Abstract Introduction The off-label use of TNF antagonists in refractory sarcoidosis is increasingly reported but data on their efficacy and safety are still insufficient. Objective To report on ...efficacy and safety of TNF antagonists in severe and refractory sarcoidosis. Methods Examination of retrospective demographic, clinical, therapeutic, and adverse event data on 132 sarcoidosis patients (58% women; mean (min-max) age 45.5 (14–78) years) given TNF antagonists (mainly infliximab, 91%) and investigation of response-linked factors. Results The overall clinical response (complete and partial) rate was 64%. TNF-antagonist efficacy (i.e., significant decrease of the ePOST score) was noted in cases with neurologic, heart, skin, and upper respiratory tract involvements. No significant difference in efficacy was found between anti-TNF used alone and TNF with immunosuppressant. The use of anti-TNF allowed reducing prednisone dosage at end of follow-up (p<0.001). Adverse events were observed in 52% of the patients; they included infections (36%) and allergic reactions (8%) and required treatment interruption in 31 cases (23%). When TNF antagonists were interrupted, 13 patients experienced relapses within 14 months on average (median follow-up: 20.5 months). Conclusion TNF antagonists were efficacious in about two-thirds of patients with severe/refractory sarcoidosis but their use led to a high rate of adverse events.
Background There are a limited number of publications on the management of gynecologic/obstetric events in female patients with hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH). ...Objective We sought to elaborate guidelines for optimizing the management of gynecologic/obstetric events in female patients with HAE-C1-INH. Methods A roundtable discussion took place at the 6th C1 Inhibitor Deficiency Workshop (May 2009, Budapest, Hungary). A review of related literature in English was performed. Results Contraception : Estrogens should be avoided. Barrier methods, intrauterine devices, and progestins can be used. Pregnancy : Attenuated androgens are contraindicated and should be discontinued before attempting conception. Plasma-derived human C1 inhibitor concentrate (pdhC1INH) is preferred for acute treatment, short-term prophylaxis, or long-term prophylaxis. Tranexamic acid or virally inactivated fresh frozen plasma can be used for long-term prophylaxis if human plasma-derived C1-INH is not available. No safety data are available on icatibant, ecallantide, or recombinant human C1-INH (rhC1INH). Parturition : Complications during vaginal delivery are rare. Prophylaxis before labor and delivery might not be clinically indicated, but pdhC1INH therapeutic doses (20 U/kg) should be available. Nevertheless, each case should be treated based on HAE-C1-INH symptoms during pregnancy and previous labors. pdhC1INH prophylaxis is advised before forceps or vacuum extraction or cesarean section. Regional anesthesia is preferred to endotracheal intubation. Breast cancer : Attenuated androgens should be avoided. Antiestrogens can worsen angioedema symptoms. In these cases anastrozole might be an alternative. Other issues addressed include special features of HAE-C1-INH treatment in female patients, genetic counseling, infertility, abortion, lactation, menopause treatment, and endometrial cancer. Conclusions A consensus for the management of female patients with HAE-C1-INH is presented.
Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) causes swelling in the skin and upper airways and pain in the abdomen because of mucosal swelling. C1-INH-HAE is frequently ...misdiagnosed, leading to delays in diagnosis, inadequate treatment, and unnecessary procedures.
To evaluate the history of misdiagnosis in patients participating in the Icatibant Outcome Survey (IOS).
The IOS is an observational study in which safety and effectiveness of icatibant have been evaluated since 2009. As part of the IOS, patients record any misdiagnoses received before being diagnosed as having C1-INH-HAE.
In January 2016, a total of 418 of 633 IOS patients with C1-INH-HAE type I or II had provided misdiagnosis data. Of these, 185 of 418 (44.3%) received 1 or more prior misdiagnoses. The most common misdiagnoses were allergic angioedema (103 of 185) and appendicitis (50 of 185). A variety of other misdiagnoses were reported, including a substantial number of gastrointestinal disorders (excluding appendicitis). Misdiagnosis rates were similar between males (41.1%) and females (46.5%) and between C1-INH-HAE type I (43.7%) and type II (51.6%). Patients with family members diagnosed as having C1-INH-HAE were significantly less likely to be misdiagnosed than patients without a family history (140 of 366 41.7% vs 38 of 58 65.5%, respectively; P = .001). Patients with a prior misdiagnosis had longer median delay to C1-INH-HAE diagnosis (13.3 years) than patients without (1.7 years; P < .001).
From this large database, approximately 50% of patients with C1-INH-HAE type I or II have previously had their conditions misdiagnosed, most commonly as allergic angioedema or appendicitis. Misdiagnosis results in marked delays in receiving the correct diagnosis, during which time patients cannot access effective, lifesaving treatment.
ClinicalTrials.gov: NCT01034969.
Hereditary angioedema (HAE) is a rare and potentially life-threatening disease. New specific treatments are available.
To identify patients' features and patients' best therapeutic option.
A 1-year, ...multicenter, retrospective study was performed. The primary objective was to examine the clinical presentation of HAE. Secondary objectives included patient characteristics, management of HAE over 12 months, and health-related quality of life using the SF-36v2 questionnaire.
One hundred ninety-three patients were included, and 69.4% were women. In the 12-month period, the mean number of HAE attacks was 7.6. Among the 568 reported attacks, localizations were the abdomen (57.1%), peripheral limbs (42.5%), upper airway (7.9%), and face (6.9%); 31.6% of attacks were severe and occurred statistically more often in women (P < .02). Compared with a population of allergic patients, all age- and sex-adjusted scores were significantly lower in patients with HAE (P < .05) except for the physical component summary. Health-related quality of life negatively correlated with the annual number of attacks and was markedly altered for patients having more than 5 attacks per year (P < .05 for all dimensions).
HAE is a severe disease that places a heavy burden on quality of life.
Disease expression in women with hereditary angioedema Bouillet, Laurence, MD, PhD; Longhurst, Hilary, MA, MRCP, PhD; Boccon-Gibod, Isabelle, MD ...
American journal of obstetrics and gynecology,
11/2008, Letnik:
199, Številka:
5
Journal Article
Recenzirano
Objective Fluctuations in sex hormones can trigger angioedema attacks in women with hereditary angioedema. Combined oral contraceptive therapies, as well as pregnancy, can induce severe attacks. The ...course of angioedema may be very variable in different women. Study Design Within the PREHAEAT project launched by the European Union, data on 150 postpubertal women with hereditary angioedema were collected in 8 countries, using a patient-based questionnaire. Results Puberty worsened the disease for 62%. Combined oral contraceptives worsened the disease for 79%, whereas progestogen-only pills improved it for 64%. During pregnancies, 38% of women had more attacks, but 30% had fewer attacks. Vaginal delivery was usually uncomplicated. Attacks occurred within 48 hours in only 6% of cases. Those more severely affected during menses had more symptoms during pregnancies, suggesting a hormone-sensitive phenotype for some patients. Conclusion The course of angioedema in women with C1 inhibitor deficiency is affected by physiologic hormonal changes; consequently, physicians should take these into account when advising on management.
A 62-year-old woman presented with hemithoracic anesthesia and acute abdominal pain following a violent psychological stress. Magnetic resonance imaging showed a thoracic hematoma with arachnoiditis ...of the spinal cord. Tomography revealed a typical aspect of segmental arterial mediolysis with multiple aneurysms and stenoses of the splanchnic arteries, confirmed by abdominal arteriography. There was no argument for hereditary, traumatic, atherosclerotic, infectious, or inflammatory arterial disease. Segmental arterial mediolysis was diagnosed on the basis of the radiologic data and probably involved both medullary and splanchnic arteries. The patient spontaneously recovered and was in good health 18 months later.
Because the endothelium is not a well-localized organ, the authors suggested that exploring endothelial plasma markers is a classical and frequently used method. ...they investigated the level of a ...combination of 3 markers: von Willebrand factor, soluble E-selectin, and endothelin-1.
Normal PAI-2 level in French FXII-HAE patients Marlu, Raphaël, MD, PhD; Deroux, Alban, MD; Du-Thanh, Aurélie, MD, PhD ...
Journal of allergy and clinical immunology,
05/2017, Letnik:
139, Številka:
5
Journal Article
Recenzirano
Odprti dostop
We read with interest the recent article by Joseph et al.1 Joseph et al explored plasminogen activator inhibitor (PAI)-1 and PAI-2 antigen levels in 23 patients with hereditary angioedema with normal ...C1 inhibitor (HAE-N) in remission; among them, 12 patients had FXII mutation. They observed a significant decrease in PAI-2 level in patients with HAE-N compared with control subjects; 11 out of 12 patients with HAE-N with FXII mutation had a marked decrease in PAI-2 levels. However, Joseph et al observed no statistically significant decrease in PAI-1 level compared with controls with a high interindividual variability. We would like to discuss a few points.
Background Aminopeptidase P (APP) plays an important role in the catabolism of kinins in human plasma, mostly for des-Arg9 -bradykinin. Impaired degradation of this active bradykinin metabolite was ...found to be associated with a decreased APP activity in hypertensive patients who experienced angioedema while being treated with angiotensin I–converting enzyme inhibitors. The pathophysiology of hereditary angioedema is presently attributed only to a quantitative/qualitative C1 inhibitor (CI-INH) defect with increased bradykinin release. Objectives In the context of androgen prophylaxis, increased CI-INH function cannot fully explain protection from angioedema attacks alone because of the limited reversion of the CI-INH defects. Therefore we hypothesized that androgen prophylaxis could enhance plasma APP activity. Methods Patients with hereditary angioedema were investigated for plasma metallopeptidase activities responsible for kinin catabolism (APP, angiotensin I-converting enzyme, and carboxypeptidase N) and for CI-INH function in treated and untreated patients. Results APP activity was asymmetrically distributed in untreated patients (n = 147): the mean value was significantly lower than the value in a reference healthy and unmedicated population (n = 116; P ≤ .001). Prophylaxis with androgen induced a significant increase in APP activity ( P ≤ .001), whereas it did not affect the other metallopeptidase activities. In both patient groups, APP activity showed a significant inverse relationship to disease severity ( P ≤ .001). Conclusion In addition to the effect on circulating CI-INH levels, the increase in APP levels brought on by androgens could contribute to a more effective control of the kinin accumulation considered to be responsible for the symptoms of angioedema.
PDF
