Clinical efficacy of a combination treatment of traditional Chinese medicine for scalp seborrheic dermatitis

To evaluate the clinical efficacy of a combination treatment of traditional Chinese medicine (TCM) in scalp seborrheic dermatitis (SSD) of differing severity.

severity of SSD and the treatment effect.At present, western medical treatments mainly include medication and physical therapy, such as antifungal drugs, anti-inflammatory drugs, and intense pulsed light.The treatment of SSD in traditional Chinese medicine (TCM) is based on syndrome differentiation and includes medicines that are consumed internally and topical application treatments.TCM considers SSD as blood hot wind-dryness syndrome, spleen and stomach dampness-heat syndrome, blood deficiency wind-dryness syndrome, and so on. 2,3Pi Fu Kang Xi Ye (PFKXY) mainly cools blood and removes dampness, reduces heat, and detoxicates, 4 Run Zao Zhi Yang Jiao Nang (RZZYJN) mainly removes wind and relieves itching, 5 while the garlicin enteric-coated tablets have an antimicrobial effect. 6In our study, SSD patients who used the above three drugs showed significant improvement in symptoms.We used a TCM combination treatment for SSD with satisfactory efficacy, and the results are reported below.

| Study respondents
We selected first-visit and second-visit patients with typical SSD who visited the Medical Research Center for Hair and Skin of our hospital.Inclusion criteria of research respondents: (1) definite diagnosis of SSD; (2) having complete evaluation data and the "16-point scale" score before and after treatment; (3) no SSD-related treatment was received 1 month before the visit to the doctor.Exclusion criteria: (1) complicated with other skin diseases such as psoriasis and contact dermatitis, or systemic diseases such as liver and kidney; (2) incomplete follow-up data; (3) has received SSD-related treatment within 1 month.

| Evaluator training
The evaluator was trained in the use of the "16-point scale," and scored the severity of SSD patients before and after treatment with this scale.Dandruff was assessed using the adherent scalp flaking score (ASFS) 10-point scale with scores from 0 to 10. Grade 0 was no dandruff, Grade 1-2 was small powdery gray and coarse dandruff, Grade 3-4 was small to medium dandruff, Grade 5-6 was large and thin dandruff loosely connected to the scalp, Grade 7-8 was adherent dandruff, and Grade 9-10 was white to yellow thicker dandruff closely attached to the scalp. 7For erythema, the site with the largest scalp area was taken for scoring: According to Kim's standard score, 8 a score of 0 is for no erythema; score of 1 is for erythema area ≤2 cm 2 ; score of 2 for erythema area >2 cm 2 <5 cm 2 ; and score of 3 is for erythema area ≥5 cm 2 .The severity of pruritus was assessed by frequency of pruritus and whether resting of the patient was affected: a score of 0 means no pruritus; 1 means occasional pruritus; 2 means frequent pruritus but not affecting normal rest; and 3 means frequent pruritus and affecting normal rest.The scores of dandruff, erythema, and pruritus were summed up to obtain a total score, with a maximum score of 16.Severity was determined based on the total score as follows: 0~5 points: mild; 6~9 points: moderate; and 10~16 points: severe.

| Respondent form
The contents included the patient's name, gender, age, serial number, number of visits, duration and course of disease, severity of the disease, 10-point scale score for adherent dandruff, erythema score, pruritus score, and whether adverse events occurred.Cortex(Baixianpi).The scalp of patients with mild SSD were intervened by PFKXY once a day for 4 weeks and the detailed treating method using PFKXY as a shampoo once a day were showed as follows: taking a one-yuan coin-sized amount of the lotion (about 8 to 10 mL) in the palm of the hand, working it gently into foam, applying the foam to the scalp, rubbing it gently for 3 min and then rinsing it off.Patients with moderate SSD were treated with PFKXY combined with capsules of RZZYJN taken orally for 4 weeks (Run Zao Zhi Yang Jiao Nang, China National Pharmaceutical Group Corporation Tongjitang [Guizhou] Pharmaceutical Co., Ltd., 24 capsules), and the topical application method was the same as that of mild SSD patients.

| Graded treatment
The compositions of RZZYJN (1000 capsules in total and 0.5 g per capsule) were listed as follows: Polygoni Multiflori Radix (Heshouwu, 291 g), Polygoni Multiflori Radix Praeparata (Zhiheshouwu, 265 g), Rehmanniae Radix (Dihuang, 429 g), Mori Folium (Sangye, 291 g), Sophorae Flavescentis Radix (Kushen, 291 g), Laportea bulbifera (Honghuoma, 150 g).The patients with moderate SSD take RZZYJN as often as four capsules once and three times a day.Treatment for patients with severe SSD was PFKXY combined with RZZYJN, and garlicin enteric-coated tablets taken orally for 4 weeks (Garlicin Enteric-coated Tablets, Xinjiang Tefeng Pharmaceutical Co., Ltd., 24 tablets).The main ingredient of garlicin enteric-coated tablets was allicin (10 mg / tablet) extracted from garlic.The patients in the three groups received continuous treatment in four tablets once and three times a day for 4 weeks, and they revisited the hospital after reaching the treatment endpoint, for assessment of the efficacy and adverse reactions.It is important to note that the intervened strategy used in present study are the routine clinical treatments for patients with mild-moderate-severe SSD.Therefore, although there was no ethical statement in this study, we strictly follow the principles stated by the Declaration of Helsinki.

| General details
We studied a total of 81 patients with SSD.Four cases failed to follow-up on time.A total of 77 cases were finally included in the study, consisting of 40 males and 37 females.The age ranged from 13.5-53 years, with an average age of 35.5 years.The duration of disease ranged from 2 weeks to 10 years, with an average duration of 7.5 months.

| Overall treatment results across groups
The scores of the 77 patients before treatment and after treatment were 7.71 ± 3.35 and 2.23 ± 1.53, respectively.The paired t-test showed a correlation of 0.672, p (correlation) = 0.000 and p (t-test) = 0.000, that is, the SSD score decreased, and the posttreatment effect was significant (Table 1).

| Treatment results of patients based on SSD severity
The patients were divided into mild, moderate, and severe SSD groups and given different treatment regimens.They were assessed using the SSD 16-point scale before and after treatment.The difference of scores before and after treatment was regarded as the treatment effect.
Treatment effect in the mild SSD group: For the 14 patients in the mild SSD group, the pre-treatment score was 3.86 ± 1.75, post-treatment score was 0.71 ± 1.07, and the treatment effect was 3.14 ± 1.83 (Table 2).The treatment effect was as per normal distribution, with correlation test p = 0.442, >0.01 and t-test p = 0.000, <0.01, that is, the correlation was not significant but the t-test was significant.It shows that after treatment, the SSD score of mild patients decreased, but the decrease in scores among individuals was inconsistent, which may be related to the large difference in scores among these patients before treatment.
Treatment effect in the moderate SSD group: For the 41 patients with moderate SSD, the pre-treatment score was 7.07 ± 0.36, post-treatment score was 2.17 ± 0.20, and the treatment effect was 4.90 ± 1.77.The treatment effect was as per normal distribution, for which the correlation test p = 0.000, <0.01, t-test p = 0.000, <0.01, that is, the correlation and t-test were significant.The SSD score of patients in the moderate SSD group decreased after treatment, and the treatment effect was significant (Table 3).
Treatment effect in the severe SSD group: For the 22 patients with severe SSD, the pre-treatment score was 11.36 ± 0.43, posttreatment score was 3.32 ± 0.29, and the treatment effect was 8.05 ± 2.21.The treatment effect was as per normal distribution, and the correlation test p = 0.379, >0.01, t-test p = 0.000, <0.01, that is, the correlation was not significant but t-test was significant, indicating that the SSD score of severe patients decreased after treatment, but the decrease of scores among individuals was inconsistent, which may be related to the large difference of scores before treatment and the end point of treatment (although most patients got better, their scores still belonged to mild SSD, and they were not completely cured) (Table 4).
After treatment, the scores in the mild and moderate SSD groups reduced to less than 2 points or even recovered, and those of severe patients reduced to about 3 points, showing only mild SSD, which indicates the effectiveness of the combination treatment with TCM.

| DISCUSS ION
SSD is a chronic, recurrent, and inflammatory skin disease, common in infants, adolescents, and adults, with scalp scales, erythema, and pruritus as the main clinical manifestations.In this study, the severity of the SSD was graded according to the "16-point scale" developed at the Medical Research Center for Hair and Skin of our hospital.The patients with mild, moderate, and severe degrees of SSD were treated with a combination treatment of graded TCM.
Overall therapeutic effect: symptom scores of all patients decreased by 5.48 ± 2.51 after treatment as compared with those

TA B L E 1
Overall treatment results for all patients (n = 77).
before treatment, and p = 0.000 using t-test, indicating that the SSD scores had significant differences before and after treatment, and the treatment was effective.The correlation coefficient was 0.658 in the correlation test, indicating that the scores before and after treatment had a strong correlation, and p = 0.000, indicating that the scores of different patients decreased consistently and the treatment effect was stable.
In this study, hierarchical statistical analysis was also performed on the scores before and after treatment according to the mild, moderate, and severe degrees of SSD.The decrease in SSD scores in the three groups of patients before and after treatment were in accordance with the normal distribution.The scores of patients with mild, moderate, and severe SSD decreased by

TA B L E 4
Evaluation of therapeutic effect in patients with severe SSD (n = 22).
after treatment, indicating that the treatment for severe patients is more complicated than that for mild and moderate patients.This may also be the reason for the inconsistency.Depending on the situation, the treatment cycle could be extended further, and follow-up treatment can be carried out to achieve better therapeutic effect or even recovery.
In this study, the "16- For patients with moderate SSD, along with topical application of PFKXY, we added oral Runzao Zhiyang Capsule, which mainly contains fleece flower root, unprocessed rehmannia root, mulberry leaf, lightyellow sophora root, and heterophyllous girardinia herb.Among them, fleece flower root and unprocessed rehmannia root are effective for nourishing blood, mulberry leaf, and lightyellow sophora root are useful in dispelling wind and reducing heat, heterophyllous girardinia herb helps in dispelling wind and eliminating dampness.
Overall, this combination can achieve the effects of nourishing yin and blood, dispelling wind, relieving itching, relaxing bowels, relieving constipation, and the like. 5Modern medical research has shown that these medicinal components contain anti-inflammatory substances, 12,13 and at the same time, fleece flower root and lightyellow sophora root also contain components, 14 which can inhibit pathogenic bacteria and improve intestinal flora, and possibly improve scalp micro-ecology through the intestine-skin axis. 15Compared with the topical application of PFKXY alone, the systemic treatment combination with RZZYJN could better nourish Yin and blood, loosen the bowel to relieve constipation, and regulate the physiological functions of each system in the patient's body, and had better therapeutic effects for moderate SSD patients.
For patient with severe SSD, we used a combination of three drugs, that is, oral garlicin enteric-coated capsules was added to the first two drugs.The main component of garlicin enteric-coated capsules is allicin extracted from garlic, which can selectively inhibit the synthesis of thiol-containing protein of pathogenic microorganisms and destroy the microbial structure to exert a wide-range resistance effect on bacteria, fungi, viruses, parasites, and other microorganisms. 16SSD patients have scalp microecological imbalance, which is mainly related to the composition changes of bacteria such as Staphylococcus and fungi such as Malassezia.Allicin is found to inhibit S. aureus. 17Studies have also shown that allicin and ketoconazole have a similar effect in the treatment of fungal skin diseases. 18The combined use of garlicin enteric-coated capsules could improve the symptoms of scalp microecological imbalance more effectively in patients with severe SSD, and contribute to the recovery of scalp microenvironment in such severe cases.
In conclusion, the graded TCM combination treatment in this study had significant effects in patients with mild, moderate, and severe SSD, and the efficacy was stable especially for patients with moderate SSD.Standardized and complete course of medication is an important guarantee for the rehabilitation of SSD patients.
We set the treatment time for patients as 4 weeks, to ensure that the vast majority of patients achieve better therapeutic effects.
Additionally, some limitations such as the regional distribution fea- SPSS 26.0 statistical software was used to analyze the data, the measurement data are expressed as (x̄ ± s), and the non-parametric test was used for comparison between groups.Bivariate correlation analysis was used for correlation analysis, and Spearman correlation coefficient was used for non-normal distribution data.The difference was statistically significant if p < 0.05.
point scale" proposed by the Medical Research Center for Hair and Skin of our hospital was used to grade the severity of SSD patients and serve as the evaluation index of treatment effect.This study is a successful attempt of clinical use of this evaluation tool.The tool is simple and easy to use, has high feasibility, and can quantify the severity of patients' symptoms.It has very good prospects for clinical use, and with continuous verification and improvements in practice, it can additionally be used for the diagnosis and treatment of SSD in the future.From the perspective of TCM syndrome differentiation, SSD patients present with symptoms such as erythema, scaling, and pruritus on the head and chest, and back, indicating that they have symptoms such as blood hot wind-dryness syndrome, spleen and stomach dampness-heat syndrome, and blood deficiency wind-dryness syndrome.Therefore, the treatment should be based on the patients' condition to clear heat and cool blood, dispel wind and relieve itching, fortify the spleen and drain dampness, moisturize dryness by nourishing blood.In modern medicine, it is believed that the pathogenesis of SSD patients includes microecological disorders, immunity, inheritance, skin lipid metabolism disorders, and barrier damage.The current treatment methods include keratolysis, antifungus, anti-inflammation, and among others.In this study, for patients with mild SSD, we used topical application and so we chose PFKXY, which mainly consists of extracts of 10 medicinal plants including honeysuckle bud and flower, peony root, rhubarb root and rhizome, liquorice root, common cnidium fruit, dandelion, purslane herb, glabrous greenbrier rhizome, garden burnet root, and densefruit pittany root-bark.Among these, honeysuckle bud and flower, dandelion, rhubarb root and rhizome, glabrous greenbrier rhizome, and purslane herb have effects of clearing heat and relieving itching,4 which can effectively alleviate the symptoms of SSD.Meanwhile, modern studies have also shown that common cnidium fruit, honeysuckle bud and flower,9 and purslane herb10 have anti-inflammatory effects and can reduce the inflammatory response in patients with SSD.Common cnidium fruit, purslane herb, and dandelion 11 have antibacterial and bacteriostatic effects and can effectively inhibit pathogenic microorganisms such as Staphylococcus aureus and regulate skin micro-ecology.Patients with mild SSD had milder symptoms, and the topical application of PFKXY to fight inflammation and regulate skin micro-ecology was able to produce better therapeutic effects.
tures of patients and smaller sample size were existed in this study, mainly manifesting as the northern-distributed region feature of the patients enrolled in this study.Therefore, various details including enlarging the sample size, broadening the population distribution region as well as racial difference will be improving in the following work, which aimed to further validate the effectiveness and safety of the combination strategies of TCM for SSD treating.AUTH O R CO NTR I B UTI O N SConception and design of the research: Zhang F. Acquisition of data: Li SR, Chen YC.Analysis and interpretation of the data: Li YL.Statistical analysis: Ren W. Obtaining financing: Zhang F. Writing of the manuscript: Li YH, Ren W. Critical revision of the manuscript for intellectual content: Zhang F. All authors read and approved the final draft.
PFKXY (Pi Fu Kang Xi Ye, Beijing Huayang Kuilong PharmaceuticalCo., Ltd., 50 mL) was applied as the treatment drugs for intervening the scalp of patients with mild SSD, which composed of the extracts of 10 different herbal medicines: Lonicerae Japonicae Flos (Jinyinhua),

test) p (correlation) Shapiro-Wilk test
after treatment, but the p > 0.05 for the correlation test meant that the t-test was significant and the correlation was not significant, indicating that the SSD score of patients with mild and severe SSD significantly decreased and the treatment was effective after treatment.However, the scores among individuals declined inconsistently.p< 0.05 in the t-test for the scores of patients with moderate SSD before and after treatment, and p < 0.05 in the correlation test, which meant that the t-test and the correlation test were significant, and it indicated that the decrease of SSD score in patients with moderate SSD after treatment was statistically significant and consistent.One of the reasons for the difference may be that in our "16-point scale" evaluation (patients ture, the sample size needs to be further enlarged for verification, and better statistical results can be obtained.After treatment, the SSD scores of mild and moderate patients reduced to less than 2 points or even 0 (recovered), and those of severe patients reduced to about 3 points (mild SSD), indicating the effectiveness of the intervention.The score for severe patients was still about 3 points N Score t p (t-**p < 0.01 compared with the pre-treatment score.TA B L E 2 Evaluation of therapeutic effect in patients with mild SSD (n = 14).**p< 0.01 compared with the pre-treatment score.TA B L E 3 Evaluation of therapeutic effect in patients with moderate SSD (n = 41).N Score t p (t-test) p (correlation) **p < 0.01 compared with the pre-treatment score.