Overview
Urticaria is an inflammatory skin disorder, resulting in formation of well circumscribed, erythematous, edematous and pruritic plaques called wheals/ hives.
****It may occur with or without angioedema.
Can be classified as acute (<6 weeks) or chronic (>6 weeks).
Etiology and triggers
Urticaria may be spontaneous, or induced:
- Spontaneous urticaria (idiopathic)
- No clear trigger identified = diagnosis of exclusion
- Type I hypersensitivity reaction ((IgE-mediated) and pseudoallergy (IgE-independent)
- Foods (especially the ‘big 9’: milk, eggs, nuts, fish, crustaceans, shellfish, wheat, soy, sesame)
- Insect stings or bites e.g. from order Hymenoptera (bees, wasps, hornets, fire ants)
- Contact allergens e.g. latex
- Medications (usually via non-IgE mediated mast cell degranulation) e.g. sulfonamides, beta-lactam antibiotics, vancomycin, anticonvulsants, NSAIDs, opioids, chemotherapy agents, radiocontrast media
- Physical urticaria
- Cold (cold urticaria)
- Sunlight (solar urticaria in sun-exposed areas)
- Heat, exercise, sweating, emotional stress (cholinergic urticaria)
- Water (aquagenic urticaria)
- Pressure (immediate or delayed pressure urticaria)
- Vibration (vibratory urticaria)
- Infection-induced urticaria (generally complement-mediated)
- Viruses (most common cause of urticaria in children) e.g. rotavirus, rhinovirus, HBV, HCV, EBV, HSV, Parvovirus B19
- Bacteria e.g. Mycoplasma pneumoniae, Group A Streptococcus, Helicobacter pylori
- Parasites and infestations e.g. Plasmodium falciparum, amoebiasis, ascariasis, strongyloidiasis, schistosomiasis, scabies
- Fungal infections e.g. dermatophytosis
- Hormonal changes
- Pregnancy
- Menstruation
- Thyroid disease
- Hormonal therapies
- Systemic conditions
- Multiple myeloma
- Cutaneous small vessel vasculitis (CSVV) (urticarial vasculitis resulting from Type II allergic response)
- Autoimmune diseases (generally cause chronic urticaria) e.g. Systemic lupus erythematosus (SLE), rheumatoid arthritis, polymyositis
Pathophysiology and presentation
The process of hive formation can be caused by various mechanisms (Type I allergic IgE response, non-IgE mediated mechanisms, Type II allergic response mediated by cytotoxic T cells, complement-mediated mechanisms, physical triggers), ultimately leading to:
- Release of histamine, bradykinin, leukotriene C4, prostaglandin D2 and other vasoactive substances from mast cells and basophils in the dermis
- Extravasation of fluid into dermis due to release of above substances, resulting in formation of urticarial lesion
- Intense pruritus as a result of histamine release
On physical examination, urticaria is characterised by the following features:
- Blanching, raised palpable wheals or hives
- Erythematous to pink in colour (central pallor with erythematous flare)
- May be linear, annular (circular) or actuate (serpiginous)
- Occur on any skin area
- Are usually transient and migratory
- Often separated by normal skin but may coalesce rapidly to form large erythematous raised lesions
- Dermatographism may occur (urticarial lesions resulting from light scratching)
- Red flags on physical examination
- Signs of anaphylaxis – abdominal pain, dizziness, shortness of breath, stridor, tachycardia, hypotension
- Angioedema – swelling is non-pitting and non- pruritic, usually occurring on mucosal surfaces of respiratory tract (lips, tongue, uvula, soft palate, laryngeal edema causing hoarseness) and GI tract (leading to severe abdominal pain)
- Individual lesions that are painful, last longer than 36-48 hours, leave residual hyperpigmentation or ecchymosis upon resolution – may suggest urticarial vasculitis
- Presence of systemic signs or symptoms – fever, arthralgias, arthritis, weight changes, bone pain, lymphadenopathy
- Sclera icterus, hepatic enlargement, hepatic tenderness
- Skin evidence of bacterial or fungal infection
Differential diagnoses (Urticaria mimics)
- Atopic dermatitis
- Allergic contact dermatitis
- IgA vasculitis
- Pityriasis Rosea
- Erythema multiforme
- Fixed drug eruptions
- Mastocytosis
- Urticarial vasculitis
- Viral exanthem
Management
- ABCDE approach in case of anaphylaxis or airway compromise due to angioedema (IM epinephrine, hemodynamic support, airway management and ventilation)
- Perform thorough clinical evaluation to identify etiology or underlying conditions, exclude urticaria mimics
- Educate patients on avoidance of identified and/or non-specific triggers
- Symptomatic management
- Second generation antihistamines (1st line) e.g. cetrizine, loratadine, fexofenadine for both acute and chronic urticaria, in scheduled doses. [First generation antihistamines avoided due to sedative effect]
- Glucocorticoids e.g prednisone in short courses <10 days for severe urticaria exacerbations. They stabilise mast cell membranes and inhibit further histamine release
- Additional therapy
- Methotrexate, colchicine, dapsone, indomethacin – may be effective for urticarial vasculitis
- Omalizumab – for chronic urticaria refractory to first line treatment
- Topical 5% doxepin cream, capsaicin, cyclosporine for refractory cases
- Cyproheptadine – to suppress recurrent cold urticaria
