Urticaria, Angioedema, and Allergic Rhinitis¶
Chapter 363 | Part 11: Immune-Mediated, Inflammatory, and Rheumatologic Disorders
KEY CLINICAL POINTS¶
- Urticaria involves superficial dermis vasodilation, while angioedema affects deeper dermis and subcutaneous tissues.
- Hereditary angioedema (HAE) is caused by C1INH deficiency, leading to bradykinin-mediated swelling.
- Allergic rhinitis is classified as seasonal (pollen) or perennial (house dust mites, animal dander).
1. DEFINITION & OVERVIEW¶
Urticaria and angioedema represent similar pathophysiologic processes occurring at different levels of the skin. Urticaria involves dilation of vascular structures in the superficial dermis, while angioedema originates from the deeper dermis and subcutaneous tissues. They often co-occur, affecting >20% of the population. Allergic rhinitis is characterized by sneezing, rhinorrhea, nasal obstruction, and conjunctival itching, with IgE-mediated immune responses.
Table 363-1 Classification of Urticaria and/or Angioedema¶
| ACUTE | CHRONIC |
|---|---|
| Drug reactions | Spontaneous/idiopathic—no identifiable trigger |
| Including (but not limited to): antimicrobials, nonsteroidal anti-inflammatory drugs (NSAIDs), radiocontrast media, opioids, angiotensin-converting enzyme (ACE) inhibitors, dipeptidyl peptidase-4 inhibitors | Autoimmune—autoimmune component |
| Vaccine reactions | Physical stimuli (inducible urticaria) |
| Food reactions | Dermatographism |
| Inhalation or contact with environmental allergens | Cholinergic urticaria |
| Transfusion reactions | Vibration, cold, pressure, water (aquagenic) |
| Stinging and biting insects | Sun (solar) |
| Toxin (scombroid) | Vascular disease—urticarial vasculitis and small vessel vasculitis |
| Infections—viral, bacterial, parasitic | Mastocytosis (cutaneous or systemic) |
| Hereditary | Hereditary angioedema (HAE) |
| C3b inhibitor deficiency | CIAS1-associated periodic fever syndromes (familial cold urticaria, Muckle-Wells syndrome) |
| ACUTE | CHRONIC |
|---|---|
| Hypereosinophilic syndrome | Schnitzler’s syndrome |
| Gleich’s syndrome | Gleich’s syndrome |
1.1 Mast Cell Mediation¶
Mast cells release histamine, lipid mediators (PGD2, LTC4), and cytokines (IL-4, IL-5, IL-13) upon IgE cross-linking. These mediators cause vasodilation, increased vascular permeability, and recruitment of inflammatory cells.
1.2 Hereditary Angioedema (HAE)¶
Caused by SERPING1 gene mutations leading to C1INH deficiency. Characterized by recurrent swelling of the face, extremities, and gastrointestinal tract, with a lack of pruritus or urticaria.
2. EPIDEMIOLOGY¶
Acute urticaria affects 15–20% of the population, with 40% of cases coexisting with angioedema. Chronic urticaria occurs in 1–2% of adults, more common in women. Allergic rhinitis prevalence in North America is 10–30%, peaking in the fifth decade. Risk factors include atopy, environmental allergens, and genetic predispositions (e.g., HAE).
2.1 Demographics¶
Women are more commonly affected than men. Chronic urticaria peaks in the third to fifth decades. Allergic rhinitis is more prevalent in children and adolescents with atopic conditions.
2.2 Risk Factors¶
Atopy, environmental allergens (pollen, dust mites), drug exposure (NSAIDs, ACE inhibitors), and genetic factors (e.g., NLRP3 mutations in familial cold urticaria).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Urticaria and angioedema result from mast cell degranulation, IgE-mediated responses, or genetic defects (e.g., HAE). Allergic rhinitis involves IgE-mediated inflammation of nasal mucosa, with allergen-specific IgE binding to mast cells and release of mediators.
3.1 Mast Cell Activation¶
IgE cross-linking triggers mast cell degranulation, releasing histamine, lipid mediators (PGD2, LTC4), and cytokines (IL-4, IL-5, IL-13). These mediators cause vasodilation, increased vascular permeability, and recruitment of inflammatory cells.
3.2 Hereditary Angioedema (HAE)¶
Caused by C1INH deficiency (SERPING1 mutations), leading to bradykinin accumulation. Characterized by recurrent swelling of the face, extremities, and gastrointestinal tract, with no pruritus or urticaria.
4. CLINICAL FEATURES¶
Acute urticaria presents with pruritic wheals (<24 h), while chronic urticaria persists >6 weeks. Angioedema involves deep swelling with pain, often affecting periorbital and perioral regions. Allergic rhinitis features include sneezing, rhinorrhea, nasal obstruction, and conjunctival itching.
4.1 Urticaria and Angioedema¶
Acute: pruritic wheals, transient swelling. Chronic: persistent lesions, may coexist with angioedema. Physical urticarias (cold, pressure, cholinergic) are stimulus-specific.
4.2 Allergic Rhinitis¶
Seasonal (pollen) or perennial (dust mites, animal dander). Features include rhinorrhea, sneezing, nasal obstruction, and conjunctival itching. Perennial rhinitis may present with thickened sinus membranes.
5. DIFFERENTIAL DIAGNOSIS¶
Urticaria: viral infections, drug reactions, autoimmune diseases (e.g., lupus). Angioedema: infections, malignancies, mastocytosis. Allergic rhinitis: nonallergic rhinitis, sinusitis, nasal polyps.
5.1 Urticaria¶
Drug reactions, infections, autoimmune disorders (e.g., SLE), mastocytosis, and physical urticarias.
5.2 Angioedema¶
Infections, malignancies, mastocytosis, HAE, and idiopathic causes.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis of urticaria/angioedema relies on history, physical exam, and allergen-specific IgE testing. Allergic rhinitis is diagnosed via history of allergen exposure, symptoms, and skin prick tests. HAE is confirmed by C1INH levels and functional assays.
Algorithm for Diagnosing and Managing Rhinitis¶
| Symptoms > 4 weeks? | Allergy Evaluation | Treatment |
|---|---|---|
| Yes | History/skin test or blood test for allergen-specific IgE | Intranasal glucocorticoids, antihistamines |
| No | Exclude medication-induced rhinitis, anatomic defects, infections | Treat as infection or nonallergic rhinitis |
6.1 Diagnostic Tests¶
Skin prick tests, serum-specific IgE, C1INH antigen/function assays, and provocation testing for physical urticarias.
6.2 Algorithm for Rhinitis¶
Figure 363-4: Algorithm for diagnosing and managing rhinitis, including stepwise treatment with antihistamines, corticosteroids, and immunotherapy.
7. MANAGEMENT & TREATMENT¶
First-line therapy for urticaria includes H1 antihistamines (loratadine, cetirizine). Severe cases may require omalizumab or corticosteroids. Angioedema is managed with C1INH replacement, icatibant, or epinephrine. Allergic rhinitis is treated with intranasal corticosteroids, antihistamines, and immunotherapy.
7.1 Urticaria¶
H1 antihistamines (first-line), omalizumab (for chronic refractory cases), corticosteroids (acute severe cases).
7.2 Angioedema¶
C1INH replacement (plasma-derived or recombinant), icatibant, epinephrine for acute attacks. Avoid ACE inhibitors in HAE.
7.3 Allergic Rhinitis¶
Intranasal corticosteroids (most effective), antihistamines, leukotriene receptor antagonists (montelukast), and immunotherapy (SCIT/SLIT).
8. PROGNOSIS & COMPLICATIONS¶
Acute urticaria is self-limiting, while chronic urticaria may persist for months. Angioedema can be life-threatening (e.g., laryngeal obstruction). Allergic rhinitis may progress to asthma or sinusitis. HAE requires long-term C1INH replacement to prevent attacks.
8.1 Complications¶
Angioedema: airway obstruction, gastrointestinal colic. Chronic urticaria: reduced quality of life. Allergic rhinitis: asthma, sinusitis, sleep disturbances.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Avoid NSAIDs and corticosteroids. Pediatrics: Physical urticarias (e.g., cold, pressure) are common. Genetic factors: HAE and mastocytosis require family screening. Immunotherapy: SCIT/SLIT for confirmed allergen-specific rhinitis.
9.1 Pregnancy¶
Avoid NSAIDs and corticosteroids. Use antihistamines cautiously (e.g., loratadine).
9.2 Pediatrics¶
Physical urticarias (e.g., cold, pressure) are common. Avoid allergen exposure in atopic children.
10. KEY POINTS & CLINICAL PEARLS¶
Urticaria and angioedema are IgE-mediated mast cell disorders. HAE is diagnosed by C1INH deficiency and family history. Allergic rhinitis is managed with intranasal corticosteroids and allergen avoidance. Immunotherapy (SCIT/SLIT) is effective for allergen-specific rhinitis.