Steven Go, MD
Allergic reactions and anaphylactic syndromes
to discontinue exposure to that antigen (e.g., new make-up, perfume, topical medication). Previous incidents and known allergies may provide a clue to the etiology of the current attack or point to specific cross-reactivities that may exist (i.e., peni- cillins and cephalosporins). Frequent previous incidents may identify carcinoid syndrome, her- editary angioedema, or factitious anaphylaxis.
What were the surrounding events when the symptoms occurred?
If the symptoms occur in conjunction with the introduction of emotional stress, a vasovagal reaction may be suspected. If the symptoms begin during or shortly after a meal, a potential food antigen is possible. Since restaurants do not generally disclose the precise ingredients in their dishes, many patients may not realize they have consumed foods that they know cause them problems. Anaphylaxis can occur in conjunction with vigorous exercise, especially in conditioned athletes in adverse climates.
Has anyone in your family had symptoms like this before?
If affirmative, hereditary angioedema should be suspected. Many antigens and exposures cause difficulty for an entire family.
Associated symptoms
Anaphylactic syndromes can present in various ways (Table 11.1). Increased vascular permeabil- ity can appear as urticaria, angioedema, and is sometimes preceded by a feeling of flushing and warmth. Laryngeal edema can quickly lead to airway compromise and may present with stri- dor, hoarseness, a feeling of airway obstruction, and dysphagia. Nasal congestion can further hamper respirations. Bronchospasm presents with dyspnea, wheezing, and “tightness” in the chest. Hypotension can present with syncope or dizziness, which are sometimes harbingers of vas- cular collapse. Other associated symptoms include gastrointestinal (GI) symptoms such as nausea, vomiting, abdominal pain, and diarrhea, which may sometimes be bloody. Signs and symptoms of shock may be present in severe cases. Uterine muscle contractions can cause pelvic cramping, and in pregnancy, miscarriage. In anaphylaxis, any of these symptoms can be present, either together or in isolation. Skin findings are present in up to 90% of cases. However, the absence of skin signs in no way rules out the presence of an anaphylactic syndrome.
Past medical
Patients with a history of cardiac or pulmonary disease are at greater risk of death. Patients tak- ing -blockers who develop anaphylaxis are
Table 11.1 Symptoms and signs of anaphylactic syndromes
Presentation Symptoms Signs
Airway edema Sensation of throat tightness, Respiratory distress, stridor, muffled voice or dysphagia, dysphonia hoarseness, coughing, sneezing, nasal congestion Angioedema Swelling without pruritis Edema: especially of face, eyelids, lips, tongue,
uvula, eyes, hands, and feet
Bronchospasm Dyspnea, chest tightness Wheezing, coughing, retractions, tachypnea Distributive shock Dizziness, syncope, near-syncope, Hypotension, tachycardia
anxiety, weakness, confusion
Gastroenteritis Nausea, vomiting, diarrhea, Diffuse abdominal pain without peritoneal signs.
bloating, abdominal cramping May have normal examination
Increased Rhinorrhea, bronchorrhea, Nasal congestion, increased tracheal and bronchial secretions increased lacrimation secretions. Drooling, tearing, conjunctival erythema Urticaria Pruritis or tingling, rash or Raised erythematous welts of various sizes on
swelling, flushing the skin surface. Usually pruritic
Allergic reactions and anaphylactic syndromes often refractory to therapy and are at extremely
high risk.
Physical examination
General appearance
The general appearance of the patient is of crucial importance. Patients experiencing allergic reac- tions who appear sick are probably ill or about to be very ill. Any difficulty speaking, respiratory distress, or agitation should provoke immediate treatment. An expressed fear of impending doom is often prescient.
Vital signs
Temperature is usually normal. Cardiovascular involvement is suggested by hypotension, tachy- cardia, and dysrhythmias. Pulse oximetry is typ- ically normal until airway compromise is nearly complete; therefore, a normal reading does not rule out airway involvement.
Integument
Inspection may reveal urticaria (Figure 11.1), angioedema, erythema, flushing, and pruritis.
Diaphoresis and/or cyanosis indicates the pres- ence of shock.
Head and neck
Inspection may reveal swelling of the eyelids, lips (Figure 11.2), tongue, and oral mucosa. Lip or facial cyanosis indicates severe respiratory
compromise. The presence of drooling, the inability to manage secretions, and the size and appearance of the uvula and tongue should all be noted. The posterior oropharynx should be inspected for patency. A hoarse or muffled voice signals potential airway compromise, as does dysphagia. Stridor should be identified. Eye itching, conjunctival injection, and tearing can occur. Nasal congestion, rhinorrhea, and sneezing may also be present.
Observing the patient’s Mallampati classification (Figure 2.8) may be useful in helping determine what type of airway stabilization method is appropriate if acute airway compromise occurs, but its role in the management of anaphylaxis has not been clearly delineated in the literature.
Lungs
Wheezing indicates bronchospasm if enough air- flow is present to wheeze. A quiet chest is an even more dangerous sign because it indicates severe compromise of the patient’s ventilatory status.
Increased respiratory effort is also dangerous.
Heart
Tachycardia is most common, but other dysrhyth- mias may be present.
Abdomen
Crampy abdominal pain as a result of edema, smooth muscle contraction or vascular engorge- ment can be present. However, true peritoneal signs should not be present. Tenesmus can also occur.
Figure 11.1
Urticaria.Courtesy: Steven Shpall, MD.
Figure 11.2
Angioedema involving the upper lip.Courtesy: Leland Robinson, MD and Steven Go, MD.
Extremities
Patients with anaphylaxis commonly have a rapid, weak, thready pulse. Cyanosis of the nail beds occurs with severe respiratory compromise.
Neurologic
Altered mental status, agitation, lightheaded- ness, or unconsciousness are signs of a severe reaction. Seizures are uncommon, but may occur.
Otherwise, the neurologic examination should be normal.
Differential diagnosis
There are numerous entities that can mimic ana- phylaxis. It can be very difficult to differentiate them in the acute phase. Therefore, clinical syn- dromes that appear to be anaphylaxis should be treated as anaphylaxis until proven otherwise (Table 11.2).
Diagnostic testing
Diagnostic testing is of little utility in the emer- gent diagnosis and management of anaphylactic syndromes in the ED.
Laboratory studies
Serum histamine and tyramine levels have been mentioned in the literature to possibly confirm the diagnosis of anaphylaxis. However, hista- mine has an extremely short half-life; therefore, a meaningful level is difficult to measure. More importantly, these tests are more appropriate to confirm the diagnosis after the patient has been stabilized. They should play no role in determin- ing whether to suspect anaphylaxis or to treat it.
Electrocardiogram and radiologic studies
Electrocardiogram (ECG) and radiologic studies are generally nonspecific. Confirmational skin testing is beyond the scope of emergency medicine.
General treatment principles
The guiding treatment principle is to rapidly determine that the patient needs treatment.
Anaphylaxis often occurs without warning, and
a delay in appropriate therapy may prove fatal.
Therefore, a high level of suspicion must be maintained. In addition, for obvious reasons, there are few prospective controlled trials for the treatment of anaphylactic shock. Therefore, it should be remembered that the treatment recom- mendations in the literature are largely based on anecdotal clinical experience.
Although the following treatment strategies should occur simultaneously, it is helpful to con- ceptualize them in a few basic categories.
Antigen removal
If the inciting antigen is still present (e.g., the stinger of a bee, article of clothing), it should be removed promptly.
Epinephrine administration
Epinephrine administration is the cornerstone of treatment. It should be given when anaphylaxis is suspected. The usual dose of epinephrine is 0.3–0.5 mg of 1 : 1000 solution given subcuta- neously (SC) or intramuscularly (IM). The IM route has been touted as being the more effica- cious. Some experts have even recommended intravenous (IV) administration, but given the potential hazards of this route (e.g., dysrhyth- mias, myocardial infarction, cerebral vascular events, organ ischemia) and the lack of conclu- sive advantages, it is probably prudent to avoid the IV route except in cases of cardiopulmonary arrest. Epinephrine should be used with care in those with known cardiac disease or pregnancy;
however, as always, the benefits of the treatment must be weighed against its risks. Epinephrine should be used with caution in patients on -blockers (see Special patients).
Airway control
The most common mistake in airway manage- ment is the failure to recognize the need for early airway control. For any patient with an allergic reaction, the status of the airway must be deter- mined, documented, and monitored closely. An oral airway is preferable to a surgical airway, if possible. If early laryngeal edema is present, early elective airway control is preferable to expectant management. By the time extreme respiratory distress develops, achieving an airway may be impossible. Rapid sequence intubation (RSI) should be used with great caution in these patients, as unseen lower airway edema may
Allergic reactions and anaphylactic syndromes
Allergic reactions and anaphylactic syndromes
Table 11.2 Differential diagnosis of anaphylaxis-like syndromes
Diagnosis Symptoms Signs Workup
Carcinoid Recurrent episodes of flushing of the face Hypotension, no urticaria. Increased serum and urine syndrome and neck, palpitations, facial swelling, GI Facial edema, malar levels of serotonin
symptoms (especially diarrhea, which can telangiectasia, flushing, metabolite, 5-HIAA be debilitating). Dyspnea may also occur wheezing. May hear murmur
if cardiac involvement
Chinese Proximity to eating MSG-containing foods. Wheezing, flushing, History. No definitive test.
restaurant Dyspnea, flushing, sweating, tightness in hypotension, and Symptoms typically syndrome the chest, burning sensation at the back dysrhythmias can occur. resolve in 2 or 3 hours (MSG of the neck into arms and chest, headache, True anaphylaxis may
symptom nausea, palpitations, oral numbness and occur complex) burning
Factitious Anxiety present No objective signs of History and examination.
anaphylaxis anaphylaxis Diagnosis of exclusion.
Munchausen’s anaphylaxis is true anaphylaxis that the patient causes surreptitiously Hereditary Swelling of lips, tongue, and upper airway Angioedema is usually Decreased C1-esterase angioedema with possible respiratory compromise. seen in the lips, face, inhibitor levels. Decreased
Sometimes abdominal pain or non-pruritic and oral mucosa. Absence serum C4. Fiberoptic swelling of extremities. Often develops after of urticaria or pruritis laryngoscopy may reveal
trauma (e.g., dental procedure). Lack of upper airway edema
antigen exposure. Family history of these events and/or history of recurrent episodes in the absence of antigen
Pheochromo- Headache, sweating, palpitations, tremor, Hypertension, fever, Elevated levels of urine cytoma nausea, weakness, constipation, weight loss, pallor, tremor, catecholamines. Hyper- abdominal pain, weight loss neurofibromas, café au lait glycemia, hypercalcemia,
spots, tachydysrhythmias erythrocytosis Scombroid Exposure to fish of the Scombridaefamily Diaphoresis, facial rash, Elevated level of urine poisoning or related fish (tuna, mackerel, mahi-mahi, urticaria, edema, abdominal histamine. FDA analysis
sardines, anchovies). Rapid onset of facial tenderness. Respiratory of tainted fish. Typical flushing, peppery taste, dizziness, distress, tongue swelling, resolution of symptoms in palpitations, nausea, headache, diarrhea, blurred vision, and vaso- within 8–10 hours
abdominal pain dilatory shock may occur
Serum Fever, malaise, headache, arthralgias, GI Fever, rash (may be scarlati- Elevated sedimentation sickness symptoms, associated with urticaria occur niform, urticarial, morbilliform, rate. Possible elevated
7–10 days after exposure to antigens or polymorphous) lymph- creatinine. CBC with adenopathy, arthritis, eosinophilia. Depressed arthralgias. Rarely cardio- complement levels pulmonary involvement
Systemic Not associated with a particular antigen Presents as anaphylaxis No available test to differ-
mastocytosis exposure entiate from anaphylaxis
Vasovagal Occurs during stress (e.g., injection, Slow, strong, steady pulse. Monitoring and ED reactions dental procedures) No pruritis. Absence Blood pressure normal or observation. Symptoms
of respiratory obstruction or skin elevated. Skin cool. Pallor relieved by recumbency
symptoms without cyanosis
MCSLC See specific disorder See specific disorder See specific disorder CBC: complete blood count; ED: emergency department; FDA: Food and Drug Administration; GI: gastrointestinal;
5-HIAA: 5-hydroxyindoleacetic acid; MCSLC: miscellaneous causes of sudden loss of consciousness (i.e., seizure, cardiac dysrhythmias, pulmonary embolism, foreign-body aspiration); MSG: monosodium glutamate.
Allergic reactions and anaphylactic syndromes
preclude an oral endotracheal airway. In such cases, giving paralytics would be unwise. If imme- diately available, fiberoptic intubation may be a safer option. In any event, equipment and person- nel necessary for the establishment of an emer- gent surgical rescue airway should ideally be close at hand when managing the airway.
Ventilatory support
Any component of bronchospasm should be treated with bronchodilators, supplemental oxy- gen, and corticosteroids. Arterial blood gases may be useful in determining the level of ventila- tory compromise, although the decision to intub- ate for ventilatory compromise remains largely a clinical one.
Circulatory support
Fluid resuscitation with normal saline or colloid should be given for hypotension and other signs of shock. Large quantities may be required to maintain a satisfactory blood pressure. Central venous pressure monitoring may be helpful in guiding therapy. For refractory cases, vasopres- sors such as norepinephrine may be required.
The patient should be kept recumbent until blood pressure stabilizes.
Secondary medications
Antihistamines can be useful in treating cuta- neous manifestations of allergic reactions, but there is debate regarding their efficacy in acute anaphylaxis. Therefore, they should be viewed as adjunctive treatments to epinephrine and fluids in this circumstance. It has been shown that in acute allergic urticaria, the addition of H2- blockers to H1-antagonists results in improved outcomes (resolution of urticaria, with or without angioedema) in patients compared with treatment with H1-blockade alone.
Corticosteroids likely have no benefit in the acute phase of anaphylaxis, given their delayed onset of action. However, they may reduce the possibility of a biphasic reaction. Therefore, they should probably be given early to all patients, unless contraindications exist.
Aminophylline has traditionally been thought to be useful in treating bronchospasm, stimulating respiratory drive, augmenting cardiac contrac- tions, and promoting diaphragmatic contractility.
However, the utility of this medication in the emergency treatment of acute bronchospasm has
been questioned in the literature, and its use remains controversial.
Norepinephrine and glucagon may be useful in refractory hypotension. Glucagon may be par- ticularly useful in hypotensive patients taking -blockers.
Special patients
Taking -blockers
-blockers are proallergenic, and also amplify the production of anaphylactic mediators which potentiate the severity of allergic reactions. - blockers may also blunt the usually favorable response to epinephrine treatment. Glucagon may be useful in treating hypotension in anaphylaxis patients who are taking -blockers. In addition, these patients may develop severe hypertension upon epinephrine administration, secondary to unopposed -adrenergic effects. Dysrhythmias may also occur. Adverse reactions may also occur during epinephrine therapy in patients who are using tricyclic antidepressants or monoamine oxi- dase inhibitors. Epinephrine should be used at reduced dosages in these cases, and phentolamine (to treat hypertension) and lidocaine (to treat dysrhythmias) should be readily available.
Resistant bronchospasm
Resistant bronchospasm may occur in patients who are taking -blockers. Sometimes higher than usual dosages or frequency of bronchodila- tors (-agonists and anticholinergics) are neces- sary for these patients. Inhaled epinephrine may be useful when SC epinephrine fails to relieve bronchospasm. Other therapies mentioned in the literature include IV magnesium, vitamin C, naloxone, atrial natriuretic factor, and glucagon;
however, evidence of benefit for these medica- tions is inconclusive.
Disposition
Much like treatment, disposition recommenda- tions in the literature are generally based on clin- ical experience.
Patients with mild allergic reactions limited to peripheral cutaneous findings (not involving the airway) without evidence of anaphylaxis may be treated symptomatically and discharged with careful follow-up instructions, including avoid- ance of the inciting antigen.
Allergic reactions and anaphylactic syndromes Patients with more severe reactions (e.g.,
mucosal swelling, wheezing), but without evidence of shock should be treated aggressively, and observed for at least 8 hours. If the patient makes a prompt recovery without complications and remains asymptomatic, he may be safely dis- charged with cautionary discharge instructions, corticosteroids to prevent a late-phase reaction, and close follow-up. In the absence of con- traindications, patients should also be given a prescription for an epinephrine injector and instructions on how to use it. However, the sub- set of these patients with significant pre-existing comorbidities (e.g., advanced age, cardiopul- monary disease) should probably be admitted for observation. In addition, some experts suggest admitting any patient who requires multiple doses of epinephrine, regardless of response to therapy.
All other patients with anaphylactic syndromes should be admitted for observation.
For all discharged patients, the prevention of future allergic reactions should be stressed. The patient should be urged to remove inciting anti- gens from their environment. This may require a physician’s note to an employer to request that the patient be allowed to avoid a workplace anti- gen. In certain cases, where desensitization for unavoidable antigens may be necessary, referral to an allergist is appropriate. Finally, the inciting antigen (if known) should be well-documented in the patient’s medical record, especially if the antigen is a medication or latex.
Pearls, pitfalls, and myths
Pitfalls
• Failure to recognize the subtle early presentation of anaphylaxis.
Table 11.3 Anaphylactic syndrome drug dosages
Drug Adult dose Pediatric dose
Parenteral adrenergic agents
Epinephrine 0.3–0.5 mg 1 : 1000 solution IM 0.01 mg/kg (minimum 0.1 ml) 1 : 1000 or SC q 15 minutes solution SC q 15 minutes
0.1 mg 1 : 10,000 solution slow 1 mcg/kg (minimum 0.1 ml) 1 : 10,000
IV push solution slow IV push
Epinephrine (intravenous) 1–10 mcg/minute titrate 0.1–1.0 mcg/kg/minute titrate to
infusion to effect effect
Inhaled-agonists
Albuterol 0.5 ml 0.5% solution in 2.5 ml 0.03–0.05 ml/kg 0.5% solution in NS nebulized q 15 minutes 2.5 ml NS via nebulizer q 15 minutes H1-receptor blockers
Diphenhydramine (Benadryl) 25–50 mg IV/IM q 4–6 hours 1–2 mg/kg IV/IM q 4–6 hours 50 mg PO q 4–6 hours 2 mg/kg PO q 4–6 hours H2-receptor blockers
Ranitidine (Zantac) 50 mg IV over 5 minutes 0.5 mg/kg IV over 5 minutes
150 mg PO bid 0.25–2 mg/kg/dose PO q 12 hours
(maximum of 150 mg q 12 hours) Cimetidine (Tagamet) 300 mg PO/IV/IM q 6 hours Not recommended for children Corticosteroids
Methylprednisolone (Solu-Medrol) 40–250 mg IV/IM q 6 hours 1–2 mg/kg IV/IM q 6 hours
Prednisone 20–60 mg PO qd 1 mg/kg PO qd
Antidote, refractory hypotension
Glucagon 1 mg IV q 6 minutes until Dosing not definitively established hypotension resolves,
followed by 5–15 mcg/minute infusion
BID: two times a day; IM: intramuscular; IV: intravenous; NS: normal saline; PO: per os; QD: four times a day;
SC: subcutaneous.
Allergic reactions and anaphylactic syndromes
• Failure to recognize the need for acute and definitive airway management.
• Failure to administer epinephrine early in the patient’s treatment.
• Failure to recognize the contraindications for RSI in anaphylaxis patients.
• Failure to anticipate difficulties in the treatment of patients taking -blockers.
• Failure to observe patients for an adequate length of time.
• Failure to admit high-risk patients.
• Failure to anticipate the possibility of a biphasic allergic reaction.
• Failure to appropriately administer and prescribe corticosteroids.
• Failure to counsel the patient to avoid antigen triggers.
• Failure to prescribe an epinephrine injector for susceptible patients and to properly instruct them regarding its use.
Myths
• Patients with anaphylaxis always look sick on initial presentation.
• Airway compromise always follows a linear time course.
• Antihistamine agents are first-line treatments for anaphylaxis.
• Once patients get better, they never relapse.
• If the patient does not react immediately after exposure to an antigen, they cannot have a significant anaphylactic reaction.
References
1. Bochner BS, Lichtenstein LM. Anaphylaxis.
New Eng J Med1991;324:1785–1790.
2. Brown AFT. Therapeutic controversies in the management of acute anaphylaxis.
J Accid Emerg Med1997;15:89–95.
3. Freeman TM. Anaphylaxis diagnosis and treatment. Primary Care1998;25:809–817.
4. Gordon BR. Prevention and management of office allergy emergencies. Otolaryn Clin North Am1994;25:119–134.
5. Heilborn H, et al. Comparison of subcutaneous injection and high-dose inhalation of epinephrine. Implications
for self-treatment to prevent anaphylaxis.
J Allergy Clin Immunol1986;78:1174–1179.
6. Jacobs RL, Rake Jr GW, Fournier DC, et al.
Potentiated anaphylaxis in patients with drug-induced beta-adrenergic blockade.
J Allergy Clin Immunol1992;92:277–296.
7. Joint Task Force on Practice Parameters.
The diagnosis and management of anaphylaxis. J Allergy Clin Immunol 1998;101:S465–S528.
8. Land GM. Anaphylactoid and anaphylactic reactions: hazards of beta-blockers. Drug Safety1995;12:299–304.
9. Lip GYH, Metcalfe MJ. Adrenaline in allergic emergencies. Br Med J1992;304:1443.
10. Lin RY, et al. Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2
antagonists. Ann Emerg Med2000;36:462–468.
11. Metcalf DD. Acute anaphylaxis and urticaria in children and adults. In:
Schocket AL (ed.). Clinical Management of Urticaria and Anaphylaxis. New York: Marcel Dekker, 1992. pp. 70–96.
12. Portier P, Richet C. D l’action
anaphylactique de certains venins. C R Soc Biol(Paris) 1902;54:170–172.
13. Roberts-Thomson P, Heddle R, Kupa A.
Adrenaline and anaphylaxis. Med J Aust 1985;142:708.
14. Sampson HA. Fatal food-induced anaphylaxis. Allergy1988;53:125–130.
15. Sim, TC. Anaphylaxis: how to manage and prevent this medical emergency. Postgrad Med1992;92:277–296.
16. Smith GB, Taylor BI. Adrenaline in allergic emergencies. Br Med J1992:304:1635.
17. Soto-Aguilar MC, deShazo RD, Waring NP.
Anaphylaxis: why it happens and what to do about it. Postgrad Med1987;82:154–170.
18. Sullivan TJ. Cardiac disorders in penicillin- induced anaphylaxis. Association with intravenous epinephrine therapy. JAMA 1982;248:2161–2162.
19. Terr AI. Anaphylaxis. Clin Rev Allergy 1985;3:3–23.
20. Valentine MD, Sheffer AL. The anaphylactic syndromes. Med Clin North Am
1969;53:249–257.
21. Winberry SL, Lieberman P. Anaphylaxis.
Immunol Allergy Clin North Am 1995;15:447–477.