Novelties in the Diagnosis and Treatment of Angioedema.

Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep layers of the skin and the mucosae. Two mediators, histamine and bradykinin, account for most cases of angioedema. Angioedema can occur with wheals as a manifestation of urticaria, and this form is frequently allergic. In the present review, we discuss nonallergic angioedema without wheals, which can be divided into 3 acquired and 4 hereditary forms. Histamine is the mediator in acquired angioedema of unknown etiology (idiopathic histaminergic acquired angioedema), whereas in other forms the main mediator is bradykinin. Angioedema can be caused by C1-inhibitor deficiency (C1-INH-hereditary angioedema and C1-INH-acquired angioedema), mutations in coagulation factor XII (FXII-hereditary angioedema), and treatment with angiotensin-converting enzyme inhibitors (ACEI-acquired angioedema). Etiology remains unclear in acquired angioedema (idiopathic nonhistaminergic acquired angioedema) and in 1 type of hereditary angioedema (hereditary angioedema of unknown origin). Several treatments are licensed for hereditary C1-INH deficiency. Plasma-derived and recombinant C1-INHs, the bradykinin receptor blocker icatibant, and the plasma kallikrein inhibitor ecallantide have been approved for on-demand treatment to reverse angioedema symptoms. Attenuated androgen and plasma-derived C1-INH are approved for prophylaxis.

Novelties in the diagnosis and treatment of angioedema

Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep layers of the skin and the mucosae. Two mediators, histamine and bradykinin, account for most cases of angioedema. Angioedema can occur with wheals as a manifestation of urticaria, and this form is frequently allergic. In the present review, we discuss nonallergic angioedema without wheals, which can be divided into 3 acquired and 4 hereditary forms. Histamine is the mediator in acquired angioedema of unknown etiology (idiopathic histaminergic acquired angioedema), whereas in other forms the main mediator is bradykinin. Angioedema can be caused by C1-inhibitor deficiency (C1-INH-hereditary angioedema and C1-INH-acquired angioedema), mutations in coagulation factor XII (FXII-hereditary angioedema), and treatment with angiotensin-converting enzyme inhibitors (ACEI-acquired angioedema). Etiology remains unclear in acquired angioedema (idiopathic nonhistaminergic acquired angioedema) and in 1 type of hereditary angioedema (hereditary angioedema of unknown origin). Several treatments are licensed for hereditary C1-INH deficiency. Plasma-derived and recombinant C1-INHs, the bradykinin receptor blocker icatibant, and the plasma kallikrein inhibitor ecallantide have been approved for on-demand treatment to reverse angioedema symptoms. Attenuated androgen and plasma-derived C1-INH are approved for prophylaxis (AU)

Angioedema se define como un edema local, autolimitado, no-inflamatorio. Se trata de un edema circunscrito debido a la trasvasación de plasma de los capilares localizados en los sustratos profundos de la piel y de las mucosas. En la mayoría de los casos están implicados dos mediadores, la histamina y la serotonina. Puede manifestarse en forma de habones como en la urticaria de origen alérgico. El angioedema de origen no alérgico es el motivo de esta revisión. Se puede presentar bajo 3 formas adquiridas y 4 formas hereditarias. La histamina es el mediador implicado en el angioedema adquirido de etiología desconocida (angioedema adquirido idiopático histaminérgico). En las otras formas se sospecha que es la serotonina el mediador principal. La etiología del angioedema puede ser identificado en 4 tipos: una deficiencia de C1-inhibidor (C1-INH-angioedema hereditario y C1-INH-angioedema adquirido), mutaciones en el factor XII de coagulación (FXII-angioedema hereditario), tratamiento con inhibidores del enzima convertidor de la angiotensina (ACEi-angioedema adquirido). En uno de los adquiridos (angioedema adquirido idiopático no histaminérgico) y en el hereditario de origen desconocido, no se ha identificado todavía su etiología. Varios tratamientos están aprobados para revertir los síntomas clínicos y se aplican en la deficiencia de angioedema hereditario por déficit de C1-INH: Derivados de plasma y C1-INHs recombinantes, icatibant como bloqueante del receptor de la bradiquinina y ecallantide como inhibidor de la kalicreina. Los andrógenos atenuados y los derivados plasmáticos de C1-INH se utilizan en la profilaxis de los ataques (AU)

Does the metabolic syndrome predict subclinical atherosclerotic damage in an asymptomatic population at intermediate cardiovascular risk?

BACKGROUND AND AIMS: It is not clear whether the metabolic syndrome (MetS) is a distinct entity or a combination of risk factors. Several studies showed the association between MetS and cardiovascular disease (CVD). Subclinical target organ damage (TOD) is a recognized marker of atherosclerosis and predictor of cardiovascular events. Increased burden of subclinical atherosclerosis was detected in individuals with MetS. We thus aimed to examine the association between MetS and cumulative or specific TOD and to assess whether MetS predicts TOD better than the risk factors included in current definitions. METHODS AND RESULTS: We recorded TOD in 979 patients at intermediate cardiovascular risk with and without MetS according to IDF and NCEP criteria. We measured common carotid intima-media thickness, left ventricular mass index (LVMI), urine albumin to creatinine ratio (UACR), and ankle-brachial index. We found no correlation between having at least one TOD and being positive for MetS. A high UACR was associated with MetS using both IDF and NCEP criteria, while only NCEP identified individuals with increased LVMI. Using a multivariate logistic regression model including MetS, age, sex, waist circumference, triglycerides, HDL cholesterol, blood pressure and blood glucose levels we found no correlations between the presence of MetS and at least one TOD. The associations with high UACR and LVMI disappeared when age, blood pressure and glycemia were counted in. CONCLUSION: Although MetS showed some relation with subclinical renal and cardiac damage, it does not predict TOD any better than the risk factors specified in the definitions.

[Syncope and work: role of the occupational physician and global risk stratification]. / Sincope e rischio lavorativo: ruolo del medico del lavoro e stratificazione globale del rischio.

Safety risk for subjects suffering from syncope while working has not been as yet addressed by occupational medicine. The present study was aimed at evaluating a new developed methodology for job tasks risk stratification in patients with syncope. During a work-shop on syncope and occupational risk, 149 occupational physicians (OP) with about 10 years of clinical experience were asked to fulfil a Visual Analogue Scale (VAS) concerning the doctor's estimated potential damage (D) to the worker and the probability of a damage to occur (P) should syncope take place during the job task. Five job tasks characterized by different risk for safety (1, driving; 2, toxic products handling; 3, job performed closed to hot surfaces o free flames; 4, surgical activity; 5, office job) were identified. OP correctly stratified the risk associated to the different job tasks in patients with syncope. Unexpectedly, task #3 was given a risk similar to that obtained in drivers. This might be of paramount clinical and social importance when patients with syncope have to return to their job tasks.

[Syncope and occupational risk survey: the role of continuing education and multidisciplinary approach]. / Indagine conoscitiva sulla percezione del problema sincope in relazione al rischio lavorativo nella pratica clinica: ruolo della formazione e dell'approccio multidisciplinare.

Syncope is a common disorder characterized most of the times by a positive clinical outcome. However, it may turn to a life threatening event even for working colleagues and third party when occurring during an high risk job. We have recently found that, out of 670 patients admitted to the Emergency Department (ED) for syncope, about 50% were potential workers, being their age between 18 and 65 years. Also, we found that in this group of patients syncope recurrence was as high as 11% at 6 months. It is unknown how physicians address the problem of the occupational risk in patients suffering from syncope and how occupational aspects are taken into account in the clinical judgment before work readmission. One hundred eighty five doctors (149 occupational physicians, OP), participating in a work-shop on syncope, were asked to fulfill a questionnaire about their clinical experience and their attention to the occupational aspects in patients after syncope. Despite long lasting clinical experience, 41% of OP did not scrutinize syncope as a relevant symptom in their daily activity. 65% of the other specialists were used to address the occupational risk aspects in their syncope patients. A multidisciplinary approach involving continuing education on safety at work might reduce work accidents due to syncope relapse and promote a safe and suitable re-employment of patients with syncope. scrutinize syncope as a relevant symptom in their daily activity. 65% of the other specialists were used to address the occupational risk aspects in their syncope patients. A multidisciplinary approach involving continuing education on safety at work might reduce work accidents due to syncope relapse and promote a safe and suitable re-employment of patients with syncope.

[Syncope and work. STePS study (Short Term Prognosis of Syncope)]. / La sincope in età lavorativa. Studio multicentrico prospettico STePS.

BACKGROUND: Recurrent syncope is a common medical problem responsible for 3-5% of emergency department (ED) accesses and 1-6% of hospital admissions. If syncope occurs in a subject working in a critical safety task, the consequences of this event might be very dangerous for the worker, colleagues, others or for the environment. Therefore, syncope management is a major problem for occupational medicine, converning the general safety at work. AIMS: To evaluate the syncope events in a group of potential workers aged 18 to 65 years; to evaluate the symptoms preceding syncope and the presence of associated illnesses and recurrent events. POPULATION AND RESULTS: This study is part of the prospective study STePS (Short Term Prognosis of Syncope), and included 305 consecutive patients (aged 18-65 years, female 56%) who had syncope as a main symptom and presented at ED of four general hospitals in the Milan area, Italy, between the 23rd of January and 30th of June 2004. The 24% of subjects were hospitalized. In 21% the syncope occurs suddenly without any preceding symptom. The 67% of subjects didn't have any important illness at the time. 50% of subjects had recurrent syncope. In four subjects another syncope occurred in a 10 day follow-up. CONCLUSIONS: occupational medicine should consider syncope scrupulously. Proper diagnostic management is important to permit a correct evaluation of work safety issues.

Blood fetal microchimerism in primary biliary cirrhosis.

The autoimmune nature of primary biliary cirrhosis (PBC) is well established. We tested the hypothesis that fetal microchimerism indicated by the persistence of circulating fetal cells in women years after pregnancy might contribute to the aetiopathogenesis of PBC through a graft-versus-host-like response. We extracted DNA from the peripheral blood cells of 36 women carefully selected from 173 consecutive PBC patients, who were matched with 36 healthy women by age, age of last son, and number of children. Both patients and controls had to have male offspring, and no history of miscarriages or blood transfusions; they could not be twins. We tested all of the samples for the presence of two specific Y-chromosome sequences (SY154 and SRY) by amplifying DNA in a nested polymerase chain reaction. Y-chromosome-specific DNA was detected in the peripheral blood cell DNA of 13 (36%) of the 36 women with PBC and in 11 (31%) of the 36 healthy controls. The two groups of PBC patients with and without male DNA sequences were similar in terms of their clinical, biochemical, and serological features. Y-chromosome sequences were found in three of the four PBC women with associated systemic sclerosis. All of the 24 Y-positive samples contained SY154 sequences, but only three PBC patients and six controls showed the presence of both SY154 and SRY sequences. This discrepancy may suggest that not only fetal cells but also fragments of fetal DNA are present in maternal circulation. Overall, our data do not support the hypothesis that fetal microchimerism plays a significant role in the onset or progression of PBC.