Analysis of the effectiveness of PDT with 5‐aminolevulinic acid in comparison to blue/red light combined with intralesional triamcinolone injection in treatment of severe inflammatory acne: A retrospective study

In this study, the therapeutic effect of 5‐aminolevulinic acid photodynamic therapy (ALA‐PDT) in comparison to blue/red light combined with intralesional triamcinolone injection for severe inflammatory acne was evaluated and analyzed.


| INTRODUC TI ON
Acne vulgaris is a common chronic inflammatory hair follicle and sebaceous gland disease, with a high incidence in adolescents.Table 1 describes the classification of acne in children and adolescents. 1,2e specific pathogenesis of this disease has not been fully clarified, which may be related to four major factors, namely hypersebaceous gland induced by the increase of androgens, abnormal keratosis of sebaceous duct opening in hair follicles, colonization of propionibacterium acne, and secondary inflammatory reaction. 3Acne is also classified as mild, moderate, and severe acne, as well as severe acute acne (Figure 1).Skin lesions in mild acne are easier to treat.However, for patients with moderate and severe acne, the pigmentation, scar, and psychosomatic health effects caused by acne are one of the difficulties faced by clinical treatment. 4Moreover, the course of acne is long, and the recurrence of the disease is likely, especially severe acne, which affects the physical and mental health of patients, increases the psychological burden of patients, and reduces the quality of life.With the development of clinical diagnosis and treatment techniques, there are more and more methods to treat acne.
In order to shorten the course of drug treatment and reduce adverse reactions, physical therapy such as red and blue light and 5-aminophenovalic acid photodynamic therapy has gradually become a hot spot in clinical research, providing new ideas and a new paradigm for the clinical treatment of severe acne. 5The acne should be treated early and actively to reduce inflammation and prevent scarring.5-aminolevulinic acid photodynamic therapy is a technique that combines the photosensitizer 5-aminolevulinic acid (ALA) with visible light illumination to induce cellular toxicity and achieve the photodynamic reaction for lesion eradication.The application of 5-aminolevulinic acid photodynamic therapy in treating actinic keratosis (AK) and basal cell carcinoma (BCC) was first introduced by Canadian researchers in 1990. 6In 2014, the Photodynamic Therapy Research Center of the Chinese Society of Dermatology was established, and the first edition of the expert consensus on the clinical application of 5-aminolevulinic acid photodynamic therapy in dermatology was published the following year. 7In recent years, 5-aminolevulinic acid photodynamic therapy has demonstrated significant efficacy in treating severe and refractory acne vulgaris, photoaging, actinic cheilitis (AC), squamous cell carcinoma (SCC), and various off-label applications, keeping pace with the rapid development of photodynamic therapy.The expert group provided comprehensive information on 5-aminolevulinic acid photodynamic therapy in the guidelines, including its mechanism of action, treatment protocols, clinical applications, adverse reactions and management, relevant precautions and care, and efficacy assessment, aiming to provide consensus opinions in these areas for dermatologists in clinical practice. 4erefore, as we already can find out from plenty of data in literature that light (blue/red or their combination) only treatment is less effective than PDT (light+ALA/MAL), this study is going to overcome the shortcoming of light therapy alone in the treatment of severe acne by comparison between ALA-PDT therapy and red blue light combined with triamcinolone injection and lidocaine injection in the treatment of severe acne.

| Patient and methods
One hundred and four cases of severe inflammatory acne who received treatment from August 2020 to August 2022 were recruited in this study.They were grouped according to the type of treatment.
The control group (group A) included 52 patients who received red and blue light combined with triamcinolone injection and lidocaine injection (1:4).The observation group (Group B) included 52 patients treated with ALA-PDT.Finally, the therapeutic effect and the occurrence of adverse reactions were compared between the two groups.number H20070027); 0.9% sodium chloride injection (Otsuka Pharmaceutical Co., LTD., Sinopark H20043271).

| Inclusion criteria
The selected patients must meet the diagnostic criteria for moderate to severe inflammatory acne with symptoms, signs and examination results, and the rash is only distributed on the face and neck of the patient.Before each treatment, the patient's facial and neck rashes were photographed and recorded.The irradiation was continued for 6 weeks.

| Group B
In this study, all patients in B were treated with ALA-PDT.The treatment measures were as follows: 5-aminolevulinic acid (Shanghai Fudan Zhangjiang Biological Medicine Co., LTD., national medicine approval number H20070027) was selected, and the concentration According to the recorded number of lesions, the removal rate of lesions was calculated as.
Lesion clearance rate = (total lesions before treatment−total lesions after treatment)/ total lesions before treatment × 100%.
Lesion clearance rate ≥ 90% was effective.The clearance rate of skin lesions was between 60% and 89%.Failure to reach any of the above conditions was invalid.Total effective rate = (lowly effective + highly effective)/ total cases × 100%.

| Comparison of the occurrence of adverse reactions between the two groups
The comparison items included erythema, flushed face, and dry and tight facial skin.

| S TATIS TIC AL ANALYS IS
In this study, SPSS 20.0 statistical software was used for statistical analysis.Measurement data were expressed as mean ± standard deviation (x ± s), and t-test was used.The statistical data were expressed as rate (%) and χ 2 test was used.p < 0.05 indicates a statistically significance difference.

| Clinical data
In A, there were 28 males 53.85% and 24 females 46.15%.Among all patients, the oldest was 34 years old, the youngest was

| Comparison of the occurrence of adverse reactions between the two groups
Fifty-two patients had local burning sensation when illuminated and

| Changes in the number of lesions before and after treatment
After 2, 4, and 6 weeks of treatment, the number of residual inflammatory and noninflammatory lesions in B was remarkably lower than that in B (p < 0.01).The specific data are shown in Table 4.

| DISCUSS ION
Acne, commonly known as pimples, is a common skin disease that occurs in teenagers.The reality shows that some patients with moderate and severe acne will appear pustules, cysts and papules in the face and neck, which seriously affect the appearance of patients.Without treatment and intervention, it is easy to leave pockmarks and have a negative impact on the physical and mental health of patients. 14For severe acne, systematic antibiotic and retinoic acid preparation are commonly used in clinical treatment.
But even with the best treatments, refractory acne is common.In addition, acne is mainly affected by teenagers.The adverse reactions of retinoic acid preparations, the psychological concerns of men and women of childbearing age about the effects on fertility and the continuous emergence of antibiotic resistance have led to the restriction of the systematic application of retinoic acid preparations and antibiotics. 15Therefore, physical therapy is a good option.Red and blue light irradiation is a popular acne treatment in recent years.7][18][19][20][21][22][23][24] Studies have shown that, 25 the value of red and blue light in the treatment of mild and moderate acne is prominent, but in the treatment of severe acne, the effect needs to be further improved.It has also been reported that photodynamic therapy is the most sufficient evidence among all the photoelectric treatments for acne. 26ALA-PDT is a kind of noninvasive photochemotherapy, which is more mature in clinical acne physiotherapy.ALA-PDT is a combination of local drug/device therapy to inhibit sebum generation and reduce the legacy of acne pits, which has multiple effects of anti-inflammatory and immune regulation.
F I G U R E 2 Bar graph of numbr of therapeutic effect for A.   The results of this study showed that the total effective rates of B after 2, 4, and 6 weeks of treatment were 28.85%, 75.00%, and 86.54%, respectively, and the total effective rates of A after 2, 4, and 6 weeks of treatment were 9.62%, 51.92%, and 69.23%, respectively.The discrepancy between A and B was statistically remarkable (χ 2 = 6.1905, 5.9713, 4.5217, p = 0.0128, 0.0145, 0.0335).
The incidence of adverse reactions in B was 5.77% lower than that in A (32.69%), and the discrepancy was statistically remarkable (χ 2 = 12.1333, p = 0.0005).To our knowledge, as reported by Meng et al., photodynamic therapy is only 79.1% effective in treating severe acne. 30While the study results of Xu et al. showed that the effective rate of treatment could reach 83.33% through using intralesional injection of triamcinolone alone. 31In addition, the adverse reactions in both groups were relieved and subsided after symptom- Light sources: alternating red and blue light irradiation; Triamcinolone injection (produced by Kunming Jida Pharmaceutical Co., LTD.; Specification: 1 mL: 40 mg).5-aminolevulinic acid (Shanghai Fudan Zhangjiang Biological Medicine Co., LTD., national medicine approval TA B L E 1 Clinical classification of acne in children and adolescents.

2. 3 . 2 | 9 2. 4 |
Exclusion criteriaPatients were not selected if they were: (1) Pregnant or lactating women; (2) Albinism, lupus erythematosus and other skin diseases;(3) Acne medication should have been used within 1 month; (4) There is cognitive impairment in the mental system and no method to cooperate with the experiment;(5) No consent from family members or incomplete basic information.Treatment intervention2.4.1 | Group ARed and blue light combined with internal skin closure treatment.Use a diode stimulated (LED) light energy therapy device (same parameters as above) for treatment.The researchers used 0.9% sodium chloride injection to clean the face of the patients, remove cosmetics, sebum secretions, dander and dust and other attachments, and the large cyst touched the rash and had a sense of fluctuations.The affected area is then disinfected with iodophor, the contents are drawn out with a sterile syringe, and triamcinolone injection is injected into the capsule (produced by Kunming Jida Pharmaceutical Co., LTD.; Specification:1 mL: 40 mg) with 2% lidocaine injection mixture (1:4) rinse properly and retain the liquid.Then alternate between red and blue light.Red light has a wavelength of (633 ± 10) nm.Blue light has a wavelength of (417 ± 10) nm.The duration of alternating red and blue light irradiation was 30 min, twice a week.Red light irradiation is mainly used for patients with serious inflammatory reaction or obvious nodules and cysts.The irradiation sequence is red light followed by blue light.

of 5 - 2 . 5 |indicators and criteria 2 . 5 . 1 |
aminolevulinic acid was configured with 5% gel.10,110.9% sodium chloride injection (Otsuka Pharmaceutical Co., LTD., Sinopark H20043271) was used for basic cleaning of the patient's face and neck, and removed obvious nodules or pus supposers in the patient.5% 5-aminolevulinic acid gel was applied to the lesions for 1-2 h.After cleaning the patient's face and neck, and wore the eye closure band and goggles, the LED photodynamic therapy instrument [Wuhan YAG Photoelectric Technology Co., LTD., Hubei Food and Drug Administration (standard) word No. 2260940 2010] was applied to receive red light irradiation treatment.The wavelength of the optical output was set to on 633 ± 10 nm, and the power density was set to 20-100 mV/cm2 The mask was adjusted so that it completely covers the patient's face, and the distance between the mask and the tip of the nose was between 10 and 15 cm.Subsequently, the initial power of illumination was set as 60 mV/cm 2 , and the illumination time was 20-30 min per time, and the power & time of illumination were reasonably adjusted according to the actual situation of patients.After that, cold spray was applied to the patient's face for 20 min.In addition, patients were advised to avoid light and keep facial moisture, and carry cold compress (30 min/ time) two to four times a day.Before each treatment, the patient's facial and neck rashes were photographed and recorded.All patients were treated once every 2 weeks for a total of three consecutive sessions.Observation Comparison of the treatment effect between the two groups After 2, 4, and 6 weeks of treatment, the therapeutic effects of A and B were observed and analyzed.The therapeutic effect was divided into lowly effective, highly effective and ineffective.Criteria12,13 :

16 patients had mild
to moderate degree of pain but all of them could tolerate it.None of the patients abandoned treatment because of pain.All the patients showed mild to moderate erythema and swelling in the skin lesions immediately after the end of light irradiation, but no obvious erythema in the skin lesions.Some patients also developed new pustules and a little exudation at the rashes, which peaked on the second and third days.Most patients do not need special treatment, 7-10 days about the resolution of their own.A small number of severe patients were treated with normal saline wet compress and prednisone tablet orally for 3 days (10 mg for three times per day), which could remarkably alleviate the problem.No ulcers or scars were found in any of the cases.Thirty-five patients developed different degrees of pigmentation 2 weeks after starting treatment.Most patients are consistent with the original acne lesions.However, there are a few patients with full-blown partial pigmentation.They all gradually subsided 8-12 weeks after completion of treatment.Within 1 week after each treatment, the patient experienced mild dryness and tightness.But the patient's condition will gradually improve over time.The adverse reactions of B included burning sensation, erythema, dryness and desquamate, itching, and pigmentation.The reactions were mild.There was remarkable discrepancy in adverse reactions between the two groups (p < 0.05) in

3 3
Bar graph of number of therapeutic effect for B. Comparison of adverse reactions between two groups [n, n(%)].
factors and provide a theoretical basis for controlling the number of inflammatory lesions.A was treated with red and blue light, which works by converting light energy into intracellular energy.Red light and blue light alternately irradiate the skin according to different conditions of skin recovery, which can change the cell structure, kill bacteria, provide a suitable environment for new cells, enhance the generation of new collagen elastin and collagen, and promote the growth of new cells.29Alternating red and blue light treatment can enhance the effect of acne treatment, combined with triamcinolone injection and docaine injection has anti-inflammatory and anti-hyperplasia effects.In our department of clinical work, it is a commonly used skin preconditioning method before red and blue light treatment, which has a good effect on acne cysts.

F I G U R E 4 4
atic treatment.According to the results, the clinical efficacy of the observation group was remarkably superior (p < 0.05), and the number of residual inflammatory and noninflammatory lesions was less in the observation After 4 weeks and 8 weeks of treatment (p < 0.01).The results Line chart of adverse reactions between two groups.Comparison of the number of lesions after treatment between the two groups (n = 52).
17 years old, and the mean age was 25.63 ± 11.05 years old.The longest course of disease was 4.5 years, the shortest was 6 months, and the mean course of disease was 2.98 ± 0.53 years.Degree of acne: Therewere 52 cases (100%) with severe acne.In B, there were 27 males 51.92% and 25 females 48.08%.Among all patients, the oldest was 35 years old, the youngest was 18 years old, and the mean age was 26.02 ± 11.12 years old.The longest course of disease was 5 years, the shortest was 5 months, and the mean course of disease was 3.02 ± 0.74 years.Degree of acne: There were 52 cases (100%) with severe acne.There was no statistical difference in gender, age and other general data between A and B (p > 0.05), proving that A and B can be compared with each other.

Table 3 and
Figure 4.
Comparison of therapeutic effect between two groups [n, n (%)].