L-9 Acne Obed

• Acne is a chronic inflammatory disease of the pilosebaceous follicle.
• The goals of the lecture are natural history, etiology, evaluation, mitigating factors, treatment, and damage control.

Acne Epidemiology

• 85% of people ages 12-24 are affected
• Continues into adulthood in up to 35% of patients.
• $2.5 billion are spent annually in the US.

Acne Pathogenesis:

• Acne is a multifactorial disorder, seen in areas with well-developed sebaceous glands.
• Key factors in pathogenesis:
  • Keratinocyte proliferation
  • Excessive sebum production
  • Cutibacterium acnes

Acne: Hyperkeratosis

• Defined as the hyperproliferation and abnormal differentiation of keratinocytes.
• Excessive and retained keratinocytes block the follicular opening, leading to entrapped sebum.
• Excessive sebum dilates the lower part of the follicle, resulting in the discharge into the dermis.

Acne: Sebum Production

• Sebum production is controlled by hormonal stimulation and fluctuates throughout life.
• DHEA and DHEAS are elevated during the first 6-12 months of life due to the androgen-producing fetal zone of the adrenal gland, which involutes over the first year of life.
• Testicular androgen production decreases substantially during the first year of life and remains stable until adrenarche.

Acne: Hormonal Influences

• Adrenarche is associated with elevated adrenal production DHEAS, serving as a precursor for the synthesis of more potent androgens within the sebaceous gland.
• Hormonal elevation in prepubescent children leads to an increase in sebum production, leading to comedonal acne.

Acne: Cutibacterium Acnes

• This gram-positive non-motile rod is found deep within the sebaceous follicle.
• Pathogenicity stems from several properties:
  • Release of enzymes and chemotactic factors.
  • Stimulation of the host response

Acne: Dietary Factors

• Multiple dietary factors play a role in the pathogenesis of acne.
• Milk can play a factor, the hormonal constituents may be sufficient to have biologic effects.
• Diets with a high glycemic index cause hyperinsulinemia, triggering a hormonal response which promotes unregulated tissue growth and enhanced androgenic synthesis.
• Obesity may be accompanied by peripheral hyperandrogenism, leading to increased sebum production.
• Smoking risks alteration of the skin microcirculation, keratinocytes, elastin, and collagen decrease the amount of antioxidants, causing alterations in sebum production.
• Improved acne has been noted with consumption of fish, specifically white fish, green fish, or blue tuna.

Acne: Clinical Features

• Closed comedones (whiteheads) are small skin-colored papules with no apparent follicular opening or associated erythema.
• Open comedones (blackheads) are dome-shaped papules with conspicuous dilated follicular openings filled with a core of keratin.
• Melanin deposition and lipid oxidation are common and responsible for the seen discoloration.
• Inflammatory acne originates with comedo formation, results in the development of papules, pustules, nodules, and cysts.

Acne: Evaluation

• History is taken along with physical examination of the acne patient.
• History includes sex, age, motivation, lifestyle/hobbies, occupation, current and previous treatments, use of cosmetics, sunscreens, cleansers, moisturizers, menstrual history, medications such as corticosteroids, oral contraceptives, anabolic steroids, other e.g. lithium, EGFR inhibitors, and any concomitant illnesses.
• Physical examination looks for skin type, skin color/phototype, distribution of acne, face, neck, chest, back, upper arms, overall degree of involvement, lesion morphology such as comedones, inflammatory papules, pustule, cysts, sinus tracts, scarring, pitted, hypertrophic, atrophic, and postinflammatory pigmentary changes

Acne Variants

• Neonatal acne occurs in more than 20% of healthy newborns, lesions typically appear around 2 weeks of age and resolve within the first 3 months. Classic lesions are small, inflammatory papules and pustules primarily on the cheeks and nasal bridge.
• Acne presenting at 3-12 months of age (as late as 18-24 months) is classified as infantile, in contrast to neonatal acne, comedo formation is prominent and pitted scarring can develop. Comedo formation is prominent and pitted scarring can develop, the pathogenesis reflects androgen production, including the elevated levels of LH stimulating testicular production of testosterone during the first 6-12 months of life and elevated DHEA produced by the infantile adrenal gland. Infantile acne typically resolves within 1-2 years of age as androgen levels decrease, but may persist.

Acne Treatment

• Early treatment is essential to prevent permanent cosmetic disfigurement.
• Erythema and post-inflammatory hyperpigmentation often persist after the acne lesions have resolved.
• Common topical therapies: benzoyl peroxide, antibiotics include clindamycin & erythromycin, sodium sulfacetamide/sulfur, retinoids, salicylic acid, azelaic acid, and dapsone.
• Common systemic therapies: oral minocycline, oral doxycycline, oral tetracycline, oral erythromycin, oral azithromycin, oral contraceptives, oral spironolactone and oral isotretinoin.
• Anti-acne activity of topical retinoids involves normalization of follicular keratinization and corneocyte cohesion. Topical retinoids have anti-inflammatory properties which can be used as monotherapy for both types of acne as well as mild inflammatory components.
• Topical antibiotics and benzoyl peroxide are enhanced by increasing the penetration of these medications into the follicle.

Acne Treatment: Antibacterial Agents

• Benzoyl peroxide reduces P. acnes within the follicle, also has comedolytic properties effective when used in combination with topical treatments. Microbial resistance has not been reported.
• Topical antibiotics are widely used alone or in conjunction with products, some commonly used antibiotics are clindamycin and erythromycin.
• Azelaic acid inhibits protein synthesis of P. acnes, it also reverses hyperkeratosis of the hair follicles, decreasing microcomedo formation.
• Dapsone is a bacteriostatic agent inhibiting folic acid synthesis.
• Winlevi binds and inhibits androgen receptors, decreasing sebum.
• Combination topical products include Epiduo, Ziana, Veltin, Acanya, Onextin, and Twyneo.
• Oral tetracycline derivatives, particularly doxycycline and minocycline, and less often macrolides suppress the growth of P. acnes and thus the production of multiple inflammatory factors. Oral antibiotics have intrinsic anti-inflammatory properties which aid in decreasing disease severity.
• Guidelines suggest shortening antibiotic therapy and using topical retinoid therapy for maintenance.
• Antibiotic courses of 3-6 months are considered in line with guidelines.
• Preferred PO antibiotics and dosing include:
  • Doxycycline 20mg-100mg QD-BID
  • Minocycline 50mg-100mg QD-BID
  • Erythromycin 250mg-500mg BID-QID
  • Sarecycline 60mg-150mg QD
  • Clindamycin 150mg-300mg TID
  • Trimethopirm 300mg BID
  • Amoxicillin 250mg-500mg BID-TID
• Blue pigmentation of the teeth and nails occurs due to Minocycline.

Acne Treatment: Hormonal Therapy

• Hormonal therapy has been established as second-line therapy for female patients with acne.
• Hormones block both ovarian and adrenal production of androgens, which are linked to the pathophysiology of acne.
• Antibiotics were more effective at 3 months but at 6 months, both antibiotics and OCP's offered equal reduction in the total number of lesions compared to placebo.
• FDA approved for acne vulgaris:
  • Ortho-Tri-Cyclen
  • Estrostep
  • Yaz/Loryna/Beyaz

Acne Treatment: Isotretinoin

• Retinoids are structural and functional analogues of vitamin A with multiple effects on cellular differentiation and proliferation, the immune system, and embryonic development.
• Oral retinoids induce long-term remission of acne.
• Dosing: 0.5mg-2mg divided BID dosing Doses as low as 0.1mg/kg/day were nearly as effective but were unlikely to produce prolonged remission.
• To obtain the greatest chance of prolonged remission, patients should receive 120-150mg/kg over their treatment course.
• Systemic retinoid therapy requires careful patient selection and monitoring due to potential teratogenicity and toxicity.
  • Hyperlipidemia
  • Transaminasemia
  • Ocular abnormalities
  • Endocrinologic abnormalities
  • Hematologic abnormalities