Candidal infection in oral lichen planus Dorian A. Hatchuel, BDS, MDent,a Edmund Peters, DDS, MSc, FRCD(C).’ John Lemmer, BDS, HDip Dent,a Johannes J, Hille, DDS, MDent.a and William T. McGaw, DDS. MSc, FRCD(C),b Johannesburg, South Africa, and Edmonton, Alberta, Canada UNIVERSITY RESEARCH,
OF THE WITWATERSRAND, AND UNIVERSITY
THE SOUTH AFRICAN
INSTITUTE
FOR MEDICAL
OF ALBERTA
The prevalence of candidal infection in lichen planus (LP) and its possible association with ulceration were independently examined in two archived series of 108 and 77 cases derived from two separate populations. To ensure that similar material was being compared, each case was histopathologically reassessed and confirmed as LP or reclassified as nonspecific lichenoid stomatitis (NSLS), lichenoid dysplasia (LD), or other (0). Three further sections, cut at 25 pm intervals, were stained with periodic acid-Schiff reagent for the identification of intraepithelial candidal pseudohyphae. As control specimens, 8 1 normal and 59 hyperkeratotic mucosal samples were similarly processed and examined. Candidal infection was found in 17.4% and 18.4% of ulcerated and nonulcerated LP cases, respectively, and in 40.0% and 18.7% of ulcerated and nonulcerated NSLS cases, respectively. One case of LD was infected. Each control series contained one infected case. The results indicate that candidal infection occurs more readily in LP and NSLS, with no apparent association with ulceration in LP. The comparatively marked increase in the infection prevalence of ulcerated NSLS cannot be statistically confirmed, and its significance remains uncertain. (ORAL SURG ORAL MED ORAL PATHOL 1990;70:172-5)
B
iopsy studies of oral lichen planus (LP) have suggested candidal infection occurs in 0.0% to 7.7% of caseswith no apparent predilection for any particular clinical type of LP.le3 Culture studies have demonstrated Candida in 37% to 50% of oral LP cases,a prevalencethat approximates the findings in a normal population. 2-4These results indicate that candidal infection in LP is not a significant factor. However, Lundstrom and coworkers2 found clinical improvement after antifungal therapy in 17 of 18 LP cases from which Candida had beencultured and noted that erosive lesions often changed to reticular lesions after this treatment. The usefulness of antifungal therapy in selected cases has been supported by other author& 6 and reflects our clinical experience. This clinical perception is not consistent with the low prevalence of candidal infection demonstrated by biopsy. aDepartment of Oral Pathology and Department of Oral Medicine and Periodontology, University of the Witwatersrand, Johannesburg, and The South African Institute for Medical Research. bDepartment of Oral Biology, Faculty of Dentistry, University of Alberta. 7/13/11742
172
Thus, the prevalence and significance of candidal infection in LP could have been underestimated. The purpose of this study was to examine this possibility by determining the prevalence of candidal pseudohyphae in 185 biopsies of LP derived from two separate populations and by comparing the candidal prevalence in the relatively symptomatic ulcerated form with the prevalence in the nonulcerated form. MATERIAL
AND METHODS
One-hundred eight biopsies submitted over a loyear period (1976-1986) to the Department of Oral Pathology, University of the Witwatersrand, and 77 biopsies submitted over a 7-year period (1979- 1986) to the Department of Oral Pathology, University of Alberta, were independently studied according to identical criteria. All the cases had been diagnosed histopathologically as LP or consistent with LP. To ensure that unequivocal and comparable cases of LP were being studied, each diagnosis was reassessedby two observers and reclassified according to criteria adapted from Krutchkoff and Eisenberg.’ These criteria are as follows: 1. Lichen planus
Candidal infection in oral lichen planus
Volume 70 Number 2
A. A bandlike infiltrate of lymphocytes within the lamina propria that intimately intermingles with the basal cell region of the epithelium. B. Liquefactive degeneration of the epithelial basal cells. Additional features considered supportive of but not essential to the diagnosis were “sawtooth” rete pegs, hyperkeratosis, and the presence of Civatte bodies. 2. Nonspeci$c lichenoid stomatitis
(NSLS)
A. Diffuse extension of a juxtaepithelial inflammatory infiltrate to involve deeper submucosal tissues,or perivascular distribution of the infiltrate. B. The presenceof a heterogenous inflammatory infiltrate. An infiltrate was considered heterogenous if it included substantial numbers of plasma cells, eosinophils, or neutrophils in any five of 10 contiguous high-power (400x) fields. 3. Lichenoid dysplasia (LD). The presence of topographic features, cytologic features, or both, of dysplasia as defined by the World Health Organization.* 4. Other (0). Pathologic entities that could be otherwise specifically diagnosed. Specific histologic features recorded in the reclassification included the presenceor absenceof inflammatory cells in the keratin layer, and ulceration. In ulcerated cases, the infiltrate was assessedin areas distant from the ulcer. To determine clinical correlation, the revised histopathologic diagnoses were matched with the recorded clinical diagnoses. The clinical diagnosis was classified as LP if the clinician submitting the biopsy had indicated this was the only clinical diagnosis or the first item in a differential diagnosis. Alternatively, the clinical diagnosis was classified as 0 if a different or no clinical diagnosis had been rendered. Control biopsies of normal mucosa and hyperkeratotic mucosawithout evidenceof any other pathologic process were obtained and processedroutinely. The normal samples were collected from random sites in the oral cavity from patients who were undergoing surgery electively or as a result of trauma. Hyperkeratotic mucosal sampleswere accessedsequentially from the archives. The Witwatersrand seriesincluded 3 1 normal and 29 hyperkeratotic samples;the Alberta series included 30 normal and 30 hyperkeratotic samples. Subsequently, three further 5 pm thick sections were cut at 25 pm intervals from each biopsy for staining with periodic acid-Schiff reagent to assess for the presenceof intraepithelial candidal pseudohy-
173
Table I. The number and percentage of infected casesafter histopathologic reclassification ReclassiJed diagnosis Lichen planus A B Total NSLS A B Total Lichenoid dysplasia A B Total Other A B Total
No. of cases
Infected cases
88 57 145
16(18.2%) 8( 14.0%) 24(16.6%)
14
3(21.4%)
2 4
1(50.0%) O(O.O% ) 1(16.7%)
4 2
1(25.0%)
6
6
A, Witwatersrand series; B, Alberta series.
phae. Infection prevalenceswere compared by statistical analysis with the Yates corrected chi-square test and Fisher’s exact test. RESULTS
Thirty-three of the 185 cases(17.8% of total before reclassification) showed candidal infection. In comparison, one infected casewas found in each of the 61 normal and 59 hyperkeratotic control mucosal samples; this difference is statistically significant (chisquare test, p < 0.05). Thirty-five of the 185 cases were ulcerated, and candidal infection was found in 22.9% of these compared with a 16.7% infection prevalence in the remaining nonulcerated cases.This difference is not statistically significant (chi-square test, p > 0.05). After histopathologic reclassification (Table I), a candidal prevalence of 16.6% was found in 145 confirmed LP casesand 25.0% in 28 NSLS cases.This difference is not statistically significant (chi-square test, p > 0.05). One of the six cases(16.7%) reclassified as LD and one of the six cases(16.7%) in the 0 category were infected; there were insufficient casesin these categories to analyze. The ulcerated and nonulcerated casesof confirmed LP showed virtually equal infection prevalences of 17.4% and 16.4%, respectively, whereas 40.0% of ulcerated NSLS cases were infected compared with 16.7% of nonulcerated NSLS cases (Table II). The apparent infection prevalence increase of the ulcerated NSLS group could not be statistically confirmed (Fisher’s exact test for small samples,p > 0.05).
174
Hatchuel et al.
ORAL SURG ORAL MED ORAL PATHOL August 1990
Fig. 1. Several candidal hyphae are evident within the keratin layer in a caseof lichen planus; no concomitant inflammatory cells are present. (Periodic acid-Schiff stain. Magnification X100.)
Table
II. The number and percentage of infected lichen planus and NSLS cases,with and without ulceration
I Lichen planus A B Total NSLS A B Total
Ulcerated cases
I
Infected ulcerated cases
Nonulcerated cases
Nonulcerated infected cases
17 6 23
3 (17.6%) m . 0
71 51 122
13 (18.3%) 7 (13.7%) 20 (16.4%)
6 4 i?i
2 (33.3%)
8
1 (12.5%)
A, Witwatersrand series; B, Alberta series.
Features of candidal infection without a concomitant inflammatory cell infiltrate in the keratin layer (Fig. 1) were found in 52.0% of confirmed LP cases, 50.0% of NSLS cases,and the single LD case. The attempt to determine whether a clinical difference exists between the histopathologically reclassified LP and NSLS categories was unsuccessful.There was a clinical diagnosis of LP in 85.7% of the NSLS casescompared with clinical LP diagnosis in 74.5% of the confirmed LP cases. DCSCUSSION
This study showsa substantially greater prevalence of candidal pseudohyphae than that suggested by previous biopsy studies.l-3 The discrepancy is difficult to explain. However, the low prevalence in
one study could have been caused by prior treatment with amphotericin B before biopsy in six of 39 patients.2 In a second study, only reticular LP forms were examined,3 and possibly this restriction excluded infected casesthat could have had an altered clinical presentation. The further possibility exists that, in some institutions, LP caseswith candidal infection could have been classified as candidiasis and thus would not be accessible in retrospective LP studies.’ Control specimens of normal and hyperkeratotic mucosa in this study, as well as findings in a previous study,9 indicate that, with the possible exception of the dorsal glossal mucosa,lo intraepithelial candiial pseudohyphae are unusual. The comparatively high prevalence of candidal pseudohyphaein the LP biop-
Volume 70 Number 2
sies suggeststhat LP could be a predisposing condition to candidal infection. The lack of an inflammatory responseto the infesting pseudohyphaein almost half of the casescould be due to infection by certain C. albicans strains capable of epithelial penetration without eliciting an inflammatory reaction.’ 1 The frequent lack of an inflammatory reaction, the small numbers of pseudohyphae in somecases,and the otherwise characteristic histopathologic appearance of LP were apparently the reasons the pseudohyphae had been previously undetected in most cases. The significance of candidal infection in LP is uncertain. The ulcerated and nonulcerated forms of confirmed LP showed virtually equal infection prevalence of 17.4% and 16.4’35,respectively. The apparent quantum increase to 40% in the infection prevalence of the ulcerated NSLS group could not be proven to an acceptable level of statistical certainty. However, if this finding can be confirmed, it suggests the possibility of a subgroup of patients with an unusually severereaction associatedwith Cundidu who would, accordingly, most benefit from antifungal therapy. There are at least three possible explanations, which are not mutually exclusive, for such a distinctive group. There could be an exacerbated reaction to infection in a select group as a result of a compromised host resistance, infection with a more virulent strain of Cundidu. or hypersensitization to candidal allergens. This reaction could cause conversion from the features of LP to the less specific features of a lichenoid stomatitis as well as ulceration. It is also possible that nonspecific lichenoid reactions to a variety of agents could share the same propensity for infection as LP. The unspecified etiologic agent resulting in the NSLS could represent a more severe insult to epithelial integrity that more readily results in ulceration after the further stressof a candidal infection. Finally, someof these casescould be unusual examples of primary candidiasis that have elicited a lichenoid reaction. Somewhat surprisingly, the group with NSLS apparently was interpreted clinically as having LP more often than was the group with histopathologically confirmed LP. However, there is a heterogeneous clinical spectrum that has been accepted as clinical LP. This spectrum includes linear, discrete papular, confluent papular, reticular, annular, pigmented, vesicular, bullous, and atrophic or erosive forms. ’ 2,l 3 It is possible that within this spectrum there are characteristics that are pathognomonic for the different histopathologic categories. Such differences would be obscured by the limitations of the retrospective data collection used in this study.
Candidul infection in oral lichen plums
175
This study emphasizesthe necessity to assessroutinely the possibility of a secondary candidal infection in oral LP or NSLS and supports clinical impressions of the value of antifungal therapy in some cases.A further tangential issue is raised regarding the controversial relationship of LP and malignancy. The frequency with which previously undetected candidal pseudohyphae were found in this study, the potential of Cundidu to cause pseudoepitheliomatous hyperplasia, and the possible relationship between candidal infection and oral carcinomaI indicate that studies of epithelial dysplasia or carcinoma in LP should specifically note the presenceor absenceof candidal infection. The authorsthank Ms. JeanCookeand Mr. DennisCarme1for their technicalassistanceand Dr. Chris C. Rachanisfor hisvaluableclinical impressionsthat partly ledto the undertakingof this study. REFERENCES 1. Holmstrup P, Dabblesteen E. The frequency of Cundidu in oral
lichen planus. Stand J Dent Res 1974;82:584-7. 2. Lundstrom IMC, Anneroth GB, Holmberg K. Cundida in patients with oral lichen planus. Int J Oral Surg 1984;13:226-38. 3. Krogh P, Holmstrup P, Thorn JJ, Vedtofte P, Pindborg JJ. Yeast species and biotypes associated with oral leukoplakia and lichen planus. ORAL SURGORAL MED ORAL PATHOL 1987;63:48-54. 4. Simon M Jr, Hornstein OP. Prevalence rate of Candidu in the oral cavity of patients with oral lichen planus. Arch Dematol Res 1980;267:317-8. 5. Dreyer WP. The clinical manifestations of oral lichen planus. J Dent Assoc S Afr 1983;38:619-24. 6. Lacy MF, Reade PC, Hay KD. Lichen planus: a theory of pathogenesis. ORAL SURGORAL MED ORAL PATHOL 1983; 56:521-6. 7. Krutchkoff DJ, Eisenberg E. Lichenoid dysplasia: a distinct histopathologic entity. ORALSURGORAL MED ORAL PATHOL 1985;30:308-15. 8. WHO Collaborating Reference Centre for Oral Precancerous Lesions. Definition of leukoplakia and related lesions. An aid to studies on oral precancer. ORAL SURGORAL MED ORAL PATHOL1978;46:518-39. 9. Roed-Petersen B, Renstrup G, Pindborg JJ. Candida in oral leukoplakias. A histologic and exfoliative cytologic study. Stand J Dent Res 1970;78:323-8. 10. Van der Wal N, Van der Waal I. Cundidu albicuns in median rhomboid glossitis. Int J Oral Maxillofac Surg 1986;15:322-5. 11. Allen CM, Beck FM. Differences in mucosal reaction related to Candida albicans isolates. J Oral Pathol 1987;16:89-93. 12. Cooke BED. The oral manifestations of lichen planus: 50 cases. Br Dent J 1954;96:1-9. 13. Scully C, El-Kom M. Lichen planus: review and update on pathogenesis.J Oral Pathol 1985;14:431-58. 14. Binnie WH, Rankin KV, Mackenzie IC. Etiology of oral squamous cell carcinoma. J Oral Path01 1983;12:11-29. Reprint requests to: Dr. Dorian A. Hatchuel Division of Diagnosis Faculty of Dentistry University of Alberta Edmonton, Alberta, Canada T6G 2N8
OF THE WITWATERSRAND, AND UNIVERSITY
THE SOUTH AFRICAN
INSTITUTE
FOR MEDICAL
OF ALBERTA
The prevalence of candidal infection in lichen planus (LP) and its possible association with ulceration were independently examined in two archived series of 108 and 77 cases derived from two separate populations. To ensure that similar material was being compared, each case was histopathologically reassessed and confirmed as LP or reclassified as nonspecific lichenoid stomatitis (NSLS), lichenoid dysplasia (LD), or other (0). Three further sections, cut at 25 pm intervals, were stained with periodic acid-Schiff reagent for the identification of intraepithelial candidal pseudohyphae. As control specimens, 8 1 normal and 59 hyperkeratotic mucosal samples were similarly processed and examined. Candidal infection was found in 17.4% and 18.4% of ulcerated and nonulcerated LP cases, respectively, and in 40.0% and 18.7% of ulcerated and nonulcerated NSLS cases, respectively. One case of LD was infected. Each control series contained one infected case. The results indicate that candidal infection occurs more readily in LP and NSLS, with no apparent association with ulceration in LP. The comparatively marked increase in the infection prevalence of ulcerated NSLS cannot be statistically confirmed, and its significance remains uncertain. (ORAL SURG ORAL MED ORAL PATHOL 1990;70:172-5)
B
iopsy studies of oral lichen planus (LP) have suggested candidal infection occurs in 0.0% to 7.7% of caseswith no apparent predilection for any particular clinical type of LP.le3 Culture studies have demonstrated Candida in 37% to 50% of oral LP cases,a prevalencethat approximates the findings in a normal population. 2-4These results indicate that candidal infection in LP is not a significant factor. However, Lundstrom and coworkers2 found clinical improvement after antifungal therapy in 17 of 18 LP cases from which Candida had beencultured and noted that erosive lesions often changed to reticular lesions after this treatment. The usefulness of antifungal therapy in selected cases has been supported by other author& 6 and reflects our clinical experience. This clinical perception is not consistent with the low prevalence of candidal infection demonstrated by biopsy. aDepartment of Oral Pathology and Department of Oral Medicine and Periodontology, University of the Witwatersrand, Johannesburg, and The South African Institute for Medical Research. bDepartment of Oral Biology, Faculty of Dentistry, University of Alberta. 7/13/11742
172
Thus, the prevalence and significance of candidal infection in LP could have been underestimated. The purpose of this study was to examine this possibility by determining the prevalence of candidal pseudohyphae in 185 biopsies of LP derived from two separate populations and by comparing the candidal prevalence in the relatively symptomatic ulcerated form with the prevalence in the nonulcerated form. MATERIAL
AND METHODS
One-hundred eight biopsies submitted over a loyear period (1976-1986) to the Department of Oral Pathology, University of the Witwatersrand, and 77 biopsies submitted over a 7-year period (1979- 1986) to the Department of Oral Pathology, University of Alberta, were independently studied according to identical criteria. All the cases had been diagnosed histopathologically as LP or consistent with LP. To ensure that unequivocal and comparable cases of LP were being studied, each diagnosis was reassessedby two observers and reclassified according to criteria adapted from Krutchkoff and Eisenberg.’ These criteria are as follows: 1. Lichen planus
Candidal infection in oral lichen planus
Volume 70 Number 2
A. A bandlike infiltrate of lymphocytes within the lamina propria that intimately intermingles with the basal cell region of the epithelium. B. Liquefactive degeneration of the epithelial basal cells. Additional features considered supportive of but not essential to the diagnosis were “sawtooth” rete pegs, hyperkeratosis, and the presence of Civatte bodies. 2. Nonspeci$c lichenoid stomatitis
(NSLS)
A. Diffuse extension of a juxtaepithelial inflammatory infiltrate to involve deeper submucosal tissues,or perivascular distribution of the infiltrate. B. The presenceof a heterogenous inflammatory infiltrate. An infiltrate was considered heterogenous if it included substantial numbers of plasma cells, eosinophils, or neutrophils in any five of 10 contiguous high-power (400x) fields. 3. Lichenoid dysplasia (LD). The presence of topographic features, cytologic features, or both, of dysplasia as defined by the World Health Organization.* 4. Other (0). Pathologic entities that could be otherwise specifically diagnosed. Specific histologic features recorded in the reclassification included the presenceor absenceof inflammatory cells in the keratin layer, and ulceration. In ulcerated cases, the infiltrate was assessedin areas distant from the ulcer. To determine clinical correlation, the revised histopathologic diagnoses were matched with the recorded clinical diagnoses. The clinical diagnosis was classified as LP if the clinician submitting the biopsy had indicated this was the only clinical diagnosis or the first item in a differential diagnosis. Alternatively, the clinical diagnosis was classified as 0 if a different or no clinical diagnosis had been rendered. Control biopsies of normal mucosa and hyperkeratotic mucosawithout evidenceof any other pathologic process were obtained and processedroutinely. The normal samples were collected from random sites in the oral cavity from patients who were undergoing surgery electively or as a result of trauma. Hyperkeratotic mucosal sampleswere accessedsequentially from the archives. The Witwatersrand seriesincluded 3 1 normal and 29 hyperkeratotic samples;the Alberta series included 30 normal and 30 hyperkeratotic samples. Subsequently, three further 5 pm thick sections were cut at 25 pm intervals from each biopsy for staining with periodic acid-Schiff reagent to assess for the presenceof intraepithelial candidal pseudohy-
173
Table I. The number and percentage of infected casesafter histopathologic reclassification ReclassiJed diagnosis Lichen planus A B Total NSLS A B Total Lichenoid dysplasia A B Total Other A B Total
No. of cases
Infected cases
88 57 145
16(18.2%) 8( 14.0%) 24(16.6%)
14
3(21.4%)
2 4
1(50.0%) O(O.O% ) 1(16.7%)
4 2
1(25.0%)
6
6
A, Witwatersrand series; B, Alberta series.
phae. Infection prevalenceswere compared by statistical analysis with the Yates corrected chi-square test and Fisher’s exact test. RESULTS
Thirty-three of the 185 cases(17.8% of total before reclassification) showed candidal infection. In comparison, one infected casewas found in each of the 61 normal and 59 hyperkeratotic control mucosal samples; this difference is statistically significant (chisquare test, p < 0.05). Thirty-five of the 185 cases were ulcerated, and candidal infection was found in 22.9% of these compared with a 16.7% infection prevalence in the remaining nonulcerated cases.This difference is not statistically significant (chi-square test, p > 0.05). After histopathologic reclassification (Table I), a candidal prevalence of 16.6% was found in 145 confirmed LP casesand 25.0% in 28 NSLS cases.This difference is not statistically significant (chi-square test, p > 0.05). One of the six cases(16.7%) reclassified as LD and one of the six cases(16.7%) in the 0 category were infected; there were insufficient casesin these categories to analyze. The ulcerated and nonulcerated casesof confirmed LP showed virtually equal infection prevalences of 17.4% and 16.4%, respectively, whereas 40.0% of ulcerated NSLS cases were infected compared with 16.7% of nonulcerated NSLS cases (Table II). The apparent infection prevalence increase of the ulcerated NSLS group could not be statistically confirmed (Fisher’s exact test for small samples,p > 0.05).
174
Hatchuel et al.
ORAL SURG ORAL MED ORAL PATHOL August 1990
Fig. 1. Several candidal hyphae are evident within the keratin layer in a caseof lichen planus; no concomitant inflammatory cells are present. (Periodic acid-Schiff stain. Magnification X100.)
Table
II. The number and percentage of infected lichen planus and NSLS cases,with and without ulceration
I Lichen planus A B Total NSLS A B Total
Ulcerated cases
I
Infected ulcerated cases
Nonulcerated cases
Nonulcerated infected cases
17 6 23
3 (17.6%) m . 0
71 51 122
13 (18.3%) 7 (13.7%) 20 (16.4%)
6 4 i?i
2 (33.3%)
8
1 (12.5%)
A, Witwatersrand series; B, Alberta series.
Features of candidal infection without a concomitant inflammatory cell infiltrate in the keratin layer (Fig. 1) were found in 52.0% of confirmed LP cases, 50.0% of NSLS cases,and the single LD case. The attempt to determine whether a clinical difference exists between the histopathologically reclassified LP and NSLS categories was unsuccessful.There was a clinical diagnosis of LP in 85.7% of the NSLS casescompared with clinical LP diagnosis in 74.5% of the confirmed LP cases. DCSCUSSION
This study showsa substantially greater prevalence of candidal pseudohyphae than that suggested by previous biopsy studies.l-3 The discrepancy is difficult to explain. However, the low prevalence in
one study could have been caused by prior treatment with amphotericin B before biopsy in six of 39 patients.2 In a second study, only reticular LP forms were examined,3 and possibly this restriction excluded infected casesthat could have had an altered clinical presentation. The further possibility exists that, in some institutions, LP caseswith candidal infection could have been classified as candidiasis and thus would not be accessible in retrospective LP studies.’ Control specimens of normal and hyperkeratotic mucosa in this study, as well as findings in a previous study,9 indicate that, with the possible exception of the dorsal glossal mucosa,lo intraepithelial candiial pseudohyphae are unusual. The comparatively high prevalence of candidal pseudohyphaein the LP biop-
Volume 70 Number 2
sies suggeststhat LP could be a predisposing condition to candidal infection. The lack of an inflammatory responseto the infesting pseudohyphaein almost half of the casescould be due to infection by certain C. albicans strains capable of epithelial penetration without eliciting an inflammatory reaction.’ 1 The frequent lack of an inflammatory reaction, the small numbers of pseudohyphae in somecases,and the otherwise characteristic histopathologic appearance of LP were apparently the reasons the pseudohyphae had been previously undetected in most cases. The significance of candidal infection in LP is uncertain. The ulcerated and nonulcerated forms of confirmed LP showed virtually equal infection prevalence of 17.4% and 16.4’35,respectively. The apparent quantum increase to 40% in the infection prevalence of the ulcerated NSLS group could not be proven to an acceptable level of statistical certainty. However, if this finding can be confirmed, it suggests the possibility of a subgroup of patients with an unusually severereaction associatedwith Cundidu who would, accordingly, most benefit from antifungal therapy. There are at least three possible explanations, which are not mutually exclusive, for such a distinctive group. There could be an exacerbated reaction to infection in a select group as a result of a compromised host resistance, infection with a more virulent strain of Cundidu. or hypersensitization to candidal allergens. This reaction could cause conversion from the features of LP to the less specific features of a lichenoid stomatitis as well as ulceration. It is also possible that nonspecific lichenoid reactions to a variety of agents could share the same propensity for infection as LP. The unspecified etiologic agent resulting in the NSLS could represent a more severe insult to epithelial integrity that more readily results in ulceration after the further stressof a candidal infection. Finally, someof these casescould be unusual examples of primary candidiasis that have elicited a lichenoid reaction. Somewhat surprisingly, the group with NSLS apparently was interpreted clinically as having LP more often than was the group with histopathologically confirmed LP. However, there is a heterogeneous clinical spectrum that has been accepted as clinical LP. This spectrum includes linear, discrete papular, confluent papular, reticular, annular, pigmented, vesicular, bullous, and atrophic or erosive forms. ’ 2,l 3 It is possible that within this spectrum there are characteristics that are pathognomonic for the different histopathologic categories. Such differences would be obscured by the limitations of the retrospective data collection used in this study.
Candidul infection in oral lichen plums
175
This study emphasizesthe necessity to assessroutinely the possibility of a secondary candidal infection in oral LP or NSLS and supports clinical impressions of the value of antifungal therapy in some cases.A further tangential issue is raised regarding the controversial relationship of LP and malignancy. The frequency with which previously undetected candidal pseudohyphae were found in this study, the potential of Cundidu to cause pseudoepitheliomatous hyperplasia, and the possible relationship between candidal infection and oral carcinomaI indicate that studies of epithelial dysplasia or carcinoma in LP should specifically note the presenceor absenceof candidal infection. The authorsthank Ms. JeanCookeand Mr. DennisCarme1for their technicalassistanceand Dr. Chris C. Rachanisfor hisvaluableclinical impressionsthat partly ledto the undertakingof this study. REFERENCES 1. Holmstrup P, Dabblesteen E. The frequency of Cundidu in oral
lichen planus. Stand J Dent Res 1974;82:584-7. 2. Lundstrom IMC, Anneroth GB, Holmberg K. Cundida in patients with oral lichen planus. Int J Oral Surg 1984;13:226-38. 3. Krogh P, Holmstrup P, Thorn JJ, Vedtofte P, Pindborg JJ. Yeast species and biotypes associated with oral leukoplakia and lichen planus. ORAL SURGORAL MED ORAL PATHOL 1987;63:48-54. 4. Simon M Jr, Hornstein OP. Prevalence rate of Candidu in the oral cavity of patients with oral lichen planus. Arch Dematol Res 1980;267:317-8. 5. Dreyer WP. The clinical manifestations of oral lichen planus. J Dent Assoc S Afr 1983;38:619-24. 6. Lacy MF, Reade PC, Hay KD. Lichen planus: a theory of pathogenesis. ORAL SURGORAL MED ORAL PATHOL 1983; 56:521-6. 7. Krutchkoff DJ, Eisenberg E. Lichenoid dysplasia: a distinct histopathologic entity. ORALSURGORAL MED ORAL PATHOL 1985;30:308-15. 8. WHO Collaborating Reference Centre for Oral Precancerous Lesions. Definition of leukoplakia and related lesions. An aid to studies on oral precancer. ORAL SURGORAL MED ORAL PATHOL1978;46:518-39. 9. Roed-Petersen B, Renstrup G, Pindborg JJ. Candida in oral leukoplakias. A histologic and exfoliative cytologic study. Stand J Dent Res 1970;78:323-8. 10. Van der Wal N, Van der Waal I. Cundidu albicuns in median rhomboid glossitis. Int J Oral Maxillofac Surg 1986;15:322-5. 11. Allen CM, Beck FM. Differences in mucosal reaction related to Candida albicans isolates. J Oral Pathol 1987;16:89-93. 12. Cooke BED. The oral manifestations of lichen planus: 50 cases. Br Dent J 1954;96:1-9. 13. Scully C, El-Kom M. Lichen planus: review and update on pathogenesis.J Oral Pathol 1985;14:431-58. 14. Binnie WH, Rankin KV, Mackenzie IC. Etiology of oral squamous cell carcinoma. J Oral Path01 1983;12:11-29. Reprint requests to: Dr. Dorian A. Hatchuel Division of Diagnosis Faculty of Dentistry University of Alberta Edmonton, Alberta, Canada T6G 2N8
