Anaphylaxis Urticaria Angioedema

Anaphylaxis Urticaria Angioedema
By:Niraj Patel, MD, MS
Section of Allergy and Immunology
Texas Children’s Hospital & Baylor College of Medicine

Objectives
* Know the clinical presentation, diagnosis and treatment of anaphylaxis.
* Understand the pathophysiology of urticaria and angioedema
* Outline an approach for evaluation and treatment of patients with urticaria and/or angioedema

What is anaphylaxis?
* Affects > 1 organ system: skin, respiratory, cardiovascular, GI symptoms
* 100,000 episodes per year in U.S.
* 1% fatality rate: shock, larnygeal edema
* IgE vs nonIgE mechanisms

Histamine
IgE-Mediated
IgE-receptor
* Protein digestion
* Antigen processing
* Some Ag enters blood

Mast cell
APC
B cell
T cell
Non-IgE Mediated
Pathophysiology: Immune Mechanisms
Causes of Anaphylaxis
* Foods – peanuts, egg, milk, shellfish, wheat, fish, soy
* Insect stings
* Drugs – PCN, NSAIDs
* Contrast media
* Opiods

Clinical Features and Diagnosis
* Skin: Erythema, pruritis, hives, angioedema
* Respiratory: laryngeal edema, wheezing, rhinitis, itching of palate, conjunctivitis
* Cardiovascular: LOC, fainting, palpitations, sense of impending doom
* GI: N/V/D, abdominal pain
* Diagnosis

Management of Systemic Reactions
Stabilize Epinephrine, IV, airway, O2 antihistamine, steroids
Observe 3 hours (mild reaction) 6 hours (severe reaction)
Prevent Epinephrine self administration Referral to an allergist

EpiPen
* EpiPen
o Injection carried with the patient at all times.
o Self-injection to lateral thigh.
o Use EpiPen, Jr. for children < 20kgs.
Urticaria
* Urticaria = Hives
* Common condition, 15-25% at some time in their lives
* Type I hypersensitivity reaction
* Causes: foods, drugs (no identifiable cause in 50%)
Urticaria vs. Angioedema
* Urticaria – superficial dermis
o Characterized by intense pruritis due to histamine effect
* Angioedema – deeper dermal and subcutaneous layers
o May be pruritic but often is a deeper and dull discomfort – burning quality

Chronic Urticaria/Angioedema (Mast cell driven)
Acute vs. Chronic Urticaria
* Acute Urticaria – lasts 6-8 weeks or less
o Viral syndromes (especially in young children)
o Insect bites or stings (fire ants, scabies)
o Food induced reactions (eat this - get that)
o Medication related (antibiotics, NSAIDs, narcotics, angioedema due to ACE inhibitors)
* Chronic Urticaria – lasting longer than 8 weeks
o Physical urticarias (dermographism, cholinergic, cold)
o Urticarial vasculitis
o Urticaria/angioedema associated with autoimmunity
o Autoimmune urticaria
o Idiopathic urticaria

Urticaria - Mechanisms
* Immunologic
* Non-Immunologic
Underlying Mechanisms of Urticaria
Physical Urticarias
Symptomatic Dermatographism
Cholinergic Urticaria
Cold-Induced Urticaria
Delayed Pressure Urticaria
Solar and Aquagenic Urticaria
Schnitzler’s Syndrome
Hypocomplementemic Urticarial Vasculitis Syndrome (HUVS)
Therapeutic Options
* Antihistamines for most with acute short-lasting urticaria
o Start with non-sedating, long-acting second generation H1 antagonists (Allegra, Zyrtec, Claritin) and supplement

with short-acting, sedating H1 antagonists prn.
* Combination therapy if H1 antagonists do not suffice (30% of cases)
* Steroids and other immunosuppressants reserved for severe urticaria associated with angioedema of oropharnyx or other

systemic signs, moderate to severe drug reactions, urticarial vasculitis, and refractory cases of CIU
H1 Antagonists
* Previously felt to be only histamine receptor blockers
* Recent research now reveals that most of the second generation antihistamines have some mild anti-inflammatory

properties
* Although less expensive, first generation antihistamines have potential for sedation and impaired performance

Why Add an H2 Antagonist?
Immunomodulation Cyclosporine / Tacrolismus
Cyclosporine
ANGIOEDEMA

* Inhibits C1r and C1s of the complement system
* Inhibits activated factor XIIa and kallikrein
* An inhibitor of factor XIa and plasmin
* Inhibits activation of C1
C1 Inhibitor Functions
Hereditary Angioedema
* Autosomal dominant with incomplete penetrance.
o Spontaneous mutations in 50%
o Diminished C4 between attacks
o Very low C4 during attacks
* HAE I
o Low levels of C1 esterase inhibitor
* HAE II
o Dysfunctional C1 INH
* HAE III (estrogen-dependent angioedema)
o Normal C1 INH amount and function
o Normal complement levels
Acquired Angioedema (AAE)
Drug Induced Angioedema
ACE Inhibitor Angioedema
Treatment of Hereditary Angioedema
* Patient education very important; test family
* No regular medication needed in many cases
* Prophylactic stanozolol or danozol
* Epsilon aminocaproic acid (EACA) an option
* Fresh frozen plasma before emergency surgery
* C1 inhibitor
* Symptomatic treatment during attacks
* Steroids and antihistamines are NOT effective!!!
Summary
* Through several mechanisms a variety of mediators may lead to urticaria or angioedema
* Clinically, a causative agent is much more often identified in acute than in chronic urticaria/angioedema
* A number of medications are available to control chronic urticaria while awaiting a spontaneous remission
* Patients with angioedema without urticaria should be tested for C1 inhibitor deficiency

Questions
Anaphylaxis Urticaria Angioedema