Transcript Allergy/Immunology for the Internist

Hien Nguyen Reeves, MD, ABAI, ABIM
Clinical instructor UBC, Kelowna, BC
Disclosures
Grants/Research Support:
 None
Speakers Bureau/Honoraria:
 Pfizer Canada, CME Speaker
Schering-Plough
Merck
Pictures
Dermatology Image Atlas
Learning Objectives
After participating in this educational program,
participants should be able to:
1. Describe the causes, signs, and symptoms of
common allergic/immunologic conditions
2. Understand diagnostic tests for these conditions
3. Discuss the appropriate treatment of these
conditions and long-term management of patients
at-risk
Mechanism of Hypersensitivity
IgE hypersensitivity
Angioedema of lips
Angioedema of eyes
Angioedema of hand
Urticaria
Cholinergic urticaria
Typical urticaria
Erythema marginatum
Urticarial vasculitis
Urticaria pigmentosa
Serum sickness
Morbilliform rash
Erythema multiforme
Dermatitis Herpetiformis
Steven-Johnsons/TEN
Bullous pemphigoid
Case
 60 yo female presents with a 1 month history of persistent
daily generalized rashes suggestive of hives. She reports
episodes started when she was treated with Ciprofloxacin
for a urinary tract infection. Within 1 week of taking the
antibiotic, she developed this rash. She has since stopped
the antibiotic but hives persist. Interestingly, she has had
several episodes of lip and eye swelling as well as hives
occurring intermittently over the past 10 years.
Angioedema not necessarily associated with the hives.
 She is taking over the counter antihistamines and oral
prednisone but they have not controlled her rashes. She
has avoided dairy and breads and has resorted to a bland
diet of soups as she thinks foods may be causing her
symptoms.
 Review of systems: Positive for chronic headaches,
fatigue, heartburn, nausea, abdominal bloating, frequent
upper respiratory infections (bronchitis, sinusitis,
pneumonias, strep throats, and utis) and ”allergy”
symptoms (rhinorrhea, watery eyes, nasal congestion all
year round worse with scents)
 PMH/PSH: HTN, GERD, Hypothyroidism, Hysterectomy,
appendectomy, cholecystectomy, tonsillectomy
 Social: ex-smoker 15 pk year, quit 10 years ago, marijuana
use weekly, but no history of IVDU or other illicit drugs ,
drinks 1 glass of red wine daily, married for 30 years but
husband just passed away. she is a retired teacher.
 Meds: Advil qd, Altace qd, Rabeprazole qd, Synthroid
qd, ASA qd, prednisone 40 mg qd
 Meds Allergies: Sulfa, Tetracycline, Cipro- rashes
 FMH: Mother had emphysema and hypothyroidism,
Father had HTN, CAD, MI at 65 yo, Sister with
hypothyroidism, Brother healthy. No one with
angioedema or infections in the family
Problem List?
Problem List
 Generalized urticaria- Acute on chronic
 Angioedema
 Drug allergies
 Recurrent infections
 GERD, Abdominal bloating
 Chronic fatigue
 Chronic rhinorrhea
 HTN
 Thyroid dz
Urticaria/angioedema definition
 Urticaria-raised erythematous lesions involving superficial
dermis, often generalized and pruritic, lasts minutes to
hours, and can recur. Acute urticaria < 6 weeks, Chronic >
6 weeks. Multiple mechanisms-mast cells, basophils
 Angioedema- self-limited nonpitting edema generally
affecting the deeper layers of skin and mucous membranes.
A result of increased vascular permeability causing the
leakage of fluid into the skin in response to vasodilators
released by immunologic mediators. 50% of pts with
chronic urticaria are said to have angioedema
- IgE, mast cells releasing histamines, leukotrienes,
prostaglandins
-Kinin and formation of bradykinin (vasodilator)
Differential & Investigations?
Classification of Urticaria
Allergy, Asthma & Clinical Immunology 2011, 7(Suppl 1):S9 doi:10.1186/1710-1492-7-S1-S9
Investigations
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CBC, Creatinine, LFT, Ferritin
Urinalysis
Anti-thyroid peroxidase, anti-thyroglobulin antibodies
H.pylori serology, biopsy
CXR, CT sinus for chronic sinusitis
 Skin test for environmental and food allergens-and
ImmunoCap (RAST) to allergens if skin test not possible- to
evaluate for atopy, poor PPV
 Check IgG, IgA, IgM, IgE.
 If IgG is low, then need to do IgG subclasses, antibody
responses to vaccines- i.e.-pneumococcal, tetanus titers, HIB,
CD markers (CD19, CD3, CD4, CD56). Hepatitis, MMR
serology may be helpful
Other studies
 Serum electrophoresis , Hepatitis B and C
serology, Monospot , antistreptolysin and anti-
DNase
 Stool samples for ova and parasite
 TTG screening, PATCH testing if warranted
 Serum tryptase
 C4, C1 esterase inhibitor (functional and qualitative) C1q,
genetic testing for HAE
 Drug testing- Penicillin skin testing, RAST to penicillin
minor determinants. If need PCN, oral challenge or
desensitization depending on history and risk of
anaphylaxis. Other drugs not standardized.
Desensitization has to be carried out every time. Testing
and desensitization contraindicated in patients with a
history of TEN/Stevens-Johnson s reaction to a drug
 No sulfite testing
 When in doubt, biopsy
Flow diagram for angioedema
Treatments for urticaria
Allergy, Asthma & Clinical Immunology 2011, 7(Suppl 1):S9 doi:10.1186/1710-1492-7-S1-S9
Cyclosporine
 Low dose (3 mg/kg) cyclosporine (CsA) effective in
treating patients with CIU in 13/19 (full remission) and
6/19 (significant relief) compared to controls over
three months
Toubi E et al Allergy 1997; 52: 312-6
 DBPC trial with 4mg/kg CsA revealed improvement in
daily urticaria score (42 points max) by 12.7 (vs. 2.3 in
placebo)
 Histamine release decreased from 36% to 5%
(p<0.0001)
 Autologous skin test also reduced in responders
Grattan CE et al. Br J Dermatol 2000; 143: 365-72
Omilazumab- Xolair, anti-IgE
Our patient results
 UA-> 100,000 Staph, elevated anti-thyroid peroxidase
abs > 1300, and positive H.pylori serology
 Skin test negative to environmental and food allergens,
IgE 330 IU/ml, IgG, IgA, IgM, CBC, LFT, Creatinine all
wnl
Case in question
 Stopped ASA and ACEI, and switched to ARB
 Treated H.pylori with triple therapy, and UTI
 Angioedema and hives resolved
 She takes Reactine and Ranitidine only as needed now,
and off oral prednisone
 Nasocorticosteroids, Atrovent nasal spray , nasal
washes prn
Key points
 Through several mechanisms a variety of mediators may
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lead to urticaria or angioedema
Clinically, a causative agent is much more often identified
in acute than in chronic urticaria/angioedema
A number of medications are available to control chronic
urticaria while awaiting a spontaneous remission
Patients with angioedema without urticaria should be
tested for C1 inhibitor deficiency
Recurrent infections, especially with other symptoms
(rashes, alopecia, diarrhea) should be worked up for
primary immunodeficiency