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

DRESS syndrome isn’t just a rash. It’s a full-body crisis triggered by a medication you likely thought was safe. Imagine waking up with a fever, swollen face, and a red, itchy rash spreading across your chest - then finding out your liver enzymes are through the roof and your white blood cells are screaming inflammation. This isn’t the flu. It’s Drug Reaction with Eosinophilia and Systemic Symptoms, or DRESS. And if you’ve been on certain drugs for more than two weeks, you’re at risk.

What DRESS Really Looks Like

DRESS doesn’t show up overnight. It creeps in. You start a new medication - maybe allopurinol for gout, carbamazepine for seizures, or an antibiotic like vancomycin. Everything’s fine for three or four weeks. Then, out of nowhere, you get a fever above 38.5°C. Your skin breaks out in flat, red spots that spread from your face down to your torso and limbs. Your lymph nodes swell. Your eyes puff up. Your lips crack and bleed. You feel exhausted, like you’ve been run over by a truck.

But here’s what makes DRESS dangerous: it’s not just skin deep. In nearly 9 out of 10 cases, internal organs get hit. The liver takes the biggest hit - over 77% of patients show liver damage, with ALT levels often spiking past 300 IU/L. Kidneys, lungs, heart, and even the pancreas can follow. Blood tests reveal eosinophils - a type of white blood cell - climbing above 1,500 cells/μL. That’s not just elevated; it’s a red flare for your immune system going rogue.

Unlike Stevens-Johnson Syndrome, where the skin peels off in sheets, DRESS doesn’t cause massive blistering. But it’s just as deadly. About 1 in 10 people who get DRESS die from it - usually because diagnosis was delayed. And that’s the problem. Most ER doctors have never seen it. A 2019 study found 30-40% of DRESS cases are misdiagnosed as viral infections or allergies. Patients often visit the ER two to five times before someone finally connects the dots.

Which Drugs Trigger DRESS?

Not every drug causes DRESS. But some are known triggers. The big three:

• Allopurinol - used for gout - accounts for nearly 28% of cases. If you carry the HLA-B*58:01 gene variant, your risk jumps dramatically. In Taiwan, they screen for this gene before prescribing allopurinol. Since 2012, DRESS cases from this drug have dropped by 80%.
• Anticonvulsants - like carbamazepine, phenytoin, and lamotrigine - make up about 24% of cases. HLA-A*31:01 is a known genetic red flag here. Carbamazepine carries a black box warning in Asia for this reason.
• Antibiotics - especially vancomycin, minocycline, and sulfonamides - are responsible for 20% of cases. Even common antibiotics like amoxicillin can trigger it in rare cases.

Other offenders include antiretrovirals, NSAIDs, and newer cancer immunotherapies like checkpoint inhibitors. The list keeps growing as more drugs enter the market. And here’s the kicker: you don’t need to be on a high dose. Even low-dose, short-term use can trigger DRESS if your genes say yes.

How Is DRESS Diagnosed?

There’s no single blood test that says “DRESS.” Diagnosis relies on a combination of clinical signs, lab results, and timing. The gold standard is the RegiSCAR scoring system. It’s a checklist doctors use to assign points for:

• Fever above 38.5°C
• Skin rash covering more than 50% of the body
• Enlarged lymph nodes
• Eosinophil count over 1,500 cells/μL
• Atypical lymphocytes in blood
• Organ involvement (liver, kidney, etc.)
• Reaction occurring 2-8 weeks after starting the drug
• Exclusion of other causes (like viral infections)

A score of 5 or higher is considered definite DRESS. 3-4 is probable. Below 3? Probably not. The system is 80% sensitive and 97% specific - meaning it rarely gives false positives.

But here’s what most hospitals miss: viral reactivation. In 60-80% of DRESS cases, HHV-6 (human herpesvirus 6) wakes up from dormancy. EBV and CMV can also reactivate. That’s not a coincidence - it’s part of the disease. Testing for these viruses isn’t routine, but it should be. It helps confirm the diagnosis and explains why the immune system goes haywire.

Why It’s So Hard to Spot

Doctors are trained to think of common things first. Fever + rash? Must be a virus. Itchy skin? Allergy. Elevated liver enzymes? Probably alcohol or fatty liver. That’s why DRESS slips through.

Primary care physicians are the most likely to miss it. A 2021 study found only 38% of them could correctly identify DRESS criteria. Academic dermatologists? 89%. That gap is deadly. Patients in community hospitals wait longer. They get sent home with antihistamines. Their organs keep getting damaged. By the time they get to a specialist, it’s often too late.

One Reddit user, u/RashWarrior, shared their story: took lamotrigine for five weeks. Developed fever and rash. Went to the ER three times. First visit: “viral.” Second: “allergic reaction.” Third: liver enzymes at 1,200. Finally diagnosed with DRESS at week seven. That’s 18 days of delay - the average for patients.

And it’s not just patients. Even some specialists don’t know about the HLA genetic links. If you’re of Asian descent and prescribed carbamazepine, you should have been screened for HLA-A*31:01. If you’re of any background and prescribed allopurinol, HLA-B*58:01 screening could have prevented this entirely. Yet in the U.S., there’s no national requirement. It’s optional. Most doctors don’t even know to ask.

What Happens After Diagnosis?

Step one: stop the drug. Immediately. No exceptions. Even if you think it’s helping your condition, the risk of death outweighs any benefit. Most patients are admitted to the hospital. Some need ICU care if their liver enzymes are above 1,000, kidneys are failing, or they’re having trouble breathing.

Step two: corticosteroids. Prednisone is the go-to. It’s not perfect - there are no large randomized trials proving it works - but every observational study shows the same thing: if you start steroids within 72 hours of diagnosis, your chances of survival jump. Response rates are 60-70%. Delayed treatment? Mortality skyrockets.

Step three: taper slowly. You can’t just stop steroids. DRESS can flare again if you do. Tapers last 3 to 6 months, dropping 5-10mg every week or two. Some patients need long-term monitoring for autoimmune complications - like thyroid disease or type 1 diabetes - that can pop up months or even years later.

For those who don’t respond to steroids, alternatives like IVIG (intravenous immunoglobulin) or mycophenolate are being tested. A phase 2 trial at Vanderbilt started in March 2023 to see if combining these drugs can reduce steroid dependence.

Can You Prevent DRESS?

Yes - but only if you know your risk.

If you’re prescribed allopurinol and you’re of African, Southeast Asian, or Han Chinese descent, ask for HLA-B*58:01 testing. It’s a simple blood test. In Taiwan, it’s mandatory. In the U.S., it’s not. But if your doctor refuses, get a second opinion. The cost of one missed diagnosis? Up to $28,500 in hospital bills - not counting lost work, chronic illness, or death.

Same goes for carbamazepine. If you’re Asian, HLA-A*31:01 screening is recommended. Even if you’re not, if you’ve had a previous drug rash, you’re at higher risk. Document every reaction - even a mild one - and tell every new doctor.

And if you’re on any new medication for more than two weeks and start feeling off - fever, rash, swollen glands - don’t wait. Go back. Say: “Could this be DRESS?” Most doctors won’t know. But if you say the name, you’ve already won half the battle.

What Happens After Recovery?

Most people recover - but not everyone returns to normal. About 1 in 5 develop long-term issues. Chronic kidney disease. Autoimmune thyroiditis. Liver fibrosis. Even diabetes. The immune system doesn’t always reset after DRESS.

Sarah Johnson, a nurse from Texas, recovered from vancomycin-induced DRESS after 8 weeks in the hospital and 6 months of tapering prednisone. She went back to work in 10 months. But she still gets monthly liver checks. She’s lucky.

Others aren’t. A 42-year-old man in a 2022 case study developed permanent kidney damage after 22 days of undiagnosed carbamazepine-induced DRESS. He needed dialysis. He was 42.

That’s why follow-up matters. Even if you feel fine, get your labs checked at 3, 6, and 12 months. Watch for fatigue, swelling, or unexplained weight gain. These aren’t just “aging” symptoms. They could be signs your immune system is still attacking your body.

Where Do We Go From Here?

Science is catching up. In March 2023, the FDA approved the first point-of-care test for HLA-B*58:01 - results in under an hour. It’s called the Verigene System. Hospitals are starting to use it. But it’s still expensive and not widely available.

Global registries are now collecting data on DRESS cases from 47 countries. Researchers are hunting for biomarkers that predict who’ll develop chronic complications. A $2.5 million NIH grant is funding that work.

Experts predict that within five years, pre-prescription HLA screening will be standard for all high-risk drugs. That could cut DRESS cases by 60-70%. But until then, awareness is your best defense.

DRESS isn’t rare. It’s underdiagnosed. It doesn’t discriminate by age, gender, or background. It strikes when you least expect it. And if you’re taking one of those high-risk drugs right now - even if you’ve been on it for months - pay attention to your body. A fever and rash aren’t just a coincidence. They could be your last warning.