Transcript Allergy (deShazo)

Richard D. deShazo, MD with thanks to the
many colleagues from whom I have
borrowed material
•
What are the major diagnostic
criteria for asthma?
• How can you separate asthma from
COPD?
• What does a positive methacholine
inhalation test mean?
3
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FEV1 improvement of 12% and 200mL after
beta-agonist is evidence for asthma according
to ATS
Decreased FEV1/FVC ratio
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20-39yr
40-59yr
60-80yr
85%
80%
70%
Methacholine challenge – not diagnostic of
asthma
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+ with 20% decrease FEV1 with <8-16mg/mL
True benefit is in negative predictive value
4
•
What test should be considered in a
young asthmatic female with recurrent
episodes of wheezing poorly
responsive to bronchodilators?
Vocal Cord Dysfunction Is Not Asthma, But May Occur In Asthmatics
Flow volume loops showing maximum inspiratory and expiratory flowvolume relationships in a patient with vocal cord dysfunction during
asymptomatic (left) and symptomatic (right) periods. Note also the
marked adduction of the vocal cords with severe reduction of the glottic
aperture during a symptomatic period (right) of airway obstruction.
6
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Female 2:1
Athletes
Bronchodilator non
responsive
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Many (up to 1/3) can
have coexist asthma
Difficulty getting breath
in
7
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What is the likely diagnosis in a man with
persistent cough, shortness of breath,
dyspnea, and episodic wheeze that developed
after working as a police officer in the 9/11
exposure area in NYC?
A 22 year old with recent onset cough and
wheeze works in a custom sailboat shop in
Biloxi sealing the inside of boats with epoxy
resins. What is the most likely low molecular
weight chemical causing his symptoms?
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Treatment – Time + corticosteroids
Occurs after a single inhalation of a caustic
irritant in a non-asthmatic
Obstruction on PFT
(+) methalcholine inhalation challenge
Limited PFT-response to beta-agonists
Not “reactive airways disease”
9
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Basically, asthma occurring because of
exposure at work.
Testing difficult, so sometimes need to do
pulmonary evaluation at the workplace. (Start
with peak flows at work versus home).
Earlier you diagnose the better, because may
lead to permanent asthma even when removed
from environment.
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Previous life-threatening asthma such as
respiratory arrest
Hospitalization or ED visit for asthma within
the last year
Use of 2 or more canisters of rescue
inhaler/month
Poor perception of hypoxia or airway
obstruction
Psychosocial disturbance
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Components of
Severity
Mild
Moderate
----Persistent----
Severe
Impairment
Intermittent
-----------------------
-----------------------
Symptoms
<2 days/weeks
>2 days/week
but not daily
>1 x/week but
not nightly
Throughout the
day
Nighttime
awakenings
<2 x/month
3-4 x/month
>1 x/week but
not nightly
Often 7 x/week
SABA use for
symptom control
(not prevention
of EIB)
< 2 days/week
>2 days/week
but not more than
1 x/d
Daily
Several times a
day
Interference with
normal activity
None
Minor limitation
Some limitation
Extremely limited
Lung function
Normal FEV1
between
exacerbations
FEV1 >80% of
predicted
FEV1/FVC
normal
FEV1 >80% of
predicted
FEV1/FVC
normal
FEV1 >60% but
<80% of
predicted
FEV1/FVC
reduced 5%
FEV1 <60% of
predicted
FEV1/FVC
reduced >5%
Risk
Exacerbations
(consider
frequency and
severity)
0-2/year
>2/year
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Rescue medicines
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Short acting agonists (SABA)
Anticholinergic
Controller medicines
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Inhaled corticosteroids (ICS)
Long acting agonists (LABA)
Leukotriene receptor antagonists (LTRA)
Combinations of ICS & LABA
Anti-IgE (omalizamab)
Others
13
Stacking Asthma Drugs
14
What Meds Should You Think
About Adding On In Severe
Asthma?
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Vocal cord dysfunction
GERD
Sinusitis
Churg-Strauss syndrome
ABPA
Compliance/technique
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Churg-Strauss Vasculitis
Sinusitis, asthma, eosinophilia, vasculitis
 Transient pulmonary infiltrates
 Small vessel vasculitis
 Neuropathies (mononeuritis multiplex)
 MPO- ab/P-ANCA test (+) in about 50%
 RX: steroids (cyclophosphamide/azathioprine in
severe)
 ? relationship to LTRA
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20
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Includes allergic bronchopulmonary
aspergillosis (ABPA) and other allergic
mycoses
Criteria
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Asthma
Fleeting pulmonary infiltrates
High total IgE (>1000 ng/mL or 417 kU/L)
Positive immediate skin test (IgE) to fungus (A.
fumigatus, etc.) or Positive RAST test
Elevated serum specific IgE to fungus (A. fumigatus,
etc.)
CT with central bronchiectasis reflects chronic
disease
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Oral corticosteroids
Follow total serum IgE and CXR
No long term studies on Itraconazole as steroid
sparing agent
22
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No increase asthma but may have allergic – like
dermatitis
Paramalignant syndrome
Peripheral blood eos count >1500 µL for at least 6
months
Absence of any other known cause of eosinophilia
Presumptive signs/symptoms of organ invasion by
eosinophils
9:1 male:female
Systemic disease
Cardiac disease (thrombosis, fibrosis, necrosis) is the
most common cause of death
FIP1L1/PDGFA fusion-gene present in some patients
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Heart
Skin, Lungs, GI tract, Nervous System
Vascular thrombosis is a feared complication
Treatment
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Steroids
Hydroxyurea
Interferon α
Gleevac (imatinib) - for FIP1L1-PDGFRα gene
rearrangement
24
•
A 50 year old woman with asthma and
atopic dermatitis has her 3rd episode of
food impaction. What findings should
be sought from endoscopy to confirm
the diagnosis?
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Atopic individuals
Usually in upper tract
Food impaction in esophagus
Mucous furrowing and white specks on
endoscopy
More than 12 eosinophils/HPF on biopsy
Food allergy in some
Treated with non-absorbable steroids
26
•
A 50 year old bird breeder has
persistent shortness of breath, cough,
and dyspnea. What should be done?
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Fever, chills, malaise, cough, dyspnea
Acute, subacute, chronic
A systemic illness
Also known as “extrinsic allergic alveolitis”
Non allergic, not IgE mediated, no eosinophilia,
no asthma except pigeon breeder’s (bird fancier’s)
lung
T-cell mediated
CXR/CT scan abnormal: ground glass/diffuse
alveolar pattern
PFT – restriction not obstruction except for pigeon
breeders
Chronic  pulmonary fibrosis
28
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Characterize chronicity looking for seasonal
variation.
Ask for family history, indoor triggers and nasal
itching.
Swollen nasal mucosa usually more blue that red.
Treat
If there is treatment failure, do allergy skin tests or
RASTs to determine specific allergen and consider
allergy shots.
Allergy shots are very effective for allergic rhinitis
and insect anaphylaxis.
29
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Nasal steroids – first line treatment
Antihistamines and leukotriene receptor
antagonists – second line (about equal efficacy
as second line agents)
To prevent symptoms on planned exposures,
chromolyn or antihistamines work best
Allergen immunotherapy by subcutaneous or
sublingual techniques
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Vasomotor rhinitis
Rhinitis medicamentosa
Nasal manifestations of systemic disease:
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Diabetes mellitus – mucor mycosis (nasal eschar;
black crust)
Wegener’s granulomatosis (saddle nose)
Midline granuloma (saddle nose)
Relapsing polychondritis (saddle nose)
Sarcoidosis (bloody crusts)
Cystic fibrosis (nasal polyps)
CSF leak – check beta 2 transferrin (very specific)
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Immunodeficiency
Cystic fibrosis
Aspirin – sensitive respiratory disease
Allergic fungal sinusitis
Anosmia is a big tip off for polyps
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Acute &
Chronic
Sinusitis
Ethmoid cell
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•
A 30 year old nurse has a severe
chronic dry and cracking dermatitis of
both hands. What should you do first?
Irritant vs. Allergic Contact Dermatitis
35
MKSAP
Most Frequently Positive Patch -Test Results
in Allergic Contact Dermatitis
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 crossreact with other metals, including nickel
36
•
A 16 year old male with asthma has a
chronic pruritic dermatitis in the
flexural areas of his elbows and knees.
What treatment would be best for this
problem?
Atopic Dermatitis (Eczema) (1)
Atopic dermatitis with involvement of a flexural surface.
The frequently involved anticubital and popliteal fossae.
38
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Increased susceptibility to
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Staph aureus, HSV (eczema herpeticum), vaccinia
Differential diagnosis
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Allergic contact dermatitis
Irritant contact dermatitis (gloves)
Cutaneous T – cell lymphoma
An adult presenting with eczematous dermatitis with an
erythrodermatous appearance by skin biopsy with
genetic studies
Atopic
dermatitis is associated with abnormalities in
the filaggrin gene which encodes for filaggrin protein
important in statium corneam moisturization
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Skin hydration/moisturization (Aquaphor)
Medium strength topical corticosteroids and
combinations (equal parts 0.1% triamcinolone
and Aquaphor)
Oral antibiotics (Staph)
Antihistamines (control itch)
Topical calcineurin inhibitors (protopic/ elidel)
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MKSAP Clinical Clues to the
Diagnosis of Selected Causes of Erythroderma
Cause
History
Physical Examination
Findings
Laboratory Findings
Atopic dermatitis
Personal or family history of
atopic dermatitis, allergic
rhinitis, or asthma; preexisting
skin lesions; severe pruritus
Lichenification
Eosinophilia; elevated
serum IgE level
Psoriasis
Personal or family history of
psoriasis; preexisting psoriatic
skin lesions; history of
corticosteroid withdrawal
Nail pitting, oil
droplet sign,
onycholysis; psoriatic
arthritis
Skin biopsy may be
diagnostic
Cutaneous T-cell
Slowly progressive; extreme,
lymphoma/Sézary intractable pruritus
syndrome
Lymphadenopathy;
painful, fissured
keratoderma; alopecia;
leonine facies
Peripheral blood smear
with >20% Sézary cells;
clonal T-cell population
in skin, blood, and/or
lymph node
Hypersensitivity
drug eruption
Facial edema; cervical
lymphadenopathy;
fine scale around nose;
hepatosplenomegaly
Leukocytosis with
eosinophilia or atypical
lymphocytosis; elevated
serum
aminotransferases;
elevated blood urea
nitrogen or serum
creatinine levels
Onset 3-6 weeks after start of a
new medication; most common
causative medications are
allopurinol, aromatic
anticonvulsants, dapsone,
NSAIDs, sulfonamides,
lamotrigine
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Classification of Urticaria
• Acute urticaria (<6 weeks)
• Chronic urticaria (>6 weeks)
•Physical urticaria (pressure, cold,
vibratory, etc.)
•Urticarial vasculitis
•Contact urticaria (touching a cat)
•Urticaria and angioedema as
components of anaphylaxis
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Classification of Physical Urticarias
Classification
Characteristics
Papular urticaria
Associated with insect bites
Cholinergic urticaria
Occurs in response to an increase in
core body temperature; lesions present
as small papules with a prominent
surrounding erythematous flare
Delayed pressure-induced urticaria
Patients often experience systemic
symptoms
Exercise-induced urticaria
On a continuum with exerciseinduced anaphylaxis; many patients
only develop symptoms if primed by
an ingested allergen prior to exercise
Solar urticaria
Some patients who appear to have
solar urticaria prove to have lupus
erythematosus or porphyria
Cold urticaria
Acquired cold urticaria is often related
to an underlying infection, whereas
familial cold urticaria represents an
autoinflammatory syndrome
Vibrational urticaria
—
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Palpable purpura is a clinical sign of a small vessel
(leukocytoclastic) vasculitis which may present as
chronic urticaria.
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•
A 68 year old female with chronic
mylogenous leukemia presents with
non itchy swelling of the lips and
throat. What diagnostic tests would be
most useful to diagnose acquired
angioedema?
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Allergic reactions and anaphylaxis
Idiopathic angioedema
Drug induced angioedema
Allergic contact dermatitis
Autoimmune conditions
Thyroid disorders
Superior vena cava syndrome and tumors
Cheilitis granulomatosa (Miescher’s cheilitis) and
Melkersson-Rosenthal syndrome
Trichinosis
Low C-4 levels
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 Autosomal Dominant
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Hiveless, itchless edema
Hereditary angioedema form more likely
to have symptoms precipitated by
trauma - dental visit, surgery, auto
accident, menses, puberty
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Visceral attacks may present as an acute
abdomen with normal findings at surgery
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Diagnosis of HAE5
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HAE 1 - low C41, 2 low C1 INH, low C1INH-F
 HAE2 - low C41, 2 normal C1 INH, low C1INH-F
 Acquired – low C41, 3 low C1 INH, low C1INH-F, low Clq
 HAE3 – normal C4 4 normal C1 INH, normal C1INH-F,
normal C1f level
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1.
2.
3.
4.
5.
Always low during attacks
SERPING1 gene abnormalities
Antibodies to C1INH
Abnormalities in Factor XII genes
Family members should be screened in all types
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Associated with lymphoproliferative disorders
 Have low C1q levels
 Mechanism unclear
 Low C1 of levels appear to reflect
autoactivation
Anti – C1 esterase inhibitor antibodies have been
described as well
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C4 – is a great screening test, but is normal in
HAE Type 3
Test for C1 esterase inhibitor level and function
to discriminate between two hereditary types
Test C1q level for the acquired form
Genetic testing for HAE Type 3
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On-demand treatment
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Treatment of attacks with upper airways symptoms is
mandatory
Acute attacks should be treated with
 C1INH (plasma derived) Berinert
 Escallantide (inhibits HMW Kininogen to bradykinen) Kalbitor
 Icatibant (bradykinen recepptor antagonist) Firazyr
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Intubation or trachestomy should be early in progressive
airway obstruction
Antifibronolytics are not to be used
Procedural prophylaxis with procedures involving the upper
airway is recommended without evidence
Pregnancy – C1INH advised
Long-term Prophylaxis
 C1INH - immunizations, screens
 Androgens – frequent screens for liver toxicity
 Antifibrolytics not recommended
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Purified (C1INHRP) or recombinant
(rhC1INH) human C1 inhibitor (various
products available worldwide)
Ecallantide, a kallikrein inhibitor (available
only in the United States)
Icatibant, a bradykinin B2 receptor antagonist
(available in the United States and the
European Union)
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•
What should be prescribed for a
patient after treatment for acute
anaphylaxis and how should it be
used?
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Usually starts with urticaria and itching but can
present with syncope, hypotension, or
erythoderma.
Most common causes are foods (peanut/ tree nut
ingestion, etc.), insect stings, drug allergy (beta
lactam)
Don’t forget latex, especially in medical spaces
No obvious trigger- think mastocytosis (check
serum mast cell tryptase) or idiopathic anaphylaxis
All who have insect anaphylaxis patients require
evaluation for venom immunotherapy
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Hypotension - supine, IV (NS)
Respiratory distress - oxygen and albuterol, intubation
Epinephrine
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1:1000 .3-.5cc IM for adults (note this is NOT the 1:10,000
dilution - (1mg/10ml) on crash carts
Can repeat in 5 minutes
If on beta blocker and not responsive to epi, consider glucagon
1mg IM, IV, SC
Can start epi infusion if not responsive to IM epi
 (1:10,000) 1-3 mg over 3 min, then 3-5mg over 3 minutes, then 410ug/min infusion
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All who recover must leave with an Epipen®.
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Consider 1 mg of glucagon IV if on beta blocker
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Cutaneous Mastocytosis
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Have urticaria pigmentosa – reddish brown or tan
macules. Darier’s sign
Indolent, benign course
Itching, burning skin, flushing, CNS symptoms
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Major
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Minor
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Multifocal dense infiltrates of mast cells in bone marrow
or extracutaneous organ
>25% mast cells are spindle-shaped or atypical
Presence of c-kit point mutation
Mast cells co-express Kit and CD2
Persistent serum tryptase >20ng/mL
Need one major and one minor, or 3 minor
Other:
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Skin involvement improves prognosis
Insect stings may induce anaphylactoid reactions in
patients with mastocytosis.
57
MKSAP
Common Drug Reaction Patterns
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“Red man syndrome” – pruritis and erythema
of face, neck, upper torso, occasionally with
hypotension
Non-immunologic release of histamine
Not IgE mediated
Rx: slow the infusion and pre-treat
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Cause the “hypersensitivity syndrome”
Deficiency of epoxide hydrolase
Fever, maculopapular rash, generalized
lymphadenopathy
Node bx resembles Hodgkin’s
Phenytoin, carbamazepine, phenobarb
Can also cause DRESS: Drug reaction with
eosinophilia and systemic symptoms. Rash,
fever, multi-organ failure
½ actually have eosinophilia
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A 21 year old college student has
recurrent sinupulmonary infections.
What test in addition to HIV should be
performed to exclude
immunodeficiency?
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T- cell (cellular immunity) – virus, fungi, protozoa,
mycobacteria and other intracellular organisms
Humoral (antibody mediated immunity) – infection
with extracellular pyogenic organisms
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Haemophilus
Pneumococcus
Streptococcus
Increased infections
Recurrent respiratory infections
Multiple systems involved
Unusual organisms
Malabsorption
Big LNs or absent LNs
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Decreased IgG, M, A, normal to increased IgE
Recurrent sinopulmonary infections
Lymph tissue present or enlarged
High incidence of autoimmune disease (22%)
Increased risk of adenocarcinoma and
lymphomas
In addition to encapsulated organisms
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Giardia, yersinia, H. pylori, and H. jejuni are
common
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Most common form of primary
immunodeficiency (1:333)
IgA <5mg/dL (VERY LOW)
Most patients with IgA def. are NORMAL
Have increased risk of infections: collagen
vascular , allergic, and GI disease, and
malignancy
Can make anti-IgA antibodies
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Leads to anaphylaxis with IgA containing blood
products
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Indicated for common variable
immunodeficiency and specific antibody
deficiency
Not indicated for IgA deficiency
Side effects
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Never transmitted of HIV
Fever, chills, HA, muscle pain.
Aseptic meningitis
Renal failure (was due to osmotic load, not as
common now), stroke, MI
66
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C2 deficiency (most common) – sepsis,
pneumonia, meningitis, pyogenic arthritis with
Strep pneumo
C2 deficiency – increased risk of rheumatoid
arthritis, SLE
Terminal Complement Components –
Neisseria sp infections
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Think about if recurrent meningitis or if unusual
strain
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Measles
Mumps
Oral Polio
Rubella
Varicella
MMR
Smallpox (vaccinia)
Flumist
68
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Influenza and Yellow fever
69
What dietary pattern do bedbugs
follow?
Bedbug Bites Often
Occur in a Series
“Breakfast, lunch, and dinner”
Lesions are usually painless and appear
as pruritic, urticarial-like papules.
Dinner
Lunch
Breakfast
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Bedbugs are nocturnal, hiding in
cracks and crevices within 10 feet
of a bed and especially on the cords
of the mattress during the day and
biting at night.
Hungry
Fed
72