Definition

  • Urticaria <6 weeks
  • Must distinguish "common" or "true" urticaria from urticarial (urticaria-like) lesions which can have a different differential diagnosis
common_urticaria_vs_urticarial.png


Differential Diagnosis of Acute (Common) Urticaria

  • Overall: infections, particularly viral infections of the upper respiratory tract (40%), followed by drugs, food (mainly seafood and fruit), and insect bites
    • Children: infections and food
    • Adults: drugs
  • The cause of acute urticaria remains unclear in up to 70% of patients

Infections

  • Viral - most common cause in children
  • Parasitic
    • Most commonly Ascaris, Ancylostoma, Strongyloides, Filaria, Echinococcus, Schistosoma, Trichinella, Toxocara, and Fasciola (typically with eosinophilia).
    • Anisakis simplex (a sea fish nematode) has been reported as possible cause of recurrent acute urticaria in areas of the world where uncooked fish is eaten frequently.

Allergic reactions (usually IgE-mediated)

  • Medications, supplements
  • Stinging and biting insects
  • Ingestions/inhalation of food allergens and additives
  • Contact with allergens (e.g. food, latex)
    • Many children have skin reactivity to a food (e.g. contact urticaria) but can tolerate that same food with oral challenge (one reason that false positive skin tests to foods are common). It is fine to continue that food in the diet despite the presence of contact urticaria.
      • Possible etiologic factors include the natural histamine content of the food, or acidity of the food
    • Cinnamic aldehyde is a common allergen causing contact dermatitis as well as contact urticaria. It is a flavoring agent and fragrance found in cola beverages, vermouth, chewing gums, mouthwashes, soaps, and toothpastes. Patients frequently cross-react with balsam of Peru.
  • Aeroallergens - consider as cause when associated with seasonal pattern, exacerbation of allergic rhinitis

Direct mast cell activation


Other

  • Aspirin, NSAIDs, coal tar dye derivatives such as tartrazine (yellow #5)
  • Idiosyncratic reaction to medications, supplements
    • Cases of challenge-proven urticaria to antihistamines have been reported
  • Autoimmune progesterone/estrogen dermatitis - rare, 50% present with true urticaria (rest with urticaria-like, eczematous, or vesiculopustular eruptions, fixed drug eruptions, stomatitis, erythema multiforme-like lesions, and anaphylaxis), appears 3-10 days before menses and resolves a few days after menses. Positive progesterone intradermal skin test. Treated with prevention of ovulation.
  • Immunologic blood transfusion reactions
  • Serum sickness - in association with fever, polyarthralgias, and/or lymphadenopathy
  • Presenting sign of chronic urticaria and/or systemic illness


Differential Diagnosis of Urticarial Lesions

  • May manifest with skin lesions other than wheals (eg, scaling and blistering), more likely to have a bilateral and symmetrical distribution, individual lesions have a long duration, and their resolution may leave marks, such as hyperpigmentation (see table above)
  • Common skin diseases:
    • Urticarial dermatitis - usually affects elderly, present with intensely pruritic long lasting patches with an urticarial (and in some areas an eczematous) appearance, with a bilateral and symmetrical distribution on the trunk or proximal extremities. Cause unknown, drugs frequently implicated, treated with steroids
    • Contact dermatitis
    • Insect bite reaction
    • Exanthematous drug eruptions
    • Urticaria pigmentosa - commonly presents with brownish maculopapular urticarial lesions that can be spontaneous or induced by rubbing, heat, and sunlight exposure; positive Darier sign after skin rubbing is elicited in most cases, residual hyperpigmentation can persist after healing
    • Subepidermal autoimmune bullous diseases
      • Includes bullous pemphigoid, gestational pemphigoid, linear IgA dermatosis, and epidermolysis bullosa acquisita
      • May present solely with urticarial lesions early in disease; cutaneous biopsy is mandatory, and the diagnosis can be easily confirmed by histologic examination plus DIF staining. Serum autoantibodies (anti-BP180, anti-BP230, and anti-desmogleins 1 and 3) also support diagnosis.
    • Pruritic urticarial papules and plaques of pregnancy (PUPPP) - appears during 3rd trimester or soon after delivery as 1-2 mm erythematous papules within abdominal striae with periumbilical sparing. Lesions then spread to the proximal extremities and coalesce to form urticarial plaques. Half also develop eczematous changes, vesicles, or targetoid lesions. Spontaneously resolves within weeks.
    • Acute annular urticaria (aka urticaria multiforme) - more common in young children, with up to 12 day course of pruritic, blanching, annular/arcuate/polycyclic, erythematous, evanescent (<24 h duration) urticaria associated with dermatographism, angioedema of hands/feet/face, fever 1-3 days, sometimes with lesions containing a dusky echymotic center (also evanescent, <24 h), often confused with erythema multiforme and serum sickness

Urticaria multiforme.png

  • Rare skin disease:
    • Autoimmune progesterone/estrogen dermatitis - see above
    • Interstitial granulomatous dermatitis (IGD) - rare, adult onset, lasts weeks to years, diverse presentations including papules, nodules, plaques, and urticarial rash, may be associated with articular involvement, and sometimes with autoimmune diseases, requires biopsy for diagnosis
    • Eosinophilic cellulitis (Wells syndrome) - localized or diffuse pruritic erythematous and edematous lesions, which evolve into plaques within a few days and resolve completely, leaving some hyperpigmentation. Bullous lesions are present in some cases. Peripheral eosinophilia may be present in the acute phase (in 50%), and biopsy shows marked eosinophilic infiltrate
    • Neutrophilic eccrine hidradenitis (NEH) - rare, self-limiting, solitary or grouped erythematous edematous papules and plaques that are asymptomatic, pruritic, or painful, seen primarily in patients with hematologic malignancies (90% of cases) s/p chemotherapy
    • Urticaria-like follicular mucinosis - rare disorder, primarily affects middle aged men, presents as fixed urticarial papules or plaques on the head or neck, within an erythematous seborrheic background. No associated systemic diseases; good prognosis.

  • Systemic diseases associated with urticarial lesions
    • Vasculitides and immunologic disorders
      • Urticarial vasculitis
      • SLE, Sjogren syndrome, dermatomyositis, mixed connective tissue disease
      • Juvenile idopathic arthritis (formerly JRA)
      • Churge-Strauss disease
      • Wegener granulomatosis
      • Polyarteritis nodosa
      • Neutrophilic urticarial dermatosis
    • Hematologic diseases
    • Autoinflammatory syndromes
      • Hereditary periodic fever syndromes
        • Familial Mediterranean fever
        • TNF receptor associated periodic fever
        • Hyperimmunoglobulinemia D with periodic fever syndrome
      • Cryopyrin-associated periodic syndromes
        • Familial cold autoinflammatory syndrome
        • Muckle-Wells syndrome
        • Neonatal onset multisystem inflammatory disease
      • Others
        • Pyogenic arthritis-pyoderma gangrenosum-acne syndrome
        • Blau syndrome
        • Chronic recurrent multifocal osteomyelitis and Majeed syndrome


Diagnosis

  • Relevant allergy testing if IgE-mediated allergic reaction suspected
  • Consider early evaluation for chronic urticaria
    • Acute urticaria practice parameter (2000) suggests a CBC/diff, urinalysis, ESR, and LFTs "primarily to identify occult underlying conditions at a stage prior to a more overt clinical presentation"
    • EAACI 2013 guideline recommends against any routine diagnostic measures in acute urticaria
  • Elevated CRP and/or IL-6 can be useful in identifying patients who are likely to be resistant to antihistamine therapy alone and therefore need systemic steroids to achieve control



Empiric treatment

  • Avoid suspected triggers
  • If a specific etiology (and therefore treatment) is unclear, consider:
    • Second generation H1 + H2 antihistamine
    • Oral corticosteroid for severe initial symptoms
      • Adults: Prednisone, 30-60 mg daily, with tapering over 5-7 days
      • Children: Prednisolone 0.5-1 mg/kg/day (max 60 mg daily), with tapering over 5-7 days



Prognosis

  • For acute urticaria, 90% of patients have complete resolution 3 weeks after onset


References