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1.
Effectiveness of Injectable Platelet-Rich Fibrin in the Treatment of Oral Lichen Planus: A Systematic Review and Meta-Analysis
Gupta, N., Bhargava, A., Saigal, S., Sharma, S., Patel, M., Prakash, O.
Cureus. 2024;16(1):e51626
Abstract
Oral lichen planus (OLP) is a chronic inflammatory condition affecting the oral mucosa. The current review investigated the potential effectiveness of injectable platelet-rich fibrin (i-PRF) as a treatment for OLP when compared to other interventions. The current review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy was implemented across databases such as PubMed, Embase, Scopus, Web of Science, CINAHL, and Google Scholar. The search utilized a combination of Boolean operators (AND, OR) and Medical Subject Headings (MeSH) terms to capture relevant studies. Comparative clinical studies focusing on i-PRF as a treatment for OLP and other interventions were included. Outcomes assessed were pain, surface area of lesions, and patient satisfaction. Review Manager 5.4 was used for statistical analysis. The Risk of Bias 2.0 (RoB 2.0) tool was used to assess the methodological quality of the studies. Three studies were included for the final analysis. The findings indicated that both the i-PRF and comparison treatment groups demonstrated reductions in pain and lesion size. The post-treatment Visual Analogue Scale (VAS) scores showed a decrease in pain intensity, and there was an improvement in lesion extension in the i-PRF-treated sites. The results also revealed increased patient satisfaction with i-PRF treatment. Adverse effects were not reported or specified in the included studies. Quantitative analysis for pain (VAS) showed a mean difference of 0.38 (95% CI: 0.63-1.40), but there was no significant difference between the i-PRF and control groups at p=0.46. Though intragroup differences showed statistically significant differences between pre and post intervention, intergroup differences were not significant for any of the assessed outcomes. The findings from this study suggest that i-PRF holds promise as a potential treatment for OLP. The use of i-PRF resulted in pain reduction, lesion size improvement, and increased patient satisfaction. However, it is important to consider the limitations of the included studies, such as variability in study designs, small sample sizes, and the limited number of studies.
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2.
Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study
Aggarwal, R., Schessl, J., Charles-Schoeman, C., Bata-Csörgő, Z., Dimachkie, M. M., Griger, Z., Moiseev, S., Oddis, C. V., Schiopu, E., Vencovský, J., et al
Arthritis research & therapy. 2024;26(1):27
Abstract
BACKGROUND Dermatomyositis is an idiopathic inflammatory myopathy characterised by rashes and progressive muscle weakness. The recent ProDERM (Progress in DERMatomyositis) study is the first large randomised, placebo-controlled trial to establish the efficacy and safety of intravenous immunoglobulin (IVIg) in adult patients with dermatomyositis. Objectives of this analysis were to closely examine the safety and tolerability of IVIg in patients from the ProDERM study. METHODS ProDERM was a double-blind, randomised, placebo-controlled, multicentre, phase 3 study. In the first period (weeks 0-16), adults with active dermatomyositis received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label extension period (weeks 16-40), all patients received IVIg for 6 additional cycles; dose reduction (1.0 g/kg) was permitted if patients were stable. Treatment-emergent adverse events (TEAEs) were documented. RESULTS The 95 patients enrolled were randomised to receive IVIg (N = 47) or placebo (N = 48) in the first period, with 5 switching from placebo to IVIg. Overall, 664 IVIg infusion cycles were administered. During the first period, 113 TEAEs were possibly/probably related to treatment in 30/52 patients (57.7%) receiving IVIg and 38 in 11 patients (22.9%) on placebo. Eight patients discontinued therapy due to IVIg-related TEAEs. Eight thromboembolic events (TEEs) occurred in six patients on IVIg; six in five patients were deemed possibly/probably related to IVIg. Patients with TEEs exhibited more baseline TEE risk factors than those without TEEs (2.4-15.2-fold higher). Lowering infusion rate reduced the rate of TEEs, and none occurred at the lower IVIg dose. No haemolytic transfusion reactions or deaths occurred. CONCLUSIONS Results from this study demonstrate that IVIg has a favourable safety profile for treatment of adult dermatomyositis patients and provides evidence that will help to inform treatment choice for these patients. Dermatomyositis patients receiving high-dose IVIg should be monitored for TEEs, and a low rate of infusion should be used to minimise TEE risk, particularly in those with pre-existing risk factors. TRIAL REGISTRATION ProDERM study (NCT02728752).
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3.
Risk factors for coronary artery abnormalities and resistance to immunoglobulin plus ciclosporin A therapy in severe Kawasaki disease: subanalysis of the KAICA trial, randomized trial for cicrosporin A as the first-line treatment
Murayama, Y., Hamada, H., Shiko, Y., Onouchi, Y., Kakimoto, N., Ozawa, Y., Hanaoka, H., Hata, A., Suzuki, H.
Frontiers in pediatrics. 2023;11:1321533
Abstract
BACKGROUND To investigate risk factors for coronary arterial abnormalities (CAAs) and resistance to treatment in patients with Kawasaki disease (KD) receiving intravenous immunoglobulin (IVIG) plus ciclosporin A (CsA) as the first-line treatment, we performed a subanalysis of baseline data of participants in the KAICA trial, a phase 3, randomized study (JMA-ILA00174). METHODS All data of the patients enrolled in the KAICA trial, who had a Gunma score ≥5 at diagnosis and had been randomly assigned to either IVIG (2 g/kg/24 h) plus CsA (5 mg/kg/day for 5 days) (n = 86) or IVIG alone (n = 87), were subjected to this study. CAA was defined by a Z score ≥2.5 observed within 4 weeks after treatment initiation. Baseline data including genotypes of KD susceptibility genes were compared between subgroups of patients for CAA or treatment response for each treatment group. Backword-forward stepwise logistic regression analyses were performed. RESULTS Pre-Z-max, defined as the maximum among Z scores on four coronary artery branches before treatment, was higher in patients with CAA in both treatment groups and was associated with CAA in IVIG plus CsA treatment group [odds ratio (OR) = 17.0]. High serum total bilirubin level was relevant to treatment resistance only in the IVIG plus CsA group (OR = 2.34). CONCLUSIONS Coronary artery enlargement before treatment is a major determinant of CAA even in KD patients treated with initial IVIG treatment intensified by addition of CsA. Baseline serum total bilirubin level was a risk factor associated with resistance to IVIG plus CsA.
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4.
Efficacy of Platelet-Rich Plasma Therapy in Oral Lichen Planus: A Systematic Review
Sriram S, Hasan S, Alqarni A, Alam T, Kaleem SM, Aziz S, Durrani HK, Ajmal M, Dawasaz AA, Saeed S
Medicina (Kaunas, Lithuania). 2023;59(4)
Abstract
Background and Objectives: Oral lichen planus (OLP) is an autoimmune, mucocutaneous, oral potentially malignant disorder (OPMD), which characteristically manifests with chronic, recalcitrant lesions, with frequent flare-ups and remissions. The precise etiopathogenesis of OLP is still debatable, although it is believed to be a T-cell-mediated disorder of an unidentified antigen. Despite the availability of various treatments, no cure for OLP exists due to its recalcitrant nature and idiopathic etiology. Platelet-rich plasma (PRP) has antioxidant, anti-inflammatory, and immunomodulatory properties, in addition to its regulatory action on keratinocyte differentiation and proliferation. These salient properties substantiate the possible role of PRP in the treatment of OLP. Our systematic review focuses on assessing the therapeutic potential of PRP as a treatment modality in OLP. Materials and Methods: We conducted a detailed literature search for studies assessing PRP as a therapeutic regimen in OLP, using the Google Scholar and PubMed/MEDLINE search engines. The search was limited to studies published from January 2000 to January 2023 and included a combination of Medical Subject Heading (MeSH) terms. ROBVIS analysis was carried out for the assessment of publication bias. Descriptive statistics were performed using Microsoft Excel. Results: This systematic review included five articles that met the inclusion criteria. Most of the included studies demonstrated that PRP treatment considerably ameliorated both objective and subjective symptoms in OLP subjects, with comparable efficacy to the standard corticosteroid treatment. Further, PRP therapy offers the added benefit of minimal adverse effects and recurrences. Conclusion: This systematic review suggests that PRP has significant therapeutic potential for treating OLP. However, further research with larger sample sizes is imperative to corroborate these findings.
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5.
Plasma exchange for acute optic neuritis in neuromyelitis optica or neuromyelitis optica spectrum disorder: a systematic review
Naphattalung, Y., Chuenkongkaew, W. L., Chirapapaisan, N., Laowanapiban, P., Sawangkul, S.
Annals of medicine. 2023;55(1):2227422
Abstract
OBJECTIVES To appraise whether plasma exchange (PLEX) effectively improves visual function for acute optic neuritis (ON) in neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD). METHODS AND ANALYSIS We searched Medline, Embase, Cochrane Library, ProQuest Central, and Web of Science to identify relevant articles published between 2006 and 2020.Eligible studies were in English and evaluated visual outcomes for people with acute ON in NMO or NMOSD treated with PLEX. They also had adequate pre- and posttreatment data. Excluded were studies with 1 or 2 case reports, or incomplete data. RESULTS Twelve studies were qualitatively synthesized (1 RCT; 1 controlled NRSI; 10 observational studies). Five before-and-after observational studies were used for quantitative synthesis. The PLEX in the 5 studies (3 to 7 cycles over 2 to 3 weeks) was performed as second-line or adjunctive therapy for acute ON in NMO/NMOSD.The qualitative synthesis revealed that visual-acuity recovery occurred between one day and 6 months after the first PLEX cycle completion. Thirty-two of 48 participants in the 5 quantitative-synthesis studies received PLEX. Relative to pre-PLEX values, visual-acuity improvements were nonsignificant at these post-PLEX time points: 1 day (SMD 0.611; 95% CI -0.620 to 1.842); 2 weeks (SMD 0.0214; 95% CI -1.250 to 1.293); 3 months (SMD 1.014; 95% CI -0.954 to 2.982); and 6 months (SMD 0.450; 95% CI -2.643 to 3.543). CONCLUSIONS There were inadequate data to determine whether PLEX effectively treats acute ON in NMO/NMOSD. Aggregate current data of this systematic review is insufficient to definitively conclude whether therapeutic PLEX is effective in improving VA in cases of NMO or NMOSD. eng
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6.
Current biologics in treatment of pemphigus foliaceus: a systematic review
Carver, C. A., Kalesinskas, M., Ahmed, A. R.
Frontiers in immunology. 2023;14:1267668
Abstract
BACKGROUND Pemphigus foliaceus (PF) differs from pemphigus vulgaris (PV) in that it affects only the skin and mucous membranes are not involved. Pemphigus is commonly treated with systemic corticosteroids and immunosuppressive agents (ISAs). More recently, biologics have been used. The current literature on biologic therapy often combines treatment of PF with PV, hence it is often difficult for clinicians to isolate the treatment of PF from PV. The purpose of this review was to provide information regarding the use of current biological therapy, specifically in PF. MATERIALS AND METHODS A search of PubMed, Embase, and other databases was conducted using keywords pemphigus foliaceus (PF), rituximab (RTX), intravenous immunoglobulin (IVIg), and biologics. Forty-one studies were included in this review, which produced 105 patients with PF, treated with RTX, IVIg, or a combination of both. Eighty-five patients were treated with RTX, eight patients with IVIg, and 12 received both RTX and IVIg. RESULTS Most patients in this review had PF that was nonresponsive to conventional immunosuppressive therapies (CIST), and had significant side effects from their use. RTX treatment resulted in complete remission (CR) in 63.2%, a relapse rate of 39.5%, an infection rate of 19.7%, and a mortality rate of 3.9%. Relapse was greater in the lymphoma (LP) protocol than the rheumatoid arthritis (RA) protocol (p<0.0001). IVIg led to CR in 62.5% of patients, with no relapses or infections. Patients receiving both biologics experienced better outcomes when RTX was first administered, then followed by IVIg. Follow-up durations for patients receiving RTX, IVIg, and both were 22.1, 24.8, and 35.7 months, respectively. DISCUSSION In pemphigus foliaceus patients nonresponsive to conventional immunosuppressive therapy or in those with significant side effects from CIST, RTX and IVIg appear to be useful agents. Profile of clinical response, as well as relapse, infection, and mortality rates in PF patients treated with RTX were similar to those observed in PV patients. The data suggests that protocols specific for PF may produce better outcomes, less adverse effects, and improved quality of life.
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7.
Efficacy of intravenous immunoglobulins (IVIg) in improving skin symptoms in patients with dermatomyositis: a post-hoc analysis of the ProDERM study
Werth, V. P., Aggarwal, R., Charles-Schoeman, C., Schessl, J., Levine, T., Kopasz, N., Worm, M., Bata-Csörgő, Z.
EClinicalMedicine. 2023;64:102234
Abstract
BACKGROUND Dermatomyositis (DM) is a rare autoimmune disease characterized by skin involvement, with or without proximal muscle weakness. Recently, following the ProDERM study, intravenous immunoglobulin (IVIg) was approved for treatment of DM. Until ProDERM evidence from large, placebo-controlled studies supporting its use for dermatological symptoms, was lacking. Here we present efficacy data from ProDERM of IVIg versus placebo for treatment of the cutaneous aspect of DM. METHODS ProDERM was a double-blind, randomized, multicenter, Phase 3 study. In the First Period (Weeks 0-16), adults with active DM received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label Extension Period (Weeks 16-40), all patients received IVIg for 6 additional cycles. Cutaneous disease was assessed using measures including modified cutaneous DM disease area and severity index activity (CDASI-A) and damage (CDASI-D) scores, and myositis disease activity assessment tool (MDAAT) including visual analogue scale (VAS). This trial is registered with ClinicalTrials.gov, NCT02728752. FINDINGS The study took place from February 2017 to November 2019. 95 patients received IVIg (N = 47) or placebo (N = 48) in the First Period. Together, 664 IVIg infusion cycles were administered (median dose, 2.0 g/kg). At Week 16, mean CDASI-A change from baseline was -9.36 (95% CI: -12.52, -6.19) in the IVIg group versus -1.16 (-3.32, 0.99) in placebo group (p < 0.0001). At the end of the Extension Period, mean changes from baseline were -10.44 (95% CI: -13.94, -6.94) and -10.03 (-13.12, -6.94), respectively. Similar changes were seen for CDASI-D and VAS of MDAAT. These observations were seen regardless of baseline disease severity. INTERPRETATION ProDERM is the first large prospective, randomized trial to demonstrate the efficacy of IVIg to improve the cutaneous manifestations of DM. IVIg treatment significantly improved dermatological symptoms in patients with DM, regardless of disease severity before treatment, suggesting that IVIg is effective for even the most severe cutaneous DM. FUNDING This study was sponsored by Octapharma Pharmazeutika Produktionsges m.b.H.
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8.
The effects of glucocorticoid plus intravenous immunoglobulin (IVIG) vs IVIG alone on platelet activation in children with Kawasaki disease
Wang, Q. Q., Zheng, L. Y., Zhao, S.
The Turkish journal of pediatrics. 2023;65(4):640-649
Abstract
BACKGROUND Even though intravenous immunoglobulin (IVIG) is a current treatment for Kawasaki disease (KD), 10-20% of patients require additional therapy. This study seeks to investigate the therapeutic effects of glucocorticoids plus IVIG on KD and to ascertain the subsequent effect on platelet activation during the acute phase. METHODS A total of 32 children with KD were randomly classified into two groups: the experimental group (16 cases) and the control group (16 cases). The control group was exposed to IVIG (2 g/kg), whereas children in the experimental group were treated with IVIG (2 g/kg) + glucocorticoid. Peripheral venous blood samples were obtained from all participants before treatment as well as three days post-treatment to test platelet activation levels with procaspase activating compound-1 (PAC-1) antibody, Toll-like receptor 4 (TLR4), interleukin-6 (IL- 6), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), and C-reactive protein (CRP). Fever duration posttreatment was documented for both groups. Additionally, the coronary arteries in both groups were evaluated during three months of treatment. RESULTS After treatment, the experimental group had remarkably lower levels of TNF-α, CRP, PCT, IL-6, PAC- 1, and TLR4 relative to the control group. The fever persistence rate was considerably elevated in the control group compared to the experimental group (log-rank, P=0.024). In addition, the z-score of coronary artery size dropped after IVIG + glucocorticoids treatment compared to the control group, although this difference was not significant. CONCLUSIONS The IVIG + glucocorticoids can quickly mitigate the inflammatory response and platelet activation. Moreover, it can also improve clinical symptoms in children with KD.
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9.
Intravenous immunoglobulin for the treatment of Kawasaki disease
Broderick, C., Kobayashi, S., Suto, M., Ito, S., Kobayashi, T.
The Cochrane Database of Systematic Reviews. 2023;1(1):Cd014884
Abstract
BACKGROUND Kawasaki disease (KD) is an acute systemic vasculitis (inflammation of the blood vessels) that mainly affects children. Symptoms include fever, chapped lips, strawberry tongue, red eyes (bulbar conjunctival injection), rash, redness, swollen hands and feet or skin peeling; and enlarged cervical lymph nodes. High fevers and systemic inflammation characterise the acute phase. Inflammation of the coronary arteries causes the most serious complication of the disease, coronary artery abnormalities (CAAs). The primary treatment is intravenous immunoglobulin (IVIG) and acetylsalicylic acid (ASA/aspirin), with doses and regimens differing between institutions. It is important to know which regimens are the safest and most effective in preventing complications. OBJECTIVES To evaluate the efficacy and safety of IVIG in treating and preventing cardiac consequences of Kawasaki disease. SEARCH METHODS The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 26 April 2022. SELECTION CRITERIA We included randomised controlled trials (RCTs) investigating the use of IVIG for the treatment of KD. We included studies involving treatment for initial or refractory KD, or both. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were incidence of CAAs and incidence of any adverse effects after treatment. Our secondary outcomes were acute coronary syndromes, duration of fever, need for additional treatment, length of hospital stay, and mortality. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS We identified 31 RCTs involving a total of 4609 participants with KD. Studies compared IVIG with ASA, another dose or regimen of IVIG, prednisolone, or infliximab. The majority of studies reported on primary treatment, so those results are reported below. A limited number of studies investigated secondary or tertiary treatment in IVIG-resistant patients. Doses and regimens of IVIG infusion varied between studies, and all studies had some concerns related to risk of bias. Primary treatment with IVIG compared to ASA for people with KD Compared to ASA treatment, IVIG probably reduces the incidence of CAAs in people with KD up to 30 days (odds ratio (OR) 0.60, 95% confidence interval (CI) 0.41 to 0.87; 11 studies, 1437 participants; moderate-certainty evidence). The individual studies reported a range of adverse effects, but there was little to no difference in numbers of adverse effects between treatment groups (OR 0.57, 95% CI 0.17 to 1.89; 10 studies, 1376 participants; very low-certainty evidence). There was limited evidence for the incidence of acute coronary syndromes, so we are uncertain of any effects. Duration of fever days from treatment onset was probably shorter in the IVIG group (mean difference (MD) -4.00 days, 95% CI -5.06 to -2.93; 3 studies, 307 participants; moderate-certainty evidence). There was little or no difference between groups in need for additional treatment (OR 0.27, 95% CI 0.05 to 1.57; 3 studies, 272 participants; low-certainty evidence). No study reported length of hospital stay, and no deaths were reported in either group. Primary treatment with IVIG compared to different infusion regimens of IVIG for people with KD Higher-dose regimens of IVIG probably reduce the incidence of CAAs compared to medium- or lower-dose regimens of IVIG up to 30 days (OR 0.60, 95% CI 0.40 to 0.89; 8 studies, 1824 participants; moderate-certainty evidence). There was little to no difference in the number of adverse effects between groups (OR 1.11, 95% CI 0.52 to 2.37; 6 studies, 1659 participants; low-certainty evidence). No study reported on acute coronary syndromes. Higher-dose IVIG may reduce the duration of fever compared to medium- or lower-dose regimens (MD -0.71 days, 95% CI -1.36 to -0.06; 4 studies, 992 participants; low-certainty evidence). Higher-dose regimens may reduce the need for additional treatment (OR 0.29, 95% CI 0.10 to 0.88; 4 studies, 1125 participants; low-certainty evidence). We did not detect a clear difference in length of hospital stay between infusion regimens (MD -0.24, 95% CI -0.78 to 0.30; 3 studies, 752 participants; low-certainty evidence). One study reported mortality, and there was little to no difference detected between regimens (moderate-certainty evidence). Primary treatment with IVIG compared to prednisolone for people with KD The evidence comparing IVIG with prednisolone on incidence of CAA is very uncertain (OR 0.60, 95% CI 0.24 to 1.48; 2 studies, 140 participants; very low-certainty evidence), and there was little to no difference between groups in adverse effects (OR 4.18, 95% CI 0.19 to 89.48; 1 study; 90 participants; low-certainty evidence). We are very uncertain of the impact on duration of fever, as two studies reported this outcome differently and showed conflicting results. One study reported on acute coronary syndromes and mortality, finding little or no difference between groups (low-certainty evidence). No study reported the need for additional treatment or length of hospital stay. AUTHORS' CONCLUSIONS The included RCTs investigated a variety of comparisons, and the small number of events observed during the study periods limited detection of effects. The certainty of the evidence ranged from moderate to very low due to concerns related to risk of bias, imprecision, and inconsistency. The available evidence indicated that high-dose IVIG regimens are probably associated with a reduced risk of CAA formation compared to ASA or medium- or low-dose IVIG regimens. There were no clinically significant differences in incidence of adverse effects, which suggests there is little concern about the safety of IVIG. Compared to ASA, high-dose IVIG probably reduced the duration of fever, but there was little or no difference detected in the need for additional treatment. Compared to medium- or low-dose IVIG, there may be reduced duration of fever and reduced need for additional treatment. We were unable to draw any conclusions regarding acute coronary syndromes, mortality, or length of hospital stay, or for the comparison IVIG versus prednisolone. Our findings are in keeping with current guideline recommendations and evidence from long-term epidemiology studies.
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10.
Effect of platelet concentrates for pain and symptom management in oral lichen planus: an evidence-based systematic review
Zhang, Y., Mao, C., Zhu, J., Yu, W., Wang, Z., Wang, Y., Kan, Q.
BMC oral health. 2023;23(1):594
Abstract
BACKGROUND Platelet Concentrate (PC) injection therapy has shown potential as a local therapy for oral lichen planus (OLP). However, its safety and efficacy have not yet been fully established. Our research compared the efficacy of PC with topical steroid treatment in alleviating pain and symptoms related to OLP. We aims to present evidence-based alternatives that dentists can use to improve patient outcomes while reducing potential side effects. METHODS We conducted a systematic search of five electronic databases up to April 2023, including Embase, Cochrane Central Register of Controlled Trials, PubMed, OVID Medline, and WanFang, to evaluate PCs' efficacy compared to topical corticosteroid therapy for OLP. The literature quality was assessed using the Cochrane ROB tool. A fixed-effects model was used to determine the Weighted Mean Difference (WMD) and Mean Difference (MD) at a 95% confidence interval (CI) for pain severity and other relevant clinical indicators. RESULTS The comparison between topical corticosteroid therapy and PCs showed no significant difference for pain relief (WMD = -0.07, CI = 95% -0.34 to 0.19), symptom improvement (MD = -0.21, CI = 95% -0.55 to 0.13), or the severity of included lesions measured by REU scores (MD = -0.25, CI = 95% -0.32 to 0.82). CONCLUSIONS Locally injected PC have been found efficient in managing oral lichen planus, indicating that they are a promising alternative option to steroid therapy for OLP patients, particularly those who have not responded favorably to steroid therapy. However, further research is needed to establish determining the recurrence rate and long-term adverse effects. TRIAL REGISTRATION The systematic review protocol has been registered in advance with the PROSPERO database (CRD42023415372).