Urticaria

Overview

Urticaria is an inflammatory skin disorder, resulting in the 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 (the 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 the dermis due to the release of the above substances, resulting in the formation of a urticarial lesion
• Intense pruritus as a result of histamine release

On physical examination, urticaria is characterized 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 the respiratory tract (lips, tongue, uvula, soft palate, laryngeal edema causing hoarseness) and the 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 a thorough clinical evaluation to identify the etiology or underlying conditions and exclude urticaria mimics
• Educate patients on the 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 stabilize mast cell membranes and inhibit further histamine release
  • Additional therapy
    • Methotrexate, colchicine, dapsone, and indomethacin may be effective for urticarial vasculitis
    • Omalizumab – for chronic urticaria refractory to first-line treatment
    • Topical 5% doxepin cream, capsaicin, and cyclosporine for refractory cases
    • Cyproheptadine – to suppress recurrent cold urticaria