C. Seinturier

Cutaneous Iontophoresis of Treprostinil in Systemic Sclerosis: A Proof‐of‐Concept Study

Ischemic digital ulcer (DU) is a serious complication of systemic sclerosis (SSc). Intravenous prostanoids are the only approved treatment for active DUs, but they induce dose‐limiting side effects and require hospitalization. Our objective was to evaluate the effect of iontophoresis (a noninvasive drug delivery method) of treprostinil in SSc patients. Three studies were conducted: a pharmacokinetic study in 12 healthy volunteers showed that peak dermal concentration was reached at 2 hours, whereas plasma treprostinil was undetected. Then, a placebo‐controlled, double‐blind incremental dose study assessed the effect of treprostinil on digital skin blood flow in 22 healthy subjects. The effect of the highest dose was then compared with that of placebo in 12 SSc patients. Treprostinil significantly increased skin blood flow in healthy subjects (P = 0.006) and in SSc patients (P = 0.023). In conclusion, digital iontophoresis of treprostinil is feasible, is well tolerated, and increases digital skin perfusion. It could be tested as a treatment for SSc‐related DUs.

Toxicité cardiaque du polidocanol : rapport d’un cas et revue de la littérature

OBJECTIVE Polidocanol foam sclerotherapy is a treatment of symptomatic venous disease. This solution is highly valued by clinicians because of its high efficacy and excellent safety profile. Systemic adverse effects are rare. Some life-threatening reactions have been reported. We report a case of respiratory and cardiac arrest, and a literature review on the cardiac toxicity of polidocanol used within and outside their licensed indications. MAIN OUTCOME MEASURES A 48-year-old woman, with a symptomatic venous disorder, CEAP grade C2, was treated by echosclerotherapy for a great saphenous vein. She developed a malaise and respiratory and cardiac arrest occurred within minutes after a 7 ml foam polidocanol injection. Cardiopulmonary resuscitation was immediately started before restoration of pulses. A literature search was done using the Medline database. RESULTS Five cases of cardiac toxicity were reported with polidocanol, but four of them were used outside their licensed indications. Because of the very suggestive chronology and the lack of any other obvious etiology, this cardiac arrest was attributed to polidocanol. Initial ST-segment elevation and negativity of anaphylaxis markers suggest a direct myocardial toxicity. CONCLUSIONS Clinicians should be aware of the possibility of little-known but potentially serious cardiac adverse reaction with polidacanol injection and be prepared to initiate cardiopulmonary resuscitation if needed.

The digital thermal hyperemia pattern is associated with the onset of digital ulcerations in systemic sclerosis during 3 years of follow-up

OBJECTIVES One of the most important skin complications in systemic sclerosis (SSc) is digital ulceration. Local thermal hyperemia (LTH) in the skin is a biphasic response to local heating involving both neurovascular and endothelial responses. Since LTH is abnormal in SSc patients, we aimed at testing whether LTH could be a prognostic tool for the onset of digital ulcers. METHODS We prospectively enrolled 51 patients with SSc. Nailfold capillaroscopy and LTH were recorded at baseline, and patients were followed for 3 years. RESULTS No patient with a LTH peak/plateau ratio ≥1 (n=19) developed digital ulcerations during the 3 year follow-up (100% negative predictive value), while 6 out of 32 patients with a LTH peak/plateau ratio <1 at enrolment presented with finger pad ulcerations within 3 years (p=0.05). In contrast, when lidocaine/prilocaine was applied to the finger pad, no relationship between thermal hyperemia and digital ulcerations was observed. CONCLUSIONS A LTH peak/plateau ratio on the finger pad greater than 1, which can easily be determined in routine clinical practice, could be used to reassure patients, whatever the subtype of SSc, about the low probability of future digital ulceration. However, the prognostic value of this parameter should be confirmed in a larger cohort.

Abnormal amplitude and kinetics of digital postocclusive reactive hyperemia in systemic sclerosis

OBJECTIVES Postocclusive reactive hyperemia is mediated by two major mediators: sensory nerves and endothelium-derived hyperpolarizing factors. We hypothesized that the skin microvascular response to 5 min ischemia would differ depending upon the hand location in patients with systemic sclerosis (SSc), primary Raynauds phenomenon (PRP) and healthy controls. METHODS Fifteen patients with SSc, 15 sex- and age-matched patients with PRP and healthy controls were enrolled. Their right hands were subjected to 5 min ischemia followed by a postocclusive hyperemia test, with local microcirculation monitoring by laser speckle contrast imaging on the dorsal face of the hand. RESULTS Postocclusive reactive hyperemia was abnormal in terms of peak and area under the curve (AUC) on all fingers except the thumb in patients with SSc and PRP compared with controls. In contrast, the kinetics of the response was longer only in SSc patients, with mean (SD) time to peak on the index, middle and ring finger were respectively 72 (58), 73 (51) and 67 (47) s for SSc; 40 (20), 40 (20) and 36 (19) s for PRP; and 34 (30), 34 (30) and 29 (24) s for controls (P=0.009 for interaction). CONCLUSIONS We observed decreased distal digital microvascular perfusion following 5 min of ischemia in patients presenting with PRP or SSc, while the kinetics was prolonged only in SSc. A dynamic assessment of digital skin blood flow using laser speckle contrast imaging following 5 min ischemia could be used as a tool to assess microvascular abnormalities in patients with Raynauds phenomenon secondary to SSc.

Une cause rare d’ischémie embolique de la main : un anévrisme isolé d’une branche de l’artère axillaire

A 48-year-old man was admitted for subacute ischemia of the right hand of sudden onset. The patient, who participated in amateur sports, had an uneventful medical history. Duplex ultrasonography revealed thrombosis of the right radial and ulnar arteries. On heparin, the clinical course was favorable and investigations to search for an embolic source revealed an aneurism of the posterior circumflex artery (arteriography). The etiological work-up was negative as was the search for other aneurismal locations. Surgical excision was carried out. Pathology examination of the surgical specimen revealed a thrombosed aneurism that had developed on an atherosclerotic plaque. Aneurisms of the posterior circumflex artery have been described in professional baseball and volleyball players, but all sports that involve repetitive movements of the arm at extension, external rotation and forced abduction can complicate such damage. Compression of the aneurismal artery by the humeral head leads to extrusion of the thrombus under pressure and to retrograde embolisation towards the leg arteries. Thus, in the same way as for hypothenar hammer syndrome, signs of distal ischemia in an athlete should lead to a search for this type of injury.

Ischémie subaiguë d'un membre inférieur et toxicité artérielle périphérique de la cocaïne chez une patiente présentant une artériopathie juvénile

Resume Une patiente de 35 ans etait hospitalisee pour ischemie subaigue de la jambe gauche compliquant une claudication de survenue recente. Il existait egalement une pâleur et une froideur des mains avec abolition des pouls radiaux. Les facteurs de risque vasculaires etaient representes par un tabagisme actif. Le bilan morphologique mettait en evidence un thrombus arteriel poplite gauche associe a des axes jambiers greles et aux membres superieurs une stenose de l’artere radiale gauche et une thrombose distale de l’artere radiale droite. Le bilan a la recherche d’une cause embolique, metabolique ou d’une thrombophilie s’averait negatif. La reprise de l’interrogatoire decelait la consommation de cannabis et la consommation recente de cocaine par prise nasale. L’evolution etait favorable sous heparinotherapie malgre la persistance plusieurs mois apres d’une ischemie d’effort des membres superieurs et d’un phenomene de Raynaud severe. Cette observation attire l’attention sur la toxicite arterielle combinee de drogues souvent consommees en association par le toxicomane. L’association tabac-cannabis est frequemment retrouvee dans les arteriopathies juveniles de type Buerger et la cocaine peut donner des lesions thrombotiques arterielles peripheriques par embole ou thrombose in situ. L’interrogatoire d’un patient porteur d’une maladie arterielle de type Buerger doit s’efforcer de rechercher la consommation d’autres toxiques associes au tabac. (J Mal Vasc 2006 ; 31 : 76-78).

Syndrome de Sneddon avec anticorps anti-mitochondries de type M5

Resume Introduction Parmi les anomalies immunologiques associees au syndrome de Sneddon figure la presence d’anticorps anti-mitochondries de type M5 (AMA-M5). Observation Chez une femme âgee de 45 ans hospitalisee pour diplopie, chez laquelle on relevait depuis plus de 20 ans des accidents obstetricaux, une ophtalmoplegie internucleaire et un livedo , le diagnostic de syndrome de Sneddon associe a un syndrome primaire des antiphospholipides (SAPL) a pu etre pose par la mise en evidence isolee d’AMA-M5. Commentaires Les AMA-M5 constituent un marqueur immunologique de SAPL au meme titre que des anticorps anti-phospholipides. Cette observation met en evidence l’interet de leur recherche en cas de forte suspicion clinique de SAPL avec normalite du test lupus anticoagulant et absence des anticorps anticardiolipide, anti-s2 glycoproteine 1 et antiprothrombine.

Thromboses aortiques « isolées » : analyse rétrospective de 10 observations

Resume Introduction Les thromboses aortiques sont le plus souvent liees a la presence de lesions atheromateuses au sein de la paroi aortique chez des patients avec des facteurs de risques cardio-vasculaires. De rares cas surviennent sur artere saine et sont alors consideres comme « isoles ». Methodologie Nous presentons une analyse retrospective de dix cas de thromboses aortiques isolees observees entre 1995 et 2004 au CHU de Grenoble. Nous avons analyse l’âge de survenue de la thrombose, le sexe des patients, les facteurs de risque cardio-vasculaire, le mode de revelation de la thrombose aortique, la localisation anatomique du thrombus et les elements du bilan etiologique effectue. Etaient exclus tous les patients avec des lesions atheromateuses de l’aorte. Resultats Le mode de revelation clinique de la thrombose etait une ischemie aigue de membre dans 8 cas sur 10. Le diagnostic etait confirme dans tous les cas par un scanner thoraco-abdominal injecte, excepte un cas ou l’echo-Doppler arteriel a permis le diagnostic initial. Dans 7 cas, la recherche d’une thombophilie pouvait etre consideree comme exhaustive, dans 8 cas avec la recherche d’un syndrome des anticorps anti-phospholipides. Deux diagnostics etiologiques ont pu etre poses : le premier cas revelait lors de la thrombose aortique une neoplasie de type adenocarcinome sans primitif retrouve, et le deuxieme etait une thrombocytemie essentielle diagnostiquee un an apres la thrombose. Huit cas sur 10 sont restes « isoles », avec un suivi moyen de 2,5 ans. Discussion On denombre dans la litterature moins d’une centaine d’observations de thrombus aortiques. Les cas survenant sur artere saine sont difficiles a denombrer et le terme de thrombus « isole » est peut-etre employe par defaut. L’hypothese d’une lesion atheromateuse focale isolee induisant un thrombus, ou des pathologies inflammatoires diagnostiquees sur l’examen anatomopathologique du thrombus l’illustrent. Les explorations morphologiques et biologiques doivent etre exhaustives, meme si elles ne suffisent pas dans la plupart des cas a poser un diagnostic. La therapeutique fait appel aux anticoagulants mais n’est pas codifiee. Le suivi clinique nous apparait comme capital devant la possible revelation de pathologies posterieurement a la survenue de la thrombose, et afin d’affiner la conduite a tenir notamment en ce qui concerne les anti-coagulants au long cours. (J Mal Vasc 2005 ; 30 : 280-90)

Paroxysmal finger haematoma - a benign acrosyndrome occurring in middle-aged women

BACKGROUND Paroxysmal finger haematoma (PFH) is an under-recognised vascular acrosyndrome with no epidemiological description to date. The aim of this work was to evaluate the prevalence, risk factors and clinical correlates of PFH in a population-based sample of subjects and to describe their semiological characteristics. PATIENTS AND METHODS This cross-sectional study of random samples of the general population in three geographic areas of France involved 802 subjects, 548 women and 254 men, aged 18 to 84 years. The diagnosis of PFH was made from a report by the subject of a history of recurrent haematoma in the fingers with a sudden, painful and unexpected occurrence. Diagnosis of associated conditions and evaluation of lifestyle variables were obtained through standardised medical interview and examination. RESULTS A history of PFH was detected in 71 subjects, with a prevalence of 1.2% in men and 12.4% in women; there was no significant regional variation. Onset before 40 years of age was rare. Besides female sex and age, no socio-economical nor lifestyle risk factors were detected. PFH was associated with Raynaud phenomenon and a history of chilblains, but no link with any health threatening disease was found. In addition to the sudden onset of pain and hematoma, the main clinical features were a frequent digital swelling during the painful attack, and their predominant location on the volar side of the first and second phalanges of the third or second fingers of the dominant hand. CONCLUSIONS PFH is a benign phenomenon, frequently found in middle-aged women, to be classified among the vascular acrosyndromes. Patients seeking medical evaluation for this disorder should be reassured.

Prévalence et sévérité de l’artériopathie oblitérante des membres inférieurs chez les patients atteints d’escarre talonnière : étude rétrospective de 42 patients

Heel pressure ulcer is a major complication in elderly hospitalized patients. The association with peripheral arterial disease (PAD) which is also a frequent disease in this population is poorly known. The aim of this study was to assess the prevalence of PAD and critical limb ischemia (CLI) in patients with heel pressure ulcer. Patients referred to the vascular medicine department for heel pressure ulcer from October 2014 to June 2015 were included in the study. The assessment of peripheral arterial disease was made with the results of ankle brachial index and/or doppler ultra sound of lower limb arteries. Toe systolic pressure and transcutaneous pressure (TcPO2) were also recorded, and the diagnosis of critical limb ischemia was made according to the TASC 2 criteria. The population was composed with 42 patients (women 43%, men 57%). The mean age was 81±11 years. Heel pressures ulcers were diagnosed in the following situations: lower limb fracture (31%), acute medical illness (21%), multiple chronic conditions (28%) and critical care unit hospitalization (7%). A peripheral arterial disease was present in 31 patients (73%), and a critical limb ischemia in 7 patients. For 18 patients, PAD was not known in their past medical history, and this was the case of 5 patients among those with critical limb ischemia. A revascularization was performed in 12 patients, and 5 patients undergo a lower limb amputation. 12 patients were died at 3 months. PAD is frequent among patients with heel pressure ulcer, and is often unknown. The functional and vital prognostic are poor, and the results of our study emphasize the importance of screening PAD in the evaluation of heel pressure ulcer risk.