Pathogenesis

Acne severity is directly related to the secretion of sebum - a higher rate causes more irritation of the duct and subsequently, increased keratin production. Release of pilosebaceous contents into the surrounding dermis triggers the inflammatory response.

This may be further aggravated by the release of exo-enzymes from the anaerobic bacterium, Propionobacterium acnes, commonly found in large quantities in the sebaceous glands of susceptible patients. (1)

Lesions result from obstruction of the pilosebaceous follicle due to increased production of the keratinised epithelium lining the duct. The cells become more cohesive and form an organised keratotic plug which seals off the duct.

This plug may then dilate the pilosebaceous orifice and be extruded onto the skin - the open comedo or blackhead; or the wall of the duct may rupture with release of the contents into the dermis - the closed comedo or whitehead (2).

Four pathophysiological processes occur to produce acne: (1,2)

• androgen driven increase in sebum production
  
  
• blockage of the sebaceous follicle by keratin and sebum
  
  
• colonisation of the follicle with Propionibacterium acnes
  
  
• inflammation

Increased androgen production causes abnormal epithelial desquamation and follicular obstruction leading to formation of the micro-comedone, the precursor lesion in acne, invisible to the naked eye. (2)

• androgens also promote sebum production, causing the obstructed follicles to fill with lipid rich material forming visible open and closed comedones
  • the increased incidence at puberty may be associated with elevated levels of androgenic hormones which control the activity of the sebaceous glands
  • serum testosterone, progesterone, glucocorticoids, insulin and insulin-like growth factors are often increased in patients with acne vulgaris and serum oestrogen levels can be low (3)
    
    
• sebum promotes bacterial growth, leading to proliferation of P acnes
  • Propionobacterium acnes, commonly found in large quantities in the sebaceous glands of susceptible patients (4)
  • releases chemicals that promote inflammation, propagated by traumatic rupture of comedones into the surrounding dermis (2)
  • inflammation presents in the form of papules, pustules, nodules and cysts
  • other local commensals - Staphylococcus epidermis and Pityrosporum ovale - may have a pathogenic role (4)
    
    
• acne severity is directly related to the secretion of sebum - a higher rate causes more irritation of the duct and subsequently, increased keratin production (4)

A family history of severe acne increases its likelihood in subsequent generations (5) and the concordance rate for the prevalence and severity of acne among identical twins is high (6)

Diet, sunlight and skin hygiene have been linked to acne, but there is little evidence relating to these (7)

There is a significant dose dependent association between smoking and acne severity (8)

High serum dehidroepiandrosterone (DHEA) and increased insulin resistance might explain the increased prevalence of acne in polycystic ovary syndrome. (9)

References:

1. Corvec S, Dagnelie MA, Khammari A, et al. Taxonomy and phylogeny of cutibacterium (formerly propionibacterium) acnes in inflammatory skin diseases. Ann Dermatol Venereol. 2019 Jan;146(1):26-30.

2. Cunliffe WJ, Holland DB, Clark SM, et al. Comedogenesis: some new aetiological, clinical, and therapeutic strategies. Dermatology. 2003;206(1):11-6.

3. Arora M. et al. Role of hormones in acne vulgaris. Clin Biochem. 2011 Sep;44(13):1035-1040

4. Bhate K, Williams HC. Epidemiology of acne vulgaris. Br J Dermatol. 2013 Mar;168(3):474-85

5. Zaenglein AL. Acne vulgaris. N Engl J Med. 2018 Oct 4;379(14):1343-52.

6. Common JEA et al. What does acne genetics teach us about disease pathogenesis? Br J Dermatol. 2019 Oct;181(4):665-676.

7. Magin P et al. A systematic review of the evidence for 'myths and misconceptions' in acne management: diet, face-washing and sunlight. Fam Pract 2005;22:62-70.

8. Dawson A, Dellavalle RP. Acne Vulgaris. Clinical Review. BMJ 2013; 346:2634

9. Tehrani F et al. Prevalence of acne vulgaris among women with polycystic ovary syndrome: a systemic review and meta-analysis. Gynecol Endocrinology 2021 May;37(5):392-405.