Download MBBS Dermatology PPT 2 Cutaneous Drug Eruptions Lecture Notes

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as an undesirable cutaneous manifestation

resulting from the administration of a

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particular drug and may result from its

overdose, predictable side effects or

unanticipated adverse manifestations.

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Mechanism of drug reactions
A ? Immunological
Are not normal pharmacological effects of the

drug but are due to hypersensitivity following

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previous exposure or chemically related

compound

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Less predictable, can develop even with low

doses

Appear after a latent period req. for immune

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reaction to develop

Hyper

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Immune effector

Clinical

sensitivity

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mechanisms

manifestations

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Type 1:

IgE bound to mast cells or

Urticaria, asthma,

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immediate/

basophils causes mast cell

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anaphylaxis

anaphylactic degranulation, release of

histamine and other

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mediators

Type 2:

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Antigenic determinants on

Pemphigus

cytotoxic

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cell surfaces are targets for

haemolytic

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IgG /IgM. Damage cells by

anaemia,

cytotoxic killing

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neutropenia,

thrombocytopenia
Hyper

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Immune effector

Clinical

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sensitivity

mechanisms

manifestations

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Type 3:

Circulating immune Vasculitis ?

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immune

complexes deposited hypersensitivity

complex

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on tissue surfaces.

vasculitis, Henoch?

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Complement

Schonlein purpura

iactivated,

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neutrophils attracted

damage tissues

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Type 4:

Effector T

delayed

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lymphocytes (CD4+

type, Tcell

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or CD8+), produce

mediated

cytokines

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and/or cytotoxic

factors

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Type 4

Immune

Inflammation

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Clinical pattern

subcategory mediators

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characterized by:

4a

Th1/Tc1 cel s:

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T cel s,

Contact dermatitis,

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IFN, TNF

macrophages

tuberculin reaction

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4b

Th2 cel s:

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Eosinophils

Maculopapular rash,

IL4/13,

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exanthemata with

IL5

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eosinophilia

4c

Cytotoxic T/NK/

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T cel s

Contact dermatitis,

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NKT cel s:

Keratinocyte

maculopapular

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granulysin,

apoptosis

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rash, druginduced

perforin,

exanthemata,

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granzyme B

bul ous eruptions

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(SJS/TEN)

4d

T cel s: IL8,

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Neutrophils

Acute generalized

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CXCL8,

exanthematous

GMCSF

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pustulosis
Mechanism of drug reactions

B ? Non immunological

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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.)

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Mechanism of drug reactions
Predictable
Side effects

Drug interactions

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Over dose

Facultative effect

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Cumulative effect-

Exacerbation of pre-

defective metabolism

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existing skin

or excretion

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conditions

Delayed toxicity

Teratogenacity

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Mutagenicity
Mechanism of drug reactions
B- Non immunological
Unpredictable
Idiosyncratic reactions

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Intolerance

Mechanism of drug reactions
Special reactions
Jarisch ? Herxheimer reaction

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Syphillitic patients treated with penicillin

develop exacerbation of existing lesions

Infectious mononucleous ? ampicillin reaction

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patients with IM when treated with ampicillin

develop an exanthematous rash
Pattern of drug reactions

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EXANTHEMATOUS ERUPTIONS

Symmetrical maculo-papular to papulo-squamous rash ;

? itchy

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Begin 1-2 wks of starting; subside in 1-2 wks of

withdrawing the drug

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Immunological reaction 4b


EXANTHEMATOUS DRUG ERUPTIONS

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Penicillin &

Ampicillin,

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Sulfonamides
Phenytoin,

Carbamazepine

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Allopurinol
Nsaids
Nevarapine

Viral rash

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Exanthematous drug

eruption

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Itching less
Pattern ? monomorphic

Itching - often severe

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with a pattern of evolution

Pattern - polymorphic

Begin ? face, acral sites then No pattern of evolution

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spread to trunk

Begin ? trunk

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Systemic symptoms: sore

Course - May progress if

throat, cough, GIT, fever

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drug continued

Asso. enanthem
Course ? usually self limiting

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URTICARIA AND ANGIOEDEMA via

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1. Direct degranulation of mast cel s ? aspirin,

indomethacin

2. Interfering with arachadonic acid metabolism

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Morphine, codeine, sulfonamides, curare,

radioactive contrasts

3. Ig ?E mediated degranulation of mast cel s

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Penicil in
4. Complement mediated mast cel degranulation
Blood products

DRUG INDUCED URTICARIA

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Common drugs
Aspirin
NSAIDs
Type I hypersensitivity

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DRUG INDUCED ANGIO-EDEMA

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ANAPHYLAXIS
Common with parenteral administration than oral

ingestion .

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Eg.Penicillin, Cephalosporins, NSAIDS,
Thiopental, Neuromascular Blocking Agents,

Opiods, Blood Transfusion (Pre, Intra-op)

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Vaccines, Toxoids, Lignocaine, Dextran,

Radiocontrasts
ERYTHRODERMA

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generalized scaling and erythema associated with

pruritus.

malaise, hypothermia or fever,

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lymphadenopathy,

Organomegaly, highoutput cardiac failure

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resolve in 2-6 wks after stopping

Carbamazepine,Phenytoin

Omeprazole, Lansoprazole

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Phenobarbital

Calciumchannel blockers

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Allopurinol

Lithium

Cotrimoxazole,

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Chlorpromazine

Penicillins

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Imatinib

Cephalosporins,

Interferon

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Heavy met

Vancomycin

als

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ATT
ART
NSAIDS
Acitretin

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DRUG INDUCED ERYTHRODERMA

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Stevens-Johnson syndrome ? Toxic
Epidermal Necrolysis(SJS-TEN) complex
Acute life threatening muco-cutaneous reactions

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characterized by extensive necrosis and

detachment of epidermis and mucosa

SJS - <10% BSA

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SJS- TEN overlap ? (10%-30%)
TEN - >30%
SJS-TEN complex
H/o drugs 1-3 wks prior
most recently added drug probable suspect

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Prodrome ? fever, headache, rhinitis, myalgia
Odynophagia, burning / stinging eyes
Initial lesion ? localized targetoid/ diffuse dusky

erythema with crinkled surface, progressively

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coalesce. Start from face down to generalization

SJS-TEN complex
Confluence of lesion extensive diffuse erythema,

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flaccid blisters develop

Nikolsky's sign ? lateral pressure over necrotic

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skin leads to epidermal detachment

Eventually large areas of erosions develop
Mucosa ? oral(100%), eyes(90%), genital(50%)
Complications ? sepsis, electrolyte imbalance,

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multiorgan failure, death


SJS-TEN complex

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Antibiotics ? sulfonamides, quinolones, ampicillin

and cephalosporins

Anticonvulsants ? barbiturates, phenytoin,

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carbamazepine, valproic acid, lamotrigine

ATT
NSAIDS ? nimesulide, salicylates, ibuprofen,

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oxicams

Cyclophosphamide, allopurinol, nevarapine

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SJS-TEN complex

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SCORTEN (SCORe of Toxic Epidermal

Necrolysis)

Age greater than 40 years

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Presence of malignancy
Heart rate >120 beats/min
Epidermal detachment >10%

of BSA at admission

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Serum urea >10 mmol/L
Serum glucose >14 mmol/L
Bicarbonate level <20 mmol/L

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vone point is attributed each of the parameters
vincreasing scores predicting higher mortality rates
Investigations

Blood C/S, Skin C/S

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CBC,ESR

Coagulation studies

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Urea and electrolytes

Mycoplasma serology

Amylase

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Antinuclear antibody

Bicarbonate

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and extractable

Glucose

nuclear antigen

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LFT

Complement
Indirect

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Creactive protein

immunofluorescence

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CXR

Drug Rash with Eosinophilia and Systemic

Sy

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-

mptoms (DRESS)syndrome/ DHS

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starts 3 weeks after starting
Drug Rash with facial edema
Eosinophilia, atypical lymphocytes,

mononucleosis

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Systemic sympyoms ? hepatitis, nephritis,

pneumonitis, myocarditis, encephalitis,

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hypothyroidism

Lymphadenopathy ? at least 2 diff. sites
Fever

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Al opurinol
Carbamazepine, Phenytoin, Lamotrigine
Vancomycin, Amoxicil in, Minocycline,

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Piperacil in, Tazobactam

Sulphasalazine, Dapsone, Sulphadiazine
Furosemide
Omeprazole

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Ibuprofen

Investigation

Hepatic - LFT, LDH, Ferritin,Coagulation screen ,Hepatitis B, C,

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EBV, CMV, HHV6, HHV7 titres

Cardiac-ECG, Echo,Cardiac enzymes (creatine kinase, troponin)
Pulmonary- CXR, PFTs

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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

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Gastrointestinal ?Amylase,Lipase,Triglycerides,Colonoscopy


DRESS/DHS

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ACUTE GENERALIZED EXATHEMATOUS

PUSTULOSIS

rapid appearance of sheets of nonfollicular

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sterile pustules

1st in flexures (neck, axil ae, inframammary,

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inguinal folds) generalize

Start within 1 day of drug, last 1-2 wks after

stopping then subside with scaling

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Mild fever, malaise, neutrophilia,
Transient hepatic, renal and pulmonary

dysfunction

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ACUTE GENERALIZED EXATHEMATOUS

PUSTULOSIS

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Aminopenicillins
Quinolones
Chloroquine and

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hydroxychloroquine

Sulphonamides
Terbinafine
Diltiazem

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FIXED DRUG ERUPTIONS
recurrent welldefined lesions occurring in the
same sites each time the offending drug is taken
well defined circular, deeply erythematous plaque,

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sometimes with central bullae; subside with slate grey

hyperpigmentation

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sites- lips, glans, palms & soles: limbs, trunk
Type IV hypersensitivity


NSAIDS(lips genitals)

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Sulphasalazine

Paracetamol

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Calciumchannel

Cotrimoxazole &

blockers

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Tetracyclines (genitals)

ACE inhibitors

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Penicil ins

Omeprazole

Metronidazole

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Iodinated contrast

Rifampicin

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Azoles systemic

Erythromycin

Complementary

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Pseudoephedrine

medicines

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Barbiturates

Food, e.g. cashew

Carbamazepine

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nuts, asparagus

FIXED DRUG ERUPTIONS
ERYTHEMA NODOSUM

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A septal panniculitis induced by a medication
Symmetrical, erythematous, tender, subcutaneous

nodules or plaques

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Typical y over the anterior aspect of the limbs.
Later become purplish before final y turning brown

Oral contraceptives

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Barbiturates

Hormonal

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replacement therapy

Isotretinoin

Sulphonamides

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Montelukast

Penicil in

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Vaccinations

(hepatitis, HPV,

Azathioprin

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rabies)

Minocycline

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GcSF

Ciprofloxacin

Complementary

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NSAIDs

medications

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Gold
Benzodiazepines
ERYTHEMA MULTIFORME

acute self limiting lesion characterized by IRIS or

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TARGETOID lesions

IRIS lesion - <3 cm, rounded lesion with 3 zones
central ? dusky erythema or purpura

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middle ? pale edema
outer - erythema with well defined margin

Sulphonamides,
Penicillin,

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Sites - face, extremities,

Quinolones,

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oral, genital mucosa,

Tetracyclins,

trunk

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Rifampicin,
Anticonvulsants,
NSAIDS,
Thiazides,

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Nevarapin

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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;

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(i ) alteration of biochemical profiles (e.g. renal or hepatic
dysfunction);
(i i) other unexplained mechanisms

Opioids

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Statins
Paclitaxel
Antimalarials
Granulocyte?macrophage colonystimulating factor
Interleukin2

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Angiotensinconverting enzyme inhibitors
Sulphonylurea derivates
Nonsteroidal antiinflammatory drugs
Hydroxyethyl starch (HES)

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DRUG INDUCED

PHOTOSENSITIVITY

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Itchy, erythematous papules, plaques on exposed

areas;

H/O photosensitivity

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drugs - quinolones, tetracyclins, sulphonamides,

griseofulvin, phenothiazine, psoralens, ampicillin,

amiodarone

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AMIODARONE INDUCED

PHOTOSENSITIVITY

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VASCULITIS

urticarial vasculitis, palpable purpura, nodular

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vasculitis, necrotic ulcers

drugs ? aspirin, indomethacin, phenylbutazone
sulphonamides, tetracyclin, ampicillin,

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erythromycin,diuretics, phenytoin, methatrexate


LICHENOID ERUPTIONS

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Lichen planus like eruption, mostly trunk
Generalized, eruptive, with prominent

eczematous and scaling component

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Mucosa, nail involvement infrequent

LICHENOID DRUG ERUPTIONS

Gold, Antimalarials,

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Mercury Amalgam,
Thiazides,
NSAIDS,
Penicillamine
Isoniazid,

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Tetracyclin,
Dapsone,
Beta Blockers
Captopril
ACNEIFORM ERUPTIONS

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Extensive papulopustular monomorphic

eruptions; absence of comedones

Suspected : sudden, abrupt onset in the absence

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of past history of acne

Trunk>face
Any age

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Corticosteroids

Dactinomycin

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Androgens and anabolic

Thiourea, thiouracil

steroids

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Epidermal growth factor

Hormonal contraceptives

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receptors inhibitors

Danazol

Imatinib

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Tricyclic antidepressants, Iodine,Bromine,Chlorine

Lithium,Valproate,Phenytoin Isoniazid, Rifampicin

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Vitamins B1, B6,

Ethionamide

Ciclosporin,Sirolimus

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Azathioprine


DRUG INDUCED PIGMENTATION

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Via - melanin synthesis ? psoralens
Cutaneous deposition of drug/metabolite ?

minocyclin, heavy metals, clofazimine

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Hormonal effect ? OCP causing melasma
Post inflammatory hyperpigmentation
other drugs ?bleomycin, cyclophosphamide,

methotrexate, hydroxyurea, 5- fluorouracil

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MINOCYCLIN INDUCED PIGMENTATION


CLOFAZIMINE INDUCED

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PIGMENTATION

ALOPECIA
Retinoids, cytotoxics, anticougulants, anti thyroids, danazol,

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OCP

HYPERTRICOSIS
PUVA, phenytoin, minoxidil, penicillamine, cys A

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HIRSUITISM
Oral steroids, anabolic steroids, OCP

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ALOPECIA HYPERTRICOSIS

Management of drug reactions

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WITHDRAW and replace with chemical y

unrelated alternatives

Mild/moderate cases

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1. antihistamines,
2.local bland emollients,
3.Topical steroids

Severe cases ?

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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

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SJS-TEN Complex
IVF replacement,
Oral liquid diet,
Nasogastric tube,
Total parenteral nutrition

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Denuded skin ? dressing
Antacids/ H2 blockers
pethidine/ tramadol,

Emperical broad spectrum antibiotics

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Eye care ? 2 hr NS/antibiotics, break synechia
SPECIFIC ? steroids,
IV Ig,
cyclosporin,
cycloposphamide,

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thaladomide,
plasmapheresis
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