Fire Needle Therapy for the Treatment of Psoriasis: A Quantitative Evidence Synthesis

Abstract

Background:

Fire needle therapy is a method of quickly piercing into acupoints with red-hot needles to treat diseases. Recently, multiple studies have reported that fire needle therapy is effective in the treatment of psoriasis; however, there are few articles systematically evaluating the effect of this therapy. Therefore, this systematic and meta-analysis study is conducted to estimate the efficacy and safety of fire needle therapy for psoriasis.

Methods:

PubMed, Embase, CNKI, VIP, CBM, CENTRAL, and Wan Fang databases were systematically searched from the dates of construction of these databases to August 24, 2019, and randomized controlled trials assessing patients with psoriasis who were treated with fire needle therapy alone or in combination with other drugs were also evaluated.

Results:

Fire needle therapy was effective in treating psoriasis (p = 0.0002; risk ratio [RR], 1.20; 95% confidence interval [CI], 1.09–1.33) with a lower recurrence rate (p = 0.005; RR, 0.48; 95% CI, 0.29–0.80). Adverse events after fire needle treatment were similar to those without fire needle treatment (p = 0.38; RR, 0.67; 95% CI, 0.28–1.63). After fire needle treatment, the number of cluster of differentiation (CD)8⁺T cells, type 1 helper cells, interleukin (IL)-2, and interferon (IFN)-γ decreased, whereas the number of CD4⁺T cells, type 2 helper cells, IL-4, IL-10, and the proportion of CD4⁺T cells and CD8⁺T cells increased.

Conclusions:

Fire needle therapy, specifically in combination with oral medicines, is effective in treating patients with psoriasis with low recurrence rates.

Introduction

Psoriasis is a chronic inflammatory skin disease, which results from the interaction between genetics and the environment, and is mediated by immunity. There are five types of psoriasis, including plaque psoriasis, guttate (droplet) or eruptive psoriasis, inverse psoriasis, pustular psoriasis, and erythrodermic psoriasis.¹ The main clinical manifestations of psoriasis are red papules or plaques, covered with multiple layers of silvery-white scales.²

Psoriasis is observed in people of all ages. A World Health Organization global report³ indicated that the prevalence of psoriasis ranged from 0.09% in the United Republic of Tanzania⁴ to 11.4% in Norway,⁵ making psoriasis a global problem that plagues ∼100 million people worldwide. In China, the prevalence of psoriasis increased from 0.123% in 1984⁶ to 0.47% in 2012.⁷ The Global Burden of Disease Study in 2010 demonstrated the high burden of psoriasis,⁸ comprising disease severity, skin symptoms, physical and psychological complications, quality of life, and medical expenses.⁹ Among them, psoriasis-related complications include coronary heart disease, metabolic syndrome,¹⁰ chronic obstructive pulmonary disease,¹¹ cardiovascular disease,¹² hyperuricemia,¹³ and so on.

The American Academy of Dermatology recommends five options for treating psoriasis, including classic systemic therapy, biologics, topical therapy, phototherapy, and photochemotherapy.¹⁴ However, considering the evident toxicities, side effects, and high economic costs of these treatments, patients with psoriasis are discouraged to receive these types of treatments. Although phototherapy is cost-effective, the lack of equipment in some medical institutions limits its application. Hence, several clinicians and researchers have been searching for better treatment options, including fish oil,¹⁵ and moving cupping therapy.¹⁶

Fire acupuncture has a long history in the treatment of psoriasis and is widely used in clinics. Fire needle therapy is considered as a characteristic Chinese medicine therapy, according to the Chinese guidelines for diagnosis and treatment of psoriasis (2018 simplified version).¹⁷ Different from ordinary acupuncture, fire needle therapy is a method of quickly piercing into acupoints with red-hot needles to treat diseases. Attention should be paid to disinfection before acupuncture, and the depth of acupuncture should be determined according to the condition of the disease, patients' physique and age, and muscle thickness and vascular depth of acupuncture points. In fire needle therapy, pulling out quickly after inserting the needle, and pressing the pinhole with cotton balls to reduce pain should be considered. Analogous to other acupuncture schemes, when a patient is hungry, in pain, unwell, or nervous during fire needle treatment, it can lead to a loss of consciousness and mobility for a short period of time. This is known as fainting during acupuncture treatment.¹⁸ The operator should pay close attention to the patient's status. If discomfort or even syncope is observed, the operator should immediately stop the treatment and take the necessary treatment measures. At present, some medical institutions are investigating the use of topical anesthesia followed by fire needle therapy to relieve pain and improve treatment compliance, including compound lidocaine cream and capsaicin ointment.^19
–21 The fire needle needs to be heated using the alcohol lamp and subsequently penetrates into the skin lesion. Thus, a microscald reaction is observed. Microscalding reactions will easily cause infection if not handled properly. Therefore, patients should avoid scratching and bathing immediately after treatment.

At present, fire needle therapy is used to treat moderate-severe acne²² and nodular prurigo.²³ Several literatures also show that fire needle therapy has beneficial effects in the treatment of psoriasis with less side effects and a low recurrence rate,²⁴ and some articles pay attention to the immune mechanism of fire needle therapy in the treatment of diseases.^25
–27 Considering that there is no systematic evaluation of fire needle therapy for psoriasis, a systematic review and meta-analysis is conducted to evaluate the effectiveness and safety of acupuncture treatment for psoriasis.

Experimental Section

This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISM) statement (Supplementary Table S1).²⁸ Furthermore, this title has been registered in the Joanna Briggs Institute (JBI).

Data sources and search strategy

Seven databases, including PubMed, Embase, CNKI, VIP, CBM, CENTRAL, and Wan Fang, were searched for literature published from the dates of construction of these databases to August 24, 2019. In the computer-based retrieval, the combination of subject words and free words was used for search. These terms mainly included “psoriasis,” “fire needle,” “fire needle therapy,” and “randomized controlled trial.” After removing duplications, two reviewers independently (X.C. and Y.L.) screened titles and abstracts of all literatures based on the inclusion criteria. The Chinese Clinical Trial Registry (www.chictr.org.cn/index.aspx) and Clinical Trials (www.clinicaltrials.gov) were also searched to identify all relevant trials.

Study selection and eligibility criteria

Randomized controlled trials (RCT) were eligible in this meta-analysis, and were used to assess the effects of fire needle therapy alone, as well as of a combination of fire needle therapy and other medications for the intervention group, such as fire needle therapy and fire needle therapy plus oral/external Chinese medicine or plus oral/external western medicine. For the control group, characteristic therapy of Traditional Chinese Medicine (TCM) and oral/external Chinese medicine or oral/external western medicine was included. In addition, articles using Psoriasis Area and Severity Index (PASI) as the main outcome indicators were included. Patients' age ranged between 18 and 70 years, regardless of sex, except for pregnant and lactating women. The inclusion criteria were as follows: patients without heart, brain, kidney, liver, gallbladder, gastrointestinal, or other biomedical diseases, patients who did not receive systematic treatment of psoriasis in the past month, and patients who voluntarily participated and provided informed consent.

Outcomes

PASI is a commonly used tool for measuring the area and severity of skin lesions in patients with psoriasis. The evaluation of the efficacy of fire acupuncture treatment of psoriasis was mainly based on the cured and markedly effective and improved rate of PASI. In addition, TCM syndrome scores, the incidence of adverse events, quality of life score, Hamilton Anxiety Rating Scale (HAM-A) score, and recurrence rate were used as the secondary outcome indicators of this study. Finally, the changes of inflammatory cells and cytokines were summarized and analyzed to provide evidence for the mechanism research.

Data extraction and risk-of-bias assessment

Two authors (X.C. and Y.L.) separately screened the title, abstract, and full text in each study. First author, publication date, sample size, psoriasis type, TCM syndrome, course of disease, interventions, outcomes, and untoward effects were extracted. If the opinions were not uniform, the authors reached a consensus through consultation.

Two reviewers (M.X. and J-K. S.) assessed the quality of studies independently. If the two reviewers disagreed on the results, another person (Y.R.) participated in the evaluation to reach an agreement. The Cochrane risk-of-bias tool²⁹ was applied to assess the risk of bias of all involved trials.

Statistical analysis

Revman 5.3 analyses were performed to calculate the risk ratio (RR), continuous outcomes, and mean differences (MDs) with 95% confidence intervals (CIs). For the dichotomous variables, RRs with 95% CI were determined to describe findings. I ² was used to indicate heterogeneity. If p was >0.1 and I ² was <50%, there was homogeneity, and a fixed model was applied. Otherwise, it was heterogeneous, and a randomized model was used. At this time, subgroup analysis was applied.

Results

Study identification and selection

Eighty-nine relevant citations were identified. After removing duplicate studies, 45 literatures were selected from those initially identified. Subsequently, the titles and abstracts of each study were screened, and 33 articles remained for detailed evaluation. Of those, one was a duplicate of a previous study, and the other was a systematic review. Seven were nonrandomized controlled trials, and the other eight were not relevant to our study. Ultimately, 16 trials^{30

–45} met the criteria and were included in this review. The comprehensive details of these trials are presented in Figure 1.

FIG. 1.

Flow chart of search strategy and study selection, according to PRISMA guidelines. PRISM, Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Characteristics of included studies

Sixteen trials involving 1267 participants were included in the analysis. Nine clinical studies^{30,31,36,38

–41,43,44} used fire needles to treat psoriasis vulgaris, six^{32,34,35,37,42,45} used fire needles to treat plaque psoriasis, and one³³ used fire needles to treat erythrodermic psoriasis. Of the trials selected that used Chinese medicine syndrome concepts, one used fire needles to treat blood dryness,³² one to treat blood heat,⁴⁰ and nine to treat blood stasis syndrome.^{30,32,35

–39,42,44} Currently, there is no clear definition to completely match the biomedical categories with Chinese medicine categories. However, fire needle therapy is commonly used to treat blood stasis syndrome of psoriasis vulgaris (including drip psoriasis and plaque psoriasis) in clinical practice. Two trials^37,45 were multicenter clinical trials conducted in three hospitals in China.

Four types of treatments, including treatment with fire needle only,^30
–32,34 fire needle plus oral medication,^{33,36,41,43,44} such as acitretin capsule and compound glycyrrhizin tablets; fire needle plus oral and topical medication,^{35,37
–39,42,45} such as calcipotriol cream and tazarotene cream; and fire needle plus Chinese herbal medicine and Chinese patent medicine,⁴⁰ the efficacy of which was mainly based on clear heat used to remove toxicity and activate blood and resolve stasis, were used in the included trials. Notably, except for one study³³ using fire needles combined with western medicine, other oral medicines were Chinese herbal medicines.^36,41,43,44

Eleven studies^{30,31,35
–37,39–42,45} reported the primary outcome and PASI scores, and the other five^{32
–34,38,44} studies described only comprehensive efficacy calculated based on the PASI scores, as PASI scores after treatment were not reported. In addition, Dermatology Life Quality Index (DLQI) score, HAM-A score, TCM syndrome score, T cells, and inflammatory cytokines were reported in some studies. Full details are presented in Table 1.

Table 1.

Characteristic of Encountered Trials

Studies, first author (year)^Ref.	Psoriasis type	TCM syndrome	Total enrolled/completers		Age, mean (SD)		Disease course, mean (SD), years		Treatment		Outcomes
Studies, first author (year)^Ref.	Psoriasis type	TCM syndrome	I	C	I	C	I	C	I	C	Outcomes
Wang (2011)³⁰	Psoriasis vulgaris	BSS	30/30	30/30	32.77 (11.78)	31.57 (11.85)	2.12 (2.18)	2.36 (2.08)	Fire needle	TO	PASI, AE
Dai (2013)³¹	Psoriasis vulgaris	—	31	31	41.87 (13.8)	39.9 (14.8)	0.5–9	1–10	Fire needle	TO	PASI, AE
Hong (2013)³²	Plaque psoriasis	BSS and BDS	27/24	28/26	34.78 (10.39)	36.86 (11.89)	2.04 (0.73)	2.64 (0.19)	Fire needle	TO	PASI, AE, RER
Hong (2013)³³	Erythrodermic psoriasis	—	40/40	40/40	36.65 (9.34)	35.76 (10.26)	1.10 (1.28)	1.32 (1.37)	Fire needle and OM	OM	PASI, AE
Huang (2013)³⁴	Plaque psoriasis	—	56/52	57/54	34.78 (10.39)	36.86 (11.89)	3.04 (1.63)	2.84 (1.59)	Fire needle	TO	PASI, AE, RER
Cui (2014)³⁵	Plaque psoriasis	BSS	12/10	8/7	41.58 (14.61)	46.25 (12.27)	13.15 (10.69)		Fire needle and OM and TO	OM and TO	PASI, DLQI, HAMA, AE, TCMSS
Huang (2014)³⁶	Psoriasis vulgaris	BSS	60	60	36.65 (9.34)	35.76 (10.26)	1.37 (1.28)	1.32 (1.37)	Fire needle and OM	OM	PASI, AE
Pan (2014)³⁷	Plaque psoriasis	BSS	37/32	34/28	45.16 (14.377)	46.88 (13.09)	14.49 (10.585)	14.76 (12.584)	Fire needle and OM and TO	OM and TO	PASI, SF-36, HAMA, AE, TCMSS
He (2014)³⁸	Psoriasis vulgaris	BSS	27	27	18–65		—		Fire needle and OM and TO	OM and TO	PASI, DLQI, TCMSS
Li (2016)³⁹	Psoriasis vulgaris	BSS	26/25	26/23	43.28 (12.76)	45.04 (13.65)	15.12 (9.52)	12.7 (9.96)	Fire needle and OM and TO	OM and TO	PASI, DLQI, HAMA, AE, TCMSS
Zhang (2016)⁴⁰	Psoriasis vulgaris	BHS	38	38	51.12 (3.87)	53.02 (3.31)	7.12 (1.02)	6.54 (1.42)	Fire needle and CHM and CPD	CPD	PASI, T cells, VEGF
Dun (2017)⁴¹	Psoriasis vulgaris	—	61	61	35.49 (10.38)	36.21 (10.32)	6.67 (2.14)	7.06 (2.26)	Fire needle and OM	OM	PASI, T cells
Wang (2017)⁴²	Plaque psoriasis	BSS	25	25	48.2 (12.1)	46.9 (13.4)	12.5 (3.8)	12.7 (3.5)	Fire needle and OM and TO	OM and TO	PASI, TCMSS
Dong (2018)⁴³	Psoriasis vulgaris	—	45	45	35.8 (5.2)	36.4 (5.6)	5.3 (3.0)	5.0 (3.3)	Fire needle and OM	OM	PASI, T cells
Deng (2019)⁴⁴	Psoriasis vulgaris	BSS	53	53	32.95 (8.12)	33.54 (7.91)	7.25 (6.76)	7.36 (6.84)	Fire needle and OM	OM	PASI, T cells, IL-2/IL-4/IL-10/IFN-γ
Pan (2019)⁴⁵	Plaque psoriasis	—	68/60	68/61	44.92 (13.07)	45.19 (12.91)	13.72 (9.56)	13.41 (11.19)	Fire needle and OM and TO	OM and TO	PASI, DLQL, TCMSS, HAMA, AE

AE, adverse events; BDS, blood dryness syndrome; BHS, blood heat syndrome; BSS, blood stasis syndrome; C, control; CHM, Chinese herbal medicine; CPD, Chinese patent drug; DLQI, Dermatology Life Quality Index; HAM-A, Hamilton Anxiety Rating Scale; I, interventions; IFN, interferon; IL, interleukin; OM, oral medication; PASI, Psoriasis Area and Severity Index; RER, recurrence rate; SD, standard deviation; SF-36, 36-item Short Form Health Survey; TCM, Traditional Chinese Medicine; TCMSS, TCM syndrome score; TO, topical ointment; VEGF, vascular endothelial growth factor.

Risk-of-bias assessment

Nine articles^{30
–32,34,35,41,42,44,45} used computer-generated random numbers to generate random assignments. Two studies used segmental randomization³³ and block randomization,³⁷ separately. One article³⁶ was randomly grouped according to the order of patients' visits. The rest of the studies only mentioned the word “randomization.” Five trials^{30
–32,34,45} mentioned the method of assigning concealment, including the envelope method and application central randomization system. Due to the particularity of fire needle treatment, six studies^{30
–32,34,35,45} were not blinded, and in four of these studies,^30
–32,34 clinical researchers, clinical data collectors, and data statisticians worked independently. The remaining studies did not describe whether blinded methods were used. There were no cases of loss in the three studies.^30,31,33 Six studies^{32,34,35,37,39,45} reported cases of loss and causes of loss, of which one described how to deal with missing values,³² and another used Intention-To-Treat (ITT) analysis.³⁷ Other studies did not describe specific analysis methods for shedding cases. The remaining trials did not describe whether there were missing cases. DLQI and HAM-A evaluation was planned in the design of one study,³⁸ but these two indicators have not been reported in the subsequent analysis of results. Details are shown in Figure 2a and b.

FIG. 2.

(a) Risk-of-bias graph. (b) Risk-of-bias summary.

Primary outcomes

In this article, each included study applied a PASI score to evaluate efficacy after treatment with fire needle therapy. Only one article reported using fire acupuncture to treat erythrodermic psoriasis so it was excluded in the meta-analysis, which suggested that all patients with psoriasis in the clinical trials included in the analysis had psoriasis vulgaris. In addition, one of the pooled trials only described PASI scores after fire needle therapy, and no comprehensive efficacy was reported. Another study evaluated the efficacy of fire needle therapy combined with Chinese herbal medicine. Therefore, these two studies were excluded from the analysis.

A total of 13 trials were included in the analysis (Table 2 and Supplementary Fig. S1). In general, fire needle therapy was effective in treating psoriasis (p = 0.0002; RR, 1.20; 95% CI, 1.09–1.33). On comparing fire needle therapy with topical treatments of skin lesions (p = 0.11; RR, 1.15; 95% CI, 0.97–1.36) and with the combination of oral and topical medications plus fire needle treatment (p = 0.44; RR, 1.14; 95% CI, 0.82–1.59), the effects were similar with no significant differences. The most effective treatment was fire needle therapy plus oral medications, which was 1.35 times better than treatment with oral medications without fire needle therapy (p = 0.0001; RR, 1.35; 95% CI, 1.16–1.57). The efficacy of the combination of fire needle therapy and Chinese herbal medicine reported by Zhang et al. was also better than that of Chinese patent medicine alone (p < 0.05). Fire needle therapy combined with oral medication for erythrodermic psoriasis was also shown to achieve satisfactory results.⁴⁰

Table 2.

Meta-Analysis of the Overall Effect of Fire Needle Therapy on Psoriasis Patients

Study or subgroup, first author (year)^Ref.	Fire needle		Control		Risk ratio Mantel-Haenszel (M-H), random (95% CI)	Study weight, %	I², %	p
Study or subgroup, first author (year)^Ref.	Events	Total	Events	Total	Risk ratio Mantel-Haenszel (M-H), random (95% CI)	Study weight, %	I², %	p
Fire needle vs. topical medication
Wang (2011)³⁰	27	30	19	30	1.42 (1.06–1.91)	10.0
Dai (2013)³¹	4	31	6	31	0.67 (0.21–2.13)	0.7
Hong (2013)³²	21	27	20	28	1.09 (0.80–1.48)	9.3
Huang (2013)³⁴	43	56	41	57	1.07 (0.86–1.33)	17.3
Subtotal (95% CI)	95	144	86	146	1.15 (0.97–1.36)	37.2	13	0.11
Fire needle+OM vs. OM
Huang (2014)³⁶	49	60	39	60	1.26 (1.01–1.57)	16.7
Dun (2017)⁴¹	44	61	29	61	1.52 (1.12–2.06)	9.4
Dong (2018)⁴³	32	45	24	45	1.33 (0.96–1.86)	8.2
Deng (2019)⁴⁴	22	53	15	53	1.47 (0.86–2.50)	3.3
Subtotal (95% CI)	147	219	107	219	1.35 (1.16–1.57)	37.7	0	0.0001
Fire needle+OM+topical medication vs. OM+topical medication
Cui (2014)³⁵	0	12	1	8	0.23 (0.01–5.05)	0.1
Pan (2014)³⁷	10	37	5	34	1.84 (0.70–4.83)	1.0
He (2014)³⁸	10	27	6	27	1.67 (0.71–3.94)	1.3
Li (2016)³⁹	2	26	3	26	0.67 (0.12–3.67)	0.3
Wang (2017)⁴²	23	25	22	25	1.05 (0.87–1.26)	22.3
Subtotal (95% CI)	45	127	37	120	1.14 (0.82–1.59)	25.1	14	0.44
Total (95% CI)	287	490	230	485	1.20 (1.09–1.33)	100	7	0.0002

CI, confidence interval.

Considering that 10 trials reported PASI scores, the clinical efficacy of fire needle therapy in the treatment of psoriasis was also analyzed from the perspective of the PASI score (Table 3 and Supplementary Fig. S2). Similar to the results of the cured and markedly effective rate analysis, the clinical effects of fire needle therapy were better than those of other interventions (p = 0.003; MD, −1.32; 95% CI, −2.19 to −0.44). However, the risk of increased PASI scores was lower after fire needle therapy was used in combination with internal and external medications to treat patients with psoriasis (p < 0.00001; MD, −0.53; 95% CI, −0.72 to −0.33).

Table 3.

Meta-Analysis of Psoriasis Area and Severity Index Scores After Fire Needle Therapy on Psoriasis Patients

Study or subgroup, first author (year)^Ref.	Fire needle			Control			Mean difference Inverse Variance (IV), Random, (95% CI)	Study weight, %	I², %	p
Study or subgroup, first author (year)^Ref.	Mean	SD	Total	Mean	SD	Total	Mean difference Inverse Variance (IV), Random, (95% CI)	Study weight, %	I², %	p
Fire needle vs. topical medication
Wang (2011)³⁰	0.45	1.42	30	0.99	1.39	30	−0.54 (−1.25 to 0.17)	12.2
Dai (2013)³¹	3.932	3.627	31	3.99	3.627	31	−0.06 (−1.86 to 1.75)	8.5
Subtotal (95% CI)			61			61	−0.48 (−1.14 to 0.19)	20.7	0	0.16
Fire needle+OM vs. OM
Huang (2014)³⁶	3.4	2.5	60	4.9	3.2	60	−1.50 (−2.53 to −0.47)	11.2
Dun (2017)⁴¹	8.59	2.17	61	15.68	3.34	61	−7.09 (−8.09 to −6.09)	11.3
Subtotal (95% CI)			121			121	−4.30 (−9.77 to 1.18)	22.6	98	0.12
Fire needle+OM+topical medication vs. OM+topical medication
Cui (2014)³⁵	3.95	1.73	12	3.46	1.04	8	0.49 (−0.73 to 1.71)	10.6
Pan (2014)³⁷	4.54	2.899	37	6.18	5.077	34	−1.64 (−3.59 to 0.31)	8.0
Li (2016)³⁹	3.27	1.38	26	3.66	1.78	26	−0.39 (−1.26 to 0.48)	11.8
Wang (2017)⁴²	0.3	0.1	25	0.8	0.4	25	−0.50 (−0.66 to −0.34)	13.2
Pan (2019)⁴⁵	4.0	0.63	68	4.64	1.037	68	−0.64 (−0.93 to −0.35)	13.1
Subtotal (95% CI)			168			161	−0.53 (−0.72 to −0.33)	56.7	16	<0.00001
Total (95% CI)			350			343	−1.32 (−2.19 to −0.44)	100	95	0.003

Secondary outcomes

TCM syndrome scores

Six trials^{35,37
–39,42,45} used TCM syndrome scores to assess the improvement of TCM syndromes in patients with psoriasis. A meta-analysis assessed whether the color of the skin lesions (p = 0.03; MD, −1.20; 95% CI, −2.32 to −0.09), the degree of skin lesion infiltration (p = 0.002; MD, −0.38; 95% CI, −0.62 to −0.13), or the condition of scaly dry skin (p < 0.00001; MD, −0.70; 95% CI, −0.96 to −0.44) was improved after treatment with fire needle therapy (Table 4 and Supplementary Fig. S3). He et al.³⁸ evaluated the comprehensive scores of TCM syndrome in patients with psoriasis after fire needle treatment, and found that the effective rate after treatment with fire needle therapy (81.5%) was significantly higher than that of the control group (66.6%, p < 0.05), which was the same as the results of Pan et al.⁴⁵

Table 4.

Traditional Chinese Medicine Syndrome Scores of Clinical Efficiency of Fire Needle Therapy in the Treatment of Psoriasis

Study or subgroup, first author (year)^Ref.	Fire needle			Control			Mean difference IV, Random, (95% CI)	Study weight, %	I², %	p
Study or subgroup, first author (year)^Ref.	Mean	SD	Total	Mean	SD	Total	Mean difference IV, Random, (95% CI)	Study weight, %	I², %	p
Color of skin lesions
Cui (2014)³⁵	4	1.05	12	3.86	1.07	8	0.14 (−0.81 to 1.09)	11.7
Pan (2014)³⁷	11.1	4.767	37	14.5	6.415	34	−3.40 (−6.05 to −0.75)	2.4
Li (2016)³⁹	9.44	2.83	26	10.78	2.47	26	−1.34 (−2.78 to 0.10)	6.7
Wang (2017)⁴²	1.8	0.9	25	3.3	1	25	−1.50 (−2.03 to −0.97)	19.0
Subtotal (95% CI)			100			93	−1.20 (−2.32 to −0.09)	39.9	74	0.03
Degree of infiltration of skin lesions
Cui (2014)³⁵	3.8	1.03	12	3.86	1.07	8	−0.06 (−1.00 to 0.88)	11.8
Wang (2017)⁴²	1	0.4	25	1.4	0.5	25	−0.40 (−0.65 to −0.15)	24.3
Subtotal (95% CI)			37			33	−0.38 (−0.62 to −0.13)	36.0	0	0.002
Scaly dry skin
Wang (2017)⁴²	1.8	0.6	25	2.5	0.3	25	−0.70 (−0.96 to −0.44)	24.1
Subtotal (95% CI)			25			25	−0.70 (−0.96 to −0.44)	24.1	Not applicable	<0.00001
Total (95% CI)			162			151	−0.72 (−1.15 to −0.28)	100	74	0.001

Adverse events

Ten trials^{30

–37,39,45} estimated the adverse events of fire needle therapy when treating individuals with psoriasis. Two studies^33,36 found no adverse events in either the experimental or the control group. Li ³⁹ only described one case of adverse reactions in the control group but did not indicate the specific type of adverse event. In the remaining studies describing adverse events, a meta-analysis showed that, overall, the incidence of side effects after fire needle treatment was similar to that without fire needle treatment (p = 0.38; RR, 0.67; 95% CI, 0.28–1.63) (Table 5 and Supplementary Fig. S4). Regarding anaphylaxis, the control group had increased incidence of anaphylaxis (p = 0.04; RR, 0.21; 95% CI, 0.05–0.95).

Table 5.

Meta-Analysis of Adverse Events of Fire Needle Therapy

Study or subgroup, first author (year)^Ref.	Fire needle		Control		Risk ratio M-H, random (95% CI)	Study weight, %	I², %	p
Study or subgroup, first author (year)^Ref.	Events	Total	Events	Total	Risk ratio M-H, random (95% CI)	Study weight, %	I², %	p
Anaphylaxis
Dai (2013)³¹	0	31	2	31	0.20 (0.01–4.00)	8.7
Hong (2013)³²	0	27	1	28	0.35 (0.01–8.12)	7.8
Hong (2013)³³	0	40	1	40	0.33 (0.01–7.95)	7.7
Cui (2014)³⁵	0	12	3	8	0.10 (0.01–1.69)	9.7
Subtotal (95% CI)	0	110	7	107	0.21 (0.05–0.95)	33.9	0	0.04
Infection
Cui (2014)³⁵	1	12	0	8	2.08 (0.09–45.45)	8.2
Pan (2014)³⁷	2	37	0	34	4.61 (0.23–92.63)	8.6
Pan (2019)⁴⁵	1	68	0	68	3.00 (0.12–72.37)	7.7
Subtotal (95% CI)	4	117	0	110	3.09 (0.52–18.35)	24.5	0	0.22
Erythema
Dai (2013)³¹	0	31	1	31	0.33 (0.01–7.88)	7.8
Subtotal (95% CI)	0	31	1	31	0.33 (0.01–7.88)	7.8	Not applicable	0.50
Dry skin
Wang (2011)³⁰	0	30	2	30	0.20 (0.01–4.00)	8.7
Subtotal (95% CI)	0	30	2	30	0.20 (0.01–4.00)	8.7	Not applicable	0.29
Causalgia
Wang (2011)³⁰	2	30	0	30	5.00 (0.25–99.95)	8.7
Subtotal (95% CI)	2	30	0	30	5.00 (0.25–99.95)	8.7	Not applicable	0.29
Itching
Wang (2011)³⁰	0	30	2	30	0.20 (0.01–4.00)	8.7
Subtotal (95% CI)	0	30	2	30	0.20 (0.01–4.00)	8.7	Not applicable	0.29
Fainting during acupuncture
Wang (2011)³⁰	1	30	0	30	3.00 (0.13–70.83)	7.8
Subtotal (95% CI)	1	30	0	30	3.00 (0.13–70.83)	7.8	Not applicable	0.50
Total (95% CI)	7	378	12	368	0.67 (0.28–1.63)	100.0	0	0.38

Quality of life

Four trials^35,37,39,45 evaluated the quality of life after treatment with fire needle therapy. One of the studies used the 36-item Short Form Health Survey Index, and the other studies used DLQI. A meta-analysis showed that the use of fire needle treatment did not significantly ameliorate the quality of life (p = 0.21; MD, −0.44; 95% CI, −1.11 to 0.24) (Table 6 and Supplementary Fig. S5).

Table 6.

Quality of Life and Anxiety of Psoriasis Patients After Fire Needle Treatment

Study or subgroup, first author (year)^Ref.	Fire needle			Control			Mean difference IV, Random, (95% CI)	Study weight, %	I², %	p
Study or subgroup, first author (year)^Ref.	Mean	SD	Total	Mean	SD	Total	Mean difference IV, Random, (95% CI)	Study weight, %	I², %	p
Quality of life
DLQI
Cui (2014)³⁵	4.3	3.43	12	5.14	3.34	8	−0.84 (−3.86 to 2.18)	5.1
Li (2016)³⁹	5.32	4.6	26	7.04	5.66	26	−1.72 (−4.52 to 1.08)	5.9
Pan (2019)⁴⁵	0.65	2.367	68	0.84	2.078	68	−0.19 (−0.94 to 0.56)	82.4
Subtotal (95% CI)			106			102	−0.32 (−1.02 to 0.38)	93.4	0	0.37
SF-36
Pan (2014)³⁷	6.52	5.207	37	8.56	6.076	34	−2.04 (−4.68 to 0.60)	6.6
Subtotal (95% CI)			37			34	−2.04 (−4.68 to 0.60)	6.6	Not applicable	0.13
Total (95% CI)			143			136	−0.44 (−1.11 to 0.24)	100	0	0.21
HAMA
Cui (2014)³⁵	6.7	4.3	12	5.71	6.16	8	0.99 (−3.92 to 5.90)	2.8
Pan (2014)³⁷	6.97	4.28	37	7.24	6.023	34	−0.27 (−2.72 to 2.18)	11.3
Li (2016)³⁹	7.32	6.0	26	7.3	8.65	26	0.02 (−4.03 to 4.07)	4.1
Pan (2019)⁴⁵	0.65	2.205	68	0.84	3.137	68	−0.19 (−1.10 to 0.72)	81.7
Total (95% CI)			143			136	−0.16 (−0.98 to 0.67)	100.0	0	0.71

Hamilton Anxiety Rating Scale

Four trials^35,37,39,45 assessed HAM-A after treatment with fire needle therapy. A meta-analysis presented that fire needle treatment did not significantly reduce the anxiety of patients with psoriasis (p = 0.71; MD, −0.16; 95% CI, −0.98 to 0.67) (Table 6 and Supplementary Fig. S6).

Recurrence rate

Two studies^32,34 reported the recurrence rate, and found that patients with psoriasis treated with fire needles had a significantly lower probability of recurrence after the symptoms had improved than those with psoriasis not treated with fire needles (p = 0.005; RR, 0.48; 95% CI, 0.29–0.80) (Table 7 and Supplementary Fig. S7).

Table 7.

Recurrence Rates of Fire Needle Therapy in the Treatment of Psoriasis

Study or subgroup, first author (year)^Ref.	Fire needle		Control		Risk ratio M-H, random (95% CI)	Study weight, %	I², %	p
Study or subgroup, first author (year)^Ref.	Events	Total	Events	Total	Risk ratio M-H, random (95% CI)	Study weight, %	I², %	p
Hong (2013)³²	6	27	13	28	0.48 (0.21–1.08)	39.6
Huang (2013)³⁴	10	56	21	57	0.48 (0.25–0.93)	60.4
Total (95% CI)	16	83	34	85	0.48 (0.29–0.80)	100.0	0	0.005

Inflammatory cells and cytokines

Four trials^40,41,43,44 examined the subtype of T cells, and two trials^40,44 assessed inflammatory cytokines after treatment with fire needle therapy. It was found that there was no significant difference between the experimental group and the control group as a whole. However, for each subgroup, the number of cluster of differentiation (CD)8⁺T cells decreased (p < 0.00001; MD, −4.30; 95% CI, −5.70 to −2.90), and the number of CD4⁺T cells (p < 0.00001; MD, 8.90; 95% CI, 6.41 to 11.39) and the proportion of CD4⁺T cells and CD8⁺T cells (p < 0.00001; MD, 0.52; 95% CI, 0.43 to 0.61) increased after fire needle treatment. There were two subgroups of CD4⁺T cells, namely type 1 helper (Th1) cells and type 2 helper (Th2) cells. After fire needle treatment, the decrease in the number of Th1 cells (p < 0.00001; MD, −0.98; 95% CI, −1.12 to −0.84) was accompanied by a decrease in the number of interleukin (IL)-2 (p < 0.00001; MD, −9.19; 95% CI, −10.46 to −7.74) and interferon (IFN)-γ (p < 0.00001; MD, −21.52; 95% CI, −24.26 to −18.78), which were secreted by Th1 cells and could mediate the inflammatory response. On the contrary, an increase in the number of Th2 cells (p < 0.00001; MD, 0.39; 95% CI, 0.32 to 0.46) was accompanied by an increase in the number of IL-4 (p < 0.00001; MD, 5.13; 95% CI, 3.33 to 6.93) and IL-10 (p < 0.00001; MD, 6.31; 95% CI, 4.43 to 8.19) secreted by Th2 cells, which inhibits the inflammatory response. Vascular endothelial growth factor (VEGF) level decreased after treatment with fire needle therapy (p < 0.00001; MD, −20.78; 95% CI, −26.22 to −15.34). Full details are shown in Table 8 and Supplementary Figures S8 and S9.

Table 8.

T Cell Subsets and Inflammatory Cytokines of Fire Needle Therapy in the Treatment of Psoriasis

Study or subgroup, first author (year)^Ref.	Fire needle			Control			Mean difference IV, Random, (95% CI)	Study weight, %	I², %	p
Study or subgroup, first author (year)^Ref.	Mean	SD	Total	Mean	SD	Total	Mean difference IV, Random, (95% CI)	Study weight, %	I², %	p
T cell subsets
CD4⁺T cells
Zhang (2016)⁴⁰	41.55	4.58	38	32.28	3.74	38	9.27 (7.39 to 11.15)	4.1
Dun (2017)⁴¹	45.63	6.42	61	34.71	6.31	61	10.92 (8.66 to 13.18)	3.2
Dong (2018)⁴³	45.1	6.7	45	34.8	6.4	45	10.30 (7.59 to 13.01)	2.4
Deng (2019)⁴⁴	39.87	6.27	53	34.65	5.32	53	5.22 (3.01 to 7.43)	3.3
Subtotal (95% CI)			197			197	8.90 (6.41 to 11.39)	13.1	80	<0.00001
CD8⁺T cells
Zhang (2016)⁴⁰	21.37	3.24	38	25.52	3.53	38	−4.15 (−5.67 to −2.63)	5.3
Dun (2017)⁴¹	23.47	4.33	61	28.56	4.19	61	−5.09 (−6.60 to −3.58)	5.3
Dong (2018)⁴³	22.9	4.4	45	28.6	4.1	45	−5.70 (−7.46 to −3.94)	4.5
Deng (2019)⁴⁴	20.09	3.46	53	22.53	4.18	53	−2.44 (−3.90 to −0.98)	5.5
Subtotal (95% CI)			197			197	−4.30 (−5.70 to −2.90)	20.5	69	<0.00001
Ratio of CD4⁺/CD8⁺
Zhang (2016)⁴⁰	1.89	0.32	38	1.33	0.37	38	0.56 (0.40 to 0.72)	11.1
Dun (2017)⁴¹	1.87	0.34	61	1.35	0.31	61	0.52 (0.40 to 0.64)	11.1
Dong (2018)⁴³	1.97	0.33	45	1.26	0.81	45	0.71 (0.45 to 0.97)	10.9
Deng (2019)⁴⁴	1.94	0.28	53	1.51	0.27	53	0.43 (0.33 to 0.53)	11.1
Subtotal (95% CI)			197			197	0.52 (0.43 to 0.61)	44.2	40	<0.00001
Th1 cells
Deng (2019)⁴⁴	2.08	0.27	53	3.06	0.45	53	−0.98 (−1.12 to −0.84)	11.1
Subtotal (95% CI)			53			53	−0.98 (−1.12 to −0.84)	11.1	Not applicable	<0.00001
Th2 cells
Deng (2019)⁴⁴	1.49	0.19	53	1.1	0.17	53	0.39 (0.32 to 0.46)	11.2
Subtotal (95% CI)			53			53	0.39 (0.32 to 0.46)	11.2	Not applicable	<0.00001
Total (95% CI)			697			697	0.46 (−0.02 to 0.94)	100	98	0.06
Inflammatory cytokines
IL-2
Deng (2019)⁴⁴	16.34	3.22	53	25.53	4.31	53	−9.19 (−10.64 to −7.74)	20.3
Subtotal (95% CI)			53			53	−9.19 (−10.64 to −7.74)	20.3	Not applicable	<0.00001
IL-4
Deng (2019)⁴⁴	27.84	5.06	53	22.71	4.39	53	5.13 (3.33 to 6.93)	20.2
Subtotal (95% CI)			53			53	5.13 (3.33 to 6.93)	20.2	Not applicable	<0.00001
IL-10
Deng (2019)⁴⁴	34.29	5.32	53	27.98	4.53	53	6.31 (4.43 to 8.19)	20.2
Subtotal (95% CI)			53			53	6.31 (4.43 to 8.19)	20.2	Not applicable	<0.00001
IFN-γ
Deng (2019)⁴⁴	30.94	5.83	53	52.46	8.34	53	−21.52 (−24.26 to −18.78)	20.1
Subtotal (95% CI)			53			53	−21.52 (−24.26 to −18.78)	20.1	Not applicable	<0.00001
VEGF
Zhang (2016)⁴⁰	45.51	13.01	38	66.29	11.12	38	−20.78 (−26.22 to −15.34)	19.2
Subtotal (95% CI)			38			38	−20.78 (−26.22 to −15.34)	19.2	Not applicable	<0.00001
Total (95% CI)			250			250	−7.86 (−18.02 to 2.29)	100	99	0.13

CD, cluster of differentiation; Th1, type 1 helper; Th2, type 2 helper.

Discussion

In this analysis, fire needle treatment of psoriasis, specifically in patients with psoriasis vulgaris, improved skin lesions with a low recurrence rate. The conclusions were different when analyzing the cured and markedly effective rate and the PASI score. However, it is certain that the effects of fire needles and external medicines were comparable, and the skin lesions of patients with psoriasis significantly improved after treatment with fire needle therapy plus oral medications. Therefore, a combination of fire needle therapy with oral medications is recommended. However, fire needle therapy does not improve quality of life and anxiety in patients with psoriasis as expected.

Any treatment has side effects, and fire needle therapy is no exception. Fainting during acupuncture treatment is one of the most noteworthy side effects of fire needle therapy for psoriasis. Fortunately, a significant majority of patients in this study did not experience fainting during acupuncture treatment, except for one patient who experienced fainting during the second fire needle treatment, because of significantly little food intake and excessive stress. In this lone case, the doctor immediately stopped the treatment and laid the patient on the treatment bed, and the patient subsequently received moxa-moxibustion therapy on the BaiHui acupoint (GV20) for 2 min. After the patient felt that the fainting subsided, the doctor provided him with boiled sugar water. After the doctor confirmed a normal pulse and blood pressure, the patient agreed to continue treatment.³⁰ In this meta-analysis, causalgia was observed in the skin lesions of two patients, and infection was observed in four patients after fire needle treatment. These symptoms disappeared after treatment, and these patients consented to continue treatment.

In all involved trials, most researchers applied fire needle therapy to treat blood stasis syndrome of psoriasis and observed positive effects. From the perspective of TCM, the distribution pattern of psoriasis syndrome is based on blood. Among them, blood heat syndrome, blood stasis syndrome, and blood dryness syndrome are the three basic syndrome types.⁴⁶ In addition, the pathologic factor, blood stasis, remains through the whole process of psoriasis.^47,48 The formation of blood stasis syndrome is considered to be an abnormality of the blood in the veins, such that the body tissues and organs may not receive sufficient blood perfusion. It is also possible to form systemic or local blood stasis, thereby causing systemic or local metabolic disorders and dysfunction.⁴⁷ Currently, a large number of studies⁴⁹ have indicated that blood stasis syndrome is closely associated with microcirculatory disorders, hemodynamic abnormalities, platelet activation, vascular endothelial injury, and inflammatory response, which is similar to the pathogenesis of psoriasis.⁵⁰ Acupuncture has a positive effect on psoriasis, which can improve blood rheology and microcirculation.⁵¹ Fire needle therapy combines the effects of acupuncture in stimulating meridian qi and moxibustion in warming yang and dispelling cold, which produces a better effect on blood heat syndrome and blood stasis syndrome.^32,36,40 Therefore, in addition to the above effects, it can regulate immunity, sterilize with high temperature, and ameliorate the body's internal environment.⁵² These may be the reasons for the low recurrence rate of fire needle treatment of psoriasis.

In all studies reporting the immune response after fire needle therapy, three described the treatment mechanism of fire needle therapy combined with oral medication, which is consistent with conclusions from the analysis of the cured and marked effective rate. In the pathogenesis of psoriasis, CD4⁺T cells exert an enormous function. They differentiate into several types through stimulation by diverse inflammatory cytokines, involving Th1, Th2, Th17, Th9, Th22, follicular Th cells, peripheral Tregs, and T regulatory type 1,⁵³ in which Th1, Th2, Th17, and Treg cells participate in the entire process of psoriasis. The pathogenesis of psoriasis includes three cycles (Fig. 3). (1) Keratinocytes (KCs)/dendritic cells (DCs)/T-cell loop⁵⁴: at an early stage of psoriasis, with the injured epidermis, KCs produce high-level CCL20, a chemokine cysteine motif chemokine ligand 20.⁵⁵ CCL20 has the ability to migrate myeloid DCs and CCR6+IL-17-producing T cells into focal skin regions.^54,56,57 Subsequently, DCs are activated by diverse stimuli, and release IL-23 and tumor necrosis factor (TNF)-α. IL-23 induces Th17 cells, which overexpress IL-17 and IL-22. Subsequently, IL-23, IL-17, and TNF-α act on KCs, resulting in epidermal hyperplasia.⁵⁸ (2) Th17/Treg balance⁵⁹: Tregs, which mainly secrete Foxp3, tumor growth factor-β, and IL-10, are responsible for maintaining their own tolerance to inhibit autoimmunity. Proinflammatory Th17 cells, excreting IL-17, IL-12, IL-22, and IL-9, contribute to the induction and spread of inflammation.⁶⁰ In psoriatic lesions, IL-6 is released by epidermal cells, resulting in the increase of Th17 cells and the Th17/Treg ratio, which is an impaired function of Treg cells.^61,62 This plays a key role in maintaining the balance of Th17 and Treg cells.^59,63 (3) Th1/Th2 proportion⁶⁴: CD4⁺T cells are differentiated into Th1 and Th2 cells by IL-12⁶⁵ and IL-4 stimulation,⁶⁶ respectively. Th1 cells secrete cytokines such as IFN-γ, IL-2, and TNF-α and migrate to the psoriatic lesions by chemokines, showing proinflammatory effects.⁵⁴ However, Th2 cells appear to secrete poor cytokines, including IL-4 and IL-10.⁶⁷ Our previous study reported that IFN-γ, IL-17, IL-23, IL-6, and TNF-α levels significantly increased, whereas IL-4 and IL-10 levels were significantly decreased in the serum of patients with psoriasis.^68,69

FIG. 3.

Immune responses of fire needle therapy plus oral medicines when treating psoriasis. Th1/Th2 proportion, Th17/Treg balance, and KC/DC/T cell loops are considered to play an essential part in pathogenesis of psoriasis. The onset of psoriasis begins with the release of IL-23 from DCs, characteristically by TNF-associated systemic inflammation. Activation of Th17 cells by IL-23 results in IL-17-mediated keratinocyte responses. After fire needle therapy, CD4⁺T cells are increased due to the increase in the number of Th2 cells, and cytokines secreted by them, such as IL-4 and IL-10. The proinflammatory CD8⁺T cells, Th1 cells, and cytokines are released by Th1 cells involving IL-2, but IFN-γ is reduced. Similarly, the decrease of IL-23 and IL-17 restores the inflammatory loop and maintains balance of Th1 and Th17. CD, cluster of differentiation; DC, dendritic cell; IFN, interferon; IL, interleukin; KC, keratinocyte; Th1, type 1 helper; Th2, type 2 helper; TNF, tumor necrosis factor.

After fire needle therapy, the number of CD4⁺T cells is increased. However, Th2 cells and cytokines secreted by these cells, such as IL-4 and IL-10, that exert an inhibitory effect are also increased. Meanwhile, the proinflammatory Th1 cells and cytokines released by these cells, including IL-2 and IFN-γ, decrease. CD8⁺T cells are increasingly believed to produce proinflammatory factors similar to those produced by CD4⁺T cells, which plays a key role in psoriasis.⁷⁰ Different from CD4⁺T cells, which are enriched and act in the dermis, CD8⁺ cells mainly migrate to the epidermis, aggravating the inflammatory response in skin lesions.⁷¹ When treated with fire needle therapy, the number of CD8⁺T cells decreases, and the ratio of CD4⁺T cells/CD8⁺T cells is increased. Therefore, it has been suggested that the changes in CD4⁺T cells may be mainly due to the increase in the number of Th2 cells. Recently, a study on imiquimod-induced psoriasis-like mice manifested that fire needle therapy ameliorated skin lesions by thinning the epidermis, inhibiting KC proliferation, reducing CD3⁺T cell infiltration, and secreting inflammatory cytokines including IL-1β, IL-17A, and IL-23p40.⁷² Since Treg cells also secrete IL-10, increased IL-10 level after fire needle treatment was shown to partially restore the function of Tregs. Similarly, a decreased IL-17 level represents a partial inhibition of Th17 function. This indicates that fire needle therapy restores the dynamic balance between Treg and Th17.

The formation of new blood vessels is also an important pathogenesis of psoriasis, in which VEGFs are considered to be an essential angiogenic factor. It is reported that VEGFs act on psoriatic lesions in two ways: one is in an indirect way, in which VEGFs derived from KCs are capable of inducing angiogenesis to produce essential nutrients to preserve the hyperproliferation of epidermis in a paracrine manner.⁶⁷ The other way is by means of VEGF receptors, which are expressed by the epidermis and are found in both the lesioned and nonlesioned areas of patients with psoriasis⁷³ that directly promote KC proliferation.⁷³ Hence, the amount of VEGF in peripheral blood circulation is associated with the degree of psoriasis activity.⁷⁴ In this study, fire needle therapy was found to relieve psoriasis primarily through the indirect manner, which inhibits the role of VEGFs in psoriasis. Fire needle therapy was able to reduce the number of VEGFs in the serum and, subsequently, control the development of psoriasis.

This study has the following limitations. First, this study does not include the types of experiments outside the RCT. If a more extensive research type is included, the research results will be more comprehensive and representative. Second, the current clinical research related to fire needle therapy cannot be designed as double-blind trial, which may lead to a bias in the results. Third, the randomization scheme and allocation concealment scheme in some studies are unclear, resulting in the limitations of the interpretation of outcomes. None of the included clinical trials claim to be designed, implemented, or reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) statement. Furthermore, there are few multicenter studies, and the sample size needs to be expanded. In addition, a PASI improvement rate of >60% (PASI60) is ideally found as a therapeutic evaluation index, but due to the low quality of the included literature, the PASI improvement rate is not uniform, including PASI60 and PASI70. Therefore, the efficacy evaluation indicator was defined as the cured and markedly effective rate, which includes the abovementioned two improvement rates. To address this issue, a multicenter randomized controlled trial of fire acupuncture for plaque psoriasis is also conducted, which is currently registered on Clinicaltrials.gov (ID: NCT03953885). In future studies, it was proposed to expand the sample size and conduct multicenter trials. Although double-blind trials are not possible, clinical researchers, clinical data collectors, and data statisticians can work independently to ensure research reliability.

Conclusions

This meta-analysis of randomized controlled trials indicates that fire needle therapy is effective in treating psoriasis vulgaris patients with a low recurrence rate, and fire needle therapy may regulate the inflammatory loop of KCs/DCs/T cells, maintain Th17/Treg balance, and preserve Th1/Th2 proportions in psoriasis. However, due to the lack of rigorously designed research, the results should be interpreted with caution. To further clarify the effectiveness and related mechanisms of fire needle therapy on psoriasis, a more rigorous design, higher quality, and larger sample size trials are required.

Ethics Approval and Consent to Participate

This study was based on previously published studies; therefore, ethical approval and patient consent are not relevant.

Authors' Contributions

This study was proposed and designed by Dr. Xin Li and Prof. Bin Li. Prof. Bin Li obtained funding. Data acquisition and extraction were conducted by X.C., Y.L., M.X., J-K. S., Y.R., S-T. C., and X-Y. S., H-J. L, Y.L., and L.L. performed the statistical analysis of all data. L.L. and X.S. drafted the article, and Dr. Xin Li critically revised it.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This research was supported by the National Key Research and Development Program of China (No. 2018YFC1705303), the National Natural Science Foundation of China (grant nos. 81874470, 81973860).

Supplementary Material

Supplementary Data

Supplementary Table S1

Supplementary Figure S1

Supplementary Figure S2

Supplementary Figure S3

Supplementary Figure S4

Supplementary Figure S5

Supplementary Figure S6

Supplementary Figure S7

Supplementary Figure S8

Supplementary Figure S9

References

Boehncke

, Schön

. Psoriasis. Lancet, 2015; 386:983–994.

, Chen

. Dermatovenereology of Integrated Traditional and Western Medicine. 3rd ed. Beijing: Chinese Press of Traditional Chinese Medicine, 2017:202.

World Health Organization. Global report on psoriasis. World Health Organization, 2016. Online document at: https://apps.who.int/iris/handle/10665/204417, accessed August 25, 2019 .

Gibbs

Skin disease and socioeconomic conditions in rural Africa: Tanzania. Int J Dermatol, 1996; 35:633–639.

Danielsen

, Olsen

, Wilsgaard

, et al. Is the prevalence of psoriasis increasing? A 30-year follow-up of a population–based cohort. Br J Dermatol, 2013; 168:1303–1310.

Chinese Psoriasis Epidemiology Investigation

Group

, Shao

, Zhang

, et al. Epidemiological investigation report on Chinese psoriasis in 1984. J Dermatol Venereol, 1989; 11:60–72.

Ding

, Wang

, Shen

, et al. Prevalence of psoriasis in China: A population-based study in six cities. Eur J Dermatol, 2012; 22:663–667.

Institute for Health Metrics and Evaluation (IHME). Global Burden of Disease Study 2010: Results by Cause 1990–2010. Seattle: IHME, 2012.

Gisondi

The multidimensional burden of psoriasis. Br J Dermatol, 2018; 179:13–14.

10.

Rodríguez-Zúñiga

MJM

, García-Perdomo

. Systematic review and meta-analysis of the association between psoriasis and metabolic syndrome. J Am Acad Dermatol, 2017; 77:657.e8–666.e8.

11.

, Kong

, Li

, et al. Association between psoriasis and chronic obstructive pulmonary disease: A systematic review and meta-analysis. PLoS One, 2015; 10:e0145221.

12.

, Lan

. Psoriasis and cardiovascular comorbidities: Focusing on severe vascular events, cardiovascular risk factors and implications for treatment. Int J Mol Sci, 2017; 18:2211.

13.

, Miao

, Wang

, et al. Association of serum uric acid levels in psoriasis: A systematic review and meta-analysis. Medicine (Baltimore), 2016; 95:e3676.

14.

American Academy of Dermatology Work

Group

, Menter

, Korman

, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: Case-based presentations and evidence-based conclusions. J Am Acad Dermatol, 2011; 65:137–174.

15.

Chen

, Hong

, Sun

, et al. Efficacy of fish oil and its components in the management of psoriasis: A systematic review of 18 randomized controlled trials. Nutr Rev, 2020; 78:827–840.

16.

Xing

, Yan

, Yang

, et al. Effects of moving cupping therapy for plaque psoriasis: Study protocol for a randomized multicenter clinical trial. Trials, 2020; 21:229.

17.

Committee on

Psoriasis

, Chinese Society of

Dermatology

. Guideline for the diagnosis and treatment of psoriasis in China (2018 simplified edition). Chin J Dermatol, 2019; 52:223–230.

18.

Qin

, Li

, Zhao

. The mechanism and effect of fainting during acupuncture treatment [In Chinese]. Nei Mongol J Tradit Chin Med, 2014; 33:61.

19.

Xie

Clinical Study of Compound Lidocaine Cream and Capsaicin Ointment in Relieving Pain of Fire Needle Therapy. Chengdu: Chengdu University of traditional Chinese Medicine, 2010.

20.

Xiu

, Wang

. Fire needle therapy for 80 cases of vitiligo [In Chinese]. Chin Acupunct, 2005; 25:251.

21.

Zhang

XL.

Observation on the efficacy of fire needle therapy on the treatment of 1200 cases of facial freckles [In Chinese]. J Tradit Chin Med, 1991; 2:40.

22.

Xing

, Yan

, Sun

, et al. Fire needle therapy for moderate-severe acne: A PRISMA systematic review and meta-analysis of randomized controlled trials. Complement Ther Med, 2019; 44:253–260.

23.

Luo

, Kuai

, Song

, et al. Efficacy and safety of fire needle therapy for nodular prurigo: A quantitative study. Evid Based Complement Alternat Med, 2019; 2019:8797056.

24.

Luo

A Review of fire acupuncture combined with drugs for psoriasis vulgaris [In Chinese]. Asia Pac Tradit Med, 2017; 13:63–64.

25.

, Cheng

, Jiao

, et al. Fire needle acupuncture regulates Wnt/ERK multiple pathways to promote neural stem cells to differentiate into neurons in rats with spinal cord injury [In Chinese]. CNS Neurol Disord Drug Targets, 2019; 18:245–255.

26.

Lin

, Lin

, Zhang

, et al. Influence of fire needle stimulation at Sihua acupoints on performance status and Th1/Th2 balance in the patients with advanced non-small cell lung cancer after chemotherapy [In Chinese]. Zhen Ci Yan Jiu, 2019; 44:136–139.

27.

, Wang

, Sun

, et al. Effect of fire-needle intervention on joint function, cartilage impairment and inflammatory response in knee osteoarthritis rats [In Chinese]. Zhen Ci Yan Jiu, 2020; 45:220–226.

28.

Hutton

, Salanti

, Caldwell

, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: Checklist and explanations. Ann Intern Med, 2015; 162:777–784.

29.

Higgins

, Green

. 2011. Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0 (updated March 2011). Cochrane Collaboration website. Online document at: http://training.cochrane.org/handbook.2011, accessed August 24, 2019 .

30.

Wang

XM.

Observation of curative effectiveness of fire-acupuncture therapy on the resting psoriasis vulgaris (blood stasis type). MSc thesis. Chengdu: Chengdu University of Traditional Chinese Medicine, 2011.

31.

Dai

XQ.

Fire needle clinical observation about the treatment of psoriasis vulgaris (stationary phase) and experimental study. MSc thesis. Chengdu: Chengdu University of Traditional Chinese Medicine, 2013.

32.

Hong

The clinical studies of fire acupuncture treating the plaque psoriasis. MSc thesis. Luzhou: Luzhou Medical College, 2013.

33.

Hong

, Chen

, Huang

Therapeutic effect of fire needle combined with Awei A capsule on erythrodermic psoriasis [In Chinese]. Shanxi J TCM. 2013; 29;34, 53.

34.

Huang

, Chen

, Dong

, et al. Clinical study on the treatment of plaque psoriasis in stationary stage with fire acupuncture. The 10th Academic Exchange Conference of Dermatology Branch of Chinese Society of Traditional Chinese Medicine and the 8th Academic Exchange Conference on Skin and Sexual Diseases of Integrated Traditional Chinese and Western Medicine in Hunan Province, Changsha, Hunan, China, October 24–26, 2013.

35.

Cui

Clinical study on treatment of plaque psoriasis with fire needle combined with Huoxue Jiedu Decoction. MSc thesis. Beijing: Beijing University of Chinese Medicine, 2014.

36.

Huang

, Hong

. Treatment of 60 cases of psoriasis vulgaris with fire needle combined with oral compound glycyrrhizin tablets [In Chinese]. J Extern Ther TCM, 2014; 23:10–11.

37.

Pan

HD.

Clinical study on treatment of plaque-type silver shoulder disease with fire needle combined with Huoxue Jiedu Decoction. MSc thesis. Beijing: Beijing University of Chinese Medicine, 2014.

38.

, Bai

, Liu

, et al. Acupuncture combined with medicine in treatment of blood stasis type psoriasis [In Chinese]. Jilin J Tradit Chin Med, 2014; 23:10–11.

39.

RT.

Clinical observation of fire needle combined with Huoxue Jiedu Decoction in treating plaque psoriasis (blood stasis syndrome). MSc thesis. Beijing: Beijing University of Chinese Medicine, 2016.

40.

Zhang

Effect of self-made Xiaoyinfang combined with fire acupuncture on blood heat syndrome of psoriasis vulgaris and its effect on T lymphocyte subsets and vascular endothelial growth factor [In Chinese]. Modern J Integr Tradit Chin West Med, 2016; 25:2688–2690.

41.

Dun

, Wang

. Effect of Liangxue Xiaofeng San combined with fire on the efficacy of psoriasis vulgaris and T cell subsets [In Chinese]. Shaanxi J Tradit Chin Med, 2017; 38:762–764.

42.

Wang

Curative observation of using fire needle combined with Huoxue Jiedu decoction in the treatment of patients [In Chinese]. J Sichuan Tradit Chin Med Psoriasis, 2017; 35:206–208.

43.

Dong

LL.

Therapeutic effect of Liangxue Xiaofeng San combined with fire acupuncture on psoriasis vulgaris and its effect on immune function [In Chinese]. World Latest Med Inform, 2018; 18:141–142.

44.

Deng

, Zhou

. Effect of Huoxue Jiedu decoction combined with fire acupuncture on blood stasis psoriasis and its influence on Th1/Th2 balance in peripheral blood of patients. Shaanxi J Tradit Chin Med, 2019; 40:103–105.

45.

Pan

, Qi

, Wang

, et al. Whether fire-needle therapy benefits plaque psoriasis: A multicenter, randomized, and controlled trial. Chin J Integr Med, 2019; 25:259–263.

46.

Zhang

, Wang

, et al. Study on the distribution and development rules of TCM syndromes of 2651 psoriasis vulgaris cases [In Chinese]. J Tradit Chin Med, 2008; 49:894–896.

47.

Yan

, Lu

, Xuan

. Investigation of the most fundamental TCM pathogenesis of psoriasis vulgaris [In Chinese]. Liaoning J Tradit Chin Med, 2012; 39:1013–1015.

48.

Qin

WZ.

Study on blood syndrome and blood regulatory of psoriasis [in Chinese]. Chin J Dermatovenereol Integr Tradit West Med, 2008; 7:1–4.

49.

CG.

Establishment and evolution of modern blood stasis syndrome [in Chinese]. Shandong J Tradit Chin Med, 2016; 35:1081–1084, 1088.

50.

Fei

, Tang

, Yang

, et al. Changes of cutaneous microcirculatory in psoriasis [in Chinese]. Chin J Dermatovenereol, 2018; 32:714–717.

51.

Xiang

, Wu

, Lu

, et al. An overview of acupuncture for psoriasis vulgaris, 2009-2014. J Dermatolog Treat, 2017; 28:221–228.

52.

Guo

, Wang

, Hu

, et al. Study on the mechanisms of fire needle therapy [in Chinese]. Guangming J Chin Med, 2016; 31:683–685.

53.

Stadhouders

, Lubberts

, Hendriks

. A cellular and molecular view of T helper 17 cell plasticity in autoimmunity. J Autoimmun, 2018; 87:1–15.

54.

Lowes

, Suárez-Fariñas

, Krueger

. Immunology of psoriasis. Annu Rev Immunol, 2014; 32:227–255.

55.

Frick

, Rubie

, Keilholz

, et al. Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectal malignancy: An overview. World J Gastroenterol, 2016; 22:833–841.

56.

Kennedy-Crispin

, Billick

, Mitsui

, et al. Human keratinocytes' response to injury upregulates CCL20 and other genes linking innate and adaptive immunity. J Invest Dermatol, 2012; 132:105–113.

57.

Getschman

, Imai

, Larsen

, et al. Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23-dependent murine model. Proc Natl Acad Sci U S A, 2017; 114:12460–12465.

58.

Ogawa

, Sato

, Minagawa

, et al. Pathogenesis of psoriasis and development of treatment. J Dermatol, 2018; 45:264–272.

59.

Deng

, Chang

, Lu

. The Inflammatory response in psoriasis: A comprehensive review. Clin Rev Allergy Immunol, 2016; 50:377–389.

60.

Fasching

, Stradner

, Graninger

, et al. Therapeutic potential of targeting the Th17/Treg axis in autoimmune disorders. Molecules, 2017; 22:134.

61.

Zhang

, Li

, Yang

, et al. Characterization of Th17 and FoxP3(+) Treg cells in paediatric psoriasis patients. Scand J Immunol, 2016; 83:174–180.

62.

Hunter

, Jones

. IL-6 as a keystone cytokine in health and disease. Nat Immunol, 2015; 16:448–457.

63.

Onderdijk

, Baerveldt

, Kurek

, et al. IL-4 downregulates IL-1β and IL-6 and induces GATA3 in psoriatic epidermal cells: Route of action of a Th2 cytokine. J Immunol, 2015; 195:1744–1752.

64.

Jadali

, Eslami

. T cell immune responses in psoriasis. Iran J Allergy Asthma Immunol, 2014; 13:220–230.

65.

Foulds

, Wu

, Seder

. Th1 memory: Implications for vaccine development. Immunol Rev, 2006; 211:58–66.

66.

Ansel

, Djuretic

, Tanasa

, Rao

. Regulation of Th2 differentiation and Il4 locus accessibility. Annu Rev Immunol, 2006; 24:607–656.

67.

Jadali

, Izad

, Eslami

, et al. Th1/Th2 cytokines in psoriasis. Iranian J Publ Health, 2007; 36:1–6.

68.

, Xiao

, Li

, et al. Immune signatures in patients with psoriasis vulgaris of blood-heat syndrome: A systematic review and meta-analysis. Evid Based Complement Alternat Med, 2016; 2016:9503652.

69.

Fan

, Li

, Ze

, et al. Expression of T-helper 17 cells and signal transducers in patients with psoriasis vulgaris of blood-heat syndrome and blood-stasis syndrome. Chin J Integr Med, 2015; 21:10–16.

70.

Hijnen

, Knol

, Gent

, et al. CD8(+) T cells in the lesional skin of atopic dermatitis and psoriasis patients are an important source of IFN-gamma, IL-13, IL-17, and IL-22. J Invest Dermatol, 2013; 133:973–979.

71.

Di Meglio

, Villanova

, Navarini

, et al. Targeting CD8(+) T cells prevents psoriasis development. J Allergy Clin Immunol, 2016; 138:274.e6–276.e6.

72.

Wang

, Fu

, Zhang

, et al. Acupuncture needling, electroacupuncture, and fire needling improve imiquimod-induced psoriasis-like skin lesions through reducing local inflammatory responses. Evid Based Complement Alternat Med, 2019; 2019:4706865.

73.

, Man

, Chen

, et al. Targeting VEGF/VEGFR in the treatment of psoriasis. Discov Med, 2014; 18:97–104.

74.

Bhushan

, McLaughlin

, Weiss

, et al. Levels of endothelial cell stimulating angiogenesis factor and vascular endothelial growth factor are elevated in psoriasis. Br J Dermatol, 1999; 141:1054–1060.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.27 MB

0.32 MB

0.23 MB

0.04 MB

0.49 MB

0.21 MB

0.38 MB

0.33 MB