Pathophysiology of Keratosis Pilaris
Keratosis pilaris results from abnormal follicular hyperkeratinization where keratin accumulates within hair follicles, creating characteristic folliculocentric keratotic papules, with genetic mutations in filaggrin (FLG) and ABCA12 genes playing a central etiologic role. 1, 2
Primary Pathogenic Mechanism
The fundamental defect in keratosis pilaris involves excessive keratin production and retention within the pilosebaceous unit 2:
- Keratin accumulation occurs within hair follicles, causing follicular plugging and the characteristic "plucked chicken skin" appearance 3
- The intracellular matrix becomes disrupted, preventing normal shedding of the horny layer of skin 4
- This creates folliculocentric keratotic papules with variable perifollicular erythema 1
Genetic and Molecular Basis
Inherited mutations drive the pathophysiology through specific biomolecular pathway disruptions 2:
- FLG gene mutations (encoding filaggrin protein) represent a primary inherited defect 1
- ABCA12 gene mutations have been implicated in disease development 1
- Aberrant Ras signaling has emerged as an important contributor to pathophysiology across keratosis pilaris subtypes 2
- The disorder represents a primary disorder of the pilosebaceous unit resulting from these inherited mutations or acquired disruptions 2
Association with Atopic Diseases
In individuals with atopic histories (eczema, asthma), the relationship is complex but not as direct as commonly assumed:
- Keratosis pilaris may be associated with ichthyosis vulgaris and palmar hyperlinearity, but is less likely directly associated with atopic dermatitis itself 1
- The genetic link appears stronger through shared filaggrin mutations rather than through atopic inflammation 1
- Atopic disease associations (hay fever, asthma, eczema) have been reported in some keratoconus literature, but this represents a different condition and should not be conflated with keratosis pilaris 5
Critical Pitfall to Avoid
Do not assume keratosis pilaris is simply a manifestation of atopic dermatitis—while both may share filaggrin gene mutations, keratosis pilaris is a distinct primary follicular disorder, not a secondary consequence of atopic inflammation 1, 2. The cosmetic appearance can cause psychosocial distress despite being asymptomatic, warranting treatment even in mild cases 6.
Histopathologic Features
The microscopic changes reflect the clinical presentation 2:
- Follicular hyperkeratosis with keratin plug formation
- Perifollicular inflammation in some variants (keratosis pilaris rubra)
- Disruption of normal follicular epithelial differentiation 2