14 - 78 - ACNE VULGARIS Flashcards
four key elements of pathogenesis of acne vulgaris:
(1) follicular epidermal hyperproliferation,
(2) sebum production,
(3) the presence and activity of Propionibacterium acnes, and
(4) inflammation and immune response.
Pathways of steroid metabolism.
* Dehydroepiandrosterone (DHEA) is a weak androgen that is converted to the more potent testosterone by 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD.
* 5-α Reductase then converts testosterone to dihydrotestosterone (DHT), the predominant hormonal effector on the sebaceous gland.
* The sebaceous gland expresses each of these enzymes.
* A, androstenedione; ACTH, adrenocorticotropin-stimulating hormone; DHEAS, dehydroepiandrosterone sulfate; DOC, deoxycortisol E, estrogen; FSH, follicle-stimulating hormone; LH, luteinizing hormone; T, testosterone.
Figure 78-7 Pathways of steroid metabolism. Dehydroepiandrosterone (DHEA) is a weak androgen that is converted to the more potent testosterone by 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD. 5-α Reductase then converts testosterone to dihydrotestosterone (DHT), the predominant hormonal effector on the sebaceous gland. The sebaceous gland expresses each of these enzymes. A, androstenedione; ACTH, adrenocorticotropin-stimulating hormone; DHEAS, dehydroepiandrosterone sulfate; DOC, deoxycortisol E, estrogen; FSH, follicle-stimulating hormone; LH, luteinizing hormone; T, testosterone.
Histopathology of acne vulgaris
The histopathology of acne vulgaris varies with the clinical lesion. Early lesions, microcomedones, demonstrate a dilated follicle with a narrow follicular orifice filled with shed keratinocytes. Closed comedones show increased distension of the follicle, creating a cystic space that contains eosinophilic keratinous debris, hair, and bacteria. Open comedones show enlarged follicular ostia, with atrophic or absent sebaceous glands. Only mild perivascular inflammation is present at this stage.
As the cystic structure enlarges, its contents begin to infiltrate the dermis, inducing an inflammatory response with neutrophils. If the lesion does not resolve, it may develop a foreign body granulomatous reaction or scarring.
CLINICAL COURSE AND PROGNOSIS
The typical age of onset of acne vulgaris varies considerably. It may start as early as 8 years of age or it may not appear until the age of 20 years or even later. The course generally lasts several years and is followed by spontaneous remission in most cases. Although the condition clears in the majority of patients by their early 20s, some have acne extending well into the third or fourth decades of life. The extent of involvement varies, and spontaneous fluctuations in the degree of involvement are the rule rather than the exception. In women, there is often variation in relation to the menstrual cycle, with a flare just before the onset of menstruation, especially in those older than 30 years of age. 108 Family history, body mass index, and diet may predict risk for development of moderate to severe acne. 109 Furthermore, prepubescent females with comedonal acne and females with high DHEAS levels are more likely to develop severe or long-standing nodular acne.
Tailoring a patient’s acne regimen with the knowledge of the pathogenesis of acne and the mechanism of action of the available acne treatments will ensure maximum therapeutic response. Treatment regimens should be initiated early and be sufficiently aggressive to prevent permanent sequelae. Often multiple treatments are used in combination so as to combat the various factors in the pathogenesis of acne (Table 78-2). The mechanism of action of the most common treatments for acne can be divided in the following categories as they relate to the pathophysiology:
- Correct the altered pattern of follicular keratinization.
- Decrease sebaceous gland activity.
- Decrease the follicular bacterial population, particularly P. acnes.
- Exert an antiinflammatory effect.
TOPICAL MEDICATIONS
U.S. Food and Drug Administration–Approved Oral Contraceptives for Acne in Women
should be considered in a female patient whose acne is severe, in the jawline or lower face distribution, sudden in onset, or associated with hirsutism or irregular menstrual periods
Hyperandrogenism
Other signs that may suggest a diagnosis of hyperandrogenism include deepening of the voice, an increase in libido, hirsutism, and acanthosis nigricans.
Proposed factors in keratinocyte hyperproiferation
- androgen stimulation
- decreased linoleic acid
- increased IL-1-a activity
- effects of P.acnes
What are the components of human sebum?
Human sebum are composed mainly of triglycerides found ubiquitously and of unique lipids, such as squalene and wax esters not found anywhere else in the body, including the surface of the skin
How does estrogen decrease sebum production?
The role of estrogen on sebum production is not well defined. The dose of estrogen required to decrease sebum production is greater than the dose required to inhibit ovulation. The mechanisms by which estrogens may work include:
(1) directly opposing the effects of androgens within the sebaceous gland,
(2) inhibiting the production of androgens by gonadal tissue via a negative feedback loop on pituitary gonadotropin release, and
(3) regulating genes that suppress sebaceous gland growth or lipid production.
What is The predominant cell type within 24 hours of comedo rupture?
lymphocyte
CD4 +lymphocytes are found around the pilosebaceous unit, and CD8 + cells are found perivascularly.
One to two days after comedo rupture, what cell becomes the predominant cell type surrounding the burst microcomedo?
neutrophils
Drug-induced acne may be caused by what medications
anabolic steroids, corticosteroids, corticotropin, phenytoin, lithium, isoniazid, vitamin B complexes, halogenated compounds, and certain chemotherapy medications, particularly with epidermal growth factor receptor (EGFR) inhibitors.
which OCPs exacerbate or induce acne vulgaris
Progestin-only contraceptives, including injectables and intrauterine devices
Women approaching or in menopause may be on hormone therapy, including progesterone, and some are treated with dehydroepiandrosterone (DHEA) or testosterone
narrow, deep scars that are widest at the surface of the skin and taper to a point in the dermis, typically less than 2 mm in diameter
Ice pick scars
wide sharply demarcated scars that do not taper to a point at the base and range in size from 1.5 to 4 mm
Boxcar scars
shallow, wide scars (often >4–5 mm) that have an undulating appearance
Rolling scars
another type of scar, which typically presents as atrophic soft papules on the upper part of the trunk
Perifollicular elastolysis
results in the formation of a microcomedo
Follicular epidermal hyperproliferation
what causes a microcomedo?
- Follicular epidermal hyperproliferation results in the formation of a microcomedo.
- The epithelium of the upper hair follicle, the infundibulum, becomes hyperkeratotic with increased cohesion of the keratinocytes, resulting in the obstruction of the follicular ostium, where keratin, sebum, and bacteria begin to accumulate in the follicle and cause dilation of the upper hair follicle, producing a microcomedo.
proposed factors in keratinocyte hyperproliferation
androgen stimulation, decreased linoleic acid, increased IL-1-α activity, and effects of P. acnes
- Dihydrotestosterone (DHT) is a potent androgen that may play a role in acne. DHT is converted from dehydroepiandrosterone sulfate (DHEA-S) by 17-β hydroxysteroid dehydrogenase (HSD) and 5-α reductase enzymes
- Compared with epidermal keratinocytes, follicular keratinocytes have increased 17-β HSD and 5-α reductase, thus enhancing DHT production
- DHT may stimulate follicular keratinocyte proliferation.
main component of sebum
triglycerides
- important in acne pathogenesis
- Triglycerides are broken down into free fatty acids by P. acnes, normal flora of the pilosebaceous unit.
- In return, these free fatty acids promote P. acnes colonization and induction of inflammation
- Lipoperoxides also found in sebum induce proinflammatory cytokines and activate the peroxisome proliferator-activated receptors (PPAR) pathway, resulting in increased sebum
P. acnes is generally believed to play a major role in the pathogenesis of acne vulgaris, in part by eliciting what?
eliciting a host inflammatory response
