Urticaria, Angioedema, & Anaphylaxis Noel Mensah-Bonsu, MD Case 1 7 yo F presents w/ a red itchy rash after playing outside in the grass all day. Parents note that she must have been bitten by numerous mosquitos. The individual ‘welts’ are on her trunk and extremities and she complains of itchiness. She has received no medications for them. Case 1 Questions Important History? Differential diagnosis? Mechanism of injury? Evaluation for acute vs. chronic urticaria? Treatment? Important History? Infectious sx, abx, NSAIDS, arthralgias Are symptoms c/w urticaria? Raised, red, itchy, mobile, resolve in 24 hrs Is angioedema occurring? Length of symptoms? Hx atopy? Differential Diagnosis acute vs. chronic? Acute urticaria Erythema multiforme, marginatum, infectiosum Drug eruption, serum sickness Insect bites Chronic urticaria urticarial vasculitis (SLE, Sjogren’s syndrome) cryoglobulinemia (Hep C), hepatitis A/B, parasitic infection, urticaria pigmentosa (mastocytosis) Mechanism of tissue injury? Urticaria results from release of inflammatory mediators and increased capillary permeability which causes edema of the superficial dermis IgE mediated Stinging insects, foods, additives, aeroallergens, contact allergens, parasitic infxns, blood products Direct mast cell activation (non-IgE) Narcotics, muscle relaxants, vancomycin, radiocontract medium Complement-mediated Viral/bacterial infections, serum sickness Evaluation? Acute Up to 80% probably infectious Chronic CBC, ESR, LFTs, TSH, antithyroid antibodies 30-50% autoimmune, autologous serum skin test Food allergy testing generally not helpful w/o clinical history Abnormal labs 21% of the time Treatment? Antihistamine 2nd generation H1: loratidine, cetirizine 1st generation H1: diphenhydramine, hydroxyzine Corticosteroids rarely necessary H2 receptor antagonists: ranitidine, famotidine Others leukotriene receptor antagonists, thyroxine, cyclosporine, dapsone, doxepin Case 2 16 yo M w/ a dozen episodes of lip and facial swelling in the last year. He recalls that during high school football, his hands and elbows often swelled after getting tackled, although he attributed the swelling to trauma. Recently, he also has experienced episodes of abdominal pain. Case 2 Questions Important History? Differential diagnosis of facial edema? Mechanism/pathogenesis? Evaluation? Treatment? Important History: Triggers? Hives/urticaria? Recurrent? Meds? Family hx? Atopy? Differential Diagnosis of facial edema? Angioedema Allergic contact dermatitis Cellulitis Lymphedema Autoimmune disease Hypothyroidism SVC syndrome Mastocytosis Mechanisms? Angioedema results from mast cell activation & degranulation w/ release of inflammatory mediators causing ↑ vascular permeability in the deep layers of the dermis and the subcutaneous tissue. Mast cell-mediated Allergic, autoimmune, direct mast cell release Kinin-related ACE inhibitor, angiotensin II receptor blocker, C1 inhibitor deficiency or dysfunction Unknown Aspirin, NSAIDS, infections Etiology of Angioedema Hereditary Acquired Allergic Idiopathic Medication-induced ACE inhibitors, ARBs Evaluation? Workup often unrevealing (90%) Based on history and physical exam Labs C4…if low, check C1 inhibitor levels Treatment: Anaphylaxis epinephrine Acute allergic angioedema Antihistamine Corticosteroids Hereditary or Acquired angioedema Dental/oral surgery prophylaxis w/ androgen C1 inhibitor concentrate FFP Medication-induced…d/c meds Case 3 12 yo M brought to ER w/ acute onset of facial swelling. Fifteen minutes later, he began to complain of SOB. His parents observed him to have some difficulty breathing. He also said that he felt very weak and dizzy. His parents brought him immediately to the ED. Case 3 Questions Differential diagnosis? What are the symptoms of anaphylaxis? Mechanism? Common causes? Evaluation? Management? Differential Diagnosis? Anaphylaxis Severe asthma Systemic mastocytosis Carcinoid syndrome Vasovagal response Drug overdose Scombroidosis Symptoms of Anaphylaxis? Skin-mucous membrane involvement Hives, pruritis, flushing, swollen lips/tongue/uvula Respiratory compromise Dyspnea, wheeze, stridor, hypoxemia Persistent GI symptoms Crampy abdominal pain, vomiting Cardiovascular: BP or symptoms associated Syncope, incontinence, collapse Mechanism? Action Mediator Vasodilation, increased Histamine vascular permeability PAF Leukotrienes C4 , D4 , E4 Neutral proteases that activate complement/kinins Prostaglandin D2 Smooth muscle spasm Leukotrienes C4 , D4 , E4 Histamine Prostaglandins PAF Cellular infiltration Cytokines, e.g., TNF Leukotriene B4 Eosinophil and neutrophil chemotactic factors PAF PAF, platelet-activating factor; TNF, tumor necrosis factor. Anaphylaxis Anapylactoid (IgE mediated) (not IgE mediated) Food Direct release of mast cell mediators Tree nuts, peanuts Drugs (opiates, NMBs) Grains Hypertonic solutions (mannitol) Eggs & dairy Exercise Shellfish Immune complex mediated Venoms Blood products Hymenoptera Gamma globulin Snake, Fire ant Antisera Therapeutic Agents Dialysis membranes Antibiotics Arachadonic acid metab modulators Vaccines NSAIDs, ASA Human proteins Tartrazine Hormones (insulin) Unknown mechanism Enzymes (streptokinase) Radiocontrast media Blood & blood products Preservatives Latex Anaphylaxis Anapylactoid (IgE mediated) (not IgE mediated) Food Direct release of mast cell mediators Tree nuts, peanuts Drugs (opiates, NMBs) Grains Hypertonic solutions (mannitol) Eggs & dairy Exercise Shellfish Immune complex mediated Venoms Blood products Hymenoptera Gamma globulin Snake, Fire ant Antisera Therapeutic Agents Dialysis membranes Antibiotics Arachadonic acid metab modulators Vaccines NSAIDs, ASA Human proteins Tartrazine Hormones (insulin) Unknown mechanism Enzymes (streptokinase) Radiocontrast media Blood & blood products Preservatives Latex Evaluation? ABG, CXR Acute Tryptase, histamine Long-term Referral to an allergist-immunologist for further evaluation, skin testing, RAST Allergen education and avoidance. Management? A/B/Cs Epinephrine Antihistamines? Corticosteroids Bronchodilators Consider glucagon for patients on beta- blockers Fluid resuscitation Vasopressors Urticaria, Angioedema and Anaphylaxis NMB Common theme? Mast cell degranulation can result in different clinical syndromes… Anaphylaxis may occur w/ or w/o angioedema and urticaria Treatment often w/ antihistamines, steroids…for anaphylaxis, always epinephrine first! Question 1 A previously healthy 5 yo F is brought to the ED soon after being stung by a “bee.” You note several raised, white-red, intensely pruritic areas on her trunk; slight swelling of her lips and eyelids; and wheezing on auscultation of her chest. The first drug she should receive is: A. Oral 1st generation antihistamine B. Oral leukotriene receptor antagonist C. Oral 2nd generation antihistamine D. Parenteral epinephrine E. Parenteral glucocorticosteroid Question 2 Among the following, life-threatening anaphylaxis in children occurs most often as a result of exposure to : A. Exercise B. Foods C. Latex D. Perioperative drugs E. Vaccines Question 3 A 10-year-old boy presents to the clinic for evaluation of an insect sting reaction. He was playing in his yard yesterday when he was stung on the right forearm by a wasp. His parents immediately placed ice over the area, but they are worried because when the child awoke today, the redness that initially was localized to the sting site had extended to involve his entire right forearm. The boy denies fever, chills, nausea, vomiting, or difficulty breathing. His vital signs on physical examination are normal. His right forearm is diffusely erythematous and warm to palpation but not tender. Of the following, this child's insect sting reaction is BEST characterized as A. Cellulitis B. Large local reaction C. Normal reaction D. Systemic anaphylaxis E. Toxic reaction Question 4 You are performing a presedation physical examination in a 3-year-old female who is scheduled to have a repeat computed tomography (CT) scan with contrast. The mother mentions that her daughter experienced diffuse hives and facial swelling 10 minutes after the contrast administration during her first CT. Of the following, the BEST way to prevent future contrast reactions is to: administer 1 L intravenous normal saline prior to the procedure perform desensitization to contrast provide pretreatment with oral antihistamines and steroids use a high-osmolar contrast agent use a contrast agent with low iodine content Take Home Anaphylaxis epinephrine Epi pen = 0.3mg epinephrine Epi pen junior = 0.15mg epinephrine Evaluation is based on history and physical exam!
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