5-Aminoketovaleric acid photodynamic therapy for acne vulgaris

  Acne is a common chronic inflammatory disease of the sebaceous glands of hair follicles with a chronic course that is prone to recurrence. It occurs as a result of a combination of pathogenic factors, including excessive sebum secretion, hyperkeratosis of the epithelium of hair follicles, excessive proliferation of Propionibacterium acnes and inflammatory reactions.
  Currently, there are many ways to treat acne. In addition to local treatment, the main clinical treatment for acne is systemic treatment with antibiotics, estrogen and progestin, and retinoic acid. With the increase of bacterial resistance and various drug-related adverse reactions, safe and effective physical therapy methods have become a new trend in the treatment of acne.
  In recent years, the treatment of acne vulgaris with 5-aminoketovaleric acid photodynamic therapy (ALA-PDT) has become a research hotspot in the field of medical aesthetics. A large number of reports at home and abroad have confirmed that ALA photodynamic therapy is a new acne treatment technology that is efficient, fast, safe, and well tolerated, but a relatively standardized protocol has not yet been established because it involves various factors such as drug concentration, encapsulation time, and light source equipment.
  To better summarize the clinical application of this technology in China and further standardize the existing treatment protocols in order to reach a consensus on treatment, the Dermatology Laser Subspecialty Committee of the Dermatologists Branch of the Chinese Medical Association organized an expert consensus workshop on ALA photodynamic therapy for acne. The meeting discussed in depth the mechanism of action, clinical recommendations, indications and contraindications of ALA photodynamic therapy for acne, and initially summarized the treatment consensus of ALA photodynamic therapy for acne in China.
  I. Mechanisms of ALA photodynamic therapy for acne
  1. Direct killing of pathogenic microorganisms such as Propionibacterium acnes: ALA photodynamic therapy can effectively remove Propionibacterium acnes. Propionibacterium acnes can synthesize and store a large number of porphyrins by itself, and when exposed to a specific light source, endogenous and exogenous porphyrins are stimulated to undergo photochemical reactions. A large number of singlet oxygen and free radicals are produced, which destroy the cell membrane of Propionibacterium acnes and lead to bacterial death.
  2. Acting on sebaceous glands, causing sebaceous gland atrophy and inhibiting sebum secretion: In normal skin, sebaceous glands have the highest uptake rate of 5-ALA, which is converted into the photosensitizer protoporphyrin IX (PpIX) highly enriched in sebaceous glands. When irradiated by light sources receiving specific wavelengths, PpIX is activated and undergoes a photochemical reaction that destroys the sebaceous glands, leading to atrophy of the highly secreting sebaceous glands, producing reversible damage to the sebaceous glands and directly reducing sebaceous gland secretion.
  During the recovery phase, a reduction in the number of follicular sebaceous gland units compared to pre-treatment was observed, but normal structure was retained. The reduction of sebaceous gland secretion changes the living environment of Propionibacterium acnes, which indirectly serves the purpose of antibacterial and sterilization.
  3.Improve the hyperkeratinization of keratin-forming cells at the mouth of the hair follicle and improve the obstruction of the opening of the sebaceous glands of the hair follicle: After photodynamic treatment, some epidermis can undergo slight necrosis. Histopathologically, vacuolization of keratin-forming cells from the middle of the spiny layer to the granular layer can be seen, and apoptosis of cells can occur, thus improving the obstruction of the follicular opening.
  4.Promote lesion healing and prevent or reduce acne scar residue: Red light penetrates well and can penetrate deeper into the skin. Mitochondria in cells absorb the most red light. After red light irradiation, the peroxidase activity of mitochondria increases and cell metabolism is enhanced, resulting in increased glycogen content, protein synthesis and adenosine triphosphate decomposition, thus enhancing cell renewal. It also enhances the phagocytosis of leukocytes and improves the immune function of the body.
  Secondly, low-dose red light irradiation can also promote the release of cytokines from macrophages, stimulate fibroblasts to proliferate, produce growth factors and promote the formation of new blood vessels, thus accelerating the repair process of damaged tissues.
  II. Clinical recommendations for ALA photodynamic therapy for acne
  Previous studies have found that ALA photodynamic therapy in acne clinical treatment, the matching of photosensitizer concentration, dose, encapsulation time and light source is very critical. Although blue light is 40 times more effective than red light in activating porphyrins, red light penetrates deeper into the skin (about 550um) than blue light (90-150um) and can better target the sebaceous glands of hair follicles.
  Therefore, the use of red light as the light source can produce a more effective photodynamic response. Existing clinical studies at home and abroad have observed that high concentration of photosensitizer and prolonged encapsulation can produce more serious adverse effects, which most patients cannot tolerate. Therefore, the photodynamic therapy with low concentration, short time sealing package and red light source is a more feasible clinical application scheme.
  1. The specific regimen is recommended as follows.
  ① 5-Amino ketovaleric acid (5-ALA), therapeutic concentration 2.5%-10% (adjustment of drug concentration according to the patient’s tolerance and response level), commonly used photosensitizer concentration is 5%;
  ② LED photodynamic therapy instrument red light (633±10) nm;
  ③ sealing time 0.5-2h, commonly used dressing time is 1h (the sealing time can be further adjusted according to the situation);
  ④ Light 20min (can be adjusted individually): light dose (72-126)J/cm2, light distance 10cm;
  ⑤ Treatment 3-4 times for a course of treatment, the recommended treatment interval is 7-14 days, at most should not exceed 4 weeks;
  ⑥Follow up for 3-6 months after treatment.
  2.Pre-treatment preparation for ALA photodynamic therapy.
  Patients should be consulted in detail about their previous diseases and medications, such as whether they have allergies to porphyrins and whether they have taken photosensitizing drugs. After full communication with the patient, sign the informed consent form. Before treatment, advise the patient not to use any cosmetics and to clean the face thoroughly; pretreat the lesion area before treatment and remove the cuticle as much as possible, etc.
  3 . Common treatment reactions and treatment in treatment.
  ① Slight flushing and edema will occur at the treatment site for 1-2 days after treatment, which is a normal phenomenon and generally does not require treatment, such as obvious skin redness and swelling, the daily cold water wet compress can be used routinely;
  ② After treatment, the skin may appear dry, the affected area cold compress or local topical moisturizer to relieve local skin dryness;
  ③ Transient aggravation of acne may occur 1-3 days after treatment (reactive acne), which generally requires no special treatment;
  Some patients may experience hyperpigmentation after treatment, which usually resolves on its own within one month. During this period, it is important to avoid direct sunlight and apply sunscreen when going out. Because ALA-mediated protoporphyrin is usually completely metabolized within 24-48 hours, long-term photosensitivity will not occur. After treatment, it is only necessary to avoid bright light for 48 hours, during which sunscreen and sun hat can be used routinely to reduce photosensitivity reactions.
  Indications and contraindications
  1. Indications.
  ① Patients with acne that is not treated by traditional methods or cannot be controlled;
  ② Patients with acne who are not suitable for treatment with antibiotics and/or retinoic acid;
  ③ Patients with acne who cannot tolerate topical medication;
  ④ Patients with more severe acne or acne with liver or kidney function impairment;
  ⑤ Patients with special occupations that are not suitable for medication (e.g. athletes, people working at height, etc.);
  (6) Patients with severe acne who are prone to scarring and cosmetic problems.
  2. Contraindications.
  ① Patients with photosensitive diseases (SLE, diffuse photosensitive dermatitis, etc.), skin photoallergy, porphyria, patients allergic to porphyrins;
  ② Patients who are allergic to any component of the topical aminoketovaleric acid hydrochloride solution;
  ③ Pregnant and lactating women;
  ④ Patients who take photosensitive drugs.
  IV. Prospects of ALA photodynamic therapy for acne vulgaris
  It has been clinically proven that photodynamic therapy with low concentration of 5-ALA, short time encapsulation, and red light as the light source can effectively treat acne vulgaris with mild adverse reactions, does not affect daily life and work, and can be repeated as one of the treatment options for acne vulgaris.