Lichen Planus of the Gingiva by JOHN
J.
JANDINSKI,
G E R A L D SHKLAR,
D.M.D.*
D.D.S.,
M.s.†
LICHEN PLANUS is now understood to be a relatively
common disease of the oral mucous membrane. Until recent years, it was considered a relatively rare dermatologic entity with occasional involvement of the oral mucosa as well as the skin.Erasmus Wilson, who gave us the first description of the disease in 1869, noted the presence of oral lesions in several of his patients. The white striations, spots, and plaque-like lesions, primarily seen on buccal mucosa and lateral borders of the tongue, were further described by Unna, in 1882, Crocker in 1882, Thibierge in 1885 and Lieberthal in 1907. The possibility of oral lesions occurring in the absence of skin involvement was first noted by Audry in 1894 and emphasized by Dubreuilh in 1906, who also demon strated that the histologic features of the oral lesions were comparable to those of skin lesions. Trautmann in 1911 summarized the entire literature up to that time, and observed that in a survey of the distribution of lesions in lichen planus patients, 26 of 157 cases (17.2%) were found to have lesions confined to the mouth, while 94 of 157 cases (59.8%) demonstrated both oral and skin involvement. Areas of the mouth most commonly af fected were found to be buccal mucosa (82%) and tongue (50%). Lips (22%), palate (17%) and gingiva (10%) were found to be less commonly involved. Gradually, it was realized that lesions of lichen planus, and particularly the oral lesions could be erosive and vesicular as well as keratotic. Poor, in 1905, first described vesiculo-bullous lesions appearing in oral mucosa, after Kaposi had originally described them on skin in 1892. Oral ulcerative lesions were reported by Milian and Fouquet in 1929, and atrophic lichen planus of the tongue was described by Lortat-Jacob et al. in 1929. Large surveys of patients with oral lichen planus were carried out by Cooke in 1954, (50 cases), Warin et al. in 1958 (45 cases), Shklar and McCarthy in 1961 (100 cases), Hermann in 1963 (60 cases), Grinspan et al. in 1966 (114 cases) and Andreason in 1968 (115 cases). 1
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Laufer and Kuffer have reviewed the literature on oral lichen planus up to 1970 and have attempted to offer a variety of statistics based on 706 cases of oral lichen planus taken from the various published surveys. The frequency of lichen planus occurring on the gingiva has been listed as approximately 10% by various authors 8, 1 5
* Department of Medicine, Duke University Medical Center, Durham, N . C . 27710. † Department of Oral Medicine and Oral Pathology, Harvard School of Dental Medicine, Boston, Massachusetts 02115.
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in distinction to the common occurrence of lesions on buccal mucosa and tongue. Andreason's recent figures involved 20% for maxillary gingiva, buccolabial surface and 9.5% for maxillary gingiva, palatal surface; 33.9% for mandibular gingiva, buccolabial surface and 7.8% for mandibular gingiva, lingual surface. We have been impressed in recent years by the large number of cases of oral lichen planus that we have been seeing, and particularly by the high incidence of gingival involvement in these cases. Furthermore, there have been many cases in which the lesions of lichen planus were completely confined to the gingivae, often making the initial diagnosis more difficult. In some of these cases, other oral lesions eventually appeared, while in other cases the disease has remained localized to the gingiva. PRESENT STUDY
We shall present material on 100 recent cases of lichen planus with gingival involvement. These patients were referred for diagnosis during the years 1968 to 1975. Ages ranged from 28 to 81. Of the 100 patients, 63 were female and 37 were male. Histologic material was available in each case, as well as clinical photographs (color transparencies) and medical history. Follow-up information has been available in almost all cases. In reviewing over 600 cases of oral lichen planus in our files, we now feel that gingival involvement is more common than previously reported. OBSERVATIONS
Clinical Appearance of Gingival Lesions As in general clinical descriptions of oral lichen planus the gingival lesions could be classified into four general categories: (1) white papular keratotic lesions, (2) vesic ulo-bullous lesions, (3) erosive or ulcerative lesions, and (4) atrophic lesions. Often there were combinations of the various clinical lesion types, particularly that of keratotic and erosive or ulcerative patterns. 1. Keratotic lesions. Gingival keratotic lesions are the most obvious lesions for diagnostic purposes and are the most apparent at the initial examination. They are seen on the attached gingiva and rarely on the gingival margin. The fundamental lesion is the small raised round papule of pinhead size (1 mm diameter) with somewhat flattened surface. The papule is hyperkeratotic and appears white in color. Large numbers of papules can be seen separately, or arranged in reticulate or lace-like patterns, linear patterns, annular or circular patterns or dense plaque-like patterns. a. Discrete papular. lesions. In discrete papular lesions the individual papules are apparent and can be seen very well with a magnifying glass. The entire attached and even the marginal gingiva appears white, but the individual papular pattern is apparent. (Plate I, Fig. 3). b. Plaque-like lesions. If the papular eruption is extremely dense, the individual papules are not easily
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FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6.
Lichen Planus of the Gingiva 725
Erosive lesions of lichen planus on gingiva, superimposed upon periodontal disease with gingival recession. Erosive lesions on buccal mucosa and erosive-keratotic lesions of palate in patient at left. Erosive keratotic lesions of lichen planus on gingiva, together with marginal gingivitis. Keratotic plaque-like lesion on tongue in patient at left. Localized erosive lesion of lichen planus in gingiva with vertical keratotic striations. Annular keratotic and erosive lesion on buccal mucosa in patient at left.
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seen as separate entities and the entire area appears to be covered with white plaque-like lesions resembling leukoplakia. Plaque-like areas may be separated by areas of pink mucosa or by red areas of erosion or atrophy. (Plate I, Fig. 5). c. Linear lesions. White linear lesions are usually seen on an erythematous background, and the stria tions appear to run in a vertical direction, parallel to the long axis of the tooth. (Plate I, Fig. 1). d. Reticulate lesions. White reticulate patterns may also occur on the attached gingiva and are similar in appearance to the reticulate lesions usually seen on buccal mucosa. The raised, white reticulate lesions are usually seen against a reddened background, when the tissue is atrophic or where ulceration has occurred. (Plate I, Fig. 8). II. Vesiculo-bullous lesions. The development of vesi cles and bullae on the attached gingiva in areas of lichen planus involvement may be confusing clinically, if the characteristic white keratotic lesions are absent. Vesic ulo-bullous involvement may appear as small vesicles that rupture to leave ulcers, or as large bullous lesions that rupture and appear as extensive areas of desquama tion or peeling off of gingiva (Plate I, Fig. 7). III. Erosive or Ulcerative Lesions. Erosive and ulcera tive lesions of lichen planus are commonly seen in gingival involvement, and are usually combined with keratotic lesions (Plate I, Figs 4 and 6). The gingival surface, in addition to demonstrating white striations or plaque-like lesions, shows red erythematous areas in intervening spaces. These areas may be pale red in erosions or deep red and even hemorrhagic in true ulcerative areas, when the entire width of epithelium has been destroyed and sloughed off. IV. Atrophic Lesions. Atrophic lesions of the gingiva are the most difficult to interpret clinically, unless there are coexistent keratotic lesions of gingiva or keratotic lesions elsewhere in the mouth. Atrophic involvement of the gingiva results in a shiny, reddened surface with areas of desquamation and subsequent erosion or ulceration. This type of gingival involvement, in the absence of other lesions, is usually interpreted clinically as so-called 'desquamative gingivitis'. However, careful observation of the entire oral cavity often reveals other lesions suggestive of lichen planus. In most cases of 'desquama
tive gingivitis' due to lichen planus involvement of the gingiva, other characteristic keratotic and ulcerative lesions are obvious, and the gingival disease does not pose a diagnostic problem (Figs. 1 to 6). In other cases the involvement may be confined to the gingiva (Plate I, Figs. 1 to 8) and the major aspect of the lesions may be erythematous-erosive. In some instances the marginal gingiva presents an erosive-desquamative pattern while the adjacent attached gingiva appears white and keratotic (Plate I, Fig. 2). Many cases of atrophic gingival lichen planus or 'desquamative gingivitis' present vesicular or bullous lesions during the course of the disease (Plate I, Fig. 7). A desquamative gingivitis in lichen planus may be superimposed on preexistent periodontitis (Figs. 7 and 8) and the clinical picture may be complicated by poor oral hygiene and marginal gingivitis due to painful symp tomatology upon use of the toothbrush (Fig. 10). Occa sionally one finds an extremely red, atrophic gingival pattern with delicate white linear striations (Fig. 9). This pattern should suggest the possibility of lichen planus. Microscopic Appearance of Gingival Lesions The microscopic picture of gingival lesions of lichen planus is comparable to that of lichen planus involvement elsewhere in the mouth, except for the fact that atrophy of the epithelium is more commonly seen, and superim posed necrosis from irritation is more common. In lesions confined to the gingiva, the initial biopsy may present a picture of nonspecific chronic inflammation with epithelial atrophy, degeneration and ulceration. A subsequent biopsy may reveal the true nature of the gingival involvement. If white lesions are present, the gingival biopsy specimen should be taken from this area, since the keratotic lesions of lichen planus are easier to interpret microscopically. Each variety of clinical lesion presents differences in the microscopic pattern. Histologically, the keratotic lesions present the classic picture composed of three main features: (1) hyperkera tosis or parakeratosis; (2) infiltration of the upper corium by a broad band of lymphocytic cells; and (3) hydropic degeneration or liquefaction degeneration of the stratum germinativum of the epithelium (Figs. 11 to 15). The extension of rete pegs in 'saw-tooth' configurations is commonly seen in skin lesions, is rarely seen in oral
PLATE I. Lichen Planus Localized to Gingiva. FIGURE 1. Keratotic lesions with striations and reticulate pattern. FIGURE 2. Red atrophic involvement of marginal gingiva and keratotic involvement of attached gingiva and adjacent mucosa. FIGURE 3. Discrete papular eruption on attached mandibular gingiva. FIGURE 4. Atrophic and desquamative involvement of maxillary gingiva. Vertical white striations are representative presence of hyperkeratotic lesions. FIGURE 5. Involvement of both maxillary and mandibular gingiva with both ulcerative and keratotic areas. The keratotic lesions are plaque-like with reticulate margins. FIGURE 6. Atrophic and desquamative lesions of maxillary gingiva and small hyperkeratotic plaque-like areas on mandibular gingiva. FIGURE 7. Rupture of large bullous lesions on mandibular gingiva, leaving an extensive area of ulceration. Keratotic lesions are seen distal to the ulcerated area. FIGURE 8. Discrete patchy keratotic and ulcerative areas involving both maxillary and mandibular gingiva.
FIGURE 1
FIGURE 2
FIGURE 3
FIGURE 4
FIGURE 5
FIGURE 6
FIGURE 7
FIGURE 8
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FIGURE 7. Erosive and ulcerative lesions of lichen planus developing in patient with periodontitis. FIGURE 8. Erosive and desquamative gingival lesions of lichen planus in patient with periodontal recession. FIGURE 9. Atrophic gingival involvement in lichen planus with fine vertical linear keratotic pattern. FIGURE 10. Patchy keratotic lichen planus involvement of maxillary gingiva and bullous, enlarged mandibular gingival papilla due to coexistent chronic gingivitis. lesions and is usually not seen in gingival keratotic lesions. The lymphocytic infiltration usually appears as a broad band directly beneath the basement membrane area in oral and skin lesions, but may be more diffusely spread in gingival lesions due to coexisting chronic marginal gingivitis. The erosive lesions appear as areas of ulceration, epithelial thinning and eventual destruction. Hemorrhage may be noted. The classic distribution of the inflamma tory infiltrate may be observed in some instances. H y dropic degeneration of the stratum germinativum is a notable feature of these lesions. The basal cells are gradu ally destroyed and the overlying epithelium becomes thin and atrophic. Eventually the epithelium undergoes necrosis and an area of ulceration appears. Ulcerated lesions of gingival lichen planus may also develop follow ing the rupture of a vesicular or bullous lesion. The bullous or vesicular lesions are of the subepithelial variety. They develop as a result of extensive edema collecting at the epithelial-connective tissue junction
following the hydropic degeneration of the stratum germinativum (Figs. 16 and 17). The vesicle or bulla contains clear fluid and occasionally hemorrhage. The broad band of lymphocytic cells in the upper corium is usually seen prior to rupture of the bulla. Once the bulla has ruptured, the'inflammatory pattern becomes less characteristic in appearance, with lymphocytic cells infiltrating into the deeper corium. The early stages of development of a lichen planus bulla often can be clearly observed at the margins of a ruptured bulla. The severe hydropic degeneration, the developing edema and the lifting up of the epithelium can be observed. Atrophic Lesions In the atrophic lesions, the epithelium is thin and there is a complete absence of rete pegs. (Fig. 18) There is little keratinization at the surface, and the stratum corneum blends into the stratum spinosum. The basal layer presents hydropic degeneration and the upper corium is densely infiltrated with lymphocytic cells, but the inflam-
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FIGURE 11. Low-power view of keratotic gingival lesion of lichen planus showing parakeratosis and band of lymphocytic cells localized to upper corium. (H & E. Original magnification, x 120.) FIGURE 12. Low-power view of keratotic gingival lesions of lichen planus showing parakeratosis, edema, and infiltrate localized to upper corium. One extended rete peg is seen. (H & E. Original magnification, x 100.) FIGURE 13. Keratotic lesion showing parakeratosis, and hydropic degeneration of cells of the stratum germinativum. (H & E. Original magnification, x 200.) FIGURE 14. High-power view showing extensive hydropic degeneration of basal layer of epithelium with penetration of lymphocytes into the epithelium. (H & E. Original magnification, x 450.) FIGURE 15. Initial vesicle formation in lichen planus resulting from destruction of basal cells. The vesiculation is subepithelial. (H & E. Original magnification, x 200.)
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matory infiltrate in gingival lesions may be great and the localization is obscured. Areas of complete ulceration and areas of erosion may be noted, and desquamation or 'peeling off of the epithelium may be evident. In addition to the dense infiltration of lymphocytes, plasma cells, polymorphonuclear leukocytes and histiocytes into the underlying corium, there is often a notable vascularity, with dilated, engorged capillaries, and hemorrhage.
pemphigoid reveal subepithelial vesicuiation, with a relatively intact basal layer of epithelium. The basic microscopic lesion is a split in the basal lamina, as described by Susi and Shklar. Many patients also present conjunctival lesions, including symblepharon (adhesions to corneal surface) (Figs. 19 to 22). A desquamative gingivitis may also occur in rare instances of bullous pemphigoid with oral involvement. However, the presence of the skin lesions will lead to the proper Differential Diagnosis diagnosis. A number of conditions must be considered in the Pemphigus usually presents with oral lesions and a differential diagnosis when lesions suggestive of lichen desquamative gingivitis may be present. However, defini planus are found on the gingiva. tive microscopic diagnosis of oral lesions is easily Desquamative gingivitis is a term that has been widely made, and usually may be confirmed with immunofluorescent studies. used for many years to describe a painful condition of the gingiva characterized by a smooth, red polished Most cases of so-called desquamative gingivitis are surface with some desquamation and hemorrhage upon probably either lichen planus or mucous membrane slight trauma. The condition was usually described in pemphigoid. Since oral lichen planus is a far more middle-aged women and was thought to be related to common disease than mucous membrane pemphigoid, it decreased estrogen secretion. McCarthy et al., in is reasonable to expect that the majority of cases of 1960, cast doubt on 'desquamative gingivitis' as a specific desquamative gingivitis would represent lichen planus, disease entity and pointed out that the clinical features of even though the gingival involvement only occurs in some so-called desquamative gingivitis could be found in a 20% of cases of oral lichen planus. variety of different conditions—dermatoses such as Keratotic lesions of gingival lichen planus may be mucous membrane pemphigoid, lichen planus and pem confused with leukoplakia. Biopsy studies should reveal phigus; hormonal problems related to oophorectomy and the true diagnosis in these cases. menopause; abnormal responses to local irritation; and MANAGEMENT chronic infections such as candidiasis. Of 40 cases studied by McCarthy et al., 17 cases were diagnosed as mucous The management of oral lichen planus is difficult and membrane pemphigoid, four cases were diagnosed as problematic. Lichen planus is now generally considered lichen planus, three cases as hormonal problems and two to be a psychosomatic disorder. The onset of the disease cases were found to be pemphigus vulgaris. The remain often follows a specific and obvious period or episode of ing cases were considered to represent abnormal re emotional stress. Once present, the oral lesions of lichen sponses to gingival irritation, or were considered idi planus do not regress rapidly, even if the specific opathic. emotional disturbance or stress has been resolved. Reas surance is essential, with the probable etiology of the Shklar, in a review of 600 patients with oral lichen disease being explained to the patient and the nonserious planus, emphasized the common occurrence of atrophic nature of the condition emphasized. We do not believe lesions of lichen planus on both gingiva and dorsum of that oral lichen planus is a precancerous condition, and tongue and suggested that most cases of so-called have found no evidence of dysplasia or dyskeratosis in desquamative gingivitis were probably cases of lichen any of our biopsies studied. planus of the atrophic or erosive variety. Diagnosis can We have used various corticosteroid creams and be made in many cases by biopsy studies or by the ointments on the gingiva, with only limited success in eventual development of keratotic lesions on the gingiva alleviating discomfort and inducing healing. The main or elsewhere in the mouth. tenance of optimal oral hygiene is essential and we sug Mucous membrane pemphigoid is a relatively rare gest a soft toothbrush and oxidizing mouthwash such as vesiculobullous disease of mucosal tissues, involving pri hydrogen peroxide USP 3% diluted with two-thirds marily oral and ocular mucous membranes. A desquama warm water to one-third peroxide. The use of systemic tive form of gingivitis has been found to be a feature of steroids is usually unwarranted in this condition and they almost all cases of mucous membrane pemphigoid. are usually not effective in low or moderate dosages. However, biopsy studies of lesions in mucous membrane 27
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FIGURE 16. Vesicuiation in gingival lichen planus. Note the lymphocytic infiltrate in the upper corium and the thin atrophic epithelium at left. (H & E. Original magnification, x 100.) FIGURE 17. High-power view of figure 16 showing degeneration of basal layer and lymphocytic infiltration. (H & E. Original magnification, x 200.) FIGURE 18. Atrophic lichen planus showing thin atrophic epithelium, localization of inflammatory infiltrate in upper corium and notable vascularity. (H & E. Original magnification, 100.)
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FIGURE 19. Erosive, desquamative and vesicular gingival involvement in mucous membrane pemphigoid. FIGURE 20. Conjunctivitis and symblepharon (adhesions) in patient above. FIGURE 21. Biopsy of mucous membrane pemphigoid showing intact basal layer separating from the corium. (Feulgen stain for DNA. Original magnification, x 100.) FIGURE 22. Biopsy of lichen planus showing absence of basal layer cells and lymphocytic infiltration of epithelium. (Feulgen stain for DNA. Original magnification, 200.) DISCUSSION
Overall impressions gained from a review of these cases include the following: 1. Gingival involvement with lesions of lichen planus is more common than we had previously thought, and represents approximately 20% of cases. 2. Usually the gingival involvement is part of an overall oral mucosal involvement. However, in approxi mately 15% of cases the lesions were confined to the gingiva. 3. If lesions of lichen planus are confined to the gingiva, diagnosis may be difficult initially, particularly if the lesions are atrophic, desquamative and vesicular, rather than keratotic. In these patients careful periodic reevaluation of clinical lesions, further biopsy studies and consideration of the patient's history eventually led to the correct diagnosis in every case. 4. Gingival lesions of lichen planus were often found to coexist with chronic marginal gingivitis due to poor oral hygiene, and with periodontitis. In the latter situa tion the clinical picture was often confusing, since the erosive lesions of lichen planus were superimposed on
an existing disease process responsible for recession, periodontal pocket formation and suppuration. 5. While most cases of oral lichen planus can be easily diagnosed on the basis of clinical features, those cases confined to the gingiva usually require biopsy studies for confirmation of initial clinical impression. Since gingival biopsy is a simple procedure, it is recommended that it be carried out in all cases where lichen planus may be suspected. 6. Many cases of so-called 'desquamative gingivitis' are cases of atrophic or erosive lichen planus and a de finitive diagnosis eventually can be made. 7. While most cases of oral lichen planus are asympto matic, gingival lesions tend to be painful or irritating and patients complain of a burning sensation and pain during eating and toothbrushing. This is due to the fact that buccal mucosal lesions are usually keratotic, while gingival lesions tend to be atrophic, erosive and des quamative. 8. Treatment of gingival lichen planus from our experience involves considerable patience and continuous reassurance by the dentist as to the nonserious nature of
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Lichen Planus of the Gingiva7 3 3
the disease. Oral hygiene must be rigorously maintained with brushing (soft bristles) and oxidizing mouthwashes (dilute hydrogen peroxide). Corticosteroid creams and ointments have occasionally been helpful in alleviating painful symptomatology, but their overall effect in the management of lichen planus has been disappointing. Systemic steroids in low and moderate dosages also have proven disappointing, and their long-term use would not be warranted for this nonserious disease. Intralesional steroid injections are occasionally effective for mucosal lichen planus but cannot be adequately used in gingival lesions. 9. As in most cases of lichen planus we were im pressed with the apparent relationship of emotional stress to the initial onset of the lesions. Patients often volunteered a history of specific emotional problems prior to the onset of the disease, and they were not sur prised to learn that the current approach to lichen planus considered a psychosomatic etiology. 10. Desquamative lesions of the gingiva may represent diseases more serious than lichen planus, such as pem phigus and mucous membrane pemphigoid. Therefore, continuous evaluation of the lesions and periodic biopsies are necessary, not only to establish a diagnosis of Lichen Planus but to rule out more serious problems. REFERENCES
1. Wilson, E.: On Leichen Planus. J Cut Med Dis Skin 3: 117, 1869. 2. Unna, P. G.: Uber die mundaffektion bei lichen ruber, monatschr. F Brakt Dermatol 1: 257, 1882. 3. Crocker, H . R.: On affections of the mucous membranes in lichen ruber vel planus, monatschr. F Brakt Dermatol 1: 161, 1882. 4. Thibierge, G.: Lesions de la muqueuse buccale dans le lichen plan, Ann Dermatol 2: 65, 1885. 5. Lieberthal, D.: Lichen planus of the oral mucosa. J Am Med Assoc 48: 559, 1907. 6. Audry, M . : Sur un type clinique de lichen plan (lichen plan debutant dur les muqueuses). J Mai Cat Syph 8: 12, 1894. 7. Dubreuilh, W.: Histologic du lichen plan des muqueuses. Ann Dermatol 7: 123, 1906. 8. Trautmann, G.: Die Krankheiten der Mundhoehle und der oberen Luftwege bei Dermatosen, Weisbaden, 1911, J. F. Bergmann. 9. Poor, V.: Zur anatomie der Schleimhaut affectionen bei lichen planus, Wilson. Dermatol Ztschr 12: 603, 1905.
10. Kaposi, M . : Lichen ruber pemphigoides, Arch Dermatol Syph 24: 340, 1892. 11. Milian, G., and Fouquet, J.: Lichen plan ulcere de la muqueuse jugale, Bull. Soc Franc Dermatol Syph 36: 1218, 1929. 12. Lortat-Jacob, L., Fernet, P., and Flandrin: Glossite atrophique par lichen plan aspect syphiloide, Bull Soc Franc Dermatol Syph 36: 1184, 1929. 13. Cooke B. E. D.: The oral manifestations of lichen planus: 50 cases. Br Dent J 96: 1, 1954. 14. Warin, R. P., Crabb, H . S. M . and Darling, A. I.: Lichen planus of the mouth. Br Med J 1: 983, 1958. 15. Shklar, G., and McCarthy, P. L.: The oral lesions of lichen planus. Observations on 100 cases. Oral Surg 14:164, 1961. 16. Hermann, D.: Lichen ruber planus der mundschleimhaut. Untersuchungen uber klinik, histologic and therapie am 60 fallen. Dtsch Zahnaerztl Z 7: 346, 1963. 17. Grinspan, D., Diaz, J., Abulafia, J., Villapol, L., Schneiderman, J., Palese, D., and Berdichesky, R.: Notre ex perience sur le lichen ruber planus de la muqueuse buccale. Ann Dermatol Syph 93: 531, 1966. 18. Andreason, J. O.: Oral lichen planus: a critical evaluation of 115 cases. Oral Surg 25: 31, 1968. 19. Laufer, J., and Kuffer, R.: Le Lichen Plan Buccal. Paris, Masson et Cie, 1970. 20. Prinz, H.: Chronic diffuse desquamative gingivitis. Dent Cosmos 74: 331, 1932. 21. Merritt, A . H . : Chronic desquamative gingivitis, J Periodontol 4: 30, 1933. 22. Sorrin, S.: Chronic desquamative gingivitis. J Am Dent Assoc 27: 250, 1940. 23. Ziskin, D., and Zegarelli, E. V.: Chronic desquamative gingivitis. Am J Ortho. Oral Surg 33: 756, 1947. 24. McCarthy, F. P., McCarthy, P. L., and Shklar, G.: Chronic desquamative gingivitis: A reconsideration. Oral Surg 13: 1300, 1960. 25. Shklar, G.: Lichen planus as an oral ulcerative disease. Oral Surg 33: 376, 1972. 26. Shklar, G., and McCarthy, P. L.: Oral lesions of mucous membrane pemphigoid: a study of 85 cases. Arch Otolaryngol 93: 354, 1971. 27. Susi, F. R. and Shklar, G.: Histochemistry and fine structure of oral lesions of mucous membrane pemphigoid. Arch Dermatol 104: 244, 1971. 28. Shklar, G., Meyer, I., and Zacarian, S.: Oral lesions in bullous pemphigoid. Arch Dermatol 99: 663, 1969. 29. Shklar, G. and Cataldo, E.: Histopathology and cytology of oral lesions of pemphigus. Arch Dermatol 101: 635, 1970. 30. Nisengard, R. J., Jablonska, S., Beutner, E. H., Shu, S., Chorzelski, T., Jazabek, M . , Blaszczyk, M . , and Rzesa, G.: Diagnostic importance of immunofluorescence in oral bullous diseases and lupus erythematosus. Oral Surg 40: 365, 1975.
J.
JANDINSKI,
G E R A L D SHKLAR,
D.M.D.*
D.D.S.,
M.s.†
LICHEN PLANUS is now understood to be a relatively
common disease of the oral mucous membrane. Until recent years, it was considered a relatively rare dermatologic entity with occasional involvement of the oral mucosa as well as the skin.Erasmus Wilson, who gave us the first description of the disease in 1869, noted the presence of oral lesions in several of his patients. The white striations, spots, and plaque-like lesions, primarily seen on buccal mucosa and lateral borders of the tongue, were further described by Unna, in 1882, Crocker in 1882, Thibierge in 1885 and Lieberthal in 1907. The possibility of oral lesions occurring in the absence of skin involvement was first noted by Audry in 1894 and emphasized by Dubreuilh in 1906, who also demon strated that the histologic features of the oral lesions were comparable to those of skin lesions. Trautmann in 1911 summarized the entire literature up to that time, and observed that in a survey of the distribution of lesions in lichen planus patients, 26 of 157 cases (17.2%) were found to have lesions confined to the mouth, while 94 of 157 cases (59.8%) demonstrated both oral and skin involvement. Areas of the mouth most commonly af fected were found to be buccal mucosa (82%) and tongue (50%). Lips (22%), palate (17%) and gingiva (10%) were found to be less commonly involved. Gradually, it was realized that lesions of lichen planus, and particularly the oral lesions could be erosive and vesicular as well as keratotic. Poor, in 1905, first described vesiculo-bullous lesions appearing in oral mucosa, after Kaposi had originally described them on skin in 1892. Oral ulcerative lesions were reported by Milian and Fouquet in 1929, and atrophic lichen planus of the tongue was described by Lortat-Jacob et al. in 1929. Large surveys of patients with oral lichen planus were carried out by Cooke in 1954, (50 cases), Warin et al. in 1958 (45 cases), Shklar and McCarthy in 1961 (100 cases), Hermann in 1963 (60 cases), Grinspan et al. in 1966 (114 cases) and Andreason in 1968 (115 cases). 1
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5
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7
8
9
10
11
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18
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Laufer and Kuffer have reviewed the literature on oral lichen planus up to 1970 and have attempted to offer a variety of statistics based on 706 cases of oral lichen planus taken from the various published surveys. The frequency of lichen planus occurring on the gingiva has been listed as approximately 10% by various authors 8, 1 5
* Department of Medicine, Duke University Medical Center, Durham, N . C . 27710. † Department of Oral Medicine and Oral Pathology, Harvard School of Dental Medicine, Boston, Massachusetts 02115.
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in distinction to the common occurrence of lesions on buccal mucosa and tongue. Andreason's recent figures involved 20% for maxillary gingiva, buccolabial surface and 9.5% for maxillary gingiva, palatal surface; 33.9% for mandibular gingiva, buccolabial surface and 7.8% for mandibular gingiva, lingual surface. We have been impressed in recent years by the large number of cases of oral lichen planus that we have been seeing, and particularly by the high incidence of gingival involvement in these cases. Furthermore, there have been many cases in which the lesions of lichen planus were completely confined to the gingivae, often making the initial diagnosis more difficult. In some of these cases, other oral lesions eventually appeared, while in other cases the disease has remained localized to the gingiva. PRESENT STUDY
We shall present material on 100 recent cases of lichen planus with gingival involvement. These patients were referred for diagnosis during the years 1968 to 1975. Ages ranged from 28 to 81. Of the 100 patients, 63 were female and 37 were male. Histologic material was available in each case, as well as clinical photographs (color transparencies) and medical history. Follow-up information has been available in almost all cases. In reviewing over 600 cases of oral lichen planus in our files, we now feel that gingival involvement is more common than previously reported. OBSERVATIONS
Clinical Appearance of Gingival Lesions As in general clinical descriptions of oral lichen planus the gingival lesions could be classified into four general categories: (1) white papular keratotic lesions, (2) vesic ulo-bullous lesions, (3) erosive or ulcerative lesions, and (4) atrophic lesions. Often there were combinations of the various clinical lesion types, particularly that of keratotic and erosive or ulcerative patterns. 1. Keratotic lesions. Gingival keratotic lesions are the most obvious lesions for diagnostic purposes and are the most apparent at the initial examination. They are seen on the attached gingiva and rarely on the gingival margin. The fundamental lesion is the small raised round papule of pinhead size (1 mm diameter) with somewhat flattened surface. The papule is hyperkeratotic and appears white in color. Large numbers of papules can be seen separately, or arranged in reticulate or lace-like patterns, linear patterns, annular or circular patterns or dense plaque-like patterns. a. Discrete papular. lesions. In discrete papular lesions the individual papules are apparent and can be seen very well with a magnifying glass. The entire attached and even the marginal gingiva appears white, but the individual papular pattern is apparent. (Plate I, Fig. 3). b. Plaque-like lesions. If the papular eruption is extremely dense, the individual papules are not easily
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FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6.
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Erosive lesions of lichen planus on gingiva, superimposed upon periodontal disease with gingival recession. Erosive lesions on buccal mucosa and erosive-keratotic lesions of palate in patient at left. Erosive keratotic lesions of lichen planus on gingiva, together with marginal gingivitis. Keratotic plaque-like lesion on tongue in patient at left. Localized erosive lesion of lichen planus in gingiva with vertical keratotic striations. Annular keratotic and erosive lesion on buccal mucosa in patient at left.
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seen as separate entities and the entire area appears to be covered with white plaque-like lesions resembling leukoplakia. Plaque-like areas may be separated by areas of pink mucosa or by red areas of erosion or atrophy. (Plate I, Fig. 5). c. Linear lesions. White linear lesions are usually seen on an erythematous background, and the stria tions appear to run in a vertical direction, parallel to the long axis of the tooth. (Plate I, Fig. 1). d. Reticulate lesions. White reticulate patterns may also occur on the attached gingiva and are similar in appearance to the reticulate lesions usually seen on buccal mucosa. The raised, white reticulate lesions are usually seen against a reddened background, when the tissue is atrophic or where ulceration has occurred. (Plate I, Fig. 8). II. Vesiculo-bullous lesions. The development of vesi cles and bullae on the attached gingiva in areas of lichen planus involvement may be confusing clinically, if the characteristic white keratotic lesions are absent. Vesic ulo-bullous involvement may appear as small vesicles that rupture to leave ulcers, or as large bullous lesions that rupture and appear as extensive areas of desquama tion or peeling off of gingiva (Plate I, Fig. 7). III. Erosive or Ulcerative Lesions. Erosive and ulcera tive lesions of lichen planus are commonly seen in gingival involvement, and are usually combined with keratotic lesions (Plate I, Figs 4 and 6). The gingival surface, in addition to demonstrating white striations or plaque-like lesions, shows red erythematous areas in intervening spaces. These areas may be pale red in erosions or deep red and even hemorrhagic in true ulcerative areas, when the entire width of epithelium has been destroyed and sloughed off. IV. Atrophic Lesions. Atrophic lesions of the gingiva are the most difficult to interpret clinically, unless there are coexistent keratotic lesions of gingiva or keratotic lesions elsewhere in the mouth. Atrophic involvement of the gingiva results in a shiny, reddened surface with areas of desquamation and subsequent erosion or ulceration. This type of gingival involvement, in the absence of other lesions, is usually interpreted clinically as so-called 'desquamative gingivitis'. However, careful observation of the entire oral cavity often reveals other lesions suggestive of lichen planus. In most cases of 'desquama
tive gingivitis' due to lichen planus involvement of the gingiva, other characteristic keratotic and ulcerative lesions are obvious, and the gingival disease does not pose a diagnostic problem (Figs. 1 to 6). In other cases the involvement may be confined to the gingiva (Plate I, Figs. 1 to 8) and the major aspect of the lesions may be erythematous-erosive. In some instances the marginal gingiva presents an erosive-desquamative pattern while the adjacent attached gingiva appears white and keratotic (Plate I, Fig. 2). Many cases of atrophic gingival lichen planus or 'desquamative gingivitis' present vesicular or bullous lesions during the course of the disease (Plate I, Fig. 7). A desquamative gingivitis in lichen planus may be superimposed on preexistent periodontitis (Figs. 7 and 8) and the clinical picture may be complicated by poor oral hygiene and marginal gingivitis due to painful symp tomatology upon use of the toothbrush (Fig. 10). Occa sionally one finds an extremely red, atrophic gingival pattern with delicate white linear striations (Fig. 9). This pattern should suggest the possibility of lichen planus. Microscopic Appearance of Gingival Lesions The microscopic picture of gingival lesions of lichen planus is comparable to that of lichen planus involvement elsewhere in the mouth, except for the fact that atrophy of the epithelium is more commonly seen, and superim posed necrosis from irritation is more common. In lesions confined to the gingiva, the initial biopsy may present a picture of nonspecific chronic inflammation with epithelial atrophy, degeneration and ulceration. A subsequent biopsy may reveal the true nature of the gingival involvement. If white lesions are present, the gingival biopsy specimen should be taken from this area, since the keratotic lesions of lichen planus are easier to interpret microscopically. Each variety of clinical lesion presents differences in the microscopic pattern. Histologically, the keratotic lesions present the classic picture composed of three main features: (1) hyperkera tosis or parakeratosis; (2) infiltration of the upper corium by a broad band of lymphocytic cells; and (3) hydropic degeneration or liquefaction degeneration of the stratum germinativum of the epithelium (Figs. 11 to 15). The extension of rete pegs in 'saw-tooth' configurations is commonly seen in skin lesions, is rarely seen in oral
PLATE I. Lichen Planus Localized to Gingiva. FIGURE 1. Keratotic lesions with striations and reticulate pattern. FIGURE 2. Red atrophic involvement of marginal gingiva and keratotic involvement of attached gingiva and adjacent mucosa. FIGURE 3. Discrete papular eruption on attached mandibular gingiva. FIGURE 4. Atrophic and desquamative involvement of maxillary gingiva. Vertical white striations are representative presence of hyperkeratotic lesions. FIGURE 5. Involvement of both maxillary and mandibular gingiva with both ulcerative and keratotic areas. The keratotic lesions are plaque-like with reticulate margins. FIGURE 6. Atrophic and desquamative lesions of maxillary gingiva and small hyperkeratotic plaque-like areas on mandibular gingiva. FIGURE 7. Rupture of large bullous lesions on mandibular gingiva, leaving an extensive area of ulceration. Keratotic lesions are seen distal to the ulcerated area. FIGURE 8. Discrete patchy keratotic and ulcerative areas involving both maxillary and mandibular gingiva.
FIGURE 1
FIGURE 2
FIGURE 3
FIGURE 4
FIGURE 5
FIGURE 6
FIGURE 7
FIGURE 8
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FIGURE 7. Erosive and ulcerative lesions of lichen planus developing in patient with periodontitis. FIGURE 8. Erosive and desquamative gingival lesions of lichen planus in patient with periodontal recession. FIGURE 9. Atrophic gingival involvement in lichen planus with fine vertical linear keratotic pattern. FIGURE 10. Patchy keratotic lichen planus involvement of maxillary gingiva and bullous, enlarged mandibular gingival papilla due to coexistent chronic gingivitis. lesions and is usually not seen in gingival keratotic lesions. The lymphocytic infiltration usually appears as a broad band directly beneath the basement membrane area in oral and skin lesions, but may be more diffusely spread in gingival lesions due to coexisting chronic marginal gingivitis. The erosive lesions appear as areas of ulceration, epithelial thinning and eventual destruction. Hemorrhage may be noted. The classic distribution of the inflamma tory infiltrate may be observed in some instances. H y dropic degeneration of the stratum germinativum is a notable feature of these lesions. The basal cells are gradu ally destroyed and the overlying epithelium becomes thin and atrophic. Eventually the epithelium undergoes necrosis and an area of ulceration appears. Ulcerated lesions of gingival lichen planus may also develop follow ing the rupture of a vesicular or bullous lesion. The bullous or vesicular lesions are of the subepithelial variety. They develop as a result of extensive edema collecting at the epithelial-connective tissue junction
following the hydropic degeneration of the stratum germinativum (Figs. 16 and 17). The vesicle or bulla contains clear fluid and occasionally hemorrhage. The broad band of lymphocytic cells in the upper corium is usually seen prior to rupture of the bulla. Once the bulla has ruptured, the'inflammatory pattern becomes less characteristic in appearance, with lymphocytic cells infiltrating into the deeper corium. The early stages of development of a lichen planus bulla often can be clearly observed at the margins of a ruptured bulla. The severe hydropic degeneration, the developing edema and the lifting up of the epithelium can be observed. Atrophic Lesions In the atrophic lesions, the epithelium is thin and there is a complete absence of rete pegs. (Fig. 18) There is little keratinization at the surface, and the stratum corneum blends into the stratum spinosum. The basal layer presents hydropic degeneration and the upper corium is densely infiltrated with lymphocytic cells, but the inflam-
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FIGURE 11. Low-power view of keratotic gingival lesion of lichen planus showing parakeratosis and band of lymphocytic cells localized to upper corium. (H & E. Original magnification, x 120.) FIGURE 12. Low-power view of keratotic gingival lesions of lichen planus showing parakeratosis, edema, and infiltrate localized to upper corium. One extended rete peg is seen. (H & E. Original magnification, x 100.) FIGURE 13. Keratotic lesion showing parakeratosis, and hydropic degeneration of cells of the stratum germinativum. (H & E. Original magnification, x 200.) FIGURE 14. High-power view showing extensive hydropic degeneration of basal layer of epithelium with penetration of lymphocytes into the epithelium. (H & E. Original magnification, x 450.) FIGURE 15. Initial vesicle formation in lichen planus resulting from destruction of basal cells. The vesiculation is subepithelial. (H & E. Original magnification, x 200.)
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matory infiltrate in gingival lesions may be great and the localization is obscured. Areas of complete ulceration and areas of erosion may be noted, and desquamation or 'peeling off of the epithelium may be evident. In addition to the dense infiltration of lymphocytes, plasma cells, polymorphonuclear leukocytes and histiocytes into the underlying corium, there is often a notable vascularity, with dilated, engorged capillaries, and hemorrhage.
pemphigoid reveal subepithelial vesicuiation, with a relatively intact basal layer of epithelium. The basic microscopic lesion is a split in the basal lamina, as described by Susi and Shklar. Many patients also present conjunctival lesions, including symblepharon (adhesions to corneal surface) (Figs. 19 to 22). A desquamative gingivitis may also occur in rare instances of bullous pemphigoid with oral involvement. However, the presence of the skin lesions will lead to the proper Differential Diagnosis diagnosis. A number of conditions must be considered in the Pemphigus usually presents with oral lesions and a differential diagnosis when lesions suggestive of lichen desquamative gingivitis may be present. However, defini planus are found on the gingiva. tive microscopic diagnosis of oral lesions is easily Desquamative gingivitis is a term that has been widely made, and usually may be confirmed with immunofluorescent studies. used for many years to describe a painful condition of the gingiva characterized by a smooth, red polished Most cases of so-called desquamative gingivitis are surface with some desquamation and hemorrhage upon probably either lichen planus or mucous membrane slight trauma. The condition was usually described in pemphigoid. Since oral lichen planus is a far more middle-aged women and was thought to be related to common disease than mucous membrane pemphigoid, it decreased estrogen secretion. McCarthy et al., in is reasonable to expect that the majority of cases of 1960, cast doubt on 'desquamative gingivitis' as a specific desquamative gingivitis would represent lichen planus, disease entity and pointed out that the clinical features of even though the gingival involvement only occurs in some so-called desquamative gingivitis could be found in a 20% of cases of oral lichen planus. variety of different conditions—dermatoses such as Keratotic lesions of gingival lichen planus may be mucous membrane pemphigoid, lichen planus and pem confused with leukoplakia. Biopsy studies should reveal phigus; hormonal problems related to oophorectomy and the true diagnosis in these cases. menopause; abnormal responses to local irritation; and MANAGEMENT chronic infections such as candidiasis. Of 40 cases studied by McCarthy et al., 17 cases were diagnosed as mucous The management of oral lichen planus is difficult and membrane pemphigoid, four cases were diagnosed as problematic. Lichen planus is now generally considered lichen planus, three cases as hormonal problems and two to be a psychosomatic disorder. The onset of the disease cases were found to be pemphigus vulgaris. The remain often follows a specific and obvious period or episode of ing cases were considered to represent abnormal re emotional stress. Once present, the oral lesions of lichen sponses to gingival irritation, or were considered idi planus do not regress rapidly, even if the specific opathic. emotional disturbance or stress has been resolved. Reas surance is essential, with the probable etiology of the Shklar, in a review of 600 patients with oral lichen disease being explained to the patient and the nonserious planus, emphasized the common occurrence of atrophic nature of the condition emphasized. We do not believe lesions of lichen planus on both gingiva and dorsum of that oral lichen planus is a precancerous condition, and tongue and suggested that most cases of so-called have found no evidence of dysplasia or dyskeratosis in desquamative gingivitis were probably cases of lichen any of our biopsies studied. planus of the atrophic or erosive variety. Diagnosis can We have used various corticosteroid creams and be made in many cases by biopsy studies or by the ointments on the gingiva, with only limited success in eventual development of keratotic lesions on the gingiva alleviating discomfort and inducing healing. The main or elsewhere in the mouth. tenance of optimal oral hygiene is essential and we sug Mucous membrane pemphigoid is a relatively rare gest a soft toothbrush and oxidizing mouthwash such as vesiculobullous disease of mucosal tissues, involving pri hydrogen peroxide USP 3% diluted with two-thirds marily oral and ocular mucous membranes. A desquama warm water to one-third peroxide. The use of systemic tive form of gingivitis has been found to be a feature of steroids is usually unwarranted in this condition and they almost all cases of mucous membrane pemphigoid. are usually not effective in low or moderate dosages. However, biopsy studies of lesions in mucous membrane 27
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FIGURE 16. Vesicuiation in gingival lichen planus. Note the lymphocytic infiltrate in the upper corium and the thin atrophic epithelium at left. (H & E. Original magnification, x 100.) FIGURE 17. High-power view of figure 16 showing degeneration of basal layer and lymphocytic infiltration. (H & E. Original magnification, x 200.) FIGURE 18. Atrophic lichen planus showing thin atrophic epithelium, localization of inflammatory infiltrate in upper corium and notable vascularity. (H & E. Original magnification, 100.)
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FIGURE 19. Erosive, desquamative and vesicular gingival involvement in mucous membrane pemphigoid. FIGURE 20. Conjunctivitis and symblepharon (adhesions) in patient above. FIGURE 21. Biopsy of mucous membrane pemphigoid showing intact basal layer separating from the corium. (Feulgen stain for DNA. Original magnification, x 100.) FIGURE 22. Biopsy of lichen planus showing absence of basal layer cells and lymphocytic infiltration of epithelium. (Feulgen stain for DNA. Original magnification, 200.) DISCUSSION
Overall impressions gained from a review of these cases include the following: 1. Gingival involvement with lesions of lichen planus is more common than we had previously thought, and represents approximately 20% of cases. 2. Usually the gingival involvement is part of an overall oral mucosal involvement. However, in approxi mately 15% of cases the lesions were confined to the gingiva. 3. If lesions of lichen planus are confined to the gingiva, diagnosis may be difficult initially, particularly if the lesions are atrophic, desquamative and vesicular, rather than keratotic. In these patients careful periodic reevaluation of clinical lesions, further biopsy studies and consideration of the patient's history eventually led to the correct diagnosis in every case. 4. Gingival lesions of lichen planus were often found to coexist with chronic marginal gingivitis due to poor oral hygiene, and with periodontitis. In the latter situa tion the clinical picture was often confusing, since the erosive lesions of lichen planus were superimposed on
an existing disease process responsible for recession, periodontal pocket formation and suppuration. 5. While most cases of oral lichen planus can be easily diagnosed on the basis of clinical features, those cases confined to the gingiva usually require biopsy studies for confirmation of initial clinical impression. Since gingival biopsy is a simple procedure, it is recommended that it be carried out in all cases where lichen planus may be suspected. 6. Many cases of so-called 'desquamative gingivitis' are cases of atrophic or erosive lichen planus and a de finitive diagnosis eventually can be made. 7. While most cases of oral lichen planus are asympto matic, gingival lesions tend to be painful or irritating and patients complain of a burning sensation and pain during eating and toothbrushing. This is due to the fact that buccal mucosal lesions are usually keratotic, while gingival lesions tend to be atrophic, erosive and des quamative. 8. Treatment of gingival lichen planus from our experience involves considerable patience and continuous reassurance by the dentist as to the nonserious nature of
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the disease. Oral hygiene must be rigorously maintained with brushing (soft bristles) and oxidizing mouthwashes (dilute hydrogen peroxide). Corticosteroid creams and ointments have occasionally been helpful in alleviating painful symptomatology, but their overall effect in the management of lichen planus has been disappointing. Systemic steroids in low and moderate dosages also have proven disappointing, and their long-term use would not be warranted for this nonserious disease. Intralesional steroid injections are occasionally effective for mucosal lichen planus but cannot be adequately used in gingival lesions. 9. As in most cases of lichen planus we were im pressed with the apparent relationship of emotional stress to the initial onset of the lesions. Patients often volunteered a history of specific emotional problems prior to the onset of the disease, and they were not sur prised to learn that the current approach to lichen planus considered a psychosomatic etiology. 10. Desquamative lesions of the gingiva may represent diseases more serious than lichen planus, such as pem phigus and mucous membrane pemphigoid. Therefore, continuous evaluation of the lesions and periodic biopsies are necessary, not only to establish a diagnosis of Lichen Planus but to rule out more serious problems. REFERENCES
1. Wilson, E.: On Leichen Planus. J Cut Med Dis Skin 3: 117, 1869. 2. Unna, P. G.: Uber die mundaffektion bei lichen ruber, monatschr. F Brakt Dermatol 1: 257, 1882. 3. Crocker, H . R.: On affections of the mucous membranes in lichen ruber vel planus, monatschr. F Brakt Dermatol 1: 161, 1882. 4. Thibierge, G.: Lesions de la muqueuse buccale dans le lichen plan, Ann Dermatol 2: 65, 1885. 5. Lieberthal, D.: Lichen planus of the oral mucosa. J Am Med Assoc 48: 559, 1907. 6. Audry, M . : Sur un type clinique de lichen plan (lichen plan debutant dur les muqueuses). J Mai Cat Syph 8: 12, 1894. 7. Dubreuilh, W.: Histologic du lichen plan des muqueuses. Ann Dermatol 7: 123, 1906. 8. Trautmann, G.: Die Krankheiten der Mundhoehle und der oberen Luftwege bei Dermatosen, Weisbaden, 1911, J. F. Bergmann. 9. Poor, V.: Zur anatomie der Schleimhaut affectionen bei lichen planus, Wilson. Dermatol Ztschr 12: 603, 1905.
10. Kaposi, M . : Lichen ruber pemphigoides, Arch Dermatol Syph 24: 340, 1892. 11. Milian, G., and Fouquet, J.: Lichen plan ulcere de la muqueuse jugale, Bull. Soc Franc Dermatol Syph 36: 1218, 1929. 12. Lortat-Jacob, L., Fernet, P., and Flandrin: Glossite atrophique par lichen plan aspect syphiloide, Bull Soc Franc Dermatol Syph 36: 1184, 1929. 13. Cooke B. E. D.: The oral manifestations of lichen planus: 50 cases. Br Dent J 96: 1, 1954. 14. Warin, R. P., Crabb, H . S. M . and Darling, A. I.: Lichen planus of the mouth. Br Med J 1: 983, 1958. 15. Shklar, G., and McCarthy, P. L.: The oral lesions of lichen planus. Observations on 100 cases. Oral Surg 14:164, 1961. 16. Hermann, D.: Lichen ruber planus der mundschleimhaut. Untersuchungen uber klinik, histologic and therapie am 60 fallen. Dtsch Zahnaerztl Z 7: 346, 1963. 17. Grinspan, D., Diaz, J., Abulafia, J., Villapol, L., Schneiderman, J., Palese, D., and Berdichesky, R.: Notre ex perience sur le lichen ruber planus de la muqueuse buccale. Ann Dermatol Syph 93: 531, 1966. 18. Andreason, J. O.: Oral lichen planus: a critical evaluation of 115 cases. Oral Surg 25: 31, 1968. 19. Laufer, J., and Kuffer, R.: Le Lichen Plan Buccal. Paris, Masson et Cie, 1970. 20. Prinz, H.: Chronic diffuse desquamative gingivitis. Dent Cosmos 74: 331, 1932. 21. Merritt, A . H . : Chronic desquamative gingivitis, J Periodontol 4: 30, 1933. 22. Sorrin, S.: Chronic desquamative gingivitis. J Am Dent Assoc 27: 250, 1940. 23. Ziskin, D., and Zegarelli, E. V.: Chronic desquamative gingivitis. Am J Ortho. Oral Surg 33: 756, 1947. 24. McCarthy, F. P., McCarthy, P. L., and Shklar, G.: Chronic desquamative gingivitis: A reconsideration. Oral Surg 13: 1300, 1960. 25. Shklar, G.: Lichen planus as an oral ulcerative disease. Oral Surg 33: 376, 1972. 26. Shklar, G., and McCarthy, P. L.: Oral lesions of mucous membrane pemphigoid: a study of 85 cases. Arch Otolaryngol 93: 354, 1971. 27. Susi, F. R. and Shklar, G.: Histochemistry and fine structure of oral lesions of mucous membrane pemphigoid. Arch Dermatol 104: 244, 1971. 28. Shklar, G., Meyer, I., and Zacarian, S.: Oral lesions in bullous pemphigoid. Arch Dermatol 99: 663, 1969. 29. Shklar, G. and Cataldo, E.: Histopathology and cytology of oral lesions of pemphigus. Arch Dermatol 101: 635, 1970. 30. Nisengard, R. J., Jablonska, S., Beutner, E. H., Shu, S., Chorzelski, T., Jazabek, M . , Blaszczyk, M . , and Rzesa, G.: Diagnostic importance of immunofluorescence in oral bullous diseases and lupus erythematosus. Oral Surg 40: 365, 1975.
