What comorbidities are associated with seborrheic keratosis?

Comorbidities Associated with Seborrheic Keratosis

Seborrheic keratosis (SK) is not meaningfully associated with systemic comorbidities and does not require screening for internal disease in routine clinical practice. The condition is a benign epidermal tumor with no established links to metabolic, cardiovascular, or inflammatory systemic conditions.

Malignancy Associations

The Leser-Trélat Sign

• The eruptive appearance of multiple seborrheic keratoses (Leser-Trélat sign) as a marker of internal malignancy is not supported by rigorous evidence. A large Swedish study of 1,752 consecutive SK cases found no significant association between eruptive SKs and internal cancer risk 1
• Among 62 patients with SK and malignancy diagnosed within one year, only 6 possibly presented with eruptive lesions; however, 5 of 62 age-matched controls without cancer also had eruptive-appearing SKs, demonstrating no meaningful difference 1
• The only statistically significant finding was a slight increased risk of cutaneous squamous cell carcinoma (relative risk 1.2), not internal malignancies 1

Pseudo-Leser-Trélat Sign

• Modern targeted cancer therapies, particularly EGFR tyrosine kinase inhibitors, can cause a pseudo-Leser-Trélat sign with eruptive SK-like lesions 2
• This represents a drug-induced phenomenon rather than a true paraneoplastic process 2
• EGFR inhibitors cause acneiform eruptions in seborrheic areas (scalp, face, neck, chest) in over 50% of patients, which may be confused with eruptive SKs 3

Dermatologic Associations

SKs have no established associations with other dermatologic conditions beyond coincidental occurrence. The evidence provided discusses seborrheic dermatitis and seborrheic blepharitis, which are entirely different conditions from seborrheic keratosis despite similar nomenclature.

Important Distinction

• Seborrheic dermatitis is an inflammatory condition associated with Malassezia fungal overgrowth, occurring in 95% of patients with seborrheic blepharitis 4
• Seborrheic keratosis is a benign epithelial tumor with no fungal etiology or inflammatory component 2, 5
• These conditions are not related and should not be conflated

Risk Factors for SK Development

Age and Sun Exposure

• SK incidence increases with age and cumulative ultraviolet light exposure 5
• The adenoid histologic subtype occurs more frequently in sun-exposed sites compared to sun-protected areas (p=0.028) 6
• This represents extrinsic skin aging rather than a systemic comorbidity 2

Genetic Factors

• Mutations in fibroblast growth factor receptor 3 (FGFR3) and other signaling molecules are frequent in SK lesions 2
• These mutations do not confer malignant potential or indicate systemic disease 2

Clinical Implications

No Screening Required

• Routine screening for systemic comorbidities in patients with SK is not indicated based on available evidence
• The presence of SK, even multiple lesions, does not warrant evaluation for internal malignancy unless other clinical features suggest cancer 1

Diagnostic Considerations

• Dermoscopy is the preferred method to differentiate pigmented SKs from melanoma and other pigmented lesions 2
• Biopsy should be performed for lesions in sun-exposed areas, as clinicopathological mismatch (including premalignant/malignant entities) occurs in 24.2% of cases, with significantly higher frequency in sun-exposed versus sun-protected sites (p=0.043) 6

Common Pitfall

The most important pitfall is confusing seborrheic keratosis with seborrheic dermatitis. The latter has multiple systemic associations (HIV, Parkinson's disease, Down syndrome, rosacea, dry eye) 4, 7, while seborrheic keratosis does not. This nomenclature similarity causes frequent clinical confusion but the conditions are pathophysiologically unrelated.