What are type 1 hypersensitivity reactions, including their mediators, clinical manifestations, and treatment strategies?

Type 1 Hypersensitivity Reactions: Mediators, Clinical Manifestations, and Treatment

Type 1 hypersensitivity reactions are IgE-mediated immediate allergic responses characterized by mast cell and basophil degranulation, resulting in the release of histamine and other inflammatory mediators that can range from mild symptoms to life-threatening anaphylaxis. 1, 2

Definition and Mechanism

• Type 1 hypersensitivity represents an acute IgE-mediated reaction that occurs when allergens cross-link IgE antibodies bound to FcεRI receptors on mast cells and basophils, triggering their degranulation 3, 4
• These reactions are part of the Gell and Coombs classification of hypersensitivity reactions, specifically designated as Type I (immediate) reactions 5, 6
• True allergic reactions are immune-mediated responses that occur reproducibly upon exposure to specific allergens at doses normally tolerated by most people 1, 2
• The onset of symptoms typically occurs within minutes to hours (1-6 hours) after exposure to the allergen 1, 7

Mediators of Type 1 Hypersensitivity

Primary Mediators (Preformed)

• Histamine: Released within 5 minutes of mast cell activation and remains elevated for 15-60 minutes; causes vasodilation, increased vascular permeability, smooth muscle contraction, and mucus secretion 5, 8
• Tryptase: Released from mast cells during degranulation; blood samples for measurement are optimally obtained 15 minutes to 3 hours after onset of reaction 5
• Other preformed mediators include proteases, proteoglycans, and chemotactic factors 4

Secondary Mediators (Newly Synthesized)

• Lipid mediators: Include leukotrienes, prostaglandins, and platelet-activating factor; contribute to bronchoconstriction, increased vascular permeability, and mucus secretion 9
• Cytokines: Released from activated mast cells and basophils; contribute to the late-phase allergic response 4, 9

Clinical Manifestations

Type 1 hypersensitivity reactions can manifest with varying severity, from localized symptoms to systemic anaphylaxis:

Cutaneous Manifestations

• Urticaria (hives), pruritus (itching), flushing, and angioedema (swelling of lips, tongue, uvula) 1, 2

Respiratory Manifestations

• Upper airway: Rhinorrhea, nasal congestion, sneezing, laryngeal edema, and stridor 7
• Lower airway: Bronchospasm, wheezing, dyspnea, and reduced peak expiratory flow 7, 5

Cardiovascular Manifestations

• Hypotension, tachycardia, dizziness, syncope, and in severe cases, cardiovascular collapse 7, 5

Gastrointestinal Manifestations

• Nausea, vomiting, abdominal cramping, and diarrhea 5, 2

Anaphylaxis

• A severe, potentially life-threatening systemic reaction involving multiple organ systems 7, 10
• Diagnostic criteria include acute onset with skin/mucous membrane involvement PLUS respiratory compromise OR reduced blood pressure 7
• Alternatively, two or more of the following occurring rapidly after allergen exposure: skin/mucous membrane involvement, respiratory compromise, reduced blood pressure, or persistent gastrointestinal symptoms 5, 7

Treatment Strategies

Immediate Management of Acute Reactions

• Epinephrine (adrenaline): First-line treatment for anaphylaxis, administered intramuscularly in the mid-outer thigh at a dose of 0.01 mg/kg (maximum 0.5 mg in adults, 0.3 mg in children) 7, 10
• Airway management: Supplemental oxygen, positioning (supine with legs elevated for hypotension, sitting upright for respiratory distress), and advanced airway management if needed 5
• Fluid resuscitation: Intravenous fluids for hypotension 5

Pharmacological Management

• Antihistamines (H1-blockers): Effective for cutaneous symptoms like urticaria and pruritus, but not a substitute for epinephrine in anaphylaxis 2, 8
• Corticosteroids: May help prevent biphasic or protracted reactions, but have delayed onset of action 5
• Bronchodilators: For bronchospasm and wheezing 5

Long-term Management

• Allergen identification and avoidance: Crucial for preventing recurrent reactions 1, 2
• Immunotherapy: Can induce tolerance to specific allergens in selected cases 4
• Prescription of epinephrine auto-injectors: For at-risk patients with history of anaphylaxis 7, 10
• Patient education: On recognition and management of allergic reactions 7
• Referral to an allergist: For comprehensive evaluation and management 1, 7

Distinguishing Features

• Type 1 hypersensitivity reactions must be distinguished from non-allergic hypersensitivity reactions that can mimic allergic symptoms 3
• Non-allergic reactions include direct mast cell degranulation (anaphylactoid reactions), complement activation related pseudo-allergy (CARPA), and bradykinin-mediated angioedema 5, 3
• Unlike true allergic reactions, non-allergic reactions do not require prior sensitization and are not mediated by IgE antibodies 5

Common Pitfalls and Caveats

• Delayed administration of epinephrine in anaphylaxis can lead to increased morbidity and mortality 7, 10
• Over-reliance on antihistamines alone for treatment of anaphylaxis is dangerous; epinephrine is the cornerstone of management 7
• Incorrectly labeling side effects as allergies can lead to unnecessary avoidance of effective medications 1, 2
• Beta-adrenergic blockers and angiotensin-converting enzyme inhibitors can increase the risk of severe anaphylactic reactions and may reduce the effectiveness of epinephrine 5
• Measurement of tryptase levels during an anaphylactic episode followed by baseline measurement can help confirm mast cell involvement 5