001828 - DRESS syndrome or Bullous pemphigoid? A losartan-induced severe exanthema beyond limits

Background

Drug hypersensitivity reactions affect more than 7% of the population. To distinguish between different DHRs is essential to assess the prognosis and management.

Materials and Methods:

A 50-year-old male with diabetes mellitus and hypertension, treated with sitagliptin/metformin since February-2025 and losartan since January-2025, started in March with a progressively extended purpuric exanthema. It was finally generalized, infiltrated, with significant desquamation, affecting >50% of the body surface. He was assessed by a dermatologist, and a skin punch-biopsy was performed. Sitagliptin and losartan were discontinued with a significant improvement. No new lesions appeared. He was referred to our allergy department.

Results

Punch-biopsy: spongiosis, apoptotic keratinocytes, mild perivascular inflammatory infiltrate. Direct IF showed a weak linear positivity for C3.

Blood tests (active phase): eosinophilia 0.68x10^3/μL, total bilirubin 1.40mg/dL. Normal renal and liver panel. After 15 days without drugs: eosinophilia 0.53x10^3/μL, normalized bilirubin (1.02mg/dL).

Blood tests (six months later): eosinophilia 350.10^3/µL, normal tryptase (5.3µg/L) and complement, negative ºantinuclear and IgG anti-BP180 and anti-BP230 antibodies.

Serological tests for common viruses: increase in IgM-EBV levels.

Patch tests with sitagliptin and losartan (10% and 1:10diluted): negative results. 

Lymphocyte Transformation Test: slightly positive result with losartan at two concentrations (stimulation index -SI- of 2.02 at 5µg/ml and 2.24 at 10µg/ml). Sitagliptin was negative at all concentrations. 

Conclusions

We present a severe exanthema defined by a combination of bullous pemphigoid and DRESS features. Severe delayed drug hypersensitivity reactions contraindicate re-exposure, being patch tests and LTT useful tools. The LLT suggests losartan as the probable trigger. The proportional increase in SI detected with losartan at 5µg/ml and higher at 10µg/ml, suggests allergic sensitization. A RegiSCAR DRESS score of 2-3 was calculated (possible case). A reactivation of herpes viruses, such as EBV, is commonly detected in DRESS. Based on the weak linear positivity for C3 detected, a non-bullous atypical bullous pemphigoid was also suspected. It has been described a drug-induced BP in patients with negative autoantibodies. No DRESS or BP secondary to any ARB(losartan) has been previously described.