Acne: Causes, Symptoms and Skin Structure

• The skin consists of the epidermis and dermis, with the dermis containing hair follicles, erector pili muscles, and sebaceous glands.
• Hair is primarily found in thin skin.
• Sebaceous glands secrete sebum, which helps maintain the skin's surface as a biological barrier against germs.

Acne

• A chronic skin disease involving blockage and/or inflammation of pilosebaceous units.
• Acne mainly affects areas with a high density of sebaceous follicles like the face, upper chest, and back.
• Acne lesions can be non-inflammatory (microcomedones) or inflammatory (papules, pustules), or a mix of both.

Causes of Acne

• Hormonal imbalances (overproduction of male sex hormones)
• Bacterial infection
• Genetics
• Certain drugs (androgens, barbiturates)
• Environmental irritants (pollution, high humidity)
• Stress
• Cosmetic application
• Squeezing or picking at blemishes
• Hard scrubbing of the skin

Symptoms and Complications

• Seborrhea (scaly red skin)
• Comedones (blackheads and whiteheads)
• Inflammatory papules (pinheads)
• Nodules (large papules)
• Pimples
• Pain
• Post-inflammatory hyperpigmentation (PIH)
• Scarring
• Psychological and emotional distress

Types of Acne

• Comedonal acne: Open (blackheads) and closed (whiteheads) comedones without inflammatory papules or nodules.
• Mild acne: Comedones with occasional inflammatory lesions, mostly limited to the face.
• Moderate acne: Comedones, inflammatory papules, and pustules involving the face and trunk.
• Severe nodular acne: Comedones, inflammatory lesions, and large nodules (greater than 5 mm) on the face and trunk, potentially leading to scarring (nodulocystic acne).

Incidence

• Acne affects 9.4% of the global population.
• About 80% of young people aged 12 to 25 years are affected.
• 20–40% of cases persist into adulthood.
• Acne is associated with a higher prevalence of depression, insomnia, attention deficiencies, anxiety, and hyperactivity disorders.

Pathogenesis

• Multifactorial, with genetics playing a key role.
• Release of inflammatory mediators into the skin.
• Follicular hyperkeratinization and plugging of the follicle.
• Follicular colonization of Propionibacteria acnes.
• Excess sebum production.
• Inflammatory responses occur before hyperkeratinization.
• Cytokines and macrophages regulate inflammatory mediators.
• Follicular hyperkeratinization involves increased keratinocyte proliferation and decreased desquamation causing sebum and keratin-filled microcomedones
• Propionibacterium acnes (P. acnes) is an anaerobic organism present in acne lesions, promoting inflammation by activating monocytes and neutrophils, leading to the production of pro-inflammatory cytokines.
• Androgen hormones promote sebum production and release.
• The sebaceous gland acts as a neuroendocrine-inflammatory organ activated by corticotrophin-releasing hormones in response to stress.

Factors That Worsen Acne

• Menstrual cycle: Hormonal variations can worsen acne.
• Anxiety and stress: Alters hormone levels.
• Humid and hot climates: Increase sweating.
• Oil-based cosmetics: Clog skin pores.
• Greasy hair products: Similar effects to oil-based cosmetics.
• Squeezing pimples: Aggravates the problem and increases risk of scarring.
• Physical pressure: Can trigger localized acne.
• Food: No proven link to acne exacerbation.

Acne Assessment

• Lesion counting: Counting open and closed comedones, papules, pustules, and nodules.
• Photographic method: Comparing patient photos with a photographic standard.
• Clinicians can assess treatment response by grading and classifying acne based on number and type of lesions, disease severity, anatomical sites, scarring, and quality of life (QOL).

Diagnosis

Scales for grading acne severity

• Cook's acne grading scale: Uses photographs to grade severity from 0 to 8 (least to most severe).
• Leeds acne grading technique: Counts acne lesions on the face, back, and chest, categorizing them as inflammatory or non-inflammatory, with scores ranging from 0 to 10 (or 12 in modified scales).
• The Pillsbury acne grading scale: Classifies acne severity from 1 (least severe) to 4 (most severe).
• Investigator's Global Assessment: Graded from clearance to worst.

Korean acne grading system

• Based on the number of papules or nodules using a seven-point severity scale.
  • Grade 0: No papules or nodules.
  • Grade 1: Fewer than 10 papules.
  • Grade 2: 10-30 papules.
  • Grade 3: More than 31 papules or less than 10 nodules.
  • Grade 4: 11-20 nodules.
  • Grade 5: 21-30 nodules.
  • Grade 6: More than 31 nodules.

High-frequency ultrasonography

• Useful tool for acne scar assessment.

Acne Treatment

Topical Therapy

• Includes benzoyl peroxide (2.5-10%) in washes, lotions, creams, and gels. Does not cause bacterial antibiotic resistance.
• Topical salicylic acid and topical retinoids (tretinoin, isotretinoin) are also used.
• Combination therapy (topical retinoid with topical antimicrobial) is effective in reducing inflammatory and non-inflammatory lesions.

Systemic therapy

• Suitable for moderate to severe inflammatory acne.
• Oral antibiotics like tetracycline are used.
• Isotretinoin is an oral retinoid effective for severe nodular acne, requiring one to two months of therapy; 20% of people need a second course.
• Women of childbearing age must have a negative pregnancy test and use effective birth control during isotretinoin therapy.

Hormonal Therapy

• Aims to prevent androgen effects on the sebaceous gland and follicular keratinocytes.
• Oral anti-androgens like spironolactone can be useful.

Physical Treatment

• Comedones can be removed mechanically with a comedone extractor, fine needle, or pointed blade.
• Topical retinoid application beforehand can make the procedure easier.
• Laser puncture of macrocomedones can also be performed.

Acne and Diet

• Dietary restriction has not been proven beneficial in treating acne.

Phototherapy

• An alternative therapeutic modality with fewer side effects compared to other treatments.
• Visible light (blue, red, or a combination) is used.

Mechanism of Action of Light-Based Therapies

• Decrease Propionibacterium acnes levels and reduce pilosebaceous unit size and function.
• Blue light (407–420 nm) is absorbed by porphyrins produced by P. acnes, causing a photochemical reaction that forms reactive free radicals and singlet oxygen species, leading to bacterial destruction. Blue light also has anti-inflammatory effects on keratinocytes.
• Red light (630-660 nm) penetrates deeper and affects sebum secretion and keratinocyte behavior. Red light can also modulate cytokines, reducing inflammation.
• Mixed light can have synergistic effects due to the antibacterial and anti-inflammatory effects of blue and red light, respectively.
• Short pulsed 1064-nm Nd:YAG laser and 1450-nm diode laser are safe for treating mild to moderate post-acne atrophic scars.

Phototherapy Parameters

• Blue and blue-red light are most effective for mild to moderate inflammatory acne lesions.
• Power: 12 J/cm2.
• Duration: 15-20 minutes per session, twice a week.
• Sessions: 8-12 sessions, depending on case severity.
• Combining light therapy with agents like topical retinoids may be more effective.

Complications of Light and Laser-Based Therapies

• Light- and laser-based treatments are generally safe when performed by trained professionals.
• Immediate post-treatment effects like mild-to-moderate pain, erythema, or minimal edema are transient and resolve spontaneously.

Ultrasound Therapy

• Applied to treat various skin conditions, including wounds, inflammatory disorders, and esthetic problems.
• Improves skin laxity, body contouring through fat reduction, and has anti-aging effects by restoring the skin barrier.
• Increases epidermal permeability by enlarging spaces between keratinocytes, which cleans the microenvironment and promotes epidermal recovery.
• Due to phonophoresis, it can be used with topical anti-erythema medication.

Application of Ultrasound

• Impulse mode dual-frequency ultrasound (1/3 MHz) at 1.0 W/cm improves skin hydration and reduces erythema.
• Combined treatment of ultrasound and lysozyme-shelled microbubbles reduces treatment duration and inhibits Propionibacterium acnes-induced inflammatory skin diseases.
• Lysozyme has antimicrobial and anti-inflammatory properties.