Basics
Description
- Urticarial lesions are best described as raised, pruritic, circumscribed erythematous papules.
- Single lesions may coalesce as they enlarge, forming generalized, raised, erythematous areas.
- Transient, typically lasting several hours
- Also known as "hives " Ł or "nettle rash " Ł
- Acute: <6 weeks ' duration
- Chronic: >6 weeks ' duration
- Other similar but non-urticarial entities:
- Angioedema
- Urticarial-like lesions
- Form in the deep dermal, subcutaneous, and submucosal layers
- Anaphylaxis
- Hypersensitivity reaction after exposure to an antigen
- Producing respiratory compromise secondary to airway edema, urticarial rash, pruritus, and hypotension; can lead to shock
Epidemiology
- Female-to-male ratio of 3:2
- No variation in race
Incidence
Lifetime incidence of 15 " ô25% é á
General Prevention
When a trigger is identified, avoidance is the main preventive measure. é á
Pathophysiology
- Immune mediated
- Antigen is cross-linked to IgE on a mast cell.
- This causes mast cell activation, leading to the release of vasoactive mediators, such as histamine, leukotrienes, prostaglandin D2, platelet-activating factor, and other vasoactive mediators.
- These vasoactive mediators cause pruritus, vasodilatation, and capillary leak, which lead to the characteristic findings.
- Common triggers include some medications such as penicillins, foods such as milk or eggs, and envenomations.
- Non " ôimmune mediated
- Degranulation of mast cells secondary to other non-IgE reactions such as physical changes, chemicals, some medications such as beta-lactams and sulfa-containing drugs, and some foods
- Autoimmune mediated
- Degranulation of mast cells caused by cross-linking of IgE by IgG or IgG binding to the high-affinity IgE (Fc Ä ÁRI) receptor on mast cells
Etiology
Acute urticaria é á
- Viral infections are thought to make up ó ł ╝80% of all cases of acute urticaria in children. Most commonly isolated causes include the following viruses:
- Epstein-Barr
- Coxsackievirus A and B
- Hepatitis A, B, and C
- Parasitic infections
- Bacterial infections (especially group A strep)
- Medications: most frequently reported include the following:
- Radiocontrast
- Foods
- Transfusion of blood products
- Food additives and dyes
- Natural remedies including cranberry, feverfew, glucosamine, and ginger
- Insect venom including bees, wasps, hornets
Chronic urticaria é á
- Idiopathic: Most have an unknown cause, but many feel that an association with an autoimmune mechanism is likely.
- Physical ( ó ł ╝20 " ô30%)
- Dermatographism (9%): Stroking of skin using mild to moderate pressure with fingernail or hard object causes linear urticaria at site of contact.
- Cholinergic (5%): diffuse erythema and elevated but pale urticarial lesions; intense pruritus; associated with sweating reflex, so often associated with overheating or exertion; may be worsened in combination with other triggers in specific combinations
- Cold (3%): Urticarial lesions present at areas of skin exposed to low temperatures; familial and nonhereditary forms
- Aquagenic: Urticarial lesions arise when the patient is exposed to water (e.g., bathtub, swimming pool).
- Delayed pressure/vibratory: Deep or prolonged pressure on skin produces significant urticaria and often angioedema. Vibratory urticaria is a form of delayed pressure urticaria caused by repetitive vibration (e.g., use of a jackhammer).
- Mast cell disease
- Urticaria pigmentosa: excessive number of mast cells in skin, bone marrow, lymph nodes, and other tissues; flares characterized by pruritus, flushing, tachycardia, nausea, and vomiting
- Systemic mastocytosis
- Systemic disease
- Rheumatologic
- Urticarial vasculitis: erythematous wheals that resemble urticaria but histologically appear as leukocytoclastic vasculitis; often presents with systemic symptoms and lasts >24 hours
- Cryopyrin-associated periodic syndromes can present with urticaria, such as Muckle-Wells syndrome: chronic recurrent urticaria, deafness, amyloidosis, and arthritis.
- Neoplasms
- Infections: parasites especially noted to cause chronic urticaria
- Autoimmune: antibodies to IgE or IgE receptor (Fc Ä ÁRI)
Diagnosis
History
- Description of rash: Lesions may not be present at time of exam due to transient nature. Digital photos are often useful.
- Duration of symptoms, acute versus chronic:
- If acute (<6 weeks), ask about
- Viral symptoms including rhinorrhea, cough, fever, congestion, malaise
- Any medications (prescription or over the counter) or any herbal remedies
- Any new foods or beverages
- Any new exposures to perfumes, chemicals, or other skin products
- If chronic (>6 weeks)
- History of previous episodes including timing, exposures, any past history of urticaria or angioedema
- Other symptoms or variations in presentation
- Symptoms of systemic diseases, such as hyperthyroidism, systemic lupus erythematosus (SLE), juvenile idiopathic arthritis, myositis, amyloidosis, infections, and lymphoma
- Duration of lesions
Physical Exam
- Appearance of rash: classic wheal and flare appearance
- Respiratory: Look for evidence of stridor, wheezing, or dyspnea. If present, be concerned for airway compromise or lower airway edema from an anaphylactic reaction.
- Facial or neck swelling: concern for possible airway compromise
- A full physical exam should be performed to look for signs of systemic disease or malignancy, such as
- Upper respiratory tract infections
- Thyromegaly
- Lymphadenopathy or splenomegaly to suggest lymphoma
- Joint examination for any evidence of connective tissue disease, arthritis, or SLE
Diagnostic Tests & Interpretation
Lab
- Testing is often fruitless unless indicated by history and physical examination.
- Skin testing may be performed if the causative agent is thought to be 1 of several food items.
- If symptoms are difficult to handle or persist >3 months, consider
- CBC with differential
- ESR
- Thyroid studies (thyroid-stimulating hormone [TSH], free T4, antithyroglobulin, and antiperoxisomal antibody)
- If symptoms are atypical, last >1 year, or are suggestive of urticarial vasculitis
- Complement studies
- ANA titer
- Liver function tests
- Skin punch biopsy
Differential Diagnosis
- Viral exanthema
- Atopic dermatitis
- Contact dermatitis
- Insect bites
- Maculopapular drug rash
- Erythema multiforme
- Plant-induced eruptions
- Henoch-Sch â Ânlein purpura
- SLE
- Autoinflammatory disease
- Systemic onset juvenile idiopathic arthritis
- Cryopyrin-associated periodic syndromes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, neonatal onset multisystem inflammatory disease (NOMID)
- Mevalonate kinase deficiency
- Tumor necrosis factor-receptor " ôassociated periodic syndrome (TRAPS)
Treatment
Emergent treatment: If with any difficulty breathing, stridor or wheezing, or other signs of anaphylaxis, give epinephrine 0.01 mL/kg of the 1:1,000 solution SC/IM. é á
Medication
- Acute urticaria
- Usually self-resolving but can treat with 2nd-generation nonsedating antihistamines
- 1st-generation antihistamines: diphenhydramine 1 mg/kg/dose or total 5 mg/kg/d divided PO q6h or hydroxyzine 2 mg/kg/day PO divided q6h for pruritus
- Chronic urticaria: See below.
First Line
- Antihistamines/H1 antagonists:
- Less sedating, longer acting, and should be mainstay of therapy
- Cetirizine (Zyrtec): Dosing varies by age from 2.5 to 10 mg daily.
- Loratadine (Claritin): 5 mg daily
- Fexofenadine (Allegra): 6 months to <2 years of age, 15 mg twice daily; 2 " ô11 years of age, 30 mg twice daily; and >12 years of age, 60 mg twice daily. 1st-generation antihistamines are effective but more sedating:
- Diphenhydramine (Benadryl): 5 mg/kg/day divided q6h
- Hydroxyzine (Atarax): 0.5 mg/kg/dose q6h
- Cyproheptadine (Periactin): 2 mg up to 3 times a day: primary treatment for cold urticaria
Second Line
Increase 2nd-generation H1 antagonist dose to maximum for age. In adult guidelines, increasing the dose up to 4-fold is more effective. é á
Third Line
- Addition of a second nonsedating 2nd-generation H1 antihistamine
- Leukotriene inhibitors: minimal additive response noted in clinical studies
- Montelukast (Singulair): 5 mg daily
- Combined H1 and H2 antagonists
- H2 antagonists: added as 2nd agent because skin cells have both H1 and H2 receptors and a synergistic effect can be achieved by addition of an H2 blocker
- Ranitidine (Zantac): 2 " ô4 mg/kg/day divided twice daily
- Doxepin (Sinequan): a tricyclic antidepressant. >12 years of age, 10 " ô50 mg/day and can slowly titer up to 100 mg/day; potent antihistamine but poorly tolerated due to sedation, hypotension, anticholinergic side effects, and massive weight gain
- Other immune-modifying agents used in chronic urticaria:
- Other nonstandard therapies have been tried in small case studies: cyclosporine, colchicine, dapsone, IV immunoglobulin (IVIG), plasmapheresis, methotrexate, cyclophosphamide, calcium channel blockers, ephedrine
- Corticosteroids: Titer to lowest effective dose. Start with standard dose of 0.5 " ô1 mg/kg/day of prednisone; often poorly tolerated secondary to substantial side effects including hypertension, immunosuppression, hyperglycemia, physical changes
- Omalizumab: Anti-IgE antibody has been shown to reduce signs and symptoms of chronic urticaria in those at maximum standard therapies.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Watch for signs and symptoms of anaphylaxis; this is the major complication.
- Patients with chronic urticaria should follow up with their physician on a regular basis to monitor symptoms and response to therapies.
Prognosis
- Chronic urticaria
- Resolution in 50% by 12 months
- Another 20% resolve by 5 years
- 10 " ô20% >20 years; many of those who continue to have symptoms are felt to have an autoimmune etiology.
- May have recurrences; physical urticaria subtypes are more likely to recur.
Complications
Anaphylaxis with resulting edema of the upper airway is the major life-threatening complication. The patient should seek immediate medical attention. é á
Additional Reading
- Bailey é áE, Shaker é áM. An update on childhood urticaria and angioedema. Curr Opin Pediatr. 2008;20(4):425 " ô430. é á[View Abstract]
- Dibbern é áDA Jr. Urticaria: selected highlights and recent advances. Med Clin North Am. 2006;90(1):187 " ô209. é á[View Abstract]
- Dibbern é áDA Jr, Dreskin é áS. Urticaria and angioedema: an overview. Immunol Allergy Clin North Am. 2004;24(2):141 " ô162. é á[View Abstract]
- Kaplan é áA, Ledford é áD, Ashby é áM, et al. Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol. 2013;132(1):101 " ô109. é á[View Abstract]
- Krause é áK, Grattan é áCE, Bindslev-Jensen é áC, et al. How not to miss autoinflammatory disease masquerading as urticarial. Allergy. 2012;67(12);1465 " ô1474. é á[View Abstract]
- Powell é áRJ, Du Toit é áGL, Siddique é áN, et al. BSACI guidelines for the management of chronic urticaria and angio-oedema. Clin Exp Allergy. 2007;37(5):631 " ô650. é á[View Abstract]
- Sheikh é áJ. Advances in the treatment of chronic urticaria. Immunol Allergy Clin North Am. 2004;24(2):317 " ô334. é á[View Abstract]
- Zuberbier é áT, Asero é áR, Bindslev-Jensen é áC, et al. EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria. Allergy. 2009;64(10):1427 " ô1443. é á[View Abstract]
Codes
ICD09
- 708.9 Urticaria, unspecified
- 708.0 Allergic urticaria
- 708.8 Other specified urticaria
- 708.1 Idiopathic urticaria
ICD10
- L50.9 Urticaria, unspecified
- L50.0 Allergic urticaria
- L50.6 Contact urticaria
- L50.8 Other urticaria
SNOMED
- 126485001 urticaria (disorder)
- 402304007 Allergic contact urticaria (disorder)
- 402408009 acute urticaria (disorder)
- 51611005 Chronic urticaria (disorder)
FAQ
- Q: When should I refer patients to a specialist, and to what specialty should I send them?
- A: Often, referral is made when a trigger cannot be identified, if it is felt to be a food or medication trigger, and/or the symptoms persist for >6 weeks. Refer to a dermatologist or allergist " ôimmunologist experienced in the evaluation and workup of urticaria.
- Q: When should treatment with corticosteroids or other nonstandard therapies be used to treat chronic urticaria?
- A: Typically, these medications carry significant side effects and should be reserved for those patients in whom the urticaria is causing significant alterations in activities of daily living.
- Q: When does a patient need to be hospitalized or observed during an episode of urticaria?
- A: Concerning signs include extensive angioedema, respiratory symptoms such as stridor or wheezing, or nausea/vomiting. Symptoms of anaphylaxis should be treated with epinephrine and the patient observed for several hours to ensure that symptoms do not recur.