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Clinical Final Exam > Drug Allergies > Flashcards

Drug Allergies Flashcards

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1
Q

What is a Macule?

How is it different from a Patch?

A

A flat area of altered colour, < 1 cm.

A patch is > 1 cm.

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2
Q

What is a Papule?

How is it different from a Nodule?

A

Papule: elevated solid lesion, < 1 cm.
A nodule is > 1 cm.
(not liquid filled).

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3
Q

What is does a plaque look like?

A

Elevated, flat topped, irregular border >1 cm.

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4
Q

What are vesicles?

How do they differ from Bulla?

A

Vesicles: clear, fluid filled blisters, < 0.5 cm.

Bulla are > 0.5 cm.

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5
Q

What is a pustule?

A

A vesicle filled with purulent exudate (pus).

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6
Q

What is a wheal?

A

An accumulation of dermal fluid (hives - elevated).

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7
Q

What is the time-frame for an immediate reaction?

What type could it be?

A 
0-1h (varies, 30m-2h).
Type 1 (severe) or possibly non-immunologic (e.g. red man syndrome)
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8
Q

What is the time-frame for an accelerated allergic reaction?

What type could it be?

A

2-72h

Could be any type.

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9
Q

What is the time-frame for a late allergic reaction?

What type could it be?

A

> 72h

Could be any type but RARELY type 1 (anaphylaxis rarely occurs after 72h)

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10
Q

What are Type I reactions (anaphylaxis) mediated by?

A

IgE antibodies.

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11
Q

Describe how Type I reactions occur.

A

Initial exposure to antigen results in IgE Ab production. Re-exposure after several weeks causes drug + carrier protein to react with IgE Ab on the surface of mast cells, resulting in mediator release.

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12
Q

What are the symptoms of a Type I reaction (anaphylaxis)?

A

Urticaria, laryngeal edema, bronchospasm, anaphylaxis.

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13
Q

What are Type II (cytotoxic) reactions mediated by?

A

IgG or IgM antibodies

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14
Q

What are some examples of Type II (cytotoxic) reactions?

A

Hemolytic anemia
Thrombocytopenia
Granulocytopenia
are Type II reactions

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15
Q

What are the 3 types of Type II (cytotoxic) reactions?

A

Hapten-cell reaction
Immune complex reaction
Autoimmune reaction

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16
Q

How are Type III immune complex reactions mediated?

A

IgG or IgM antibodies.

They form circulating complexes then lodge in tissues.

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17
Q

What is another name for Type III reactions?

A

“Arthus Reaction” or Serum Sickness hypersensitivity reactions

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18
Q

When do Type III reactions generally occur?

What are they a reaction to?

A

5-21 days after exposure.
An allergic reaction to antibiotics
(e.g. cefaclor is 15x more likely to cause Serum Sickness than amoxicillin)

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19
Q

How do Type III reactions differ from Type II?

A

Type III are non-hematologic.

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20
Q

What are Type III reactions characterized by?

A

Fever
Arthralgias (joint pain)
Skin rash
Lymphadenopathy (swollen lymph nodes)

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21
Q

When do Type II (cytotoxic) reactions generally occur?

A

7 days after exposure.

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22
Q

What cells do Type IV reactions involve?

What are they NOT mediated by?

A

Activation of T cells; and may involve macrophages, eosinophils, or neutrophils as well.
They are not mediated by antibodies.

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23
Q

When do Type IV reactions generally occur?

A

Delayed - after 3 days.

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24
Q

How many Type IV subtypes are there?

A

4 subtypes

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25
What is activated in Type IVa reactions? | What is secreted?
Type IVa: Activation of macrophages. Secretion of INF gamme, TNF-alpha, and IL-18.
26
What is an example of Type IVa reactions?
Some forms of contact dermatitis (cheap jewelry, perfumes)
27
What is secreted in Type IVb reactions? What does this promote?
Type IVb: Secretion of cytokines IL-4, -5, -13. Promotes B-cell production of IgE and IgG4, macrophage, mast cell, and eosinophil responses.
28
What condition is Type IVb involved in?
Involved in bronchi of patients with Allergic Asthma.
29
What are examples of Type IVb reactions?
Certain types or morbilliform or maculopapular rashes are Type IVb mediated. DRESS is also a Type IVb reaction.
30
In Type IVc reactions, what to T cells induce, and where?
T cells induce apoptosis in cells of inflamed tissue - such as hepatocytes or keratinocytes.
31
What are Type IVc reactions involved in?
The pathogenesis of several types of drug-induced delayed type hypersensitivity (DTH) reactions.
32
What are some examples of drug-induced delayed type hypersensitivity reactions? (Type IVc)
**Erythema Multiforme (EM) **Stevens-Johnson Syndrome (SJS) **Toxic-epidermal Necrolysis (TEN) (Some contact dermatitis Maculopapular reactions Bullous drug eruptions Drug-induced hepatitis) ***need to be treated right away if patient has these.
33
What is characteristic of Type IVd reactions?
T-cell mediated "sterile" neutrophilic inflammation - pustules everywhere but no organism is present.
34
What is an example of Type IVd reaction?
Acute generalized exanthematous pustulosis (AGEP)
35
``` Erythema Multiforme (IVc): What does it begin with? What does it form after 24-48h? (characteristic) ```
Begins with eruption of erythmatous, raised skin patches. These are pruritic and have sudden onset. The center of the lesion clears and forms characteristic "target" appearance in 24-48h.
36
Where do the target lesions occur in EM?(can help differentiate from serum sickness)? How are they usually distributed?
Lesions appear on 1 mucosal surface, as well as on hands and feet. Distributed symmetrically.
37
What is EM usually associated with, and what can you look for because of this? What is it less commonly caused by (<20%)?
Associated with herpes virus - look for vesicles of Herpes (clear fluid). Less commonly due to drugs.
38
Stevens-Johnson Syndrome (SJS): | How do the lesions differ from EM? (location, appearance)
SJS has lesions break out at multiple sites - 2 or more mucosal surfaces involved (EM has only 1) -- lining of mouth, throat, genital region, eyes. Also may NOT see target lesions.
39
EM is a severe ________ reaction, and SJS is a severe _______ disorder (and has what symptom as a result?)
EM: cutaneous SJS: systemic SJS has fever present.
40
What is the typical onset of SJS? | But how long do we consider a possibility for the symptoms to be drug related?
4 days to 3 weeks | consider up to 8 weeks as a possibility
41
What is SJS and TENS commonly caused by?
Drugs Sulfonamides Beta-lactams (penicillins, cephalosporins, carbapenems) NSAIDs Anticonvulsants (carbamazepine, phenytoin, phenobarbital, lamotrigine) **generally if you have a reaction to one drug, avoid the other drugs in the class
42
What can't you use in SJS or TENS? Why?
Can't use desensitization - only works for IgE mediated reactions.
43
``` What is the BSA involvement to be classified as: SJS? SJS/TENS overlap? -- in what patients is this most common? TENS? ```
SJS: <10% Overlap: 10-30% -- more common in HIV, possibly lupus TENS: > 30%
44
What is TENS characterized by?
Top layer of skin peeling off in sheets (systemic skin disorder)
45
What does the affected skin look like? What may develop, and what is the patient treated like?
Scalded appearance, may develop blisters - treat as burn patient.
46
What does DRESS stand for? | What is it also known as?
DRESS = Drug rash, eosinophilia, & systemic symptoms. | AKA drug-induced hypersensitivity syndrome; or anticonvulsant hypersensitivity syndrome.
47
What is the typical onset of DRESS?
4 days to 3 weeks
48
What are the hallmarks of DRESS?
Facial edema and erythema
49
What may the rash become? Where, especially?
May become pruritic, especially on lower legs
50
Are mucous membranes involved in DRESS?
No - mucous membranes are not involved in DRESS
51
What drugs is DRESS often associated with?
Anticonvulsants, allopurinol, NSAIDs, sulfonamides, dapsone, thiazides
52
Can you use desensitization in DRESS?
No
53
What can give the appearance of anaphylaxis? | Why is it not a true anaphylactic reaction?
Drugs that release histamine can cause wheezing, rash, hypotensions (e.g. red-man syndrome from vanco) Not true anaphylaxis because it's not IgE mediated.
54
What is the enzyme detectable only after anaphylaxis? | When should the levels be tested to differentiate the reaction?
Mast cell tryptase - released from mast cells after anaphylaxis. Test serum tryptase levels between 1-4h after the reaction.
55
What do penicillin allergies classically appear as? | When does it appear?
Erythmatous, maculopapular rash. | Appears late in treatment course.
56
What type of penicillin allergy can be retreated?
Late-appearing maculopapular rashes.
57
Tell me about urticaria (hives) to penicillin: Onset? Mediated by? Would you give penicillin again?
Occurs within 1h of administration (immediate type) IgE mediated More serious - never give again.
58
In penicillin skin testing, what characterizes accelerated reactions (2-72h)?
An allergic reaction to the major metabolite (penicilloyl) - most common antibody formation. Less serious
59
In penicillin skin testing, what characterizes immediate reactions (<2h)?
An allergic reaction to parent compound or secondary metabolite (penicillin or penicillate) (minor) - least frequent Ab formation More serious
60
Do corticosteroids alter the interpretation of the skin test?
no
61
What can mask the reaction of the skin test?
Antihistamines
62
What should you avoid if patients have a positive skin test
Penicillins
63
If a patient has a history of anaphylaxis or urticaria to penicillins, what should not be used?
Cephalosporins
64
Tell me about the sulfonamide rash: Onset Symptoms What may it progress to?
Reactions typically delayed (5-10d). Fever, followed by morbilliform eruption. May progress to SJS or TENs
65
What is desensitization now referred to?
Induction of drug tolerance
66
What is desensitization?
Temporary induction of drug tolerance through exposing patient to minute quantities, then rapidly increasing concentrations of drug exposure (e.g. over 6-12h) until full doses can be tolerated
67
What type of immune mechanisms can desensitization be used for?
IgE-mediated immune mechanisms
68
To identify the culprit of a reaction, which medications should be stopped first?
The newest medications should be stopped first
69
What does treatment consist of?
Symptom control - topical corticosteroids and systemic antihistamines for pruritis
70
What is the graded challenge?
Administering a graduated amount under close supervision
71
What is the graded challenge used for?
Used to exclude drug allergy in those who you suspect to be unlikely allergic to the drug. Does not modify the allergic response (desensitization does)
72
What are the contraindications to the graded challenge?
If you suspect Type I (IgE mediated) reaction - could induce anaphylaxis. If they have history of blistering dermatitis (SJS, TENS) or severe hypersensitivity reactions (DRESS)

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