Acne is an extremely complex disease with an interplay of multiple pathogenetic factors that involve abnormalities in epidermal keratinization, androgen secretion, increased sensitivity to circulating androgens, sebaceous function, bacterial growth, inflammation, and immunity. There are four basic mechanisms involved in the pathogenesis of acne vulgaris:
1. Hyperkeratinization of the sebaceous duct.
2. Colonization with Propionibacterium acne (P. acne).
3. Increased sensitivity to circulating androgens.
4. Inflammation.
Acne begins in the pilosebaceous follicle that has a small pilary structure and a large sebaceous gland. The follicular canal is composed of two portions, the superficial upper section, the acroinfundibulum that is structurally similar to the epidermis and the lower infrainfundibulum. The earliest event is the formation of the microcomedo, which is clinically unapparent, but gives rise to inflammatory acne. Defective desquamation of
the infrainfundibular portion of the follicular lining results in the epithelium coming off in sheets instead of shedding as fine particles. These are incapable of exiting through the follicular orifice. This results in a plug of keratinous material which distends the sebaceous follicle, forming a comedone. Comedogenesis is thus the accumulation of corneocytes in the pilosebaceous duct. This could be due to either hyperproliferation of ductal keratinocytes, inadequate separation of the ductal corneocytes (increased stickiness) or a combination of both factors.
Androgens also play a role in comedogenesis. The enzyme 5 alpha-reductase (type 1) is present in the infrainfundibulum part of the duct and the sebaceous gland. Antiandrogen therapy results in decreased comedogenesis.4 The microcomedo may stay as it is, may resolve spontaneously with the hair cycle, enlarge
into a closed or open comedone or it may become an inflamed acne lesion, from which scarring is more likely.
The trigger for the inflammation of the microcomedo is the Propionibacterium acnes (P. acne), which resides in the microcomedo and activates the inflammatory and immune responses. Greater the immunity, greater is the inflammatory response and higher chances of scarring. Inflammation plays a major role in the development of lesions and in acne scarring. In fact evidence is emerging that subclinical inflammation occurs even before comedo formation and acne is primarily a cronic inflammatory disease. Recent reports have shown that P. acne activate the toll-like receptor 2 on monocytes and neutrophils, which leads to the production of multiple proinflammatory cytokines, including IL-12, IL-8, and tumor necrosis factor.5 The process of inflammation leads to a rupture of the follicular wall, with inflammation extending into the dermis. Acne scar begins when noninflammatory comedone evolves into an inflammatory lesion and begins the process of wound healing in the dermis.
Phases of Wound Healing:
The wound healing process has three primary phases
1. Phase of inflammation.
2. Phase of proliferation.
3. Phase of maturation or remodeling.
The three phases of wound healing are overlapping. This multistep process is regulated by several cytokines that include epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), basic fibroblast growth factor (bFGF), mitogenactivated protein kinases (MAPs), and metalloproteinases (MMPs). Sato et al have reported that P. acnes not only facilitate sebum production in the sebaceous gland, but also augment the formation of acne scars due to enhanced extracellular matrix degradation by augmenting the expression of proMMPs-1 and -9 in human monocytes and that of proMMP-2 in human dermal fibroblasts.
Phase of inflammation lasts from 24 to 48 hours and may persist up to 2 weeks in some cases. It is characterized by erythema. Platelets, neutrophils and macrophages release cytokines and control this process.
In the phase of proliferation there is cellular migration and proliferation, re-epithelialization, angiogenesis and fibroplasia.
Epidermal repair takes place by migration of adjacent keratinocytes into the wound and their proliferation and differentiation in order to restore an intact stratified epidermis.
This usually takes 24 to 48 hours. Dermal repair begins 3 to 4 days after injury or disease and is characterized by granulation tissue formation which includes new blood vessels (angiogenesis) and
accumulation of fibroblasts and ground substance (fibroplasia).
The fibroblasts synthesize various proteins like collagen, proteoglycan, fibronectin and elastin, which help in forming the extracellular matrix. Collagen synthesis continues at a maximal rate for 2 to 4 weeks and slows down subsequently.
The phase of remodeling, starts approximately 21 days after injury and it involves the degradation and reorientation of the collagen fibers. This remodelling of collagen, which is the last step in tissue repair, is modulated by matrix metalloproteases (MMPs),which cause the damage, and tissue inhibitors of metalloproteases (TIMPs), which contain the damage. When the ratio of MMPs/TIMPs is low, atrophic scars occur and, conversely, when the ratio is high, hypertrophic scars occur. This phase continues for months to a year to form a mature scar. An early immature scar appears red due to dense capillary network
following inflammation, and as it matures, capillaries regress, the redness reduces and the actual color of the scar becomes evident.
An older or mature scar may be hypopigmented or normal skin colored. In darker skins and patients who have excessive sun exposure, the scars commonly get hyperpigmented and tend to be persistent. Therefore it is important to protect the early scars from sun exposure to prevent darkening. An inadequate response to tissue repair results in diminished deposition of collagen and formation of an atrophic scar while an exuberant
response results in a hypertrophic scar. In acne, atrophic scars are more common as compared to hypertrophic scars.