[Diagnostic journey of type 1 Gaucher Disease patients: A survey including internists and hematologists]. / Parcours diagnostique des patients atteints de maladie de Gaucher de type 1 : enquête auprès de médecins internistes et hématologues.

INTRODUCTION: Gaucher disease (GD) is a rare genetic lysosomal storage disorder caused by a beta-glucocerebrosidase deficiency and responsible for a lysosomal storage disorder. GD is characterized by haematological, visceral and bone involvements. The aim of this study was to describe the diagnostic journey of type 1 GD patients as well as the role of the internist. METHODS: A retrospective multicentric study involving type 1 GD patients has been conducted in 16 centers, between 2009 and 2011. RESULTS: Fifty-five type 1 GD patients were included, under the care of an internist or an haematologist. They were originally hospitalized in 8 different specialized units. Diagnosis was established by bone-marrow aspiration in 22 patients (40%), by enzymatic assay of glucocerebrosidase activity in 15 patients (27%), and by bone-marrow biopsy in 9 patients (16%). The use of enzymatic assay became more frequent after 1990. The delay between first hospitalization due to GD symptoms and definitive diagnosis was less than one year for 38 patients. Patients with suspected GD were mainly referred to an internist physician. CONCLUSION: GD seems to be better recognized and quickly diagnosed since 1990 in spite of the multiplicity of journeys. The role of the internist seems important.

The Clinical Relevance of Antifibrillarin (anti-U3-RNP) Autoantibodies in Systemic Sclerosis.

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several antinuclear autoantibodies useful to diagnosis and prognosis. The aim of the present multicentric study was to determine the clinical relevance of antifibrillarin autoantibodies (AFA) in patients with SSc. The clinical features of 37 patients with SSc positive for AFA (AFA+) and 139 SSc patients without AFA (AFA-) were collected retrospectively from medical records to enable a comparison between AFA- and AFA+ patients. Antifibrillarin autoantibodies were screened by an indirect immunofluorescence technique using HEp2 cells and identified by an in-house Western blot technique and/or an EliA test. Comparing AFA+ and AFA- patients, AFA+ patients were significantly younger at disease onset (36.9 versus 42.9; P = 0.02), more frequently male (P = 0.02) and of Afro-Caribbean descent (65% versus 7.7%; P < 0.001). At diagnosis, the Rodnan skin score evaluating the cutaneous manifestations was higher (13.3 versus 8.7; P = 0.01) and myositis was also more common in the AFA+ group (31.4% versus 12.2%; P < 0.01). Patients with AFA+ were not associated with diffuse cutaneous SSc or with lung involvement and no difference in survival was observed. Antifibrillarin autoantibodies are associated with patients of Afro-Caribbean origin and can identify patients with SSc who are younger at disease onset and display a higher prevalence of myositis.

[Periungueal capillaroscopy: an easy and reliable method to evaluate all microcirculation diseases]. / Capillaroscopie périunguéale : une évaluation simple et fiable de toute pathologie de la microcirculation.

Periungueal capillaroscopy is a simple and reliable non-invasive technique allowing evaluation of cutaneous microcirculation. It was promoted for decades in patients with Raynaud's phenomenon in order to differentiate between the benign primary Raynaud's phenomenon and the secondary form in connective tissue diseases, especially systemic sclerosis. Nevertheless, the value of this procedure has also been shown in numerous pathologies such as diabetes or cardiovascular diseases. This literature review points to the versatility of this useful exam and its results in a large spectrum of diseases with microvascular involvement.

[Lightning strike and lesions outside the brain: Clinical cases and a review of the literature]. / Les atteintes extra-cérébrales de la foudre : vignettes cliniques et revue de la littérature.

INTRODUCTION: Every year, 240,000 people are struck by lightning worldwide, causing injuries leading to significant handicaps. Most of the symptoms involve brain lesions; neuromuscular sequelae and myelopathy are less common. OBSERVATIONS: We describe five cases of patients struck by lightning with various clinical presentations. The first patient presented painful paresthesias in both upper limbs that disappeared 18 months later; the injury was a plexopathy. The second patient developed proximal weakness in the upper-left limb due to a myopathy. Two patients presented with various motor weaknesses in the lower limbs due to motor neuron disease and myelopathy. The last patient had a transient tetraplegy, which resolved in 5minutes; the diagnosis was keraunoparalysis. DISCUSSION: Lightning injuries can have many consequences depending on the different mechanisms involved. The clinical presentation is often due to a very focal lesion without any secondary extension. Motor neuron disease probably results from post-traumatic myelopathy. We discuss the ALS-electrocution association, frequently described in the literature. CONCLUSION: Various peripheral nerve and spinal cord lesions can be seen in lightning strike victims involving myelopathy, motor neuron, muscle and plexus. Clinical syndromes are often atypical but outcome is often favorable.

[Cannabinoid hyperemesis syndrome: about 6 cases]. / Syndrome d'hyperémèse cannabique : à propos de 6 cas.

INTRODUCTION: The cannabinoid hyperemesis syndrome (CHS) is characterized by cyclic episodes of nausea, vomiting, and abdominal pain, and occurs in young adults with long-term cannabis use. The feature of this syndrome is the relief of symptoms with hot showers. We report here six cases report. CASE REPORTS: Three women and 3 men, chronic consumers of cannabis, presented with typical features of the CHS, but the syndrome remained undiagnosed until then: nausea, vomiting, abdominal pain with morning ascendancy and loss of weight occurring in adult's of less than 50 years. The symptoms were improved by taking repeated hot showers. The medical investigations were negative. After addictologist care and cannabis weaning, digestive symptoms disappeared. CONCLUSION: The CHS is based on a clinical diagnosis. When undiagnosed, clinical presentation leads to a medical wandering and to the realization of repeated, expensive, and sometimes invasive exams. The physiopathology is not clear. The treatment relies on the definitive cannabis weaning.

[Perioperative management of patients with systemic scleroderma]. / Prise en charge périopératoire du patient sclérodermique.

Systemic sclerosis (SSc) is an auto-immune disease characterized by vasculopathy and the combination of microangiopathy and tissue collagen deposit leading to skin, digestive, pulmonary, myocardial and renal injuries. These repercussions could be challenging for anesthesiologists and associated with difficulties in airway management, and occurrence of congestive right heart failure or acute kidney crisis. The aim of this review is to review the physiopathology and the progression of the SSc, as well as to provide a strategy of perioperative management of these patients.

Primary-care physicians' patient referral patterns to private versus public hospitals for orthopaedic or trauma surgery-- French Sentinels® database, 1997-2011.

BACKGROUND: In France, primary-care physicians referring patients for admission can choose between public and private hospitals. The factors that govern their choices are unknown. METHODS: Among all patient admissions reported from 1997 to 2011 by primary-care physicians participating in the Sentinels(®) network, we identified those due to orthopaedic conditions or trauma. We then identified the factors associated with referral to a private hospital rather than to a public hospital. RESULTS: Of 45,960 admissions reported to Sentinels(®) in 1997-2011, 2794 (6.1%) were for orthopaedic/trauma care. The main reasons for admission were hip fractures (27.5%), elective orthopaedic surgery (15.5%), fractures of the humerus (5.9%), wrist fractures (5.4%), soft-tissue lesions of the forearm or hand (5.0%), and spinal injuries (4.5%). Private hospitals were chosen more often for orthopaedic/trauma patients than for patients with other conditions (40% vs. 21.6% of cases, P<0.0001). When fracture of the humerus was used as the reference, referral to private hospitals was significantly more common for elective surgery (odds ratio, 3.30 [2.02-5.40]) and hip fracture (odds ratio, 1.50 [1.03-2.18]) and significantly less common for spinal injuries (odds ratio, 0.35 [0.19-0.66]). Other factors associated with referral to private hospitals were patient age, admission decision during an office visit or in a non-emergent setting, and admission decision made by the patient's usual physician. CONCLUSION: Specific factors seem to govern decisions by primary-care physicians to refer orthopaedic/trauma patients to private vs. public hospitals. Identical pricing scales for private and public hospitals will be implemented soon in France, a change that requires further analyses. LEVEL OF EVIDENCE: Level IV.

Long-term outcome in idiopathic granulomatous mastitis: a western multicentre study.

AIM: To investigate the presentation, disease course and long-term outcome of a western cohort of idiopathic granulomatous mastitis (IGM) and to analyse the impact of different therapeutic strategies. METHODS: Multicentre retrospective study of 23 women followed over an extended period. Patients were recruited in nine French internal medicine departments. RESULTS: The median follow-up was 6 years. IGM presented commonly as a single inflammatory unilateral extra-areolar lump of varying size. Clinical course was heterogeneous and frequently remitting/relapsing. Most patients had at least one recurrence (18/23, 78%). The mean number of recurrences was 1.3 ± 1.5. Seven women had a bilateral evolution. Twelve women received steroids (corticosteroids). Only two of these did not respond to corticosteroids, whereas six relapsed when dose was tapered off. Nine patients received colchicine and/or hydroxychloroquine. First-line treatment consisted of excisional surgery in eight cases. At the date of last interview, 91% of the patients declared to be healed, 15 being free of treatment. However, 12/21 (57%) reported significant sequelae (unsightly scars: eight and/or lasting pain: six). Unsightly scars were not more prevalent in patients who had received steroids whereas they tended to be more frequent after breast excisional surgery. In addition, we found that excisional surgery did not prevent recurrences more successfully than a conservative approach. CONCLUSIONS: Despite its retrospective nature, this Caucasian series provides novel information regarding long-term outcomes in IGM and argues in favour of conservative approaches. The value of immunomodulatory drugs such as colchicine or hydroxychloroquine deserves further investigation.

[High plasmatic concentration of vitamin B12: an indicator of hepatic diseases or tumors]. / Concentration plasmatique élevée de la vitamine B12 : un indicateur des maladies hépatiques ou tumorales.

PURPOSE: To identify the diseases that are associated with a high plasma concentration of vitamin B12 and to measure the strength of this association. PATIENTS AND METHODS: Retrospective study including all admissions between 1st May, 2005 and 30th April, 2008 in the UMAG pole departments (emergency, internal medicine, acute geriatrics and medical intensive care) with a test for plasma vitamin B12. The association between each of medical information system codes (solid tumors, malignant hematologic process, and renal disease) and a high or low vitamin B12 concentration was measured by odds ratios (OR) from logistic models taking into account repeated admissions, with adjustment for age and the weighted Charlson index. RESULTS: Among 3702 admissions, 12% had a B12 more than 820pg/ml, 10.4% a B12 less than 180pg/ml and 77.6% a normal B12 concentration. After adjustment for age and the weighted Charlson index, high concentration of vitamin B12 was associated with interstitial renal diseases (OR 2.7; 95% CI: [1.7-4.2]), and cirrhosis or hepatitis (OR 4.3; [2.9-6.4]). After additional adjustment for these parameters, it was still associated with tumors (OR 1.8; [1.2-2.6]), malignant hematologic diseases (OR 2.1; [1.3-3.5]), metastasis (OR 2.9; [1.5-5.9]), liver metastasis (OR 6.2; [2.7-14.5]), liver carcinoma (LC) (OR 3.3; [1.1-10.4]), liver tumors other than LC (OR 4.7; [1.2-17.9]) and lymphoma (OR 3.2; [1.6-6.4]) but not with myeloma (OR 1.9; [0.6-1.4]). Low concentration of B12 was associated with myeloma (OR 2.9; [1.3-6.6]). CONCLUSION: Finding a high plasma concentration of vitamin B12 should lead to a systematic search for a hepatic disease or a tumor, and particularly for a hepatic localization of a tumor.

[Pulmonary embolism revealed by a seizure: a case report and literature review]. / Embolie pulmonaire révélée par une crise convulsive : à propos d'un cas et revue de la littérature.

INTRODUCTION: Pulmonary embolism is a frequent disorder with a diagnostic approach based on probability estimation. Nevertheless, in some cases, prognosis may be impaired by delayed diagnosis resulting from atypical presenting manifestations. CASE REPORT: We report a 37-year-old woman, admitted for a seizure as the presenting manifestation of pulmonary embolism, and review nine additional similar cases reported in the literature since 1945. Seizures were always generalized tonico-clonic in nature without a past medical history of epilepsy in any case. Tachycardia was noted in nine patients over ten. Prognosis was usually severe leading to death by cardiovascular deficiency in 70% of cases. CONCLUSION: These observations suggest a systematic suspicion of pulmonary embolism in the presence of generalized convulsion with persistent tachycardia after resolution of the episode and no past medical history of seizures. More research is necessary to assess the role of d-dimer testing in these situations.

[Patients' beliefs about long-term glucocorticoid therapy and their association to treatment adherence]. / Le ressenti des patients vis-à-vis d'une corticothérapie orale prolongée influence l'adhérence déclarée à ce traitement.

BACKGROUND: In patients treated with systemic glucocorticoids (GCs), it is unknown if beliefs about the treatment are associated with level of reported adherence. PATIENTS AND METHODS: Cross-sectional study conducted in two departments of internal medicine during a six-month period. All patients receiving long-term GCs therapy were asked to fill in a questionnaire regarding their beliefs about (specific scale of the Beliefs about Medicines Questionnaire) and their adherence to (four-item Morisky-Green scale) GCs. Logistic regression analysis was used to assess association between beliefs about GCs and adherence to treatment. RESULTS: One hundred and eighty one questionnaires were analysed (women: 79%, median age [IQR]: 47 [33-61] years, median duration of treatment: 18 [7-72] months, median daily dosage of prednisone equivalent: 10 [6-20] mg). Among these 181 patients, 83 (46%) reported a "concern" score equal to or higher than the "necessity" score. Nineteen percent of patients reported a low adherence level. In multivariate analysis, these patients were significantly younger (OR: 0.96 [0.93-0.98] per increasing year of age, P=0.002) and reported more frequently a "concern" score higher than a "necessity" score (OR: 3.08 [1.27-7.46], P=0.01) as compared to patients reporting a high adherence level. CONCLUSION: Informing patients about the "necessity" of GCs and taking into account their "concerns" about adverse events or their fear of becoming dependent on the medication may improve their adherence to treatment.

Fabry disease 'The New Great Imposter': results of the French Observatoire in Internal Medicine Departments (FIMeD).

Fabry disease (FD) is an X-linked lysosomal storage disorder due to α-galactosidase A deficiency. It is associated with a broad range of clinical symptoms, resulting in frequent misdiagnosis and diagnostic delay, which may impact on patient outcomes. This retrospective observational study of 58 FD patients referred to 10 internal medicine departments in France aimed to review differential diagnoses received prior to diagnosis and examines diagnostic delay. The average age at the time of diagnosis was 27.6 years (range: 10-60) and 42.2 years (range: 9-77) among the 23 males and 35 females analyzed, respectively. Most common symptoms that led to FD diagnosis were family history of FD (12 males and 27 females), followed by pain in extremities (10 males and 5 females), and angiokeratoma (8 males and 4 females). Eighteen patients had received alternative diagnoses prior to FD diagnosis, including a female patient with four previous diagnoses. Four case reports are presented, which illustrate the diagnostic 'odyssey' and delayed diagnosis often experienced by patients. Clinicians should consider a diagnosis of FD when presented with a wide range of symptoms, thus helping to shorten the diagnostic delay and facilitating early therapy with enzyme replacement therapy to improve patient outcomes.

Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis.

Elevated serum CC chemokine ligand (CCL)18 reflects lung fibrosis activity in systemic sclerosis (SSc) and could be an early marker of lung function worsening. Therefore, we sought to evaluate whether serum CCL18 levels at baseline could predict worsening of lung disease in SSc. In this prospective study, 83 SSc patients were analysed longitudinally over a 4-yr observation period for the risk of occurrence of combined deleterious events, defined as a 10% decrease from baseline of total lung capacity or forced vital capacity % predicted, or death, according to serum CCL18 at inclusion. Receiver operating characteristic (ROC) curve analysis was performed for prediction of events during the first year after inclusion. The best cut-off level of serum CCL18 for prediction of a combined event within the follow-up period was 187 ng · mL(-1), with 53% sensitivity and 96% specificity (area under the ROC curve 0.86; p < 0.001). After a mean ± SD follow-up of 33.7 ± 10.8 months, a higher rate of disease progression occurred in the group with serum CCL18 levels >187 ng · mL(-1). The adjusted hazard ratio was 5.36 (95% CI 2.44-11.75; p < 0.001). In summary, serum CCL18 is an accurate predictive biomarker for the identification of patients with a higher risk of subsequent scleroderma lung disease worsening.

[Late onset Becker muscular dystrophy. A case report and literature review]. / Dystrophie musculaire de Becker à révélation tardive. À propos d'un nouveau patient et de 12 observations de la littérature.

INTRODUCTION: The first manifestations of Becker's muscular dystrophy usually occur during childhood, as Duchenne's muscular dystrophy, a related disease. However, clinical presentation is usually more heterogeneous and less severe. CASE REPORT: We report a 54-year-old man who presented with a late onset of Becker's muscular dystrophy, and review 12 additional similar cases previously reported in the literature. The disease onset ranged from 30 to 65 years old. Genetic deletion involved mainly exons 45 to 55 with variable phenotype: distal muscular hypertrophy in four cases, cardiac involvement (electrocardiography, radiography or echocardiography) in six out of the 12 studied cases. Compared to the paediatric form, functional impairment was milder, as only three patients after seven to 20 years of follow-up were wheelchair bound. CONCLUSION: The first manifestations of Becker's muscular dystrophy may occur after the age of 30 with heterogeneous phenotypes. Severity and limb disability is milder in these patients.

Association of the CD226 Ser(307) variant with systemic sclerosis: evidence of a contribution of costimulation pathways in systemic sclerosis pathogenesis.

OBJECTIVE: The nonsynonymous polymorphism rs763361 of the CD226 gene, which encodes DNAX accessory molecule 1, which is involved in T cell costimulation pathways, has recently been identified as a genetic risk factor for autoimmunity. The purpose of this study was to test for association of the CD226 rs763361 polymorphism with systemic sclerosis (SSc) in European Caucasian populations. METHODS: CD226 rs763361 was genotyped in 3,632 individuals, consisting of a discovery sample (991 SSc patients and 1,008 controls) and a replication sample (999 SSc patients and 634 controls). All study subjects were of European Caucasian origin. Expression of CD226 was assessed on peripheral blood mononuclear cells obtained from 21 healthy donors genotyped for CD226 rs763361. RESULTS: The CD226 rs763361 T allele was found to be associated with SSc in both the discovery and the replication samples, showing the following results in the combined populations: odds ratio (OR) 1.22 (95% confidence interval [95% CI] 1.10-1.34), P = 5.69 × 10(-5) . The CD226 T allele was also associated with various SSc subsets, highlighting a potential contribution to disease severity. The most remarkable associations of the CD226 TT risk genotype were observed with the diffuse cutaneous SSc subtype, the anti-topoisomerase I antibody-positive, and SSc-related fibrosing alveolitis subsets: OR 1.86 (95% CI 1.42-2.43), P = 5.15 × 10(-6) , OR 1.82 (95% CI 1.38-2.40), P = 2.16 × 10(-5) , and OR 1.61 (95% CI 1.25-2.08), P = 2.73 × 10(-4) , respectively. CD226 expression was not significantly influenced by CD226 rs763361 genotypes whatever the T cell subtype investigated. CONCLUSION: Our results establish CD226 as a new SSc genetic susceptibility factor underlying the contribution of costimulation pathways in the pathogenesis of SSc. Further work is nevertheless needed to define the causal variant at the CD226 locus as well as the functional consequences.

[Systemic sclerosis and pregnancy]. / Sclérodermie et grossesse.

Pregnancy in women diagnosed with systemic sclerosis is an infrequent situation with a generally favourable outcome according to the most recent studies. Women with systemic sclerosis who wish to become pregnant should obtain preconception counselling in order to withdraw teratogenic drugs and to carefully assess the disease activity. Severe organ impairment, early diffuse systemic sclerosis and pulmonary hypertension ought to discourage patients from pregnancy, as these situations are at high risk of complications for both mother and fetus during pregnancy and puerperium. During pregnancy, the most frequent maternal complication is worsening of gastroesophageal reflux, and the most severe complications are renal crisis and flaring arterial pulmonary hypertension. Angiotensin converting enzyme inhibitors are indicated at any stage of the pregnancy if renal crisis is suspected. Adverse obstetric outcomes are dominated by prematurity which may be the consequence of intra-uterine growth restriction or preeclampsia. Those complications might account for systemic sclerosis-associated vasculopathy, or for the presence of antiphospholipid antibodies. Patients with a previous history of placental insufficiency might benefit from treatment with aspirin, low dose anticoagulants or even nitric oxide donors. During the pregnancy, abnormal bilateral uterine artery Doppler is a predictor of vascular insufficiency and might guide initiation of further preventive treatments. Multicentric prospective cohort studies are warranted to identify more precisely the predictors of pregnancy-related complications and to define the best management of these patients.