Lecture 14 Part 1

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Questions and Answers

What is the primary cause of Coumadin necrosis?

Depletion of protein C causing thrombosis (correct)

Concurrent use of heparin

Increased levels of procoagulant factors

Direct skin exposure to Coumadin

Which demographic is at the greatest risk for developing Coumadin necrosis?

Obese men

Children under 10

Elderly patients

Overweight women (correct)

What condition leads to a transient hypercoagulable state when initiating Coumadin therapy?

Excessive vitamin K intake

Depletion of protein S

Depletion of protein C (correct)

Increased platelet count

What prevents Coumadin necrosis during the initiation of Coumadin therapy?

Concurrent heparin therapy Signup and view all the answers

Which anatomical areas are most affected by Coumadin necrosis?

Skin overlying subcutaneous fat Signup and view all the answers

What is a characteristic time frame for the onset of DRESS after starting the medication?

2-6 weeks Signup and view all the answers

Which of the following symptoms is commonly associated with DRESS?

Facial edema with erythema Signup and view all the answers

Which organ system is least likely to be affected by DRESS?

Gastrointestinal Signup and view all the answers

What laboratory finding is almost always present in cases of DRESS?

Eosinophilia Signup and view all the answers

What is one common group of drugs that are known to cause DRESS?

Aromatic anticonvulsants Signup and view all the answers

Which of the following metabolic deficiencies is often associated with DRESS caused by aromatic anticonvulsants?

Epoxide hydrolase deficiency Signup and view all the answers

What is the primary treatment approach for managing DRESS?

Quickly diagnosing and stopping the relevant medication Signup and view all the answers

Which of the following statements about slow acetylators in the context of DRESS is accurate?

They accumulate toxic metabolites leading to DRESS. Signup and view all the answers

What are common initial findings on physical examination that may indicate a systemic drug reaction?

Lymphadenopathy, skin blisters, and target lesions Signup and view all the answers

Which laboratory studies should be ordered for patients with suspected drug reactions?

Complete blood count, liver function studies, and urinalysis Signup and view all the answers

What is a characteristic feature of Acute Generalized Exanthematous Pustulosis (AGEP)?

Erythema in groin and axillae with tiny pustules Signup and view all the answers

What is the primary cause of AGEP according to the provided information?

T-cell mediated cytokine response Signup and view all the answers

What type of medications are the most common causes of AGEP?

β-lactam antibiotics and macrolides Signup and view all the answers

What significance does the timing of rash onset have in AGEP diagnosis?

It usually starts within 1-2 days after medication initiation Signup and view all the answers

What are potential complications if AGEP treatment does not involve stopping the causative medication?

Fluid management issues and possible vasculitis Signup and view all the answers

How should AGEP be managed in clinical practice?

Stop the suspected medication if possible Signup and view all the answers

What is the primary difference in the percentage of skin sloughing that distinguishes SJS from TEN?

SJS is ≤10% sloughing, TEN is ≥30% sloughing Signup and view all the answers

Which medication is least likely to be associated with TEN/SJS?

Beta-blockers Signup and view all the answers

What percentage of skin sloughing defines SJS/TEN overlap?

10% to 30% Signup and view all the answers

Which of the following best describes the mechanism of action of FasLigand in TEN/SJS?

FasLigand binds Fas on keratinocytes, initiating apoptosis Signup and view all the answers

What is the recommended high-dose treatment for TEN/SJS delivered early in the disease?

Intravenous immunoglobulin (IVIG) Signup and view all the answers

What role does the accumulation of toxic drug metabolites play in TEN/SJS?

It leads to immune activation and overexpression of FasLigand Signup and view all the answers

In cases of TEN, what other anatomical structures can experience sloughing besides the skin?

Esophageal lining and trachea lining Signup and view all the answers

How does erythema multiforme primarily differ from SJS and TEN?

It typically affects less than 10% of body surface area with minimal mucosal involvement Signup and view all the answers

What common characteristics define a typical drug rash?

Pink-to-red macules, papules, and plaques without scale Signup and view all the answers

Which demographic factors increase the incidence of typical drug rashes?

Increasing age and increasing numbers of medications Signup and view all the answers

What is the mechanism by which the typical drug rash occurs?

Antigen presenting cells internalizing the drug-protein complex and initiating an immune response Signup and view all the answers

When does a typical drug rash usually begin after medication exposure?

1-14 days after the first dose of the medication Signup and view all the answers

What should be done with medications identified as potential causes of a drug rash?

Stop if safe to do so and consider alternatives Signup and view all the answers

Which of the following is NOT a common causative drug class for typical drug rashes?

Beta-blockers Signup and view all the answers

What symptom should be evaluated in a patient with a suspected drug rash to rule out systemic hypersensitivity?

Dark colored urine Signup and view all the answers

What kind of treatments are typically used for managing a typical drug rash?

Symptomatic treatment with oral antihistamines and topical steroids Signup and view all the answers

What is the typical duration for resolving the syndrome caused by toxic metabolites?

2-6 weeks Signup and view all the answers

What is the recommended treatment if the disease is limited to skin involvement and peripheral eosinophilia?

Topical steroids Signup and view all the answers

What is a significant consequence for patients who experience DRESS due to an aromatic anticonvulsant?

All aromatic anticonvulsants are strictly prohibited for life. Signup and view all the answers

What should be monitored in patients who have experienced DRESS several months after the episode?

Thyroid function studies Signup and view all the answers

What is the rarity of Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson Syndrome (SJS)?

About 1 case per million people per year Signup and view all the answers

What common condition increases the risk of developing TEN and SJS?

Immunosuppression Signup and view all the answers

What characterizes the rash associated with TEN and SJS?

Begins as painful erythematous macules Signup and view all the answers

How long after starting the causative medication do TEN and SJS typically manifest?

1-3 weeks Signup and view all the answers

Study Notes

Cutaneous Drug Reactions

Divided into limited cutaneous, systemic, and serious reactions
Drug rash/limited cutaneous reactions are common in hospitalized patients, increasing with age and number of medications, and more common in females.
Characterized by pink-to-red macules, papules, plaques without scaling, often itchy.
Frequently described as exanthematous or maculopapular, but specific descriptions (e.g., 1-3 cm pink plaques, covering 60% body, accentuated in warm areas) are preferred.
Commonly caused by beta-lactam antibiotics, sulfa drugs, and anticonvulsants.
Rash onset can range from 1-14 days after the first dose and last up to 14 days after stopping the medication.
T-cell-mediated processes; drug binds to protein, complex is internalized by antigen-presenting cell, then presented to drive immune reaction.
Treatment is symptomatic with oral antihistamines and topical steroids. Any drug started within two weeks prior to rash onset should be considered as a possible cause, even if stopped. Substitute with safe alternative if possible.
Evaluating for fever, sore throat, shortness of breath, dark urine are crucial for systemic drug hypersensitivity suspicion.
Physical examination should include lymphadenopathy, purpura, mucous membrane abnormalities, blisters, and target lesions.

Acute Generalized Exanthematous Pustulosis (AGEP)

Less common than typical cutaneous drug reactions.
Characterized by erythema, often in the groin, axillae, or inner thighs, with tiny pustules (1 mm) visible on close inspection.
Pustules and erythema can spread rapidly over the body. Spiking fevers and elevated neutrophil counts are common.
Commonly caused by beta-lactam antibiotics, macrolides, and calcium-channel blockers.
Onset of rash and fever usually within 1-2 days of starting offending drug.
T-cell mediated reaction, likely mediated by neutrophils.
Treatment involves stopping the causative drug, which was started within 3 days of rash onset.

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)

About as common as AGEP but far less than regular drug rashes.
Onset later than other drug eruptions (2-6 weeks after starting drug).
Initially appears similar to typical drug rash, but quickly develops widespread, confluent erythema with skin swelling. Face and neck often involved first.
Facial edema with erythema and sore throat, and significant lymphadenopathy are strongly suggestive of DRESS.
Treatment focuses on stopping the causative medication.

Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson Syndrome (SJS)

Rare, related diseases caused by medication adverse reactions.
Characterized by epidermal death and sloughing, differing only in the extent of skin involvement.
TEN affects at least 30% of skin, while SJS affects less than 10%
TEN and SJS typically emerge 1-3 weeks after initiating the drug.
Rash begins as painful, erythematous macules on the trunk and/or palms progressing to dusky erythema with sloughing of epidermis, blister or sheet-like.
Mucous membranes are often involved.
Treatment involves immediate cessation of causative agent and supportive care.

Coumadin Necrosis

Uncommon adverse reaction to coumadin therapy.
Often affects overweight women.
Starts with pain, followed by erythema progressing to purpura and necrosis, frequently in skin overlying fat (breast, thighs, buttocks).
Caused by thrombosis in small vessels of subcutaneous fat due to a transient hypercoagulable state. Temporary depletion of anticoagulants (protein C, etc) precedes the clotting.
Prevention involves initiating heparin therapy before starting coumadin to prevent the temporary coagulopathies.

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Description

This quiz covers cutaneous drug reactions, including limited cutaneous, systemic, and serious types. Explore the characteristics, common causes, and treatment options for drug-related rashes, with emphasis on T-cell-mediated processes. Assess your understanding of the specific descriptions and treatments associated with these reactions.