Coagulation disorders during treatment with cefazolin and rifampicin: rare but dangerous.

We describe a 79-year-old man with spondylodiscitis and unknown pathogen, treated with cefazolin and rifampicin. He developed a massive digestive hemorrhage. Prothrombin time was prolonged with severe vitamin-K-dependent clotting-factor deficiency. Severe bleeding can occur during cefazolin and rifampicin use. This deficiency should be assessed before prescribing cefazolin-rifampicin and prothrombin time monitored.

[Fabry disease]. / Maladie de Fabry.

Fabry disease. Fabry disease is an X-linked disorder in which lysosomal alpha-galactosidase A is lacking, leading to enzyme-substrate accumulation and tissues dysfunction. Acroparesthesia, angiokeratoma, familial nephropathy or hypertrophic cardiomyopathy should suggest Fabry disease. Enzymatic assay allows diagnosis in men but genetic assay is needed for women. Enzyme replacement therapy is available since 2001 and a pharmacologic chaperone since 2016.

Maladie de Fabry. La maladie de Fabry est une maladie rare, monogénique, liée à l'X, où un déficit enzymatique en alpha-galactosidase A lysosomale provoque l'accumulation intracellulaire de son substrat à l'origine de dysfonctions d'organe. On doit l'évoquer aussi bien chez l'homme que chez la femme, en particulier devant des acroparesthésies à électropyogramme normal, des angiokératomes, une insuffisance rénale familiale ou une cardiopathie hypertrophique possiblement isolée et sans obstacle à l'éjection. Le diagnostic se fait par dosage enzymatique chez l'homme et par analyse génétique chez la femme. Trois traitements sont disponibles : deux enzymothérapies substitutives depuis 2001, une molécule chaperon depuis 2016.

[Autoimmune hemolytic anemias]. / Anémies hémolytiques auto-immunes.

Autoimmune hemolytic anemias. Autoimmune hemolytic anemias (AIHA) are a rare cause of acquired hemolytic anemia, linked to the presence of an autoantibody directed against one or more antigens expressed on the surface of the red blood cell and certified by a positive direct antiglobulin test (DAT). AIHA can be non regenerative (10-20% of cases) and DAT may be negative (5% of cases). There are two main forms: warm antibodies AIHA (IgG positive TDA +/- C3d) and cold antibodies AIHA (C3d positive TDA), which differ in their underlying causes and treatment. Warm antibodies AIHA are in 50% of cases associated to B-cell chronic lymphoid leukemia, variable common immune deficiency, systemic lupus or drug; the treatment is based on short corticosteroid therapy (3 to 6 months) and rituximab is the 2nd line treatment. Cold antibodies AIHA are of two types: either post-infectious (mycoplasma, EBV), or linked to cold agglutinin disease that is indolent B clonal hemopathy; the treatment is primarily symptomatic and relies on cold protection measures. Corticosteroid therapy and splenectomy are ineffective. In cases of severe anemia, treatment with rituximab alone or in combination with chemotherapy is indicated.

Anemies hemolytiques auto-immunes. Les anémies hémolytiques auto-immunes sont une cause rare d'anémie hémolytique acquise, liée à la présence d'un auto-anticorps dirigé contre un ou plusieurs antigènes exprimé(s) à la surface du globule rouge et le plus souvent attestée par un test direct à l'antiglobuline (TDA) positif. Rarement, les anémies hémolytiques auto-immunes peuvent être arégénératives (10- 20 % des cas), et le TDA peut être négatif (5 % des cas). On en distingue deux formes principales : les anémies hémolytiques auto- immunes à anticorps chauds (TDA positif de type IgG +/- C3d) et les anémies hémolytiques auto-immunes à anticorps froids (TDA positif de type C3d), qui diffèrent par leurs causes sous-jacentes et par leur traitement. Les anémies hémolytiques auto-immunes à anticorps chauds sont dans 50 % des cas « secondaires ¼ à une hémopathie lymphoïde B, un déficit immunitaire commun variable, un lupus systémique, ou induites par un médicament ; le traitement repose sur une corticothérapie courte (3 à 6 mois), et le rituximab est le traitement de 2e ligne. Les anémies hémolytiques auto-immunes à anticorps froids sont de deux types : soit postinfectieuses (mycoplasme, virus d'Epstein-Barr), soit liées à une maladie des agglutinines froides, qui est une hémopathie clonale B indolente ; le traitement est avant tout symptomatique et repose sur les mesures de protection vis-à-vis du froid. La corticothérapie et la splénectomie sont inefficaces. En cas d'anémie marquée, un traitement par rituximab seul ou combiné à une chimiothérapie est indiqué.

Cornea verticillata and acroparesthesia efficiently discriminate clusters of severity in Fabry disease.

BACKGROUD: Fabry disease (OMIM #301 500), the most prevalent lysosomal storage disease, is caused by enzymatic defects in alpha-galactosidase A (GLA gene; Xq22.1). Fabry disease has historically been characterized by progressive renal failure, early stroke and hypertrophic cardiomyopathy, with a diminished life expectancy. A nonclassical phenotype has been described with an almost exclusive cardiac involvement. Specific therapies with enzyme substitution or chaperone molecules are now available depending on the mutation carried. Numerous clinical and fundamental studies have been conducted without stratifying patients by phenotype or severity, despite different prognoses and possible different pathophysiologies. We aimed to identify a simple and clinically relevant way to classify and stratify patients according to their disease severity. METHODS: Based on data from the French Fabry Biobank and Registry (FFABRY; n = 104; 54 males), we applied unsupervised multivariate statistics to determine clusters of patients and identify clinical criteria that would allow an effective classification of adult patients. Thanks to these criteria and empirical clinical considerations we secondly elaborate a new score that allow the severity stratification of patients. RESULTS: We observed that the absence of acroparesthesia or cornea verticillata is sufficient to classify males as having the nonclassical phenotype. We did not identify criteria that significantly cluster female patients. The classical phenotype was associated with a higher risk of severe renal (HR = 35.1; p <10-3) and cardiac events (HR = 4.8; p = 0.008) and a trend toward a higher risk of severe neurological events (HR = 7.7; p = 0.08) compared to nonclassical males. Our simple, rapid and clinically-relevant FFABRY score gave concordant results with the validated MSSI. CONCLUSION: Acroparesthesia and cornea verticillata are simple clinical criteria that efficiently stratify Fabry patients, defining 3 different groups: females and males with nonclassical and classical phenotypes of significantly different severity. The FFABRY score allows severity stratification of Fabry patients.