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World J Stomatol. May 20, 2015; 4(2): 87-95
Published online May 20, 2015. doi: 10.5321/wjs.v4.i2.87
Treatment of mouth and jaw diseases with intralesional steroid injection
Alparslan Esen, Kubilay Işık, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Necmettin Erbakan University, 42050 Konya, Turkey
Doğan Dolanmaz, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Selcuk University, 42250 Konya, Turkey
Author contributions: All authors contributed equally to this work but especially Esen A wrote the manuscript; Esen A and Işık K contributed to reviewing the literature; Dolanmaz D designed the aim of the editorial.
Conflict-of-interest: Authors notify no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Alparslan Esen, DDS, PhD, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Necmettin Erbakan University, Ankara Cd. No: 74/A, Karatay, 42050 Konya, Turkey. dtaesen@hotmail.com
Telephone: +90-332-2200026 Fax: +90-332-2200045
Received: September 3, 2014
Peer-review started: September 4, 2014
First decision: November 27, 2014
Revised: December 30, 2014
Accepted: January 15, 2015
Article in press: January 17, 2015
Published online: May 20, 2015

Abstract

Many lesions of the oral region are treated with surgical methods such as curettage and resection. Chemotherapy and radiation therapy with or without surgical intervention can be used as an adjunct in some cases. Intralesional steroid injection is a conservative procedure which is already used in various regions of the body and joints. This technique is used also for a number of mouth and jaw lesions. Localized langerhans cell histiocytosis, central giant cell granuloma, oral submucous fibrosis, oral lichen planus, lichen sclerosus of the oral mucosa, lymphatic malformations and orofacial granulomatosis can be considered among these diseases. The purpose of this review is to investigate the effects of intralesional steroid injections in the treatment of oral diseases.

Key Words: Intralesional injections, Steroids, Langerhans Cell histiocytosis, Giant cell granuloma, Oral submucous fibrosis, Oral lichen planus, Orofacial granulomatosis

Core tip: Intralesional steroid injections are often used in the lesion occurred in oral and maxillofacial region in recent years. Especially in large lesions, it can be applied as an alternative or adjunct to surgical procedures. It is an effective treatment method, because, without the need for major surgical procedures and providing patient comfort.



INTRODUCTION

Corticosteroids are one of the most widely used drugs due to their anti-inflammatory, anti-allergic and immunosuppressive effects. Today they are used as systemic, topical, intra-articular and intralesional in the clinic. They were first used systemically in a patient with severe rheumatoid arthritis in 1948 by Hench et al[1]. Consequently a further 15 patients were successfully treated. In 1950, their discovery of the effect of cortisone brought Hench, Edward and Reichstein the Nobel Prize in Medicine and Physiology[2]. Beneficial effects of intra-articular corticosteroid (hydrocortisone acetate) injection was first published in 1951[3]. In 1956, prednisolone was introduced by Rothermich and Phillips[4] as an satisfactory and more potent alternative for intra-articular injections. Boland and Liddle[5] compared methylprednisolone with prednisolone and found them equally effective. Triamcinolone acetonide was applied in the treatment of dermatoses by Robinson[6] in 1958. Later, triamcinolone hexacetonide was reported to be a potent synthetic corticosteroid for intra-articular usage[7]. In the 1970s, corticosteroids were administered in intra-osseous lesions such as bone cysts[8-10]. Intralesional steroid injection (ISI) has been performed in both of bone and mucosal lesions of oral and maxillofacial region since 1980. Currently, this method is widely accepted as an alternative or aid to surgical treatment especially in large reactive lesions.

In this review, we review the hard and soft tissue lesions of oral region that can be treated with intralesional steroid injections. Under the each disease’s title, we also discuss the action mechanism of steroids.

DISEASES THAT CAN BE TREATED WITH ISI
Bone lesions

Localized langerhans cell histiocytosis (eosinophilic granuloma) and central giant cell granuloma.

Soft tissue lesions

Soft tissue lesions include oral submucous fibrosis; oral lichen planus; oral lichen sclerosis; lymphatic malformations; and orofacial granulomatosis.

LOCALIZED LANGERHANS CELL HISTIOCYTOSIS (EOSINOPHILIC GRANULOMA)

Langerhans’ cell histiocytosis (LCH), formerly known as histiocytosis-X, is a disease characterized by cell proliferation exhibiting phenotypic characteristics of Langerhans cells[11]. There are three clinical forms of the disease: Letterer-Siwe disease, Hand-Schüller-Christian syndrome and Localized Langerhans Cell Histiocytosis (LLCH) or eosinophilic granuloma[12].

Letterer-Siwe disease is an acute disseminated form of LCH and characterized by hepatosplenomegaly, lymphadenopathy, anemia, skin rash, and bone lesions with dissemination. It usually affects young children and follows an acute or sub-acute course.

Chronic disseminated form of the LCH is called Hand-Schüller-Christian syndrome and it is usually associated with a triad of exophthalmos, diabetes insipidus and punched-out bone lesions. This form of the disease typically affects the patients in the second and third decades or older age[13].

LLCH, a localized disease. It accounts for 60%-70% of LCH cases and it can be found as solitary or multifocal bone defects. While mandible, skull and ribs are most often affected in children, long bones and vertebrae are more frequently involved in adults. The disease peaks in the first three decades and males are affected twice as females[14]. Possible symptoms are swelling, pain and tenderness over the lesion’s site. General malaise, fever, headache, toothache, bleeding, loose teeth and sensory disturbances may accompany as well. It is also possible not to see any symptoms[15]. The lesions appear as radiolucent areas with well-demarcated borders in radiographic views. Pathologic fractures may arise due to resorption of the overlying cortical bone[16]. Treatment options of LLCH include resection or curettage, chemotherapy, radiotherapy or a combination of them[17]. Spontaneous healing has been reported, too[18].

Treatment of the LLCH with ISI

Currently there is not a clear treatment protocol for the ISI in the LLCH. Previously a few studies have been reported. In 1980, Cohen et al[19] first employed this technique in eosinophilic granulomas of the bones. While they did a single dose of methylprednisolone directly into the lesions in various parts of the body, in mandibular lesions they did a second injection. Jones et al[16] applied single intralesional dose of 165 mg methylprednisolone to a mandibular LCH and reported complete resolution of the lesion after 8 mo. Others[20] have described a case with multifocal LCHs in the mandible, who failed to respond to radiotherapy and systemic therapy with prednisone and etoposide. On a weekly basis, the authors injected 2 mL of 25 mg/mL triamcinolone into the lesion for six times. Complete remission was reached by the 15 mo. Putters et al[21] treated three LLCH cases of the mandible in a one-stage procedure. They performed intralesional injections of 80, 40, and 80 mg of methylprednisolone succinate, respectively. The lesions showed radiologically and clinically complete remission after 6 mo. In another case[22], 200 mg of intralesional methylprednisolone injection was used in a mandibular lesion and complete resolution had been achieved after 17 mo. Esen et al[23] reported a case of LLCH of the mandible, which also caused a non-displaced pathologic fracture. They started repeated ISIs and the fracture line disappeared within 14 mo without using any reduction or fixation methods. By the end of the 36-mo follow-up, the lesion was entirely healed. In a later paper[24], two patients were treated in one-stage procedures with intralesional methylprednisolone injections. The lesions healed clinically and radiologically 35 and 15 mo after treatment.

Action mechanism of steroids

Many questions remain to be clarified to understand the therapeutic effects of corticosteroids in LLCH. It is unknown whether they suppress T lymphocytes, the Langerhans cells, eosinophils or stimulate osteogenesis. It has been suggested[8,25] that corticosteroid microcrystals can break the connective tissue of the cystic wall and allow secondary osteogenic repair or IL-1 is inhibited by steroids. Even though these hypotheses may explain the improvement in bone cysts, it does not apply to LLCH, because there is no membrane covering the lesion.

As evident from the literature, ISI is a successful method in cases of LLCH. It is an effective treatment method, because, without the need for major surgical procedures and providing patient comfort.

CENTRAL GIANT CELL GRANULOMA

The central giant cell granuloma (CGCG) was first described by Jaffe[26] in 1953. CGCG occurs almost solely within the jaws and it is a benign proliferation of fibroblasts and multinucleated giant cells. It typically presents as a solitary radiolucent lesion of the mandible or maxilla. The lesions occur twice as often in the mandible than in the maxilla. It is predominantly found in young adults before the age 30 with a female preponderance[27]. Based on its clinical behavior, CGCG has been classified as non-aggressive and aggressive lesion. Non-aggressive lesions tend to grow slowly and do not perforate the cortical bone. Recurrence usually is not seen after treatment. Aggressive lesions are characterized by rapid growth, pain, expansion or perforation of the cortical bone, root resorption, and a high recurrence tendency[28]. The traditional treatment of CGCG is curettage or resection depending on the lesion’s behavior, size, location, and radiographic appearance. Non-surgical treatment methods are systemic administration of calcitonin, intralesional injection of corticosteroids and administration of α-interferon[29-32].

Treatment of the CGCG with ISI

The treatment of CGCG with corticosteroids was first reported by Jacoway et al[33] in 1988. They suggested is a 50/50 mixture of 2% lidocaine with 1:100000 epinephrine and triamcinolone acetonide (TA) to inject 2 mL/1 cm of lesion as seen on a panoramic radiography and to repeat this six times at weekly intervals. Later, Terry and Jacoway[34] presented four patients treated with steroids in 1994. A weekly done ISI during six weeks resulted in a complete resolution in three patients, while one patient needed additional surgery. Kermer et al[35] published another case of CGCG treated with corticosteroids in the same year. Rajeevan and Soumithran[36] reported that intralesional triamcinolone acetonide was administered to a 17-year-old girl who had CGCG in 1998. They indicated that almost healing the lesion of the left mandible was observed after the sixth month. In 2000, Khafif et al[37] applied the same protocol to a 36-year-old female patient who had a CGCG of maxilla and they reported that a complete remission was seen after two years. Kurtz et al[38] also used ISI to a 10-year-old CGCG patient in 2001. They reported that the proper healing was seen after 5 years. In 2002, Carlos et al[39] added four new cases to the literature. They reported that the lesions showed clinically and radiologically recovery approximately 6-7 years after treatment except for one case in which partial remission was observed. Abdo et al[40] reported that a recurrent CGCG in a 14-year-old girl in the anterior region of the mandible was treated successfully by ISI in 2005. Sezer et al[41] also reported that an 11-year-old boy with a CGCG is successfully treated with intralesional corticosteroid injections after 3 years follow-up in the same year. Comert et al[42] preferred to use prednisolone in their patient who had CGCG of the maxilla. They reported that a partial recovery was achieved and a limited surgery could be performed. Wendt et al[43] employed ISI for a maxillary CGCG with a 1:1 triamcinolone acetonide (10 mg/mL) and 0.5% bupivacaine. The solution was injected into the lesion for a period of 11 wk. After 6-years follow-up, the treatment was found to be successful clinically and radiographically. Mohanty and Jhamb[44] performed same protocol and reported that two patients were successfully treated with triamcinolone acetonide injections. Nogueira et al[45] contributed to literature with 21 new cases in 2010 using ISI with triamcinolone hexacetonide. Two patients did not responded to the treatment and surgical resection was needed; a moderate improvement noted in four patients (curettage in two patients) and 15 of the cases showed good response (curettage in one patient). Shirani et al[46] performed ISI in an aggressive and extensive case and they could not get the answer to the treatment. Ferretti et al[47] applied the same protocol to 16-year-old female patient who had CGCG and they reported that a complete remission was seen after 4 years follow up. Rachmiel et al[48] performed combination therapy consisting of ISI, calcitonin nasal spray and curettage in a 24-year-old female patient and found that no recurrence after 5-year follow-up. da Silva et al[49] treated a 36-year-old male with a CGCG crossing the midline of mandible with ISI combined with alendronate sodium for the control of systemic bone resorption. They reported that no recurrence or side effects at the end of four years. Finally, Fonseca et al[50] reported that intralesional triamcinolone acetonide was administered to a 15-year-old boy who had CGCG. They indicated that partial resolution of the lesion was observed after the sixth month.

Action mechanism of steroids

There are several theories about the action mechanism of ISI in the CGCG. Osteoclasts achieve bone resorption by secreting lysosomal proteases. These agents mediate the process by creating an extracellular medium. It has been showed[51,52] that 17β-estradiol (E2) could directly inhibit osteoclastic bone resorption. Moreover, at concentrations effective for inhibiting bone resorption, E2 could also induces osteoclast apoptosis.

On the basis of the aforementioned experimental evidence the mechanism of corticosteroids in the treatment of these lesions is suggested as inhibition of the extracellular production of lysosomal proteases and steroidal apoptotic action on osteoclast-like cells. These two mechanisms could cause cessation of bone resorption[39].

According to literature, ISI is an effective method in patients with CGCG. However, it is not always possible to obtain a positive response to the treatment in the multilocular or aggressive lesions. Hence, in such cases, it is necessary to apply surgical or combined treatment methods. In addition, serum calcium, phosphorus and parathyroid hormone levels should be examined on suspicion of hyperparathyroidism after definitive diagnosis result of the incisional biopsy. It should be noted that the images of brown tumor and CGCG can’t be distinguished histologically. And before starting the ISIs, possible diabetes mellitus and the presence of peptic ulcers or any infection should be questioned.

ORAL SUBMUCOUS FIBROSIS

Oral submucous fibrosis (OSF) is a chronic disease of the oral mucosa. It affects the pharynx, oral cavity, upper third of the esophagus and it is characterized by inflammation and a progressive fibrosis of sub-epithelial tissues[53]. Connective tissue fibers of the lamina propria and deeper parts change, which in turn lead to mucosal stiffness and limitation in mouth opening[54]. OSF is considered as high-risk precancerous disease[53-55]. Several factors contributing to OSF include general nutritional or vitamin deficiencies and hypersensitivity to various dietary constituents. The primary factor appears to be chewing of the areca (betel) nut. Genetic factors are thought to be involved in the etiology. It has been reported that a polymorphism of the promoter region of the matrix metalloproteinase 3 gene is common in OSF and may contribute to development of the disease[27]. The potential morbidities of OSF are restriction of mouth opening, difficulty with swallowing, mastication, speech, and a burning sensation as well. It has a mortality potential because of the possibility of transformation into squamous cell carcinoma[55]. Both nonsurgical and surgical treatment options have been suggested. Nonsurgical options are ISIs, hyaluronidase and interferon gamma. Surgery primarily targets to improve the mouth opening and comprises the excision of the fibrous bands, skin grafts and splitting of the temporalis tendon.

Treatment of the OSF with ISI

Treatment is generally intended to increase the mouth opening and to decrease the burning sensation. For early-stage submucous fibrosis cases, the results are better with non-surgical methods. In intralesional applications, the triamcinolone acetonide is the most preferred agent but different substances are also applied such as salvianolic acid B (SA-B) and lycopene. As far as we know, Gupta and Sharma[56] were the first who successfully treated the OSF with local injections of chymotrypsin, hyaluronidase, and dexamethasone. Later, sub-mucosal steroid injection and hyaluronidase or topical vitamin A, topical steroid application and oral iron preparations were applied by Borle and Borle[57] in 326 patients with oral submucous fibrosis. Khanna et al[58] presented 100 patients in their clinical study in which the author implemented intralesional injection of triamcinolone acetonide in patients with very early and early-stage of OSF cases while they performed surgical intervention in advanced cases. Satisfactory results were reported in long-term follow up. Kumar et al[59] applied the lycopene and lycopene combined with ISI of betamethasone in OSF patients. They reported that positive clinical response was obtained in both study groups when compared with placebo. Singh et al[60] compared the efficacy of hydrocortisone acetate and hyaluronidase at weekly interval vs triamcinolone acetonide and hyaluronidase at 15 d interval. They notified no significant differences in symptom or sign scores and any histopathological improvement between the groups. The authors conclude that treatment regimen of triamcinolone acetonide and hyaluronidase was more convenient to the patients because of less number of visits required and of cost efficiency. No side effects were seen[60]. Rao[61] treated the patients with OSF using alpha lipoic acid in addition to the ISI of betamethasone and hyaluronidase. He reported that the alpha lipoic acid group exhibited better relief of symptoms as compared to the controls and he concluded that the use of an antioxidant, alpha lipoic acid, along with conventional therapy of ISI is effective in the management of OSF. Jiang et al[55] investigated that the effectiveness of triamcinolone acetonide and (SA-B) intralesional combined injection in the treatment of oral submucous fibrosis (OSF) and they concluded that the triamcinolone acetonide + SA-B intralesional injections improved mouth open and burning sensation in these OSF patients. Shetty et al[62] examined the efficacy of spirulina as an antioxidant adjuvant to corticosteroid injection in management of oral submucous fibrosis. They treated the OSF patients in a group with spirulina+ betamethasone and placebo capsules + betamethasone in other group. They reported that the mouth opening and burning sensation was found to be statistically very highly significant in favor of the spirulina group.

Some complications can be seen after the procedure in the OSF cases. Chen et al[63] observed facial candida albicans cellulitis in a diabetes mellitus patient with oral submucous fibrosis after ISI treatment. Therefore, it should be noted that some complications can arise due to the predisposing factors such as immunodeficiency (HIV), immune-suppression (systemic treatments with corticosteroids), chronic illness, obesity, diabetes, malnutrition, vitamin deficiency, alcohol misuse, tobacco smoking and intravenous drugs abuse.

Action mechanism of steroids

According to the hypothesis of Tsai et al[64], some alkaloids (arecoline, arecaidine) inhibit fibroblast phagocytosis and this contributes for the development of OSF. ISIs could cause an enhancement of fibroblast collagen phagocytosis. Juxta-epithelial inflammatory cell infiltration and then progressive hyalinization of the lamina propria and deeper connective tissues are associated with early OSF[55,65,66]. Use of ISI have been directed to chronic juxta-epithelial inflammation[55-57,60]. The steroids can prevent or suppress inflammatory reactions, so they fight with fibrosis by decreasing fibroblastic proliferation and collagen deposition[55,65,66]. Therefore, it can be more successful when the steroid injections administered in the early stages of the disease. According to the literature, triamcinolone acetonide or betamethasone appears to be a suitable choice.

ORAL LICHEN PLANUS

Oral lichen planus (OLP) is a chronic mucocutaneous disease of unknown cause, with oral lesions occurring most commonly in women over 30 years of age. Incidence of OLP is between 0.2% and 2% in the population. Different types of OLP have been described as reticular, plaque form, erosive, atrophic, or bullous. Intraorally, the buccal mucosa, tongue and the gingiva are commonly involved although other sites may be rarely affected. Oral mucosal lesions present alone or with concomitant skin lesions. The most common type is the reticular form which is characterized by numerous interlacing white keratotic lines or striae that produce an annular or lacy pattern[27,67]. The plaque form of OLP tends to resemble leukoplakia clinically but has a multifocal distribution. In the erosive form, the central area of the lesion is ulcerated. A fibrinous plaque or pseudomembrane covers the ulcer. The erithematous or atrophic type appears as red patches with very fine white striae. It may be seen in conjunction with reticular or erosive variants. Patients complain of pain, burning, sensitivity and generalized discomfort in particularly erosive and atrophic types[27,67]. The risk of malignant transformation varies between 0.4% and 5% over periods of observation from 0.5 to 20 years[68]. A few studies have reported that the malignant potential of OLP and hepatitis C virus infection apparently increased the risk for oral squamous cell carcinoma[69-71]. Patients with reticular and other asymptomatic OLP lesions usually require no active treatment but symptomatic lesions may also need treatment. Nonsurgical treatments are systemic drug therapy, topical corticosteroids-calcineurin inhibitors - retinoids, injection of steroids and ultraviolet irradiation. The other methods are surgery, laser therapy and cryosurgery[67].

Treatment of the OLP with ISI

According to literature, intra- and sublesional treatment of OLP with triamcinolone acetonide was reported by Sleeper[72] for the first time in 1967. The author reported that after 72 h, examination of the lesions showed 45% to 50% involution with corresponding relief of symptoms. In three cases the entire lesion disappeared in two weeks. In the other four cases with larger lesions, approximately 10% to 15% of the lesion remained, but the patients were completely symptom free. In 1974, Randell and Cohen[73] applied dexamethasone in patients with OLP and they reported successful results. Then Zegarelli[74,75] performed ISI with triamcinolone acetonide and methylprednisolone in patients with erosive or ulcerative OLP. Xia et al[76] studied with 45 patients with clinical and histologically confirmed ulcerative OLP. Each participant received 0.5 mL intralesional triamcinolone acetonide injection (40 mg/mL) on one side and other side was left as control. The treated areas gave rapid relief of signs and symptoms, while the control areas showed minimal decrease. Thirty-eight (84.4%) patients demonstrated complete response in ulceration size. No complications were noted with triamcinolone acetonide injections. They concluded that intralesional triamcinolone acetonide injection in ulcerative OLP is effective and safe in achieving lesion and pain regression. Xiong et al[77] compared the intralesional polysaccharide nucleic acid fraction of bacillus Calmette-Guerin (BCG-PSN) and triamcinolone acetonide in patients with erosive OLP. They randomly assigned 56 OLP patients receive either intralesional injection of 0.5 mL BCG-PSN every other day (n = 31) or 10 mg triamcinolone acetonide (a positive-controlled group, n = 25) every week for 2 wk. After the cessation of treatment, patients were followed up for 3 mo. After 2-wk treatment, 27 of 31 BCG-PSN-treated patients (87.1%) and 22 of 25 TA-treated patients (88.0%) healed. There were no statistical differences between the two groups in erosive areas and pain scores. They concluded that topical intralesional BCG-PSN injection is as effective as triamcinolone acetonide for erosive OLP. Lee et al[78] investigated intralesional injection vs mouth rinse of triamcinolone acetonide in 40 patients with OLP in terms of pain and burning sensation. They concluded that the efficacies of both treatments were similar. The rate of adverse effects was significantly lower for intralesional injection of triamcinolone acetonide than mouth rinse of TA. In another clinical study, intralesional triamcinolone acetonide plus oral prednisolone was applied by Kuo et al[79] in 50 patients with erosive OLP. They reported that although the patients showed complete response in 90% of cases after three weeks, recurrence of erosive or ulcerative lesion was observed after 3-24 (mean 12) mo of follow-up in all of these cases. Liu et al[80] analyzed the efficacy and safety of intralesional betamethasone in the treatment of erosive OLP. They implemented intralesional betamethasone 1.4 mg to the experimental group and 8 mg intralesional triamcinolone acetonide to the control group once a week for two weeks in 61 patients with erosive OLP. They found that 93.1% of participants were healed after two intralesional injections of 1.4 mg betamethasone, and 66.7% of participants were healed after two intralesional injections of 8 mg triamcinolone acetonide and authors concluded that intralesional betamethasone was a more effective way to treat erosive OLP.

According to the literature, triamcinolone acetonide is the most preferable agent as intralesional injection in patients with OLP. Recently, betamethasone seems to be also effective. General usage of triamcinolone acetonide is to dilute 10 to 20 mg in 0.5 mL saline or 2% lidocaine, then to inject into the lesion once 1 wk for 2 times[81]. Injections are administered into the connective tissue below the erosive lesion from the adjacent normal mucosa. The treatment is absolutely required in patients with erosive and erythematous types due to the daily life is affected by pain and burning sensation. Generally, patient comfort is provided and the lesions disappeared within one to two weeks after ISI. However, recurrence of the lesions may occur on the long-term follow-up. Disadvantages include mucosal atrophy, difficulty to deposit sufficient quantities into gingival lesions and painful injection[82].

Action mechanism of steroids

While the etiology of OLP is not clear, it has been suggested that it could be caused by a immune response with an inflammatory cell population composed of T lymphocytes[83,84]. When the steroids are injected directly into the connective tissue below the lesions, they can suppress T cells and show a strong anti-inflammatory and immunosuppressive effect[80].

OTHER DISEASES

Other oral diseases treated with ISI are very limited in the literature. Azevedo et al[85] used intralesional injection of triamcinolone acetonide in patients with oral lichen sclerosis. The authors reported that the patients showed improvement and elasticity of oral tissues enhanced. Luo and Gun[86] found that intralesional injection of pingyangmycin with triamcinolone acetonide was more effective than pingyangmycin alone for management of lymphatic malformations in oral and maxillofacial region. Anjomshoaa et al[87] performed intralesional injections of triamcinolone acetonide in a patient with follicular lymphoid hyperplasia. In addition, they reported that complete resolution of the lesion was obtained at 7-mo follow-up. Another disease in which ISI could be effective is orofacial granulomatosis (OFG). It is an uncommon disease, usually presents as recurrent or persistent swelling of the soft tissues in the orofacial region, predominantly on lips, causing significant cosmetic and functional problems[88,89]. The reason of this disease is unknown. OFG may also be part of the triad of Melkersson-Rosenthal syndrome (MRS) and some consider it a monosymptomatic form of MRS[90,91]. Sakuntabhai et al[92] used high-volume intralesional triamcinolone acetonide injections (3 to 10 mL of 10 mg/mL) and they reported that intralesional triamcinolone injections reduced lip swelling. However, Mignogna et al[91] performed small volume, high concentrate, delayed release, intralesional injection of triamcinolone acetonide in patients with OFG. They reported that all patients remained without recurrences or with cosmetically acceptable slight lip enlargement for a mean time of 19 mo and this method was very affective and it did not require nerve blockage. The same researchers investigated the long-term outcome in patients treated with intralesional triamcinolone acetonide injections and reported that complete clinical remission were obtained in all patients for a mean time of 56.3 ± 18.2 mo[93]. Several other clinical studies have reported that injections of intralesional steroids are clinically successful method in patients with OFG[88,89,94].

Exogenous corticosteroids are usually classified based on their relative glucocorticoid and mineralocorticoid potency as well as duration of their effects. The most potent glucocorticoids are also the most potent suppressors of the hypothalamic pituitary adrenal axis. While short-acting steroids (e.g., Cortisol) are effective for less than 12 h, intermediate-acting steroids (Prednisone, Prednisolone, Methylprednisolone and Triamcinolone) can stay active for 12-36 h and long-acting steroids (Betamethasone, Dexamethasone and Flumethasone) are effective for more than 36 h[95]. Most prominent properties of corticosteroids are their anti-inflammatory, anti-allergic and analgesic effects. Glucocorticoids help keeping normal vascular permeability and stabilize lysosomal and cellular membranes. On the other hand, in acute inflammation, they decrease vascular permeability and inhibit the migration of polymorphonuclear lymphocytes into tissues. They also induce apoptosis in normal lymphoid cells; inhibit the clonal expansion of T and B lymphocytes; and reduce the eosinophils, basophils, and monocytes in the circulation. Glucocorticoids have different effects on neutrophils. They hinder margination of neutrophils and increase the release of mature neutrophils from the bone marrow.

However, they may also decelerate wound healing[95]. Long-term use of corticosteroids can cause osteoporosis, hypertension, electrolyte imbalance, hyperglycemia, delayed wound healing, and a tendency for infections. There are some contraindications for steroids such as history of allergy, peptic ulcer, Cushing syndrome, uncontrolled diabetes, renal failure, anticoagulation usage, fungal diseases and varicella zoster infection[96]. Although intralesional injection can be performed easily, several precautions should be taken during the processing. The injection must always be made using sterile procedures and anatomy of the area should be known. Adjacent nerves should be kept away and intravenous injections should be avoided because of the possibility of systemic effects such as adrenal suppression[96].

CONCLUSION

ISI is one of the most preferable non-surgical methods for the treatment of mucosal or bone reactive lesions occurred in oral and maxillofacial region. The accumulating evidence suggests that ISI is well tolerated by patients, the likelihood of postoperative complications is less than those of other methods and patient complaints diminish rapidly. Especially in large lesions, it can be applied as an alternative or adjunct to surgical procedures. This method is also minimally invasive and relatively inexpensive.

Footnotes

P- Reviewer: Popli DB S- Editor: Ji FF L- Editor: A E- Editor: Jiao XK

References
1.  Hench PS, Kendall EC. The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone; compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis. Proc Staff Meet Mayo Clin. 1949;24:181-197.  [PubMed]  [DOI]  [Cited in This Article: ]
2.  Lundberg IE, Grundtman C, Larsson E, Klareskog L. Corticosteroids--from an idea to clinical use. Best Pract Res Clin Rheumatol. 2004;18:7-19.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 23]  [Cited by in F6Publishing: 27]  [Article Influence: 1.4]  [Reference Citation Analysis (0)]
3.  Hollander JL, Brown EM, Jessar RA, Brown CY. Hydrocortisone and cortisone injected into arthritic joints; comparative effects of and use of hydrocortisone as a local antiarthritic agent. J Am Med Assoc. 1951;147:1629-1635.  [PubMed]  [DOI]  [Cited in This Article: ]
4.  Philips VK, Rothermich NO. Local injection of prednisolone TBA in the treatment of rheumatic diseases. Ohio Med. 1957;53:45-46.  [PubMed]  [DOI]  [Cited in This Article: ]
5.  Boland EW, Liddle GW. Metabolic and antirheumatic activities of 6-methylprednisolone (medrol). Ann Rheum Dis. 1957;16:297-306.  [PubMed]  [DOI]  [Cited in This Article: ]
6.  Robinson RC. Treatment of dermatoses with local application of triamcinolone acetonide, a new synthetic corticoid; a preliminary report. Bull Sch Med Univ Md. 1958;43:54-57.  [PubMed]  [DOI]  [Cited in This Article: ]
7.  Kendall PH. Triamcinolone hexacetonide. A new corticosteroid for intra-articular therapy. Ann Phys Med. 1967;9:55-58.  [PubMed]  [DOI]  [Cited in This Article: ]
8.  Scaglietti O, Marchetti PG, Bartolozzi P. The effects of methylprednisolone acetate in the treatment of bone cysts. Results of three years follow-up. J Bone Joint Surg Br. 1979;61-B:200-204.  [PubMed]  [DOI]  [Cited in This Article: ]
9.  Campanacci M, De Sessa L, Bellando Randone P. [Bone cyst (review of 275 cases; results of the surgical treatment and early results of closed treatment with methylprednisolone acetate)]. Chir Organi Mov. 1975;62:471-482.  [PubMed]  [DOI]  [Cited in This Article: ]
10.  Savastano AA. The treatment of bone cysts with intracyst injection of steroids. Injection of steroids will largely replace surgery in the treatment of benign bone cysts. R I Med J. 1979;62:93-95.  [PubMed]  [DOI]  [Cited in This Article: ]
11.  Komp DM. Langerhans cell histiocytosis. N Engl J Med. 1987;316:747-748.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 45]  [Cited by in F6Publishing: 45]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
12.  Lichtenstein L. Histiocytosis X; integration of eosinophilic granuloma of bone, Letterer-Siwe disease, and Schüller-Christian disease as related manifestations of a single nosologic entity. AMA Arch Pathol. 1953;56:84-102.  [PubMed]  [DOI]  [Cited in This Article: ]
13.  Miloro M, Ghali GE, Larsen P, Waite P.  Peterson’s Principles of Oral and Maxillofacial Surgery: 3rd ed. UK: B C Decker Inc 2004; 665-666.  [PubMed]  [DOI]  [Cited in This Article: ]
14.  Key SJ, O’Brien CJ, Silvester KC, Crean SJ. Eosinophilic granuloma: resolution of maxillofacial bony lesions following minimal intervention. Report of three cases and a review of the literature. J Craniomaxillofac Surg. 2004;32:170-175.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 41]  [Cited by in F6Publishing: 46]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
15.  Ardekian L, Peled M, Rosen D, Rachmiel A, Abu el-Naaj I, Laufer D. Clinical and radiographic features of eosinophilic granuloma in the jaws: review of 41 lesions treated by surgery and low-dose radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87:238-242.  [PubMed]  [DOI]  [Cited in This Article: ]
16.  Jones LR, Toth BB, Cangir A. Treatment for solitary eosinophilic granuloma of the mandible by steroid injection: report of a case. J Oral Maxillofac Surg. 1989;47:306-309.  [PubMed]  [DOI]  [Cited in This Article: ]
17.  Nauert C, Zornoza J, Ayala A, Harle TS. Eosinophilic granuloma of bone: diagnosis and management. Skeletal Radiol. 1983;10:227-235.  [PubMed]  [DOI]  [Cited in This Article: ]
18.  Namai T, Yusa H, Yoshida H. Spontaneous remission of a solitary eosinophilic granuloma of the mandible after biopsy: a case report. J Oral Maxillofac Surg. 2001;59:1485-1487.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 24]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
19.  Cohen M, Zornoza J, Cangir A, Murray JA, Wallace S. Direct injection of methylprednisolone sodium succinate in the treatment of solitary eosinophilic granuloma of bone: a report of 9 cases. Radiology. 1980;136:289-293.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 117]  [Cited by in F6Publishing: 121]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
20.  Watzke IM, Millesi W, Kermer C, Gisslinger H. Multifocal eosinophilic granuloma of the jaw: long-term follow-up of a novel intraosseous corticoid treatment for recalcitrant lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90:317-322.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 29]  [Cited by in F6Publishing: 34]  [Article Influence: 1.4]  [Reference Citation Analysis (0)]
21.  Putters TF, de Visscher JG, van Veen A, Spijkervet FK. Intralesional infiltration of corticosteroids in the treatment of localised langerhans’ cell histiocytosis of the mandible Report of known cases and three new cases. Int J Oral Maxillofac Surg. 2005;34:571-575.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 44]  [Cited by in F6Publishing: 36]  [Article Influence: 1.9]  [Reference Citation Analysis (0)]
22.  Moralis A, Kunkel M, Kleinsasser N, Müller-Richter U, Reichert TE, Driemel O. Intralesional corticosteroid therapy for mandibular Langerhans cell histiocytosis preserving the intralesional tooth germ. Oral Maxillofac Surg. 2008;12:105-111.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 16]  [Cited by in F6Publishing: 15]  [Article Influence: 0.9]  [Reference Citation Analysis (0)]
23.  Esen A, Dolanmaz D, Kalayci A, Günhan O, Avunduk MC. Treatment of localized Langerhans’ cell histiocytosis of the mandible with intralesional steroid injection: report of a case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109:e53-e58.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 23]  [Cited by in F6Publishing: 25]  [Article Influence: 1.8]  [Reference Citation Analysis (0)]
24.  Lee SH, Yoon HJ. Intralesional infiltration of corticosteroids in the treatment of localized Langerhans cell histiocytosis of the mandible: report of two cases. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116:e255-e260.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 12]  [Cited by in F6Publishing: 13]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
25.  Yasko AW, Fanning CV, Ayala AG, Carrasco CH, Murray JA. Percutaneous techniques for the diagnosis and treatment of localized Langerhans-cell histiocytosis (eosinophilic granuloma of bone). J Bone Joint Surg Am. 1998;80:219-228.  [PubMed]  [DOI]  [Cited in This Article: ]
26.  Jaffe HL. Giant-cell reparative granuloma, traumatic bone cyst, and fibrous (fibro-oseous) dysplasia of the jawbones. Oral Surg Oral Med Oral Pathol. 1953;6:159-175.  [PubMed]  [DOI]  [Cited in This Article: ]
27.  Regezi JA, Sciubba JJ, Jordan RCK.  Oral Pathology: Clinical Pathologic Correlations. Holland: Elsevier Health Sciences 2012; .  [PubMed]  [DOI]  [Cited in This Article: ]
28.  Chuong R, Kaban LB, Kozakewich H, Perez-Atayde A. Central giant cell lesions of the jaws: a clinicopathologic study. J Oral Maxillofac Surg. 1986;44:708-713.  [PubMed]  [DOI]  [Cited in This Article: ]
29.  Whitaker SB, Waldron CA. Central giant cell lesions of the jaws. A clinical, radiologic, and histopathologic study. Oral Surg Oral Med Oral Pathol. 1993;75:199-208.  [PubMed]  [DOI]  [Cited in This Article: ]
30.  Minić A, Stajcić Z. Prognostic significance of cortical perforation in the recurrence of central giant cell granulomas of the jaws. J Craniomaxillofac Surg. 1996;24:104-108.  [PubMed]  [DOI]  [Cited in This Article: ]
31.  de Lange J, Rosenberg AJ, van den Akker HP, Koole R, Wirds JJ, van den Berg H. Treatment of central giant cell granuloma of the jaw with calcitonin. Int J Oral Maxillofac Surg. 1999;28:372-376.  [PubMed]  [DOI]  [Cited in This Article: ]
32.  de Lange J, van den Akker HP, van den Berg H. Central giant cell granuloma of the jaw: a review of the literature with emphasis on therapy options. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104:603-615.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 180]  [Cited by in F6Publishing: 161]  [Article Influence: 9.5]  [Reference Citation Analysis (0)]
33.  Jacoway JR. Central giant cell granuloma: An alternative to surgical therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1988;66:572.  [PubMed]  [DOI]  [Cited in This Article: ]
34.  Terry B, Jacoway J. Management of central giant cell lesions: an alternative to surgical therapy. Oral Maxillofac Surg Clin North Am. 1994;6:579-600.  [PubMed]  [DOI]  [Cited in This Article: ]
35.  Kermer C, Millesi W, Watzke IM. Local injection of corticosteroids for central giant cell granuloma. A case report. Int J Oral Maxillofac Surg. 1994;23:366-368.  [PubMed]  [DOI]  [Cited in This Article: ]
36.  Rajeevan NS, Soumithran CS. Intralesional corticosteroid injection for central giant cell granuloma. A case report. Int J Oral Maxillofac Surg. 1998;27:303-304.  [PubMed]  [DOI]  [Cited in This Article: ]
37.  Khafif A, Krempl G, Medina JE. Treatment of giant cell granuloma of the maxilla with intralesional injection of steroids. Head Neck. 2000;22:822-825.  [PubMed]  [DOI]  [Cited in This Article: ]
38.  Kurtz M, Mesa M, Alberto P. Treatment of a central giant cell lesion of the mandible with intralesional glucocorticosteroids. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91:636-637.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 41]  [Cited by in F6Publishing: 45]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
39.  Carlos R, Sedano HO. Intralesional corticosteroids as an alternative treatment for central giant cell granuloma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;93:161-166.  [PubMed]  [DOI]  [Cited in This Article: ]
40.  Abdo EN, Alves LC, Rodrigues AS, Mesquita RA, Gomez RS. Treatment of a central giant cell granuloma with intralesional corticosteroid. Br J Oral Maxillofac Surg. 2005;43:74-76.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 48]  [Cited by in F6Publishing: 52]  [Article Influence: 2.7]  [Reference Citation Analysis (0)]
41.  Sezer B, Koyuncu B, Gomel M, Günbay T. Intralesional corticosteroid injection for central giant cell granuloma: a case report and review of the literature. Turk J Pediatr. 2005;47:75-81.  [PubMed]  [DOI]  [Cited in This Article: ]
42.  Comert E, Turanli M, Ulu S. Oral and intralesional steroid therapy in giant cell granuloma. Acta Otolaryngol. 2006;126:664-666.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 16]  [Article Influence: 0.9]  [Reference Citation Analysis (0)]
43.  Wendt FP, Torriani MA, Gomes AP, de Araujo LM, Torriani DD. Intralesional corticosteroid injection for central giant cell granuloma: an alternative treatment for children. J Dent Child (Chic). 2009;76:229-232.  [PubMed]  [DOI]  [Cited in This Article: ]
44.  Mohanty S, Jhamb A. Central giant cell lesion of mandible managed by intralesional triamcinolone injections. A report of two cases and literature review. Med Oral Patol Oral Cir Bucal. 2009;14:E98-102.  [PubMed]  [DOI]  [Cited in This Article: ]
45.  Nogueira RL, Teixeira RC, Cavalcante RB, Ribeiro RA, Rabenhosrt SH. Intralesional injection of triamcinolone hexacetonide as an alternative treatment for central giant-cell granuloma in 21 cases. Int J Oral Maxillofac Surg. 2010;39:1204-1210.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 47]  [Cited by in F6Publishing: 38]  [Article Influence: 2.7]  [Reference Citation Analysis (0)]
46.  Shirani G, Abbasi AJ, Mohebbi SZ, Shirinbak I. Management of a locally invasive central giant cell granuloma (CGCG) of mandible: report of an extraordinary large case. J Craniomaxillofac Surg. 2011;39:530-533.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 19]  [Article Influence: 1.4]  [Reference Citation Analysis (0)]
47.  Ferretti C, Muthray E. Management of central giant cell granuloma of mandible using intralesional corticosteroids: case report and review of literature. J Oral Maxillofac Surg. 2011;69:2824-2829.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 30]  [Cited by in F6Publishing: 32]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
48.  Rachmiel A, Emodi O, Sabo E, Aizenbud D, Peled M. Combined treatment of aggressive central giant cell granuloma in the lower jaw. J Craniomaxillofac Surg. 2012;40:292-297.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 21]  [Article Influence: 1.6]  [Reference Citation Analysis (0)]
49.  da Silva NG, Carreira AS, Pedreira EN, Tuji FM, Ortega KL, de Jesus Viana Pinheiro J. Treatment of central giant cell lesions using bisphosphonates with intralesional corticosteroid injections. Head Face Med. 2012;8:23.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 26]  [Cited by in F6Publishing: 27]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
50.  Fonseca FP, Ribeiro AC, Santos-Silva AR, Vargas PA, Lopes MA. Fine needle aspiration cytology and intralesional steroid injection in a central giant cell granuloma affecting the gingiva: a new clinical approach. Braz Dent J. 2013;24:420-427.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 11]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
51.  Kremer M, Judd J, Rifkin B, Auszmann J, Oursler MJ. Estrogen modulation of osteoclast lysosomal enzyme secretion. J Cell Biochem. 1995;57:271-279.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 54]  [Cited by in F6Publishing: 56]  [Article Influence: 1.9]  [Reference Citation Analysis (0)]
52.  Kameda T, Mano H, Yuasa T, Mori Y, Miyazawa K, Shiokawa M, Nakamaru Y, Hiroi E, Hiura K, Kameda A. Estrogen inhibits bone resorption by directly inducing apoptosis of the bone-resorbing osteoclasts. J Exp Med. 1997;186:489-495.  [PubMed]  [DOI]  [Cited in This Article: ]
53.  Pillai R, Balaram P, Reddiar KS. Pathogenesis of oral submucous fibrosis. Relationship to risk factors associated with oral cancer. Cancer. 1992;69:2011-2020.  [PubMed]  [DOI]  [Cited in This Article: ]
54.  Angadi PV, Rao SS. Areca nut in pathogenesis of oral submucous fibrosis: revisited. Oral Maxillofac Surg. 2011;15:1-9.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 65]  [Cited by in F6Publishing: 80]  [Article Influence: 6.2]  [Reference Citation Analysis (0)]
55.  Jiang XW, Zhang Y, Yang SK, Zhang H, Lu K, Sun GL. Efficacy of salvianolic acid B combined with triamcinolone acetonide in the treatment of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115:339-344.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 15]  [Cited by in F6Publishing: 11]  [Article Influence: 0.9]  [Reference Citation Analysis (0)]
56.  Gupta D, Sharma SC. Oral submucous fibrosis--a new treatment regimen. J Oral Maxillofac Surg. 1988;46:830-833.  [PubMed]  [DOI]  [Cited in This Article: ]
57.  Borle RM, Borle SR. Management of oral submucous fibrosis: a conservative approach. J Oral Maxillofac Surg. 1991;49:788-791.  [PubMed]  [DOI]  [Cited in This Article: ]
58.  Khanna JN, Andrade NN. Oral submucous fibrosis: a new concept in surgical management. Report of 100 cases. Int J Oral Maxillofac Surg. 1995;24:433-439.  [PubMed]  [DOI]  [Cited in This Article: ]
59.  Kumar A, Bagewadi A, Keluskar V, Singh M. Efficacy of lycopene in the management of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103:207-213.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 93]  [Cited by in F6Publishing: 75]  [Article Influence: 4.2]  [Reference Citation Analysis (0)]
60.  Singh M, Niranjan HS, Mehrotra R, Sharma D, Gupta SC. Efficacy of hydrocortisone acetate/hyaluronidase vs triamcinolone acetonide/hyaluronidase in the treatment of oral submucous fibrosis. Indian J Med Res. 2010;131:665-669.  [PubMed]  [DOI]  [Cited in This Article: ]
61.  Rao PK. Efficacy of alpha lipoic acid in adjunct with intralesional steroids and hyaluronidase in the management of oral submucous fibrosis. J Cancer Res Ther. 2010;6:508-510.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 12]  [Article Influence: 0.9]  [Reference Citation Analysis (0)]
62.  Shetty P, Shenai P, Chatra L, Rao PK. Efficacy of spirulina as an antioxidant adjuvant to corticosteroid injection in management of oral submucous fibrosis. Indian J Dent Res. 2013;24:347-350.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 28]  [Cited by in F6Publishing: 30]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
63.  Chen HM, Shih CC, Yen KL, Wang SM, Kuo YS, Kuo MY, Chiang CP. Facial Candida albicans cellulitis occurring in a patient with oral submucous fibrosis and unknown diabetes mellitus after local corticosteroid injection treatment. J Oral Pathol Med. 2004;33:243-245.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 12]  [Cited by in F6Publishing: 12]  [Article Influence: 0.6]  [Reference Citation Analysis (0)]
64.  Tsai CC, Ma RH, Shieh TY. Deficiency in collagen and fibronectin phagocytosis by human buccal mucosa fibroblasts in vitro as a possible mechanism for oral submucous fibrosis. J Oral Pathol Med. 1999;28:59-63.  [PubMed]  [DOI]  [Cited in This Article: ]
65.  Canniff JP, Harvey W, Harris M. Oral submucous fibrosis: its pathogenesis and management. Br Dent J. 1986;160:429-434.  [PubMed]  [DOI]  [Cited in This Article: ]
66.  Sirsat SM, Pindborg JJ. Subepithelial changes in oral submucous fibrosis. Acta Pathol Microbiol Scand. 1967;70:161-173.  [PubMed]  [DOI]  [Cited in This Article: ]
67.  Scully C, Carrozzo M. Oral mucosal disease: Lichen planus. Br J Oral Maxillofac Surg. 2008;46:15-21.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 247]  [Cited by in F6Publishing: 276]  [Article Influence: 16.2]  [Reference Citation Analysis (0)]
68.  van der Meij EH, Schepman KP, Smeele LE, van der Wal JE, Bezemer PD, van der Waal I. A review of the recent literature regarding malignant transformation of oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;88:307-310.  [PubMed]  [DOI]  [Cited in This Article: ]
69.  Bombeccari GP, Guzzi G, Tettamanti M, Giannì AB, Baj A, Pallotti F, Spadari F. Oral lichen planus and malignant transformation: a longitudinal cohort study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112:328-334.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 88]  [Cited by in F6Publishing: 102]  [Article Influence: 7.8]  [Reference Citation Analysis (0)]
70.  Shen ZY, Liu W, Zhu LK, Feng JQ, Tang GY, Zhou ZT. A retrospective clinicopathological study on oral lichen planus and malignant transformation: analysis of 518 cases. Med Oral Patol Oral Cir Bucal. 2012;17:e943-e947.  [PubMed]  [DOI]  [Cited in This Article: ]
71.  Gandolfo S, Richiardi L, Carrozzo M, Broccoletti R, Carbone M, Pagano M, Vestita C, Rosso S, Merletti F. Risk of oral squamous cell carcinoma in 402 patients with oral lichen planus: a follow-up study in an Italian population. Oral Oncol. 2004;40:77-83.  [PubMed]  [DOI]  [Cited in This Article: ]
72.  Sleeper HR. Intralesional and sublesional injection of triamcinolone acetonide for oral lichen planus. Yale J Biol Med. 1967;40:164-165.  [PubMed]  [DOI]  [Cited in This Article: ]
73.  Randell S, Cohen L. Erosive lichen planus. Management of oral lesions with intralesional corticosteroid injections. J Oral Med. 1974;29:88-91.  [PubMed]  [DOI]  [Cited in This Article: ]
74.  Zegarelli DJ. Topical and intralesional steroid therapy of oral lichen planus. N Y State Dent J. 1980;46:432, 434-436.  [PubMed]  [DOI]  [Cited in This Article: ]
75.  Zegarelli DJ. Multimodality steroid therapy of erosive and ulcerative oral lichen planus. J Oral Med. 1983;38:127-130.  [PubMed]  [DOI]  [Cited in This Article: ]
76.  Xia J, Li C, Hong Y, Yang L, Huang Y, Cheng B. Short-term clinical evaluation of intralesional triamcinolone acetonide injection for ulcerative oral lichen planus. J Oral Pathol Med. 2006;35:327-331.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 40]  [Cited by in F6Publishing: 45]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
77.  Xiong C, Li Q, Lin M, Li X, Meng W, Wu Y, Zeng X, Zhou H, Zhou G. The efficacy of topical intralesional BCG-PSN injection in the treatment of erosive oral lichen planus: a randomized controlled trial. J Oral Pathol Med. 2009;38:551-558.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 43]  [Cited by in F6Publishing: 45]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
78.  Lee YC, Shin SY, Kim SW, Eun YG. Intralesional injection versus mouth rinse of triamcinolone acetonide in oral lichen planus: a randomized controlled study. Otolaryngol Head Neck Surg. 2013;148:443-449.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 33]  [Cited by in F6Publishing: 37]  [Article Influence: 3.4]  [Reference Citation Analysis (0)]
79.  Kuo RC, Lin HP, Sun A, Wang YP. Prompt healing of erosive oral lichen planus lesion after combined corticosteroid treatment with locally injected triamcinolone acetonide plus oral prednisolone. J Formos Med Assoc. 2013;112:216-220.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 46]  [Cited by in F6Publishing: 47]  [Article Influence: 3.9]  [Reference Citation Analysis (0)]
80.  Liu C, Xie B, Yang Y, Lin D, Wang C, Lin M, Ge L, Zhou H. Efficacy of intralesional betamethasone for erosive oral lichen planus and evaluation of recurrence: a randomized, controlled trial. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116:584-590.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 24]  [Cited by in F6Publishing: 20]  [Article Influence: 1.8]  [Reference Citation Analysis (0)]
81.  Kini R, Nagaratna D, Saha A. Therapeutic management of oral lichen planus: A review for the clinicians. World J Dent. 2011;2:249-253.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 13]  [Cited by in F6Publishing: 13]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
82.  Scully C, Beyli M, Ferreiro MC, Ficarra G, Gill Y, Griffiths M, Holmstrup P, Mutlu S, Porter S, Wray D. Update on oral lichen planus: etiopathogenesis and management. Crit Rev Oral Biol Med. 1998;9:86-122.  [PubMed]  [DOI]  [Cited in This Article: ]
83.  Villarroel Dorrego M, Correnti M, Delgado R, Tapia FJ. Oral lichen planus: immunohistology of mucosal lesions. J Oral Pathol Med. 2002;31:410-414.  [PubMed]  [DOI]  [Cited in This Article: ]
84.  Zhao ZZ, Savage NW, Sugerman PB, Walsh LJ. Mast cell/T cell interactions in oral lichen planus. J Oral Pathol Med. 2002;31:189-195.  [PubMed]  [DOI]  [Cited in This Article: ]
85.  Azevedo RS, Romañach MJ, de Almeida OP, Mosqueda-Taylor A, Vega-Memije ME, Carlos-Bregni R, Contreras-Vidaurre E, López-Jornet P, Saura-Inglés A, Jorge J. Lichen sclerosus of the oral mucosa: clinicopathological features of six cases. Int J Oral Maxillofac Surg. 2009;38:855-860.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 22]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
86.  Luo QF, Gan YH. Pingyangmycin with triamcinolone acetonide effective for treatment of lymphatic malformations in the oral and maxillofacial region. J Craniomaxillofac Surg. 2013;41:345-349.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 15]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
87.  Anjomshoaa I, Bulford LA, Dym H, Woo SB. Florid follicular lymphoid hyperplasia of the hard palatal mucosa managed with intralesional steroids: a case report and review of the literature. J Oral Maxillofac Surg. 2013;71:1202-1208.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 9]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
88.  Alajbeg I, Rogulj AA, Hutinec Z. Orofacial granulomatosis treated with intralesional triamcinolone. Acta Dermatovenerol Croat. 2011;19:165-169.  [PubMed]  [DOI]  [Cited in This Article: ]
89.  Martini MZ, Galletta VC, Pereira EM, De Sousa SC, Lemos CA, Migliari DA. Orofacial granulomatosis of the lip: a report of 2 cases with histological and immunohistochemical analyses and intralesional corticotherapy. Minerva Stomatol. 2010;59:579-581.  [PubMed]  [DOI]  [Cited in This Article: ]
90.  van der Waal RI, Schulten EA, van der Meij EH, van de Scheur MR, Starink TM, van der Waal I. Cheilitis granulomatosa: overview of 13 patients with long-term follow-up--results of management. Int J Dermatol. 2002;41:225-229.  [PubMed]  [DOI]  [Cited in This Article: ]
91.  Mignogna MD, Fedele S, Lo Russo L, Adamo D, Satriano RA. Effectiveness of small-volume, intralesional, delayed-release triamcinolone injections in orofacial granulomatosis: a pilot study. J Am Acad Dermatol. 2004;51:265-268.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 17]  [Reference Citation Analysis (0)]
92.  Sakuntabhai A, MacLeod RI, Lawrence CM. Intralesional steroid injection after nerve block anesthesia in the treatment of orofacial granulomatosis. Arch Dermatol. 1993;129:477-480.  [PubMed]  [DOI]  [Cited in This Article: ]
93.  Mignogna MD, Pollio A, Leuci S, Ruoppo E, Fortuna G. Clinical behaviour and long-term therapeutic response in orofacial granulomatosis patients treated with intralesional triamcinolone acetonide injections alone or in combination with topical pimecrolimus 1%. J Oral Pathol Med. 2013;42:73-81.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 14]  [Cited by in F6Publishing: 14]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
94.  El-Hakim M, Chauvin P. Orofacial granulomatosis presenting as persistent lip swelling: review of 6 new cases. J Oral Maxillofac Surg. 2004;62:1114-1117.  [PubMed]  [DOI]  [Cited in This Article: ]
95.  Schwartzman RA, Cidlowski JA. Glucocorticoid-induced apoptosis of lymphoid cells. Int Arch Allergy Immunol. 1994;105:347-354.  [PubMed]  [DOI]  [Cited in This Article: ]
96.  Cardone DA, Tallia AF. Joint and soft tissue injection. Am Fam Physician. 2002;66:283-288.  [PubMed]  [DOI]  [Cited in This Article: ]