Type I Hypersensitivity Reaction

Etiology

Type I hypersensitivity results from an exaggerated immune response to a typically harmless antigen. A wide range of antigens and conditions can trigger type I hypersensitivity reactions. Common examples include:

• Pollen from trees, grasses, and weeds
• Pet dander
• Dust mites
• Mold spores
• Foods such as tree nuts, including almonds, walnuts, and cashews; shellfish; milk; eggs; wheat; and soy
• Medications such as β-lactam and sulfonamide antibiotics
• Latex
• Insect stings
• Heat
• Cold
• Exercise
• Viral and bacterial infections
• Chemicals and additives in food and cosmetics
• Mastocytosis
• Galactose-α-1,3-galactose—a sugar molecule found in mammalian meat
• Blood products [2][6][7][8][9]

Patients with certain mast cell disorders, such as mastocytosis and mast cell activation syndrome, carry a higher associated risk of anaphylaxis. Affected patients are at risk for severe or spontaneous anaphylaxis. Recent studies reveal that Hymenoptera venoms, followed by food and medications, are the most common causes of anaphylaxis in adults. Triggering factors are more challenging to identify in affected children, with 67% remaining unidentified.[10][11]

Epidemiology

According to the United States Centers for Disease Control and Prevention, approximately 33% of adults and 25% of children have allergies, eczema, or food allergies, with allergic rhinitis being the most common.[12][13][14] Among adults, 25.7% have seasonal allergies, 7.3% have eczema, and 6.2% have food allergies. In children, the prevalence is 18.9% for seasonal allergies, 10.8% for eczema, and 5.8% for food allergies. The prevalence of these conditions and asthma continues to rise.[15][16][17]

White non-Hispanic adults are more likely to have allergic rhinitis, whereas Black adults and children have higher rates of food allergies. Asthma is most common among American Indian, Alaska Native, and Black populations. Globally, the lifetime prevalence of anaphylaxis ranges from 0.05% to 2% in adults and 0.04% to 1.8% in children. This condition accounts for up to 0.26% of hospital admissions, with a mortality rate of 0.5% to 1%.[17] Anaphylaxis triggers vary by age—food in young children, insect venom in school-aged children, and medications in teenagers.[17] Peanuts and tree nuts are the leading causes of fatal anaphylaxis in children, whereas cow's milk and seafood are also significant triggers in specific populations.

Pathophysiology

Type I hypersensitivity requires initial sensitization in an individual who is genetically predisposed. Sensitization begins with exposure to an allergen, commonly through inhalation, ingestion, or skin contact. Antigen-presenting cells, such as dendritic cells, macrophages, or B cells, process the allergen and migrate to regional lymph nodes, where they present the antigen to naïve T cells. In individuals predisposed to allergic responses, these T cells preferentially differentiate into Th2 cells.[18] The Th2 subset secretes cytokines, including interleukin (IL)-4, IL-5, IL-9, and IL-13, which are central to the allergic response.

Simultaneously, B cells internalize the allergen and process it through the major histocompatibility complex class II (MHC II) pathway. B cells present the antigen-MHC II complex to Th2 cells, which recognize the complex through their T-cell receptor. CD40 on the B cells also binds with CD40L on the Th2 cell surface, stimulating the release of IL-4 and IL-13 by the Th2 cell. Costimulatory interaction between CD40 on the B cell and CD40L on the Th2 cell is essential for B-cell activation and isotype switching from IgM to IgE. IL-4 and IL-13 further drive this class switching. The resulting allergen-specific IgE binds to high-affinity FcεRI receptors on the surface of mast cells and basophils. Upon reexposure, the antigen can cross-link the previously bound IgE on mast cells and basophils, triggering the release of a range of preformed and newly synthesized inflammatory mediators. These mediators include:

• Histamine
• Tryptase
• Proteoglycans
• Chymase
• Leukotriene B4, C4, E4, and D4
• Prostaglandin D2 and F2-α
• Thromboxane A2
• Platelet-activating factor
• Adenosine
• Bradykinin
• Tumor necrosis factor-α
• IL-4, IL-5, IL-6, and IL-13 [19][20]

Some mediators released during type I hypersensitivity reactions attract eosinophils and neutrophils, which further amplify the inflammatory response.[21] Recruited eosinophils, along with other leukocytes such as monocytes and T cells, contribute to late-phase reactions, which typically occur several hours after the initial allergen exposure. Gastrointestinal symptoms associated with food allergies, such as abdominal pain or vomiting, may reflect late-phase responses.

In individuals with repeated or chronic exposure to allergens, such as those sensitized to pet dander, ongoing inflammation can develop. Eosinophils and T cells primarily drive this response and can lead to tissue remodeling, functional impairment, and persistent symptoms. Eosinophil-derived mediators, including major basic protein and eosinophil peroxidase, can cause direct tissue damage and contribute to the structural changes observed in chronic allergic conditions.

History and Physical

Historical and physical examination findings vary depending on the organ systems involved.

Allergic Rhinitis

Allergic rhinitis, also known as allergic rhinosinusitis, typically presents with a history of recurrent sneezing, rhinorrhea, nasal congestion, and pruritus of the eyes, nose, or palate. Patients may also report symptoms such as postnasal drip, persistent cough, fatigue, and sleep disturbances. Symptoms may be intermittent and worsen during specific seasons or persist year-round due to indoor allergens. Children may experience academic difficulties or behavioral changes, whereas adults may note reduced concentration, productivity, and overall quality of life.[22][23]

On physical examination, characteristic findings may include infraorbital edema and darkening, also known as allergic shiners; a transverse nasal crease from habitual nose rubbing; pale or bluish nasal mucosa with turbinate edema; and clear rhinorrhea. Other signs include Dennie-Morgan lines under the eyes, cobblestoning of the posterior pharynx, and retracted tympanic membranes or serous fluid in the middle ear due to dysfunction of the eustachian tube.

Anaphylaxis

Anaphylaxis can be challenging to recognize clinically, depending on which organ systems are affected. Nearly 90% of patients present with some skin or mucosal findings, including generalized urticaria, itching or flushing, swollen lips, tongue, or uvula, periorbital edema, or conjunctival swelling.[24] Clinicians must remember that urticaria, flushing, and itching may have resolved by the time the patient presents for treatment. 

Respiratory symptoms, such as nasal congestion and discharge, sneezing, throat and ear itching, voice changes, a sensation of the throat closing, stridor, shortness of breath, wheezing, or cough, are the second most common feature, occurring in nearly 85% of patients.[25][26]

Both gastrointestinal and cardiovascular symptoms occur in 45% of patients. Potential symptoms include nausea, vomiting, diarrhea, abdominal pain, syncope, hypotension, tachycardia, and dizziness. In infants and toddlers, anaphylaxis may present differently. A 2024 study identified tachycardia, vomiting, cough, and altered mental status as symptoms that may be more common in this age group.[25]

Food Hypersensitivity

Oral allergy syndrome is the most common form of food allergy in adults, affecting individuals who are sensitized to pollen. Heat-labile proteins in fruits and vegetables are cross-reactive with allergenic pollen proteins. Affected patients experience itchiness and swelling of the mouth, face, lips, tongue, and throat within minutes of eating raw fruits and vegetables. For example, patients allergic to ragweed can react to melons and bananas. Additional gastrointestinal symptoms that may manifest during a type I hypersensitivity reaction include nausea, vomiting, abdominal cramping, and diarrhea.[27]

Urticaria and Angioedema

Urticaria presents as raised, well-circumscribed, erythematous plaques, often with central pallor and intense pruritus. On darker skin tones, the color can range from skin-colored to red, pink, brown, or purplish. Lesions vary in size and shape, appear suddenly, and typically develop over minutes to hours, resolving within 24 hours. Urticaria can affect the entire body. However, areas where skin rubs together or clothing compresses the skin may reveal more pronounced findings.

In contrast, angioedema presents as localized subcutaneous or submucosal swelling resulting from the leakage of fluid into interstitial tissues. Angioedema most commonly affects the face, lips, tongue, throat, extremities, and genitals. Patients with mast cell–mediated angioedema often present with associated symptoms such as urticaria, flushing, generalized pruritus, bronchospasm, throat tightness, hypotension, and, in some cases, colicky abdominal pain when the bowel wall is involved.

Clinicians should remain alert for signs of airway involvement, such as laryngeal or orolingual swelling, which may require immediate airway management. Bowel wall angioedema, although less common, can mimic acute abdominal emergencies. 

Atopic Dermatitis

Atopic dermatitis presents with age-specific clinical features and varies in severity, disease stage, and skin tone. Dry skin and severe pruritus are hallmark features. In infants and young children, it typically manifests as pruritic, red, scaly, and crusted lesions on the cheeks, scalp, and extensor surfaces, often sparing the diaper area. In patients with darker skin, lesions may appear hyperpigmented, violaceous, or gray, and erythema may not be readily apparent. Acute cases may feature vesicles and serous exudate. In older children and adolescents, lesions appear as thickened, hyperpigmented plaques in flexural areas, particularly the antecubital and popliteal fossae, wrists, ankles, and neck. Adolescents may also exhibit a dark, net-like pattern of hyperpigmentation on the neck. In adults, the condition often involves the face, neck, and hands, with variable flexural presentation. Lesions are typically absent in the axillary, gluteal, or groin regions.[28]

Across all age groups, chronic scratching can lead to skin thickening and the development of fissures. Common associated findings classically referred to as atopic stigmata include periorbital darkening, Dennie-Morgan folds, white dermographism, keratosis pilaris, palmar hyperlinearity, pityriasis alba, and postinflammatory hyper- or hypopigmentation. 

Allergic Asthma

The presenting symptoms and examination findings associated with allergic asthma depend on the severity of the condition. Exposure to allergens leads to bronchoconstriction, resulting in symptoms such as wheezing, coughing, or chest tightness. Patients may also present with hypoxia, tachypnea, a prolonged expiratory phase, or cyanosis. Additional findings in infants and children include retractions, perioral cyanosis, nasal flaring, and difficulty feeding. Repeated, long-term exposure to allergens can result in chronic airway changes.

Evaluation

Obtaining a detailed history from the patient or their companion is essential in evaluating a patient with a suspected type I hypersensitivity reaction. Key historical information includes the following:

• Signs and symptoms 
• Chronology of events
• History of new exposures, such as foods or medications
• History of previous exposure to the potential allergen
• Prior history of allergic reactions 
• History of atopy, such as allergic rhinitis, asthma, eczema, or food allergies
• Presence of fever  

Allergic Rhinitis

Allergic rhinitis is primarily a clinical diagnosis based on symptoms and physical examination findings. Skin prick testing, the preferred method, and serum-specific IgE can confirm sensitization; however, clinicians generally reserve testing for unclear triggers or poor treatment responses. Imaging is unnecessary unless chronic rhinosinusitis or facial structural abnormalities are suspected.

Anaphylaxis

Patients with suspected anaphylaxis require continuous monitoring of vital signs due to the risk of rapid deterioration. Diagnosis is primarily clinical, given the broad and sometimes atypical symptom range. Laboratory tests can support diagnosis retrospectively. When feasible, serum tryptase should be drawn within 15 minutes to 3 hours of symptom onset, although levels may remain elevated for up to 6 hours. A normal tryptase does not exclude anaphylaxis, particularly in food-related or normotensive cases. Persistent elevation beyond 24 hours may indicate mastocytosis. Plasma histamine peaks within 5 to 15 minutes but normalizes within 1 hour, limiting its use unless obtained during a hospital-based event.

Based on the National Institute of Allergy and Infectious Diseases and Food Allergy and Anaphylaxis Network guidelines, anaphylaxis is highly probable if a patient satisfies any one of the following criteria:

• Criterion 1: An acute onset of illness involving the skin or mucosa, manifesting as hives, flushing, or oropharyngeal swelling, accompanied by respiratory compromise such as wheezing, stridor, and hypoxemia or hypotension with signs of end-organ dysfunction. According to guidelines, reduced blood pressure is defined as follows:
  • Infants (1 month to 1 year): Systolic blood pressure <70 mm Hg
  • Children (1 to 10 years): Systolic blood pressure <70 mm Hg + [2 × age]
  • Adolescents (11 to 17 years): Systolic blood pressure <90 mm Hg
  • Adults: Systolic blood pressure <90 mm Hg or a decrease of ≥30% from baseline

• Criterion 2: Patients develop 2 or more of the following signs or symptoms after allergen exposure—skin or mucosal involvement, respiratory compromise, hypotension, or persistent gastrointestinal symptoms such as abdominal pain or vomiting.

• Criterion 3: Hypotension occurring within minutes to hours of known allergen exposure.

Following an episode of anaphylaxis, patients should be referred to an allergy specialist to confirm the diagnosis and identify the specific trigger. Allergen-specific IgE testing or skin testing, such as prick, scratch, or intradermal methods, can be used to assess sensitization.[29] A positive skin test shows a wheal-and-flare response within 15 to 20 minutes. Although more invasive tests reduce false negatives, they increase the risk of provoking anaphylaxis.

Evaluation for cross-reactivity with related allergens may be warranted. False negatives can occur, particularly within the 4-week refractory period following the reaction. If tests are initially negative, repeat skin or serum testing after 4 to 6 weeks may be necessary.[30][31] Clinicians can also consider provocation testing when clinical suspicion remains high despite negative results.[32]

Food Hypersensitivity

Evaluation of suspected IgE-mediated food allergy begins with a comprehensive history and physical examination, followed by skin-prick testing, serum-specific IgE testing, or oral food challenges as necessary. Skin-prick testing has a high sensitivity but low specificity and is best for patients with a high or low pretest probability to confirm or exclude allergy. Clinicians should avoid large screening panels due to high false-positive rates, which can lead to unnecessary dietary restrictions, nutritional deficiencies, and reduced quality of life, especially in children. Sensitization does not confirm clinical allergy, and patients should not eliminate foods tolerated without symptoms based solely on test results.

Serum-specific IgE testing is an alternative when skin testing is not feasible. Although higher IgE levels may suggest an increased likelihood of a reaction, they do not predict the severity of the reaction, and negative levels do not exclude the possibility of allergy.[33][34] Oral food challenges, conducted under supervision, are helpful when test results are inconclusive, when assessing tolerance development, or when clarifying cross-reactivity or suspected sensitivities.

Urticaria and Angioedema 

Urticaria has diverse causes. IgE-mediated urticaria is suspected when symptoms occur within minutes to 2 hours of allergen exposure. Most new-onset cases resolve spontaneously without further workup. Limited evaluation is necessary in the presence of suspected treatable infection, systemic disease, urticarial vasculitis, or an IgE-mediated reaction. Identifying IgE-mediated cases is essential to prevent anaphylaxis on reexposure. Allergy test results must be interpreted in conjunction with the clinical history, as positive tests indicate sensitization but not necessarily clinical allergy, and negative results do not rule it out.

Angioedema may be mast cell–mediated, bradykinin-mediated, or idiopathic. Mast cell–mediated forms often present with symptoms such as urticaria, flushing, pruritus, bronchospasm, throat tightness, or hypotension. In the absence of these features, bradykinin-mediated angioedema is more likely and may result from C1 inhibitor deficiency or angiotensin-converting enzyme inhibitor use. Diagnosis is primarily clinical, and testing is generally low yield unless an allergen or bradykinin-mediated cause is suspected. Skin-prick testing and serum IgE levels can help identify relevant allergens in type I hypersensitivity. Please see StatPearls' companion resource, "Angioedema," for further information.

Atopic Dermatitis

Atopic dermatitis is primarily a clinical diagnosis. Laboratory tests and skin biopsies are not necessary, but they may help rule out other conditions. The American Academy of Dermatology outlines diagnostic criteria categorized into essential, important, and associated features.

The essential features, which must be present to establish the diagnosis, are as follows:

• Pruritus
• Eczematous dermatitis in an age-specific distribution
• Chronic, relapsing course [72]

The important criteria, which support the diagnosis and are present in most cases, are as follows:

• Onset before the age of 2
• Personal or family history of atopy, such as eczema, asthma, or allergies
• Dry skin in the past year [72]

The associated criteria, which suggest the diagnosis but are nonspecific, are as follows:

• Atypical vascular responses such as facial pallor or white dermatographism
• Periocular findings such as lichenification and Dennie-Morgan lines
• Keratosis pilaris, pityriasis alba, ichthyosis, and hyperlinear palms
• Perioral or periauricular eczema and prurigo nodules
• Perifollicular lichenification
• Sparing of the groin and axilla [72]

Allergic Asthma

Pulmonary function testing is the primary method for diagnosing asthma. Spirometry measures the forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC). A reduced FEV₁/FVC indicates airflow obstruction. Repeat spirometry after administering a bronchodilator, such as albuterol, indicates the reversibility of the obstruction. A 10% or higher improvement in the FVC or FEV₁ is a significant response. Allergy testing is generally not helpful in diagnosing asthma, except in patients with a history of asthma symptoms that develop when exposed to specific allergens, those with persistent symptoms, in cases where clinicians suspect exposure to specific allergens in the home, or those with persistent moderate-to-severe asthma despite adequate treatment.

Imaging is typically unnecessary in patients with asthma unless symptoms are new in patients older than 40 or those presenting with any of the following symptoms:

• Fever
• Chronic purulent sputum production
• Hemoptysis
• Weight loss
• Clubbing
• Inspiratory crackles
• Hypoxemia
• Moderate-to-severe airflow obstruction that does not resolve after administering a bronchodilator

Drug provocation tests and graded challenges are additional tests to assess the status of potential drug allergies.[41] During the test, clinicians administer the offending drug in gradually increasing increments.[72] Potential uses for drug provocation tests include proving that a patient can tolerate a specific drug when skin and serum IgE tests are negative. Additionally, clinicians may use the drug provocation test to find alternative effective medications for future use or to test cross-reactivity. Graded challenges occur when patients require current treatment with the drug. Clinicians perform both the drug provocation test and graded challenge on patients who are likely to tolerate the medication.[73] These tests are not appropriate in patients with a history of an anaphylactic reaction to a medication.    

Treatment / Management

The treatment for type I hypersensitivity depends on the patient's presentation and the etiology of the reaction.[35][36](A1)

Allergic Rhinitis

Management of allergic rhinitis begins with allergen avoidance and nasal saline irrigation using at least 200 mL of distilled, sterilized, or boiled water per nostril. A nasal glucocorticoid spray is a first-line pharmacological treatment. For patients avoiding steroids or who are unresponsive to them, nasal antihistamines such as azelastine or cromolyn are alternatives. Combination sprays, such as azelastine-fluticasone, are options for patients requiring dual therapy. For as-needed steroid use, patients begin nasal steroids 2 days before and continue for 2 days after allergen exposure. For seasonal symptoms, treatment should begin 1 week before the start of the pollen season.

Nonsedating oral antihistamines, such as cetirizine or fexofenadine, are appropriate for mild or intermittent symptoms or for patients who prefer not to use nasal sprays. These oral antihistamines can be used as a supplement to nasal steroids for persistent symptoms, particularly for itching and sneezing, although they are less effective for nasal congestion. For as-needed use, patients take antihistamines 2 hours before exposure, except loratadine, which requires 8 hours. For patients with allergic rhinitis and conjunctivitis, combining a nasal steroid with antihistamine eye drops, such as olopatadine or azelastine, offers better efficacy and reduced dry eye symptoms compared to pairing with oral antihistamines.[37][38]

Anaphylaxis

Anaphylaxis is a life-threatening emergency that demands immediate action. If possible, remove the triggering agent right away. Administering intramuscular (IM) epinephrine into the lateral thigh without delay is the most critical step. Repeat IM or intravenous (IV) doses may be needed. Unless prevented by airway swelling, the patient should be placed in a supine position with legs elevated to support blood flow. For pregnant patients, the left lateral position is used to avoid compressing the vena cava. These positions help maintain organ perfusion and prevent sudden cardiovascular collapse.

High-flow oxygen should be administered using a nonrebreather mask at 15 L/min, and IV access should be established promptly. For stable patients, IV fluids should be started at 125 mL/h of normal saline for adults and at weight-based maintenance rates for children. Intubation should be anticipated in the presence of any respiratory distress, stridor, voice changes, or visible airway swelling. For patients who remain hypotensive after epinephrine, clinicians should begin aggressive fluid resuscitation. Adults typically require 1 to 2 L of normal saline rapidly, whereas children require 20 mL/kg boluses over 5 to 10 min, repeated as needed. Lactated Ringer may lead to metabolic alkalosis; however, large volumes of normal saline can cause hyperchloremic metabolic acidosis, so some experts choose to switch to lactated Ringer when large volumes of normal saline are necessary.

Epinephrine Dosing

The recommended dose of epinephrine is 0.01 mg/kg, up to a maximum of 0.5 mg, which may be repeated every 5 to 15 minutes as necessary. About 35% of patients require a second dose. In the United States, epinephrine ampules are now labeled as 1 mg/mL (formerly 1:1000). Autoinjectors are available in 0.1, 0.15, and 0.3 mg doses.

When using autoinjectors or when there may be delays in weight-based dosing, the guidelines should be followed:

• Less than 10 kg: Use a 0.1 mg autoinjector or draw 0.1 mL of 1 mg/mL solution; 0.15 mg is acceptable if 0.1 mg is unavailable
• 10 to 25 kg: Use a 0.15 mg autoinjector or draw 0.15 mL
• 25 to 50 kg: Use a 0.3 mg autoinjector or draw 0.3 mL
• More than 50 kg: Draw 0.5 mL; if unavailable, use a 0.3 mg autoinjector [39][40][41]
(A1)

Experts define refractory anaphylaxis as persistent symptoms after 3 epinephrine doses and supportive care. These patients may require an IV epinephrine infusion:

• Adults: Start at 0.1 µg/kg/min, titrate every 2 to 3 minutes by 0.05 µg/kg/min; typical range: 0.05 to 0.2 µg/kg/min
• Pediatrics: 0.1 to 1 µg/kg/min

Intranasal epinephrine is a newly approved formulation for the treatment of anaphylaxis in children 4 or older who weigh at least 15 kg (33 lbs). For patients weighing 15 to 29 kg, a 1 mg intranasal dose is recommended. For patients weighing 30 kg or more, a 2 mg dose is indicated. In the absence of clinical improvement, an additional spray may be administered into the same nostril after 5 minutes.[39][42][43]

Glucagon 

Clinicians may use glucagon for refractory anaphylaxis, particularly in patients who are taking β-blockers, as these medications can reduce the effectiveness of epinephrine. Glucagon bypasses β-adrenergic receptors by directly activating adenylate cyclase, thereby increasing intracellular cyclic AMP, which improves cardiac output and reduces bronchospasm. Common adverse effects include nausea and vomiting; therefore, placing the patient in the left lateral decubitus position is advisable to prevent aspiration. The dosing of glucagon is as follows:

• Adults receive 1 to 5 mg IV over 5 minutes.
• Pediatric patients receive 20 to 30 µg/kg (maximum 1 mg) IV over 5 minutes.
• Following the initial dose, both adults and children can receive an infusion of 5 to 15 µg/min, titrated to achieve the desired effect.[26][44][45]
(B3)

Additional Agents

Bronchodilators, such as albuterol, may relieve bronchospasm but do not replace epinephrine. The route of administration, whether inhaler, mask, or nebulizer, depends on the patient's needs.[26] H1 antihistamines, such as diphenhydramine and cetirizine, relieve itching and hives, serving as an additional adjunctive treatment to help manage symptoms associated with anaphylaxis. The dosing of cetirizine is as follows:

• Adults and children 12 or older receive 10 mg IV over 1 to 2 minutes.
• Children aged 6 to 11 receive 5 to 10 mg of IV medication.
• Infants and children aged 6 months to 5 years receive 2.5 mg IV.

The appropriate dosing of diphenhydramine is as follows:

• Adults and children 12 or older receive 25 to 50 mg administered intravenously over 5 minutes every 4 to 6 hours, as needed to a maximum of 400 mg per 24 hours.
• Children weighing less than 50 kg receive 1 to 2 mg/kg/dose, with a maximum dose of 50 mg every 6 hours, up to a maximum of 200 mg per 24 hours or 5 mg/kg.

Combining an H1 antihistamine with an H2 antihistamine, such as famotidine, may help patients achieve a better reduction in urticaria symptoms. However, antihistamines should not be used as monotherapy, as they do not mitigate upper or lower airway obstruction, shock, or hypotension. Antihistamines have not been shown to affect hospitalization rates or epinephrine requirements. Some studies suggest that when H2 antagonists are given IV, they may increase rates of hypotension. The recommended dose of famotidine is 20 mg for adults and 0.25 mg/kg for children, up to a maximum dose of 20 mg.

Glucocorticoids

Glucocorticoids have a delayed onset and limited evidence of benefit, but clinicians may consider their use in patients with persistent symptoms.[30][46] Recent pediatric guidelines recommend restricting the use of glucocorticoids to cases involving ongoing or severe symptoms, such as significant wheezing or hypotension that is unresponsive to initial therapies. Methylprednisolone (1-2 mg/kg to a maximum dose of 125 mg for 1-2 days) or dexamethasone (0.6 mg/kg to a maximum dose of 10 mg) administered IV, IM, or orally are potential choices. Clinicians may prefer dexamethasone due to its longer duration and single-dose use.(A1)

Other Vasopressors

Clinicians may consider additional vasopressors such as norepinephrine, vasopressin, or dopamine for patients with refractory hypotension. 

Methylene Blue

Methylene blue may help in rare cases by increasing vascular tone. The recommended dose is 1 to 2 mg/kg IV over 20 to 60 minutes. Patients with pulmonary hypertension, glucose-6-phosphate dehydrogenase deficiency, or acute lung injury should not receive methylene blue.[47][48]

Upon discharge, patients with a history of anaphylaxis should have an epinephrine autoinjector in hand or a prescription for 2 autoinjectors, along with clear instructions to pick them up immediately. Patients should be educated on the signs and symptoms of anaphylaxis and provided with a written emergency plan with clear instructions in the event of recurrence. Patients should also consult an allergist to confirm the diagnosis.

Food Hypersensitivity

Patients primarily manage food allergies through strict avoidance of trigger foods and prompt medication use in the event of accidental exposure. However, some patients opt to develop a higher tolerance to certain foods, such as peanuts, hen's eggs, and cow's milk, through oral immunotherapy. Patients typically start with a small daily dose of the food allergen, which is gradually increased every few weeks until they achieve a maintenance dose. Although oral immunotherapy has been unable to achieve complete and permanent tolerance to foods, patients can increase their tolerance, thereby increasing the amount they can consume before experiencing symptoms. Increasing a patient's allergic threshold may serve to decrease the incidence of reactions due to accidental exposure and reduce anxiety about possible anaphylaxis and death. Tolerance wanes once patients discontinue therapy. Omalizumab, an anti-IgE monoclonal antibody, also raises the reaction threshold and is an option for treating food allergies, in conjunction with food avoidance.[49][50](A1)

Urticaria and Angioedema

Treatment begins with a second-generation H1 antihistamine, such as cetirizine, which is preferred over first-generation agents due to its similar efficacy and fewer adverse effects, including sedation and anticholinergic effects.[51] Clinicians begin with standard dosing and increase up to 2 to 3 times if needed. Patients continue antihistamines until lesions resolve and no new ones appear for 1 to 2 days.[52][53](A1)

Studies on the use of glucocorticoids in combination with antihistamines reveal conflicting results. A recent study looking at evidence-based treatment of acute urticaria reveals no benefit of adding glucocorticoids to antihistamines.[54] However, a second recent systematic review and meta-analysis of randomized clinical trials shows that glucocorticoids may be beneficial for patients with a low or moderate probability of improvement with antihistamines alone but at a higher risk of associated adverse effects.[55](A1)

If symptoms persist after several days of antihistamine therapy, clinicians may consider prednisone at 30 to 60 mg/d for adults or prednisolone at 0.5 to 1 mg/kg/d, up to a maximum dose of 60 mg, for children, tapered over 5 to 7 days. Patients should continue antihistamines during and for several days after the steroid course to prevent recurrence. Patients who continue to develop urticaria on most days of the week for 6 weeks or longer are likely to develop chronic urticaria. Please see StatPearls' companion resource, "Chronic Urticaria," for further information. Unless symptoms are severe, the routine use of H2 antihistamines is unnecessary.

Angioedema associated with anaphylaxis is treated in the same manner as anaphylaxis. Patients with respiratory distress, stridor, drooling, tongue edema, or significant edema of the floor of the mouth require intubation. Likewise, angioedema associated with an allergic reaction is treated in the same manner as acute urticaria. 

Atopic Dermatitis

The mainstay of therapy for atopic dermatitis is the elimination of any factors that exacerbate symptoms, such as excessive bathing without moisturizing the skin, exposure to cold or low-humidity environments, overheating and sweating, and exposure to harsh chemicals or detergents. Affected patients with mild-to-moderate symptoms should apply proper skin emollients in addition to topical corticosteroids for up to 2 weeks. Alternative topical therapies for areas at high risk of skin atrophy, such as the face, include topical calcineurin inhibitors (tacrolimus or pimecrolimus), topical crisabitol, and topical ruxolitinib for children older than 12. To prevent recurrence once cleared, patients should apply topical corticosteroids or calcineurin inhibitors once a day, 2 or 3 times per week. 

Patients with persistent symptoms or moderate-to-severe disease despite topical therapy should receive the immunomodulatory agents dupilumab, tralokinumab, or lebrikizumab. Patients may still use topical corticosteroids as needed. Oral Janus kinase inhibitors, such as abrocitinib or upadacitinib, are an alternative initial systemic therapy or an option for patients who do not respond to immunomodulators. Narrowband UV-B phototherapy is an alternative option that may be somewhat limited by the requirement for a phototherapy schedule of 2 to 3 times per week in the clinician's office.

Allergic Asthma

Allergen avoidance is essential in allergen-induced asthma. According to the National Asthma Education and Prevention Program and the Global Initiative for Asthma guidelines, the type of asthma treatment is determined by age and symptom severity. Please see StatPearls' companion resources, "Asthma" and "Pediatric Asthma," for further information. 

For patients with persistent symptoms despite avoidance and standard therapy, allergen immunotherapy may be considered. Subcutaneous or sublingual immunotherapy is indicated for confirmed IgE-mediated allergies and is administered in escalating doses to build tolerance. Desensitization promotes isotype switching from IgE to IgG, benefiting about 67% of patients for at least 2 to 3 years after treatment completion.[57] Patients must carry and receive proper education on the use of an epinephrine autoinjector before starting immunotherapy.[58][59] Omalizumab is an additional option for moderate-to-severe allergic asthma not controlled with standard treatment.

Differential Diagnosis

The differential diagnosis is broad and may include the following conditions:

• Nonallergic asthma
• Chronic obstructive pulmonary disease
• Pneumothorax
• Epiglottitis
• Vocal cord dysfunction
• Hereditary angioedema
• Irritable bowel syndrome
• Intolerance of FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols)
• Pancreatic insufficiency
• Toxic reactions to seafood, such as saxitoxin accumulation in shellfish
• Upper respiratory tract infection
• Acute or chronic sinusitis
• Vasovagal syncope
• Myocardial infarction
• Panic attack or anxiety disorder
• Urticaria due to an infectious process or other stimulus, such as heat or cold
• Shock
• Seizure
• Stroke
• Vancomycin infusion reaction
• Carcinoid syndrome
• Mastocytosis
• Foreign body aspiration
• Acute and chronic sinusitis [56][57][58][59][60]

Pertinent Studies and Ongoing Trials

Several emerging therapies and innovative approaches are currently being investigated to enhance the prevention and management of allergic diseases and anaphylaxis.

• Ligelizumab, a next-generation anti-IgE monoclonal antibody with a higher binding affinity than omalizumab, is currently in Phase 3 trials and may improve outcomes in allergic diseases, with potential applications in the prevention of anaphylaxis and the management of food allergies.[61][62]
• Epicutaneous immunotherapy, which promotes tolerance through transdermal allergen exposure, is under investigation for IgE-mediated allergies to cow's milk and peanuts, as well as eosinophilic esophagitis associated with cow's milk allergy. Additionally, preclinical studies are underway for egg allergy.[63] 
• Researchers are investigating mast cell–targeted therapies, including tryptase inhibitors, such as APC-366; lactoferrin; and Bruton tyrosine kinase inhibitors, such as acalabrutinib, to prevent mast cell degranulation in disorders such as mastocytosis and idiopathic anaphylaxis.
• Early-stage messenger RNA-based therapies aim to induce immune tolerance by encoding allergen fragments in nanoparticles, thereby shifting the immune response from a Th2-dominated to a Th1-dominated state.[64]
• Novel needle-free epinephrine delivery systems, including sublingual formulations, are being developed to enhance emergency access and facilitate early intervention.[65][66] Other emerging strategies include a Phase II trial for a peanut peptide vaccine and peanut OMIT delivered through toothpaste.

Prognosis

The prognosis of type I hypersensitivity depends on the severity and type of reaction. Without prompt recognition and treatment, angioedema, anaphylaxis, or severe asthma can be fatal within minutes. Mild-to-moderate IgE-mediated angioedema typically resolves within days with antihistamines and glucocorticoids; similarly, acute urticaria resolves in approximately two-thirds of patients within 6 weeks. Despite being chronic conditions, allergic rhinitis, asthma, and atopic dermatitis generally have favorable outcomes when managed appropriately. Children often outgrow allergies to cow's milk, eggs, soy, and wheat, whereas allergies to peanuts, tree nuts, fish, and shellfish are more likely to persist.

Complications

The following lists include potential complications associated with type I hypersensitivity reactions and their treatments:

Allergic Rhinitis

• Decreased cognitive function
• Sleep apnea
• Increased risk of bacterial sinusitis
• Worsening asthma
• Otitis media
• Hearing loss
• Headaches
• Complications related to treatment
  • Nasal septum perforation
  • Epistaxis
  • Glaucoma and cataracts
  • Thrush
  • Altered taste and smell
  • Adrenal insufficiency
  • Reduced growth in children with long-term use of nasal or inhaled corticosteroids

Anaphylaxis

• Death
• Myocardial ischemia
• Renal failure
• Anoxic brain injury
• Arrhythmia

Food Hypersensitivity

• Food avoidance and malnutrition
• Anxiety
• Decreased social interactions

Urticaria and Angioedema

• Adrenal insufficiency due to glucocorticoids
• Hyperglycemia due to glucocorticoids
• Airway obstruction and death
• Decreased cognitive performance with antihistamine use

Atopic Dermatitis

• Eczema herpeticum
• Secondary bacterial infection
• Skin hyper- or hypopigmentation
• Sleep disturbance
• Neurodermatitis

Allergic Asthma

• Airway remodeling
• Decreased physical activity and deconditioning
• Osteoporosis, cataracts, and glaucoma due to glucocorticoids
• Reduced growth in children with long-term use of nasal or inhaled corticosteroids
• Poor work and school productivity