Cessation of oral anticoagulants in antiphospholipid syndrome.

Objective To study the outcome of patients with antiphospholipid syndrome (APS) after oral anticoagulant treatment cessation. Methods We performed a retrospective study of patients with APS experiencing cessation of oral anticoagulant and enrolled in a French multicentre observational cohort between January 2014 and January 2016. The main outcome was the occurrence of recurrent thrombotic event after oral anticoagulation cessation. Results Forty four APS patients interrupted oral anticoagulation. The median age was 43 (27-56) years. The median duration of anticoagulation was 21 (9-118) months. Main causes of oral anticoagulant treatment cessation were switch from vitamin K antagonists to aspirin in 15 patients, prolonged disappearance of antiphospholipid antibodies in ten, bleeding complications in nine and a poor therapeutic adherence in six. Eleven (25%) patients developed a recurrent thrombotic event after oral anticoagulation cessation, including three catastrophic APS and one death due to lower limb ischemia. Antihypertensive treatment required at time of oral anticoagulants cessation seems to be an important factor associated with recurrent thrombosis after oral anticoagulant cessation (15.2% in patients with no relapse versus 45.5% in patients with recurrent thrombosis, p = 0.038). Oral anticoagulant treatment was re-started in 18 (40.9%) patients. Conclusion The risk of a new thrombotic event in APS patients who stopped their anticoagulation is high, even in those who showed a long lasting disappearance of antiphospholipid antibodies. Except for the presence of treated hypertension, this study did not find a particular clinical or biological phenotype for APS patients who relapsed after anticoagulation cessation. Any stopping of anticoagulant in such patients should be done with caution.

Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients.

BACKGROUND: Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. PATIENTS AND METHODS: Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade <3/5 in more than half the muscle groups at the motor neurological level. Inability to run or another significant ambulation-unrelated disability was considered as 'unfavourable neurological outcome'. RESULTS: Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. CONCLUSION: Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use.

Evidence for various calcium sites in human hair shaft revealed by sub-micrometer X-ray fluorescence.

New information about calcium status in human scalp hair shaft, deduced from X-ray micro-fluorescence imaging, including its distribution over the hair section, the existence of one or several binding-types and its variation between people, is presented. The existence of two different calcium types is inferred. The first one corresponds to atoms (or ions) easily removable by hydrochloric acid, located in the cortex (granules), in the cuticle zone and also in the core of the medulla, which can reasonably be identified as calcium soaps. The second type consists of non-easily removable calcium atoms (or ions) that are located in the medulla wall, probably also in the cuticle, and rather uniformly in the cortex; these calcium atoms may be involved in Ca(2+)-binding proteins, and their concentration is fairly constant from one subject to another. In addition to its nonuniform distribution across the hair section, the second striking feature of the first type calcium content is its high variability from one subject to another, by up to a factor 10. We expect this information to be useful for analyzing in more detail the relationship between hair calcium and environmental and medical factors.

[Tuberous sclerosis without mental impairment, diagnosed in adulthood]. / Sclérose tubéreuse de Bourneville sans altération intellectuelle, diagnostiquée à l'âge adulte.

INTRODUCTION: Tuberous sclerosis complex (TSC) is an autosomal dominant inherited phakomatosis, usually diagnosed in childhood and characterized by cutaneous and neurological tumors, the latter often leading to epilepsy and mental retardation. EXEGESIS: We report a case of TSC diagnosed in a 33-year-old man, without any known family history of phakomatosis, presenting with facial angiofibromas, hypomelanotic macules, a giant-cell astrocytoma and retinal phakomas without any mental impairment or epilepsy. CONCLUSION: TSC may occur in patients who do not have any family history of phakomatosis because de novo mutations are frequent. TSC may be diagnosed in adulthood since a high phenotypic variability is observed. Facial angiofibromas are highly suggestive of tuberous sclerosis complex. They should lead to brain imaging in search for astrocytoma, subependymal nodules and cortical tubers which number is directly correlated with the risk of seizures and the degree of mental impairment.

[Therapeutic intensification and autologous stem cell transplantation in autoimmune diseases]. / Intensification thérapeutique et autogreffe de cellules souches hématopoïétiques pour le traitement des maladies auto-immunes.

THE PATHOPHYSIOLOGY of most autoimmune diseases is often poorly understood. EXPERIMENTAL CONSIDERATIONS and clinical experience suggest that high doses immunoablation followed by stem cell transplantation is a therapeutic option to consider for certain severe autoimmune disorders. THE CONCEPT OF RESTORING NORMAL IMMUNE REACTIVITY must in part br true since current results of 466 transplants (445 autologous, 21 allogeneic) patients suffering from various autoimmune diseases show a beneficial outcome in approximately 2/3 of the patients. TO IMPROVE THE EFFICACY AND SAFETY OF SUCH AN AGGRESSIVE PROCEDURE in patients with potentially affected vital organs by the underlying autoimmune disease, it is especially important to follow international consensus guidelines and to centrally collect clinical data for in depth analysis in the EBMT International Stem Cell Project for Autoimmune Disease in Basel, Switzerland. PHASE III STUDIES ARE RUNNING FOR SYSTEMIC SCLEROSIS (Astis, Autologous Stem cell Transplantation International Rheumatoid Arthritis Trial) started in 2003. A STUDY PROJECT IS PLANNED FOR MULTIPLE SCLEROSIS (Astims, Autologous Stem cell Transplantation International Multiple Sclerosis).

[Chronic venous insufficiency and microcirculation. Physiopathologic and therapeutic reflections]. / Insuffisance veineuse chronique et microcirculation. Réflexions physiopathologiques et thérapeutiques.

In patients with chronic venous insufficiency, tissular damage occurs as a consequence of microcirculatory disturbances. Venular distension, venulo-arteriolar reflex and probably valves in collecting venules are the only microcirculatory protective mechanisms against venous pressure overload. Edema is primarily a consequence of increased capillary hydrostatic pressure. However, the increase of endothelial macromolecular transport and a true lymphatic microangiopathy are important contributive factors. Venous ulceration is hypoxic although the amount of total blood flow is normal in the surrounding tissue. Several hypothesis were proposed for explaining this nutritional steal: arterio-venous shunt vessels have never been shown consistently, peri-capillary fibrin deposition might block oxygen diffusion, and last but not least, the abnormal geometrical arrangement of the capillary bed is facilitating functional shunting. On a therapeutic point of view, behind the classical hemodynamic therapy, the microvascular approach to chronic venous insufficiency supports the use of lymphatic manual drainage for controlling edema and rheologic therapy for improving skin capillary perfusion.

[Erythrocyte aggregation and its repercussions on conjunctival microcirculation in man. Morphometric study and biological correlates]. / L'agrégation érythrocytaire et son retentissement sur la microcirculation conjonctivale chez l'homme. Etude morphométrique et corrélations biologiques.

This study, involving the application of morphometric techniques to the conjunctival capillary bed in man, revealed a rarefaction of functional capillary density in patients with arteriolar sludge. Overall, in the population sample studied, capillary density and the degree of erythrocyte aggregation were correlated to erythrocyte sedimentation rate, despite the existence of discordant cases. These discordances were partially reduced by taking the hematocrit into account. Furthermore, multifactorial analysis of these parameters showed that hematocrit had an inhibitory action on erythrocyte aggregation which was more marked in vitro than in the microcirculation in vivo. By contrast, in vivo aggregation was more influenced by serum albumin levels. In both cases fibrinogen appeared to be the most significant pro-aggregant factor.

[New targets of antiphospholipid antibodies]. / Les nouvelles cibles des anticorps "antiphospholipides".

"Antiphospholipid" antibodies (aPL) are a heterogenous group of autoantibodies with clinical importance because of their association with thrombotic events, both venous and arterial. Traditionally, aPL have been assayed using phospholipid-dependent tests and are classified as lupus anticoagulants and anticardiolipin antibodies (ACA), based on the method of detection. Most antibodies associated with the aPL syndrome and detected in standard assays are actually directed against two phospholipid-binding plasma proteins, beta 2 glycoprotein I and prothrombin. These antibodies can also be detected in immunoassays (ELISA) utilizing purified protein antigens, in the absence of phospholipids. The main advantage of beta 2 GPI-ELISA compared with conventional cardiolipin-ELISA appearing from initial clinical studies is greater specificity for the aPL syndrome, due to (i) ignorance of "authentic" ACA that interact directly with cardiolipin; (ii) detection of species specific anti-beta 2 GPI antibodies poorly reactive with bovine beta 2 GPI in the cardiolipin-ELISA. Other proteins proposed as target antigens of aPL are protein C, protein S, annexin V, high- and low-molecular weight kininogens, the latter being involved in the binding of antibodies to phosphatidylethanolamine. The possibility that particular autoantibodies (or combinations of autoantibodies) explain the observed clinical spectrum of the aPL syndrome is attractive, but much remains to be learned about their pathogenicity and origin in order to improve diagnosis and therapy.

[Diagnostic delay in Horton's disease. Analysis of the diagnostic delay based on a retrospective study of 130 cases]. / Le retard diagnostique dans la maladie de Horton. Analyse du délai diagnostique à partir d'une étude rétrospective de 130 cas.

Temporal arteritis (Horton's disease) is a multifocal granulomatous arteritis which affects elderly people. Its prognosis depends upon the risk of blindness. In a retrospective study of 130 patients we paid special attention to the delay in diagnosis and its relation to the occurrence of ophthalmic complications. In 73 patients (56.2%), this delay exceeded 3 months and reached more than one year in 22 of them. It was not influenced by age or sex. In requests for admission, the diagnosis of temporal arteritis was suggested in only 28 of the 130 cases; 17.7% of the patients were blind. There was a significant increase in the occurrence of ophthalmic lesions when the diagnosis was delayed by 2 to 6 months. In 6 cases, blindness had been preceded by transient amaurosis. These findings confirm that temporal arteritis is belatedly diagnosed by practitioners and that blindness could be avoided by an earlier diagnosis.

[Systemic mastocytosis: incidence and risks of vasomotor seizures]. / Mastocytose systémique: fréquence et risques des crises vasomotrices.

We report on 9 cases of systemic mastocytosis which underline the frequency and the potential severity of this disease. All patients had intercritical signs (usually urticaria). Seven patients had also typical crises with flush and vascular collapses are observed together, doctors should measure histamine blood level and perform correct biopsy.

[Diagnostic strategy in uveitis: a prospective study in 125 cases]. / Prise en charge diagnostique des uvéites. A propos d'une étude prospective de 125 patients.

BACKGROUND: The diagnosis of uveitis is a difficult one and subject to much debate between ophthalmologists and internists. In 1992, we carried out a prospective study to assess the importance of the internist's consultation, the contribution of an extensive laboratory evaluation and to propose a well considered diagnostic strategy. MATERIAL: and methods: From 1992 to 1995, all patients seen at consultation at the Grenoble University Hospital had a complete ophthalmologic evaluation, an internist's consultation, an extensive laboratory evaluation and a follow-up for at least 6 months. RESULTS: One hundred twenty five patients were included. The rate of diagnosis was 72%. The internist's help was useful in at least 68% of the diagnoses. Laboratory and radiography tests provided pertinent information in 77% of the cases. Follow-up allowed finding 11% of the diagnoses. The analysis of the clinical and laboratory tests enabled us to establish a diagnostic strategy chart where the key pint is clinical and ophthalmologic evaluation. A minimal laboratory evaluation systematically performed for all cases of uveitis is proposed and, according to some characteristics of uveitis, a well-targeted laboratory evaluation is recommended. CONCLUSION: This diagnostic strategy enabled establishment of the diagnosis in 92% of the cases and limited laboratory evaluation for 68 patients. We are performing a new prospective study to better validate this diagnostic chart.

Hematological malignancy associated with polymyositis and dermatomyositis.

The aims of this present study were to: 1) assess the characteristics of hematological malignancies in polymyositis/polymyositis (PM/DM) patients; and 2) determine predictive variables of hematological malignancies in PM/DM patients. We retrospectively reviewed the medical records of 32 patients (14 PM, 18 DM) associated with hematological malignancies. In our 32 PM/DM patients, hematological malignancy was concurrently identified (18.8%) or occurred during the course of PM/DM (31.2%); although, PM/DM more often preceded hematological malignancy onset (50%). We observed that the types of hematological malignancies varied, consisting of: B-cell lymphoma (n=20), T-cell lymphoma (n=4), Hodgkin's disease (n=2), multiple myeloma (n=1), myelodysplastic syndrome without excess of blasts (n=3), hairy cell (n=1) and acute lymphocytic leukemia (n=1). In 21 patients of our 32 patients with PM/DM-associated hematological malignancy (65.6% of cases), PM/DM paralleled the course of hematological malignancy. Finally, we observed that patients with PM/DM-associated hematological malignancies had a poor prognosis, the survival status ranging from 96.9%, 78.1% and 51.4% at 1, 3 and 5years, respectively. Interestingly, we found that patients with hematological malignancies, compared with those without were older and more frequently had DM; on the other hand, these patients less commonly exhibited: joint involvement (p=0.017), interstitial lung disease (p=0.06) and anti-Jo1 antibody (p=0.001). Taken together, our study underscores that the association between PM/DM and hematological malignancy, especially lymphoma, should not be ignored. Our findings also suggest that antisynthetase syndrome may be a protective factor of hematological malignancy in PM/DM patients.

[Immunoallergic reaction with hepatitis induced by minocycline]. / Réaction immuno-allergique avec hépatitite induite par la minocycline.

We report the case of a 19-year old black West Indian woman who had been treated for acne for two years with oral minocycline (50 mg per day) and topical of benzoyle peroxide (5%). She was admitted for fatigue, arthralgia, myalgia and widespread pruritus. We observed several skin lesions of hyperpigmentation, biological signs of hepatitis, and significant levels of antinuclear, anti-mitochondrial and anti-smooth muscle antibodies. Minocycline was immediately stopped. Two months later, all of the biological abnormalities had disappeared but the skin lesions seemed to be irreversible. Minocycline is largely used for the treatment of acne and may induce severe immuno-allergic reactions. Several cases of induced lupus, autoimmune hepatitis, eosinophilic pneumonia, hypersensitivity syndrome, serum-sickness-like illness and Sweet's syndrome have already been described. These side effects are rare but may be life-threatening. So, minocycline should be used as a second-line treatment for acne and should be avoided in black people whom seem to be at risk of such reactions. If, despite those precautions, minocycline-induced immuno-allergic reactions occur, the treatment should be immediately stopped and never prescribed again.