Cutaneous Drug Eruptions Flashcards by Caitlin McMullen

What is a drug eruption?

An adverse drug reaction affecting the skin, which can be immunological (allergic) or non-immunological (non-allergic)

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What are the two broad categories of drug eruptions?

Immunologically mediated (allergic) and non-immunological (non-allergic

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What are the four types of immunologically mediated drug eruptions?

Type I (Anaphylactic)
Type II (Cytotoxic)
Type III (Immune Complex Mediated)
Type IV (T-Cell Mediated Delayed Hypersensitivity)

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What are the symptoms of a Type I (Anaphylactic) immunologically mediated drug eruption?

Urticaria, angioedema

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What are the symptoms of a Type II (Cytotoxic) immunologically mediated drug eruption?

Blistering reactions, pemphigus, pemphigoid

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What are the symptoms of a Type III (Immune Complex Mediated) immunologically mediated drug eruption?

Purpura, vasculitis, rash

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What are the symptoms of a Type IV (T-Cell Mediated Delayed Hypersensitivity) immunologically mediated drug eruption?

Erythema, rash

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Give examples of non-immunological drug eruptions

Eczema
Drug-induced alopecia
Phototoxicity
Skin erosion (e.g., topical 5-fluorouracil)
Atrophy due to topical corticosteroids
Psoriasis
Pigmentation changes
Cheilitis, xerosis

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What are some patient risk factors for drug eruptions?

(1) More common in young adults than infants/the elderly

(2) More common in females

(3) Genetic predisposition

(4) Viral infections (HIV, EBV, CMV), cystic fibrosis

(5) Previous drug reaction or positive skin test

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What are some drug risk factors for drug eruptions?

(1) β-lactam compounds, NSAIDs, high molecular weight drugs

(2) Topical route administration

(3) Higher dose and longer half-life

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What is the most common type of drug eruption?

Exanthematous drug eruptions (90%)

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What type of hypersensitivity reaction is an exanthematous drug eruption?

Type IV (T-cell mediated delayed hypersensitivity)

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What are common drugs associated with exanthematous drug eruptions?

(1) Antibiotics (β-lactams, sulfonamides)

(2) NSAIDs

(3) Anti-epileptics (carbamazepine, phenytoin)

(4) Allopurinol, chloramphenicol

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When do exanthematous drug eruptions typically occur?

4-21 days after first taking the drug (delayed)

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What are indicators of a severe drug reaction?

(1) Mucous membrane & face involvement

(2) Fever >38.5℃
(3) Blisters, purpura, necrosis
Skin pain

(4) Lymphadenopathy, arthralgia
(5) Respiratory symptoms (dyspnoea, wheezing)

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What type of hypersensitivity reaction is urticaria from drugs?

Type I (IgE-mediated, immediate)

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What drugs cause acneiform drug eruptions?
Also what is this reaction?

Glucocorticoids (steroid acne)
Androgens,
Lithium
Isoniazid
Phenytoin

= An acneiform drug eruption is a type of skin reaction caused by certain medications that leads to a sudden onset of acne-like lesions. Unlike typical acne, these lesions:
(1) all look similar, usually papules and pustules without comedones)
(2) Often widespread
(3) Not associated with blackheads or whiteheads

What drugs are associated with drug-induced bullous pemphigoid?

(1) ACE inhibitors
(2) Penicillin
(3) Furosemide
(4) Metronidazole

What is a fixed drug eruption?

A well-demarcated round/ovoid plaque that recurs at the same site on re-exposure to the drug

What drugs are associated with fixed drug eruptions?

(1) Antibiotics (tetracycline, doxycycline)

(2) Paracetamol
(3) NSAIDs
(4) carbamazepine

What are Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)?

Severe mucocutaneous reactions with 1. blistering
2. epidermal detachment
3. mucosal ulceration

What sign is positive in SJS?

Nikolsky sign
(skin sloughing with gentle pressure)

How is SJS managed?

Withdraw drug
avoid skin trauma
IV fluids
analgesia
specialist review

What does DRESS stand for?

Drug Reaction with Eosinophilia and Systemic Symptoms

What are the key features of DRESS?

(1) Widespread erythema, facial oedema (2) Fever, lymphadenopathy (3) Hepatosplenomegaly (4) 2-6 weeks after drug exposure

What causes phototoxic drug reactions?

1. Drug metabolites react with UV light (UVA) → 2. free radicals → 3. direct cell damage → 4. rash

What are the clinical features of phototoxic drug reactions?

1. Exaggerated sunburn (quinine, thiazides) 2. Pigmentation (psoralens, doxycycline) 3. Skin fragility (tetracyclines, naproxen)

What is the first step in managing a drug eruption?

Discontinue the suspected drug

Severe cutaneous adverse reactions (SCAR) - dermatological emergencies include what?

DRESS AGEP SJS-TENS

What is the minimum percentage of body surface skin involvement to warrant a diagnosis of Stevens-Johnson syndrome?

10%

What is the pathophysiology of Stevens-Johnson syndrome?

Epidermal necrosis with minimal associated inflammation

A 32-year-old man presents to A&E with a severe rash that has developed over the last 24 hours following the administration of antibiotics for a urinary tract infection. He has a temperature of 42°C, blood pressure of 80/40 mmHg, respiratory rate of 24 breaths per minute and a heart rate of 92 beats per minute. On examination, there are numerous erosions and ulcerations of the eyes, lips and mouth. The doctors suspect a diagnosis of Stevens-Johnson syndrome. What is the definitive investigation to diagnose Stevens-Johnson syndrome?

Skin biopsy

A 38-year-old woman presents acutely to the emergency department feeling generally unwell with fever and painful skin lesions. She said that she first noted target-shaped lesions on her hands and forearms two days earlier, which had since ulcerated with skin sloughing and begun to involve her mouth. Past medical history includes asthma, temporal lobe epilepsy, and a recent admission to hospital with acute appendicitis. She takes budesonide inhaler twice daily with PRN salbutamol, and had started lamotrigine two months previously for her epilepsy. She worked with children in a nursery, was married with 2 children of her own, and denied recent travel, pets, smoking and drinking alcohol. What is the most likely cause of the patient's symptoms? and why?

Stevens-Johnson syndrome (SJS) = (1) Fever + painful skin lesions (2) Target lesions progressing to ulceration and skin sloughing (3) Mucosal involvement (mouth ulcers) (4) Recent drug exposure (lamotrigine started 2 months ago)

What drugs are commonly associated with SJS?

Antibiotics (1) Sulfonamides = co-trimoxazole, sulfadiazine (2) Beta-lactams = penicillins, cephalosporins (3) Erythromycin (4) Ciprofloxacin (5) Carbamazepine (6) Phenytoin (7) Lamotrigine (8) Phenobarbital (9) Oxicams = piroxicam (10) Ibuprofen (rare) (11) Allopurinol = Used for gout; a common cause of SJS/TEN, especially in certain populations with genetic predisposition (e.g. HLA-B*58:01 in Asians) (12) Other Drugs Paracetamol (rare) Nevirapine (HIV medication)

A 22-year-old is admitted to the intensive care unit with an extensive blistering and necrotic skin rash affecting the whole body including the mucous membranes. The patient was treated for an infection by her GP the previous week. Given the diagnosis, which medication was she most likely to have been prescribed?

Toxic epidermal necrolysis = Co-amoxiclav

A 25-year-old man presents to the emergency department with a new rash. He has a history of HIV and around 5 days ago was prescribed prophylactic co-trimoxazole as his CD4 count was 323 cells per cubic millimetre. His temperature is 39.4ºC, his heart rate is 105 bpm, and his blood pressure is 85/64 mmHg. On examination, a diffuse erythematous maculopapular rash is present. When rubbing the rash, new blisters form and the skin slides off. The rash covers 56% of his total body surface area, including the oral mucosa. What term best describes this finding?

Nikolsky's sign

A 30-year-old woman started taking phenytoin a week ago for seizure prophylaxis. She later developed fever, sore throat and red eyes. Her skin is erythematous and has a scalded appearance extensively. Erosions appear when her skin is rubbed gently. Based on the most likely diagnosis, what is a known complication of this dermatological condition?

Electrolyte derangement and volume loss = patient has Toxic epidermal necrolysis

A 41-year-old female presents to Accident and Emergency with a painful skin rash of sudden onset. The last few days she has felt unwell with a severe diabetic foot infection and the GP treated her with an antibiotic she had never tried before. On examination, she has a diffuse erythematous rash with macules, targetoid lesions and flaccid blisters. She also has painful ulcers on her lips, eyes and genitals What is this describing?

Stevens-Johnson Syndrome (SJS)

A 30-year-old man on long-term prednisone for an autoimmune condition develops a widespread papular rash on his chest and back, resembling acne but without comedones. What is the most likely diagnosis?

Acneiform drug eruption

You are called to see a 91-year-old woman due to a skin rash. She has had a long admission following a fall and a clavicular fracture. Her rehabilitation has been limited due to symptomatic postural hypotension, and she is on day 5 of a course of pivmecillinam for a urinary tract infection. On examination, there are large, flaccid blisters over her arms and trunk with an erythematous macular rash. There are purpuric areas over her chest. In some areas, there is desquamation of the blisters, exposing red dermis. She has red, crusted lips with multiple deep ulcers inside her mouth. What is the most likely diagnosis? and why

Stevens-Johnson syndrome The patient has recently been started on pivmecillinam = a penicillin-based medication, and has subsequently developed a blistering skin rash Often, SJS is preceded by a 1-3 day history of flu-like illness before the eruption starts, most commonly on the chest and then spreading to the face and limbs. Sole and palms are usually spared

Mucosal involvement is prominent and severe in what disease?

Steven johnson syndrome