SM 261: Drug Reactions and Blistering Disorders

Question 1

How are drug induced skin reactions classifed?

Answer 1

By timing: immediate ( < 1hr) vs delayed ( > 6hr)

Question 2

What is an immediate drug induced reaction?

Answer 2

A reaction that occurs less than 1 hour of the the last administered dose of a drug

Question 3

What are examples of immediate drug induced reactions?

Answer 3

Angioedema, Urticaria (hives), and Analphylaxis

AUA

Question 4

What is a delayed drug induced reaction?

Answer 4

A reaction occuring after 6 hours of the last administered dose of a drug

Question 5

What are examples of delayed drug induced reactions?

Answer 5

Exanthemous Eruptions, Fixed Drug Eruptions, Systemic Reactions, and Vasculitis

Question 6

What is a Urticarial drug reaction?

Answer 6

An immediate drug reaction that can occur with or without angioedema

Caused by NSAIDs and Opiates

Question 7

What drugs can cause Utricaria without Angioedema?

Answer 7

NSAIDS and Opiates

Question 8

What drugs can cause Utricaria with Angioedema?

Answer 8

ACEi

Question 9

What should a complete drug history involve?

Answer 9

The 7 I’s of drug use:

Instilled
Inhaled
Ingested
Inserted
Injected
Incognito
Intermittent

Question 10

What is the most important factor in determining if a rash is medication-related?

Answer 10

Timing, based off of a drug timeline

Question 11

What are risk factors for drug reactions?

Answer 11

Female, prior history of reaction, recurrent exposure, HLA type, HIV/EBV

Question 12

What does EBV predispose a reaction to?

Answer 12

Aminopenicillins

Question 13

What is an Exanthematous Drug reaction?

Answer 13

A reaction that is limited to the skin, with erythematous macules and papules initially appearing on the trunk and spreading centrifugally to the extremities in a symmetric fashion around 7-10 days after a drug

Question 14

When does an Exanthematous drug reaction occur and when does it end?

Answer 14

7 - 10 days after starting the dug, and lasts 2-3 days after stopping

Question 15

If someone is having an Exanethematous drug reaction, is it ever OK to continue giving the drug?

Answer 15

Yes, if the eruption is not too severe and the medication cannot be substituted

Question 16

What are long term effects of an Exanthematous drug reaction?

Answer 16

None

Question 17

What is the treatment for an Exanthematous drug reaction?

Answer 17

Steroids + antihistamines

Question 18

What should you do if a patient presents with a rash and facial edema?

Answer 18

Order a CBC and LFT’s - possible Eosinophilic reaction known as DRESS

Question 19

What is DRESS?

Answer 19

Drug Reaction with Eosinophilia and Systemic Symptoms; macular exanthem + centrofacial swelling + fever/malaise that begins 3 weeks after starting a drug and lasts many weeks after a drug is stopped

Question 20

When does an DRESS occur and when does it end?

Answer 20

DRESS occurs 3 weeks after starting a drug and lasts several weeks after a drug - potentially fatal

Question 21

What are long term effects of DRESS?

Answer 21

Possibly fatal, depending on the organ systems involved in the systemic reaction

Question 22

How should a patient with DRESS be managed?

Answer 22

Consider severity of reaction + involved organs: order CBC, LFT, BUN/Creatinine and review medications

Stop all suspect medications and discontinue non-essential medications

Question 23

What is the treatment for mild DRESS?

Answer 23

Stop all suspect medications; if mild, use topical steroids and antihistamines, if severe, use systemic steroids

Question 24

What is the treatment for severe DRESS?

Answer 24

Stop all suspect medications; begin systemic steroids and gradually taper

Question 25

What is Erythema Multiforme?

Answer 25

A self-limited but recurrent disease with the onset of papular "target" lesions occurring over 24 hours in acrofacial sites (face/hands/feet)

Question 26

What are the two types of Erythema Multiforme?

Answer 26

Erythema Multiforme Major and Erythema Multiforme Minor

Question 27

What does Erythema Multiforme Minor look like?

Answer 27

Papular target lesions with little or no mucosal involvement or systemic symptoms

Question 28

What does Erythema Multiforme Major look like?

Answer 28

Papular target lesions with severe mucosal involvement and systemic symptoms that develop in < 24hours

Question 29

Which drug usually causes Erythema Multiforme?

Answer 29

HSV and Mycoplasma Pneumoniae, not a drug reaction

Question 30

Does Erythema Multiforme progress to Toxic Epidermal Necrolysis?

Answer 30

Typically, no

Question 31

What reactions are part of the Epidermal Necrolysis Spectrum?

Answer 31

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Question 32

What are SJS and TEN?

Answer 32

Both are rare, potentially fatal cutaneous reactions to drugs characterized by mucocutaneous tenderness, erythema, and skin erosion

Question 33

Compare SJS and TEN?

Answer 33

Both involve extensive necrosis and detachment of the epidermis and mucosal surfaces, but SJS is < 10% of body surface area and TEN is > 30% of body surface area with overlap in between

Question 34

Are SJS and TEN emergencies?

Answer 34

Yup

Question 35

When are SJS and TEN more dangerous?

Answer 35

Greater skin involvement, increasing age, and comorbids

Question 36

When do TEN and SJS occcur?

Answer 36

7 - 21 days after starting a drug

Question 37

What causes SJS and TEN?

Answer 37

Extensive death of Keratinocytes via apoptosis mediated by Fas-FasL signalling

Question 38

How are SJS and TEN managed?

Answer 38

Stop the drug, and supportive care

Question 39

What drugs are high risk for SJS/TEN?

Answer 39

NSAIDS, Sulfa antibiotics, and Anticonvulsants

Question 40

How does SJS present?

Answer 40

Fever and myalgia 1-3 days before skin changes, skin changes initially on the face and upper trunk symmetrically, dusky red to purpuric macules (atypical targets) which coalesce and involve mucous membranes

Question 41

What areas are initially involved in SJS?

Answer 41

Face and upper trunk and proximal extremities: symmetric, erythematous dusky red to purpuric macules

Question 42

What are complications of SJS?

Answer 42

Corneal damage, fluid/electrolyte problems, and secondary injection

Question 43

Why should you consult Optho for SJS?

Answer 43

Corneal damage

Question 44

What are systemic warning signs of a potentially severe drug reaction?

Answer 44

Fever, malaise, etc. and Lymphadenopathy

Question 45

What are cutaneous warning signs of a potentially severe drug reaction?

Answer 45

Erythroderma, facial involvement + swelling, mucous membrane involvement, and purpura

Question 46

What is a Vesicle?

Answer 46

A blister that forms from cells separating in the Epidermis or at the Epidermal/Dermal layer

Question 47

How can intraepidermal and subepidermal blisters be differentiated?

Answer 47

Intraepidermal blisters are flaccid and easily broken; Subepidermal blisters are tense and intact

Question 48

What is the Nikolsky sign?

Answer 48

Epidermal separation caused by lateral pressure to edge of blister/normal-appearing skin = intraepidermal blister

Question 49

What is Dermatitis Herpetiformis?

Answer 49

The skin version of Celiac, caused by gluten sensitivity: causes pruritic papulovesicles on extensor sufaces, buttocks and back

Question 50

What causes Dermatitis Herpetiformis?

Answer 50

Deposition of IgA on the Papillary Dermis leading to neutrophil recruitment in response to dietary gluten allergy

Question 51

What causes the immune reaction in Dermatitis Herpetiformis?

Answer 51

Genetic predisposition for gluten sensitivity + diet high in gluten = formation of IgA to gluten Transglutaminase, which cross reacts with epidermal Transglutaminase

Question 52

If the IgA in gluten allergy is directed against Gluten Transglutaminase, why does it effect the skin?

Answer 52

IgA cross-reacts with Epidermal Keratinocyte Transglutaminase, leading to the deposition of IgA on the skin and causing Dermatitis Herpetiformis

Question 53

What causes Pemphigus Vulgaris?

Answer 53

IgG Autoantibodies to Desmogleins resulting in superficial Bullae

Question 54

Who does Pemphigus Vulgaris effect?

Answer 54

People in their 50's - 60's

Question 55

What is the treatment to Pemphigus Vulguars?

Answer 55

Immunosuppression

Question 56

What type of antibody does Pemphigs Vulgaris use, and where does it effect the skin?

Answer 56

IgG targeted against Epidermal Desmosomes

Question 57

What is Bullous Pemphigoid and what does it target?

Answer 57

Bullous Pemphigoid are autoantibodies to the hemidesmosome, resulting in deep, tense bullae on flexoral surfaces

Question 58

Who does Bullous Pemphigoid effect?

Answer 58

The Elderly

Question 59

How is Bullous Pemphigoid treated?

Answer 59

TDAP: Tetracycline, Dapsone, Azathioprine, Prednisone

Question 60

Where in the dermis does Bullous Pemphigoid split skin?

Answer 60

Subepidermally, since it targets the Hemidesmosome

Question 61

What are Porphyrias?

Answer 61

A group of inherited disorders resulting from deficiencies in heme biosynthesis enzymes

Question 62

What is Porphyria Cutanea Tardia and how does it present on skin?

Answer 62

A disorder caused by decreased activity of Uroporphyrinogen Decarboxylase that causes photosensitvity and skin fragility with blistering in sun-exposed sites

Question 63

What disease is associated with Porphyria Cutanea Tardea?

Answer 63

Liver disease such as alcoholism and Hepatitis C

Question 64

How is Porphyria Cutanea Tardia diagnosed?

Answer 64

Urine porphyrins and pink fluorecent urine under Woods light