Brazilian Journal of Pharmaceutical Sciences Review http://dx.doi.org/10.1590/s2175-97902019000418077 Intralesional corticosteroid injection as an effective treatment method for oral lesions: a meta-analysis Narges Gholizadeh1, Maryam-Sadat Sadrzadeh-Afshar 2, Nafiseh Sheykhbahaei3* 1Oral & Maxillofacial Medicine Department, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran, 2Oral & Maxillofacial Medicine Department, School of Dentistry, Aja University of Medical Sciences, Tehran, Iran, 3Oral & Maxillofacial Medicine Department, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran Intralesional corticosteroid injection (ICSI) is known as one of the main methods used for treating a wide range of lesions. It also results in a high concentration of drugs at lesion sites, with minimal systemic absorption. Thus, this study aimed to provide a review of the intralesional corticosteroid injection (ICSI) indications in the treatment of oral lesions. To this end; relevant key words were searched in the databases of PubMed, Google Scholar, Scopus, ScienceDirect, and UpToDate in the present study. Accordingly, the results of a total number of 62 case reports or case series articles were used in this study and the positive therapeutic effects of intralesional corticosteroid injection (ICSI) in 23 common oral lesions were reported. The most common type of intralesional steroid in the treatment of oral lesions was triamcinolone. No significant difference was also observed in terms of pain in patients following the use of steroid alone or in combination with anesthetic agents; moreover, the reported side effects of this method were exceptionally rare and transient. It was concluded that the intralesional corticosteroid injection (ICSI) could be one of the effective therapeutic methods with no significant problems in many oral lesions such as inflammatory, immunologic, and vascular ones due to its higher therapeutic effects than other topical forms of steroids and fewer side effects than systemic corticosteroid. Keywords: Intralesional corticosteroid injection. Triamcinolone. Betamethasone. Oral lesions. Oral disorders. Steroid injection. INTRODUCTION acute peptic ulcer, depression, severe psychosis, and active fungal and bacterial infections must be taken Intralesional corticosteroid injection (ICSI), into account. In addition, the ICSI is preferable to introduced as a medical treatment in 1951, has become the topical corticosteroids such as creams, ointments, one of the main methods used alone or in combination mouthwashes, gels, and foams due to bypassing of with other procedures for treating a wide range of diseases mucous membranes, reduced risk of mucosal atrophy, as well as benign and malignant proliferations in the head higher drug concentrations, and longer durability in and the neck (Egbert et al., 2001; Buckmiller, Francis, lesion sites (Laisuan et al., 2017). Nowadays, various Galde, 2008; Ffrooz, Tehranchia‐Nia, Ahmed, 1995). medications are available for the ICSIs; however, The ICSI leads to a high concentration of drugs at lesion physicians commonly prescribe triamcinolone and sites, with minimal systemic absorption; therefore, it has betamethasone derivations. The most important point no common side effects of systemic form or even reduces in this therapeutic approach is that the efficacy and the them (Goldman, 1962; Saravanan et al., 2014). However, potential complications of the injection are dependent in cases wherein high or repeated doses of injection are on its usage method (Ffrooz, Tehranchia‐Nia, Ahmed, required, systemic corticosteroid considerations such 1995). This injection is performed at offices without as hypertension, heart failure, uncontrolled diabetes, special supplies and equipment. Prior to injection; the history of any allergies, systemic problems, and the use *Correspondence: N. Sheykhbahaei. Oral & Maxillofacial Medicine of medications such as aspirin and warfarin must be Department, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran. Tel: +98-9128090967 / Fax: +98-2181633501. E-mail: taken from patients. Although the local anesthesia can [email protected] be used at the site, it is not usually necessary because Braz. J. Pharm. Sci. 2020;56:e18077 Page 1 / 15 N. Gholizadeh, M.-S. Sadrzadeh-Afshar, N. Sheykhbahaei the pain created by the ICSI is similar to the injection MATERIAL AND METHODS of the anesthetic substance (Saravanan et al., 2014). If the injectable material is a suspension, it must be shaken The data collection was fulfilled through searching well before injection. Corticosteroids, either pure or in the databases of PubMed, Google Scholar, Scopus, diluted, with saline or anesthetics can be further applied. ScienceDirect, and UpToDate using relevant keywords In most oral lesions, 0.1 to 0.2 mL of the substance is including corticosteroid injection, intralesional injection, also injected into four sides of a lesion, and it is normally triamcinolone injection, betamethasone injection, oral recommended not to increase the total dosage more than lesions, oral disorders, and steroid injection, alone or in 2 mL in each session. For this purpose, insulin syringe is combination. In this search, no time limit was considered, the most suitable injection device. Moreover, the forms the last access to different platforms was in September used for the ICSI do not need to be kept in refrigerator 2018, and the search results were restricted to articles thanks to their high shelf life (Richards, 2010). published in English. The inclusion criteria for the articles Immediate side effects of the injection include composed of: pain, bleeding, infection, and allergic reaction, as well 1 - Clinical trial articles as delayed complications including atrophy of skin or 2 - Case reports or case series articles mucous membranes, and hyper- or hypo-pigmentation 3 - Treatment of oral lesions or structures related to of the lesion site (Saravanan et al., 2014; Laisuan et al., oral cavity; e.g. salivary glands, temporomandibular 2017). Although these indications are not very common, joint, lips, sinuses and oropharynx, no skin, or other the possible cause of complications is the lymphogenous sites of the body. spread of corticosteroid suspension, which brings 4 - Intralesional injection of steroids and no other forms about dermal and epidermal changes such as thinning of corticosteroids of the epithelium, loss of rete ridges, necrosis of epithelial and small blood vessels, interference with RESULTS synthesis of melanin from melanocytes, reduction of mucopolysaccharides, and loss of elastic properties Following the completion of the search process, 600 of tissues. In this line, the incidence of tissue atrophy abstracts were obtained and about 200 relevant abstracts depends on injection depth and local concentration were reviewed and nearly 80 full-text articles in PDF obtained after injection (Hengge et al., 2006; Friedman, format were selected. In total, 62 articles were included Butler, Pittelkow, 1988; Schetman, Hambrick, Wilson, in this study. 1963). The ICSI in children can also cause abnormalities in their growth and immune system (Buckmiller, Francis, DISCUSSION & Glade, 2008). Although the occurrence of these complications is very rare, it leads to some worries in The most common causes to use corticosteroid some patients and reduces levels of collaboration in drugs in oral medicine are their anti-inflammatory, anti- treatments. Therefore, the efficacy of this therapeutic proliferative, immunosuppressive, and vasoconstrictive approach depends on the effective communications effects which appear to be largely mediated by several by physicians with patients along with awareness mechanisms such as functioning on stromal capillaries to concerning benefits and possible complications (Del decrease erythema, directing regulation of corticosteroid- Rosso, Friedlander, 2005). The ICSI is a safe and cost- responsive genes by steroid-receptor complex, having effective process. Accordingly, the employment of this indirect control over transcription through blockage method in the treatment of skin lesions has been highly of effects of other transcription factors such as NF-kB, reported and approved. Nevertheless, no comprehensive inhibiting transcription of various pro-inflammatory review has been so far carried out on applying it in oral cytokine genes including interleukin IL-1, IL-2, IL-6, lesions, administration patterns, drug types and dosages, interferon gamma (IFN-γ), and tumor necrosis factor- and treatment outcomes. Considering the relatively high alpha, stimulating expression of anti-inflammatory prevalence rates of oral diseases and the potential of cytokines genes such as transforming growth factor-B benefits of this method, it can be utilized in the treatment and IL-10, making shifts in T-helper type 1 (TH1) to of numerous oral lesions. Thus, this study aimed to TH2 ratio, and decreasing trafficking of lymphocytes present a review of the ICSI indications and treatment to lesion sites by diminishing vascular permeability and details in oral lesions to provide more reliable evidence inhibiting proliferation of various cell types including T for clinicians. lymphocytes (Norris, 2005). Therefore, steroids are mostly Page 2 / 15 Braz. J. Pharm. Sci. 2020;56:e18077 Intralesional corticosteroid injection as an effective treatment method for oral lesions: a meta-analysis employed in treatment of disorders that are inflammatory, the immune system