Drug reaction with eosinophilia and systemic symptoms

Background

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%

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

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