Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Signs, Causes, and What to Do

DRESS syndrome is one of the most dangerous drug reactions you’ve never heard of - until it’s too late. It doesn’t strike quickly like an allergic rash. It creeps in weeks after you start a new medication, often mimicking the flu, then explodes into a full-body crisis. Fever. Swollen lymph nodes. A widespread rash. Liver failure. And in 1 out of 10 cases, death. This isn’t a rare curiosity - it’s a hidden killer hiding in plain sight, especially among people taking common drugs like allopurinol or carbamazepine.

What DRESS Syndrome Actually Looks Like

DRESS doesn’t start with a simple itch. It begins with fatigue, a low-grade fever, and a sore throat - symptoms you might blame on a cold or the flu. Then, 2 to 8 weeks after starting a new medication, the real signs appear. A red, flat, measles-like rash spreads across your torso, arms, and face. Your lymph nodes swell. Your temperature spikes above 38°C. And your blood test shows something strange: too many eosinophils.

Eosinophils are white blood cells that normally fight parasites. In DRESS, they go haywire, attacking your organs. Up to 90% of patients have them in dangerous numbers - over 1,500 per microliter. That’s not just a lab anomaly. It’s a warning sign your body is turning on itself.

But the rash is just the tip. The real danger is inside. Your liver takes the hardest hit. In 70% to 90% of cases, liver enzymes like ALT and AST spike above 1,000 U/L - sometimes over 2,800. Your kidneys may fail. Your lungs swell. Your heart beats irregularly. Some patients develop thyroid problems, diabetes, or even autoimmune diseases like Graves’ disease months after the rash clears.

Which Drugs Trigger DRESS?

Not every drug causes this. But a few are notorious. Allopurinol - the common gout medication - is responsible for nearly half of all DRESS cases. The risk skyrockets if you have kidney disease. In people with an eGFR below 60, one in every 200 allopurinol users develops DRESS.

Antiepileptic drugs like carbamazepine, phenytoin, and lamotrigine are next on the list. These are often prescribed for seizures, bipolar disorder, or nerve pain. Sulfonamide antibiotics like sulfamethoxazole-trimethoprim (Bactrim) are also common triggers, especially in HIV-positive patients.

What makes these drugs dangerous? It’s not the dose. It’s your genes. If you carry the HLA-B*58:01 gene variant - common in people of Asian, African, or Hispanic descent - your risk of allopurinol-induced DRESS jumps 55-fold. That’s why Taiwan now requires genetic testing before prescribing allopurinol. Since 2015, DRESS cases from allopurinol dropped by 75% there.

DRESS vs. SJS and TEN: Why It’s Different

People often confuse DRESS with Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN). All three are severe drug reactions. But they’re not the same.

SJS and TEN show up fast - within 1 to 4 weeks. They cause blistering, skin peeling, and massive mucous membrane damage. Up to 40% of TEN patients die. DRESS? It shows up later. The skin doesn’t peel off. Instead, it’s a flat, red rash. Mucosal damage happens in only 30% to 50% of cases. But DRESS attacks your internal organs. And it doesn’t end when the rash fades.

Here’s the kicker: DRESS is often tied to a hidden viral reactivation. In 60% to 70% of cases, human herpesvirus 6 (HHV-6) wakes up 2 to 4 weeks after symptoms start. This isn’t just a coincidence. The virus may be fueling the immune chaos, making the reaction worse and longer-lasting.

How Doctors Diagnose It - And Why It’s So Hard

There’s no single blood test for DRESS. Diagnosis relies on a checklist called the RegiSCAR criteria. You need hospitalization plus at least three of these:

• Acute skin rash
• Fever over 38°C
• Swollen lymph nodes
• Eosinophilia (over 1,500 cells/μL or 10% of white blood cells)
• Atypical lymphocytes in the blood
• Organ involvement (liver, kidney, lungs, heart, etc.)

Here’s the problem: most doctors don’t think of DRESS. A 2020 study found only 35% of internal medicine residents could correctly identify it. Patients often see three or more doctors before getting the right diagnosis. One patient on a rare disease forum spent 6 weeks in limbo, her liver enzymes climbing, before a dermatologist finally connected the dots.

Doctors who miss DRESS often mistake it for a viral infection, mononucleosis, or even lupus. The key clue? Timing. If you got sick 3 to 6 weeks after starting a new drug - especially allopurinol or an antiseizure med - DRESS should be on the table.

What Happens If You Don’t Act Fast

Delay kills. If you keep taking the drug after symptoms start, your chance of dying jumps from 5% to 15%. The longer you wait, the more your organs are damaged. Liver failure can become irreversible. Kidney damage may need lifelong dialysis. Some patients develop chronic autoimmune conditions years later.

One patient, SarahR87, shared her story on the National Organization for Rare Disorders forum. After starting allopurinol for high uric acid, she developed a rash and fever. Her doctors thought it was a virus. Her AST hit 2,840 U/L - more than 50 times normal. She spent 45 days in the hospital. She survived. But her liver never fully recovered.

That’s why the first rule is non-negotiable: stop the drug immediately. Don’t wait for a diagnosis. If you’re on allopurinol, carbamazepine, or Bactrim and you develop a fever and rash after 2 weeks, stop the medication and go to the ER.

Treatment: Steroids, Support, and Survival

Once the drug is stopped, treatment begins. Most patients need hospitalization - often in intensive care. The main weapon? Corticosteroids. Prednisone or methylprednisolone at 0.5 to 1 mg per kg of body weight daily. That’s usually 40 to 80 mg a day. Treatment lasts 4 to 8 weeks, then tapers slowly. Stopping too soon can cause a rebound.

Supportive care is just as critical. You need daily blood tests to track liver enzymes, kidney function, and eosinophil counts. Infection control is vital - your skin is compromised, and your immune system is overwhelmed. Bacteria like MRSA and fungi like Candida can invade. Antibiotics and antifungals are often needed.

For the most severe cases, newer treatments are emerging. In 2022, a study showed anakinra - a drug used for rheumatoid arthritis - cut hospital stays from 18.5 days to 11.2 days when added to steroids. Tocilizumab, another immune-modulating drug, is now being tested in clinical trials for steroid-resistant DRESS.

Long-Term Risks and What Comes After

DRESS doesn’t disappear when the rash fades. About 20% to 30% of survivors have lasting organ damage. Kidney function may never return to normal. Thyroid problems like Hashimoto’s or Graves’ disease can appear months later. Some patients develop type 1 diabetes or autoimmune hepatitis.

A 2022 survey of 150 DRESS survivors found 27% needed ongoing nephrology care. Another 15% required endocrine follow-up. That’s why long-term monitoring is part of recovery. You need blood tests every 3 to 6 months for at least a year - and sometimes longer.

And here’s something rarely discussed: you may never be able to take the triggering drug again. Even a tiny amount can restart the reaction. That means if you had DRESS from allopurinol, you can’t use it again. Your doctor will switch you to febuxostat - a safer alternative for gout - especially if you have kidney disease.

How to Protect Yourself

If you’re prescribed allopurinol and you’re of Asian, African, or Hispanic descent, ask for HLA-B*58:01 testing before starting. It’s a simple blood test. If you’re positive, your doctor can choose a different medication. In the U.S., this isn’t standard yet - but it should be.

If you’re on any of these drugs - allopurinol, carbamazepine, phenytoin, lamotrigine, or sulfonamides - know the warning signs: fever, rash, swollen glands, fatigue. If they appear after 2 to 8 weeks, don’t wait. Stop the drug. Call your doctor. Go to the ER.

And if you’ve had DRESS before? Tell every doctor you see. Put it in your medical record. Wear a medical alert bracelet. This isn’t just a one-time event. It’s a lifelong risk.

DRESS is rare. But it’s not mysterious. It’s predictable. And with awareness, it’s preventable. The next time someone says, ‘It’s just a rash,’ remember - sometimes, it’s not.