Transcript Allergy and Immunology Internal Medicine Board Review 2014

Patricia Stewart, MD
Assistant Professor of Medicine and Pediatrics
University of Mississippi Medical Center
[email protected]
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I do not have a financial interest/arrangement
of affiliation that could be perceived as a real
or apparent conflict of interest in the context
of the subject of this presentation.
Thank you to Dr. Lindsey McMullan for
original slide set, now modified.
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Allergy/Immunology 2%
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Anaphylaxis
Asthma (also listed in Pulmonary)
Rhinitis/Sinusitis/Conjunctivitis
Food allergy
Urticaria and angioedema (also listed in Derm)
Skin disorders
Drug allergy
Primary immunodeficiency
Allergic complications of transfusions
Autoimmune systemic disorders
*As of January 2015
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Allergy
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Rhinitis
Asthma
Urticaria
Angioedema
Anaphylaxis
Drug Allergy
Atopic Derm/Contact Derm
Eosinophilic Esophagitis
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Immunology
◦ Basic overview
◦ Complement
deficiencies
◦ CVID
◦ Selective IgA deficiency
◦ Vaccines:
 Indications for
withholding live
vaccines
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Type I
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Type II
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Type III
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Type IV
◦ IgE mediated
◦ Immediate (anaphylaxis, etc)
◦ Symptoms from mast cell degranulation
◦ Antibody (IgG, IgM, some IgA) mediated
◦ Cytotoxic
◦ Ex: PCN induced autoimmune hemolytic anemia
◦ Immune Complex mediated
◦ IgG, IgM, activated complement, neutrophils
◦ Ex: Serum Sickness
◦ Delayed hypersensitivity, T cell mediated
◦ Ex: TB skin test, contact dermatitis
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A 32 y/o F has a history of seasonal allergic rhinitis in the
spring which has typically been well controlled however
she has noticed persistent, clear, rhinorrhea and nasal
congestion for the past 3 months. She has no pets, no
mold exposure, and symptoms do not improve with travel.
She has no facial or dental pain. Current daily medications
include cetirizine, pseudoephedrine, oxymetazoline nasal
spray. She is otherwise healthy. Physical exam is
remarkable only for slightly edematous, erythematous
nasal turbinates with clear nasal drainage.
Which is the most appropriate diagnosis?
A: Vasomotor rhinitis
B: Chronic rhinosinusitis
C: Wegener’s (Granulomatosis with polyangiitis)
D: Rhinitis medicamentosa
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Inflammation of nasal mucosa causing:
rhinorrhea, nasal itching, sneezing, congestion,
post nasal drainage
Allergic rhinitis
◦ Seasonal or perennial (or both)
◦ Can confirm with skin test or in-vitro specific IgE
antibody assay
◦ Rx:
 environmental control
 First line med: Intranasal steroids
 Second line meds: PO antihistamines, Leukotriene receptor
antagonists
 Allergy immunotherapy (shots or dissolvable tablets)
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URI related rhinitis
◦ Do not select antibiotics
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Non-allergic Rhinitis
◦ Other names:
 Vasomotor: reaction to neurogenic/vagal stimuli
 NARES (non allergic rhinitis with eosinophilia syndrome)
◦ Negative allergy testing
◦ Rx: Again, Intranasal steroids
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Rhinitis medicamentosa
◦ Refractory congestion due to chronic use of topical
nasal decongestants
◦ Rx: withdraw the nasal decongestant
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Other etiologies:
◦ Mechanical obstruction (septal deviation, polyps)
◦ Sinusitis
◦ Wegener’s
 Key words: systemic illness, ulcerations
◦ Cystic fibrosis
 Key words: young, malnourished, polyps, chronic
sinusitis, infertility, chronic/recurrent bronchitis
◦ Medications: propranolol, alpha-methyldopa
◦ CSF leak
 Key words: Unilateral Dx: check beta-2 transferrin
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Rhinitis with Nasal Polyps
Tip off- anosmia
Immunodeficiency
Cystic fibrosis
Aspirin Exacerbated Respiratory Disease (Aspirin
Sensitive Asthma)
◦ Allergic Fungal Sinusitis
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 Key Words: hyper-attenuation on CT scan
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Pregnancy Rhinitis
◦ Congestion and rhinitis limited to pregnancy
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Testing
◦ Spirometry
◦ Methacholine Challenge
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Classify based on risk and severity
◦ Most severe characteristic
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Start treatment at appropriate levels
◦ preferred vs alternative therapies
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A 35 y/o Female comes in for evaluation of wheezing,
shortness of breath, and chest tightness. She has taken no
medication for these symptoms which occur approximately
3 times weekly for the past month without nocturnal
awakenings. She has a history of childhood asthma, but
until now has had no asthma or allergy symptoms.
Spirometry performed in your office shows an FEV1 of 90%
predicted and FEV1/FVC ratio of 85. Physical exam is
unremarkable.
Which of the following is the next best option?
A: order bronchial challenge testing
B: start inhaled budesonide twice daily
C: set her up for allergy testing
D: Start inhaled corticosteroid/long acting albuterol
combination therapy
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Suggestive symptoms in conjunction with
testing
Spirometry/PFTs
◦ Decreased FEV1/FVC ratio
◦ Response to beta-agonist
 FEV1 improvement of 12% AND 200 mL
◦ Normal Spirometry does not rule out asthma
1. National Asthma Education and Prevention Program Expert Panel Report 3 (NAEPP EPR3);
http://www.nhlbi.nih.gov/files/docs/guidelines/asthgdln.pdf
2. Interpretative strategies for lung function tests. Pellegrino R, Viegi G, Brusasco V, et. Al.
Eur Respir J. 2005 Nov;26(5):948-68.
Normal
Reversible
Non-reversible
◦ Does NOT diagnose asthma
◦ DOES indicate airway hyper-responsiveness (AHR)
 Perform when symptomatic
◦ NPV is good- if negative- rules OUT asthma
◦ Positive is 20% decrease in FEV1
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A 45 y/o M with a long standing history of asthma and allergies
to dust mites comes in for evaluation. Despite therapy with
ICS/LABA combination with appropriate technique, appropriate
environmental control, and a recently completed course of
immunotherapy, he continues to require his short acting
albuterol 3 times a week. He is not a smoker. He has required 4
courses of oral steroids in the past year. Today physical is
notable only for occasional expiratory wheeze, and FEV1 of 70%
with normal inspiratory loop. Review of previous lab work is
notable for IgE of 200 IU/mL, absolute eosinophil count of 230,
positive specific IgE to dust mites, and a normal chest x-ray.
The next most appropriate treatment is?
A: omalizumab
B: repeat allergy immunotherapy
C: long acting inhaled anticholinergic
D: Have him evaluated for vocal cord dysfunction
From National Asthma Education and Prevention Program. Expert Panel Report 3:
guidelines for the diagnosis and management of asthma. Bethesda, Md.:NIH/Nationa
Heart, Lung, and Blood Institute; 2007.
http://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/full-re
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Step up/down
From National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the
diagnosis and management of asthma. Bethesda, Md.:NIH/National Heart, Lung, and Blood Institute;
2007.
http://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/full-report
From National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and
management of asthma. Bethesda, Md.:NIH/National Heart, Lung, and Blood Institute; 2007.
http://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/full-report
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Rescue Medications
◦ Short acting beta-agonists (SABA)
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Controller Medications
◦ Inhaled Corticosteroids (ICS)
◦ Long acting Beta Agonists (LABA)
 Black Box (BB) Warning- in asthma, do not give alone
◦ Leukotriene Receptor antagonists (LTRA)
◦ ICS/LABA combinations
◦ Omalizumab- anti-IgE
 Black Box warning (anaphylaxis)
 Dosing- based on IgE and weight
◦ Others:
 Oral Steroids
 Theophylline (know drug interactions ex: levels
increase with fluoroquinolones, macrolides, st john’s
wort, amiodarone, diltiazem, cimetidine and levels
decrease with rifampin, phenytoin, phenobarb,
cannabis, carbamazepime)
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A 50 y/o M with a long history of asthma treated in a different
state comes to establish care with you. He requires his albuterol
multiple times daily despite being on an ICS/LABA combo and
leukotriene modifier with excellent compliance. He only gets
slight relief. He has never smoked and has no other medical
problems. He states that the last 2 months of living in his new
house with no carpets, pets, or mold exposure and a Hepa Filter
are the best his asthma has ever been. Review of previous
records indicates an IgE of 150 IU/mL, normal chest x-ray, and
allergic sensitization to cats and dogs. Physical exam is
remarkable only for occasional expiratory wheeze. Spirometry is
significant for FEV1 of 70%, FEV1/FVC of 72%. FEV1 improves
20% after nebulized albuterol and he notices tremendous benefit.
Which is the most appropriate treatment?
A: Double the dose of his inhaled steroids
B: start Omalizumab
C: Assess inhaler technique
D: Add daily prednisone
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A 25 y/o F has had worsening of her asthma after
being well controlled on a medium dose inhaled
steroid. She now uses short acting albuterol for
wheezing 3-4 times a week but has not noticed
increased rhinitis, post nasal drip, heartburn, or
fever. She demonstrates appropriate inhaler
technique. Physical exam is notable only for soft endexpiratory wheezes in all lung fields.
Which is the most appropriate treatment?
A: Add short acting anticholinergic
B: Give penicillin antibiotics
C: Add long acting albuterol
D: Double dose of inhaled steroids
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Consider
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GERD
Sinusitis
Compliance/technique
Alternative diagnosis
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Exercise induced asthma- symptoms with
exercise only
◦ During or after exercise
 Peaks 5-10 minutes after stopping activity, resolve < 30 min
◦ Screen with exercise testing: 15% reduction FEV1
◦ Rx: Pretreat with SABA 10-15 min before exercise
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Cough Variant Asthma
◦ Cough is predominant or only symptom
◦ Distinguish from other causes of chronic cough (rhinitis,
GERD, etc)
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Occupational Asthma
◦ Symptoms at work
◦ Significant improvement on weekends, vacations
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A 44 y/o F is seen for worsening of asthma. She was previously
controlled on ICS/LABA combo, with short acting albuterol. She
is now having daily wheezing, dyspnea, and a productive cough.
Other than a history of seasonal allergies which are controlled,
she is healthy. Inhaler technique is good. PE is remarkable only
for expiratory wheezing in all lung fields. Lab evaluation is
notable for 13% eosinophils, IgE of 1200 ng/mL, and CXR with
patchy upper lobe infiltrate and increased bronchial markings.
CT chest reveals mucous plugging and central bronchiectasis.
Which is the next most appropriate diagnostic step?
A: Bronchoscopy with BAL and biopsy
B: aspergillus IgE testing
C: Sweat chloride
D: Sputum gram stain and culture
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A 47 y/o M with h/o asthma and allergies comes for
f/u due to increase in nonproductive cough. He has
also noticed a paresthesia in his left leg and
decreased grip in his right hand. Physical is notable
for BP of 150/100, scattered expiratory rhonchi on
lung exam, and decreased strength in R hand and L
foot. Your CBC is remarkable for 32% eosinophilia
What is the next best test to establish the diagnosis?
A: ANCA testing
B: CXR
C: full PFTs
D: MRI brain
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A 24 y/o F is seen in the urgent care clinic for sudden
onset of asthma exacerbation. She has a history of
sudden exacerbations requiring unscheduled visits, but
between exacerbations, pulmonary function testing and
physical are unremarkable. She takes inhaled
fluticasone and short acting albuterol. Physical is
remarkable for audible wheezing on both inspiration
and expiration. Wheezing is heard only in central lung
fields. She is mildly tachycardic, but physical exam is
otherwise unremarkable. She does not respond to
nebulized albuterol and ipratropium x 3 or IV
corticosteroids and continues to wheeze. O2 sat is 98%
on room air.
Part 1: What is the next most appropriate step?
A: CXR
B: IV magnesium
C: IM corticosteroids
D: laryngoscopy
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A 24 y/o F is seen in the urgent care clinic for sudden onset
of asthma exacerbation. She has a history of sudden
exacerbations requiring unscheduled visits, but between
exacerbations, pulmonary function testing and physical are
unremarkable. She takes inhaled fluticasone and short acting
albuterol. Physical is remarkable for audible wheezing on
both inspiration and expiration. Wheezing is heard only in
central lung fields. She is mildly tachycardic, but physical
exam is otherwise unremarkable. She does not respond to
nebulized albuterol and ipratropium x 3 or IV corticosteroids
and continues to wheeze. O2 sat is 98% on room air.
Part 2: What is the most appropriate addition to her routine
therapy?
A: Addition of long acting albuterol
B: daily corticosteroids
C: Speech therapy
D: omalizumab
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Everything that wheezes is not asthma
◦ Heart failure, COPD, upper airway obstruction, others
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ABPA/ABPM (allergic bronchopulmonary
aspergillosis (mycosis))
◦ Dx:
 Asthma or Cystic Fibrosis
 Elevated IgE
 Asthmatic: > 1000 ng/mL or 417 IU/L
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Positive IgE test to A. fumigatus, other molds
Positive Aspergillus IgG
Immediate skin test reactivity to A. fumigatus, other molds
Eosinophilia
Radiographic pulmonary findings
 Opacities on CXR
 Bronchiectasis on HRCT
◦ Rx: oral steroids, follow IgE
For further reading if needed:
Greenberger PA et. al. Allergic Bronchopulmonary Aspergillosis.
J Allergy Clin Immunol Pract. 2014: 2(6):703-708.
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Churg Strauss
◦ Now called Eosinophilic granulomatosis with
polyangiitis
◦ Sinusitis, asthma, eosinophilia, vasculitis
◦ Transient pulmonary infiltrates
◦ Small vessel vasculitis
◦ Neuropathies (mononeuritis multiplex)
◦ MPO/P-ANCA
◦ Rx: oral steroids +/- cyclophosphamide
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VCD (vocal cord dysfunction)
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Female 2:1
Athletes
Bronchodilator non-responsive
Mimics asthma, recurrent wheezing (may also have
stridor)
Difficulty getting breath IN (Asthma- expiration)
Can occur with or without asthma
Flattening of inspiratory curve on spirometry
If symptomatic: laryngoscopy
Rx: Speech therapy, behavior modification, patient
education
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A 35 y/o Female comes in for evaluation of wheezing,
shortness of breath, and chest tightness. She has taken no
medication for these symptoms which occur approximately
3 times weekly for the past month without nocturnal
awakenings. She is 18 weeks pregnant. She has a history
of childhood asthma, but until now has had no asthma or
allergy symptoms. Spirometry performed in your office
shows an FEV1 of 90% predicted and FEV1/FVC ratio of 85.
Physical exam is unremarkable.
Which of the following is the next best option?
A: order bronchial challenge testing
B: start inhaled budesonide twice daily
C: set her up for allergy testing
D: Start inhaled corticosteroid/long acting albuterol
combination therapy
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Step up therapy indications similar for nonpregnant
◦ Safer to be exposed to medications with limited data (ex:
LABA, SABA) than have ongoing symptoms and
exacerbations
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Class B:
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PO: cetirizine, loratadine, montelukast
intranasal: budesonide
Inhaled: budesonide
Injectable: Omalizumab (anti-IgE) but be aware of BB
warning for anaphylaxis
Do NOT pick skin prick testing, start allergy
immunotherapy, or perform bronchial challenge
in the pregnant patient
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A 32 y/o F is in the urgent care clinic with widespread
pruritic wheals, each lasting 2-4 hours. This is the 3rd day
she has had this rash. She does not have any other
symptoms and does not have swelling. Diphenhydramine
has minimally helped the itching, but is making her very
sleepy. She takes no other medications and is otherwise
healthy. Physical exam is remarkable only for scattered
edematous, indurated wheals to her face, trunk, upper and
lower extremities b/l. She also has marked
dermatographism.
What is the next best step in management?
A: skin biopsy
B: admission to the hospital
C: start her on cetirizine and ranitidine
D: treat with high potency topical steroid
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A 52 y/o F is being evaluated for a 1 month history of
daily wheals which are pruritic, but also have a burning
quality. Each lesion persists around 48 hours. After
resolution, some lesions are leaving a bruise. They occur
on all extremities and her trunk, but are the worst on her
lower extremities. The only other associated signs are
some pain in her hands and her feet that she has
attributed to the extremely cold weather, and a recent
slight discoloration in her urine.
What is the next best step in management?
A: Skin biopsy
B: admission to the hospital
C: check thyroid antibodies
D: treat with high potency topical steroid
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Classification:
◦ Acute urticaria (< 6 weeks)
◦ Chronic urticaria (> 6 weeks)
◦ Physical urticaria (pressure, cold, vibratory,
cholinergic, etc)
◦ Urticarial Vasculitis
◦ Contact urticaria
◦ Urticaria and angioedema as components of
anaphylaxis
Attribution: By James Heilman, MD
http://creativecommons.org/licenses/by-sa/3.0) via Wikimedia Commons
http://commons.wikimedia.org/wiki/File:Hives2010.JPG
Image not altered
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Urticaria Diagnosis Points
◦ Hallmark: rapid appearance of pruritic wheals which
disappear within 24 hours
 Lesions lasting >24 hours or palpable purpura raise
concerns for urticarial vasculitis or other underlying
disease- Perform Biopsy
 Can also check CBC , ESR/CRP, complement levels, Hep
B/C, cryoglobulins, SPEP
◦ DO NOT work up for or diagnose HAE if the patient
has urticaria. HAE patients do not have hives
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Treatment
◦ Acute urticaria: remove inciting source (food, drug,
etc)
◦ Chronic urticaria:
 Rx: H1 +/- H2 blocker
 Do NOT pick oral or systemic steroids- only indicated
in VERY symptomatic patients with urticaria in short
term
 NEW: Omalizumab was approved by the FDA for
chronic idiopathic urticaria resistant to antihistamines
in 2014. Dosing is either 150 mg SC qmonth or 300
mg SC qmonth. NOT dependent on IgE levels or weight
(different from dosing for asthma)
Classification
Characteristics
Cholinergic
urticaria
Occurs in response to an increase in core body
temperature; lesions present as small papules with a
prominent surrounding erythematous flare
Dermatographism Rapidly induced by pressure
Delayed
pressure-induced
urticaria
Patients often experience systemic symptoms
Swelling and burning of palms and soles may occur
Exercise-induced
urticaria
On a continuum with exercise-induced anaphylaxis;
many patients only develop symptoms if primed by an
ingested allergen prior to exercise
Solar urticaria
Mast cell activation in certain wavelengths of light
Acquired Cold
urticaria
Mediated by IgE or cryoglobulin
Could be related to underlying infection
Risk of shock with immersion in cold water
Test with 5 minute ice cube challenge
Familial Cold
urticaria
Not actually have degranulation of mast cells
Associated fevers, chills, myalgias
Autoinflammatory syndrome
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A 25 y/o F is being seen in the ED for mild laryngeal
angioedema, lip and tongue swelling, and severe abdominal
cramping. She tells you that as a child, she didn’t like to ride
bikes due to genital swelling afterward, and over the past several
months she has had unexplained, recurrent severe abdominal
cramping despite extensive, unrevealing lab work up and various
medications which have not helped. This is the first time she has
had any type of upper airway symptoms. She is an only child; her
maternal uncle and her cousin have similar symptoms. Physical
exam is remarkable for obvious angioedema of both lips, a
mildly enlarged tongue. Abdomen is not distended and only
mildly TTP. Vitals are normal, she speaks easily in complete
sentences, and O2 sat is 100% on room air. ENT is on the way to
evaluate the degree of laryngeal edema.
Part #1: Which of the following will best establish the diagnosis
A: ex-lap
B: extensive allergy testing to foods
C: SPEP and UPEP
D: C4 and C1 esterase inhibitor function
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A 25 y/o F is being seen in the ED for mild laryngeal angioedema, lip and
tongue swelling, and severe abdominal cramping. She tells you that as a
child, she didn’t like to ride bikes due to genital swelling afterward, and over
the past several months she has had unexplained, recurrent severe
abdominal cramping despite extensive, unrevealing lab work up and various
medications which have not helped. This is the first time she has had any
type of upper airway symptoms. She is an only child; her maternal uncle and
her cousin have similar symptoms. Physical exam is remarkable for obvious
angioedema of both lips, a mildly enlarged tongue. Abdomen is not
distended and only mildly TTP. Vitals are normal, she speaks easily in
complete sentences, and O2 sat is 100% on room air. ENT is on the way to
evaluate the degree of laryngeal edema.
Part #2: Which of the following would be the most appropriate
treatment to give this patient in the emergency room?
A: Epinephrine 1:1000, 0.3 mg IM
B: Epinephrine 1:10,0000 IV drip
C: high dose glucocorticoids
D: C1 esterase inhibitor
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Sudden, temporary edema of localized area (ie
lips, face, genitals, hands, feet)
Abdominal pain may indicate bowel wall edema
If there is urticarial, it is NOT HAE
ACE Inhibitors- typically face/lip/tongue- can be
> 6 months after drug initiation
◦ Rx: stop ACE-I
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Treatment for non-HAE angioedema
◦ If airway compromise or hypotension:
 Epinephrine, epinephrine, epinephrine- 1st line
 Could then add antihistamines, corticosteroids
◦ No airway compromise or hemodynamic instability:
 Antihistamines, corticosteroids
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Angioedema WITHOUT urticarial
May have abdominal pain that is recurrent and
unexplained
Type 1,2- autosomal dominant
No hives, no itch
Triggers can include:
◦ Trauma, dental visit, surgery, menses, puberty
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Treat acute attacks with:
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C1-esterase inhibitor concentrate
ecallantide (plasma kallikrein inhibitor)
icatibant (Bradykinin B2 receptor antagonist)
!!Epinephrine is NOT effective!!
Type 1
Type 2
Acquired
HAE with normal C1 INH
C1
Low
esterase
level
Normal
Low
Normal
C1
Low
esterase
function
Low
Low
Normal
C1q
Normal
Normal
Low
Normal
C4
Low
Low
Low
Normal
Other
info
Inherited Inherited Associated
with
lymphoproliferative
disorders
No family
history
• Autosomal dominant
• Females more likely
• Tends to present after
puberty
• Attacks may be fewer and
less frequent with more
facial and less
abdominal/multiorgan
involvement
• Triggers also include
increased estrogen states
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A 28 y/o M is seen in the ED for shortness of breath after a
bee sting to his arm 15 minutes ago. He also feels
nauseated, and his lips are starting to feel puffy. Physical
is notable for BP of 100/60, PR 100, RR 22, T 98.6. He is
agitated, lip is noticeably swollen, and wheezing is heard
in all lung fields. There is no evidence of laryngeal swelling
and no rash.
Which of the following is the most appropriate therapy?
A: IV diphenhydramine and IV methylprednisolone
B: IV epinephrine, IV methylprednisolone, IM
diphenhydramine
C: IM epinephrine, inhaled albuterol
D: inhaled albuterol, IV fluids, IV diphenhydramine and
reassurance
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Life-threatening reaction
◦ IgE Dependent
 Common Causes:
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Food (peanut/nut, shellfish etc.)
Medications (PCN, NSAID)
Insect Stings (hymenoptera or fire ant bites)
Latex
◦ Non-IgE Dependent
 Common Cause:
 Radiocontrast media
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Timing:
◦ 30 min- 2 hours after injected substance
◦ Can progress and get worse or be biphasic
Rx: EPINEPHRINE 0.3 mg of 1:1000 given IM in vastus
lateralis
◦ Add ins: albuterol for bronchospasm, IV fluids for
hypotension, steroids for late phase response,
antihistamines for cutaneous symptom relief
◦ Standard life support (oxygen, airway assessment,
arrhythmia intervention, etc.)
◦ If on beta-blocker and refractory to epinephrinegive glucagon
◦ Clinical Pearl: Lay them Down. (sitting up
associated with fatal anaphylaxis)
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Other Points:
◦ Elevated tryptase (within first several hours) can
confirm
◦ Patients should be discharged with autoinjectable
epinephrine
◦ Anaphylaxis from insect sting needs evaluation for
possible venom immunotherapy
◦ No obvious trigger- consider mastocytosis (check
tryptase at baseline) or idiopathic anaphylaxis
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Cutaneous mastocytosis
◦ Urticaria pigmentosa: macule which forms wheal
with gentle stroking (Darier’s sign)
◦ Indolent, benign course
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Systemic mastocytosis
◦ Increased mast cells in tissues
 Multi-organ complaints (flushing, GI complaints, etc.
◦ Consider if severe anaphylaxis from insect sting
◦ Dx: baseline tryptase elevated is indicative
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A 55 y/o F is being evaluated for an itchy rash that she has had
for 3 days. She also feels like her face is puffy. Her only
medication is an anticonvulsant that she takes for epilepsy. This
medication was changed 3 weeks ago. Physical is notable for T:
101.3, PR: 103, BP: 135/80, RR: 14, face is slightly edematous,
she has mild generalized erythema with papules coalescing into
plaques on her trunk and extremities diffusely. There are no
lesions on her mucosal surfaces. Tender lymph nodes are
palpated in the cervical, axillary, and inguinal regions.
Laboratory is remarkable for 13% eosinophilia on CBC, and ALT
of 328 u/L, and AST of 362 u/L.
Which of the following is the most likely diagnosis?
A: Toxic epidermal necrolysis
B: IgE mediated drug reaction
C: Drug reaction with eosinophilia and systemic symptoms
D: acute viral infection

A 43 y/o F is evaluated after sustaining a dog bite to her
calf 2 days ago. The wound is tender, red, and warm. She
is up to date on her tetanus vaccination, and the dog is
determined to not have rabies. She has an anaphylactic
response to penicillins. Physical exam is notable for
Temperature of 102.6, necrotic appearing wound with
significant warmth, erythema, and tenderness to touch to
the left calf. There is no inguinal lymphadenopathy.
Which of the following is the most appropriate treatment?
A: ampicillin-clavulanate
B: azithromycin
C: clindamycin
D: ciprofloxacin plus clindamycin
Drug Mediated Skin
Eruption
Description/Other info Common Culprits
Maculopapular and
morbilliform
(small discrete
papules)
Most common type.
Distribution:
symmetric, truncal
rarely on palms or
soles
Antibiotics
diuretics
Many others
Associated: fever and
pruritus
Onset: 8-10 days after
initiation
Urticarial
Second most common
type- with or without
angioedema
Onset: a few days after
initiation
Antibiotics, contrast
Most could cause
Drug Mediated Skin
Eruption
Description/Other info Common Culprits
Erythema multiforme,
SJS, TEN
Spectrum:
target lesions (EM)
involvement of
mucous membranes
with systemic
symptoms (SJS)
life-threatening loss
of epidermis (TEN)
EM: herpes and mycoplasma
pneumoniae as causes, less
often a medication
SJS/TEN: Anticonvulsants,
sulfonamides, beta-lactams,
NSAIDs, sertraline,
pantoprazole, tramadol,
allopurinol
SJS: 10% body
involvement
HLA can be important for
TEN: at least 30% body some (Abacavir,
involvement
carbamazepime)
Nikolsky’s sign may be
present, may send
biopsy
Drug Mediated Skin
Eruption
Description/Other info Common Culprits
Fixed Drug Eruption
Discrete, often round
or oval lesions that
recur in exactly the
same spot when rechallenged with the
drug
Antibiotics, antifungals,
NSAIDs, acetaminophen,
anticonvulsants, barbituates
Red Man Syndrome
Body flushing,
hypotension, muscle
pain
Vancomycin, ciprofloxacin
- From histamine
release, not IgE
mediated allergy
AGEP
(acute generalized
exanthematous
pustulosis)
Widespread erythema
with small pustules
sometimes with fever,
leukocytosis,
occasionally
eosinophila
Antibiotics, antimalarials,
terbinafine, diltiazem
Drug Mediated Skin
Eruption
Description/Other info Common Culprits
DRESS (Drug reaction
with eosinophilia and
systemic symptoms)
Overlapping
symptoms, may be a
continuum or same
thing
and
Drug Induced
Hypersensitivity
Syndrome (DISH)
Facial edema,
erythema, fever,
lymphadenopathy, in
DRESS- eosinophilia,
can have hepatitis and
nephritis. Can notice
purpura, blistering,
skin pain, skin
necrosis, chills,
lethargy
Onset: within 12
weeks of initiation
May persist for weeks
Anticonvulsants
Drug Mediated Skin
Eruption
Description/Other info Common Culprits
Photosensitive skin
reaction
Phototoxic: severe
Diuretics, tetracycline,
sunburn after drug
amiodarone,
exposure (tetracycline) fluoroquinolones,
sulfonamides, psoralens,
Photoallergic: rash
phenothiazines
after days or months
of use (sulfonamides)
Onset: any time
Medication
Common Reactions
Skin
Testing
Available?
Rx (other than
avoid)
Radiocontrast Non-IgE mast cell
degranulation
No
Low osmolar
agent and pretreat
Vancomycin
Red Man
No
Slow infusion
and pre-treat
ASA, NSAIDs
Several types both IgE
mediated and non-IgE
mediated
No
Avoidance
Penicillins
IgE mediated or delayed
reactions (immune
complex, morbilliform,
etc)
Yes for IgE
only: skin
test, do not
pick
RAST/ELISA
IgE mediated
only:
Desensitize if
must have (ie
pregnant with
syphilis)
Other typesonly avoidance

A 53 y/o F has a pruritic rash on both hands. She
works as a hair stylist and notices the rash improves
when she goes on vacations. Topical corticosteroids
are helpful, but the rash returns quickly when she
stops them. Physical exam is remarkable for
erythematous, scaling patches to her fingers, wrists,
and the dorsum of both hands.
Which of the following is the next most appropriate
step in diagnosis?
A: Skin prick testing to dust mites
B: Patch testing
C: KOH preparation
D: skin biopsy



Flexural surfaces
Intermittent flares
Etiology multifactorial
◦ Includes genetics, environment (ex: allergens),
immune system (ex: filaggrin mutations)

Differential Diagnosis
◦ Allergic contact dermatitis, Irritant dermatitis,
Cutaneous T cell lymphoma

Treatment:
◦
◦
◦
◦
Moisturization
Topical Steroids PRN during flares
Topical calcineurin
Treat infection if needed


Can be difficult to distinguish irritant vs
allergic
Allergic (ACD)- Type IV sensitivity reaction
(delayed)
◦ Look for erythema, edema, vesicles, bullae
◦ Dx ACD: Patch Test
◦ Rx: avoidance of triggers, topical steroids
Allergen
Common Route of Patient Exposure
Nickel sulfate
Jewelry
Neomycin
Topical antibiotics
Balsam of Peru (marker for
fragrance allergy)
Cologne or perfume
Fragrance mix
Most personal care products; products labeled
“unscented” may contain masking fragrances
Thimerosal (frequently
positive, but rarely relevant)
Eye-care products (eye drops, contact lens
solutions); preservative in some vaccines
Sodium gold thiosulfate
Jewelry; dental work
Quaternium-15
(formaldehyde-releasing
preservative)
Personal care products
Formaldehyde
Personal care products
Bacitracin
Topical antibiotic; may cross-react with
neomycin
Cobalt chloride
Blue paint; vitamin B12 (cyanocobalamin); may
cross-react with other metals, including nickel

A 45 y/o man is evaluated for a 5-year history of solid-food
dysphagia. Solid foods such as meats and breads tend to
stick at the mid-esophagus. His symptoms have been
progressively increasing. He has occasional heartburn but no
weight loss or trouble swallowing liquids. He has been seen in
the ER for food impaction. He takes no medications. Physical
examination is normal. Endoscopy reveals rings and furrows
in the esophagus, and mid-esophageal biopsies show 16
eosinophils/hpf.
Which of the following is the most appropriate next
step in his management?
A: Initiate swallowed aerosolized corticosteroids
B: Food allergy testing
C: Esophageal Dilation
D: Initiate PPI


General presentation in adults is food
impaction and solid-food dysphagia
Dx: EGD with biopsy, >15 eosinophils per
HPF and exclude GERD (PPI trial, other)
◦ Other findings on EGD: rings, longitudinal furrows,
sometimes strictures (not pathognomonic)

Rx: swallowed aerosolized corticosteroids

Innate Immune System


Responds quickly, but not specifically
Adaptive Immune System

Respond specifically but more slowly
 Humoral
 Cell-mediated

HLA determines self vs non-self
◦ Class I HLA: HLA-A, B, C
◦ Class II HLA: HLA- DP, DQ, DR

3 pathways
◦ Classical Pathways:
 C1, C2, C4, C3-C9
 Screen with CH50 (checks all components C1-C9)
◦ Alternative Pathway:
 Factor B, Factor D, Properdin, C3-C9
◦ Lectin Pathway:
 Mannose-binding lectin, MASP1, MASP2, C3-C9

C5-9 combine to form membrane attack
complex (MAC)- they are the common
terminal pathway

IgG:




main Ig in serum, major Ig in immune response
Part of a memory response
Passes through placenta, activates complement
4 subtypes: IgG1, IgG2, IgG3, IgG4

IgA:

IgM:

IgE:
 Works primarily in mucosal tissues
 Secreted in breast milk
 2 subtypes: IgA1, IgA2
 First Ig type produced in an infection
 Activates complement
 Lowest concentration in serum
 Involved in allergic disease

A 19 y/o college sophomore is following up with you after
hospitalization 2 weeks ago for meningococcal meningitis.
HIV antibody was negative. He had an episode of
meningococcal meningitis last year after starting school
when an outbreak went through his dorm. He received the
meningococcal vaccination when he was 15 y/o. He is
otherwise healthy, and takes no medications. He is
currently living in a dorm. Physical exam today is
unremarkable.
Which of the following is most likely to establish a
diagnosis?
A: CH50 (total hemolytic complement level)
B: IgG and meningococcal titers
C: CD4 count
D: IgG, IgM, IgA

HAE
◦ AD, C1-inhibitor

C1, C2, C4 deficiencies
◦ Recurrent sinopulmonary infections
◦ Encapsulated bacteria
◦ Some have increased incidence in rheumatoid
disease (SLE)

C3 deficiency
◦ Severe pyogenic infections

Terminal complement deficiency (C5-9)
◦ Recurrent Neisseria infections (menigococcal or
gonococcal)
 Look for recurrent meningitis or septicemia
◦ Dx: Start by checking CH50 (total complement)
◦ Rx: Varies based on deficiency. Consideration for
vaccinating frequently (ex: meningococcal vaccine
q3 years for terminal complement deficiency) and
prophylactic antibiotics

A 21 y/o college student is following up with you after
hospitalization for pneumonia 6 weeks ago. She had one
other episode of pneumonia 2 years ago. She has asthma,
and received both the pneumococcal vaccine and tetanus
vaccine just before she started college her freshman year.
She tells you that she gets 3-4 sinus infections every year,
had an episode of giardiasis as a freshman, and her older
brother has lymphoma. Physical exam is unremarkable.
Review of her hospital chart indicates that HIV antibody is
negative.
Which of the following is the next best step in
establishing the diagnosis?
A: CD4 count
B: IgA, IgG, IgM levels
C: delayed hypersensitivity testing to tetanus
D: CH50 (total hemolytic complement)

An 18 y/o F comes to see you for evaluation. She was in an
MVC and required blood transfusion in the emergency
room to which she anaphylaxed. She has a history of well
controlled asthma, peanut anaphylaxis, and allergic
rhinitis to tree pollen. She gets otitis media about once a
year despite tympanostomy tubes, and is treated for
sinusitis 2-3 times yearly. She is otherwise healthy.
Physical exam is unremarkable on today’s visit.
Which of the following is the most likely diagnosis?
A: CVID
B: contamination of tubing with peanut product
C: selective IgA deficiency
D: terminal complement deficiency

Most common PID presenting in adult life
◦ Hypogammaglobulinemia AND inability to make antibodies
◦ Recurrent bacterial infections
◦ GI manifestations include giardia, chronic diarrhea,
malabsorption
◦ Some with autoimmune problems
◦ Some with granulomatous manifestations (noncaseating)
◦ Increased risk for lymphomas


Dx: Check IgG, IgA, IgM and titers to
pneumococcal and tetanus vaccinations
Rx: immunoglobulin replacement therapy (IVIg or
SCIg)






Most common immunodeficiency
Low IgA only
Most are asymptomatic
If symptomatic- usually respiratory infections
(upper/lower), otitis
May have autoantibodies to IgA- can
anaphylax to transfusion (wash blood first)
WATCH OUT: Do NOT give immunoglobulin
replacement therapy



http://www.cdc.gov/vaccines/
Contraindicated for ALL vaccines: prior
serious allergic reaction to the vaccine or any
component of the vaccine
Live vaccines
◦ Withhold in pregnancy
◦ Generally withhold in immunodeficiency
(particularly cell-mediated)
 Some exceptions
 HIV with CD4 > 200 may be able to receive these
vaccines
Vaccine
Important
Points
Indications
Do Not Give to
Varicella
Live
- 2 doses
Childhood vaccine
13 y/o and older- 2 doses
28 days apart if never had
vaccine or chickenpox
Pregnant women
(should not get
pregnant x 1 month)
- Caution in
immunocompromised
Herpes
Zoster
Live
>= 60 y/o regardless of
zoster history
Do not give in
immunocompromised
HPV
Not live
- 3 doses
Bivalent- females only
Quadrivalent- males or
females
Approved 9-26
Start at 11,12
Catch up 13- 26 F
13-21 M (permitted to 26)
Not recommended in
pregnancy
Ok to give if already
HPV+
Vaccine
Importa Indications
nt Points
Do Not Give to
MMR
Live
Childhood vaccine
Give dose to young adult if
cannot document
immunity/immunization
Immunocompromised
pregnancy
Adolescents,
Students in dorms, military:
1 dose
Asplenia, HIV, Complement
deficiency- 2 doses
Booster q5 years for asplenia,
complement deficiency
Pregnancy- only give if
really needed
Meningococcal Not live
1 > 16
y/o
Booster
if < 16
Hep B
Not live
3 doses
Hep A
Not live
2 doses
Childhood
Adults-at risk of either
exposure or morbidity, travel,
if they desire
Childhood
Adults: MSM, IVD users, travel
endemic area, chronic liver
disease (not Hep B/C if liver
ok)
1: D
2: A
3: A
4: C
5: C
6: B
7: A
8: part 1- D, part 2-C
9: B
10: C
11:
12:
13:
14:
15:
16:
17:
18:
19:
20:
A
part 1-D, part 2-D
C
C
D
B
D
A
B
C
Information on the slides are compilations of the following references:
 Text Books:

◦
Adkinson NF, Bochner BS, Burks AW, et al. Middleton’s Allergy Principles and Practice. 8th
Ed. Philadelphia, PA: Saunders; 2014.
◦
Adkinson NF, Bochner BS, Busse WW, Holgate ST, Lemanske RF, Simons FE. Middleton’s
Allergy Principles and Practice. 7th Ed. St Louis MO: Mosby; 2009.
◦
Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 7th Ed. Philadelphia,
PA: Saunders; 2012.
◦
Bellanti JA. Immunology IV: Clinical Applications in Health and Disease. Bethesda, MD: I Care
Press; 2012.
Board Review Materials:
◦
◦
MKSAP 16
Med Study Internal Medicine Review Core Curriculum 13th Edition (2009/2010)
Board Review materials were used to assist with case presentations and to ensure
appropriate topics and key words were covered. Text Book references were used to
ensure the science and specifics are the most up to date and accurate information.
Individual Journal Articles Referenced on applicable slides if appropriate