The three major types of OLP are the following:

– reticular form, which is characterized by mucosal keratotic configurations;

– atrophic form, in which the keratoses are combined with red or erythematous changes;

– erosive form, which combines shallow ulcerations with the white and red changes found in the reticular and atrophic forms.⁴

OLP can develop on any mucosal surface, including the lips, but most frequently develops on the buccal mucosa. The lesions often are bilateral and develop on more than one mucosal surface. However, the presentation can be limited to one site. Although OLP seldom goes into remission, progression is infrequent.

OLP is found more frequently in women, and the onset occurs most often after the fourth decade of life. OLP has not been associated with any specific conditions such as diabetes or allergies, the role of stress remains debatable, and a correlation with hepatitis C is being investigated.⁴

Treatment is administered primarily to control symptoms, since there is no established cure. Symptoms can range from none, with the patient being unaware of the presence of intraoral lesions, to extremely painful lesions, which may interfere greatly with eating and thus significantly affect the quality of life. Close follow-up is suggested, not only to monitor medications for discomfort, but because of an established risk, albeit small, of squamous-cell carcinoma developing in areas of OLP.^5,6 Systemic and topical corticosteroids have been the most reproducibly effective medications to control symptoms and signs of the disease.^7–9

The purpose of this study was to evaluate the most recent patient characteristics and profiles, assess the degree of signs and symptoms, and describe treatment responses in patients with OLP who were referred and examined in our oral medicine clinic during a four-year period. Evaluating progression of OLP and longer-term control of signs and symptoms also was an important objective to aid in understanding this disease.

	MATERIALS AND METHODS

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Patients and inclusion criteria. Two hundred twenty-nine patients who had been seen by three of us (N.C.-W., S.S., F.L.-N.) in the oral medicine clinic at the University of California, San Francisco, or UCSF, between September 1996 and August 2000 and who had been diagnosed with OLP were included in this retrospective, descriptive study. The group included patients who were being seen for the first time, as well as patients attending for a follow-up visit. Only patients who had been given a diagnosis of OLP were included. This diagnosis was based on clinical and histopathologic findings.

All of the patients had clinical oral lesions consistent with OLP, and 171 patients (75 percent) had undergone biopsies. Of patients who underwent biopsies, 116 (68 percent) exhibited pathognomonic microscopic changes for OLP and 43 (25 percent) experienced microscopic changes consistent with, but not pathognomonic for, OLP. In the remaining 12 patients (8 percent) whose biopsy specimens showed a nonspecific mucositis, the clinical lesions were unquestionably pathognomonic for OLP. The 54 patients (24 percent) who did not undergo biopsies had oral lesions that demonstrated classical features of OLP (data were missing for another four patients).

Data collection. We designed a data extraction form to collect the following information from patient records: age, sex, medical history, family history and social history, as provided at the first UCSF clinic visit. Information on the initial clinical presentation, treatments rendered, responses to treatment, side effects and changes in clinical presentation over time also was obtained from patient records. We calculated a score for signs and symptoms to quantitate the severity of OLP and to reflect patient responses and progress in an objective manner. A sign-and-symptom score at the initial visit was obtained for all patients in the study (n = 229).

Quantitative scale for signs and symptoms. For patients with intraoral manifestations of more than one type of OLP, we recorded the most severe type present. A score for signs was assigned on the basis of increasing severity, as follows: 1 = reticular, 2 = atrophic and 3 = erosive. In follow-up observations, we assigned a 0 if there was no evidence of OLP. Symptoms were given a score of 0 for asymptomatic patients, 1 for patients with mild symptoms that did not affect quality of life, 2 for moderate symptoms that were bothersome to the patients and needed medical attention, and 3 for severe symptoms that significantly interfered with patients’ quality of life. Therefore, severity scores, which quantified signs plus symptoms, ranged from 0 to 6.

Treatment. Because OLP is not a curable disease, we offered treatment to help control the symptoms, and in the case of erosive OLP, to heal ulcers. The most predictably beneficial medication has been topical corticosteroids, systemic corticosteroids or both because of their profound anti-inflammatory properties (Figures 1 through 3). For topical applications, we used potent corticosteroid forms, which included 0.05 percent fluocinonide gel (Lidex, Medicis), 0.05 percent fluocinonide ointment mixed with equal parts Orabase paste (Colgate-Palmolive Co.), 0.05 percent clobetasol gel (Temovate, GlaxoSmithKline) or 0.05 percent clobetasol ointment mixed with equal parts Orabase paste. Patients were instructed to apply these medications to the lesions one to four times daily.

View larger version (122K): [in this window] [in a new window]   Figure 1. Classical clinical presentation of reticular oral lichen planus in a 42-year-old asymptomatic woman. The lesions occurred bilaterally on the buccal mucosa. The disease was discovered during a routine dental examination, and the disease duration was estimated to be about one year.

View larger version (102K): [in this window] [in a new window]   Figure 2. A. Atrophic form of lichen planus occurring on the gingiva of a 55-year-old man. He had complained of bleeding on brushing and soreness for about five months The patient was in good health otherwise. B. Two months after daily application of a fluocinonide (Lidex, Medicis)–Orabase paste (Colgate-Palmolive Co.), all signs and symptoms were controlled. The daily use of the paste was continued indefinitely to avoid recurrence.

View larger version (115K): [in this window] [in a new window]   Figure 3. A. Painful, erosive oral lichen planus, or OLP, of the left buccal mucosa in an otherwise healthy 60-year-old man. He had no other complaints or findings, and the results of a recent physical examination were within normal limits. The gold crowns were placed after the OLP appeared, because the dentist thought that the lesion might have been due to some old molar amalgam restorations, although this was unlikely. B. Daily doses of prednisone (60 milligrams) for one week led to complete remission. After one month, the disease recurred, but was controlled indefinitely with topical corticosteroid treatment.

Treatment responses. We measured short-term responses to treatment according to the severity score at the end of the first treatment regimen (in most cases, one to two weeks) minus the severity score at the first clinic visit, reflecting possible improvement in symptoms and signs. This response was calculated for patients who required treatment at the first visit and who returned for a one- to two-week follow-up visit (n = 139).

We measured patients’ long-term response according to the severity score at the last follow-up visit minus the severity score at the first clinic visit. This response was determined for patients who had at least one additional follow-up visit after the initial one- to two-week follow-up visit (n = 139) and for patients who did not return for the one- to two-week follow-up visit but who did return at a later time for one or more follow-up visits (n = 24).

Statistical analysis. We calculated summary statistics. The continuous outcomes were determined to be nonnormal according to the Shapiro-Wilk test,¹⁰ so we used nonparametric methods. Wilcoxon signed rank test was used to determine whether there was an overall response to treatment. The Mann-Whitney test was used to compare age at onset between men and women.

	RESULTS

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Patient profile. Table 1 shows the distribution of age and sex for patients with each type of OLP.

Patients reported a mean duration of OLP, as determined by the first recognition of signs, symptoms or both, of 76 months (standard deviation, or SD, = 83.5 months; range, one to 384 months; median, 36 months). Buccal mucosa was the most common site, with most patients exhibiting multiple sites of involvement. Twenty-six patients (11 percent) reported skin involvement. Associated diseases at the initial clinic visit were as follows: diabetes, 10 patients (4.4 percent [two patients type 1, eight patients type 2]); history of hypertension, 43 patients (19 percent); and known immunopathic diseases, eight patients (3.5 percent) (discoid lupus, ulcerative colitis, psoriasis or rheumatoid arthritis). Hepatitis C virus, or HCV, exposure status was known for 31 patients, 14 (45 percent) of whom were HCV-antibody positive.

Ninety-six (42 percent) of the 229 patients reported in their medical history that they had some type of allergy, including sensitivities to foods, drugs, pollen, dust, cats, gold, iodine, latex, perfumes, nickel, plastics, molds, soaps and bleach. However, these could not be verified as true allergies.

Patients reported that they also were taking the following medications: eight patients (3.5 percent), antidiabetic drugs; 42 patients (18 percent), antihypertensive drugs; and 13 patients (6 percent), antidepressants. Sixty women (26 percent) reported that they were receiving hormone replacement therapy.

Seventy patients (31 percent) reported that they had ever smoked or used tobacco in any form. Of these patients, 50 were former smokers and 20 were current smokers at the time of the initial clinic visit.

Family history was known for 80 patients (35 percent); of these, 10 had blood relatives with known OLP, and the rest did not know of any relatives who had OLP.

Symptoms and treatment. Symptoms at the first visit correlated in general with the signs of OLP, with the least severe pain associated with the reticular form and the most severe pain associated with the erosive form (Table 2, page 906).

Treatment was effective in reducing symptoms of oral lichen planus.

We prescribed topical steroids alone to 69 (30 percent) of the 229 patients at the initial examination. The remaining 43 patients (19 percent) were not treated (minimal or no symptoms), but were followed up with periodic oral examinations. The choice of drug depended on the severity of symptoms, concurrence by the patient’s physician and patient preference. Prednisone was used mainly for patients with moderate-to-severe symptoms. In a few cases, prednisone was not used because of medical conditions such as gastric ulcers or because of patients’ reluctance to take systemic corticosteroids.

During the follow-up period (Table 2), 33 percent of patients required short courses of systemic prednisone during periods of flare-ups.

Responses to treatment. Treatment was effective in reducing symptoms of OLP and in healing ulcers and reducing erythema (Tables 2 and 3, page 907).

Of these 163 patients, 85 (52 percent) had the same type of OLP at the last follow-up visit that they had initially, 21 (13 percent) experienced progression to a more severe type and 41 (25 percent) experienced improvement to a less severe type. We defined remission as no evidence of clinical disease and no symptoms. Complete spontaneous remission without treatment occurred in eight (5 percent) of the 163 patients. An additional eight patients (5 percent) had no clinical evidence of disease and no symptoms, but they used topical steroids occasionally.

Side effects of corticosteroid treatment. Among the 117 patients treated with prednisone at the first clinic visit, the most common reported side effects were insomnia (15 patients [13 percent]), mood swings (10 patients [8.5 percent]), fatigue (three patients, [2.5 percent]) and water retention (three patients [2.5 percent]). Other rare side effects (1 percent or less of patients) included headaches, nausea, dizziness, diarrhea, increase in urinary frequency and increased appetite. Patients receiving long-term maintenance therapy with topical steroids reported no systemic side effects. However, oral candidiasis was an occasional complication, with 37 (16 percent) of the 229 patients needing antifungal therapy at some point during the follow-up period.

Oral squamous-cell carcinoma. Four patients (1.7 percent) developed OLP-associated oral squamous-cell carcinoma during the follow-up period at the UCSF oral medicine clinic. The sites of oral carcinoma in these four patients were the lower lip, mandibular retromolar region, gingiva and maxillary tuberosity. In all four cases, the patients had OLP in these oral sites before the development of oral squamous-cell carcinoma. In three patients, this had been confirmed via a biopsy, while one patient (with retromolar squamous-cell carcinoma) received a clinical diagnosis of OLP. The age at diagnosis of OLP in these patients was 61, 30, 38 and 70 years, while the age at diagnosis of squamous-cell carcinoma was 70, 54, 52 and 79 years, respectively.

	DISCUSSION

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 
When interpreting the results, we need to keep in mind that the UCSF oral medicine clinic is a tertiary referral clinic, and the study sample reflects the findings in this selected group of patients. All patients with a diagnosis of OLP who were seen between September 1996 and August 2000 were included in the study, even if their first visit was sometime before this period. (Following accepted ethical guidelines, we did not obtain written consent from patients because this was an observational study that used information from patient records.) This may have led to the selection of severe cases and cases involving progressive disease, since symptomatic patients might be more likely to return for follow-up care. However, the patient characteristics and profile of our study group are similar to those of most reported OLP studies, indicating similarities among patients referred to care centers.¹¹

Treating the symptoms of oral lichen planus is extremely important in addressing quality-of-life issues.

Another consideration is that in this observational study, treatment was based on the severity of the disease, and often more than one treatment modality was used (for example, systemic and topical steroids). Therefore, the efficacy or effectiveness of different treatment modalities cannot be compared, and we have reported treatment responses without stratifying according to the type of therapy.

Because OLP is an incurable disease, treating the symptoms is extremely important in addressing quality-of-life issues. Use of the required potent medications always involves a consideration of drug benefits weighed against potential adverse side effects. Therefore, systemic corticosteroids must be used cautiously and with discretion. However, according to our objective assessments, the combination of systemic and topical corticosteroid regimens over time can offer significant benefits with minimal risk of unpleasant side effects.

The choice of treatment obviously depends on the severity of discomfort, the patient’s overall health and compliance issues. However, in this study, there was no question that an initial short course of systemic corticosteroids had the advantages of predictability, ease of compliance and patient optimism necessary for a positive long-term outlook in regard to living with OLP.

In some patients, occasional short-term daily dosages of systemic prednisone were sufficient for adequate clinical control of symptoms. In other patients, fairly regular topical applications were both necessary and effective for the desired control of discomfort. In any event, corticosteroid use must be tailored to each patient’s needs and responses. This study was not designed to compare the effectiveness of specific prednisone regimens or the type of topical agents. However, based on our clinical experience, administration of one daily dose of systemic corticosteroids in the morning is preferable to divided doses. The schedule for using topical steroids varied among patients since the goal of treatment was acceptable comfort and compliance with application regimens. Preference for gels or pastes varied among patients. Clinical studies have indicated no time-related adverse side effects.^8,9 In addition, drug tolerance and eventual therapeutic ineffectiveness with daily use of topical steroids have not been found.⁸ Although complete remission with or without corticosteroids may occur, it is unlikely.

In some patients, and for reasons we cannot explain, a more long-term use of systemic prednisone was required to control symptoms. Occasionally, this included the need for synergistic use of azathioprine¹² to achieve adequate local immunosuppression. In these instances, patients and their physicians cooperated well in regard to monitoring, which greatly assisted in control of symptoms and avoidance of adverse sequelae. The main complaint of patients receiving prednisone treatment involved insomnia. Medical considerations included calcium supplements to minimize bone loss, potassium for diuresis, glucose control, monitoring blood pressure and ophthalmologic examinations.

In this study, fungal overgrowth of normal oral flora by Candida sp. (most often C. albicans) leading to candidiasis was infrequent, and was associated primarily with the use of topical corticosteroids. This can be explained by the local conversion of epithelial cell glycogen to glucose, which selectively nurtures candidal proliferation. Systemic or topical antifungal medications controlled this occasional problem.

We also describe the long-term outcomes for patients with OLP. It is clear that symptoms persist indefinitely. However, it also was evident that, overall, the judicious use of systemic corticosteroids, topical corticosteroids or both to control lymphocyte-epithelial reactions was more beneficial than detrimental in improving patients’ quality of life, which is often so diminished by the pain and uncertainty associated with OLP. For example, after long-term follow-up of patients with the most severe form of OLP (erosive), the percentage with moderate-to-severe pain was reduced from 90 to 35 percent. It also was apparent that in some patients, the signs and form of OLP were reduced to less-severe types as a result of corticosteroid treatment.

The question of risk of malignant transformation poses a continual diagnostic problem.^5,6,13 The risk is extremely low; therefore, we do not consider OLP to be a premalignant lesion. However, we do recognize that there is a slight increased risk of oral squamous-cell carcinoma in people who have OLP compared with those who do not have OLP. Consequently, periodic follow-up examinations are important.

	CONCLUSION

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION REFERENCES

 
As the results of this study show, the response of patients with OLP to a short course of systemic corticosteroids often is quite remarkable. However, symptoms and signs tend to recur after this treatment. Because long-term corticosteroid use can result in serious side effects, we typically use topical steroids for maintenance therapy. Although not as effective as systemic corticosteroids, topical steroids can result in significant improvement in signs and symptoms when combined with occasional short-course systemic steroid treatment. Clinicians need to monitor patients for side effects, including oral candidiasis, and possible malignant transformation.

View larger version (138K): [in this window] [in a new window]   Dr. Chainani-Wu is a postdoctoral fellow, Department of Stomatology, School of Dentistry, University of California, San Francisco.

View larger version (127K): [in this window] [in a new window]   Dr. Silverman is a professor, Department of Stomatology, School of Dentistry, University of California, San Francisco, P.O. Box 0422, 521 Parnassus Ave., San Francisco, Calif. 94143, e-mail "ssjr{at}itsa.ucsf.edu". Address reprint requests to Dr. Silverman.

View larger version (108K): [in this window] [in a new window]   Dr. Lozada-Nur is a professor of clinical oral medicine, Department of Stomatology, School of Dentistry, University of California, San Francisco.