A study of ultrasonography for the treatment of Qingre Liangxue decoction on blood-heat psoriasis

Jia-Yan Li ,Li-Li Ma ,Yi-Miao Fang

1The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310053,China.2Department of Dermatology,The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310006,China.

Abstract Objective:The clinical effectiveness of blood-heat psoriasis treated by Qingre Liangxue decoction and ultrasound imaging changes of lesions was observed.Methods:Patients with blood-heat psoriasis were selected and randomly grouped into two groups: the treatment group taking the Qingre Liangxue decoction orally,the control group taking the Compound Glycyrrhizin Tablets orally,both groups applying topical emollient lotion for a 12-week treatment period.Ultrasound images of target lesions and healthy skin were collected at different treatment times.Results:The epidermal thickness thought,the dermal density incremented as well as the subepidermal low-echogenic band (SLEB) width narrowed in both groups during the treatment.Conclusion:Qingre Liangxue decoction has signified efficiency in the treatment of blood-heat psoriasis,and high-frequency ultrasound has the advantages of non-invasive,timely and objective in the evolution.

Keywords: Qingre Liangxue decoction;high-frequency ultrasonography;epidermal thickness;dermal density;subepidermal low-echogenic band

Background

Psoriasis is a chronic skin disease with erythema and scale,which is difficult to treat.Blood-heat type is more common in progressive psoriasis vulgaris,and its clinical features are bright red plaque color,increasing or rapidly expanding lesions,multi-layer scales,or obvious itching,and other symptoms such as sore throat,fever,dry stool and red urine.Previous evaluation indexes,such as Psoriasis Area and Severity Index (PASI),are subjective.With the development of ultrasonography,dermatologists can observe the changes in the psoriatic lesions’ epidermis and dermis with the help of ultrasonic scaner.Qingre Liangxue decoction is an agreement prescription for psoriasis specialist outpatient service in dermatology department of The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine (hereinafter referred to as our hospital),which has been used for the treatment of blood-heat psoriasis for a long time.In this study,we observe the ultrasound imaging changes before and after the treatment of blood-heat psoriasis patients with target lesions and healthy skin,and evaluate the effectiveness of Qingre Liangxue decoction in treating blood-heat psoriasis,and discuss the role of high-frequency ultrasonography (HFUS) in the treatment evaluation of psoriasis.

Methods

Subjects of study

A total of 98 psoriatic patients were qualified for the study in the period from January 2021 to July 2021,referred blood-heat type diagnosed in dermatology clinic of our hospital,randomly divided into treatment group (49 cases) and control group (49 cases)according to the time sequence of visits.Referring to the diagnostic criteria of blood-heat psoriasis in Guidelines for Clinical Evidence-based Practice of Traditional Chinese Medicine for Psoriasis Vulgaris,it is included: (1) Bright red lesions,thick plaques,multiple scales,increasing or rapidly expanding new lesions with itching,upset,red urine,dry stool,red or crimson tongue,wiry pulse or more than one symptom;(2) The age ranged from 18 to 70 years old.Exclusion: (1) History of external drugs such as powerful glucocorticoid and tretinoin preparation for internal and external use in 1 month;(2) History of systematic use of immunosuppressants within 6 months;(3) History of using biological agents within 1 year;(4) lactation,pregnancy and planned pregnancy within 6 months;(5)Unable to follow up on schedule;(6) refused to participate in this study.

This study has been approved by the Ethics Committee of The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine (2021-KL-179-01).All the participants signed informed consent form.

Research programme

The treatment group was treated with oral prescription about Qingre Liangxue decoction (Bubalus bubalis30 g,Smilax glabra30 g,Arnebia euchroma20 g,Rehmannia glutinosa20 g,Isatis indigotica15 g,Sophora japonica10 g,Paeonia suffruticosa10 g,Scutellaria baicalensis10 g,Nidus Vespae10 g,Curcuma Longa10 g,Rheum palmatum10 g).2 doses a day,taken separately in the morning and evening,each dose 200 mL,which is decocted by the Chinese medicine pharmacy of our hospital.The control group was given compound glycyrrhizin tablets,50 mg once,three times a day,produced by Akiyama Tablets Co.,Ltd.(Grant number: Sinopharm Zhunzi J20130077).All skin lotion for external use.

Ultrasonic image acquisition

Instrument: Ultrasound SkinScanner-DUB,purchased from Tpm Medical Co.,Ltd.,with a probe center frequency of 22 MHz.

Location selection: Select a representative lesion as the target for ultrasonic detection;The ultrasonic detection site of healthy skin was selected 2 cm outside the edge of lesion.

Operation steps: Let the patient select the appropriate position,expose the skin,and disinfect the outer port of the probe;Apply a proper amount of coupling agent evenly to the target lesions of patients;The probe is located directly above the target,collecting and retaining clear target images,and using the software with its own measuring tools to collect data from the images.

Statistical analysis

SPSS 25.0 was used for statistical analysis.Measurement data were in accordance with the normal distribution expressed by,age comparison between groups using independent samplet-test,gender comparison using Chi-square test,repeated measurement data between groups using repeated measurement analysis of variance.P＜0.05 was statistically significant.

Results

Comparison of basic information between two groups

There were 49 cases in the treatment group(27 males and 22 females,age: 37.31±1.36 years) and 27 males and 22 females in the control group (age: 38.82±1.54 years).There was no significant difference in age and gender between the two groups (Table 1).

Comparison of healthy skin in different parts between the two groups

There was no significant difference in epidermal thickness,dermal density and SLEB width between the treatment group and the control group at the same site (P＞0.05).No obvious SLEB was found in healthy skin of all parts under ultrasound.The density of normal dermis in different parts of the same group was statistically different[1] (P＜0.05),so the target lesions in different parts were grouped and compared (Table 2).

Comparison of target lesions in different parts before and after treatment between the two groups

The dermal density of lower limbs in the treatment group was different in different treatment time(pretherapy and 2 weeks,2 weeks and 12 weeks,P＜0.001),while in the control group,it was different only pretherapy and 12 weeks (P=0.035,pretherapy and 2 weeks,2 weeks and 12 weeks,P＞0.05);The difference between different treatment time groups:2 weeks treatment: 3.00±0.542(P＜0.001),12 weeks treatment: 4.94 ± 0.95 (P＜0.001).Epidermal thickness,dermal density and SLEB width of trunk and upper limbs,epidermal thickness and SLEB width of lower limbs in two groups were significantly improved with the prolongation of treatment time,with Treatment for 12 weeks but no interactive effect.There were differences in upper limb dermis density,trunk dermis density and lower limb SLEB width between the two groups (P＜0.05),and there was no interaction between time and treatment.The therapeutic effect of the treatment group was better than that of the control.The remaining indexes had no inter-group effect among different groups at the same time (Table 3,Figure 1).

Figure 1 Comparison of epidermal thickness,dermal density,and SLEB width

Figure 2 Ultrasonic images of psoriatic target lesions at different treatment time including.(A) pretherapy;(B) after 2 weeks treatment and(C) after 12 weeks treatment.Arrows indicated dissolution of SLEB.

Table 1 Basic information

Table 2 Epidermal thickness,dermal density and SLEB width of healthy skin in different parts ()

Table 2 Epidermal thickness,dermal density and SLEB width of healthy skin in different parts ()

SLEB,subepidermal low-echogenic band

Table 3 Comparison of epidermal thickness,dermal density and SLEB width of target lesions before and after treatment()

Table 3 Comparison of epidermal thickness,dermal density and SLEB width of target lesions before and after treatment()

SLEB,subepidermal low-echogenic band

Discussion and conclusion

Psoriasis is a chronic inflammatory skin disease,which is difficult to treat.Early treatment will have a great impact on the overall follow-up treatment.It is an important means to accurately judge the changes of psoriasis severity during the treatment.Morphology is the main method used to evaluate the severity of psoriasis in multinational clinical guidelines nowadays [2-5],such as PASI,body surface area (BSA),Physician's Global Assessment (PGA) etc.PASI has been widely used in clinical trials since 1978 which evaluates the area of erythema,infiltration,desquamation and lesions in various parts of the body,and has relatively high clinical application value.However,PASI score is less sensitive to changes in the case of small lesion area while it can not reflect the change in time when the new rash occurs and the old rash subsides at the same time.Histological examination isobjective but invasive,and should not be observed by continuous skin biopsy.In order to make up for the limitations of the above-mentioned clinical evaluation methods for psoriatic lesions,in recent years,domestic and foreign guidelines and consensus put forward the use of skin ultrasound to monitor psoriatic lesions [4-8],so as to objectively measure the response of lesions to treatment methods.In this study,the frequency of ultrasound is 22 MHz,which belongs to high frequency ultrasound.Under which,ultrasound images can visualize the changes of psoriatic lesions completely,so it is suitable for clinical dynamic observation of psoriatic lesions [7,9-11].Ultrasound images of healthy skin show that the epidermis is a hyperechoic band with smooth and neat edges,and the dermis with moderate echo is below it.

Qingre Liangxue decoction is the experience prescription of Prof.Ma for Blood-heat psoriasis,which is mostly progressive psoriasis.Its pathogenesis is that exogenous pathogens are in the fur,which cannot be solved externally,and heat is transformed into erythema,and heat enters the camp blood,forcing blood to go in error.Therefore,its core is that there is heat in blood,which gradually forms the diagnosis and treatment idea of"distinguishing blood as the main factor and treating from blood".Previous studies have proved that this recipe can reduce the levels of epidermal growth factor (EGF) [12] and vascular endothelial growth factor (VEGF) [13] in serum of patients with psoriasis,thus inhibiting the proliferation of keratinocytes and dermal vessels,and alleviating the desquamation and infiltration of lesions;In addition,this recipe can regulate the expression of miR-21 [14],correct the abnormality of psoriasis-related miRNA gene,restore the natural disordered immune function to normal,inhibit the abnormal proliferation and division of keratinocytes,and finally improve the PASI score index and traditional Chinese medicine (TCM) syndrome score of psoriasis patients.

Compound glycyrrhizin tablets can anti-inflammatory and anti-allergic,and can be used in the treatment of psoriasis clinically,which is recommended for guidelines [7].Glycyrrhetinic acid is the main active metabolite of its main component glycyrrhizin.The results of [15] show that glycyrrhetinic acid may play a role in treating psoriasis by inhibiting the proliferation and promoting apoptosis of keratinocytes.So we select compound glycyrrhizin tablets as the control group in this study.

The results of this study showed that the target lesions of psoriasis in the treatment group and the control group were significantly improved at 2 weeks and 12 weeks after intervention by Qingre Liangxue decoction and compound glycyrrhizin tablets,among which the former had a better effect.The results suggested that the upper limb lesions were most obviously improved under the intervention of Qingre Liangxue decoction in the treatment of blood-heat psoriasis.

Under ultrasound,the epidermis of patients with blood-heat psoriasis is thicker than that of a healthy epidermis.The increase of epidermal thickness may be caused by the proliferation of keratinocytes and desquamation caused by incomplete keratinization.After treatment,the epidermal thickening improved and was close to normal,which was consistent with the reduction of lesions and scales.Therefore,we speculated that Qingre Liangxue decoction could inhibit the abnormal proliferation of keratinocytes and reduce scales.

Histology of psoriatic lesions showed hyperplasia of spinous layer,inflammatory reaction and neovascularization caused by infiltration of dermal T cells and neutrophils in dermis.The change of dermal density may be caused by inflammatory reaction leading to vascular hyperplasia and local edema in dermis,which is characterized by hypoechoic or even anechoic under ultrasound.The anechoic area is SLEB.Studies have shown that the width of SLEB is correlated with the degree of infiltration [9],so the change of SLEB may be an index worthy of attention.

We found that SLEB could be seen in all lesions of blood-heat psoriasis,which was consistent with the pathological manifestations of progressive psoriasis.After 2 weeks treatment,SLEB was obviously narrowed,and at 12 weeks,SLEB gradually subsided and the dermal echo gradually increased with the treatment time,and approached the normal (Figure 2).In the two groups at different times and different improvement degrees,the SLEB value decreased significantly.Therefore,we think that in the ultrasound images of psoriasis,SLEB is a most sensitive index than epidermal thickness and dermal density in the improvement process of lesions,that is,the more obvious the erythema and infiltration of lesions,the wider the SLEB.At the same time,combined with our previous research,it is suggested that Qingre Liangxue decoction may improve the treatment of psoriasis by inhibiting vascular proliferation,alleviating dermal edema and alleviating inflammatory reaction.

We observed the dynamic changes of lesions in the process of gradual healing of psoriasis treated with Qingre Liangxue decoction,concluding that skin ultrasonography can provide objective evaluation index for the therapeutic effect of psoriasis,which is worthy of further promotion in clinic.