Angioedema
(Last Updated - 6/4/2007)

-closely related to urticaria
-urticaria involves only the superficial dermis vs. angioedema which involves deeper skin layers including the sub-Q tissue
-< 6 weeks duration --> acute (usually 24-72 hrs)
-> 6 weeks duration --> chronic
-incidence increases after adolescence (highest in 3rd decade)

-Charaterizations:
     -rapid-onset
     -well-circumscribed wheals w/ erythematous, raised, serpigionous borders w/ blanched centers that may coalesce to become giant wheals
     -pruritic
     -may involve any body area --> scalp to soles (most commonly face / extremities)
     -lesions appear in crops lasting 24-72 hrs. --> old ones fade and new ones erupt (various stages)
     -self-limited in nature (usually) --> unless airway management issues
     -direct reproduction w/ triggering stimulus
     -equivocally elevated IgE level or peripheral eosinophilia

-Classification:
     1) IgE-Dependent:
          A) Specific Ag Sensitivity Angioedema --> pollens, foods, drugs (Ex.) Warfarin (Coumadin)), fungi, molds, Hymenoptera (bees/wasps) venom or helminths (worms)
          B) Physical Angioedema --> should be distinguishable by history
               I) Dermographism:
                    -occurs in ~1-4% of cases
                    -characterized by a linear wheal at the site of a brisk physical stroke along the skin
               II) Cold Angioedema:
                    -local irritation at areas exposed to cold (Ex.) ice)
               III) Solar Angioedema:
                    -same as above #II but with sun exposure
               IV) Vibratory Angioedema:
                    -possible occupational relation
               V) Pressure Angioedema:
                    -history will indicate sustained stimulus (Ex.) straps, belts or running)
               VI) Cholinergic Angioedema:
                    -characterized by small-sized wheals (1-2 mm) surrounded by large areas of erythema
                    -may be precipitated by fevers, hot baths or showers
                    -presumedly due to increased core body temperatures
               VII) Exercise-Related Angioedema:
                    -differentiate from cholinergic because lesions are not preceded by increased core body temperatures and wheals are conventionally-sized

     2) Complement-Mediated:
          A) Hereditary Angioedema
               -autosomal dominant pattern of inheritance
               -due to a deficiency of C1-esterase inhibitor (C1INH):
                    -results in uncontrolled activation of the early components of the complement system
               -Types:
                    -Type 1:
                         -characterized by a deficiency of C1-esterase inhibitor (C1INH)
                    -Type 2:
                         -Ag intact but C1-esterase inhibitor (C1INH) non-functional
               -Diagnosis:
                    -suggested by the family history
                    -characterized by angioedema w/out urticaria
                    -characterized by lack of pruritis
                    -equivocal laryngeal edema
                    -equivocal recurrent GI attacks of colic
               -Treatment:
                    I) Attenuated Androgens or Isolated C1-esterase Inhibitor (C1INH) Infusions
                         -not for use in children or pregnant women
                    II) Anti-Fibrinolytic Agents
                         -Sigma-Aminocaproic Acid
                              -avoid in patients w/ thrombotic / ischemic tendencies
          B) Acquired Angioedema
               Types (As Above For Hereditary):
                    -Type 1:
                         -characterized by a deficiency of C1-esterase inhibitor (C1INH)
                    -Type 2:
                         -Ag intact but C1-esterase inhibitor (C1INH) non-functional
          C) Necrotizing Vasculitis --> immune complex disease
               -more common in females
               -associated with arthralgias
               -characterized by an elevated ESR
               -may be normo- or hypocomplementemic
               -typically lasts > 72 hrs
               -confirm diagnosis via skin biopsy --> fibrinoid venular necrosis
          D) Serum Sickness --> immune complex disease
          E) Reactions To Blood Products

     3) Non-Immunologic:
          A) Direct Mast Cell-Releasing Agents:
               -Opiates
               -Antibiotics
               -Curare
               -D-Tubocurarine
               -Radiocontrast Media
          B) Arachidonic Acid Metabolism-Altering Agents:
               -Aspirin
               -NSAID's
               -Azo Dyes
               -Benzoates

     4) Idiopathic

-Histology:
     -collagen bundles in affected areas separate widely --> allows venule dilation
     -perivenular infiltrate:
          -lymphocytes, eosinophils, neutrophils, mast cells --> degradation products --> Histamine

-Treatment (In Order of Progression):
     1) H₁-antihistamines (Ex.) Chlorpheniramine or Diphenhydramine (Benadryl))
     2) Less Sedating H₁-antihistamines (Ex.) Loratadine (Claritin) or Cetirizine (Zyrtec))
     3) Cyproheptadine (Periactin) or Hydroxyzine (Atarax)
     4) Doxepin (Sinequan) (both H₁ and H₂ antihistamine)
     5) Add Hydroxychloroquine (Plaquenil) or Colchicine to #3 or #4 above
     6) Systemic Glucocorticoids --> last option EXCEPT in:
          -pressure urticaria / vasculitic urticaria
     *** Topical Glucocorticoids of no value ***


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References:

1) Harrison's Principles of Internal Medicine - 15th Edition - 2001. Chapter 310.
2) Robbins Pathologic Basis of Disease - 6th Edition - 1999. Chapter 27.