Anaphylaxis - Pathology PDF

Preview

Summary

Anaphylaxis - Influence of this disease on body homeostasis, problems related to the medical and nursing areas and main points of clinical analysis in hospital and emergency....

Description

Anaphylaxis The anaphylaxis is a serious systemic hypersensitivity reaction which may include hypotension or airway compromise. The most accepted definition of anaphylaxis is that of Sampson et al., that is, a serious allergic reaction, which is quick onset and can cause serious complications, including death. This reaction occurs in a potentially fatal cascade, caused by the release of mediators from mast cells and basophils in an immunoglobulin E (IgE) dependent manner. Anaphylactoid reaction, in turn, describes the clinically indistinguishable responses from anaphylaxis, which are not IgE mediated and do not require a sensitizing exposure. The final pathway in the anaphylactic or anaphylactoid reaction is the same, and the term “anaphylaxis” is now used to refer to both, involving or not a reaction with IgE. Radiological contrast, for example, is an agent that causes the anaphylactoid reaction. Hypersensitivity describes an inadequate immune response to generally harmless antigens, while anaphylaxis represents the most drastic and severe form of immediate hypersensitivity. Anaphylactic shock is represented by cardiovascular collapse and insufficient blood flow. When evaluating patients with suspected anaphylaxis, it is important to remember that mild acute allergic reactions can evolve with severe systemic response, anaphylaxis and death.

Neither age, occupation, race, sex, nor geographic factors increase the risk of anaphylaxis. Most studies indicate that atopic individuals are not at increased risk for anaphylaxis with insect bites or reactions to non-atopic medications. Asthma and a previous episode of anaphylaxis, however, are risk factors for severe or fatal anaphylaxis. Another known factor that increases the risk of developing anaphylaxis is prior exposure to a sensitizing antigen and prior anaphylaxis. The recurrence rate for anaphylaxis is 40 to 60% for insect bites, 20 to 40% for radiocontrast agents when re-exposure occurs, and 10 to 20% for penicillin. The prevalence of less severe allergic reactions in the emergency department is much higher, but data are rarely reported; anaphylaxis reactions appear to be having a higher incidence, particularly in the young population. Currently, the most common causes of severe anaphylaxis are the use of antibiotics, such as penicillin, contact with insects and the use of certain foods. Among antibiotics, ß-lactams such as penicillin cause 400 to 800 deaths a year in the US, with a systemic allergic reaction in 1 in 10,000 exposures. Hymenoptera sting is currently the second most common cause of anaphylaxis. In the pediatric population, food allergy is the major cause of anaphylaxis.

Pathophysiology and Etiology Epidemiology

The incidence and prevalence of anaphylaxis are difficult to determine as these cases are often underreported. The estimated incidence is 4 to 50 cases per 100,000 inhabitants per year, with a prevalence of 0.05 to 2%, accounting for 1 in 2,300 emergency room visits in the UK and 1 in every 250 admissions in the US .

The basic underlying mechanisms of allergic reactions are mast cell degranulation and the release of mediators by basophils. Causes of cell degranulation include cross-linking with IgE, complement activation, or direct activation or modulation of arachidonic acid. In the studies by Gel and Coombs, the allergen-IgE-histamine sequence and its action on receptors were demonstrated .

The IgE-mediated mechanism is also called the type I hypersensitivity mechanism; in this case, the allergen binds to the Fab segment of IgE, which, later, will activate and release protein kinases present in basophils and mast cells. The result of this phosphorylation cascade leads to an increase in intracellular calcium and granule exocytosis with release of mediators stored in the granules of those cells, which include histamine, tryptase, chymase, among others. The four classic mechanisms of hypersensitivity are: Cross-linking of two adjacent IgE molecules on a mast or basophil cell by a multivalent antigen. IgG and IgM reaction to cell surface antigens, resulting in complement activation and cytotoxicity. Soluble antigen-antibody complexes that activate the complement system. Activation of T lymphocytes. “Classic” anaphylaxis (IgE-mediated hypersensitivity) requires two separate exposures to an antigen and a hapten. Antigen is a molecule, commonly a protein, that can stimulate an immune response on its own. Haptens are small molecules, such as penicillin, that are unable to stimulate an immune response unless they are coupled to endogenous proteins (eg, albumin), resulting in an antigen complex large enough to be recognized. On the first exposure, the antigen or haptenprotein complex is processed by macrophages and dendritic cells; then presented externally on the cell surface bound to the major histocompatibility complex (MHC)-2. Helper T cells recognize the antigen-CPH-2 complex and subsequently induce the proliferation and differentiation of plasma cells. In the presence of interleukin (IL)-4, these plasma cells produce and release IgE antibody into the bloodstream. The IgE antibody has an antigen-specific variable region that induces

the immune response, and the constant region binds to high-affinity IgE receptors present in large amounts on mast cells and basophil cells. This sensitization process takes days or weeks, resulting in a latent period during which there is no clinical response to the antigen. After the latency period due to re-exposure to the antigen, a reaction occurs with the activation of degranulation with release of chemical mediators. Examples of IgE-mediated reaction triggers include antibiotics, food, and Hymenoptera stings. Complement-mediated anaphylactic reactions occur mainly after administration of blood products secondary to the formation of immune complexes. Non-immunological anaphylaxis occurs when an exogenous substance causes mast cell degranulation by direct stimulation of the mast cells or by unknown mechanisms. These reactions are often referred to as anaphylactoids. Examples of anaphylactoid reactions include reaction to radiocontrast dyes, neuromuscular blockers, opiates, and dextrans. The mechanism of radiocontrast reactions is uncertain; however, the cause is believed to be the activation of complement and coagulation systems, related, in part, to the high osmolarity of the dyes. Since the advent of non-ionic contrast dyes, the incidence of reactions has dramatically decreased. Opioids and neuromuscular blockers cause direct release of mediators. ASA and other nonsteroidal drugs cause anaphylactic symptoms through a process that involves the modulation of cyclooxygenase and arachidonic acid. Among asthmatics, 5 to 10% have these reactions, which include bronchospasm, bronchorrhea, rhinorrhea, and, rarely, hypotension. Selective COX-2 inhibitors appear to be safe for ASA-sensitive asthmatic patients. Idiopathic anaphylaxis is a diagnosis of exclusion, which occurs when no causative agent can be identified. Patients experience recurrent attacks, with no triggers identified after extensive evaluation. They often need

extended treatment with prednisone every other day to maintain remission of attacks. The causes of anaphylaxis in adults vary between the different series, the main ones being: food (33 to 34%) stings of insects of the order Hymenoptera (bees and wasps, 14%) medications (13 to 20%) exercise (7%) immunotherapy (3%) latex and plasma transfusion (less than 1% of cases) no cause identified (19 to 37%) Clinical manifestations Anaphylaxis is the most severe form of allergic reaction, even causing life-threatening, often involving respiratory or cardiovascular impairment, with manifestations presenting at different times, for example, the time between allergen contact and death can range from 5 minutes after drug injection, from 10 to 15 minutes after an insect bite, and 35 minutes in food-related anaphylaxis . Clinical signs of systemic allergic reactions include diffuse urticaria and angioedema, and may involve other systems such as neurological and gastrointestinal. Symptoms may include abdominal pain or cramps, nausea, vomiting, diarrhea, bronchospasm, rhinorrhea, conjunctivitis, arrhythmias, and/or hypotension. The speed at which symptoms occur is associated with their severity, which may be within hours of exposure. Can the clinical picture follow a uniphasic course in 75 to 80% of cases or a biphasic course? in the second case, symptoms disappear or show partial improvement and return about 1 to 8 hours later; this period can extend up to 24 hours and occurs in 3 to 20% of patients. The clinician should be aware that even mild urticaria can progress to anaphylaxis and even death. The “classic” presentation of anaphylaxis begins with pruritus, skin rash, and

urticaria; these cutaneous manifestations are present in more than 85% of cases. Upper airway symptoms such as a runny nose, itchy nose and sneezing may also occur, which are accompanied by a feeling of fullness in the throat, anxiety, a feeling of tightness in the chest, shortness of breath, dizziness; and the progression of symptoms can lead to decreased level of consciousness, respiratory and circulatory failure and collapse. On physical examination, the presence of wheezing and stridor is common. In its most severe form, loss of consciousness and cardiorespiratory arrest can ensue. The complaint of “lump in the throat” and hoarseness foreshadows life-threatening laryngeal edema in patients with other symptoms of anaphylaxis. Gastrointestinal manifestations include nausea, vomiting, diarrhea and cramping abdominal pain. In most severely ill patients, signs and symptoms begin within 60 minutes of exposure. In general, the faster the onset of symptoms, the more severe the reaction, as evidenced by the fact that half of deaths from anaphylaxis occur within the first hour. Once the initial signs and symptoms subside, patients are at risk for a relapse of symptoms. The effect is caused by a second phase of mediator release, peaking 4 to 8 hours after initial exposure, and presenting clinically 3 to 4 hours after the initial clinical manifestations have resolved. Late-phase allergic reactions are mainly mediated by the release of cysteine leukotrienes, which react slowly. Diagnosis The diagnosis of anaphylaxis is made by history and physical examination, and laboratory tests are of little help. Anaphylaxis should be considered clinically when involvement of two or more systems is noted, with or without hypotension or airway compromise (eg, a combination of skin, respiratory, and gastrointestinal or cardiovascular changes). Diagnosis is easily

made with a clear history of exposure, such as a bee sting. Tryptase is a neutral protease of unknown function in anaphylaxis, which is found only in mast cell granules and is released with degranulation. Serum tryptase levels are elevated for several hours and are useful for further confirmation of a suspected anaphylaxis. Often, as in food allergy, the precipitating substance may not be known. Diagnostic criteria for anaphylaxis were developed by Sampson et al and include: 1. Abrupt onset of symptoms: occurring from minutes to a few hours with involvement of the skin, mucous membranes, and at least one of the following: (a) respiratory involvement; (b) pressure decrease with symptoms of organ dysfunction. 2. Occurrence of two or more of the following symptoms after exposure to an allergen: (a) skin or mucosal involvement; (b) respiratory involvement; (c) blood pressure decrease or associated symptoms; (d) persistent gastrointestinal symptoms. 3. Blood pressure drop after exposure to an allergen to which the patient is predisposed: the criterion in adults is systolic blood pressure (SBP) below 90mmHg or a drop of 30% from the patient's baseline levels. The presence of any of these three criteria makes the diagnosis of anaphylaxis highly likely. Differential diagnosis The differential diagnosis of anaphylactic reactions is extensive, including: vasovagal reactions; myocardial ischemia; arrhythmias; asthmatic state; epiglottitis; hereditary angioedema; strange body; airway obstruction; carcinoid syndrome; mastocytosis;

vocal cord dysfunction. The most common differential diagnosis of anaphylaxis is a vasovagal reaction, which is characterized by hypotension, pallor, bradycardia, sweating, weakness, and sometimes syncope. The differential diagnosis of asthmatic manifestations is asthma itself, aspiration of a foreign body, pulmonary embolism and acute respiratory distress syndrome (Sara). Systemic mastocytosis and mastoid cell leukemia can also present similar manifestations and are necessarily differential diagnoses. The diagnosis of anaphylaxis is clinical, and the finding of elevated histamine levels is useless, as they may have already decreased during dosing. Treatment Given the possibility of developing lifethreatening complications, acute allergic reactions should be screened quickly in the emergency department. Anaphylaxis, defined as airway compromise or hypotension, is obviously an emergency and must be quickly evaluated. The first step is to avoid the precipitating factor, for example, by interrupting the infusion of medication that started the anaphylactic condition. Management in the emergency department begins with the primary ABC (airway, breathing, circulation) and resuscitation maneuvers as needed, and venous access must be obtained. First-line therapies for anaphylaxis (eg, epinephrine, intravenous fluids, and oxygen) have an immediate effect during the acute phase of anaphylaxis, noting that epinephrine is the most important measure in the management of severe anaphylaxis. Vital signs, intravenous access, oxygen, cardiac monitoring, pulse oximetry, and measurements should be obtained immediately. Protecting the airway is the priority. The airway should be examined for signs and symptoms of angioedema (eg, uvula edema, stridor, respiratory distress, hypoxia). If angioedema is

producing respiratory distress, intubation should be performed promptly, as delay can result in complete airway obstruction. The patient should be given enough oxygen to maintain arterial oxygen saturation greater than 90%. Initial flows of 8 to 10L/min are recommended until oximetry monitoring is achieved, and the goal is to maintain oxygen saturation >92%. Despite the importance of interrupting exposure to the causative agent, invasive measures to interrupt this exposure, such as gastric lavage, are not recommended. Adrenaline, despite its importance, is little used in emergency services according to studies. If the patient has signs of cardiovascular impairment, epinephrine can be used intravenously (IV) and should initially be given as a 1:100,000 dilution. This can be done by putting 0.1mg epinephrine (0.1ml in a 1:1,000 dilution) into 10ml of solution and infusing in 510min (a rate of 1-2ml/min). If the patient is refractory to the initial bolus, epinephrine infusion can be started by placing 1mg (1.0mL of a 1:1,000 dilution) in 500mL of dextrose or saline solution at an infusion rate of 1 to 4/kg/ min (0.5 to 2mL/min), titrating the effect. Doctors are often hesitant to give IV epinephrine because of its side effects (tachycardia, arrhythmia, tremor). It should be noted that the starting dose for adults is very diluted; it is given over 5 to 10 minutes, and can be stopped immediately if arrhythmia or chest pain occurs. For less severe symptoms, epinephrine can be used intramuscularly (IM). The dose is 0.3 to 0.5mg (0.3 to 0.5ml of the 1:1,000 dilution) repeated every 5 to 10min according to response or relapse. Most patients do not need more than a single dose. IM epinephrine provides a greater and faster peak than subcutaneous administration and should be the treatment of choice. Also, injections into the thigh are more effective in achieving peak blood levels than injections into the deltoid muscle. If the patient is refractory to treatment despite repeated intramuscular epinephrine, an epinephrine infusion should be

instituted. Caution is warranted in patients using ß-blockers, as severe hypertension secondary to unopposed adrenergic discharge can occur. It should be remembered that these patients ideally should have adequate venous access obtained; ideally two 14- or 16-gauge accessions. If hypotension is present, it is usually the result of distributive shock and responds to resuscitation with crystalloid fluids. Patients should receive a bolus of 1 to 2L (10 to 20mL/kg in children) concurrently with the epinephrine infusion. Second-line therapy includes corticosteroids, antihistamines, asthma medications, and glucagon. These drugs are used to treat anaphylaxis refractory to first-line treatments or in association with complications and also to prevent recurrences. Regarding these medications, some considerations can be made: Corticosteroids. All patients with anaphylaxis should receive corticosteroids. Methylprednisolone: 1.2mg/kg in children; up to a maximum dose of 125mg or hydrocortisone at a dose of 200 to 300mg, IV (5 to 10mg/kg in children up to a maximum dose of 300mg) is appropriate. Methylprednisolone produces less fluid retention than hydrocortisone and is preferred for the elderly and patients in whom fluid retention would be problematic (eg, kidney failure and heart failure). After discharge, especially in patients with persistent cutaneous manifestations on glucocorticoids, a 40mg dose of prednisone can be maintained for 3 to 5 days. Antihistamines . The vast majority of patients with anaphylaxis receive antihistamines, but their benefit appears to be limited to cutaneous manifestations. Most authors recommend the use of H1-blocking antihistamines for all patients with anaphylaxis; these medications include diphenhydramine, 25 to 50mg, IV. The use of H2 blockers may be beneficial in patients with urticaria and associated cutaneous manifestations, but it is not beneficial in other manifestations of anaphylaxis; if ranitidine is used, it is recommended as 50mg diluted in 20–

100mL of saline or dextrose and infused within 5 minutes. The use of H2 blockers is common in refractory urticaria; however, evidence of benefit from controlled trials does not exist. Cimetidine should not be used in elderly patients, with multiple comorbidities with renal or hepatic dysfunction, or whose anaphylaxis is complicated by the use of a beta-blocker. After the initial intravenous dose of steroids and antihistamines, the patient can use oral medication. In case of bronchospasm, the use of selective bronchodilators, such as intermittent or continuous nebulization with albuterol or fenoterol, should be instituted. As might be expected, asthmatics are often more refractory to the treatment of allergic diseases. In severe bronchospasm, other treatments, such as anticholinergics and magnesium sulfate, may be used. Anticholinergic agents should be added to nebulized salbutamol in severe acute bronchospasm. Magnesium sulfate improves lung function and reduces hospital admissions when administered in severe acute asthma and without major adverse effects; the dose of magnesium sulfate is 2g, IV, for 20 to 30 minutes in adults and 25 to 50 mg/kg in children. There are still no data on the role of leukotriene receptor antagonists in the treatment of anaphylaxis. Glucagon . The concomitant use of ß-blockers by the patient is a risk factor for prolonged severe anaphylaxis. In one study, five patients who had severe prolonged reactions were being treated with ß-blockers. For those using ßblockers with refractory hypotension, glucagon should be used in a dose of 1mg, IV, every 5min until the hypotension resolves, followed by an infusion of 5 to 15mcg/min. Side effects include nausea, vomiting, hypokalemia, dizziness and hyperglycemia. Patients with treatment-refractory unstable anaphylaxis should be admitted to the ICU. There is still a description of the use of extracorporeal membrane oxygenation in

patients with refractory anaphylaxis. All patients receiving epinephrine should be observed; however, observation time is based on experience. If the patient remains asymptomatic after appropriate treatment after 4 hours of ...