DRESS Syndrome (Drug Reaction with Eosinophilia): Critical Overview & Management Guide

Key Takeaways

• DRESS syndrome is a life‑threatening drug reaction that usually appears 2-8 weeks after exposure to a high‑risk medication.
• The RegiSCAR scoring system is the gold‑standard for diagnosis, offering >90% sensitivity when viral reactivation markers are included.
• Immediate drug withdrawal, systemic corticosteroids, and close organ monitoring are the cornerstone of treatment.
• HLA‑B*58:01 and HLA‑A*31:01 screening dramatically lowers incidence for allopurinol and carbamazepine.
• Long‑term follow‑up is essential because up to 30% of survivors develop chronic autoimmune sequelae.

DRESS syndrome is a severe cutaneous adverse reaction (SCAR) that combines a widespread rash, fever, eosinophilia, and multi‑organ involvement after a drug trigger. It is also known as drug‑induced hypersensitivity syndrome (DIHS) and carries a mortality rate of about 10%. Early recognition saves lives, but the latency period of 2-8 weeks often blinds clinicians who expect reactions to happen within days.

DRESS syndrome demands a systematic approach: stop the offending drug, confirm the diagnosis with RegiSCAR, assess organ damage, and start systemic therapy without delay.

What Is DRESS and Why Does It Matter?

The syndrome was first described in 1950 as phenytoin hypersensitivity and formally named DRESS in 1996. It sits between acute generalized exanthematous pustulosis (AGEP) and Stevens‑Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in severity. Unlike SJS/TEN, DRESS features prolonged fever, facial edema, and striking eosinophilia (>1,500 cells/µL). The systemic inflammation can cripple the liver, kidneys, lungs, heart, or pancreas, making it a true medical emergency.

Epidemiology & Risk Factors

Incidence varies from 1 per 1,000 to 1 per 10,000 drug exposures, with higher rates in Asia (up to 15 per 10,000 hospital admissions). High‑risk drugs account for most cases:

• Allopurinol - ~28% of reports
• Carbamazepine - ~24%
• Various antibiotics (especially vancomycin) - ~20%
• Anticonvulsants (lamotrigine, phenytoin) - ~15%

Genetic predisposition is key. HLA‑B*58:01 carriers have an 80% higher odds of allopurinol‑related DRESS, while HLA‑A*31:01 raises carbamazepine risk. Nations that mandate pre‑prescription HLA screening (e.g., Taiwan) have cut incidence by up to 80%.

Clinical Presentation

Typical signs appear 2-8 weeks after drug start:

• Rash: morbilliform, often beginning on the face and upper trunk, spreading to cover 80‑90% of body surface within days.
• Facial edema (≈68% of cases) and lip crusting (≈52%).
• Fever >38.5 °C in 98% of patients.
• Lymphadenopathy (≈75%).
• Eosinophilia >1,500 cells/µL in 70% and atypical lymphocytes in 60%.

Organ involvement is the rule, not the exception (≈90% of cases). The liver is hit most often - ALT can exceed 300 IU/L, sometimes soaring past 1,000 IU/L. Renal, pulmonary, cardiac, and pancreatic injury occur less frequently but dramatically increase mortality.

How DRESS Differs From Other SCARs

These differences help clinicians avoid misdiagnosis - a common problem that delays proper care by an average of 19 days.

Diagnosing DRESS: The RegiSCAR Scoring System

Developed in 2007 and updated in 2023, RegiSCAR assigns points for seven criteria: fever, enlarged lymph nodes, eosinophilia, atypical lymphocytes, skin rash extent, organ involvement, and exclusion of alternative diagnoses. A score ≥5 is "definite" DRESS, 4 is "probable," and ≤3 is "possible." Adding viral reactivation markers (HHV‑6, EBV, CMV) boosts sensitivity from 80% to 92%.

Practical steps:

1. Discontinue every non‑essential medication immediately (within 24 h of suspicion).
2. Order CBC with differential, LFTs, serum creatinine, and urinalysis.
3. Screen for HHV‑6 DNA, EBV IgM, CMV PCR, and hepatitis serologies.
4. Calculate RegiSCAR points. Use the freely available mobile app for quick scoring.
5. Document HLA genotype if the culprit drug is known (e.g., HLA‑B*58:01 for allopurinol).

Management Principles

There is no randomized trial that definitively proves a single regimen, but observational data converge on three pillars:

• Drug withdrawal - the most decisive factor; delays beyond 48 h raise mortality by 2‑fold.
• Systemic corticosteroids - oral prednisone 1 mg/kg/day or IV methylprednisolone for severe organ damage. Taper over 3-6 months, reducing 5-10 mg weekly once labs normalize.
• Organ‑specific support - ICU monitoring for ALT >1,000 IU/L, creatinine >2.0 mg/dL, or respiratory failure; consider N‑acetylcysteine for liver injury, renal replacement therapy if needed.

Adjuncts gaining traction:

• IVIG (2 g/kg over 2‑3 days) - helpful when viral reactivation is documented.
• Mycophenolate mofetil - steroid‑sparing alternative in chronic cases.
• Cyclosporine - used in some Asian cohorts with rapid eosinophil decline.

Always involve a multidisciplinary team: dermatology, internal medicine, infectious disease, and pharmacy.

Prognosis, Follow‑Up, and Long‑Term Risks

Survivors face a 30% chance of developing autoimmune thyroiditis, type 1 diabetes, or lupus‑like syndromes within two years. Regular follow‑up labs every 3 months for the first year are recommended. Patients should also be educated about future drug avoidance and the need for HLA testing before re‑exposure to high‑risk agents.

Current Research & Emerging Tools

Key developments in 2023‑2025 include:

• The FDA‑cleared point‑of‑care HLA‑B*58:01 test (Verigene) enables same‑day screening before allopurinol prescription.
• Phase 2 trials combining IVIG with mycophenolate show 70% remission at 12 weeks, offering a steroid‑sparing pathway.
• A global DRESS registry now hosts >1,200 cases, providing real‑world data on drug culprits and outcomes.
• Biomarker panels incorporating cytokine spikes (IL‑5, IL‑13) aim to predict chronic autoimmune sequelae.

Within the next five years, experts predict universal HLA screening for all high‑risk drugs, potentially slashing incidence by 60‑70%.

Practical Checklist for Clinicians

• Suspect DRESS if fever + rash + eosinophilia appear 2-8 weeks after a new medication.
• Stop the drug immediately; document the action.
• Order labs: CBC, LFTs, renal panel, viral PCRs, and HLA typing if relevant.
• Calculate RegiSCAR score; aim for ≥5 before confirming.
• Start systemic steroids; plan a slow taper.
• Monitor organ function daily for the first 72 hours, then every 48 hours until stable.
• Consider IVIG or steroid‑sparing agents for refractory or steroid‑intolerant patients.
• Arrange multidisciplinary case review and discharge planning with dermatology follow‑up.

Patient Stories: The Human Side of DRESS

On the DRESS Syndrome Foundation forum, 78% of respondents described multiple ER visits before a correct diagnosis. One patient, a 34‑year‑old teacher on lamotrigine, spent three weeks in the hospital before her liver enzymes spiked to 1,200 IU/L, prompting a DRESS diagnosis and a 10‑week prednisone taper. She now advocates for HLA screening in primary care.

Conversely, a 42‑year‑old man with carbamazepine‑induced DRESS suffered permanent renal damage because his kidney function deteriorated unnoticed for 22 days. This case underscores why early organ monitoring is non‑negotiable.

Bottom Line

DRESS syndrome sits at the intersection of dermatology, immunology, and internal medicine. Prompt drug cessation, rigorous use of the RegiSCAR tool, and early systemic therapy are the only proven ways to tilt the odds toward survival and recovery. As genetics and rapid diagnostics improve, the future looks brighter, but clinicians must stay vigilant today.