Jurnal_DVE_ppt_Benito Gasperzzzzzzz.pptx

Acne

1. Benito Arino Gasperz 2023-84-118 dr. Rita Sugiono Tanamal , Sp.DVE Acne vulgaris: A review of the pathophysiology, treatment, and recent nanotechnology based advances

2. Journal

3. Background

4. Background Acne Vulgaris is a chronic inflammatory skin condition affecting the pilosebaceous follicles, impacting over 85% of teenagers and often continuing into adulthood, particularly in women. It is projected to affect 9.4% of the global population, ranking as the eighth most common skin disease. The condition leads to both inflammatory (papules, pustules, nodules, and cysts) and non-inflammatory lesions (open/blackheads and closed/whiteheads) on areas such as the face, neck, upper back, and chest. There are various forms of acne, including neonatal acne, work-related acne, and acne induced by medications. These forms resemble acne vulgaris but differ in clinical severity and accompanying symptoms. Acne is treatable but not curable and can cause scarring and pigmentation issues, leading to long-term treatment needs.

5. Background Research on Acne Treatment : There is growing interest in acne treatment regimens, with numerous studies addressing the disease's pathophysiology and therapy approaches . Recent Advances in Therapy : The latest developments involve combination therapies targeting multiple pathogenic factors behind acne. Topical retinoids , which normalize abnormal keratinization and have anti-inflammatory properties, are among the promising treatments . Treatment Overview : This article provides a clear overview of acne types, their pathogenesis, and detailed conventional treatment strategies . Emerging Treatments : The review highlights current trial-stage formulations and those commercially available, along with a discussion of recent advances and potential clinical studies in acne treatment.

6. Main Text

7. Main text There are various factors that play a role in pathogenesis of acne, including Genetics Environment Hormones Stress Smoking M edications , and Cosmetics This factors can cause or worsen acne vulgaris. Acne can lead to physical and emotional discomfort, as well as permanent scarring and psychological effects such as anxiety and depression.

8. Due to the mentioned factors, the pathogenesis of acne is multifactorial, involving four main causes: E xcessive sebum production H yperproliferation of Cutibacterium acnes (formerly known as Propionibacterium acnes) bacteria Abnormal hyperkeratinisation of pilosebaceous follicles Inflammatory mechanisms.

9. Excessive sebum production Increased sebum production in hair follicles, influenced by androgen hormones such as testosterone and Insulin Growth Hormone (IGH-1), is a major cause of acne formation. There is a clear correlation between increased sebum production and the severity and frequency of acne lesions, making this factor an important consideration for patients with acne vulgaris.

10. Abnormal hyperkeratinisation of pilosebaceous follicles In healthy follicles, keratinocytes are normally shed into the lumen, but in acne patients, keratinocytes undergo hyperproliferation and fail to shed properly. This leads to the accumulation of desquamated corneocytes , along with lipids and monofilaments, within the pilosebaceous follicle.

11. Hyperproliferation of Propionibacterium acnes Propionibacterium acnes (now known as Cutibacterium acnes ) is a major pathogen in the pathophysiology of inflammatory acne. This anaerobic, lipophilic, gram-positive bacterium colonizes sebaceous follicles due to their high sebum production and anaerobic environment. C. acnes releases lipase enzymes that metabolize triglycerides in sebum into glycerol and fatty acids, contributing to the formation of comedones and inflammation on the skin.

12. Inflammatory mechanisms When the immune system detects P. acnes , an inflammatory process begins. P . acnes induces inflammation by producing chemotactic agents like lymphocytes, neutrophils, and macrophages. This leads to follicle damage, rupture, and the release of bacteria, fatty acids, and lipids into the dermis, causing inflammatory lesions such as pustules, nodules, cysts, and papules. Non-inflammatory lesions are smaller and contain less pus. Neutrophils also produce reactive oxygen species (ROS), which damage the follicular epithelium and contribute to acne inflammation, triggering various types of inflammatory acne lesions.

13. DNA Methylation Under environmental stress, epigenetic modifications, which link genetics and the environment, can alter gene expression. DNA methylation, a widely studied form of epigenetic modification, has gained attention in dermatology due to its role in inflammatory skin diseases, autoimmune conditions, and cancer. DNA methylation has been shown to play a role in the pathogenesis of inflammatory skin diseases like hidradenitis suppurativa , atopic dermatitis, psoriasis, and other inflammatory skin disorders. Epigenetics is also important in the development of acne vulgaris, offering insights into molecular mechanisms and potential therapeutic approaches .

14. Types of acne lesion Acne vulgaris is the most common form of acne, accounting for 99% of all cases. It is divided into two types of lesions: non-inflammatory, which consists of open and closed comedones , and inflammatory, which includes papules, pustules, nodules, and cysts. Comedones are further categorized into closed comedones , also known as whiteheads, and open comedones , referred to as blackheads .

15. Blackhead A blackhead is a non-inflammatory acne lesion that forms due to the accumulation of excess oil and dead skin cells that clog the hair follicle. Blackheads are referred to as open comedones because the surface of the skin remains open and appears dark, typically black or brown. Blackheads are a mild form of acne that usually appear on the face, arms, chest, neck, back, and shoulders.

16. Whitehead A whitehead is a small bump and a non-inflammatory acne lesion that occurs when oil, bacteria, and skin cells clog the pores of the hair follicle. Whiteheads are called closed comedones because the bump is covered and appears white. Whiteheads can develop in various areas of the body, but they most commonly appear in the T-zone, which includes the nose, chin, and forehead .

17. Papules Inflammation is the skin's tissue response to bacteria, excess oil production, and excessive androgen activity, with symptoms such as swelling, warmth, redness, and pain. Lesions that experience inflammation are called papules and are considered a transitional stage between non-inflammatory and inflammatory lesions. Papules appear on the skin as small, pink bumps with a diameter of less than 5 mm and do not contain pus.

18. Pustules A pustule is a small bump and an inflammatory lesion that occurs due to clogged pores caused by excess oil and dead skin cells. Pustules contain fluid or pus in their center. They usually appear as white pimples surrounded by red and irritated skin. Pustules can develop in various parts of the body but are most commonly found on the shoulders, chest, back, face, neck, armpits, genital area, and hairline .

19. Nodules A nodular acne is a severe form of inflammatory acne that occurs when pores are clogged with bacteria, excess oil, and dead skin cells. This combination typically leads to whiteheads or blackheads, but if the infection penetrates deeper into the skin's surface, the pores and surrounding area become red, swollen, and form small bumps. Nodular acne cannot be treated with over-the-counter medications alone and can last for weeks or even months. Nodules are similar to papules, but they are larger, measuring about 5–10 mm in diameter, and often appear along the jawline or chin .

20. Cysts Cystic acne is a severe form of inflammatory acne that develops beneath the skin due to pores clogged with bacteria, dead skin cells, and oil. People with oily skin of all ages are more susceptible to this condition. Cysts typically appear as large, white or red lesions that are painful and contain pus, sometimes leading to scarring. Cystic acne can occur in various parts of the body, but it is most commonly found on the face, arms, shoulders, back, chest, and neck. Most individuals with cystic acne experience both inflammatory and non-inflammatory acne symptoms .

21. Prevalence of acne Acne vulgaris is the eighth most common skin disease globally, with a prevalence of 9.38%. Acne affects 35% to nearly 100% of teenagers, and in adults, the prevalence is 0.74 %. The higher prevalence in adults may be due to more healthcare visits and greater awareness. A high-glycemic diet may also contribute to acne prevalence. A study by Mohiuddin found that the prevalence of acne in Indonesia is relatively high, reaching around 87.5%. The Global Burden of Disease study shows a prevalence of 85%, with acne most commonly found in individuals aged 12-25 years. Acne typically begins during puberty or prepuberty at ages 12-15 and peaks in severity between 17-21 years, with 10% of cases occurring in the 35-44 age range .

22. Conventional medication for acne treatment

23. Conventional medication for acne treatment The primary goal of acne vulgaris treatment is to manage and treat existing lesions by controlling Sebum secretion Abnormal hyperkeratinization of the pilosebaceous follicles Propionibacterium infection . Therefore, the main treatment options include A nti-inflammatory Antibacterial Medications administered topically, systemically, or orally, as well as physical methods such as optical therapy, cryotherapy, comedo extraction, cryoslush therapy, and intralesional corticosteroids. On the other hand, combination therapy (topical and oral) is more effective in addressing acne pathogenesis.

24. Topical treatment Topical therapies have the advantage of applied directly to the affected area, reducing systemic absorption and increasing exposure to the pilosebaceous follicles. These treatments come in various forms such as creams, gels, lotions, solutions, and washes, and are typically used for mild to moderate acne. In addition to retinoids , antibiotics are also used topically. Skin irritation is a common side effect, and treatment can last 6–8 weeks or continue for years .

25. Retinoid Topical retinoid therapy is the most commonly used first-line treatment for both non-inflammatory and inflammatory acne. The primary goals of retinoids are to reduce sebum production, regulate comedo formation, repair damaged epithelial layers, treat hyperpigmentation and scarring, reduce the development of acne lesions, and control the growth of existing comedones . However, this therapy is a lengthy process that may take more than three months to heal acne. Drawbacks of topical retinoids include skin dryness and irritation. Tretinoin , Adapalene , and Tazarotene are frequently used as retinoids for acne treatment.

26. Trenitoin This is a vitamin A derivative with anti-inflammatory properties, commonly used alongside other retinoids in acne vulgaris treatment. It helps normalize the epithelial layer, preventing pilosebaceous unit blockage and reducing sebum production. Available as creams, gels, and ointments, it has been used topically for over three decades. Topical use has mild side effects, such as sun sensitivity and redness, while oral consumption for leukemia treatment may cause headaches, dry skin, hair loss, itching, and muscle pain .

27. Adapalene This topical retinoid is commonly used to treat mild to moderate acne. It offers more benefits compared to other retinoids like Tretinoin and Tazarotene and is considered the first-line therapy for acne treatment. It helps reduce follicular hyperkeratinization and inflammation caused by acne. Side effects are minimal, including redness, irritation, and itching of the skin .

28. Tazarotene Tazarotene is a newer topical retinoid used to treat acne vulgaris. It is considered a second-line treatment when tretinoin or adapalene fails. It helps reduce hyperkeratinization and hyperproliferation of Propionibacterium acnes in the patient's epidermal layer. Tazarotene is often combined with benzoyl peroxide or antibiotics to treat inflamed acne, as it also has anti-inflammatory properties. Combination therapy is more effective than monotherapy, though skin irritation and redness are common side effects .

29. Antibiotics Topical antibiotics are commonly used to treat mild to moderate inflammatory acne. They work by targeting P. acnes, reducing inflammatory lesions on the skin. However, not all topical antibiotics (like chloramphenicol and tetracycline) are effective for acne treatment due to ineffectiveness and undesirable side effects. Erythromycin and clindamycin are the most commonly used topical antibiotics. Using them in combination with benzoyl peroxide and topical retinoids is more effective in preventing bacterial resistance than monotherapy. When applied to the skin, topical antibiotics reduce P. acnes colonization and inflammation in acne patients .

30. Erythromycin Erythromycin is a topical antibiotic used to treat acne patients. When applied to the skin, it helps reduce P. acnes colonization in the pilosebaceous follicles and decreases inflammation. Researchers have observed that erythromycin has a 60% bacterial resistance rate, which is undesirable and may lead to the development of new topical antibiotics in the future .

31. Clindamycin Clindamycin is a semi-synthetic topical antibiotic used to treat acne patients. It has similar properties to erythromycin, inhibiting P. acnes on the skin surface and reducing inflammation. Monotherapy with topical antibiotics should be avoided for treating acne vulgaris, and combination therapy is encouraged for better results .

32. Combinational topical treatment Combination topical therapy offers many benefits compared to monotherapy. Other topical treatments used in combination therapy for acne include benzoyl peroxide , salicylic acid , niacinamide , azelaic acid , and dapsone .

33. Combinational topical treatment Benzoyl Peroxide (BPO) : Used for mild to moderate acne, BPO kills P. acnes by releasing oxygen. Combining it with antibiotics improves effectiveness. Side effects include itching and irritation. Salicylic Acid : Exfoliates the skin, keeping pores clear. It treats mild acne and may cause irritation or dryness. Niacinamide : Reduces sebum and inflammation, treating mild to moderate acne and helping with skin damage, redness, and wrinkles. Azelaic Acid : An antibacterial and anti-inflammatory agent, more effective in combination therapy. It can cause redness and irritation. Dapsone : Antibacterial and anti-inflammatory, effective for mild to moderate acne. It’s cost-effective but not a first-line treatment.

34. Systemic treatment Since microcomedones play a crucial role in the development of both inflammatory and non-inflammatory lesions, topical retinoids should be considered as first-line therapy for acne treatment. Oral systemic treatment is recommended when patients do not respond to topical treatments or when nodular lesions or scarring occur. Systemic treatment is essential for preventing social stigma and psychological distress in acne patients. Oral antibiotics , hormonal medications , and isotretinoin are the most commonly used systemic treatments for acne vulgaris .

35. Isotrenitoin Isotretinoin is the most recommended retinoid for systemic treatment and is a derivative of vitamin A. Previously, it was the only medication capable of suppressing acne long-term and was used as a first-line treatment for nodular or severe inflammatory acne. It is also used for patients with mild to moderate acne who previously failed to respond to oral or topical treatments. Isotretinoin is considered a first-line treatment for severe acne on the face and torso, acne that leaves scars, and acne causing psychological distress. Isotretinoin is the only available medication that addresses all four pathogenic causes of acne. It works by causing de-differentiation of sebaceous glands, leading to decreased sebum production and altering the skin's bacterial flora , which ultimately reduces P. acnes colonization in hair follicles. Keratinocytes are also affected as a result. The typical duration of isotretinoin therapy is 16-24 weeks , and due to its side effects, patients must be closely monitored.

36. Antibiotics Oral antibiotics are prescribed for moderate to severe, inflamed acne that resists previous topical treatments or affects large body areas. Common antibiotics include erythromycin, clindamycin, azithromycin, roxithromycin , fluoroquinolones (levofloxacin), tetracyclines (doxycycline, minocycline), and co- trimoxazole . These antibiotics suppress P. acnes growth and inflammation. Tetracyclines are widely used due to their anti-inflammatory and antibacterial properties, with doxycycline and minocycline preferred over tetracycline for better fat solubility and lower digestive discomfort. Long-term antibiotic use can lead to resistance , so combination therapy with topical agents like benzoyl peroxide or retinoids is recommended, limiting treatment to 12 weeks .

37. Hormonal medication Hormonal therapy is an alternative treatment for acne in adult women and adolescents. It targets androgen effects on sebaceous glands , which depend on androgens. Hormones are often given as oral contraceptive pills, which inhibit sebum production triggered by testosterone , increasing sex hormone-binding globulin and lowering active free testosterone in the body. Acne in women can be treated with oral contraceptives alone or in combination with other treatments. Hormonal effects are seen after 3-6 months, and treatment is recommended for at least 12 months. Spironolactone, an androgen receptor blocker , is combined with oral contraceptives to reduce acne-related inflammation in women .

38. Recent advancement and commercial products

39. Recent advancement and commercial products Recent advances in acne research focus on inhibiting mechanisms involved in acne formation, targeting receptors, cytokines, and pro-inflammatory mediators. Nutrition, skin microbiome, genetics, and follicular bacteria play key roles in acne therapy. Nitric oxide (NO)-releasing medications are a promising new strategy due to their anti-inflammatory, antibacterial, and antioxidant properties. Isotretinoin (ISO) is effective for long-term acne remission but has side effects, including teratogenicity and skin reactions. Combination therapy and dose adjustments are crucial to minimize side effects and improve treatment outcomes. Despite progress, few acne treatments have passed clinical trials, and most available treatments are either topical or systemic, with few combining both.

40. Conclusions

41. Conclusions Acne is a common inflammatory skin condition that often leads to depression and social embarrassment, especially in adults. The four main pathogenic factors play a crucial role in acne development, guiding researchers to create various treatments. To maximize the effectiveness of both existing and new treatments, a thorough understanding of the irritants that cause microcomedone formation and the transformation of non-inflammatory lesions into inflammatory ones is essential. Traditional treatments, such as topical, systemic, and physical therapies, are well-known, but resistance to drugs and antibiotics remains a challenge. Furthermore, monotherapy is insufficient for comprehensive acne treatment. As a result, dermatologists and other medical professionals continue to search for more effective drug candidates, innovative treatment methods, and combination therapies to better manage acne .

42. Thank You