DRUG INDUCED DERMATOLOGICAL
M.Vinay Kumar Chakravarthy.
Jun 25, 2014 1
Skin is the organ most frequently affected by the
adverse drug reactions.
Virtually all drugs may induce skin reactions.
Although most drug related skin eruptions are not
serious, some are severe and potentially life
threatening, such as Steven’s Johnson Syndrome
and Toxic epidermal Necrolysis.
Drug eruptions can also occur as part of a
spectrum of multiorgan involvement, for example in
drug induced systemic Lupus Erythematosus.
Jun 25, 2014 2
The cause of skin reactions is often unknown.
Although many have an allergic or toxic basis.
Allergic reactions may be independent of dose and can persist
long after the causative drug has been withdrawn.
In penicillin hypersensitivity reactions, for example, the skin
condition may worsen for seven to 10 days after the drug is
In contrast, toxic reactions are dose-dependent and skin
symptoms generally resolve fairly soon after the causative
agent is withdrawn.
Jun 25, 2014 3
Genetic factors may be an important influence; for example,
acetylator status may predispose to sulphonamide reactions.
Hepatic disease, renal disease, systemic lupus erythematosus
and AIDS are some of the disease states associated with an
increased risk of skin reactions.
The route of administration can influence drug allergy; in
general, topical application has the greatest propensity to
induce allergy, followed by parenteral then oral
Jun 25, 2014 4
Cutaneous drug reactions may be classified with respect to
pathogenesis and clinical morphology.
They may be mediated by immunologic and nonimmunologic
Immunologic reactions require host immune response and may
result from IgE-dependent, immune complex-initiated,
cytotoxic, or cellular immune mechanisms.
Jun 25, 2014 5
Nonimmunologic reactions may result from nonimmunologic
activation of effector pathways, overdosage, cumulative toxicity,
side effects, ecologic disturbance, interactions between drugs,
metabolic alterations, or exacerbation of preexisting
Common Drug Rashes
• Fixed-drug eruption
• Phototoxic reactions
Serious Drug Rashes
• Toxic epidermal
Jun 25, 2014 6
It can be difficult to diagnose a drug eruption confidently.
Many reactions cannot be distinguished from naturally occurring
eruptions so misdiagnosis is common and this may unnecessarily
limit the future use of a particular medication.
Furthermore, patients are often taking more than one drug,
making it more difficult to confirm the cause.
Drugs suspected of causing skin reactions should usually be
withdrawn and not used again in that patient.
Symptomatic treatment with calamine lotion or systemic
antihistamines may be required. For more serious reactions,
systemic corticosteroids may be indicated.
Jun 25, 2014 7
Pencillins and sulfonamides frequently cause these
• DRUGS THAT COMMONLY
Jun 25, 2014 9
FIXED DRUG ERUPTION:
The site of eruption is fixed, i.e, when the individual takes the
causative drug again the eruption generally recurs within 8 hrs
at exactly same site as was previously affected.
FDEs are caused by the activation of cytotoxic T lymphocytes
in the basal layer by drugs. Common causative drugs are
NSAIDs, tetracyclines, sulfa drugs, phenacetin,
food additives etc.,
The sites mainly affected are the hands, feet and perianal
It consists of erytematous round or oval lesions of a dusky
brown colour sometimes featuring blisters or vesicles.Jun 25, 2014 10
Healing occurs over 7 to 10 days after the causative drug is
Topical corticosteroids may help to reduce the intensity of the
DRUGS THAT CAUSE
FIXED DRUG ERUPTION
Jun 25, 2014 11
URTICARIA (nettle-rash or hives )
Medically, urticaria may be defined as skin eruption, which is
allergic (or non-allergic) in origin and is characterized by
profound itching, red circular or irregularly shaped eruptions on
any part of the body
Urticaria lesions present as raised, itchy, red blotches or weals
that are pale in the centre and red around the outside.
Drug-induced urticaria may occur after the first exposure to a
drug or after many previously well-tolerated exposures.
Urticaria is characterized as acute when it lasts 6 weeks or
less and chronic when it persists beyond this.
Jun 25, 2014 12
Jun 25, 2014 13
It is essential to take a detailed medication history when
a patient presents with urticaria, remembering that
pharmaceutical excipients may be a trigger.
Management of urticarial reactions involves stopping the
causative agent and treatment with an oral antihistamine.
DRUGS THAT MAY CAUSE
ACE inhibitors Anaesthetics
(local and general)
Enzymes (eg, streptokinase)
Jun 25, 2014 14
Psoriasis and Psoriasiform Eruptions:
Psoriasis is a chronic disorder, which means it can last a long
time and can come back frequently.
Psoriasis most commonly appears as thick, flaky patches of
skin that may be silver or red.
A number of drugs can induce psoriasis in patients with no
previous history or can worsen pre-existing psoriasis.
In patients with pre-existing psoriasis, symptoms usually
developed within the first month of treatment but in those
with no previous history they developed after at least two
Jun 25, 2014 15
In psoriasis, skin cells reproduce many times faster than
normal and live only three to four days. The dead cells build up
on the skin, forming thick, flaky patches.
Practolol was withdrawn as it causes a serious syndrome
termed the oculomucocutaneous syndrome, featuring a
psoriasiform rash, xerophthalmia due to lachrymal gland
fibrosis, otitis media, sclerosing peritonitis and a lupus-like
Topical treatments such as corticosteroids or calcipotriol may
Jun 25, 2014 16
• SOME DRUGS THAT MAY
Jun 25, 2014 17
Vasculitis is an extreme reaction to a drug, infection, or foreign
substance that leads to inflammation and damage to blood
vessels of the skin.
Several drugs can induce both systemic vasculitis with
cutaneous manifestations and cutaneous vasculitis without other
About 10% of cases of acute cutaneous vasculitis are believed to
be drug induced.
Purple-colored spots and patches, which get pale when pressure
is placed on them (purpura), Skin lesions usually located on the
legs, buttocks, or trunk, Blisters on the skin.
Jun 25, 2014 18
The skin lesions may persist for up to 4 weeks or longer, and
in some cases become yellow-brown upon healing.
Drug therapy should be stopped at the first suspicion and the
condition usually subsides thereafter.
Systemic corticosteroids and immunosuppressants may be of
some benefit in severe cases.
SOME DRUGS FREQUENTLY
IMPLICATED IN VASCULITIS
Jun 25, 2014 19
As the name implies, it can present with a variety of patterns.
Erythema multiforme (EM) is a cutaneous response triggered by
various infections and drugs.
There may be blisters, papular lesions or erythematous areas.
A characteristic lesion is one of concentric rings, variously
described as target, iris or bullseye shaped.
The classic pattern affects the hands, feet and limbs.
Erythema multiforme may be due to vaccination, a variety of
topical medications, and some environmental substances (eg,
Jun 25, 2014 20
When the condition is suspected, all drugs, especially those
introduced within the past month, should be discontinued,
since there is a risk of progression to Stevens Johnson
syndrome or toxic epidermal necrolysis.
SOME DRUGS THAT MAY
Jun 25, 2014
STEVEN JOHNSON SYNDROME:
It is the most severe form of erythema multiforme and is
characterized by ulcerated lesions on the skin and mucous
It is a serious, sometimes fatal inflammatory disease.
Involvement of the mucosa is common, so the mouth, eyes and
genitalia may be affected.
A painful conjunctivitis may occur in the eye frequently with a
pus discharge and may lead to loss of vision.
Stevens Johnson Syndrome is frequently drug induced.
A large number of drugs have been implicated as a cause of SJS.
Penicillins, tetracyclines, sulfonamides and NSAIDs are among
the most common.Jun 25, 2014 22
This syndrome is distinct from Toxic Epidermal
Necrolysis(TEN), but there is a degree of overlap as severe
forms of SJS can evolve into TEN and several drugs can
produce both entities.
The estimated incidence of SJS ranges between 1.2 and 6
per million population per year. In about 50 % of cases the
cause is not known.
The fatality rate is believed to be about 5 per cent.
Drugs that may be responsible for the reaction should be
Treatment involves systemic corticosteroids, fluid
replacement and antibiotics, if required.
Jun 25, 2014 23
DRUGS THAT MAY CAUSE
STEVENS JOHNSON SYNDROME.
Jun 25, 2014 24
TOXIC EPIDERMAL NECROLYSIS:
Toxic epidermal necrolysis (TEN), or Lyell’s syndrome, is a rare
variety of erythema with acute epithelial necrosis affecting all
areas of the skin.
The disorder is characterised by widespread full-thickness
epidermal necrosis with involvement of more than 30% of the
body surface area.
Commonly, there is severe involvement of the mucous
membranes (oropharynx, eyes and genitalia).
The estimated incidence ranges from 0.4 to 1.2 per million
population per year. It has a high associated mortality
Jun 25, 2014 25
The conjunctivae are commonly affected 1–3 days before the
appearance of skin lesions. Buccal, nasopharyngeal and pulmonary
tract desquamation and erosion may be present.
Identification of the causative drug is often difficult. In
general, most drugs causing TEN have been given in the previous
Phenytoin-induced TEN can occur at any time between 2 and
8 weeks after initiation of therapy, and may progress despite
discontinuation of the drug.
The antiepileptic lamotrigine causes serious skin reactions.
About 1:1000 adults treated develop Toxic epidermal
Jun 25, 2014 26
Involves the careful protection of exposed dermis and
eroded mucosal surfaces, managing fluid and electrolyte
balance, nutritional support, and close monitoring for evidence
Antibiotic therapy should be given at the first sign of sepsis,
rather than prophylactically.
Immunosuppressive agents such as cyclophosphamide have
also been given to some patients, with claimed benefits.
The place of systemic corticosteroids in the management of
TEN is controversial.
Jun 25, 2014 27
• DRUGS THAT MAY CAUSE
NSAIDs (especially oxicam
Jun 25, 2014 28
Two types include phototoxic eruptions and photoallergic
Phototoxic eruptions are due to absorption of UV light (usually
UVA) by the drug, which causes a release of energy and
damage to cells. Looks like a bad sunburn, which may blister.
Photoallergic eruptions are a lymphocyte-mediated reaction
caused by exposure to UVA, which converts the drug to an
immunologically active compound that activates lymphocytes,
causing an eczematous reaction in a photodistribution.
Usually due to topical agents including fragrances and biocides
Jun 25, 2014 29
Both types can be caused by phenothiazines, chlorpromazine,
sulfa, and NSAIDS, although phototoxic reactions are more
common with these agents.
Less frequent Antidepressants
Jun 25, 2014 30
Management points to be considered when a patient have
experienced a Drug Eruption.
• Take an accurate medication history. Note details of all current and recent
medication, including over-the-counter medicines, herbal and homoeopathic
preparations, and injections, including vaccines or contrast media.
• Note the times when each medicine was first taken relative to the onset of
the reaction, and check whether the patient has taken these medicines
• Some skin reactions, particularly urticaria, may be due to sensitivity to
pharmaceutical excipients. If this type of reaction is present, it is worth noting
the proprietary (brand) names of medicines taken as well as the generic
• Ask the patient if they have a previous history of drug sensitivity, contact
dermatitis, connective tissue disease or atopic disease with asthma or
Jun 25, 2014 31
• Examine the rash to determine what type it is and whether it appears
to be a drug eruption.
• Record clearly in the patient’s notes any known or suspected ADR, with
details of the presumed cause. Tell the patient or relatives, and preferably give
a written note so that future exposure can be avoided.
• Take great care in prescribing for the patient subsequently. Clarify that
compound preparations do not contain potentially harmful constituents.
• Notify suspected ADRs to the relevant regulatory authority. This
information is essential for identifying new drug safety hazards and
enables the study of factors associated with ADRs.
Jun 25, 2014 32
www.ncbi.nlm.nih.gov › Journal List › Br Med J › v.1(6168); Apr 7, 1979
Jun 25, 2014 33