Applications of corticosteroids in oral diseases – A narrative review

Aishwarya Umesh Lohokare; Shams Ul Nisa; Amit Mhapuskar; Kinjal Shankar Lakhani

doi:10.4103/srmjrds.srmjrds_138_22

REVIEW ARTICLE

Year : 2023 | Volume : 14 | Issue : 1 | Page : 41-47

Applications of corticosteroids in oral diseases – A narrative review

Aishwarya Umesh Lohokare¹, Shams Ul Nisa¹, Amit Mhapuskar¹, Kinjal Shankar Lakhani²
¹ Department of Oral Medicine and Radiology, Bharati Vidyapeeth (Deemed to be University) Dental College and Hospital, Pune, Maharashtra, India
² Department of Oral and Maxillofacial Surgery, Bharati Vidyapeeth (Deemed to be University) Dental College and Hospital, Pune, Maharashtra, India

Date of Submission	19-Nov-2022
Date of Decision	03-Feb-2023
Date of Acceptance	04-Feb-2023
Date of Web Publication	18-Mar-2023

Correspondence Address:
Dr. Aishwarya Umesh Lohokare
Department of Oral Medicine and Radiology, Bharati Vidyapeeth (Deemed To Be University) Dental College and Hospital, Pune, Maharashtra
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/srmjrds.srmjrds_138_22

Abstract

Background: The anti-inflammatory and immunomodulatory properties of corticosteroids aids in the treatment of oral diseases both topically and systemically. Furthermore, its significance in medical emergencies like adrenal crisis and anaphylactic shock cannot be understated. Aim: The purpose of the current review article was to provide and simplify the application of steroids used in oral mucosal diseases. Methods: An online search was conducted using databases such as PubMed, Web of Science, Scopus, and Google Scholar to find articles with the terms “corticosteroids”, “oral medicine”, “recent advancements”, “dental applications”, “oral lichen planus”, “oral submucous fibrosis”, and “oral aphthous ulcers”. Results: A total of 34 articles were included and analyzed for this review. Conclusion: The overall effectiveness of medications depends on knowledge of the illness process, accurate diagnosis, and periodic follow-up.

Keywords: Corticosteroids, oral lichen planus, oral sub mucous fibrosis, recurrent aphthous stomatitis

How to cite this article:
Lohokare AU, Ul Nisa S, Mhapuskar A, Lakhani KS. Applications of corticosteroids in oral diseases – A narrative review. SRM J Res Dent Sci 2023;14:41-7

How to cite this URL:
Lohokare AU, Ul Nisa S, Mhapuskar A, Lakhani KS. Applications of corticosteroids in oral diseases – A narrative review. SRM J Res Dent Sci [serial online] 2023 [cited 2023 Mar 31];14:41-7. Available from: https://www.srmjrds.in/text.asp?2023/14/1/41/372001

Introduction

East Germany was the first to explore the use of testosterone on their Olympic weightlifters in the 1940s. Philip Hench, Edward Kendall, and Tadeus Reichstein received the Nobel Prize in medicine and physiology in 1950 for their “investigations of the hormones of the adrenal cortex.”^[1] Corticosteroids are well known for their actions by inhibiting the inflammatory process and its immunological effects since decades. This nature of steroids regulates the body's defense responses.^[2] Normally, the adrenal gland produces 24–30 mg of cortisol per day and up to 300 mg when under stress. The body's circadian rhythm regulates the release of cortisol, which is also governed by a negative feedback process involving the pituitary, brain, and adrenal glands. Estrogens, androgens, progestogens, glucocorticoids, and mineralocorticoids are the several subtypes of steroid hormones. The two main corticosteroids in humans which are normally secreted are hydrocortisone in a daily dose of 10–20 mg/kg and aldosterone at 0.125 mg/day. The glucocorticoids, androgens, and mineralocorticoids are the three hormone families that the adrenal cortex produces. Corticosteroids have been used both topically and systemically in an array of oral diseases and conditions such as oral submucous fibrosis, vesiculobullous diseases, and recurrent aphthous stomatitis (RAS). Moreover, its importance in medical emergencies such as anaphylactic shock and adrenal crisis cannot be overlooked. No wonder, cortisol (hydrocortisone) is called the “life-protecting hormone” and aldosterone, the “lifesaving hormone.”^[3]

Corticosteroids are the most commonly prescribed drugs in oral medicine. However, emphasis on the exact mechanism of its action should be given for its accurate applications in oral diseases. The glucocorticoid-induced protein expressions can hinder the signaling pathways that were activated by proinflammatory stimuli and consequently blocks the expression of the pro-inflammatory genes. Sound knowledge of these drugs can help in the formulation of newer drugs for treating autoimmune and inflammatory diseases affecting the oral mucosa with minimum side effects. The purpose of the current review article is to provide the mechanism of action, applications, contraindications, and side effects as well as a precise guideline for use of corticosteroids in oral mucosal disorders.

Methods

An online search was conducted using databases such as PubMed, Web of Science, Scopus, and Google Scholar. The keywords used for the article search were corticosteroids, oral medicine, recent advancements, dental applications, oral lichen planus (OLP), oral submucous fibrosis, and oral aphthous ulcers. The search was limited to studies that were published before July 2022.

Results

A total of 34 articles were included and analyzed for this review.

Discussion

Corticosteroids aid to reduce inflammation by inhibiting phospholipase A2 and preventing the synthesis of prostaglandins, leukotrienes, and compounds linked to thromboxane. Corticosteroids can relieve lysozyme membranes, reduce capillary permeability, and stop the synthesis of inflammatory mediators, all of which stop diapedesis. The production of bradykinin, a potent vasodilator, is also decreased.^[4],[5]

Pharmacology of Corticosteroids

Corticosteroids have a broad range of physiologic and metabolic effects, but their properties determine their pharmaceutical effectiveness. White blood cell function is inhibited by glucocorticoids, which also stabilize the lysozyme membrane, prevent activation of plasminogen, and reduce the production of inflammatory mediators including prostaglandins and leukotrienes.^[6]

Mechanism of Action

Anti-inflammatory action and immunosuppressive action

The anti-inflammatory and immunosuppressive effects of corticosteroids are mediated by receptors. The anti-inflammatory effect of corticosteroids results in reduced arterial dilatation and permeability, which in turn leads to a reduction in edema, fibrin deposition, leucocyte movement, and kinin production which plays an important role in the inflammation of the tissue. The glucocorticoid receptor is located intracellularly which on binding, affects gene transcription and causes inhibition of gene expression and translation for inflammatory leukocytes and structural cells. This results in downregulation of inflammatory response by reduction of proinflammatory cytokines, chemokines, cell adhesion molecules, and other enzymes. The anti-inflammatory and immunosuppressive (desired) effects of glucocorticosteroids are usually mediated by the high-potency transrepression mechanism through deacetylation by histone deacetylase 2 whereas; the metabolic and toxic (undesired) effects are usually manifested by the transactivation mechanism through acetylation by HAT (histone acetyltransferase) as shown in [Figure 1]. The immune-suppressive actions of corticosteroids occur at high concentrations which inhibit the production of B cells and T cells resulting in (1) decreased production of lymphokines, (2) even in physiological quantities, T-cell response to autologous tissue is mostly abolished, and (3) reduction of cytolytic activity of lymphocytes against allogeneic cells.^[2]

Figure 1: Mechanism of action. GC: Glucocorticoid, GR: Glucocorticoid receptor, HAT: Histone acetyltransferase, HDAC2: Histone deacetylase 2, NF-kB: Nuclear factor kappa B, CBP/CREBP: Cyclic adenosine monophosphate response element binding protein, GRE: Glucocorticoid response elements, GLIZ: Glucocorticoid-induced leucine zipper, SLPI: Secretory leukoprotease inhibitor, MKP-1: Mitogen-activated protein kinase phosphatase 1

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Application of Corticosteroids in Oral Diseases

Oral submucous fibrosis

Oral submucous fibrosis (OSMF) was defined by Pindborg and Sirsat as “an insidious, chronic disease affecting any part of the oral cavity and sometimes the pharynx. Although occasionally preceded by and/or associated with vesicle formation, it is always associated with juxtaepithelial inflammatory reaction followed by fibroelastic change of the lamina propria, with epithelial atrophy leading to stiffness of the oral mucosa and causing trismus and inability to eat.” Burning, discomfort, and ulceration are examples of clinical signs and symptoms.^[7] [Table 1] provides the functional staging of OSMF and its drug administration.^[7],[8]

Table 1: Stage-wise management of oral sub-mucous fibrosis

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Oral lichen planus

Although the cause of lichen planus, an autoimmune-mediated chronic inflammatory illness, is unknown, investigations have shown that cytotoxic T lymphocytes play a role in both the clinical signs and the disruption of basal keratinocytes. The six clinical kinds of OLP identified by Andreasen are reticular, plaque-like, papular, erosive, bullous, and atrophic, the last two of which are unpleasant and uncomfortable.^[9]

Topical

0.1% triamcinolone acetonide (TA) (with adhesive base) applied twice daily until lesions disappear.^[9]

Systemic corticosteroids for refractory oral lichen planus

Prednisolone: 40–80 mg/kg for 6–7 days tapered by 5 mg/week to avoid withdrawal symptoms.^[6]

Erythema and ulcerations in OLP are managed by systemic administration of 40–80 mg of prednisolone for 5–7 days.

For moderate cases, the oral dose of prednisone given is 10–20 mg/day and severe cases are treated with a dose of 35 mg/day (0.5 mg/kg daily).^[3]

Erythema multiforme

Hypersensitivity reaction manifested as a result of immune response to infections or medications is termed erythema multiforme. It consists of concentric, symmetrically distributed macules, papules, and distinctive “target” lesions with a preference for the distal extremities. Primary treatment is systemic administration of prednisone 0.5–1.0 mg/kg/day or pulse methylprednisolone 1 mg/kg/day for 3 days.^[10] Intravenous pulsed dosage methylprednisolone 3 daily infusions of 20–30 mg/kg up to a maximum of 500 mg administered for a period of 2–3 h. Until lesions heal, aqueous clobetasol propionate mouthwash is used topically.^[3]

Pemphigus

A heterogeneous set of autoimmune chronic blistering skin illnesses known as pemphigus include acantholysis, which is the loss of cell-to-cell adhesion. Pemphigus can affect mucous membranes as well as the skin and is characterized by Immunoglobulin (Ig) G autoantibodies directed against epidermal desmosomes.^[1],[2] [Table 2] shows drug dosage for mild and severe pemphigus cases.

Table 2: Pharmacotherapy of pemphigus (A) mild pemphigus; (B) severe pemphigus^[10]

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Patients with dermal spread: 100–200 mg prednisolone is administered until remission and then the dose can be slowly tapered to 40–50 mg daily.^[11]

Mucous membrane pemphigoid

Mucous membrane pemphigoid is a rare, chronic, autoimmune disease manifested as blisters and scars of oral and ocular mucosa. It is characterized by linear IgG, IgA, or C3 deposition along the epithelial basement membrane zone.

Low-risk patients

Corticosteroids: Prednisone 0.5–1.0 mg/kg/day for 3 days.

Severe disease

Corticosteroids: Prednisone 1–2 mg/kg/day; or dexamethasone 100 mg/day for 3 days (pulse therapy); or intravenous pulse therapy at 0.5–1.0 g for 3 days. Multiple oral lesions are treated with prednisone of 1–2 mg/kg/day and cyclophosphamide 0.5–2 mg/kg/day, azathioprine 1–2 mg/kg/day, or mycophenolate mofetil 2–2.5 g/day.^[12],[13]

Bullous pemphigoid

“Bullous pemphigoid” is a diverse collection of autoimmune, chronic, subepithelial blistering illnesses that mostly affect the mucous membranes and occasionally the skin. Immunofluorescence shows linear deposits of IgG, IgA, or C3 along the epithelial basement membrane zone. 15–20 mg/day or 0.3 mg/kg/day for 3–4 days of prednisolone or Clobetasol propionate cream (10–30 g daily) is given in mild cases of the disease until the lesion heals. A moderate form of disease is managed by 40 mg/day or 0.6 mg/kg/day of prednisolone for 3–4 days or a combination therapy of clobetasol propionate cream (10–30 g daily) and dapsone (1.0–1.5 mg/kg/day) is used until lesion heals. A severe form of disease is treated by 50–70 mg or 0.75–1 mg/kg/day of prednisolone or Oral prednisolone w (0.5 mg/kg/day) supplemented for 2–4 days.^[12] The resistant lesions are managed by intralesional therapy of injection of TA 3–10 mg/ml bi-weekly for 2–3 weeks.^[13]

Systemic lupus erythematosus

There are two types of lupus erythematosus: Systemic (acute) and discoid (chronic). Discoid lupus erythematosus is a chronic inherited illness characterized by blisters, inflammation, and scarring that favors the face, ears, and scalp. Systemic lupus erythematosus (SLE) is a long-term condition with various symptoms and an often waxing and waning history. It may be necessary to administer 10–20 mg of systemic prednisone daily or on alternate days.^[4] The main medications used to treat SLE are potent topical steroids and antimalarials.^[14] [Shown in [Table 3]].

Table 3: Pharmacotherapy in treatment of systemic lupus erythematosus

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Bell's palsy

Bell's palsy, is an acute facial nerve condition that is characterized by pain that initiates in the mastoid area causing full or partial paralysis of movement on the unilateral side of the face. This self-limiting, nonfatal illness has an abrupt start and is caused by nonsuppurative facial nerve inflammation within the stylomastoid foramen. Prednisone is recommended for immunocompetent individuals at a tapering dose of 1 mg/kg/day (maximum 60–80 mg) in the 1^st week.

Proposed guidelines

Signs are seen in 3 weeks of onset: Prednisone 1 mg/kg/d, with a progressive taper.^[3]

Ramsay hunt syndrome

Ramsay Hunt syndrome is caused by the Varicella zoster virus (VZV), which is responsible for about 12% of facial nerve palsies. VZV is also the source of “shingles,” which usually manifests as crusted skin ulcerations with the typical painful dermatomal distribution of vesicles. The syndrome may be characterized by otalgia, cutaneous vesicles, and ageusia in the same side of the anterior tongue along with facial palsy. Steroids and possibly antiviral treatment are used to treat these situations. Prednisone 60–80 mg daily for the first 5 days of treatment, followed by a 5-day taper.^[15],[16]

Post herpetic neuralgia

Acute Herpes Zoster patients who experience Post Herpetic Neuralgia (PHN) endure persistent neuropathic pain in 25% of cases, which is a significant clinical issue. This symptom denotes nerve injury in the area. Persistent pain even on the healing of blisters. Prednisone 40 mg once a day for 10 days, followed by a gradual reduction over the next 3 weeks, is an effective way to lower the incidence of PHN.^[17]

Recurrent aphthous ulcers

The most prevalent oral ulceration in the general population is RAS, popularly known as “canker” sores. Most ulcers affect nonkeratinized mucosa and are often tiny ovoid in shape with a yellowish pseudo-membrane and surrounded by a red halo. Ulcers typically cure between 7 and 14 days. According to size and quantity, RAS is categorised into three categories: minor, large, and herpetic form ulcers.

Local pharmacological treatments

Topical corticosteroids- TA cream 0.05%–0.5% 3–10 times a day or Clobetasol propionate cream 0.025%.^[30] The two medications used for local oral administration most frequently in RAS are TA (in an adhesive paste containing 0. 1% of the steroid) and hydrocortisone hemi succinate (as pellets of 2.5 mg). Fluocinonide, betamethasone, or clobetasol are examples of high-potency topical steroids that can be applied directly to lesions to speed healing and minimize lesion size. Two out of three times a day, after food.^[18]

Systemic pharmacological treatments

Corticosteroids (25 mg/day of oral prednisone as the initial dose, followed by 2 months of gradual dose decrease).^[18] Levamisole is an antihelminthic medication that has been used in clinical studies to treat aphthous ulcers. It acts as an immunosuppressant at higher dosages and an immune enhancer at lower dosages.^[11] The daily dosage is 150 mg, with or without the use of steroids (15 mg prednisone).^[12] It acts by reinstating the immunological function of T cells, B lymphocytes, monocytes, and macrophages.^[14],[29]

Central giant cell granuloma

An intraosseous benign lesion of the jaw is called a central giant cell granuloma, Children and young adults seem to be the main populations affected. It is an asymptomatic lesion, and on routine radiographic inspection, it frequently becomes visible. Both nonaggressive and aggressive giant cell lesions have been observed, with recurrence being noted in cases of aggressive lesions. On radiographs, central giant cell lesions appear as monocular or multilocular radiolucent lesions.

TA may also be given topically because it inhibits the lesion's angiogenic potential. The regimen, which was first published in 1988, calls for injecting 2% lidocaine, 1: 100,000 epinephrine, and triamcinolone (KenalogR) into a lesion that measures 1 cm in diameter, repeating this 6 times at weekly intervals.^{[19],[20],[24]}

In order to treat giant cell lesions in bone, Dr. Francies V. Howell of La Jolla, California, came up with an alternative nonsurgical approach. Following was his protocol:

A biopsy is performed for histological diagnosis
Intralesional therapy of a solution containing an equal amount of a local anesthetic (Marcaine 0.5% with epinephrine 1: 200,000) and triamcinolone (10 mg/ml) (Kenalog-10). The suggested dosage of this mixture was 2 ml per estimated 2 cm of radiolucency (Howell FV: personal communication). The injections were given on a weekly basis for 6 weeks.^[32]

Melkersson rosenthal syndrome

A clinical illness known as Melkersson–Rosenthal syndrome is characterized by the triad of orofacial edema, facial nerve palsy, and tongue furrowing. Local edema may be treated for 2–4 weeks with intralesional TA (1–1.5 mL of 10–20 mg/mL solution) and lignocaine.^[31]

Prednisolone is often given in doses of 1–1.5 mg/kg/day. Depending on the severity of the illness and the patient's response, a tapering dose is started over a period of 3–6 weeks.^[17]

Temporomandibular disorders

Intra-articular corticosteroids have been shown to be effective in lowering Temporomandibular disorders-related pain, edema, and dysfunction. Intra-articular methylprednisolone diluted with lidocaine may significantly reduce joint pain and other symptoms for 4–6 weeks, according to a controlled trial on Temporomandibular Joint arthritis patients.^[17]

Hemangiomas

Vascular abnormalities called hemangiomas can develop at birth. In a ratio of 2:1, females are more likely to have them. Before the first decade of life, more than half of the cases are clinically noted. They manifest on the skin as macular spots that range in color from red to pink to blue and occasionally as raised lesions with bruit. They seem to reach puberty and stop developing after that.^[33] In 1993, Takato, et al. reported a case of a baby with a massive parotid hemangioma linked to Kasabach Merritt syndrome. Daily prednisone medication (8 mg/d) started when the infant was 44 days old. The left parotid was simultaneously exposed to daily doses of 9 MeV radiation totaling 15 Gy (11 fractions). At 60 days of age, irradiation was stopped. Following up after 8 years revealed that the remnant hemangioma had disappeared without any facial nerve damage or asymmetry. Symmetrical parotid glands were visible on a computed tomography scan. This child received radiotherapy (15 Gy) along with prednisone (2 mg/kg/d).^[34]

Contraindications of Corticosteroids

Corticosteroids are contraindicated in diabetes, osteoporosis, eye disorders, fungal infections, pregnancy, immune deficiency, and skin infections.^[21],[22]

Side Effects of Corticosteroids

Topical corticosteroids

The most common include atrophy, striae, rosacea, perioral dermatitis, acne, and purpura. Hypertrichosis, pigment alteration, delayed wound healing, and exacerbation of skin infections are less frequent.^[23]

Systemic corticosteroids

Hypothalamic–pituitary–adrenal axis suppression, withdrawal symptoms that are suppression of the hypothalamic–pituitary–adrenal axis may persist for as long as 9–12 months following steroid withdrawal if steroid doses are administered in the supraphysiological range for longer than 2 weeks. In general, higher doses, longer duration of usage, and frequent daily administration are all correlated with the severity of pituitary Adrenocorticotropic hormone (ACTH) suppression hence gradual tapering of the dose is recommended. The side effects from corticosteroid therapy include proximal muscle weakness, osteopenia, the unmasking of latent diabetes mellitus, sodium retention and/or elevation of mean arterial blood pressure, adverse psychiatric reactions, development of glaucoma, reactivation of latent infections, weight gain, osteoporosis, and insomnia.^{[25],[26],[27],[28]}

Conclusion

Corticosteroids have their optimum use in the treatment of both acute and chronic illnesses. Aldosterone is known as the “life-saving hormone,” whereas corticosteroids are stated to as the “life-protecting hormone” due to their extensive use. Thus, it may be inferred that corticosteroids are crucial in the management of lesions affecting the oral and dermatological sites along with their importance in medical emergencies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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