Critical Reviews in Oral Biology & Medicine

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Update On Oral Lichen Planus: Etiopathogenesis and Management

C. Scully, M. Beyli, M. C. Ferreiro, G. Ficarra, Y. Gill, M. Griffiths, P. Holmstrup, S. Mutlu, S. Porter and D. Wray
Crit. Rev. Oral Biol. Med. 1998; 9; 86
DOI: 10.1177/10454411980090010501

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UPDATE ON ORAL LICHEN PLANUS:
ETIOPATHOGENESIS AND MANAGEMENT
Crispian Scullyl*
Mehmet Beyli2
Miguel C. Ferreiro3
Giuseppe Ficarra4
Yehuda Gill5
Mark GriIfiths6
Palle Holmstrup7
Serdar Mutlu2
Stephen Porter]
David Wray8

Report of the European Working Group in Oral Medicine, Villars, Switzerland, 1995: 1London (UK), 21stanbul (Turkey), 3Santiago de Compostela (Spain), 4Florence (Italy), 5Haifa (Israel),
6Bristol (UK), 7Copenhagen (Denmark), and 8Glasgow (UK); *to whom correspondence should be addressed, at Eastman Dental Institute for Oral Health Care Sciences, University of London,
256 Gray's Inn Road, London WC1 X 8LD, United Kingdom, www.eastman.ucl.ac.uk
ABSTRACT: Lichen planus (LP) is a relatively common disorder of the stratified squamous epithelia, which is, in many ways,
an enigma. This paper is the consensus outcome of a workshop held in Switzerland in 1995, involving a selection of clinicians
and scientists with an interest in the condition and its management. The oral (OLP) eruptions usually have a distinct clinical
morphology and characteristic distribution, but OLP may also present a confusing array of patterns and forms, and other dis-
orders may clinically simulate OLP. Lesions may affect other mucosae and/or skin. Lichen planus is probably of multifactorial
origin, sometimes induced by drugs or dental materials, often idiopathic, and with an immunopathogenesis involving T-cells
in particular. The etiopathogenesis appears to be complex, with interactions between and among genetic, environmental, and
lifestyle factors, but much has now been clarified about the mechanisms involved, and interesting new associations, such as
with liver disease, have emerged. The management of lichen planus is still not totally satisfactory, and there is as yet no defin-
itive treatment, but there have been advances in the control of the condition. There is no curative treatment available;
immunomodulation, however, can control the condition. Based on the observed increased risk of malignant development,
OLP patients should be offered regular follow-up examination from two to four times annually and asked to report any
changes in their lesions and/or symptoms. Follow-up may be particularly important in patients with atrophic/ulcerative/erosive
affections of the tongue, the gingiva, or the buccal mucosa. Much more research is required into the genetic and environmen-
tal aspects of lichen planus, into the premalignant potential, and into the possible associations with chronic liver, and other,
disorders. More clinical studies are required into the possible efficacy of immunomodulatory drugs such as pentoxifylline and
thalidomide.
Key words. Lichen planus, lichenoid lesions, stomatitis, carcinoma, premalignancy.

Introduction
Lichen planus (LP) is a relatively common disorder of
the stratified squamous epithelia (Duske and Frick,
1982; Scully and El-Kom, 1985; Conklin and Blasberg,
1987; Jungell, 1991). Most dental practitioners must see
patients with LP, but not all recognize this. The oral
(OLP) eruptions usually have a distinct clinical morphol-
ogy and characteristic distribution, but OLP may also
present a confusing array of patterns and forms, and
other disorders may clinically simulate OLP. Lesions may
affect mucosae and/or skin.
The etiopathogenesis appears to be complex, with
interactions between and among genetic, environmental,
and lifestyle factors, but much has now been clarified
about the mechanisms involved, and interesting new
associations, such as with liver disease, have emerged.
The management is still not totally satisfactory, and
there is as yet no definitive treatment, but there have
been advances in the control of the condition.
This paper is the consensus outcome of a European
workshop held in 1995.
Epidemiology
LP is a fairly common mucocutaneous disease. OLP affects
from 0.1 to about 4% of individuals, depending on the
population sampled (Bruszt, 1962; Bouquot and Gorlin,

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 Figure 1. Striated oral lichen planus.

Figure 3. Plaque-like form of oral lichen planus on tongue.

Figure 2. Papular oral lichen planus.

1986; Axell, 1987; Axell and Rundquist, 1987; Hogewind

and Van der Waal, 1988; Axell et al., 1990; Salonen et cil,
1990; Ban6czy and Rigo, 1991, Albrecht et al, 1992). OLP
generally is a disease of the middle-aged and elderly
(Silverman and Griffith, 1974), and the female-to-male
ratio is about 2:1 (Sklavounou and Laskaris, 1983). OLP
is rare in children (Scully et al., 1994).
Oral Lesions
The clinical lesions of OLP normally include chronic
bilateral white reticular affections, typically in the poste-
rior buccal mucosa (about 90% of cases), on the tongue
(about 30%), or on the alveolar ridge/gingiva (about Figure 4. Erosive oral lichen plonus.
13%), but rarely on the palate or lip vermilion (Ax6ll and
Rundquist, 1987). Very occasionally, LP is seen on the the lesions diagnosed as bullous LP are actually superfi-
lips alone (Itin et al., 1995; Allan and Buxton, 1996). The cial mucoceles (Eveson, 1988).
lesions usually consist of white lace-like slightly elevated While often asymptomatic, OLP may be associated
patterns (Fig. 1) and/or papules (Fig. 2) (Andreasen, with chronic atrophic ulcerative erosive lesions which
1968; Silverman et cil, 1991; Holmstrup et al, 1988). Other commonly give rise to pain (Thorn et al, 1988). The preva-
types of clinical manifestations-such as plaque-type lence of atrophic lesions of OLP in the adult Swedish
(Fig. 3) or atrophic lesions, ulcerations (Fig. 4), or bul- population is reported to be 0.56% and that of erosive
lae-may be present simultaneously. At least some of lesions 0.16%: among 410 diagnosed cases of OLP, 134

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 TABLE 1
Patients with Atrophic and Ulcerative/Erosive Lesions in Larger Cohorts of OLP Patients
Total No. of Patients Atrophic Lesions
Kovesi and Banoczy, 1973
Silverman and Griffith, 1974
Silverman etal., 1985b
Thorn et al., 1988
Silverman etal., 1991
Herrmann, 1992
*Erosive lesions were comprised of erythematous mucosa, erosive changes, and pseudo-membrane formations.
(32.7%) had atrophic lesions and 32 (7.8%) exhibited ero-
sive lesions (Axell, 1976). In referred cohorts of OLP
patients, those with atrophic and ulcerative/erosive
lesions often constitute a higher proportion of the
patients; in the larger reported cohorts (Table 1), OLP
patients with atrophic lesions accounted for 5 to 44%,
whereas those with ulcerative/erosive lesions accounted
for 9 to 46%.
It is noteworthy that, in some cases of OLP, the clin-
ical manifestations change completely over the years
(Thorn et al., 1988), one such development being the for-
mation of plaque-type lesions which may even be pre-
sent without other clinical lesions suggestive of OLP and
can present clinically as leukoplakia. One study has
reported on the course of the various clinical forms of
OLP (Thorn et al., 1988): Among 611 patients followed
from one to 26 years (mean, 7.5 years) (Table 2), 44% had
atrophic lesions at the initial visit, but in 23% of the
patients, these lesions had disappeared by the time of
the latest consultation, and another 12% had developed
atrophic lesions. Similar dynamics are characteristic of
the ulcerative lesions of OLP.
One analysis of the possible relationships between
and among age, sex, systemic disease, medication,
tobacco usage, and the presence of the various clinical
forms of OLP demonstrated that atrophic lesions were
TABLE 2
Atrophic and Ulcerative Lesions in 611 Oral
Lichen Planus Patients (Thorn et al., 1988)
Atrophic Ulcerative
A* 44% 9%
B 23% 6%
C 12% 2%
D 33% 5%
*A: present on admission.
B: disappeared at latest examination.
C: developed at latest examination.
D: present at latest examination (D = A - B + C).
88
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Ulcerative/ Pain or
Erosive Lesions Discomfort
(n) (%) (%) (%)
326 5 28 91
200 60* 68.5
570 22 46 75
611 44 9 43
214 30 41 73
919 39 16 -
most often found in individuals over 60, but no other cor-
relations were found to explain the initial presence of
atrophic or ulcerative lesions (Thorn et al., 1988). An
interesting finding was that more plaque-type lesions
developed in patients who initially had atrophic and/or
ulcerative lesions than in those without (Thorn et al.,
1988). However, another study showed atrophic or ero-
sive lesions to be more typically seen in the tongue and
sites other than the buccal mucosa than are reticular
lesions of LP, and the erosive forms were more likely than
the non-erosive to be associated with systemic disorders
such as chronic liver disease or diabetes mellitus (Bagan
et al., 1992). There is also evidence that it is these forms
of OLP that are more likely to develop carcinoma
(Barnard et al., 1993).
As mentioned above, atrophic and ulcerative/erosive
lesions of OLP are often associated with pain. As seen
from Table 1, pain or discomfort was recorded in 43 to
91% of the patients included in larger cohorts of OLP
patients. Obviously, the referred groups of patients are
selected, an important factor in the selection being the
presence of symptoms.
Gingival Lesions
In about 10% of patients with OLP, the lesions are con-
fined to the gingiva alone (Scully and El-Kom, 1985),
sometimes making the diagnosis more difficult
(Jandinski and Shklar, 1976) because, although it can give
rise to a number of different clinical appearances on the
gingiva, LP often causes desquamative changes (Daniels
and Quadra-White, 1981) similar to those seen in sever-
al other mucocutaneous disorders (Fig. 5), especially
pemphigoid (Rogers et al., 1982), dermatitis herpeti-
formis, or linear IgA disease (Porter et al., 1990, 1992). The
gingival lesions in LP fall into one or more of the follow-
ing categories (Jandinski and Shklar, 1976): Keratotic
lesions are usually present on the attached gingiva as
small raised round white papules of pinhead size with a
flattened surface. These keratotic lesions can be further
classified as: papular, plaque-like, linear, and reticular
("Honiton lace" ) or annular. Vesiculo-bullous lesions are
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quite uncommon on the gingiva and when present can
cause difficulties in diagnosis. Atrophic lesions produce
desquamative gingivitis-the most commonly seen type
of gingival LP Erosive lesions also produce desquama-
tive gingivitis and are often quite difficult to interpret
unless there are coexistent keratotic lesions on the gin-
giva or elsewhere in the mouth.
Complications of OLP
The main complication of OLP is the reduced quality of life
related to soreness or pain, particularly in atrophic or ulcer-
ative/erosive lesions. Candidosis can also complicate OLP,
especially when the more potent topical corticosteroids are
used. Most important, however, is the risk of malignant
change which has been recognized over recent years. OLP
may also have associations with systemic diseases.
CANDIDOSIS
Some patients with oral LP have oral carriage of candida
species or subclinical or frank candidosis, and this may
account for soreness in at least some symptomatic
patients (Holmstrup and Dabelsteen, 1974; Simon and
Hornstein, 1980; Dreyer, 1983; Lacy etal., 1983, Lundstrbm
et cil., 1984; Krogh et cii, 1987a,b; Hatchuel et ci., 1990;
Vincent et al., 1990; Albrecht et cl., 1992; Ostman etal., 1994).
Culture studies have demonstrated Candida in the
mouths of 37 to 50% of OLP cases, but this finding is
close to that in general population samples (Simon and
Hornstein, 1980, Lundstrom et ci., 1984, Krogh et cil.,
1987a,b). Candidal infection of OLP lesions has been
demonstrated in biopsies in between 0 and 17% of cases
with no apparent predilection for any clinical type of OLP
(Holmstrup and Dabelsteen, 1974; Lundstrbm et cit.,
1984b; Krogh et al., 1987a,b; Hatchuel et al. 1990).
Interestingly, however, clinical improvement of OLP has
been reported as the result of antimycotic treatment
(Lundstrom et cit., 1984). Treatment with corticosteroids
may predispose to candidosis (see below).
MALIGNANT DEVELOPMENT
The most important complication of OLP is development
of squamous cell carcinoma. Numerous case reports and
about 25 follow-up studies have focused on this aspect,
as recently reviewed by Barnard et al. (1993), but the topic
is still subject to some controversy (Krutchkoff et al.,
1978; Krutchkoff and Eisenberg, 1985; Eisenberg and
Krutchkoff, 1992; Holmstrup, 1992b)
The major problem in this discussion is the inclusion
criteria used in the follow-up studies. Since there are no
universally accepted specific diagnostic criteria for OLP,
the diagnostic approaches of the studies vary. Some are
based on a diagnosis of OLP established solely on clini-
cal features (Kovesi and Ban6czy, 1973, Silverman and
Griffith, 1974, Murti et al., 1986), others have used micro-
scopical criteria (Barnard et al., 1993), and yet others have
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9g11)86-122 I1998)
Figure 5. Desquamative gingivitis.
included both clinical and histological criteria (Fulling,
1973; Silverman et alc, 1985b, 1991, Holmstrup et ci., 1988,
Herrmann, 1992; Voute et cil, 1992).
It has long been known that the histopathologic fea-
tures of OLP may include characteristics of epithelial dys-
plasia (MacDonald and Rennie, 1975, Holmstrup and
Pindborg, 1979; Kaugars and Svirsky, 1982; De long et cil.,
1984), and it has been proposed that lesions initially diag-
nosed clinically and/or histologically, such as lichen
planus, may have actually been premalignant dysplasias
with lichenoid appearances (Krutchkoff et al., 1978;
Krutchkoff and Eisenberg, 1985, Eisenberg and Krutchkoff,
1992). Obviously, patients with histologic features qualify-
ing for the diagnosis of epithelial dysplasia at the time of
entering a follow-up study on OLP should really be exclud-
ed from studies of possible malignant development
(Holmstrup et ac., 1988), but the lack of consistently reli-
able well-defined objective criteria of epithelial dysplasia
adds to the confusion (Pindborg et al., 1985).
Further, features of epithelial dysplasia are not
exclusive to premalignant lesions, and such histologic
changes may be reactive rather than pre-neoplastic:
Dysplastic features may be seen in a variety of obviously
benign lesions, including denture-induced hyperplasia
(MacDonald and Rennie, 1975). Therefore, even the find-
ing of minor histologic features of epithelial dysplasia in
OLP lesions does not necessarily suggest a pre-neoplas-
tic nature of these lesions.
However, even with these reservations, the results of
the follow-up studies on the development of squamous
cell carcinoma in lesions diagnosed as OLP are surpris-
ingly uniform. Those studies involving more than 200
patients and with a defined period of follow-up are
shown in Table 3 The frequency of malignant change
ranges from 0.4 to 3.3%, the periods of observation being
from 0.5 to over 20 years.
The most surprising result, however, was that of
Sigurgeirsson and Lindelof (1991), who found no
increased risk of malignancy in skin lesions of 2071
Crit Rev Oral Biol Med
 TABLE 3
Studies of Malignant Changes in Oral Lichen Planus Including More than 200 Patients
Authors (Year) Country Patients Patients Known Frequency Observation
with LP to Develop of Malignant Period (yrs)
Oral Cancer Change (%)
Janner et al. (1967) Germany 585 9 1.7 1-24
Abramova (1968) Russia 436 5 1.1 5-8
Shklar (1972) USA 600 3 0.5 1-15
Fulling (1973) Denmark 225 1 0.4 3.6
Kovesi and B6n6czy (1973) Hungary 274 1 0.4 1 > 10
Silverman et al. (1985) USA 570 7 1.2 5.6
Murti etal. (1986) India 702 3 0.4 5.1
Holmstrup et aI. (1988) Denmark 611 9 1.5 1-26 (mean, 7.5
Sigurgeirsson and Lindelof (1991) Sweden 2071 * 8 0.4 9.9
Silverman etal. (1991) USA 214 5 2.3 0.5-> 10 (mean, 7.5)
Barnard etal. (1993) UK 241 8** 3.3 10
*The 2071 patients had cutaneous lichen planus with no information on oral manifestations, but they developed oral carcinomas.
**Eight patients developed invasive carcinoma and another patient carcinoma in situ.
patients with cutaneous lichen planus but found an plasia in the lesions suggests a premalignant potential.
increased risk of oral cancer (0.4%). The authors gave no Whether the lack of c-erb-B-2 proto-oncogene expression
information about oral involvement with LP but, assu- seen in some OLP (Kilpi et al., 1995) is indicative that
ming that between 15% and 75% of their patients had these lesions are premalignant is not yet known.
OLP, they estimated a frequency of malignant develop- The reasons for malignant development in OLP
ment at 0.55% to 2.6% over a period of almost 10 years. lesions are unknown. Smoking and alcohol exposure
As to the type of OLP most likely to undergo malig- are not invariable-e.g., they were not seen in half the
nant change, several authors have reported cases of the Danish study (Holmstrup et al., 1988)-so
atrophic/ulcerative/erosive OLP lesions as the lesions other factors should be considered. One factor may be
with the greatest preponderance for malignant develop- Candida albicans, since this has been associated with
ment (Kovesi and Banoczy, 1973; Silverman et al., 1985b, malignant development in some leukoplakias (lepsen
1991; Murti et al., 1986; Barnard et al., 1993). Further, in and Winther, 1965; Renstrup, 1970; Roed-Petersen et al.,
some of the studies, a location preponderance was 1970; Cawson and Binnie, 1977), and such yeasts have
revealed, most carcinomas developing in either the been identified in OLP (Holmstrup and Dabelsteen,
tongue or gingiva (Holmstrup et al., 1988; Silverman et at., 1974; Simon and Hornstein, 1980; Krogh et al., 1987a,b).
1991; Barnard et al., 1993) or in the buccal mucosa Another possibility is that herpes simplex virus or a
(Silverman and Griffith, 1974). human papillomavirus, both of which have been impli-
Thus, in persons with lesions diagnosed as OLP, it is cated as risk factors in oral carcinogenesis and found in
important to emphasize that there appears to be a OLP, are involved (Cox et al., 1993). Alternatively, some
greater risk of developing oral cancer than in the general other agent may be causal.
population. Those lesions diagnosed as OLP clearly
appear to fulfill the WHO criterion of a precancerous con- Extra-oral Lesions
dition, "a generalised state associated with a significant LP is a mucocutaneous disease which can affect any
increased risk of cancer" (Holmstrup et al., 1988). stratified squamous epithelia, particularly the skin and
Another important aspect is the occurrence of ery- appendages. The prevalence of cutaneous LP in the
throplakic lesions in OLP patients (Holmstrup and general population is from 0.9 to 1.2% (Schmidt, 1961;
Pindborg, 1979). These lesions are sharply demarcated Boyd and Neldner, 1991). Cutaneous LP generally
and slightly depressed red lesions, and histological occurs in individuals between the ages of 25 and 60
examination usually reveals epithelial dysplasia, but in years, shows no racial predilection or real sex prefer-
some instances they may harbor a frank squamous cell ence [though some authors have reported a higher
carcinoma, or the lesion may undergo malignant change. prevalence in women (Boyd and Neldner, 1991)], and is
These erythroplakic lesions appear to develop in about rare in children, with a prevalence of 2-3% of all patients
1% of the OLP patients, and the finding of epithelial dys- (Brice et al., 1980).

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 TABLE 4
Clinical Forms and Paiterns of Cutaneous Lichen Planus

Classic
Ungual
Actinic
Hypertrophic
Vesiculobullous
Miscellaneous
Perforating
Erythematous - Pigmentosus
Exfoliative Planopilaris
Familial - Ulcerative
Guttate Zosteriform
Linear - Koebnerization
Modified from Boyd and Neldner (1991).
,:W
they may have an erythematous or a white striated
appearance (Fig. 8) (Arndt, 1987).
LP of the vaginal wall shows a reticulated aspect
similar to that of oral lesions. Vulvar lesions consist of

Figure 6. Lichen planus characteristically localized on the flexor sur-

face of the wrist. Note the multiple papules which were pruritic.

CUTANEOus LP
The cutaneous lesions of LB typically consist of slightly
erythematous to violaceous papules characteristically on
the flexor surfaces of the forearms either as isolated
lesions or in aggregate patterns, but there are several
variants (Fig. 61 (Table 4). Rapules are flat-topped with an
angular shape and may show a fine transparent superfi-
cial scale. A lacy network of white lines may be present
on many papules (Wickham's striae)p Although any skin
area may be involved, the arms, legs, and back are the
most common sites (Fig 7). Cutaneous LB may be an
intensely pruritic eruption which usually resolves within
one to two years, but about 20% of affected individuals
a
are asymptomatic (Arndt, 1987,Boyd and Neldner 19911.
Hyperpigmentation may bs aoweque and ineoften quite
marked but temporary.
GENITAL LP
The male genitalia are affected in 25mof cases b of LB.
Principally, the glans penis though the shaft, scrotum, Figure 7. Diffuse papular lichen planus of the dorsum skin (by
and perineum can also be involved The lesions may be courtesy of Dr. Nicola Pimpinelli, Institute of Dermatology,
the typical papules, often in an annular configuration, or University of Florence).

9( 1 86-122
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Figure 8. Lichen planus of the penis. Erosion and white reticu-
late pattern of lichen planus appear evident.
lichenoid papules, white patches, or erythematous
lesions with variable degrees of atrophy (Fig. 9) (Soper et
al., 1988, Eisen, 1994). Symptoms such as pruritus, burn-
ing, and pain during sexual intercourse may be present
When LP is seen involving the vulva, vagina, and gin-
giva, this has been described as the vulvo-vaginal-gingi-
val syndrome (Edwards, 1989; Pelisse, 1989; Bermejo et
al., 1990; Eisen, 1994) The oral lesions are typically of
desquamative gingivitis.
UNGUAL LP
Nail lesions are usually associated with typical cuta-
neous and oral lesions and have been reported in 1-16%
of patients (Scott and Scott, 1979). Characteristic fea-
tures are longitudinal striation, splitting and grooving,
friability, and rupture of the free edge of the involved
nail. Nail destruction may occur in severe lesions.
However, it is important to stress that these manifesta-
tions are not pathognomonic, since trauma, fungal infec-
tion, drug reactions, or other systemic conditions can
give rise to similar changes.
ACTINIC LP
Actinic LP is uncommon but develops on the skin
exposed to sunshine, such as the dorsum of the arms
and hands, on the forehead, face, and neck. Generally,
the scalp and nails are spared Pruritus is absent or min-
imal, and lesions appear as hyperpigmented, violaceous
to blue-brown papules with well-defined margins.
Scaling is not evident This type of LP is seen more com-
monly in women and outdoor workers, especially in the
spring and summer. Sunlight does appear to be the pre-
cipitating factor, and lesions have been provoked experi-
mentally with UVB (Isaacson et al., 1981, Salman et al_
1989). Actinic LP has no relationship to lichenoid actinic
solar keratoses; indeed, this condition shows no
anatomic predilection and presents a red to brown color,
scaling, and histological cellular atypia.
92
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t.,i:
ft..:
~'.. t... ::.
Figure 9. Lichen planus of vulva. Note the white patches which
can be mistaken for leukoplakia or more worrisome lesions (by
courtesy of Dr. Nicola Pimpinelli, Institute of Dermatology,
University of Florence).
HYPERTROPHIC LP
Features of hypertrophic LP are red-brown or violaceous
verrucous plaques which most often develop on the legs
(Fig, 10). Lesions may be isolated or multiple and
become confluent, covering the entire anterior tibial
area This variant is quite common among patients with
familial LP (Mahood, 1983).
VESICULOBULLOUS LP
Bulla formation in LP is unusual (except in LP pem-
phigoides) and may affect about 3 5% of patients
(Altman and Perry, 1961). One type of lesion is referred to
as bullous LP, where vesicles and bullae develop in direct
connection to previous areas or present patches of LB
Bullae appear tense, and Nikolsky's sign may be positive.
In these cases, biopsy usually reveals histological fea-
tures compatible with both LP and a subepithelial bulla.
MISCELLANEOUS CUTANEOUS LESIONS
These include a group of more rare patterns and forms that clin-
icians sometimes have difficulty recognizing and classifying:
Crit Rev Oral Biol Med99(l):86-122 (1998)

Figure 10. Hypertrophic lichen planus on the lower legs (by
courtesy of Dr. Nicola Pimpinelli, Institute of Dermotology,
University of Florence).
Annular LP characteristically involves the penis,
showing a papule that expands centrifugally.
Lichen planopilaris, more common in women, shows
a spinous pattern due to follicular involvement of hair-
bearing areas (Fig. II). When localized on the scalp, it
may cause alopecia.
Erythematous LP is seen as brightly erythematous,
soft papules which show the typical histologic features of
LP
LP pemnphigoides is an overlap syndrome in which
bullae develop on both lesional and non-lesional skin. It
is considered to be an association between LP and bul-
lous pemphigoid, although recent studies have demon-
strated that the antigens of LP pemphigoides may be dif-
ferent from those associated with classic bullous pem-
phigoid (Oomen et al., 1986; Okoki et al., 1990).
Histopathology shows features of LP, but direct immuno-
fluorescence demonstrates a linear deposition of IgG
and C3 similar to that usually observed in bullous pem-
phigoid. Occasional patients with LP pemphigoides have
lesions of the oral mucosa (Allen el al., 1987).
LP-lupus overlap syndrome is the coexistence of
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Crit Rev Oral Biol Med
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Figure 11. Lichen planopilarias. The disease involves the hair fol-
licles (by courtesy of Dr. Nicola Pimpinelli, Institute of
Dermatology, University of Florence).
both LP and lupus erythematosus. The clinical differenti-
ation from LP may be very difficult (Copeman et ul, 1979).
Familial LP develops in members of the same family
and is seen especially among sisters (Mahood, 1983, Lin
et al 1986). This form of LP may become generalized,
relapses are frequent, and, in about 40% of cases, lesions
appear before the age of 20 (Mahood, 1983)
Other forms include rare patterns such as pigmento-
sus, linear, exfoliative, guttate, and zosteriform LP
(Fellner, 1980; Harder and Kasha, 1990) Koebnerization
is a common occurrence in LP, especially in areas previ-
ously subjected to trauma such as burns, friction,
wounds, or UV light (Fig. 12).
Associations of OLP with Systemic Disease
In discussions of the association of OLP with systemic
diseases (Table 4), consideration must be given to some
possible confounding factors. First, OLP is relatively com-
mon. Thus, it is likely that a small percentage of patients
with OLP could coincidentally suffer from systemic dis-
ease not necessarily linked causally with LB Second, OLP
is seen predominantly in individuals over 50 years old,
and this also increases the chances of coincidental sys-
temic disease Third is the difficulty in the differential
diagnosis between oral LP and lichenoid reactions, and,
although these are probably separate nosological enti-
ties, it is almost impossible to distinguish them on mere
clinical examination and even sometimes histologically.
Because many different drugs (see Table 5) can be
involved in the pathogenesis of lichenoid reactions, some
reports of LP apparently associated with systemic disease
are likely to be due to drug side-effects rather than
specific associations with the systemic disease
Etiology
Virtually all diseases result from the interplay of host,
lifestyle, and environmental factors, and OLP is no
93
Oral Biol by on June 26, 2010
Med
93

Figure 12. Lichen planus of the lumbar region. The lesions
appear red-purple. The linear arrangement illustrates the
Koebner phenomenon (by courtesy of Dr. Nicola Pimpinelli,
Institute of Dermatology, University of Florence).
exception. Cell-mediated immunity appears to play a
major role in the pathogenesis of OLP, possibly initiated
by endogenous or exogenous factors in persons with a
genetic predisposition to the development of LP
In the induction phase, key events presumably
include the action of an endogenous or exogenous
agent(s)-such as contact sensitizers, drugs, or micro-
organisms-which binds to keratinocytes. Keratinocytes
then may act as 'signal transducers", capable of conver-
ting these stimuli into producing cytokines, adhesion
molecules, and chemotactic factors responsible for the
initiation of "antigen-independent" inflammation. This
phase may facilitate or promote an amplification or
effector phase with additional production of tumor-
necrosis factor alpha (TNF(x) and interferon gamma (IFN-
-y), and keratinocyte/T-cell/antigen-presenting dendritic
cell associations (Walsh et al, 1 990a,b; Barker et al., 1991)
The pathogenesis is discussed fully on page 100.
(1) GENETIC BACKGROUND
Studies have generally demonstrated only weak associa-
94
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TABLE 5
Drugs Causing Lichenoid Drug Reactions
Allopurinol Captopril Chloroquine
Chlorpropamide Dapsone Gold salts
Labetalol Mepacrine Methyldopa
NSAIDs Oxyprenolol Penicillamine
Phenothiazines Practolol Propranolol
Tetracycline Thiazides Tolbutamide
Triprolidine
After Scully and Cawson, 1 998
tions between HLA antigens and LP (Lowe et al., 1976b;
Saurat et al., 1977; Powell et al., 1986, With and Rostom,
1994), but in Chinese patients an increase in HLA-DR9
and Te 22 antigens has been noted (Lin et al., 1990) In
Caucasoids, there are no consistent class or 11 HLA
associations reported (Porter et al., 1993).
(2) DENTAL MATERIALS
Most patients with OLP have no evidence of any associ-
ation with dental restorative materials (Hietanen et al.,
1987). However, contact with or proximity to restorations
involving amalgams or other materials causes some
lichenoid reactions-that is to say, lesions that clinically
and histologically resemble LP closely, but have an iden-
tifiable etiology. These reactions are presumably due to
allergic or toxic reactions to compounds released or gen-
erated, the Koebner phenomenon, or possibly plaque
accumulated on the surfaces of the restorations
(Holmstrup, 1991)
Metal restorations
Some lesions resembling OLP may occur in direct rela-
tion to amalgam restorations (Lundstrom, 1984; Lind et
al., 1986; Bolewska et al., 1990a,b), and some of these oral
lesions may improve after substitution of the amalgam
by other materials (Finneetal., 1982; Jolly etal., 1986; Lind
et al., 1986; Bolewska et al 1990a,b; Jameson et al., 1990;
Skoglund and Egelrud, 1991; Laine et al., 1992; Bircher et
al., 1993; Skoglund, 1994, Henriksson etal., 1995, Smartet
al., 1995, Bratel et al., 1996; Ibbotson et al., 1996), though
this is often not the case with gingival lesions
(Henriksson et al., 1995)
Significant reactions to mercuric salts on skin-test-
ing may be seen in some patients with OLP (Finne et al.,
1982, Eversole and Ringer, 1984; Mobacken et al., 1984a;
lames et al., 1987; Ostman et al., 1994), though others
have not found this (Hietanen et al., 1987) Finne et al.
(1982) demonstrated mercury sensitivity by patch testing
in 62% of 29 patients with OLP and only 3.2% of a control
group, and oral lesions regressed in a few patients when
their amalgams were removed (Finne et al., 1982).
Reactions to mercuric chloride have been reported
(Skoglund and Egelrud, 1991; Smart et al., 1995). These
Crit Rev Oral Biol Med
9(1 ):86-122 (I 998)
findings have been supported, and recently, in studies by
Skoglund (1994), a patch test positivity against mercury
was found in 39.6% of 48 patients. Of those who had a
positive patch test to mercury, 94.7% showed regression
of lesions after removal of amalgams, but even 82.6% of
those who showed no reaction to mercury on patch test-
ing also showed regression after removal of amalgams.
Epicutaneous patch tests are of little prognostic value
(Skoglund, 1994; Ibbotson et al., 1996). Oral mucosal
lesions of lichenoid character might be associated not
with allergy to mercury, but with mechanical or galvanic
insults; their interpretation calls for intra-oral patch test-
ing (Axell et al., 1986).
Fryholm et al. (1969) suggested a reaction to the cop-
per in dental alloys among patients with OLP, and elec-
trogalvanic reactions have been implicated by others
(Banoczy et al., 1979; Holland, 1980). There may also be
occasional reactions to gold restorations (Conklin and
Blasberg, 1987), although this has not been substantia-
ted. There is also a report of OLP in relation to cobalt in
a restoration (Torresani et al., 1994).
Non-metallic restorations
Composite restorations have also been implicated in
oral lichenoid reactions (Lind, 1988), and so the whole-
sale replacement of amalgams as a possible treatment is
not necessarily warranted.
(3) DRUGS
The possible association of drugs with lesions similar to
LP was noted when quinacrine and mepacrine, used as
antimalarials during World War II, were seen to cause
lichenoid lesions (Schmitt et al., 1945; Savage, 1958).
Apart from these drugs, gold was probably the most
common agent recognized as initiating an LP-like erup-
tion (Penneys et al., 1974). Gold salts can cause a range of
mucocutaneous lesions (Hakala et al., 1986), of which
oral lichenoid lesions may be the first (Brown et al., 1993;
Laeijendecker and Van loost, 1994).
The drugs now most commonly implicated in OLP-
like lesions are the non-steroidal anti-inflammatory
drugs and the angiotensin-converting enzyme inhibitors
(Potts et al 1987, Firth and Reade, 1989; Robertson and
Wray, 1992; Van Dis and Parks, 1995). Other drugs known
to cause lichenoid eruptions include thiazides, diuretics,
penicillamine, beta-blockers, quinine and quinidine,
para-amino salicylic acid, phenothiazines, carba-
mazepine, allopurinol, lithium, lorazepam, ketoconazole,
streptomycin, isoniazid, metopromazine, levopromazine,
amiphenazole, pyrimethamine, levamisole, beta-block-
ing agents, cinnarizine, flunarizine, gold, cyanamide (cal-
cium carbamide), and many others (Table 5) (Shatin et al.,
1953; Groth, 1961; Baker et al., 1964; Dinsdale et al., 1966;
Roberts and Marks, 1981; Chau et al., 1984; Hogan et al.,
1985; Colvard et al., 1986; Markitziu et al., 1986; Torrelo et
9t9)1)86 122(1998)
1)-86-122 l 1998) Crit Rev Oral Biol
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at., 1990). Occasionally, there are reactions to multiple
drugs (Wiesenfeld et al., 1982). The list of drugs implica-
ted lengthens almost weekly and, interestingly, includes
a number of agents which have also been used in the
therapy of lichen planus, particularly dapsone
(Downham, 1978), levamisole (Kerby et al., 1980), tetracy-
cline (Fitzpatrick, 1963), and interferon (see below).
However, many of the reports claiming associations have
been single case reports, and many of the drugs impli-
cated in cutaneous lichenoid reactions have not been
shown to be associated with oral lesions.
Clinical identification of lichenoid drug reactions
has been based largely on subjective criteria.
Sometimes, there does seem to be a tendency for these
oral lesions to be unilateral (Lamey et al., 1995) and ero-
sive (Potts et al., 1987), but these features are by no
means invariable. Histology may help; lichenoid lesions
may have a more diffuse lymphocytic infiltrate and con-
tain eosinophils and plasma cells, and there may be
more colloid bodies than in classic LP, but there are no
specific features (Van den Haute et al., 1989), and
immunostaining is usually non-contributory, though
basal cell cytoplasmic antibodies may be found (Lamey
et at., 1995) albeit less reliably than in cutaneous drug
reactions (Van Joost, 1974; McOueen and Behan, 1982;
Gibson et al., 1986; Watanabe et al., 1991). The most reli-
able means to diagnose lichenoid reactions is if the reac-
tion remits with drug withdrawal and returns on re-chal-
lenge, but frequently this is not possible because of the
need for patient safety to be ensured.
Regarding drugs as causal agents of these reactions,
a number of questions remain. For example, why can the
same drug bring about different clinical manifestations?
How can quite different chemical structures coincide in
the clinical expression of their side-effects? and how can
some drugs belonging to the same family (such as as
antimalarials) both produce a lichenoid reaction and at
the same time find some use in the treatment of OLP
(Eisen, 1993a)?
(4) INFECTIOUS AGENTS
Oral LP has been suggested to be related to bacteria
such as a Gram-negative anaerobic bacillus (Jacob and
Helmbold, 1933) and spirochetes (Lehnhoff, 1948), but
this has not been confirmed (Postma, 1937; Fry and
Withers, 1969). Lichenoid reactions have been seen in
syphilis (Lochner and Pomeranz, 1974), chronic bladder
infection (Shelley and Shelley, 1989), and intestinal ame-
biasis (Wahba-Yahav, 1989), though in both latter cases
the lesions appeared to clear following metronidazole
treatment. Beneficial effects of plaque control in OLP
have been described (Erpenstein, 1985; Holmstrup et al.,
1990).
Several studies have shown an increased prevalence
of candida species-in both mycological and histologi-
95
95
 TABLE 6
LP: Associations with Liver Disease

Author (Year) Subjects Results

Rebora et al. (1 982) 37 non-erosive LP 13.5% of chronic active hepatitis
Rebora and Rongioletti (1 984) 44 non-erosive LP 1 1.3% of chronic active hepatitis
Powell (1 984) 3897 LP (retrospective) 1 .3% cirrhosis
Mobacken et a!.(1 984b,c) 54 oral LP (38 erosive) 2 cirrhosis* + 4 slightly abnormal liver tests
Korkij et al. (1984) 136 LP 12% liver disease**
Katz and Pisanty (1985) 15 oral erosive LP 2 slightly abnormal liver tests
Monk (1985) 55 LP 5.4% liver disease
Scully et al. (1984) 113 oral LP (25 erosive) 7.9% abnormal liver test
Ayala et al. (1986) 21 oral erosive LP 64.2% chronic liver disease
Cottoni etaI. (1988) 62 LP (39 mucous involvement) 25.8% chronic liver disease
GISED (1990) 577 LP Liver disease is a risk factor for LP
Gandolfo et al. (1992) 96 oral LP 24% liver disease
El Kabir et al. (1993) 180 oral LP 2.5% abnormal liver tests***
Bagan et al. (1994) 187 oral LP 21.39% abnormal liver tests
*1 primary biliary cirrhosis + 1 cryptogenic cirrhosis.
**Significantly higher than the control group.
***No significant difference from the control groups.

cal studies of OLP (Simon and Hornstein, 1980;
Lundstrom et al., 1984; Krogh et al., 1987a,b; Hatchuel et
al., 1990; Vincent et al., 1990)-and clinical improvement
may be seen with anti-fungal therapy (Silverman et al.,
1991; Eisen, 1993a). The involvement of viral agents in
OLP has been suggested (Scully and El-Kom, 1985).
Lichenoid lesions may be seen in HIV infection (Ficarra et
al., 1993). Human papillomaviruses (HPV) have been
found in lesions of LP (Maitland et al., 1987; Jontell et al.,
1990; Kashima et al., 1990), but any causal role remains
speculative. Viral antigens might be expressed on the
affected keratinocyte surface membrane, just as are the
human major histocompatibility antigens. The joint
observations that mucosal nerve fibers closely oppose
basal keratinocytes, and that keratinocyte expression of
receptors (CD2 1) for Epstein-Barr virus (EBV) is upregu-
lated in lesions of OLP, support the concept that low-
grade and/or persistent infection of epithelial cells with
herpesviruses may be a possible etiologic factor in LP
(Walsh et al., 1990a,b). Interestingly, humoral responses
to EBV appear to be altered in OLP (Pedersen, 1996).
The role of hepatitis viruses is discussed below.
(5) AUTOIMMUNITY
The possible contribution of autoreactivity to the patho-
genesis of OLP has been suggested on the basis of stud-
ies demonstrating changes in T-lymphocytes in the
peripheral blood, including a depressed number of CD4+
and CD45RA+ cells in OLP patients compared with age-
and sex-matched healthy controls (Voltz, 1989). These
results and those of others who found a reduced sponta-
neous proliferation of peripheral blood lymphocytes
from OLP patients, activity mediated by CD4+ and
CD45RA+ cells, suggest involvement of these cells
(Konttinen et al., 1989). OLP may occasionally be associ-
ated with autoimmune disorders, and, interestingly,
reduced CD4+ and CD45RA± cells have been reported in
some of these autoimmune disorders, possibly setting
off autoreactivity responses by an impaired cellular
immune system.
Chronic liver disease
Since the first report of five cases of erosive LP associa-
ted with severe liver disease (Rebora, 1981), several stud-
ies have suggested this possible relationship (Table 6).
The liver diseases that seem to be most strongly related
to OLP are chronic liver diseases, especially chronic
active hepatitis (CLD) and primary biliary cirrhosis (PBC).
Most cases of oral lichenoid lesions in PBC have been
associated with penicillamine treatment (Powell and
Rogers, 1981; Seehafer et al., 1981; Powell et al., 1982), but
some have not (Graham-Brown et al., 1982; Powell et al.,
1982; Oleaga et cil., 1995). Chronic active hepatitis, how-
ever, is the chronic liver disease (CLD) that does seem to
be associated with LP in certain circumstances.
The clinical presentation of OLP seems to be influ-
enced by the concomitant disease: the erosive form has
been reported as more commonly associated with CLD
(Bagan et al., 1992). The association, especially of the ero-
sive type of OLP, with chronic active hepatitis has been
suggested in papers dating as far back as 1978, which
were conducted on a small number of Italian patients

96 Grit Rev
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 TABLE 7
LP: Associations with Autoimmune Disease*

Disease Reference(s)
I I

Alopecia areata
Dermatitis herpetiformis
Dermatomyositis
Hashimoto's thyroiditis
Hyperthyroidism
Lupus erythematosus
Morphea
Myasthenia gravis
Pemphigus foliatus
Pemphigus vulgaris
Pernicious anaemia
Rheumatoid arthritis
Sj6gren's syndrome
Scieroderma
Vitiligo
*See Table 6 for liver disease.
GISED, 1991; Tan, 1974a,b; Brenner et al., 1979; Mann et a!., 1982; Shuttleworth et a/., 1986b
Bologa and Valda, 1971; Grupper et al., 1972
Tan, 1974a,b
Okoki et al., 1990
Cottoni etal., 1991, 1988
Davies et al., 1977; Van der Horst et al., 1983
Brenner et al., 1979; Connelly et al., 1985
Tan, 1972; Aronson et al., 1978; Miller, 1971; Samman, 1974
Neuman-Jensen et al., 1980
Neuman-Jensen et al., 1980; Lotem et al., 1989; Lee, 1987
Shultleworth et al., 1986; Rustin, 1986; Lundstr6m et al., 1982
Blasberg et al., 1984; Kaplan et al., 1995
Zijdenbos et al., 1985; Gart, 1994; Bermejo Fenoll and Lopez Jornet, 1991
Parodi et al., 1995; Brenner et al., 1979
Coltoni et al., 1988; Tan, 1974; Mann et al., 1982; Porter et al., 1994; Brenner et al., 1979

(Rebora et al., 1978). The results obtained from later
research carried out in southern Europeans, particularly
in Spain and Italy (Ayala et al., 1986; Cottoni et al., 1988;
del Olmo et al., 1989; GISED, 1990), and also in Japanese
(Nagao et al., 1995a) are consistent with this association,
but the situation appears to be different in Anglo-
Saxons: El-Kabir et al. (1993) did not find a significant
association between OLP and CLD in England, nor have
studies of American, Israeli, Scandinavian, and British
patients shown a high prevalence of liver disease in
patients with OLP (Powell et al., 1983; Mobacken et al.,
1984c; Scully et al., 1984; Wiles and Lynch, 1984; Katz and
Pisanty, 1985). Conversely, a study of a large number of
patients with chronic liver disease found only a very low
prevalence of LP (Golding et al., 1973).
In a comprehensive multicenter study carried out in
Italy (GISED, 1990), it was suggested that the clinical
observation that CLD is a risk factor for lichen planus,
although not a specific marker of it, suggested the
involvement of other hepatotropic viruses that are possi-
bly transmitted in a way similar to hepatitis viruses, such
as cytomegalovirus, or Epstein-Barr virus. However, there
is no evidence for this. In the above studies, hepatitis B
virus (HBV) was not examined, but it has been recently
stated that this could be a causal agent of LP-associated
liver disease (Pawlotsky et al., 1994), since several reports
have suggested a relationship between HBV and LP
(GISED, 1990; Rebora et al., 1992).
The association of LP with CLD has now been partly
explained following the identification of hepatitis C virus
(HCV) as the main cause of non-A, non-B hepatitis. HCV
may be associated with LP, at least in some countries of
southern Europe (Bagan et al., 1994; Gandolfo et al., 1994)
and in lapan (Nagao et al., 1995a). HCV viral sequences
have been found in the serum in patients with LP (Jubert
et al., 1994), and any of the three main HCV genotypes
may be implicated (Pawlotsky et al., 1995a,b). HCV-RNA was
found to be of high prevalence in a controlled study of 78
Spanish patients with erosive OLP (Sanchez-Perez et al.,
1996), and several other reports have shown associations
between HCV and LP (Bagan et al., 1994), on serological
grounds. LP has been diagnosed in up to 5% of patients
with HCV infection (Bagan et al., 1994), its onset can be
related to HCV acquisition (Mokni et al., 1991), and a
recent study indicated that up to 60% of OLP subjects
with abnormal liver tests may be HCV-seropositive
(Gandolfo et al., 1994). There is also a higher prevalence
of LP in patients with chronic HCV infection than in con-
trols (Pawlotsky et al., 1994), and, at least in some coun-
tries, patients with OLP often have HCV infection (Nagao
etal., 1995a).
Autoimmune CLD can be classified as classic
"lupoid" (type 1) hepatitis and that associated with anti-
bodies to liver-kidney microsomes (anti-LKM 1) as type 2,
young age at onset, likely to be female, and responding
favorably to immunosuppressive therapy. The finding by
Mishiro et al. (1990) of non-A, non-B hepatitis-specific
antibodies directed at a host-derived epitope (anti-GOR)
calls for reclassification of CLD. There appear to be two
sub-types of anti-LKM 1 chronic active hepatitis Subtype
2a has high-titer anti-LKMI but neither anti-HCV nor
anti-GOR antibodies; subtype 2b has low anti-LKM I
titers but high anti-GOR, and is HCV-associated,
responds poorly to immunosuppressive therapy, and is
seen mainly in older females (Michel et al., 1992).
Interestingly, about 80% of autoimmune hepatitis type 2

97
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in Italy is type 2b, and less than 10% is this type in
England, and thus interpretation of anti-HCV seroposi-
tivity depends not only on the test used and the patient's
clinical background, but also on geographic and/or
genetic factors (Lenzi et al., 199 1; Michel et al., 1992).
All of these considerations have contributed to a
new perspective on the autoimmune theory of LP
etiopathogenesis. However, the occurrence of anti-LKM I
antibodies in patients with LP is only occasional (Divano
et al., 1992), and CLD patients with LP show the same
prevalence of anti-GOR antibodies as CLD patients with-
out LP (Divano et al., 1994). On the contrary, LP exacer-
bations (Manns et al., 1991) and remissions (Boccia et al.,
1993) have been described in patients with LP and HCV
under interferon alpha therapy, and the association of LP
with HCV has not infrequently been found in patients
receiving alpha interferon (Cottoni et al., 1991; Mokni et
at., 1991; D'Agay-Abensour et al., 1992; Divano et al., 1992;
Protzer et al., 1993; Sassigneux et al., 1993; Strumia et al.,
1993; Miralles et al., 1994; Papini et al., 1994). On the other
hand, interferon has sometimes improved LP (Doutre et
al., 1992; Frider et al., 1995). Treatment of hepatitis C may
also improve OLP (Nagao et al., 1995b). Could the various
subtypes of autoimmune hepatitis type 2 account for
such a variable response to treatment with interferon?
If LP is the result of a stereotype cell-mediated reac-
tion to a variety of antigens, no doubt HCV is not the only
accountable infectious agent; other viral agents such as
HBV (Doutre et at., 1992) may play a role.
Other autoimmune diseases
Associations of LP with several different autoimmune
diseases have been documented (Boyd and Neldner,
1991) (Table 7). However, the HLA types such as HLA-D8,
or DR3, or DR4, typically seen in autoimmune disorders,
are not seen in LP. Furthermore, a study comparing more
than 50 LP patients with the same number of matched
subjects failed to reveal a significantly increased preva-
lence of autoimmune diseases in the study group
(Shuttleworth et al., 1986).
An LP-specific antigen (LPSA) in the granular or spi-
nous layer of cutaneous LP has been described (Olsen et
al., 1983), but while this may be present in up to 80% of
examined LP patients, it is inconsistently present (Olsen et
al., 1983). Circulating antibodies to LPSA are regarded as a
marker of the disease rather than as essential to the
pathogenesis of LP (Camisa et al., 1986). LPSA is infre-
quently detected in OLP tissue, although some patients
may have antibodies to LPSA (Camisa et al., 1986).
Recently, another autoantibody to keratinocytes of LP has
been described (Lin et al., 1991) but needs further study.
Many authors, reporting cases of concomitant LP
and well-recognized autoimmune diseases, have sug-
gested a common pathogenesis. However, with the
exception of one study that showed an epidemiological
98Gi.e rlBo
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correlation between alopecia areata and LP (GISED,
1991), this hypothesis has never been proved.
(6) IMMUNODEFICIENCIES
Cutaneous LP is more strongly associated with defects of
T-cell function such as thymoma (Tan, 1974a,b; Aronson
et al., 1978) or HIV (Ficarra et al., 1993; Berger and Dhar,
1994; Rippis et al., 1994; Fitzgerald et al., 1995) than it is
with humoral immunodeficiencies (Flaumenbaum et al.,
1982), though LP has been observed in hypogammaglob-
ulinemia (Tan, 1974). OLP may also be seen in HIV dis-
ease (Ficarra et al., 1993).
There is no consistent alteration in the serum levels
of immunogloblins in OLP. Decreased levels of IgM and
IgA (Stankler, 1975; Jacyk and Greenwood, 1978; Nigram
et al., 1987) and increased IgA and increased IgG
(Sklavounou et al., 1983) have been reported. However,
varied levels of IgA, IgG (Grupper et al., 1972; Jacyk and
Greenwood, 1978; Scully, 1982), IgM (Grupper et al., 1972;
Scully, 1982; Sklavounou et al., 1983), IgE (Scully, 1982),
and IgD (Scully, 1982) have been observed in LP, and
serum levels of complement components are normal
(Sklavounou et al., 1983), as is B2 microglobulin (Scully
and Boyle, 1982).
(7) FOOD ALLERGIES
A small minority of patients with OLP or lichenoid
lesions have been shown to react to certain foods (Eisen,
1993a) and some to food additives such as cinnamon-
aldehyde (Maibach, 1986; Allen and Blozis, 1988).
(8) STRESS
Stress has been widely held to be an important etiologi-
cal factor in OLP, but there have been remarkably few
studies (Lowenthal and Pisanti, 1984). Most studies have
not objectively examined the stress levels. In 1961,
Altman and Perry reported that, of 197 patients with LP,
"10% were aware of a precipitating stressful incident at
the onset of their LP" (Altman and Perry, 1961). The con-
comitance of LP, especially in its oral form, with situa-
tions of emotional stress or anxiety thus entered the lit-
erature. A statistically significant difference was indeed
found in the psychological profiles of patients affected
by OLP as compared with those of controls in one study
(Hampf et al., 1987), and others have found that patients
with OLP had a tendency to be depressed (Bergdahl et al.,
1995), but this association may be no more than anec-
dotal, since others have largely refuted this (Allen et al.,
1986; MacLeod, 1992; McCartan, 1995), though the anxi-
ety levels of patients may be raised (McCartan, 1995)
(Table 8).
The chronic discomfort that can afflict patients with
OLP can of course be itself a stressing factor and may
partially explain the cases in which this association has
been documented.
e ()612(98
9(l):86-122 (1998)
 TABLE 8
Studies of Psychogenic Basis for LP
Author (Year) Subjects Questionnaires
Allen et al. (1986) 48 Social readjustment scale
State-trait anxiety inventory
Hampf et al. (1987) 56 Cornell Medical Index
MacLeod (1992) 30 GHQ28
McCartan (1995) 50 HAD
Catell 16 PF
(9) HABITS
Although most patients with OLP show no increased
prevalence of cigarette smoking (Neumann-Jensen et al.,
1977), smoking has been suggested to be an etiological
factor in some Indian communities (Pindborg et al., 1972;
Murti et al 1986). Betel nut chewing is also more preva-
lent in Indian patients with OLP than in those without
(Pindborg et al 1972; Daftary et al., 1980).
(10) TRAuMA
Trauma as such has not been quoted as an etiological
factor in lichen planus, although it may be the mecha-
nism by which other etiological factors exert their effects.
( 11) DIABETES AND HYPERTENSION
Another well-investigated association of LP is that
with diabetes mellitus (Table 9). Some authors have
reported impaired glucose metabolism in a high per-
centage of OLP patients (Lundstrom, 1983), but these
results have not been confirmed by others (see Table 9),
and in any event, it is now widely recognized that
impaired glucose tolerance is not synonymous with dia-
betes. Indeed, several studies have now shown only low
prevalences of OLP in large groups of diabetic subjects
(Borghelli et al., 1993; Lozada-Nur et al., 1985; Albrecht et
al., 1992; Van Dis and Parks, 1995), such that the sug-
gested association may be only coincidental or caused
by anti-diabetic or other drugs. Nevertheless, in diabet-
ics with OLP, there may be a higher prevalence of lingual
involvement and of erosive lesions (Bagan et al., 1993).
Blood pressure, when evaluated in LP, appears as an
independent variable with no significant correlation
found (Chattopadhyay, 1992; Christensen et al., 1997a),
despite suggestions to the contrary. Grinspan described
seven cases of OLP associated with diabetes and hyper-
tension (Grinspan et al, 1966), a triad which became
known as Grinspan's syndrome. This is still seen but is
probably a coincidental combination of the three com-
mon disorders or may be a lichenoid reaction provoked
by the drugs used to control diabetes or hypertension
(Lamey et al., 1990).
9(1):86-122
9(1) 86-12) (1998)
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Results
No significant differences between cases and control
LP patients statistically more mentally disturbed than controls
No significant differences between cases and controls
Anxiety raised in 50%. No depression.
(12) MALIGNANT NEOPLASMS
Lichenoid lesions have been observed on the skin and/or
mucosae of patients affected by a range of different neo-
plasms. The clinical presentation of LP associated with
malignancies most commonly seems to be the bullous
type, sometimes lichen planus-pemphigoides, and on
some occasions it can clinically mimic paraneoplastic
pemphigus. LP has been reported in patients with breast
cancer (Choudhary et al, 1988), metastatic adenocarcino-
ma (Helm et al., 1994), retroperitoneal sarcoma (Helm et
al., 1994), stomach cancer (Okoki et al., 1990), thymoma
(Tan, 1974a,b; Aronson et al., 1978; Flamenbaum et al.,
1982; Cottoni et al., 1988; Helm et al 1994), Castleman's
tumor (Ashinoff et al., 1989; Jansen et al., 1995), cranio-
pharyngioma (Magnusson, 1967), pituitary adenoma
(Magnusson, 1967), and non-Hodgkin's lymphoma
(Feuerman and Sandbank, 1971; Helm et al., 1994).
(13) BOWEL DISEASE
The association between ulcerative colitis and LP, report-
ed in many papers (Lundstrom et al, 1982; Cusano and
Errico, 1984; Cox et al., 1986; Cottoni et al., 1988; Dhawan
and Fields, 1989) has been documented as "epidemio-
logically evident" by a multicenter case-control survey
(GISED, 1991). Other bowel diseases occasionally
described concomitant with LP include coeliac disease
(Lundstrom et al., 1982; Fortune and Buchanan, 1993)
and Crohn's disease (Kano et al., 1995), though others
have not found these associations (Scully et al., 1993).
(14) MISCELLANEOUS ASSOCIATIONS
LP has occasionally been associated with other condi-
tions, including psoriasis (Shiohara et al., 1989; Naldi et
al., 1990; Delaney et al., 1993), lichen sclerosis (Marren et
al., 1994), urolithiasis (Halevy and Feuerman, 1983),
agents used to treat gallstones (Ellul et al., 1992), mesan-
gioproliferative glomerulonephritis (Cottoni et al., 1988),
erythema dyschromicum (Berger et al., 1989), and Turner's
syndrome with endocrinopathies (Kurgansky and
Burnett, 1994).
A number of studies have failed to demonstrate any
99
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99
 TABLE 9
Prevalence of Carbohydrate Metabolism Abnormalities among Patients with LP
Authors (year) Country Lichen No. Percent with Methods
Planus of Abnormality in of
Site Patients Carbohydrate Detection
Metabolism
Jolly (1972) Australia Oral 33 85 OGTTa
Powell et al. (1974) England Cutaneous/oral 21 62 OGTT
Lowe et al. (1 976a) England Cutaneous/oral 40 42 OGTT
Christensen et al. (1 997b) Denmark Oral 123 14.6 FPGb/OGTT
Bussel etal. (1979) England Oral 47 12.8 OGTT
Lacy et al. (1983) Australia Oral 108 6 History
Lundstr6m (1983) Scandinavia Oral 40 28 OGTT
Lozada-Nur et al. (1985) United States Oral 99 3 FPG
Silverman et al. (1985) United States Oral 570 5.8 FPG
Nigam et al. (1987) India Cutaneous/oral 56 30.3 OGTT
Chattopachyay (1992) India Oral 192 Same as controls FPG
0OGTT = oral glucose tolerance test.
bFPG = fasting plasma glucose.

obvious association between deficiency states and
lichen planus, and, although folly and Nobile (1977)
claimed a therapeutic benefit from replacement therapy
with vitamins B1, B6,and C, this has yet to be confirmed.
Pathogenesis
There are extensive data to suggest that immunological
mechanisms, mainly cellular, are fundamental to the
pathogenesis of lichen planus. Epidermotropic, MHC-
specific, autoreactive T-cells can produce a histopatho-
logical picture indistinguishable from that of LP when
injected into the footpads of syngeneic mice (Saito et al.,
1986), and patients with chronic graft-vs.-host disease
may develop cutaneous and oral lesions clinically and
histopathologically similar to those of LP (Farmer, 1986;
Boyd and Neldner, 1991). Finally, therapies that suppress
cell-mediated immunity, e.g., cyclosporin (Mozzanica et
al., 1991) and etretinate (Simon, 1990; Simon and
Hunyadi, 1990), both reduce the lymphocyte infiltrate
and induce clinical improvement. A lymphocytic
immunological reaction against the epithelial basal cells
is the mechanism responsible (Nickoloff et al., 1987;
Walsh et al., 1990a,b), but the responsible antigen is as
yet unidentified.
There are structural alterations reported in LP in the
epithelial basement membrane (Peng et al., 1986), extra-
cellular matrix proteins and integrins (Becker and
Schuppan, 1995), and in basal keratinocyte cytoplasm
(Lamey et al., 1995), cytokeratin (Boisnic et al., 1995), and
nuclear (Parodi and Cardo, 1990) antigens. It is assumed
that an antigenic modification of the cellular surface trig-
gers a tissue reaction, via the dendritic antigen-presen-
ting cells in the epithelium and mesenchyme, in which
CD4+ T-lymphocytes play a pivotal role. Indeed, these
lymphocytes are the main component of the inflamma-
tory infiltrate so clearly observed in early lesions of LP,
with long-standing lesions containing a greater number
of CD8+ T-lymphocytes (Matthews et al., 1984; Kilpi, 1987;
Sugerman et al., 1994). The lesional lymphocytic infiltrate
in LP is comprised principally of T-cells, including CD4+
and CD8+ lymphocytes (Bhan et al., 1981; De Panfilis et al.,
1983; Buechner, 1984; Matthews et al., 1984; Ishii, 1987;
Takeuchi et al., 1988; Walsh et al., 1990a,b; Akasu et al.,
1993; Robertson and Wray, 1993; Eversole et al., 1994).
There may be a gradual CD8+ accumulation with disease
progression, and there is also a variation in the distribu-
tion of T-cells within the lesions, the majority of intra-
epithelial T-cells being CD8+ and the proportion of CD8+
being higher in the superficial than in the deep lamina
propria (Kilpi, 1987; Jungell et al., 1989).
Immunohistochemical studies indicate that activated T-
cells (e.g., expressing HLA-DR) can lie close to the dam-
aged epithelial basement membrane (Eversole et al.,
1994) and sometimes close to areas of epithelial erosion
(Gabriel et at., 1985; Kilpi, 1987). The majority of T-lym-
phocytes within the epithelium itself express the cx3 T-cell
receptor (TCR) and are memory T-cells; a small proportion
of the infiltrating T-cells express the ct TCR (Walsh et al.,
1990a,b), and in addition, the majority of isolated clones
display suppressor activity, although clones with substan-
tial helper activity may also be present (Gadenne et al.,
1994; Sugerman et al., 1994). T-cell lines from lesional skin
are predominantly CD8+, and they are commonly V 1 J I-a
population not normally found in healthy skin or mature

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peripheral lymphoid tissue (Michie et al., 1989; Dupuy et
al., 1990; Alaibacetal., 1992).
The increased frequency in OLP lesions of T-cells
expressing T-cell receptors Va2 and Vb3 suggests a reac-
tion to some unidentified superantigen (Simark-
Mattsson et al., 1994). Cytokines such as tumor necrosis
factor-alpha (TNF) are expressed in the epithelium in
OLP and may be important in pathogenesis (Sugerman et
al., 1996). The lesional lymphocytes in LP express several
cytokines such as interleukin-2, TNF, and interferon
alpha, which induce not only the expression of HLA-DR
on the basal keratinocytes (Walsh et al., 1990a,b; Farthing
et al., 1992) but also the activation of dendritic cells
(Pitigala-Arachchi et al., 1989), including Langerhans cells
(Farthing et al., 1990; Walsh et al., 1990a,b), and attract
more lymphocytes. There are some differences in these
changes between those seen in drug-induced lichenoid
lesions and in idiopathic LP. In idiopathic LP, Langerhans
cells are MHC class-Il-positive, but this expression is
reduced in drug-induced lesions; and only in idiopathic
LP are CD25+ cells (presumed to be activated
Langerhans cells) seen (Walsh et al., 1990a,b). The role of
dendritic cells that express CD3 and CD45RA but not CD 1
antigens is unclear (Walsh et al., 1990a,b). Other mole-
cules, like heat shock protein (Sugerman et al., 1995), may
be expressed in OLP, and intercellular adhesion mole-
cule-I (ICAM-1) and vascular cell adhesion molecule-l
(VCAM-I) may also be expressed (Konter et al., 1990;
Walton et al., 1994) under the influence of interferon-
gamma and facilitate the lymphocyte-to-keratinocyte
adherence which determines keratinocyte cell death by
apoptosis (Wantzin et al., 1988). The hallmark result of
this immunological process is vacuolar degeneration,
lysis of basal epithelial cells, and, ultimately, liquefac-
tion of the basal cell layer. In classic LP lesions, an
intense band-like infiltrate of lymphocytes obliterates
the interface between epithelium and lamina propria.
Apoptosis of keratinocytes leads to the formation of
Civatte bodies. The keratin layer may thicken, and an
increased granular layer is found.
Defects in peripheral blood and lesional lympho-
cytes of patients with LP have been described, though
their precise etiological significance is unclear.
Spontaneous lymphocyte proliferation may be reduced
(Konttinen et al., 1989; Malmstrc5m et al., 1989), possibly
due to a reduction in circulating nafve CD4+ cells
(CD4+CD45RA+) and an increase in CD4+CD45RO+ and
CD29+ (putative memory) cells (Walsh et al., 1989), the
latter perhaps reflecting a change in lymphocyte recircu-
lation caused by pre-activation in vivo. Mitogen-stimula-
ted lymphocyte proliferation may also be impaired
(Karagouni et al., 1994; Yamamoto et al., 1994) in some
but not all examined patients. In addition, the produc-
tion of some cytokines (e.g., TNF-cx, interleukin-2, inter-
feron-ox, and interleukin-6) but not all (e.g., interleukin-I
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3 and lymphotoxin) by mitogen lphytohemagglutinin
(PHA)l-stimulated peripheral blood lymphocytes can be
reduced in LP (Karagouni et al., 1994). Reduced cytokine
production by the lymphocytes may be corrected with
PHA and phorbol myristate acetate (PMA) but not
PMA+Interleukin-2 (IL-2), indicating that any defect in
cytokine production is due to T-cell hyporesponsiveness
rather than numerical differences or deletions of T-cell
subsets, such as the reduced CD4+ (Walsh et al., 1990a)
or increased CD8+ lymphocytes (Yamamoto et al., 1990),
as occasionally found in LP. Serum levels of tumor necro-
sis factor alpha (TNF-cx), IL-4, and IL-6 may be elevated
(Yamamoto et al., 1991; Karagouni et al., 1994), reflecting
the chronic inflammatory nature of LP, the TNF-cx being
produced by activated T-cells, macrophages, and mast
cells (Jontell et al., 1986).
The current evidence thus suggests that there may
be an increased suppressor T-cell activity within the LP
lymphocyte infiltrate, that there may be an imbalance
between T-help and T-suppressor activity, and that per-
haps this is a fundamental determinant of the immuno-
logical activity of this infiltrate. Nevertheless, care must
be taken in extrapolating from these in vitro data, since
analysis of cloned T-cells may not reflect the complete
spectrum of immunoregulatory interactions between
lymphocyte subpopulations in the lesional infiltrate
(Reinhold et al., 1990; Sugerman et al., 1994). In addition,
the data on the T-cell lines are limited.
T-lymphocytes of LP tissue generate increased levels
of interleukin-6 (IL-6) and granulocyte-macrophage
colony-stimulating factor (GM-CSF) and can be stimula-
ted to produce more TNF-ox by IL-13, IL-6, and GM-CSF,
more IL-6 by IL-1I3 and GM-CSF, and more GM-CSF by
IL-1r and IL-6 than do peripheral blood mononuclear
cells (Yamamoto et al., 1994), suggesting that local
cytokine production may be important in the perpetua-
tion of LB.
In vitro studies indicate that keratinocytes from OLP
produce interferon-gamma (IFN), IL-6, and TNF-x in
response to IL-13, lipopolysaccharide, and PMA. This
potential of keratinocytes to produce large amounts of
cytokines could result in the activation of the infiltrating
T-cells and the proliferation of B-lymphocytes. The pro-
duction of GM-CSF may account for the early infiltration
of monocytes and macrophages into the lesions, though
the fact that the chemotactic activity of agents produced
by LP keratinocytes is not notably influenced by anti-
macrophage colony-stimulating factor antibody (anti-M-
CSF), and is only partially reduced by anti-GM-CSF anti-
body, suggests that chemotactic agents other than GM-
CSF are generated (Yamamoto et al., 1994).
While the keratins produced by keratinocytes of LP
are not perhaps notably influenced by the inflammatory
infiltrate (Maeda et al., 1994), keratinocytes are clearly
affected, since the expression of MHC class II antigens,
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101
calcium-binding surface antigen 27E10, and ICAM (see
below) is increased (Kunz et al., 1992), particularly in
areas adjacent to the inflammatory infiltrate in the lami-
na propria.
The numbers of Langerhans cells may be normal in
the LP lesions (Sloberg et al., 1984; Farthing et al., 1990) or
increased (Bhan et al., 1981; Tosca et al., 1983; Regezi et al.,
1985; Pitigala-Arachchi et al., 1989; Rich and Reade, 1989;
Akasu et al., 1993). These cells may be more dendritic,
suggesting an increased surface antigen expression or
elevated dendritic growth, and there is a significant
increase in HLA-DP and HLA-DQ (Farthing et al., 1990)
and perhaps HLA-DR expression (Sloberg et al., 1984),
possibly induced by local cytokine production.
Macrophage-related factor Xllla-positive dendrocytes
(morphologically and phenotypically distinct from
Langerhans cells) are also significantly increased in
number and size in LP (Akasu et al., 1993; Regezi et al.,
1994).
Intercellular adhesion molecule 1 (ICAM-1; CD54)-
a member of the immunoglobulin superfamily of adhe-
sion molecules-is important in the binding and
transendothelial migration of leukocytes toward sites of
inflammation, by virtue of its binding lymphocyte func-
tion antigen 1 (LFA- I,CD I Ia/CD 18, present on all circu-
lating lymphocytes) and MAC-1 (CDI lb/CD18) on
myeloid cells and some lymphoid cells. ICAM-l is pres-
ent on the endothelium of blood vessels of normal and
LP-involved oral mucosa (Walton et al., 1994), but there is
often increased expression on basal and parabasal ker-
atinocytes, intra-epithelial Langerhans cells,
macrophages, and CD4+ and CD8+ lymphocytes within
the lamina propria in LP (Simon and Hunyadi, 1990;
Eversole et al., 1994; Walton et al., 1994). While increased
keratinocyte ICAM-1 expression is not always present
(Walsh et al., 1990a; Verdickt et al., 1992), elevation of
ICAM-1 expression on keratinocytes may correlate with
sites of T-cell infiltration into the epithelium (Griffiths et
al., 1989a; Konter et al., 1991; Boehncke et al., 1992) and be
induced by IFN-y or TNF.
Lymphocyte function antigen-I (LFA-1) expression
on CD4+ and CD8+ lymphocytes is increased in LP, being
most prominent on those lymphocytes impinging on the
epithelio-mesenchymal junction (Ohta et al., 1992). LFA-
3, a major signaling molecule for T-cell activation, is also
increased in OLP (Kirby et al., 1995). It is thus possible
that increased expression of ICAM-1 together with ele-
vated LFA-1 and LFA-3 levels facilitates the local accu-
mulation of T-cells in LP.
Increased endothelial expression of vascular cell
adhesion molecule- I (VCAM- 1; CD 106), another member
of the immunoglobulin superfamily, may also be seen in
LP. In cutaneous LP, there is elevated VCAM- 1 expression
consistently observed on vascular endothelium associa-
ted with the inflammatory infiltrate (Groves et al., 1993),
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but in OLP there is inconsistent VCAM-1 expression,
VCAM-1-positive blood vessels being adjacent to, rather
than within, the area of inflammatory infiltrate (Walton et
at., 1994).
Recent studies indicate that laminin and types IV
and VII collagen extracellular matrix are significantly
increased at the epithelio-mesenchymal junction in OLP
and thus may bind to B! integrins on the surfaces of infil-
trating lymphocytes (Eversole et al., 1994). In addition,
fibrinogen is deposited at the basement membrane zone
and adjacent areas of lymphocyte accumulation
(Eversole et at., 1994), although fibrinogen-binding integ-
rins (CDI Ic and CD61), normally found on platelets and
B-lymphocytes, are only faintly expressed (Eversole et al.,
1994).
The above data certainly indicate that there are a
number of mechanisms at work that encourage the local
accumulation of leukocytes, in particular lymphocytes, at
sites of LP. In particular, ICAM-1 expression by ker-
atinocytes will induce T-cell adherence via LFA-1.
Interaction of MHC class II antigens with the T-cell recep-
tor (TCR) may activate T-cells. Expression of ICAM-l and
MHC class II antigens may then be increased by local
cytokine production. Nevertheless, the precise trigger for
these immunological events remains unclear.
Thus, in lesional tissue, the local infiltrate consists
predominantly of activated T-lymphocytes, and local
expression of cytokines and altered adhesion molecule is
increased (see below). There is currently little consistent
evidence that humoral immune mechanisms are impli-
cated in the development of lichen planus. Within
lesional and perilesional tissue, there is no consistent or
pathognomonic deposition of immunoglobulins, fibrino-
gen, or complement components. IgM may be present at
the basement membrane zone in a minority of examined
lesions (Baart de la Faille-Kuyper and Baart de la Faille,
1974; Konrad et al., 1979; Mora et al., 1983) and fibrin and
fibrinogen (Baart de la Faille-Kuyper and Baart de la
Faille, 1974; Konrad et al., 1979; Schi0dt et al., 1981), and
C3, C4, and C5 may be present at the BMZ (Schi0dt et al.,
1981). IgM, C3, and C4 are found in colloid bodies (Baart
de la Faille-Kuyper and Baart de la Faille, 1974), and IgA,
IgG, Cl, and C5 may be occasionally present (Konrad et
al., 1979; Mora et al., 1983). Autoantibodies are rarely
found.
Management of Lichen Planus
DIAGNOSIS
LP must be differentiated from lichenoid lesions, leuko-
plakias, and diseases such as lupus erythematosus and
overlap syndromes (Scully and El-Kom, 1985), lichen
sclerosus and overlap syndromes (MacLeod and
Soames, 1991; Marren et al., 1994), and chronic ulcerative
stomatitis (Jarenko et al., 1990; Beutner et al., 1991;
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Church and Schlosser, 1992), disorders that particu- TABLE 10
larly may clinically and histologically resemble LP,
and malignancy must be excluded. The history and Empirical Treatments for Oral Lichen Planus
lesions in other sites may assist the diagnosis if that
is not clinically clear. Anti-microbials Drugs
The characteristic clinical aspects of OLP may be
sufficient to make a correct diagnosis if there are Antibiotics Doxycycline
classic skin lesions, but oral biopsy examination Anti-fungals Azoles
with histopathologic and immunofluorescent stud- Polyenes
ies confirms or helps make a diagnosis in problem- Griseofulvin
atic cases and helps exclude malignancy. The Anti-malarials Dapsone
histopathologic criteria used are usually hyperortho- Hydroxychloroquine
or hyperparakeratosis, degenerative changes to the Anti-virals Interferon beta
basal cells, and a band-like subepithelial infiltrate Immunomodulators
composed of lymphocytes and histiocytes. Corticosteroids Topical: Betamethasone
Histologically, the principal feature of OLP is the Clobetasol
dense band-like lymphocytic infiltration of the Fluocinonide
superficial stroma and basement membrane zone Hydrocortisone
associated with liquefactive degeneration of basal Triamcinolone
epithelial cells. Another feature is the presence of Intra-lesional: Dexamethasone
Civatte bodies (hyaline bodies, colloid bodies, Hydrocortisone
cytoid bodies), which are dyskeratotic basal ker- Methyl prednisolone
atinocytes that have undergone premature kera- Triamcinolone
tinization and have been extruded into the papillary Systemic: Prednisolone
mesenchyme. Plasma cells and melanophages Cytotoxics Azathioprine
Hormones ACTH
sometimes are also present (Ellis, 1967). Immunostimulants Levamisole
Immunopathological alterations appear neither spe- Immunosuppressants Cyclosporin
cific nor exclusive to LP, though they can help Phenytoin
exclude other disorders. In LP, direct immunofluo-
rescence shows fibrin and fibrinogen in a linear pat- Retinoids
tern at the basal membrane zone in a high number of Etretinate
lesions. IgM and complement components, princi- Iso-tretinoin
pally C3, C4, and C5, have also been observed, and Temarotene
colloid bodies stain positively to IgM, C3, and C4 Fenretinide
(Konrad et al., 1979; Daniels and Quadra-White, 1981; Surgery
Schi0dt et al., 1981; Laskaris et al., 1982; Van Hale and Conventional
Cryosurgery
Rogers, 1987; Eversole, 1994). However, it is impor- Laser surgery
tant to stress that these findings when combined Grafting
with histopathology are only highly suggestive, and UV radiation
not diagnostic, of LP. UV light
When lichen planus occurs on the gingiva and PUVA
no other mucosal or cutaneous site (Vincent et al.,
1990), the diagnosis can be especially difficult.
Keratotic lesions of gingival lichen planus may Therefore, a biopsy is usually required for a defini-
sometimes be confused with keratosis or leukoplaki tive diagnosis, and immunofluorescence may be useful
especially when in a plaque form. The differential dia to make a distinction between diseases. Biopsies from
nosis of lesions presenting with desquamative gingivit gingival and buccal mucosal LP show similar pathology
alone is often more difficult. Many cases are caused 1 at each site, the only difference being the presence of
LP, but pemphigoid, pemphigus, dermatitis herpel HLA-DP expression by keratinocytes in the gingiva
formis, linear IgA disease, lupus erythematosus, ar (Walsh et al., 1990a). The reason for this, according to the
other conditions must be excluded, and sometimes authors, is the presence of pre-existing or superimposed
similar appearance may be seen in allergic or oth gingival inflammation. Therefore, while it may be easier
abnormal responses and chronic infections such as ca to biopsy the gingiva, biopsies of gingival lesions are not
didosis (Nisengard and Rogers, 1987; Porter et al., 199 always diagnostic, because the histopathologic features
1992) of lichen planus may be altered by a non-specific gin-

103
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 Diagnosis
- history
- drug history
- medical history
- clinical evaluation
- histology (HE, PAS)
- immunohistochemistry (IF); liver function tests; exclude diabetes
Improve oral hygiene
Symptomatic Asymptomatic
Consider amalgam removal Reassurance only
Candidosis No candidosis
I
Mild symptoms Severe symptoms Mild symptoms Severe symptoms
I I I
Topical steroid Burst systemic Topical steroid Burst systemic ancd
(Triamcinolone (Prednisolone and topical steroi(
or fluocinonide) 1 0 mg qid)
Antimycotic Topical steroid
(Nystatin or and antimycotic
amphotericin)
Ulcers resistant to healing
Symptomatic Symptomatic Symptomatic Intralesional Symptomatic
maintenance maintenance maintenance steroid injection maintenance
Topical and/or therapy therapy therapy
Antimycotic Topical and/or Topical only
Antimycotic
Figure 13. Algorithm for the management of oral lichen planus. Adapted from Oliver and Winkelman (1 993). HE = hematoxylin and eosin. PAS
= perodic-acid-Schiff.

givitis (Vincent et al., 1990). Where possible, therefore, it
is better to biopsy non-gingival lesions.
TREATMENTS IN ORAL LICHEN PLANUS
In general terms, non-erosive lichen planus is asympto-
matic, and, in the absence of soreness, treatment is often
not warranted, since none of the available treatments is
specific or universally successful, and all can have
adverse effects. Patients with erosive lichen planus, how-
ever, often present significant management problems,
and the need to reduce morbidity perpetuates a contin-
uing search for novel therapies. A vast array of empirical
treatments has been reported in the literature (Table 10),
indicative of the continuing search for a solution.
An approach to therapy, based on the evidence from
reported studies, is suggested in Fig. 13 (based on Oliver
and Winkelman, 1993). When atrophic or ulcerative/ero-
sive lesions are present, there are particular problems,
because toothbrushing may be complicated by gingival
pain and bleeding (Holmstrup et al., 1990). This situation
frequently results in the accumulation of dental plaque,
which may adversely influence the course of OLP.
Oral hygiene procedures in OLP patients must be
effective but gentle. Intensive oral hygiene procedures
may produce subjective and objective improvement of
the lesions (Erpenstein, 1985; Holmstrup et al., 1990) and
can also eliminate Candida from most lesions
(Holmstrup et al., 1990).
Attention should then be paid to the possibility of
dental restorations inducing the lesions, since they may
sometimes improve after replacement of amalgam with
other restorative materials (Bolewska et at., 1990a,b;
Skoglund and Egelrud, 1991; Smart et al., 1995; Ibbotson
etal., 1996).
The Koebner phenomenon, or isomorphic response,
is a common feature in lichen planus, characterized by
the occurrence of LP changes in areas subjected to trau-
ma (Stankler and Ewan, 1974; Boyd and Neldner, 1990).
Almost any type of irritant may provoke a Koebner reac-
tion (Voute, 1994). Mechanical trauma or irritants such
as sharp filling margins or rough surfaces are often pre-
sent in patients with OLP (Erpenstein, 1985) and should
therefore receive attention.
There is an increased prevalence of candidal carriage
and infection among patients with OLP, and the corti-
costeroids and other immunomodulators used in thera-

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py predispose to candidosis; furthermore, symptoms
may be exacerbated by candidal overgrowth or infection.
Anti-fungal therapy is thus often helpful adjunctive ther-
apy. Anti-fungal treatment of erosive lesions from which
Candida had been isolated by culture often changes the
lesions to reticular lesions (Dreyer, 1983; Lacy et al., 1983;
Hatchuel et al., 1990). A further theoretical support for the
use of antimycotic treatment in some cases of OLP is the
potential of Candida albicans to produce carcinogenic N-
nitrosobenzylmethylamine (Krogh et al., 1987a,b). The
improvements can be achieved with either polyene or
azole antifungals (Lacy et al., 1983; Eisen, 1993a; Vincent
et al., 1990).
Griseofulvin has also been used empirically (Sehgal
et al, 1972; Massa and Rogers, 1981; Aufdemorte et al.,
1983; Lamey et al., 1987; Araujo et al., 1990), but others
have not found significant benefit (Bagan et al., 1985;
Matthews and Scully, 1992; Naylor, 1990), and the
adverse effects may preclude the use of griseofulvin.
The main empirical treatments for OLP, shown in
Table 10, are mainly immunosuppressive and include
particularly the topical corticosteroids in various forms
(Mumford and Morgan, 1956; Kovesi and Banoczy, 1973;
Randell and Cohen, 1974; Tyldesley and Harding, 1977;
Greenspan et al., 1978; Silverman et al., 1985a),
cyclosporin (Eisen et al., 1990a,b; Ho et al., 1990; Ho and
Conklin, 1991), vitamin A analogues (Gunther, 1973;
Sloberg et al., 1979, 1983; Hersle et al., 1982; Ferguson et
al., 1984; Handler, 1984; Stans and Bergfeld, 1984;
Zegarelli, 1984; Woo, 1985), and hydroxychloroquine
(Eisen, 1993b). However, all of these drugs can have side-
effects, not all have been reliably effective, and recurrences
of the lesions are common after the cessation of therapy.
Therefore, the need for better alternatives is obvious.
Corticosteroids
Corticosteroids are the mainstay of treatment of OLP
(Vincent et al., 1990). Topical hydrocortisone can some-
times be of benefit, although triamcinolone topically is a
much more widely used remedy either as a paste or a
lozenge (Rushton, 1962; Zegarelli et at., 1969). An oral
suspension of triamcinolone has also been used recent-
ly with beneficial effect (Vincent et al., 1990) as it has in
polyhydroxybutyrate or polylactic acid (Deasy et at.,
1989). Betamethasone valerate pellets (Cawson, 1968) or
aerosol (Tyldesley and Harding, 1977) is also effective, as
confirmed in a double-blind study of 19 patients
(Greenspan et al., 1978). Corticosteroids of this potency,
used for several weeks, appear to produce no significant
adrenal suppression (Plemons et al., 1990), despite some
concern (Beckman, 1981).
Recently, more potent fluorinated steroids have
been examined for their usefulness in OLP. Fluocinonide
(fluocinolone acetonide), 0.05% to 0.1%, is effective in a
paste form (Lozada and Silverman, 1980; Silverman et al.,
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1991) and has been independently shown to be effective
in another recent double-blind placebo-controlled study
(Voute et al., 1993). Fluocinonide 0. 1% in a carboxymethyl
cellulose base has been shown to be more effective than
a similar triamcinolone acetonide preparation (Roed-
Petersen and Roed-Petersen, 1992; Thongprasom et al.,
1992), though candidosis may complicate this treatment
(Thongprasom et al., 1992). Fluocinonide has thus
become the first-line treatment for many practitioners
involved in the management of OLP (Plemons et al.,
1990).
Clobetasol propionate has also been shown to be
effective in OLP (Conklin and Blasberg, 1987; Lozada-Nur
et al., 1994). A recent double-blind clinical trial of clobetasol
propionate in 60 patients indicated that clobetasol was
more effective at controlling lesions than fluocinonide,
but candidosis was observed in 13 of 55 patients (Lozada-
Nuretal., 1994).
For intransigent erosive lesions, intra-lesional
steroids can be effective. Intra-lesional injections may be
with hydrocortisone (Sallay, 1969), dexamethasone
(Randell and Cohen, 1974), triamcinolone acetonide
(Weidan, 1963; Sleeper, 1967; Zegarelli, 1980), or methyl
prednisolone (Ferguson, 1977; Zegarelli, 1983). The
injections can be extremely effective at inducing the
healing of lesions but have a very localized effect, involve
the use of systemic medication, and are operator-inten-
sive.
For recalcitrant lesions, systemic corticosteroids, if
given in sufficient doses, will control the majority of
cases of erosive OLP. Cortisone (Hopkins et al., 1952;
Mumford and Morgan, 1956), prednisolone, prednisone
(Vincent et al., 1990), or methyl prednisolone (Snyder et
al., 1982) is used. Systemic adverse effects are common,
however, with the use of systemic corticosteroids, even
with short courses of just two weeks (Lozada et al., 1984),
and, interestingly, a greater level of symptom control was
achieved in one study with topical corticosteroids than
with systemic corticosteroids or a combination of the
two (Silverman et al., 1991).
Adrenocorticotrophic hormone has been used as an
alternative to systemic corticosteroids (Kristjansen and
Reymann, 1953; Meara, 1955; Mumford and Morgan,
1956), although this has not been tried specifically in
OLP and appears to confer no particular advantages.
Cyclosporin
Cyclosporin has been used as a topical mouthwash with
some benefit in four patients with OLP (Frances et al., 1988),
and this has been confirmed (Balato et al., 1989).
Subsequently, Eisen et al. (1990a,b) used cyclosporin again
as a mouthwash, but in significantly higher doses of 500 mg
three times daily for eight weeks, and showed improvement
in patients with atrophic and erosive OLP. Further beneficial
effects have also been claimed (Ho et al., 1990;
10
ritRevOratBio Me
105
Silverman et at., 1991; Gorsky and Raviv, 1992; Pacor et al.,
1994; Harpenau et al., 1995), including in its use in a bioad-
hesive paste (Gombos et al., 1992). The cost of medication
is prohibitive, however, and certainly precludes its routine
use, and some workers have found little (Porter et al.,
1994b; Becherel et al., 1995) or no significant beneficial
effect (Dartanel et al., 1991; Fornasa and Catalano, 1991;
Ho and Conklin, 1991; Levell et al., 1991; Itin et al., 1992).
Topical cyclosporin therefore appeared to offer little if any
advantage over other preparations, and a recent con-
trolled trial has confirmed this (Sieg et al., 1995). In the
published studies, systemic absorption has been low, and
therefore systemic cyclosporin would probably offer no
advantage. The nephrotoxicity of cyclosporin also contra-
indicates systemic use.
Azathioprine
Azathioprine has been widely used as a steroid-sparing
agent. However, the efficacy of such a regime has been
reported for OLP (Lozada, 1981; Silverman et al., 1991;
Lear and English, 1996). Further studies are required to
optimize the appropriate dose regime, and considera-
tion must be given to the adverse effects of azathioprine,
not least being the long-term possible induction of
malignancies.
Levamisole
Levamisole has recently been tried as a immunomodula-
tor in OLP (Sun et al., 1994). Significant immune alter-
ations took place within the patients studied, although
clinical efficacy has not been established, and the side-
effects of levamisole preclude its routine use (Sharps,
1978). Combined therapy with low-dose prednisolone,
however, may be helpful in the control of severe erosive
OLP (Lu et al., 1995).
Interferon
A single study on the use of topical human interferon
beta in OLP has been reported, with apparently complete
resolution in the ten patients tested (Sato et al., 1985).
No further studies have been carried out to confirm
these findings.
Glycyrrhizin
There is a single report of the successful treatment of
OLP with glycyrrhizin (Nagao et al., 1995b).
Retinoids
Since the first use of retinoids in the treatment of OLP in
the 1970s (Ebner et al., 1973; Gunther, 1973), many studies
have been carried out. The use of systemic vitamin A or ana-
logues, which can be effective against OLP (Sloberg et al.,
1983), was initially restricted by their toxicity (Stuttgen,
1975). The vitamin A analogue etretinate has been used
(Schuppli, 1978; Hersle et al., 1982) because of its greater
106CrtRvOaBilMd91:612(98
106 Crit Rev Oral Biol Med 9(l):86-122 (1998)
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therapeutic index, and it can be useful where there are cuta-
neous or genital lesions in addition to OLP (Baudet-
Pommel et al., 1991; Gorsky and Raviv, 1992; Eisen, 1994).
Systemic isotretinoin has also been used with effect (Woo,
1985; Camisa and Allen, 1986), but a newer, as-yet-unavail-
able alternative is isotretinoin as a gel, which appears to
have fewer side-effects and is also efficacious in the man-
agement of OLP (Giustina et al., 1986). Tretinoin (Baudet-
Pommel et al., 1991) and acitretin (Laurberg et al., 1991) have
also been used. Temarotene is a new retinoid analogue
which does not cause undesirable side-effects and has been
shown to be efficacious in an open pilot study of 25 patients
(Bollag and Ott, 1989). Another newish retinoid with mini-
mal side-effects that has proved beneficial in the treatment
of OLP is fenretinide (4-HPR) (Tradati et al., 1994).
Despite the wealth of literature suggesting the efficacy
of retinoids, these have not proved to be a universally pop-
ular remedy (Baudet-Pommmel et al., 1991), though if used
topically they may have benefits outweighing the disadvan-
tages (reviewed in Eisen, 1993a).
Anti-microbials
Despite the lack of any evidence for an infectious etiolo-
gy for OLP, empirical anti-microbial therapies have been
used as treatment, alone or as adjunctive therapy. There
has been a suggested benefit from the use of penicillin
(Hard and Holmberg, 1954; Samman, 1961), although
chloramphenicol and tetracyclines (MRC, 1954), inclu-
ding doxycycline (Eisen, 1994), have been shown to be of
no particular value, despite some reports of benefit
(Ronbeck et al., 1990).
Anti-malarials
Anti-malarials have also been used in the management
of OLP, although, as stated previously, these can them-
selves be responsible for lichenoid drug reactions.
Recently, clinical efficacy has been claimed for hydroxy-
chloroquine sulphate in an open trial with improvement
in nine of ten patients (Eisen, 1993b).
Dapsone
Trials of dapsone in the treatment of OLP have revealed
some benefit (Falk et al., 1985; Beck and Brandup, 1986),
but in gingival LP, there have been disappointing results,
and the significant adverse effects, particularly of hemol-
ysis and headache, generally preclude the use of dap-
sone (Matthews et al., 1991; Eisen 1994).
Phenytoin
In a single study of 30 patients with cutaneous lichen
planus, four of whom had oral lesions, two of those with
OLP had complete healing of their lesions on phenytoin
therapy (Bogaert and Sanchez, 1990). No other studies to
date have been carried out to confirm or deny the signif-
icance of these findings.
 NON-DRUG THERAPIES
Surgery
Surgery has sometimes been used to remove lesions of
OLP Surgical excision (Emslie and Hardman, 1970;
Vedtofte et al., 1987) as well as cryosurgery (Malmstrom
and Leikomaa, 1980; Loitz and O'Leary, 1986) and CO2
laser have been used (Frame et al., 1984; Horch et al.,
1986; Luomanen, 1992). Gingival lichen planus has also
been specifically treated by cryosurgery (Tal and Rafkin,
1986). Free soft-tissue grafts have also been used for
localized areas of erosive OLP (Hovick and Kalkwarf,
1987). Surgically removed lesions of OLP may recur but
not invariably (Vedtofte et al., 1987), and, occasionally,
oral surgical procedures evoke lesions, presumably via a
Koebner phenomenon (Katz et al, 1988).
Ultraviolet irradiation
Ultraviolet radiation has also been used with apparent
success in a number of different studies.
Photochemotherapy with psoralens and long-wave ultra-
violet-A (PUVA) was first used by lansen et al. (1987) in a
pilot study of OLP in which eight patients all responded
to treatment. The same group later expanded their find-
ings to 17 patients, with similar results (Lehtinen et al.,
1988, 1989). They subsequently optimized their system in
a comparison of the minimum phototoxic dose for the
oral mucosa, which they found to be 2-3 times less sen-
sitive than skin (Kuusilehto et al., 1990). PUVA used with
8-methoxypsoralen given 12 times produced an improve-
ment in 56% of sites (Lundquist et al., 1995). Chen (1989)
used ultraviolet-A without a systemic or topical photo-
sensitizer in 35 patients, and found that 87% significant-
ly improved. Apart from these two groups, however, this
treatment has not been available for the patient popula-
tion at large.
Other techniques
Several other non-drug therapies have been used in an
attempt to control OLP Some of these, such as magne-
tism (Kupriianova et al., 1989) and reflexotherapy
(Maksimovskaia et al., 1991), have been only single
reports.
Treatment of desquamative gingivitis
Management of desquamative gingivitis caused by OLP
is often unsatisfactory (Nisengard and Rogers, 1987). The
most important and easiest phase of the treatment is the
re-assurance of the patient and improvement of the gen-
eral oral hygiene (Erpenstein, 1985; Holmstrup et al.,
1990). The use of tetracycline in the treatment of desqua-
mative gingivitis has had some positive effect, suggest-
ing that bacteria or other plaque substances might be
involved in the development of desquamative gingivitis
9(9(1)86 122(1098)
l )-86 122 (1998) Crit Rev Oral Biol Med
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(Ronbeck et al., 1990), though others have had little suc-
cess with the same drug, doxycycline (Eisen, 1994).
Topical corticosteroids are useful in the manage-
ment of gingival lichen planus and desquamative gin-
givitis, although they are often only transiently effective
in the treatment of gingival lesions (Eisen, 1993a), since
the obtaining of an appropriate vehicle for the applica-
tion of the corticosteroids is often problematic. These
problems can be overcome by the use of either a flexible
splint to cover the gingivae or gingival veneers (Wray and
McCord, 1987).
New treatment methods such as topical application
of isotretinoin (Eisen, 1994), temarotene (Bollag and Ott,
1989), and cyclosporin (Eisen et al., 1990a,b; Eisen, 1994;
Porter et al., 1994b) have been tried, all with limited success.
Treatment with free gingival grafts has also been
suggested where the complaint could not be resolved
with other methods (Tamizi and Moayedi, 1992).
Follow-up of Patients with Lichen Planus
Based on the observed increased risk of malignant devel-
opment, OLP patients should be offered regular follow-
up examination two to four times annually and asked to
report any changes in their lesions or symptoms. Follow-
up may be particularly important in patients with atroph-
ic/ulcerative/erosive affections of the tongue, the gingiva,
or the buccal mucosa.
Summary
Lichen planus is a common affliction, probably of multi-
factorial origin, sometimes induced by drugs or dental
materials, often idiopathic, and with an immunopatho-
genesis involving T-cells in particular. There is no cura-
tive treatment available; immunomodulation, however,
can control the condition.
Much more research is required into the genetic and
environmental aspects of lichen planus, into the prema-
lignant potential, and into the possible associations with
chronic liver and other disorders. More clinical studies
are required into the possible efficacy of immunomodu-
latory drugs such as pentoxifylline and thalidomide.
REFERENCES
Akasu R, From L, Kahn H (1993). Lymphocyte and
macrophage subsets in active and inactive lesions of
lichen planus. Am J Dermatol Path 15:217-223.
Alaibac M, Morris 1, Yu R, Chu AC (1992). T lymphocytes
bearing the -y5 T-cell receptor: a study in normal
human skin and pathological skin conditions. Br I
Dermatol 127:458-462.
Abramova El (1968). Lichen ruber planus of the oral cavity.
Derm Woch 154:315-323.
Albrecht M, Banoczy J, Dinya E, Tamas G Jr (1992).
Occurrence of oral leukoplakia and lichen planus in
107
Oral Biol Med
107
 diabetes mellitus. l Oral Pathol Med 21:364-366.
Allan SJR, Buxton PK (1996). Isolated lichen planus of the
.lip. Br J Dermatol 135:145-146.
Allen CM, Blozis GG (1988). Oral mucosal reactions to
cinnamon-flavored chewing gum. I Am Dent Assoc
116:664-667.
Allen CM, Beck FM, Rossie KM, Kavi T1 (1986). Relation of
stress and anxiety to oral lichen planus. Oral Surg Oral
Med Oral Pathol 61:44-46.
Allen CM, Camisa C, Grimwood R (1987). Lichen planus
pemphigoides: report of a case with oral lesions. Oral
Surg 63:184-188.
Altman J, Perry HO (1961). The variations and course of
lichen planus. Arch Dermatol 84:179-191.
Andreasen JO (1968). Oral lichen planus: a clinical evalu-
ation of 115 cases. Oral Surg Oral Med Oral Pathol 25:31-
41.
Araujo OE, Flowers FP, King MM (1990). Griseofulvin: a
new look at an old drug. DICP 24:851-854.
Arndt KA (1987). Lichen planus. In: Dermatology in gen-
eral medicine. 3rd ed. Fitzpatrick TB, Eisen AZ, Wolff
K, editors. New York: McGraw-Hill, pp. 967-973.
Aronson IK, Soltani K, Paik K, Rubenstein D, Lorincz AL
(1978). Triad of lichen planus, myasthenia gravia, and
thymoma. Arch Dermatol 114:255-258.
Ashinoff R, Cohen R, Lipkin G (1989). Castleman's tumor
and erosive lichen planus: coincidence or associa-
tion? Report of a case. J Am Acad Dermatol 21:1076-
1080.
Aufdemorte TB, DeVillez RL, Gieseker DR (1983).
Griseofulvin in the treatment of three cases of oral
erosive lichen planus. Oral Surg Oral Med Oral Pathol
55:459-462.
Axell T (1976). A prevalence study of oral mucosal lesions
in an adult Swedish population. Odontol Revy 27(Suppl
36):1-103.
Axell T (1987). Occurrence of leukoplakia and some other
white lesions among 20,333 adult Swedish people.
Community Dent Oral Epidemiol 15: 46-5 1.
Axell T, Rundquist L (1987). Oral lichen planus-a demo-
graphic study. Community Dent Oral Epidemiol 15:52-56.
Axell T, Spiechowicz E, Glantz P-O, Andersson G, Larsson
A (1986). A new method for intraoral patch-testing.
Contact Dermatitis 15:58-62.
Axell T, Zain RB, Siwamogstham P, Tantiniran D,
Thampipit 1 (1990). Prevalence of oral soft tissue
lesions in out-patients at two Malaysian and Thai
dental schools. Community Dent Oral Epidemiol 18:95-
99.
Ayala F, Balato N, Tranfaglia A, Guadagnino V, Orlando R
(1986). Oral erosive lichen planus and chronic liver
disease. J Am Acad Dermatol 14: 139-140.
Baart de la Faille-Kuyper EH, Baart de la Faille H (1974).
An immunofluorescence study of lichen planus. Br J
Dermatol 90:365-371.
108
Downloaded from http://cro.sagepub.com by on June 26, 2010
Bagan IV, Silvestre Fl, Mestre S, Gisbert C, Bermejo A,
Agramont 1 (1985). Treatment of lichen planus with
griseofulvin. Report of seven cases. Oral Surg Oral Med
Oral Pathol 60:608-610.
Bagan IV, Milian-Masanet MA, Penarrocha-Diago M,
Jimenez Y (1992). A clinical study of 205 patients with
oral lichen planus. J Oral Maxillofac Surg 50:116-118.
Bagan JV, Donat JS, Penarrocha M, Milian MA, Sanchis IM
(1993). Oral lichen planus and diabetes mellitus. A
clinico-pathological study. Bull Group Int Rech Sci
Stomatol et Odontol 36:3-6.
Bagan JV, Aguirre JM, del Olmo IA, Milian A, Penarrocha
M, Rodrigo IM, et al. (1994). Oral lichen planus and
chronic liver disease: a clinical and morphometric
study of the oral lesions in relation to transaminase
elevation. Oral Surg Oral Med Oral Pathol 78:337-342.
Baker H, Hughes DTD, Pegum JS (1964). Lichenoid erup-
tion due to amiphenazole. Br I Dermatol 76:186-190.
Balato N, De Rosa S, Bordone S, Ayala F (1989).
Dermatological application of cyclosporine. Arch
Dermatol 125:1430-1431.
Banoczy 1, Rigo 0 (1991). Prevalence of oral precancerous
lesions within a complex screening system in
Hungary. Community Dent Oral Epidemiol 19: 265-267.
Banoczy J, Roed-Petersen B, Pindborg 1 (1979). Clinical
and histologic studies on electrogalvanically induced
oral white lesions. Oral Surg Oral Med Oral Pathol
48:319-323.
Barker INWN, Mitra RS, Griffiths CEM, Dixit VM, Nickoloff
Bl (1991). Keratinocytes as indicators of inflamma-
tion. Lancet 337:211-214.
Barnard NA, Scully C, Eveson JW, Cunningham S, Porter
SR (1993). Oral cancer development in patients with
oral lichen planus. J Oral Pathol Med 22:421-424.
Baudet-Pommel M, Janin-Mercier A, Souteyrand P
(1991). Sequential immunopathologic study of oral
lichen planus treated with tretinoin and etretinate.
Oral Surg Oral Med Oral Pathol 71:197-202.
Becherel P-A, Chosidow 0, Boisnic S, Moyal-Barraco M,
Pelisse M, Reigneau 0, et al. (1995). Topical
cyclosporine in the treatment of oral and vulvar ero-
sive lichen planus: a blood level monitoring study.
Arch Dermatol 131:495-496.
Beck HI, Brandup F (1986). Treatment of erosive lichen
planus with dapsone. Acta Derm Venereol (Stockh)
66:366-367.
Becker J, Schuppan D (1995). Altered expression of extra-
cellular matrix proteins and integrins in oral lichen
planus (OLP). I Oral Pathol Med 24:159-164.
Beckman BI (1981). Valisone aerosol spray contraindica-ted
in mucous membranes (letter). J Am Acad Dermatol 4:233.
Bergdahl J, Ostman P-O, Anneroth G, Ferris FPR Skoglund
A (1995). Psychological aspects of patients with oral
lichenoid reactions. Acta Odontol Scand 53:238-241.
Berger RS, Hayes TJ, Dixon SL (1989). Erythema
(1998)
Crit Rev
Crit Rev Oral
Oral Biol Med
Biol Med 9(l):86-122 (1998)
 dyschromicum perstans and lichen planus: are they
related? I Am Acad Dermatol 21:438-442.
Berger TG, Dhar A (1994). Lichenoid photoeruptions in
human immunodeficiency virus infection. Arch
Dermatol 130:609-613.
Bermejo A, Bermejo MD, Roman P, Botella R, Bagan IV
(1990). Lichen planus with simultaneous involvement
of the oral cavity and genitalia. Oral Surg 69:209-216.
Bermejo Fenoll A, Lopez lornet MP (1991). Oral lichen
planus and Sjbgren's syndrome. 2 cases of associa-
tion. Avances en Odontoestomatol 7:29-33, 36, 38 (in
Spanish).
Bhan AK, Harris NL, Murphy GF, Milm M Jr (1981). T cell
subsets and Langerhans cells in lichen planus: in situ
characterisation using monoclonal antibodies. Br I
Dermatol 105:617-622.
Bircher Al, von Schultness A, Henning G (1993). Oral
lichenoid lesions and mercury sensitivity. Contact
Dermatitis 29:275-276.
Blasberg B, Dorey JL, Stein HB, Chalmers A, Conklin RI
(1984). Lichenoid lesions of the oral mucosa in
rheumatoid arthritis patients treated with penicil-
lamine. I Rheum 11:348-351.
Boccia S, Gamberini S, Dalla Libera M (1993). Lichen
planus and interferon therapy for hepatitis C.
Gastroenterology 105:1921 1922.
Boehncke W-H, Kellner I, Konter U, Sterry W (1992).
Differential expression of adhesion molecules on
infiltrating cells in inflammatory dermatoses. I Am
Acad Dermatol 26:907-913.
Bogaert H, Sanchez E (1990). Lichen planus: treatment of
thirty cases with systemic and topical phenytoin. Int I
Dermatol 29:1 57-1 58.
Boisnic S, Ouhayoun J-P, Branchet MC, Frances C,
Beranger IY, Le Charpentier Y, et al. (1995). Alteration
of cytokeratin expression in oral lichen planus. Oral
Surg Oral Med Oral Pathol 79:207-215.
Bolewska J, Hansen HJ, Holmstrup P, Pindborg JJ,
Stangerup M (1990a). Oral mucosal lesions related to
silver amalgam restorations. Oral Surg Oral Med Oral
Pathol 70:55-58.
Bolewska J, Holmstrup P, Moller-Madsen B, Kenrad B,
Danscher G (1990b). Amalgam associated mercury
accumulations in normal oral mucosa, oral mucosal
lesions of lichen planus and contact lesions associa-
ted with amalgam. J Oral Pathol Med 19:39-42.
Bollag W, Ott F (1989). Treatment of lichen planus with
temarotene. Lancet ii:974.
Bologa EL, Valda F (1971). Ruckbildung begrifener lichen
ruber planus mitnachfolgender dermatitis herpeti-
formis Duhring. Dermatol Monatschr 157:447-452.
Borghelli RF, Pettiniari IL, Chuchurru IA, Stirparo MA
(1993). Oral lichen planus in patients with diabetes:
an epidemiologic study. Oral Surg Oral Med Oral Pathol
75:498-500.
9(1)861221998)
9(l):86-122 (1998)
Downloaded from http://cro.sagepub.com by on June 26, 2010
Bouquot IE, Gorlin RI (1986). Leukoplakia, lichen planus
and other oral keratoses in 23,616 white Americans
over the age of 35 years. Oral Surg Oral Med Oral Pathol
61:373-381.
Boyd AS, Neldner KH (1990). The isomorphic response to
Koebner. Int I Dermatol 29:401-410.
Boyd AS, Neldner KH (1991). Lichen planus. Am Acad
Dermatol 25:593-612.
Bratel I, Hakeberg M, lontell M (1996). Effect of replace-
ment of dental amalgam on oral lichenoid reactions.
Dent 24:41-45.
Brenner W, Diem E, Gschnait F (1979). Coincidence of
vitiligo, alopecia areata, onychodystrophy, localized
scleroderma and lichen planus. Dermatologica 159:356-
360.
Brice SL, Barr RI, Rattet JP (1980). Childhood lichen
planus-a question of therapy. Am Acad Dermatol
3:370-376.
Brown RS, Hays GL, Flaitz CM (1993). Treatment of gold
salt-induced oral lichen planus: report of a case. Cutis
51:183-185.
Bruszt P (1962). Stomato-onkologisch reihenuntersuchun-
gen in sieben gemeinden Sundungarns. Schweiz
Monatschr Zahnheilkd 72:758-766.
Buechner SA (1984). T-cell subsets and macrophages in
lichen planus. Dermatologica 169:325-329.
Buetner EH, Chorzelski TP, Parodi A (1991). Ten cases of
chronic ulcerative stomatitis with stratified epitheli-
um-specific antinuclear antibody. I Am Acad Dermatol
24:781-782.
Bussel SN, Smales FC, Sutton RBO, Duckworth R (1979).
Glucose tolerance in patients with lesions of the oral
mucosa. Br Dent J 146:186-188.
Camisa C, Allen CM (1986). Treatment of oral erosive
lichen planus with systemic isotretinoin. Oral Surg
Oral Med Oral Pathol 62:393-396.
Camisa C, Allen CM, Bowen B, Olsen RG (1986). Indirect
immunofluorescence of oral lichen planus. I Oral
Pathol 15:218-220.
Cawson RA (1968). Treatment of oral lichen planus with
betamethasone. Br Med 1 2:86-89.
Cawson RA, Binnie WH (1977). Candida leukoplakia and
carcinoma-a possible relationship. In: Oral prema-
lignancy. Dabelsteen E, Mackenzie IC, Squier CA, edi-
tors. Iowa: University of Iowa Press, pp. 59-66.
Chattopadhyay A (1992). Arterial blood pressure and
blood glucose levels in oral lichen planus patients in
Calcutta (India). Indian I Dent Res 3:84-89.
Chau NY, Reade PC, Rich AM, Hay KD (1984).
Allopurinol-amplified lichenoid reactions of the oral
mucosa. Oral Surg Oral Med Oral Pathol 58:397-400.
Chen HR (1989). A newly developed method for treat-
ment of oral lichen planus with ultraviolet irradiation.
J Formosan Med Assoc 88:248-252.
Choudhary SD, Gupta S, lain VK (1988). Lichen planus
109
Crit
Crit
Rev Oral Biot Med
Rev Oral Biol
109
 hypertrophicus with carcinoma breast in a male
patient (a case report). Indian I Dermatol 33:40-41.
Christensen E, Holmstrup P, Wiberg-j0rgensen F,
Neumann-Jensen B, Pindborg JJ (1977a). Arterial
blood pressure in patients with oral lichen planus. I
Oral Pathol 6:139-142.
Christensen E, Holmstrup P, J0rgensen FW, Jensen BN,
Pindborg II (1977b). Glucose tolerance in patients
with oral lichen planus. J Oral Pathol 6:143-151.
Church LF, Schlosser RH (1992). Chronic ulcerative stoma-
titis associated with stratified epithelial specific
antinuclear antibody. Oral Surg 73:579-582.
Colvard MD, Nadimi H, Gargiulo AV (1986). Ativan
(lorazepam) induced lichenoid reaction of the human
attached gingiva: case report. Periodont Case Rep 8:69-
70.
Conklin RJ, Blasberg B (1987). Oral lichen planus.
Dermatol Clin 5:663-673.
Connelly MG, Winkelmann RK (1985). Coexistence of
lichen sclerosus, morphea and lichen planus. Report
of four cases and review of the literature. J Am Acad
Dermatol 12:844-851.
Copeman PWN, Scroeter AL, Kierland RR (1979). An
unusual variant of lupus erythematosus or lichen
planus. Br J Dermatol 83:269-272.
Cottoni F, Solinas A, Piga MR, Tocco A, Lissia M,
Cerimele D (1988). Lichen planus, chronic liver dis-
eases, and immunologic involvement. Arch Dermatol
Res 280(Suppl):S55-S60.
Cottoni F, Tedde G, Solinas A, Deplano A (1991). Lichen
planus associated with anti-liver-kidney microsome-
positive chronic active hepatitis and hyperthyroidism.
Arch Dermatol 127:1730-1731.
Cox M, Maitland N, Scully C (1993). Human herpes sim-
plex-l and papillomavirus type 16 homologous DNA
sequences in normal, potentially malignant and
malignant oral mucosa. Oral Oncol 29(B):215-219.
Cox NH, Finlay AY, Watkinson G (1986). Atypical lichen
planus associated with ulcerative colitis. Dermatologica
173:294-296.
Cusano F, Errico G (1984). Lichen planus and ulcerative
colitis. Arch Dermatol 120:994-995.
D'Agay-Abensour L, Benamouzig R, De Belilovsky C,
Cordoliani F, Halphen M, Rambaud IC (1992). Lichen
planus during chronic hepatitis C treated with inter-
feron alpha. Gastroenterol Clin Biol 16:610-611.
Daftary DK, Bhonsie RB, Musti RB, Pindborg JJ, Mehta FS
(1980). An oral lichen planus-like lesion in Indian
betel tobacco chewers. Scand J Dent 88:244-245.
Daniels TE, Quadra-White C (1981). Direct immunofluo-
rescence in oral mucosal disease: a diagnostic analy-
sis of 130 cases. Oral Surg 51:38-47.
Dartanel S, Sahin M, Eksioglu M, Karabay Y (1991).
Behandlung des oralen erosiven lichen planus mit
topischem Cyclosporin A (Cs-A). Z Hautkr66:148-149.
110
1 10
Downloaded from http://cro.sagepub.com by on June 26, 2010
Davies MG, Gorkiewicz A, Knight A, Marks R (1977). Is
there a relationship between lupus erythematosus
and lichen planus? Br J Dermatol 96:145-154.
De long WF, Albrecht M, Banoczy J, van der Waal I (1984).
Epithelial dysplasia in oral lichen planus. A prelimi-
nary report of a Dutch-Hungarian study of 100 cases.
Int J Oral Surg 13:221-225.
De Panfilis G, Manara G, Sansoni P, Allegra F (1983). T-
cell infiltrate in lichen planus. Demonstration of acti-
vated lymphocytes using monoclonal antibodies. i
Cutan Pathol 10:52-58.
Deasy PB, Collins AE, Burke FM, Shanley DB (1989). In
vitro and in vivo evaluation of a bondable compact for
the prolonged delivery of triamcinolone acetonide to
the oral cavity in patients with lichen planus.
Pharmaceut Acta Helv 64:276-279.
del Olmo IA, Bagan IV, Rodrigo JM, Serra MA, Wassel AH,
Aparisi L, et al. (1989). Oral lichen planus and hepatic
cirrhosis (letter). Ann Int Med 110:666.
Delaney TA, Smith NP (1993). Lichen planus mimicking
and coexisting with psoriasis in a Black patient.
Australasian J Dermatol 34:59-62.
Dhawan SS, Fields K (1989). Lichen planus and ulcerative
colitis; is there a relationship? (case report) Int I
Dermatol 28:534.
Dinsdale RCW, Ormerod TP, Walker AE (1966).
Amiphenazole sensitivity with oral ulceration. Br Dent
1 121:460-462.
Divano MC, Parodi A, Rebora A (1992). Lichen planus,
liver kidney microsomal (LKMI) antibodies and
hepatitis C virus antibodies. Dermatol 185:132-133.
Divano MC, Parodi A, Rebora A (1994). Anti-GOR anti-
bodies in lichen planus. Dermatology 188:205-206.
Doutre MS, Beylot C, Couzigou P, Long P, Royer P, Beylot
1 (1992). Lichen planus and virus C hepatitis: disap-
pearance of the lichen under interferon alpha therapy
(letter). Dermatology 184:229.
Downham TF (1978). Spironolactone-induced lichen
planus (letter). I Am Med Assoc 240:1138.
Dreyer WP (1983). The clinical manifestations of oral
lichen planus. J Dent Assoc S Afr 38:619-624.
Dupuy P, Heslan M, Fraitag S, Hercend T, Dubertret L,
Bagot M (1990). T-cell receptor-gamma/delta bearing
lymphocytes in normal and inflammatory human
skin. I Invest Dermatol 94:764-768.
Duske JI, Frick WG (1982). Lichen planus-oral manifes-
tations and suggested treatments. J Oral Maxillofac
Surg 40:240-244.
Ebner H, Mischer P, Raff M (1973). Lokal behandlung des
lichen rubber planus der mundehlermhaut mit
Vitamin A saure. Z Hautkr 48:735-740.
Edwards L (1989). Vulvar lichen planus. Arch Dermatol
125:1677-1680.
Eisen D (1993a). The therapy of oral lichen planus. Crit
Rev Oral Biol Med 4:141-158.
Grit Rev Oral
Crit Rev Oral Biol
Biol Med
Med
9(1)86-122
9(i):86-122 (1998)
Eisen D (1993b). Hydroxychloroquine sulfate (Plaquenil)
improves oral lichen planus: an open trial. J Am Acad
Dermatol 28:609-612.
Eisen D (1994). The vulvovagina-gingival syndrome of
lichen planus. Arch Dermatol 130:1379-1382.
Eisen D, Ellis CN, Duell EA, Griffiths CEM, Voorhees JJ
(1990a). Effect of topical cyclosporine rinse on oral
lichen planus: a double-blind analysis. N Engl I Med
323:290-294.
Eisen D, Griffiths CEM, Ellis CN, Nikoloff BI, Voorhees IJ
(1990b). Cyclosporin wash for oral lichen planus.
Lancet 335:535-536.
Eisenberg E, Krutchkoff DI (1992). Lichenoid lesions of
oral mucosa. Diagnostic criteria and their importance
in the alleged relationship to oral cancer. Oral Surg
Oral Med Oral Pathol 73:699-704.
El-Kabir M, Scully C, Porter S, Porter K, MacNamara E
(1993). Liver function in UK patients with oral lichen
planus. Clin Exp Dermatol 18:12-16.
Ellis FA (1967). Histopathology of lichen planus based on
analysis of one hundred biopsy specimens. I Invest
Dermatol 48:143-148.
Ellul IP, Groves R, Walters JR (1992). Lichen planus asso-
ciated with chenodeoxycholic acid and ursodeoxy-
cholic acid for gallstone dissolution. Digest Dis Sci
37:628-630.
Emslie ES, Hardman FG (1970). The surgical treatment of
oral lichen planus. Trans St John's Hosp Dermatol Soc
56:43-44
Erpenstein H (1985). Periodontal and prosthetic treat-
ment in patients with oral lichen planus. J Clin
Periodontol 12:104- 112.
Eversole LR (1994). Immunopathology of oral mucosal
ulcerative, desquamative and bullous diseases.
Selective review of the literature. Oral Surg 77:555-
557.
Eversole LR, Ringer M (1984). The role of restorative met-
als in the pathogenesis of oral lichen planus. Oral
Surg Oral Med Oral Pathol 57:383-387.
Eversole LR, Dam 1, Ficarra G, Hwang C-Y (1994).
Leukocyte adhesion molecules in oral lichen planus:
a T cell mediated immunopathologic process. Oral
Microbiol Immunol 9:376-383.
Eveson JW (1988). Superficial mucoceles: pitfall in clini-
cal and pathological diagnosis. Oral Surg 66:318-322.
Falk DK Latour DL, King LE (1985). Dapsone in the treat-
ment of erosive lichen planus. I Am Acad Dermatol
12:560-570.
Farmer ER (1986). The histopathology of graft-versus-
host disease. Adv Dermatol 1:173-188.
Farthing PM, Matear P, Cruchley AT (1990). The activation
of Langerhans cells in oral lichen planus. I Oral Pathol
Med 19:81-85.
Farthing PM, Matear P, Cruchley AT (1992). Langerhans
cell distribution and keratinocyte expression of HLADR
12~l98)
9(1)6 Git Rv Oal Bd Me
9(l)-86-122 (1998) Crit Rev Oral Biol Med
Downloaded from http://cro.sagepub.com by on June 26, 2010
in oral lichen planus. J Oral Pathol Med 21:451-455.
Fellner MJ (1980). Lichen planus. Int I Dermatol 19:71-75.
Ferguson MM (1977). Treatment of erosive lichen planus
of the oral mucosa with depot steroids. Lancet ii:771-
772.
Ferguson MM, Simpson NB, Hammersley N (1984). The
treatment of erosive lichen planus with a retinoid-
etretinate. Oral Surg Oral Med Oral Pathol 58:283-287.
Feuerman E, Sandbank M (1971). Lichen planus pem-
phigoides with extensive melanosis. Arch Dermatol
104:61-67.
Ficarra G, Flaitz CM, Gaglioti D, Piluso S, Milo D, Adler-
Storthz K, et al. (1993). White lichenoid lesions of the
buccal mucosa in patients with HIV infection. Oral
Surg Oral Med Oral Pathol 76:460-466.
Finne K, Goransson K, Winkler L (1982). Oral lichen
planus and contact allergy to mercury. Int I Oral Surg
11:236-239.
Firth NA, Reade PC (1989). Angiotensin-converting
enzyme inhibitors implicated in oral mucosal
lichenoid reactions. Oral Surg 67:41-44.
Fitzgerald E, Purcell SM, Goldman HM (1995).
Photodistributed hypertrophic lichen planus in asso-
ciation with acquired immunodeficiency syndrome: a
distinct entity. Cutis 55:109-111.
Fitzpatrick TB (1963). Lichen planus-like drug eruption.
Arch Dermatol 88:352.
Flamenbaum HS, Safai B, Siegel FP, Pahwa S (1982).
Lichen planus in two immunodeficient hosts. J Am
Acad Dermatol 6:918-920.
Fornasa CV, Catalano P (1991). Effect of local applica-
tions of ciclosporin in chronic ulcerative lichen
planus (letter). Dermatol 182:65.
Fortune F, Buchanan JAG (1993). Oral lichen planus and
coeliac disease. Lancet 341:1154-1155.
Frame JW, Das Gupta AR, Dalton GA, Rhys-Evans PH
(1984). Use of the carbon dioxide laser in the man-
agement of premalignant lesions of the oral mucosa.
I Laryngol Otol 98:1251-1260.
Frances C, Boisnic S, Etienne S, Szirglas H (1988). Effect
of the local application of cyclosporine A on chronic
erosive lichen planus of the oral cavity. Dermatologica
177:194-195.
Frider B, Sookoian S, Castano G, Giavino G, Choulela E
(1995). Lichen planus, chronic hepatitis C and inter-
feron. Hepatology 21:1764-1765.
Fry L, Withers M (1969). Lichen planus: failure to culti-
vate viruses or mycoplasma. Br I Dermatol 80:384.
Fryholm KO, Frithiof L, Fernstrnm A, M6berger G, Blom
SF, Bj0rn E (1969). Allergy to copper derived from
dental alloys as a possible cause of oral lesions of
lichen planus. Acta Derm Venereol 49:268-281.
Fulling HI (1973). Cancer development in oral lichen
planus: a follow-up study of 327 patients. Arch
Dermatol 108:667-669.
11
III
Gabriel SA, Jenson AB, Hartmann D, Bottomley WK
(1985). Lichen planus: possible mechanisms of
pathogenesis. I Oral Med 40:56-59.
Gadenne A-S, Strucke R, Dunn D, Wagner M, Bleicher P,
Bigby M (1994). T-cell lines derived from lesional skin
of lichen planus patients contain a distinctive popu-
lation of T-cell receptor y8-bearing cells. ] Invest
Dermatol 103:347-351.
Gandolfo S, Gallo V, Carbone M, Zulian P, Carrozzo M
(1992). Oral lichen planus and liver pathology. 1. The
prevalence of liver damage in a case load of 96
patients with oral lichen planus. Minerva Stomatol
41:203-207.
Gandolfo S, Carbone M, Carrozzo M, Gallo V (1994). Oral
lichen planus and hepatitis C virus (HCV) infection: is
there a relationship? A report of 10 cases. I Oral Pathol
Med 23:119-122.
Gart GS (1994). Ulcerative and oral lichen planus associ-
ated with sicca syndrome and primary biliary cirrho-
sis. Cutis 53:249-250.
Gibson LE, Van Hale HM, Schroeter AL (1986). Direct
immunofluorescence for the study of cutaneous drug
eruptions. Acta Derm Venereol (Stockh) 66:39-44.
GISED (Gruppo Italiano Studi Epidemiologici in
Dermatologia) (1990). Lichen planus and liver dis-
eases: a multicentre case-control study. Br Med I
300:227-230.
GISED (Gruppo Italiano Studi Epidemiologici in
Dermatologia) (1991). Epidemiological evidence of
the association between lichen planus and two
immune-related diseases: Alopecia areata and ulcer-
ative colitis. Arch Dermatol 127:688-691.
Giustina TA, Stewart JCB, Ellis CE, Regezi T, Annesley T,
Woo TY, et al. (1986). Topical application of
isotretinoin gel improves oral lichen planus. J Arch
Dermatol 22:534-536.
Golding Pl, Smith M, Williams R (1973). Multisystem
involvement in chronic liver disease: studies on the
incidence and pathogenesis. Am J Med 55:772-782.
Gombos F, Capello B, Gaeta GM, La Rotonda MI, Serpico
R, Miro A (1992). La ciclosporina in formulazione
bioadesiva nella terapia del lichen planus orale erosi-
vo. Minerva Stomatol 41:385-389.
Gorsky M, Raviv M (1992). Efficacy of etretinate (Tigason)
in symptomatic oral lichen planus. Oral Surg Oral Med
Oral Pathol 73:52-55.
Graham-Brown RAC, Sarkany I, Sherlock S (1982). Lichen
planus and primary biliary cirrhosis. Br J Dermatol
106:699-703.
Greenspan JS, Yeoman CM, Harding SM (1978). Oral
lichen planus. A double-blind comparison of treat-
ment with betamethasone valerate aerosol and pel-
lets. Br Dent 1 144:83-84.
Griffiths CEM, Nickoloff BJ (1989a). Keratinocytes intra-
cellular adhesion molecule-i (ICAM- 1) expression
112 Crit
Crit Rev Oral Biol
Rev Oral Biol Med
Med
Downloaded from http://cro.sagepub.com by on June 26, 2010
precedes dermal T lymphocyte infiltration in allergic
contact dermatitis (Rhus dermatitis). Am J Pathol
135:1045-1053.
Griffiths CEM, Voorhees 11, Nickoloff BI (1989b).
Characterisation of intercellular adhesion molecule- 1
and HLA-DR expression in normal and inflamed skin:
modulation by recombinant gamma interferon and
tumor necrosis factor. J Am Acad Dermatol 20:617-629.
Grinspan D, Diaz J, Villapol LO, Schneiderman 1,
Berdichesky R, Palese D, et al. (1966). Lichen ruber
planus de la muquense buccale. Son association a un
diabete. Bull Soc Franc Dermatol Syph 73:898-899.
Groth 0 (1961). Lichenoid dermatitis resulting from
treatment with the phenothiazine derivative metopro-
mazine and laevopromazine. Acta Derm Venereol (Stockh)
41:168-177.
Groves RW, Ross EL, Barker INWN, MacDonald DM
(1993). Vascular cell adhesion molecule- 1: expression
in normal and diseased skin and regulation in vivo by
interferon gamma. I Am Acad Dermatol 29:67-72.
Grupper C, Bourgeois-Spinasse J, Buisson (1972).
Duhring-Broq disease followed by or associated with
lichen planus. Bull Soc Fr Syph 79:231-232.
Gunther SH (1973). Vitamin A acid in the treatment of
oral lichen planus. Arch Dermatol 107:277.
Hakala M, Van Assendelft AHW, Ilonen I, Jalava S,
Tiilikainen A (1986). Association of different HLA
antigens with various toxic effects of gold salts in
rheumatic arthritis. Ann Rheum Dis 48:177-182.
Halevy S, Feuerman El (1983). Urolithiasis in lichen
planus (letter). Arch Dermatol 119:364.
Hampf BG, Malmstrom MI, Aalberg VA, Hannula JA,
Vikkula J (1987). Psychiatric disturbance in patients
with oral lichen planus. Oral Surg Oral Med Oral Pathol
63:429-432.
Handler HL (1984). Isotretinoin for oral lichen planus
(letter). I Am Acad Dermatol 10:674.
Hard S, Holmberg P (1954). Penicillin treatment of lichen
ruber planus. Acta Derm Venereol (Stockh) 34:72.
Harder MK, Kasha EE (1990). Pruritic zosteriform erup-
tion. Arch Dermatol 126:665-668.
Harpenau LA, Plemons IM, Rees TD (1995). Effectiveness
of a low dose of cyclosporine in the management of
patients with oral erosive lichen planus. Oral Surg Oral
Med Oral Pathol 80:161-167.
Hatchuel DA, Peters E, Lemmer J, Hille IJ, McGraw WT
(1990). Candidal infection in oral lichen planus. Oral
Surg Oral Med Oral Pathol 70:172-175.
Helm TM, Camisa C, Liu AY, Valenzuela R, Bergfeld WF
(1994). Lichen planus associated with neoplasia: a
cell-mediated immune response to tumor antigens? I
Am Acad Dermatol 30:219-224.
Henriksson E, Mattsson U, Hakansson 1 (1995). Healing
of lichenoid reactions following removal of amalgam.
I Clin Periodontol 22:287-284.
9(l):86-122 (1998)
Herrmann D (1992). Karzinomentstehung bei oralem
Lichen planus. Langzeituntersuchung an 919 patien-
ten. Dtsch Zahndrtztl Z 47:877-879.
Hersie K, Mobacken H, Sloberg K, Thilander H (1982).
Severe oral lichen planus: treatment with an aromat-
ic retinoid (etretinate). Br I Dermatol 106:77-80.
Hietanen J, Pihlman K, Forstrbm L, Linder E, Reunala T
(1987). No evidence of hypersensitivity to dental
restorative metals in oral lichen planus. Scand I Dent
Res 95:320-327.
Ho VC, Conklin R1 (1991). Effect of topical cyclosporine
rinse on oral lichen planus (letter). N Engl J Med
325:435.
Ho VC, Gupta AK, Ellis CN, Nickoloff BJ, Voorhees II
(1990). Treatment of severe lichen planus with
cyclosporine. J Am Acad Dermatol 22:64-68.
Hogan Dl, Murphy F, Burgess WR, Epstein ID, Lane PR
(1985). Lichenoid stomatitis associated with lithium
carbonate. J Am Acad Dermatol 13:243-246.
Hogewind WFC, van der Waal 1 (1988). Prevalence study
of leukoplakia in a selected population of 1000
patients from the Netherlands. Community Dent Oral
Epidemiol 16:302-305.
Holland R (11980). Galvanic currents between gold and
amalgam. Scand I Dent Res 988:269-272.
Holmstrup P (1991). Reactions of the oral mucosa rela-
ted to silver amalgam. J Oral Pathol Med 20:1-7.
Holmstrup P (1992a). Oral mucosa and skin reactions
related to amalgam. Adv Dent Res 6:120-124.
Holmstrup P (1992b). The controversy of a premalignant
potential of oral lichen planus is over. Oral Surg Oral
Med Oral Pathol 73:704-706.
Holmstrup P, Dabelsteen E (1974). The frequency of
Candida in oral lichen planus. Scand I Dent Res 82:584-
587.
Holmstrup P, Pindborg ]] (1979). Erythroplakic lesions in
relation to oral lichen planus. Acta Dermatol (Stockh)
59(Suppl):77 84.
Holmstrup P, Thorn ]1, Rindrum J, Pindborg 11 (1988).
Malignant development of lichen planus-affected oral
mucosa. I Oral Pathol 17:219-225.
Holmstrup P, Schiotz AW, Hyug D, Westergaard W (1990).
Effect of dental plaque control on gingival lichen
planus. Oral Surg Oral Med Oral Pathol 69:585-590.
Hopkins IG, Kesten BM, Nelson CT (1952). Pituitary
adrenocorticotrophic hormone (ACTH) and cortisone
in diseases of the skin. Arch Derm Syphilol Chicago
65:401.
Horch H, Gerlach KL, Schaefer HE (1986). CO2 laser
surgery of oral premalignant lesions. Oral Maxillofac
Surg 15:19-24.
Hovick Cl, Kalkwarf KL (1987). Treatment of localised oral
erosive lichen planus lesions with free soft tissue
grafts. Periodont Case Rep 9:21-24.
Ibbotson SH, Speight EL, MacLeod RI, Smart ER,
9(1) 86-122 (11998)
9(l):86-122 1998) Crit
Crit Rev Oral Biol Med
Rev Oral
Downloaded from http://cro.sagepub.com by on June 26, 2010
Lawrence CM (1996). The relevance and effect of
amalgam replacement in subjects with oral lichenoid
reactions. BrI Dermatol 134:420-423.
Isaacson D, Turner ML, Elgart ML (1981). Summertime
actinic lichenoid eruption (lichen planus actinicus). I
Am Acad Dermatol 4:404-411.
Ishii T (1987). Immunohistochemical demonstration of T
cell subsets and accessory cells in oral lichen planus.
I Oral Pathol 16:356-361.
Itin P, Surber C, Buchner S (1992). Lack of effect after
local treatment with a new cyclosporin formulation in
recalcitrant erosive oral lichen planus. Dermatol
185:262-265.
Itin PH, Schiller P, Gilli L, Buechner SA (1995). Isolated
lichen planus of the lip. Br Dermatol 132:1000-1002.
Jacob FM, Helmbold TR (1933). Bacteriologic studies on
lichen planus: preliminary report. Arch Derm Syphilol
27:472.
Jacyk WK, Greenwood BM (1978). Serum immunoglobu-
lins in Nigerian patients with lichen planus. Clin Exp
Dermatol 3:83-84.
James J, Ferguson MM, Forsyth A, Tulloch N, Lamey P-1
(1987). Oral lichenoid reactions related to mercury
sensitivity. Br J Oral Maxillofac Surg 25:474-480.
Jameson MW, Kardos TB, Kirk EE, Ferguson MM (1990).
Mucosal reactions to amalgam restorations. I Oral
Rehabil 17:293-301.
Jandinski JJ, Shklar G (1976). Lichen planus of the gingi-
va. J Periodontol 47:724-733.
Janner M, Muissus E, Rohde B (1967). Lichen planus as a
possible precancerous condition. Derm Woch 153: 513-
518.
Jansen CT, Lehtinen R, Happonen RR, Lehtinen A,
Soderlund K (1987). Mouth PUVA: new treatment for
recalcitrant oral lichen planus. Photodermatology 4:165-
166.
Jansen T, Plewig G, Anhalt G1 (1995). Paraneoplastic pem-
phigus with clinical features of erosive lichen planus
associated with Castleman's tumor. Dermatol 190:245-
250.
larenko WM, Beutner EH, Kumar V (1990). Chronic ulcer-
ative stomatitis associated with a specific immuno-
logic marker. I Am Acad Dermatol 22:215-220.
Jepsen H, Winther JE (1965). Mycotic infection in oral
leukoplakia. Acta Odontol Scand 23:239-256.
Jolly M (1972). Lichen planus and its association with
diabetes mellitus. Med I Aust 1:990-992.
Jolly M, Nobile S (1977). Vitamin status of patients with
oral lichen planus. Aust Dent 22:446-450.
Jolly M, Moule Al, Bryant RW, Freeman S (1986).
Amalgam related chronic ulceration of oral mucosa.
Br Dent J 160:434-437.
Jontell M, Watts S, Wallstrom M, Levin L, Sloberg K
(1990). Human papilloma virus in erosive oral lichen
planus. J Oral Pathol Med 19:273-277.
113
BioI Med
11 3
lontell M, Hansson HA, Nygreen H (1986). Mast cells in
oral lichen planus. J Oral Pathol 15:273-275.
Jubert C, Pawlotsky JM, Putget F, Andre C, DeForges L,
Bretagne S, et al. (1994). Lichen planus and hepatitis
C virus-related chronic active hepatitis. Arch Dermatol
130:73-76.
lungell P (1991). Oral lichen planus. A review. Int I Oral
Maxillofac Surg 20:129-135.
lungell P, Konttinen YT, Nortamo P, Malmstrom M (1989).
Immunoelectron microscopic study of distribution of
T cell subsets in oral lichen planus. Scand I Dent Res
97:361-367.
Kano J, Shiohara T, Yagita A, Nagashima M (1995).
Erythema nodosum, lichen planus and lichen nitidus
in Crohn's disease: report of a case and analysis of T
cell receptor V gene expression in the cutaneous and
intestinal lesions. Dermatology 190:59-63.
Kaplan S, McDonald E, Marino C (1995). Lichen planus in
patient with rheumatoid arthritis treated with sul-
fasalazine. J Rheum 22:191-192.
Karagouni EE, Dotsika EN, Sklavounou A (1994).
Alteration in peripheral blood mononuclear cell func-
tion and serum cytokines in oral lichen planus. i Oral
Pathol Med 23:28-35.
Kashima HK, Kutcher M, Kessis T, Levi LS, de Villiers EM,
Shah K (1990). Human papillomavirus in squamous
cell carcinoma, leukoplakia, lichen planus and clini-
cally normal epithelium of the oral cavity. Ann Otol
Rhinol Laryngol 99:55-61.
Katz 1, Goultschin I, Benoliel R, Rotstein I, Pisanti S
(1988). Lichen planus evoked by periodontal surgery.
I Clin Periodontol 15:263-265.
Katz M, Pisanty S (1985). Oral erosive lichen planus and
chronic active hepatitis (letter). I Am Acad Dermatol
12:719.
Kaugars GE, Svirsky JA (I1982). An update on the dysplas-
tic/carcinomatous transformation of oral lichen
planus. I Oral Med 37:75-79.
Kilpi AM (1987). Activation marker analysis of mononu-
clear cell infiltrates of oral lichen planus in situ. Scand
I Dent Res 95:174-180.
Kilpi AM, Rich AM, Konttinen YT, Reade PC (1995). The
expression of c-erb-B-2 protein in the keratinocytes of
oral mucosal lichen planus. Br I Derm 133:847-852.
Kirby AC, Olsen 1, Farthing PM, Porter SR (1995).
Expression of lymphocyte function-associated anti-
gen 3 in oral lichen planus. Oral Diseases 1:193-197.
Kirby JD, Black M, McGibbon D (1980). Levamisole
induced lichenoid eruptions. J R Soc Med 73:208-
211.
Konrad K, Pehamberger H, Holubar K (1979).
Ultrastructural localization of immunoglobulin
and fibrin in lichen planus. J Am Acad Dermatol
1:233-239.
Konter U, Kellner I, Hoffmeister B, Sterry W (1990).
114
Downloaded from http://cro.sagepub.com by on June 26, 2010
Induction and upregulation of adhesion receptors in
oral and dermal lichen planus. I Oral Pathol Med
19:459-463.
Konter U, Kellner 1, Hoffmeister B, Sterry W (1991).
Gesteigerte expression von adhasionsmolekulen bei
oralem lichen planus. Dtsch Z Mund Kiefer Gesichts Chir
15:69-74.
Konttinen YT, lungell P, Bergroth V, Hampf G, Kamppinen
P, Malmstrom M (1989). PHA stimulation of peripher-
al blood lymphocytes in oral lichen planus.
Abnormality localised between interleukin-2 receptor
ligand formation and gamma-interferon secretion. J
Clin Lab Immunol 28:33-37.
Korkij W, Chuang TY, Soltani K 91984). Liver abnormali-
ties in patients with lichen planus. A retrospective
case-control study. I Am Acad Dermatol 1:609-615.
Kovesi G, Banoczy J (1973). Follow-up studies in oral
lichen planus. Int I Oral Surg 2:13-19.
Kristjansen A, Reymann F (1953). ACTH therapy in lichen
ruber planus. Acta Derm Venereol (Stockh) 33:205.
Krogh P, Hald B, Holmstrup P (1987a). Possible mycolog-
ical etiology of oral mucosal cancer: catalytic poten-
tial of infecting Candida albicans and other yeasts in
production of N-nitrosobenzylmethylamine.
Carcinogenesis 8:1 543-1548.
Krogh P, Holmstrup P, Thorn JI, Vedtofte P, Pindborg JI
(1987b). Yeast species and biotypes associated with
oral leukoplakia and lichen planus. Oral Surg Oral Med
Oral Pathol 63:48-54.
Krutchkoff Dl, Eisenberg E (1985). Lichenoid dysplasia: a
distinct histopathologic entity. Oral Surg Oral Med Oral
Pathol 60:308-315.
Krutchkoff DJ, Cutler L, Laskowski S (1978). Oral lichen
planus: the evidence regarding potential malignant
transformation. I Oral Pathol 7:1-7.
Kunz M, Roth J, Sorg C, Kolde G (1992). Epidermal
expression of the calcium binding surface antigen
27E 10 in inflammatory skin diseases. Arch Dermatol Res
284:386-390.
Kupriianova TA, Markov BP, Vilkova LA, Barabash AG
(1989). The use of a permanent magnetic field in the
combined treatment of lichen ruber planus of the oral
mucosa. Stomatologiia (Mosk)(VIM) 68:33-34.
Kurgansky D, Burnett JW (1994). Widespread lichen
planus in association with Turner's syndrome and
multiple endocrinopathies. Cutis 54:108-110.
Kuusilehto A, Lehtinen R, Jansen CT (1990). Comparison
of the minimal phototoxic dose in topical 4,5',8-
trimethylpsoralen PUVA treatment of Caucasian skin
and of oral mucous membrane. Acta Derm Venereol
(Stockh) 70:508-509.
Lacy MF, Reade PC, Hay KD (1983). Lichen planus: a the-
ory of pathogenesis. Oral Surg Oral Med Oral Pathol
56:521-526.
Laeijendecker R, Van loost TH (1994). Oral manifesta-
(1998)
Grit Rev
Crit Rev Oral
Oral Biol Med
Biol Med 9(l):86-122 (1998)
 tions of gold allergy. I Am Acad Dermatol 30:205-209.
Laine I, Kalimo K, Forssell H, Happonen R-P (1992).
Resolution of oral lichenoid lesions after replacement
of amalgam restorations in patients allergic to mer-
cury compounds. Br I Dermatol 126:10-15.
Lamey PI, Boyle MA, Simpson NB, Ferguson MM (1987).
A pilot study of griseofulvin therapy in erosive oral
lichen planus. J Oral Med 42:233-235.
Lamey P-I, Gibson J, Barclay SC, Miller S (1990).
Grinspan's syndrome: a drug-induced phenomenon?
Oral Surg Oral Med Oral Pathol 70:184-185.
Lamey P-I, McCartan BE, MacDonald DG, MacKie RM
(1995). Basal cell cytoplasmic autoantibodies in oral
lichenoid reactions. Oral Surg Oral Med Oral Pathol
79:44-49.
Laskaris G, Sklavonou A, Angelopoulos A (1982). Direct
immunofluorescence in oral lichen planus. Oral Surg
53:483-487.
Laurberg G, Geiger IM, Hjorth N, Holm P, Hou-Jensen K,
Jacobsen KU, et al. (1991). Treatment of lichen planus
with acitretin. J Am Acad Dermatol 24:434-437.
Lear IT, English JSC (1996). Erosive and generalised
lichen planus responsive to azathioprine. Clin Exp
Dermatol 21:56-57.
Lee CW (1987). Pemphigus vulgaris coexisting with gen-
eralized lichen planus. J Dermatol 14:388-391.
Lehnhoff C (1948). Spirochaetes in aetiologically obscure
diseases. Acta Derm Venereol (Stockh) 28:295.
Lehtinen R, Happonen R-P, Kuusilehto A, Jansen C
(1988). A clinical trial of PUVA treatment in oral lichen
planus. Int J Oral Maxillofac Surg 17:84-86.
Lehtinen R, Happonen RP, Kusilehto A, Jansen C (1989).
A clinical trial of PUVA treatment in oral lichen
planus. Proc Finn Dent Soc 85:229-233.
Lenzi M, Johnson Pi, McFarlane IG, Ballardini G, Smith
HM, McFarlane BM, et al. (1991). Antibodies to hepati-
tis C virus in autoimmune liver disease: evidence for
a geographical heterogeneity. Lancet 338:277-280.
Levell NJ, MacLeod RI, Marks JM (1991). Lack of effect of
cyclosporin mouthwash in oral lichen planus. Lancet
337:796-797.
Lin AN, Srolovitz H, Billick RC (1986). Familial lichen
planus. Cutis 37:135-136.
Lin SC, Sun A (1990). HLA-DR and DQ antigens in
Chinese patients with oral lichen planus. I Oral Pathol
Med 19:298-300.
Lin SC, Sun A, Wu U-C, Chiang C-P (1991). Presence of
antibasal cell antibodies in oral lichen planus. J Am
Acad Dermatol 26:943-947.
Lind P (1988). Oral lichenoid reactions related to com-
posite restorations. Acta Odontol Scand 46:63-65.
Lind PO, Hurlen B, Lyberg T, Aas E (1986). Amalgam-
related oral lichenoid reaction. Scand J Dent Res
94:448-451.
Lochner IC, Pomeranz JR (1974). Lichenoid secondary
9(1):86 122 (1998)
9(l):86-122
Downloaded from http://cro.sagepub.com by on June 26, 2010
syphilis. Arch Dermatol 109:81-83.
Loitz GA, O'Leary IP (1986). Erosive lichen planus of the
tongue treated with cryosurgery. l Oral Maxillofac Surg
44:580-582.
Lotem M, Ingber A, Sandbank M, Hazaz B (1989). Lichen
planus pemphigoides with features of lichen planus
and pemphigus vulgaris. Arch Dermatol 125:707-708.
Lowe NJ, Cudworth AG, Clough SA, Bullen MF (1976a).
Carbohydrate metabolism in lichen planus. Br J
Dermatol 95:9-12.
Lowe NJ, Cudworth AG, Woodrow IC (1976b). HLA anti-
gens in lichen planus. Br I Dermatol 96:169-171.
Lowenthal V, Pisanti S (1984). Oral lichen planus accor-
ding to the modern medical model. l Oral Med 39:224-
226.
Lozada F (1981). Prednisolone and azathioprine in the
treatment of patients with vesiculoerosive oral dis-
eases. Oral Surg Oral Med Oral Pathol 52:257-260.
Lozada F, Silverman J (1980). Topically applied fluocino-
nide in an adhesive base in the treatment of oral
vesiculoerosive diseases. Arch Dermatol 116:190-201.
Lozada F, Silverman J, Migliorati C (1984). Adverse side
effects associated with prednisone in the treatment of
patients with oral inflammatory ulcerative diseases. l
Am Dent Assoc 1091:269-270.
Lozada-Nur F, Luangjarmekorn L, Silverman S Ir, Karam I
(1985). Assessment of plasma glucose in 99 patients
with oral lichen planus. J Oral Med 40:60-61.
Lozada-Nur F, Miranda C, Maliksi R (1994). Double-blind
clinical trial of 0.05% clobetasol propionate ointment
in orabase and 0.05% fluocinonide ointment in
orabase in the treatment of patients with oral vesicu-
loerosive diseases. Oral Surg Oral Med Oral Pathol
77:598-604.
Lu S-YM, Chen W-J, Eng H-L (1995). Dramatic response
to levamisole and low-dose prednisolone in 23
patients with oral lichen planus. Oral Surg Oral Med
Oral Pathol 80:705-709.
Lundquist G, Forsgren H, Gajecki M, Emtestam L (1995).
Photochemotherapy of oral lichen planus: a con-
trolled study. Oral Surg 79:554-558.
Lundstrbm 1 (1983). Incidence of diabetes mellitus in
patients with oral lichen planus. Int l Oral Surg 12:147-
152.
Lundstrbm IMC (1984). Allergy and corrosion of dental
materials in patients with oral lichen planus. Int 1 Oral
Surg 13:16-24.
Lundstrom IMC, Anneroth GB, Holmberg K (1984).
Candida in patients with oral lichen planus. Int 1 Oral
Surg 13:226-238.
Lundstrom WI, Anneroth GC, Bergsted HF (1982).
Salivary gland function and changes in patients with
oral lichen planus. Scand I Dent Res 90:443-458.
Luomanen M (1992). Experience with a carbon dioxide
laser for removal of benign oral soft-tissue lesions.
1
115
Crit Rev Oral Biol Med
Ci e rlBo
 Proc Finn Dent Soc 88:49-55.
MacDonald DG, Rennie JS (1975). Oral epithelial atypia
in denture-induced hyperplasia, lichen planus and
squamous cell papilloma. Int I Oral Surg 4:40-45.
MacLeod RI (1992). Psychological factors in oral lichen
planus (letter). Br Dent J 1 73:88.
MacLeod RI, Soames JV (1991). Lichen sclerosus et
atrophicus of the oral mucosa. Br 1 Oral Maxillofac Surg
89:64-65.
Maeda H, Reibel 1, Holmstrup P (1994). Keratin staining
pattern in clinical normal and diseased oral mucosa
of lichen planus patients. Scand J Dent Res 102:210-215.
Magnusson B (1967). Lichen ruber bullosus and tumors
in internal organs. Dermatologica 134:166-172.
Mahood IM (1983). Familial lichen planus. Arch Dermatol
119:292-294.
Maibach HI (1986). Cheilitis: occult allergy to cinnamic
aldehyde. Contact Dermatitis 15:106-107.
Maitland NJ, Cox MV, Lynas C, Prime SS, Meanwell CA,
Scully C (1987). Detection of human papillomavirus
DNA in biopsies of human oral tissue. Br I Cancer
56:245-249.
Maksimovskaia LN, Barashkov GN, Trestov NG (1991).
The methods of modern reflexotherapy in the com-
bined treatment of patients with erosive-ulcerative
processes of the oral mucosa. Stomatologia (Mosk) 4:36-
37.
Malmstrbm M, Leikomaa H (1980). Experience with
cryosurgery in the treatment of oral lesions. Proc Finn
Dent Soc 76:117-123.
Malmstrom M, Konttinen YT, lungell P (1989).
Lymphocyte activation in oral lichen planus. Proc Finn
Dent Soc 85:109- 117.
Mann RI, Wallington TB, Warin RP (1982). Lichen planus
with late onset hypogammaglobulinaemia: a causal
relationship? Br J Dermatol 106:357-360.
Manns M, Griffin KJ, Sullivan KF, Johnson EF (1991).
LKMI autoantibodies recognise a short linear
sequence in P450 1ID6. J Clin Invest 88(L):1370-1378.
Marren P, Millard P, Chia Y, Wojnarowska F (1994).
Mucosal lichen sclerosus/lichen planus overlap syn-
dromes. Br J Dermatol 131.118-123.
Markitziu A, Katz J, Pisanty S (1986). Lichenoid lesions of
oral mucosa associated with ketaconazole. Mykosen
29:317-322.
Marren P, Millard P, Chia Y, Wojnarowska F (1994).
Mucosal lichen sclerosis/lichen planus overlap syn-
dromes. Br I Dermatol 131:118-123.
Massa MC, Rogers S III (1981). Griseofulvin therapy of
lichen planus. Acta Derm Venereol 61:547-550.
Matthews RW, Pinkney RC, Scully C (1991). The manage-
ment of desquamative gingivitis with dapsone. Ann
Dent 48:41-43.
Matthews RW, Scully C (1992). Griseofulvin in the treat-
ment of oral lichen planus: adverse drug reactions but
1166
11 Crit Rev
Crit
Rev Oral Biol Med
Downloaded from http://cro.sagepub.com by on June 26, 2010
little beneficial effect. Ann Dentistry 51:10-11.
Matthews JB, Scully CM, Potts AJC (1984). Oral lichen
planus: an immunoperoxidase study using mono-
clonal antibodies to lymphocyte subsets. Br J Dermatol
111:587-595.
McCartan BE (1995). Psychological factors associated
with oral lichen planus. J Oral Pathol Med 24:273-275.
McQueen A, Behan WMH (1982). The "string of pearls"
phenomenon-an immunofluorescent serological
finding in patients screened for adverse drug reac-
tions. Am I Dermatopathol 4:155-159.
Meara RH (1955). Lichen planus treated with ACTH
(abstract). Trans St John's Hospital Derm Soc 34:17.
Michel G, RitterA, Gerken G, Buschenfelde KH, Decker R,
Manns MP (1992). Anti-GOR and hepatitis C virus in
autoimmune liver diseases. Lancet 339:267-269.
Michie SA, Abel PA, Hoppe RT, Warnke RA, Wood GS
(1989). Expression of T-cell receptor antigens in
mycosis fungoides and inflammatory skin lesions. I
Invest Dermatol 93:116-120.
Miller TN (1971). Myasthenia gravis, ulcerative colitis
and lichen planus. Proc R Soc Med 64:37-38.
Miralles 1, Pujol RM, Moragas JM (1994). Liquen plano y
hepatitis C. Descripcion de 13 casos. Actas Dermo-Sif
85:603-606.
Mishiro S, Hoshi Y, Takeda K, Yoshikawa A, Gotanda T,
Takahashi K, et al. (1990). Non-A, non-B hepatitis anti-
bodies directed at host derived epitope: implication
for an autoimmune process. Lancet 336:1400-1403.
Mobacken H, Hersle K, Sloberg K, Thilander H (1984a).
Oral lichen planus: hypersensitivity to dental restora-
tion material. Contact Dermatol 10:1 1-1 5.
Mobacken H, Nilsson LA, Olsson R, Sloberg K (1984b).
Incidence of liver disease in chronic lichen planus of
the mouth. Acta Derm Venereol 64:70-73.
Mobacken H, Nilsson L, Olsson R, Sloberg K (1984c).
Lichen planus and the liver (letter). Acta Dermat
Venereol (Stockh) 64:570.
Mokni M, Rybojad M, Puppin D Jr, Catala S, Venezia F,
Djian R, et al. (1991). Lichen planus and hepatitis C
virus (case report). I Am Acad Dermatol 24:792.
Monk B (1985). Lichen planus and the liver. I Am Acad
Dermatol 12:122-124.
Mora RG, Nesbitt LT, Brantley LB (1983). Lichen planus
pemphigoides: clinical and immunofluorescent find-
ings in four cases. I Am Acad Dermatol 8:331-336.
Mozzanica N, Cattaneo A, Legori A, Pigatto P, Finzi AF
(1991). Immunohistologic evaluation of the effect of
cyclosporine treatment on the lichen planus immune
infiltrate. I Am Acad Dermatol 24:550-554.
MRC (Medical Research Council) (1954). Systemic anti-
biotics in certain dermatoses (abstract). Br Med I
1:856.
Mumford PB, Morgan JK (1956). The use of cortisone in
lichen planus. Br J Dermatol 68:258-260.
(1998)
Oral Biol Med
9(l):86-122 (1998)
Murti PR, Daftary DK, Bhonsie RB, Gupta PC, Mehta FS,
Pindborg 11 (1986). Malignant potential of oral lichen
planus: observation in 722 patients from India. I Oral
Pathol 15:71-77.
Nagao Y, Sata M, Tanikawa K, Itoh K, Kameyama T
(1995a). Lichen planus and hepatitis C virus in the
Northern Kyushu region of Japan. Eur J ClGn Invest
25:910-914.
Nagao Y, Sata M, Tanikawa K, Kameyama T (1995b). A
case of oral lichen planus with chronic hepatitis C
successfully treated by glycyrrhizin. l Jpn Assoc Infect Dis
69:940-944.
Naldi L, Sena P, Cainelli T (1990). About the association
of lichen planus and psoriasis. Dermatologica 181:9-80.
Naylor GD (1990). Treating erosive lichen planus with
griseofulvin: a report of four cases. Quintessence Int
21:943-947.
Neumann-Jensen B, Holmstrup P, Pindborg IJ (1977).
Smoking habits of 611 patients with oral lichen
planus. Oral Surg 43:410-415.
Neumann-Jensen B, Worsaae N, Dabelsteen E, Ullman S
(1980). Pemphigus vulgaris and pemphigus foliaceus
coexisting with oral lichen planus. Br I Dermatol
102:585-590.
Nickoloff BJ, Lewinsohn DM, Butcher EC (1987).
Enhanced binding of peripheral blood mononuclear
leucocytes to alpha interferon treated cultured ker-
atinocytes. Am J Dermatol 9:413-418.
Nigram PK, Sharma L, Agrawal JK, Singh G, Khurana SK
(1987). Glucose tolerance studies in lichen planus.
Dermatologica 175:284-289.
Nisengard Rl, Rogers RS (1987). The treatment of
desquamative gingival lesions. J Periodontol 58:167-
172.
Ohta Y Yonemoto K, Asai T, Yaguchi A (1992). Lichen
planus annularis: An immunohistochemical study. I
Dermatol 19:414-419.
Okoki H, Nashiro K, Tsuchida T, Seki Y, Tamaki K (1990).
Lichen planus pemphigoides: case report and results
of immunofluorescence and immunoelectron micro-
scopic study. J Am Acad Dermatol 22:626-63 1.
Oleaga JM, Gardeazabal J, Sanz de Galdeano C, Diaz Pl
(1995). Generalized lichen planus associated with pri-
mary biliary cirrhosis which resolved after liver trans-
plantation (case report). Acta Derm Venereol 75:87.
Oliver GF, Winkelman RK (1993). Treatment of lichen
planus. Drugs 45:56-65.
Olsen RG, Du Plessis DP, Barron C, Schulz EJ, Villet W
(1983). Lichen planus dermopathy: demonstration of
a lichen planus specific epidermal antigen in affected
patients Clin Lab Immunol 10:9-15.
Oomen C, Temmerman L, Kint A (1986). Lichen planus
pemphigoides. Clin Exp Dermatol 11:92-96.
Ostman P-0, Anneroth G, Skoglund A (1994). Oral lichen
planus lesions in contact with amalgam fillings: a
9(1)86
9(l) 22(1998)
86-122 (1998)
Downloaded from http://cro.sagepub.com by on June 26, 2010
clinical, histologic and immunohistochemical study.
Scand I Dent Res 102:172-179.
Pacor ML, Biasi D, Urbani G, Lombardo G, Lunardi C
(1994). The efficacy of cyclosporin for topical use in
oral lichen planus. Minerva Stomatol 43:129-132.
Papini M, Bruni PL, Bettacchi A, Liberati F (1994).
Sudden onset of oral ulcerative lichen in a patient
with chronic hepatitis C on treatment with alfa-inter-
feron. Int I Dermatol 33:221-222.
Parodi A, Cardo PP (1990). Patients with erosive lichen
planus may have antibodies directed to a nuclear
antigen of epithelial cells: a study on the antigen
nature. J Invest Dermatol 94:689-693.
Parodi A, Gallo R, Rebora A (1995). Lichen planus pre-
senting with erythema-multiforme-like bullous
lesions in a patient with systemic scleroderma.
Dermatol 190:156-159.
Pawlotsky I-M, Ben Yahia M, Andre CH, Voisin MC,
Intrator L, Roudot-Thoraval F, et al. (1994).
Immunological disorders in C virus chronic active
hepatitis: a prospective case-control study. Hepatology
19:841-848.
Pawlotsky I-M, Benchiki H, Pellet C, Duval J, Dhumeaux
D, Revuz 1. et al. (1995a). Lichen planus and hepatitis
C virus (HCV)-related chronic hepatitis: evaluation of
HCV genotypes (letter). Br I Dermatol 133:666-667.
Pawlotsky I-M, Tsakiris L, Roudot-Thoraval F, Pellet C,
Stuyver L, Duval I, et al. (1995b). Relationship between
hepatitis C virus genotypes and sources of infection
in patients with chronic hepatitis C. I Infect Dis
171:1607-1610.
Pedersen A (1996). Abnormal EBV immune status in oral
lichen planus. Oral Diseases 2:125-128.
Pelisse M (1989). The vulvo-vaginal-gingival syndrome: a
new form of erosive lichen planus. Int J Dermatol
28:381 -384.
Peng T, Nisengard RJ, Levine Ml (1986). Gingival base-
ment membrane antigens in desquamative lesions of
the gingiva. Oral Surg Oral Med Oral Pathol 61:584-589.
Penneys NS, Ackerman AB, Gottlieb NL (1974). Gold der-
matitis. Arch Dermatol 109:372-376.
Pindborg II, Mehta FS, Daftary DK, Gupta RC, Bhonsle RB
(1972). Prevalence of oral lichen planus among 7639
Indian villagers in Kerala, South India. Acta Derm
Venereol (Stockh) 52:216-220.
Pindborg 1, Reibel 1, Holmstrup P (1985). Subjectivity in
evaiuating oral epithelial dysplasia, carcinoma in situ
and initial carcinoma. l Oral Pathol 14:698-708.
Pitigala-Arachchi A, Crane II, Scully C, Prime S (1989).
Epithelial dendritic cells in pathological human oral
tissues. J Oral Pathol Med 18:11-16.
Plemons IM, Rees TD, Zachariak NY (1990). Absorption of
topical steroid and evaluation of adrenal suppression
in patients with erosive lichen planus. Oral Surg Oral
Med Oral Pathol 69:688-693.
117
Crit Rev
Crit Rev Oral
Oral Biol Med
Biol Med 117
Porter K, Klouda P, Scully C, Bidwell J, Porter S (1993).
Class I and II HLA antigens in British patients with
oral lichen planus. Oral Surg Oral Med Oral Pathol
75:176-180.
Porter SR, Scully C, Midda M, Eveson IW (1990). Adult
linear IgA disease manifesting as desquamative gin-
givitis. Oral Surg 70:450-453.
Porter SR, Bain SE, Scully C (1992). Linear IgA disease
manifesting as recalcitrant desquamative gingivitis.
Oral Surg 74:179-182.
Porter S, Scully C, Eveson JW (1994a). Coexistence of
lichen planus and vitiligo is coincidental. Clin Exp
Dermatol 19:366.
Porter SR, Scully C, Eveson 1W (1994b). The efficacy of
topical cyclosporin in the management of desquama-
tive gingivitis due to lichen planus. Lancet ii:753.
Postma C (1937). Experiments in the culture of the
organism of lichen planus by lacob and Helmbolds
method. Arch Derm Syphilol 36:836.
Potts AJC, Hamburger I, Scully C (1987). The medication
of patients with oral lichen planus and the associa-
tion of nonsteroidal anti-inflammatory drugs with
erosive lesions. Oral Surg Oral Med Oral Pathol 64:541-
543.
Powell FC (1984). Lichen planus and chronic active
hepatitis. I Am Acad Dermatol 10:841.
Powell FC, Rogers RS (1981). Primary biliary cirrhosis,
penicillamine and lichen planus (letter). Lancet ii:525.
Powell FC, Rogers RS, Dickson ER (1982). Lichen planus.
Primary biliary cirrhosis and penicillamine (letter). Br
I Dermatol 107:616.
Powell F, Rogers R, Dickson E (1983). Lichen planus, pri-
mary biliary cirrhosis and penicillamine. Br I Dermatol
9: 540-545.
Powell FC, Rogers RS, Dickson ER, Moore SB (1986). An
association between HLA-DR1 and lichen planus. Br I
Dermatol 1 14:473-478.
Powell SM, Ellis IP, Ryan TI, Vickers HR (1974). Glucose
tolerance in lichen planus. Br I Dermatol 91:73-75.
Protzer U, Ochsendorf ER, Leopolder-Ochsendorf A,
Holtermuller KH (1993). Exacerbation of lichen
planus during interferon alfa-2a therapy for chronic
active hepatitis C. Gastroenterol 104:903-905.
Randell S, Cohen L (1974). Erosive lichen planus.
Management of oral lesions with intralesional corti-
costeroid injections. I Oral Med 29:88-91.
Rebora A (1981). Lichen planus and the liver. Lancet
i i:805-806.
Rebora A, Rongioletti F (1984). Lichen planus and chron-
ic active hepatitis. J Am Acad Dermatol 10:841.
Rebora A, Patri P, Rampini E, Crovato F, Ciravegna G,
Rebora A, et al. (1978). Erosive lichen planus and cir-
rhosis hepatitis. Ital Gen Rev Dermatol 15:123-131.
Rebora A, Rongioletti F, Canepa A (1982). Chronic
active hepatitis and lichen planus. Acta Derm
118 Crit Rev
Crit Rev Oral Biol Med
Oral Biol Med
Downloaded from http://cro.sagepub.com by on June 26, 2010
Venereol 62:35 1-352.
Rebora A, Robert E, Rongioletti F (1992). Clinical and
laboratory presentation of lichen planus patients with
chronic liver disease. I Dermatol Sci 4:38-41.
Regezi IA, Stewart IC, Lloyd RV, Headington 11 (1985).
Immunohistochemical staining of Langerhans cells
and macrophages in oral lichen planus. Oral Surg
60:396-402.
Regezi IA, Daniels TE, Saeb F, Nickoloff BI (1994).
Increased submucosal factor XIIIa-positive dendro-
cytes in oral lichen planus. I Oral Pathol Med 23:14-18.
Reinhold U, Pawelec G, Fratila A, Leippold S, Bauer R,
Kreysel HW (1990). Phenotypic and functional charac-
terisation of tumor infiltrating lymphocytes in myco-
sis fungoides: continuous growth of CD4+CD45RA+ T-
cell clones with suppressor-inducer activity. I Invest
Dermatol 94:304-309.
Renstrup G (1970). Occurrence of Candida in oral leuko-
plakias. Acta Pathol Microbiol Scand Sect B 78:421-424.
Rich AM, Reade PC (1989). A quantitative assessment of
Langerhans cells in oral mucosal lichen planus and
leukoplakia. Br I Dermatol 120:223-228.
Rippis GE, Becker B, Scott G (1994). Hypertrophic lichen
planus in three HIV-positive patients: a histologic and
immunological study. I Cutan Pathol 21:52-58.
Roberts DL, Marks R (1981). Skin reactions to carba-
mazepine. Arch Dermatol 117:273-275.
Robertson WD, Wray D (1992). Ingestion of medication
among patients with oral keratoses including lichen
planus. Oral Surg Oral Med Oral Pathol 74:183-185.
Robertson WD, Wray D (1993). Immunohistochemical
study of oral keratoses including lichen planus. I Oral
Pathol Med 22:180-182.
Roed-Petersen B, Roed-Petersen 1 (1992). Occlusive
treatment of atropic and erosive oral lichen planus
with clobetasole proprionate 0.05% ointment. Tandl
Tidsskr 1:4-7.
Roed-Petersen B, Renstrup G, Pindborg II (1970).
Candida in oral leukoplakias. A histologic and exfo-
liative cytologic study. Scand I Dent Res 78:323-328.
Rogers RS, Sheridan P1, Nightingale SH (1982).
Desquamative gingivitis: clinical, histopathologic,
immunopathologic and therapeutic observations. I
Am Acad Dermatol 7:729-735.
Ronbeck BA, Lind PO, Thrane PS (1990). Desquamative
gingivitis: preliminary observations with tetracycline
treatment. Oral Surg Oral Med Oral Pathol 69:694-697.
Rushton RI (1962). Treatment of ulcerative mouth lesions
with orabase. Br I Dermatol 74:462-464.
Rustin MH (1986). A case of atrophic lichen planus in
association with Addisonian pernicious anaemia. Clin
Exp Dermatol 11:188-190.
Saito K, Tamura A, Narimatsu H, Tadakuma T, Nagashima
M (1986). Cloned auto-la-reactive T cells elicit lichen
planus-like lesion in the skin of syngeneic mice. I
(1998)
9(l):86- 122 (1998)
 Immunol 137:2485-2495.
Sallay K (1969). Lichen oris kexelese intrafocalisan adott
hydrocortison mikrokristaly suspensioval. Fogory Szeml
62:257.
Salman SM, Kibbi AG, Zaynoun S (1989). Actinic lichen
planus: a clinicopathologic study of 16 patients. I Am
Acad Dermatol 20:226-231.
Salonen L, Axell T, Hellden L (1990). Occurrence of oral
mucosal lesions, the influence of tobacco habits and
an estimate of treatment time in an adult Swedish
population. I Oral Pathol Med 19:170-176.
Samman PD (1961). Lichen planus: an analysis of 200
cases. Trans St lohn's Hosp 46:36.
Samman PD (1974). Discussion of thymoma, acquired
hypogammaglobulinaemia, lichen planus and alope-
cia areata. Proc R Soc Med 67:186.
Sanchez-Perez 1, Castro M, Buezo GF, Fernandez-Herrera
1, Borque Ml, Garcia-Diez A (1996). Lichen planus and
hepatitis C virus: prevalence and clinical presentation
of patients with lichen planus and hepatitis C virus
infection. Br J Dermatol 134:715-719.
Sassigneux P, Michel P, Joly P, Colin R (1993). Eruptive
mucocutaneous lichen planus during treatment of
chronic hepatitis C with interferon alpha. Gastroenterol
Clin Biol 17:764.
Sato M, Yoshida H, Yanagawa T, Yura Y, Urata M, Nitta T,
et al. (1985). Therapeutic effect of human fibroblast
interferon on premalignant lesions arising in the oral
mucosa. Int J Oral Surg 14:184-194.
Saurat IH Lemarchand F, Hors J, Nunez-Roldan A,
Gluckman E, Dausset 1 (1977). HLA markers and lym-
phocytotoxins in lichen planus. Arch Dermatol
133:1719-1724.
Savage 1 (1958). Lichenoid dermatitis due to chloro-
quine. Dermatol 70:181.
Schi0dt M Holmstrup P, Dabelsteen E, Ullman S (1981).
Deposits of immunoglobulins, complement, and fibrino-
gen in oral lupus erythematosus, lichen planus, and
leukoplakia. Oral Surg Oral Med Oral Pathol 51:603-608.
Schmidt H (1961). Frequency, duration and localization
of lichen planus. Acta Derm Venereol (Stockh) 41:164-171.
Schmitt CL, Alpins 0, Chambers G (1945). Clinical inves-
tigation of a new cutaneous entity. Arch Dermatol Syph
52:226-228.
Schuppli R (1978). The efficacy of a new retinoid (RO 10-
9359) in lichen planus. Dermatologica 157:60-63.
Scott MJ, Scott MI (1979). Ungual lichen planus. Arch
Dermatol 115:1197-1199.
Scully C (1982). Serum IgG, IgA, IgM, IgD and IgE in
lichen planus: no evidence for a humoral immunode-
ficiency. Clin Exp Dermatol 7:163-167.
Scully C, Boyle P (1982). B2 microglobulin in lichen
planus. I Dent Res 61:758-760.
Scully C, Cawson RA (1998). Medical problems in dentistry.
61h ed. Oxford: Butterworth-Heinemann (in press).
9(1) 86 122 (1998) Crit Rev Oral Biol Med
Ci
g(l):86-122
Downloaded from http://cro.sagepub.com by on June 26, 2010
Scully C, El-Kom M (1985). Lichen planus: review and
update in pathogenesis. l Oral Pathol Med 14:431-438.
Scully C, Potts 1, Hamburger 1, Wiesenfels S, McKee 11, El
Kom M (1984). Lichen planus and liver disease: how
strong is the association? J Oral Pathol 14:224-226.
Scully C, Porter SR, Eveson JW (1993). Oral lichen planus
and coeliac disease. Lancet 341:1660.
Scully C, Almeida OPD, Welbury R (1994). Oral lichen
planus in childhood. Br J Dermatol 131:131-133.
Seehafer JR, Roger RS, Fleming CR, Dickson ER (1981).
Lichen planus-like lesions caused by penicillamine in
primary biliary cirrhosis. Arch Dermatol 117:140-142.
Sehgal VN, Abraham GJS, Malik GB (1972). Griseofulvin
therapy in lichen planus. A double-blind control trial.
Br I Derm 87:383-385.
Sharps RS (1978). Lichen planus treated with levamisole.
J Cont Educ Dermatol 17:32.
Shatin H, Canizares 0, Worthington El (1953). Lichen
planus like drug eruption due to para-aminosalicylic
acid. Report of 5 cases-two showing mouth lesions.
I Invest Dermatol 21:135-138.
Shelley WB, Shelley ED (1989). Urinary tract infection as
a cause of lichen planus: metronidazole therapy. J Am
Acad Dermatol 10:905-907.
Shiohara T, Hayakawa 1, Nagashima M (1989). Psoriasis
and lichen planus: coexistence in a single patient. Are
both diseases mutually exclusive? Dermatologica
179:178-182.
Shklar G (1972). Lichen planus as an oral ulcerative dis-
ease. Oral Surg 33:376-388.
Shuttleworth D, Graham-Brown RAC, Campbell AC
(1986). The autoimmune background in lichen
planus. Brl Dermatol 115:199-203.
Sieg P, von Doarus H, von Zitzewitz V, Iven H, Farber L
(1995). Topical cyclosporin in oral lichen planus: a
controlled, randomized prospective trial. Br I Dermatol
132:790-794.
Sigurgeirsson B, Lindelof B (1991). Lichen planus and
malignancy. An epidemiologic study of 2071 patients
and a review of the literature. Arch Dermatol 127:1684-
1688.
Silverman S Jr, Griffith M (1974). Studies on oral lichen
planus. 11. Follow-up on 200 patients, clinical charac-
teristics, and associated malignancy. Oral Surg Oral
Med Oral Pathol 37:705-710.
Silverman S Ir, Lozada-Nur F, Migliorati C (1985a).
Clinical efficacy of prednisone in the treatment of
patients with oral inflammatory ulcerative diseases: a
study of fifty-five patients. Oral Surg Oral Med Oral
Pathol 59:360-363.
Silverman S Ir, Gorsky M, Lozada-Nur F (1985b). A
prospective follow-up study of 570 patients with oral
lichen planus: persistence, remission and malignant
association. Oral Surg Oral Med Oral Pathol 60:30-34.
Silverman S Jr, Gorsky M, Lozada-Nur F, Giannotti K
1
119
 (1991). A prospective study of findings and manage-
ment in 214 patients with oral lichen planus. Oral Surg
Oral Med Oral Pathol 72:665-670.
Simark-Mattsson C, Bergenholtz G, Jontell M, Tarkowski
A, Dahlgren UI (1994). T cell receptor V-gene usage in
oral lichen planus: increased frequency of T cell
receptors expressing Vcx2 and V133. Clin Exp Immunol
98:503-507.
Simon M Jr (1990). Immunopathological aspects of
etretinate therapy in lichen planus. I Dermatol 17:282-
286.
Simon M Jr, Hornstein OP (1980). Prevalence rate of
Candida in the oral cavity of patients with oral lichen
planus. Arch Dermatol Res 267:317-318.
Simon M Jr, Hunyadi J (1990). Etretinate suppresses
ICAM-1 expression by lesional keratinocytes in heal-
ing cutaneous lichen planus. Arch Dermatol Res
282:412-414.
Sklavounou AD, Laskaris G (1983). Frequency of desqua-
mative gingivitis in skin diseases. Oral Surg 56:141-144.
Sklavounou AD, Laskaris G, Angelopoulos AP (1983).
Serum immunoglobulins and complement (C'3) in
oral lichen planus. Oral Surg Oral Med Oral Pathol
55:47-5 1.
Skoglund A (1994). Value of epicutaneous patch testing
in patients with oral mucosal lesions of lichenoid
character. Scand I Dent Res 102:216-222.
Skoglund A, Egelrud T (1991). Hypersensitivity reactions
to dental materials in patients with lichenoid oral
mucosal lesions and in patients with burning mouth
syndrome. Scand J Dent Res 99:320-328.
Sleeper HR (1967). Intralesional and sublesional injec-
tion of triamcinolone acetonide for oral lichen
planus. Yale I Biol Med 40:164-165.
Sloberg K, Hersle K, Mobacken H, Thilander H (1979).
Topical tretinoin therapy and oral lichen planus. Arch
Dermatol 115:716-718.
Sloberg K, Hersle K, Mobacken H, Thilander H (1983).
Severe oral lichen planus: remission and mainte-
nance with vitamin A analogues. l Oral Pathol 12:473-
477.
Sloberg K, Ionsson R, lontell M (1984). Assessment of
Langerhans cells in oral lichen planus using mono-
clonal antibodies. J Oral Pathol 13:516-524.
Smart ER, MacLeod RI, Lawrence CM (1995). Resolution
of lichen planus following removal of amalgam
restorations in patients with proven allergy to mer-
cury salts: a pilot study. Br Dent 1 178:108-112.
Snyder RA, Schwartz RA, Schneider JS, Elias PM (1982).
Intermittent megadose corticosteroid therapy for
generalised lichen planus. I Am Acad Dermatol 6:1089-
1090.
Soper DE, Patterson JW, Hurt WG, Fantl JA, Blaylock WK
(1988). Lichen planus of the vulva. Obstet Gynecol
71:832-836.
120
Downloaded from http://cro.sagepub.com by on June 26, 2010
Stankler L (1975). Deficiency of circulating IgA and IgM in
adult patients with lichen planus. Br I Dermatol 93:25-
27.
Stankler L, Ewan SW (1974). The effects of experimental
skin damage in patients with lichen planus. A prelim-
inary communication. Br I Dermatol 90:25-28.
Stans ME, Bergfeld WF (1984). Treatment of oral lichen
planus with low-dose isotretinoin. I Am Acad Dermatol
11:527-528.
Strauss RA, Fattore L, Soltani K (1989). The association
of mucocutaneous lichen planus and chronic liver
disease. Oral Surg Oral Med Oral Pathol 68:406-410.
Strumia R, Venturini D, Boccia S, Gamberini S, Gullini S
(1993). UVA and interferon-alpha therapy in a patient
with lichen planus and chronic hepatitis C. Int I
Dermatol 32:386.
Stuttgen G (1975). Oral vitamin A acid therapy. Acta Derm
Venereol 55:174-175.
Sugerman PB, Savage NW, Seymour GJ (1994). Phenotype
and suppressor activity of T-lymphocyte clones
extracted from lesions of oral lichen planus. Br I
Dermatol 131:319-324.
Sugerman PB, Savage NW, Xu Ll, Walsh LI, Seymour G1
(1995). Heat shock protein expression in oral lichen
planus. I Oral Pathol Med 24:1-8.
Sugerman PB, Savage NW, Seymour GI, Walsh LI (1996).
Is there a role for tumour necrosis factor-alpha (TNF)
in oral lichen planus? J Oral Pathol Med 25:219-224.
Sun A, Chiang CP, Chiou PS, Wang JT, Liu BY, Wu YC
(1994). Immunomodulation by levamisole in patients
with recurrently aphthous ulcers or oral lichen
planus. I Oral Pathol Med 4:172-177.
Takeuchi Y, Tohnai 1, Kaneda T, Nagura H (1988).
Immunohistochemical analysis of cells in mucosal
lesions of oral lichen planus. I Oral Pathol 17:367-373.
Tal H, Rafkin B (1986). Cryosurgical treatment of gingival
lichen planus: report of a case. J Am Dent Assoc
113:629-631.
Tamizi M, Moayedi M (1992). Treatment of gingival lichen
planus with a free gingival graft: a case report.
Quintessence Int 23:249-251.
Tan RSH (1974a). Ulcerative colitis, myasthenia gravis,
atypical lichen planus, alopecia areata, vitiligo. Proc R
Soc Med 67:195-196.
Tan RSH (1974b). Thymoma, acquired hypogammaglob-
ulinaemia, lichen planus, alopecia areata. Proc R Soc
Med 67:196-198.
Thongprasom K, Luangjarmekorn L, Sererat T, Taweesap
W (1992). Relative efficacy of fluocinolone acetonide
compared with triamcinolone acetonide in treatment
of oral lichen planus. J Oral Pathol Med 21:456-458.
Thorn JJ, Holmstrup P, Rindrum J, Pindborg IJ (1988).
Course of various clinical forms of oral lichen planus.
A prospective follow-up study of 611 patients. J Oral
Pathol 17:213-218.
(1998)
Crit Rev Oral
Crit Rev Oral Biol Med
Biol Med 9(l):86-122 (1998)
Torrelo A, Soria C, Rocamora A, Moreno R, Ledo A (1990).
Lichen planus-like eruption with esophageal involve-
ment as a result of cyanamide. I Am Acad Dermatol
23:1168-1169.
Torresani C, Nannini R, Bondi A, Guadagni M, Manara GC
(1994). Erosive lichen planus due to sensitization to
cobalt chloride. Clin Exp Dermatol 19:535-536.
Tosca A, Varelzidis A, Michaelopoulous M, Georgala S,
Stratigos 1 (1983). In situ identification of mononu-
clear cells in lichen planus. Dermatologica 167:113-
120.
Tradati N, Chiesa F, Rossi N, Grigolato R, Formelli F,
Costa A. et al. (1994). Successful topical treatment of
oral lichen planus and leukoplakias with fenretinide
(4-HPR). Canc Lett 76:109- 111.
Tyldesley WR, Harding SM (1977). Betamethasone valer-
ate aerosol in the treatment of oral lichen planus. Br
I Dermatol 96:659-662.
Van den Haute V, Antoine IL, Lachapelle JM (1989).
Histopathological discriminant criteria between
lichenoid drug eruptions and idiopathic lichen
planus: retrospective study on selected samples.
Dermatologica 179:10-13.
Van der Horst JC, Cirkel PKS, Nieboer C (1983). Mixed
lichen planus-lupus erythematosus disease. A dis-
tinct entity? Clinical, histopathological,
immunopathological studies in six patients. ClGn Exp
Dermatol 8:631-640.
Van Dis ML, Parks ET (1995). Prevalence of oral lichen
planus in patients with diabetes mellitus. Oral Surg
Oral Med Oral Pathol 79:696-700.
Van Hale HM, Rogers RS (1987). Immunopathology of
oral mucosal inflammatory diseases. Dermatol Clin
5:739-750.
Van Joost T (1974). Incidence of circulating antibodies
reactive with basal cells of skin in drug reactions. Acta
Derm Venereol (Stockh) 54:183-188.
Vedtofte P, Holmstrup P, Hansen EH, Pindborg J1 (1987).
Surgical treatment of premalignant lesions of the oral
mucosa. lnt J Oral Maxillofac Surg 16:656-664.
Verdickt GM, Savage NW, Dodd NM, Walsh LI (1992).
Expression of the CD54 (ICAM- 1) and CD 11 a (LFA- 1)
adhesion molecules in oral mucosal inflammation. I
Oral Pathol Med 21:65-69.
Vincent SD, Fotos PG, Baker KA, Williams TP (1990). Oral
lichen planus: the clinical, historical and therapeutic
features of 100 cases. Oral Surg Oral Med Oral Pathol
70:165-171.
Voltz MI (1989). Flow cytometric analysis of peripheral
blood lymphocyte subsets in oral lichen planus (the-
sis ) Oueensland, Australia: University of
Queensland.
Voute ABE (1994). Oral lichen planus. A clinical study
(thesis). Amsterdam: University of Amsterdam.
Voute AB, De long WF, Schulten EAJ, Snow GB, van der
9(1)86 122)1998)
9(1):86-122 i1998)
Downloaded from http://cro.sagepub.com by on June 26, 2010
Waal 1 (1992). Possible premalignant character of oral
lichen planus. The Amsterdam experience. J Oral
Pathol Med 21:326-329.
Voute AB, Schulten EA, Langendijk PN, Kostense P1, van
der Waal 1 (1993). Fluocinonide in an adhesive base
for treatment of oral lichen planus. A double-blind,
placebo-controlled clinical study. Oral Surg Oral Med
Oral Pathol 75:181-185.
Wahba-Yahav AV (1989). Intestinal amebiasis, lichen
planus, and treatment with metronidazole. I Am Acad
Dermatol 20:1128-1129.
Walsh LI, Tseng PW, Savage W, Seymour GI (1989).
Expression of CDw29 and CD45R antigens on epithelial
cells in oral lichen planus. I Oral Pathol Med 18:360-365.
Walsh LI, Ishii T, Savage NW, Gemmell E, Seymour GI
(1990a). Immunohistologic analysis of epithelial cell
populations in oral lichen planus. I Oral Pathol Med
19:177-181.
Walsh LJ, Savage NW, Ishii T, Seymour GI (1990b).
Immunopathogenesis of oral lichen planus. I Oral
Pathol Med 19:389-396.
Walton LI, Thornhill MH, Farthing PM (1994). VCAM-1
and ICAM-1 are expressed by Langerhans cells,
macrophages and endothelial cells in oral lichen
planus. I Oral Pathol Med 23:262-268.
Wantzin GL, Ralfkiaer E, Lisby S, Rothlein R (1988). The
role of intercellular adhesion molecules in inflamma-
tory skin reactions. Br I Dermatol 119:141-145.
Watanabe C, Hayashi T, Kawada A (1991).
Immunofluorescence study of drug-induced lichen
planus-like lesions. I Dermatol 8:473-477.
Weidan AL (1963). Treatment of psoriasis and other der-
matoses with intralesional injections of triam-
cinolone acetonide. Curr Ther Res 5:7.
Wiesenfeld D, Scully C, MacFarlane EE (1982). Multiple
lichenoid drug reactions in a patient with Ferguson-
Smith disease. Oral Surg 54:527-529.
Wiles JC, Lynch P1 (1984). Lichen planus and liver disease.
I Am Acad Dermatol 10:671-672.
With AG, Rostom Al (1994). HLA antigens in Arabs with
lichen planus. Clin Exp Dermatol 19:236-237.
Woo TY (1985). Systemic isotretinoin treatment of oral
and cutaneous lichen planus. Cutis 35:385-393.
Wray D, McCord IF (1987). Labial veneers in the manage-
ment of desquamative gingivitis. Oral Surg Oral Med
Oral Pathol 64:41-42.
Yamamoto T, Yoneda K, Ueta E, Osaki T (1990). Cellular
immunosuppression in oral lichen planus. I Oral
Pathol Med 19:464-470.
Yamamoto T, Yoneda K, Ueta E, Higota J, Osaki T (1991).
Serum cytokine levels in patients with oral mucous
membrane disorders. I Oral Pathol Med 20:275-279.
Yamamoto T, Osaki T, Yoneda K, Ueta E (1994). Cytokine
production by keratinocytes and mononuclear infil-
trates in oral lichen planus. Oral Pathol Med 23:309-315.
121
Crit Rev Oral Biol Med
Crit Rev Oral Biol Med
121
Zegarelli D (1980). Topical intralesional steroid therapy
of oral lichen planus. NY State Dent 1 46:432.
Zegarelli Dl (1983). Multimodality steroid therapy of ero-
sive and ulcerative oral lichen planus. J Oral Med
38:127-130.
Zegarelli Dl (1984). Treatment of oral lichen planus with
topical vitamin A acid. l Oral Med 39:186-191.
Zegarelli F, Kutscher A, Mehrhof A (1969). Long-lasting
lozenges with triamcinolone acetonide. NY State J Med
69:2463-2464.
Zijdenbos LM, Starink TM, Spronk CA (1985). Ulcerative
lichen planus with associated sicca syndrome and
good therapeutic result of skin grafting. I Am Acad
Dermatol 13:667-668.

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Crit Rev Oral
Oral Biol Med
Biol Med 9(l):86-122 (1998)
Downloaded from http://cro.sagepub.com by on June 26, 2010