Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): What You Need to Know

What Is DRESS Syndrome?

DRESS is a rare but dangerous drug reaction that triggers a severe immune response. It stands for Drug Reaction with Eosinophilia and Systemic Symptoms, and it’s also called Drug-Induced Hypersensitivity Syndrome (DIHS). Unlike a simple rash or mild allergy, DRESS affects multiple organs and can be life-threatening. It doesn’t happen to everyone who takes a drug-it’s unpredictable, and only a small number of people develop it. But when it does, it’s serious.

People with DRESS usually start feeling sick 2 to 8 weeks after taking the medicine that caused it. That’s a long delay compared to most allergic reactions, which show up within hours or days. This delay is why so many patients see multiple doctors before getting the right diagnosis. Symptoms begin with fever, swollen glands, and feeling tired-like the flu. Then, a widespread red rash appears, often looking like measles. The rash can cover large parts of the body and may blister or peel slightly, but it doesn’t detach like in Stevens-Johnson Syndrome.

Why Eosinophilia Matters

One of the clearest signs of DRESS is a spike in eosinophils-a type of white blood cell. In healthy people, eosinophils make up less than 5% of total white blood cells. In DRESS, they jump to over 10%, sometimes even above 1,500 cells per microliter. This isn’t just a lab curiosity. These cells release toxic proteins that damage the liver, kidneys, lungs, and other organs. In fact, 95% of confirmed DRESS cases show this eosinophilia. It’s one of the main reasons doctors suspect DRESS instead of a regular viral rash or another drug reaction.

Another key clue is the presence of atypical lymphocytes-abnormal-looking immune cells that show up in about 85% of cases. Together, these two lab findings-high eosinophils and strange-looking lymphocytes-help separate DRESS from other rashes. If a patient has a fever, rash, and these blood changes after taking a medication, DRESS should be on the list.

Common Culprit Drugs

Not all drugs cause DRESS. But some are far more likely to trigger it. The top offenders are:

• Allopurinol (used for gout)-responsible for 40-50% of all cases
• Antiepileptic drugs like carbamazepine, phenytoin, and lamotrigine-account for 20-30%
• Sulfonamide antibiotics like sulfamethoxazole-cause 10-15%

Allopurinol is especially risky for people with kidney problems. If someone has an eGFR below 60, their risk of DRESS jumps to 1 in 200. That’s why doctors in the U.S. and Europe now recommend testing for the HLA-B*58:01 gene before prescribing allopurinol to high-risk patients-especially those of Asian descent. This genetic test cuts DRESS cases by up to 75% in places like Taiwan where it’s used routinely.

Other drugs linked to DRESS include minocycline, vancomycin, and some antiretrovirals. If you’ve recently started a new medication and developed a fever and rash, stop the drug and call your doctor immediately.

How DRESS Differs from SJS and TEN

Many people confuse DRESS with Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN). They’re all severe skin reactions, but they’re very different.

DRESS vs. SJS/TEN: Key Differences

Feature	DRESS Syndrome	SJS/TEN
Onset after drug start	2-8 weeks	1-4 weeks
Main skin rash	Morbilliform (measles-like)	Target lesions, blistering
Epidermal detachment	Minimal or none	10-30% (SJS), >30% (TEN)
Mucosal involvement	30-50%	Over 90%
Key immune cells	CD4+ T cells, eosinophils	CD8+ T cells, granulysin
Mortality rate	~10%	SJS: 5-10%, TEN: 30-40%

Unlike SJS/TEN, which destroy the skin’s outer layer, DRESS attacks internal organs. The liver is most commonly affected-70-90% of patients have liver damage, with ALT levels sometimes spiking above 1,000 U/L. Kidneys, lungs, and even the heart can be involved. This systemic damage is what makes DRESS so dangerous.

Hidden Trigger: Viral Reactivation

One of the most surprising discoveries about DRESS is that it often triggers a hidden virus. In 60-70% of cases, human herpesvirus 6 (HHV-6)-a virus most people carry quietly in their bodies-gets reactivated 2 to 4 weeks after symptoms start. This isn’t a coincidence. Researchers believe the immune chaos caused by the drug reaction wakes up the virus, and the virus then worsens the inflammation.

This viral reactivation explains why DRESS symptoms can linger for weeks or even months. It also explains why some patients get a second wave of fever or rash after they seem to be improving. Doctors now routinely test for HHV-6 DNA in the blood when DRESS is suspected. If it’s positive, they monitor more closely for complications.

Diagnosis Is Hard-But There’s a Tool

Because DRESS looks like so many other conditions, it’s often missed. A 2020 study found that only 35% of internal medicine residents could correctly identify a DRESS case. That’s why experts created the RegiSCAR scoring system. It’s a checklist doctors use to decide if a case is likely DRESS.

To meet the RegiSCAR criteria, a patient must be hospitalized and have at least three of these:

• Acute skin rash
• Fever over 38°C
• Swollen lymph nodes
• Eosinophilia above 1,500/μL or over 10%
• Atypical lymphocytes in blood
• One or more internal organs affected
• Reaction lasting 15+ days

The more criteria met, the higher the confidence. A score of 4 or more means “definite DRESS.” A score of 2-3 means “probable.” This tool helps doctors avoid misdiagnosing it as hepatitis, mononucleosis, or even lupus.

How It’s Treated

The most important step is stopping the drug that caused it-within 24 hours if possible. Delaying this increases the risk of death from 5% to 15%. Once the drug is out, treatment focuses on calming the immune system.

Most patients need hospital care. About half will require corticosteroids like prednisone or methylprednisolone. Dosing is usually 0.5 to 1 mg per kg of body weight per day, given for 4 to 8 weeks, then slowly tapered. Stopping too early can cause a rebound flare. In severe cases, doctors are now testing newer drugs like anakinra (an IL-1 blocker) and tocilizumab (an IL-6 blocker), which have shortened hospital stays in early trials.

Infection control is critical. Because the skin is damaged and the immune system is overwhelmed, patients are at high risk for serious infections-like MRSA, E. coli, or fungal infections. Antibiotics and antifungals are often given preventively.

Long-Term Risks and Recovery

DRESS doesn’t always go away cleanly. About 20-30% of survivors have lasting organ damage. The most common is chronic kidney disease, especially after allopurinol-induced DRESS. Others develop thyroid problems like Graves’ disease or autoimmune hepatitis. One patient in a Reddit case report developed full-blown thyroiditis five weeks after recovery.

Recovery takes time. Most people feel better in 2-4 weeks, but full recovery can take months. Blood tests need to be checked regularly for up to a year. Some patients need lifelong follow-up with nephrologists or endocrinologists.

Despite the risks, outcomes are much better when DRESS is caught early. A 2021 case report showed a patient given high-dose steroids within days of diagnosis recovered completely in 14 days. That’s why awareness matters.

What You Can Do

If you’re on allopurinol, carbamazepine, or a sulfa drug and you develop a fever and rash-even weeks after starting the medicine-don’t wait. Call your doctor. Don’t assume it’s just a virus or a mild allergy. Ask: Could this be DRESS?

If you’ve had DRESS before, never take the same drug again. Keep a list of all drugs you’ve reacted to and share it with every doctor you see. Consider wearing a medical alert bracelet.

For families and caregivers, know that recovery is slow. Fatigue, mood changes, and brain fog are common. Support groups like the DRESS Syndrome Foundation offer patient navigators who help people find specialists and avoid misdiagnosis. Since 2018, they’ve helped over 1,200 people cut their diagnostic delays in half.

What’s Next for DRESS?

Research is moving fast. The European Registry of Severe Cutaneous Adverse Reactions (EuroSCAR) is developing a point-of-care test that combines HHV-6 levels, eosinophil markers, and clinical scores to diagnose DRESS in under an hour. That could change emergency room practices.

Meanwhile, guidelines are shifting. The American College of Rheumatology now recommends febuxostat instead of allopurinol for patients with kidney disease to avoid DRESS entirely. If this becomes standard, we could prevent 1,200 to 1,500 cases a year in the U.S. alone.

As more people take medications for chronic conditions-especially older adults-the number of DRESS cases is expected to rise by 25% by 2030. But with better screening, faster diagnosis, and smarter drug choices, many of those cases can be stopped before they start.