In this review we celebrate a century of progress since the initial description of the physiologic and pathologic roles of histamine and 70 years of progress since the introduction of H1 ...-antihistamines for clinical use. We discuss histamine and clinically relevant information about the molecular mechanisms of action of H1 -antihistamines as inverse agonists (not antagonists or blockers) with immunoregulatory effects. Unlike first (old)–generation H1 -antihistamines introduced from 1942 to the mid-1980s, most of the second (new)–generation H1 -antihistamines introduced subsequently have been investigated extensively with regard to clinical pharmacology, efficacy, and safety; moreover, they are relatively free from adverse effects and not causally linked with fatalities after overdose. Important advances include improved nasal and ophthalmic H1 -antihistamines with rapid onset of action (in minutes) for allergic rhinitis and allergic conjunctivitis treatment, respectively, and effective and safe use of high (up to 4-fold) doses of oral second-generation H1 -antihistamines for chronic urticaria treatment. New H1 -antihistamines introduced for clinical use include oral formulations (bilastine and rupatadine), and ophthalmic formulations (alcaftadine and bepotastine). Clinical studies of H3 -antihistamines with enhanced decongestant effects have been conducted in patients with allergic rhinitis. Additional novel compounds being studied include H4 -antihistamines with anti-inflammatory effects in allergic rhinitis, atopic dermatitis, and other diseases. Antihistamines have a storied past and a promising future.
Anaphylaxis is a severe, generalized allergic or hypersensitivity reaction that is rapid in onset and may cause death. Epinephrine (adrenaline) can be life-saving when administered as rapidly as ...possible once anaphylaxis is recognized. This clinical report from the American Academy of Pediatrics is an update of the 2007 clinical report on this topic. It provides information to help clinicians identify patients at risk of anaphylaxis and new information about epinephrine and epinephrine autoinjectors (EAs). The report also highlights the importance of patient and family education about the recognition and management of anaphylaxis in the community. Key points emphasized include the following: (1) validated clinical criteria are available to facilitate prompt diagnosis of anaphylaxis; (2) prompt intramuscular epinephrine injection in the mid-outer thigh reduces hospitalizations, morbidity, and mortality; (3) prescribing EAs facilitates timely epinephrine injection in community settings for patients with a history of anaphylaxis and, if specific circumstances warrant, for some high-risk patients who have not previously experienced anaphylaxis; (4) prescribing epinephrine for infants and young children weighing <15 kg, especially those who weigh 7.5 kg and under, currently presents a dilemma, because the lowest dose available in EAs, 0.15 mg, is a high dose for many infants and some young children; (5) effective management of anaphylaxis in the community requires a comprehensive approach involving children, families, preschools, schools, camps, and sports organizations; and (6) prevention of anaphylaxis recurrences involves confirmation of the trigger, discussion of specific allergen avoidance, allergen immunotherapy (eg, with stinging insect venom, if relevant), and a written, personalized anaphylaxis emergency action plan; and (7) the management of anaphylaxis also involves education of children and supervising adults about anaphylaxis recognition and first-aid treatment.
Background Although anaphylaxis is recognized as an important life-threatening condition, data are limited regarding its prevalence and characteristics in the general population. Objective We sought ...to estimate the lifetime prevalence and overall characteristics of anaphylaxis. Methods Two nationwide, cross-sectional random-digit-dial surveys were conducted. The public survey included unselected adults, whereas the patient survey captured information from household members reporting a prior reaction to medications, foods, insect stings, or latex and idiopathic reactions in the previous 10 years. In both surveys standardized questionnaires queried anaphylaxis symptoms, treatments, knowledge, and behaviors. Results The public survey included 1,000 adults, of whom 7.7% (95% CI, 5.7% to 9.7%) reported a prior anaphylactic reaction. Using increasingly stringent criteria, we estimate that 5.1% (95% CI, 3.4% to 6.8%) and 1.6% (95% CI, 0.8% to 2.4%) had probable and very likely anaphylaxis, respectively. The patient survey included 1,059 respondents, of whom 344 reported a history of anaphylaxis. The most common triggers reported were medications (34%), foods (31%), and insect stings (20%). Forty-two percent sought treatment within 15 minutes of onset, 34% went to the hospital, 27% self-treated with antihistamines, 10% called 911, 11% self-administered epinephrine, and 6.4% received no treatment. Although most respondents with anaphylaxis reported 2 or more prior episodes (19% reporting ≥5 episodes), 52% had never received a self-injectable epinephrine prescription, and 60% did not currently have epinephrine available. Conclusions The prevalence of anaphylaxis in the general population is at least 1.6% and probably higher. Patients do not appear adequately equipped to deal with future episodes, indicating the need for public health initiatives to improve anaphylaxis recognition and treatment.
In this rostrum we aim to increase awareness of anaphylaxis in infancy in order to improve clinical diagnosis, management, and prevention of recurrences. Anaphylaxis is increasingly reported in this ...age group. Foods are the most common triggers. Presentation typically involves the skin (generalized urticaria), the respiratory tract (cough, wheeze, stridor, and dyspnea), and/or the gastrointestinal tract (persistent vomiting). Tryptase levels are seldom increased because of infant anaphylaxis, although baseline tryptase levels can be increased in the first few months of life, reflecting mast cell burden in the developing immune system. The differential diagnosis of infant anaphylaxis includes consideration of age-unique entities, such as food protein–induced enterocolitis syndrome with acute presentation. Epinephrine (adrenaline) treatment is underused in health care and community settings. No epinephrine autoinjectors contain an optimal dose for infants weighing 10 kg or less. After treatment of an anaphylactic episode, follow-up with a physician, preferably an allergy/immunology specialist, is important for confirmation of anaphylaxis triggers and prevention of recurrences through avoidance of confirmed specific triggers. Natural desensitization to milk and egg can occur. Future research should include validation of the clinical criteria for anaphylaxis diagnosis in infants, prospective longitudinal monitoring of baseline serum tryptase levels in healthy and atopic infants during the first year of life, studies of infant comorbidities and cofactors that increase the risk of severe anaphylaxis, development of autoinjectors containing a 0.1-mg epinephrine dose suitable for infants, and inclusion of infants in prospective studies of immune modulation to prevent anaphylaxis recurrences.
Platelet-activating factor (PAF) is an important mediator of anaphylaxis in animals, and interventions that block PAF prevent fatal anaphylaxis. The roles of PAF and PAF acetylhydrolase, the enzyme ...that inactivates PAF, in anaphylaxis in humans have not been reported.
We measured serum PAF levels and PAF acetylhydrolase activity in 41 patients with anaphylaxis and in 23 control patients. Serum PAF acetylhydrolase activity was also measured in 9 patients with peanut allergy who had fatal anaphylaxis and compared with that in 26 nonallergic pediatric control patients, 49 nonallergic adult control patients, 63 children with mild peanut allergy, 24 patients with nonfatal anaphylaxis, 10 children who died of nonanaphylactic causes, 15 children with life-threatening asthma, and 19 children with non-life-threatening asthma.
Mean (+/-SD) serum PAF levels were significantly higher in patients with anaphylaxis (805+/-595 pg per milliliter) than in patients in the control groups (127+/-104 pg per milliliter, P<0.001 after log transformation) and were correlated with the severity of anaphylaxis. The proportion of subjects with elevated PAF levels increased from 4% in the control groups to 20% in the group with grade 1 anaphylaxis, 71% in the group with grade 2 anaphylaxis, and 100% in the group with grade 3 anaphylaxis (P<0.001). There was an inverse correlation between PAF levels and PAF acetylhydrolase activity (P<0.001). The proportion of patients with low PAF acetylhydrolase values increased with the severity of anaphylaxis (P<0.001 for all comparisons). Serum PAF acetylhydrolase activity was significantly lower in patients with fatal peanut anaphylaxis than in control patients (P values <0.001 for all comparisons).
Serum PAF levels were directly correlated and serum PAF acetylhydrolase activity was inversely correlated with the severity of anaphylaxis. PAF acetylhydrolase activity was significantly lower in patients with fatal anaphylactic reactions to peanuts than in patients in any of the control groups. Failure of PAF acetylhydrolase to inactivate PAF may contribute to the severity of anaphylaxis.
The incidence rate of anaphylaxis is increasing, particularly during the first 2 decades of life. Common triggers include foods, medications, and insect stings. Clinical diagnosis is based on a ...meticulous history of an exposure or event preceding characteristic symptoms and signs, sometimes but not always supported by a laboratory test such as an elevated serum total tryptase level. Physician-initiated investigation of patients with anaphylaxis whose symptoms and signs are atypical sometimes leads to important insights into previously unrecognized triggers and mechanisms. In idiopathic anaphylaxis, in which no trigger can be confirmed by means of skin testing or measurement of specific IgE, the possibility of mastocytosis or a clonal mast cell disorder must be considered in addition to the possibility of a previously unrecognized trigger. Long-term risk reduction in patients with anaphylaxis focuses on optimal management of relevant comorbidities such as asthma and other respiratory diseases, cardiovascular disease, and mastocytosis or a clonal mast cell disorder; avoidance of the relevant confirmed allergen trigger; and relevant immunomodulation such as medication desensitization, venom immunotherapy, and possibly in the future, immunotherapy with food. Emergency preparedness for recurrence of anaphylaxis in community settings includes having epinephrine (adrenaline) autoinjectors available, knowing when and how to use them, and having a written, personalized anaphylaxis emergency action plan and up-to-date medical identification. Randomized controlled trials of the pharmacologic interventions used in an acute anaphylaxis episode are needed.
First-line and adjuvant treatment for food-induced anaphylaxis1114 6.3.2. Despite the risk of severe allergic reactions and even death, there is no current treatment for FA: the disease can only be ...managed by allergen avoidance or treatment of symptoms. ...the diagnosis of FA may be problematic, given that nonallergic food reactions, such as food intolerance, are frequently confused with FAs. Due to these concerns, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, working with more than 30 professional organizations, federal agencies, and patient advocacy groups, led the development of "best practice" clinical guidelines for the diagnosis and management of FA (henceforth referred to as the Guidelines).1 Based on a comprehensive review and objective evaluation of the recent scientific and clinical literature on FA, the Guidelines were developed by and designed for allergists/immunologists, clinical researchers, and practitioners in the areas of pediatrics, family medicine, internal medicine, dermatology, gastroenterology, emergency medicine, pulmonary and critical care medicine, and others. Bronchodilator (β2-agonist): albuterol MDI (child: 4-8 puffs; adult: 8 puffs) or Nebulized solution (child: 1.5 ml; adult: 3 ml) every 20 minutes or continuously as needed H1 antihistamine: diphenhydramine 1 to 2 mg/kg per dose Maximum dose, 50 mg IV or oral (oral liquid is more readily absorbed than tablets) Alternative dosing may be with a less-sedating second generation antihistamine H2 antihistamine: ranitidine 1 to 2 mg/kg per dose Maximum dose, 75 to 150 mg oral and IV Corticosteroids Prednisone at 1 mg/kg with a maximum dose of 60 to 80 mg oral or Methylprednisolone at 1 mg/kg with a maximum dose of 60 to 80 mg IV Vasopressors (other than epinephrine) for refractory hypotension, titrate to effect Glucagon for refractory hypotension, titrate to effect Child: 20-30 μg/kg Adult: 1-5 mg Dose may be repeated or followed by infusion of 5-15 μg/min Atropine for bradycardia, titrate to effect Supplemental oxygen therapy IV fluids in large volumes if patients present with orthostasis, hypotension, or incomplete response to IM epinephrine Place the patient in recumbent position if tolerated, with the lower extremities elevated Therapy for the patient at discharge First-line treatment:
Patients with severe or difficult-to-treat asthma are an understudied population but account for considerable asthma morbidity, mortality, and costs. The Epidemiology and Natural History of Asthma: ...Outcomes and Treatment Regimens (TENOR) study was a large, 3-year, multicenter, observational cohort study of 4756 patients (n = 3489 adults ≥18 years of age, n = 497 adolescents 13-17 years of age, and n = 770 children 6-12 years of age) with severe or difficult-to-treat asthma. TENOR's primary objective was to characterize the natural history of disease in this cohort. Data assessed semiannually and annually included demographics, medical history, comorbidities, asthma control, asthma-related health care use, medication use, lung function, IgE levels, self-reported asthma triggers, and asthma-related quality of life. We highlight the key findings and clinical implications from more than 25 peer-reviewed TENOR publications. Regardless of age, patients with severe or difficult-to-treat asthma demonstrated high rates of health care use and substantial asthma burden despite receiving multiple long-term controller medications. Recent exacerbation history was the strongest predictor of future asthma exacerbations. Uncontrolled asthma, as defined by the 2007 National Heart, Lung, and Blood Institute guidelines' impairment domain, was highly prevalent and predictive of future asthma exacerbations; this assessment can be used to identify high-risk patients. IgE and allergen sensitization played a role in the majority of severe or difficult-to-treat asthmatic patients.
The World Allergy Organization (WAO) Guidelines for the assessment and management of anaphylaxis provide a unique global perspective on this increasingly common, potentially life-threatening disease. ...Recommendations made in the original WAO Anaphylaxis Guidelines remain clinically valid and relevant, and are a widely accessed and frequently cited resource. In this 2015 update of the evidence supporting recommendations in the Guidelines, new information based on anaphylaxis publications from January 2014 through mid- 2015 is summarized. Advances in epidemiology, diagnosis, and management in healthcare and community settings are highlighted. Additionally, new information about patient factors that increase the risk of severe and/or fatal anaphylaxis and patient co-factors that amplify anaphylactic episodes is presented and new information about anaphylaxis triggers and confirmation of triggers to facilitate specific trigger avoidance and immunomodulation is reviewed. The update includes tables summarizing important advances in anaphylaxis research.
World Allergy Organization anaphylaxis guidelines: Summary Simons, F. Estelle R., MD, FRCPC; Ardusso, Ledit R.F., MD; Bilò, M. Beatrice, MD ...
Journal of allergy and clinical immunology,
03/2011, Letnik:
127, Številka:
3
Journal Article
Recenzirano
Odprti dostop
When indicated at any time during the episode, additional important steps include administering supplemental oxygen and maintaining the airway, establishing intravenous access and giving fluid ...resuscitation, and initiating cardiopulmonary resuscitation with continuous chest compressions before rescue breathing.\n Intravenous Chlorpheniramine or Diphenhydramine; Oral Cetirizine) Beta-2 Adrenergic Agonistsa (eg. Intravenous Hydrocortisone or Methylprednisolone; Oral Prednisone or Prednisolone) Strength of recommendation for use in anaphylaxisb C C C Pharmacologic effects At H1-receptor, inverse agonist effect; stabilize receptors in inactive conformation; decrease skin and mucosal symptoms At beta-2 receptor, increase bronchodilation Switch off transcription of activated genes that encode pro-inflammatory proteins; decrease late phase allergic response Clinical relevance Decrease itch, flush, urticaria, sneezing, and rhinorrhea, but are not life-saving because they do not prevent or relieve obstruction to airflow or hypotension/shock Decrease wheeze, cough and shortness of breath but are not life-saving because they do not prevent or relieve upper airway obstruction or hypotension/shock Onset of action takes several hours; therefore, are not life-saving in initial hours of an anaphylactic episode; used to prevent and relieve protracted or biphasic anaphylaxis; however, these effects have not been proven Potential adverse effects (usual dose) First-generation drugs cause drowsiness, somnolence, and impaired cognitive functionc Tremor, tachycardia, dizziness, jitteriness Unlikely during a short course Potential adverse effects (overdose) Extreme drowsiness, confusion, coma, respiratory depression, paradoxical central nervous system stimulation, eg. seizures in infants and children Headache, hypokalemia, vasodilation Unlikely Comment From 0 to 14 different H1-antihistamines,c and different dose regimens, are listed as adjunctive medications in anaphylaxis guidelines; role not proven Use in anaphylaxis is extrapolated from use in acute asthma; if given as adjunctive treatment for bronchospasm not relieved by epinephrine, should optimally be delivered by face mask and nebulization From 0 to 3 different glucocorticoids,d and different dose regimens,d are listed as adjunctive medications in anaphylaxis guidelines; role not proven Table 8 Second-Line Medications for Anaphylaxis Treatment Medication Epinephrine/adrenaline auto-injectora Epinephrine from an ampule/syringeb or prefilled syringec (alternative but not preferred formulations) Other aspects of discharge management Anaphylaxis emergency action plan (personalized, written) Medical identification (eg, bracelet, wallet card) Medical record electronic flag (or chart sticker) Emphasize the importance of follow-up, preferably with an allergy/immunology specialist Assessment of sensitization to allergen Before discharge, consider assessing sensitization to allergens suggested in the history of the acute episode, by measuring serum IgE levels to relevant allergen(s), if the test is availabled 3-4 weeks after the episode, confirm allergen sensitization using skin testse Challenge/provocation tests might be needed in some patients, for example, with food or medication allergy, in order to assess risk of future anaphylactic episodes furtherf Long-term risk reduction: avoidance and/or immunomodulation Food-triggered anaphylaxis: avoidance of relevant food(s) Stinging insect-triggered anaphylaxis: avoidance of stinging insects; subcutaneous venom immunotherapy (protects up to 80-90% of adults and 98% of children) Medication-triggered anaphylaxis: avoidance of relevant medications; if indicated, medically supervised desensitization in a healthcare setting according to published protocols Idiopathic anaphylaxis: for frequent episodes, consider glucocorticoid and H1-antihistamine prophylaxis for 2-3 months Optimal management of asthma and other concomitant diseases Table 9 Recommendations at Time of Discharge From the Healthcare Setting
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