urticaria (hives)

Introduction

Wheal (swelling) & flare (redness) response to histamine release.

Classification

• acute: daily for < 6 weeks
• chronic: daily for > 6 weeks

Etiology

• food allergy
  • common cause of acute urticaria
    • shellfish, peanuts, tree nuts
  • occurs within 30 minutes of eating food
  • almost never causes chronic urticaria
  • food additives almost never cause chronic urticaria
  • pollen-food allergy syndrome (ragwood allergy & ingestion of melons)
• pharmacologic agents (common, perhaps most common cause)
  • aspirin
  • barbiturates
  • captopril
  • enalapril
  • penicillins (can occur up to 14 days after treatment)
  • sulfonamides
  • NSAIDs
• insect bite or sting (lesions can last > 24 hours)
• airborne allergens
  • pollens
    • pollen-food allergy syndrome
  • mold & house dust mites not associated with urticaria
• contact allergens
  • animal dander
  • latex
  • plants
• infections:
  • bacterial (H pylori)
  • viral (hepatitis B)
  • fungal
  • helminth
• intravenous radioactive iodine contrast agent
• transfusion reactions
• physical factors
  • demographism (writing on the skin)
  • vibratory urticaria, vibratory angioedema
  • solar urticaria
  • localized heat urticaria
  • cold-induced urticaria - generally noted within minutes
  • aquatic urticaria
  • pressure urticaria
    • immediate 5-10 minutes
    • delayed 4-6 hours: may be associated with systemic symptoms (i.e. fever, systemic inflammation)
  • cholinergic urticaria
    • following hot shower or exercising in humid environment
    • typically around neck, wheals small
• autoimmune disease
  • cryoglobulinemia
  • lupus erythematosus
  • rheumatoid arthritis
  • Sjogren's syndrome
  • serum sickness
  • premenstrual urticaria (antibodies to IgE & progesterone implicated)
  • Hashimoto's thyroiditis (hypothyroidism)
  • Grave's disease (hyperthyroidism)
  • Diabetes mellitus type 1
  • may occur up to 10 years after onset of urticaria
  • autoimmune diseases are 17 times more common in patients with idiopathic urticaria than in general population
• malignancies
  • acquired complement C1 & C1 inhibitor depletion
  • Hodgkin's disease
  • non-Hodgkin's lymphoma
• urticaria pigmentosum (systemic mastocytosis)
• urticarial vasculitis
• hereditary disorders
  • hereditary angioedema
  • familial cold urticaria
  • C3b inactivator deficiency
  • amyloidosis with deafness & urticaria
• chronic idiopathic urticaria
  • may be autoimmune disorder
  • may be due to IgG directed against alpha chain of IgE receptor on mast cells
  • hepatitis C
  • Schnitzler syndrome
• psychogenic factors & hyperthyroidism can exacerbate urticaria, but cannot be sole cause
• idiopathic (common,50%)

Epidemiology

• occurs in 20-25% of population at some time
• chronic urticaria (daily for > 6 weeks)
  • more common in adults
  • female:male ratio is 2:1

Pathology

• release of histamine & other mediators from mast cells possibly related to IgE-mediated release
  • 1/2 of patients with chronic idiopathic urticaria have IgE autoantibodies or antibodies against high-affinity IgE receptors on mast cells & basophils
• dilation of blood vessels with extravasation of fluid into the interstitium
• mixed infiltrate of leukocytes surrounding dilated vessels
• urticaria involves the epidermis & upper regions of the dermis in contrast to angioedema which involves deeper layers of the dermis & subcutaneous tissue

Clinical manifestations

• wheal (swelling) & flare (redness)
• elevated, well circumscribed, erythematous, edematous, pruritic lesions
  • serpinginous or annular rings with central clearing
  • outer border more brightly inflamed than center
  • papules or plaques
  • edema is non-pitting
  • can be linear, annular, circular, or arcuate
  • complete blanching of lesions with pressure
• angioedema of the face, hands & feet (not lips) in majority of patients
• in acute urticaria, lesions are transient
  • lesions appear quickly
  • episodes generally resolve spontaneously within 24-48 hours; most last 2-18 hours
  • urticaria due to insect bite or sting can last > 24 hours
  • lesions generally resolve without scarring or discoloration
  • lesions may recur in a new area with little or no period of remission
• chronic idiopathic urticaria
  • recurrent episodes of urticaria lasting > 6 weeks
    • episodes occur immediately & resolve quickly
  • episodes of angioedema generally occur, either alone or concurrently
  • 40% still have urticaria after 10 years
• tiny pinpoint hives are characteristic of cholinergic urticaria

* images

Laboratory

• diagnosis of acute urticaria is generally clinical & laboratory testing is generally not necessary prior to initiating treatment
• skin biopsy for suspected urticarial vasculitis
  • lesions lasting > 24-48 hours
  • lesions leaving discoloration
  • increased ESR or CRP
• urticaria of more than 6 weeks duration
  • complete blood count (CBC) with differential
    • eosinophilia suggests parasitic infection
      • strogyloidiasis, filariasis, trichinosis (periorbital edema)
  • increased erythrocyte sedimentation rate (ESR) or serum C-reactive protein (CRP) suggests vacsulitic urticaria
  • urinalysis
  • limited chemistry panel
  • MKSAP19 recommends against antinuclear antibodies (ANA)
  • thyroid function studies
  • serum complement, serum C3, serum C4
    • serum C4 screens for C1 esterase inhibitor deficiency
    • measurement of C1 esterase inhibitor not indicated
  • serum protein electrophoresis
  • routine lab testing generally not helpful
  • testing for food additives is rarely indicated
• serum IgE levels may be elevated with allergen exposure
  • MKSAP19 recommends against specific IgE measurements
• serum tryptase if anaphylaxis due to mastocytosis suspected

Radiology

• chest X-ray for urticaria of more than 6 weeks duration

Complications

• angioedema of the lips
  • patients with urticarial lesions around the mouth should be evaluated & monitored for airway obstruction
    • ICU admission is mentioned
• autoimmune disease may occur up to 10 years after onset of chronic urticaria - probably related more to a common etiology rather than a direct complication

Differential diagnosis

(lesions lasting > 24 hours)

• erythema multiforme
  • concentric annular rings of urticaria can be mistaken for target lesion of erythema multiforme
• urticarial vasculitis
  • lesions painful or burning rather than pruritic
  • lesions last > 24 hours
  • lesions resolve in 3-5 days with bruising (purpura/ecchymoses)
  • joint involvement suggests underlying autoimmune disease
  • skin biopsy for diagnosis
• serum sickness
  • fever, adenopathy, arthralgias, antigen or drug exposure
  • measure serum CRP, ESR, & serum complement, serum C3, serum C4
• anaphylaxis/angioedema
  • subcutaneous or submucosal form of urticaria due to extravasation of fluid into interstitial tissues
  • angioedema may occur with or without urticaria & may be a component of anaphylaxis
  • localized swelling, indistinct margins, normal or faint color
• parasitic infection:
  • strongyloidiasis, filariasis, trichinosis (esp periorbital edema)
  • marked eosinophilia
• livedo reticularis
• contact dermatitis
  • develops hours to days after contact with the offending agent
    • lasts for days to weeks

Management

• general
  • avoid mast cell degranulation
  • assess risk of angioedema
  • avoid workup unless specific cause suggested by history & physical examination
• pharmacologic agents
  • topical antipruritic lotions/creams
    • avoid topical antihistamines (ineffective, may result in contact dermatitis)
  • histamine H1-antagonists
    • non-sedating antihistamines treatment of choice for chronic or recurrent urticaria
      • loratadine (Claritin)
      • fexofenadine (Allegra)
      • cetirizine or levocetirizine (nonsedating antihistamine)
    • non-sedating antihistamines also treatment of choice for drug-induced urticaria
    • hydroxyzine (Atarax) 25-50 mg PO every 4-6 hours
    • diphenhydramine (Benadryl)
      • 25-50 mg PO every 4-6 hours
      • 10 mg IV cetirizine as effective as 50 mg IV diphenhydramine, with fever adverse effects
    • chlorpheniramine
    • doxepin (TCA with H1-antagonist activity)
  • addition of H2-antagonist for treatment of chronic or recurrent urticaria
    • can induce remission in 60-80% of patients
    • cimetidine, ranitidine, famotidine
    • doxepin with both H1- & H2-antagonist properties is often useful in treatment of chronic urticaria
  • leukotriene antagonist if no response to above
    • monteleukast, zafirlukast
    • benefit possible when added to antihistamines
      • do not meet minimal clinical importance thresholds
  • trial of calcium channel blocker
  • oral prednisone if very symptomatic
    • not useful added to an antihistamine
  • immumosuppressive agents may be necessary for chronic autoimmune urticaria
    • methotrexate
    • hydroxychloroquine
    • mycophenolate
    • azathioprine
    • cyclosporine
    • omalizumab (Xolair) an IgE monoclonal antibody
    • ligelizumab is another IgE monoclonal antibody
  • other immunomodulatory agents
  • colchicine
  • dapsone
  • antibiotics for H pylori infection
  • psychotherapy
    • biofeedback
    • stress relaxation
  • transcutaneous electrical nerve stimulation (TENS)
  • pulsed ultraviolet actinotherapy
• urticarial reactions lasting longer than 24-48 hours should be biopsied to rule out vasculitis & erythema multiforme
• patient education
  • avoid offending agent
  • food is the most common cause of acute urticaria
  • avoid NSAIDs (increased availability of arachidonate may worsen urticaria)
  • etiology of chronic urticaria (> 6 weeks duration) is unlikely to be identified
  • patients with angioedema shoud be instructed on the use of subcutaneous epinephrine & should carry an epinephrine autoinjector at all times

More general terms

• sign/symptom
• figurate dermatitis (rings, arcs)

More specific terms

• urticaria multiforme

Additional terms

• urticaria pigmentosa (UP)
• urticarial vasculitis

Patient information

urticaria patient information