3) Drug Eruptions Flashcards
1
Q
Exanthematous (morbilliform) drug reactions
A
- 2% of individuals exposed to drugs
- Accounts for 95% of cutaneous reactions
- Highest rates associated with antibiotics
2
Q
Exanthematous (morbilliform) drug reactions mechanism
A
- Possibly a delayed type T-cell mediated immune reaction
- Genetic predisposition, underlying viral disease, and administration of multiple medications
3
Q
Exanthematous (morbilliform) drug reactions characteristics
A
- Erythematous maculopapular rash in trunk and proximal extremities
- Developing within 5-14 days
- May occur as early as 2-3 days in previously sensitized patients
4
Q
Exanthematous (morbilliform) drug reactions symptoms
A
- Pruritis (usually in legs or area of dependence)
- Low grade fever
- Mild eosinophilia
- Mucosal involvement is absent
5
Q
Exanthematous (morbilliform) drug reaction diagnosis
A
- Resolution in 7-14 days or with discontinuation of offending drug
- DDx includes viral & bacterial exanthems, systemic disease rashes, and cutaneous diseases
6
Q
Exanthematous (morbilliform) warning signs of more serious condition
A
- Erythroderma
- High fever
- Facial edema
- Mucositis
- Skin tenderness
- Blistering
7
Q
Exanthematous (morbilliform) drug reaction treatment
A
- Removal of offending drug
- Symptomatic relief with topical corticosteroids and oral antihistamines
- High potency topical corticosteroid applied once or twice daily for pruritic relief (or oral histamines until subsides)
8
Q
Exanthematous (morbilliform) drug reaction eliciting drugs
A
- Penicillin
- Cephalosporin
- Macrolides
- Quinolones
- Tuberculostatic
- Sulfonamides
- Anticonvulsants
- NSAIDs
- Paracetamol
- RTIs
9
Q
Acute generalized exanthematous pustulosis (AGEP)
A
- 1-5 per million, rare
- 90% of cases caused by drugs
- Most often antibiotics, antifungals, calcium channel blockers, and antimalarials
10
Q
Acute generalized exanthematous pustulosis (AGEP) mechanism
A
- Thought to be T-cell mediated neutrophilic inflammation involving drug specific CD4/8, cytokines, and chemokines
11
Q
Acute generalized exanthematous pustulosis (AGEP) characteristics
A
- Dozens to hundreds of nonfollicular, sterile pustules beginning on the face and extending to trunk and limbs
- May occur a few hours to days after drug has been introduced
- Median time for antibiotics was one day while others were 11 days
12
Q
Acute generalized exanthematous pustulosis (AGEP) signs/symptoms
A
- Dozens to hundreds of pinhead-sized pustules
- Fever > 38 ˚ C
- Leukocytosis w > 7,000 neutrophils
- Pustular smear negative for bacteria
13
Q
Acute generalized exanthematous pustulosis (AGEP) diagnosis
A
- Typical signs (one or more) presenting with an acute, febrile pustular eruption a few hours to days after starting a new drug
14
Q
Acute generalized exanthematous pustulosis (AGEP) DDx
A
- Generalized acute pustular psoriasis
- Stevens-Johnson syndrome/toxic epidermal necrolysis
- Sneddon-Wilkinson disease
- Bullous impetigo
15
Q
AGEP treatment
A
- Removal of offending drug, supportive cate, and symptomatic treatment
- Supportive care involves moist dressings and antiseptic solutions during pustular phase
- Symptomatic relief includes medium potency topical corticosteroids and oral antihistamines
16
Q
AGEP eliciting drugs
A
- Aminopenicillins
- Macrolides
- Quinolones
- Sulfonamides
- Hydroxychloroquine
- Terbinafine
- Diltiazem
17
Q
New onset urticaria
A
- Common (20% of population)
- Allergic reactions to medication, food, or insect bites/stings
- Common viral and bacterial infections
- Classified as acute (< 6 weeks) or chronic (> 6 weeks) –> 2/3 fall under acute classification
18
Q
New-onset urticaria mechanism
A
- Involves cutaneous mast cells in the superficial dermis which release histamine and vasodilatory mediators causing itching and localizing swelling
19
Q
New-onset urticaria lesions
A
- Intensely pruritic appearing as circumscribed, raised, erythematous plaques with central pallor
- Shape may be round, oval, or serpinginous ranging from < 1cm to several cm
- May enlarge and usually disappear within 24 hours
20
Q
New-onset urticaria characteristics
A
- Transient w/out residual affect
- Non painful, but pruritic lesions
- With or without angioedema
- May affect any area of the body
- Many associated triggers as seen in chart
- Infections are associated with over 80% of acute urticarial reactions in pediatric population
- Antibiotics are most frequently implicated in
- causing IgE-mediated urticaria (beta-lactams)
21
Q
New-onset urticaria diagnosis
A
- Clinical one based on your H&P as well as characteristic lesions
- Resolution of individual lesions from the eruption in about 24
hours - DDx includes atopic dermatitis, contact dermatitis, insect bites, bullous pemphigoid, or erythema multiforme minor, etc.
22
Q
New-onset urticaria must r/o anaphylaxis
A
- Generalized, rapid onset and evolution
- Related to an allergen which may resolve on its own or require respiratory and/or CV support along with emergency treatment
23
Q
New-onset urticaria treatment
A
- Initial treatment: short term relief of pruritus and angioedema if present
- Two-thirds of cases are self limiting and will resolve spontaneously
- Second generation H1 antihistamines are first line treatment drugs in mild cases
- If symptoms are moderate to severe, then addition of an H2 antihistamine is recommended
- Patients with prominent angioedema and persistent symptoms despite treatment with H1 & H2 antihistamines, then a glucocorticoid should be added in a short term dose (~5-7 days)
24
Q
Fixed drug eruption
A
- Seen in about 2-3% of population taking the drug
- Accounts for 14-22 percent of
cutaneous drug reactions - Most often implicated are the
antibacterial sulfonamides, antibiotics, NSAIDs, analgesics, and hypnotics
25
Q
Fixed drug eruption mechanism
A
- Believed to be due to intraepidermal CD8 T-
cell with an effector-memory phenotype - These have been found to be established in these type of lesions and remain quiescent until re-challenged
26
Q
Fixed drug eruption characteristics
A
- Well demarcated, round to oval, single (usually) or a small number of dusky red or violaceous macules that evolve into plaques
- Once resolved, leave post inflammatory hyperpigmentation
27
Q
Fixed drug eruption presentation
A
- Usually a solitary lesion
- Present 30 minutes to 8 hours after drug
administration - Resolve spontaneously in 7-10 days after discontinuation of offending drug
- Pustular smear negative for bacteria
28
Q
Fixed drug eruption diagnosis
A
- Clinical based on lesion morphology as well as detailed history that should include any new drugs in past hours to days
- Spontaneous resolution within 7-10 days after discontinuation of the offending drug
- DDx includes Stevens-Johnson Syndrome/toxic epidermal necrolysis, Erythema Multiforme, Bullous Pemphigoid, Large- Plaque Parapsoriasis, etc.
29
Q
Fixed drug eruption treatment
A
- Removal and avoidance of offending drug
- Symptomatic treatment for relief of pruritis includes medium to high potency topical corticosteroids and oral antihistamines
- Systemic or topical provocation test are helpful when identifying culprit drug when unclear or if multiple are suspected
30
Q
Fixed drug eruption eliciting drugs
A
- Penicillins
- Tetracyclines
- Quinolones
- Sulfonamides
- Dapsone
- NSAIDs/acetaminophen
- Barbiturates
- Antimalarials
31
Q
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
A
- Rare condition that is drug induced and potentially life threatening
- Characterized by a long latency period (2-8 wks)
- Most often antiepileptics and allopurinol, followed by
sulfonomides and vancomycin
32
Q
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
presentation
A
- Potentially life-threatening, drug-induced hypersensitivity reaction that includes skin eruption, hematologic abnormalities lymphadenopathy, and internal organ involvement
- Morbilliform eruption progressing into a diffuse, confluent, and infiltrated erythema with follicular accentuation
- Usually > 50% of body surface area and/or two or more of facial edema, infiltrative lesions, scaling, and purpura
33
Q
DRESS mechanism
A
- Likely involves a strong, drug specific immune response carried out by CD4/8
34
Q
DRESS presentation
A
- Begins usually in face and upper trunk
- Involves 50% or more of BSA
- Facial edema in 50% of cases
- Leukocytosis with eosinophils >
700/microL - Increased ALT
- Reactivation of HHV-6 and other viruses
- Patients have a > 90% of having at least one organ involved, while 50-60% will have two or more organs involved
- Exfoliative dermatitis in 20-30% of patients when BSA is > 90%
35
Q
DRESS diagnosis
A
- Suspected when a new drug was started 2-6 weeks and presents with a skin eruption as described, fever (38 to 40˚ C), facial edema, and enlarged lymph nodes
- Laboratory testing, skin biopsy, herpesvirus screening/testing, and imaging studies may aid in diagnosis
- DDx includes acute generalized exanthematous pustulosis, Stevens-Johnson Syndrome/toxic epidermal necrolysis, hypereosinophilic syndromes, acute cutaneous lupus erythematosus, etc.
36
Q
DRESS treatment
A
- ID/withdrawal of offending drug with supportive care
- Avoidance of new medication
- Most recover weeks to months after drug withdrawal
- Supportive care for severe cutaneous reactions may require hospitalization as well as fluids, electrolytes, and nutritional support for those with exfoliative dermatitis
- Absence of severe organ involvement: high potency topical corticosteroids
- Severe lung/kidney involvement: systemic corticosteroids
37
Q
DRESS prevention
A
- Strict avoidance of offending drug
- Increased risk w/ cross-reacting drugs that are chemically related (such as antiepileptics)
38
Q
DRESS eliciting drugs
A
- Antiepileptics
- Allopurinol
- Febuxostat
- Olanzapine
- Sulfonamides
- Dapsone
- Minocycline
- Vancomycin
39
Q
Drug induced pigmentation
A
- Diffuse cutaneous hyperpigmentation with a increased production of melanin and/or the deposition of drug complexes or metals in the dermis are responsible for the skin discoloration
- Usually resolves with discontinuation of offending agent (but may be prolonged months to years)
40
Q
Drug induced pigmentation variations
A
- Linear
- Reticulate
- Non patterns
41
Q
Pseudoporphyria
A
- Unknown incidence
- Most often caused by medications including NSAIDs, antibiotics, diuretics, and antineoplastic agents
- Protracted course
42
Q
Pseudoporphyria incidence
A
- Unknown
- Study reported 10% of children taking naproxen for juvenile idiopathic arthritis developed this condition
43
Q
Pseudoporphyria mechanism
A
- Unknown
- Considered photodynamic phototoxic drug reaction
- May occur a few hours to months after exposure to causative agent, but characteristically will persist for months to years
44
Q
Pseudoporphyria presentation
A
- Skin fragility, bullae, and vesicles in sun-exposed areas of the body
- Typically dorsum of hands, forearms, face, as well as lower legs and feet
- Normal porphyrin levels
45
Q
Pseudoporphyria histology
A
- Subepidermal blister with scant perivascular lymphocytic infiltrate
- IgG, IgM, C3, and fibrinogen at dermal-epidermal junction and in vessel walls on direct immunofluorescence
46
Q
Pseudoporphyria diagnosis
A
- Cutaneous manifestations as described above along with histological findings, normal porphyrin levels, potentially phototoxic medication use, or UVA exposure
- Resolution may take months to years after discontinuation of the drug
- One study of 16 patients resulted in six month resolution of five patients but persited an average of 2.5 years for the remaining 11
- DDx includes Porphyria cutanea tarda, Epidermolyisis bullous acquisita, Bullous pemphigoid, Pemphigus, etc.
47
Q
Pseudoporphyria treatment
A
- Removal of offending drug if any, and photoreception (including avoidance of tanning beds)
- Education and discuss expectations with regards to the protracted course of the condition
- Medications known to induce condition
48
Q
Erythema multiforme (EM)
A
- Uncommon, likely less than one percent
- Most frequent in young adults, 20-40 years of age, slight male predominance
- Most common cause is infection, usually herpes simplex virus (HSV)
- EM Minor refers to without mucosal disease, EM Major is with mucosal involvement
49
Q
Erythema multiforme incidence
A
- Unknown
- Available data is based on HSV-associated EM which thought to involve a cell-mediated immune response directed against viral antigens deposited in lesional skin
50
Q
Erythema multiforme hallmark
A
- Target lesions
- Begins as round erythematous papules evolving into classic target lesion which consists of a dusky central area or blister, a dark red inflammatory zone surrounded by pale ring of edema, and an erythematous halo at extreme periphery
51
Q
Erythema multiforme presentation
A
- Symmetric distribution of target lesions to the face, neck, palms, soles, and extensor surfaces of acral extremities
- Mucus membrane involvement with cutaneous lesions in
EM major - Severe cases may have elevated ESR, WBC, and liver enzymes
52
Q
Erythema multiforme diagnosis
A
- Based on the history of the eruption and clinical findings of the hallmark target lesions
- Skin biopsy may helpful to establish the diagnosis
- History of HSV infection should be questioned in all patients
- Less than 10% are associated with medication so HSV infection should be considered in all patients
- Appears over 3-5 days and resolves in about 2 weeks
- DDx includes Urticaria, Stevens-Johnson Syndrome, Fixed Drug Eruption, Pemphigoid, Rowell Syndrome, Cutaneous Small Vessel Vasculitis, etc.
53
Q
Erythema multiforme treatment
A
- Normally self limiting where treatment varies with severity and is targeted to reduce pain or pruritis if present
- Symptomatic relief includes medium potency topical corticosteroids and oral antihistamines with anesthetic mouthwash, while painful oral manifestations usually necessitate systemic glucocorticoids
- In the severe recurrent variant of EM associated with
HSV, continuous antiviral therapy is recommended
54
Q
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)
A
- Seen in about 2-7 cases per million, rare
- Leading trigger are
medications - Most often implicated are allopurinol, aromatic anticonvulsants, antibacterial
sulfonamides, and “oxicam”
NSAIDs
55
Q
SJS and TEN mechanism
A
- Incompletely understood
- Studies suggest that drug-specific CD8+ cytotoxic T cells, along with natural killer (NK) cells are thought to be the major inducers of keratinocyte apoptosis
56
Q
SJS and TEN presentation
A
- Fever exceeding 39˚C, and influenza-like symptoms precede by 1-3 days
- Exanthematous eruption is some, skin tenderness and/or blistering
- Cutaneous and mucosal lesions are usually ill-defined, coalescing erythematous macules with pruritic centers
- As progresses, lesions become vesicles and bullae and in a few days the skin begins to slough
57
Q
SJS and TEN signs and symptoms
A
- Prodrome with fever exceeding 39˚C
- Cutaneous and mucosal lesions (> 90%)
- Cases with < 10% of skin detachement are considered SJS, while those with 30% or more are considered TEN; 10-30% are overlap SJS/TEN
- Nikolsky sign
- Abnormal labs include anemia and lymphopenia
58
Q
SJS and TEN diagnosis
A
- There is no accepted universal diagnosis criteria
- Dx based on aforementioned clinical features as well as recent drug exposure
- Skin biopsy is useful for confirming the diagnosis
- Clinical course lasts 8-12 days while re-epithelialization may
begin after several days and typically requires 2-4 weeks - DDx includes generalized acute pustular psoriasis, generalized bullous fixed drug eruption, erythema multiforme, Staphylococcal scalded skin syndrome, etc.
59
Q
SJS and TEN treatment
A
- Mainstay of treatment of removal of offending drug, supportive care, wound care, pain control, and fluids and nutrition
- Supportive care is along the
main principles of burn injuries - Monitoring for superinfections because sepsis is a major cause of death
