1. Updates in Urticaria Susan Fox, MMS, PA-C
University Consultants in Allergy and Immunology
Rush University Medical Center
Updates in Urticaria

2. Urticaria
Hives; a vascular reaction of the upper dermis marked by transient appearance of slightly elevated patches (wheals) which are redder or paler than the surrounding skin and often attended by severe itching

3. Pathophysiology
Results from the release of histamine and other vasoactive substances from mast cells and basophils in the dermis.
These substances cause movement of fluid into the dermis, leading to the urticarial lesion.
The intense pruritus of urticaria is a result of histamine released into the dermis.

4. Urticaria
Acute IgE-mediated urticaria is the most benign form of anaphylaxis.
It usually occurs independently, but it may be accompanied by the more serious clinical manifestations of anaphylaxis: angioedema and anaphylactic shock.

5. Case study 1
The mom of an 8 mo female calls the PCP office after hours with c/o itchy, red bumps around the mouth after eating.
The bumps, “look like mosquito bites”.
Mom states that she has no other symptoms.

6. Case study 1
Symptoms started 10 minutes after mom had given her scrambled eggs, rice cereal and mashed banana.
The PCP advised mom to give Benadryl mg/5ml, 2.5 ml.
Was advised to avoid all foods eaten and f/u with her the next day.
If symptoms worsen – angioedema of the face, tongue, throat; sob – call 911

7. Acute Urticaria Is usually self-limited Symptoms can come and go
Commonly resolves within 24 hours but may last up to 6 weeks

8. Etiology - Acute
Often is undetermined (some sources report that the cause is undetermined in more than 60% of cases).
Known causes include the following:
Infections (eg, pharyngitis, GI infections, genitourinary infections, respiratory infections, fungal infections)
Foods (shellfish, fish, eggs, cheese, chocolate, nuts, berries, tomatoes)
Drugs ( penicillin, sulfonamides, salicylates, NSAIDs)
Environmental factors (pollens, chemicals, plants, danders, dust, mold)
Latex
Undue skin pressure, cold, or heat
Emotional stress
Exercise
Pregnancy (i.e., pruritic urticarial papules and plaques of pregnancy [PUPPPs])

9. Work-up A careful history should be taken to find the etiology.
The history and physical examination should direct any diagnostic studies.
Laboratory studies generally are not indicated.

10. Treatment - Acute Antihistamines
Primarily the older, sedating antihistamines that block the H1 receptors, are the first line of therapy for urticaria.
Diphenhydramine and hydroxyzine are the most commonly used H1-blocking antihistamines.
They act more rapidly than the minimally sedating H1-blocking antihistamines.
These medications are potentially sedating, and the patient should not be allowed to drive within 6 hours of their administration.
Efficacious in relieving the pruritus and rash of acute urticaria in most cases

11. Treatment - Acute
If acute urticaria persists for more than hours, the minimally sedating antihistamines should be prescribed
Fexofenadine, loratadine, desloratadine, cetirizine, and levocetirizine.
In patients with poor response to antihistamines, a brief course of oral corticosteroids might also be required while attempting to eliminate suspected triggers and develop an effective treatment plan

12. Case study 1 – F/u visit
She has eaten rice cereal and banana before many times, but had eaten eggs once prior.
After taking a thorough history, there were no other factors except the foods eaten that may have contributed to the hives.
Because symptoms were improving, mom decided not to give Benadryl and all hives resolved within 30 minutes and have not recurred.

13. Ongoing care
sIgE testing was performed to egg white, egg yolk, banana, rice
(+) to egg white (class 3). All other foods were negative
Was advised to avoid egg and f/u with allergy. Why? To follow the egg allergy.

14. Chronic urticaria (CU)

15. Case study 2
A 49 y/o female presents to clinic with a 7 week h/o hives
Symptoms started suddenly without any inciting event
“I started itching and I couldn’t stop”
PCP was started the pt on Benadryl 25 mg every 12 hours with some relief, but hives still recur on a daily basis and worsen at night

16. Etiology - Chronic
Autoimmune disorders (SLE, rheumatoid arthritis, polymyositis, thyroid autoimmunity); up to 50% of chronic urticaria is autoimmune 
Cholinergic - induced by emotional stress, heat or exercise
Chronic medical illness – thyroid disease, malignant neoplasms, lupus, lymphoma, and many others
The etiology of chronic urticaria is undetermined in at least 80-90% of patients.
Rarely, IgE-mediated reactions from foods, drugs, or other allergens might result in CU.

17. History
After taking a thorough history, the pt does not have any evidence of an underlying cause
She is in good health and takes HCTZ 25 mg for HTN. She has been taking this for 3 years

18. Physical Exam
Blanching, raised, palpable wheals, which can be linear, annular (circular), or serpiginous.
Occur on any skin area and are usually transient and migratory.
Often separated by normal skin, but may coalesce rapidly to form large areas of erythematous, raised lesions that blanch with pressure.

19. Work-up
In some patients with CU, diagnostic testing might be warranted after a thorough history and physical examination is performed.
Limited routine laboratory testing can be performed to exclude underlying causes.
Targeted laboratory testing based on clinical suspicion is appropriate.
Extensive testing for rare causes of CU or immediate hypersensitivity skin testing for inhalants or foods is not necessary. 
Journal of Allergy and Clinical Immunology 2014;133:

20. Basic Work-up
For chronic or recurrent urticaria, basic laboratory studies may based on history include:
CBC with differential
CMP
Erythrocyte sedimentation rate (ESR)
CRP
TSH
H. pylori
LFT’s
Oftentimes, pts want labs performed to provide ‘‘reassurance value’’ for the patient and his or her family members

21. More Targeted Work-up Autoimmune disorders Chronic medical illness
SLE
rheumatoid arthritis
Polymyositis
thyroid autoimmunity
Chronic medical illness
malignant neoplasms
lymphoma

22. Step Treatment for CU
Journal of Allergy and Clinical Immunology 2014;133:

23. Case study 2 - treatment
Because she is not responding to Benadryl, start a 2nd generation antihistamine, Zyrtec 10 mg daily. If not better within a few days, increase to BID and start a H2 blocker, famotidine 20 mg BID

24. Case study 2 – phone call
Pt calls to tell you that she is somewhat better, but the “itching is horrible at night”.

25. Journal of Allergy and Clinical Immunology 2014;133:1270-77

26. What to do when symptoms won’t go away?

27. Run?

28. Consult Consult Allergy/Immunology
Will consider starting omalizumab or cyclosporine. Why?
The most evidence is available for these medications

29. Others
Many other alternative therapies have been used in patients with refractory CU; however, the level of evidence supporting their use is lower than with omalizumab or cyclosporine.
Anti-inflammatory agents, including dapsone, sulfasalazine, hydroxychloroquine, and colchicine, have limited evidence for efficacy in patients with CU and some require laboratory monitoring for adverse effects.

30. Once serious causes have been ruled out…
Provide
Reassurance

31. Case study 2
Because the pt was not responding to high dose H1/H2 blockers and montelukast.
AND c/o sedation with other anthistamines, she was started on omalizumab 300 mg every month.
She denies having any hives after 2 months of starting.

32. Thank you!

33. References Journal of Allergy and Clinical Immunology 2014;133:1270-77
Up-to-Date. New-Onset Urticaria. Literature review current through: Aug | This topic last updated: May 14, 2015.
Up-to-Date. Chronic Urticaria: Standard management and patient education. Literature review current through: Aug | This topic last updated: Feb 19, 2015.

34. Susan Fox, MMS, PA-C University Consultants in Allergy and Immunology Rush University Medical Center