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Clinical Final Exam > Drug Allergies > Flashcards

Drug Allergies Flashcards

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
Q

What is activated in Type IVa reactions?

What is secreted?

A

Type IVa:
Activation of macrophages.
Secretion of INF gamme, TNF-alpha, and IL-18.

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26
Q

What is an example of Type IVa reactions?

A

Some forms of contact dermatitis (cheap jewelry, perfumes)

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27
Q

What is secreted in Type IVb reactions? What does this promote?

A

Type IVb:
Secretion of cytokines IL-4, -5, -13.
Promotes B-cell production of IgE and IgG4, macrophage, mast cell, and eosinophil responses.

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28
Q

What condition is Type IVb involved in?

A

Involved in bronchi of patients with Allergic Asthma.

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29
Q

What are examples of Type IVb reactions?

A

Certain types or morbilliform or maculopapular rashes are Type IVb mediated.
DRESS is also a Type IVb reaction.

30
Q

In Type IVc reactions, what to T cells induce, and where?

A

T cells induce apoptosis in cells of inflamed tissue - such as hepatocytes or keratinocytes.

31
Q

What are Type IVc reactions involved in?

A

The pathogenesis of several types of drug-induced delayed type hypersensitivity (DTH) reactions.

32
Q

What are some examples of drug-induced delayed type hypersensitivity reactions? (Type IVc)

A

**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
Q

What is characteristic of Type IVd reactions?

A

T-cell mediated “sterile” neutrophilic inflammation - pustules everywhere but no organism is present.

34
Q

What is an example of Type IVd reaction?

A

Acute generalized exanthematous pustulosis (AGEP)

35
Q 
Erythema Multiforme (IVc):
What does it begin with?
What does it form after 24-48h? (characteristic)
A

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
Q

Where do the target lesions occur in EM?(can help differentiate from serum sickness)?
How are they usually distributed?

A

Lesions appear on 1 mucosal surface, as well as on hands and feet.
Distributed symmetrically.

37
Q

What is EM usually associated with, and what can you look for because of this?
What is it less commonly caused by (<20%)?

A

Associated with herpes virus - look for vesicles of Herpes (clear fluid).
Less commonly due to drugs.

38
Q

Stevens-Johnson Syndrome (SJS):

How do the lesions differ from EM? (location, appearance)

A

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
Q

EM is a severe ________ reaction, and SJS is a severe _______ disorder (and has what symptom as a result?)

A

EM: cutaneous
SJS: systemic
SJS has fever present.

40
Q

What is the typical onset of SJS?

But how long do we consider a possibility for the symptoms to be drug related?

A

4 days to 3 weeks

consider up to 8 weeks as a possibility

41
Q

What is SJS and TENS commonly caused by?

A

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
Q

What can’t you use in SJS or TENS? Why?

A

Can’t use desensitization - only works for IgE mediated reactions.

43
Q 
What is the BSA involvement to be classified as:
SJS?
SJS/TENS overlap?
-- in what patients is this most common?
TENS?
A

SJS: <10%
Overlap: 10-30%
– more common in HIV, possibly lupus
TENS: > 30%

44
Q

What is TENS characterized by?

A

Top layer of skin peeling off in sheets (systemic skin disorder)

45
Q

What does the affected skin look like? What may develop, and what is the patient treated like?

A

Scalded appearance, may develop blisters - treat as burn patient.

46
Q

What does DRESS stand for?

What is it also known as?

A

DRESS = Drug rash, eosinophilia, & systemic symptoms.

AKA drug-induced hypersensitivity syndrome; or anticonvulsant hypersensitivity syndrome.

47
Q

What is the typical onset of DRESS?

A

4 days to 3 weeks

48
Q

What are the hallmarks of DRESS?

A

Facial edema and erythema

49
Q

What may the rash become? Where, especially?

A

May become pruritic, especially on lower legs

50
Q

Are mucous membranes involved in DRESS?

A

No - mucous membranes are not involved in DRESS

51
Q

What drugs is DRESS often associated with?

A

Anticonvulsants, allopurinol, NSAIDs, sulfonamides, dapsone, thiazides

52
Q

Can you use desensitization in DRESS?

A

No

53
Q

What can give the appearance of anaphylaxis?

Why is it not a true anaphylactic reaction?

A

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
Q

What is the enzyme detectable only after anaphylaxis?

When should the levels be tested to differentiate the reaction?

A

Mast cell tryptase - released from mast cells after anaphylaxis.
Test serum tryptase levels between 1-4h after the reaction.

55
Q

What do penicillin allergies classically appear as?

When does it appear?

A

Erythmatous, maculopapular rash.

Appears late in treatment course.

56
Q

What type of penicillin allergy can be retreated?

A

Late-appearing maculopapular rashes.

57
Q

Tell me about urticaria (hives) to penicillin:
Onset?
Mediated by?
Would you give penicillin again?

A

Occurs within 1h of administration (immediate type)
IgE mediated
More serious - never give again.

58
Q

In penicillin skin testing, what characterizes accelerated reactions (2-72h)?

A

An allergic reaction to the major metabolite (penicilloyl) - most common antibody formation.
Less serious

59
Q

In penicillin skin testing, what characterizes immediate reactions (<2h)?

A

An allergic reaction to parent compound or secondary metabolite (penicillin or penicillate) (minor) - least frequent Ab formation
More serious

60
Q

Do corticosteroids alter the interpretation of the skin test?

A

no

61
Q

What can mask the reaction of the skin test?

A

Antihistamines

62
Q

What should you avoid if patients have a positive skin test

A

Penicillins

63
Q

If a patient has a history of anaphylaxis or urticaria to penicillins, what should not be used?

A

Cephalosporins

64
Q

Tell me about the sulfonamide rash:
Onset
Symptoms
What may it progress to?

A

Reactions typically delayed (5-10d).
Fever, followed by morbilliform eruption.
May progress to SJS or TENs

65
Q

What is desensitization now referred to?

A

Induction of drug tolerance

66
Q

What is desensitization?

A

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
Q

What type of immune mechanisms can desensitization be used for?

A

IgE-mediated immune mechanisms

68
Q

To identify the culprit of a reaction, which medications should be stopped first?

A

The newest medications should be stopped first

69
Q

What does treatment consist of?

A

Symptom control - topical corticosteroids and systemic antihistamines for pruritis

70
Q

What is the graded challenge?

A

Administering a graduated amount under close supervision

71
Q

What is the graded challenge used for?

A

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
Q

What are the contraindications to the graded challenge?

A

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)

Clinical Final Exam (5 decks)

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