urticaria and angioedema urticariaangioedema. etiology of urticarial reactions: allergic triggers...
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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
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
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
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)
Histopathology
Polymorphous perivascular infiltrate
NeutrophilsEosinophilsMononuclear cells
Sparse perivascular lymphocytes
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
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.
• 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
Common Causes of Acute Urticaria
IdiopathicImmune-mediated (IgE)
– foods (shellfish, nuts)– drugs
Noimmune-mediated – opiates
Nonspecific– viral infections (influenza)– bacterial infections (occult abscess, mycoplasma)
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
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)
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
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
Four-week Treatment Period:
Fexofenadine HCl
Mean Pruritus Scores/Mean Number of Wheals/Mean Total Symptom Scores