Lidove O, Kaminsky P, Hachulla E, Leguy‐Seguin V, Lavigne C, Marie I, Maillot F, Serratrice C, Masseau A, Chérin P, Cabane J, Noel E; on behalf of the FIMeD investigators. 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.
Summary
Aim: Fabry’s disease is an X‐linked inherited lysosomal storage disorder caused by the deficient activity of alpha‐galactosidase A. The interrelationships between clinical symptoms in Fabry ...patients have not yet been fully established. Using cluster and multivariate analysis, the aim of the study was to determine the relationships among clinical symptoms and organ involvement, and predictive clinical symptoms for disease severity.
Methods: Clinical data obtained from 108 French Fabry patients were retrospectively collected and analysed using multiple correspondence analysis and hierachical ascendant classification. Multivariate analysis was also performed to determine among clinical symptoms predictors for cardiac disease (HRT), renal involvement (KDN) and brain complication (STR).
Results: The cohort comprised 41 male patients (aged 28.9 ± 11.6 years) and 67 female patients (aged 40.4 ± 15.5 years). Three main clusters of clinical symptoms could be delineated, characterising disease progression: the first cluster grouped digestive disorders (found in 30% of the patients) and exercise intolerance (32%), the second, cluster dyshidrosis (47%), acroparesthesia (67%), angiokeratoma (44%) and cornea verticillata (54%), the third, cluster grouped KDN (30%), HRT (39%) and STR (25%) and hearing loss (44%). In univariate analysis, the patient age predicted HRT and KDN, dyshidrosis predicted HRT and STR, angiokeratoma predicted KDN and cornea verticilla and hearing loss predicted KDN, HRT and STR. In multivariate analysis, hearing loss and age were independent predictors of organ complication.
Conclusion: Among the various interrelated clinical symptoms occurring in Fabry disease, patients with dyshidrosis and particularly hearing disorders appear to be at higher risk of organ complications.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of systemic vasculitis in which cardiac involvement is frequent and severe, and accounts for half of EGPA‐related deaths. ...ANCA‐positive EGPA differs from ANCA‐negative EGPA in that the former is significantly associated with renal involvement, peripheral neuropathy and biopsy proven vasculitis, whereas the latter is associated with cardiac involvement. Herein, we report a case of EGPA with myocarditis in a woman, who was successfully treated with steroids and cyclophosphamide. This report highlights the importance of diagnosing cardiac involvement in EGPA early, especially in ANCA‐negative patients.
Scalp vein thrombosis is an unusual complication during giant cell arteritis. Revealed by headache, it can be misdiagnosed as a disease relapse. An ultrasound scan should rapidly be performed to make ...the diagnosis, avoiding inappropriate treatment escalation.
Systemic lupus erythematosus (SLE) has been described as a cause of thrombotic microangiopathy, especially thrombotic thrombocytopenic purpura (TTP). Haemolytic‐uraemic syndrome (HUS) is less ...frequent in SLE. We report a case of such an association during an episode of severe lupus nephritis in a young woman, who was successfully treated with steroids, cyclophosphamide and especially plasma exchange with plasma replacement. This report highlights the importance of recognising atypical HUS in SLE patients by looking for schistocytes in case of haemolytic anemia with a negative antiglobulin test, in order to begin plasma exchange.
The discovery of a hyperferritinemia is most of the time fortuitous. The diagnostic approach aims at looking for the responsible etiology and at verifying if an iron hepatic overload is present or ...not. Three diagnostic steps are proposed. The clinical elements and a few straightforward biological tests are sufficient at first to identify one of the four main causes: alcoholism, inflammatory syndrome, cytolysis, and metabolic syndrome. None of these causes is associated with a significant iron hepatic overload. If the transferring saturation coefficient is raised (>50%) a hereditary hemochromatosis should be discussed. Secondly, less common disorders will be discussed. Among these, only the chronic hematological disorders either acquired or congenital are at risk of iron hepatic overload. Thirdly, if a doubt persists in the etiologic research, and the serum ferritin level is very high or continues to rise, it is essential to verify that there is no iron hepatic overload. For that purpose, the MRI with study of the iron overload is the main test, which will guide the therapeutic attitude. Identification of more than a single etiology occurs in more than 40% of the cases.
Diffuse and abundant sweating in a middle age patient evolving for several weeks should raise suspicion of malignant lymphoma and infectious or neuroendocrine disorders before considering a drug ...origin. We report a patient who presented with severe and invalidating excessive sweating related to hydromorphone therapy for vertebral pain. Amongst their many reported side-effects, excessive sweating disappearing with discontinuation of the drug have been reported with some opiates.
It is unclear whether hereditary hemorrhagic telangiectasia (HHT) patients can tolerate antithrombotic therapies (AT) including antiplatelet (AP) and/or anticoagulant (AC) agents.
Primary endpoint ...was tolerance to AT in HHT. Secondary endpoints were to identify factors associated with major bleeding events (MBE) and premature discontinuation of AT.
Retrospective multicenter study in French national HHT Registry patients exposed to AT.
We included 126 patients with 180 courses of AT. Median follow-up was 24 11–52 months. Mean age was 65.6 ± 13.1 years. The first 3 months of AT exposure had an increased risk of hospitalization for hemorrhage (p < 0.001) and transfusions (p < 0.001). MBE (n = 63) occurred more frequently in the first 3 months of AT exposure (p < 0.001). Premature discontinuation of AT occurred in 61 cases. Rate of premature discontinuation was 29 % under both AP and AT therapy but significantly higher under dual AP therapy (n = 4/7, 57 % p = 0.008). Risk factors for MBE were: age ≥ 60 years (HR 2.34 1.12;4.87, p = 0.023), prior hospitalization in the 3 months before starting AT for hemorrhage (HR 3.59 1.93;6.66, p < 0.001) or transfusion (HR 3.15 1.61;6.18, p = 0.001), previous history of gastro-intestinal bleeding (HR 2.71 1.57;4.65, p < 0.001) or MBE (HR 4.62 2.68;7.98, p < 0.001). Frequency of MBE did not differ between groups except for a higher risk in the dual AP group (HR 3.92 1.37;11.22, p = 0.011).
Tolerance of AC or AP therapy was similar in HHT population but not dual AP therapy. We identified risk factors for MBE occurrence or premature discontinuation under AT.
•Similar tolerability of antiplatelet and anticoagulant therapies in HHT•Dual antiplatelet therapy is not tolerated in HHT and should be avoided•Risk factors in HHT patients for major bleeding events (MBE) occurrence or premature discontinuation under antithrombotics are ≥60 years old, previous history of MBE or gastrointestinal bleeding, hospitalizations for bleeding in the last 3 months to help guide clinicians prescribing antithrombotic medication•Direct oral anticoagulants, notably apixaban, appear well tolerated by HHT patients
Des sueurs profuses, généralisées, évoluant depuis plusieurs semaines chez un patient d’âge moyen doivent faire rechercher une étiologie lymphomateuse, infectieuse ou neuroendocrine avant d’envisager ...une origine médicamenteuse. Nous rapportons l’observation d’un patient souffrant d’un tableau d’hypersudation, particulièrement sévère et invalidante liée à la prise d’hydromorphone (Sophidone LP
®) pour des douleurs rachidiennes. Parmi les nombreux effets secondaires potentiels des opiacés, des épisodes d’hypersudation résolutifs à l’arrêt sont décrits lors de l’utilisation de certaines molécules.
Diffuse and abundant sweating in a middle age patient evolving for several weeks should raise suspicion of malignant lymphoma and infectious or neuroendocrine disorders before considering a drug origin. We report a patient who presented with severe and invalidating excessive sweating related to hydromorphone therapy for vertebral pain. Amongst their many reported side-effects, excessive sweating disappearing with discontinuation of the drug have been reported with some opiates.
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