[Angioedema prophylaxis]. / Prophylaxe von Angioödemen.

Angioedema is a spontaneous, edematous swelling of the deep layers of the skin or mucous membrane. Angioedema in the respiratory tract is potentially life-threatening. The classification of angioedema into mast-cell-mediated (e. g. urticaria) or bradykinin-mediated (e. g. hereditary angioedema) is important for correct and rational treatment. Generally, two therapeutic strategies are available for angioedema treatment. On-demand treatment of angioedema symptoms that already have emerged aims to stop the further development of the attack and, thus, limits the severity and duration of the attack. This strategy is well established in the treatment of patients with hereditary angioedema, whereas in chronic spontaneous urticaria on-demand therapy plays no role in the guideline recommendations. In contrast, the therapeutic strategy of prophylaxis aims to prevent the occurrence of spontaneous and induced attacks as far as possible. Prophylaxis is the sole therapy strategy for chronic urticaria and is applied at all stages of the treatment algorithm. In the case of hereditary angioedema, on-demand therapy can be complemented by prophylaxis after careful and individual indication. In hereditary angioedema, prophylaxis is currently gaining in importance due to improved treatment options. Patients who use a prophylactic regime are much less likely to be forced to wait for the unpredictable occurrence of an attack and then to react with an on-demand treatment. Prophylactic treatment takes place at times determined by the patient himself, in contrast to treatment on an as-needed basis. The loss of unpredictability is a decisive moment in improving the quality of life.

A Multicenter Study of IgE Sensitization to Anisakis simplex and Diet Recommendations.

BACKGROUND: Allergy to Anisakis simplex (s.) is spreading due to the increased consumption of raw, smoked or marinated fish. In man, Anisakis s. can directly attack the gastrointestinal mucosa, provoking a parasitosis known as anisakiasis, or giving rise to the formation of IgE and, finally, inducing IgE-mediated reactions like urticaria, angioedema and anaphylactic shock. During recent years, a dietary approach to Anisakis s. infestation has also been addressed. METHODS: A total of 620 patients with urticaria, angioedema, or both and a history of anaphylaxis following consumption of raw, smoked or marinated fish were recruited, evaluated for specific IgE levels to Anisakis s. and subjected to Skin Prick test. Following 18 month fish-free diet, patients were reevaluated at 6, 12 and 18 months, respectively. Patients undergoing diet were selected among those who had a clinical history with multiple accesses to first aid. RESULTS: After 6-month fish-free diet, we recorded an improvement of symptoms and a remarkable reduction of specific IgE levels. The extension of the diet over 6 months in some cases resulted in a further reduction of specific IgE levels. CONCLUSION: Data obtained confirm the importance of a fish-free diet in patients with severe symptoms since a new antigenic exposure coincides with a relapse of symptoms and increased IgE levels. This last point should be kept in mind and carefully evaluated in patients at risk for anaphylaxis or angioedema.

Cardiovascular and Diabetic Medications That Cause Bradykinin-Mediated Angioedema.

Medication-induced angioedema is a bradykinin-mediated process that results from increased production or decreased degradation of bradykinin. These reactions are documented for several cardiac medications including blockers of the renin-angiotensin-aldosterone system (RAAS). Other cardiovascular and diabetes medications further increase the risk of medication-induced angioedema, particularly with concomitant use of RAAS inhibitors. Dipeptidyl peptidase IV inhibitors are a class of oral diabetic agents that affect bradykinin and substance P degradation and therefore can lead to angioedema. Neprilysin inhibitors are a separate class of cardiac medications, which includes sacubitril, and can lead to drug-induced angioedema especially when used in combination with RAAS inhibitors. This article discusses the proposed mechanisms by which these medications cause angioedema and how medication-induced angioedema differs from mast cell-mediated angioedema. It also details how to recognize medication-induced angioedema and the treatment options available.

Attempted suicide by ingestion of hair dye containing p-phenylenediamine: a case report.

Para-phenylenediamine is widely used as a chemical in hair dyes and in combination with henna. This dye is used to paint the body for decorative reasons, to speed the processing time of henna and to intensify the results. Para-phenylenediamine is widely used in the Middle East, North Africa and India. Several reports have been published of the fatal ingestion of hair dye containing para-phenylenediamine. Here, we describe the case of a 14-year-old girl who ingested the compound but whose prompt treatment prevented her death. Ingestion of para-phenylenediamine produces a typical triad of angioneurotic oedema, rhabdomyolysis and acute tubular necrosis. Awareness of signs of these associated conditions in our patient, together with a comprehensive history, facilitated appropriate treatment to be instituted. We document the steps we took to enable her complete physical recovery.

Perioperative course in patients with hereditary or acquired angioedema.

PURPOSE: Two types of bradykinin-mediated angioedema, hereditary angioedema (HAE) and acquired angioedema (AAE), result from deficiency or dysfunction of C1 esterase inhibitor, leading to an overproduction of bradykinin, which can lead to vascular permeability and life-threatening angioedema of the airway. The objective of this study was to review perioperative outcomes in a series of patients with HAE and AAE and to review current knowledge about anesthetic complications in patients with HAE or AAE. METHODS: Medical records were retrospectively reviewed for perioperative complications in patients with HAE or AAE who underwent general anesthesia from January 1, 2000, to December 31, 2014, at our institution. RESULTS: Twenty-four patients (13 with HAE, 10 with AAE, and 1 with unspecified angioedema) underwent 38 instances of general anesthesia with airway manipulation. All except 4 received prophylactic therapy. One patient, a 67-year-old woman who was pretreated with stanozolol and fresh frozen plasma required reintubation after postoperative airway edema developed. CONCLUSION: Life-threatening episodes of angioedema of the airway occur infrequently, but they can occur in patients who received pretreatment and in patients who have previously undergone anesthesia uneventfully. Anesthesiologists must be ready to emergently manage a difficult airway and must be familiar with recommendations provided in consensus guidelines for the treatment of HAE and AAE patients.

Avoidance of nonsteroidal anti-inflammatory drugs after negative provocation tests in urticaria/angioedema reactions: Real-world experience.

Drug provocation tests (DPTs) are the gold standard in diagnosing nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity; however, only few data about follow-up of patients with negative DPTs are actually available. The aim of this study was to assess patients' behavior in taking NSAIDs again and to evaluate NSAID tolerability after negative allergological workup. This is a follow-up study involving patients evaluated for history of cutaneous reactions (urticaria and or angioedema) after NSAID intake and with negative DPTs with the suspected NSAID. Patients were asked during a phone interview about the intake of NSAIDs, tolerance, or reasons of avoidance. The negative predictive value (NPV) of NSAIDs DPTs was calculated. One hundred eleven of 142 patients were successfully contacted; 46/111 (41.44%) took the same NSAID previously tested with two adverse reactions reported (4.34%). Fifty-three of 111 (47.74%) patients did not take the same NSAID, but 34 of them took at least another strong cyclooxygenase (COX) 1 inhibitor, with 1 adverse reaction (2.94%) and 19 of them took only weak COX-1 inhibitors. Twelve of 111 patients (10.8%) did not take any NSAID. Reasons for drug avoidance were mainly fear of reactions (70.8%) and no need (29.2%). NPV, overall, was 96.97% (95% confidence interval, 91-99%). Although NSAID hypersensitivity diagnosis was ruled out by oral provocation test, the majority of patients with a history of urticaria/angioedema avoided the intake of the tested NSAIDs for fear of new reactions, particularly when strong COX-1 inhibitor NSAIDs were involved. The high NPV value of DPT resulting from this study should reassure NSAID intake.

A cross-sectional questionnaire assessing patient and physician use of short-term prophylaxis for hereditary angioedema.

BACKGROUND: Current guidelines recommend short-term prophylaxis (STP) before invasive procedures to prevent hereditary angioedema (HAE) attacks; however, adherence to these guidelines may be variable because this indication lacks Food and Drug Administration approval in the United States. OBJECTIVE: To ascertain the STP experiences of patients with HAE and HAE-treating physicians. METHODS: Online questionnaires focusing on STP experiences were distributed by the US Hereditary Angioedema Association to the first 250 patients with HAE and to registered HAE-treating physicians. SAS 9.3 was used to perform descriptive statistics and to test the difference between patients who underwent procedures and those who did not using Pearson χ(2) test, Fisher exact test, and 2-sample t test. RESULTS: For the patient survey, 219 respondents met the criteria for HAE type 1 and 2; 37 (17%) underwent 66 invasive procedures, and all reported receiving STP. Eight patients (22%) reported failed STP, but only 3 required on-demand therapy. For STP, anabolic steroids and plasma-derived C1 inhibitor were the most and second-most commonly used, respectively. For the physician survey, 37 physicians reported caring for 433 patients with HAE. Depending on the procedure, 19% to 54% of physicians used STP and 30% to 86% prescribed on-demand therapy; 69% and 78% of physicians prescribed plasma-derived C1 inhibitor as STP for minimally invasive and invasive procedures, respectively. Physicians reported excellent efficacy for the STP treatments used. CONCLUSION: Physicians reported excellent outcomes using primarily newer STP therapies, namely plasma-derived C1 inhibitor, which was discordant to patient-reported outcomes using older STP therapies, namely anabolic steroids. Well-controlled STP studies are needed to clarify use for patients with HAE in the United States.

Urticaria and angioedema in pregnancy and lactation.

Urticaria is part of the management of pregnancy, labor, delivery, and the puerperium in some women. The urticaria can be acute, chronic, or physical, presenting with whealing, angioedema, or both. Contact urticaria can occur. Acquired angioedema, usually with urticaria, must be differentiated from hereditary angioedema. An approach to management of these conditions in pregnancy is proposed.

Angioedema without urticaria in childhood.

BACKGROUND: There has been no separate study investigating angioedema without urticaria (Aw/oU) exclusively in children so far. The purpose of this study was to investigate the frequency, clinical presentation, etiology, management and follow-up of Aw/oU in children. METHODS: This is a prospective study that included all consecutive patients with a history of Aw/oU referred to our clinic between January 2011 and May 2012. A standard diagnostic and therapeutic algorithm was applied to all patients. RESULTS: The frequency of Aw/oU was found to be 1.6% during the study period. An etiological factor could be found in only 45 patients (49%). The causes of Aw/oU were infection (21%), allergy (14%), thyroid autoimmunity (TA)-related (8%) and nonsteroid anti-inflammatory drug hypersensitivity (6%), and idiopathic angioedema (51%). There was no hereditary type I, II or acquired type of angioedema or rare syndromes associated with Aw/oU. The median follow-up was 16 months (range: 12-30 months). Antihistamine prophylaxis was initiated at therapeutic doses in 20 patients with frequently recurrent angioedema due to idiopathic and euthyroid TA-related Aw/oU for 3 months. These patients responded to antihistamine prophylaxis for 3 months. Four patients relapsed after cessation of prophylaxis at the end of 3 months. Antihistamine prophylaxis was prolonged to 6 months in three patients and to 9 months in one patient. CONCLUSIONS: Angioedema without urticaria in children is a rare condition and no etiology can be identified in half of them. Antihistamine treatment alone is sufficient, and prognosis is good in recurrent non hereditary cases in a short-term follow-up period.

A practical, clinical approach to the assessment and management of suspected insulin allergy.

BACKGROUND: Although allergic reactions to insulin are uncommon, they can be difficult to diagnose and management may be very difficult in subjects with Type 1 diabetes with severe allergy. Access to allergists and specialist diagnostic tests is limited and few diabetes specialists are familiar with desensitization as a means of treating allergy. People with diabetes may develop symptoms which mimic insulin allergy but are attributable to other conditions. CASE REPORTS: Here we describe three cases of insulin allergy. One patient presented with severe, albeit localized, urticarial reactions at injection sites. The most severe case was a woman with recent-onset Type 1 diabetes who presented with grade 2 anaphylaxis. The third patient presented with generalized urticaria and angioedema. Insulin allergy was confirmed in all three cases. METHODS: Assessment involved measurement of immunoglobulin and anti-insulin antibody levels. Skin testing was performed in two cases. Treatments included desensitization in one case, alternative insulin preparations, antihistamines and continuous subcutaneous insulin infusion. In all three cases of insulin allergy there has been successful resolution of symptoms. CONCLUSIONS: The clinical assessment and investigation in cases of suspected insulin allergy is described, along with detailed algorithms for skin testing and desensitization. This case series demonstrates an approach to challenging cases of suspected insulin allergy which will be helpful for diabetes specialists.