[Paraneoplastic neurological syndromes]. / Les syndromes neurologiques paranéoplasiques.

Neurological paraneoplastic syndromes are non-metastatic complications of systemic cancers, often resulting from an immune response triggered by the crossed expression of neuronal antigens by tumour cells. Several neurological syndromes such as cerebellar degeneration, sensory neuronopathy, limbic encephalitis, encephalomyelitis or the Lambert-Eaton myasthenic syndrome are most often paraneoplastic and require prompt cancer screening, particularly if the patient shows risk factors for cancer. Although there are many exceptions to this rule, a given syndrome is often associated with a particular antibody and the corresponding tumour. A prompt diagnosis of neurological paraneoplastic syndrome is of major importance as it often reveals the underlying tumour. The treatment relies on both the elimination of the neoplasia and the control of the immune response.

Les syndromes neurologiques paranéoplasiques sont des complications neurologiques non métastatiques de cancers systémiques résultant, le plus souvent, d'une réaction immunitaire croisée dirigée contre des antigènes neuronaux membranaires ou intracellulaires. Certains de ces syndromes paranéoplasiques sont classiques comme les ataxies cérébelleuses, les neuronopathies sensitives ou ganglionopathies, l'encéphalite limbique, les encéphalomyélites ou le syndrome de Lambert-Eaton. Devant de tels tableaux cliniques, une étiologie paranéoplasique doit, surtout chez les patients présentant des facteurs de risque, être systématiquement recherchée. Bien que cette règle souffre de nombreuses exceptions, il y a souvent concordance entre un syndrome clinique spécifique, un type d'anticorps et une tumeur associée. Le diagnostic d'un syndrome neurologique paranéoplasique est essentiel puisqu'il révèle souvent le cancer sous-jacent. Le traitement comporte deux axes principaux : celui du cancer responsable et le contrôle de la réponse immunitaire.

[An illustrative case of the POEMS syndrome]. / Cas clinique. Un cas illustratif de POEMS syndrome.

POEMS syndrome is a rare and invalidating entity characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and dermatoses. The diagnosis of this condition is often late and challenging due to the heterogeneity of clinical forms. The light chains secreted by the clonal plasmocytes cause overproduction of VEGF (Vascular Endothelial Growth Factor) responsible for the appearance of the clinical manifestations of POEMS. The diagnostic approach is based on different clinical and biological criteria. Patients with a solitary plasmacytoma are candidates for radiotherapy treatment. Patients with diffuse bone involvement or bone marrow infiltration are best treated by systemic drugs. The response to treatment may take several months before clinical and biological improvement. Early diagnosis and dedicated management limit the clinico-functional impact of POEMS.

Le POEMS syndrome est une entité rare et invalidante caractérisée par une polyneuropathie, une organomégalie, une endocrinopathie, une gammapathie monoclonale et des atteintes dermatologiques. Le diagnostic de cette infection est souvent tardif et représente un véritable défi au vu de l'hétérogénéité des formes cliniques. Les chaînes légères sécrétées par les plasmocytes clonaux entraînent une surproduction de VEGF (Vascular Endothelial Growth Factor) responsable de la plupart des manifestations cliniques du POEMS. La démarche diagnostique repose, en pratique, sur des critères cliniques dont les principaux sont la polyneuropathie et la gammapathie monoclonale. Le bilan d'extension reprend le dosage du VEGF, l'électrophorèse et l'mmunofixation des protéines sériques. Un bilan radiologique permet d'objectiver des lésions osseuses ostéosclérotiques ou des adénopathies et l'électromyogramme la polyneuropathie. Les patients qui souffrent d'un plasmocytome en l'absence d'une infiltration médullaire de plasmocytes clonaux sont des candidats au traitement par radiothérapie. Les patients avec une atteinte osseuse diffuse ou une localisation médullaire recevront un traitement systémique. La réponse au traitement peut prendre plusieurs mois avant une amélioration clinique et biologique. Un diagnostic précoce et une prise en charge spécifique limitent l'impact clinico-fonctionnel du POEMS.

[How I explore a proteinuria]. / Comment j'explore une protéinurie.

The measurement of proteinuria is a very simple tool to screen and manage kidney diseases. Its predictive role is also relevant from a cardiovascular point of view. However, the interpretation of the results is not always easy. Indeed, there are several different methods to detect or measure proteinuria (or albuminuria), varying from the measurement on a 24-hour urine collection to the simplest detection with dipsticks or measurement on a random urine sample. Some methods are measuring total proteins, whereas others are measuring more specifically albuminuria. For all methods, pitfalls exist and will be discussed. A positive result must be confirmed by a quantitative measurement on 24-hour collection or on a first morning sample (this last one can only be interpreted as a ratio to urinary creatinine excretion). Lastly, we will briefly discuss the management of a patient with a new diagnosis of proteinuria (or albuminuria).

La recherche d'une protéinurie est un outil simple de dépistage et de suivi de la maladie rénale. Elle a aussi un rôle prédictif important, que ce soit au niveau néphrologique ou cardiovasculaire. Son interprétation n'est cependant pas toujours simple. Il existe, en effet, différentes méthodes pour évaluer la protéinurie (ou l'albuminurie) qui vont d'une mesure sur la récolte de 24h à l'utilisation simple de la bandelette réactive (« tigette ¼) sur un échantillon urinaire. Certaines méthodes permettent la recherche et/ou la quantification de la protéinurie dite totale, alors que d'autres mesurent plus exclusivement l'albuminurie. Pour toutes les méthodes et pour tous les dosages, des pièges diagnostiques existent et seront discutés. Un résultat positif doit systématiquement être confirmé quantitativement sur un second échantillon soit à partir d'urine de 24h, soit sur un échantillon du matin (la mesure sur échantillon n'étant interprétable que si elle est rapportée à l'excrétion urinaire de créatinine). Enfin, nous tracerons les grandes lignes de la prise en charge d'un patient chez qui une protéinurie (ou une albuminurie) est découverte.

El síndrome tirogástrico autoinmune: sus efectos sobre los micronutrientes y la tumorigénesis gástrica / The Thyrogastric Autoimmune Syndrome: Its Effects on Micronutrients and Gastric Tumorigenesis

El síndrome autoinmune tirogástrico (SAT) fue descrito en pacientes en quienes el suero presentaba reacciones cruzadas de anticuerpos dirigidos contra los antígenos de células parietales gástricas y tiroideas. A través de dos casos describimos el espectro patológico de este síndrome. El primero asocia una tiroiditis de Hashimoto y una anemia perniciosa, desarrollando durante el seguimiento un tumor neuroendocrino gástrico. El segundo caso presenta una enfermedad de Graves y una gastritis autoinmune, secundaria a Helicobacter Pylori: esta última es reversible luego de tratamiento. Se considera que la poliendocrinopatía autoinmune de tipo III (dentro de la cual puede inscribirse el síndrome tirogástrico) es rara, pero no lo es en nuestra experiencia. Un total de 13 % (32/240) de los pacientes con tiroiditis que hemos seguido prospectivamente, tienen también una gastritis autoinmune. Helicobacter pylori está claramente implicado en el 16 % de estos casos con gastritis autoinmune. Infección, malabsorción y gastritis son potencialmente reversibles después del tratamiento de erradicación bacteriana. En el 84 % restante de los pacientes con gastritis y tiroiditis, no se encuentran pruebas serológicas o histológicas de Helicobacter pylori. La autoinmunidad gástrica es entonces irreversible, y conduce a una hipergastrinemia, hipoclorhidria y atrofia gástrica severa. La hipergastrinemia estimula la hiperplasia de las células enterocromafines, con riesgo de progresión a un tumor neuroendocrino. Proponemos un esquema diagnóstico novedoso para mejor caracterización del síndrome tirogástrico. Exponemos la literatura sobre el tema y discutimos a partir de algunos modelos animales pertinentes sobre la autoinmunidad gástrica infecciosa. Rev Argent Endocrinol Metab 51:37-43, 2014 Los autores declaran no poseer conflictos de interés.

The thyrogastric autoimmune syndrome (TAS) was described in patients in whom the serum cross-reacted both with gastric parietal cells antigens and thyroid antigens. We report two cases illustrating the spectrum of pathological features of TAS. The first one is a case of Hashimoto’s Thyroiditis associated with pernicious anemia, further developing a gastric neuroendocrine tumor during follow up. The second one is a case of Graves’ disease and autoimmune reversible gastritis, While type III autoimmune polyendocrinopathy (which includes TAS) is considered to be rare, this was not the case in our experience. A total of 13 % (32/240) of the patients with thyroiditis that we have prospectively followed have also autoimmune gastritis. Helicobacter pylori is clearly implicated in 16 % of the cases of autoimmune gastritis. Infection, malabsorption and gastritis are potentially reversible after bacterial eradication treatment. In the remaining 84 % of patients with gastritis, no histological or serological evidence of Helicobacter pyloriwas found. Gastric autoimmunity is then irreversible, leading to gastric severe atrophy, hypochlorhydria and hypergastrinemia. Hypergastrinemia stimulates enterochromaffin cell hyperplasia, progressing eventually to neuroendocrine tumors. We propose a diagnostic approach to improve the characterization of TAS, including a literature review and discussing some relevant animal models of infectious gastric autoimmunity. Rev Argent Endocrinol Metab 51:37-43, 2014 No financial conflicts of interest exists.

[Concerns about glycated haemoglobin and the limitations of its interpretations]. / A propos de l'hémoglobine glyquée: les limites de son interpretation.

Determining the level of glycated haemoglobin, in particular its major fraction called HbA(1c), is an attractive tool in the management of diabetic patients. In fact, it provides a global evaluation of the glycemic control's level through the past 8-12 weeks. However, this tool must be used with caution. First of all, it does not allow to examine the glycemic kinetics since it represents a glycemic average. Secondly, it does not allow to appreciate the glycemic evolution through the full day. This dosage needs then sometimes to be complemented by fingersticks blood glucose testing. Last but not least, caution is advised in interpreting the results because a number of physiological, pathological and technical factors might interfere with HbA(1c) measurement. It is therefore important that physicians keep a critical view of the values obtained. The paper reviews the different methods used to determine the level of glycated haemoglobin and their limitations. It also emphasizes the medical situations in which over- and under-estimation of the real HbA(1c) value could occur. It does not address the specific issue of the new expression values of HbA(1c) in mmol/mol instead of %. Moreover, the medical situations in which over- and underestimation of the real HbA(1c) value could occur will be described.

[The thyrogastric syndrome: its effects on micronutriments and gastric tumorigenesis]. / Le syndrome auto-immun thyro-gastrique: ses effets sur les micronutriments et la tumorigenèse gastrique.

The thyrogastric autoimmune syndrome (TAS) was described in patients in whom the serum cross-reacted both with gastric parietal cells antigens and thyroid antigens. We report two cases illustrating the spectrum of pathogical features of TAS. The first case associates Hashimoto's thyroiditis and anemia perniciosa,and develops a gastric neuroendocrine tumor during follow up. The second case presents with a Graves' disease and an autoimmune reversible gastritis, secondary to Helicobacter pylori. Whereas type III autoimmune polyendocrinopathy is rare, TAS is frequent in our experience. Some 13% (32/240) of patients that we have prospectively followed affected with thyroiditis have also autoimmune gastritis. Helicobacter pylori is clearly implicated in 16% of autoimmune gastritis cases. Infection, malabsorption and gastritis are potentially reversible after bacterial eradication treatment. In the other 84% of gastritis patients, no histological or serological proof of Helicobacter pylori is found. Gastric autoimmunity is then irreversible, leading to gastric severe atrophy, hypochlorhydria and hypergastrinemia. Hypergastrinemia stimulates enterochromaffin cell hyperplasia, possibly progressing to neuroendocrine tumors. We propose a diagnostic approach to improve the characterization of TAS. We review the literature on the subject and discuss some interesting animal models of infectious gastric autoimmunity.

[Rhupus: when rheumatoid arthritis meets lupus]. / Le rhupus: à la frontière entre polyarthrite rhumatoïde et lupus érythémateux disséminé.

There exists diseases in rheumatology fulfilling classification criteria for either rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). They are called "rhupus". We retrospectively analyzed the data base "GLIMS" of the CHU de Liège from the starting date of november 2005 until april 2011 to identified those patients that were positive for the anti-sDNA antibody marker of SLE and for the anti-CCP antibody, marker of RA. Fourteen patients were identified and two other patients were added, one suffering from SLE, and the other from RA, and likely to be rhupus. Of the 16 patients analyzed, 9 were real RA with anti-dsDNA antibodies induced by anti-TNF-alpha therapies. Seven were candidates to be rhupus and 6 were retained. They were all women, with a median age of 51 years and in addition were all anti-SS-A antibody positive.

Comparison of the platelet concentrations obtained in platelet-rich plasma (PRP) between the GPS™ II and GPS™ III systems.

INTRODUCTION: Platelet growth factors are known for their ability to speed up tissue healing (bone, skin, tendons, muscle). Various techniques make it possible to collect this platelet-rich plasma or PRP. METHODS: This study compares the platelet concentrations obtained from five patients using GPS™ III, which has recently come onto the market, with those obtained using GPS™ II. RESULTS AND CONCLUSION: We obtain a platelet concentration that is six to nine times greater with GPS ™ II and GPS™ III, but there is no significant difference between the concentrations of PRP obtained with the two systems.

[Interest of monoclonal antibodies in biomedical laboratory analysis]. / Intérêt des anticorps monoclonaux dans le laboratoire d'analyses biomédicales.

Immunoassays, or assays with antibodies as reagents, are widely used in medical laboratories. These assays are used to identify and quantify various substances in biological fluids, such as specific proteins (various tissue markers, markers of inflammation, hormones, coagulation factors...) or immunoglobulins (viral or bacterial antibodies, auto-antibodies...) and even both viral antigens and antibodies (HIV virology). The use of monoclonal antibodies allowed, through their specificity for a single epitope of the target molecule, the development of increasingly sophisticated immunoassays. In particular, the use of monoclonal antibodies with microarrays permits the simultaneous determination of various proteins (inflammatory profile, cardiac profile, specifics IgE...) quickly and accurately. Very important tools in the clinical laboratory, immunoassays techniques are, however, subject to various analytical interferences which may be responsible for significant changes in the test results.

[How I explore ... review of the principals of antibodies]. / Comment j'explore ... revue des principaux auto-anticorps.

Auto-immune diseases represent the 3rd cause of morbidity after cardiovascular and oncologic diseases. They often occur in young subjects. Their presence is not synonymous of disease and must be associated to clinical signs to be pathological. However, their discovery can require a complement of investigations and the possibility of a follow-up because some auto-antibodies are predictive of disease. This paper is concerned with the main autoantibodies that can be picked out at the laboratory of immunology. Some technical explanations and INAMI rules are explained too.

[Comparison of five techniques to detect anti-Saccharomyces cerevisiae antibodies (ASCA) in serum for diagnosing Crohn's disease]. / Comparaison de cinq techniques de détection des anticorps anti-Saccharomyces cerevisiae (ASCA) dans le sérum pour le diagnostic de la maladie de Crohn.

OBJECTIVE: the anti-Saccharomyces cerevisiae antibodies (ASCA) are diagnostic markers found in Crohn's disease patients. The aim of this study was to compare three Elisa (enzyme linked immunosorbent assay) kits with the indirect immunofluorescence (IFI) technique and an immunodot for ASCA detection. MATERIALS AND METHODS: we compared the results obtained using IFI (IgA and IgG) and Elisa (IgA and IgG) in 139 patients (37 Crohn's disease). An immunodot (IgA+IgG) was tested in a sub-group of 24 patients (18 Crohn's disease). RESULTS AND DISCUSSION: for the different techniques by Elisa (IgA or IgG), the sensitivity ranged from 65% to 76%, the specificity from 88% to 98%, the positive predictive value (PPV) from 84% to 94% and the negative predictive value (NPV) from 88% to 93%. For IFI, the sensitivity was 81%, the specificity 100%, the PPV 100% and the NPV 93%. The immunodot showed a specificity and PPV of 100% and NPV of 33%. CONCLUSION: the detection of the ASCA is useful in the diagnosis of Crohn's disease. IFI appears as the method of choice for its excellent sensitivity and specificity, and affordable costs.

[Homocysteine and cardiovascular risk]. / Homocystéine et risque cardio-vasculaire.

Homocystinuria is an uncommon genetic disease characterized by a marked increase of serum homocysteine (HCY), an intermediate of methionine metabolism. In patients with homocystinuria, hyperhomocysteinemia promotes the development of atherosclerotic lesions and is responsible for premature coronary artery disease. Recently, several studies have also demonstrated that moderate hyperhomocysteinemia--not necessarily linked to an inborn metabolic defect--may also be considered as an independant risk factor for cardiovascular disease. The main mechanisms of HCY atherogenic action are thought to be LDL oxydation, inhibition of vascular endothelium growth combined with stimulation of smooth muscular cells proliferation, and interference with the coagulation and fibrinolytic systems. Cofactors of key enzymes in HCY metabolism, folic acid, vitamin B12 and vitamin B6, may be given, alone or in combination, for the treatment of hyperhomocysteinemia. Homocysteinemia can be assessed by basal plasma HCY concentration and/or by HCY levels measured after a methionine loading test. Mainly measured till now in specialized laboratories using rather complex techniques (HPLC, GCMS, amino acid analyser ...), HCY determination is today spreading widely owing to the development of automated immunoassays.