Derm #2: Cutaneous Drug Reactions

Front 1

What are the most common types of cutaneous drug reactions?

What drug classes are most commonly related to adverse skin reactions?

Back 1

>90% morbilliform drug exanthems
(5% are urticarial allergic reactions)

A-team: Antibiotics and Anticonvulsants

Front 2

When is a drug reaction considered "serious"?

What are some risk factors for drug reactions?

Back 2

Serious- results in death, life threatening, results in disability, or prolongs hospital stay

Risk factors: women, ↑ # of drugs, older age, immunosuppressed, other conditions (viral, HIV, CMV etc.)

Front 3

Non-allergic CDR (cutaneous drug reactions):

- Chemotherapy
- Anticoagulants
- Arygria

Back 3

Chemo--> allopecia (hair loss)

Anticoagulants--> purpura (from disrupted coagulation)

Arygria--> blue nails/skin from silver handling (jewelry makers)

Front 4

Non-allergic CDR (cutaneous drug reactions):

- Tetracycline/Minocin
- Amiodarone
- AZT

Back 4

Tetracycline: deposits in teeth

Amiodarone: deposits in shins

AZT: can cause nail to turn blue

Front 5

Candida, an antibiotic, can cause what adverse drug reaction?

Delayed toxicity from arsenic use results in _____.

Back 5

Candida --> oral thrush

Arsenic --> arsenic keratosis (yellow spots), and sometimes even SCC (squamous cell carcinoma)

Front 6

Patients who are in a drug-induced coma can have what pathologic skin finding? How does this occur?

Back 6

Coma bullae (depressing circulation/respiration from coma and pressure causes hypoxia --> necrosis of epidermis/glands --> formation of bullae/vesicles)

Front 7

What is mastocytosis? What should you watch out for when prescribing medications such as ASA and NSAIDs to a person with this condition?

Back 7

Mastocytosis: excess of mast cells in the body/skin. Certain drugs can cause dose-dependent release of mast cell mediators causing reaction.

Front 8

What is the Jarisch-Herxheimer phenomenon?

Back 8

Indirect drug induced reaction from antibiotic use. Dying bacteria release endotoxins/microbial agents and can cause sxs such as: Fever, Lymphadenopathy, Arthralgias,transient Macular/Urticarial eruption

Ex: PCN for symphilis, ketoconazole for fungal infection, etc.

Front 9

How do allergic reactions differ from nonallergic cutaneous drug reactions?

Back 9

- Not dose dependent
- Self limited
- occur 7-20 days (1-3 wks) post administration of med
- Blood/tissue EOSINOPHILIA may occur

Front 10

What are the two most severe allergic cutaneous drug reactions?

Back 10

SJS (Stevens-Johnson syndrome) <5%

TEN (Toxic Epidermal Necrolysis) 25-35+ % mortality- sepsis is primary cause of death

Front 11

What does a history for suspected drug reaction entail?

Back 11

1. Complete list of current and past 2 mos medications (OTC and herbal)

2. Timeline (dose, duration, frequency, route, etc.)

Front 12

Allergic Reactions-

Type I to IV based on Gell-Coombs Classification

Back 12

Type I: Classic Ig-E mediated (immediate hypersensitivity)
Type II: Cytotoxicity
Type III: Immune complex
Type IV: Delayed type hypersensitivity (t-cell mediated)

Front 13

What class of Allergic reactions does this CDR fall into? What is the time course like?

Back 13

Type I (IgE-mediated). Drug IgE complex bind to mast cells and basophils --> histamine and inflammatory mediators released. MINUTES TO HRS after exposure.

*This is Urticaria (angioedema, bronchospasm, pruritis, etc. can develop as well)

Front 14

What class of Allergic reactions does this CDR fall into? What is the time course like?

Back 14

Type II (cytotoxic)- Specific IgG and IgM directed at drug-haptens. Initiates Complement/ cell-mediated cytotoxicity. VARIABLE in time/course.

Ex: neutropenia, hemolytic anemia, pemphigus (seen in pic)

Front 15

What class of Allergic reactions does this CDR fall into? What is the time course like?

Back 15

Type III (immune-complex mediated)- Drug-antibody complexes deposit on tissue and cause complement activation/inflammation. Ex: serum sickness, glomerulonephritis. 1-3 WEEKS POST EXPOSURE.

*this is vasculitis (associated with fever, systemic sxs).

Front 16

What class of Allergic reactions does this CDR fall into? What is the time course like?

Back 16

Type IV (delayed, cell mediated hypersensitivity). MHC presentation of drugs to T cells with cytokine and inflammatory mediator. 2-14 DAYS POST EXPOSURE.

Ex: SJS/TEN, pic shows a lichenoid drug reaction

Front 17

What is an exanthematous drug eruption? How does it appear?

Back 17

Aka. Morbilliform drug eruption. Typically TYPE IV.

Fine macules/papules that become confluent and blanch. Tends to be symmetric, mostly truncal. Develops within 2 wks after drug onset. (may occur with low grade fever).

Front 18

How does an exanthematous drug eruption change over time? What does it look like when it's resolving?

Back 18

First bright red-pink macules. --> As it resolves, turns red/brown and desquamates.

*patient has postinflammatory desquamation following exanthematous CDR (resolving fluid and inflammation)

Front 19

What are some histologic features of Exanthematous drug eruption?

Back 19

1. Perivascular lymphocytic infiltrate (some eosinophils)
2. Few necrotic keratinocytes
3. Mild peripheral eosinophilia (20-40% of pts)

*also note spongiosus (fluid in skin).

Front 20

What drugs are most commonly implicated in Exanthematous drug eruptions?

Describe the pathophysiology of how drug intake leads to this reaction.

Back 20

A-team: Antibiotics (amox, TMP-SMX, etc.), Anticonvulsants, Allopurinol

Drug hapten binds APC --> presented to T-cell which is activated and increase in number

2nd exposure--> CD4, CD8 T-cells bind hapten --> perforin/granzyme released --> inflammation, necrosis of keratinocytes

Front 21

What treatments would you consider in an exanthematous drug eruption?

Back 21

1st- remove the offending agent
2- supportive care (topical steroids and emollients for desquamation).

Front 22

What is DRESS (drug hypersensitivity syndrome)?

Back 22

DRESS = drug reaction with eosinophilia and systemic sxs

Classic Triad = Fever, Rash, Systemic symptoms. Typically occurs with 1st exposure (1-8 wks after). AEDs (phenytoin, CBZ, phenobarb), Sulfonamides, Allopurinol, Tetracycline

Front 23

What is the Hallmark feature of DRESS (seen on clinical exam)?

Back 23

Red Facial Swelling!

Skin eruption seen in 87% of patients! (can be morbilliform exanthem, exfoliative -red and scaly- follicular, SJS/TEN)

Front 24

What are some features of DRESS seen on histology?

Back 24

- dense lymphocytic infiltrate in papillary dermis
- eosinophils
- papillary dermal edema
- occasional atypical lymphocytes

Front 25

What is the pathophysiology of DRESS?

What would your workup entail?

Back 25

Falls under Type IV. Different processes depending on drug

1. Immune reaction --> IL-5 release by T cells, induce eosinophilia.
2. Detoxification defects in epoxide hydrolase

CBC, Urine, BUN, Cr, Liver enzymes (LFT), Thyroid (TFT)

Front 26

What are some treatment options for DRESS syndrome?

Back 26

- Recognition/withdrawal of agent!!!

- Systemic corticosteroids (taper slowly)
- antipyretics
- antihistamines

Front 27

What is an Urticarial Allergic Drug Eruption? What are common drug perpetrators?

Back 27

2nd most common CDR (5%).
Drugs: salicylates, NSAIDS, Tartrazine dyes (yellow dyes), contrast media, etc.

Pink wheals, varied in size, lasting <1 day. Pruritis (itching)

Front 28

What are histologic features of urticarial allergic drug eruption?

What is a "Complex" Urticarial drug eruption

Back 28

Histology: intact epidermis, dilated blood vessels in the papillary dermis.

Lymphocytic inflammation - scattered around blood vessels. pink eos seen.

Complex= occurs with other problems (anaphylaxis, angioedema, etc.).

Front 29

What are the two broad categories for photosensitive drug eruptions?

How would you treat them?

Back 29

1. Phototoxic, 2. Photoallergic

Treat both with: removing drug, topical corticosteroids, minimize sun exposure, SUNSCREEN!

Front 30

What type of photosensitive drug eruption is this? What are common offending agents?

Back 30

Phototoxic reaction

-Doxycycline, NSAIDs, Fluoroquinolones
- Light interacts with drugs/metabolites. Looks like exaggerated sunburn (and stings!)

Front 31

What type of photosensitive drug eruption is this? How does it differ from the other, more common, photosensitivity reaction?

Back 31

Photoallergic- UV light makes drug into photoallergen (induces immune response).TYPE IV response.

Less common than phototoxicity. Pruritic, can look like dermatitis. Histology -lymphocyte & inflammation of superficial and deep layer.

*unlike Phototoxicity= necrotic keratinocytes, some edema, but SPARSE perivascular infiltrate of lymphocytes.

Front 32

Describe the histologic changes in Photoallergic reaction.

What drugs are classically involved?

Back 32

- Epidermal spongiosis
- Superficial and deep perivascular infiltrate (lymphocytes and histiocytes)

Drugs: Thiazides, sulfonamide abx, sulfonylureas

Front 33

What is EAC-like cutaneous drug reaction? What drugs are commonly involved?

Back 33

Erythema annulare centrifugum

Urticarial, oval patches with cigarette paper like scale.

Drugs: baribiturates, captopril, labetalol

Front 34

What does the histologic picture of EAC-like CDR look like?

Back 34

-Mounds of parakeratosis can be seen at surface (representing the trailing scales)

- there is also perivascular inflammation

Front 35

This type of reaction can occur in response to what drugs?

How do you treat it?

Back 35

Acneiform Drug Reaction= resembles acne, monomorphic follicular pustules/papules but NO COMEDONES.

Drugs: halogens, haldoperidol, INH, lithium
Rx: topical steroids

Front 36

What is this type of cutaneous drug reaction called and what might have caused it?

Back 36

Acneiform cutaneous drug eruption (from overuse of steroids).

Front 37

What type of allergic reaction is leukocytoclastic vasculitis?

How does it appear?

Back 37

LCV- Type III IMMUNE REACTION (in post capillary venule)

Begins 7-21 days after drug onset (on dependent locations). Looks like crops of red macules --> followed by PALPABLE PURPURA --> and then ulceration.

Front 38

What does the histologic picture of LCV look like?

Back 38

- Vascular destruction/necrosis
- Fibrin deposition in vessels
- Leukocytoplasia: neutrophils rupture

Front 39

What does a Fixed Drug Eruption look like?

Back 39

A CDR that recurs at same site (typically 1-2 wks after initial exposure, and hours after recurrent exp)

-Dusky, red round macule. Can become bullous. When it heals it becomes hyperpigmented.

Front 40

Common sites of fixed drug reactions?

Back 40

Genitalia, perianal, lips, hands/feet (really any location)

New= acute, red/purple
older= brown/hyperpigmented

Front 41

What features do you see on histology of a fixed drug eruption?

Back 41

- Vacuolar interface dermatitis (damage to the epidermis at the DEJunction). Causes melanocyte pigment to drop down.

- Superifical and deep inflammation seen, polys and eos

- Dermal melanophages (that eat up pigment and look brown).

Front 42

What are the most commonly implicated drugs that cause Fixed Drug Reactions?

How do you treat FDRs?

Back 42

- phenolphtalein
- tetracycline
- NSAIDs

Rx: d/c offending agent, topical corticosteroids

Front 43

What is this cutaneous drug reaction called (note: it may also be associated with infections).

What drugs are implicated?

Back 43

Erythema Nodosum (tender, subcutaneous nodules on shins. from inflammation in the fat).

Drugs: Abx, amiodarone, gold, OCPs

- Rx: rest (tends to spontaneously resolve), NSAIDS, potassium iodide

Front 44

What is this type of drug reaction called?

What is it characterized by?

Back 44

Lichenoid Drug Eruption. Represent inflammation stuck to epithelium

PPPP- pruritic, polygonal, papules/plaques.

Front 45

What is seen on the histology of Lichenoid Drug Eruption? How does it differ from Lichen planus?

Back 45

Histology: inflammation in band like pattern stuck onto the DEJ (like lichen stuck onto rock).

Unlike Lichen Planus, Lichenoid Drug eruption has scattered EOSINOPHILIC infiltrate.

Front 46

What meds are associated with Lichenoid Drug Eruption?

Back 46

antimalarials, lasix, gold, thiazide

Front 47

What is exfoliative erythroderma?

Back 47

Wide spread erythema and scaling (no blisters). Can follow exanthematous drug eruption.

No mucous membranes involved. Patients can have systemic sxs (fever, malaise, hypothermia, tachycardia).

Front 48

What does AGEP stand for? What do patients typically present with?

Back 48

Acute Generalized Exanthematous Pustulosis

Pt. presents with abrupt eruption of follicular pustules on face that spreads to trunks/ lower extremities. They also have Fever, increased WBC, and Eosinophilia.

Within a few weeks, patients may experience desquamation.

Front 49

What type of pustules do you see in AGEP? why?

What does the AGEP look like on histology?

Back 49

Sterile pustules (neutrophils but no bacteria! because it's a drug reaction).

Histology: spongiosus (fluid in the epidermis) and neutrophils forming collections in the epidermis

Front 50

What drugs are primarily implicated in AGEP?

What is the pathophsyiology of the reaction?

Back 50

- Beta lactam abx
- Macrolides
- Terbinafine
- Herbal medications

*Pathophys: T cell mediated response --> tissue destruction via CD8 cells and CD4 cells. Secretion of cytokines to attract polys and result in pustule formation