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Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD). Data on use of prostanoids in this particular subset of patients are lacking. We aimed to describe the characteristics of patients with PAH-CTD treated with prostanoids and the outcomes under treatment.In this multicenter retrospective study, all patients treated with prostanoids since 2006 were included. Data on PAH and CTD were collected at the time of prostanoid introduction and under treatment.Twenty-one patients were included, of whom 20 (95%) had limited cutaneous systemic sclerosis. Nineteen patients were treated with oral monotherapy or combination before addition of prostanoid. Treprostinil was the most used molecule (57% of patients). At the time of prostanoid introduction, 90% of patients were considered at high risk for death. Among patients who had right heart catheterization during follow-up, there was no significant difference in haemodynamics. No extrarespiratory worsening of the CTD was reported. The 1-year survival under prostanoid was 62%. In univariate analysis, NYHA functional class was associated with survival under treatment.This study provides original data on use of prostanoids in a cohort consisting mainly of systemic sclerosis. It underlines the difficulty to achieve a standardized assessment in this subset of patients. Safety profile was comparable with data reported in idiopathic PAH.

Pharmaceutical prescription in systemic sclerosis is guided by national and international recommendations. This study's primary objective was to describe and analyze these prescriptions among patients of our cohort. We also aimed to assess drug compliance among our patients.This is a monocentric observational study on two cohorts of patients with systemic sclerosis; a primary cohort comprising ambulatory patients, who were prospectively included, with exhaustive prescription's data collection; and a secondary cohort included patients asked to fill in a self-questionnaire on treatment compliance.The main cohort included 157 patients, including 31 cases of diffuse systemic sclerosis. A vasodilator drug for Raynaud's phenomenon was prescribed in 75 patients (47.9%) and a specific treatment for pulmonary arterial hypertension in 10 patients (6.4%). Immuno-modulators/immunosuppressants was prescribed in 62 patients (39.5%), who received prednisone (n=37, 23.6%), mycophenolate mofetil (n=14, 8.9%), hydroxychloroquine (n=12, 7.6%) and colchicine (n=22, 14%). Treatment for "gastro-intestinal tract involvement" was prescribed for 106 patients (67.5%) and treatment of a scleroderma renal crisis with an angiotensin-converting enzyme inhibitor for 6 patients (3.8%). Among the 42 patients in the secondary cohort, 21.4% reported a good compliance, mostly older patients (P=0.045) or those who had not experienced adverse events (P=0.009).This study provides original real-life data illustrating the heterogeneity of prescription habits in systemic sclerosis. As previously reported, treatment compliance was insufficient.

Introduction L’hypophosphoremie (hPho) est une anomalie biologique rare definie par un seuil de phosphore Observation Une patiente de 19 ans etait hospitalisee pour une boulimie evoluant depuis 3 ans, avec episodes de vomissements, d’utilisation de laxatifs et une potomanie avec un IMC a 17 kg/m2. Son traitement comprenait une supplementation calcique, une pilule œstroprogestative et des complements alimentaires. Elle presentait une anemie a 9,3 g/dl normocytaire (VGM a 85,5 fL). Le bilan retrouvait une denutrition : hypoprotidemie avec hypoalbuminemie a 32 g/L, une ferritine a 8 yg/L, une carence en vitamine D3. Les dosages de B12, folates, la calcemie, le bilan hepatique, le ionogramme et la fonction renale etaient normaux. La phosphoremie etait normale a 1,29 mmol/L. Une perfusion de 500 mg de CMF etait realisee. Six jours apres la perfusion, l’ionogramme montrait une hypophosphoremie a 0,55 mmol/L isolee. Le ionogramme urinaire retrouvait une phosphaturie a 15,6 mmol/L, une creatininurie a 6,1 mmol/L soit un taux de reabsorption du phosphore abaisse a 67 % (norme > 85 %). Le PH urinaire etait normal a 6 sans glycosurie, de meme que la PTH. Une supplementation en phosphore etait debutee par phosphoneuros 100 gouttes matin et soir et la supplementation par fer oral a ete reprise, permettant une normalisation du bilan en 1 mois. Quatre de nos patients recevant des perfusions de CMF sur les 3 mois suivants ont developpe une hypophosphoremie entre parfois profonde, resolutive par supplementation orale en phosphore. Discussion Les effets indesirables de la CMF tels que les cephalees, les nausees ou les reactions au point d’injection sont desormais bien connus. Les prescriptions croissantes de ce traitement en raison de son efficacite et sa duree d’injection courte ont permis l’identification de nouveaux effets indesirables notamment biologiques a type d’hPho qui sont desormais bien documentes. Fierz et al. rapportent un cas similaire d’hPho severe a 0,18 mmol/L chez une jeune femme presentant un trouble du comportement alimentaire [1] . Ils suggerent d’augmenter les apports alimentaires en phosphate avant et au cours de la supplementation martiale intraveineuse et d’utiliser la CMF avec prudence chez les patients presentant une malnutrition. Klein et al. rapportent un cas d’hPho chez un patient suivi pour une maladie de Crohn recevant des perfusions regulieres de CMF ayant developpe une osteomalacie ayant regresse apres arret des perfusions et la supplementation en phosphore [2] . Ils soulevent ainsi le probleme du risque d’osteomalacie chez les patients recevant des perfusions intraveineuses de fer de facon reguliere et presentant des hypophosphatemie severe et asymptomatique. Zoller et al. insistent egalement sur ce risque d’osteomalacie et precisent le mecanisme qui serait en lien avec une augmentation de l’excretion renale du phosphore mediee par le FGF23 des fibroblastes [3] . Il semblerait que cet effet indesirable soit plus specifique au CMF puisqu’un essai clinique randomise multicentrique comparant ferumoxytol versus CMF mettait en evidence une hypophosphatemie dans 0,4 % dans le groupe ferumoxytol et 38,7 % dans le CMF avec une diminution du taux moyen de phosphore de 40 % a 2 semaines dans le groupe CMF. Conclusion L’hypophosphoremie est un effet indesirable frequent et peu connu sous CMF qu’il convient de depister du fait du son caractere asymptomatique et des complications potentielles notamment l’osteomalacie.

Resume Introduction Il existe une discordance entre le faible nombre de cas d’atteintes cardiaques symptomatiques au cours de la granulomatose de Wegener (GW) rapportes dans la litterature et la frequence de ces atteintes dans les series autopsiques. Observations Quatre observations de GW avec manifestation cardiaque sont rapportees, associees a une atteinte des voies aeriennes (trois fois), renale (trois fois) ou pulmonaire (trois fois). Il s’agissait d’une cardiomyopathie dilatee chez deux patients, d’un bloc auriculoventriculaire complet avec pericardite (un patient) et d’une myopericardite (un patient). Un patient etait asymptomatique. Chez trois patients, l’atteinte cardiaque etait contemporaine de la decouverte de la GW. L’evolution etait defavorable pour trois patients. Conclusion La frequence des manifestations cardiaques dans la GW est probablement sous-estimee en raison de la grande variabilite de la presentation clinique. Ces manifestations sont associees a un mauvais pronostic. Un depistage cardiologique (clinique, electrocardiographique et echocardiographique) systematique et regulier est donc necessaire.

Resume Introduction La face est une localisation frequente de la sclerose cutanee au cours de la sclerodermie systemique. Les principales manifestations stomatologiques comprennent la limitation de l’ouverture buccale, la xerostomie, l’atrophie cutanee, la nevralgie du V3. L’objectif de cette etude est de decrire les manifestations buccofaciales des patients sclerodermiques issus de notre cohorte. Methodes Entre mars et octobre 2006, une consultation de stomatologie a ete incluse dans le suivi systematique des patients sclerodermiques vus en consultation ou en hopital de jour de medecine interne et de dermatologie. Chaque patient a fait l’objet d’un recueil de donnees demographiques, cliniques et biologiques. Le recueil comportait la mesure de l’ouverture buccale, les tests au sucre et de Schirmer, l’analyse de l’orthopantomogramme, ainsi qu’une evaluation du retentissement des symptomes sur la qualite de vie par echelle visuelle analogique (EVA entre 0 et 10). Resultats Cette etude a inclus 30 patients (87 % de femmes, âge moyen 58,6 ± 13,6 ans). La sclerodermie systemique (cutanee limitee n = 20, diffuse n = 10) evoluait depuis huit ans en moyenne. Les manifestations buccofaciales identifiees etaient les suivantes : atrophie cutanee (n = 28), rhagades peribuccales (n = 25), telangiectasies (n = 21), limitation de l’ouverture buccale (n = 20), xerostomie (n = 20), xerophtalmie (n = 16), elargissement du ligament alveolo-dentaire (n = 10), erosions osseuses (n = 2), nevralgie du V3 (n = 1). La xerostomie etait davantage percue comme genante (EVA moyenne = 3,8) que la limitation de l’ouverture buccale (EVA moyenne = 2,6). La xerostomie, decrite comme le second symptome le plus genant de la sclerodermie, etait significativement associee a la forme cutanee limitee (p = 0,045) et a la presence d’anticorps anticentromere (p = 0,002). La limitation de l’ouverture buccale etait correlee a l’atteinte œsophagienne (p = 0,025). Conclusion Chez des patients sclerodermiques vus en consultation de stomatologie, les manifestations buccofaciales apparaissent frequentes et occasionnent une gene fonctionnelle majeure dominee par la limitation de l’ouverture buccale, souvent associee a une atteinte œsophagienne. La xerostomie est frequente et volontiers observee dans les formes limitees avec anticorps anticentromeres. L’evolution des anomalies radiologiques a type d’elargissement du ligament alveolo-dentaire (33 % des cas) ou d’osteolyse (7 %) est mal connue.

Jaccoud's arthropathy (JA) is a chronic and non-erosive deforming arthropathy, usually affecting the hands. JA pathophysiology is poorly known but involves periarticular structures such as tendons and the joint capsule. JA is associated with various conditions including the connective tissue disease, especially systemic lupus erythematosis. JA has been rarely described and studied in systemic sclerosis.We report the clinical histories of 3 patients with systemic sclerosis (ScS) who developed JA. One patient had a systemic limited disease and the 2 others a cutaneous limited disease ; mean age of the patients was 79.3 years. Systemic sclerosis was diagnosed respectively 19, 1 and 21 years prior to the development of JA. One of the 3 patients had a past clinical history of discoid lupus. For 1 out of the 3 patients, JA appeared whereas the ScS was completely stable. The disease was still active in the 2 remaining patients, with concurrent pulmonary hypertension diagnosis. Deformities increased during years (Z thumbs, ulnar deviation), leading to mild to severe disability. No benefit from either prednisone (n=2) or a combination of prednisone and methotrexate (n=1) was obtained.We described 3 cases of Jaccoud's arthropathy among our scleroderma cohort of 296 patients (1%). This arthropathy worsens hand functional disability. Its pathophysiology is unknown and optimal therapeutic approach remains to establish.

Resume L’antithrombine (AT) appartient a la famille des inhibiteurs de serine protease. Son deficit constitutionnel est fortement thrombogene, notamment sur le plan veineux. Le deficit peut etre soit quantitatif (type I) soit qualitatif (type II) et differentes mutations sont desormais decrites. Le deficit de type II heparin binding site (HBS) correspond a une anomalie de liaison de l’AT a l’heparine. Ce deficit, a l’etat homozygote, est souvent lie a des manifestations thromboemboliques veineuses recidivantes. De tres rares cas de thromboses arterielles recidivantes sont decrits, principalement chez des enfants ou adultes jeunes. Nous rapportons l’observation d’une jeune patiente presentant des thromboses arterielles recurrentes dans le cadre d’un deficit de type II de type HBS, avec presence de la mutation Leu99Phe a l’etat homozygote deja rapportee dans la litterature. Cette observation illustre l’indication du bilan biologique de thrombophilie chez des patients jeunes, presentant des thromboses arterielles inexpliquees.

Clinical reasoning and treatment challenges within the scope of general practice led to the development of an internal medicine assistance line provided by Nantes University Hospital. The primary outcome of this study was to describe callers' profile, their requests and answers provided.A prospective, cross-sectional, observational, descriptive study was undertaken. For each call were identified the calling physician, her/his specialty and work setting, the call's object and adequacy, the answer provided, the time needed to connect with the assistance line, the time devoted by the internal medicine physician to provide an answer to the request, and whether the assistance line prevented a visit to the emergency room. Each calling physician was then called back to obtain demographic and professional characteristics, and data relating to the call and to the assistance line.Sixty-three days were analyzed and 276 calls identified. The 237 identified calling physicians were mainly females (54%, n=93), with a mean age of 46 years, graduated from Nantes University (65%, n=86), practicing ambulatory general medicine (69%, n=164) in Loire-Atlantique department area (82%, n=176) for a mean duration of 15 years. Calls were mostly associated with diagnostic challenges (61%, n=166) concerning clinical issues (57%, n=155). A sole telephone advice was the main type of answer provided (56%, n=147) and a visit to the emergency room was prevented for 17% of calls.The assistance line activity is adequate with its missions and seems to facilitate patients' healthcare delivery advocating for the development of similar structures in other units. Improvements relating to the information, availability and physicians' training should be considered.

A few cases of sarcoidosis have been reported in the course of chronic hepatitis C, with or without alpha-interferon treatment. We report a 54-year-old woman who presented a typical sarcoidosis in this context. The sarcoidosis involved skin, lungs and eyes. There are data in the literature supporting a pathogenic link between alpha-interferon and sarcoidosis: alpha-interferon possessing a non-specific immunologic inductor. The treatment of the sarcoidosis in this context is difficult and has to be adjusted to both the severity of the sarcoidosis and the viral hepatitis. Although sarcoidosis induced by alpha-interferon is rare, clinicians must be aware of this association.

Whatever their aetiology, monoclonal gammopathies can be associated to several clinical features. Mechanisms are various and sometimes unknown. Skin is frequently involved and may represent a challenging diagnosis. Indeed, skin manifestations are either the presenting features and isolated, or at the background of a systemic syndrome. Our objective was to review the various skin manifestations that have been associated with monoclonal gammopathies.

Autoimmune neutropenias (AIN) are classically divided into primary AIN and secondary AIN. The latter are associated with autoimmune disorders, hematologic malignancies, primary immune deficiencies, drug exposure or infections. In this review we will focus on the major aetiologies of AIN, their differential diagnosis, the various methods in biological diagnosis, and the treatment.

Antithrombin (AT) is a natural anticoagulant and serine protease inhibitor. Hereditary AT deficiencies are uncommon and are associated with a higher risk of venous thrombo-embolism (VTE) compared to other thrombophilias. They are either quantitative (type I) or qualitative (type II) and various mutations have been reported. The II HBS deficiency is caused by a defect in the heparin-binding region (HBS) of AT. This homozygous deficiency increases the risk of VTE. The association with arterial thrombosis is weak but a few cases have been reported. We report a 20-year-old female with recurring arterial thrombosis associated with an AT type II HBS deficiency, due to a homozygous mutation Leu99Phe. In young patients, with recurrent and unexplained arterial thrombosis, a biologic thrombophilia has to be comprehensively searched.

Discordance exists between the results of post-mortem studies and the low number of clinical reported cases of cardiac involvements in Wegener's granulomatosis.Data from four patients were studied retrospectively. Three patients had associated airway localization and three had kidney involvement. All patients had positive test for anti-PR3 antineutrophil antibodies. Two patients presented with dilated cardiomyopathy (one with terminal cardiac failure), another patient with complete atrioventricular block and pericarditis, and the remaining one with myopericarditis. One patient was asymptomatic. For three of these patients, the cardiac manifestations were contemporary of the diagnosis of Wegener's granulomatosis and had a severe disease course.Cardiac events in Wegener's granulomatosis are probably underestimated, given the various type of heart damage and the clinical presentation. Cardiac involvement seems to be associated with a poor prognosis. Thus, we recommend systematic and regular cardiac assessment in the follow-up of patients with Wegener's granulomatosis.

Relapsing polychondritis (RP) is a rare disorder characterized by recurrent inflammatory episodes involving various cartilages. The clinical course of RP is variable, and dermatologic manifestations are uncommon. We report a 73-year-old patient who presented with a neutrophilic dermatosis (Sweet's syndrome) as the initial manifestation of RP. There was no evidence for a myelodysplastic syndrome, as it has been previously reported with RP, but the patient was followed-up for an indolent and untreated chronic lymphocytic leukaemia. Complete remission was obtained with oral corticosteroids. This report highlights the clinical spectrum of the RP.

A few cases of sarcoidosis have been reported in the course of chronic hepatitis C, with or without alpha-interferon treatment. We report a 54-year-old woman who presented a typical sarcoidosis in this context. The sarcoidosis involved skin, lungs and eyes. There are data in the literature supporting a pathogenic link between alpha-interferon and sarcoidosis: alpha-interferon possessing a non-specific immunologic inductor. The treatment of the sarcoidosis in this context is difficult and has to be adjusted to both the severity of the sarcoidosis and the viral hepatitis. Although sarcoidosis induced by alpha-interferon is rare, clinicians must be aware of this association.

The face is frequently involved in systemic sclerosis. The main stomatologic manifestations include limited mouth opening, xerostomia, skin atrophy, trigeminal neuralgia. The objective of this study was to describe oral and facial manifestations observed in scleroderma patients from our cohort.Between March and October 2006, a stomatologic consultation was included in the follow-up of scleroderma patients seen during consultation or daily hospital in internal medicine or dermatology units. Demographic, clinical and biological data were collected. Stomatologic examination comprised measure of the mouth opening, sugar's and Schirmer's tests, orthopantomogram analysis, and evaluation of the repercussion of symptoms on quality of life using a visual analogical scale (VAS between 0 and 10).This study included 30 patients (women 87 %, mean age 58.6 + or - 13.6 years). Mean duration of systemic sclerosis (n=20 limited cutaneous form, n=10 diffuse form) was eight years. Stomatologic manifestations were: skin atrophy (n=28), peribuccal rhagades (n=25), telangiectasia (n=21), decreased mouth opening (n=20), xerostomia (n=20), xerophtalmia (n=16), periodontal ligament space widening (n=10), bone resorptions (n=2), trigeminal neuralgia (n=1). Xerostomia was considered more discomforting (mean VAS=3.8) than decreased mouth opening (mean VAS=2.6). Xerostomia was the second more discomforting sign of scleroderma and was significantly associated to the limited cutaneous form (p=0.045) and to anticentromeres antibodies expression (p=0.002). Decreased mouth opening was correlated to oesophageal involvement (p=0.025).Oral and facial manifestations are frequently observed in scleroderma patients. These manifestations lead to major functional discomfort, mainly due to decreased mouth opening that seems to be frequently associated to oesophageal involvement. Xerostomia is also frequent and is commonly observed in anticentromere antibodies positive cutaneous limited forms of systemic sclerosis. Evolution of radiographic abnormalities like periodontal ligament space widening (33 % of cases), or osteolytic lesions (7 %) is poorly known.