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Urticaria and Angioedema Urticaria Angioedema
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Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Dec 26, 2015

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Page 1: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Urticaria and Angioedema

Urticaria Angioedema

Page 2: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Etiology of Urticarial Reactions:

Allergic Triggers

Acute UrticariaDrugs

Foods

Food additives

Viral infections–hepatitis A, B, C–Epstein-Barr virus

Insect bites and stings

Contactants and inhalants (includes animal dander and latex)

Chronic UrticariaPhysical factors–cold–heat–dermatographic–pressure–solar

Idiopathic

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The Pathogenesis of Chronic Urticaria:

Cellular Mediators

Page 4: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Histamine as a Mast Cell Mediator

Page 5: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Role of Mast Cells in Chronic Urticaria:

Lower Threshold for Histamine Release

Release threshold decreased by:Cytokines & chemokines

in the cutaneous microenvironment

Antigen exposureHistamine-releasing factorAutoantibodyPsychological factors

Release threshold increased by:CorticosteroidsAntihistaminesCromolyn (in vitro)

Cutaneous mass cell

Page 6: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

An Autoimmune Basis for Chronic

Idiopathic Urticaria: Antibodies to IgE

Page 7: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Initial Workup of Urticaria

Patient historySinusitisArthritisThyroid diseaseCutaneous fungal infectionsUrinary tract symptomsUpper respiratory tract infection

(particularly important in children)Travel history (parasitic infection)Sore throatEpstein-Barr virus, infectious

mononucleosisInsect stingsFoodsRecent transfusions with

blood products (hepatitis)Recent initiation of drugs

Physical examSkinEyesEarsThroatLymph nodesFeetLungsJointsAbdomen

Page 8: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Laboratory Assessment for

Chronic Urticaria

Possible tests for selected patientsStool examination for ova

and parasitesBlood chemistry profileAntinuclear antibody titer (ANA)Hepatitis B and CSkin tests for IgE-mediated

reactions

Initial testsCBC with differentialErythrocyte sedimentation rateUrinalysis

RAST for specific IgEComplement studies: CH50

CryoproteinsThyroid microsomal antibodyAntithyroglobulinThyroid stimulating hormone (TSH)

Page 9: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Histopathology

Polymorphous perivascular infiltrate

NeutrophilsEosinophilsMononuclear cells

Sparse perivascular lymphocytes

Page 10: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.
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Urticaria/Angioedema

Definition– affects more than 20% of the population at some time in their lives– smooth, evanescent, edematous lesion (wheals)– heat, drugs, infections, and emotional stress are the most frequent

triggers

Classification– acute if duration < 6 wks, otherwise chronic– 3 major groups: (a) immunologic urticaria; (b) non-immunologic

urticaria; c: idiopathic urticaria

Page 12: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Allergic reactions: AngioedemaAllergic reactions: Angioedema

Usually localised (to head & neck) but may be more generalised (especially GI) +/- urticaria. Presents as swelling of the face, neck and oropharynx. Represents mast cell degranulation in skin deep to dermis vs. superficial dermis in urticaria.

• InheritedInherited - C1 esterase inhibitor deficiency due to mutation (autosomal dominant) of the C1-INH gene.

• AcquiredAcquired - usually autoantibodies to C1-INH in the context of autoimmune disease or lymphoproliferative disorders. Rarer reports of hypercatabolism of C1-INH in infection.

• Drug-inducedDrug-induced - commonest culprit ACE inhibitors.

Page 13: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

• MechanismMechanism probably related to massive elevation of BK but unclear why it can appear days to years after 1st dosing.

• IncidenceIncidence probably <0.1% - Afro-Caribbean and renal/cardiac transplant patients may be at increased risk.

• Treatment Treatment is usually with standard therapy for an anaphylactic reaction +/- inhaled Epi but not mast cell dependent! If airway threatened, intubation or tracheostomy If airway threatened, intubation or tracheostomy needed.needed.

• Under recognisedUnder recognised especially in milder forms. ACE inhibitors should be stopped and an AT2 receptor antagonist substituted if necessary (e.g. Losartan) BUT isolated reports have appeared of angioedema with these agents!

• NewNew combined ACE/NEP inhibitors suffer same problem.

ACE inhibitors & AngioedemaACE inhibitors & Angioedema

Page 14: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Common Causes of Acute Urticaria

IdiopathicImmune-mediated (IgE)

– foods (shellfish, nuts)– drugs

Noimmune-mediated – opiates

Nonspecific– viral infections (influenza)– bacterial infections (occult abscess, mycoplasma)

Page 15: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Urticaria Associated With

Other Conditions

Collagen vascular disease (eg, systemic lupus erythematosus)

Complement deficiency, viral infections (including hepatitis B and C), serum sickness, and allergic drug eruptions

Chronic tinea pedis

Pruritic urticarial papules and plaques of pregnancy (PUPPP)

Schnitzler’s syndrome

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Therapy for Urticaria

Abbreviated search for triggers– treat the treatable causes

Anti-histamines – Short-acting (Benadryl, Atarax)– Long-acting (Claritin, Reactine)

Corticosteroids– start around 1 mg/kg/day (single or divided doses)

Page 31: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Treatment of Urticaria:

Pharmacologic Options

Antihistamines, othersFirst-generation H1

Second-generation H1

Antihistamine/decongestant combinations

Tricyclic antidepressants (eg, doxepin)

Combined H1 and H2 agents

Beta-adrenergic agonistsEpinephrine for acute urticaria

(rapid but short-lived response)Terbutaline

CorticosteroidsSevere acute urticaria–avoid long-term use–use alternate-day regimen

when possibleAvoid in chronic urticaria

(lowest dose plus antihistamines might be necessary)

MiscellaneousPUVAHydroxychloroquineThyroxine

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H1-Receptor Antagonists:

Pros and Cons for Urticaria and Angioedema

First-generation antihistamines (diphenhydramine and hydroxyzine)

Advantages: Rapid onset of action, relatively inexpensive

Disadvantages: Sedating, anticholinergic

Second-generation antihistamines (astemizole, cetirizine, fexofenadine, loratadine)

Advantages: No sedation (except cetirizine); no adverse anticholinergic effects; bid and qd dosing

Disadvantages: Prolongation of QT interval; ventricular tachycardia (astemizole only) in a patient subgroup

Page 33: Urticaria and Angioedema UrticariaAngioedema. Etiology of Urticarial Reactions: Allergic Triggers Acute Urticaria l Drugs l Foods l Food additives l Viral.

Four-week Treatment Period:

Fexofenadine HCl

Mean Pruritus Scores/Mean Number of Wheals/Mean Total Symptom Scores

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An Approach to the Treatment of

Chronic Urticaria