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The aim of this study was to describe special features of patients with systemic sclerosis (SSc) diagnosed after the age of 70.This is a retrospective study of patients aged above 70 years at the time of diagnosis of SSc and followed at an internal medicine unit between 2000 and 2015. Co-morbidities and clinical characteristics were analyzed, as well as survival at 1, 2 and 3 years.Of 246 patients, 27 (11%) were included (89% women, 96% Caucasians, age 78.3±4.5 years). Synchronous cancer was noted in 3 patients. SSc was mostly limited cutaneous only (24/27), with telangiectasia (63%), gastroesophageal reflux (59%) and digital ulcers (22%), and was associated with anti-centromere antibody (69%). Interstitial lung disease was not frequent (29%). Pulmonary arterial hypertension (PAH) was suspected at diagnosis of SSc in 14 cases (52%), but only 5 patients had undergone heart catheterization, with severe PAH in 3 cases. Survival at 1 and 3 years was 85.2% and 66.7%, and was worse in the case of suspected PAH, at 78.6% and 57.1% respectively.Cases of SSc diagnosed after 70 years are mostly limited cutaneous forms. Suspicion of PAH is frequent, and PAH may be the main initial sign of the disease for patients at this age. There may be association with synchronous cancer. Survival is poor.

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.

Summary Background Imatinib mesylate is a potent inhibitor of platelet-derived growth factor and transforming growth factor-β signalling pathways which may play a role in systemic sclerosis (SSc)-associated skin changes. Objectives We aimed primarily at assessing the efficacy of imatinib mesylate in scleroderma skin fibrosis. Methods We performed a phase II double-blinded trial on patients with scleroderma with either morphoea involving > 20% of body surface area or SSc with extensive skin involvement: modified Rodnan Skin Score (mRSS) ≥ 20/51. Each patient was randomized to receive either imatinib mesylate 400 mg or placebo daily for a total of 6 months, and then was followed up 6 months after therapy discontinuation. Skin fibrosis was assessed by mRSS and measurement of the dermal thickness using skin biopsies performed at inclusion and at 6 months of treatment. In addition, quality of life (Dermatology Life Quality Index and modified Health Assessment Questionnaire for Scleroderma) was recorded at each visit, and pulmonary function before and after intervention. Results Twenty-eight patients were included in the study with a mean age of 48·9 years (range 30–71): 25 had a diagnosis of a SSc and three of diffuse cutaneous scleroderma. Demographic data, frequency of organ involvement of SSc and mRSS were comparable between groups. At 6 months, the proportion of variation of mRSS from inclusion was not statistically significantly different between the two groups (median +0·10 in imatinib group vs. −0·16 in placebo group, P = 0·098). Similarly, changes in dermal thickness, quality of life and diffusion capacity for carbon monoxide were not significantly different between groups. Conclusions This study failed to demonstrate the efficacy of imatinib 400 mg daily to improve skin fibrosis of diffuse scleroderma after 6 months of treatment based on validated outcome measurements.

Systemic lupus erythematosus (SLE) and small-sized vessel vasculitis are usually two distinguishable autoimmune diseases. However, a vasculitis may be found in the course SLE but rarely corresponds to an ANCA-associated vasculitis (AAV). We report four cases of de novo SLE associated with AAV, our aim being to discuss the clinical significance of this association. We included four patients fulfilling the criteria for both SLE and AAV and followed in two different university hospitals between 1996 and 2009. In light of a 20-year literature review (25 described clinical cases), we discussed the etiopathogeny of such an association. All patients presented a severe renal involvement (creatininemia ranging from 120 to 370 μmol/l) and thrombopenia (ranging from 45,000 to 137,000 platelets/mm(3)). The other main clinical symptoms were arthritis (n = 3), serositis (n = 2) and intra-alveolar hemorrhage (n = 2). An inflammatory syndrome was noticed at diagnosis in all cases. ANCAs were MPO-ANCAs in all cases. Two out of these four patients were also diagnosed with antiphospholipid syndrome. The frequency of this association seems not fortuitous. Although the etiopathogenic mechanisms of such an association remain to be more precisely described, several clinical, histological and immunological features support the hypothesis of the existence of a SLE-AAV overlapping syndrome. Moreover, clinicians must be aware of such an overlapping syndrome, notably because its initial presentation can be very severe.

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.

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.

Dear Editor, Polymyalgia rheumatica (PMR) is frequently associated with giant cell arteritis (GCA). It has rarely been reported as a paraneoplastic syndrome. We report a case of occult Hodgkin’s lymphoma presented as PMR. After negative results with large and costly investigations, [(18)F]-FDG positron emission tomography (PET) helped with the diagnosis. A 56-year-old woman, without any significant disease, presented with polyarthralgia. She had, for 6 months, rhizomelic pains associated with fever (38.5°C). She denied weight loss or sweating. Physical examination also revealed myalgia and finger tenosynovitis. There was no adenopathy or hepatosplenomegaly. Laboratory analysis revealed 8.8 g/dl haemoglobin and a leukocyte count of 16,600/mm. C-reactive protein was elevated at 97 mg/l. Creatine phosphokinase was normal. Blood cultures and serology for cytomegalovirus, Epstein–Barr virus, Mycoplasma pneumoniae, brucellosis, hepatitis virus and human immunodeficiency virus were negative, as were antinuclear and anticytoplasmic neutrophilic antibodies. Chest X-ray, echocardiography and total computed tomography were normal. Gastro-duodenal and pulmonary fibroscopy was negative. Bone marrow aspiration, temporal artery, salivary glands and osteomedullar biopsies were negative. A diagnosis of PMR was given. Steroids were started at 20 mg/day but were not effective. Prednisone 1 mg/kg/day controlled symptoms within 24 h of treatment and was effective during the first 4 months. As the patient remained dependent on high-dose steroids (prednisone 20 mg/day), biological and radiological tests were performed a second time. Since they were normal, PET was performed. It showed a single cervical hypermetabolic fixation due to subclinical adenopathy (Fig. 1). A surgical biopsy diagnosed a nodular lymphocytepredominant Hodgkin’s lymphoma. As a result of this localised Hodgkin’s lymphoma, ABVD chemotherapy was begun (doxorubicin, bleomycin, vinblastine, dacarbazine), associated with steroid withdrawal. Chemotherapy improved articular symptoms and led to 3 years complete remission of both haematological disease and paraneoplastic syndrome. Paraneoplastic syndromes are rare and generally associated with solid tumours. Hypertrophic osteoarthropathy, acute polyarticular polyarthritis, seronegative rheumatoid arthritis and Remitting Seronegative Symmetrical Synovitis with Pitting Edema are the most frequently reported. Classical PMR is usually associated with giant cell arteritis. In view of an unusual presentation (weight loss, fever or corticodependency), neoplasia has to be carefully considered, because PMR without GCA can precede neoplasia for many months [1]. Indeed, paraneoplastic PMR occurs during solid neoplasia and myelodysplastic syndromes but has been reported rarely in the course of lymphomas. To our knowledge, only two cases have been reported in the literature [2]. PET might be useful in paraneoplastic syndromes to screen for primitive neoplasia [3–5]. Even though PET has been used effectively in neurological C. Durant (*) :B. Hervier :A. Masseau :M. Hamidou Service de Medecine Interne, CHU Hotel Dieu, 1, place Alexis Ricordeau, 44093 Nantes Cedex, France e-mail: Cecile.durant@chu-nantes.fr