Download MBBS Dermatology PPT 2 Cutaneous Drug Eruptions Lecture Notes

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