[11.16] Cutaneous Drug Reactions V2.pdf

Any undesirable event related to the use of drugs that causes a change in the structure and function of the skin, appendages, and mucous membranes

What is the definition of an Adverse Cutaneous Drug Reaction (ACDR)?

Oral, IV, IM, or topical

What routes of drug administration can lead to ACDRs?

3 billion

How many prescriptions are given by doctors in the US annually?

60,000

How many drug products are available in the US?

2,000

How many active ingredients are found in US drug products?

3 percent

What is the prevalence of ACDRs in developed countries?

5 percent

What is the prevalence of ACDRs in developing countries?

Increases morbidity, mortality, and healthcare costs

What are the three main impacts of ACDRs on patients?

2 percent

What percentage of reported ACDRs are considered severe and fatal?

ACDRs

What is the most frequent adverse reaction to drugs?

Recognize ACDRs immediately, remove the offending culprit, and intervene

What are the three main roles of a physician when dealing with ACDRs?

Immunologic and non-immunologic

What are the two primary categories of ACDR pathogenesis?

Gel and Coombs

What is the name of the most widely accepted classification system for immunologic reactions?

Allergic, Cytotoxic, Immune Complex, and Delayed

What does the acronym ACID stand for in the context of immunologic reactions?

Type 1

Which immunologic reaction type is known as Allergic?

Type 2

Which immunologic reaction type is known as Cytotoxic?

Type 3

Which immunologic reaction type is known as Immune Complex?

Type 4

Which immunologic reaction type is known as Delayed?

Drug IgE complex binding to mast cells

What is the mechanism of a Type 1 immunologic reaction?

Histamine

What is the primary inflammatory mediator released from mast cells in Type 1 reactions?

Minutes

What is the typical timing for a Type 1 immunologic reaction?

Urticaria, angioedema, and anaphylaxis

What are three clinical manifestations of a Type 1 reaction?

NSAIDs and Penicillin

What are two examples of drugs that cause Type 1 reactions?

IgM and IgG antibodies directed at drug hapten coated cells

What is the mechanism of a Type 2 immunologic reaction?

Blood Rh factor and major blood group antigens

What are examples of intrinsic surface antigens targeted in Type 2 reactions?

Drug coated cell

What is an example of an extrinsic surface antigen targeted in Type 2 reactions?

Activation of the complement system, antibody dependent cell mediated cytotoxicity, and opsonization

What are the three mechanisms of cell destruction in Type 2 reactions?

Natural Killer or NK cells

Which cells bind to the antigen antibody complex via Fc receptors in Type 2 reactions?

Granzymes and perforin

What substances do NK cells release to cause cell death in Type 2 reactions?

Apoptosis

What is the mechanism of cell death in Type 2 hypersensitivity?

Hemolysis and purpura

What are the primary skin manifestations of Type 2 reactions?

Variable

What is the timing for a Type 2 immunologic reaction?

Ecchymosis, pallor, jaundice, and pale conjunctiva

What are four signs of drug induced hemolytic anemia?

Tissue deposition of drug antibody complexes

What is the mechanism of a Type 3 immunologic reaction?

Activation of complement

What follows the deposition of complexes in Type 3 reactions to cause tissue damage?

Small size

Why do some immune complexes persist in the circulation instead of being cleared?

Joints, kidneys, and blood vessels

Where do small immune complexes typically deposit?

Arthritis

What is caused by immune complex deposition in the joints?

Nephritis

What is caused by immune complex deposition in the kidneys?

Vasculitis

What is caused by immune complex deposition in the blood vessels?

1 to 3 weeks

What is the typical timing for a Type 3 reaction to manifest in the skin?

Serum sickness, vasculitis, and urticaria

What are three manifestations of Type 3 reactions?

MHC presentation of drug to T cells

What is the mechanism of a Type 4 immunologic reaction?

T cell mediated

What is the classification of Type 4 reactions regarding cell involvement?

Type 4

Which is the only cell mediated immunologic mechanism?

Topical medications

What type of drug antigens are mostly involved in Type 4 ACDRs?

Sensitization and clonal expansion of specific T helper cells

What occurs upon initial exposure to a drug antigen in a Type 4 reaction?

Memory T cells

What is produced by TH1 cells during the first exposure of a Type 4 reaction?

Macrophages and CD8 plus T cells

Which cells are activated upon subsequent exposure in a Type 4 reaction?

Cytokines

What do memory T cells produce upon reactivation to recruit inflammatory cells?

Contact dermatitis, exanthematous eruptions, and photoallergic reactions

What are three manifestations of Type 4 reactions?

2 to 7 days

What is the typical timing for a Type 4 reaction?

Erythema, inflammation, and swelling

What are three skin findings in Type 4 contact dermatitis?

Exacerbation of pre existing disease

What non immunologic mechanism describes drugs worsening psoriasis?

Dorsal forearms and face

What are two common sites for photosensitivity reactions?

Pigmentary changes

What is the non immunologic term for drug induced color changes in the skin?

Lipodystrophy

What is the non immunologic term for drug induced fat changes?

Argyria

What condition is caused by the accumulation of silver in the skin?

Hair loss due to chemotherapeutic drugs

What is a common non immunologic adverse effect of cancer treatment?

Idiosyncratic reaction

What is the term for the rash seen in mononucleosis patients treated with ampicillin?

Candidiasis

What condition is caused by an imbalance of flora due to antibiotic treatment?

Jarisch Herxheimer phenomenon

Which non immunologic reaction occurs during the treatment of syphilis?

Purpura

What skin manifestation results from an overdosage of anticoagulants?

Exanthematous Eruption

What is the most common form of drug eruption?

95 percent

What percentage of drug eruptions are exanthematous?

Morbilliform Eruption

What is another name for an exanthematous eruption?

Generalized and symmetric

What is the distribution of an exanthematous eruption?

Starts on the trunk then spreads peripherally

What is the progression pattern of exanthematous lesions?

1 to 2 weeks

What is the typical onset timing for an exanthematous eruption?

7 to 14 days

How long does an exanthematous eruption typically last?

Desquamation

How does an exanthematous eruption typically end?

Macules and papules

What are the primary lesions in an exanthematous eruption?

Penicillins, sulfonamides, and anti epileptic medications

What are three common drug classes that cause exanthematous eruptions?

Urticarial Eruptions

What is the second most common clinical manifestation of ACDRs?

Wheal and flare

What type of reaction characterizes urticaria?

Erythematous edematous swellings

What is the description of urticarial wheals?

10 to 20 percent

What percentage of urticaria cases are caused by drugs?

Pruritus, flushing, nausea, diarrhea, abdominal pain, congestion, laryngeal edema, bronchospasm, and hypotension

What are nine systemic symptoms caused by histamine release?

Evanescent

What term describes lesions that come and go?

30 minutes to 24 hours

What is the typical duration for urticarial lesions?

Never more than 24 hours

What is the maximum amount of time an urticarial wheal stays in the same spot?

IgE, immune complexes, or non immunologic

What are the three potential pathogenic mechanisms for urticaria?

Pantal pantal

What is the Tagalog term for wheals?

Angioedema

What swelling of the eyes and mouth often accompanies urticaria?

Fixed Drug Eruptions

Which ACDR is characterized by lesions appearing at the exact same spot whenever the culprit drug is taken?

Solitary bright red or dusky red macule

What is the hallmark lesion of a fixed drug eruption?

Burning or stinging

What sensations typically accompany a fixed drug eruption?

Genitalia and peri anal area

What are the two common skin locations for fixed drug eruptions?

Edematous plaques or bullae

What might a fixed drug eruption macule evolve into?

Fever, malaise, and abdominal pain

What are three systemic symptoms of fixed drug eruptions?

Ibuprofen, naproxen, sulfonamides, and tetracyclines

What are four drugs commonly implicated in fixed drug eruptions?

Violaceous patches

What color do fixed drug eruptions often appear as on the skin?

Contact Dermatitis

Which ACDR is a Type 4 reaction from topical medications?

Allergic and Irritant

What are the two types of contact dermatitis?

Antibiotics, preservatives, and perfumes

What are three components of topical medications that cause allergic contact dermatitis?

Acids or bases

What substances typically cause irritant contact dermatitis?

Days to weeks

What is the timing of onset for allergic contact dermatitis?

Hours to days

What is the timing of onset for irritant contact dermatitis?

Requires previous sensitization

What is a key requirement for allergic contact dermatitis that irritant contact dermatitis lacks?

Erythematous dry to moist patches or plaques

What is the appearance of contact dermatitis?