# Clinical Cases: Hypersensitivity Reactions

## Case 1: Anaphylaxis (Type I Hypersensitivity)

### Patient Demographics
- **Age:** 24 years old
- **Sex:** Male
- **Ethnicity:** Hispanic

### Chief Complaint
Difficulty breathing and rash after eating at a restaurant

### History of Present Illness
A 24-year-old man is brought to the emergency department by ambulance after developing difficulty breathing, hives, and throat tightness approximately 15 minutes after eating pad thai at a restaurant. He initially felt itching in his mouth and throat, which rapidly progressed to a generalized itchy rash and sensation that his tongue was swelling. He became lightheaded and short of breath. His girlfriend administered his epinephrine auto-injector before calling 911.

### Past Medical History
- Peanut allergy diagnosed in childhood (prior mild reactions with hives)
- Asthma (mild intermittent)
- Allergic rhinitis

### Medications
- Albuterol inhaler PRN
- Epinephrine auto-injector (carries but states has not needed in years)

### Physical Examination
- **General:** Anxious, diaphoretic man in moderate respiratory distress
- **Vital Signs:** T 37.2C, HR 125, RR 28, BP 85/50, SpO2 92% on room air
- **HEENT:** Lip and tongue edema; uvula edema; stridor present; periorbital swelling
- **Skin:** Diffuse urticarial rash over trunk and extremities; flushing
- **Lungs:** Diffuse wheezing bilaterally; poor air movement
- **Cardiovascular:** Tachycardic, regular rhythm; no murmurs
- **Abdomen:** Mild cramping on palpation

### Emergency Department Course
| Time | Intervention | Response |
|------|--------------|----------|
| 0 min | EMS: IM epinephrine 0.3mg (pre-arrival) | Partial improvement |
| 15 min | Second IM epinephrine 0.3mg | HR 105, BP 95/60 |
| 15 min | IV fluids 1L NS bolus, diphenhydramine 50mg IV, methylprednisolone 125mg IV | Continued improvement |
| 45 min | Nebulized albuterol | Wheezing resolved |
| 4 hours | Monitoring | Stable, mild urticaria persists |

### Clinical Image
![Urticaria Pattern](case_01_image.jpg)

*Image illustrating urticarial wheals characteristic of Type I hypersensitivity reaction. These raised, erythematous, pruritic plaques result from mast cell degranulation and histamine release. Image source: Course lecture materials.*

### Diagnosis
**Anaphylaxis due to peanut allergy** (Type I IgE-mediated hypersensitivity)

### Discussion
Anaphylaxis is a severe, potentially life-threatening systemic Type I hypersensitivity reaction:

**Pathophysiology:**
- Prior sensitization leads to allergen-specific IgE production
- IgE binds high-affinity FcepsilonRI receptors on mast cells
- Re-exposure: Allergen cross-links surface-bound IgE
- Mast cell degranulation releases preformed mediators (histamine, tryptase)
- Newly synthesized mediators (leukotrienes, prostaglandins) amplify response

**Effects of mast cell mediators:**
| Mediator | Effects |
|----------|---------|
| Histamine | Vasodilation, increased permeability, bronchoconstriction, pruritus |
| Leukotrienes C4/D4/E4 | Prolonged bronchoconstriction, mucus secretion |
| Prostaglandin D2 | Vasodilation, bronchoconstriction |
| Tryptase | Tissue damage (useful diagnostic marker) |

**Anaphylaxis diagnostic criteria (2 or more):**
- Skin/mucosal involvement (urticaria, angioedema, flushing)
- Respiratory compromise (bronchospasm, stridor, hypoxia)
- Cardiovascular (hypotension, end-organ dysfunction)
- Gastrointestinal (cramping, vomiting)
- After exposure to known or likely allergen

**Why epinephrine is first-line:**
- Alpha-1 agonist: Reverses vasodilation, reduces angioedema
- Beta-1 agonist: Increases cardiac output
- Beta-2 agonist: Bronchodilation, stabilizes mast cells

### Treatment
1. **Immediate:** Epinephrine IM (anterolateral thigh), repeated every 5-15 min if needed
2. **Supportive:** IV fluids for hypotension, supplemental oxygen
3. **Adjuncts:** Antihistamines, corticosteroids (prevent biphasic reactions)
4. **Monitoring:** 4-6 hour observation for late-phase reactions
5. **Discharge:** Epinephrine auto-injector prescription, anaphylaxis action plan
6. **Follow-up:** Allergist referral for skin testing, education, and consideration of oral immunotherapy

---

## Case 2: Allergic Contact Dermatitis (Type IV Hypersensitivity)

### Patient Demographics
- **Age:** 38 years old
- **Sex:** Female
- **Ethnicity:** Caucasian

### Chief Complaint
Intensely itchy rash on neck and earlobes for 5 days

### History of Present Illness
A 38-year-old woman presents with a severely pruritic rash that began on her earlobes 5 days ago and has spread to her neck and upper chest. The rash is characterized by small blisters and redness. She recently celebrated her 10th wedding anniversary and received new jewelry from her husband, including nickel-containing costume earrings and a necklace that she has worn daily for the past week. She has had similar but milder reactions to jewelry in the past.

### Past Medical History
- History of "sensitive skin" to jewelry
- Seasonal allergic rhinitis

### Physical Examination
- **General:** Uncomfortable due to pruritus, scratching affected areas
- **Vital Signs:** Normal
- **Skin:**
  - Bilateral earlobes: Erythema, vesicles, weeping, crusting at earring sites
  - Neck: Linear and geometric pattern of erythematous papules and vesicles corresponding to necklace contact
  - Upper chest: Scattered erythematous papules extending beyond contact area
  - No lesions on palms, soles, or mucous membranes

### Diagnostic Testing
**Patch testing performed at follow-up (48 and 96-hour readings):**
| Allergen | 48-hour | 96-hour | Interpretation |
|----------|---------|---------|----------------|
| Nickel sulfate | 2+ | 3+ | Positive (strong) |
| Cobalt chloride | 1+ | 2+ | Positive |
| Gold sodium thiosulfate | - | - | Negative |
| Fragrance mix | - | - | Negative |
| Balsam of Peru | - | - | Negative |

### Diagnosis
**Allergic Contact Dermatitis to Nickel** (Type IV delayed-type hypersensitivity)

### Discussion
Allergic contact dermatitis is a Type IV (cell-mediated) hypersensitivity reaction:

**Pathophysiology:**
- **Sensitization phase:** Nickel (hapten) penetrates skin, binds to carrier proteins
- Langerhans cells uptake hapten-protein complex, migrate to lymph nodes
- Present to naive T cells, generating hapten-specific memory T cells
- **Elicitation phase:** Re-exposure activates memory T cells at contact site
- T cells release IFN-gamma, TNF-alpha, recruiting inflammatory cells
- Keratinocyte apoptosis by CD8+ cytotoxic T cells

**Why nickel allergy is so common:**
- Nickel is the most common contact allergen worldwide
- Prevalence higher in women (ear piercing, jewelry exposure)
- Nickel found in: costume jewelry, belt buckles, watchbands, cell phones, coins, surgical instruments

**Distinguishing allergic from irritant contact dermatitis:**
| Feature | Allergic Contact | Irritant Contact |
|---------|------------------|------------------|
| Mechanism | Immune (Type IV) | Direct cytotoxicity |
| Sensitization | Required | Not required |
| First exposure | No reaction | Can cause reaction |
| Timing | 24-96 hours | Immediate to hours |
| Distribution | May spread beyond contact | Limited to contact area |
| Symptoms | Pruritus | Burning, stinging |

**Patch testing interpretation:**
- 1+ = Erythema, infiltration
- 2+ = Erythema, papules, infiltration
- 3+ = Vesicles, bullae

### Treatment
1. **Allergen avoidance:** Remove nickel-containing jewelry; use nickel-free alternatives (surgical steel, titanium, 18K gold)
2. **Acute management:** Topical corticosteroids (medium-high potency for body)
3. **Symptomatic relief:** Oral antihistamines for pruritus
4. **Patient education:**
   - Check labels for nickel content
   - Apply clear nail polish to metal surfaces that contact skin
   - Nickel spot test kits available
5. **Occupational considerations:** Some professions have higher nickel exposure

---

## Case 3: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

### Patient Demographics
- **Age:** 55 years old
- **Sex:** Male
- **Ethnicity:** African American

### Chief Complaint
Fever, rash, and facial swelling 4 weeks after starting allopurinol

### History of Present Illness
A 55-year-old man presents with 5 days of fever, progressive rash, and facial swelling. He was started on allopurinol 4 weeks ago for recurrent gout attacks. Five days ago, he developed low-grade fever and a faint rash on his trunk that has progressed to involve his entire body. He reports facial puffiness, especially around his eyes, sore throat, and generalized malaise. He denies dyspnea, cough, or abdominal pain.

### Past Medical History
- Gout with recurrent flares
- Hypertension
- Chronic kidney disease stage 3
- Type 2 diabetes

### Medications
- Allopurinol 100mg daily (started 4 weeks ago)
- Lisinopril 10mg daily
- Metformin 1000mg twice daily

### Physical Examination
- **General:** Ill-appearing man with prominent facial edema
- **Vital Signs:** T 39.1C, HR 98, RR 18, BP 135/82
- **HEENT:** Periorbital and facial edema; pharyngeal erythema; no oral ulcers
- **Skin:** Diffuse morbilliform eruption with areas of confluence; involving >80% BSA; facial edema; no mucosal involvement; no vesicles or skin sloughing; no Nikolsky sign
- **Lymphatics:** Cervical, axillary, and inguinal lymphadenopathy
- **Abdomen:** Hepatomegaly (liver edge 4cm below costal margin); mild RUQ tenderness

### Laboratory Workup
| Test | Result | Reference Range |
|------|--------|-----------------|
| WBC | 18,500/uL | 4,500-11,000/uL |
| **Eosinophils** | **28% (AEC 5,180/uL)** | <5% (AEC <500/uL) |
| Atypical lymphocytes | Present | Absent |
| Hemoglobin | 12.8 g/dL | 14-18 g/dL |
| Platelets | 145,000/uL | 150,000-400,000/uL |
| **AST** | **420 U/L** | 10-40 U/L |
| **ALT** | **510 U/L** | 7-56 U/L |
| Alkaline phosphatase | 185 U/L | 44-147 U/L |
| Total bilirubin | 2.1 mg/dL | 0.1-1.2 mg/dL |
| Creatinine | 2.4 mg/dL (baseline 1.8) | 0.7-1.3 mg/dL |
| HHV-6 PCR | Positive | Negative |

### Diagnosis
**Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome** due to allopurinol

### Discussion
DRESS is a severe cutaneous adverse reaction (SCAR) representing a Type IV hypersensitivity with unique features:

**Pathophysiology:**
- T cell-mediated drug hypersensitivity
- Delayed onset (2-8 weeks after drug initiation)
- Viral reactivation (HHV-6, EBV, CMV) plays a role in pathogenesis
- HLA associations: HLA-B*58:01 strongly associated with allopurinol-DRESS (especially in Asian populations)

**RegiSCAR criteria for DRESS diagnosis:**
- Hospitalization required
- Suspected drug reaction
- Fever >38C
- Enlarged lymph nodes
- At least one internal organ involvement
- Blood count abnormalities (eosinophilia and/or atypical lymphocytes)

**High-risk drugs for DRESS:**
- Allopurinol
- Aromatic anticonvulsants (carbamazepine, phenytoin, lamotrigine)
- Sulfonamides
- Dapsone
- Vancomycin

**This patient's features supporting DRESS:**
- Latency period: 4 weeks (typical 2-8 weeks)
- Morbilliform rash with facial edema
- Fever, lymphadenopathy
- Eosinophilia with atypical lymphocytes
- Hepatitis (most common internal organ involvement)
- HHV-6 reactivation

**Distinguishing DRESS from other severe drug reactions:**
| Feature | DRESS | SJS/TEN | AGEP |
|---------|-------|---------|------|
| Onset | 2-8 weeks | 1-3 weeks | 1-2 days |
| Mucosal | Rare | Prominent | Rare |
| Skin | Morbilliform | Blisters, necrosis | Pustules |
| Eosinophilia | Common | Rare | Neutrophilia |
| Organ involvement | Common | Rare | Rare |

### Treatment
1. **Immediate:** Stop allopurinol (and any other potential causative drugs)
2. **Corticosteroids:** Prednisone 1-1.5 mg/kg/day for severe disease
3. **Supportive care:** IV fluids, monitoring hepatic and renal function
4. **Prolonged taper:** Steroids over 8-12 weeks (rapid taper risks relapse)
5. **Monitor for complications:**
   - Autoimmune sequelae (thyroiditis) can develop weeks to months later
   - Fulminant hepatitis (may require consideration of liver transplant)
6. **Future avoidance:** Allopurinol contraindicated; consider febuxostat with caution
7. **Consider HLA testing:** HLA-B*58:01 screening before allopurinol in high-risk populations
8. **Mortality:** 5-10% even with treatment

**Important:** Resolution is slow; eosinophilia and organ involvement may persist for weeks