Acne Vulgaris Xử trí

Đánh giá

Acne Grading Systems  

There is currently no recommended universal grading or classifying system for acne. However, several scoring methods are being used by different associations, with grading and lesion counting being the most commonly used methods. The number of lesions, type of acne, disease severity, anatomical site/s, and propensity for scarring should be considered when determining the acne score for management purposes. Some scoring methods being used include the Echelle de Cotation des Lesions d’Acne (ECLA) or Acne Lesion Score Scale, Leeds technique, Global Acne Grading System, Investigator Global Assessment (IGA), postacne hyperpigmentation index (PAHPI), Comprehensive Acne Severity System (CASS), and the Acne Quality of Life Scale (AQCL) among others.

Comprehensive Acne Severity System (CASS)

CASS may be used for grading acne severity in clinical practice where inspection is done at 2.5 meters away for acne on the face, chest, and back.

Grading severity depends on the lesions present:

• Grade 0 (clear): Lesions are absent or unnoticeable, with very scattered comedones and papules
• Grade 1 (almost clear): Lesions are hardly visible from 2.5 meters away, with a few scattered comedones, few small papules and very few pustules
• Grade 2 (mild): Lesions are easily noticeable with less than half of the affected area involved; there are many comedones, papules, and pustules
• Grade 3 (moderate): Lesions affect more than half of the area, with numerous comedones, papules, and pustules
• Grade 4 (severe): Lesions are very visible in the entire area and covered with comedones, numerous pustules and papules, and a few nodules and cyst
• Grade 5 (very severe): Highly inflammatory acne covering the affected area, with nodules and cyst present

Severity Classification by Lehman

This classification is usually overestimated by the patient and underestimated by the physician.

References: Lehmann HP, Robinson KA, Andrews JS et al. Acne therapy: A methodologic review. J Am Acad Dermatol. 2002;47:231-240; Nast A, Dréno B, Bettoli V, et al. European evidenced-based (S3) guideline for the treatment of acne-update 2016 – short version. J Eur Acad Dermatol Venereol. 2016 Aug;30(8):1261-1268
*Includes comedonal and mild papulopustular acne
**Further subdivided into moderate papulopustular acne and moderate nodular acne
*** Further divided into severe papulopustular acne, severe nodular acne, and conglobate acne


Other Considerations  

Grading schemes that rely on the above lesion counts are usually of greater use in clinical studies rather than in clinical studies. It may be better to focus on the most severe lesions present. The proper treatment of the most severe lesions usually covers all lesser lesions.

Nguyên tắc điều trị

The management of acne vulgaris is based on the types of acne lesions and the severity of acne, patient history (history of previous acne treatments, childbearing potential), with all contributing factors identified and treated accordingly. It must be noted that topical therapy is the primary form of treatment for mild acne. While for moderate to severe acne, the principal form pf treatments are topical and systemic therapies. 

Goals of Therapy  

The goals of therapy are to induce clearance of acne lesions, to prevent physical and psychological complications, and to maintain remission and prevent relapse.  

Phases of Pharmacological Therapy  

The phases of pharmacological therapy include an initial or induction phase where acne remission is induced using topical or systemic agents, and a maintenance phase where using topical agents has been shown to control acne, prevent relapses, and minimize sequelae.

Pharmacological therapy

Topical Agents  

Topical agents are used for induction of remission and maintenance phases of treatment. They are applied directly on the skin which increases exposure of the pilosebaceous units to the treatment while limiting systemic absorption. They are also the principal treatment for patients with mild acne and useful for patients with moderate acne. It must be noted that Asian skin is different from Caucasian skin, thus in prescribing topical agents, this should be taken into consideration; Asian skin is more prone to post-inflammatory hyperpigmentation.

Retinoids  

Example drugs: Adapalene, Tazarotene, Tretinoin, Trifarotene  

Retinoids are comedolytic and occasionally anti-inflammatory. These reduce the formation of acne precursor lesions (microcomedones), limit the development of new lesions, promote desquamation of the follicular epithelium, and reduce inflammatory and non-inflammatory lesions. These are effective first-line agents in the treatment of comedonal (non-inflammatory) and inflammatory acne. Additionally, these are used as monotherapy for uninflamed, mild, comedonal acne, and in combination with antibiotics for inflamed lesions and moderate to severe acne. Retinoids act as agonists of retinoic acid receptors (RAR) (eg RAR-α, RAR-β, RAR-γ) which transcriptionally regulate cell proliferation, differentiation, and inflammation.

Adapalene may be useful as a monotherapy in mild to moderate forms of acne by reducing both inflammatory and non-inflammatory lesions. It is a potent modulator of keratinization, cellular differentiation, and inflammatory process. It is the most tolerated topical retinoid and is more effective and less irritating than Tretinoin for the treatment of inflammatory and non-inflammatory lesions. Studies show that RAR-β/γ-selective Adapalene downregulates key genes in the epidermis suggesting increased keratinocyte turnover and altered differentiation. Newer generations with more RAR selectivity may have more favorable clinical profile and lower risk of off-target effects compared to non-selective agents or agents acting on RAR-α and RAR-β (eg Tretinoin, Isotretinoin).

Tazarotene has been shown to reduce the number of non-inflammatory lesion counts in mild to moderate acne. It modifies the accumulation and cohesion of corneocytes, and the inflammation process. Lastly, it is associated with a higher incidence of erythema, burning, pruritus, and peeling than Tretinoin or Adapalene.

Tretinoin is effective as monotherapy in the treatment of non-inflammatory and mild to moderate inflammatory acne. It normalizes the keratinization process within the hair follicle and prevents formation of comedones. However, patients should be warned that they may suffer from pustular flare during the first few weeks of therapy; patients should not stop therapy because this flare indicates accelerated resolution of existing acne. There is also a Tretinoin gel microsphere which is a formulation designed to improve tolerability of topical Tretinoin. The microspheres allow for gradual release of medication which may limit delivery to the lower layers of the skin. They may also reduce irritation and therefore increase patient compliance. Lastly, there is a Tretinoin polyprepolymer-2 (PP-2) which is a drug delivery system that retains the drug on and in the upper layers of the skin, limiting irritation. This may be better tolerated because of the decrease in irritation.

Trifarotene is a gamma-selective retinoid cream suitable for acne on the face and the trunk. It has comedolytic, anti-inflammatory, and anti-pigmenting properties. It may cause mild transient erythema, scaling, dryness, and stinging. 

Acne Vulgaris_Management 1

• Should not be used as monotherapy for moderate to severe acne or as maintenance therapy for acne
• Recommend that topical antibiotics be used in combination with Benzoyl peroxide or a retinoid
• When possible, treatment duration is only up to 12 weeks

Erythromycin and Clindamycin are equally effective in treating moderate acne. On the other hand, Dapsone 5% gel, which possesses both antimicrobial (bacteriostatic) and anti-inflammatory properties, is used as an option for patients with mild to moderate acne preferably in combination with a topical retinoid. Sodium sulfacetamide, which is available alone or combined with Sulfur, acts as a keratolytic and may be used for patients with mild to moderate acne. Lastly, Minocycline was recently approved for moderate to severe acne vulgaris.  

Salicylic acid  

Salicylic acid may be used in mild to moderate acne or as an adjunctive agent when patients are intolerant of standard therapy. It is commonly found in facial cleansers. It is also the third choice for maintenance therapy. It has mild comedolytic and anti-inflammatory effects. Various products containing Salicylic acid are available. Please see the latest MIMS for specific formulations & prescribing information.

Clascoterone  

Clascoterone is an androgen receptor inhibitor which is approved for the treatment of acne vulgaris in patients ≥12 years of age. It is an alternative topical therapy for patients who fail to respond sufficiently to initial therapies.

Considerations When Choosing Topical Agent  

Patient Skin Type  

For oily skin, gel or solution are preferred. In hot, humid countries, acne lotion containing Salicylic acid and Resorcinol is useful to make the skin dry. On the other hand, creams or ointment are usually preferred for dry skin.  

Combinations  

If >1 topical agent is being used, it is best to instruct the patient to apply 1 agent in the morning, and the other agent at night. Combination topical therapy for the treatment of acne is found to be more effective and is preferrable than topical antibiotic alone. The combination should consist of agents from different classes (eg Benzoyl peroxide plus topical antibiotic, Benzoyl peroxide plus topical retinoid, Tretinoin plus topical antibiotic, Azelaic acid plus Lymecycline/Doxycycline, topical antibiotic plus topical retinoid plus Benzoyl peroxide). The retinoid-Benzoyl peroxide combinations are limited because of the instability of retinoids (except Adapalene). However, they are the recommended first-line therapy in patients with inflammatory acne, comedonal acne, or both.  

Products containing a fixed combination of agents from different classes are also available. Fixed combination products may be more convenient and may increase patient compliance. Recommended fixed-dose topical combinations include Benzoyl peroxide and topical retinoid, Benzoyl peroxide and topical antibiotic, and topical retinoid and topical antibiotic. Adapalene plus Benzoyl peroxide is the first topical fixed combination therapy for severe inflammatory acne. It has greater efficacy seen as early as the first week of treatment compared with monotherapy. It may also be used alone or in combination with other therapies before oral Isotretinoin is prescribed. Lastly, Adapalene plus Benzoyl peroxide plus Doxycycline is an alternative to Isotretinoin in patients with severe acne who are intolerant or unwilling to take Isotretinoin.

Oral Agents  

Oral agents are the preferred treatment option for acne resistant to topical therapy, acne with high scarring potential, or in patients with nodular acne.

Antibiotics  

Antibiotics must never be used as monotherapy for moderate to severe acne. They are typically used for moderate to severe inflammatory acne that does not respond to topical combinations or for acne with high scarring potential. The choice of antibiotic is based on the side effect profiles and the local patterns of resistance. The maximum course of treatment should be 3 to 4 months, but treatment response assessment should be at 6 to 8 weeks. Antibiotics suppress the growth of C acnes which helps reduce the production of inflammatory factors.

Antibiotic resistance with Azithromycin use has been reported. Azithromycin should be used with caution in patients at risk for severe adverse effects such as toxic epidermal necrolysis, but it is less associated with side effects compared to Erythromycin. Lastly, Azithromycin may be used in patients with contraindications to Tetracyclines and in pregnant women.  

Erythromycin has a direct anti-inflammatory effect by reducing neutrophil chemotactic factors and reactive oxygen species. It is considered as an alternative agent when other therapies have failed and can be used for pregnant women. It is associated with less anti-inflammatory activity and more gastrointestinal side effects than Tetracycline. It must be noted that there tends to be more resistance of C acnes to Erythromycin than to Tetracycline. However, there is decreased risk of photosensitivity in Erythromycin compared to Tetracycline.

Doxycycline is considered an excellent first-line agent for inflammatory and moderate to severe acne. However, C acnes resistance has also been reported.  

Lymecycline is considered as a first-line therapy in combination with other agents for moderate to severe acne. There is less frequent occurrence of gastrointestinal and dermatological side effects with Lymecycline.  

Tetracycline is considered as a first-line agent for moderate to severe inflammatory acne as an alternative to Doxycycline. It can penetrate into the follicular canal. The development of C acnes resistance is a potential problem, however, and should be suspected if acne worsens after several months of treatment.  

Minocycline may be used as a second-line antibiotic treatment for inflammatory and moderate to severe acne. Notably, there are fewer reports of C acnes resistance in Minocycline compared to Tetracycline and Doxycycline. However, there is a tendency to produce rare serious side effects that is greater in Minocycline than in Tetracycline and Doxycycline.

Sarecycline is a narrow-spectrum tetracycline with high activity against C acnes, S aureus, and S pyrogenes. It may cause teratogenic effects (eg adverse events in infants’ bone and teeth development). It may be used in patients ≥9 years of age for the treatment of non-nodular inflammatory moderate to severe acne. Sarecycline should not be administered with oral retinoids as it may increase intracranial pressure. Patients may take Sarecycline regardless of food intake. It also has reduced potential for antibiotic resistance.  

Co-trimoxazole is considered a third-line therapy when other therapies have failed. It is effective in patients refractory to other oral antibiotics or for Gram-negative acne. A low but possible risk for major side effects should be considered.

Isotretinoin (13-cis Retinoid acid) 

Isotretinoin is recommended as a first-line therapy for very severe (cystic and conglobate) acne. It is the most effective agent for severe acne and nodulocystic acne and provides a prolonged remission period. It is highly lipophilic. It reduces sebum secretion, comedogenesis, ductal and surface C acnes by 80%. It has also been shown to have anti-inflammatory properties. Treatment is usually for 20 weeks with continuation of improvement for up to 5 months after ending treatment. However, relapse may occur in 15% of patients; factors for higher risk of relapse after treatment include severe seborrhea, young age, family history of acne, and prepubertal and truncal acne. It is a known teratogen and therefore, childbearing-aged females must be tested for pregnancy prior to therapy. Severe adverse effects may limit its use. Low-dose Isotretinoin may be used to reduce the frequency and severity of adverse effects. It can only be prescribed by dermatologists. The initiation of Isotretinoin treatment in patients <18 years of age who are unresponsive or with contraindications to other therapies require agreement by two independent healthcare professionals.

Corticosteroids  

Oral corticosteroids may be considered in patients with severe acne who suffer from acne flare after initiation of oral Isotretinoin therapy and in patients with acne fulminans.  

Intralesional Agents  

Intralesional Corticosteroids  

Example drug: Triamcinolone acetate  

Intralesional corticosteroids may be used for severe, large, nodulocystic lesions. Local adverse effects include skin atrophy, pigmentary changes, and telangiectasia. 

Adjunctive Therapies  

Chemical Peels (Other than Salicylic acid)  

Example drugs: Glycolic acid, Lactic acid, Trichloroacetic acid  

The mechanism of action of chemical peels is to inhibit tyrosinase activity. It involves facial resurfacing wherein removal of the epidermis stimulates re-epithelialization and skin rejuvenation. Chemical peels may reduce hyperpigmentation and skin superficial scarring. They have also been found to be safe, effective, and can significantly improve moderate acne in Asians.

Keratolytic Agents  

Example drugs: Resorcinol, Sulfur  

Keratolytic agents such as Resorcinol and Sulfur may be used as adjunctive treatment together with other anti-acne agents. 

Other Therapies for Acne  

Comedo removal can be done for treatment-refractory comedones. Additionally, tea tree oil (Melaleuca alternifolia) reduces the number of lesions in mild to moderate acne. While Psidium guajava extract has antimicrobial effects against C acnes. It must be noted that though herbal and complementary therapies seem to be well tolerated, data on the safety and efficacy of these therapies are limited.

Adjunctive Hormonal Therapy  

Oral Contraceptives  

Example drugs: Ethinyl estradiol/Norgestimate, Ethinyl estradiol/Norethindrone acetate, Ethinyl estradiol/Norethindrone acetate/Ferrous fumarate, Ethinyl estradiol/Drospirenone, Ethinyl estradiol/Drospirenone/Levomefolate, Ethinyl estradiol/Gestodene  

Combined oral contraceptive (COC) (estrogen and progestin) is an alternative for women with moderate to severe acne who do not respond to conventional acne therapies or with lesions limited to lower half of the face.  

Absolute contraindications to COCs include:

• <21 days postpartum
• ≥35 years of age and smoking history of ≥15 cigarettes per day
• Hypertension (≥160/≥100 mmHg)
• Coronary artery disease/cerebrovascular disease
• Deep vein thrombosis, pulmonary embolism, known thrombogenic mutations
• Major surgery with prolonged immobilization
• Valvular heart disease with complications (eg atrial fibrillation, pulmonary hypertension)
• Peripartum cardiomyopathy with normal or impaired cardiac function for <6 months or moderate or severely impaired cardiac function
• Migraine with aura or no aura if >35 years old
• Current breast cancer
• Diabetes with complications
• Acute viral hepatitis, decompensated liver cirrhosis, liver tumor, hepatocellular adenoma
• Systemic lupus erythematosus with positive or unknown antiphospholipid antibodies
• Solid organ transplantation complicated by acute or chronic graft failure, rejection or cardiac allograft vasculopathy

Relative contraindications to COCs include:

• Breastfeeding patient 21 to 29 days postpartum
• Breastfeeding patient 30 to 42 days postpartum, with other VTE risk factors
• Non-breastfeeding patient 21 to 42 days postpartum, with other VTE risk factors
• >35 years of age and smoking history of <15 cigarettes per day
• Hypertension (140-159/90-99 mmHg)
• Multiple risk factors for cardiovascular disease and hyperlipidemia 
• Peripartum cardiomyopathy with normal or mildly cardiac function for ≥6 months
• History of breast cancer >5 years ago with no recurrence
• Mild compensated liver cirrhosis, previous COC-induced cholestasis, gallbladder disease, concurrent medication with potential for transaminitis
• History of malabsorptive procedures (Roux-en-Y gastric bypass or biliopancreatic diversion)

Progestin-only oral contraceptives are not effective and may aggravate acne. It must also be noted that responses may not be observed until after 3 to 6 months of treatment, and some patients may experience a flare of symptoms during early cycle. Lastly, androgen-modulating properties are attributed to the estrogen component, decreases androgen production and reduces excess testosterone by increasing sex-hormone binding globulin production, thereby deactivating free androgen receptors; suppresses sebum formation.


Cyproterone acetate  

Cyproterone acetate is an anti-androgen agent that is given with either Ethinyl estradiol or a contraceptive.  

Spironolactone  

Spironolactone is an alternative anti-androgen therapy with potential to significantly improve acne severity and sebum production. It is an alternative for women with moderate to severe acne and unresponsive to conventional therapy or unwilling to take Isotretinoin. It decreases testosterone production, inhibits testosterone and dihydrotestosterone binding to dermal androgen receptors, inhibits 5-alfa-reductase, and increases steroid hormone-binding globulin. 

Flutamide  

Flutamide is a nonsteroidal selective androgen receptor blocker being studied for the use in the management of acne. However, Flutamide-induced fatal hepatitis limits the use of this agent for acne, unless benefit outweighs the risk.

Nonpharmacological

Patient Education  

Good communication between clinician and patient is important. Non-compliance is the most common cause of treatment failure in acne vulgaris. Additionally, adolescents may be sensitive to how they are perceived by their healthcare provider due to low self-esteem brought about by the disease. By giving the patient clear guidelines and realistic expectations, non-compliance can be avoided. The patient should also be aware that the treatment will control acne, not cure it. It must be noted that many acne sufferers anticipate treatment failure or worsening of the disease; proper advice and guidance should be provided. Long-term therapy is required to control lesions. Acne tends to be less active as age increases. Patients should be informed that acne medication will take up to 8 to 12 weeks to work and there is no “quick-fix”. For individuals who use make-up, oil-free, non-comedogenic products should be used, and should be removed at the end of the day.

Diet and Acne  

There are no specific recommendations available for the correlation of diet and acne severity, therefore patient advice should be individualized. Several studies have suggested that food with high glycemic content, chocolate and dairy may be associated with acne, therefore a low glycemic index diet and avoidance of chocolate and dairy consumption may be encouraged in patients. 

Skin Care Recommendations  

An effective skincare routine improves patients’ self-esteem, quality of life and self-image. It is recommended that the affected area be washed twice daily with pH-balanced mild soap or cleanser, pat dry then apply acne treatment. Cleansers should be non-irritating, non-allergic, non-comedogenic, non-acnegenic, and alcohol-free while removing dirt and excessive lipids. Frequent washing, especially with harsh soaps, may aggravate the condition. Topical acne therapy needs to be applied as a thin coat to all acne-prone areas, not just to individual lesions.  

Proper selection of topical formulation may decrease side effects and increase compliance: Creams and lotion for very dry skin, gel and solutions for very oily skin, and cream-based cleansers should be avoided. If skin becomes dry from topical treatments, the patient may use oil-free, hypoallergenic, non-comedogenic, alcohol-free, and fragrance-free moisturizers. Sunscreen is used if photosensitizing antibiotics or retinoids are prescribed. Photoprotection is necessary to reduce the risk of sunburn, photoaging, and triggering of underlying skin condition. Sunscreen can also be applied indoors to help protect from visible light (blue light from computers, cell phones, indoor lighting) which patients are exposed to for longer periods of time while staying indoors during the pandemic. 

Importantly, picking at lesions should be avoided. Traumatizing lesions can lead to increased inflammation, prolonged resolution, and increased chance of scarring. Lastly, acne should not be covered by tight-fitting clothing or bandages.

Dermatocosmetics  

Dermatocosmetics or “cosmeceuticals” are used as adjuncts to standard acne therapy and aid in decreasing side effects (eg irritation, dryness, photosensitivity) and the need for topical antibiotics. They include skin cleansers, comedolytics, corneolytics (eg retinaldehyde, retinol, Alpha hydroxy acids [AHA], beta hydroxy acid [BHA], polyhydroxy acid [PHA]), moisturizers, sebum-controlling agents (eg methacrylate polymers, aluminum starch octenylsulccinate, zinc gluconate, Nicotinamide/Niacinamide, Triethyl citrate, ethyl linoleate, 2% L-Carnitine, Erythromycin-zinc formulation), anti-inflammatory/antimicrobial agents (eg tyrothricin, tea tree oil, aloe vera, propolis, licochalcone A, Triclosan), antioxidants (eg green tea extract, vitamin C), sunscreens, skin-lightening agents, camouflage products, and hydrocolloid acne patches. It also emphasizes the importance of cleansing, treatment, moisturization, and photoprotection in holistic skin care. They improve symptoms and reduce side effects from topical therapy. Additionally, they can modulate the skin microbiome in acne, making it a potential alternative in the treatment of acne without the risk of antibacterial resistance. Moderate use of non-greasy moisturizers and water-based cosmetics is usually well-tolerated, but a gradual decrease in the use of cosmetics is encouraged as acne improves.

Energy-Based Devices  

Intense Pulsed Light (IPL)  

IPL targets C acnes by activating the formation of reactive oxygen (O₂) species from porphyrins produced by C acnes when exposed to visible light. It causes decrease in sebum output by directly damaging the sebaceous glands. 

Laser Therapy  

Examples: Ablative and non-ablative lasers (Erbium glass laser, neodymium-doped yttrium aluminum garnet laser (Nd:YAG), pulsed dye laser, non-ablative fractional laser, yellow laser)

The mechanism behind laser therapy is photocoagulation or photothermal injury causing bactericidal effect and reduction in the size of the sebaceous gland. Pulsed dye laser reduces inflammation and erythema. 

Light-based Therapy  

Blue light therapy has a shorter wavelength and bactericidal effect on C acnes via the production of reactive O₂ species in the bacteria. While red light can penetrate deeper tissues which can lead to anti-inflammatory reactions and promote skin repair.  

Photodynamic Therapy (PDT)  

PDT involves the use of light to activate photosensitive products like 5-aminolevulinic acid (ALA), methyl aminolevulinate (MAL), and indocyanine green (ICG). It may also be used as an adjunct to medical therapy until its effectiveness has been better validated. PDT also causes structural damage to bacterial cell membranes, decreases bacterial populations, and results in reduction of inflammatory acne lesions by 59 to 67%. Among the different modalities, ALA-PDT is the most extensively studied. It provides the best results when used to treat inflammatory and cystic acne.  

PDT treatment can be administered in 8 to 15 minutes and is generally well tolerated. Notably, an average of three treatments can yield significant long-term improvement. Lastly, sun avoidance and protection are necessary for up to 48 hours following therapy.

Acne Vulgaris_Management 2

• Acne conglobata
• Nodulocystic acne
• Uncertainty with the diagnosis
• Mild to moderate acne unresponsive to two courses of treatment
• Scarring or pigmentary changes
• Moderate to severe acne unresponsive to treatment combined with antibiotics
• Psychological distress or mental health disorder due to acne
• Disease or medication may be a contributing factor to acne
• Specialized physical treatment (eg incision, drainage) indicated
• Urgent referral is indicated when acne fulminans is being considered