Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Dermatology PPT 2 Cutaneous Drug Eruptions Lecture Notes
CUTANEOUS DRUG ERUPTIONS
Definition
An adverse cutaneous drug eruption is defined
as an undesirable cutaneous manifestation
resulting from the administration of a
particular drug and may result from its
overdose, predictable side effects or
unanticipated adverse manifestations.
Mechanism of drug reactions
A ? Immunological
Are not normal pharmacological effects of the
drug but are due to hypersensitivity following
previous exposure or chemically related
compound
Less predictable, can develop even with low
doses
Appear after a latent period req. for immune
reaction to develop
Hyper
Immune effector
Clinical
sensitivity
mechanisms
manifestations
Type 1:
IgE bound to mast cells or
Urticaria, asthma,
immediate/
basophils causes mast cell
anaphylaxis
anaphylactic degranulation, release of
histamine and other
mediators
Type 2:
Antigenic determinants on
Pemphigus
cytotoxic
cell surfaces are targets for
haemolytic
IgG /IgM. Damage cells by
anaemia,
cytotoxic killing
neutropenia,
thrombocytopenia
Hyper
Immune effector
Clinical
sensitivity
mechanisms
manifestations
Type 3:
Circulating immune Vasculitis ?
immune
complexes deposited hypersensitivity
complex
on tissue surfaces.
vasculitis, Henoch?
Complement
Schonlein purpura
iactivated,
neutrophils attracted
damage tissues
Type 4:
Effector T
delayed
lymphocytes (CD4+
type, Tcell
or CD8+), produce
mediated
cytokines
and/or cytotoxic
factors
Type 4
Immune
Inflammation
Clinical pattern
subcategory mediators
characterized by:
4a
Th1/Tc1 cel s:
T cel s,
Contact dermatitis,
IFN, TNF
macrophages
tuberculin reaction
4b
Th2 cel s:
Eosinophils
Maculopapular rash,
IL4/13,
exanthemata with
IL5
eosinophilia
4c
Cytotoxic T/NK/
T cel s
Contact dermatitis,
NKT cel s:
Keratinocyte
maculopapular
granulysin,
apoptosis
rash, druginduced
perforin,
exanthemata,
granzyme B
bul ous eruptions
(SJS/TEN)
4d
T cel s: IL8,
Neutrophils
Acute generalized
CXCL8,
exanthematous
GMCSF
pustulosis
Mechanism of drug reactions
B ? Non immunological
Usually predictable
Affects all patients who take adequate amount
Large amount of drug usually req. to initiate reaction
May develop with first dose (no latent period req.)
Mechanism of drug reactions
Predictable
Side effects
Drug interactions
Over dose
Facultative effect
Cumulative effect-
Exacerbation of pre-
defective metabolism
existing skin
or excretion
conditions
Delayed toxicity
Teratogenacity
Mutagenicity
Mechanism of drug reactions
B- Non immunological
Unpredictable
Idiosyncratic reactions
Intolerance
Mechanism of drug reactions
Special reactions
Jarisch ? Herxheimer reaction
Syphillitic patients treated with penicillin
develop exacerbation of existing lesions
Infectious mononucleous ? ampicillin reaction
patients with IM when treated with ampicillin
develop an exanthematous rash
Pattern of drug reactions
EXANTHEMATOUS ERUPTIONS
Symmetrical maculo-papular to papulo-squamous rash ;
? itchy
Begin 1-2 wks of starting; subside in 1-2 wks of
withdrawing the drug
Immunological reaction 4b
EXANTHEMATOUS DRUG ERUPTIONS
Penicillin &
Ampicillin,
Sulfonamides
Phenytoin,
Carbamazepine
Allopurinol
Nsaids
Nevarapine
Viral rash
Exanthematous drug
eruption
Itching less
Pattern ? monomorphic
Itching - often severe
with a pattern of evolution
Pattern - polymorphic
Begin ? face, acral sites then No pattern of evolution
spread to trunk
Begin ? trunk
Systemic symptoms: sore
Course - May progress if
throat, cough, GIT, fever
drug continued
Asso. enanthem
Course ? usually self limiting
URTICARIA AND ANGIOEDEMA via
1. Direct degranulation of mast cel s ? aspirin,
indomethacin
2. Interfering with arachadonic acid metabolism
Morphine, codeine, sulfonamides, curare,
radioactive contrasts
3. Ig ?E mediated degranulation of mast cel s
Penicil in
4. Complement mediated mast cel degranulation
Blood products
DRUG INDUCED URTICARIA
Common drugs
Aspirin
NSAIDs
Type I hypersensitivity
DRUG INDUCED ANGIO-EDEMA
ANAPHYLAXIS
Common with parenteral administration than oral
ingestion .
Eg.Penicillin, Cephalosporins, NSAIDS,
Thiopental, Neuromascular Blocking Agents,
Opiods, Blood Transfusion (Pre, Intra-op)
Vaccines, Toxoids, Lignocaine, Dextran,
Radiocontrasts
ERYTHRODERMA
generalized scaling and erythema associated with
pruritus.
malaise, hypothermia or fever,
lymphadenopathy,
Organomegaly, highoutput cardiac failure
resolve in 2-6 wks after stopping
Carbamazepine,Phenytoin
Omeprazole, Lansoprazole
Phenobarbital
Calciumchannel blockers
Allopurinol
Lithium
Cotrimoxazole,
Chlorpromazine
Penicillins
Imatinib
Cephalosporins,
Interferon
Heavy met
Vancomycin
als
ATT
ART
NSAIDS
Acitretin
DRUG INDUCED ERYTHRODERMA
Stevens-Johnson syndrome ? Toxic
Epidermal Necrolysis(SJS-TEN) complex
Acute life threatening muco-cutaneous reactions
characterized by extensive necrosis and
detachment of epidermis and mucosa
SJS - <10% BSA
SJS- TEN overlap ? (10%-30%)
TEN - >30%
SJS-TEN complex
H/o drugs 1-3 wks prior
most recently added drug probable suspect
Prodrome ? fever, headache, rhinitis, myalgia
Odynophagia, burning / stinging eyes
Initial lesion ? localized targetoid/ diffuse dusky
erythema with crinkled surface, progressively
coalesce. Start from face down to generalization
SJS-TEN complex
Confluence of lesion extensive diffuse erythema,
flaccid blisters develop
Nikolsky's sign ? lateral pressure over necrotic
skin leads to epidermal detachment
Eventually large areas of erosions develop
Mucosa ? oral(100%), eyes(90%), genital(50%)
Complications ? sepsis, electrolyte imbalance,
multiorgan failure, death
SJS-TEN complex
Antibiotics ? sulfonamides, quinolones, ampicillin
and cephalosporins
Anticonvulsants ? barbiturates, phenytoin,
carbamazepine, valproic acid, lamotrigine
ATT
NSAIDS ? nimesulide, salicylates, ibuprofen,
oxicams
Cyclophosphamide, allopurinol, nevarapine
SJS-TEN complex
SCORTEN (SCORe of Toxic Epidermal
Necrolysis)
Age greater than 40 years
Presence of malignancy
Heart rate >120 beats/min
Epidermal detachment >10%
of BSA at admission
Serum urea >10 mmol/L
Serum glucose >14 mmol/L
Bicarbonate level <20 mmol/L
vone point is attributed each of the parameters
vincreasing scores predicting higher mortality rates
Investigations
Blood C/S, Skin C/S
CBC,ESR
Coagulation studies
Urea and electrolytes
Mycoplasma serology
Amylase
Antinuclear antibody
Bicarbonate
and extractable
Glucose
nuclear antigen
LFT
Complement
Indirect
Creactive protein
immunofluorescence
CXR
Drug Rash with Eosinophilia and Systemic
Sy
-
mptoms (DRESS)syndrome/ DHS
starts 3 weeks after starting
Drug Rash with facial edema
Eosinophilia, atypical lymphocytes,
mononucleosis
Systemic sympyoms ? hepatitis, nephritis,
pneumonitis, myocarditis, encephalitis,
hypothyroidism
Lymphadenopathy ? at least 2 diff. sites
Fever
Al opurinol
Carbamazepine, Phenytoin, Lamotrigine
Vancomycin, Amoxicil in, Minocycline,
Piperacil in, Tazobactam
Sulphasalazine, Dapsone, Sulphadiazine
Furosemide
Omeprazole
Ibuprofen
Investigation
Hepatic - LFT, LDH, Ferritin,Coagulation screen ,Hepatitis B, C,
EBV, CMV, HHV6, HHV7 titres
Cardiac-ECG, Echo,Cardiac enzymes (creatine kinase, troponin)
Pulmonary- CXR, PFTs
Autoimmune ?ANA,Complement, ANCA
Renal ?Urea,creatinine,Calcium,Urinalysis,Renal ultrasound
Neurological -Microscopy, C/S CSF, CT/MRI head, EEG
Endocrine- Thyroid function test, Blood glucose
Infection- Blood cultures, Mycoplasma serology,PCR for HSV
Gastrointestinal ?Amylase,Lipase,Triglycerides,Colonoscopy
DRESS/DHS
ACUTE GENERALIZED EXATHEMATOUS
PUSTULOSIS
rapid appearance of sheets of nonfollicular
sterile pustules
1st in flexures (neck, axil ae, inframammary,
inguinal folds) generalize
Start within 1 day of drug, last 1-2 wks after
stopping then subside with scaling
Mild fever, malaise, neutrophilia,
Transient hepatic, renal and pulmonary
dysfunction
ACUTE GENERALIZED EXATHEMATOUS
PUSTULOSIS
Aminopenicillins
Quinolones
Chloroquine and
hydroxychloroquine
Sulphonamides
Terbinafine
Diltiazem
FIXED DRUG ERUPTIONS
recurrent welldefined lesions occurring in the
same sites each time the offending drug is taken
well defined circular, deeply erythematous plaque,
sometimes with central bullae; subside with slate grey
hyperpigmentation
sites- lips, glans, palms & soles: limbs, trunk
Type IV hypersensitivity
NSAIDS(lips genitals)
Sulphasalazine
Paracetamol
Calciumchannel
Cotrimoxazole &
blockers
Tetracyclines (genitals)
ACE inhibitors
Penicil ins
Omeprazole
Metronidazole
Iodinated contrast
Rifampicin
Azoles systemic
Erythromycin
Complementary
Pseudoephedrine
medicines
Barbiturates
Food, e.g. cashew
Carbamazepine
nuts, asparagus
FIXED DRUG ERUPTIONS
ERYTHEMA NODOSUM
A septal panniculitis induced by a medication
Symmetrical, erythematous, tender, subcutaneous
nodules or plaques
Typical y over the anterior aspect of the limbs.
Later become purplish before final y turning brown
Oral contraceptives
Barbiturates
Hormonal
replacement therapy
Isotretinoin
Sulphonamides
Montelukast
Penicil in
Vaccinations
(hepatitis, HPV,
Azathioprin
rabies)
Minocycline
GcSF
Ciprofloxacin
Complementary
NSAIDs
medications
Gold
Benzodiazepines
ERYTHEMA MULTIFORME
acute self limiting lesion characterized by IRIS or
TARGETOID lesions
IRIS lesion - <3 cm, rounded lesion with 3 zones
central ? dusky erythema or purpura
middle ? pale edema
outer - erythema with well defined margin
Sulphonamides,
Penicillin,
Sites - face, extremities,
Quinolones,
oral, genital mucosa,
Tetracyclins,
trunk
Rifampicin,
Anticonvulsants,
NSAIDS,
Thiazides,
Nevarapin
ERYTHEMA MULTIFORME
DRUG INDUCED PRURITUS
Primary, via neuronal/central nervous system interaction.
Secondary pruritus
(i) direct skin effects, e.g. induction of drug rash, xerosis;
(i ) alteration of biochemical profiles (e.g. renal or hepatic
dysfunction);
(i i) other unexplained mechanisms
Opioids
Statins
Paclitaxel
Antimalarials
Granulocyte?macrophage colonystimulating factor
Interleukin2
Angiotensinconverting enzyme inhibitors
Sulphonylurea derivates
Nonsteroidal antiinflammatory drugs
Hydroxyethyl starch (HES)
DRUG INDUCED
PHOTOSENSITIVITY
Itchy, erythematous papules, plaques on exposed
areas;
H/O photosensitivity
drugs - quinolones, tetracyclins, sulphonamides,
griseofulvin, phenothiazine, psoralens, ampicillin,
amiodarone
AMIODARONE INDUCED
PHOTOSENSITIVITY
VASCULITIS
urticarial vasculitis, palpable purpura, nodular
vasculitis, necrotic ulcers
drugs ? aspirin, indomethacin, phenylbutazone
sulphonamides, tetracyclin, ampicillin,
erythromycin,diuretics, phenytoin, methatrexate
LICHENOID ERUPTIONS
Lichen planus like eruption, mostly trunk
Generalized, eruptive, with prominent
eczematous and scaling component
Mucosa, nail involvement infrequent
LICHENOID DRUG ERUPTIONS
Gold, Antimalarials,
Mercury Amalgam,
Thiazides,
NSAIDS,
Penicillamine
Isoniazid,
Tetracyclin,
Dapsone,
Beta Blockers
Captopril
ACNEIFORM ERUPTIONS
Extensive papulopustular monomorphic
eruptions; absence of comedones
Suspected : sudden, abrupt onset in the absence
of past history of acne
Trunk>face
Any age
Corticosteroids
Dactinomycin
Androgens and anabolic
Thiourea, thiouracil
steroids
Epidermal growth factor
Hormonal contraceptives
receptors inhibitors
Danazol
Imatinib
Tricyclic antidepressants, Iodine,Bromine,Chlorine
Lithium,Valproate,Phenytoin Isoniazid, Rifampicin
Vitamins B1, B6,
Ethionamide
Ciclosporin,Sirolimus
Azathioprine
DRUG INDUCED PIGMENTATION
Via - melanin synthesis ? psoralens
Cutaneous deposition of drug/metabolite ?
minocyclin, heavy metals, clofazimine
Hormonal effect ? OCP causing melasma
Post inflammatory hyperpigmentation
other drugs ?bleomycin, cyclophosphamide,
methotrexate, hydroxyurea, 5- fluorouracil
MINOCYCLIN INDUCED PIGMENTATION
CLOFAZIMINE INDUCED
PIGMENTATION
ALOPECIA
Retinoids, cytotoxics, anticougulants, anti thyroids, danazol,
OCP
HYPERTRICOSIS
PUVA, phenytoin, minoxidil, penicillamine, cys A
HIRSUITISM
Oral steroids, anabolic steroids, OCP
ALOPECIA HYPERTRICOSIS
Management of drug reactions
WITHDRAW and replace with chemical y
unrelated alternatives
Mild/moderate cases
1. antihistamines,
2.local bland emollients,
3.Topical steroids
Severe cases ?
ANAPHYLAXIS -
inj adrenaline (1:1000), 0.3- 0.5ml s.c/ i.m.
inj chlorpheramine maleate (10-20mg), i.v.
inj hydrocortisone 100mg i.v.
observation for at least 6 hrs after stabilization
SJS-TEN Complex
IVF replacement,
Oral liquid diet,
Nasogastric tube,
Total parenteral nutrition
Denuded skin ? dressing
Antacids/ H2 blockers
pethidine/ tramadol,
Emperical broad spectrum antibiotics
Eye care ? 2 hr NS/antibiotics, break synechia
SPECIFIC ? steroids,
IV Ig,
cyclosporin,
cycloposphamide,
thaladomide,
plasmapheresis
THE END
This post was last modified on 07 April 2022