What are acneiform eruptions?

What Are Acneiform Eruptions?

Acneiform eruptions are follicular skin reactions characterized by inflammatory papules and pustules that resemble acne but lack comedones (blackheads/whiteheads), most commonly occurring as adverse effects of certain medications, particularly anticancer agents targeting the epidermal growth factor receptor (EGFR). 1

Clinical Characteristics

The defining feature that distinguishes acneiform eruptions from true acne vulgaris is the absence of comedones. 1 The lesions present as:

• Follicular papules and pustules distributed in an acneiform pattern 1
• Sterile inflammatory eruptions confirmed on histopathology 1
• Monomorphous lesions (all appearing similar, unlike the varied lesions of acne vulgaris) 2
• Associated symptoms including pruritus, stinging, burning, pain, and xerosis (dry skin) 1, 3

Distribution Pattern

The eruption typically follows a predictable anatomical distribution:

• Initially affects areas with high sebaceous gland density: face (forehead, nose, cheeks), scalp, upper chest, and back 1
• Can extend to extremities including forearms and buttocks (unusual locations that help distinguish from typical acne) 1, 2
• Cosmetically sensitive areas are predominantly involved, significantly impacting quality of life 1

Timing and Onset

Acneiform eruptions develop within days to weeks after drug initiation, distinguishing them from acne vulgaris which develops gradually 1, 2. The typical timeline includes:

• Onset within first 2-4 weeks of starting causative medication 1
• Sudden appearance rather than gradual development 2
• May improve with time but rarely resolves completely while the causative agent continues 1

Most Common Causes

EGFR inhibitors are the most frequent culprits, causing acneiform eruptions in 75%-90% of patients (all grades) and 10%-20% (grade 3/4 severity) 1. These include:

• Small-molecule tyrosine kinase inhibitors (TKIs): erlotinib, afatinib, dacomitinib, osimertinib, lapatinib, gefitinib 1
• Monoclonal antibodies: cetuximab, necitumumab, pertuzumab, panitumumab 1
• MEK inhibitors: trametinib, binimetinib, cobimetinib (74%-85% incidence, all grades) 1

Other causes include various drug-induced reactions, though EGFR inhibitors represent the predominant etiology in contemporary practice 3, 2.

Pathophysiology

The mechanism involves disruption of normal skin homeostasis:

• EGFR blockade leads to abnormal keratinocyte maturation and differentiation 1
• Release of inflammatory chemokines (CXCLs and CCLs) recruits inflammatory cells 1
• Dense periadnexal inflammatory infiltrate with macrophages, Langerhans cells, T cells, mast cells, and neutrophils 1
• Growth arrest and increased apoptosis in keratinocytes 1
• Damage to basal epidermis, sweat glands, sebaceous glands, and hair follicles 1

Histopathological Features

Biopsy reveals distinctive findings:

• Follicular papules and pustules in acneiform distribution 1
• Sterile eruption (no infectious organisms) 1
• Neutrophilic infiltration in acute reactions 1
• Epidermal atrophy and follicular structure loss in chronic cases 1
• Absence of comedones on microscopic examination 1

Clinical Significance and Impact

Despite being classified as grade 1-2 severity in most cases, acneiform eruptions have disproportionate impact on quality of life compared to their clinical grading. 1 Key considerations include:

• Psychosocial impact: cosmetic disfigurement, low self-esteem, social isolation 1
• Treatment interruptions: 76% of oncologists report dose interruptions due to acneiform rash 1
• Treatment discontinuations: 32% of oncologists discontinue therapy due to rash severity 1
• Bacterial superinfection: occurs in up to 38% of cases 1
• Paradoxical prognostic indicator: rash severity correlates positively with anticancer therapy response 1

Important Distinguishing Features from Acne Vulgaris

Critical diagnostic clues that differentiate acneiform eruptions from true acne include:

• No comedones (primary distinguishing feature) 1
• Sudden onset within days rather than gradual development 2
• Occurrence beyond typical acne age 2
• Widespread involvement including unusual locations 2
• Monomorphous appearance of lesions 2
• Temporal relationship to medication initiation 2
• Clearing after drug discontinuation, sometimes leaving secondary comedones 2

Common Pitfalls

Do not mistake acneiform eruptions for drug hypersensitivity or allergy—this is a pharmacological effect, not an allergic reaction, and patients should continue necessary anticancer therapy with appropriate dermatological management rather than discontinuing potentially life-saving treatment 4.