Cannot Miss Diagnosis
The classic skin manifestation is urticaria (ie, hives). Lesions are red and raised, and they sometimes have central blanching. Intense pruritus occurs with the lesions. Borders of the lesions are usually irregular, and the sizes vary markedly. There may only be a few small or large lesions that become confluent, forming giant urticaria. At times, the entire dermis is involved with diffuse erythema and edema. Hives can occur anywhere on the skin.
In a local reaction, lesions occur in the vicinity of the site of a cutaneous exposure (eg, insect bite). The involved area is erythematous, edematous, and pruritic. If only a local skin reaction (as opposed to generalized urticaria) is present, systemic manifestations (eg, respiratory distress) are less likely. Local reactions (even if severe) are not a predictor of systemic anaphylaxis on re-exposure.
Lesions typical of angioedema may also be present in anaphylaxis. The lesions involve the mucosal surfaces and the deeper layers of the skin. Angioedema is usually nonpruritic, and the lesions are nonpitting. Lesions most often appear on the lips, palms, soles, and genitalia.
Upper airway compromise may occur when the tongue or oropharynx is involved. Complete airway obstruction is the most common cause of death in anaphylaxis. In angioedema due to angiotensin-converting enzyme (ACE) inhibitors, there is marked edema of the tongue and lips that may obstruct the airway. When the upper airway is involved, stridor may be noted. The patient may have a hoarse or quiet voice and may lose ability to speak as the edema progresses.
Wheezing is common when patients have lower airway compromise due to bronchospasm or mucosal edema.
Cardiovascular exam is normal in mild cases. In more severe cases, compensatory tachycardia occurs due to loss of vascular tone. Intravascular volume depletion may take place as a consequence of capillary leakage. These mechanisms also lead to the development of hypotension. Relative bradycardia also has been reported.
Penicillin and cephalosporin antibiotics are the most commonly reported medical agents in cases of anaphylaxis. This is a function of their immunogenicity and their ubiquitous use. Due to their molecular and immunologic similarity, cross-sensitivity may exist. It often has been stated that 10% of patients allergic to an antibiotic in one class will be allergic to those in another class. More recent reports suggest that the actual incidence of cross-reactivity is lower, perhaps 1%, with most reactions being mild.
Reactions tend to be more severe and rapid in onset when the antibiotic is given parenterally.
Anaphylaxis may occur in a patient with no prior history of drug exposure.
Aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) are commonly implicated in allergic reactions and anaphylaxis. Bronchospasm is common in patients with reactive airway disease and nasal polyps. Cross-reactivity may occur between the various NSAIDs.
IV radiocontrast media
IV administered by radiocontrast media causes an anaphylactoid reaction that is clinically identical to true anaphylaxis, and it is treated in the same way. The reaction is not related to prior exposure.
Shellfish or iodine allergy is not a contraindication to use of IV contrast.
Approximately 1-3% of patients who receive hyperosmolar IV contrast will experience a reaction. Use of low molecular weight contrast decreases the incidence of reactions to approximately 0.5%. Personnel, medications, and equipment needed for treatment of allergic reactions should always be available when these agents are administered. Informed consent should be obtained prior to administration.
Reactions to radiocontrast are usually mild (most commonly urticarial), with only rare fatalities reported. The risk of a fatal reaction has been estimated at 0.9 cases/100,000 exposures.
Mucosal exposure (eg, GI, genitourinary [GU]) to radiocontrast agents has not been reported to cause anaphylaxis; therefore, a history of prior reaction is not a contraindication to GI or GU use of these agents.
Pretreatment with antihistamines or corticosteroids and use of low molecular-weight agents leads to lower rates of anaphylactoid reactions to IV contrast. Consider these measures for patients who have prior history of reaction, since rate of recurrence is estimated at 17-60%. Atopic and asthmatic patients are also at increased risk of reaction. In addition, allergic reaction is more difficult to treat in those taking beta-blockers.
Food allergy is common. The symptoms are usually mild and limited to the GI tract, but full-blown anaphylaxis can occur. Fatalities are rare. Commonly implicated foods include nuts (especially peanuts), legumes, fish and shellfish, milk, and eggs.
Latex allergy is an increasingly recognized problem in medical settings where use of gloves and other latex products is prevalent. Most reactions are cutaneous or involve the mucous membranes.
Anaphylactic reactions occur and have been reported with seemingly benign procedures (eg, Foley catheter insertion, intraperitoneal exposure to gloves during surgery).
Other Problems to be Considered
Monosodium glutamate poisoning (ie, Chinese restaurant syndrome)
The diagnosis of anaphylaxis is clinical and does not rely on laboratory testing. When typical symptoms are noted in association with a likely exposure, diagnosis is virtually certain. Ancillary testing may be useful in assessing severity of reaction, although this is primarily a clinical judgment. When the diagnosis is unclear, ancillary testing may help establish the diagnosis.
Cardiac monitoring in patients with severe reactions and in those with underlying cardiovascular disease is important, particularly when adrenergic agonists are used in treatment. Pulse oximetry is also useful.
Patients with symptoms of severe anaphylaxis should first receive high-flow oxygen, cardiac monitoring, and IV access. These measures are appropriate for an asymptomatic patient who has a history of serious reaction and has been re-exposed to the inciting agent.
Additional treatment depends upon the condition of the patient and the severity of the reaction. Measures beyond basic life support (BLS) are not necessary for patients with purely local reactions.
Airway patency should be assessed immediately due to the potential for compromise secondary to edema or bronchospasm. Active airway intervention may be difficult due to laryngeal or oropharyngeal edema. In this circumstance, it may be preferable to defer intubation attempts and ventilate with a bag/valve/mask apparatus while awaiting the effect of medications. In extreme circumstances, cricothyrotomy may be lifesaving. Inhaled beta-agonists are used to counteract bronchospasm and should be given to patients who are wheezing.
The IV line should be of large caliber because of the potential requirement for large-volume IV fluid resuscitation. Isotonic crystalloid solutions (ie, normal saline, Ringer lactate) are preferred. A keep vein open (KVO) rate is appropriate for patients with stable vital signs and only cutaneous manifestations. If there is hypotension or tachycardia, administer a fluid bolus of 20 mg/kg for children and 1 L for adults.
Further fluid therapy will depend upon patient response. Large volumes may be required in the profoundly hypotensive patient.
Administer epinephrine to patients with systemic manifestations of anaphylaxis. When there is mild cutaneous reaction, an antihistamine alone may be sufficient, thus the potential adverse effects of epinephrine can be avoided. Patients on beta-blocker medications may not respond to epinephrine. In these cases, glucagon may be useful. Antihistamines (eg, H1 blockers), such as diphenhydramine are important and should be given for all patients with anaphylaxis or generalized urticaria.
Corticosteroids are used in anaphylaxis primarily to decrease the incidence and severity of delayed or biphasic reactions. Corticosteroids may not influence the acute course of the disease; therefore, they have a lower priority than epinephrine and antihistamines.
Further intervention depends upon severity of the reaction and the affected organ system(s).
Airway patency should be rapidly assessed in patients with systemic signs or symptoms. If intubation is required, it may be difficult because of upper airway or facial edema. Epinephrine may rapidly reverse airway compromise, and bag/valve/mask ventilation may be effective in the interim when intubation is not possible. Surgical airway intervention using standard cricothyrotomy is an option when orotracheal intubation or bag/valve/mask ventilation is not effective.
Wheezing or stridor are indications of bronchospasm or mucosal edema. Treatment with epinephrine and inhaled beta-agonists is effective for these indications.
Recommendations to treat refractory bronchospasm with corticosteroids have been made because of their effectiveness in reactive airway disease. As in asthma therapy, the onset of action is delayed for several hours. Aminophylline has also been recommended for bronchospasm in anaphylaxis and may be more rapidly effective than corticosteroids.
Hypotension in anaphylaxis is usually due to vasodilatation and capillary fluid leakage. Epinephrine is the primary pharmacologic treatment for these findings. H1-blocking antihistamines may also have a role in reversing hypotension. Some authors also recommend H2-blocking agents. Large volume fluid resuscitation with isotonic crystalloid often is needed to support the circulation in patients with cardiovascular manifestations of anaphylaxis.
Refractory hypotension should first be treated with large volumes of crystalloid and repeated doses of epinephrine or a continuous epinephrine infusion. If this is not effective, other pressors with alpha-adrenergic activity, such as levarterenol or dopamine, may be considered.
Mediators of anaphylaxis are not considered to have direct myocardial toxicity. In patients with preexisting heart disease, ischemic myocardial dysfunction may occur due to hypotension and hypoxia. Epinephrine may still be necessary in patients with severe anaphylaxis, but the potential for exacerbating ischemia should be kept in mind. If pulmonary congestion or evidence of cardiac ischemia is present, fluid resuscitation should be more cautious.
Patients taking beta-blockers may be resistant to the effects of epinephrine. Larger than usual doses may be needed. Glucagon may be effective in this circumstance because it increases intracellular cyclic adenosine monophase (cAMP) levels by a mechanism that does not depend upon beta-receptors.
Cutaneous effects of anaphylaxis are uncomfortable but not life threatening. Patients often respond promptly to epinephrine and H1 antihistamines. Some authors state that corticosteroids help prevent recurrence of symptoms (both cutaneous and systemic) that may occur 6-8 hours after successful treatment (so-called biphasic reaction). H2 blockers may have an added effect.
GI symptoms in anaphylaxis respond to H1 antihistamines and epinephrine.
Most patients with anaphylaxis may successfully be treated in the ED, followed by being discharged.
Treatment success may operationally be defined as complete resolution of symptoms, which is followed by a short period of observation. The purpose of observation is to monitor for recurrence of symptoms (ie, biphasic anaphylaxis).
Patients who fail to respond fully, who have a recurrent reaction, who suffer a secondary complication (eg, myocardial ischemia), who experience a significant injury from syncope, or who need intubation will require hospital admission. As with many other conditions, a lower threshold for admission should be considered when patients are at the extremes of age or when they have significant comorbid illness.
Inpatient care is dictated by the manifestation(s) of anaphylaxis that presents. Essentially, it consists of continuing the care initiated in the ED.
Consider ICU admission for patients with persistent hypotension. The primary means of support are adrenergic agents (eg, epinephrine, dopamine) and fluid resuscitation. Persistent hypotension in the face of pressors and fluid resuscitation is an indication for invasive hemodynamic monitoring with evaluation of cardiac function and peripheral vascular resistance. Use of these parameters provides the basis for objective decisions regarding the use of fluids and pressors.
Inpatient management of airway compromise consists of continuation of parenteral and inhaled adrenergic agents and corticosteroids that were initiated in the ED.
Cutaneous manifestations of anaphylaxis are treated with repeated doses of antihistamines.
Discharged patients who have been successfully treated for anaphylaxis usually should continue antihistamines for 2-5 days to prevent recurrence. When corticosteroids have been used as part of the initial treatment, it is common practice to continue that treatment for a short period.
The following regimens are commonly used by clinicians though there is very little hard data concerning the natural history of anaphylaxis. The evidence for efficacy of H2-blocker antihistamines is particularly sparse. The newer, nonsedating antihistamines have not been studied in the context of treatment for anaphylaxis.
Preventive therapy for anaphylaxis is dependent upon identifying the inciting agent. When the agent has been identified, the key to prevention is avoidance. There are certain prophylactic or preventative therapies that may be employed when re-exposure cannot be avoided. When the inciting agent is not obviously known from the history, allergy testing may be useful in identifying it. When the allergen is a therapeutic agent for which subsequent usage is medically necessary, there are desensitization or pretreatment protocols that may be employed.
Complications from anaphylaxis are rare, and most patients completely recover. Myocardial ischemia may result from hypotension and hypoxia, particularly when there is underlying coronary artery disease.
Ischemia or arrhythmias may result from treatment with pressors. Prolonged hypoxia also may cause brain injury. At times, a fall or other injury may occur when anaphylaxis leads to syncope.
Caution patients who are discharged after an episode of anaphylaxis to avoid exposure to an inciting agent. When no inciting agent has been identified, consider referral to an allergist to identify the cause of anaphylaxis.