| How is immunological pathogenesis of cutaneous drug reactionss? | • Type I: IgE dependent: urticaria, angioedema,
anaphylaxis. Ex: insulin
• Type II: cytotoxic reactions: hemolysis, purpura.
Ex: peni, cerebral, sulfa drugs, rifampicin
• Type III: IC: Vasculitis, serum sickness, urticaria
Ex: quinine, chlorpromazine, salicylates,
sulfonamides
• Type IV: Delayed HS: eczema, rash, photoallergy. Ex: topical (neomycin, ketoprofen) |
| How are cutaneous drug reactions? | • It is always careful to consider drugs as a cause of a
rash
• Most cutaneous drug reactions are inflammatory,
generalized and symmetric
• Diagnosis is established by their clinical features,
including morphology and timing
• Histology (skin biopsy) can be helpful
• Document the drug reaction in the patient's chart
with the medication and description of the reaction |
| What are most common drug reactions? | • Exanthematous drug reaction
• Fixed drug eruption
• Urticaria
• Photosensitive drug reaction
• Drug related eosinophilia with systemic
syndrome (DRESS)
• Epidermal necrolysis: Stevens-Johnson
syndrome (SJS) and toxic epidermal necrolysis
(TEN) |
| What are benign drug reactions? | • Rash
• Urticaria
• Photosensitivity
• Fixed drug eruption |
| What are immediate vs delayed reactions? | • Classification of drug induced cutaneous reaction
according to timing:
• Immediate reactions: occur less than 1h of the
last administered dose: urticaria, angioedema,
anaphylaxis
• Delayed reactions: occur more than 1h but
usually more than 6h and occasionally weeks to
months after the start of administration:
Exanthematous eruption, FDE, SJS, TEN, vasculitis |
| How is non-immunological pathogenesis of cutaneous drug reactions? | • Dose: nasal spray containing silver nitrate.
anticoagulants and purpura
• Secondary side effects: cyclophosphamide and
alopecia
• Direct effect on mast cells: aspirin, NSAIDs,
Phototoxicity |
| What are roles of allergy in drug reactions? | • Allergy testing are limited value in evaluating
adverse cutaneous reactions to medications
• Penicillin is the exception to this rule: pencillin
skin testing is the preferred method to
evaluate a possible type I - IgE mediated
penicillin allergy (urticaria due to peni)
• This test also includes the major and minor
determinant mixes (metabolites of peni) |
| How is a complete drug hx done? | The seven I's
• Instilled (eye drops, ear drops)
• Inhaled (steroids, β adrenergic)
• Ingested (capsules, tablets, syrups)
• Inserted (suppositories)
• Injected (IM, IV)
• Incognito (herbs, homeopathic, vitamins, nontraditional medicine, OTC)
• Intermittent (medications not mentionned) |
| What are risk factors of drug reactions? | • Female
• Prior history of drug reaction
• Recurrent drug exposure: repeated courses of drug therapy with the
same drugs are associated with higher rates of adverse drug
reactions
• HLA-B type: 1502 (carbamazepine and SJS/TEN)
5701 (abacavir and Dress), 5801 (allopurinol and SJS/TEN)
• Reactions to aminopenicillin in EBV infection
• HIV+ patients have high rate of dermatologic skin reactions to drug as
to sulfones and other drugs |
| How is drug timeline reaction? | • Timing of drug initiation with relation to the rash
onset
• Preparing a drug timeline could be helpful in this
process
• Start with the onset of the rash at Day 0 then
work backwards and forwards
• For the exanthematous drug eruption the
initiation of the medication is often 7 to 10 days
before first onset and shorter (24-48h) for repeat
exposures |
| What are exanthematous drug eruptions? | • The most common of all cutaneous drug
eruptions (90%)
• Limited to the skin (no mucous lesions)
• Erythematous macules and papules appear on
the trunk and spread centrifugally to the
extremities with a symmetric fashion
• Pruritus and mild fever may be present
• Rash appears 7 to 10 days after drug initiation
if it is the first episode, 24 to 48h after repeat
drug initiation |
| How is clinical course and tx of exanthematous drug reactions? | • Resolves in a few days to a week after the
medication is stopped
• May continue the medication safely if the
eruption is not too severe and the medication
cannot be substituted
• Resolves without sequelae (scaling,
desquamation)
• Treatment: topical steroids, oral
antihistamines and reassurance |
| What are fixed drug eruptions? | • FDE is characterized by the formation of one
or more round or oval patches or plaques that
will recur at the same site (fixed) with reexposure to the drug
• Common drug culprits include: tetracyclines,
metronidazole, phenolphtaleine, sulfonamide,
barbituriques, NSAID's, salicylate, food
coloring (yellow) |
| How is FDE tx? | • Lesions will resolve days to weeks after the
drug is discontinued
• Postinflammatory hyperpigmentation (PIH)
may persist beyond this time frame
• Non-eroded FDE can be treated with a potent
topical corticosteroid ointment
• Eroded cutaneous FDE can be treated with a
protective antibacterial ointment and a
dressing untill the skin reepithelialisation
• Adress pain especially for mucosal lesions |
| What is urticaria? | • Lesions will resolve days to weeks after the
drug is discontinued
• Postinflammatory hyperpigmentation (PIH)
may persist beyond this time frame
• Non-eroded FDE can be treated with a potent
topical corticosteroid ointment
• Eroded cutaneous FDE can be treated with a
protective antibacterial ointment and a dressing untill the skin reepithelialisation
• Adress pain especially for mucosal lesions |
| What is photosensitivity? | • History: occurred a few hours after sun exposure.
• Location on the uncovered areas
• Photoallergy: eczema patient areas, sometimes
extension on the covered areas and minimal exposures
(very down DEM) actuation
• Phototoxicity: doses of medication and dependent
UVA: Actinic Erythema, bubbles, Onycholysis
• Endogenous: metabolic (Porphyria), lupus, idiopathic
(Burns)
• Contact: plants, perfumes, topical medications... |
| How is natural hx of photosensitivity? | Occurs few hours after sunexposure.
Located on sunexposed areas
Photoallergy: eczema of suexposed areas with spreading on covered areas, induced by minimal sunexposure (MED very low)
Phototoxicity: doses of drugs UVA dependent: actinic erythema, blisters..
Systemic : metabolic (porphyrias), lupus, polymorphous light eruption. |
| What is drug-induced HS syndrome? | • Syn. Drug related eosinophilia with systemic
syndrome (DRESS)
• Skin eruption with systemic symptoms and internal
organ involvement (heart, kidney, liver)
• Typical signs and symptoms: exanthem,
erythematous centrofacial swelling, fever, malaise,
lymphadenopathy, ad involvement of other organs
(liver, kidneys)
• >70% have eosinophilia
• Liver function tests (LFTs) abnormalities and/or
hepatosplenomegaly are helpful diagnostic clues |
| How is clinical course of DIHS? | • Signs and symptoms start at the 3rd week (1
to 12 weeks) after starting the medication or
after increasing the dose
• They may persist and recur for many weeks
even after cessation of drug treatment
• Fatality rate may be up to 10% |
| How is DIHS tx? | • Stop suspect medication (s)
• If not severe: topical steroids and systemic
antihistamines, and continue to follow lab
values
• If severe: systemic steroids (prednisone
1mg/kg/day) and taper very gradually over
weeks to months as syndrome can recur as
the dose reduces
• Severely ill patients may need to be hospilized
in an ICU setting |
| What is steven-johnson's syndrome/ toxic epidermal necolysis? | • SJS and TEN are acute life-threatening mucocutaneous
reactions
• Characterized by extensive necrosis and detachment of the epidermis and mucosal surfaces
• They represent similar processes but differ in severity based on body surface area (BSA) that is involved
• SJS/TEN is a dermatologic emergency
• Mortality rate varies from 5-12%, and >20% for TEN
• Old age, significant comorbid conditions, and
greater extent of skin involvement correlate with poor prognosis |
| What are drugs causing SJS/TEN? | • Over 100 different drugs have been associated
with SJS/TEN. The most high risk are: SATAN
• Sulfa ATB, sulfasalazine
• Allopurinol
• Tetracyclines, thiacetazone
• Anticonvulsivants (carbamazepine,
lamotrigine, phenobarbital, phenytoin)
• NSAID's
• Nevirapine |
| How is clinical presentation of SJS? | • Onset wihin 8 weeks after drug initiation
• Fever, headache, rhinitis, and myalgias may
precede mucocutaneous lesions by 1-3 days
• Eruption is initially symmetric and distributed
on the face, upper trunk, and proximal
extremities
• Pain is a prominent symptom due to necrosis
• Lesions may extend rapidly to the rest of the
body |
| How is hx of SJS lesions? | • Initial skin lesions are erythematous, irregulary
shaped, dusky red to purpuric macules (atypical
targets), which progressively coalesce
• Dark center of atypical target lesions may blister
evolving to flaccid blisters
• The necrotic epidermis is easily detached at
pressure points or by frictional trauma
• Patients are classified into 3 groups depending on
the BSA: SJS<10% SJS/TEN 10-30% SJS/TEN>30% |
| How is mucus membrane involvement in SJS? | • Can precede skin eruption
• Begins with erythema followed by painful erosions of the oral, ocular, and genital mucosa
• A significant percentage of patients with
ocular involvement will suffer permanent ocular sequelae, even blindness |
| What are SJS complications? | • Corneal damage
• Oral cavity
• GU damage (adhesions, urethral/introital
erosions)
• Pulmonary damage (bronchitis, bronchiectasis)
• Fluid and electrolyte disturbances
• Nutrition requirements
• Secondary infection (bacteremia, sepsis) |
| How is SJS tx? | • Early recognition and withdrawal of the offending
and supportive care
• In case of doubt, all non-life-sustaining drugs
should be stopped
• Care should be proceed in a burn unit for patients
with significant BSA involvement
• Multidisciplinary approach
• Specific therapies: IV Ig, Cyclosporine, etanercept
according to the stage of the disease and the centers experience |
