What causes acne?

Causes of Acne Vulgaris

Acne vulgaris is caused by a multifactorial pathogenesis involving follicular hyperkeratinization, sebum production, Cutibacterium acnes (formerly Propionibacterium acnes) colonization, and inflammatory mechanisms affecting the pilosebaceous follicles of the skin. 1

Primary Pathogenic Factors

• Follicular hyperkeratinization: Abnormal keratinization of the pilosebaceous duct leads to obstruction of sebum outflow, forming microcomedones that are the precursors to all acne lesions 2

• Increased sebum production: Stimulated primarily by androgens, excessive sebum creates an environment favorable for bacterial proliferation 1

• Microbial colonization: Cutibacterium acnes, a Gram-positive anaerobic rod, proliferates in the obstructed follicle and contributes to inflammation 1, 3

• Inflammatory response: Complex inflammatory mechanisms involving both innate and acquired immunity lead to the development of inflammatory lesions 1, 2

Hormonal Influences

• Androgens: Play a central role in sebum production and acne development through:

  • Stimulation of sebaceous gland activity 4
  • Local amplification of androgenic activity within sebaceous glands 5
  • Increased sensitivity of sebaceous glands to normal androgen levels 6

• Other hormones that influence sebum production include:

  • Growth hormone
  • Insulin-like growth factor-1
  • Insulin
  • Corticotropin-releasing hormone
  • Glucocorticoids 7, 4

Risk Factors

• Genetic predisposition: Family history is a significant risk factor for acne development 1, 5

• Age: Increasing age during adolescence (affects approximately 85% of teenagers) 1, 7

• Oily skin type: Contributes to excess sebum production 1

• Hormonal disorders: Conditions like polycystic ovarian syndrome, Cushing syndrome, congenital adrenal hyperplasia, and androgen-secreting tumors can exacerbate acne 7, 4

• Medications: Certain drugs can trigger or worsen acne, including:

  • Testosterone
  • Progesterone
  • Corticosteroids
  • Lithium
  • Phenytoin
  • Isoniazid
  • Vitamins B2, B6, and B12
  • Halogens
  • Epidermal growth factor inhibitors 7

Pathophysiological Sequence

1. Initial phase: Increased sebum production and follicular hyperkeratinization lead to microcomedo formation 2, 6

2. Progression: Obstruction of the follicular canal creates an environment favorable for C. acnes proliferation 5

3. Inflammatory response: C. acnes triggers inflammation through:

   • Production of inflammatory enzymes
   • Activation of innate immunity
   • Recruitment of inflammatory cells 2, 6

4. Clinical manifestation: Development of comedones, papules, pustules, or nodules depending on the severity of inflammation 1

Clinical Impact

• Psychological effects: Acne can cause significant psychological morbidity, including depression, anxiety, poor self-image, and suicidal ideation 1

• Physical consequences: Permanent scarring may occur, particularly with more severe inflammatory acne 1

• Economic burden: The direct cost of acne is estimated to exceed $3 billion per year in the US alone 1

Understanding these pathogenic factors is essential for developing effective treatment strategies that target the multiple aspects of acne development 2.