Efficacy of acupoint injection in the treatment of chronic eczema and its influence on peripheral blood T cells

Abstract

BACKGROUND

Chronic eczema significantly impacts daily life, social interactions, and quality of life; however, no curative treatment has been identified.

AIM

To determine the clinical efficacy of acupoint injection for chronic eczema and its influence on peripheral blood T cells.

METHODS

Eighty patients with chronic eczema treated at our hospital between June 2022 and March 2023 were randomly assigned to a control group (n = 40), which received conventional Western medicine treatment, or an observation group (n = 40), which received routine Western medicine treatment plus acupoint injection of triamcinolone acetonide. Response and adverse reaction rates, as well as differences in the levels of serum cytokines IFN-γ, IL-2, IL-4, and IL-10 before and after treatment were investigated.

RESULTS

No difference in overall response rates were found between the observation and control groups (100% vs 90%, respectively; P > 0.05); however, the observation group had a higher marked response rate than the control group (87.5% vs 52.5%; P < 0.05). Both groups had decreased Eczema Area and Severity Index scores and increased pruritus after treatment (P < 0.05), particularly in the observation group (P < 0.05). The observation group had an adverse reaction rate of 2.5% (1/40), which did not differ significantly from that of the control group (P > 0.05). The observation group exhibited higher post-treatment INF-γ and IL-2 but lower IL-4 levels than the control group (P < 0.05); however, no significant inter-group difference was observed in post-treatment IL-10 levels (P > 0.05).

CONCLUSION

Acupoint injection of triamcinolone acetonide is safe and effective in treating chronic eczema. Its therapeutic mechanism is related to the regulation of peripheral blood T cell levels, inhibition of inflammatory reactions, and mitigation of immune imbalance.

Key Words: Eczema; Acupoint injection; T cells; Immune imbalance

Core Tip: No cure has been found for chronic eczema. In this study, patients with eczema were treated with either routine Western medicine treatment or routine Western medicine treatment plus acupoint injection of triamcinolone acetonide. The clinical efficacy of the two treatment regimens was validated based on therapeutic efficacy, incidence of adverse reactions, and changes in serum cytokine INF-γ and IL-2/4/10 levels before and after treatment. Acupoint injection of triamcinolone acetonide was found safe and effective in treating chronic eczema, and its therapeutic mechanism is related to regulating peripheral blood T cell levels, inhibiting inflammatory reactions, and regulating immune imbalance.

INTRODUCTION

Eczema is a type of inflammatory dermatosis triggered by multiple internal and external factors. It is characterized by polymorphic skin lesions, exudation tendency, and intense pruritus[1] and has a high and continuously increasing incidence. Among different eczema types, chronic eczema has the highest incidence. It causes severe, lingering, long-lasting skin itching that is prone to recurrence, seriously affecting patients’ daily living activities, social interactions, and quality of life[2]. No completely curative treatment has yet been found for chronic eczema[3]. Topical glucocorticoid preparations are still the mainstay of eczema treatment, and antihistamines can be appropriately selected according to the patient’s condition to relieve itching and inflammation[4]. Traditional Chinese medicine (TCM) characteristic therapy offers unique properties and advantages that would help treat and prevent eczema[5]. Li et al[6] found that the Gu-Ben-Hua-Shi formula can significantly improve atopic dermatitis symptoms in mice. Its therapeutic mechanism is based on the regulation of the NLRP3 signaling pathway. Zhu et al[7] reported that Wenguanmu ointment can inhibit symptoms of 2,4-dinitrochlorobenzene-induced eczema in a mouse model by inhibiting the CKLF-1/NF-κB pathway. According to Thanik et al[8], TCM variously promotes the recovery of skin lesions, improving the quality of life of patients with moderate to severe eczema.

This study investigated the clinical efficacy of acupoint injection in the treatment of chronic eczema and elucidated its mechanism of action.

MATERIALS AND METHODS

General data

We selected 80 patients with chronic eczema who visited the dermatology clinic of Jinshan Hospital of Fudan University between June 2022 and March 2023. The patients were randomly assigned to the control or observation groups (n = 40 each). The observation group included 25 men and 15 women aged 58.68 ± 14.85 years on average, with a median course of 6.5 months. In the control group, the male-to-female ratio, mean age, and median disease course were 23:17, 62.50 ± 17.11 years, and 6 months, respectively. No significant inter-group differences were observed in general demographic data (P > 0.05), suggesting comparability (Table 1).

Table 1 General data analysis.

Factors	Observation group (n = 40)	Control group (n = 40)	χ2/t/Z	P value
Sex			0.208	0.648
Male	25 (62.5)	23 (57.5)
Female	15 (37.5)	17 (42.5)
Age	58.68 ± 14.85	62.50 ± 17.11	-1.068	0.289
Course of disease	6.50 (5.00, 16.50)	6.00 (4.00, 12.00)	-0.560	0.575

Inclusion criteria

The inclusion criteria were as follows: (1) Meeting the clinical diagnostic criteria for chronic eczema; (2) Age > 18 years, regardless of sex or ethnicity; and (3) Voluntary participation with informed consent provided.

Exclusion criteria

Patients were excluded based on the following criteria: (1) Known allergies to triamcinolone acetonide and/or lidocaine hydrochloride injection; (2) Dainting during previous acupuncture treatment; (3) Pregnant or lactating; (4) Topical use of hormonal drugs within the last 15 d; (5) Oral treatment with hormones, immunosuppressants, or retinoids in the last 30 d; (6) Serious heart, liver, kidney, or other visceral disease; malignant tumors; mental illness; or other skin diseases; and (7) Infectious diseases.

Methods

The control group were treated with 10 mg ebastine tablets, taken orally once a day (Approval No.: Imported Drug Registration No. H20140855; Industrias Farmaceuticas Almirall, S.A.). In addition, betamethasone dipropionate, clotrimazole, and gentamycin sulfate cream (II) (Approval No.: Medical Product Registration Certificate No. HC20110013; Bright Future Pharmaceutical Laboratories Limited; Specification: 20 g) was applied once in the morning and once in the evening. In addition to the above treatment, the observation group received acupoint injection of 28–32 mg triamcinolone acetonide (Approval No.: SFDA Approval No. H53021604; Kunming Jida Pharmaceutical Co., Ltd.; Specification: 1 mL: 40 mg) with 2 mL lidocaine (Approval No.: SFDA Approval No. H20023777; Shanghai Harvest Pharmaceutical Co., Ltd.; Specification: 5 mL: 0.1 g). The medication was injected into the contralateral Quchi and Xuehai acupoints in equal parts once a week. Both groups were treated continuously for 4 wk. The current research was approved by the Ethics Committee of Jinshan Hospital of Fudan University (Approval No.: JIEC 2022-S22). Informed consent was obtained from all the patients prior to participation.

Response evaluation

Primary outcome measures: The skin lesion area and severity index were assessed before and after treatment by referring to the Eczema Area And Severity Index (EASI)[9].

Skin lesion area: The proportion of the skin lesion area to the rest of the body (upper limbs, lower limbs, trunk, head, and neck) was calculated, with 0 points for no rash; 1 point for < 10% rash; 2 points for 10%–19%; 3 points for 20%–49%; 4 for 50%–69%; 5 for 70%–89%; and 6 for 90%–100%.

Severity of skin lesions: Manifestations of skin lesions, such as erythema (E), edema/papulation (I), exudation/crusting (C), exfoliation (Ex), and lichenization (L), were assessed. Each clinical manifestation was assigned a score of 0–3 points (0: none; 1: mild; 2: moderate; and 3: severe) based on severity, with a half score (0.5 point) allowed. The severity of the skin lesion was scored based on the total skin lesion (E + I + C + Ex + L) score.

EASI score = head area score × head severity (E + I + C + Ex + L) score × 0.1 + upper limb area score × upper limb severity (E + I + C + Ex + L) score × 0.2 + trunk area score × trunk severity (E + I + C + Ex + L) score × 0.3 + lower limb area score × lower limb severity (E + I + C + Ex + L) score × 0.4. Therapeutic efficacy was assessed before and after treatment using the Symptom Score Reduction Index (SSRI): SSRI = [(pretreatment symptom score − posttreatment symptom score) / pretreatment symptom score] × 100%.

SSRI > 90% indicated a cure; 60% ≤ SSRI ≤ 90% indicated a marked response; 20% ≤ SSRI ≤ 59% indicated an improvement; and SSRI < 20% indicated a non-response. The overall and marked response rates were calculated as follows: Overall response rate (ORR) = (cure cases + marked response cases + improvement cases) / total cases × 100%; Marked response rate = (cured cases + marked response cases) / total cases × 100%.

Secondary outcome measures: Patients were evaluated for pruritus before and after treatment using the Visual Analogue Scale (VAS) according to the symptom management theory. A 10-cm-long linear ruler was used for the assessment, with one end indicating 0 points (no itching) and the other 10 points (most severe itching. The middle section indicated varying degrees of itching. The patient was asked to mark the point on the ruler that best represented the intensity of itching. The results were calculated using a 10-point scale, with a higher score indicating a greater degree of itching.

Serum inflammatory cytokines: Before and after treatment, venous blood (4 mL) was collected on an empty stomach in the early morning and centrifuged (3000 rpm for 10 min). The upper layer containing liquid serum was collected and frozen at −80°C for further testing. Operated in strict accordance with the specifications, IFN-γ and IL-2/4/10 contents were analyzed using an enzyme-linked immunosorbent assays kits strictly according to the manufacturer’s instructions (Shanghai Keshun Biotechnology Co., Ltd.).

Safety observation and evaluation: Adverse reactions and severity and skin damage severity after treatment were recorded. In addition, local symptoms, such as skin irritation, erythema, desquamation, dryness, pruritus, and skin atrophy, at the acupoint injection site were noted. Laboratory safety tests that were performed before and after treatment included routine tests for blood and urine, liver and renal functions, and blood sugar. Detailed records were kept of the symptoms, occurrence time, duration, correlation with the test drugs (irrelevant, possibly irrelevant, possibly relevant, and relevant), measures taken, and outcomes of adverse reactions. The adverse reaction rate was then calculated as follows: Adverse reaction rate = number of cases of adverse reactions / total cases × 100%.

Statistical analyses

The data were analyzed using SPSS 25.0, and statistical significance was set at P < 0.05. Normally distributed continuous data were expressed as mean ± SD and analyzed using the independent samples t-test and paired-samples t-test to identify inter- and intra-group differences, respectively. Data with non-normal distribution were expressed as median (quartiles) and compared for inter- and intra-group differences using the Mann–Whitney rank sum test and Wilcoxon rank sum test, respectively. Categorical variables were expressed as number (percentage) and analyzed using the chi-square test or Fisher’s exact probability test.

RESULTS

Comparison of clinical efficacy

All 80 patients completed the treatment as required, with no withdrawals (see Figure 1 for post-treatment cases). No significant difference in ORR was observed between the observation and control groups (100% vs 90%, respectively; P > 0.05). However, the observation group showed a significantly higher marked response rate than that of the control group (87.5% vs 52.5%, respectively; P < 0.05; Table 2).

Figure 1 Observation group treatment chart. A and B: Before and after back treatment; C and D: Before and after calf treatment.

Table 2 Comparison of effective rates, n (%).

Groups	n	Curative effect				Response rate	Marked response rate
		Non-response	Response	Marked response	Cure
Observation group	40	0 (0.0)	5 (12.5)	31 (77.5)	4 (10.0)	40 (100.0)	35 (87.5)
Control group	40	4 (10.0)	15 (37.5)	19 (47.5)	2 (5.0)	36 (90.0)	21 (52.5)
χ2							11.667
P value						0.1161	0.001

Comparison of EASI scores and pruritus incidence (VAS)

The two groups did not differ significantly in pretreatment EASI and VAS scores (P > 0.05). However, the post-treatment EASI score in the observation group was lower than that in the control group (P < 0.05). In both groups, the EASI scores decreased significantly from the baseline after treatment (P < 0.05). Both groups also showed lower VAS scores after treatment (P < 0.05), particularly in the observation group (P < 0.05; Table 3).

Table 3 Comparison of Eczema Area and Severity Index and Visual Analogue Scale scores (points).

Groups	n	EASI score				VAS score
		Before treatment	After treatment	t value	P value	Before treatment	After treatment	t value	P value
Observation group	40	7.52 ± 3.25	2.22 ± 1.30	12.002	0	6.05 ± 1.54	1.98 ± 1.07	21.747	0
Control group	40	7.30 ± 3.96	3.19 ± 2.52	9.058	0	6.08 ± 1.72	2.93 ± 1.27	12.498	0
t value		0.278	−2.17			−0.069	−3.615
P value		0.782	0.034			0.945	0.001

Comparison of serum cytokines before and after treatment

Forty healthy people who concurrently underwent physical examination at our hospital were selected for comparison. INF-γ and IL-2 Levels were lower, whereas IL-4 and IL-10 Levels were higher, in the observation group than in the control group (P < 0.05; Table 4). The two patient groups did not differ significantly in pretreatment levels of INF-γ, IL-2, IL-4, and IL-10 (P > 0.05). However, the observation group exhibited higher INF-γ and IL-2 and lower IL-4 levels than the control group after treatment (P < 0.05), No significant inter-group difference was found in post-treatment IL-10 levels (P > 0.05). The INF-γ and IL-2 levels in the observation group were significantly higher than the baseline after treatment, whereas IL-4 and IL-10 were significantly lower (P < 0.05). In the control group, no significant change was observed in INF-γ levels before and after treatment (P > 0.05). However, IL-2 levels were higher and IL-4 and IL-10 were lower after treatment (P < 0.05; Table 5).

Table 4 Comparison of INF-γ, IL-2, IL-4, and IL-10 levels between the case and control groups.

Parameters	Case group	Healthy control group	t value	P value
INF-γ	311.75 ± 136.86	399.17 ± 129.35	-2.582	0.011
IL-2	35.54 ± 19.11	57.25 ± 20.51	-4.479	0.000
IL-4	79.40 ± 9.62	60.72 ± 9.99	7.712	0.000
IL-10	66.00 ± 8.78	56.16 ± 6.90	4.659	0.000

Table 5 Comparison of INF-γ, IL-2, IL-4, and IL-10 levels between the observation and control groups before and after treatment.

Parameters	Time point	Observation group	Control group	t value	P value
INF-γ	Before treatment	321.29 ± 135.22	302.21 ± 139.53	0.621	0.536
	After treatment	394.88 ± 115.70a	334.38 ± 137.47	2.13	0.036
IL-2	Before treatment	38.15 ± 19.98	32.93 ± 18.07	1.224	0.225
	After treatment	56.51 ± 18.00a	47.13 ± 20.04a	2.203	0.031
IL-4	Before treatment	81.01 ± 8.78	77.79 ± 10.25	1.508	0.136
	After treatment	61.31 ± 7.60a	67.20 ± 9.00a	−3.165	0.002
IL-10	Before treatment	65.94 ± 8.85	66.06 ± 8.83	−0.063	0.95
	After treatment	60.55 ± 11.86a	62.00 ± 8.84a	−0.623	0.535

^aP < 0.05 vs baseline.

Adverse reactions and recurrence

No serious adverse reactions occurred in either group. No symptoms of local skin irritation, hirsutism, atrophy, or telangiectasia were observed after the topical use of hormones. No abnormalities were noted in routine tests for blood and urine, liver and kidney functions, and blood sugar before or after treatment. In the observation group, soreness and discomfort at the local injection site were relieved within 24 h after acupoint injection, and no weakness of limbs was noted. Furthermore, no skin atrophy or depigmentation of concave pigment was observed at the acupoint injection site. The adverse reaction rate in the observation group was 2.5%, attributed to one patient who developed trunk folliculitis on the third week of treatment, which resolved after topical medication. The adverse reaction rate in the control group was 0. Three patients in the observation group experienced recurrence 1 month after the end of treatment, which was a recurrence rate of 7.5%. Comparatively, 7 cases in the control group recurred, with a recurrence rate of 17.5%; however, the EASI and VAS scores were lower than the baseline. The two groups showed no marked differences in adverse reaction and recurrence rates (P > 0.05; Table 6).

Table 6 Adverse reaction and recurrence rates, n (%).

Groups	Adverse reactions	Recurrence
Observation group	1 (2.5)	3 (7.5)
Control group	0 (0.0)	7 (17.5)
χ2		1.829
P value	1.000	0.176

DISCUSSION

Eczema is a common and frequently occurring disease in dermatology, with an incidence of 7.5% in China and 10.7% in the United States[10]. Eczema is caused by immune dysfunction, which is often associated with delayed allergic reactions[11,12]. The expression of inflammatory cytokines in the skin of patients with eczema is significantly increased compared with that in healthy individuals[13]. Research indicates that the pathogenesis of eczema may be related to imbalanced T cell subsets (Th1/Th2)[14]. Th1/Th2 cell subpopulations can regulate each other through the different cytokines they secrete[15]. Th1 cells primarily secrete IFN-α, IL-2, IFN-γ, and TNF-β, which are called Th1-type cytokines[16]. IFN-γ, as the representative Th1-type cytokine, has pro-inflammatory effects, and its main activity centers in immune regulation[17]. It is an important immunomodulatory factor in the body that promotes Th1 cell maturation and inhibits Th2 cell proliferation. It not only suppresses Th2 cell production of IL-4 but also inhibits B cell secretion of IgE, thereby inhibiting hypersensitivity reactions caused by high IgE levels[18]. Th2 cells primarily secrete IL-4, IL-5, IL-10, and IL-13, among others, which are called Th2-type cytokines[19]. IL-4, as the representative Th2-type, exerts anti-inflammatory effects[20]. IL-4 can inhibit Th1 cells and their functions, induce B cells to produce IgE, promote B cell proliferation, induce low-affinity receptor for IgE expression, and play a vital role in modulating IgE production, thereby participating in the development of allergic diseases[21,22]. Abnormal Th2-type cytokine secretions are strongly related to the occurrence, development, and prognosis of eczema[23].

Chronic eczema falls into the category of “wet sores” in TCM, which is mainly caused by wind-dampness-heat soaking the skin due to insufficiency of natural endowment; improper diet-induced movement; transformation disorders of the spleen and stomach; endogenous dampness and heat; exogenous wind-heat; and interactions between internal and external pathogens[15]. Therefore, treatment should involve cooling blood, dispelling wind, and relieving itching. Quchi is the confluence of the large intestine channel of hand-Yangming, which is good for clearing heat and relieving exterior syndrome; dispelling wind and eliminating rash; and regulating meridians, Qi, and blood combined with the characteristics of Yangming meridian[24]. Xuehai is the acupoint of the spleen meridian of foot-Taiyin, which can regulate spleen meridian Qi, modulate spleen transport function, promote blood circulation, and nourish blood to dispel wind[25]. The combination of the two acupoints based on syndrome differentiation functions in dispelling wind-evil, relieving itching, clearing heat, and removing dampness[26]. Acupoint injection is a modified TCM treatment that combines acupuncture stimulation with the properties of Western drugs and their penetrating effects on acupoints, exerting a comprehensive therapeutic effect[27]. Triamcinolone acetonide is a long-acting glucocorticoid with potent and lasting anti-inflammatory and anti-allergic effects[28]. Local injection can inhibit the transformation of B cells into plasma cells and interfere with humoral immunity[29] Furthermore, it stabilizes the lysosomal membrane, inhibits leukocytes and macrophages from migrating outside the blood vessels, and reduces inflammation[30]. It can also increase mast cell stability and reduce histamine release[31]. In the current study, the post-treatment EASI and VAS (pruritus assessment) scores of both groups decreased from baseline, with even lower scores in the observation group. Moreover, a significantly higher marked response rate was noted in the observation group. Hence, the combination of Western medicine and acupoint injection is effective in alleviating clinical symptoms and reducing severity of chronic eczema, with remarkable clinical effects. In terms of safety, no significant inter-group difference was found in the total adverse reaction rate, demonstrating the favorable safety profile of the combination therapy. Furthermore, the higher post-treatment serum INF-γ and IL-2 levels and lower IL-4 levels in the observation group indicates that acupoint injection of triamcinolone acetonide can promote IFN-γ and IL-2 (Th1-type cytokine) secretion, and inhibit the IL-4 (Th2-type cytokine) secretion, thereby correcting the Th1/Th2 imbalance in patients with chronic eczema at the cytokine level.

CONCLUSION

Acupoint injection of triamcinolone acetonide can effectively treat chronic eczema by regulating immune balance to improve the T lymphocyte level and inhibit inflammatory reactions. In addition, the treatment is effective in alleviating clinical symptoms with obvious curative effects and confers convenience and safety, which indicates is potential clinical application.