Lichenoid Drug Eruption

Case Overview

Presented by Dr. Tom Davis, Sagis Diagnostics
Educational dermpath case series for dermatology residents

Patient: 79-year-old male
Lesion Location: Bilateral helices, trunk, and proximal extremities

A biopsy of reddish-brown scaling papules and plaques was performed. Take a moment to review the histologic images below, do you know how Dr. Davis came to this diagnosis?

(Low-power histologic view: bisected shave biopsy with lichenoid infiltrate obscuring the dermo-epidermal junction)

(Medium-power: compact hyperkeratosis and parakeratosis in the stratum corneum)

(High-power: scattered necrotic keratinocytes in the epidermis)

(Super high-power: mixed inflammatory infiltrate with lymphocytes, melanophages, and eosinophils)

Key Histologic Findings

On examination, several defining features stand out:

• Lichenoid inflammatory infiltrate obscuring the dermo-epidermal junction beneath a hyperplastic epidermis
• Compact hyperkeratosis and parakeratosis within the stratum corneum
• Scattered necrotic keratinocytes within the epidermis
• Mixed lichenoid infiltrate containing lymphocytes, melanophages, and numerous eosinophils

Differential Diagnosis: Three Common Mimickers

When evaluating a lichenoid interface dermatitis like this, several differentials come to mind. Let’s walk through the three most likely contenders and highlight what sets them apart.

1️⃣ Lichen Planus

Etiology: Idiopathic T-cell–mediated autoimmune reaction targeting basal keratinocytes; no drug association

Histology:

• Cornified layer thickened by compact orthokeratosis — no parakeratosis
• Hypergranulosis of the epidermis
• Band-like, pure lymphocytic infiltrate at the dermo-epidermal junction
• Civatte (colloid) bodies from necrotic basal keratinocytes
• Saw-toothing of the rete ridges

Key Distinction: Lichen planus features compact orthokeratosis without parakeratosis and hypergranulosis, which are absent in lichenoid drug eruption. Most critically, the infiltrate in lichen planus is a pure lymphocytic band devoid of eosinophils — eosinophils being the single most useful histologic clue pointing toward a drug etiology.

2️⃣ Drug-Induced Erythema Multiforme

Etiology: Immune-mediated hypersensitivity reaction; commonly triggered by infections (HSV) or medications

Histology:

• Basket-weave cornified layer (rather than compact hyperkeratosis)
• Prominent necrotic keratinocytes throughout the full thickness of the epidermis
• Vacuolar alteration along the dermo-epidermal junction
• Much less dense infiltrate of lymphocytes compared to lichenoid processes
• Subepidermal blistering in severe cases

Key Distinction: Erythema multiforme shares the presence of epidermal necrotic keratinocytes but differs fundamentally in infiltrate density and distribution — it has a sparse, vacuolar pattern at the DEJ rather than a dense band-like lichenoid infiltrate. The basket-weave stratum corneum (vs. compact hyperkeratosis with parakeratosis) and absence of eosinophils help clinch the distinction.

3️⃣ Pityriasis Lichenoides Chronica (PLC)

Etiology: Clonal T-cell lymphoproliferative disorder of uncertain etiology; considered a benign CD8+ T-cell–mediated process

Histology:

• Parakeratotic cornified layer containing neutrophils
• Necrotic keratinocytes in the epidermis
• Patchy (rather than band-like) lichenoid infiltrate of pure lymphocytes
• Extravasated erythrocytes in the papillary dermis
• No significant eosinophils

Key Distinction: PLC shares parakeratosis and epidermal necrotic keratinocytes with lichenoid drug eruption, but the infiltrate is patchy and purely lymphocytic — lacking the dense, mixed infiltrate with eosinophils that characterizes lichenoid drug eruption. The presence of neutrophils within parakeratotic scale and extravasated erythrocytes in the dermis are additional clues favoring PLC. Clinical drug history is decisive.

The Final Diagnosis:

Lichenoid Drug Eruption

The correct diagnosis is confirmed by the constellation of compact hyperkeratosis with parakeratosis, scattered necrotic keratinocytes, a dense lichenoid infiltrate obscuring the dermo-epidermal junction, and — most critically — a mixed inflammatory infiltrate with numerous eosinophils. This combination, in the setting of recent initiation of Apalutamide (Erleada), is diagnostic of lichenoid drug eruption.

Key Takeaways for Residents:

• Eosinophils in a lichenoid infiltrate are the most important clue to a drug etiology and should always prompt a careful medication review when they are seen.
• Lichenoid drug eruption is distinguished from lichen planus by parakeratosis, necrotic keratinocytes, and a mixed infiltrate with eosinophils.
• Apalutamide (Erleada) causes drug eruptions in ~25% of patients; lichenoid reactions have a median onset of approximately 4 months after drug initiation.
• Lichenoid drug eruptions are also common with checkpoint inhibitors, tyrosine kinase inhibitors, and anti-TNFα biologics, as well as traditional medications including antihypertensives, antimalarials, NSAIDs, lipid-lowering agents, oral hypoglycemics, and antibiotics.
• Always correlate histology with clinical history — the temporal relationship between drug initiation and eruption onset is diagnostically essential.

📚 Quick Summary

💬 Final Thought

Lichenoid drug eruption is a classic dermatopathology look-alike that rewards careful high-power examination. Remember: when eosinophils crash a lichenoid party, think drug eruption — and go hunting for the culprit medication. In the era of novel oncologic agents like apalutamide, checkpoint inhibitors, and tyrosine kinase inhibitors, the dermatopathologist’s ability to recognize lichenoid drug eruptions is more clinically impactful than ever.

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