Buxton: Rashes

Question 1

What are the more common cutaneous drug reactions?

Answer 1

cumulative toxicity
overdose
photosensitivity
drug-drug interactions

Question 2

when the immune response to a drug results in an increased or exaggerated response

Answer 2

hypersensitivity

Question 3

Drugs and their metabolites act as (blank) making some proteins immunogenic inducing either a cell-mediated or humoral response.

Answer 3

haptens

Question 4

A drug substance that is capable of reacting with a specific antibody but cannot induce the formation of antibodies unless bound to a carrier protein or other molecule.
Also called incomplete antigen, partial antigen.

Answer 4

haptens

Question 5

(blank) reactions are caused by the formation of drug/antigen-specific IgE that cross-links with receptors on mast cells and basophils leading to immediate release of chemical mediators, including histamine and leukotrienes.

Answer 5

Type 1

Question 6

Clinical features of Type 1 hypersensitivity reactions?

Answer 6

pruritus 
urticaria
angio-oedema
bronchoconstriction
anaphylaxis

Question 7

Drugs most commonly responsible for type 1 hypersensitivity reactions?

Answer 7

aspirin
opioids
penicillins

Question 8

These reactions are based on IgG or IgM-mediated mechanisms.

These involve binding of antibody to cells with subsequent binding of complement and cell rupture.

Answer 8

Type II hypersensitivity

Question 9

Clinical features of type II sensitivity reactions?

Answer 9

blood cell dyscrasias

ex: haemolytic anemia and thrombocytopenia

Question 10

These reactions are mediated by intravascular immune complexes that arise when drug antigen and antibodies, usually of IgG or IgM class, are both present in the circulation, with the antigen present in excess.
Slow removal of immune complexes by phagocytes leads to their deposition in the skin and the microcirculation of the kidneys, joints and gastrointestinal system

Answer 10

Type III hypersensitivity

Question 11

Examples of type III hypersensitivity reactions

Answer 11

serum sickness

vasculitis

Question 12

These reactions are mediated by T cells causing ‘delayed’ hypersensitivity reactions

Answer 12

Type 4 hypersensitivity

Question 13

Examples of type 4 hypersensitivity reactions

Answer 13

contact dermatitis

delayed skin tests to TB

Question 14

The clinical manifestations of drug hypersensitivity depend on various factors, including…

Answer 14

the chemical or structural features of the drug
the genetic background of the affected individual
the specificity and function of the drug-induced immune response

Question 15

the classic drugs acting as haptens, but are reported to cause type 1 IgE mediated (immediate-type) hypersensitivity reactions as well as non-IgE mediated reactions, including morbilliform eruptions, erythema multiforme and Stevens–Johnson syndrome.

Answer 15

Penicillins

Question 16

There is a high incidence of hypersensitivity reactions in patients with altered immune status, for example due to viral infections (Epstein–Barr virus or HIV). Give an example.

Answer 16

increased risk of trimethoprim/sulfamethoxazole hypersensitivity in HIV patients

Question 17

T/F: Many drug reactions cannot be distinguished from naturally occurring eruptions.

Answer 17

True, misdiagnosis is very common

Question 18

What are some examples of diagnostic uncertainty when it comes to rashes

Answer 18

A morbilliform rash may be due to viral infection or an antibiotics, and may limit the use of a particular medication

Patients may be taking multiple medications, making it difficult to establish which is responsible

If a patient is taking two drugs, one of the drugs might be more likely to cause the particular type of cutaneous eruption than the other

Question 19

How can timing be used to determine what drug is responsible for causing a skin reaction?

Answer 19

in general, the onset occurs soon after the introduction of the causative drug

**When examining a list of medicines taken by a patient with a rash, new drugs taken within the previous month are the most likely cause.

Question 20

What are two exceptions to the timing rule?

Answer 20

hypersensitivity reactions to penicillins can occur several weeks after the drug has been discontinued

gold can cause late reactions, too

Question 21

Drugs suspected of causing skin reactions should usually be (blank) and not used again in that patient, although the risk–benefit potential needs to be considered before discontinuing any necessary medicines.

Answer 21

withdrawn

Question 22

What are these?

mucous membrane involvement
blisters or skin detachment
high fever
angio-edema or tongue swelling
facial edema
skin necrosis
lymphadenopathy
dyspnoea.

Answer 22

signs suggestive of a severe reaction

Question 23

In most cases drug eruptions are (blank), resolving gradually after the causative drug is withdrawn.

Knowledge of the (blank) of the implicated drugs can be important; for medications with long (blank), the time to resolution may be several weeks or more.

Answer 23

reversible; half-lives; half-lives

Question 24

What are these?

Acetaminophen 
Allopurinol
Antimicrobials: cephalosporins, penicillins, chloramphenicol, erythromycin, gentamicin, amphotericin, antituberculous drugs, nalidixic acid, nitrofurantoin, sulfonamides
Antifungals (allylamine type: Terbinafine)
Barbiturates
Captopril
Carbamazepine
Furosemide 
Gold salts 
Lithium 
Phenothiazines 
Phenylbutazone 
Phenytoin
Thiazides

Answer 24

Drugs commonly causing exanthematous reactions

Question 25

This drug usually is well tolerated at recommended therapeutic doses. Rash and other allergic reactions occur occasionally. The rash usually is erythematous or urticarial, but sometimes it is more serious and may be accompanied by drug fever and mucosal lesions. Patients who show hypersensitivity reactions to the salicylates only rarely exhibit sensitivity

Answer 25

Acetaminophen

Question 26

The use of (blank) has been associated anecdotally with neutropenia, thrombocytopenia, pancytopenia, hemolytic anemia, and methemoglobinemia. Kidney damage has been reported, and liver damage is a prominent feature of overdose.

Answer 26

acetaminophen

Question 27

What causes a fixed drug eruption? How does a fixed drug eruption present? What might the patient complain of? Where does the eruption occur?

Answer 27

drugs or chemicals alone; erythematous round or oval lesion of a reddish, dusky purple or brown color, sometimes with blisters; initially, one lesion appears but many others may follow; pt may complain or itching or burning; can occur on any part of the skin or mucous membranes (hands, feet, tongue, penis, perianal areas)

Question 28

What does it mean that a drug eruption is "fixed?"

Answer 28

whenever the pt takes the causative drug, the eruption will occur at exactly the same site **healing will occur over 7-10 days after the drug is stopped

Question 29

3 drugs frequently implicated in fixed drug eruptions?

Answer 29

sulfonamides tetracyclines NSAIDs

Question 30

the second most common form of cutaneous drug reaction after exanthematous reactions.

Answer 30

drug-induced urticaria

Question 31

How do urticarial lesions present?

Answer 31

raished, itchy, red blotches or wheals that are pale in the center and red around the outside

Question 32

Drug-induced urticaria may occur after the first exposure to a drug or after many previously (blank) exposures. The onset is more (blank) than with other drug eruptions; lesions usually develop within 36 hours of initial drug exposure. Individual lesions rarely persist for more than 24 hours. On rechallenge, lesions may develop within (blank)

Answer 32

well-tolerated; rapid; minutes

Question 33

a vascular reaction resulting in increased permeability and fluid leakage, leading to edema of the deep dermis, subcutaneous tissue or submucosal areas

Answer 33

angioedema

Question 34

Is angioedema more or less common than urticaria? What areas are usu affected?

Answer 34

less common; tongue, lips, eyelids, genitalia **unilateral or bilateral

Question 35

one of the most common causes of angioedema

Answer 35

ACE inhibitors

Question 36

T/F: It has been shown that continuing use of ACE inhibitors after the first episode of angioedema results in a markedly increased rate of recurrence, with serious morbidity. ACE inhibitors should therefore be withdrawn immediately in any patient who presents with angioedema, and they are contraindicated in patients with a history of idiopathic angioedema.

Answer 36

True

Question 37

In what two ways do ACE inhibitors cause angioedema?

Answer 37

1. block renin-angiotensin mediated vasoconstriction | 2. prevent breakdown of bradykinin leading to formation of NO and prostacyclin

Question 38

What are these: Drugs acting thru IgE receptors to the drug on mast cells triggering degranulation Drugs that cause mast cell degranulation Drugs that pharmacologically promote/exacerbate urticaria Immune complex formation precipitation and activation of complement Excpients in the medication that provoke allergic or pseudoallergic reactions

Answer 38

drugs causing urticaria/angioedema

Question 39

Some drugs can cause or exacerbate acne. Name a few.

Answer 39

``` ACTH corticosteroids androgens (in females) oral contraceptives isoniazid phenytoin lithium ```

Question 40

can unveil psoriasis in susceptible patients or aggravate existing psoriasis

Answer 40

Lithium

Question 41

List some drugs that may cause psoriasiform eruptions or exacerbate psoriasis

Answer 41

``` ACE inhibitors beta-blockers chloroquine digoxin G-CSF gold lithium interferons NSAIDs ```

Question 42

small cutaneous extravasations of blood. It is an occasional feature of drug-induced skin eruptions, and in some cases it is the main characteristic

Answer 42

purpura

Question 43

Purpura is often caused by thrombocytopenia or platelet dysfunction, but drugs can also cause damage to small blood vessels and cause changes in vascular permeability. Give some examples of such drugs.

Answer 43

``` aspirin quinine sulfonamides atropine penicillin ```

Question 44

refers to inflammation of the blood vessels leading to raised purpuric lesions mainly on the legs

Answer 44

vasculitis

Question 45

2 types of vasculitis that can be induced by drugs

Answer 45

systemic vasculitis | cutaneous vasculitis

Question 46

What is the mechanism behind vasculitis?

Answer 46

type III hypersensitivity reaction with immune complex deposition in postcapillary blood vessels

Question 47

This drug is associated with a hypersensitivity syndrome that typically manifests as a vasculitis involving one or more organ systems.

Answer 47

propylthiouracil

Question 48

3 diseases with a continuous spectrum of disease: pts present with fever and flu-like symptoms before skin eruption skin eruption affects hands, feet, limbs the most may present with blisters, papular lesions, erythematous areas involvement of the mucosa is common

Answer 48

erythema multiforme Stevens-Johnson syndrome toxic epidermal necrolysis

Question 49

When do the severe non-urticarial drug eruptions like Stevens-Johnson typically occur?

Answer 49

1-2 weeks after treatment

Question 50

What is the major precipitating cause of toxic epidermal necrolysis?

Answer 50

medications

Question 51

This syndrome comprises fever, malaise, myalgia, arthralgia, and extensive erythema multiforme of the trunk and face. It is frequently drug induced. There may be skin blistering and mucosal erosion covering up to 10% of the body surface area. This syndrome is distinct from TEN, but there is a degree of overlap

Answer 51

Stevens-Johnson Syndrome

Question 52

Denotes a reaction occurring when a photosensitising agent in or on the skin reacts to normally harmless doses of ultraviolet or visible light.

Answer 52

photosensitivity

Question 53

A widespread eruption suggests exposure to a (blank) photosensitizing agent, whereas a localized eruption indicates a reaction to a (blank) topical photosensitizer

Answer 53

systemic; locally applied

Question 54

This drug is associated with a 30–50% incidence of photosensitivity. Symptoms develop within 2 hours of sun exposure, as a burning sensation followed by erythema. A small number of affected patients develop slate-grey pigmentation on light-exposed areas. Light sensitivity may persist for up to 4 months after the drug is stopped.

Answer 54

Amiodarone

Question 55

This drug may cause a phototoxic response when given in high doses. The reaction is characterized by a burning, painful erythema within minutes of exposure to sunlight, either directly or through windows. Erythema may persist for more than 24 hours. Occasionally, a golden-brown or slate-grey pigmentation, predominantly of exposed sites, may be seen

Answer 55

Chlorpromazine

Question 56

Many skin diseases are followed by changes in skin (blank). | In particular, after fixed drug eruptions there may be residual (blank)

Answer 56

color; pigmentation

Question 57

This drug can cause a brown patchy pigmentation on light-exposed areas

Answer 57

Phenytoin

Question 58

How are drugs that induce hair loss classified?

Answer 58

by the phase of the hair follicle cycle that is affected

Question 59

In anagen effluvium, what cycle of hair growth is interrupted?

Answer 59

cessation of active anagen growth - hairs are shed within days or weeks with tapered or broken roots

Question 60

(blank) is associated with alkylating agents such as cyclophosphamide, cytotoxic antibiotics such as bleomycin, vinca alkaloids, and platinum compounds.

Answer 60

alopecia

Question 61

(blank) may be useful to partially prevent hair loss in patients undergoing chemotherapy.

Answer 61

scalp hypothermia

Question 62

an excessive growth of coarse hair with masculine characteristics in a female. This is a consequence of androgenic stimulation of hormone sensitive hair follicles.

Answer 62

hirsutism

Question 63

Drugs that commonly cause hirsutism

Answer 63

``` testosterone danazol corticotropin anabolic steroids glucocorticoids ```

Question 64

Patients with drug-induced hirsutism may also present with other dermatological signs of virilization, such as (blank)

Answer 64

acne

Question 65

the growth of terminal and/or vellus hair on areas of the body where the hair is usually short, such as the forehead and cheeks.

Answer 65

hypertrichosis

Question 66

(blank) may produce hypertrichosis in 50% of transplant recipients, with the excess growth being most marked on the face and upper back.

Answer 66

Cyclosporin

Question 67

Drugs that can cause hypertrichosis?

Answer 67

``` androgens cyclosporin diazoxide methoxsalen minoxidil nifefipine penicillamine phenytoin verapamil ```

Question 68

T/F: In phototoxic drug eruptions it is always necessary to stop the medication, even if protection from the sun is possible.

Answer 68

false, if sun protection is possible, it may be best OK to remain on the drug

Question 69

A known cause of photosensitivity reactions

Answer 69

NSAIDs