Urticaria and Angioedema: Symptoms, Causes, and Treatment

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
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Causes
Idiopathic- 90% of chronic cases
Infections- most acute cases
IgE 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
IgE mediated reactions
Medications- antibiotics, etc.
Stinging insects
Foods and food additives
Latex
Contact with allergens
Transfusions
IgE 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 10d course
Cost effective to R/O penicillin allergy,
especially pre surg and IV abx
IgE- 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 Syndrome-
recent 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 IgE 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
H1 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
H2; ranitidine out, famotidine first
choice, 20 bid; less effective
Leukotriene antagonists
Montelukast (Singulair); short half
life though 1x/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 IgE, not IgE bound to
mast cells
Injections 150 or 300 mg every 2-
4 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
C1 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!!!
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Urticaria, commonly known as hives, and angioedema are skin conditions characterized by red, raised welts and swelling. Urticaria typically lasts less than 24 hours and can occur anywhere on the body, while angioedema involves episodic swelling of subcutaneous or submucosal tissues. Causes include infections, allergic reactions, physical stimuli, and systemic diseases. Antibiotic allergies in children may be overdiagnosed. Sinusitis can be a common cause of chronic hives. Treatment may involve antihistamines, corticosteroids, and identifying triggers through allergy testing.

  • Urticaria
  • Angioedema
  • Allergies
  • Skin Conditions
  • Treatment

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

  2. 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

  3. j

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

  5. 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

  6. 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

  7. IgE mediated reactions Medications- antibiotics, etc. Stinging insects Foods and food additives Latex Contact with allergens Transfusions

  8. IgE 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 10d course Cost effective to R/O penicillin allergy, especially pre surg and IV abx

  9. IgE- 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

  10. 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

  11. 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?

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

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

  14. Mast Cell Disorders Mastocytosis- Abnormal number of mast cells Mast Cell Activation Syndrome- recent 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

  15. 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 IgE reactions only Skin tests; most sensitive Blood tests; more expensive, less sensitive

  16. 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

  17. Treatment Antihistamines H1 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 H2; ranitidine out, famotidine first choice, 20 bid; less effective Leukotriene antagonists Montelukast (Singulair); short half life though 1x/d Zafirlukast (Accolate); dosing bid

  18. 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

  19. Xolair (omalizumab) Refractory hives (also asthma) Monoclonal antibody Binds to free IgE, not IgE bound to mast cells Injections 150 or 300 mg every 2- 4 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

  20. Angioedema Less Common Rule out hereditary angioedema C1 esterase deficiency If tests (+), many new drugs If tests (-), treatment same as hives; preventive antihistamines, but steroids first line therapy Workup and evaluation same

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

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