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Oral Mucous Membrane Pemphigoid Associated with Lichen Planus: a Subtype of Lichen Planus Pemphigoides?
Ishii, Seto, et al Asian J Oral MaxillofacYamada, Surg 2004;16:135-138. CASE REPORTS
Oral Mucous Membrane Pemphigoid Associated with Lichen Planus: a Subtype of Lichen Planus Pemphigoides? Hiroyuki Yamada,1 Hiroaki Ishii,1 Kanichi Seto,1 Yoshio Kuwashima2 1 First Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, Yokohama, and 2Department of Laboratory Medicine, Hanyu General Hospital, Hanyu, Japan
Abstract Lichen planus pemphigoides is a rare bullous disorder with bullae arising from papules of lichen planus and from normal-appearing skin. Oral cavity-limited lichen planus pemphigoides has never been reported. This report presents a 47-year-old woman who had oral mucous membrane pemphigoid with lichen planus. This lesion is not known among existing clinical diagnoses. When considering the heterogeneous nature of lichen planus pemphigoides, this case may be classified as a variant of lichen planus pemphigoides. Key words: Lichen planus, Oral cavity, Pemphigoid
Introduction Cicatricial pemphigoid (CP), including oral mucous membrane pemphigoid (OMMP), is an autoimmune subepithelial blistering disease where autoantibodies react with various antigens in the epithelial basement membrane zone. These antigens include bullous pemphigoid (BP) 180kD and 230kD antigens, laminin-5, and others.1,2 Clinical features include a chronic course, scarring nature, and predilection for the mucosal surfaces, although oral lesions heal without scarring.1,2 CP with lichen planus (LP) is a rare combination, and a few cases have been reported3 and labelled as LP pemphigoides (LPP). LPP is a bullous disorder characterised by tense bullae on LP lesions and also on clinically uninvolved skin.4 Some authors have considered it to be a coexistence of BP and LP.5 However, whether LPP is a definite disease entity or a simple co-existence of BP and LP has not been resolved.4,6,7 Correspondence: Hiroyuki Yamada, First Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, 230-8501 Japan. Tel: (81 45) 581 1001; Fax: (81 45) 582 0459; E-mail: [email protected]
Asian J Oral Maxillofac Surg Vol 16, No 2, 2004
This report is of a novel case of CP (OMMP) with LP, both lesions being limited to the oral cavity. The category that this lesion should be classified in remains a subject for discussion.
Case Report A 47-year-old woman was referred to the Department of Oral and Maxillofacial Surgery at Hanyu General Hospital, Japan, for investigation of a reddish lesion of the buccal mucosa. The patient had had bilateral lesions in the buccal mucosa for 1 year and had sometimes noticed a few bullae. The patient’s history was unremarkable. At physical examination, erythema with white striae arranged in a reticular pattern were observed in the buccal mucosa bilaterally. Desquamative gingivitis was also observed on both the upper and lower gingiva. No bullae, ulcer, or scarring were found in the oral cavity. There were no skin lesions. A clinical diagnosis of oral LP was made. Two months later, 2 bullae in the left buccal mucosa, measuring 2 mm and 0.5 mm in diameter, respectively, were observed on the reddish buccal mucosa with white striae (Figure 1). A biopsy was performed at the posterior portion of the left buccal mucosa, which included the 2 bullae. In addition, reddish mucosa adjacent to the bullae was taken for 135
Mucous Membrane Pemphigoid Associated with Lichen Planus
immunological examination. Given the suspected diagnosis of CP, the patient was referred to the departments of dermatology, internal medicine, and
Figure 1. Bullae on the buccal mucosa with white striae (arrowsheads).
ophthalmology at Hanyu General Hospital. Consequently, no lesion other than that on the oral mucosa was found. The patient did not require further treatment because her condition was not severe. After 2 years and 6 months since the first presentation, the lesion has shown no major change, and the condition remains limited to the oral cavity. Microscopic Examination Hematoxylin and eosin-stained sections revealed a subepithelial bulla (Figure 2a). An inflammatory infiltrate, mainly eosinophils and lymphocytes, was observed in the subepithelial tissue and cavity of the bulla. Adjacent to the bulla, hyperparakeratotic epithelia with irregular elongation of rete ridges were found (Figures 2b and 2c). Band-like infiltration of lymphocytes around the elongated rete ridges was also noticed (Figure 2d).
a
b
c
d
Figure 2. Photomicrograph showing (a) the subepithelial bulla (hematoxylin and eosin; original magnification x 50); (b) the epithelium adjacent to the bulla — hyperparakeratotic epithelia with the elongated rete ridge was noted (hematoxylin and eosin; original magnification x 50); (c) infiltration of eosinophils and lymphocytes into the subepithelial tissue and into the cavity of the bulla (hematoxylin and eosin; original magnification x 100); and (d) dense (band-like) infiltrate of lymphocytes around the elongated rete ridges (hematoxylin and eosin; original magnification x 100).
136
Asian J Oral Maxillofac Surg Vol 16, No 2, 2004
Yamada, Ishii, Seto, et al
a
b
Figure 3. Photomicrograph showing (a) linear deposition of immunoglobulin G to the basement membrane zone (direct immunofluorescence; original magnification x 100); and (b) linear deposition of complement 3 to the basement membrane zone (direct immunofluorescence; original magnification x 100). Abbreviations: E = epithelium; S = subepithelial tissue.
Immunological Examination The direct immunofluorescent staining showed linear deposition of immunoglobulin G (IgG) and complement 3 (C3) at the basement membrane zone (Figures 3a and 3b). The indirect immunofluorescence studies on monkey oesophagus using the patient’s serum were negative. According to the clinical, histopathological, and immunological findings, the patient was diagnosed with OMMP associated with LP.
Discussion It is difficult to categorise this patient because of the complex nature of mucous membrane pemphigoid1 and the rare occurrence and heterogeneity of LPP.3,4 Nevertheless, we propose that this patient could have an extreme subtype of LPP, with the lesion limited to the oral cavity, and is therefore the first reported case in the literature. Recently, the term ‘immune-mediated subepithelial blistering disease (IMSEBD)’ has been emphasised when considering the general term ‘pemphigoid’. In the oral cavity, the disease has been observed as CP.2 However, when CP is limited to the oral cavity, its clinical course is self-limiting and specific antibody reaction is noted, hence the term OMMP was proposed.2 At first, this patient was thought to have the characteristics of OMMP because of the clinical course, histopathology, and immunological findings. When considering LPP, one important question is whether the disease is only a co-incidence of LP and BP.3,4 Hsu et al reported the immunopathological similarity between LPP and BP — IgG antibodies of patients with LPP react with 180kD BP antigen.6 Asian J Oral Maxillofac Surg Vol 16, No 2, 2004
Zillikens et al identified a novel epitope in the 180kD BP antigen that reacts with sera from patients with LPP.7 Thorough analysis may be necessary to understand the precise relationship between the nature of LPP antisera and IMSEBD. Conversely, this indicates that the possibility of co-existence of LP and BP in LPP could not be well explained on an immunological basis. The clinical presentation of LPP and BP could be dissenting evidence against the co-existence theory — LPP is predominant in young males and it blisters the extremities, while BP is predominant in elderly females and it blisters the trunk or flexural aspect of the upper extremities.4 Several patients with LPP with lesions in the oral cavity have also been reported to have skin lesions.3,4,8-10 The first immunology-based report of LPP was by Allen et al in 1987.8 Willsteed et al reported that 3 of 9 patients with LPP had an oral lesion.4 Bouloc et al reported 2 of 5 patients with LPP had findings of CP based on immunoelectron microscopy.3 As described, all these oral lesions had associated skin lesions, and no report has been published dealing with oral cavity-limited LPP. In categorising this condition, the possibilities include the lesion being a variant of LPP, a new disease entity other than LPP, or a simple co-existence of CP (OMMP) and LP. Further immunological examinations (i.e., immunoblot or immunoprecipitation) were not performed. Thus it was not possible to distinguish this condition from LPP on immunological grounds. However, if one considers that LPP is a heterogeneous condition,3,4 it is more likely to be a variant of LPP than a new disease entity, 137
Mucous Membrane Pemphigoid Associated with Lichen Planus
although it is difficult and impractical to exclude the possibility of ‘co-existence’ of the 2 rare lesions. Based on the possibility that CP (including OMMP) can occur in LPP other than BP,3 the most reliable diagnosis for the present case is LPP, limited to the oral cavity and with its pemphigoid-element taking an OMMP-pattern. Absence of skin lesions was merely recorded in this report, but further analysis would be desirable. As a differential diagnosis, the following 3 conditions should be considered; • primary LPP (having the potential for skin involvement) • bullous LP • epidermolysis bullosa acquisita (EBA) with LP. In this patient, all these conditions were excluded as follows. Primary LPP was excluded because of the long-term (2 years and 6 months) absence of skin lesions in this patient — in most patients with LPP, oral and skin lesions are found simultaneously.3,4,8,9 In 1 patient, severe erosive stomatitis preceded skin lesions by 1 year and 8 months.10 Immunofluorescence studies clearly excluded bullous LP (due to hydropic degeneration of the basal cell layer in the lichenoid plaque).4 EBA was excluded as localisation of EBA only to the mucosal surface is very rare, and only 1 patient with EBA in the oesophagus has been reported.11 EBA with LP of the oral cavity has not been reported in the literature. The mild clinical course, non-scarring nature, and desquamative gingivitis in the present patient support the diagnosis of OMMP1,2 rather than EBA, although definite differentiation requires immunological studies. In summary, this patient was diagnosed with OMMP associated with LP according to the clinical, histopathological, and immunological findings. We speculate that this was an extreme subtype of LPP because of the oral localisation. This is the first reported case in the literature. To confirm this, longterm clinical follow-up is now necessary.
References 1. Scully C, Carrozzo M, Gandolfo S, Puiatti P, Monteil R. Update on mucous membrane pemphigoid: a heterogeneous immune-mediated
138
subepithelial blistering entity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88: 56-68. 2. Dayan S, Simmons RK, Ahmed AR. Contemporary issues in the diagnosis of oral pemphigoid: a selective review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88: 424-430. 3. Bouloc A, Vignon-Pennamen MD, Caux F, Teillac D, Wechsler J, Heller M, Lebbé C, Flageul B, Morel P, Dubertret L, Prost C. Lichen planus pemphigoides is a heterogeneous disease: a report of five cases studied by immunoelectron microscopy. Br J Dermatol 1998;138:972-980. 4. Willsteed E, Bhogal BS, Das AK, Wojnarowska F, Black MM, Mckee PH. Lichen planus pemphigoides: a clinicopathological study of nine cases. Histopathology 1991;19:147-154. 5. Lang PG, Maize JC. Coexisting lichen planus and bullous pemphigoid or lichen planus pemphigoides. J Am Acad Dermatol 1983;9:133-140. 6. Hsu S, Ghohestani RF, Uitto J. Lichen planus pemphigoides with IgG autoantibodies to the 180 kd bullous pemphigoid antigen (type XVII collagen). J Am Acad Dermatol 2000;42: 136-141. 7. Zillikens D, Caux F, Mascaro JM, Wesselmann U, Schmit E, Prost C, Callen JP, Brocker EB, Diaz LA, Giudice GJ. Autoantibodies in lichen planus pemphigoides react with a novel epitope within the C-terminal NC16A domain of BP 180. J Invest Dermatol 1999;133:117-121. 8. Allen CM, Camisa C, Grimwood R. Lichen planus pemphigoides: report of a case with oral lesions. Oral Surg Oral Med Oral Pathol 1987; 63:184-188. 9. Maceyko RF, Camisa C, Bergfeld WF, Valenzuela R. Oral and cutaneous lichen planus pemphigoides. J Am Acad Dermatol 1992;27:889-892. 10. Reynaers A, Degreef H. Severe erosive stomatitis: association with immunological diseases? Dermatology 1997;194:411-415. 11. Schattenkirchner S, Lemann M, Prost C, Caux F, Guigui B, Cadot M Bertheau P, Grteau C Heller M. Localized epidermolysis bullosa acquisita of the esophagus in a patient with Crohn’s disease. Am J Gastroenterol 1996;91:1657-1659.
Asian J Oral Maxillofac Surg Vol 16, No 2, 2004
Oral Mucous Membrane Pemphigoid Associated with Lichen Planus: a Subtype of Lichen Planus Pemphigoides? Hiroyuki Yamada,1 Hiroaki Ishii,1 Kanichi Seto,1 Yoshio Kuwashima2 1 First Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, Yokohama, and 2Department of Laboratory Medicine, Hanyu General Hospital, Hanyu, Japan
Abstract Lichen planus pemphigoides is a rare bullous disorder with bullae arising from papules of lichen planus and from normal-appearing skin. Oral cavity-limited lichen planus pemphigoides has never been reported. This report presents a 47-year-old woman who had oral mucous membrane pemphigoid with lichen planus. This lesion is not known among existing clinical diagnoses. When considering the heterogeneous nature of lichen planus pemphigoides, this case may be classified as a variant of lichen planus pemphigoides. Key words: Lichen planus, Oral cavity, Pemphigoid
Introduction Cicatricial pemphigoid (CP), including oral mucous membrane pemphigoid (OMMP), is an autoimmune subepithelial blistering disease where autoantibodies react with various antigens in the epithelial basement membrane zone. These antigens include bullous pemphigoid (BP) 180kD and 230kD antigens, laminin-5, and others.1,2 Clinical features include a chronic course, scarring nature, and predilection for the mucosal surfaces, although oral lesions heal without scarring.1,2 CP with lichen planus (LP) is a rare combination, and a few cases have been reported3 and labelled as LP pemphigoides (LPP). LPP is a bullous disorder characterised by tense bullae on LP lesions and also on clinically uninvolved skin.4 Some authors have considered it to be a coexistence of BP and LP.5 However, whether LPP is a definite disease entity or a simple co-existence of BP and LP has not been resolved.4,6,7 Correspondence: Hiroyuki Yamada, First Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, 230-8501 Japan. Tel: (81 45) 581 1001; Fax: (81 45) 582 0459; E-mail: [email protected]
Asian J Oral Maxillofac Surg Vol 16, No 2, 2004
This report is of a novel case of CP (OMMP) with LP, both lesions being limited to the oral cavity. The category that this lesion should be classified in remains a subject for discussion.
Case Report A 47-year-old woman was referred to the Department of Oral and Maxillofacial Surgery at Hanyu General Hospital, Japan, for investigation of a reddish lesion of the buccal mucosa. The patient had had bilateral lesions in the buccal mucosa for 1 year and had sometimes noticed a few bullae. The patient’s history was unremarkable. At physical examination, erythema with white striae arranged in a reticular pattern were observed in the buccal mucosa bilaterally. Desquamative gingivitis was also observed on both the upper and lower gingiva. No bullae, ulcer, or scarring were found in the oral cavity. There were no skin lesions. A clinical diagnosis of oral LP was made. Two months later, 2 bullae in the left buccal mucosa, measuring 2 mm and 0.5 mm in diameter, respectively, were observed on the reddish buccal mucosa with white striae (Figure 1). A biopsy was performed at the posterior portion of the left buccal mucosa, which included the 2 bullae. In addition, reddish mucosa adjacent to the bullae was taken for 135
Mucous Membrane Pemphigoid Associated with Lichen Planus
immunological examination. Given the suspected diagnosis of CP, the patient was referred to the departments of dermatology, internal medicine, and
Figure 1. Bullae on the buccal mucosa with white striae (arrowsheads).
ophthalmology at Hanyu General Hospital. Consequently, no lesion other than that on the oral mucosa was found. The patient did not require further treatment because her condition was not severe. After 2 years and 6 months since the first presentation, the lesion has shown no major change, and the condition remains limited to the oral cavity. Microscopic Examination Hematoxylin and eosin-stained sections revealed a subepithelial bulla (Figure 2a). An inflammatory infiltrate, mainly eosinophils and lymphocytes, was observed in the subepithelial tissue and cavity of the bulla. Adjacent to the bulla, hyperparakeratotic epithelia with irregular elongation of rete ridges were found (Figures 2b and 2c). Band-like infiltration of lymphocytes around the elongated rete ridges was also noticed (Figure 2d).
a
b
c
d
Figure 2. Photomicrograph showing (a) the subepithelial bulla (hematoxylin and eosin; original magnification x 50); (b) the epithelium adjacent to the bulla — hyperparakeratotic epithelia with the elongated rete ridge was noted (hematoxylin and eosin; original magnification x 50); (c) infiltration of eosinophils and lymphocytes into the subepithelial tissue and into the cavity of the bulla (hematoxylin and eosin; original magnification x 100); and (d) dense (band-like) infiltrate of lymphocytes around the elongated rete ridges (hematoxylin and eosin; original magnification x 100).
136
Asian J Oral Maxillofac Surg Vol 16, No 2, 2004
Yamada, Ishii, Seto, et al
a
b
Figure 3. Photomicrograph showing (a) linear deposition of immunoglobulin G to the basement membrane zone (direct immunofluorescence; original magnification x 100); and (b) linear deposition of complement 3 to the basement membrane zone (direct immunofluorescence; original magnification x 100). Abbreviations: E = epithelium; S = subepithelial tissue.
Immunological Examination The direct immunofluorescent staining showed linear deposition of immunoglobulin G (IgG) and complement 3 (C3) at the basement membrane zone (Figures 3a and 3b). The indirect immunofluorescence studies on monkey oesophagus using the patient’s serum were negative. According to the clinical, histopathological, and immunological findings, the patient was diagnosed with OMMP associated with LP.
Discussion It is difficult to categorise this patient because of the complex nature of mucous membrane pemphigoid1 and the rare occurrence and heterogeneity of LPP.3,4 Nevertheless, we propose that this patient could have an extreme subtype of LPP, with the lesion limited to the oral cavity, and is therefore the first reported case in the literature. Recently, the term ‘immune-mediated subepithelial blistering disease (IMSEBD)’ has been emphasised when considering the general term ‘pemphigoid’. In the oral cavity, the disease has been observed as CP.2 However, when CP is limited to the oral cavity, its clinical course is self-limiting and specific antibody reaction is noted, hence the term OMMP was proposed.2 At first, this patient was thought to have the characteristics of OMMP because of the clinical course, histopathology, and immunological findings. When considering LPP, one important question is whether the disease is only a co-incidence of LP and BP.3,4 Hsu et al reported the immunopathological similarity between LPP and BP — IgG antibodies of patients with LPP react with 180kD BP antigen.6 Asian J Oral Maxillofac Surg Vol 16, No 2, 2004
Zillikens et al identified a novel epitope in the 180kD BP antigen that reacts with sera from patients with LPP.7 Thorough analysis may be necessary to understand the precise relationship between the nature of LPP antisera and IMSEBD. Conversely, this indicates that the possibility of co-existence of LP and BP in LPP could not be well explained on an immunological basis. The clinical presentation of LPP and BP could be dissenting evidence against the co-existence theory — LPP is predominant in young males and it blisters the extremities, while BP is predominant in elderly females and it blisters the trunk or flexural aspect of the upper extremities.4 Several patients with LPP with lesions in the oral cavity have also been reported to have skin lesions.3,4,8-10 The first immunology-based report of LPP was by Allen et al in 1987.8 Willsteed et al reported that 3 of 9 patients with LPP had an oral lesion.4 Bouloc et al reported 2 of 5 patients with LPP had findings of CP based on immunoelectron microscopy.3 As described, all these oral lesions had associated skin lesions, and no report has been published dealing with oral cavity-limited LPP. In categorising this condition, the possibilities include the lesion being a variant of LPP, a new disease entity other than LPP, or a simple co-existence of CP (OMMP) and LP. Further immunological examinations (i.e., immunoblot or immunoprecipitation) were not performed. Thus it was not possible to distinguish this condition from LPP on immunological grounds. However, if one considers that LPP is a heterogeneous condition,3,4 it is more likely to be a variant of LPP than a new disease entity, 137
Mucous Membrane Pemphigoid Associated with Lichen Planus
although it is difficult and impractical to exclude the possibility of ‘co-existence’ of the 2 rare lesions. Based on the possibility that CP (including OMMP) can occur in LPP other than BP,3 the most reliable diagnosis for the present case is LPP, limited to the oral cavity and with its pemphigoid-element taking an OMMP-pattern. Absence of skin lesions was merely recorded in this report, but further analysis would be desirable. As a differential diagnosis, the following 3 conditions should be considered; • primary LPP (having the potential for skin involvement) • bullous LP • epidermolysis bullosa acquisita (EBA) with LP. In this patient, all these conditions were excluded as follows. Primary LPP was excluded because of the long-term (2 years and 6 months) absence of skin lesions in this patient — in most patients with LPP, oral and skin lesions are found simultaneously.3,4,8,9 In 1 patient, severe erosive stomatitis preceded skin lesions by 1 year and 8 months.10 Immunofluorescence studies clearly excluded bullous LP (due to hydropic degeneration of the basal cell layer in the lichenoid plaque).4 EBA was excluded as localisation of EBA only to the mucosal surface is very rare, and only 1 patient with EBA in the oesophagus has been reported.11 EBA with LP of the oral cavity has not been reported in the literature. The mild clinical course, non-scarring nature, and desquamative gingivitis in the present patient support the diagnosis of OMMP1,2 rather than EBA, although definite differentiation requires immunological studies. In summary, this patient was diagnosed with OMMP associated with LP according to the clinical, histopathological, and immunological findings. We speculate that this was an extreme subtype of LPP because of the oral localisation. This is the first reported case in the literature. To confirm this, longterm clinical follow-up is now necessary.
References 1. Scully C, Carrozzo M, Gandolfo S, Puiatti P, Monteil R. Update on mucous membrane pemphigoid: a heterogeneous immune-mediated
138
subepithelial blistering entity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88: 56-68. 2. Dayan S, Simmons RK, Ahmed AR. Contemporary issues in the diagnosis of oral pemphigoid: a selective review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88: 424-430. 3. Bouloc A, Vignon-Pennamen MD, Caux F, Teillac D, Wechsler J, Heller M, Lebbé C, Flageul B, Morel P, Dubertret L, Prost C. Lichen planus pemphigoides is a heterogeneous disease: a report of five cases studied by immunoelectron microscopy. Br J Dermatol 1998;138:972-980. 4. Willsteed E, Bhogal BS, Das AK, Wojnarowska F, Black MM, Mckee PH. Lichen planus pemphigoides: a clinicopathological study of nine cases. Histopathology 1991;19:147-154. 5. Lang PG, Maize JC. Coexisting lichen planus and bullous pemphigoid or lichen planus pemphigoides. J Am Acad Dermatol 1983;9:133-140. 6. Hsu S, Ghohestani RF, Uitto J. Lichen planus pemphigoides with IgG autoantibodies to the 180 kd bullous pemphigoid antigen (type XVII collagen). J Am Acad Dermatol 2000;42: 136-141. 7. Zillikens D, Caux F, Mascaro JM, Wesselmann U, Schmit E, Prost C, Callen JP, Brocker EB, Diaz LA, Giudice GJ. Autoantibodies in lichen planus pemphigoides react with a novel epitope within the C-terminal NC16A domain of BP 180. J Invest Dermatol 1999;133:117-121. 8. Allen CM, Camisa C, Grimwood R. Lichen planus pemphigoides: report of a case with oral lesions. Oral Surg Oral Med Oral Pathol 1987; 63:184-188. 9. Maceyko RF, Camisa C, Bergfeld WF, Valenzuela R. Oral and cutaneous lichen planus pemphigoides. J Am Acad Dermatol 1992;27:889-892. 10. Reynaers A, Degreef H. Severe erosive stomatitis: association with immunological diseases? Dermatology 1997;194:411-415. 11. Schattenkirchner S, Lemann M, Prost C, Caux F, Guigui B, Cadot M Bertheau P, Grteau C Heller M. Localized epidermolysis bullosa acquisita of the esophagus in a patient with Crohn’s disease. Am J Gastroenterol 1996;91:1657-1659.
Asian J Oral Maxillofac Surg Vol 16, No 2, 2004