# Anaphylaxis: Recognition, Epinephrine Use, and Disposition

## Introduction

Anaphylaxis is a severe, potentially life-threatening systemic hypersensitivity reaction that demands immediate recognition and treatment. Despite its clinical urgency, anaphylaxis remains underdiagnosed and undertreated, with epinephrine being significantly underutilized in both emergency and outpatient settings. Internal medicine residents must be proficient in the rapid identification and management of this condition.

## Pathophysiology

- **IgE-mediated degranulation** of mast cells and basophils is the most common mechanism
- Release of **histamine, tryptase, prostaglandins, and leukotrienes** produces systemic vasodilation, increased vascular permeability, and bronchospasm
- Non-IgE-mediated anaphylaxis (anaphylactoid reactions) can occur via direct mast cell activation (e.g., radiocontrast, opioids)
- **Biphasic reactions** occur in 5-20% of cases, typically within 8-12 hours of the initial episode

![Mast cell degranulation and mediator release in anaphylaxis](images/anaphylaxis-pathophysiology.png)

## Clinical Presentation and Diagnostic Criteria

### NIAID/FAAN Criteria (Any ONE of Three)

- **Criterion 1**: Acute onset (minutes to hours) with skin/mucosal involvement PLUS respiratory compromise OR hypotension
- **Criterion 2**: Two or more of the following after exposure to a likely allergen: skin/mucosal involvement, respiratory compromise, hypotension, persistent GI symptoms
- **Criterion 3**: Hypotension after exposure to a known allergen for that patient

### Organ System Involvement

- **Skin/Mucosal** (80-90%): urticaria, angioedema, flushing, pruritus
- **Respiratory** (70%): stridor, wheezing, dyspnea, hypoxia
- **Cardiovascular** (45%): hypotension, tachycardia, syncope, cardiac arrest
- **Gastrointestinal** (45%): nausea, vomiting, abdominal cramping, diarrhea

### Common Triggers

- **Foods**: peanuts, tree nuts, shellfish, milk, eggs
- **Medications**: beta-lactam antibiotics, NSAIDs, neuromuscular blocking agents
- **Hymenoptera stings**: bees, wasps, hornets
- **Idiopathic**: no identifiable trigger in 20% of cases

![Algorithm for clinical recognition of anaphylaxis](images/anaphylaxis-diagnostic-algorithm.png)

## Management

### First-Line Treatment: Epinephrine

- **Intramuscular epinephrine** (1:1000 concentration, 0.01 mg/kg, max 0.5 mg) into the mid-anterolateral thigh
- Repeat every 5-15 minutes as needed
- **There are NO absolute contraindications** to epinephrine in anaphylaxis
- Delayed administration is associated with increased mortality and biphasic reactions
- IV epinephrine infusion (1-10 mcg/min) for refractory hypotension

### Adjunctive Therapies

| Agent | Dose | Role | Important Notes |
|-------|------|------|-----------------|
| Epinephrine IM | 0.3-0.5 mg (1:1000) mid-thigh | FIRST-LINE | Repeat q5-15 min; no contraindications |
| NS bolus | 1-2 L (20 mL/kg) | Volume resuscitation | For hypotension |
| Albuterol | 2.5-5 mg nebulized | Bronchospasm | Adjunct if persistent wheezing |
| Diphenhydramine | 25-50 mg IV | H1-antihistamine | NOT a substitute for epinephrine |
| Famotidine | 20 mg IV | H2-antihistamine | May reduce cutaneous symptoms |
| Methylprednisolone | 125 mg IV | Biphasic reaction prevention | Limited evidence |
| Glucagon | 1-5 mg IV | Beta-blocker patients | Refractory hypotension |

- **IV fluid resuscitation**: 1-2 L normal saline bolus for hypotension (up to 20 mL/kg in the first hour)
- **Albuterol** nebulization for bronchospasm not responsive to epinephrine
- **H1-antihistamines** (diphenhydramine 25-50 mg IV): symptom relief only; NOT a substitute for epinephrine
- **H2-antihistamines** (famotidine 20 mg IV): may reduce cutaneous symptoms
- **Glucocorticoids** (methylprednisolone 125 mg IV): theoretical benefit for biphasic reactions, but no strong evidence

### Refractory Anaphylaxis

- Consider **glucagon** 1-5 mg IV for patients on beta-blockers
- **Vasopressin** for catecholamine-resistant shock
- **Methylene blue** has emerging evidence for vasoplegia in severe cases

![Emergency management algorithm for anaphylaxis](images/anaphylaxis-management-algorithm.png)

## Disposition and Follow-Up

### Observation Period

- Minimum **4-6 hours** observation after symptom resolution for uncomplicated cases
- Extended observation (12-24 hours) for severe presentations, prior biphasic reactions, or delayed epinephrine administration
- **ICU admission** for refractory symptoms, hemodynamic instability, or need for epinephrine infusion

### Discharge Planning

- Prescribe **epinephrine auto-injector** (two devices) and provide training on proper use
- Develop a written **anaphylaxis emergency action plan**
- Refer to **allergy/immunology** for confirmatory testing and trigger identification
- Short course of oral corticosteroids (prednisone 40-60 mg daily for 3-5 days) is commonly prescribed but evidence is limited
- Educate on **medical alert identification** (bracelet or necklace)

## Key Clinical Pearls

- Epinephrine is the ONLY first-line treatment for anaphylaxis; antihistamines and steroids are adjuncts, not substitutes
- Absence of skin findings does NOT exclude anaphylaxis; up to 10-20% of patients lack cutaneous manifestations
- Serum tryptase (drawn within 1-3 hours of symptom onset) supports the diagnosis but a normal level does not exclude it
- Always prescribe two epinephrine auto-injectors at discharge, as up to 35% of cases require a second dose

## References

1. Shaker MS, Wallace DV, Golden DBK, et al. Anaphylaxis: A 2020 Practice Parameter Update, Systematic Review, and GRADE Analysis. *J Allergy Clin Immunol*. 2020;145(4):1082-1123.
2. Cardona V, Ansotegui IJ, Ebisawa M, et al. World Allergy Organization Anaphylaxis Guidance 2020. *World Allergy Organ J*. 2020;13(10):100472.
3. Lieberman P, Nicklas RA, Randolph C, et al. Anaphylaxis: A Practice Parameter Update 2015. *Ann Allergy Asthma Immunol*. 2015;115(5):341-384.
4. Campbell RL, Li JTC, Nicklas RA, et al. Emergency Department Diagnosis and Treatment of Anaphylaxis: A Practice Parameter. *Ann Allergy Asthma Immunol*. 2014;113(6):599-608.