UCSF Continuing Medical Education - Continuing Education...(allergic rhinitis, allergic asthma,...

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10/18/2019

Iris M. Otani, MD

Quality Improvement Director

Associate Program Director, Allergy/Immunology Fellowship

UCSF Continuing Medical Education

Current Approaches to Allergy and Immunology:

Focus on Urticaria, Angioedema, and Allergy Tests

Disclosure

I have no relevant financial relationships with any companies related to the content of

this course.


3

Educational Objectives

▪ Recognize and treat anaphylaxis

▪ List causes of urticaria and describe initial management

▪ Name 2 physiologic pathways for angioedema and state

implications for treatment

▪ Identify situations where allergy testing is useful

1. Sackesen C et al. Pediatr Dermatol 2004;21(2):102

2. 2. Mortureux P et al. Arch Dermatol 1998;134(3☺319

3. Plumb J et al. Arch Pediatr Adolesc Med 2001;155(9):1017

4. Imbalzano E et al. Allergy Asthma Proc 2016;37(1):18

5. Minciullo PL et al. Allergy Asthma Proc 2014;35(4):295

4

A 24 year old woman presents to your office with hives for two weeks. She had a cold one week prior to the onset of hives. Diphenhydramine 25 mg provides relief, but hives return. Each hive lasts for < 24 hours and does not leave bruising. What is the most likely cause of her hives?

A. Detergent allergy

B. Autoimmune disease (urticarial vasculitis)

C. Shrimp allergy

D. Viral infection > 80% of acute urticaria


5

What history is concerning for anaphylaxis?

▪ 2 or more of the following

Simons FER et al. WAO anaphylaxis guidelines JACI 2011;127(3):587-593

▪ Acute onset after exposure to allergen

Allergen = substance that causes an allergic reaction

What can cause anaphylaxis?

▪ Food + Exercise (+/- ASA, EtOH cofactors)

- Wheat, shrimp, legumes (peanut, soy), tree nuts, tomato

- Exercise 2-3 hours after ingestion


During or within 1 hour after


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Prescribe auto-injectable epinephrine if history concerning for anaphylaxisOnly medication with mortality benefit

▪ Timing

▪ Location

▪ Route

▪ Dose

▪ As soon as possible

▪ Anterolateral thigh

▪ Intramuscular

▪ 0.3 mg (~0.01 mg/kg)

Kanani et al. Urticaria and angioedema. Allergy Asthma and Clinical Immunology 20188

Causes of Hives


Bernstein JA et al. The diagnosis and management of acute and chronic urticaria: 2014 update. JACI 2014 May;133(5):1270-79

Which of the following tests are recommended for patients with chronic urticaria (CU)?

A. ANA

B. CBC/d, ESR/CRP, AST/ALT, TSH

C. Food allergy testing (specific IgE)

D. Thyroid autoantibodies (TPO, thyroglobulin)

Hsu ML and Li LF. British Journal of Dermatology 2012 166;4(747-752)

Sanchez J et al. Dermatology Research and Practice 2018 https://doi.org/10.1155/2018/670305210

Food Allergy Testing is not Recommended

▪ Many patients report food as a trigger of hives (> 30%)

▪ False positives common with food allergy testing (50-60%)

- 17.5% CU patients had positive skin / blood allergy test to

food

- 0% had hives when they ate that food


Confino-Cohen R JACI 2012;129(5):1307

Najib AAAAI 2009;103(6):49611

Thyroid disease is seen more commonly in CU

▪ Hypothyroidism: 10% CU patients vs 0.6% controls

▪ Hyperthyroidism: 3% vs 0.5%

▪ Thyroid autoantibodies: 30% vs 5-10%

- Don’t predict abnormal thyroid function

- Severe / Persistent CU

12

Chronic Urticaria (CU) and AutoimmunityChecking antibodies not routinely recommended

▪ Thyroid autoantibodies (30%)

▪ ANA: 30% CU patients have

weakly positive speckled ANA in

absence of SLE

▪ Fc epsilon receptor antibody

(40% CU patients)

Saini and Kaplan, JACI Practice 2018;6:97-106


13

When to consider more testing for CU

History Possible dx Testing

Hives last > 24 hours

Petechiae / Purpura

Arthralgia / Arthritis

Renal disease

urticarial vasculitis ANA, ESR, CRP

C3, C4, C1q

Hepatitis B+C serology

Cryoglobulin

Skin biopsy

Fatigue

Fevers

Arthralgia / Arthritis

Schnitzler SPEP with IF

Serum free light chains

Skin biopsy

Davis JACI Practice 2018

Gusdorf L and Lipsker D. Schnitzler Syndrome: a review. Curr Rheumatol Rep 2017 Aug;19(8):46

Sanchez J et al. JACI Practice 2017;5:464-70:14

Many patients with CU have physical triggers

▪ 76% report physical trigger

▪ 36% positive challenge

▪ 25% pressure-induced dermographism

▪ Mastocytosis

▪ Tryptase

▪ 13.4% cold-induced urticaria


15

Other ‘non-allergy’ triggers of hivesPatients may need to avoid one or more of these to prevent CU flares



Toubi E et al. Clinical and laboratory parameters in predicting chronic urticaria duation: a prospective study of 139 patients. Allergy 2004;35:869-87316

CU ManagementAnti-histamines +/- Montelukast +/- omalizumab

Fexofenadine 360 BID

Cetirizine 20 BID

Singulair Prednisone

40 mg/day

3 days

~30% persist

> 5 years

despite tx



Urticaria only

40%

Angioedema only

10%Urticaria

+

Angioedema

50%

Urticaria – mediated by histamine released by mast cells

Angioedema can co-exist → presence/absence of

angioedema doesn’t change diagnostic considerations

Angioedema –

Presence / Absence of hives is important diagnostic clue

Histamine-mediated OR bradykinin-mediated

Barmettler S et al. Allergy Asthma Proc 20:7-13, 201918

Bradykinin

Kallikrein

High Molecular

Weight Kininogen

Bradykinin

Vasodilation, Edema

Endothelial Cell

B2R

C1 INH

Inactive BK

ACE


19

A 56-year-old woman presents to your clinic with chief complaint of lip swelling / angioedema. She denies any associated hives. She does not have a family history of angioedema. She does not have dermographism on physical examination. Which of the following is the next best step?

A. Review medications to see if patient takes ACE inhibitor

B. Check C1inhibitor level

C. Check tryptase

D. Check food allergy testing

Baram M et al. JACI Pract 2013 Sep-Oct;1(5)442-5.20

ACE inhibitor induced angioedema

▪ Most common cause of angioedema in emergency

department and hospital

▪ 0.1-0.2% incidence among patients on ACE inhibitors

~12%

~6%

55% during first 90 days


Hallberg et al., Annals Pharmacotherapy 2017;51(4):293-300

Morimoto et al., J Eval Clin Pract. 2004 Nov;10(4):499-50921

What about ACE inhibitor cough? Are ARBs ok?

ACE inhibitor induced cough is a risk factor for angioedema

ARBs are ok

(but recommend not starting for

~1 year since last angioedema

episode)

Otani and Banerji. Immunol Allergy Clin N Am 2017;37:497-51122

Lab tests for bradykinin-mediated angioedema

▪ Autosomal Dominant

▪ (+) family history of

angioedema

▪ Onset ~11 years of age

C1inh

level

C1inh

function

C4 C1q

HAE Type I <30% <30% Low Normal

HAE Type II Normal <30% Low Normal

Acquired Normal

Low

Low <30% Low

Hereditary Angioedema▪ Acquired

- Lymphoproliferative malignancy

- Autoimmune disease

▪ No family history of angioedema

▪ Onset after 40 years of age

Acquired Angioedema


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Identifying bradykinin-mediated angioedema important for next management steps

▪ Doesn’t respond to anti-histamines, steroids, epinephrine

▪ Laryngeal edema

▪ Targeted medications available

Kallikrein

High Molecular

Weight Kininogen

Bradykinin

Endothelial CellB2R

C1 INH Kallikrein

inhibitor

B2R

antagonist

Inactive BK

ACE

Barmettler S et al. Allergy Asthma Proc 20:7-13, 2019

24

Allergy Testing …


25

Allergen = substance that causes an allergic reaction

Adapted from American Academy of Allergy, Asthma & Immunology. Rhinitis. The Allergy Report.

Volume 1: Overview of Allergic Diseases. Milwaukee, Wis: AAAAI; 2000:6.

AIT Practice Parameter 3rd update JACI 201026

outdoor seasonal allergens

- trees - grass - weed -

indoor perennial allergens

- dust mites - animals - cockroach -

85~90% sensitivity and specificity

(Skin Test > specific IgE)

Allergy Testing is reliable for –


27

Allergy Shots (allergic rhinitis, allergic asthma, atopic dermatitis)

→ A

llerg

en

qu

an

tity

→ Time

Build-up phase:

Injections 1-2/week

vial 1vial 1

4m2m 6m

Average duration is 3-5 years

Maintenance phase:

1x/month

Adapted from American Academy of Allergy, Asthma & Immunology. Rhinitis. The Allergy Report.

Volume 1: Overview of Allergic Diseases. Milwaukee, Wis: AAAAI; 2000:6.

AIT Practice Parameter 3rd update JACI 201028

Can be problematic

Value of testing depends

on clinical history

Skin testing helpful

Specific IgE not helpful


Sampson HA et al. Food Allergy: A practice parameter update – 2014. JACI 2014;134:5

Nowak A et al. Non-IgE-mediated gastrointestinal food allergy. JACI 2015;135(5)29

Adverse Reactions to Food

IgE-mediated

Classic Food Allergy

Oral Allergy Syndrome

Mixed

Atopic Dermatitis

Eosinophilic Esophagitis

Non-IgE-mediated

Celiac disease

30

Which history is consistent with food allergy?A. 45 year old presents with hives 30-60 minutes after eating peanut.

Patient does not have a history of seasonal allergies.

B. 25 year old presents with mouth itching and no other symptoms

immediately when eating peanut. Patient has a history of severe

seasonal allergies.

C. 36 year old presents with fatigue, malaise, abdominal bloating, and

distention. Patient notes occasional joint swelling that worsens after

meals although not with any particular food.

D. 27 year old presents with long-standing difficulty swallowing that is

worse when eating red meat. The patient reports that some other

members of his family have had similar difficulty with swallowing.

The patient has a history of atopic dermatitis and seasonal

allergies.


Stukus DR and Mikhail I. Curr Allergy Asthma Rep 2016;16(5):34.31

Food Allergy Testing

Sensitization

Detection of IgE

specific to foods

through skin prick

or blood tests

(specific IgE)

Allergy

Clinical History!!

&

Sensitization

Negative Predictive Value > 95%

Positive Predictive Value < 50%

Unnecessary food elimination

Ordering food allergy testing for

patients without history of classic

food allergy can have significant

negative consequences

Sampson HA et al. Food Allergy: A practice parameter update – 2014. JACI 2014;134:532

Symptoms of Classic Food Allergy

Minutes to 2 hours after ingesting food

Symptoms are reproducible after specific food


33

Patient A: Hives 30-

60 min after every

peanut ingestion

Patient B: Mouth

itching after eating

peanuts. Severe

seasonal allergies.

© 2019 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Wang J et al. Component Testing for pollen-related, plant-derived food allergies. Uptodate accessed 9/30/201934

Oral Allergy Syndrome

Food

Allergy

OAS

Peanut Ara h 2 Ara h 8

Hazelnut Cor a 9 /

14

Cor a 1

Walnut Jug r 1 Jug r 5


35

Patient C: 36 year old presents with fatigue, malaise, abdominal bloating, and distention. Patient notes occasional joint swelling that worsens after meals although not with any particular food.

36

Eosinophilic Esophagitis (EoE)

▪ 27 year old presents with long-standing difficulty

swallowing that is worse when eating red meat. The

patient reports that some other members of his family

have had similar difficulty with swallowing. The patient

has a history of atopic dermatitis and seasonal allergies.

Apergel and Aceves JACI 2018;142:1-8

Lucendo AJ et al. Ann Allergy Asthma Immunol 2014 Dec;113(6):624-9.

Alsalamah M et al. Am J Gastroenterol 2016 May;111(5):752-3.


Apergel and Aceves JACI 2018;142:1-8

Lucendo AJ et al. Ann Allergy Asthma Immunol 2014 Dec;113(6):624-9.

Alsalamah M et al. Am J Gastroenterol 2016 May;111(5):752-3.37

EoE and Food

▪ Skin testing not helpful to identify which foods trigger EoE

▪ Food allergy patients on oral food immunotherapy → EoE (2.72%)

▪ Food elimination → food allergy

Other

(8%)

Egg/Wheat

(25%) Milk

(67%)

3 food

triggers

(30%)

2 food

triggers

(30%)

1 food

trigger

(30-50%)

© 2019 UpToDate, Inc. and/or its affiliates. All Rights Reserved.38

Venom / Stinging Insects

Anaphylaxis Skin Testing, Epinephrine50% risk for anaphylaxis

< 5% risk for anaphylaxis

Same as general population

Normal reaction

Large local reaction

Cutaneous systemic

20% have positive testing


Bush RK et al. JACI 2006;117(2). The medical effects of mold exposure.39

Which patient would benefit from mold skin testing?

A. 54 year old man presents with a recent diagnosis of severe

persistent asthma that is not responding to increasing doses of

inhaled and oral steroids. A total IgE level is 1343. Chest CT shows

bronchiectasis.

B. 46 year old man with headaches and generalized fatigue over the

last several months. A total IgE level is 40. He is concerned about a

possible allergy to the black mold in his bathroom.

C. 32 year old woman with eye irritation and rhinorrhea at work in a

damp office where there was water leakage last year. Her

symptoms resolve when she is out of the office.

40

Established Effects

• IgE-mediated mold

sensitization worsens

asthma, allergic

bronchopulmonary

aspergillosis (ABPA),

allergic fungal

rhinosinusitis (AFRS)

• Hypersensitivity

Pneumonitis

Toxic Effects

-Mycotoxins-

• Improbable that home

or office mycotoxin

exposures would lead

to a toxic adverse

health effects

Irritant Effects

-Volatile organic compounds-

-Particulates (spores, hyphae)-

• Irritant effects involve

the mucus membranes

of the eyes and upper

and lower respiratory

tracts and are transient

• Symptoms or signs

persisting weeks after

exposure should not be

ascribed to irritant

exposure

No credible evidence that exposure to molds induces a state of immune

dysregulation (eg, immunodeficiency or autoimmunity).

Bush RK et al. JACI 2006;117(2). The medical effects of mold exposure.

De Brunhoff, J. Babar the King (Babar Series).

Patient APatient C


41

Educational Objective 1Recognize and treat anaphylaxis

▪ 2 or more of the following

▪ Acute onset after exposure to allergen


Educational Objective 2List causes of urticaria and describe initial management

High dose antihistamines

Omalizumab


43

Educational Objective 3Name 2 physiologic pathways for angioedema and state implications for treatment

Kallikrein

High Molecular

Weight Kininogen

Bradykinin

Endothelial CellB2R

C1 INH

Kallikrein

inhibitor

B2R

antagonist

Omalizumab

Angioedema + Urticaria Angioedema w/o Urticaria

44

Educational Objective 4Identify situations where allergy testing is useful

Food, Venom, Mold

Value of testing depends

on clinical history

Medication

Skin testing helpful

Specific IgE not helpful

Seasonal outdoor allergen

Perennial indoor allergen

Skin testing best

Specific IgE helpful


Questions?

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