Approach

Initial management of the acute reaction is usually based entirely on history, exam findings, and clinical suspicion. Any indication of anaphylaxis should prompt immediate supportive care, as loss of airway patency and cardiovascular collapse may occur rapidly. Stabilization and treatment of life-threatening conditions are most often performed simultaneously. All patients with signs of a systemic reaction, especially hypotension, airway swelling, or difficulty breathing, should receive immediate intramuscular epinephrine (adrenaline) in the anterolateral thigh.[42][43][44][45][46]

Close monitoring is still necessary in less severe reactions (or reactions responding to treatment), as rapid deterioration or rebound from treatment is possible.​[3][28]​​​[47]​ Patients with biphasic reactions or severe reactions that have not responded well to treatment may require prolonged observation in the emergency room (ER).[3]​ Any return of symptoms should lead to retreatment and may indicate a need for hospital admission. Regardless of severity, all patients with a diagnosis of anaphylaxis should be kept under observation until signs and symptoms have fully resolved.[2]

Coexisting cardiovascular disease should be noted because some treatments can stress a susceptible heart.[48] Caution and close monitoring should be used when treating these patients. However, pre-existing heart disease is not a contraindication to treatment of suspected anaphylactic reactions.

Cardiopulmonary arrest

If the patient is in cardiopulmonary arrest, cardiopulmonary resuscitation with intubation and ventilation, intravenous fluid replacement, and intravenous epinephrine are indicated.[49]​ See also Anaphylaxis.

Systemic reactions

It is important to remember to reevaluate the patient frequently as their condition may deteriorate quickly.

Primary airway, breathing, and circulation assessment: abnormalities in any of these aspects signal the need for immediate intervention (immediate treatment and preparation for transfer to ER or advanced care setting):

  • Airway patency and ability to maintain airway

  • Evidence of tongue or throat swelling

  • Swallowing of own secretions or the presence of drooling

  • Problems with spontaneous breathing, dyspnea, wheeze, cough, air hunger

  • Palpable pulses, pulse rate, and rhythm

  • Skin flushing (vasodilated) or skin pallor with clamminess (vasoconstricted)

  • Positioning: supine (or on side) if hypotensive, but may need to be more upright if severe dyspnea.

Cardiopulmonary assessment and supportive measures

  • Airway patency must be maintained, as airways can close within minutes when surrounding tissues swell.

  • Supplemental oxygen should be considered for all patients with anaphylaxis regardless of their respiratory status, and must be administered to any patient with respiratory or cardiovascular compromise and to those who do not respond to initial treatment with epinephrine.[2]

  • Early prophylactic intubation or even cricothyrotomy may be necessary, especially if there is inspiratory stridor.[2]

  • Any subjective findings (e.g., feeling of swelling or tightness in the throat or oropharynx) or objective findings (e.g., stridor, hoarseness, visualized glottic or tongue edema, cyanosis) warrant preparation for emergency airway management.

  • Cardiovascular collapse should be treated with aggressive volume resuscitation (isotonic solutions, e.g., 0.9% normal saline or Ringer lactate) and vasopressor infusion.

  • Patients requiring airway support or treatment for cardiovascular collapse must be moved to the ER or critical care setting as rapidly as possible.

  • Unless precluded by shortness of breath or vomiting, the patient should be placed in a supine position with legs elevated (shock or Trendelenburg position).[49]​ This will augment venous return, and thereby increase preload and enhance cardiac output.

  • Regardless of severity of reaction, all patients with a diagnosis of anaphylaxis should be kept under observation until signs and symptoms have fully resolved, and may require extended observation or admission.[3]​​

  • Any retained stingers should be removed as soon as they are identified.

Epinephrine (adrenaline)

  • All patients with signs of a systemic reaction, especially hypotension, airway swelling, or difficulty breathing, should receive immediate intramuscular epinephrine in the anterolateral thigh.[42][43][44][45][46] The dose may be repeated every 5-15 minutes as needed.​[1]​​[3]​ Administration in the anterolateral thigh is superior to intramuscular administration in the deltoid or a subcutaneous injection.[50][51]

  • Intravenous epinephrine is administered to patients in cardiopulmonary arrest, and to profoundly hypotensive patients who have not responded to intravenous fluids and several doses of intramuscular epinephrine.[2][52]​ Continuous infusion of epinephrine, titrated to effect, is reserved for experienced practitioners. No intravenous dose regimen is universally recognized.

  • The alpha-1, beta-1, and beta-2 agonist actions of epinephrine play a key role in reversing the effects of anaphylaxis. Stimulation of the alpha-1 receptors leads to increased vascular tone and thus reversal of the effects of massive vasodilation triggered by immune mediators. However, alpha-1 stimulation can also lead to severe hypertension, especially in those with poorly controlled hypertension. Beta-1 receptor stimulation has positive inotropic and chronotropic effects (i.e., the heart rate and contractility are increased), but an overshooting response can result in unwanted tachycardia, potentially harming a patient with coronary artery disease. Beta-2 agonism causes bronchodilation and impairs release of mediators from mast cells and basophils.

  • A prescription for two epinephrine auto-injectors must be given following any episode of anaphylaxis.​​​[2][5][28][53]​ The patient or caregiver should carry both at all times and be familiar with their use.​​[24][54]

Inhaled beta-2 agonists

  • Persistent respiratory symptoms following administration of epinephrine may benefit from inhaled beta-2 agonists.[4]

Glucagon

  • Patients treated with beta-blockers may be refractory to treatment with alpha-/beta-agonists. Glucagon works by bypassing the adrenergic receptors and directly activating cyclic adenosine monophosphate intracellularly. However, the resulting tachycardia can be detrimental in patients with severe coronary artery disease.[1]

  • Glucagon often causes nausea and vomiting, which may further prompt the need for definitive airway control.

  • Antiemetics may be used in conjunction with glucagon treatment.

Corticosteroids

  • Guidelines vary regarding recommendations for the use of corticosteroids in sting allergy

  • Corticosteroids, if used, should not replace epinephrine as the first-line of treatment for anaphylaxis and may be prescribed as adjunctive therapy following administration of epinephrine.[2]

  • Corticosteroids may decrease the risk of symptoms associated with anaphylaxis including urticaria; however, the data supporting the use of corticosteroids are limited due to difficulties in performing controlled studies.[55][56]

  • Guidelines published in 2020 advise against administering corticosteroids to prevent biphasic anaphylaxis. This is based on limited evidence suggesting that there is no clear benefit in terms of risk reduction.[2]

  • Corticosteroid treatment works in a delayed fashion to decrease vascular permeability and blunt the immune response to the inciting antigen.

H1 antagonists and H2 antagonists

  • Use of H1 and H2 antagonists is limited to relief of itching, hives, and rhinorrhea. Their use should never delay or replace the use of intramuscular epinephrine.[57][58]

  • Antihistamines antagonize the effects of histamine release at cellular receptors, decreasing itching, erythema, and rash.

  • In general nonsedating H1 antagonists should be used in preference to sedating H1 antagonists, although there may be a role for sedating H1 antagonists at night if symptoms are interrupting sleep.[59]

  • H2 antagonists can be used to further potentiate the antihistamine effect, although evidence of benefit is very limited.

  • Topical antihistamines should be avoided as they probably do not add any beneficial effect when patients are already on systemic antihistamines. They can also be irritating to the skin and can lead to contact dermatitis.[59]

Stinger removal

  • Retained stingers should be removed because they may still contain venom

  • The venom sac is emptied within 30 seconds after exposure; therefore, the stinger should be removed as quickly as possible

  • Traditional teaching suggests that squeezing the stinger (e.g., with tweezers) can inject more venom into the patient. The stinger should be removed by gently scraping the stinger with the edge of a plastic ID card (e.g., driver's license or similar object). Time to removal is more important than method in minimizing the amount of venom injected.[60]

Analgesia

  • Analgesia with acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID) can decrease swelling and pain at the site of the bite or sting.​[24][32]​​ These drugs can be tapered by the patient according to their symptoms.

  • Caution with NSAIDs should be used in patients currently taking aspirin or anticoagulants, patients with sensitivity to these drugs, or patients with risk factors for ulcers, gastrointestinal bleeding, or thromboembolic disease.

Local reactions

Supportive care

  • Local pain and swelling at the site of the bite or sting can be reduced with cold compress application and elevation of the affected limb.[32]​ The compress should have a cloth barrier between the ice and skin to prevent local tissue damage. Applying the cold compress on and off at 15-minute intervals is a common regimen.

  • The wound should be cleaned with soap and water. Surgical consult may be needed for severe or progressive local reactions at the site of suspected brown recluse spider bites.

  • Fire ant pustules should be left intact. If opened, these lesions can serve as a portal for secondary infection. They should be kept clean and covered.[22][23][Figure caption and citation for the preceding image starts]: Pseudopustule formation following fire ant stingCourtesy of Theodore Freeman [Citation ends].com.bmj.content.model.Caption@cca0acf

  • All skin wounds should be assessed for tetanus prophylaxis. Tetanus-prone wounds (deep/dirty/necrotic/severe recluse spider envenomation) should receive tetanus prophylaxis if the last immunization was >5 years ago.[61] Nontetanus-prone wounds (e.g., stings/black widow spider bite) should trigger treatment if last immunization was >10 years ago.

Stinger removal

  • Retained stingers should be removed because they may still contain venom.[Figure caption and citation for the preceding image starts]: Honeybee stinging fleshCourtesy of Rick Vetter [Citation ends].com.bmj.content.model.Caption@37e125c

  • The venom sac is emptied within 30 seconds after exposure; therefore, the stinger should be removed as quickly as possible

  • Traditional teaching suggests that squeezing the stinger (e.g., with tweezers) can inject more venom into the patient. The stinger should be removed by gently scraping the stinger with the edge of a plastic ID card (e.g., driver's license or similar object). Time to removal is more important than method in minimizing the amount of venom injected.[60]

Corticosteroids

  • Guidelines vary regarding recommendations for the use of corticosteroids in sting allergy

  • In practice, many clinicians use oral corticosteroids for large local reactions; however, there is a lack of strong evidence to support the efficacy of this treatment.[32]​ In severe cases of insect sting reaction there may be a role for a short course of oral corticosteroids.[32]

  • Corticosteroid treatment works in a delayed fashion to decrease vascular permeability and blunt the immune response to the inciting antigen.

H1 antagonists and H2 antagonists

  • Use of H1 and H2 antagonists is limited to relief of itching, hives, and rhinorrhea.[57][58]

  • Antihistamines antagonize the effects of histamine release at cellular receptors, decreasing itching, erythema, and rash

  • In general nonsedating H1 antagonists should be used in preference to sedating H1 antagonists, although there may be a role for sedating H1 antagonists at night if symptoms are interrupting sleep.[59]

  • H2 antagonists can be used to further potentiate the antihistamine effect, although evidence of benefit is very limited

  • Topical antihistamines should be avoided as they probably do not add any beneficial effect when patients are already on systemic antihistamines. They can also be irritating to the skin and can lead to contact dermatitis.[59]

Analgesia

  • Treatment with acetaminophen or an NSAID can decrease swelling and pain at the site of the bite or sting.​[24][32] ​These drugs can be tapered by the patient according to their symptoms. 

  • Caution with NSAIDs should be used in patients currently taking aspirin or anticoagulants, patients with sensitivity to these drugs, or patients with risk factors for ulcers, gastrointestinal bleeding, or thromboembolic disease.

Patients with black widow or recluse spider bites may require extra specific treatments (see below).

Black widow spider bites

Most black widow spider bites produce only localized pain at the site of the wound; fatalities are exceedingly rare.[37]

Additional analgesia with opioids may be needed for more severe bites or patients with low pain tolerance.[37][Figure caption and citation for the preceding image starts]: Black widow (Latrodectus species); the red hourglass marking is not always this shape and may not be presentCourtesy of Rick Vetter [Citation ends].com.bmj.content.model.Caption@799031e7[Figure caption and citation for the preceding image starts]: Black widow (Latrodectus species)Courtesy of Bill Banner [Citation ends].com.bmj.content.model.Caption@386987e3

Severe muscle spasms may be relieved with benzodiazepines.[37]​ Autonomic instability may lead to profound tachycardia and hypertension. These usually resolve as pain is addressed. In patients who may not tolerate these effects, beta-blockers may be a reasonable treatment.

There are several black widow spider antivenoms available commercially.[62][63] Treatment with antivenom has historically been thought to reduce the pain and duration of symptoms. Evidence from randomized controlled trials is mixed: one Australian study showed little (if any) difference between antivenom and placebo; other studies suggest there may be a modest benefit for selected patients, although further evidence is needed.[63]​​[64][65]

Indications vary by species, geographic location, and specific symptoms, but may include:[37][66]

  • Continued or severe pain despite aggressive opioid analgesia

  • Autonomic instability (uncontrolled hypertension)

  • Respiratory difficulties

  • Pregnancy

  • Persistent symptoms despite supportive care.

The decision to use antivenom must include weighing the severity of the symptoms against the safety of antivenom treatment. Although rare, reactions to antivenom can include serum sickness (which manifests as fever, joint pain, and rash) and life-threatening anaphylaxis.[37]

Recluse spider bites

Most Loxosceles species bites can be managed with local wound care.[Figure caption and citation for the preceding image starts]: Brown recluse spider (Loxosceles species); note violin shape darker coloration on cephalothorax and 3 pairs of eyes at the base of the violinCourtesy of Rick Vetter [Citation ends].com.bmj.content.model.Caption@581194bb[Figure caption and citation for the preceding image starts]: Brown recluse spider (Loxosceles species)Courtesy of Rick Vetter [Citation ends].com.bmj.content.model.Caption@1b72d800​ Additional analgesia with opioids may be needed for more severe bites or patients with low pain tolerance.

Antibiotics are not indicated initially in confirmed bites (although frequently the diagnosis is uncertain and cellulitis is the first differential considered) but should be considered in those with signs or symptoms of infection.[37]​ Antibiotic treatment is often started empirically because the diagnosis of spider bite is often unclear, and infections are the other major consideration in the differential diagnosis list. Antibiotic coverage should be appropriate for cellulitis in line with local susceptibility patterns for community-acquired MRSA.

Despite their reputation, only a small number of recluse spider bites become necrotic.[27][Figure caption and citation for the preceding image starts]: Lesions from reported brown recluse (Loxosceles species) envenomationCourtesy of Theodore Freeman [Citation ends].com.bmj.content.model.Caption@243ba104[Figure caption and citation for the preceding image starts]: Lesions from reported brown recluse (Loxosceles species) envenomationCourtesy of Theodore Freeman [Citation ends].com.bmj.content.model.Caption@772b3acf​ Dapsone has been used to prevent or slow the development of necrosis and reduce pain in necrotic lesions but it should not be used routinely.[37]​ No controlled trials have been conducted in humans, and data in animal models have been contradictory.[25] Patients should also be screened for glucose-6-phosphate dehydrogenase deficiency, as dapsone can cause severe hemolytic anemia in these patients. It is not necessary to start dapsone treatment immediately for it to be beneficial, and screening results are usually available within a day.

Continued necrosis may need surgical debridement and subsequent skin grafting for full healing, although this is a rare occurrence.[37]​ Necrotic tissue presents a prime substrate for secondary infection. Patients should be taught appropriate wound care and to be aware of signs of infection (e.g., fever, pus formation).

Antivenoms are available in some South American countries, but not in the US. Some animal studies suggest efficacy at limiting necrosis, but no good human studies are available.[62]

Secondary infection

Antibiotics should only be prescribed if there are symptoms and signs of infection.[67] Antibiotics should be directed at common skin pathogens (staphylococcal and streptococcal species) and directed by local resistance patterns.

Black widow spider bites do not become necrotic, and antibiotics are not needed unless signs of secondary infection develop over the next few days.

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