[Hereditary angioedema and its new treatments: An update]. / Mise au point sur les angiœdèmes héréditaires et leurs nouvelles thérapeutiques.

Hereditary angioedema, with or without deficient C1 inhibitor level or function, is a rare disease characterized by recurrent attacks of noninflammatory subcutaneous and/or submucosal edema. It may be life-threatening and substantially affects quality of life. Attacks may be spontaneous or induced, in a setting of emotional stress, by infections or physical trauma, in particular. As the key mediator is bradykinin, this angioedema does not respond to the usual treatments of mast cell-mediated angioedema (antihistamines, corticosteroids, adrenaline), which is much more frequent. Therapeutic management of hereditary angioedema first consists in treating severe attacks with a selective B2 bradykinin receptor antagonist or a C1 inhibitor concentrate. The latter or an attenuated androgen (danazol) can be used for short-term prophylaxis. Therapeutic solutions conventionally proposed for long-term prophylaxis (danazol, antifibrinolytics [tranexamic acid], C1 inhibitor concentrate) vary in efficacy and/or pose problems of safety or ease of use. Kallikrein inhibitors (subcutaneous lanadelumab, oral berotralstat) recently made available as disease-modifying treatment constitute an important advance in long-term prophylaxis of hereditary angioedema attacks. The advent of these new drugs is accompanied by a new ambition for patients: optimize control of the disease and thereby minimize its impact on quality of life.

[Acquired angioedema due to C1-inhibitor deficiency: CREAK recommendations for diagnosis and treatment]. / Angiœdèmes par déficit acquis en C1-inhibiteur : recommandations du CREAK pour le diagnostic et la prise en charge.

Acquired angioedema with C1-inhibitor deficiency is a rare and peculiar entity belonging to the spectrum of bradykinin angioedemas. It usually occurs in subjects over 60 years old, and is mostly associated with a B-cell lymphoid hemopathy or a monoclonal gammopathy. The diagnosis relies on at least one angioedema episode, lasting more than 24 h, and on the decrease of functional C1-inhibitor. Low C1q is observed in 90% of patients, and an anti C1-inhibitor antibody is found in 50% of patients. The treatment of severe attacks relies on icatibant or C1-inhibitor perfusions. Long term prophylaxis in patients with frequent attacks requires treatment of the associated hemopathy if so. In case of idiopathic angioedema, tranexamic acid and danazol may be used, provided that there is-no thrombophilia; as well as rituximab as second-line treatment. Inhibitors of kallikrein still need to be evaluated in this therapeutic indication.

Angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study.

BACKGROUND: Bradykinin-mediated angioedema (AE) is a complication associated with thrombolysis for acute ischemic stroke. Risk factors are unknown and management is discussed. OBJECTIVES: To clarify risk factors associated with bradykinin-mediated AE after thrombolysis for acute ischemic stroke. METHODS: In a case-control study conducted at a French reference centre for bradykinin angiœdema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angiœdema, were compared to controls treated with thrombolysis treatment without angiœdema. RESULTS: Fifty-three thrombolysis-related AE were matched to 106 control subjects. The sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). The upper airways were involved in 37 (70%) cases. Three patients required mechanical ventilation. Patients with bradykinin-mediated angiœdema were more frequently women [33 (62%) vs. 44 (42%); P = 0.01], had higher frequency of prior ischemic stroke [12 (23%) vs. 9 (8%); P = 0.01], hypertension [46 (87%) vs. 70 (66%); P = 0.005], were more frequently treated with angiotensin-converting enzyme inhibitor [37 (70%) vs. 28 (26%); P < 0.001] and were more frequently hospitalized in intensive care medicine [ICU; 11 (21%) vs. 5 (5%); P = 0.004]. In multivariate analysis, factors associated with thrombolysis-related AE were female sex [odds ratio (OR), 3.04; 95% confident interval (CI), 1.32-7.01; P = 0.009] and treatment with angiotensin-converting enzyme inhibitors [(OR), 6.08; 95% (CI), 2.17-17.07; P < 0.001]. CONCLUSIONS: This case-control study points out angiotensin-converting enzyme inhibitors and female sex as risk factors of bradykinin AE associated with thrombolysis for ischemic stroke.

[Vasculitis of the hepatic artery: A case of a single-organ vasculitis]. / Vascularite de l'artère hépatique : à propos d'un cas d'atteinte d'organe isolée.

INTRODUCTION: Vasculitis usually have a systemic involvement. Rare cases of localized vasculitis have been described, but the exclusive involvement of the hepatic artery is exceptional. We report the case of a patient who developed a vasculitis of the right and left hepatic arteries. CASE REPORT: A 63-year-old woman presented with unexplained abdominal pain. A computed tomography of the abdomen was suggestive of vasculitis of the hepatic arteries, showing a sequence of stenosis and aneurysmal dilatations of the hepatic arteries. There were no other arterial involvement, in particular of the abdomen and the brain. No other systemic disease or infection was found. The outcome was favorable, with corticosteroids alone. DISCUSSION: The exclusive involvement of the hepatic artery is an exceptional form of localized vasculitis, with only one other case reported. This diagnosis could therefore be discussed, in the presence of unexplained hepatic hematoma or pain.

[Insulin edema in hepatic glycogenosis]. / Œdème insulinique au cours d'une glycogénose hépatique.

INTRODUCTION: Hepatic glycogenosis is a rare syndrome, which includes poorly controlled diabetes mellitus, hepatomegaly, delayed puberty, and growth delay. Insulin edema is sometimes associated. CASE REPORT: An 18-year-old woman presented with diffuse edema, hepatomegaly, amenorrhea, uncontrolled diabetes, and elevated transaminases and cholestasis. Hepatic ultrasonography and abdominal computed tomographic scan confirmed the hepatomegaly. The liver biopsy showed a massive glycogenosis and the diagnosis of hepatic glycogenosis was confirmed. Too large doses of insulin were responsible of diffuse edema. Diabetes equilibration and diminution of insulin intakes allow correction of this disorder. CONCLUSION: Excess of insulin can lead to excessive hepatic glycogen storage by activation of glycogenosis enzymes. Biological manifestations consist on elevated liver enzymes and hyperlactatemia. There is a link between administration of high dose of insulin and edema. Hepatic glycogenosis should be suspected when diabetes is uncontrolled and be considered as a differential diagnosis of steatosis. It may be associated and revealed by insulin edema directly related to excessive insulin intakes.

[Sudden death occurring after anti-Hu associated paraneoplastic cerebellar degeneration and dysautonomia revealing a small cell lung carcinoma]. / Mort subite au cours d'une dégénérescence cérébelleuse subaiguë paranéoplasique avec dysautonomie associée aux anticorps anti-Hu révélant un cancer bronchique à petites cellules.

INTRODUCTION: Paraneoplastic syndromes are a rare cancer complication with a frequent subacute evolution. OBSERVATION: A 62-year-old man was admitted presenting with a cerebellar syndrome and orthostatic hypotension with dysautonomia. Anti-Hu antibody research was positive. A subcarinal adenopathy biopsy found out a small cell lung carcinoma. Despite a treatment with immunoglobulin and chemotherapy, the patient died suddenly, after a raise of dysautonomia symptoms. CONCLUSION: Sudden death observations represent exceptional complications of paraneoplastic syndrome. They might be secondary to arrhythmias, ictal asystol or laryngospasm. Systematic research of paroxystic heart arrhythmias with holter-ECG in paraneoplastic syndrome may prevent sudden deaths.

[Auditory and vestibular findings in Fabry disease: a study of 25 patients]. / Atteintes ORL de la maladie de Fabry : à propos de 25 observations.

PURPOSE: Fabry disease (FD, OMIM 301500) is an X-linked lysosomal storage disorder due to deficient activity of the enzyme alpha-galactosidase A. Males and females exhibit severe organ involvement. The high incidence of otological symptoms was recently reported. PATIENTS AND METHODS: Monocentric and retrospective study of twenty-five patients with FD (13 families; seven males and 18 females). The patients underwent audiological assessment before initiation and during enzyme replacement therapy. We also analysed neurologic heart and kidney status. RESULTS: Twenty patients (80%; 13 females and seven males) complained of otologic symptoms. Audiological evaluation showed a sensorineural hearing loss in 17 patients, bilateral in 16 out of them. Vestibular examination showed a functional impairment in two patients (one female, one male). Correlations were found between hearing loss and either kidney disease (73,3%), neurological complications (100%) and cardiomyopathy (80%). Fourteen patients (56%; seven females, seven males) received enzyme replacement therapy. Improvement or stabilization of the audiological evaluation was reported in seven patients, whereas worsening was observed in three patients. CONCLUSION: This study confirms the high frequency of audiological involvements in females and males with FD. Our analysis suggests that the frequency of hearing loss is increased in the presence of renal or neurologic involvement or cardiomyopathy. There is no clinically significant efficacy of enzyme replacement therapy on hearing function. Although the pathophysiology remains unknown, a vascular mechanism responsible of the inner ear involvement seems to be privileged.

Standardization of automated analyses of oculomotor fixation and saccadic behaviors.

In an effort towards standardization, this paper evaluates the performance of five eye movement classification algorithms in terms of their assessment of oculomotor fixation and saccadic behavior. The results indicate that performance of these five commonly used algorithms vary dramatically even in the case of a simple stimulus evoked task using a single, common threshold value. The important contributions of this paper are: 1) evaluation and comparison of performance of five algorithms to classify specific oculomotor behavior 2) introduction and comparison of new standardized scores to provide more reliable classification performance 3) logic for a reasonable threshold value selection for any eye movement classification algorithm based on the standardized scores and 4) logic for establishing a criterion-based baseline for performance comparison between any eye movement classification algorithms. Proposed techniques enable efficient and objective clinical applications providing means to assure meaningful automated eye movement classification.

[Adenosine deaminase is useful for the diagnosis of peritoneal tuberculosis in patients with end-stage renal failure]. / Le dosage d'adénosine déaminase est utile pour le diagnostic de tuberculose péritonéale chez le patient dialysé

INTRODUCTION: End-stage renal failure patients are particularly at risk for tuberculosis, especially for peritoneal tuberculosis. Microbiological diagnosis remains hazardous in many cases. CASE REPORT: We report on a case of peritoneal tuberculosis in an end-stage renal failure patient. The diagnosis was suspected on the basis of adenosine deaminase dosage in peritoneal fluid, allowing an early presumptive treatment and a favourable outcome with a 3 years follow-up. DISCUSSION: The measurement of adenosine deaminase activity in ascites represents a diagnostic advance in tuberculous peritonitis among end-stage renal failure patients.

A comparison of two methods for facilitating clinical data integration by medical students.

Two important charting strategies to help students organize patients' data are Weed's problem-oriented medical record (POMR) and Russell's condition diagram (CD). The authors conducted the present study in 1987 to determine whether either was superior for clinical data integration. Sophomore medical students at The University of Texas Medical School at San Antonio indicated whether they preferred the POMR, the CD, or neither. They were then divided into three study groups according to their preferences, with the POMR and CD groups receiving 80 hours of training and the control group receiving only the standard preclinical training. Each student then examined a standardized patient and wrote an open-ended report about the patient's medical problem. After examining a second patient, students were asked to write a structured report providing information about each of ten components of diagnosis. Both the CD and the POMR groups scored numerically higher on the structured type of report than did the controls, but only the CD group scored significantly higher. The CD group also scored higher than did the POMR group on both types of report, but the differences were not statistically significant. This study indicates that the clinical reasoning of medical students can be enhanced by focused training in either the CD or the POMR methods. It suggests that the CD format may be particularly helpful for students with lower academic achievement.