What are the skin histological findings of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)?

Histological Findings of DRESS Syndrome

The histopathological findings of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) are characterized by a combination of patterns including interface dermatitis, spongiosis, keratinocyte damage, and a perivascular lymphocytic infiltrate, with the severity of keratinocyte necrosis correlating with disease severity. 1

Key Histopathological Features

Epidermal Changes

• Spongiosis: Present in approximately 55% of cases, associated with non-severe DRESS 1
• Keratinocyte damage: Observed in 53% of cases 1
  • Confluent keratinocyte necrosis correlates with severe DRESS 1
• Interface dermatitis: Present in 74% of cases, frequently involving cutaneous adnexae 2
• Eczematous pattern: Seen in 40% of cases 2

Dermal Changes

• Vascular changes: Present in 88% of cases 1
• Perivascular lymphocytic infiltrate: Invariably present 1
  • Contains eosinophils, neutrophils, and/or atypical lymphocytes in 57% of cases 1
• Dermal eosinophils: Surprisingly present in only 20% of cases despite peripheral eosinophilia 3, 2
• Neutrophils: Present in 42% of cases 2
• Deep dermal involvement: Observed only in DRESS (not in milder drug reactions) 4
• Leukocytoclastic vasculitis: Exclusively seen in DRESS 4

Cellular Infiltrate Characteristics

• CD8+ and granzyme B+ lymphocytes: Higher proportion in severe DRESS with erythroderma and/or bullae 2
• Atypical lymphocytes: Found in 28% of biopsies, mostly expressing CD8 2
• Cutaneous T-cell clone: Rarely found (6% of cases) 2

Diagnostic Patterns

DRESS shows multiple inflammatory patterns in a single biopsy, which is a distinguishing feature 2:

1. Eczematous pattern: 40% of cases
2. Interface dermatitis pattern: 74% of cases
3. Acute generalized exanthematic pustulosis-like pattern: 20% of cases
4. Erythema multiforme-like pattern: 24% of cases

The presence of two or three of these patterns in a single biopsy is significantly more common in DRESS than in non-drug-induced dermatoses 2.

Histopathological Progression

The number of histopathological changes per section increases gradually from maculopapular exanthema (MPE) to systemic MPE and DRESS 4:

• Keratinocyte damage: Rare in MPE, regularly found in systemic MPE, frequent in DRESS
• Inflammatory infiltrate density: Progressively increases from MPE to systemic MPE to DRESS
• Atypical lymphocytes: Absent in MPE, present in systemic MPE, more frequent in DRESS

Clinical Correlation

It's important to note that histopathology alone is not sufficient for diagnosing DRESS. The histopathological changes must be correlated with clinical information on cutaneous and systemic involvement 3. The diagnosis is based on a combination of criteria including clinical features, laboratory findings, and histopathology 5.

Diagnostic Pitfalls

• No single histopathological pattern is pathognomonic for DRESS 1, 3
• Dermal eosinophils may be absent despite peripheral eosinophilia 3
• Histopathological changes can be interpreted generically as drug-induced dermatitis 3

Early recognition of these histopathological features, especially when multiple patterns coexist in a single biopsy, should alert clinicians to the possibility of DRESS syndrome, allowing for prompt discontinuation of the culprit drug and appropriate management to reduce morbidity and mortality.