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Lichen planus pemphigoides: Report of a case with oral lesions
Lichen planus pemphigoides: Report of a case with oral lesions Carl M. Allen, D.D.S., M.S.D.,* Charles Camisa, M.D.,** Ronald Grimwood, M.D.,*** Columbus, Ohio OHIO
STATE
UNIVERSITY
COLLEGE
OF DENTISTRY
AND
DEPARTMENT
and
OF MEDICINE
Lichen planus pemphigoides is a rare condition characterized by the coexistence of lichen planus and bullous pemphigoid. Oral lesions have been reported but have not been studied immunopathologically. We describe a 59-year-old white man with cutaneous and oral lesions of lichen planus pemphigokfes. Biopsies were done on these lesions, and the specimens were examined by routine light microscopy and immunofluorescent techniques. Fine keratotic striae on the anterior buccal mucosa were clinically consistent with oral lichen planus. Perilesional tissue associated with ulceration of the posterior buccal mucosa showed histologic and immunopathologic changes consistent with bullous pemphigoid. (ORAL SURG. ORAL MED. ORAL PATHOL. 1!387;63:184-8)
L
ichen planus pemphigoides (LPP) is a rare dermatologic diseasecharacterized by the coexistence of lichen planus (LP) and bullous pemphigoid (BP) in the same patient.le3Typical cutaneous lesions of LP develop initially, followed within several weeks by the development of vesicles and bullae both in association with the LP lesions and on clinically normal skin. Early reports of this condition may have inadvertently included casesof bullous LP, however, with the advent of immunofluorescence testing, the two disorders can be separated immunopathologicall~.~ Unlike bullous LP, LPP demonstrates both bound and circulating immunoreactants to the basement membrane zone (BMZ).5,6 This article reports the clinical, microscopic, and immunopathologic findings of the oral lesions in a patient who fulfilled the diagnostic criteria for LPP. CASE REPORT History
A 59-year-old white man with a 2-year history of type II diabetes mellitus-managed with an oral hypoglycemic agent, chlorpropamide (Diabinese)-developed a pruritic rash on his left arm in April 1985. The skin eruption was believed to be caused by chlorpropamide; the family
Professor, Section of Diagnostic Services. **Assistant Professor and Director, Division of Dermatology. ***Assistant Professor, Division of Dermatology. *Assistant
184
physician prescribed a different medication, glyburide (Micronase). By the middle of July, the pruritic lesions had spreadto the entire body,sparingonly the face. A skin biopsy at that time revealedLP, and the patient was treated with a topical corticosteroid. No relief was obtained with this regimen, and after 1 week blisters developed diffusely on the patient’s body. A tapering course of oral prednisone (60 to 20 mg daily in 18 days) did not producerelief, andthe patient wasreferredto the Ohio
State University Hospitals. Clinical examination
Physical examination showed numerous violaceous, flat-
toppedpapulesand plaquesdistributed on the skin of the arms, hands, chest, back, legs, and feet (Fig. 1). Numerous excoriations were also evident. Scattered vesicles and bullae were observed both in association with the violaceous skin lesions and on skin that clinically appeared normal. Intraorally, the anterior aspect of the buccal mucosa exhibited a fine pattern of 1 to 2 mm keratotic striae. Both the right and left posteriorbuccal mucosashowedsolitary shallow ulcerations measuring 0.8 cm in diameter. These ulcerations were not associatedwith the plane of occlusion, and no keratotic striae were observed at their periphery (Figs. 2 and 3). No intact oral vesicles or bullae were seen. Microscopic
examination
The skin lesion on which a biopsy was done showed
typical features of cutaneouslichen planus. Histologic
Lichen planus pemphigoides
Volume 63 Number 2
185
Fig. 1. Clinical photograph of cutaneous lesions of lower leg. Both violaceous, flat-topped papules and bullae are seen.
Fig. 2. Clinical photograph of left buccal mucosa showing ulceration with no associated peripheral keratotic striae. Perilesional tissue was obtained from the anterior margin of this lesion.
examination of tissue obtained from the periphery of the left buccal mucosal ulceration showed epithelial separation at the BMZ with a mild lymphohistiocytic infiltrate in the superficial connective tissue. No evidence of hyperkeratosis or vacuolar degeneration of the basal cell layer was observed (Fig. 4). lmmunofluorescence
microscopy
Direct and indirect immunofluorescence studies’ were carried out as previously described. Additional studies8 were performed to include indirect immunofluorescence
with the patient’s serum on 1.0 M sodium chlorideseparated human foreskin and indirect autologous studies9 with the patient’s serum against his own lichen planus lesional skin as previously described. The direct immunofluorescent specimensfrom both the perilesional skin and the oral mucosa showed a smooth linear deposit at the BMZ for both IgG and C3 (Fig. 5). The indirect immunofluorescent studies were positive with a linear smooth BMZ staining of the monkey esophagusat a final serum dilution of 1:1000. The indirect studies on the sodium chloride-separated skin showed a positive continu-
186
Allen, Camisa, and Grimwood
Oral Surg. February,1987
Fig. 3. Ulceration of right buccal mucosa, approximating facial surface of mandibular second molar. Subtle, fine keratotic striae are apparent anterior and superior to this lesion.
Fig. 4. Photomicrograph of oral perilesional tissue showing subepithelial clefting and intact basal cell layer. (original magnification, X25.)
ous linear band of fluorescence along the epidermal edge (roof) of the separation. This pattern is consistent with bullous pemphigoid and rules out epidermolysis bullosa acquisita. The indirect autologus studies were negative for the lichen planus-specific antigen. Clinical course
The patient’s oral hypoglycemic agent was discontinued, and he was placed on a 2500-calorie diet that resulted in fair control of his blood glucose. In addition, systemic isotretinoin, 40 mg daily, and occlusive steroid dressings, applied twice daily for 4-hour intervals, were initiated. The clinical responsewas good; the cutaneous lesions and oral
ulcerations healed, and there was no evidence of new lesions developing. DISCUSSION
LPP is a rare dermatologic disease that requires clinical, histologic, and immunologic evaluation to establish the correct diagnosis. Immunologic studies that adequately characterize this condition have been available only during the past 15 years. Before the development of these techniques, disorders such as bullous LP likely have been described as LPP.3 Most authorC4. lo-t2agree that LPP can be defined
Volume 63 Number 2
Lichen planus pemphigoides
187
Fig. 5. Photomicrograph
of direct immunofluorescence of buccal mucosa showing linear deposition of C3 at basement membrane zone.
as the simultaneous occurrence of LP and BP in the same patient. Controversy persists as to whether this appearance of both LP and BP represents a matter of chance’* or alternatively, that a pathogenetic link exists between the two conditions. Some investigators1-3*13 have hypothesized that the disruption of the basal cell layer-BMZ area observed in LP may exposeor otherwise alter BMZ proteins, which leads to host antibody production against those proteins, with the subsequentdevelopment, both clinically and immunopathologically, of a condition that resembles BP. This hypothesis is attractive in view of the temporal relationship of the lesions; typically LP precedes the onset of vesicles and bullae by several weekss3 Damage to the BMZ in LP may release other antigens besides BP antigen, which leads to the production of autoantibodies that produce a BP-like illness. One such disease, epidermolysis bullosa acquisita (EBA), may mimic BP or cicatricial pemphigoid clinically, histologically, and immunopathologically.‘4 With EBA, immunoelectron microscopy shows that immunoreactants are deposited below the lamina densa rather than in the lamina lucida as in BP. The simple 1.0 M sodium chloride-“split” skin indirect immunofluorescent assay shows that the circulating anti-BMZ antibodies in EBA are deposited in the floor of the blister, whereas in BP they localize in the roof, as was shown in our case. Immunoelectron microscopy was not used on any of the lesions on which we performed biopsies. Oral lesions have been described in some casesof LPP; however, reports of LPP in the dental literature
are scanty.15 Clinical descriptionsL*3~16 of the oral lesions generally are consistent with oral LP of either the reticular or the erosive type. Histologic examination of an oral lesion was reported to be consistent with oral LP in at least one case’; however, most oral lesions were examined only clinically. We have demonstrated that LPP may be associated with oral lesions that have clinical characteristics of either LP or BP. Our patient had subtle keratotic striae of the anterior buccal mucosae, which resembled oral LP, but biopsies were not performed. Biopsy of perilesional tissue associated with ulceration of the posterior buccal mucosa, however, showed histologic features suggestive of pemphigoid rather than LP. Moreover, immunofluorescent studies demonstrated deposition of IgG and C3 in a linear pattern at the BMZ, consistent with pemphigoid. To our knowledge, this is the first report of immunopathologic studies of an oral lesion in LPP. REFERENCES
1. Sting1 G, Holubar K. Coexistence of lichen planus and bullous pemphigoid: an immunopathological study. Br J Dermatol 1975;93:313-20 2. Sobel S, Miller R, Shatin H. Lichen planus pemphigoides: Immunofluorescence findings. Arch Dermatol 1976;112: 1280-3 3. Mora RG, Nesbitt LT, Brantley JB. Lichen planus pemphigoides: Clinical and immunofluorescent findings in four cases. J Am Acad Dermatol 1983;8:331-6. 4. Lang PG, Maize JC. Coexisting lichen planus and bullous pemphigoid or lichen planus pemphigoides? J Am Acad Dermatol 1983;9:133-40. 5. Beutner EH, Chorzelski TP, Bean SF, eds. Immunopathology of the skin, ed. 2nd New York: 1979; John Wiley & Sons, p. 22.
188
Allen, Camisa, and Grimwood
Oral Surg. February, 1987
6. Lever WF, Schaumburg-Lever G. Histopathology of the skin. 6th ed. Philadelphia: 1983; JB Lippincott, p. 155. 7. Grimwood RE, Huff JC, Weston WL. A simple and improved method for direct and indirect immunofluorescent staining. J Am Acad Dermatol 1985;13:768-71. 8. Gammon WR, Briggaman MD, Inman AO, Queen LL, Wheeler CE. Differentiating anti-lamina lucida and antisublamina densa anti-BMZ antibodies by indirect immunofluorescence on 1.0 M sodium chloride-separated skin. J Invest Dermatol 1984;82:139-44. 9. Camisa C, Neff JC, Olsen RG. Use of indirect immunofluorescence in the lupus erythematosus/lichen planus overlap syndrome: An additional diagnostic clue. J Am Acad Dermatol 1984;11:1050-9. IO. Mora R, Nesbitt LT, Brantley JB. Lichen ruber pemphigoides [Reply to letter.] J Am Acad Dermatol 1983;9:6067.
Il. Hintner H, Tappeiner G, Honigsmann H, Wolff K. Lichen planus and bullous pemphigoid. Acta Derm Venereol (Stockh) 1979;59 (Suppl. 85):71-6.
BOUND VOLUMES AVAILABLE
12. Souteyrand P, Pierini AM, Femandez-Bussey R, Thivolet J, Cambazard F. Lichen planus pemphigoides: Entity or association? Dermatologica 1981;162:414-6. 13. Rekant SI. Lichen planus and bullous pemphigoid (letter). Arch Dermatol 1976;112:1613. 14. Gammon WR, Briggaman RA, Woodley DT, Heald PW, Wheeler CE. Epidermolysis bullosa acquisita-a pemphigoidlike disease. J Am Acad Dermatol 1984;11:820-32. 15. Scully C, El-Kom M. Lichen planus: Review and update on pathogenesis. J Oral Path01 1985;14:431-58. 16. Prost C, Tesserand F, Laroche L, Dallot A, Verola 0, Morel P, Dubertret L. Lichen planus pemphigoides: An immunoelectron microscopic study. Br J Dermatol 1985;113:31-6. Reprint requests to:
Dr. Carl M. Allen 305 West 12th Ave. Columbus, OH 43210
TO SUBSCRIBERS
Bound volumes of ORAL SURGERY, ORAL MEDICINE and ORAL PATHOLOGY are available to subscribers (only) for the 1986 issues from the Publisher, at a cost of $38.00 ($50.00 international) for Vol. 61 (January-June) and Vol. 62 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable buckram with the journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact The C. V. Mosby Company, Circulation Department, 11830 Westline Industrial Drive, St. Louis, Missouri 63146, USA; phone (800) 325-4177, ext. 351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular journal subscription.
STATE
UNIVERSITY
COLLEGE
OF DENTISTRY
AND
DEPARTMENT
and
OF MEDICINE
Lichen planus pemphigoides is a rare condition characterized by the coexistence of lichen planus and bullous pemphigoid. Oral lesions have been reported but have not been studied immunopathologically. We describe a 59-year-old white man with cutaneous and oral lesions of lichen planus pemphigokfes. Biopsies were done on these lesions, and the specimens were examined by routine light microscopy and immunofluorescent techniques. Fine keratotic striae on the anterior buccal mucosa were clinically consistent with oral lichen planus. Perilesional tissue associated with ulceration of the posterior buccal mucosa showed histologic and immunopathologic changes consistent with bullous pemphigoid. (ORAL SURG. ORAL MED. ORAL PATHOL. 1!387;63:184-8)
L
ichen planus pemphigoides (LPP) is a rare dermatologic diseasecharacterized by the coexistence of lichen planus (LP) and bullous pemphigoid (BP) in the same patient.le3Typical cutaneous lesions of LP develop initially, followed within several weeks by the development of vesicles and bullae both in association with the LP lesions and on clinically normal skin. Early reports of this condition may have inadvertently included casesof bullous LP, however, with the advent of immunofluorescence testing, the two disorders can be separated immunopathologicall~.~ Unlike bullous LP, LPP demonstrates both bound and circulating immunoreactants to the basement membrane zone (BMZ).5,6 This article reports the clinical, microscopic, and immunopathologic findings of the oral lesions in a patient who fulfilled the diagnostic criteria for LPP. CASE REPORT History
A 59-year-old white man with a 2-year history of type II diabetes mellitus-managed with an oral hypoglycemic agent, chlorpropamide (Diabinese)-developed a pruritic rash on his left arm in April 1985. The skin eruption was believed to be caused by chlorpropamide; the family
Professor, Section of Diagnostic Services. **Assistant Professor and Director, Division of Dermatology. ***Assistant Professor, Division of Dermatology. *Assistant
184
physician prescribed a different medication, glyburide (Micronase). By the middle of July, the pruritic lesions had spreadto the entire body,sparingonly the face. A skin biopsy at that time revealedLP, and the patient was treated with a topical corticosteroid. No relief was obtained with this regimen, and after 1 week blisters developed diffusely on the patient’s body. A tapering course of oral prednisone (60 to 20 mg daily in 18 days) did not producerelief, andthe patient wasreferredto the Ohio
State University Hospitals. Clinical examination
Physical examination showed numerous violaceous, flat-
toppedpapulesand plaquesdistributed on the skin of the arms, hands, chest, back, legs, and feet (Fig. 1). Numerous excoriations were also evident. Scattered vesicles and bullae were observed both in association with the violaceous skin lesions and on skin that clinically appeared normal. Intraorally, the anterior aspect of the buccal mucosa exhibited a fine pattern of 1 to 2 mm keratotic striae. Both the right and left posteriorbuccal mucosashowedsolitary shallow ulcerations measuring 0.8 cm in diameter. These ulcerations were not associatedwith the plane of occlusion, and no keratotic striae were observed at their periphery (Figs. 2 and 3). No intact oral vesicles or bullae were seen. Microscopic
examination
The skin lesion on which a biopsy was done showed
typical features of cutaneouslichen planus. Histologic
Lichen planus pemphigoides
Volume 63 Number 2
185
Fig. 1. Clinical photograph of cutaneous lesions of lower leg. Both violaceous, flat-topped papules and bullae are seen.
Fig. 2. Clinical photograph of left buccal mucosa showing ulceration with no associated peripheral keratotic striae. Perilesional tissue was obtained from the anterior margin of this lesion.
examination of tissue obtained from the periphery of the left buccal mucosal ulceration showed epithelial separation at the BMZ with a mild lymphohistiocytic infiltrate in the superficial connective tissue. No evidence of hyperkeratosis or vacuolar degeneration of the basal cell layer was observed (Fig. 4). lmmunofluorescence
microscopy
Direct and indirect immunofluorescence studies’ were carried out as previously described. Additional studies8 were performed to include indirect immunofluorescence
with the patient’s serum on 1.0 M sodium chlorideseparated human foreskin and indirect autologous studies9 with the patient’s serum against his own lichen planus lesional skin as previously described. The direct immunofluorescent specimensfrom both the perilesional skin and the oral mucosa showed a smooth linear deposit at the BMZ for both IgG and C3 (Fig. 5). The indirect immunofluorescent studies were positive with a linear smooth BMZ staining of the monkey esophagusat a final serum dilution of 1:1000. The indirect studies on the sodium chloride-separated skin showed a positive continu-
186
Allen, Camisa, and Grimwood
Oral Surg. February,1987
Fig. 3. Ulceration of right buccal mucosa, approximating facial surface of mandibular second molar. Subtle, fine keratotic striae are apparent anterior and superior to this lesion.
Fig. 4. Photomicrograph of oral perilesional tissue showing subepithelial clefting and intact basal cell layer. (original magnification, X25.)
ous linear band of fluorescence along the epidermal edge (roof) of the separation. This pattern is consistent with bullous pemphigoid and rules out epidermolysis bullosa acquisita. The indirect autologus studies were negative for the lichen planus-specific antigen. Clinical course
The patient’s oral hypoglycemic agent was discontinued, and he was placed on a 2500-calorie diet that resulted in fair control of his blood glucose. In addition, systemic isotretinoin, 40 mg daily, and occlusive steroid dressings, applied twice daily for 4-hour intervals, were initiated. The clinical responsewas good; the cutaneous lesions and oral
ulcerations healed, and there was no evidence of new lesions developing. DISCUSSION
LPP is a rare dermatologic disease that requires clinical, histologic, and immunologic evaluation to establish the correct diagnosis. Immunologic studies that adequately characterize this condition have been available only during the past 15 years. Before the development of these techniques, disorders such as bullous LP likely have been described as LPP.3 Most authorC4. lo-t2agree that LPP can be defined
Volume 63 Number 2
Lichen planus pemphigoides
187
Fig. 5. Photomicrograph
of direct immunofluorescence of buccal mucosa showing linear deposition of C3 at basement membrane zone.
as the simultaneous occurrence of LP and BP in the same patient. Controversy persists as to whether this appearance of both LP and BP represents a matter of chance’* or alternatively, that a pathogenetic link exists between the two conditions. Some investigators1-3*13 have hypothesized that the disruption of the basal cell layer-BMZ area observed in LP may exposeor otherwise alter BMZ proteins, which leads to host antibody production against those proteins, with the subsequentdevelopment, both clinically and immunopathologically, of a condition that resembles BP. This hypothesis is attractive in view of the temporal relationship of the lesions; typically LP precedes the onset of vesicles and bullae by several weekss3 Damage to the BMZ in LP may release other antigens besides BP antigen, which leads to the production of autoantibodies that produce a BP-like illness. One such disease, epidermolysis bullosa acquisita (EBA), may mimic BP or cicatricial pemphigoid clinically, histologically, and immunopathologically.‘4 With EBA, immunoelectron microscopy shows that immunoreactants are deposited below the lamina densa rather than in the lamina lucida as in BP. The simple 1.0 M sodium chloride-“split” skin indirect immunofluorescent assay shows that the circulating anti-BMZ antibodies in EBA are deposited in the floor of the blister, whereas in BP they localize in the roof, as was shown in our case. Immunoelectron microscopy was not used on any of the lesions on which we performed biopsies. Oral lesions have been described in some casesof LPP; however, reports of LPP in the dental literature
are scanty.15 Clinical descriptionsL*3~16 of the oral lesions generally are consistent with oral LP of either the reticular or the erosive type. Histologic examination of an oral lesion was reported to be consistent with oral LP in at least one case’; however, most oral lesions were examined only clinically. We have demonstrated that LPP may be associated with oral lesions that have clinical characteristics of either LP or BP. Our patient had subtle keratotic striae of the anterior buccal mucosae, which resembled oral LP, but biopsies were not performed. Biopsy of perilesional tissue associated with ulceration of the posterior buccal mucosa, however, showed histologic features suggestive of pemphigoid rather than LP. Moreover, immunofluorescent studies demonstrated deposition of IgG and C3 in a linear pattern at the BMZ, consistent with pemphigoid. To our knowledge, this is the first report of immunopathologic studies of an oral lesion in LPP. REFERENCES
1. Sting1 G, Holubar K. Coexistence of lichen planus and bullous pemphigoid: an immunopathological study. Br J Dermatol 1975;93:313-20 2. Sobel S, Miller R, Shatin H. Lichen planus pemphigoides: Immunofluorescence findings. Arch Dermatol 1976;112: 1280-3 3. Mora RG, Nesbitt LT, Brantley JB. Lichen planus pemphigoides: Clinical and immunofluorescent findings in four cases. J Am Acad Dermatol 1983;8:331-6. 4. Lang PG, Maize JC. Coexisting lichen planus and bullous pemphigoid or lichen planus pemphigoides? J Am Acad Dermatol 1983;9:133-40. 5. Beutner EH, Chorzelski TP, Bean SF, eds. Immunopathology of the skin, ed. 2nd New York: 1979; John Wiley & Sons, p. 22.
188
Allen, Camisa, and Grimwood
Oral Surg. February, 1987
6. Lever WF, Schaumburg-Lever G. Histopathology of the skin. 6th ed. Philadelphia: 1983; JB Lippincott, p. 155. 7. Grimwood RE, Huff JC, Weston WL. A simple and improved method for direct and indirect immunofluorescent staining. J Am Acad Dermatol 1985;13:768-71. 8. Gammon WR, Briggaman MD, Inman AO, Queen LL, Wheeler CE. Differentiating anti-lamina lucida and antisublamina densa anti-BMZ antibodies by indirect immunofluorescence on 1.0 M sodium chloride-separated skin. J Invest Dermatol 1984;82:139-44. 9. Camisa C, Neff JC, Olsen RG. Use of indirect immunofluorescence in the lupus erythematosus/lichen planus overlap syndrome: An additional diagnostic clue. J Am Acad Dermatol 1984;11:1050-9. IO. Mora R, Nesbitt LT, Brantley JB. Lichen ruber pemphigoides [Reply to letter.] J Am Acad Dermatol 1983;9:6067.
Il. Hintner H, Tappeiner G, Honigsmann H, Wolff K. Lichen planus and bullous pemphigoid. Acta Derm Venereol (Stockh) 1979;59 (Suppl. 85):71-6.
BOUND VOLUMES AVAILABLE
12. Souteyrand P, Pierini AM, Femandez-Bussey R, Thivolet J, Cambazard F. Lichen planus pemphigoides: Entity or association? Dermatologica 1981;162:414-6. 13. Rekant SI. Lichen planus and bullous pemphigoid (letter). Arch Dermatol 1976;112:1613. 14. Gammon WR, Briggaman RA, Woodley DT, Heald PW, Wheeler CE. Epidermolysis bullosa acquisita-a pemphigoidlike disease. J Am Acad Dermatol 1984;11:820-32. 15. Scully C, El-Kom M. Lichen planus: Review and update on pathogenesis. J Oral Path01 1985;14:431-58. 16. Prost C, Tesserand F, Laroche L, Dallot A, Verola 0, Morel P, Dubertret L. Lichen planus pemphigoides: An immunoelectron microscopic study. Br J Dermatol 1985;113:31-6. Reprint requests to:
Dr. Carl M. Allen 305 West 12th Ave. Columbus, OH 43210
TO SUBSCRIBERS
Bound volumes of ORAL SURGERY, ORAL MEDICINE and ORAL PATHOLOGY are available to subscribers (only) for the 1986 issues from the Publisher, at a cost of $38.00 ($50.00 international) for Vol. 61 (January-June) and Vol. 62 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable buckram with the journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact The C. V. Mosby Company, Circulation Department, 11830 Westline Industrial Drive, St. Louis, Missouri 63146, USA; phone (800) 325-4177, ext. 351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular journal subscription.