Exploring Acne Treatments: From Pathophysiological Mechanisms to Emerging Therapies
Abstract
:1. Introduction
2. Pathophysiology of Acne
2.1. Genetic and Environmental Factors
2.1.1. Genetic Factors
2.1.2. Environmental Factors
2.2. Hormonal Influences
2.3. Microbiome
2.4. Inflammation
3. Current Treatment Strategies
3.1. Topical Treatments
3.1.1. Topical Retinoids
- First-Generation Retinoids
- b.
- Second-Generation Retinoids: There are no available second-generation topical formulations of retinoids.
- c.
- Third-Generation Retinoids
- d.
- Fourth-Generation Retinoids
3.1.2. Topical Benzoyl Peroxide
3.1.3. Topical Antibiotics
- (a)
- (b)
- Erythromycin: A possible alternative to clindamycin. However, concerns exist about higher rates of C. acnes resistance to topical erythromycin compared with clindamycin [126]. Therefore, it should be combined with other agents like BPO (Benzamycin®). Erythromycin is available as a monotherapy (gels, swabs, solutions). It is generally well tolerated, but can cause skin irritation [126].
- (c)
- Minocycline: A tetracycline derivative. Topical minocycline 4% foam (Amzeeq™) demonstrates greater effectiveness than its vehicle alone [140,141]. This lipophilic formulation readily moves into the pilosebaceous unit [142]. While its precise mechanism is not fully understood, its potent antibacterial effects are well documented [142]. Studies indicate effectiveness in improving acne within 12 weeks, with continued improvement observed at 52 weeks [142,143]. Minocycline foam is generally well tolerated in trials, with the most frequent side effects being increased creatinine phosphokinase levels and headaches [140,141]. Topical minocycline 4% foam for acne has received FDA approval but has not yet been approved in the EU.
3.1.4. Topical Azelaic Acid
3.1.5. Topical Salicylic Acid
3.1.6. Topical Dapsone
3.1.7. Topical Sulfur and Sodium Sulfacetamide
- (a)
- Sulfur: Exhibits mild antibacterial and keratolytic properties, helping loosen dead skin cells to prevent clogged pores [162]. Sulfur interacts with the cysteine within skin cells to form hydrogen sulfide, disrupting disulfide bonds for its keratolytic effect [163]. Newer nanoparticle preparations may offer enhanced effectiveness against Staphylococcus bacteria, a contributor to acne pathogenesis [164,165]. Sulfur on its own can treat mild to moderate acne, but its results are improved when combined with sodium sulfacetamide or BPO [166,167,168,169,170].
- (b)
- Sodium sulfacetamide: A bacteriostatic agent that disrupts bacterial DNA synthesis by inhibiting para-aminobenzoic acid [126]. Typically formulated as a topical lotion with 10% sodium sulfacetamide and 5% sulfur, it demonstrates significant acne lesion reduction (50–69% after 8 weeks; 78% after 12 weeks) [166,171].
3.1.8. Topical Clascoterone
Treatment Examples | Mechanism of Action | Indications | Common Side Effects | References |
---|---|---|---|---|
Retinoids (e.g., tretinoin, adapalene) | Normalizes follicular epithelial desquamation; anti-inflammatory | Mild to severe acne, depending on the formulation | Dryness, photosensitivity, initial acne flare-up | [3,103,104,105,106,107,108,109,111,112,113,114,115,116,120,122,123,124,125,126,177,178] |
Benzoyl peroxide | Kills bacteria; peels out the inner lining of the hair follicle, causing skin peeling | Mild to moderate acne | Dryness, irritation, potential bleaching of clothes | [130,131,132,133,134,135,136,138,146,179,180,181,182,183] |
Antibiotics (e.g., clindamycin) | Antimicrobial; reduces inflammation | Mild to moderate inflammatory acne | Skin irritation, resistance development | [126,135,139,140,141,142,143,144] |
Azelaic acid | Kills bacteria; normalizes keratinization; anti-inflammatory | Mild to moderate acne | Pruritus, burning sensation | [106,145,146,147,148] |
Salicylic acid | Helps break down blackheads and whiteheads; anti-inflammatory | Mild acne, comedonal acne | Skin irritation, dryness | [135,146,149,150,151,152] |
Sulfur and sodium sulfacetamide | Antibacterial and keratolytic effects | Mild to moderate acne, rosacea | Dryness, skin irritation | [126,162,163,164,165,166,167,168,169,170,171] |
Clascoterone (topical antiandrogen) | Blocks androgen receptors in the skin; reduces sebum production and inflammation | Moderate to severe acne | Local irritation, erythema | [173,174,175,176] |
Treatment | Formulation, Dose, Frequency | Common Side Effects | References |
---|---|---|---|
Tretinoin/Clindamycin | Gel 0.025%/1.2% daily | Xerosis, irritation, allergic contact dermatitis, erythema | [102] |
Tretinoin/Benzoyl peroxide | Cream 0.1%/3% once daily | Xerosis, irritation, allergic contact dermatitis, erythema | [127] |
Adapalene/Benzoyl peroxide | Gel 0.1%/2.5% once daily or 0.3%/2.5% once daily | Xerosis, irritation, allergic contact dermatitis, erythema | [102] |
Benzoyl peroxide/Clindamycin | Gel 5%/1% once daily or 3.75%/1.2% once daily or 2.5%/1.2% once daily | Xerosis, irritation, allergic contact dermatitis, erythema, bleaching of fabrics | [132,133,134] |
Benzoyl peroxide/Erythromycin | Gel 5%/3% once daily | Xerosis, irritation, allergic contact dermatitis, erythema, bleaching of fabrics | [138] |
Clindamycin/Benzoyl peroxide/Adapalene (IDP-126) | Gel 1.2%/3.1%/0.15% | Xerosis, irritation, allergic contact dermatitis, erythema | [128] |
Novel combined formulation in development: Minocycline/Adapalene (FCD105) | Foam 3%/0.3% | Xerosis, irritation, allergic contact dermatitis, erythema | [129] |
3.2. Systemic Treatments
3.2.1. Oral Antibiotics
3.2.2. Hormonal Therapies
3.2.3. Oral Retinoids
Treatment Examples | Mechanism of Action | Indications | Common Side Effects | References |
---|---|---|---|---|
Oral antibiotics (e.g., tetracycline, doxycycline) | Antimicrobial, reduce inflammation | Moderate to severe acne | Gastrointestinal upset, photosensitivity | [135,144,184,185,186,187,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206] |
Hormonal therapies (e.g., oral contraceptives, spironolactone) | Regulate hormonal imbalance, reduce sebum production | Hormonally influenced acne, adult women | Mood changes, breast tenderness, thrombosis risk | [135,146,207,208,209,210,211,214,215,217,218] |
Isotretinoin | Reduces sebaceous gland size and sebum production, anti-inflammatory | Severe scarring acne or acne not responsive to other treatments | Dryness, teratogenicity, elevated liver enzymes | [68,135,184,204,220,221,222,223,224,225,226,227,228,233,234,235,236,237,238,239,240,241,242] |
3.3. Procedural Therapies
Treatment Type | Mechanism of Action | Indications | Common Side Effects | References |
---|---|---|---|---|
Photodynamic therapy | Activates photosensitizing agents that kill bacteria and reduce sebum production | Severe acne, acne resistant to other treatments | Redness, swelling, skin sensitivity to sunlight | [246,248,249,250,251] |
Blue-light therapy | Kills C. acnes bacteria using blue light without damaging the skin | Mild to moderate acne | Temporary redness and dryness | [252,253,254,255] |
Chemical peel | Causes the top layer of skin to peel off, helps clear debris from pores | Mild to severe acne, depending on the peel’s strength | Redness, peeling, potential scarring | [126,263,270,271] |
Intralesional steroid injection | Anti-inflammatory action and decrease in sebum production | Moderate to severe acne | Local atrophy | [277] |
3.4. Diet Modifications
Supplement Examples | Mechanism of Action | Indications | Common Side Effects | References |
---|---|---|---|---|
Omega-3 fatty acids | Anti-inflammatory, modulates sebum production | Various acne types | Fishy aftertaste, gastrointestinal upset | [284,285] |
Vitamin D | Modulates immune system, may reduce skin inflammation | Various acne types | Rare, potentially increased calcium levels | [288,289,290,291,292,293] |
Zinc | Reduces inflammation and bacterial growth and modulates the immune system | Various acne types | Nausea, metallic taste | [69,286,294,295] |
4. Emerging Therapies
Therapy Type | Mechanism of Action | Result | References |
---|---|---|---|
Hyaluronic acid | Acts as a major component of the extracellular matrix, downregulating lipid synthesis in a dose-dependent manner through its interaction with cellular receptors. | Significantly decreases sebum production, improving skin hydration and reducing oily skin appearance. | [298] |
Cannabidiol | Interacts with the skin’s endocannabinoid system, helping to maintain skin health and function, while exerting anti-inflammatory and sebostatic properties. | Reduces inflammation and normalizes sebum production, leading to fewer acne outbreaks. | [299,300,301,302,303,304,305] |
Biologic treatments (e.g., TNF-α inhibitors like adalimumab; IL-17 and IL-23 inhibitors like secukinumab) | Modulates the immune response by targeting and inhibiting specific cytokines involved in inflammation. | Reduces inflammation and the severity of acne symptoms, improving the overall skin condition. | [85,306,307,308,309,310] |
Gut microbiome (microbial transplantation) | Transfers a healthy microbiome from a donor to an acne-prone recipient, fostering a microbial environment similar to that of individuals without acne. | The recipient’s skin microbiome adopts characteristics beneficial for preventing acne, reducing lesion formation. | [311] |
Topical probiotics | Promotes the production of antimicrobial substances from beneficial bacteria and competes with pathogenic microbes on the skin. | Reduces pro-inflammatory cytokine levels and acne severity, promoting a healthier skin barrier. | [312,313,314,315,316,317,318] |
Oral probiotics | Enhances the systemic immune function and modulates local inflammatory responses through increased levels of anti-inflammatory cytokines like IL-10. | Demonstrates a decrease in acne lesions and an overall improvement in skin clarity. | [319,320,321,322,323] |
Vaccines | Targets C. acnes and its virulence factors, like CAMP factor 2, to reduce microbial-induced inflammation. | Leads to a significant reduction in acne-related inflammation and lesion count. | [324] |
Bacteriophages | Specifically targets and kills C. acnes bacteria, thereby directly reducing the bacterial load and associated inflammation. | Early research suggests a potential reduction in acne severity and improved skin condition. | [325,326] |
Designed antimicrobial peptides (dAMPs) | Provides targeted antimicrobial activity against resistant strains of C. acnes, while also modulating the immune response. | Reduces acne outbreaks and severity through effective bacterial control and reduced inflammation. | [327,328,329,330,331] |
Phosphodiesterase (PDE) inhibitors | Increases the levels of cyclic adenosine monophosphate (cAMP), which leads to a decreased inflammatory response in the skin. | Shows promising reduction in inflammatory acne lesions, contributing to clearer skin. | [332,333] |
5. Optimal Therapeutic Strategies for Varied Acne Severities
5.1. Acne Severity Grading
5.2. Most Effective Treatment Combinations for Each Type
5.2.1. Mild to Moderate Acne
5.2.2. Moderate to Severe Acne
5.2.3. Severe, Nodular, or Treatment-Resistant Acne
6. Discussion and Conclusions
Funding
Conflicts of Interest
References
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Kim, H.J.; Kim, Y.H. Exploring Acne Treatments: From Pathophysiological Mechanisms to Emerging Therapies. Int. J. Mol. Sci. 2024, 25, 5302. https://doi.org/10.3390/ijms25105302
Kim HJ, Kim YH. Exploring Acne Treatments: From Pathophysiological Mechanisms to Emerging Therapies. International Journal of Molecular Sciences. 2024; 25(10):5302. https://doi.org/10.3390/ijms25105302
Chicago/Turabian StyleKim, Hyun Jee, and Yeong Ho Kim. 2024. "Exploring Acne Treatments: From Pathophysiological Mechanisms to Emerging Therapies" International Journal of Molecular Sciences 25, no. 10: 5302. https://doi.org/10.3390/ijms25105302