original papers Adv Clin Exp Med 2011, 20, 4, 495 501 ISSN 1230-025X Copyright by Wroclaw Medical University Małgorzata Radwan-Oczko, Zbigniew Kozłowski Oral Lichen Planus Lesion Assessment in Relation to General Health and Oral Symptoms Ocena kliniczna zmian liszaja płaskiego błony śluzowej jamy ustnej w powiązaniu z ogólnym stanem zdrowia i objawami w jamie ustnej Department of Oral Pathology, Chair of Periodontology, Wroclaw Medical University, Poland Abstract Background. Lichen planus is a chronic inflammatory mucocutaneous disease with an unclear pathogenesis. Oral lesions may occur anywhere and in various clinical forms white, red or red-white, alone or coexistent with skin lesions. Objectives. This study was aimed to assess the clinical presentation of oral lichen planus lesions in relation to general health and oral symptoms. Material and Methods. The authors investigated a group of patients with oral lichen planus lesions consisting of 30 women and 10 men between the ages of 25 80 years. Results. White oral lichen planus lesions were found in 33 patients and red lichen lesions in 11 patients. The range of duration of the pathology was from 1 to 144 months. The most frequently present form was the reticular oral lichen planus form. Buccal mucosa was the most common site of involvement. Candida infection was confirmed in 10 patients. Systemic diseases were reported in 16 patients. As is characteristic for lichen planus, concurrent skin lesions were detected in 5 subjects and nail lesions in 3 patients. In no cases was there malignant transformation. Conclusions. OLP is a chronic disease with broad clinical presentations and symptoms. It is said that, after a long time, some lesions may undergo malignant transformation. All irritating factors should be avoided. Patients should be examined periodically. It is important to pay special attention in erosive, bullous or atrophic forms (Adv Clin Exp Med 2011, 20, 4, 495 501). Key words: oral lichen planus, lichen planus skin lesions, general health. Streszczenie Wprowadzenie. Liszaj płaski jest chorobą przewlekłą skóry i błon śluzowych o niejasnej patogenezie. Zmiany na błonie śluzowej w jamie ustnej mogą występować wszędzie i w wielu postaciach klinicznych jako zmiany białe, czerwone lub biało czerwone. Mogą pojawiać się tylko w jamie ustnej lub towarzyszyć zmianom skórnym. Cel pracy. Ocena kliniczna obecności zmian liszaja płaskiego błony śluzowej jamy ustnej w powiązaniu z ogólnym stanem zdrowia badanych i objawami w jamie ustnej. Materiał i metody. Zbadano grupę 30 kobiet i 10 mężczyzn w wieku 25 80 lat ze zmianami liszaja płaskiego błony śluzowej jamy ustnej. Wyniki. Zmiany białe liszaja płaskiego stwierdzono u 33, a czerwone u 11 badanych. Czas trwania choroby wynosił 1 144 miesięcy. Najczęściej występowała postać siateczkowa liszaja płaskiego. Rejonem najczęstszej obecności zmian była błona śluzowa policzków. Infekcję Candida potwierdzono u 10 pacjentów. U 16 badanych występowały choroby ogólnoustrojowe. Typowe dla liszaja płaskiego współistniejące zmiany skórne stwierdzono u 5 pacjentów, a na płytkach paznokciowych zaobserwowano je u 3 osób. U żadnego z pacjentów nie stwierdzono transformacji nowotworowej w obrębie zmian. Wnioski. Ustna postać liszaja płaskiego jest chorobą o przewlekłym przebiegu z różnym obrazem klinicznym zmian. Towarzyszą jej również różne objawy w jamie ustnej. Uważa się, że po dłuższym czasie występowania patologii niektóre zmiany mogą przekształcić się w nowotwór. Pacjenci powinni unikać wszystkich potencjalnych czynników miejscowo drażniących i pozostawać pod stałą okresową kontrolą. Wzmożoną uwagą lekarza dentysty powinni być objęci chorzy ze zmianami postaci nadżerkowej, pęcherzowej i zanikowej liszaja płaskiego (Adv Clin Exp Med 2011, 20, 4, 495 501). Słowa kluczowe: liszaj płaski błony śluzowej jamy ustnej, zmiany skórne liszaja płaskiego, choroby układowe.
496 M. Radwan-Oczko, Z. Kozłowski Lichen planus is a chronic mucocutaneous inflammatory disease, the etiopathogenesis of which remains obscure. It may affect the skin, mucous membranes, genitalia and nails. The prevalence of lichen planus varies according to different studies but is rather rare, from 0.9% to no more than 2% of the adult general population [1]. Oral lichen planus (OLP) involves the mucous membrane and this may accompany skin lesions or may be the only manifestation of the disease. On the basis of numerous studies, various hypotheses have been proposed for the pathogenesis of lichen planus. Immunologic reactions (e.g. cell-mediated immune response, autoimmune response, humoral immunity), and infectious agents, genetic predisposition, trauma and also psychological status in relation to stress have been suggested as etiological factors. Usually it is more common among women and middle-aged people, although in some cases it can also appear in young and elderly patients. It can affect from 0.1% to 4% of the population [2 5]. Oral lichen planus can occur anywhere in the oral cavity. Usually it appears as bilateral or multiple more-or-less symmetrical lesions situated mainly on the posterior buccal mucosa. Besides this location, the sites affected in order of frequency are the gums, lips, tongue, floor of the mouth and palate, though these lesions have been described as uncommon. Clinically, OLP has many different presentations. The reticular, papular and plaquelike forms are white keratotic lesions, usually painless. Red-white, erosive, atrophic and bullous forms are associated with a burning sensation and, especially in combination with irritating and spicy food, may cause severe pain. The most common of oral lichen planus is the reticular form, which is present as a lacelike network of slightly raised gray to white lines, most often on the buccal mucosa or rarely on the gums or the lips (Fig. 1). The papular form is uncommon. It presents small white pinpoint papules and can be overlooked during a quick, non-specific oral examination. Plaque-like OLP occurs as homogenous multifocal white patches and may resemble homogenous leukoplakia. The dorsum of the tongue is the typical site for this lesion (Fig. 2). In the atrophic form, redness of the oral mucosa is diffused with typical white striae around the lesion (Fig. 3). When the attached gums are involved, it can also manifest with erythematous gingival desquamation (Fig. 4). In the erosive form of oral lichen planus, the well-defined erosions or ulcers Fig. 2. Plaque-like OLP dorsum of the tongue Ryc. 2. Postać płytkowa liszaja płaskiego na powierzchni grzbietowej języka Fig. 1. OLP reticular form buccal mucosa Ryc. 1. Postać siateczkowa liszaja płaskiego na błonie śluzowej policzka Fig. 3. OLP atrophic form buccal mucosa Ryc. 3. Postać atroficzna liszaja płaskiego błony śluzowej policzka
Lichen Planus Oral Lesions and General Health 497 Fig. 4. Desquamative gingivitis Ryc. 4. Złuszczające zapalenie dziąseł are covered with a pseudo-membrane or fibrinous plaque. When they are disturbed or burst, the lesions are extremely painful and difficult to treat. The bullous form is rarer than the other forms of OLP. Small bullae or vesicles are present, that tend to rapture easily and leave an ulcerated and painful surface. OLP lesions may be infected by different Candida species with higher frequency than in healthy oral mucosa [4, 6 8]. In connection with the different clinical forms, there is also different microscopic appearance. It is possible to see parakeratosis, acanthosis, degenerating basal keratinocytes that form colloid bodies and epithelial basement membrane changes. Oral lichen planus lesions and oral lichenoid lesions (OLL) may also often be a diagnostic dilemma for both dental clinicians and pathologists. OLL has an identifiable etiology but may, clinically and histologically, resemble OLP lesions. OLL may present a more diffuse lymphocytic infiltrate and may contain eosinophils and plasma cells, and more colloid bodies than in real OLP. When it occurs in combination with dental materials (including amalgams, composite resins and cobalt) it is described as a contact lichenoid reaction. Apart from those oral lichenoid reactions induced by drugs, have been reported with non-steroidal antiinflammatory agents, angiotensin-converting enzyme inhibitors and beta-blockers [6, 9]. OLP is considered a premalignant condition although there is considerable controversy regarding its malignant transformation. Some authors have put forth a theory that true OLP is a benign disorder and that many of the reported cases when OLP developed into oral cancer are in fact not OLP, but rather dysplastic lesions related with lichenoid lesions. On the other hand, it has been said that patients with chronically inflamed oral mucosa may be at increased risk for malignant transformation [6, 8, 10 12]. Because of such a variety of OLP clinical presentation, the differential diagnosis of OLP includes: chronic candidiasis, mucous membrane pemphigoid, pemphigus vulgaris, oral lichenoid lesions (OLL), lichenoid drug reactions, contact lichenoid reactions, leukoplakia, graft-versus-host disease (GVHD) and erythema multiforme [8]. A wide spectrum of topical and systemic therapies has been used in the treatment of OLP. The standard treatment is carried out in symptomatic lesions and consists of the topical use of antifungal ointments, corticosteroids, immunosuppressive agents calcineurin inhibitors and retinoids, depending on the severity of the disease and the patient s medical history [8, 10]. Material and Methods An observational retrospective and questionnaire study was made on patients of the Department of Periodontology and Oral Pathology, Wrocław Medical University, Poland. The study group consisted of 40 subjects, at ages ranging from 25 to 80 years. Data was collected on parameters such as patient age, gender, the clinical form of the OLP and its location. The questionnaire included information about the duration of disease, who found the lesions, and the patients oral complaints, general health and drugs applied. The results obtained were analyzed using Pearson s correlation and chi-square test with Yates correction. The level of significance was set to 0.05. Results The mean age of the 40 investigated OLP patients was 55.85 ± 14.36 years. There were 30 women and 10 men. In 14 cases, the presence of the lesions was discovered by the patients, because of unspecified discomfort and/or sensitivity, burning sensations and pain. In most cases (26) the patients were unaware of the presence of the lesions which were found by the dentist during a routine oral examination. As to the clinical presentation, 33 patients showed lesions corresponding to the white oral lichen form, which included reticular (29 subjects) and plaque (4 subjects) forms. Red lichen lesions, which included atrophic-erosive forms, were present in 11 cases and 6 of them were documented as desquamative gingivitis. In 4 patients, there were 2 different forms of OLP, so there were 44 lesions present (Table 1). The range of duration of the pathology was from 1 month to 144 months (mean duration 25.71 ± 39.65 months).
498 M. Radwan-Oczko, Z. Kozłowski Table 1. Characteristics of investigated features Tabela 1. Charakterystyka badanych cech Number (Liczba) N = 40 Women (Kobiety) N = 30 Men (Mężczyźni) N = 10 n % n % n % Discovered by the patient (Wykrył pacjent) 14 35 12 30 2 5 Found by the dentist (Wykrył lekarz) 26 65 18 45 8 20 OLP (Liszaj błony śluzowej jamy ustnej) 40 100 30 75 10 25 Reticular form (Postać siateczkowa) 29 72.5 20 50 9 22.5 Atrophic/erosive form (Postać atroficzno-nadżerkowa) 11 27.5 9 22.5 2 5 Plaque-like form (Postać tarczkowa) 4 10 3 7.5 1 2.5 A histological examination was performed in only 5 questionable cases and 3 of them were located on the floor of the mouth. In the group investigated, the OLP lesions were present in typical sites. Buccal mucosa was the most common site of involvement in 34 patients. In order of frequency, gingival mucosa in 17, tongue in 10 and both lips and the floor of the mouth were affected in 3 patients (Table 2). There were no observed lesions on the palate mucosa. No statistical correlation was found between the gender of the patients and the sites and forms of lichen planus lesions. When considering the age (Table 3), most patients with OLP, 50%, were at the age of 51 60 years. Oral symptoms and complaints related to dryness were found in two cases. A metallic taste was noted by 10 patients, and they all had amalgam fillings or metal prosthetic crowns, but without direct contact with the lesions. Candida infection was confirmed by evaluation smear for Candida in 10 cases. 3 of the patients were smokers. Systemic diseases were reported in 16 patients. These were hypertension in 13 and diabetes in 3 subjects. 5 patients had concurrent skin lesions, in 1 the genitalia were involved. Another 3 patients showed pterygium formation of the nails (Fig. 5). Patients were not able to give information which lesions, mucous or skin, developed first. There were positive correlations between OLP and age, hypertension, duration of hypertension and Candida infection (Table 4). In the treatment, antifungal ointments, topical steroids, immunosuppressive agents and vitamin A, and Solcoseryl dental adhesive paste and linseed were used. Discussion Oral lichen planus affects the oral mucous membrane with a variety of clinical presentations Table 2. Sites and the incidence of OLP lesions Tabela 2. Miejsca obecności i częstość zmian liszaja płaskiego Site (Miejsce) Number (Liczba) N = 40 Women (Kobiety) N = 30 Men (Mężczyźni) N = 10 n % n n Buccal mucosa (Błona śluzowa policzka) Gingival mucosa (Błona śluzowa dziąsła) Lingual mucosa (Błona śluzowa języka) Floor of the mouth (Błona śluzowa dna jamy ustnej) 34 85 28 6 17 42.5 15 2 10 25 7 3 3 7.5 1 2 Lips (Błona śluzowa warg) 3 7.5 2 1
Lichen Planus Oral Lesions and General Health 499 Table 3. The incidence of OLP lesions according to age Tabela 3. Częstość zmian liszaja płaskiego w odniesieniu do wieku Age years (Wiek lata) Number of patients (Liczba pacjentów) 20 30 3 31 40 2 41 50 5 51 60 20 61 70 5 71 80 5 Fig. 5. Nail lesions related to lichen planus Ryc. 5. Zmiany na płytkach paznokci w przebiegu liszaja płaskiego Table 4. The correlations between OLP lesions and evaluated features Tabela 4. Korelacje między zmianami liszaja płaskiego błony śluzowej jamy ustnej a badanymi cechami OLP (Liszaj błony śluzowej jamy ustnej) Reticular form (Postać siateczkowa) Atrophic/erosive form (Postać atroficzna/ erozyjna) Feature (Cecha) r p = r p = r p = Age (Wiek) 0.4995 0.001 0.4951 0.001 0.5100 0.001 Hypertension (Nadciśnienie) Duration of hypertension (Czas trwania nadciśnienia) Candida overgrowth/ Infection (Wzrost/infekcja Candida) 0.9983 0.00 0.9990 0.00 0.9991 0.00 0.9444 0.000 0.9419 0.000 0.9452 0.000 0.9983 0.00 0.9990 0.00 0.9993 0,00 r = the correlation coefficient. p = level of statistical significance. including white and red-white lesions. In our study, the incidence of the type of the OLP lesions and involved sites were consistent with previous studies. The most common was the reticular form, present in 72.5% of investigated patients diagnosed with OLP. Atrophic/erosive forms were present in 11 patients. In 6 cases, the atrophic/ erosive form involved attached gums, with symptoms of chronic desquamative gingivitis (DG). Desquamative gingivitis is a descriptive term for inflamed, peeling gums. It is a clinical nonpathognomonic term rather than a distinct diagnosis and may be present as an oral clinical symptom of various systemic mucocutaneous diseases including lichen planus. The patients experience discomfort and intense pain, sensitivity to spicy food and irritation from toothbrushing or rinsing solutions (Fig. 3). This clinical state may be complicated and worsened by inflammation related to the presence of bacterial plaque, because of a lack of proper hygiene. It should be underlined that, other than in OLP, desquamative gingivitis may also be a symptom of pemphigus vulgaris and pemphigoid and chronic ulcerative stomatitis (CUS) [7]. In investigated group, the authors did not find a lot of coexistent general symptoms or disorders. Only three subjects had changes of the nails in a clinical presentation of pterygium formation and four patients showed characteristic skin lichen lesions. In the dental literature the skin involvement ranges from 6% to 44% of the patients with OLP. Conversely, about 70% of patients with lichen planus skin lesions present oral lesions [1]. Although present in only 13 cases (32.5%), in this study we have found a correlation between OLP lesions and hypertension and the duration of hypertension treatment.
500 M. Radwan-Oczko, Z. Kozłowski 3 patients suffered from diabetes type II, noninsulin-dependent, and 2 of them complained of a dry mouth. It has been shown that in some patients, a dry mouth appears to be linked to OLP lesions, although a real association cannot be determined. Research carried out by Colquhoun and Ferguson revealed Sjögren syndrome and related xerostomia in 10.4% of patients with OLP [13]. The results obtained in other investigations showed the presence of Candida species in about 37% of oral LP lesions [10]. The study confirmed this relationship in 25% of the patients investigated. Candida overgrowth and infection exacerbates OLP symptoms, therefore antifungal treatment can improve the clinical state and can also reduce the potential of Candida to produce carcinogens such as N-nitrosobenzylmethylamine. Topical steroids are used to limit pain and inflammation. The immunosuppressive drug Tacrolimus ointment 0.1% is useful, effective, safe and well tolerated in atrophic, erosive-bullous OLP lesions. However it was shown that lesions may relapse after discontinuation of the treatment. Retinoids such as vitamin A gel 0.1 or Isotretinoin can eliminate or reduce white, reticular, plaque-like forms, but lesions also relapsed after some weeks when treatment was discontinued [10, 14, 15]. Almost all OLP patients are subjected to topical treatment for long periods with some breaks of time. Immunosuppressive drugs are thought to be able to trigger malignant transformation. However, this hypothesis is still not clear. On the other hand erosive and atrophic forms in particular undergo malignant transformation [8, 10]. In the investigated group, the average duration of oral lesions amounted to more than 2 years, and the longest was 12 years. Despite this long time, there was no malignant transformation. The exacerbation or flare-ups of OLP lesions may be triggered by spicy and/or acidic foods, mechanical irritations and by stress. Therefore, patients should be informed and instructed how to avoid factors that trigger the disease and how to keep good oral hygiene, which is necessary. Regular and thorough examination of the oral cavity and general symptoms is of high importance. Even patients without any symptoms, who are not given treatment, require regular visits for review, sooner if they get any symptoms. It would seem essential to inform the patients with OLP of the possible link between the lesions and development of oral cancer. References [1] Lozada-Nur F, Miranda C: Oral lichen planus: epidemiology, clinical characteristics and associated diseases. Seminars in Cutaneus Med and Surg 1997, 16, 273 277. [2] Roopashree MR, Gondhalekar RV, Shashikanth MC, George J, Thippeswamy SH: Pathogenesis of oral lichen planus a review. J Oral Pathol Med 2010, 39, 729 734. 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Lichen Planus Oral Lesions and General Health 501 [14] Gorouhi F, Solhpour A, Beitollahi JM, Afshar S, Davari P, Hashemi P, Kashani MN, Firooz A: Randomized trials of pimecrolimus cream versus triamcinolone acetonide paste in the treatment of oral lichen planus. J Am Acad Dermatol 2007, 57, 806 813. [15] Masaki M, Sato T, Sugawara Y, Sasano T, Takahashi N: Detection and identification of non-candida albicans species in human oral lichen planus. Microbiol Immunol 2011, 55, 66 70. Address for correspondence: Małgorzata Radwan-Oczko Department of Oral Pathology Chair of Periodontology Wroclaw Medical University Krakowska 26 50-425 Wrocław Poland Tel.: +48 71 784 03 84 E-mail: moczko@am.wroc.pl Conflict of interest: None declared Received: 23.02.2011 Revised: 31.03.2011 Accepted: 1.08.2011