The skin is the largest organ in the body, and adverse skin reactions due to drug exposure are a common problem. The exact mechanism for many of the drug-induced skin diseases is not fully understood and may result from both immune and non-immune mechanisms.

1. SALVA SAFDAR
PharmD,
Sultan-ul-Uloom College of Pharmacy,
Hyderabad.
Guided by: Dr S P SRINIVAS NAYAK,
Assistant professor ,SUCP, HYD.

2. INTRODUCTION
 The skin is the largest organ in the body, and adverse skin
reactions due to drug exposure are a common problem.
 The exact mechanism for many of the drug-induced skin
diseases is not fully understood and may result from both
immune and non-immune mechanisms.
 Properties of a drug that increase the risk of a drug-induced
hypersensitivity reaction are:
 1) molecular weight >4,000 Da (e.g., insulin, erythropoietin)
 2) presence of foreign proteins or large polypeptides of
nonhuman origin (streptokinase, beef or pork insulin) or
 3) the ability of the parent drug or its active metabolite to bind to
a carrier protein and form a complete antigen (penicillins and
sulphonamides).

3.  Drug induced skin diseases is defined as any skin disorders caused by
a drug or medication.Classified as either acute or chronic.
 Acute disorders:
1.erythematous eruptions
2.urticaria, angioedema, and anaphylaxis
3.fixed-drug eruptions
4. hypersensitivity syndrome
5.Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis
(TEN)
6.warfarin-induced skin necrosis
7.drug induced vasculitis(VIT)
8.acute generalized exanthematous pustulosis (AGEP) and
9.photosensitivity.
 Chronic disorders:
1.drug-induced lupus
2.drug-induced acne and
3.pigmentary changes.

4. Drug Induced Dermal Disorders
Acute Chronic
lupus
Acne
Pigmentary
changes
Erythematous
Urticaria,angioedema
Fixed drug
hypersensitivity
SJS and TEN
Warfarin induced
VIT
AGEP
Photosensitivity

5.  Acute Drug-Induced Skin Disorders:
 1.Erythematous Eruptions:
 These reactions are the most common ADRs involving the skin.
 This eruption is considered as type IV delayed cell-mediated
hypersensitivity reaction.
 The eruption typically occurs 4 to 14 days after the causative drug
is initiated ; however, the reaction may occur 1 to 2 days after
discontinuation of the drug.
 Upon a second exposure, the eruption may occur more rapidly.
 Common causative agents:
Penicillins, Cephalosporins, Sulfonamides, Anticonvulsants and
Allopurinol(xanthine oxidase inhibitor).

6.  2.Urticaria, Angioedema, and Anaphylaxis:
 Urticaria is defined as a rash of round, red welts on the skin that itch
intensely, sometimes with dangerous swelling, caused by an allergic
reaction, typically to specific foods.
 It is characterized by pruritic monomorphic erythematous and
edematous papules and plaques.
 The onset of symptoms is rapid, sometimes within minutes, and the
papules and plaques last from a few hours to 24 hours.
 Angioedema is defined by involvement of dermal and subcutaneous
tissues and is described as pale or pink swelling that affects the face,
buccal mucosa, tongue, larynx, and pharynx.
 Anaphylaxis may complicate Urticaria and Angioedema and may
involve additional body systems, leading to shock and death.
 Common causative agents:
NSAIDs, antimicrobials ,anticancer drugs , ACE inhibitors.

7.  3.Fixed-Drug Eruptions:
 These eruptions present as pruritic, red, raised lesions that may
blister or develop into plaques.
 A burning or stinging sensation may also be noted.
 Lesions typically develop in minutes to days of drug initiation and
typically resolve within days; however, hyperpigmentation may
remain for months.
 When the causative agent is readministered, the lesions reoccur in the
same area as the primary eruption.
 Removal of the offending drug is the primary treatment.
 Common causative agents:
NSAIDs, barbiturates, tetracyclines, sulfonamides, amphetamines,
codeine.

8.  4.Drug Hypersensitivity Syndrome:
 This syndrome is also known as Drug Rash with Eosinophilia and
Systemic Symptoms (DRESS)
 It is a severe exanthematous eruption with fever, lymphadenopathy,
and multi-organ involvement.
 Rash and fever are usually the first symptoms.
 The face, upper trunk, and extremities are originally involved, with
inclusion of facial edema.
 Severe hepatitis is responsible for many of the fatalities associated with
this syndrome.
 DRESS typically occurs 1 to 6 weeks after introduction of the causative
agent.
 Common causative agents:
Allopurinol,sulfonamides,anticonvulsants,dapsone,minocycline.

9.  5.Stevens-Johnson Syndrome (SJS) and Toxic
Epidermal Necrolysis (TEN):
 SJS and TEN are rare, life-threatening syndromes.The eruptions are drug-
induced approximately 70% of the time.
 The risk is greatest in those patients infected with HIV.
 The exact mechanisms are unknown; however, early lesion
immunopathologic patterns infer a cell-mediated cytotoxic reaction to
epidermal cells.
 Symptoms are very acute, and begin within 4 weeks of drug exposure.It
have also been documented to occur days after drug withdrawal.
 Initial symptoms include a prodromal phase of fever, sore throat, and
stinging eyes.
 The skin blisters and mucous erosions occur 1 to 2 days later, with extensive
epidermal detachment and sloughing.
 The rash may cover the entire body. Initially, the lesions are irregularly
shaped, erythematous, purpuric macules that progressively coalesce.
 Common causative agents:
NSAIDs,anticonvulsants,nevirapine,allopurinol.

10.  6.Warfarin-Induced Skin Necrosis:
 Warfarin tissue necrosis is a rare but serious disorder that may
occur 3 to 5 days after the initiation of warfarin.
 Red, painful plaques form that develop into necrosis,
hemorrhagic blisters, and ulcers.
 Patients are at increased risk if a hereditary deficit in protein C
is present, due to the hypercoagulable state during initiation of
therapy.
 Warfarin should be discontinued and, vitamin K, heparin and
monoclonal antibody–purified protein C concentrate is
administered.
 Common causative agents:
Warfarin

11.  7.Drug-Induced Vasculitis (DIV):
 This is defined as any case of inflammatory vasculitis caused by a
specific drug.
 Patients may present with palpable purpuric lesions or a
maculopapular-rash(made of both flat and raised skin lesions).
 Ulcers, nodules, hemorrhagic blisters, or Raynaud’s disease(caused
by peripheral blood vessels overreacting to cold mostly affecting fingers
and toes)may also be present, and additional organ systems may be
involved.
 DIV may occur 7 to 21 days after initial drug exposure; however, the
interval may be variable.
 Withdrawal of the causative agent may lead to rapid resolution.
 Drugs from almost every class have been associated with DIV.
 Common causative agents:
Allopurinol, cimetadine, penicillins, cephalosporins, NSAIDs,
flouroquinolones, minocycline.

12.  8.Acute Generalized Exanthematous
Pustulosis (AGEP):
 AGEP is a rare, acute, pustular eruption.
 While the etiology may be viral or a reaction to mercury, greater than
90% of cases are drug induced.
 AGEP is characterized by a fever and diffuse erythema.
 Burning and itching accompany the eruption.
 Patients may experience facial edema, swelling of the hands, and
mucous membrane involvement.
 The eruption may last 1 to 2 weeks and is followed by superficial
desquamation(peeling).
 Treatment consists of drug withdrawal and occasionally a systemic
antipruritic agent or brief use of systemic corticosteroids.
 Common causative agents:
Macrolides,aminopenicillins,diltaizem,quinolones,antimalarials.

13.  9.Photosensitivity:
 This is an adverse skin reaction triggered by doses of sunlight that
are normally harmless.
 It may be idiopathic or result from either endogenous photosensitizers
or exogenous causes, such as drugs.
 Photosensitivity reactions may manifest as either a photo-allergic or
phototoxic reaction.
 Drugs that induce a phototoxic reaction absorb ultraviolet A (UVA)
light; no immunologic mechanisms are involved.
 Phototoxicity is characterized by rapid onset of a burning
sensation,clinically, patients present with an exaggerated sunburn,
followed by hyperpigmentation.
 A photoallergy clinically appears as an acute, subacute, or chronic
dermatitis.
 Common causative agents:
 Phototoxicity: Amiodarone, quinolones, methotrexate, furosemide.
 Photoallergy: sulfonamides, sulfonylureas,thaizides,chloroquine.

14.  Chronic Drug-Induced Skin Disorders
 1.Drug-Induced Lupus (DIL):
 The most prevalent clinical findings of DIL are musculoskeletal (e.g.,
arthralgias, myalgias, arthritis) and constitutional (e.g., fever,
malaise, anorexia, weight loss) symptoms.
 Cutaneous symptoms such as the classic butterfly rash are rare in DIL,
except in the case of quinidine and hydralazine.
 Rechallenge with the offending agent may produce symptoms within 1
to 2 days.
 Drugs associated with lupus are categorized as high risk, moderate risk,
low risk, and risk.
 TYPES:
 A)Subacute cutaneous lupus erythematosus(SCLE)
 B)Systemic lupus erythematosus(SLE)

15.  Subacute Cutaneous Lupus Erythematosus (SCLE), a form of
drug-induced lupus, is most commonly associated with antihypertensives
(calcium channel blockers, ACE inhibitors, beta-blockers, and
thiazide diuretics), HMG-CoA reductase inhibitors, oral antifungals
(terbinafine, griseofulvin), antidepressants (bupropion), and tumor
necrosis factor (TNF) inhibitors (etanercept, infliximab, adalimumab).
 Drug-induced SCLE (DI-SCLE) presents with similar clinical and serologic
symptoms as idiopathic lupus.
 Systemic Lupus Erythematosus (SLE) typically presents in
women of childbearing age, whereas individuals presenting with DIL are
characteristically of advanced age, with an equal distribution between
males and females.
 DIL may also have a higher predominance in individuals who are slow
drug acetylators.
 DIL typically resolves within weeks after the removal of the causative
agent.
 Common causative agents:
High risk:Ptocainamide and hydralazine.
Moderate risk:Quinidine.
Low risk:Isoniazide,methyldopa,minocycline.

16.  2.Drug-Induced Acne:
 Drug-induced acne accounts for approximately 1% of drug-
induced skin reactions.
 Pustular eruptions are typically observed on the face and upper
trunk.
 The eruption occurs 1 to 3 weeks after the causative agent is
initiated.
 Inhaled corticosteroids in patients with asthma have also been
documented to cause acne.
 Topical acne treatment may be utilized to treat the eruption,
which is typically reversible once the causative drug is
withdrawn.
 Common causative agents:
Corticosteroids, androgenic hormones, some anticonvulsants,
isoniazide, azathioprine , oral contraceptives.

17.  3.Drug-Induced Pigmentary Changes:
 Pigmentary changes induced by various drugs may be caused by
different mechanisms, including the enhancement of melanin
production, the deposition of drugs or metabolites, or the post-
inflammatory changes secondary to phototoxicity.
 The effects are more likely to be observed on areas exposed to the sun.
 Drugs commonly associated with hyperpigmentation,
hypopigmentation, and depigmentation.
 Pigmentary changes may fade over time or may be permanent in a
small number of patients.
 Common causative agents:
Hyperpigmentation :minocycline, amiodarone, oralcontraceptives,
antimalarials, anticancer drugs, NSAIDs.
Hypopigmentation :topical tretinoin, corticosteroids.
Depigmentation:Monobenzyl ether of hydroquinone,
phenols,quinones.

18. TREATMENT
 Discontinue the causative agent.
 Provide supportive care and symptomatic relief,
including use of corticosteroids and sunscreen.
 Educate patient on avoiding similar eruptions in the
future.
 If appropriate,councel patient on sun avoidance and
use of sunscreen.