J Dent Res 84(4):302-308, 2005
© 2005 International and American Associations for Dental Research
REVIEWS
CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE |
Vesiculo-erosive Oral Mucosal Disease—Management with Topical Corticosteroids: (2) Protocols, Monitoring of Effects and Adverse Reactions, and the Future
M.A. González-Moles1,*, and
C. Scully2
1 Professor of Oral Medicine, Departamento de Medicina Oral, School of Dentistry, Facultad de Odontología, Universidad de Granada, Campus de Cartuja sn, 18071, Granada, Spain; and
2 Dean and Director of Studies and Research, Eastman Dental Institute for Oral Health Care Sciences, University College London, University of London, UK;
* corresponding author, magonzal{at}ugr.es
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ABSTRACT
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Although topical corticosteroids (TCs) are the most widely used drugs in oral medicine, and specifically in the treatment of vesiculo-erosive oral mucosal disease, there are few evidence-based data for the correct use of these drugs. In this review, we outline the most widely used protocols, the most common reasons for treatment failure, and the adverse effects documented in the literature.
KEY WORDS: erosive lesions • oral mucosa • topical corticosteroids
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(I) PARAMETERS USED FOR INITIAL PATIENT ASSESSMENT AND FOLLOW-UP OF TREATMENT EFFICACY
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The clinical judgment of a well-informed professional is crucial in the selection of the appropriate topical corticosteroid (TC) treatment for any particular patient. Some essential clinical parameters must be considered, whose values and evolution reflect the severity of the disease and the success or failure of the treatment.
Pain
Pain is one of the most important parameters and the one of greatest concern to the patient. Thus, most authors use pain as a marker of the severity and evolution of oral erosive lesions (Silverman et al., 1985, 1991; Lozada-Nur et al., 1994a; Robinson et al., 1997; Lo Muzio et al., 2001; González-Moles et al., 2002a,b, 2003). Many authors apply scales to achieve the most objective pain assessment possible. Lozada-Nur et al.(1994a) used a numerical scale: absence of pain (from 0.1 to 0.5), mild pain (from 1.0 to 1.5), moderate pain (from 2.0 to 2.5), and severe pain (3). They categorized the response to treatment as: disappearance of pain (100% recovery), excellent response (75% recovery), good response (50–74% recovery), considerable response (25–49% recovery), poor response (0–24% recovery), and worsening of the pain.
Lo Muzio et al.(2001) used a 10-cm visual analogue scale, where 7 = worse/more pain, 6 = pain similar to that prior to treatment, 5 = marked pain, 4 = moderate pain, 3 = mild pain, 2 = slight pain, 1 = very slight pain, and 0 = absence of pain. Robinson et al.(1997) used a visual analogue scale with scores ranging from 0 = absence of pain to 10 = severe pain.
Silverman et al.(1985) established a disease index (DI) to evaluate the initial presentation and the evolution of pain and other signs of the process throughout the treatment. The DI, a ratio between signs/symptoms at the beginning and end of treatment, was determined by numeric values of 1–4, according to the severity of the disease, assigned before and after the treatment. A ratio greater than 1 was considered beneficial, whereas a ratio below 1 might indicate a worsening of the patient’s condition and call into question the value of the treatment used.
Type of Lesion, Extent, and Location
The presence of ulcers (Silverman et al., 1985; Lozada-Nur et al., 1994a; González-Moles et al., 2002a,b, 2003), erythema (Silverman et al., 1985; Lozada-Nur et al., 1994a), and atrophy of the oral mucosa (Lozada-Nur et al., 1994a; González-Moles et al., 2002a, b, 2003) is also of great importance.
The criteria applied generally relate to the extent of mucosal surface involved. Carbone et al.(1999) and Thongprasom et al.(1992) assessed the severity of lesions and symptoms in patients with lichen planus as: 5 = white striae with erosion > 1 cm; 4 = white striae with erosion < 1 cm; 3 = white striae with atrophy > 1 cm2; 2 = white striae with atrophy < 1 cm; 1 = white striae only; and 0 = no lesion. The intensity of the symptoms was assessed according to a four-point scale: 3 = severe symptoms; 2 = moderate symptoms; 1 = mild symptoms; and 0 = absence of symptoms. Complete resolution was defined as the disappearance of all atrophic-erosive lesions after six months of treatment, with or without persistence of small white striae, and by the presence of only mild clinical symptoms or their complete absence.
Quality of Life
Very few authors have addressed the effect of the disease on the normal daily activities of the patient, i.e., the quality of life (González-Moles et al., 2002a,b, 2003; McGrath et al., 2003). This is a parameter of great interest, since it reflects the level of disability produced by the disease and describes the degree to which treatment enables the patient to return to routine daily activities. Specifically, González-Moles et al. (2002a, b, 2003) considered that the disease hampers the patient’s ability to eat, drink, talk, and relate to others. In their follow-up of these patients, these authors assessed the outcome, depending on the information supplied by the patient, as complete, excellent, good, poor, or failed.
Oral Hygiene
Finally, especially in patients with erosive lesions that affect the gingiva, it is important to assess the level of oral hygiene (Lozada-Nur and Miranda, 1997; González-Moles et al., 2002a,b, 2003). In these patients, the pain and gingival bleeding may often lead to inadequate oral hygiene, resulting in poor plaque control, and exacerbation of erosive and periodontal disease. Furthermore, the gingival inflammation resulting from the lack of oral hygiene can be wrongly interpreted as a lack of response to TC treatment (González-Moles et al., 2003). For these reasons, the patients require clear instruction in oral hygiene and, as soon as their clinical gingival status permits, should undergo an oral prophylaxis that should be repeated every 3–4 months, according to the needs of the patient (Lozada-Nur and Miranda, 1997). In this context, one study (Holmstrup et al., 1990) reported that correct oral hygiene alone can significantly reduce the clinical signs and symptoms of some erosive gingival diseases.
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(II) TREATMENT FAILURES
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Some patients who are candidates for treatment with TCs fail to respond adequately to this therapy. Before accepting that a patient has not responded to therapy with TCs, the clinician should evaluate some correctable causes of failure in the treatment.
Incorrect Diagnosis
One type of failure results from an incorrect diagnosis and thus, an inappropriate indication for TC therapy. This is especially relevant in patients with oral lichen planus (Lozada-Nur and Miranda, 1997), where the possibility of confusion with a lichenoid reaction is always present (Vincent et al., 1990) (Table). A correct diagnosis of the different erosive diseases of the mucosa that require treatment with TCs often requires a biopsy to be taken, and the site for this biopsy must be correctly selected. In fact, there is some debate as to whether the biopsy sample should include both erosive and healthy areas (at the border of the ulcer) for the histopathological study of the epithelial detachment pattern and the location of the blister (Fig. 1
). Peri-lesional tissue is less likely to lead to false-negative results, especially when direct immunofluorescence techniques are used (Chan et al., 2002). In any case, it is inappropriate for the biopsy to include only eroded tissue, where the epithelium cannot be observed (Scully et al., 1999). Furthermore, gingival biopsies can be confusing, because the histopathological data can be affected by a non-specific gingivitis (Vincent et al., 1990; Scully et al., 1999). A refined surgical technique is required, which ensures the integrity of the tissues obtained in the biopsy and prevents artefacts that can complicate the diagnostic process and induce errors.
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Figure 1. Histopathological image of a lesion in a patient with mucous membrane pemphigoid. The biopsy was taken from the border of the erosive lesion, including erosive and non-erosive areas, allowing the pattern of epithelial detachment to be studied (HE x40).
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Choice of a TC of Inadequate Potency
Another correctable cause of treatment failure is the choice of a TC of inadequate potency for the severity of the disease and/or of an inappropriate vehicle (Lozada-Nur and Miranda, 1997). Severe erosive lesions of the oral mucosa should be treated with a high-potency TC (clobetasol 17-propionate) (Lozada-Nur et al., 1991; González-Moles and Bagan-Sebastian, 2000; Lo Muzio et al., 2001; González-Moles et al., 2002a,b, 2003). In lesions with milder symptoms, control can be attempted with drugs of lower potency. Where there are extensive, deep, or numerous erosive lesions, the best approach is to use aqueous solutions of TC, which allows the drug to access all affected areas and guarantees the prescribed contact time (González-Moles et al., 2002a, b). In the opinion of some (González-Moles and Bagan-Sebastian, 2000; González-Moles et al., 2002a,b, 2003), adherent vehicles are indicated for lesions that are single and accessible or scant and small, such as the use of a tray for application of the drug to lesions in the gingiva or palate. The application of gels or other vehicles that contain alcohol should be avoided, because patient compliance is compromised by the pain caused when the vehicle makes contact with the lesion.
Poor Patient Compliance
Some patients develop an aversion to TC therapy because of the granular texture (Lozada-Nur et al., 1991) or taste of the adhesive paste, and the possibility of adding artificial sweeteners to the formulation has been proposed (González-Moles et al., 2002a,b, 2003). Another major cause of treatment failure or exacerbation of the disease (Vincent et al., 1990) stems from the patients’ ignorance of the aims of the treatment. The patients should clearly understand that, in many cases, they are suffering from chronic or recurrent diseases whose natural tendency to resolution is unknown. For this reason, they should be clearly warned that the treatment can have an indeterminate and possibly long duration, and that they should never modify or abandon the treatment without the express recommendation of the specialist.
It is also important to know which clinical signs and symptoms reveal a failure of the treatment, or a partial response, and which do not. The persistence of pain or ulceration or of interference in the patient’s daily activity provides unequivocal data that the response to treatment is inadequate. However, the persistence (Vincent et al., 1990) or worsening of white keratotic striae in patients with lichen planus does not indicate treatment failure, because TCs have little effect on them, and striae may become even more evident during treatment (González-Moles et al., 1996) (Fig. 2). Non-painful atrophy of the oral mucosa should be considered in a similar way. It has been shown (González-Moles et al., 2002a, b, 2003) that atrophy is the clinical sign that responds least to TC treatment, and some authors consider the transformation of a painful erosive lesion into a painless atrophic lesion as a treatment success (González-Moles et al., 2002a,b, 2003).
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Figure 2. Patient with oral lichen planus treated with 0.05% clobetasol propionate. The image shows aggravation of the white striae of lichen planus: (A) before treatment, (B) at 1 month after treatment.
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(III) LOCAL COMPLICATIONS
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The development of candidiasis after topical corticosteroid treatment may be incorrectly considered a treatment failure. The appearance of erythematous candidiasis, and the burning sensation it produces, can mimic the symptoms of erosive or atrophic lesions, and may be interpreted by inexperienced clinicians as a treatment failure. Antifungal drugs can resolve this problem. The most frequent adverse effect produced by the use of oral TCs is oral candidiasis, in either erythematous (Vincent et al., 1990; Lozada-Nur et al., 1991, 1994a, Lozada-Nur et al., b; Lozada-Nur and Miranda, 1997) or pseudomembranous (Lo Muzio et al., 2001) forms. Oral candidiasis appears in up to 25–55% of patients using TCs (Vincent et al., 1990; Lozada-Nur et al., 1991, 1994a; Lo Muzio et al., 2001) and can cause considerable discomfort (a burning sensation in the mouth). It can also be a source of confusion for the clinician. According to some authors (Lozada-Nur et al., 1994a; González-Moles et al., 2002a,b, 2003), the predisposing factors for the development of candidiasis are the potency and concentration of the corticosteroid, the vehicle used, and the healthy candida carrier state. Indeed, healthy carriers have a significantly higher risk of developing oral candidiasis after the use of TCs (Lozada-Nur et al., 1994a). Another important risk factor for the onset of candidiasis is the vehicle used to apply the TC (González-Moles et al., 2002a,b). The use of aqueous mouthrinses, compared with adhesive vehicles, appears to be a greater predisposing factor, presumably because all of the oral mucosa is exposed to the drug’s immunosuppressant effect, and because the drug-lesion contact time is likely to be longer, for the same prescribed time, than that achieved with adherent vehicles (González-Moles et al., 2002a, b, 2003).
The potency and concentration of the drug also influence the likelihood of candidiasis. Oral candidiasis has been reported to appear in 25–55% of patients treated with clobetasol propionate (Lozada-Nur et al., 1991, 1994a; Lo Muzio et al., 2001), with a lower proportion of patients affected at clobetasol concentrations of 0.025% (Lozada-Nur et al., 1991) compared with 0.05% (Lozada-Nur et al., 1994a; Lo Muzio et al., 2001). The use of high concentrations in aqueous vehicles can even lead to the appearance of candidiasis secondary to the use of low-potency corticosteroids; in one study, 39% of patients treated with 0.1–0.2% triamcinolone acetonide for symptomatic oral lichen planus subsequently developed candidiasis (Vincent et al., 1990).
Fortunately, oral candidiasis is easily prevented or treated with antifungals. When a high-potency TC is used in aqueous solution or in a tray, some authors recommend that an antifungal drug be combined with the TC from the start of treatment (González-Moles et al., 2002a, b, 2003). They recommend the addition of 100,000 IU/cc nystatin to the 0.05% clobetasol propionate in aqueous solution or orabase. This procedure is justified by the innocuous nature of nystatin, its low cost, and the high probability that candidiasis will appear in patients treated with this higher concentration of clobetasol propionate. When this approach was applied, excellent outcomes were obtained, with no cases of candidiasis (González-Moles et al., 2002a,b, 2003).
Other minor adverse effects associated with the use of TCs in the oral cavity are stomatopyrosis, hypogeusia, and oral hairy leukoplakia (Lozada-Nur et al., 1991, 1994a).
Likewise, the use of TCs can, in rare cases, be associated with a hypersensitivity reaction in the oral mucosa (Bircher et al., 1996).
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(IV) SYSTEMIC ADVERSE EFFECTS OF TCS
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Until recently, most authors considered that, apart from candidiasis, the adverse effects of oral TCs were infrequent, mild, and easily resolved (Lozada, 1980; Lozada-Nur et al., 1991, 1994a, Lozada-Nur et al., b). This idea probably resulted from the use of moderate- or low-potency TCs (Plemons et al., 1990; Lozada-Nur et al., 1991). However, since clobetasol propionate and other potent topical corticosteroids were introduced, there have been increasing reports of adverse effects secondary to the systemic absorption of these drugs (Walsh et al., 1993; Lozada-Nur and Miranda, 1997; González-Moles et al., 2002a,b).
Data from studies of the use of TCs on skin have clearly showed that the intact skin acts as a barrier against the systemic absorption of TCs (Feldman and Maibach, 1965; Scheuplein et al., 1969; Squier and Johnson, 1975; Addy, 1980; Carr and Wieland, 1996). In contrast, when the surface layers are altered or removed, the systemic absorption increases considerably (Malkinson, 1958). The absorption of TCs is also greater in diseases that alter the skin, such as psoriasis (Schaefer et al., 1977), and in diseases associated with atrophy and ulcerations of the oral mucosa, especially where these are extensive (González-Moles et al., 2002a, b).
The adverse effects that derive from the systemic absorption of corticosteroids include: suppression of the hypothalamus-hypophysis-adrenal (HPA) axis; Cushingoid appearance (moon face); hypertension due to sodium and liquid retention; potassium diuresis; hyperglycemia from glycogen conversion; immunosuppressant effect due to lymphocyte alterations, with the subsequent appearance of opportunistic infectious diseases (oral candidiasis) (Lozada-Nur et al., 1991); mood changes; psychosis; insomnia; capillary fragility with propensity for bruising; gastrointestinal disorders with predisposition for peptic ulcers and bleeding (Ronbeck et al., 1990); weight gain; headaches; and body fat redistribution (buffalo hump). Longer-term effects include cataract formation and osteoporosis from calcium loss (Allenby et al., 1975; Adinoff and Hollister, 1983; Lozada-Nur and Miranda, 1997).
Systemic adverse affects have been documented following exposure to TCs. These include an increase in the plasma cortisol and suppression of the HPA axis (Plemons et al., 1990; Lozada-Nur et al., 1991; Walsh et al., 1993; Lozada-Nur and Miranda, 1997; Lo Muzio et al., 2001; González-Moles et al., 2002a,b), which arises due to a negative feed-back mechanism in which a reduction in the adrenocorticotropic hormone suppresses the natural production of cortisol (Holroyd and Wynn, 1983). In this situation, patients may be unable to respond to periods of stress with an adequate production of cortisol (Selye, 1950; Gilman et al., 1985). Previous studies in skin demonstrated that the adrenal suppression starts to become evident 24 hrs after the onset of treatment with topical steroids (Scoggins, 1962; Gill and Baxter, 1964; Kirketerp, 1964) and is most profound over the first seven days (Walsh et al., 1993). Factors that influence adrenal suppression from oral TCs are the type of corticosteroid, the dose, the vehicle, and the individual susceptibility (Lehner and Lyne, 1969, 1970; Williamson et al., 1980). The degree of HPA axis suppression must be assessed in any TC-treated patient who develops a severe adverse effect, by measuring the urinary free cortisol, plasma cortisol levels, response to the administration of systemic ACTH or plasma cortisol levels during insulin-induced hypoglycemia, or by using the CRH stimulation test, among others (Livanou et al., 1967; Editorial, 1975; Schlaghecke et al., 1992). This is especially important if the patient will undergo surgical or other stress. It is prudent to treat these patients in the same way as any patient with secondary adrenaline insufficiency, advising them to wear a medical alert bracelet or necklace and to carry with them an alert card and, probably, a 1-mL syringe containing 4 mg dexamethasone phosphate. In general, minor dental procedures do not require a preventive supplement of systemic corticosteroids unless complications are predicted (Robinson et al., 1997).
Other documented adverse effects associated with TCs include the development of moon face (Fig. 3) (Lozada-Nur and Miranda, 1997; González-Moles et al., 2002a,b) and hirsutism (Fig. 4) (González-Moles et al., 2002a,b). González-Moles et al. (2002a, b) observed moon face in 9% of a series of patients treated with 0.05% clobetasol propionate in aqueous solution. This complication was defined as mild in all cases and was detected between weeks 4 and 6 of treatment. The problem was completely resolved after week 8 by a reduction in the frequency of mouthrinses. In this same study, hirsutism appeared in two female patients (6% of cases) at weeks 4 and 6 of treatment and was resolved by a cosmetic depilation. The same authors also noted a marked vascular fragility in two patients treated with 0.05% clobetasol propionate (unpublished observation) (Fig. 5). These effects suggest absorption of the steroid through the extensive erosive areas of the oral mucosa (González-Moles et al. 2002a,b).
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Figure 3. (A) Patient who developed moon face during treatment with 0.05% clobetasol propionate in aqueous solution. (B) Complete resolution after reduction of the mouthrinse frequency.
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Figure 4. Patient with hirsutism secondary to the use of 0.05% clobetasol propionate in aqueous solution.
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Figure 5. Hemorrhagic effusions in the oral mucosa (A) of a patient with oral lichen planus treated with 0.05% clobetasol propionate in aqueous solution. The same effusions can also be observed in the skin of another patient (B).
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Various factors can increase the risk of severe adverse effects: the use of high-potency TCs at elevated concentrations, overdosage, the presence of open blood vessels on the ulcerated surfaces, the presence of large erosive and atrophied areas, and the increased pressure of the solution on the ulcerated surface from rinsing (González-Moles et al., 2002a,b). Note should also be taken of reports (Frey FJ et al. 1981; Frey BM et al., 1982; Lozada et al., 1983) that the release rate of endogenous adrenal cortisol may be related to the risk of adverse effects. In fact, some authors (Lozada-Nur et al., 1991) have recommended that endogenous cortisol levels be monitored when TCs are to be used for a long period, so that this risk can be assessed.
The judicious use of TCs diminishes the risk of adverse effects (Carruthers et al., 1975; Westerhof, 1989; Lozada-Nur et al. 1991; Lozada-Nur and Miranda, 1997; Lo Muzio et al., 2001; González-Moles et al., 2003). An unnecessarily high potency or concentration should never be prescribed. Aqueous solutions should be avoided whenever the clinical presentation of the disease permits an alternative vehicle to be used, because they expose the whole mucosa to the corticosteroid. It also appears highly likely, based on the experience with systemic corticosteroids, that the risk of adverse effects diminishes when the applications are reduced to alternate days. Some authors (Lozada-Nur and Miranda, 1997; González-Moles et al., 2002a,b, 2003) recommend changing to alternate-day applications as soon as a substantial improvement of the clinical symptoms is achieved, and progressively reducing the frequency of the therapy for as long as the clinical improvement of the patient is maintained.
Once again, we underline the importance of the clinical training and experience of the specialist and the need for a consensus to be reached on the clinical criteria for the assessment of these patients.
The potential risk of adverse effects means that patients receiving TC treatment must be very closely monitored, especially when high-potency corticosteroids in aqueous solutions are applied three or more times a day for extensive lesions of the oral mucosa (Lozada-Nur et al., 1991; González-Moles et al., 2002a,b, 2003). Patients should be followed up every two weeks during the induction phase and every month after the disease has been controlled and the frequency of applications has begun to be reduced. In maintenance regimens, when the disease is kept under control with applications on alternate days, the follow-up sessions can be six-monthly (González-Moles et al., 2002a, b, 2003). At each follow-up session, the blood pressure, blood glucose levels, and weight are recorded, an examination is performed for the presence of oral candidiasis, moon face, buffalo hump, hirsutism, and hemorrhagic effusions, and the patient is interviewed about any incidence of mood changes or insomnia (Lozada-Nur et al., 1991; González-Moles et al., 2002a, HREF="#GONZALEZ-MOLES-ETAL-2002B">b, 2003).
If adverse effects are present, it is mandatory that the clinician determine the plasma cortisol levels (Pimlott and Walker, 1983) and the degree of HPA axis suppression.
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(V) UNANSWERED QUESTIONS AND NEW RESEARCH DIRECTIONS
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Many issues remain to be addressed regarding the correct use of TCs in oral medicine and regarding newer immunosuppressants such as tacrolimus. One most important question is what should be done with patients after the disease has been controlled by the chronic use of a TC. At present, scientific data are inadequate for us to know how these patients will react if the drug is completely withdrawn (Lozada-Nur et al., 1994a). It is hard to accept that a patient must remain indefinitely under TC treatment after the disease has been perfectly controlled. It therefore seems essential that we investigate how these patients respond after complete withdrawal of the treatment. In this context, it was observed that 65% of patients treated with clobetasol propionate and 55% of patients treated with fluocinonide maintained their clinical improvement 12 months after the cessation of the treatment (Carbone et al., 1999), and that 22% of patients treated for two weeks with fluocinonide remained stable 10 months after stopping the drug (Lozada-Nur and Silverman, 1980). However, lower-potency steroids appear to have a shorter-lived effect after their withdrawal. In one study on lichen planus, where fluocinonide or triamcinolone was used for 24–32 wks, less than 6% of patients were symptom-free 12 months after stopping the drug (Thongprasom et al., 1992). These results appear to indicate that the long-term application of high-potency drugs, especially clobetasol propionate, provides substantially longer disease-free periods after withdrawal of the drug, as well as helping to control the disease (Carbone et al., 1999). Therefore, it seems reasonable to attempt the complete withdrawal of TCs, after a slow reduction of their application, in patients whose disease has been controlled by these drugs. When clobetasol propionate is used, a prolonged period of stability can be expected in a substantial percentage of cases, although both the physician and the patient should be aware of the possibility of a recurrence, which would mean starting the treatment again.
One must also define a correct therapeutic approach to patients who develop adverse effects to the TCs before clinical control of the disease has been achieved. The ethical position is to withdraw the drug, which raises the question of what to do with patients whose well-being is severely compromised by the lesions.
Comparative data are required before we can determine the responses of patients who are changed to a different or less-potent TC or to a vehicle that limits the area of the mucosa exposed to the drug. It is also necessary to establish the parameters that allow us to predict patient populations at risk of developing adverse effects after TC use. Thus, it should be scientifically determined whether the measurement of endogenous cortisol can identify patients who are predisposed to develop adverse effects (Frey FJ et al., 1981).
In conclusion, several questions about the use of TCs in oral medicine remain unanswered and warrant a concerted effort by researchers in this area.
Received April 8, 2004;
Accepted September 3, 2004
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REFERENCES
|
|---|
Addy M (1980). The oral mucosa absorption and tissue distribution of triamcinolone acetonide in the dog studied by autoradiography. Arch Oral Biol 25:809–817.[ISI][Medline]
Adinoff AD, Hollister JR (1983). Steroid-induced fractures and bone loss in patients with asthma. N Engl J Med 309:265–268.[Abstract]
Allenby CF, Main RA, Marsden RA, Sparkes CG (1975). Effect on adrenal function of topically applied clobetasol propionate (Dermobate). Br Med J 4:619–621.
Bircher AJ, Pelloni F, Langauer S, Müller D (1996). Delayed hypersensitivity reactions to corticosteroids applied to mucous membranes. Br J Dermatol 135:310–313.[ISI][Medline]
Carbone M, Conrott D, Carrozzo M, Broccoletti R, Gandolfo S, Scully C (1999). Topical corticosteroids in association with miconazole and chlorhexidine in the long-term management of atrophic-erosive oral lichen planus: a placebo-controlled and comparative study between clobetasol and fluocinonide. Oral Diseases 5:44–49.[ISI][Medline]
Carr RD, Wieland RG (1996). Corticosteroid reservoir in the stratum corneum. Arch Dermatol 94:81–84.
Carruthers JA, August PJ, Staughton RCD (1975). Observations on the systemic effect of topical clobetasol propionate ointment. Br Med J 4:203–204.
Chan LS, Razzaque Ahmed A, Anhalt GJ, Bernauer W, Cooper KD, Elder MJ, et al. (2002). The first international consensus on mucous membrane pemphigoid. Arch Dermatol 138:370–379.[Abstract/Free Full Text]
Editorial (1975). Steroid therapy of the adrenals. Lancet 2:537.[ISI][Medline]
Feldman RJ, Maibach HI (1965). Penetration of C14 hydrocortisone through normal skin: the effect of stripping and occlusion. Arch Dermatol 91:661–666.
Frey BM, Frey FJ, Holford NH, Lozada F, Benet LZ (1982). Prednisolone pharmacodynamics assessed by inhibition of the mixed lymphocyte reaction. Transplantation 33:578–584.[ISI][Medline]
Frey FJ, Amend WJC, Lozada F, Frey BM, Benet LZ (1981). Endogenous hydrocortisone, a possible factor contributing to the genesis of Cushingoid habitus in patients on prednisone. J Clin Endrocinol Metab 5:1076–1080.
Gill KA, Baxter DL (1964). Plasma cortisol suppression by steroid creams. Arch Dermatol 89:734–740.
Gilman AG, Goodman LS, Rall TW, Murad R, editors (1985). The pharmacological basis of therapeutics. New York: Macmillan Publishing Company, pp. 1459–1489.
González-Moles MA, Bagan-Sebastian JV (2000). Alendronate-related oral mucosa ulcerations. J Oral Pathol Med 29:514–518.[ISI][Medline]
González-Moles MA, González-Moles S, Ruiz Ávila I, Esteban F, Galindo Moreno P, Rodríguez Archilla A (1996). Epithelial response to the immunitary aggression in oral lichen planus. Acta Stomatol Belg 3:119–123.
González-Moles MA, Morales-García P, Rodríguez-Archilla A (2002a). Clobetasol mouthwash is effective for severe oral erosive lesions. Dent Abstr 47:268.
González-Moles MA, Morales-García P, Rodríguez-Archilla A, Ruiz-Ávila I, González-Moles S (2002b). Treatment of severe chronic oral erosive lesions with clobetasol propionate in aqueous solution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 93:264–270.[ISI][Medline]
González-Moles MA, Morales-García P, Rodríguez-Archilla A, Ruiz-Ávila I, Mesa-Aguado F, Bascones-Martínez A, et al. (2003). Treatment of severe erosive gingival lesions by topical application of clobetasol propionate in custom trays. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 95:688–692.[ISI][Medline]
Holmstrup P, Schiotz AW, Westergaard J (1990). Effect of dental plaque control on gingival lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 69:585–590.
Holroyd SV, Wynn RL (1983). Clinical pharmacology in dental practice. St. Louis: C.V. Mosby.
Kirketerp M (1964). Systemic effects of local treatment with fluocinolone acetonide applied under a plastic film. Acta Dermato-Venereol 44:54–58.
Lehner T, Lyne C (1969). Adrenal function during topical oral corticosteroid treatment. Br Dent J 4:138–141.
Lehner T, Lyne C (1970). Adrenal function during topical oral treatment with triamcinolone acetonide. Br Dent J 129:164–167.[Medline]
Livanou T, Ferriman D, James VHT (1967). Recovery of hipothalamo-pituitary-adrenal function after corticosteroid therapy. Lancet 2:856–859.[ISI][Medline]
Lo Muzio L, Della Valle A, Mignogna MD, Pannone G, Bucci P, Bucci E (2001). The treatment of oral aphthous ulceration or erosive lichen planus with topical clobetasol propionate in three preparations: a clinical and pilot study on 54 patients. J Oral Pathol Med 30:611–617.[ISI][Medline]
Lozada F (1980). Topically applied fluocinonide in an adhesive base in the treatment of oral vesiculoerosive diseases. Arch Dermatol 116:898–901.[Abstract]
Lozada F, Frey F, Benet L (1983). Prednisolone clearance: a possible determinant for glucocorticoid efficacy in patients with oral vesiculoerosive diseases. J Dent Res 62:575–577.[Abstract/Free Full Text]
Lozada-Nur F, Miranda C (1997). Oral lichen planus: topical and systemic therapy. Sem Cutan Med Surg 16:295–300.
Lozada-Nur F, Silverman S (1980). Topically applied fluocinonide in adhesive base in the treatment of oral vesiculo-erosive diseases. Arch Dermatol 116:898–901.
Lozada-Nur F, Huang MZ, Zhou G (1991). Open preliminary clinical trial of clobetasol propionate ointment in adhesive paste for treatment of chronic oral vesiculoerosive diseases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 71:283–287.
Lozada-Nur F, Miranda C, Maliksi R (1994a). Double-blind clinical trial of 0.05% clobetasol propionate ointment in orabase and 0.05% fluocinonide ointment in orabase in the treatment of patients with oral vesiculoerosive diseases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 77:598–604.
Lozada-Nur F, Robinson J, Regezi JA (1994b). Oral hairy leukoplakia in nonimmunosuppressed patients: report of four cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 78:599–602.
Malkinson FD (1958). Studies on the percutaneous absorption of C14 labelled steroids by the use of a gas flow cell. J Invest Dermatol 31:19–28.[ISI][Medline]
McGrath C, Hegarty AM, Hodgson TA, Porter SR (2003). Patient-centred outcome measures for oral mucosal disease are sensitive to treatment. Int J Oral Maxillofac Surg 32:334–336.[ISI][Medline]
Pimlott SJ, Walker DM (1983). A controlled clinical trial of efficacy of topically applied fluocinonide in the treatment of recurrent aphthous ulceration. Br Dent J 154:174–177.[ISI][Medline]
Plemons JM, Rees TD, Zachariah NY (1990). Absorption of a topical steroid and evaluation of adrenal suppression in patients with erosive lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 69:688–693.
Robinson JC, Lozada-Nur F, Frieden I (1997). Oral pemphigus vulgaris: a review of the literature and a report on the management of 12 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 84:349–355.[ISI][Medline]
Ronbeck BA, Lind PO, Thrane S (1990). Desquamative gingivitis: preliminary observations with tetracycline treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 69:694–697.
Schaefer H, Zesch S, Stuttgen G (1977). Penetration, permeation, and absorption of triamcinolone acetonide in normal and psoriatic skin. Arch Dermatol Res 258:241–249.[ISI][Medline]
Scheuplein RJ, Blank IH, Brauner GJ, MacFarlane DJ (1969). Percutaneous absorption of steroids. J Invest Dermatol 52:63–70.[ISI][Medline]
Schlaghecke R, Kornely E, Santen RT, Ridderskamp P (1992). The effect of longterm glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone. N Engl J Med 326:226.[Abstract]
Scoggins RB (1962). Decrease of urinary corticosteroids following application of fluocinolone acetonide under an occlusive dressing. J Invest Dermatol 42:473–474.
Scully C, Carrozzo M, Gandolfo S, Puiatti P, Monteil R (1999). Update on mucous membrane pemphigoid: a heterogeneous immune-mediated subepithelial blistering entity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88:56–68.[ISI][Medline]
Selye H (1950). Stress and the general adaptation syndrome. Br Med J 4667:1383–1392.
Silverman S, Lozada-Nur F, Migliorati C (1985). Clinical efficacy of prednisone in the treatment of patients with oral inflammatory ulcerative diseases: a study of fifty-five patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 59:360–363.
Silverman S Jr, Gorsky M, Lozada-Nur F, Giannotti K (1991). A prospective study of findings and management in 214 patients with oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 72:665–670.
Squier CA, Johnson NW (1975). Permeability of oral mucosa. Br Med Bull 31:169–175.[Free Full Text]
Thongprasom K, Luang Jarmekorn L, Seretat T, Taweesap W (1992). Relative efficacy of fluocinolone acetonide compared with triamcinolone acetonide in the treatment of oral lichen planus. J Oral Pathol Med 21:456–458.[ISI][Medline]
Vincent SD, Baker KA, Williams TP (1990). Oral lichen planus: the clinical, historical, and therapeutic features of 100 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 70:165–171.
Walsh P, Aeling JL, Huff L, Weston WL (1993). Hypothalamus-pituitary-adrenal axis suppression by superpotent topical steroids. J Am Acad Dermatol 29:501–503.[ISI][Medline]
Westerhof W (1989). Treatment of bullous pemphigoid with topical clobetasol propionate. J Am Acad Dermatol 20:458–461.[ISI][Medline]
Williamson LW, Lorson EL, Sobón DB (1980). Hypothalamic-pituitary-adrenal-suppression after short-term dexamethasone therapy for oral procedures. J Oral Surg 38:20–28.[ISI][Medline]
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