In the name of God

Dr. F. Shariati

In medicine

Most drug-induced cutaneous reactions are mild and

disappear when the offending drug is withdrawn.

Drugs can also cause hair and nail changes, affect the

mucous membranes, or cause itching without outward

skin changes

Drug eruptions are diagnosed mainly from the:

medical history

clinical examination

However, they can mimic a wide range of other conditions

Drug Eruptions

A drug-induced reaction should be considered

in any patient who is taking medications

and who suddenly develops a symmetric

cutaneous eruption

Drug Eruptions

to ccurs in approximately 2-5% of inpatients and in

greater than 1%-3% of outpatients

The serious drug eruptions occur in around 1 in

1000 patients

Drug Eruptions

Drug Reaction mortality : 1.8% percent

Mortality rates for Stevens-Johnson syndrome (SJS) has a less than 5%,

whereas the rate for TEN approaches 20- 30%; most patients die from sepsis

Drug Eruptions

Classification By appearance

The most common type of eruption is a morbilliform resembling measles or erythematous rash, (but the appearance

may also be…….. )

By mechanism

The underlying mechanism can be immunological in drug or non-immunological

By drug

The culprit can be both a prescription drug or an over- counter medication.(antibiotic, analgesic,herbal supplement)

Physiopathology of Cutaneous Drug Reaction

Allergic Reaction (Immunologic) less than 6-10%

Non allergic Reaction (Non Immunologic) More than . 90%

Drug Eruptions

Non - allergic Drug Reaction Over Dose Side Effects Cumulative Toxicity Delayed Toxicity Facultative Effects Drug Interaction Metabolic Changes Teratogenicity of Fetus Activation of Effector Pathways Exacerbation of Diseases Chromosomal Damage by Drug Intolerance and Idiosyncrasy Jarisch — herxheimer reaction Infectious mono - , ampicillin reaction

Drug Eruptions: clinical appearance

Drug-induced exanthems Urticaria Angioedema/anaphylaxis DRESS Sydrome Hypersensitivity vasculitis Exfoliative dermatitis/Erythroderma SJS/TEN Fixed drug eruption Photosensitivity

Drug-induced Exanthems Account for close to 75% of all drug eruptions.

Morbilliform, maculopapular eruptions. Most commonly implicated medications are the most commonly

prescribed medications (antibiotics, sulfa). Usually begin in generalize areas .

Often associated with pruritis, low-grade fever, eosinophilia. Onset within 2 weeks of starting a new drug, or within days of re-

exposure. Delayed (type IV) hypersensitivity is most likely etiology.

More common in patients with altered immunity, such as those with HIV or mononucleosis (“ampicillin rash”).

Treatment is dicontinuation of the drug. Antihistamines, topical steroids, and topical antipruritics may also help.

Drug-induced Exanthems

Urticaria:

Time to onset: immediate, accelerated (hours), or delayed (days).

immunological(Type I hypersensitivity reactions) :antibiotics (especially PCN, cephalosporins, and sulfonamides), local anesthetics, radiocontrast media, blood products, and gamma globulin.

Non-immune urticaria: Mast cell degranulation by non-IgE mechanisms: opiate analgesics, anesthetic, muscle relaxants, and Vancomycin (Red Man Syndrome).

Angioedema/Anaphylaxis

Caused by degranulation of mast cells in the deeper

dermis and subcutaneous tissues.

May occur along with urticaria (50% of cases)

Can be life-threatening if it causes laryngeal edema or

tongue swelling.

Can be non-mast cell mediated, as in the case of ACE-

inhibitors.

Angioedema/Anaphylaxis

DRESs SyndromeDrug Rash with Eosinophilia and Systemic Symptoms

Formerly called Hypersensitivity Syndrome (HSS)

Typically presents with rash and fever (87%), classically erythematous follicular papules and pustules, but may also include

bullae or purpura. Other severe systemic manifestations such as arthralgias,

lymphadenopathy (75%), hepatitis (51%), or hematologic abnormalities (30%). interstitial nephritis (11%),

Hematologic abnormalities include eosinophilia, thrombocytopenia, neutropenia, and atypical lymphocytosis.

Other symptoms: pruritis, nephritis, oliguria, hepato-renal syndrome, and asthenia.

DDx includes SJS/TEN, hypereosinophilic syndrome, and Still’s disease.

Skin biopsy is non-specific.

DRESS Syndrome Common causes: aromatic anticonvulsants (oxcarbazepine,

carbamazepine, phenytoin, phenobarbital, etc.) and sulfonamides. Other drugs implicated:

lamotrigine allopurinol NSAIDs Captopril fluoxetine dapsone metronidazole minocycline antiretrovirals.

Hypersensitivity vasculitis(DHS)

American College of Rheumatology proposed the following five criteria. The presence of three or more had a sensitivity of 71% and a specificity of 84% for the diagnosis

Age > 16 Use of possible offending drug in temporal relation to symptoms Palpable purpura Maculopapular rash Biopsy of a skin lesion showing neutrophils around an arteriole or

venule. Most likely due to drugs that can act as haptens to stimulate the

immune response: PCN, cephalosporins, sulfonamides, phenytoin, and allopurinol.

Additional findings: fever, urticaria, arthralgias, low complement (CH50) levels, and elevated ESR.

Hypersensitivity vasculitis

Exfoliative dermatitis/ Erythroderma

Erythroderma is defined as a cutaneous reactional state with

chronic erythema and scale involving greater than 50% of the

body surface area.

Usually begins as an eczematous or morbilliform eruption and

progresses.

Drugs including, gold, arsenic, mercury, PCN, and barbituates, are

implicated in about 10% of cases.

Erythroderma: Marked inflammation and scaling which can result from a variety of medical conditions.

SJS/TEN Stevens-Johnson Syndrome and toxic epidermal necrolysis are likely

two manifestations on the same spectrum. The disease is best termed SJS when epidermal detachment involves less than 10% of the body surface area, whereas TEN involves greater than 30%.

SJS is distinct from erythema multiforme major, which is usually caused by infections and runs a benign course. SJS is usually drug induced and can be fatal.

SJS and TEN usually occur 1-3 weeks after exposure, but can occur more rapidly with re-exposure, which suggests an immunologic mechanism.

Mucosal involvement is seen in 90% of cases, including painful crusts and erosions on the oral mucosa, conjuntivae, and genital mucosa.

Toxic epidermal necrolysis

Fixed Drug Eruptions

Drug eruption that occurs at the same location every time a particular medication is used.

Begins as an erythematous, edematous plaque with a grayish center or frank bullae, then progresses to

dark, post-inflammatory pigmentation. Sites include the mouth, genetalia, face, and acral

areas. Causes include phenolphthalein, tetracyclines,

barbituates, sulfonamides, NSAIDs, and salicylates.

fixed_drug_eruption_

Fixed drug eruption

PHTOSENSITIVE DRUG ERUPTION

Photosensitive drug eruption:

thiazidesphenothiazines sulfa drugs tetracyclinesOthers

Characteristic Drug Changes

Pigmentation of teeth due to tetracyclines

LICHENOID DRUG REACTION

TypeII/III reaction lasix, captopril,

chloroquin, gold, beta blockers, aldomet, penicillamine, thiazides, sulfa, many others

*features diff. From LP:

parakeratosis,hypogranulosis,EOS spongiosis,

plasmacells,many EOS

LUPUS-LIKE SYNDROM

Skin lesions:malar or butterfly rashOffending drugs:

procaineamid,hydralazin, INH,methyldopa,

chlorpromazin,penicillamine,PUVA,others

Silver : lunula discoloration

D-penicillamine: Yellow nail

Cytotoxics: Beau’s lines

Minocycline: blue nails

Investigations

• If history and physical examination are not sufficient for diagnosis, Biopsy e.g. by showing eosinophils in

morbilliform eruptions or numerous neutrophils without vasculitis

CBC count with differential may show leukopenia, thrombocytopenia, and eosinophilia in patients with serious drug eruptions

Confluent necrosis of the epidermis in toxic epidermal necrolysis

Perivascular mixed inflammatory infiltrate with eosinophils characteristic of drug induced urticaria

Treatment

• Once the offending drug has been identified, it should be promptly stopped.

• since traces of the drug may persist for long periods, and some reactions, continue for many days without reexposure to the drug

• Patients with morbilliform eruptions can continue medication even in presence of rash as the eruption often resolves, especially if the individual is being treated for a serious disease

• Treatment of a drug eruption depends on the specific type of reaction

Therapy for exanthematous drug eruptions is supportive in nature.

First-generation antihistamines are used mild topical steroids (e.g. hydrocortisone(moisturizing lotions, especially during the late

desquamative phase

stage

• Topical steroids may provide some relief

• If signs and symptoms are severe, a 2-week course of systemic corticosteroids (prednisone, starting at 40- 60 mg) will usually stop the symptoms and prevent further progression of the eruption within 48 hours of the onset of therapy

Good Luck