Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS)

This page covers the medical criteria, tests and long-term follow-up. For a plain overview of the triggering drugs and how it compares with other reactions, see our main page on DRESS syndrome.

Why it is called "drug reaction with eosinophilia"

The name lists the features. Eosinophils are white blood cells involved in allergy. In DRESS, drug-specific T cells activate and release signals that call in large numbers of eosinophils (a state called eosinophilia), which then infiltrate the skin, liver, kidneys, lungs or heart. "Systemic symptoms" means the reaction is not limited to the skin. Not every patient has a high eosinophil count, which is why Japanese specialists use the alternative name drug-induced hypersensitivity syndrome (DiHS).

Reactivation of latent herpesviruses, especially HHV-6, and sometimes EBV or CMV, is common 2 to 4 weeks into the illness and is linked to relapses and a more severe course.

Common triggers and genetic risk

Genetic testing for some of these HLA types is recommended before starting certain drugs in higher-risk populations, for example HLA-B*58:01 before allopurinol in people of Han Chinese, Thai or Korean descent.

Symptoms and timeline

1. Prodrome: fever and malaise, sometimes a sore throat, 2 to 8 weeks after starting the drug.
2. Rash: a measles-like rash that spreads to cover more than half the body, often with facial swelling, which is a strong clue. It may become scaly, purple or have small pustules.
3. Lymph nodes: enlarged in two or more areas.
4. Organ involvement: the liver in most cases, then the kidneys, lungs and heart.
5. Course: symptoms often keep worsening for days after the drug is stopped, and can relapse during recovery.

Diagnosis: RegiSCAR criteria

Doctors combine history, examination and blood tests. The RegiSCAR scoring system grades how likely the diagnosis is, scoring points for:

• Fever of 38.5 °C (101.3 °F) or higher
• Enlarged lymph nodes in at least two sites
• Raised eosinophils (higher counts score more)
• Atypical lymphocytes on the blood film
• Rash covering more than 50% of the body, with features typical of DRESS, and a skin biopsy consistent with it
• Organ involvement
• Illness lasting 15 days or more
• Other causes ruled out, such as viral infections, autoimmune disease and Stevens-Johnson syndrome

A total below 2 means DRESS is excluded, 2 to 3 possible, 4 to 5 probable, and 6 or more definite.

Typical tests include a full blood count, liver and kidney function, urine tests, troponin and an ECG to check the heart, thyroid tests, viral tests including HHV-6, and a skin biopsy. Patch testing for the culprit drug may be done later, 6 months or more after recovery.

Treatment

• Stop the suspected drug immediately, and avoid starting unnecessary new medicines, which can trigger flares.
• Supportive care: fluids, nutrition, skin care with emollients and close monitoring.
• Mild cases without serious organ damage may be treated with strong topical steroids.
• Systemic corticosteroids are the standard for moderate or severe DRESS. The dose is reduced slowly over at least 6 to 8 weeks, often longer, because rapid tapering causes relapses.
• Second-line options for cases that do not respond include cyclosporine and, in specialist centers, other immune treatments.

Complications and long-term follow-up

Acute complications include liver failure, kidney injury, myocarditis (heart muscle inflammation), pneumonitis and secondary infection. Most deaths are from liver or heart failure.

Weeks to years after recovery, a minority develop autoimmune disease, most often thyroid disease (Graves disease or Hashimoto thyroiditis), and less often type 1 diabetes, autoimmune hemolytic anemia or lupus. Thyroid function is usually checked for at least a year afterward.

After DRESS:

• Record the drug as a severe drug allergy and carry a wallet card or medical alert.
• Avoid the drug and its cross-reacting relatives for life. Never use re-challenge to test.
• First-degree relatives may share the same HLA risk and should tell their doctors.

Frequently asked questions

What are the RegiSCAR criteria for DRESS?

RegiSCAR is a scoring system that adds points for fever, swollen lymph nodes, eosinophilia, atypical lymphocytes, extent and type of rash, organ involvement, an illness lasting at least 15 days, and exclusion of other causes. A score of 6 or more indicates definite DRESS, 4 to 5 probable and 2 to 3 possible.

How long after starting a drug does DRESS appear?

Usually 2 to 8 weeks, with most cases around 3 to 6 weeks. This long delay sets it apart from hives or anaphylaxis, which start within minutes to hours, and from ordinary drug rashes, which typically appear within 1 to 2 weeks.

How long does it take to recover from DRESS?

Most people need several weeks in hospital and at home, and steroid treatment commonly continues for 2 to 3 months or longer. Relapses can occur during the taper. Full recovery of skin and liver often takes months, and follow-up for thyroid and other autoimmune problems continues for at least a year.

Can you have DRESS without eosinophilia?

Yes. A minority of patients never develop a raised eosinophil count, and in others it rises only after a delay. The diagnosis then relies on the other features, which is why the term drug-induced hypersensitivity syndrome is also used.

Is DRESS syndrome contagious or inherited?

It is not contagious, even though herpesviruses reactivate during it. It is not inherited as a disease, but certain inherited HLA gene types raise the risk with specific drugs, so close relatives may be advised to avoid the same medicine or be tested first.