD3+ defect was sustained in group A, with an opposite trend and a faster CD4+ reconstitution profile in group B. The T cell repertoire was skewed before and until 1 year after HSCT, with shared expansions before and after transplant in a given individual. TREC values correlated negatively with C-reactive protein levels (rs = −0.41, P = 0.001) and positively with CD19+ (rs = 0.35, P = 0.001) and CD20+ (rs = 0.34, P = 0.002) lymphocyte counts. Conclusion B and T lymphocyte populations remained disturbed for at least 1 year after HSCT in SSc patients, which may reflect the persistence of an underlying disease mechanism.

Objective Screening allows for early management of pulmonary arterial hypertension (PAH), a severe complication of systemic sclerosis (SSc). Since no consensus has been reached on the method and criteria for optimal screening, we sought to develop an algorithm based on symptoms, Doppler echocardiography, and right heart catheterization (RHC) for application to a nationwide multicenter SSc population in France. Methods This prospective study was conducted from September 2002 to July 2003 by experts at 21 SSc centers. At each center, SSc patients without severe pulmonary function abnormalities underwent Doppler echocardiography by an experienced cardiologist. Patients with a peak velocity of tricuspid regurgitation (VTR) of >3 meters/second or 2.5–3 meters/second with unexplained dyspnea were asked to undergo RHC to confirm PAH according to international guidelines. Results Of the 599 patients analyzed, 29 had known PAH and 33 had suspected PAH, based on Doppler echocardiography, and underwent RHC. Of these 33, 18 were found to have PAH, 3 had left ventricular dysfunction, and 12 had no PAH. Newly diagnosed cases of PAH were of mild severity (mean ± SD pulmonary artery pressure [mPAP] 30 ± 9 mm Hg, mean ± SD total pulmonary resistance [TPR] 524 ± 382 dynes × second/cm5). Hemodynamic findings in patients with known PAH were mPAP 49 ± 17 mm Hg and TPR 1,007 ± 615 dynes × second/cm5. The estimate of PAH prevalence was 7.85% (95% confidence interval 5.70–10.00). Conclusion This screening algorithm, based on dyspnea, Doppler echocardiographic evaluation of VTR, and RHC, enabled early detection of PAH at a mild stage. Whether mild PAH will evolve to severe PAH in reported cases and whether this early diagnosis translates into improved prognosis for patients with mild PAH will be evaluated in the ongoing 3-year followup of this cohort.

Resume Propos. – L'hypertension arterielle pulmonaire (HTAP) est une complication severe de la sclerodermie systemique. Sa prevalence dans la litterature varie de 5 a 35 %. Un depistage systematique annuel est recommande afin d'etablir un diagnostic et une prise en charge precoces ; mais aucun algorithme n'est a ce jour clairement defini. Methodes. – Sur la base d'une revue de la litterature, d'une evaluation des besoins medicaux et des pratiques, un comite multidisciplinaire d'experts a elabore un algorithme de depistage de l'HTAP dans la sclerodermie. Resultats. – Cet algorithme repose sur une methodologie echo-doppler cardiaque rigoureuse. Un patient est considere comme etant a haut ou faible risque d'HTAP en fonction de la vitesse maximale du flux d'insuffisance tricuspidienne. Un catheterisme cardiaque droit (de repos et/ou d'effort) est realise chez les patients a haut risque d'HTAP pour confirmation du diagnostic d'HTAP. Une etude observationnelle transversale multicentrique francaise (« ItinerAIR Sclerodermie »), va etre conduite dans 21 centres hospitaliers et impliquant 100 investigateurs reunis en reseaux multidisciplinaires. Perspectives. – Les resultats permettront de confirmer l'applicabilite en situation pragmatique de l'algorithme de depistage, de decrire la prevalence de l'HTAP dans les sous-groupes de sclerodermie, le profil de risque d'HTAP et la valeur de la DLCO comme facteur predictif d'HTAP, et ainsi de proposer des recommandations precises de depistage.

GREAT PROGRESS: The understanding of the physiopathology of Horton's syndrome has been made in view of the prevalence of the disease, the access to affected tissue and new molecular biology techniques. And it is now possible to specify the intricacy between the genetic, immunological and vascular components. HORTON'S SYNDROME, A GENETIC DISEASE: The preferential association of the disease with some alleles pf the HLA DR4 group has helped to emphasize the fundamental role of a few amino acids of the second hypervariable area of the HLA-DR molecule. An immunogenetic predisposition appears favourable, or even necessary, for the development of the disease. HORTON'S SYNDROME, AN IMMUNOLOGICAL DISEASE: The temporal arteries of patients presenting with Horton's syndrome are infiltrated by polymorphous inflammatory cells, fundamentally including CD4 T-cell lymphocytes, macrophages, and a few giant cells. Some CD4 lymphocytes have undergone clonal proliferation and show signs of recent antigenic recognition. A fraction of them secrete interferon gamma, which plays a crucial role in the onset, maintenance and orientation of the immunological response. The macrophages play multiple roles notably in maintaining the inflammatory reaction, but also in the destruction of certain structures of the arterial wall. HORTON'S SYNDROME, A VASCULAR DISEASE: The destruction of the arterial wall at the acute stage of the disease appears responsible, sometimes later on, for aneurismal dilatations observed on the aorta of certain patients. Moreover, intimal hyperplasia (mediated by the PDGF (platelet derived growth factor) A and B) and thrombosis (related to the inflammation) join up in reducing the arterial flow and enhancing the risk of ischemic complications during the acute stage. PATHOGENESIS, HYPOTHESES: Various candidate-antigens have been incriminated in the onset of the inflammatory reaction during Horton's syndrome. Some epidemiological and molecular studies are in favour of an exogenous antigen, possibly infectious, but no evidence has been demonstrated in the studies published. A parietal, endogenous antigen might also be at the origin of the cascade of events described during this disease.

Resume La mastocytose systemique est une maladie rare correspondant a une proliferation mastocytaire avec localisation tissulaire multiviscerale. Bien que l’atteinte hepatique soit frequente au cours des mastocytoses systemiques, elle n’est que tres exceptionnellement revelatrice. Nous rapportons ici deux observations de mastocytose systemique dont la symptomatologie hepatique d’installation tres rapide a ete revelatrice, insuffisance hepatocellulaire dans un cas et ictere dans l’autre. Ces deux observations montrent que la mastocytose systemique, comme d’autres pathologies tumorales, peut se reveler par une symptomatologie hepatique. Cette symptomatologie hepatique revelatrice est variable, de meme que les lesions anatomo-pathologiques hepatiques. La clef du diagnostic est la mise en evidence d’une infiltration tissulaire par des mastocytes tumoraux identifies a l’aide d’immunomarquages avec les anticorps anti-tryptase et/ou -CD117 (c-kit).

Resume Propos. – L'ulcere de Mooren (UM) est une ulceration corneenne peripherique inflammatoire chronique avec depots conjonctivaux d'immunoglobulines d'etiologie indeterminee. Cette pathologie rare serait due a un processus auto-immun cellulaire et humoral. Elle est souvent rebelle, avec un risque de perforation corneenne qui met en jeu le pronostic anatomique de l'œil. Lorsque les traitements corticoides et chirurgicaux procurent des resultats mediocres, la chimiotherapie a ete proposee, mais ses effets secondaires en limitent l'usage. Methode. – Suivi longitudinal de trois patients atteints d'UM rebelles aux traitements conventionnels, traites par bolus intraveineux mensuels de 1 g de cyclophosphamide (Cy). Resultats. – Un patient de 24 ans, presentant un UM perfore de l'œil gauche malgre une keratoplastie lamellaire associee a une corticotherapie intraveineuse, a pu cicatriser sa cornee au terme de 9 mois de traitement par Cy. Un patient de 50 ans presentant un UM de l'œil gauche, rebelle, a recu durant 20 mois du Cy qui a permis une cicatrisation corneenne. Un patient de 70 ans, presentant des UM bilateraux avec une lesion corneenne preperforative de l'œil droit, a obtenu la cicatrisation apres resection conjonctivale et 4 mois de traitement par Cy. Nous n'avons pas note d'effets secondaires avec ce mode d'administration contrairement aux donnees de la litterature sur les chimiotherapies orales. Conclusion. – Nous rapportons l'efficacite du traitement des UM rebelles aux traitements conventionnels par Cy en bolus intraveineux mensuels de 1 g. Ce traitement pourrait etre propose dans les cas d'UM rebelles.

Haematopoietic stem cell transplantation (HSCT) has been proposed for refractory autoimmune diseases, including systemic sclerosis (SSc). A sequential Bayesian phase I-II clinical trial was conducted in SSc patients to assess the feasibility, the tolerance and the efficacy of autologous HSCT. Peripheral blood stem cells (PBSC) were collected using cyclophosphamide (4 g/m2) and recombinant human granulocyte colony-stimulating factor (5 micro g/kg/d) and reinfused after positive CD34+ selection. Conditioning used cyclophosphamide (200 mg/kg) or melphalan (140 mg/m2) according to cardiac function. The main end-point was the failure of the procedure, defined by failure of either PBSC mobilization, CD34+ selection or intensification procedure, or by procedure-related death. Among the 12 enrolled patients, three failures occurred: one PBSC mobilization, one CD34+ selection and one CD34+ intensification. Probability of graft failure was estimated at 0.286 (95% confidence interval: 0.095-0.54). Autologous PBSC (n = 10) or bone marrow (n = 1) transplantation was actually performed in 11 patients with one procedure-related death. Median time to neutrophil (> 0.5 x 10(9)/l) and platelet (> 25 x 10(9)/l) haematopoietic reconstitution was 12 and 10 d respectively. After 18 months (range 1-26), eight out of 11 patients have shown major or partial response. Non-myeloablative conditioning, followed by a T cell-depleted autologous PBSC or bone marrow transplantation, appears feasible with low toxicity in severe SSc with short-term clinical benefits.

Resume Propos. – Les perforations de la cloison nasale sont principalement d'origine traumatique. Parmi les autres causes possibles, nous detaillerons celles induites par les maladies systemiques. Actualites et points forts. – De nombreuses maladies systemiques peuvent entrainer une perforation de la cloison nasale, en particulier la granulomatose de Wegener, le lupus erythemateux systemique et/ou le syndrome des antiphospholipides, la sarcoidose ou les cryglobulinemies. Cependant, il est difficile d'estimer la frequence des perforations de la cloison nasale dans chacune des maladies systemiques. Les manifestations cliniques sont polymorphes et non specifiques : obstruction nasale, rhinorrhee, epistaxis, sifflement, croutes mais des formes asymptomatiques de decouvertes fortuites sont frequentes. Les biopsies du septum nasal souvent pratiquees a but etiologique sont en general d'un rendement faible. Cependant, elles peuvent orienter le diagnostic lorsqu'elles montrent un granulome ou une vascularite. Les differents mecanismes physiopathologiques evoques sont ischemiques, infectieux et inflammatoires. Perspectives et projets. – Il est important de rechercher une maladie systemique devant une perforation nasale dont l'explication n'est pas evidente. De meme, en presence d'une maladie systemique connue, l'examen des fosses nasales, meme en l'absence de signes rhinologiques, devrait etre systematique.

Resume Les anevrismes mycotiques sont rares, longtemps asymptomatiques mais potentiellement fatals en l’absence de traitement avant la phase tardive de rupture. Associes classiquement a Streptococcus pyogenes et Staphylococcus aureus, ils impliquent frequemment aujourd’hui Salmonella, notamment chez les sujets âges, immunodeprimes ou en contexte iatrogene. Souvent localises a l’aorte abdominale, ils peuvent plus rarement sieger dans d’autres localisations. Le traitement associe une antibiotherapie efficace a une resection chirurgicale des lesions infectees avec revascularisation. Nous rapportons une observation d’anevrisme poplite rompu associee a une septicemie a Salmonella bredney.

Cyclophosphamide (CYC) is not always effective in patients with scleroderma-related interstitial lung disease (SSc-ILD), hence the need for biomarkers able to predict beneficial responses to CYC therapy. We therefore assessed whether baseline alveolar concentration of nitric oxide (CANO) could predict the favourable response to CYC therapy in patients with SSc-ILD. Nineteen non-smoker patients with SSc-ILD, were enrolled and treated with 6 courses of CYC (0.75 g/m2/monthly) for lung function decline the year before inclusion, and followed-up for 2 years period. We assessed the proportion of favourable response to CYC, defined as improvement of forced vital capacity (FVC) or total pulmonary capacity (TLC) more than 10% between the inclusion and each following visit, according to the validated cut-off of CANO at 8.5 ppb identifying progressive SSc-ILD subset. At inclusion, 7 patients out of 19 had CANO >8.5 ppb. Clinical parameters were comparable between patients with high (>8.5 ppb) and low level of CANO (≤8.5 ppb). After CYC therapy, and during the follow-up, 9 out of 19 patients had favourable response to CYC therapy, 10 did not meet responder's criteria, from whom 4 patients died from respiratory failure. Six out of 7 patients with CANO >8.5 ppb at inclusion had favourable response to CYC therapy, while only 3 out of 12 patients with CANO ≤8.5 ppb responded favourably to CYC therapy (p=0.001). High level of CANO >8.5 ppb reflecting alveolar inflammation identify SSc patients with a greater chance to benefit from CYC treatment with a significant lung function improvement.

Objective.To estimate the prevalence, determine the subgroups at risk, and the outcomes of patients with systemic sclerosis (SSc) and gastric antral vascular ectasia (GAVE).Methods.We queried the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) network for the recruitment of patients with SSc-GAVE. Each case was matched for cutaneous subset and disease duration with 2 controls with SSc recruited from the same center, evaluated at the time the index case made the diagnosis of GAVE. SSc characteristics were recorded at the time GAVE occurred and the last observation was collected to define the outcomes.Results.Forty-nine patients with SSc and GAVE were included (24 with diffuse cutaneous SSc) and compared to 93 controls with SSc. The prevalence of GAVE was estimated at about 1% of patients with SSc. By multivariate analysis, patients with SSc-GAVE more frequently exhibited a diminished (< 75%) DLCO value (OR 12.8; 95% CI 1.9–82.8) despite less frequent pulmonary fibrosis (OR 0.2; 95% CI 0.1–0.6). GAVE was also associated with the presence of anti-RNA-polymerase III antibodies (OR 4.6; 95% CI 1.2–21.1). SSc-GAVE was associated with anemia (82%) requiring blood transfusion (45%). Therapeutic endoscopic procedures were performed in 45% of patients with GAVE. After a median followup of 30 months (range 1–113 months), survival was similar in patients with SSc-GAVE compared to controls, but a higher number of scleroderma renal crisis cases occurred (12% vs 2%; p = 0.01).Conclusion.GAVE is rare and associated with a vascular phenotype, including anti-RNA-polymerase III antibodies, and a high risk of renal crisis. Anemia, usually requiring blood transfusions, is a common complication.

Resume Propos. – Lˈhemophilie acquise est une affection rare, touchant plus volontiers lˈadulte, liee au developpement dˈun autoanticorps dirige contre le facteur VIII. Actualites et points forts. – Elle se caracterise par des complications hemorragiques souvent severes pouvant etre mortelles dans 15 a 20 % des cas. Cependant des remissions spontanees sont possibles et en fait, son histoire naturelle tout comme sa cause restent pour une part meconnues. Elle est souvent associee a diverses affections, notamment auto-immunes, a certaines hemopathies lymphoproliferatives ou encore au post-partum ou a certains medicaments. Le traitement comporte deux volets : dˈune part traiter les complications hemorragiques avec leur risque de morbidite et de mortalite et, dˈautre part, eliminer lˈautoanticorps. En fait aucun consensus nˈexiste pour chacune des deux parties du traitement du fait de la rarete de lˈanomalie et de lˈabsence dˈun nombre suffisant dˈetudes prospectives. En bref, la prise en charge des complications hemorragiques fait appel avant tout a des concentres de complexe prothombinique ou a du facteur VII recombinant active ou encore au facteur VIII porcin. La corticotherapie associee au cyclophosphamide permet une elimination de lˈanticorps dans pres de deux tiers des cas. Cependant dˈautres traitements ont ete proposes tels les associations prednisone et azathioprine ou cyclophosphamide et vincristine ou encore les immunoglobulines polyvalentes indiscutablement efficaces chez certains patients ou les techniques dˈimmunoadsorption. Perspectives et projets. – La rarete de lˈaffection, la diversite des contextes de survenue, lˈabsence de consensus sur la prise en charge therapeutique rendent indispensables la constitution de cohorte de traitement et de suivi dans le cadre dˈetudes prospectives multicentriques.

A peripheral neuropathy occurs rarely during the course of an inflammatory myopathy. Once the classical aetiologies of peripheral neuropathies are ruled out, the diagnosis of neuromyositis can be accepted. We report a patient with dermatomyositis who presented a peripheral neuropathy revealed by dysautonomia. The presence of associated vasculitis led us to consider that this constituted the mechanism of the neurological involvement.