Table of contents
Approach to Angioedema
- On History:
- Is it angioedema? (ask for lips, eyelids, genitals, extremities). Raised erythematous plaques lasting LESS THAN 48hrs.
- Hives or no hives (aka Urticaria.. determines whether it's mast-cell mediated or not.. see chart)
- Systemic Symptoms? (resp, GI, CVS)
- Triggers (food, drugs, insect, exercise, cold)
(Source: Recreated from University of Toronto Lecture for undergraduate medicine in 2013)
Type IV
- "Delayed Hypersensitivity" reaction mediated by "T-cells
- T-cell Mediated Mechanism
- e.g. contact dermatitis, DRESS syndrome
- Examples:
- DRESS
- TB Skin Test (Delayed hypersensitivity)
- Poison Ivy
Anaphylaxis
- Acute Life Threatening immunologic reactions
- Mechanism:
- Severe allergic reaction occurs in response to:
- Food / Environmental Proteins
- Insect venom
- Drugs
- Latex
- Blood transfusions
- Other allergens.
- Radiocontrast (special, b/c activates mast cells directly w/o IgE intermediary).
- Due to IgE activation on basophils and mast cells, releasing histamine + other inflammatory cytokines.
- Requires previous sensitization to the allergen, but often occurs without a known exposure hx.
- Severe allergic reaction occurs in response to:
- Clinical Features
- Reaction can be immediate, in several hours post-exposure, or days post exposure.
- Skin: Urticaria
- CV: Tachycardia (sometimes bradycardia)
- Hypotension (histamine increases vascular permeability), large losses of circulating volume.
- Airway: Stridor, Horseness, Wheezing
- GI: Cramping abdo pain, vomiting, diarrhea
- Angioedema (localized tissue edema)
- Often lips, tongue, upper airway, GI tract, extremities.
- Often a component of anaphylaxis, but can occur alone without other features of anaphylaxis
- Possibly triggered by exposures (esp ACEi) or inherited/acquired disorder.
- Highly likely if:
- Acute onset of illness (minutes to hours) with involvement of skin, mucosal tissue or both (hives, pruritis, flushing, swollen lips/tongue, uvula) AND one of :
- Resp compromise (dyspnea, wheeze-bronchospasm, stridor, hypoxemia)
- Reduced BP or associated symptoms (hypotonia, syncope)
- Two or more of following rapidly after exposure to a likely allergen: (≥2)
- Involvement of skin/mucosal tissue or both.
- Respiratory compromize
- Reduced BP
- .... (one more)
- Acute onset of illness (minutes to hours) with involvement of skin, mucosal tissue or both (hives, pruritis, flushing, swollen lips/tongue, uvula) AND one of :
- Another Definition:
-
Anaphylaxis Definition (Very controversial, how to define), but one common definition is:
- Severe allergic reaction to any stimulus, having sudden onset involving at least two body organs with multiple symptoms.
-
- Familial C1 Esterase Deficiency (aka familial angioedema)
- IMPORTANT: does not respond to standard anaphylaxis agents (not IgE mediated)
- Hereditary: (Often following trauma or illness, starts early in life)
- Acquired: in Lymphoproliferative disorders
- Airway management is essential due to laryngeal edema
- Identified as one of three criteria (on up to date and purple book)
- Management:
- Nowadays rarely fatal, often patients die from laryngeal edema (airway emergency)
- Mainstay of therapy:
- Supportive: Oxygen, IV fluids
- Inhaled B2-agonist
- Ventolin, albuterol or racemic epinephrine can reduce bronchospasm and airway edema
- *Epinephrine *
- IM preferred (SC is unreliable and slow absorption)
- Epinephrine IM 0.3-0.5mL (1:1000 [1 mg/mL] solution) (0.3-0.5mg)
- If does not work, then repeat q5-15m
- Inject in anterolateral aspect of mid-third of thigh deep in muscle. (guidelines!)
- Epinephrine IM 0.3-0.5mL (1:1000 [1 mg/mL] solution) (0.3-0.5mg)
- IV (recommended only if profoundly hypotensive, in arrest, or unresponsive to IM epi)
- Epinephrine IV 1mL (1:10,000 [0.1 mg/mL] solution) [0.1mg] aq sol'n infused over 5-10min, can repeat q10-20m.
- IV Infusion --> Can create an infusion w/ crystalloid. (epinephrine IV 2-8 mcg/min)
- For laryngeal edema can use:
- 0.25mL of 1:100 epi sol'n (10mg/mL) added to 2mL of isotonic saline.
- High dose, sustained dosing may be needed for severe anaphylaxis or with B-blocker use.
- can also add glucagon 5-15 mcg/min IV infusion to provide another mechanism of sympathetic stimulation if B-blocker is used)
- IM preferred (SC is unreliable and slow absorption)
- Antihistamines and steroids sometimes used to prevent worsening or recurrence.
- Neither antihistamines nor steroids have sown to improve outcomes in anaphylaxis. Neither would reverse bronchospasm quickly enough.
- Antihistamines are typically effective for urticaria (not shock or airway)
- Steroids are effective to prevent delayed recurrence.
- Neither antihistamines nor steroids have sown to improve outcomes in anaphylaxis. Neither would reverse bronchospasm quickly enough.
- Airway Support
- NIPPV can be used, but intubation may be needed to prevent airway closure
- Airway management is DIFFICULT, may need advanced techinques and anasthesia
- Steroids
- In theory prevents second phase reaction. (10-15% of anaphylaxis possible)
- methylprednisolone 125mg IV or prednisone 50mg PO q6h
- (Not critical, likely doesn't help that much, but we still often do it - prevents 2nd phase reaction)
- Other:
- REMOVE B-BLOCKERS (get unopopsed alpha activity, get vagal stimulus and become bradycardic)
- Give Glucagon 1mg amp q5-10m.
- REMOVE B-BLOCKERS (get unopopsed alpha activity, get vagal stimulus and become bradycardic)
- Concerns:
- 1. Airway Obstruction (Main cause of fatality)
- Look for stridor, facial/tongue swelling, drooling, inability to talk.
- 2. Bronchospasm
- 3. Distributive Shock
- IV epinephrine infusion (IV form raises risk of arrhythmia, rapid rise in BP, MI, stroke... CAREFUL!)
- 1. Airway Obstruction (Main cause of fatality)
- Discharge therapy
- Epinephrine Auto-Injector
- H1 +/- H2 antagonists (cetirizine/fexofenadine)
- Corticosteroids
- Proximity to medical therapy for 36-48hrs
- Referral to Allergy/Immunology
- Education (autoinjector use, etc..)
- Source: Massachusetts Manual and MKSAP16
Urticaria
- Acute <6w
- Chronic >6w
- Types:
- type I (IgE mediated) Hypersensitivity (Mast cells)
- Type II (Antibody mediates) Hypersensitivity
- Complement activation causing direct cell degranulation (mismatched blood)
- Type III (Immune complex mediated) Hypersensitivity
- Some autoimmune diseases
- Other autoimmune (CSU0
- Nonimmunologic urticaria
- Exogenous substances, etc..
- Idiopathic
- Management:
- H1 receptor antagonists (1st line)
- Diphenhydramine only IV option
- Oral: Cetirizine (Reactine)
- Diphenhydramine (Benadryl) + Hydroxyzine (Atarax) for hospital inpatients
- Cogntive reduction + sedating
- Diphenhydramine (Benadryl) + Hydroxyzine (Atarax) for hospital inpatients
- NOTE: other 2nd generation H1 antagonists
- Cetirizine (Reactine)
- Fexofenadine (Allegra)
- ... etc..
- H2 antihistamines (ranitidine) combination additive to H1 antihistamines.
- Glucocorticoids
- Reduce inflammatory histamines (stabilize mast cell membranes preventing degranulation)
- H1 receptor antagonists (1st line)
Chronic Spontaneous Urticaria (CSU)
- Aka Chronic idiopathic Urticaria (CIU)
- 50% --> autoimmune
- 50% --> response to ill-defined viral illness
- Autologous serum skin test (IgG against FeER).
- Associated with autoimmune thyroid disease
- Rarely ass'd with: SLE, HepB, HepC, lymphoma, etc..
- Diagnosis:
- Symptom + patient driven
- Often skin testing not indicated (to prove to patient that this is not due to food allergy)
- CBC, diff, ESR, CRP, Anti-thyroid antibodies, C3/C4, TSH
- Other: QIG, SPEP, LST, HepB/C, ANA, H.pylori serology, etc..
- Treatment:
- 1st line: licensed does (5-10mg cetirizine, 60-120 of fexofenadine, 10 loraradine, 5mg desloratadine)
- 2nd line: up tot four-fold up-dosing of 2nd gen AH
- 3rd line: Add ranitidine and/or montelukast
- 3rd line: other option is omalizumab (Xolair) - $$$ [anti-IgE ab]
- 5rth line:
- Plaquenil 200mg BID (if ANA positive)
- Cyclosporine
Angioedema
- Same as urticaria, but deeper layer
- Varying presentation (localized non-pitting edema)
- Not pruritic (can angioedema and urticaria together)
- Lips, eyes, ear lobes, genitals (tissues that are easily extendable)
- Workup:
- CBC, diff, acute phase reactants, thyroperixodase antibodies, ANA, hepatitis, Hpylori, D-dimer
- Acute: C4 level, allergic investigations
- Chronic: C1 estarse inhibitor assay, etc..
- CBC, diff, acute phase reactants, thyroperixodase antibodies, ANA, hepatitis, Hpylori, D-dimer
- Causes:
- Allergic (IgE mediated)
- Autoimmune angioedema/urticaria (Extension of CSU spectrum)
- Hereditary Angioedema (C1 esterase inhibitor - either not enough or not working)
- Screen: Chronically low C4 levels, C1 assay
- Type I Low C1 esterase inh.
- Type II - NO C1 esterase inh.
- Type III - C1 inhibitor assay normal, must do gene testing for Factor XII?
- Drugs (ACEi, NSAIDs, opioids) - if on ACE - dx'ed unless proven otherwise.
- Usually happens in 1st year, but possible later.
- Can takes weeks/months to resolve (when stop drug)
- Can last hours to 2-3 days.
- Management:
- Epi, steroids, antihistamines
- Hereditary: Can have C1 estarse given back to treat. (acquired + hereditary)
Drug Reactions
DRESS
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Prev called "Anticonvulsant Hypersensitivity Syndrome"
- Severe potentially life-threatening systemic drug hypersensitivity syndrome
- Type IV hypersensitivity reaction --> Onset of the syndrome is delayed, usually occurring 10 days to several weeks after the start of the causative medication.
- Common triggers: (Up to 6w post exposure)
- Sulfonamide antibiotics
- Allopurinol
- Anticonvulsants (CLASSIC)
- Vancomycin (new, b/c increased use)
- Symptoms:
- Exanthem rash on the face, trunk, and extremities, and they often have facial edema.
- SYSTEMIC Inflammation:
- Fever
- Rash (not itchy, but uncomfortable)
- Lymphadenopathy (75%)
- Hypotension (If Severe)
- Hepatitis
- Nephritis
- Eosinophilia
- Fever (
- Difficult to distinguish inadequate response to abx and sepsis vs. systemic drug reaction.
- Management:
- Stop the suspected medication immediately
- switch to another medication that is unlikely to cross-react
- Supportive care
- Systemic Glucocorticoids (reduce systemic inflammation and lower the risk of end-organ damage)
- IV pulse steroids
- Stop the suspected medication immediately
Desensitization
- Only works for Type I, IgE-mediated reaction
- progressively higher q20-30min until full dose is tolerated.
- IV or oral (safer as oral, but harder practically)
- Once desensitized, drug must be continued daily for state to persist; disappears over days to weeks of drug is stopped.
- Must be done with pump, mini bags, and often need high level nursing care (i.e. Step-down ICU)
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