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urticaria (hives)

Wheal (swelling) & flare (redness) response to histamine release. Classification: - acute: daily for < 6 weeks - chronic: daily for > 6 weeks Etiology: 1) food allergy a) common cause of acute urticaria - shellfish, peanuts, tree nuts b) occurs within 30 minutes of eating food [29] c) almost never causes chronic urticaria d) food additives almost never cause chronic urticaria [11] e) pollen-food allergy syndrome (ragwood allergy & ingestion of melons) 2) pharmacologic agents (common, perhaps most common cause) a) aspirin b) barbiturates c) captopril d) enalapril e) penicillins (can occur up to 14 days after treatment) [26] f) sulfonamides g) NSAIDs [29] 3) insect bite or sting (lesions can last > 24 hours) 4) airborne allergens - pollens - pollen-food allergy syndrome - mold & house dust mites not associated with urticaria [29] 5) contact allergens a) animal dander b) latex c) plants 6) infections: a) bacterial (H pylori) b) viral (hepatitis B) c) fungal d) helminth 7) intravenous radioactive iodine contrast agent 8) transfusion reactions 9) physical factors a) demographism (writing on the skin) b) vibratory urticaria, vibratory angioedema c) solar urticaria d) localized heat urticaria e) cold-induced urticaria - generally noted within minutes f) aquatic urticaria g) pressure urticaria 1] immediate 5-10 minutes 2] delayed 4-6 hours: may be associated with systemic symptoms (i.e. fever, systemic inflammation) h) cholinergic urticaria 1] following hot shower or exercising in humid environment 2] typically around neck, wheals small 10) autoimmune disease a) cryoglobulinemia b) lupus erythematosus c) rheumatoid arthritis d) Sjogren's syndrome e) serum sickness f) premenstrual urticaria (antibodies to IgE & progesterone implicated) g) Hashimoto's thyroiditis (hypothyroidism) h) Grave's disease (hyperthyroidism) i) Diabetes mellitus type 1 k) may occur up to 10 years after onset of urticaria l) autoimmune diseases are 17 times more common in patients with idiopathic urticaria than in general population [8] 11) malignancies a) acquired complement C1 & C1 inhibitor depletion b) Hodgkin's disease c) non-Hodgkin's lymphoma 12) urticaria pigmentosum (systemic mastocytosis) 13) urticarial vasculitis 14) hereditary disorders a) hereditary angioedema b) familial cold urticaria c) C3b inactivator deficiency d) amyloidosis with deafness & urticaria 15) chronic idiopathic urticaria a) may be autoimmune disorder b) may be due to IgG directed against alpha chain of IgE receptor on mast cells c) hepatitis C [4] d) Schnitzler syndrome 16) psychogenic factors & hyperthyroidism can exacerbate urticaria, but cannot be sole cause 17) idiopathic (common,50%) [26] Epidemiology: 1) occurs in 20-25% of population at some time [26] 2) chronic urticaria (daily for > 6 weeks) a) more common in adults b) female:male ratio is 2:1 Pathology: 1) 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 [8] 2) dilation of blood vessels with extravasation of fluid into the interstitium 3) mixed infiltrate of leukocytes surrounding dilated vessels 4) urticaria involves the epidermis & upper regions of the dermis in contrast to angioedema which involves deeper layers of the dermis & subcutaneous tissue Clinical manifestations: 1) wheal (swelling) & flare (redness) 2) elevated, well circumscribed, erythematous, edematous, pruritic lesions a) serpinginous or annular rings with central clearing b) outer border more brightly inflamed than center c) papules or plaques d) edema is non-pitting e) can be linear, annular, circular, or arcuate [26] f) complete blanching of lesions with pressure [26] 3) angioedema of the face, hands & feet (not lips) in majority of patients [26] 4) 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 [26] - lesions generally resolve without scarring or discoloration - lesions may recur in a new area with little or no period of remission [4] 5) chronic idiopathic urticaria a) recurrent episodes of urticaria lasting > 6 weeks - episodes occur immediately & resolve quickly [26] b) episodes of angioedema generally occur, either alone or concurrently c) 40% still have urticaria after 10 years 6) tiny pinpoint hives are characteristic of cholinergic urticaria [26] * images [15,16] Laboratory: 1) diagnosis of acute urticaria is generally clinical & laboratory testing is generally not necessary prior to initiating treatment [4] 2) skin biopsy for suspected urticarial vasculitis a) lesions lasting > 24-48 hours b) lesions leaving discoloration c) increased ESR or CRP 3) urticaria of more than 6 weeks duration a) complete blood count (CBC) with differential - eosinophilia suggests parasitic infection - strogyloidiasis, filariasis, trichinosis (periorbital edema) b) increased erythrocyte sedimentation rate (ESR) or serum C-reactive protein (CRP) suggests vacsulitic urticaria c) urinalysis d) limited chemistry panel e) MKSAP19 recommends against antinuclear antibodies (ANA) [4] f) thyroid function studies g) serum complement, serum C3, serum C4 [4] - serum C4 screens for C1 esterase inhibitor deficiency [28] - measurement of C1 esterase inhibitor not indicated [4] h) serum protein electrophoresis [4] i) routine lab testing generally not helpful [6,23] j) testing for food additives is rarely indicated [11] 4) serum IgE levels may be elevated with allergen exposure - MKSAP19 recommends against specific IgE measurements [4] 5) serum tryptase if anaphylaxis due to mastocytosis suspected Radiology: - chest X-ray for urticaria of more than 6 weeks duration Differential diagnosis: (lesions lasting > 24 hours) 1) erythema multiforme - concentric annular rings of urticaria can be mistaken for target lesion of erythema multiforme [4] 2) urticarial vasculitis [30] - lesions painful or burning rather than pruritic - lesions last > 24 hours [4] - lesions resolve in 3-5 days with bruising (purpura/ecchymoses) - joint involvement suggests underlying autoimmune disease - skin biopsy for diagnosis [4] 3) serum sickness - fever, adenopathy, arthralgias, antigen or drug exposure - measure serum CRP, ESR, & serum complement, serum C3, serum C4 [4] 4) 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 5) parasitic infection: - strongyloidiasis, filariasis, trichinosis (esp periorbital edema) - marked eosinophilia 6) livedo reticularis 7) contact dermatitis [26] - develops hours to days after contact with the offending agent - lasts for days to weeks [26] Complications: - angioedema of the lips - patients with urticarial lesions around the mouth should be evaluated & monitored for airway obstruction - ICU admission is mentioned [4] - 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 [8] Management: 1) general a) avoid mast cell degranulation b) assess risk of angioedema c) avoid workup unless specific cause suggested by history & physical examination [4] 2) pharmacologic agents a) topical antipruritic lotions/creams - avoid topical antihistamines (ineffective, may result in contact dermatitis) [4] b) histamine H1-antagonists - non-sedating antihistamines treatment of choice for chronic or recurrent urticaria [29] - loratadine (Claritin) - fexofenadine (Allegra) - cetirizine or levocetirizine (nonsedating antihistamine) - non-sedating antihistamines also treatment of choice for drug-induced urticaria [31] - 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 [24] - chlorpheniramine - doxepin (TCA with H1-antagonist activity) c) addition of H2-antagonist for treatment of chronic or recurrent urticaria - can induce remission in 60-80% of patients - cimetidine, ranitidine, famotidine [4] - doxepin with both H1- & H2-antagonist properties is often useful in treatment of chronic urticaria d) leukotriene antagonist if no response to above - monteleukast, zafirlukast [4] - benefit possible when added to antihistamines [33] - do not meet minimal clinical importance thresholds [33] e) trial of calcium channel blocker [4] f) oral prednisone if very symptomatic [4] - not useful added to an antihistamine [19] g) immumosuppressive agents may be necessary for chronic autoimmune urticaria - methotrexate - hydroxychloroquine - mycophenolate - azathioprine - cyclosporine [4] - omalizumab (Xolair) an IgE monoclonal antibody [7,12,13,25] - ligelizumab is another IgE monoclonal antibody [22,25] h) other immunomodulatory agents a) colchicine b) dapsone [21] i) antibiotics for H pylori infection [4] j) psychotherapy - biofeedback - stress relaxation k) transcutaneous electrical nerve stimulation (TENS) l) pulsed ultraviolet actinotherapy 3) urticarial reactions lasting longer than 24-48 hours should be biopsied to rule out vasculitis & erythema multiforme 4) patient education a) avoid offending agent b) food is the most common cause of acute urticaria c) avoid NSAIDs (increased availability of arachidonate may worsen urticaria) d) etiology of chronic urticaria (> 6 weeks duration) is unlikely to be identified e) patients with angioedema shoud be instructed on the use of subcutaneous epinephrine & should carry an epinephrine autoinjector at all times [4]

Related

urticaria pigmentosa (UP) urticarial vasculitis

Specific

urticaria multiforme

General

sign/symptom figurate dermatitis (rings, arcs)

References

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