[A study of 19 cases of allergy to heparins with positive skin testing]. / Étude de 19 cas d'allergie aux héparines prouvée par des tests cutanés.

BACKGROUND: Allergic hypersensitivity to unfractioned or low-molecular-weight heparins is uncommon but is known, and in particular the most common form is localized dermatitis, although such cases have seldom turned into maculopapular exanthema. Since cross-reactions with other heparins are frequent, identification of therapeutic alternatives is essential. PATIENTS AND METHODS: This retrospective study included patients referred to the Department of Dermatology and Allergology at Tenon Hospital between 2000 and 2012 with suspicion of allergy to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) and sensitized to at least one heparin (i.e. positive skin tests to at least one heparin). The heparins and hirudins used were tested in the forearm by means of intradermal skin tests. All patients were contacted in 2012 to establish whether they had used some form of heparin since the cutaneous allergy tests. RESULTS: Nineteen patients had at least one positive skin test for heparin; 1 patient had presented anaphylactic shock, while 18 others had presented localized eczema (12) or generalized dermatitis (6). The heparin most often responsible for these adverse reactions was enoxaparin (13/19). An LMWH was responsible in most cases (18 vs. 1 with UFH). Of these 18 patients, 16 also presented positive skin tests for UFH, 9 for synthetic heparinoid and 1 for hirudin. 11/19 patients were tested for fondaparinux (a synthetic pentasaccharid) and all had negative skin tests. 5/7 patients with negative skin tests had taken fondaparinux without any visible reaction, whereas 2 who also tested negative experienced localized eruption at the injection site. DISCUSSION: Our results underline the greater frequency of delayed hypersensitivity reactions compared with immediate reactions to heparins. Skin tests can help to identify substitution molecules. Fondaparinux might be an alternative but certain diagnosis relies on rechallenge.

Molecular Beams with Energies above One Electron Volt.

By using as sources supersonic jets of hydrogen or helium containing small concentrations of heavier molecules we have been able to obtain molecular beams with kinetic energies of the heavy molecules well into the range above I electron volt. A variety of molecules have been successfully accelerated. Intensities of 10(16) to 10(17) heavy molecules per steradian-second have been achieved at these high energies.

Comparison of two basophil activation markers CD63 and CD203c in the diagnosis of amoxicillin allergy.

BACKGROUND: To confirm allergy to beta-lactam (BL), a basophil activation test in flow cytometry based on CD63 up-regulation was described. CD203c is a more recent basophil activation marker and up to day there is no consensus about which marker is the more sensitive one. CD203c has not yet been evaluated in the diagnosis of BL allergy. OBJECTIVE: The aim of the study was to compare the reliability of CD203c to CD63 for the diagnosis of amoxicillin (AX) allergy, which is nowadays the most frequent BL allergy. METHODS: Twenty-seven patients with an immediate positive skin test (ST) to AX, 20 had had anaphylaxis with AX and 7 had urticaria and/or angioedema, were compared with 14 controls with no allergy to BL and to six patients with delayed positive ST to AX. RESULTS: In the anaphylaxis group, AX induced up-regulation of CD203c in the basophils of 12 patients out of 20 (60%) and of CD63 in four patients (20%) (P<0.02). Two patients out of seven with urticaria or angioedema had a positive result with CD203c and CD63. In patients who had anaphylaxis, ampicillin (AMP) induced CD203c up-regulation in eight out of 12 (67%) patients tested, and CD63 up-regulation in 4 out of 12 (33%) (all patients who had anaphylaxis could not be tested with AMP). False-positive results were observed with CD203c as well as CD63, and for 10 patients indeed this was confirmed by a negative drug provocation test. The origin of conflicting results between CD63 and CD203c might be at least the targeting of basophils based on anti-IgE labelling. Among IgE(+) gated cells, by means of CD33, a marker of monocytes, a contamination up to 50% by monocytes was detected. In contrast to CD63, CD203c is an activation marker specific of basophils with a basal low-level expression in resting basophils. Thus, IgE and CD203c double targeting of basophils avoids the contamination by monocytes. CONCLUSION: CD203c seems to be a more sensitive activation marker of basophils than CD63 for the diagnosis of amoxicillin allergy.

Autoantibodies to phospholipids and to the coagulation proteins in AIDS.

In HIV-1 infection, an increased prevalence of anticardiolipin autoantibodies (aCL) and lupus anticoagulant (LA) has been described. In order to see if these antibodies are isolated or, like in autoimmune diseases, associated with hematological disorders and with antibodies to other phospholipids and to proteins of coagulation, we investigated 3 groups of patients: 1. 342 HIV-1 infected patients, 2. 145 control patients including 61 systemic lupus erythematosus (SLE) patients, 58 patients with a connective tissue disease, 15 patients with stroke, 11 patients with syphilis and 3. 100 blood donors. In HIV-1 infection antiprothrombin (aPrT) antibodies were present in 2% of patients, the prevalence of antiphosphatidylcholine antibodies (aPC) (50%) was almost as high as aCL (64%), and 39% had both antibodies. Absorption on liposomes of the latter revealed an heterogeneous mixture of aCL and aPC or cross-reacting antibodies. In contrast with SLE, anti-beta 2-glycoprotein I (4%), LA (1%), biological false positive test for syphilis (0.3%), thrombosis (p < 0.001) were uncommon. In HIV-1 infection, antiphospholipid antibodies do not associated with features linked to them in SLE or syphilis.

Characteristics of clometacin-induced hepatitis with special reference to the presence of anti-actin cable antibodies.

The clinical, biochemical, histopathological and immunological features of 30 cases of clometacin-induced hepatitis are described. The age range of the patients was 32-84 years with a notable female predominance of 29:1. The hepatitis was highly cytolytic with high values of transaminases but with little or no cholestasis. Gammaglobulins were higher than 18 g/l in 73% of the cases. 25 liver biopsies were performed and showed acute hepatitis with a predominant centrilobular necrosis in 17; chronic aggressive hepatitis was noted in 8 cases but 1 showed concomitant cirrhotic changes. Anti-tissue antibodies were looked for in all cases. Anti-smooth muscle antibodies of anti-actin cable type (titre 1/80 to 1/2, 560) were detected in 19 cases, anti-nucleus antibodies in 16 cases which were associated to the former in 14 cases. The above findings show that clometacin produces a hepatitis syndrome quite akin to autoimmune chronic active hepatitis (lupoid hepatitis) and to the hepatopathy induced by oxyphenisatin.

Recurrent stroke and vascular events in elderly patients with anticardiolipin antibodies: a prospective study.

The presence of anticardiolipin antibodies (aCL) is a recognized risk factor for ischaemic stroke and a predictor of recurrent ischaemic events in young patients, but the significance of positive aCL tests is uncertain in the elderly. We evaluated the frequency of aCL and the risk of recurrence of stroke and other vascular events in a series of 242 consecutive patients aged over 60 years, admitted for brain infarction. All underwent aCL immunoreactivity (ELISA; measured by IgG antiphospholipid, GPL, units) and transoesophageal echocardiography and were later examined or contacted by telephone (mean 2.33 +/- 1.25 years, max. 4). Fifty patients (21 %) had at least l0 GPL units aCL. There were no differences between these and the other patients in the results of transoesophageal echocardiography, including mitral or aortic valvular thickening, atrial thrombus, atrial spontaneous contrast, strands, and aortic plaques thickness. None had IgG higher than 80 GPL units or was positive for anti-beta2 glycoprotein I. Patients with at least 10 GPL units more often had a past history of cerebral infarction than patients lower aCL level. However, the incidence of recurrent stroke was 4.5 per 100 person-year in patients with more than 10 GPL units, and 2.7 per 100 person-year in those with more than 10 GPL units. Kaplan-Meier analysis for any vascular events showed no differences between the two groups. In contrast to young patients, elderly patients with 10 or more GPL units aCL and negative for anti-beta2 glycoprotein I do not seem to have a higher risk of vascular events.

Long-term follow-up study of 164 patients with definite systemic sclerosis: classification considerations.

To evaluate the usefulness of recently proposed schemes of classification for systemic sclerosis an extensive cross-sectional study of a series of 164 consecutive patients with long-term systemic sclerosis was undertaken. There were 47 cases of proximal sclerosis, 93 of distal sclerosis and 24 of complete CREST syndrome. The study included clinical, visceral, immunological and follow-up data. In addition, a quantitative clinical score was calculated for each patient, thus providing indications for prognosis. Data were expressed according to three conventional systems of classification: The ARA system, the diffuse versus limited systemic sclerosis system and the early cutaneous involvement system. The most reliable indications of severe outcome were: proximal sclerosis, trunk skin involvement, presence of anti Scl 70 autoantibody, pulmonary and/or heart involvement and age. Diagnosis and prognosis were not generated by the same items. Prognosis indicators proved more accurate for groups than for individuals. Mortality was 1 death per 149 patient X years of follow-up from diagnosis. We conclude that the ARA criteria for classification should be recognized as a standard, but patients with complete CREST syndrome should be included in the distal group. Other systems of classification, principally 2-way versus 3-way criteria, allow different subsets of patients that correlate with prognosis and the severity of the disease, and could be used for therapeutic purposes.

Optical probe for local void fraction and interface velocity measurements.

In view of the importance of obtaining unsteady local void fraction and interface velocities in liquid-vapor two-phase flows, an optical probe with a controlled tip geometry was developed and is described. In order to minimize the disturbances caused to the flow field by the presence of the probe, its dimensions have been miniaturized. The electronic and hydrodynamic responses of the probe were investigated experimentally. The probe was found to be sensitive to both the interface velocities and the phase present at the probe tip. A possible explanation for the behavior of the probe is presented. Within the velocity range checked and with proper calibration, the optical probe described can be used to determine both local void fractions and interface velocities.

Radio-frequency probe for bubble size and velocity measurements.

A radio frequency (rf) probe that can provide local void fraction and interface velocity measurements in a gas-liquid two-phase flow was developed. The probe response to bubble passage was investigated with single-bubble controlled experiments. For a fixed geometry, the probe response was dependent on the dielectric constant of the medium surrounding the probe tip (air or water) and on the frequency of the carrier signal supplied to the probe. Bubble lengths (< 1 cm) and average bubble approach velocities (< 160 cm/s) were independently measured by two light sources and detectors placed at a known distance from each other and sensing the passage of each bubble. By choosing a sensitive probe tip length of 2.75-3 mm, the rf probe output provided enough information to determine the bubble length and velocity. The results obtained by the two independent methods show reasonable agreement (+/-10%).

[Antinuclear antibodies in primary biliary cirrhosis]. / Les anticorps antinucléaires de la cirrhose biliaire primitive.

Antinuclear and antinuclear membrane autoantibodies are detected by indirect immunofluorescence in sera of 62 p. 100 of primary biliary cirrhosis patients; when anti-SS-A (Ro) and anti-SS-B (La) autoantibodies were included, 70 percent of patients had at least one type of antinuclear antibody. Of 89 patients with primary biliary cirrhosis, 30 had either Raynaud's phenomenon, Sjögren's syndrome or the CREST syndrome. Some antinuclear antibodies, anticentromere and speckled S1 type, seem to correlate with the associated connective tissue disease. Antibodies showing the S3 pattern (multiple nuclear dots) and antibodies to nuclear membrane may be present independently of an association with connective tissue disease. In the classical technical conditions used to detect anti-tissue and anti-mitochondrial autoantibodies on tissue sections, antinuclear antibodies like anti-centromere or S3 may not be detected and/or identified. Primary biliary cirrhosis patient sera for antinuclear antibodies determination must be screened by at least two assays: indirect immunofluorescence on a human cell line, like HEp-2, and immunodiffusion. The last assay must be performed even if antinuclear antibodies are undetected by immunofluorescence.

[Idiopathic portal hypertension associated with connective tissue disease similar to systemic lupus erythematosus]. / Hypertension portale idiopathique associée à une collagénose proche du lupus érythémateux disséminé.

A case of idiopathic portal hypertension associated with connective disease resembling systemic lupus erythematosus is described. The patient was a 50-year-old woman with splenomegaly, ascites, esophageal varices, and pancytopenia, but without extrahepatic portal obstruction or cirrhosis of the liver. Electron microscopy of the liver showed perisinusoidal fibrosis. High titers of autoantibodies against proliferating cell nuclear antigen (PCNA) were found in the sera as well as in ascites; anti-DNA antibodies appeared after anti-PCNA antibodies and remained thereafter at a moderate titer. The possibility of an immunological process in the pathogenesis of idiopathic portal hypertension is discussed.

[Prevalence and role of anticardiolipin antibodies in Crohn disease]. / Prévalence et rôle des anticorps anticardiolipine dans la maladie de Crohn.

OBJECTIVES: Anticardiolipin antibodies belong to the group of antiphospholid antibodies, and may be seen in association with endothelial damage and recurrent vascular thrombosis. The aim of our study was to determine in patients with Crohn's disease the frequency of anticardiolipin antibodies, and to correlate their presence with clinical activity and treatment of the disease. METHODS: One hundred and thirty-eight sera from patients with Crohn's disease and 118 from age-matched controls were tested for IgG anticardiolipin antibodies. In the Crohn's disease group, we determined whether the patients had a past history of vascular thrombosis, a clinically active intestinal disease, or a current immunosuppressive therapy (steroids or azathioprine). RESULTS: Anticardiolipin antibodies were found significantly more often in patients with Crohn's disease than in controls: 11.0% versus 2.5%, P < 0.02. Three patients with Crohn's disease had a past history of vascular thrombosis, but none of them had anticardiolipin antibodies. The presence of anticardiolipin antibodies was not correlated with the fact that patients had a clinically active disease (P = 0.77), or a current immunosuppressive therapy at the time of the serological test (P = 0.95). CONCLUSIONS: There is a significantly high prevalence of patients with anticardiolipin antibodies during Crohn's disease. The positivity of the test does not seem to be correlated to the existence of a past history of vascular thrombosis, nor to the clinical activity of the disease.

[Prevalence and significance of non-specific anti-organelle antibodies of the liver in chronic viral hepatitis C]. / Prévalence et signification des anticorps anti-organites non spécifiques du foie au cours des hépatites chroniques virales C.

OBJECTIVES: The aim of this study was to evaluate the prevalence and the clinical signification of non organ specific autoantibodies in chronic hepatitis C. METHODS: We studied retrospectively 158 consecutive patients (97 with chronic hepatitis C, 24 with chronic hepatitis B, 67 with alcoholic cirrhosis) and 100 blood-donors. RESULTS: The prevalence of anti-nuclear and anti-smooth muscle antibodies was lower in blood donors than in patients (P < 0.001), but was comparable among the 3 groups of patients. The anti-liver-kidney microsome type 1 antibodies were detected only in patients with chronic hepatitis C (6%). The serum gammaglobulin level was significantly higher in patients with hepatitis C and anti-nuclear antibody titers > or = 1/50. The anti-smooth muscle antibodies detected in patients with hepatitis C had no anti-actin specificity. The response to interferon was not related to the detection of non organ specific autoantibodies before treatment. CONCLUSION: Anti-nuclear or anti-smooth muscle antibodies are not characteristic of hepatitis C virus infection.

[Autoantibodies in the diagnosis of vascular diseases]. / Contribution des auto-anticorps au diagnostic des maladies vasculaires.

Vascular abnormalities are frequent in connective tissue disease. In this kind of patients a lot of autoantibodies are observed. To screen them a strategy must be selected according to the connective tissue disease that is suspected. When the diagnosis is unknown the tests must screen a great number of autoantibodies and this is the case for indirect immunofluorescence assays, at the opposite when the diagnosis is known antibodies specific for the disease should be screened. Some antibodies are specific for a disease this is the case for antibodies directed against double stranded DNA, centromere, extractable nuclear antigens Sm, RNP, Scl-70, Pm-Scl, Jo1, neutrophil cytoplasmic antigen proteinase 3, and beta 2-glycoprotein I the cofactor of anti-cardiolipin antibodies. Anti-SS-A(Ro) antibodies are very frequent in autoimmune diseases and they are not specific for anyone of them. Some autoantibodies are frequent in autoimmune and also in non autoimmune diseases and this is the case for antibodies directed against phospholipids, single stranded DNA, histones, rheumatoid factor. The detection of antibodies depends on the assays used for screening, that is why results should mention the assay used for their detection. The standardization of the detection of the autoantibodies especially when quantitative results are requested, is not yet performed enough. So to obtain reproducible results when monitoring a patient the screening must be done by the same assay in the same laboratory.

[Hashimoto's thyroiditis and silicone breast implants: 2 cases]. / Thyroïdite de hashimoto et prothèses mammaires en silicone: 2 observations.

The silicone implant controversy wavers between reassuring epidemiological studies and about 300 case reports of patients developing a definite or incomplete/atypical connective tissue disease (CTD) after receiving a silicone gel-filled breast implant (SBI). Since Hashimoto's thyroiditis (HT) is rarely reported in this context, we report here two new cases of HT associated with a history of bilateral cosmetic SBIs. The first patient was a 45-year-old white woman who had SBIs in 1976. In 1991 she developed HT, evolving to thyroid deficiency which was compensated with levothyroxine treatment. In addition, the patient complained of fatigue, arthralgia, morning stiffness and developed a sicca syndrome necessitating artificial tears. The 1995 evaluation disclosed the presence of antinuclear antibodies at a titre of 1/640, and high level anti-thyroid microsomal antibodies (1/256,000). Gamma globulins rose to 22.6%. Thyroid ultrasonography showed an enlarged thyroid gland with a diffusely hypoechogenic pattern. The implants were painful, and in 1996 they were removed. Microscope examination of the fibrous capsule surrounding the prostheses showed extremely dense connective tissue with fibrosis. The second patient was a 55-year-old white woman who had SBIs in 1984. In 1995, she developed HT with clinical pain and tenderness of the thyroid gland, with mild hyperthyroidism and positive antithyroglobulin antibodies, and was given corticosteroid treatment for 5 months. In 1996, the implants were again painful and the patient developed positive antinuclear antibodies with a titre of 1/200. Ultrasonography showed a heterogeneous thyroid gland, and implant removal was advised. Hashimoto's thyroiditis is recognized as a subset of chronic auto-immune thyroiditis, and its association with SBI is rare. In these 2 observations, an association without relation is possible, but a future survey of similar cases seems warranted.

[Descriptive and comparative study of technical methods used for the detection of antinuclear antibodies]. / Etude descriptive et comparative des méthodes et techniques utilisées pour la détection des anticorps antinucléaires.

There has been rapid progress in techniques for the detection of antinuclear antibodies. The methods most widely used at present are indirect immunofluorescence, Ouchterlony double immunodiffusion, passive haemagglutination and the Farr test. Antinuclear antibodies recognise several antigens. With a few exceptions, indigenous DNA is specific to DLE and is seen in more than 80 p. cent of patients. Other antibodies are less constant but equally specific: anti-Sm in DLE, antinucleolus in scleroderma. By contrast, the antibodies present in Sjögren's syndrome and anti-ENP would not seem to be specific to any single disease and the quite widely found anti-DNA is of little diagnostic interest.

[Why are some allergens enzymes?]. / Pourquoi certains allergènes sont-ils des enzymes?

In the last ten years, progress in the field of allergy research has led to the purification of some of the major allergens and to a better knowledge of their physico-chemical properties. A number of studies have shown that some allergens have enzymatic activities. Molecular biology has provided the means to clone and sequence genes encoding these allergens and to produce recombinant allergens in yeast and bacteria. Epitope mapping of natural and synthetic allergens, using polyclonal or monoclonal antibodies and cell-stimulation tests, has also contributed greatly to the understanding of their immunogenicity and allergenicity. Analysis of these new data allow us to explain why some allergens are enzymes.

[Evaluation of a radioimmunologic technique for the detection of anti-native DNA antibodies]. / Evaluation d'une technique radio-immunologique pour la détection des anticorps anti-ADN natif.

The anti-native DNA antibodies were measured by a radioimmunoassay (RIA) type Farr assay in the sera from 648 patients: 108 with active or inactive systemic lupus erythematosus (SLE), 181 with clinical symptoms of another connective tissue disease, 171 with liver diseases, 29 with different pathology and 159 normal sera were obtained from a blood bank. The anti-DNA kit has been calibrated against the first international units/ml. This assay has proved to be sensitive and specific, and appears to be reliable for the diagnosis and follow-up of SLE patients. The authors propose a new reference cut-off level higher than producer's one.

[Contribution of immunoenzymatic technics to the assay of anti-native DNA antibodies in the biological diagnosis of lupus erythematosus disseminatus]. / Apport des techniques immunoenzymatiques au dosage des Ac anti-ADN natif dans le diagnostic biologique du lupus érythémateux disséminé.

Anti native DNA antibodies (anti nDNA Ab), which are a highly specific feature of systemic lupus erythematosus (SLE) were measured by 3 methods: an enzyme linked immunosorbent assay (ELISA), an indirect immunofluorescence test on Crithidia luciliae (IFCL) and the Farr assay (reference test). 114 sera from patients with SLE or another connective tissue disease or without autoimmune rheumatic disease were tested. This study showed that ELISA seemed to be a more sensitive and specific test than IFCL (classical test). ELISA was also as sensitive as the Farr assay. ELISA should replace IFCL for the diagnosis and the follow up of patients with SLE. In other connective tissue diseases, ELISA might give more positive results. Thus these had to be confirmed, especially in the case of low antibodies levels, by using another method (e.g., the Farr assay).

[Anti-mitochondrial antibodies type 5 are markers of antiphospholipid syndrome]. / Les anticorps antimitochondries de type 5 sont des marqueurs du syndrome des antiphospholipides.

In order to investigate the clinical value of anti-mitochondrial antibodies type 5 (anti-M5), we carried out a retrospective study on 48 patients with these antibodies. Seventeen of these 48 patients (35%) satisfied at least 4 criteria of the revised American Rheumatism Association classification of SLE. Twenty-nine (61%) had at least one clinical manifestation of anti-phospholipid syndrome; thirteen had symptoms consistent with primary anti-phospholipid syndrome; five had isolated recurrent thrombosis; five had Evans' syndrome; four had auto-immune haemolytic anaemia; two had immunologic thrombocytopenia. Two of the 48 patients had no clinical manifestations, but only anti-M5 and a false laboratory test for syphilis (FBTS). Our data confirm that patients with anti-M5 have a high prevalence of: 1) thrombosis (42% had three or more deep thromboses) and fetal loss (21%); 2) auto-immune cytopenia with idiopathic thrombocytopenic purpura (29%) and auto-immune haemolytic anaemia (54%); 3) laboratory markers of anti-phospholipid syndrome (lupus anticoagulant (71%), FBTS (95%) and anticardiolipin antibodies (aCL) (71%). For 32 patients with anti-M5, anti-beta 2 glycoprotein I antibodies were also tested; 12 (38%) were positive, all of whom had IgG aCL, ie none had anti-beta 2GPI antibodies without aCL. There was no association between the presence of anti-beta 2GPI antibodies and recurrent thrombosis among patients with anti-M5. All these findings suggest that anti-M5 is another marker of the antiphospholipid syndrome. Even though the prevalence of anti-M5 is low, especially in SLE, it was the only marker of the anti-phospholipid syndrome in two patients; this appears to justify routine screening for these antibodies.