Drug reaction with eosinophilia and systemic symptoms

Background

• T-cell mediated severe cutaneous adverse reaction

Clinical Manifestations

• Prodrome of fever, malaise, sore throat, dysphagia, pruritus, and a burning sensation on the skin, followed by rash
• Symptoms include fever, facial edema (which can cause new oblique earlobe creases), maculopapular rash, lymphadenopathy, eosinophilia, atypical lymphocytosis (earliest and most common hematologic finding), and multiorgan dysfunction
  • Includes hepatitis (most common organ after skin), glomerulonephritis, arthritis, pneumonitis, and carditis
• Rash is typically morbilliform and spreads to involve more than 50% total body surface area
  • Lesions can be urticarial, eczematous, lichenoid, exfoliative, erythrodermic, targetoid, purpuric, vesicular, pustular, alone or in combination
  • About half have mild mucosal involvement
• Typical onset 2 to 8 weeks after starting medication
• Commonly-associated medications:
  • Antibiotics
    • Vancomycin-associated DRESS is more common in European descendants, with the HLA-A*32:01 allele
    • Trimethoprim-sulfamethoxazole
  • Antiepileptic medications: lamotrigine and carbamazepine
  • Allopurinol
• High mortality around 5%

DRESS Scoring System

• Developed for RegiSCAR, though I can't seem to find a primary reference

Criteria

Criterion	-1	0	1	2	Notes
Fever ≥38.5ºC	No/U	Yes
Enlarged lymph nodes		No/U	Yes		>1 cm in ≥2 areas
Eosinophilia
—Eosinophils (if WBC ≥4), or			0.7-1.49	≥1.5
—Eosinophils (if WBC <4)			10-19.9%	≥20%
Atypical lymphocytes		No/U	Yes
Rash
—Skin rash (%BSA)		No/U	>50%
—Skin rash suggesting DRESS	No	U	Yes		≥2 of: purpuric lesions (other than legs), infiltration, facial edema, psoriasiform desquamation
—Biopsy suggesting DRESS	No	Yes/U
Organ involvement
—Liver involvement		No/U	Yes		Maximum score of 2
—Kidney involvement		No/U	Yes
—Muscle or heart involvement		No/U	Yes
—Pancreas involvement		No/U	Yes
—Other organ involvement		No/U	Yes
Resolution ≥15 days	No/U	Yes
Exclusion of other causes			Yes		at least 3 tests were done and negative: HAV, HBV, HCV, ANA, blood cultures, Mycoplasma, Chlamydia

Interpretation

Interpretation	Points
Definite	≥6
Probable	4-5
Possible	2-3
Not DRESS	≤1

Management

• Cessation of offending medication
• Most common treatment is prednisone 0.5 to 1 mg/kg (or equivalent glucocorticoid), tapered over 6 to 12 weeks once there is clinical improvement
  • No strong evidence to support this practice
• If no improvement with prednisone at regular doses, can consider pulse steroids for 3 days
• People have also tried IVIG, Mycobacterium, cyclosporine, cyclophosphamide, and several biologics (anti-IL5, anti-CD20, JAK inhibitors)
• Resolution is slow, and can recur or relapse, and some patients are left with chronic complications

Further Reading

• The DRESS Syndrome: A Literature Review. Am J Med. 2011;124(7):588-597. doi: 10.1016/j.amjmed.2011.01.017
• Drug Reaction with Eosinophilia and Systemic Symptoms. NEJM. 2024. Doi: 10.1056/NEJMra2204547