Pathology · Year 2 · from Pathology

Case 1: Anaphylaxis - Type I Hypersensitivity

Patient Demographics

• Age: 28 years
• Sex: Female
• Occupation: Software engineer

Chief Complaint

"I can't breathe and my throat is closing up."

History of Present Illness

A 28-year-old woman is brought to the emergency department by ambulance after developing sudden onset of difficulty breathing, throat tightness, and generalized itching at a restaurant. She was eating dinner when she noticed tingling of her lips about 10 minutes after starting her meal. Within minutes, she developed hives all over her body, swelling of her lips and tongue, throat tightness, difficulty breathing, and lightheadedness. Her meal contained shrimp, which she has eaten many times before without problems. However, she recalls having "mild hives" after eating crab 3 months ago, which resolved on its own. Paramedics administered epinephrine 0.3 mg IM en route, with partial improvement.

Past Medical History

• Seasonal allergies (allergic rhinitis)
• Mild asthma (uses albuterol PRN, rare)
• Possible shellfish allergy (recent mild reaction to crab)

Allergies

• Penicillin (childhood rash - unclear details)

Physical Examination (On ED Arrival)

• Vital Signs: BP 88/54 mmHg, HR 122 bpm, RR 28/min, O2 sat 91% on room air
• General: Anxious, diaphoretic, using accessory muscles
• HEENT: Angioedema of lips and tongue; uvula edematous; stridor audible
• Skin: Diffuse urticaria (raised, erythematous, pruritic wheals) over trunk and extremities
• Respiratory: Inspiratory stridor, diffuse wheezing bilaterally
• Cardiovascular: Tachycardic, weak peripheral pulses

Immediate Assessment

Anaphylaxis - Clinical criteria met:

1. Acute onset involving skin (urticaria) AND
2. Respiratory compromise (stridor, wheezing, hypoxia) AND
3. Hypotension

Pathophysiology - Type I (IgE-Mediated) Hypersensitivity

Sensitization Phase (Prior Exposure):

1. Initial exposure to allergen (shellfish proteins)
2. Allergen processed by APCs, presented to Th2 cells
3. Th2 cells produce IL-4 and IL-13, promoting B cell class switching to IgE
4. Allergen-specific IgE produced and binds to FcepsilonRI receptors on mast cells and basophils (sensitization complete)

Effector Phase (Current Exposure):

1. Re-exposure to allergen (shrimp proteins cross-react with crab)
2. Allergen cross-links IgE antibodies on mast cell surface
3. Cross-linking triggers mast cell degranulation within SECONDS
4. Release of preformed mediators:

• Histamine: Vasodilation, increased vascular permeability, bronchoconstriction, pruritus
• Tryptase: Mast cell activation marker (diagnostic)
• Heparin, proteases

1. Synthesis of new mediators (late phase):

• Leukotrienes (LTC4, LTD4): Prolonged bronchoconstriction
• Prostaglandins (PGD2): Vasodilation, bronchoconstriction
• Cytokines: Sustain inflammatory response

Clinical Manifestations by System:

Treatment

IMMEDIATE - First-Line Treatment:

1. EPINEPHRINE (Most Critical Intervention):

• Epinephrine 0.3-0.5 mg IM (1:1000 concentration) into anterolateral thigh
• Repeat every 5-15 minutes if no improvement
• Patient received one dose en route; give second dose now

Why Epinephrine Works:

• Alpha-1 agonism: Vasoconstriction (reverses hypotension, reduces angioedema)
• Beta-1 agonism: Increased cardiac output
• Beta-2 agonism: Bronchodilation, inhibits mast cell mediator release

2. Positioning:

• Trendelenburg (legs elevated) if hypotensive
• Sitting up if respiratory distress predominates
• Do not have patient sit or stand suddenly (risk of cardiac arrest)

3. Airway Management:

• High-flow oxygen
• Prepare for intubation if worsening stridor/angioedema
• Consider early intubation before complete airway obstruction

4. IV Access and Fluids:

• Large-bore IV access
• Normal saline 1-2 L bolus for hypotension (may need several liters)
• Anaphylaxis causes massive third-spacing

SECOND-LINE Adjunctive Treatments:

5. Antihistamines:

• H1 blocker: Diphenhydramine 25-50 mg IV
• H2 blocker: Famotidine 20 mg IV
• Help with urticaria and pruritus; do NOT replace epinephrine

6. Glucocorticoids:

• Methylprednisolone 125 mg IV or hydrocortisone 200 mg IV
• Onset delayed (4-6 hours); used to prevent biphasic reaction
• Does NOT treat acute symptoms

7. Bronchodilators:

• Albuterol nebulizer for bronchospasm not responding to epinephrine

8. If Refractory Hypotension:

• Epinephrine infusion (1-10 mcg/min)
• Vasopressors (norepinephrine) if needed

Clinical Course

• Second IM epinephrine given with improvement in BP (102/68) and breathing
• Intubation not required; stridor resolved
• Urticaria improved with antihistamines
• Observed for 6 hours for biphasic reaction (occurs in 1-20% of cases)
• Discharged with epinephrine auto-injector prescription and allergy referral

Discharge Plan

Prescriptions:

1. Epinephrine auto-injector (EpiPen): Carry at ALL times; prescribe 2 devices
2. Diphenhydramine 25 mg: Take every 6 hours for 3 days for residual symptoms
3. Prednisone 50 mg daily x 3 days: Prevent biphasic/protracted reaction

Education:

1. Strict shellfish avoidance (all crustaceans: shrimp, crab, lobster, crawfish)
2. Cross-reactivity: ~75% cross-react between crustacean species
3. Read all food labels; ask about ingredients at restaurants
4. Know how to use epinephrine auto-injector
5. Seek emergency care immediately after using epinephrine

Referrals:

1. Allergist/immunologist for confirmatory testing (skin prick test, specific IgE)
2. Consider evaluation of penicillin allergy (may be outgrown)

Clinical Pearl

Epinephrine is the ONLY first-line treatment for anaphylaxis - antihistamines and steroids are adjuncts only. Delayed epinephrine administration is associated with increased mortality. Biphasic anaphylaxis (recurrence of symptoms hours after initial resolution) occurs in up to 20% of cases, which is why observation for 4-6 hours and steroid administration are recommended. Serum tryptase, if drawn within 1-2 hours of onset, can help confirm mast cell activation and support the diagnosis. All patients with anaphylaxis should be prescribed epinephrine auto-injectors and referred to an allergist.

Clinical Image

Clinical photograph demonstrating urticaria (hives) with characteristic raised, erythematous, pruritic wheals. Urticaria results from histamine-mediated vasodilation and increased vascular permeability in type I hypersensitivity reactions.

Image Source: Wikimedia Commons - "Urticaria" License: CC BY-SA 3.0 URL: https://commons.wikimedia.org/wiki/File:Urticaria.jpg

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