Author: Dong Shiyu, Sun Yixian Memorial Hospital, Sun Yat sen University

Reviewed by: Chen Chuxiong, Sun Yixian Memorial Hospital, Sun Yat sen University

Acne is a chronic inflammatory skin disease of hair follicle sebaceous gland unit, which usually occurs in adolescence, mainly involving the face, accompanied by erythema, pigmentation and scar. At present, the pathogenesis of acne has not been fully clarified, which is mainly related to the excessive secretion of lipid from sebaceous glands, abnormal keratinization of sebaceous gland ducts of hair follicles, proliferation of hair follicle microorganisms such as Propionibacterium acnes, inflammation and immune response.

As the severity of acne varies from patient to patient, acne can be divided into 3 degrees and 4 grades according to the nature of skin lesions, namely, mild (Grade I): only acne; Moderate (Grade II): inflammatory papules; Moderate and severe (Grade III): pustules appear; Severe (Grade IV): nodules and cysts. The doctor formulates individualized treatment plan for patients according to the grading, so as to achieve the optimal treatment effect.

The drugs used to treat acne mainly include retinoic acid, benzoyl peroxide, antibacterial drugs, antiandrogens and glucocorticoids, as well as a variety of physical and chemical therapies, including photodynamic therapy, red and blue light, laser and photon therapy, and chemical stripping therapy.

There are a variety of acne treatment methods on the market, some of which have uncertain efficacy, lack of evidence-based medical evidence support, and individual methods even cause damage to patients. For this reason, Yixian pharmacist combined with the clinical guidelines to sort out the precautions for drug use for your reference.

1、 Retinoids for external use

Mechanism of action: improve the keratinization of hair follicle sebaceous gland duct, dissolve micro acne and acne, anti-inflammatory, prevent and improve the pigmentation and acne scar after acne inflammation. Adapalene is well tolerated and is usually used as a first-line drug.

Representative drugs: retinoic acid, tazarotene, adapalene

Scope of application:

① Single first-line medication for mild acne;

② Combination medication for moderate acne;

③ The first choice of acne maintenance treatment;

Caution: Wash the acne before going to bed, and apply the medicine to the acne after it is dry. In case of aggravation of skin lesions, measures such as lower initial concentration, small range trial, and reduced use times can be taken.

Adverse reactions: mild skin irritation may occur locally, such as erythema and scaling, accompanied by tightness and burning, which can be gradually tolerated with time. If the irritation is serious, it is recommended to stop taking the drug. This kind of medicine has photodegradation, which will increase the skin’s sensitivity to ultraviolet rays. Avoid sun exposure or apply sunscreen drugs. Retinoic acid and adapalene for external use are class C drugs for pregnancy. Pregnant women should use them with caution. Tazarotene is class X of pregnancy and should not be used by pregnant women.

2、 Oral retinoids

Action mechanism: It inhibits the lipid secretion of sebaceous glands, regulates the abnormal keratinization of sebaceous gland ducts of hair follicles, improves the anaerobic environment of hair follicles, thereby reducing the reproduction of Propionibacterium acnes, anti inflammation and preventing scar formation. It is currently the only oral drug for the four key pathophysiological links of acne. Isoretinoic acid is the first choice of oral retinoic acid drugs at home and abroad.

Representative drugs: isotretinoic acid, viaminate

① The first-line treatment of severe acne with nodular cyst;

② Substitution therapy for moderate or severe acne with poor effect of other treatment methods;

③ Acne patients with scar or scar forming tendency should use it as early as possible;

④ Other treatments for acne with frequent recurrence were ineffective;

⑤ Acne with severe seborrhea;

⑥ Mild to moderate acne, but patients have a need for rapid treatment;

⑦ Acne variants, such as eruptive acne and polymerized acne, can be used after the use of antibacterial drugs and glucocorticoids to control inflammation.

Note for use: These drugs should be taken with fat meal to increase the bioavailability of oral absorption. The course of treatment is usually no less than 16 weeks, and generally takes effect in 3-4 weeks.

Adverse reaction: the common adverse reaction is dry skin and mucous membrane. It is recommended to use it together with skin barrier repair agent. Long term use before puberty may cause premature closure of epiphysis, hyperosteogeny, osteoporosis, etc., so children under 12 years old should try not to use it. Such drugs have teratogenic effects. Female patients of childbearing age must strictly use contraception 1 month before treatment, during treatment and 3 months after treatment. Isoretinoic acid may cause mental system disorder, and patients with obvious depressive symptoms or depression should use it with caution. Isoretinoic acid may be related to benign intracranial pressure rise, and its combination with tetracyclines may increase the occurrence of this adverse reaction and avoid simultaneous use. Isoretinoic acid may be related to dyslipidemia, including elevated levels of triglycerides and cholesterol in serum, and blood lipid levels should be monitored regularly. In view of the case reports of severe skin damage after the use of isotretinoin in foreign countries, such as erythema multiforme, it is recommended that patients should go to the hospital in time in case of severe skin damage.

3、 Benzoyl peroxide

Action mechanism: release new ecological oxygen and benzoic acid, kill propionibacterium acne, anti-inflammatory and slightly dissolve acne. The drug can be used alone or in combination with retinoic acid or external antibacterial drugs.

Scope of application: The first external drug for inflammatory acne.

Caution: In order to avoid mild irritation, it is recommended to start from low concentration and try it in a small range. Drugs have oxidation and bleaching effects on clothes or hair, and should be avoided as far as possible.

Adverse reactions: common adverse reactions include local erythema, dryness and skin peeling, which are self limiting. The oxygen free radicals released by benzoyl peroxide can lead to the deactivation of all trans retinoic acid. It is recommended that both of them be used externally in different periods.

4、 External antibacterial agents

Action mechanism: anti acne propionibacterium, anti inflammation

Representative drugs: erythromycin, lincomycin, clindamycin, chloramphenicol, metronidazole, and fusidic acid

Scope of application: superficial inflammatory acne such as papules and pustules

Note for use: Because external antibacterial drugs are easy to induce drug resistance of Propionibacterium acnes, it is not recommended to use alone or for a long time, but recommended to use with benzoyl peroxide, external retinoic acid or other drugs.

Adverse reactions: few irritation reactions occur. Common skin irritation symptoms include erythema, dry burning pain, etc. Systemic adverse reaction symptoms such as diarrhea or pseudomembranous colitis are rare. Antibacterial drugs for external use are Class B drugs for pregnancy. Studies have proved that they are non teratogenic and generally safe to use during pregnancy.

5、 Oral antibacterial agents

Action mechanism: Anti acne propionibacterium, anti inflammation. Tetracycline drugs such as doxycycline and minocycline are preferred. Patients who cannot tolerate or have contraindications should consider using macrolides such as erythromycin, roxithromycin, azithromycin, etc.

Representative drugs: doxycycline, minocycline, erythromycin, roxithromycin, azithromycin

① The first choice for patients with moderate to severe acne and the alternative treatment method for patients with moderate acne with poor external treatment effect;

② In the early stage of severe acne patients with severe inflammatory reaction, oral antibacterial drugs can be used first, then oral retinoic acid drugs can be used sequentially, or oral antibacterial drugs can be used instead when the effect of oral retinoic acid drugs is not obvious;

③ Early treatment of acne variants such as eruptive acne or polymeric acne;

Note for use: adequate treatment course of oral antibacterial drugs should be guaranteed to avoid intermittent use, but it is recommended that the duration should not exceed 8 weeks; The combination of tretinoin or benzoyl peroxide can effectively improve the efficacy and reduce the drug resistance of Propionibacterium acnes.

Adverse reactions: There are many types of adverse reactions of tetracyclines, but they are relatively rare, such as vaginal candidiasis, gastrointestinal discomfort, photosensitive reaction, pigment deposition and benign intracranial hypertension in susceptible women. Combined with oral retinoic acid may induce or aggravate benign intracranial hypertension. Tetracyclines should not be used in pregnant women, lactating women and children under 8 years of age. Macrolides can be used instead. Minocycline may cause vestibular involvement (such as dizziness and vertigo), rarely lupus like syndrome and benign intracranial hypertension (such as headache). The drug should be stopped immediately after the occurrence.

6、 Antiandrogens

Action mechanism: inhibit the generation of androgen precursors, act on androgen metabolizing enzymes and androgen receptors in the skin, reduce or antagonize the action of androgen activity, thereby reducing the secretion of lipid from sebaceous glands and improving acne. These drugs are mainly applicable to female acne patients.

Representative drugs: estrogen, progesterone, spironolactone, metformin

① Acne with hyperandrogenism;

② Female post adolescent acne;

③ Acne that is obviously aggravated in premenstrual period;

④ Poor response to oral antibiotics or even oral retinoic acid, or rapid relapse after drug withdrawal;

Note for use: It is applicable to female acne patients, especially those with polycystic ovary syndrome, obesity, hirsutism, insulin resistance or hyperinsulinemia, and obviously aggravated in premenstrual period.

Adverse reactions: oral contraceptives may cause irregular uterine bleeding, breast pain, nausea, weight gain, venous and arterial thrombosis, chloasma, etc. The patient’s medical history and treatment history should be evaluated before use. Taking medicine on the first day of the menstrual period can reduce the risk of uterine bleeding. Drugs containing drospirone may reduce the risk of weight gain. Pay attention to sun protection during medication to reduce the occurrence of chloasma. The adverse reactions of spironolactone are generally dose dependent, including hyperkalemia, irregular menstruation, gastrointestinal reactions, lethargy, dizziness, headache, and the patient’s blood potassium level should be monitored within the first month after administration. Spironolactone has teratogenic effect and is forbidden for pregnant women.

7、 Glucocorticoid

Action mechanism: small dose inhibits the secretion of renal derived androgen, while large dose has anti-inflammatory and immunosuppressive effects.

Scope of application: early treatment of severe inflammatory acne.

Note for use: It is mainly used for fulminant acne, polymerized acne, and severe acne with severe inflammatory reaction. The course of treatment does not exceed 4 weeks, and it is usually combined with oral isotretinoin.

8、 Chinese patent medicine

The choice of Chinese patent medicine should be based on the degree of skin damage and different syndromes. If it belongs to the wind heat syndrome of the lung meridian, it should be used to dredge the wind and expel the lung, clear away heat and disperse the knot. Such Chinese patent medicine is like Gardenia Jinhua Pill; If it belongs to the syndrome of damp heat in the spleen and stomach, it is better to clear away heat and promote dampness. For example, Yiqing capsule can be used to relieve constipation by taking Fangfeng Tongsheng pill, and for loose stool by taking Shenling Baizhu pill; If it belongs to the syndrome of phlegm and blood stasis, it should be treated to promote blood circulation and remove blood stasis and phlegm, such as tanshinone capsule and angelica kushen pill; If Chong Ren does not regulate syndrome, it is better to regulate Chong Ren, regulate Qi and promote blood circulation, such as Xiaoyao Pill, Zhibai Dihuang Pill, etc.

Acne, how to choose medicine?

For mild acne, topical retinoids or benzoyl peroxide gel can be used alone.

For moderate acne, it is necessary to consider the combination of drugs. Common combinations of drugs include retinoic acid drugs for external use+benzoyl peroxide+/- external antibiotics, or benzoyl peroxide+external antibiotics. Attention should be paid to the use of drugs for external use in a small range, which can reduce the stimulus response. If the stimulus response is serious, it is recommended to stop the drug.

For moderate and severe acne, it is not enough to use external medicine alone. Usually, oral medicine combined with external medicine is required, because the combination of multiple drugs can cover more aspects of the pathogenesis of acne and produce therapeutic synergy. Oral antibiotics+external retinoic acid+/- benzoyl peroxide+/- external antibiotics or oral isotretinoic acid can be considered.

For severe acne, oral retinoic acid+/- benzoyl peroxide/topical antibiotics can be considered, or oral antibiotics+benzoyl peroxide/topical antibiotics can be taken first, followed by oral isotretinoic acid; Or oral antibiotics+external retinoic acid+/- benzoyl peroxide, oral glucocorticoids can also be selected.

Note that most of the drugs described above are prescription drugs, which must be used under the guidance of a doctor. Do not use drugs without authorization. In addition, the treatment of acne is a long-term process. In order to reduce and prevent the recurrence of acne, it is usually necessary to use drugs to maintain treatment for 3-12 months. External retinoic acid is the first-line drug for acne maintenance treatment. It can also be combined with benzoyl peroxide or low concentration of fruit acid or functional skin care products. Women can choose to take oral antiandrogen drugs to maintain treatment. See Table 1 for recommended treatment of common acne.

Table 1 Recommended Treatment Scheme for Acne

Severity

Mild (Grade I)

Moderate (Grade II)

Moderate and severe (Grade III)

Severe (Grade IV)

First line selection

Retinoic acid for external use

Retinoic acid for external use+benzoyl peroxide+/- antibacterial drugs for external use or benzoyl peroxide+antibacterial drugs for external use

Oral antibiotics+external retinoic acid+/- benzoyl peroxide+/- external antibiotics

Oral isotretinoic acid+/- benzoyl peroxide/topical antibacterial agents. Those with strong inflammatory reaction can take oral antibiotics+benzoyl peroxide/topical antibiotics first, and then take oral isotretinoin

Second line selection

Benzoyl peroxide, azelaic acid, fruit acid, traditional Chinese medicine

Oral antibiotics+external retinoic acid

+/-Benzoyl peroxide+/- external antibiotic, azelaic acid, red blue light, salicylic acid or compound acid, traditional Chinese medicine

Oral isotretinoic acid, red and blue light, photodynamic therapy, laser therapy, salicylic acid or compound acid, traditional Chinese medicine

Oral antibacterial drugs+topical retinoic acid+/- benzoyl peroxide, photodynamic therapy, glucocorticoids (polymerized acne can be treated with oral

Isoretinoic acid (combined use), traditional Chinese medicine

Female patients

Oral antiandrogens

Maintenance treatment

Retinoic acid for external use+/- benzoyl peroxide

Physical and Chemical Therapy

In addition to drug therapy, physical and chemical therapy also has good effects, such as photodynamic therapy can inhibit sebum secretion, kill propionibacterium acnes, regulate immunity, improve sebaceous duct keratosis, and prevent or reduce acne scars. Blue light irradiation alone can kill propionibacterium acnes and anti-inflammatory, while red light irradiation alone can repair tissues. Near-infrared wavelength laser can inhibit sebaceous gland secretion and anti-inflammatory; Strong pulsed light and pulsed dye laser are beneficial to the disappearance of red marks in the later stage of acne. Chemical exfoliation refers to reducing the adhesion of keratinocytes, accelerating the exfoliation and renewal of epidermal cells, stimulating the synthesis of dermal collagen and tissue repair, and mildly anti inflammation by using fruit acid, salicylic acid and complex acid.

reference

[1] China acne treatment guidelines expert group Chinese acne treatment guidelines (2019 revision) [J] Journal of Clinical Dermatology, 2019, v.48 (09): 65-70

[2] Oudenhoven M D , Kinney M A , Mcshane D B , et al. Adverse Effects of Acne Medications: Recognition and Management[J]. American Journal of Clinical Dermatology, 2015, 16(4):231-242.

Scope of application:

Scope of application:

Scope of application:

Oral antiandrogens

Oral antiandrogens

Quality product recommendation: acne treatment set