Cutaneous drug reactions and DRESS !

Rashes caused by medicines, from a common itchy measles-like rash to DRESS, a rare severe reaction with fever and organ damage.

Updated 2026-11-01

Structures involved

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Why it happens

What it is

Skin reactions caused by medicines are among the most frequent adverse drug events. Most are benign exanthematous (maculopapular) eruptions, but some are severe cutaneous adverse reactions, such as DRESS (drug reaction with eosinophilia and systemic symptoms), which involves fever, rash and internal organ damage.

Who gets it

Drug eruptions affect a significant share of hospitalised patients, most often as exanthematous rashes. DRESS is rare but has a mortality of up to around 10 percent. In Colombia and Latin America aromatic anticonvulsants, allopurinol, sulfonamides and antituberculosis drugs are among the classic culprits.

Causes

Aromatic anticonvulsants (carbamazepine, phenytoin, phenobarbital, lamotrigine)
Allopurinol
Sulfonamides (including sulfamethoxazole and sulfasalazine) and dapsone
Beta-lactam antibiotics, vancomycin, minocycline and antituberculosis drugs
Nevirapine, abacavir and other antiretrovirals

Risk factors

Specific HLA types (for example HLA-B*58:01 with allopurinol, HLA-B*15:02 with carbamazepine in some populations)
Reactivation of herpesviruses (HHV-6, EBV, CMV) during the reaction
HIV infection, which raises the risk of drug eruptions
Kidney impairment (higher drug levels, for example with allopurinol)
Previous reaction to the same or a related drug

Pathophysiology

Most drug eruptions are delayed (type IV) T-cell-mediated reactions. In DRESS, drug-specific T cells expand massively, eosinophils are recruited and latent herpesviruses (especially HHV-6) reactivate, which sustains inflammation in the skin, liver, kidney, lung and heart. This explains the long delay after starting the drug and the slow, relapsing course even after the drug is stopped.

Classification

Exanthematous (maculopapular, morbilliform) eruption: the most common; appears 4 to 14 days after starting the drug
Urticaria and angioedema (immediate, IgE-mediated); may be part of anaphylaxis
Fixed drug eruption: round dusky plaques that recur at the same site each time the drug is taken
DRESS: fever, widespread rash, facial swelling, lymphadenopathy, eosinophilia and organ involvement, 2 to 8 weeks after starting the drug
Stevens-Johnson syndrome and toxic epidermal necrolysis; acute generalised exanthematous pustulosis (AGEP)

Symptoms and signs

Symmetric red macules and papules starting on the trunk and spreading to the limbs, with itching
In fixed drug eruption: one or a few round violaceous patches, often on the lips, genitals or hands
In DRESS: high fever, spreading rash that can become erythroderma, and facial swelling
In DRESS: enlarged lymph nodes in several regions
In DRESS: signs of organ involvement, such as jaundice, dark urine, reduced urine output, cough or chest pain

Diagnosis

Clinical: Detailed medication history including timing of every new drug in the last two months; the timing pattern points to the culprit. DRESS is confirmed with scoring criteria (RegiSCAR) combining fever, rash, lymphadenopathy, blood abnormalities and organ involvement.
Tests: Complete blood count (eosinophilia, atypical lymphocytes), liver function, kidney function and urinalysis, troponin and thyroid function in DRESS; herpesvirus PCR (HHV-6). Skin biopsy when the type of reaction is unclear. Patch testing or specialist allergy evaluation after recovery, never rechallenge after a severe reaction.
Imaging: Chest imaging and echocardiography when lung or heart involvement is suspected.

Differential diagnosis

Viral exanthems (measles, rubella, EBV, dengue)
Stevens-Johnson syndrome and toxic epidermal necrolysis
Erythema multiforme
Sepsis with rash and haemophagocytic syndrome
Lymphoma and hypereosinophilic syndrome

Goal of treatment

Identify and stop the culprit drug immediately, support failing organs and record the allergy so the drug is never given again.

Treatment

Acute: Withdraw the suspected drug and any non-essential medicines at once; choose a structurally unrelated alternative.
Medical: Mild exanthematous eruptions: oral antihistamines and topical corticosteroids. DRESS with organ involvement: systemic corticosteroids tapered slowly over weeks to months; cyclosporine or other agents for resistant cases.
Conservative: Supportive care: emollients, skin care, fluids and nutrition; hospital care for DRESS.
Follow-up: Nursing priorities: daily skin assessment, vital signs, fluid balance, liver and kidney tests and eosinophil count; clearly label the allergy in the record and on an alert card.

Complications

Drug-induced hepatitis and acute liver failure (the main cause of death in DRESS)
Interstitial nephritis and acute kidney injury
Pneumonitis and myocarditis
Late autoimmune disease after DRESS (thyroiditis, type 1 diabetes)
Relapse of DRESS when corticosteroids are tapered too fast

Prognosis

Exanthematous rashes clear within one to two weeks after stopping the drug. DRESS improves slowly over weeks to months, may relapse, and carries a mortality of up to about 10 percent, mostly from liver failure.

Prevention

Document every drug allergy clearly and check before prescribing
HLA screening before high-risk drugs in populations where it is recommended (for example HLA-B*58:01 before allopurinol)
Avoid structurally related drugs after a severe reaction

Test yourself

Think of the answer, then tap the question to see it.

When does DRESS typically begin after starting the culprit drug?

Between 2 and 8 weeks, later than most other drug eruptions.

Which three drugs are classically associated with DRESS?

Aromatic anticonvulsants (carbamazepine, phenytoin), allopurinol and sulfonamides.

Which organ involvement is most common and causes most deaths in DRESS?

The liver (drug-induced hepatitis).

What is a fixed drug eruption?

A round dusky or violaceous plaque that recurs at exactly the same site each time the drug is taken.

What is the single most important step in any suspected drug eruption?

Stop the culprit drug immediately and document the allergy.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Drug allergies: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Drug hypersensitivity syndrome. DRESS (DermNet, 2026).

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Representative model, for educational purposes only.

Skin highlighted on the Durgical 3D model