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.
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.