Urticaria

Urticaria is an inflammatory skin disorder characterized by hives (wheals) with or without angioedema. Urticaria is classified as acute (≤ 6 weeks duration) or chronic (> 6 weeks duration). Causes of urticaria vary and include food allergies, environmental factors (e.g., cold, heat), and systemic conditions (e.g., vasculitis, infections, malignancy). Acute urticaria is often self-limited, and a trigger may not be identified. Chronic urticaria usually requires further testing (e.g., in vivo allergy skin tests) to establish the cause and assess for underlying conditions (e.g., autoimmune diseases). The mainstay of treatment is second-generation antihistamines and avoidance of identified triggers and/or management of underlying conditions.

• Urticaria: : an inflammatory skin disorder characterized by hives with or without angioedema ^[1]
• Hives: (wheals): well-circumscribed, pruritic, and erythematous plaques (round, oval, or serpiginous) that can be several centimeters in diameter ^[1]
• Acute urticaria: urticaria that lasts ≤ 6 weeks ^[1]
• Chronic urticaria: continuous or intermittent urticaria that lasts > 6 weeks ^[1]

Urticaria may be spontaneous or induced. ^[2]

Type I hypersensitivity reaction (HSR) and pseudoallergy ^[2]

• Foods, especially the big 9 food allergens, i.e.: ^[3]
  • Animal products: milk, eggs, fish, shellfish
  • Legumes: tree nuts, peanuts, soybeans
  • Other: wheat, sesame
• Insect stings or bites, e.g., Hymenoptera stings
• Contact allergens, e.g., latex
• Medications (IgE or non-IgE-mediated), e.g.:
  • Sulfonamides
  • Antibiotics, e.g., beta-lactams, vancomycin
  • Anticonvulsants
  • NSAIDs, opioids
  • Chemotherapy agents
  • Radiocontrast media

Physical urticaria triggers ^[2]

• Cold exposure
• Sunlight
• Pressure
• Vibration

Infectious diseases (infection-induced urticaria) ^[2]

• Viruses, e.g., rotavirus, rhinovirus, HBV, HCV, EBV, HSV, parvovirus B19
• Bacteria, e.g., Mycoplasma pneumoniae, group A streptococcus, Helicobacter pylori
• Parasitic infections, e.g., Anisakis simplex, Plasmodium falciparum

Systemic conditions ^[2]

• Cutaneous small-vessel vasculitis (CSVV)
• Multiple myeloma

Hormonal changes ^[2]

• Pregnancy
• Menstruation
• Hormonal therapies
• Thyroid disease

Other ^[2]

• Cholinergic urticaria: heat, exercise, sweating
• Emotional stress
• Aquagenic urticaria (water)

• Trigger (urticaria may occur spontaneously) → mast cell activation and degranulation in the superficial dermis → microvasculature hyperpermeability → edema ^[1]
• Pseudoallergy causes direct release of vasoactive substances from mast cells without IgE involvement. ^[4]

Urticaria is not always a type I HSR. ^[1][4]

• ABCDE approach
• If diagnostic criteria for anaphylaxis are met:
  • Administer IM epinephrine.
  • Initiate immediate hemodynamic support (e.g., IV fluids, supplemental oxygen).
  • Alert the ICU and/or consult anesthesiology.
  • See “Management of anaphylaxis” and “Management of angioedema” for treatment algorithms.
• If there is airway compromise: See “Airway management and ventilation in anaphylaxis.”
• Perform a thorough clinical evaluation.
• Exclude urticaria mimics.
• Consider the need for additional diagnostics based on the clinical evaluation.
• Provide symptomatic urticaria management for all patients.

Signs of anaphylaxis include abdominal pain, dizziness, shortness of breath, stridor, and tachycardia. ^[1]

Acute urticaria is often self-limited, and laboratory studies are usually not required. ^[1]

Focused history ^[1][5][6]

• Approximate date of onset (acute vs. chronic)
• Recent exposures, e.g.:
  • New foods (e.g., in infants)
  • Medical interventions (e.g., imaging studies with contrast, vaccinations, medications)
  • Travel or time spent in nature
• Duration and associated symptoms
  • Typical hives
    • Lesions resolve within 24 hours ^[1][5]
    • Pruritis or a burning sensation
  • Atypical hives
    • Lesions persist > 24–48 hours
    • May be painful
• Personal and/or family history
  • Urticaria or isolated angioedema (including any treatment received)
  • Atopy
  • Type I HSR (e.g., to food, medications, latex)
  • Systemic diseases (e.g., RA, SLE, T1DM)

Focused examination ^[1][5][6]

• Clinical features of angioedema, e.g., facial edema, inspiratory stridor
• Typical hives
  • Well-circumscribed, erythematous round, oval, or serpiginous plaques
  • Variable size: may be several centimeters in diameter
  • Blanchable with pressure
  • No residual hyperpigmentation
• Atypical hives
  • Purpuric (may indicate an underlying systemic condition)
  • Residual hyperpigmentation
• Assess for dermographism.
• Record the distribution of the lesions, e.g., limited to exposed areas in patients with physical urticaria.
• Ask for pictures if there are no lesions at the time of evaluation.

Features of atypical hives include duration more than 24–48 hours for an individual lesion, pain, residual hyperpigmentation, and purpura, and they may suggest an underlying systemic condition (e.g., CSVV). ^[1][2]

The following applies to hives with or without angioedema. For isolated angioedema, see “Angioedema.”

Approach ^[1][2][5][6]

• Acute urticaria
  • Routine diagnostic studies are not indicated for spontaneous, typical hives.
  • Obtain targeted testing for patients with:
    • Atypical hives
    • Identified potential triggers (e.g., food allergy, drug hypersensitivity reaction, infection)
• Chronic urticaria: There is no consensus on the optimal evaluation of chronic urticaria; consult an allergist. ^[5]
  • Typical hives and suspected chronic spontaneous urticaria: initial diagnostic tests followed by targeted testing
  • Atypical hives or suspected chronic inducible urticaria: targeted testing based on clinical suspicion

Initial diagnostic tests ^[5]

• CBC with differential
• Inflammatory markers, e.g., CRP, ESR
• Specialized testing: anti-TPO, total IgE
• Consider additional tests, e.g., liver enzymes, LDH, TSH ^[1]

Targeted testing ^[1][5]

• Allergy testing
  • Hypersensitivity blood tests
  • In vivo allergy skin tests
  • Challenge tests (e.g., graded challenge test, oral food challenge) to rule out unlikely drug or food hypersensitivity reactions
• Physical urticaria provocation tests: based on the suspected cause or trigger ^[2][5]
  • Scratching the skin for suspected dermographism
  • Ice cube in a plastic bag for suspected cold urticaria
  • Exercise or hot bath for suspected cholinergic urticaria
• Autoimmune disease workup
  • Laboratory studies
    • ANAs, ANCA, RF, complement levels
    • Thyroid autoantibodies
  • Skin biopsy: if vasculitis is suspected
• Infectious disease workup
  • Hepatitis B serology and hepatitis C serology
  • HIV screening
  • Stool analysis for ova and parasites
• Malignancy workup
  • Serum and urine protein electrophoresis for multiple myeloma
  • Biopsy of affected organs, e.g., bone marrow biopsy for leukemia

Causes of acute urticaria

Causes of chronic urticaria

Hashimoto thyroiditis is the most frequent autoimmune disease associated with chronic spontaneous urticaria. ^[2]

General principles ^[1][5][6]

• Provide symptomatic management of urticaria with a second-generation antihistamine (e.g., cetirizine).
• Educate patients on avoidance of identified triggers and nonspecific triggers such as stress and NSAIDs. ^[5]
• A trigger for acute urticaria may not be identified; most cases are self-limited. ^[5]
• Management of chronic spontaneous urticaria consists of identifying and treating underlying conditions, e.g., infections, malignancy.
• Follow-up should be performed after 2–6 weeks to assess the response. ^[1]

Symptomatic urticaria management ^[2][5][6]

• Second-generation antihistamines: first line
  • Indications: acute; (off-label) and chronic urticaria
  • Agents: cetirizine , loratadine , OR fexofenadine
  • Use should be scheduled rather than on demand until hives resolve.
• Glucocorticoids (in consultation with a specialist) ^[2][5]
  • Indication: severe urticaria exacerbations
  • Short courses (< 10 days) of systemic glucocorticoids (e.g., prednisone) may be considered.
• Additional therapy: combination therapy with second-generation antihistamines
  • Indication: refractory chronic urticaria
  • Agents
    • Omalizumab (off-label) ^[5]
    • Cyclosporine (off-label) ^[2]
    • Other agents, e.g., montelukast, famotidine, biologic agents (low level of evidence)

Approximately 60% of acute urticaria cases resolve within 1 week. ^[2]

First-generation antihistamines should be used with caution, especially in older adults and children, due to their potential serious adverse effects (e.g., sedation, motor function impairment). ^[1][5]

• Atopic dermatitis
• Fixed drug eruptions
• Contact dermatitis
• Erythema multiforme
• Papular urticaria
• IgA vasculitis
• Pityriasis rosea
• Viral exanthem
• Urticaria pigmentosa
• CSVV, e.g., urticarial vasculitis ^[7]
• Cryoglobulinemic vasculitis
• See also “Overview of annular skin lesions.”

Urticaria in children ^[5]

• Epidemiology
  • Pediatric acute urticaria most commonly occurs in children < 3 years of age.
  • Chronic urticaria is less common and has a more favorable prognosis in children than in adults.
• Etiology
  • Generally the same as for adults
  • Viral infections, food allergies, and drug hypersensitivity reactions are more common in young children than in older children.
• Management: Diagnosis and management are typically the same as for adults; see “Management.”

Urticaria in pregnant and breastfeeding individuals ^[5]

• Etiology is generally the same as for other adults; especially consider hormonal causes, e.g.:
  • Estrogen-dependent angioedema (type III hereditary angioedema)
  • Gestational pemphigoid
  • Polymorphic eruption of pregnancy
• Management ^[5]
  • Use shared decision-making to determine the risks and benefits of systemic medications during pregnancy.
  • Antihistamines
    • Avoid first-generation antihistamines.
    • Second-generation antihistamines can be considered.
  • Omalizumab is generally considered to be safe.
  • Cyclosporine is associated with embryotoxicity. ^[5]