Association of Fcγ receptor IIIA variant with a subset of anti-topoisomerase I-positive patients in systemic sclerosis: a descriptive pilot study.

Hypothesizing a pathophysiological role of anti-topoisomerase I antibodies (anti-topo I) through autoantibody-dependent cell-mediated cytotoxicity (ADCC) and cytotoxic effectors expressing receptors for the Fc portion of IgG in systemic sclerosis (SSc), 267 SSc patients (56 with anti-topo I and 102 with anti-centromere antibodies (ACA)) were genotyped for the functional FCGR3A-V158F polymorphism. A descriptive analysis of patients according to their clinical and immunological status and FCGR3A-158 V/F genotypes was performed using multiple correspondence analysis. This descriptive analysis revealed an association between the FCGR3A-158 VV genotype and the presence of anti-topo I. By contrast, no relationship was found between FCGR3A polymorphism and the presence of ACA. SSc patients with anti-topo I appear to be more frequently homozygous for the high-affinity FcγRIIIA-coding allele, suggesting that some autoantibodies may be pathogenic through ADCC.

[Cutaneous polyarteritis nodosa and Crohn's disease: An association not to be ignored]. / Périartérite noueuse cutanée et maladie de Crohn : une association à ne pas méconnaître.

INTRODUCTION: Cutaneous polyarteritis nodosa (CPAN) is an entity which needs to be acknowledged, since it can have a spontaneously adverse outcome. We report two cases of CPAN associated with Crohn's disease. CASE REPORTS: The first patient was suffering from Crohn's disease for 9 years when she was referred for a necrotic toe. A diagnosis of necrotizing angeitis was confirmed by histological examination of a skin biopsy. Despite systemic corticosteroids, the lesions became more severe, requiring immunosuppressive treatment. The second patient was a female patient referred with forefoot ischemia. Cutaneous histology confirmed the diagnosis of necrotizing angeitis that responded favourably to corticosteroid treatment. The patient had been diagnosed with Crohn's disease 2 months previously. CONCLUSION: CPAN differed from systemic PAN by the absence of visceral involvement. Its association with Crohn's disease, although uncommon, must be recognized as it affects treatment and monitoring.

[College of the French Vascular Medicine Teachers (CEMV) statement: Arterial Doppler waveforms analysis (simplified Saint-Bonnet classification)]. / Recommandations du Collège des enseignants de médecine vasculaire (CEMV) : analyse des flux artériels Doppler (classification de Saint-Bonnet simplifiée).

Lower extremity peripheral artery disease is a frequent disease. Arterial Doppler waveforms analysis is a key element in vascular medicine, especially to diagnose lower peripheral artery disease. Although Doppler waveforms are often used, descriptions are highly heterogeneous. This review presents the simplified Saint-Bonnet classification that is tought to vascular medicine residents in order to homogenize arterial flow description.

[Dilated cardiomyopathy, diabetes and deafness related to a mutation of mitochondrial DNA]. / Cardiomyopathie dilaté, diabète et surdité liés à une mutation de l'ADN mitochondrial.

Mitochondrial diseases may cause hypertrophic cardiomyopathy or, less commonly, dilated cardiomyopathy. The authors describe a case of a 46 year old woman with dilated cardiomyopathy associated with diabetes and deafness. This association is suggestive of the MIDD syndrome and the demonstration of metabolic abnormalities (raised serum lactic acid, abnormal lactate/pyruvate ratio) was compatible with a mitochondrial disease. This diagnosis was confirmed by finding an A3243G mutation of the mitochondrial DNA.

[Elastic stockings and compression therapy, arguments favoring more rational use]. / Contention-compression élastique, plaidoyer et proposition pour une utilisation raisonnée.

Elastic stockings and compression therapy are often considered as a major tool in the prevention and in the treatment of chronic venous insufficiency and of lymphedema. Nevertheless we must note that this therapeutic option is both underused and misused. We discuss the reasons for this paradox and the expected modes of action and pathophysiological benefits, and finally propose a prescription guide (indications, dosage, practice details) for a rational use of elastic stockings and compression therapy.

[Unilateral isolated Raynaud's phenomenon leading to diagnosis of multifocal giant-cell arteritis complicated with renal ischemia]. / Phénomène de Raynaud unilatéral isolé révélateur d'une artérite à cellules géantes multifocale (maladie de Horton) compliquée d'ischémie rénale.

We report a case of a 76-year-old woman with isolated unilateral Raynaud phenomenon revealing giant-cell arteritis with diffuse arterial lesions and bilateral renal artery stenosis. Doppler ultrasonography showed bilateral stenosis of the subclavian and axillary arteries. Angio-CT PET enlightened diffuse arterial lesions, mainly involving the aorta and the brachial and femoral arteries as well as bilateral renal ostial stenosis with right kidney ischemia. Diagnosis of giant-cell arteritis was made on the temporal artery biopsy. Corticosteroid therapy led to rapid clinical and radiological improvement. Clinical manifestations of giant-cell arteritis may be atypical. Diffuse arterial disease may exist in the absence of cephalic symptoms or significant inflammatory biological features. Ostial renal artery stenosis may induce potentially threatening renal ischemia.

Is anti-topoisomerase I a serum marker of pulmonary involvement in systemic sclerosis?

STUDY OBJECTIVE: To determine the value of the level of anti-topoisomerase I (anti-topo I) to evaluate lung involvement defined by abnormal high-resolution computed tomography (HRCT) score and pulmonary function tests (PFTs) in systemic sclerosis (SS). PATIENTS: Forty-eight patients with SS, 20 with lung involvement and 28 with no lung involvement. DESIGN: PFT measurement, HRCT scoring of lung involvement, and anti-topo I assay by enzyme-linked immunosorbent assay. Normal anti-topo I level was defined as < 30. RESULTS: There was a significant association between cutaneous extent and anti-topo I level (6.5% of patients with limited cutaneous scleroderma had abnormal anti-topo I levels vs 70.6% of patients with diffuse cutaneous scleroderma, p = 0.0001). In patients with diffuse cutaneous scleroderma, pulmonary involvement was associated with a higher percentage of abnormal anti-topo I level: 91.7% vs 20% (p = 0.010). In patients with diffuse cutaneous scleroderma, a significant association was found between the class of anti-topoII level and total lung capacity (median, 69 in patients with abnormal anti-topo I level vs 87 in patients with normal anti-topo I level, p = 0.010), between the class of anti-topo I level and HRCT score (median, 12 in patients with abnormal anti-topo I level vs 5 in patients with normal anti-topo I level, p = 0.05). CONCLUSION: Anti-topo I can be considered as a marker of lung involvement in patients with diffuse cutaneous scleroderma.

Relationship between abnormalities on high-resolution CT and pulmonary function in systemic sclerosis.

STUDY OBJECTIVES: To determine the predictive value of abnormalities on high-resolution CT (HRCT) on pulmonary disease in systemic sclerosis. PATIENTS: Fifty-two patients suffering from systemic sclerosis. DESIGN: Pulmonary disease was defined by pulmonary function test abnormalities, ie, total lung capacity (TLC) <80% of predicted value and/or diffusion of carbon monoxide (DLCO) <75% of predicted value, without any pulmonary event other than systemic sclerosis in the medical history. Patients were divided in two groups, group A with pulmonary disease (29 patients) and group B without pulmonary disease (23 patients). HRCT abnormalities were scored on whole lungs. A decision matrix was constructed to determine sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates. A receiver operating characteristic curve was constructed to determine the best compromise between sensitivity and specificity. RESULTS: HRCT total scores were higher in group A (9.0+/-4.3) than in group B (5.0+/-2.8) (p < 0.001) and they correlated with TLC (r =-0.39, p < 0.005) and DLCO (r = -0.50, p < 0.0002). An HRCT score of 7 corresponded to the best compromise between sensitivity (0.60) and specificity (0.83), with a positive predictive value of 0.82. Taking into account a value of 10 for the HRCT score increased specificity to 1 but decreased sensitivity to 0.41. CONCLUSION: A minimum score of 7 would be required to consider HRCT abnormalities in systemic sclerosis as predictive of pulmonary disease. An HRCT score of 10 makes it possible to establish the diagnosis of lung involvement severe enough to impair pulmonary function.

Protein-energy malnutrition in elderly medical patients.

STUDY OBJECTIVE: To evaluate (1) the prevalence of protein-energy malnutrition in elderly patients; (2) the changes in nutritional status during the hospital stay; and (3) (main objective) the relationship between simple nutritional parameters and short-term in-hospital mortality. DESIGN: Prospective time series at admission and on the 15th day of hospitalization. SETTING: Medical care unit in a teaching hospital. PARTICIPANTS: Consecutive sample of 324 hospitalized patients greater than or equal to 70 years (86.4% of eligible patients). Norms of measurements were obtained from a referred sample of healthy control subjects (26 males and 36 females). MAIN OUTCOME MEASURES: Mid-arm circumference, triceps skinfold thickness, serum albumin, prealbumin, and retinol-binding protein levels were measured in patients at admission and on the 15th day. RESULTS: (1) Prevalence of PEM was 30% in male and 41% in female patients. (2) Both mid-arm circumference and serum albumin level decreased over the first 15 days of hospital stay (53 patients, paired t test, P less than 0.05). Triceps skinfold thickness did not change. (3) A step-wise discriminant-function analysis determined the utility of the parameters at admission as predictors of in-hospital mortality before the 15th day. Mid-arm circumference, triceps skinfold thickness, albumin, and prealbumin levels, as well as age, are predictors of in-hospital mortality, with 73% sensitivity, 69% specificity, and 70% of correctly classified patients of both sexes. CONCLUSIONS: Parameters used are predictors for short-term in-hospital mortality of elderly patients hospitalized in an acute medical unit. The lean body mass is preferentially mobilized for energy during hospitalization.

Schnitzler's syndrome (urticaria and macroglobulinemia) dramatically improved with corticosteroids.

The authors report the case of a 65-year-old man who had an evolving case of Schnitzler's syndrome with lytic bone lesions which was unresponsive to several drugs, and which dramatically improved with small quantities of corticosteroids. Schnitzler's syndrome, first described in 1974, is defined by chronic non-pruritic urticaria, osteocondensation, and monoclonal IgM dysproteinemia without features of lymphoproliferative disease, and is associated with fever, deterioration of the general health and biological signs of inflammation. Only 22 cases of Schnitzler's syndrome have been reported hitherto and there is no known effective treatment, H1 and H2 blockers, dapsone, colchicine, chloroquine, cyclophosphamide, chlorambucil and azathioprine having proven useless in the few patients treated. Corticosteroids may be effective, however, especially against the urticaria.

Experience with immunoglobulins in thyroid autoimmunity.

The physiopathology of Graves' ophthalmopathy is poorly understood. Therefore, the best treatment of Graves' ophthalmopathy is still a matter of debate. Steroids, X-ray therapy, surgery and more recently cyclosporine, plasma exchange and somatostatine analogs have been tried. There is no doubt that we are dealing with an autoimmune process. The use of immunoglobulins has been shown to be safe and efficient.

Successful treatment of ergotism with Iloprost--a case report.

A 34-year-old woman was hospitalized for severe acute arterial insufficiency of the limbs. Overuse of ergotamine derivative was acknowledged by the patient, who had a long history of migraine headaches. An arteriogram showed diffuse arterial spasm and occlusion of right leg distal arteries. Intravenous infusion of a stable prostacyclin analog (Iloprost) was administered. Rapid and complete improvement of arteriospasm was noted within a few hours, confirmed by a further arteriogram. This appears to be one of the rare case reports of successful limb salvage by use of Iloprost for ergotism.

[Diagnosis and treatment of Raynaud's phenomenon]. / Diagnostic et traitement du phénomène de Raynaud.

Raynaud's phenomenon is a common, paroxysmal acrosyndrome, affecting about 4% of the general population. Most of the time it is a purely functional condition: Raynaud's disease. However, in rare cases, there is an organic cause and it is then known as Raynaud's phenomenon. In view of its prevalence, a simple, atraumatic, low cost and reliable work-up should be performed to guide diagnosis. This is based on the findings of clinical examination, capillaroscopy, antinuclear factor antibody tests and X ray of chest and hands. Only a few cases will require more specialised investigation with arteriography and autoimmune studies. The commonest causes are arterial and connective tissue diseases, especially scleroderma. However, occupational hazards, toxic and iatrogenic drug-induced aetiologies should not be overlooked. With the exception of patients who have a curable underlying disease, most cases require vasodilator therapy, the keystone of which over the last decade has been the calcium channel blockers. Only patients who are severely handicapped by their acrosyndrome should be given drug therapy.

[Serologic diagnosis and epidemiology of acute delta hepatitis in Indre-et-Loire]. / Diagnostic sérologique et épidémiologique des hépatites aiguës delta en Indre-et-Loire.

A 6 years retrospective study (1981-1986) of 153 consecutive cases of HBsAg positive acute hepatitis was carried out to assess the prevalence of delta virus infections in the Indre-et-Loire a district of the Loire Valley in France. Diagnostic value of the various serum markers of delta infection, i. e. HDAg, anti-HD and anti-HD IgM, were evaluated using immunoenzyme assays. During the survey, 22 cases of delta hepatitis were diagnosed (12 co-infections, 10 superinfections). They all involved young adults, 21 of them were drug-addicts, and one young woman was the consort of a drug-addict. In Indre-et-Loire, delta virus infection was responsible for half of acute HBsAg positive hepatitis among drug-users in the last 3 years of our study. Clinical and biological features of acute delta hepatitis were compared to those of the other HBsAg positive hepatitis: two cases of fulminant hepatitis occurred among the 12 co-infections; 4 of 6 superinfection that could be followed up to 6 months developed biopsy-proven chronic active hepatitis. Delta Ag was found constantly during the first week of the disease, its disappearance was always followed by a seroconversion to anti-HD after four weeks. Anti-delta IgM was an inconstant and late marker: it was detected within the first 4 weeks in only one case (a co-infection); it persisted only in superinfections. Our study shows that delta Ag is an efficient serum marker for the early diagnosis of acute delta hepatitis.

[Diabetic arteriopathy. Microcirculation, an inevitable therapeutic objective]. / Artériopathie diabétique. La microcirculation, un objectif thérapeutique incontournable.

The most severe stages of arteriopathy often involve multifocal macrovascular lesions leading to defective perfusion of the distal tissues and subsequent dysfunction of the microcirculation. Diabetic autonomous neuropathy facilitates and aggravates this endothelial dysfunction. Loss of vasomotricity, platelet and white cell activation, and cytokine release lead to an obstruction of the capillaries and alteration or even destruction of the endothelium. At this stage, the lesions are irreversible and tissue vitality is definitively compromised. The goal of medical treatment is to delay the development of dysfunction and subsequent destruction of the microcirculation before, during and after restoration of sufficient flow through the macrocirculation lesions by angioplasty and/or surgery. Extrapolating from in vitro and animal studies, two mediators, EDRF (NO) and prostacycline, could theoretically inactivate inappropriate activated cells and re-establish flow. Besides their vasodilator proprieties, NO and prostacycline have a synergetic inhibitory effect on platelet and leukocyte activation. The role of platelet antiaggregates and heparins in this stage of severe chronic ischemia remains to be determined. The relative failures of therapeutic drug trials conducted since the end of the eighties demonstrates the importance of intervening before the microcirulation disorders become too severe. Until new compounds are developed, therapeutic progress can be achieved by more precise and earlier detection of alterations in the microcirculation to enable optimal management of arteriopathy of the lower limbs with surgery or angioplasty.

[Peripheral vascular complications of beta-blocking agents]. / Les complications vasculaires périphériques des bêta-bloquants.

Beta-blocking agents may induce vascular syndromes related to environmental temperature, accentuation of arterial diseases, gangrene of the extremities. Incidence and severity are variable with beta-blocking agent's properties: cardioselectivity, intrinsic sympathomimetic activity, cardiac depression, and with the patient's disease. The risk of complication is greater with hypertension disease because of the reduction of arterial compliance and quantitative and qualitative alterations of adrenergic receptors.

[Study of the plethysmographic amplification factor during vasodilator treatment. Healthy subject versus primary Raynaud phenomenon]. / Etude du facteur d'amplification en pléthysmographie sous traitement vasodilatateur. Sujet sain versus phénomène de Raynaud primaire.

Digital arterial circulation before and after administration of a vasodilator orally was explored by mercury gauge pulsed plethysmography and photoplethysmography in 12 patients with primary Raynaud's phenomenon and results compared with those of 10 healthy volunteers. The amplification factor F, ratio of amplitude in reactive hyperemia over amplitude at rest was determined in the index before and after 8 mg daily of dihydroergokryptine over 4 weeks. Before treatment, for each of the two plethysmographic technics, a significant increase in mean factor F values was noted in the patients with Raynaud's phenomenon when compared with healthy controls. This is due to a decline in digital arterial flow at rest. Using the mercury gauge plethysmograph, a significant reduction in factor F was observed after vasodilator treatment corresponding to an increase in digital flow at rest without increase in flow during hyperemia. Using photoplethysmography, no significant variation in factor F was noted after treatment. Mercury gauge plethysmography, which measures global digital blood flow appears to be a more sensitive method than photoplethysmography, which measures dermal and hypodermal blood flow, for follow-up of effects of vasodilator treatment on Raynaud's phenomenon.

[White clot syndrome. Arterial and venous thromboses during heparin therapy with thrombopenia after bone surgery]. / Le syndrome du caillot blanc. Thromboses artérielles et veineuses sous héparinothérapie avec thrombopénie après chirurgie osseuse.

The authors observed 9 patients submitted to prophylactic treatment with adequately doses subcutaneous heparin, for orthopaedic or traumatic surgery (chiefly total hip arthroplasty) who presented between the 7 and 9 day after starting heparin therapy, thrombotic complications including recurrent arterial occlusions and venous thrombosis associated with a profound thrombocytopenia, with a maximum platelet count below 30,000 per cubic millimeter. A rapid increase of platelet count after heparin withdrawal is observed, and the profound thrombocytopenia seems to be immune mediated with heparin dependent platelet antibodies, in most of the reported cases. We propose a platelet count for all surgical patients with heparin therapy, and if a thrombocytopenia appears, with a platelet count in the range of: 80,000 clinical inspection and platelet aggregation investigations, and immediate cessation of heparin therapy at 30,000 platelets/mm3.

[Paradoxical embolism: a cause of cerebral stroke in the young subject]. / L'embolie paradoxale: une cause d'accident ischémique cérébral du sujet jeune.

We report the case of a 45 year old patient who presented ischemic stroke due to the migration of a sural thrombus through a patient foramen ovale (PFO) during a Valsalva manoeuvre. The presence of PFO should be systematically evoked in case of ischemic events, especially stroke in younger adults. The diagnosis is facilitated by two-dimensional contrast echography with intravenous administration of an echo-detectable contrast agent. The clinical context and the origin of the venous thrombus in a superficial vein which remained during a stripping procedure with migration through the communicating veins of the leg were exceptional.