M. Longy-Boursier

Tocilizumab in refractory adult Still's disease

There is an unmet need for the treatment of adult Stills disease (ASD), the pathogenesis of which may involve interleukin‐6 (IL‐6). We report the first series of patients with ASD treated with tocilizumab (TCZ), a humanized anti–IL‐6 receptor antibody.

Cardiac complications of halofantrine: a prospective study of 20 patients

Halofantrine, increasingly used for treatment of Plasmodium falciparum malaria, is a normally well-tolerated amino-alcohol with very few side-effects, but torsades de pointes ventricular tachycardia due to halofantrine has been reported in a few patients with a congenital long QT interval (Romano-Ward syndrome). We performed a prospective study of the cardiac effect of halofantrine in 20 patients with 48 h ambulatory electrocardiographic (ECG) monitoring; the halofantrine levels in their serum were also determined. Minimal ECG changes were noted, with lengthening of the QT interval without clinical symptoms. This effect was dose-dependent and can be very severe in cases of pre-existing cardiopathy; it also occurs in patients without any pre-existing cardiopathy. In order to reduce the likelihood of such incidents, which are admittedly rare, we suggest performing electrocardiography on all patients before initiating treatment with halofantrine.

Assessment of liver fibrosis with transient elastography and FibroTest in patients treated with methotrexate for chronic inflammatory diseases: a case-control study.

BACKGROUND & AIMS Although methotrexate (MTX) is used in the effective treatment of inflammatory disorders, its use is hampered by the risk of liver fibrosis. Non-invasive methods for the diagnosis of liver fibrosis, such as transient elastography (FibroScan) and FibroTest could be useful for monitoring MTX-liver toxicity. The aim of this case-control study was to determine factors associated with liver fibrosis in a large cohort of patients requiring MTX. METHODS Consecutive adults with various benign inflammatory diseases were prospectively assessed using FibroScan and FibroTest when they were treated with MTX (cases) or before beginning treatment (controls). RESULTS Among 518 included patients, 44 patients (8.5%) had FibroScan and/or FibroTest results suggesting severe liver fibrosis. In a multivariate analysis, factors associated with abnormal markers of liver fibrosis were the body mass index >28 kg/m(2) and high alcohol consumption. Neither long MTX duration nor cumulative doses were associated with elevated FibroScan or FibroTest results. CONCLUSIONS Severe liver fibrosis is a rare event in patients treated with MTX and is probably unrelated to the total dose. Patients with other risk factors for liver disease should be closely monitored with non-invasive methods before and during MTX treatment.

Immune Thrombocytopenic Purpura after Recombinant Hepatitis B Vaccine: Retrospective Study of Seven Cases

Recombinant hepatitis B vaccine is usually well tolerated. Clinical and laboratory test manifestations with immunologic mechanisms have nonetheless been described following use of this vaccine. We retrospectively report 7 cases of thrombocytopenia occurring within 3 months (7 weeks on the average) of 1 or following injections of recombinant hepatitis B vaccine. Four boys and 3 girls, average age 12 y, were involved. Three had a history of immune thrombocytopenic purpura. Four had haemorrhagic manifestations. The haemogram showed thrombocytopenia (24 x 10(9)/l on the average) without alterations of the other lines. Infectious and immune aetiologies were excluded in all cases. The course varied after treatment by corticosteroids, high-dose intravenous immunoglobulin, or both. After describing the different manifestations subsequent to recombinant hepatitis B vaccination, we discuss post-vaccinal thrombocytopenias (vaccines in question, mechanisms) and the reality of this entity.

Postvaccinal inflammatory neuropathy: peripheral nerve biopsy in 3 cases

Abstract  Autoimmune inflammatory polyneuropathy (PN) can be triggered by vaccination. We report 3 such cases. A 36‐year‐old female nurse presented 15 days after a hepatitis B vaccination (HBV) with acute sensory disturbances in the lower limbs. She had severe ataxia but no weakness. Cerebrospinal fluid (CSF) protein level was 84 mg/100 mL, with 3 lymphocytes. A 66‐year‐old man presented 21 days after HBV with severe motor and sensory PN involving all 4 limbs. A 66‐year‐old man presented 15 days after a yellow fever vaccination with progressive motor and sensory PN involving all 4 limbs and bilateral facial paralysis. CSF protein level was 300 mg/100 mL, with 5 lymphocytes. Six weeks later, a tracheostomy was performed. In these 3 patients, the nerve deficits lasted for months. In each case, peripheral nerve biopsy showed KP1‐positive histiocytes but no T‐lymphocytes in the endoneurium. On ultrastructural examination, there was axonal degeneration in the first 2 cases; in case 2, a few myelinated fibers exhibited an intra‐axonal macrophage but the myelin sheath was preserved. There was only 1 example of macrophage‐associated demyelination in case 2, but these were numerous in case 3. It is likely that in the first 2 cases, an autoimmune reaction against some axonal or neuronal components was triggered by HBV. It induced an acute sensory ataxic PN in case 1 and an acute motor and sensory axonal neuropathy (AMSAN) in case 2. The third patient had a chronic inflammatory demyelinating PN, likely triggered by yellow fever vaccination.

Abcès amibien du foie : analyse de 20 observations et proposition d'un algorithme thérapeutique

Purpose. – The management of amoebic liver abscess includes antiamoebic drugs combined or not with percutaneous puncture or surgical drainage. This study was to suggest a decision tree for the therapeutic approach of such feature. Methods. – We report a retrospective analysis of 20 imported cases with amoebic liver abscesses admitted at the Department of Tropical Diseases during 1995–1999 at the Bordeaux University Hospital Centre, France, and a review of the literature. Results. – The twenty patients were 14 males and 6 females, mainly 20 to 40 years old. The clinical presentation was mainly accounting a painful liver enlargement with hyperthermia. The echographic picture was mostly represented by a unique liver element located at the liver right lobe. They were numerous in an HIV infected patient. Thirteen patients have been treated using a medical therapeutic approach. A percutaneous puncture has been necessary for 4 cases. A percutaneous drainage has been realised for two patients as regard to the persistence of the hepatalgia occurrence. A surgical drainage has been experienced by two patients after a lack of efficacyof a percutaneous drainage, after rupture of an abscess treated medically, respectively. A review of the literature and the analysis of the 20 cases history have been used to determine a therapeutic algorithm. Conclusion. – The occurrence of immediate complications at onset must indicate a first line surgical drainage procedure. Beside this situation, risk factors for rupture must be assessed (high size abscess, pejorative localization), as well as poor prognosis feature (liver failure, bacteraemia). If no pejorative condition occurs, a first-line exclusive medical approach can be undertaken with a clinical efficacy evaluation at H72. Otherwise, the indication of the percutaneous drainage must be discussed.

Concurrent herpes simplex type 1 necrotizing encephalitis, cytomegalovirus ventriculoencephalitis and cerebral lymphoma in an AIDS patient.

Unlike cytomegalovirus (CMV) ventriculoencephalitis, herpes simplex virus type 1 necrotizing encephalitis has only rarely been observed in AIDS patients. A 40-year-old bisexual man was followed for an HIV1 infection from 1987 onwards. In June 1993 he was referred for sudden confusion, left hemiparesia and fever. The blood contained less than 10 CD4 lymphocytes/mm3. The patient remained comatose and febrile, and died 4 weeks later. In coronal sections of the brain there was necrosis of the internal parts of the left temporal lobe, necrosis of certain areas of the ventricular walls and a small tumor at the top of the right frontal lobe, which proved to be a polymorphic high-grade lymphoma. CMV ventriculoencephalitis lesions were prominent in the ventricular walls of the oecipital lobes and there was a strong nuclear signal for CMV using in situ hybridization. Herpes simplex virus type 1 was shown in the nuclei and cytoplasm of certain neurons and astrocytes in the borders of the necrotized temporal lobe areas by immunohistochemistry, in situ hybridization and electron microscopy, whereas in situ hybridization and immunohistochemistry for CMV were negative in such areas. Necrotizing type 1 encephalitis must not be overlooked in immunodeficient patients.

Le deficit immunitaire commun variable de l'adulte : etude clinique, biologique et immunologique chez 17 patients

Resume Propos. – Le deficit immunitaire commun variable (DICV) regroupe des patients atteints d’un desordre immunitaire qui s’exprime par un defaut primaire de synthese des immunoglobulines. Si les manifestations cliniques revelatrices du DICV sont dominees par des infections des voies aeriennes superieures, d’autres evenements cliniques plus originaux existent comme des affections auto-immunes ou une granulomatose evocatrice de sarcoidose. Methodes. – Il s’agit d’une etude retrospective portant sur 17 patients repondant a la definition du DICV. Parmi eux, 12 ont eu une etude de leurs sous-populations lymphocytaires avec expression de l’HLA-DR, marqueur d’activation des lymphocytes T. Resultats. – Il s’agit de 17 patients, 7 hommes et 10 femmes. L’âge moyen de debut des symptomes est de 23 ans et l’âge moyen au moment du diagnostic est de 39 ans. Tous les patients decrivent des infections a repetition (principalement des infections des voies aeriennes superieures et des pneumopathies). Une malade presente une mycobacteriose digestive. Les autres evenements digestifs sont domines par des diarrhees chroniques en rapport avec une atrophie villositaire, une giardiase ou une hyperplasie nodulaire lymphoide. Sept malades presentent des manifestations auto-immunes (diabete insulinodependant, purpura thrombopenique idiopathique, polyarthrite rhumatoide) et 7 ont une splenomegalie. Trois patients ont une granulomatose diagnostiquee sur une piece de splenectomie ou une biopsie ganglionnaire. Dix patients ont une lymphopenie T, 2 une lymphopenie B, 5 ont un rapport CD4/CD8 Conclusions. – Notre travail permet de distinguer 2 groupes de patients avec un DICV selon le degre d’activation lymphocytaire T. Une classification de ces malades est utile pour definir des groupes homogenes permettant de realiser des etudes fonctionnelles et genetiques qui devraient conduire a la decouverte de defauts moleculaires heterogenes.

Plasmocytome pulmonaire : à propos de deux nouvelles observations et revue de la littérature

Introduction. – Extramedullary plasmacytoma is an uncommon plasma cell malignancy mainly located to the upper aerodigestive tract. Primary pulmonary plasmacytoma is extremely rare. Exegesis. – We report two new cases of primary pulmonary plasmacytoma and then proceed to a review of the literature concerning 35 similar cases previously described. Conclusion. – Complete or partial responses were obtained in 24 cases (65%). Five patients (14%) have developed multiple myeloma within 3 years following plasmacytoma diagnostic. In spite of sustained responses with radiotherapy or chemotherapy, surgical resection while feasible remains the first therapeutic option.

Aspects épidémiologiques, cliniques, biologiques et évolutifs de la leptospirose : à propos de 30 observations recueillies en Aquitaine

Thirty cases of leptospirosis serologically proved, are reviewed: contaminating circonstances were often determined. We observed mainly: acute fever, myalgia, jaundice, hemorrhages and acute renal failure (7 hemodialysis). Two patients died (acute respiratory failure, meningo-encephalitis with hemoptysis).