Search

This article discusses an ad hoc data collection form created by a multiprofessional working group validated by the Centres for Evaluation and Information on Pharmacodependence in France regarding the cutaneous complications among high-dose buprenorphine injection users. Data collected from patients include medical history, demographic data, demographic data and drugs related to the cutaneous complications.

Reassesses cases of an inflammatory muscle disorder with an unknown cause emerging in France. The disorder as characterized by a distinctive pathological pattern of macrophagic myofasciitis; The main presumptive diagnoses as polymyositis and polymyalgia rheumatica; Symptoms; Treatment; Methods; Results; Discussion.

Malgré les bonnes sensibilités et spécificités des recherches d'ANCA anti-MPO et anti-PR3, le diagnostic des vascularites associées aux ANCA (VAA) est parfois difficile. Les recommandations actuelles préconisent d'obtenir une confirmation histologique du diagnostic. En cas de glomérulonéphrite et en l'absence de contre-indication, la biopsie rénale s'impose et apporte des données diagnostiques et pronostiques. Les autres sites biopsiables manquent de sensibilité, particulièrement au niveau du tractus respiratoire. Peu de données évaluant la biopsie musculaire sont disponibles. L'objectif de ce travail était d'étudier la sensibilité de la biopsie musculaire (BM) dans les VAA, et rechercher une corrélation à un profil clinicobiologique ou évolutif. Nous avons conduit une étude monocentrique rétrospective sur notre cohorte de patients suivis pour une VAA entre 1995 et 2018, chez qui une BM avait été réalisée. Nous avons exclu les patients chez qui la BM était faite à l'occasion d'une rechute. Les patients étaient classés selon l'algorithme de l'European Medicines Agency : granulomatose avec polyangéite (GPA), polyangéite microscopique (PAM), granulomatose éosinophilique avec polyangéite (GEPA). Cent un patients de notre cohorte ont eu une biopsie musculaire. Un seul patient a eu une complication de la biopsie (hématome, puis surinfection). Soixante-dix-huit patients ont été inclus, dont 45 avaient une biopsie positive soit une sensibilité (Se) de 57,7 % ; 17/33 biopsies positives parmi les GPA, 16/25 parmi les PAM et 12/20 parmi les GEPA, soit des sensibilités respectivement de 51,5 %, 64 % et 60 %. Dans le groupe GPA-PAM, en analyse multivariée, le résultat de la BM était corrélé avec la présence d'anti-MPO (76 % vs 48 %, p = 0,016), le sexe féminin (67 % vs 36 %, p = 0,038), et le taux de neutrophiles (10,8 G/L vs 7,6 G/L, p = 0,024). La positivité de la biopsie n'était pas associée à une évolution particulière (décès, survie sans rechute). Dans le groupe GEPA, la positivité de la BM était associée au sexe féminin (p = 0,046) et à un plus faible taux de créatinine (p = 0,03). La biopsie musculaire est un outil performant pour obtenir la confirmation histologique d'une vascularite associée aux ANCA. Sa sensibilité semble meilleure que les autres potentiels sites biopsiques non-rénaux, notamment ORL (Se = 21–23 %). Les facteurs associés à sa positivité sont le type d'ANCA (anti-MPO), le sexe féminin et le taux de neutrophiles. Si elle ne peut pas se substituer à la biopsie rénale en cas de glomérulonéphrite, elle devrait être discutée dans les autres situations, particulièrement en présence des facteurs sus-cités ou de contre-indication à la biopsie rénale. Dans notre étude, le résultat de la biopsie musculaire n'avait pas de valeur pronostique. [ABSTRACT FROM AUTHOR]

Exercise intolerance may be suggestive of metabolic myopathy or mitochondrial disorders. We report a family where 7 female subjects presented with various degree of exercise intolerance since childhood. A common and original feature shared by affected members was the increased volume of the masseter muscle systematically occurring after feeding, making them looking like a hamster. Limb muscle size was not affected by effort. Patients also complained of keloid scars and for some of them of congenital cataract. The index case underwent full examination including clinical assessment, electromyography, electro-retinography, muscle biopsy, pulmonary function testing, exercise test, genetic testing. Clinical and EDX examinations were normal. Exercise test was brief due to muscle fatigue but induced an important increase of lactates and lactate/pyruvate ratio. Morphological analysis and standard immunochemistry of the muscle biopsy were normal but analysis of the respiratory chain complexes from the muscle biopsy displayed a combined defect in the complexes I, III, and IV encoded by mitochondrial DNA, associated with an increase of complex II and citrate synthase. An increased number of muscle mtDNA copies was observed reflecting a probable mitochondrial proliferation. Whole mtDNA sequencing revealed the homoplasmic m.15992A > T variant in the mitochondrial tRNA (Pro) gene (MT-TP). This mutation does not affect the codon reading but modifies the efficiency of aminoacylation or of post-transcriptional modification, leading to less efficient translation. It was also found in 3 affected members apart from index case and is very likely to be pathological. The relationships between the gene mutation and the unusual clinical phenotype are not clear but are worthy of interest. [ABSTRACT FROM AUTHOR]

Mutations in the Fukutin-Related Protein gene ( FKRP ) account for a broad spectrum of phenotypes ranging from severe congenital muscular dystrophies to much milder limb-girdle muscular dystrophy (LGMD2I). In both, weakness and wasting of shoulder-girdle muscles, primary restrictive respiratory and cardiac involvement are classical features. To our knowledge, facial dysmorphic features have not been reported yet. The first woman developed, at age 12, a progressive pelvic weakness. Two biopsies were performed showing a dystrophic pattern with normal classical immunohistochemistry. At age 38, she was confined in a wheelchair and suffered from respiratory insufficiency. She also had a mild cardiomyopathy. As she presented macroglossia, analysis of the FKRP gene was performed and two compound mutations p.Leu276Ile and p.Glu343X were found. The second woman was born of a consanguineous union. From childhood, she had difficulties running and rising from the floor. At 12, she developed a limb-girdle weakness that confined her in a wheelchair at age 26. Vital capacity was normal, as well as US heart exam. Muscular biopsy showed classical dystrophic features with normal immunohistochemistry and Western blot. She had no macroglossia but her face looked alike our first FKRP patient. Indeed, both women presented hypertelorism, large palpebral fissures, depressed nasal bridge, prognathism and thick lips being responsible for a dramatic physical resemblance although they were unrelated. FKRP gene analysis was therefore performed and a homozygous mutation p.Leu276Ile was found. Limb-Girdle weakness associated with macroglossia and calf hypertrophy are classical clues for FKRP gene sequencing. Some mutations have more frequent macroglossia or calf hypertrophy than others. But facial dysmorphia has not been reported in this disease so far. This dysmorphia represent a real diagnosis help in our second patient and should be searched each time a LGMD patient is considered. [ABSTRACT FROM AUTHOR]

Among congenital myopathies, X-linked recessive myotubular myopathy is one of the most severe forms. The majority of patients present with severe hypotonia at birth and respiratory insufficiency and most of them die in the first year of life. However, there is phenotypic variability. Here, we report two patients carrying a missense mutation in MTM1 gene and presenting with a mild phenotype. The first boy was born on time with respiratory insufficiency and generalised hypotonia. He required ventilator support for 3 weeks, and then he went home without specific care. He walked at 11 month. He is now 24 and can run, practices canoe and works as a salesperson. At the exam, he presents mild proximal weakness and restrictive syndrome with no ventilator support (VC = 57%). His brother was born on time with respiratory insufficiency and hypotonia. He stayed in intensive care unit for 6 weeks, then went home without support. He walked at 18 months. Respiratory involvement was more severe than his brother with a severe restrictive syndrome (VC = 33%) but the young man refused non-invasive night-time ventilation proposed at the age of 16. Being now 20, he can walk without any difficulty but cannot run. Clinical exam reveals a mild proximal weakness. Both patients underwent muscle biopsy showing the typical centronuclear myopathy pattern. Molecular analysis of MTM1 gene found a hemizygous mutation c.575A>G in exon 8 leading to a missense p.Tyr192Cys. A decreased level of the MTM1 protein was observed by western blot analysis on lymphoblasts. To date, about 300 different mutations in around 540 families have been identified in MTM1 gene, including point mutations, insertions and small and large deletions and duplication. Around 70% of patients presenting with a mild or moderate phenotype carries a missense mutation, which is also the most frequent type of mutation. Another patient has been described with the same mutation (c.575A>G) and presented also with a mild phenotype. [ABSTRACT FROM AUTHOR]

Hereditary Fibrosing Poikiloderma (HFP) with tendon contracture and pulmonary fibrosis has been described in a South-African family with autosomal dominant inheritance by Khumalo et al. in 2006. Recently, we confirmed the existence of this new syndrome by reporting four additional cases and identified the causative gene called FAM111B (NM_198947.3) by whole exome sequencing. Here we report the clinical and molecular data of seven independent patients: four males and three females (ages 3–38). Key features consist of: (i) congenital poikiloderma, hypotrichosis, hypohidrosis; (ii) muscle contractures in particular triceps surae and/or biceps brachii muscle contractures; (iii) progressive muscular weakness with a proximal and distal pattern and (iv) progressive pulmonary fibrosis. Muscle MRI showed extensive fatty infiltration confirmed by muscle biopsy. Histological examination of skeletal muscle revealed a partial loss of muscle tissue associated with extensive fibrofatty tissue infiltration regardless of age. There was no indication of denervation, necrosis, or inflammation. Microscopy of the skin showed a sclerodermiform aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two mutations were shared respectively by three and two patients). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain of function or dominant negative mutations resulting in FAM111B enzymatic activity changes. Functional studies are ongoing to better understand the pathophysiology of this entity. In conclusion, HFP with tendon contracture, myopathy and pulmonary fibrosis, a phenotypically recognisable syndrome, is caused by autosomal dominant mutations in FAM111B gene. These findings provide genetic evidence for a new pathogenetic pathway for muscle impairment. [ABSTRACT FROM AUTHOR]