Urticaria and Angioedema Jim Harris MD Allergy and

Urticaria and Angioedema Jim Harris, MD Allergy and Immunology South Bend Clinic

Definition • Urticaria (hives, welts, “whelps”) – Area of redness and swelling of various sizes, with flare, raised , +/- central pallor – Itching (pruritis) – Time course <24 hrs, skin returns to normal – Can occur anywhere on body • Angioedema – – – episodic submucosal or subcutaneous swelling Skin normal color Affects extremities- hands, feet, face, genitals Lasts hours to several days Painful, numb, or tingling, rather than itching • Acute urticaria - < six weeks duration • Chronic spontaneous urticaria-AKA chronic idiopathic urticaria – – Greater than 6 weeks duration 50% hives only 40% hives and angioedema 10% mostly angioedema

j

Causes Idiopathic- 90% of chronic cases Infections- most acute cases Ig. E mediated allergic reactions Direct mast cell activation Nonsteroidal anti-inflammatories (NSAID’s) • Physical stimuli • Systemic Diseases • • •

Causes • Infections – Viral, parasitic, bacterial; antibiotics – Up to 80% in pediatrics – Study: 88 peds seen in ER w/ infection, on B-lactam antibiotics (penicillins/cephalosporins) and rash, 47/88 hives; on later challenge with same antibiotic, only 4/88 reacted – Conclusion: allergy to antibiotics overdiagnosed in children

Infection • Sinusitis; acute and chronic • Most common identifiable cause of chronic hives in children • Can be subtle • Xrays can be helpful; esp CT • Hives may persist even after treatment • Often need abx for 2 -4 weeks, even surgery, to clear

Ig. E mediated reactions • • • Medications- antibiotics, etc. Stinging insects Foods and food additives Latex Contact with allergens Transfusions

Ig. E mediated • Medications – Virtually all, but especially antibiotics – Penicillins and cephalosporins most common; may be labeled for life! – 98% of PEN reactions resolve over 10 years – Skin testing confirms, even w/ hx anaphylaxis, that allergy resolved – May further confirm with oral challenge; single dose vs 10 d course – Cost effective to R/O penicillin allergy, especially pre surg and IV abx

Ig. E- Foods • Usually within 30” of ingestion • Can cause chronic sxs • Children: milk, egg, peanut, tree nuts, seeds; many resolve • Adults: shellfish, peanut, tree nuts; milk, egg • Food additives: – Yellow dye #5 (tartrazine) – Red dye #4 and #40 - ADHD in kids

Direct Mast Cell Activation Cause histamine release Narcotics- codeine, morphine Muscle relaxants- perioperative Vancomycin- Red man syndrome Certain foods- tomatoes, strawberries • Radiocontrast media- can block with meds • • •

Physical Stimuli • • Cold or heat induced Vibration Pressure Exercise- 2 types: – Cholinergic urticaria – Exercise induced anaphylaxis • Solar (vs polymorphous light eruption) • Aquagenic- contact with water! • Stress?

Dermatographism • AKA Dermographism • Induced by stroking the skin • Often have chronic itch even if no hives • Differential: – Dry skin – Neurodermatitis (anxiety)

Systemic Causes • Infections – Sinusitis, prostatitis – Hepatitis • • • Autoimmune- lupus, RA Renal disease Cancer- lymphoma, myeloma Thyroid disease Hormonal- often cyclical Mast Cell Disorders

Mast Cell Disorders • Mastocytosis– Abnormal number of mast cells • Mast Cell Activation Syndromerecent phenomena- 2007 – Normal cells, abnl histamine release – Hives, usually chronic – Chronic rhinitis – Autonomic dysfunction • • Irritable bowel, cystitis Headaches, sleep dysfunction Fibromyalgia Ehlers-Danlos/ hyperflexible – Anaphylaxis

Evaluation • History- events at or before onset – May be complex and detailed • Physical exam – be sure they have hives! Sinuses, HSM, nodes • Tests- limited, based on hx – Systemic: CBC, ESR, CRP, CMP, TSH; ANA, RA – Tryptase, +/- 24 hr urine studies – Xray- chest (lymphoma), sinus – Foods: for Ig. E reactions only – Skin tests; most sensitive – Blood tests; more expensive, less sensitive

Skin Biopsy ? • When? – Lesions last >24 hrs – Painful not pruritic – Respond only to steroids • What? – Often non-specific – Eos, neutrophils, lymphocytes – Immuno tests for vasculitis; deposition of complement and antibodies – Best done by dermatology

Treatment • Antihistamines – H 1 antagonists • Second generation preferred- Allegra, Zyrtec (to 4/d) at least BID • First generation- more sedating, but may be more effective; hydroxyzine up to 100 bid • Benedryl- most sedating, short half life – H 2; ranitidine out, famotidine first choice, 20 bid; less effective • Leukotriene antagonists – Montelukast (Singulair); short half life though 1 x/d – Zafirlukast (Accolate); dosing bid

Treatment • Prednisone/ systemic steroids – Do not block mast cell degranulation, but… – Do reduce inflammatory mediators – Many ways to dose • • Cyclosporin/ Dapsone. H pylori? Thyroid antibodies? Diet- no change, except MCAS Biologics – Xolair (omalizumab) – Others pending

Xolair (omalizumab) • Refractory hives (also asthma) • Monoclonal antibody • Binds to free Ig. E, not Ig. E bound to mast cells • Injections 150 or 300 mg every 24 weeks; well tolerated • 0. 1% risk of anaphylaxis; Epipen. • In 12 week study… – 44% complete resolution of hives – 66% reduction in itching • Cancer Risk? Minimal

Angioedema Less Common Rule out hereditary angioedema C 1 esterase deficiency If tests (+), many new drugs If tests (-), treatment same as hives; preventive antihistamines, but steroids first line therapy • Workup and evaluation same • • •

Questions? • Thank you for your attention • Thanks to Beacon and Jenai • Happy Holidays!!!