Drug Reactions Flashcards
Epidemiology of drug reactions
- One of most common skin problems in-patient and clinical
- Simple exanthems (75-95%) and urticarial (5-6%) vast majority
- Factors of age, female gender, concomitant viral infections (esp HIV and EBV) increase risk
- Certain drugs associated with certain reaction patterns
Most frequent offenders in drug reactions
- antibiotics
- anticonvulsants
- NSAIDS
Pathophysiology of type I reaction
- drug-induced urticarial, angioedema and anaphylaxis
- preformed IgE antibodies recognize drug-protein complexes -degranulation of mast cells - release of histamine and pro-inflammatory cytokines.
- usually require previous exposure to offending drug.
- immediate type reaction, so can occur within minutes**
Pathophysiology of type IV reaction
- morbilliform drug eruptions, fixed drug eruption, DRESS, and AGEP
- T cells lymphocytes recognize the drug–protein complex - stimulate cytokines - inflammatory reaction on the skin.
- delayed type reaction, so 5-7 days
What is the MC type of cutaneous drug reaction?
Exanthematous/morbilliform reaction
Etiology of exanthematous/morbilliform reaction
- insidious onset, within first 2 weeks of tx to 2 wks after stopping medication
- systemic involvement low (simple reaction)
- widespread erythematous macules/papules.
- begins proximally, then generally and can become confluent
- pruritus prominent
Which drugs commonly cause exanthematous/morbilliform reactions?
Antibiotics, especially penicillins and Trim-Sulfa most common, especially with EBV, CMV, HIV
Tx of exanthematous/morbilliform reactions
- identify offending drug and D/C if possible
- topical or oral steroids
- antihistamines to help with pruritus
- eruption clears within 2 weeks after stopping agent
- desquamation expected
Define urticaria/angioedema
Pruritic wheals (mid-dermal swelling) and/or angioedema (deeper dermal/subcutaneous swelling, often to face, mucous membranes) *Can be associated with anaphylactic rxn with bronchospasm
Pathophysiology of urticaria/angioedema
- Mast cell degranulation - release of histamine and other inflammatory molecules**
- ASA and NSAIDS most common nonimmunologic - alter prostaglandin metabolism, enhancing mast cell degranulation
- Immunologic urticaria MC associated with PCN and related (i.e. augmentin)
- -IgE antibodies formed
Which drugs frequently cause urticaria/angioedema?
ACE inhibitors/ARBs and Angioedema- probably normal pharmacologic effect of the drug by increasing tissue kinin levels
Tx of urticaria/angioedema
- Identify and withdraw offending drug
- Non-sedating H1 blocking agents: need up to 4x allergic rhinitis dosage
- Additional H2 blocker, leukotriene antagonist, or sedating H1 blocker may be considered
- Systemic steroids
- Subcutaneous epi with anaphylaxis
Define fixed drug reaction
Recur at the same site with each exposure to medication
Describe appearance of fixed drug reaction
- Solitary, at times multiple, erythematous to violaceous patch or plaque
- Well defined.
- Evolves to target lesion, may blister and erode
Body sites of fixed drug reaction
Common sites include the lips, genitals, and extremities
Meds that induce fixed drug reaction
NSAIDS (esp. naproxen), tetracyclines, sulfonamides/sulfa drugs, salicylates
Describe Acute Generalized Exanthematous Pustulosis (AGEP)
- Acute febrile eruption with leukocytosis
- Sudden onset, avg. 5 days after med started
- Non-follicular sterile pustules occurring on a diffuse, edematous erythema
- Widespread desquamation follows
- Mucous membranes involved 20%
- Neutrophilia in 90%
Define DRESS Syndrome
drug rash with eosinophilia and systemic symptoms
When does DRESS occur?
later in tx course than simple exanthems, more than 2 weeks up to months after med instituted
How do patients present with DRESS?
Fever, malaise, and facial edema (esp. periorbitally) with lymphadenopathy**
Describe rash with DRESS
- Early morbilliform eruption (tiny, fine erythematous macules and papules) which may progress to generalized exfoliative dermatitis/erythroderma
- Mucous membranes can be involved
DRESS labs
- Eosinophilia
- atypical lymphocytosis
- elevated LFTs or renal fxn
- Can also cause pneumonitis and carditis
What are MC drugs to cause DRESS?
- anticonvulsants
- sulfonamides
Tx of hypersensitivity syndromes (i.e. DRESS)
- Identify the offending drug and D/C immediately**
- Some pt clear with just discontinuing the med
- Liver/renal involvement consider systemic steroids
- Often low dosage required for months
- Rash and hepatitis may persist for weeks after the drug is discontinued
Patient education regarding DRESS
- the individual must be aware their specific drug hypersensitivity and that other drugs of the same class can cross-react.
- these drugs must never be re-administered.
- patient should wear a medical alert bracelet.
List the conditions considered mucocutaneous blistering disease
- Erythema multiforme (EM)
- Stevens-Johnson Syndrome (SJS)
- Toxic Epidermal Necrolysis (TEN)
Define erythema multiforme (EM)
- Acute, self-limited, but sometimes recurrent immune-mediated mucocutaneous disease
- Separated into EM minor and EM major
What causes EM?
- 90% of cases of EM are caused by infections, with herpes simplex virus (HSV) the most common
- Can be drug-induced- barbituates, antibiotics (especially sulfa and penicillins), anticonvulsants, and NSAIDS
How does EM present?
- Abrupt onset of skin lesions.
- May or may not recall symptoms of an infection in the days to weeks prior to their outbreak
- Target lesion is classic but can be variable**
EM minor etiology
Self limited dz, young adults, sometimes recurrent, lasting 1-4 weeks
EM minor lesion presentation
- Lesions begin as sharply demarcated erythematous macules, becoming raised and edematous. Several cm in diameter
- Classic target/iris lesion- 3 zones
- Central dusky purpura (+/-bullous), elevated edematous pale ring, and surrounding macular erythema
- Lesions mainly to extremities, starting on dorsal hands and feet and moving toward torso.
- *Not usually symptomatic!
Are mucous membranes involved in EM minor?
Nope :)
Etiology of EM major
-Frequently accompanied by febrile prodrome, +/- arthralgia
EM major lesion presentation
Face and extremities - involves the trunk more than EM minor (papular,erythematous)
EM major
- Mucous membrane involvement is prominent***
- Involves oral mucosa but also genital and/or ocular mucosa
Tx of EM
- Treat the suspected infectious disease or to discontinue the causal drug
- Oral antihistamines and topical steroids for symptom relief
- Coexisting or recent HSV infection, early treatment with oral acyclovir (Zovirax)or suppressive tx for recurrent EM: refer to Derm if this doesn’t control
- Oral pain- topical “swish and spit” mixtures containing lidocaine, Benadryl
- Refer to ophthalmology with eye involvement
- Hospital admission for supportive care, particularly if severe oral involvement restricts drinking
Which conditions are considered bullous drug reactions?
Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)
Define bullous drug reaction
- Acute life-threatening mucocutaneous reactions characterized by extensive necrosis and detachment of the epidermis**
- Considered to be variants of the same disease spectrum differing in body surface area involved.
Epidermal detachment % in SJS
< 10%
Epidermal detachment % in SJS/TEN overlap
10-30%
Epidermal detachment % in TEN
> 30%
Cause of bullous drug reactions
- Idiopathic or drug reaction, drug reaction is primary
- Incidence of approximately 1 to 2 cases per 1 million, frequency higher in older and HIV
Drugs that cause SJS/TEN in adults
TMP-SMX, nevirapine, lamotrigine, carbamazepine, NSAIDS, allopurinolf
Drugs that cause SJS/TEN in children
sulfonamides and other antibx, antiepileptics, and acetaminophen
Onset of SJS/TEN
- Onset after med exposure from 3 wks to few days
- Prodrome of fever, influenza-like sxs 1-3 days prior to eruption
S/sx of SJS/TEN
Signs of mucosal irritation (dysphagia, dysuria, and conjunctivitis) are often present for several days before the onset of cutaneous lesions
Spread of lesions in SJS/TEN
- Skin lesions appear on face and trunk and rapidly spread – painful skin
- Lesions are macular erythema followed by desquamation or atypical target lesions with purpuric centers that form bullae, then slough
- Usually 2 or more mucosal surfaces involved, oral mucosa and conjunctiva most frequent
What is + Nikolsky sign?
- skin peels away with laterally applied pressure.
- indicates a separation of the upper epidermis from the lower epidermis
Presentation of SJS/TEN
- Sheet-like loss of skin**
- Erythema and painful erosions to mucous membranes: can be severe
Dx of SJS/TEN
- skin bx to confirm dx and r/o other mucocutaneous blistering dz
- preferred site is leading edge of intact blister
Tx of SJS/TEN
- Immediate discontinuation of offending med or d/c all unnecessary meds
- Management is similar to extensive burn- hemodynamic stabilization, caloric replacement, infection prophylaxis, aggressive skin, eye, and mucous membrane care
Mortality SJS/TEN
- Sepsis is major cause of death**
- Mortality rate is almost 10% with SJS, 30% for patients with SJS/TEN, almost 50% with TEN.
What is MC long term sequelae of SJS/TEN?
Referral to ophthalmology with eye involvement
