What is the pathogenesis and etiology of acne?

Pathogenesis and Etiology of Acne

Acne vulgaris is a multifactorial inflammatory disease of the pilosebaceous follicles involving four key pathogenic factors: follicular hyperkeratinization, increased sebum production, Cutibacterium acnes (formerly Propionibacterium acnes) colonization, and complex inflammatory mechanisms. 1

Key Pathogenic Mechanisms

1. Follicular Hyperkeratinization

• Abnormal desquamation of follicular epithelium leads to obstruction of the pilosebaceous canal 2
• Follicular keratinocytes in comedones possess increased numbers of desmosomes and tonofilaments at the ultrastructural level 3
• This ductal hypercornification results in microcomedone formation, the precursor to all acne lesions

2. Sebum Production

• Androgen-stimulated sebaceous gland secretion plays a critical role 1
• Isotretinoin's therapeutic effect is partly through inhibition of sebaceous gland function and reduction in sebum secretion 4
• Sebum creates an environment favorable for C. acnes proliferation
• Hormonal factors influence sebum production:
  • Androgens stimulate sebaceous gland activity 1
  • Insulin and insulin-like growth factor-1 contribute to sebaceous gland stimulation 5
  • In women, polycystic ovarian syndrome (PCOS) is a common cause of elevated androgens leading to acne 1, 6

3. Microbial Colonization

• C. acnes (formerly P. acnes) is a Gram-positive anaerobic rod implicated in acne pathogenesis 1
• Some C. acnes strains are pathogenic while others are commensal in the skin 1
• C. acnes produces several proinflammatory mediators:
  • Lipases, proteases, and hyaluronidases 7
  • Chemotactic factors that promote leukocyte migration 3
• Antibiotics used in acne treatment have both antimicrobial and anti-inflammatory effects 1

4. Inflammatory Mechanisms

• Inflammation involves both innate and acquired immunity 1
• C. acnes activates toll-like receptors (TLRs) and CD14 on keratinocytes and sebocytes 7
• Inflammasome activation occurs in early stages of inflammation 5
• Neutrophils and macrophages infiltrate around hair follicles in inflamed lesions 3
• Proinflammatory lipid profile contributes to inflammation 5

Additional Contributing Factors

Genetic Factors

• Family history of acne is a risk factor for acne development 1

Neurogenic Factors

• Stress can exacerbate acne through neurogenic pathways 3
• Substance P, which can be elicited by stress, promotes both proliferation and differentiation of sebaceous glands 3

Hormonal Imbalance

• In women with irregular periods and acne, hormonal testing may reveal:
  • Elevated LH/FSH ratio (>2) suggesting PCOS 6
  • Elevated testosterone (>2.5 nmol/l) common in PCOS 6
  • Reduced insulin sensitivity (glucose/insulin ratio >4) 6

Clinical Implications

• Understanding these pathogenic factors guides rational therapy targeting specific mechanisms:

  • Retinoids address follicular hyperkeratinization 1, 2
  • Hormonal therapies target sebum production 1, 6
  • Antimicrobials address C. acnes colonization 1, 8
  • Anti-inflammatory agents target the inflammatory cascade 1

• Acne can cause significant physical and psychological morbidity:

  • Permanent scarring
  • Poor self-image
  • Depression and anxiety 1
  • The health-related quality of life impact is comparable to chronic conditions such as asthma, psoriasis, and arthritis 1

Common Pitfalls in Diagnosis and Management

• Overlooking hormonal causes, particularly PCOS in women with both acne and menstrual irregularities 6
• Focusing only on acne treatment without addressing underlying hormonal causes 6
• Ordering unnecessary microbiologic testing, which is not recommended by guidelines except when Gram-negative folliculitis is suspected 1, 6
• Not recognizing the psychological impact of acne, which can be severe and comparable to chronic diseases 1

By understanding these pathogenic mechanisms, clinicians can implement targeted therapeutic approaches addressing the specific factors contributing to acne development in individual patients.