Oral isotretinoin significantly inhibits the secretion of sebaceous glands, regulates the keratinization of follicular sebaceous ducts, improves the anaerobic environment of follicles and reduces the reproduction of Propionibacterium acnes, is anti-inflammatory and prevents scar formation. Because it can act on the four key pathophysiological aspects of acne, it is currently the most effective anti-acne drug, and acne patients with clear indications should take it as soon as possible.
Indications.
1.Nodular cystic acne.
2, moderate or severe acne where other treatments are not effective.
3, acne with scarring or a tendency to form.
4, acne with frequent recurrence.
5, acne with severe excess seborrhea.
6, mild or moderate acne but where the patient has a need for rapid healing.
7, acne patients with severe psychological stress.
8, acne variants such as fulminant acne and convergent acne, can be used after the use of antibiotics and glucocorticoids to control the inflammatory response.
Oral dose: Small doses of 0.25 mg/(g/d) and 1 mg/(kg/d) have similar clinical efficacy, so it is recommended to start with a dose of 0.25-0.5 mg(/kg/d)
This will increase patient compliance. The cumulative dose is significantly correlated with acne recurrence, so a cumulative dose of 60 mg/kg is recommended, and the dose can be gradually reduced to discontinuation after the acne has largely resolved and no new rash has appeared. The duration of treatment depends on the extent of lesion regression and the dose of the drug, which should usually be 16 weeks.
Isotretinoin is a derivative of vitamin A. Because of its extensive biological activity in the body, it can produce adverse reactions similar to hypervitaminosis A. However, most of them can be recovered after discontinuation of the drug, and serious adverse reactions are rare or uncommon. The most common adverse reactions are mainly dry skin and mucous membranes, especially dry mouth and lips. Rarely, it can cause musculoskeletal pain, elevated blood lipids, abnormal liver enzymes and eye involvement, which usually occurs in the first 2 months of treatment. Long-term high doses may cause premature epiphyseal closure, osteomalacia and osteoporosis, so it is not used in children <12 years old. Isotretinoin has clear teratogenic effects, and female patients should use strict contraception during the 1 month before treatment and 3 months after treatment, and if they become pregnant accidentally during treatment, abortion must be treated. In addition, the correlation between isotretinoin causing depression or suicide and drug use is unclear. Since acne itself can cause low self-esteem and depression in patients, it is recommended that it should not be used by patients who already have depressive symptoms or who are depressed.
Antibiotics
Propionibacterium acnes plays an important role in the inflammatory response to acne, so antibacterial treatment targeting Propionibacterium acnes is one of the common treatments for acne, especially moderate and severe acne. However, both topical and oral antibiotics may cause drug resistance in Propionibacterium acnes and non-Propionibacterium acnes, which is an issue of great concern. Therefore, it is important to standardize the selection and regimen of antibacterial drugs or combine them with other therapies to improve the efficacy and prevent drug resistance.
Indications.
1. Preferred systemic drug therapy for patients with moderate to severe acne.
2. Patients with severe acne, especially in the early stages when inflammation is severe, can be treated with antibiotics first, followed by sequential use of isotretinoin, and can be switched to antibiotic therapy when isotretinoin is not effective.
3, acne variants such as fulminant acne and convergent acne.
Drug selection: The choice of oral antibiotics for acne is based on the following four conditions
1. Sensitivity to Propionibacterium acnes.
2. A combination of non-specific anti-inflammatory effects.
3, drug distribution in the hair follicle sebaceous glands in a high concentration domain adverse reactions are small. In accordance with the above conditions, tetracyclines such as doxycycline and minocycline should be preferred, and macrolides such as erythromycin, azithromycin and clarithromycin can be considered when they cannot be used. Others such as sulfamethoxazole-methoprene compound xinomycin can also be used as appropriate, but beta-lactams and quinolones antibiotics should not be chosen. Tetracycline is poorly absorbed orally and highly resistant, while new generation tetracyclines such as minocycline, doxycycline and lymetetracycline should be preferred. Patients who are resistant to oral tetracycline are usually resistant to doxycycline as well, but minocycline is still effective in most of these patients. Clarithromycin, roxithromycin, and levofloxacin, which are currently commonly used antibiotics for systemic infections, should be avoided for the treatment of acne to reduce the chance of drug-resistant bacteria developing. In case of acne recurrence, antibiotics that have been effective in previous treatments should be selected and avoided to be changed at will.
Dosage and regimen: The dosage and regimen of antibiotics used to treat acne should be standardized. Usually the dose of minocycline and doxycycline is 100~200 mg/d usually 100 mg/d). You can take 1 or 2 oral doses of tetracycline 1.0 g/d, divided into 2 oral doses of erythromycin 1.0 g/d on an empty stomach, divided into 2 oral doses. The course of treatment is 6~8 weeks.
Precautions: Care should be taken to avoid or reduce the development of drug resistance when treating acne with antibiotics, measures include
1. Avoiding individual use, especially long-term topical application.
2. Treatment should be started in adequate doses and should not be reduced for maintenance once effective.
3, 2 to 3 weeks after treatment without efficacy should be promptly discontinued or replaced with other antibiotics, and pay attention to the patient’s compliance domain to ensure an adequate course of treatment and avoid intermittent use.
4. Propionibacterium acnes is a parasitic bacterium of normal skin, and treatment is aimed at effectively inhibiting its reproduction rather than achieving complete elimination, so the dose should not be increased or the course of treatment extended without principle, let alone as a maintenance treatment or even as a measure to prevent relapse.
5, conditions can be monitored for drug resistance of Propionibacterium acnes to guide rational clinical application.
6. Combined topical benzoyl peroxide can reduce the generation of drug resistance in Propionibacterium acnes.
7. Combined phototherapy or other therapies can be used when available to reduce the use of antibiotics. In addition, attention should be paid to adverse drug reactions in treatment, including the more common gastrointestinal reactions, drug rash, liver damage, photosensitivity reactions, vestibular involvement such as dizziness, vertigo and benign intracranial pressure elevation disorders such as headache. Rare adverse reactions include lupus-like syndrome, especially when applying ? minocycline when applied. It should be used with caution or prohibited for patients with long-term alcohol consumption, hepatitis B, photosensitive dermatitis, etc. Tetracyclines should not be used in pregnant women, women during the Asr lactation period and children <16 years old, when macrolide antibiotics can be considered. Minocycline may be partially mitigated by dividing the daily dose of minocycline into oral doses, or by using an extended-release dosage form once a night. The drug should be discontinued promptly when serious adverse reactions occur or are intolerable to the patient, and treated symptomatically. Pay attention to drug interactions when combining macrolides and tetracyclines with other systemic drug therapy.
Hormones
Anti-androgens. Androgens play an important role in the pathogenesis of acne, but most acne patients have normal androgen levels in their peripheral blood, so routine endocrine testing is not necessary. For patients with a history and physical examination suggesting hyperandrogenism such as acne in prepubertal children, precocious puberty, masculine signs and symptoms in female patients, as well as those with scanty menstruation, hirsutism, androgenic alopecia, infertility or polycystic ovaries, laboratory tests such as free testosterone, DHEAs, luteinizing hormone and follicle stimulating hormone can be performed to aid in the diagnosis. Indications: Acne hormone therapy consists of two parts:First, anti-androgen therapy, only for female patients, with the following indications.
1, acne with hyperandrogenic manifestations, such as rashes often occurring in the middle and lower third of the face, especially severe acne in the jaw area with or without menstrual irregularities and hirsutism.
2. Female post-pubertal acne.
3, acne that is significantly aggravated during the premenstrual period.
4. Those who respond poorly to conventional treatment such as systemic antibiotics or even systemic treatment with retinoic acid, or who relapse rapidly after stopping the medication.
Drug selection, dosage, treatment course and precautions
1. Contraceptive pills: They are the most commonly used drugs in anti-androgen therapy. Birth control pills are mainly composed of estrogen and progestin, of which the progestin component can be used for acne treatment if it has an anti-androgen effect. The mechanism of action of oral contraceptives for acne treatment: estrogen and progestin can counteract the effects of androgens and also act directly on the sebaceous glands of hair follicles to reduce sebum secretion and inhibit the formation of acne. Currently, commonly used contraceptives include ethinylestradiol cyproterone and estradiol drospirenone. Each tablet contains 2 mg of cyproterone acetate + 35 μg of ethinyl estradiol, and one tablet is taken daily for 21 d starting on the first day of the menstrual cycle, followed by 7 d of discontinuation and 2 d of repetition after menstruation. Absolute contraindications to oral contraceptives include pregnancy, history of venous thrombosis or heart disease, and smokers >35 years of age. Relative contraindications include hypertension, diabetes, migraine, breastfeeding, breast cancer, and liver cancer. Possible adverse reactions include small amounts of uterine bleeding, breast tenderness, nausea, weight gain, deep vein thrombosis, and chloasma, with initiation of the drug on the first day of menstruation helping to reduce uterine bleeding. Weight gain is associated with sodium hydration due to estrogen, and the use of drospirenone containing contraceptives will reduce the incidence of this adverse effect. The probability of deep vein thrombosis and cardiovascular disease is related to the patient’s age, smoking status, amount of smoking, positive family history of venous or arterial thromboembolism in early life, obesity, hyperlipidemia, hypertension, migraine, etc. Therefore, avoid use in patients with these factors. Pay attention to sun protection during the medication period to reduce the occurrence of chloasma spots.
2, spironolactone: trade name: androstenedione, is an aldosterone compound, and is also a common drug for anti-androgen therapy. Mechanism of action: competitively inhibit the binding of dihydrotestosterone to the receptors of skin target organs, thus inhibiting the function of sebaceous glands; inhibit 5a reductase and reduce the conversion of testosterone to dihydrotestosterone. The recommended dose is 1~2mg/kg daily for 3-6 months. Adverse effects include positive dose-related incidence of menstrual irregularities, nausea, drowsiness, fatigue, dizziness, headache, and hyperkalemia. It is contraindicated in pregnant women. It is not recommended for male patients as they may experience breast development and breast tenderness after use.
Glucocorticoids
Physiological small doses of glucocorticosteroids have an inhibitory effect on nephrogenic androgen secretion and can be used for anti-adrenogenic androgen therapy; larger doses of glucocorticosteroids have anti-inflammatory and immunosuppressive effects, so short courses of higher doses of glucocorticosteroids can control inflammation in patients with severe acne. Recommended use.
1, fulminant acne: Prednisone 20-30 mg/d, which can be given orally in 2-3 doses for 4-6 weeks and then gradually reduced and started in combination or replaced with isotretinoin.
2, convergent acne prednisone 20~30 mg/d for 2~3 weeks, tapered to discontinuation over 6 weeks.
3. Physiologic doses of prednisone 5 mg or dexamethasone 0.75 mg, taken nightly, can inhibit the production of androgen precursors by the adrenal cortex and ovaries. For patients with premenstrual acne, prednisone should be started 7 to 10 d before each menstrual period until the onset of menstruation. Long-term high doses of glucocorticoids should be avoided to avoid adverse reactions, including hormonal acne or folliculitis, which can complicate the condition.