Adverse Cutaneous Drug Reactions Flashcards
What are the five main factors that differentiate drug rashes?
Pathogenesis (immunologic, non-immunologic, idiopathic) Appearance Onset Severity Prognosis
What is the difference between non-immune mediated and immune-mediated drug eruptions?
- Non-immune mediated do not involve typical immunologic mechanisms
- Immune-mediated occur through immune pathways (e.g., Type I-IV hypersensitivity) or are associated with immune response
What are six examples of non-immune mediated cutaneous drug reactions? ( + example of causative agent)
- Alopecia (chemotherapy, oral retinoids)
- Bruising (coumadin, heparin, long-term prednisone)
- Candidiasis (mucosal and cutaneous - broad spectrum antibiotics, steroids)
- Phototoxicity (tetracycline, doxycycline, thiazides, furosemide, etc.)
- Drug-induced skin pigmentation (minocycline, silver)
- Coumadin-induced skin necrosis (coumadin)
Describe cutaneous phototoxicity drug reactions and their causative agents
Sunburn-like reaction after sun exposure without need for immune system involvement
- Caused by tetracycline, doxycycline, thiazides, furosemide
- Note: Minocycline rarely causes photosensitivity
Describe drug-induced skin pigmentation and its causative agents
- Drug deposits in skin (silver, minocycline - enters acne scars and gives them a dark colour, amiodarone - grey patches)
- Induction of melanin pigment (flagellate hyperpigmentation of bleomycin, melasma with oral contraceptives - pigment on cheekc, forehead, chin)
Describe coumadin-induced skin necrosis
Rare but serious condition starting at the onset of therapy
- Anticoagulant protein Cis suppressed at greater rate than procoagulant factors, putting patients at risk of paradoxical thrombotic events
- Often will start heparin first to avoid this
- Skin breaks down and dies (often in fatty tissue)
What drugs can cause a flare in psoriasis?
Lithium
Beta blockers
Etc.
What is erythema nodosum? What drugs can cause a flare or induction of erythema nodosum?
Painful subcutaneous nodules on lower legs and inflammation within fat
- Caused by oral contraceptives and sulfonamides
What are three types of immune-mediated cutaneous drug reactions?
- Type I reaction (IgE mediated)
- Type III reaction (serum sickness-like reaction)
- Type IV reaction (T-cell mediated)
Describe Type I reactions and their possible causative agents
- IgE mediated reactions
- Cause hives, angioedema with individual lesions usually lasting less than 24 hours
- Termed a “true allergy”
- Beta-lactams, ASA, penicillin are potential causative agents
- Angioedema can be associated with ACE inhibitors
- May need to treat with epinephrine if severe; otherwise diphenydramine is sufficient
Describe a Type III reaction and possible causative agents
How long for onset of the reaction?
- Vasculitis
- Involves small blood vessels and typically starts 7-21 days after initiation of drug therapy
- Palpable purpura, usually on lower extremities
- Beta-lactam antibiotics, thiazides, allopurinol are potential causative agents
Describe a type IV reaction
- Allergic contact dermatitis
- Lesions are eczematous blisters with itching, leads to inflammation
- Can also have photoallergic CD which needs light exposure and topical/systemic drug
Describe the mechanism of delayed-type hypersensitivity reactions and the two stages
- Sensitization = Chemicals enter skin –> complex with carrier proteins in skin –> complete allergen –> presented to and primes T cells
- Elicitation = Second exposure –> Primed memory T cells –> Release cytokines and chemotactic factors
- Some chemicals may cause elicitation in the primary sensitization (e.g., poison ivy)
What are eight types of idiopathic and/or idiosyncratic drug reactions?
- Hypersensitivity reaction
- Morbilliform eruption/exanthematous
- Pustular eruptions
- Bullous eruptions
- Fixed drug eruptions
- Lichenoid eruptions
- Cutaneous pseudolympoma
- Drug-induced lupus
Describe hypersensitivity reaction, their symptoms, onset, and typical causative drug agents?
Idiosyncratic reaction
- DRESS = Drug reaction with eosinophilia and systemic symptoms
- Initially look like morbilliform reactions but can be more severe with systemic symptoms (fever, lymphadenopathy, hepatitis, kidney and CNS dysfunction, eosinophilia)
- Higher rates of mortality
- Occur later, up to several months after initiating drug therapy
- Typical causative agents: Anticonvulsants, allopurinol, sulfonamides, etc.
Describe morbilliform eruptions, their symptoms, onset, and typical causative agents
Idiosyncratic reaction (most common)
- Erythematous macules and papules that are itchy and start on trunk and spread
- Occur within one week of exposure and resolve within 7-14 days (becomes brownish-red, top layer of skin peels)
- Causative agents: Beta-lactams, sulfonamides, anti-epileptics, thiazides; some are more common with viral infections = HIV + sulfa; mono + amoxicillin
Describe three different types of pustular eruptions and different causative agents
Idiosyncratic reaction
- Acute generalized exanthematous pustulosis (AGEP) = diffuse, erythematous pustules/lesions - often caused by beta-lactams or macrolides
- Acneiform eruptions from oral steroids
- Pustular psoriasis from withdrawal of corticosteroids
What are the three main types of bullous eruptions
Idiosyncratic reaction
- Erythema multiforme (EM) - target lesion on palms and soles, bullseye appearance
- Stevens Johnson Syndrome
- Toxic Epidermal Necrosis
All of these involve skin and mucosa with varying severity
What is toxic epidermal necrosis?
Large surfaces of skin are rapidly denuded (generalized burn, skin peels in sheets)
- Mucosal membrane is severely affected
- High mortality rate
What are the typical culprits of bullous eruptions? How are the eruptions treated?
- Anticonvulsants, sulfonamides, NSAIDs, allopurinol, etc.; can also be caused by infections (but if reaction is severe, it likely is a drug)
- Treat by discontinuing offending agent
- TEN may benefit from IVIg (not steroids)
- Mild SJS can be treated with systemic steroids
What are fixed drug eruptions? What are their symptoms? What are typical causative agents?
Idiosyncratic reaction
- Uncommon reaction where few lesions occur in fixed sites with each administration of the drug
- Erythematous or dusky red plaques or ulcerative; may be widespread (generalized FDE); often has strong predilection towards genitals
- Causative agents include acetaminophen, NSAIDs, sulfa, etc.
- Likely is a localized Type IV hypersensitivity
What are lichenoid eruptions? What are the symptoms and onset? What are common causative agents?
Idiosyncratic reaction
- Resemble lichen planus (pruritic, purple, planar, polygonal papules (5 Ps)) usually affecting distal limbs; fine white scale on top
- Drug induced lichenoid eruptions are usually located on the trunk and have a more reddish hue
- Often develops 2 months up to 3 years after drug therapy initiation
- Common causative agents: Beta-blockers, ACE inhibitors
What is cutaneous pseudolymphoma? What typically causes it?
Idiosyncratic reaction
- Stimulation of lymphoma on skin pathology
- Caused by anticonvulsants
- Typically has an indolent course (painless, not problematic)
What is drug-induced lupus? What are the two types? What are the symptoms of each and the causative agents?
Idiosyncratic reaction
- Systemic lupus = Pains, aches, weight loss, heart and lung involvement, vasculitis; no specific cutaneous findings but may have livedo reticularis (lacy purple rash on legs); caused by hydralazine, isoniazid, minocycline**
- Subacute cutaneous lupus erythematous (SCLE) = Cutaneous form of lupus with annular, erythematous, scaly eruptions exacerbated by sun (systemic symptoms are rare and mild); caused by thiazide diuretics, terbinafine, NSAIDs, etc.
