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Adult linear immunoglobulin A disease manifesting as desquamative gingivitis
Adult linear immunoglobulin A disease manifesting as desquamative gingivitis S. R. Porter, BSc, FDSRCS, PhD, C. Scully, BSc, FDSRCPS, FFDRCSI, AIDS, MD, PhD, MRCPath, M. Midda, FDSRCS, FFDRCSI, and J. W. Eveson, BSc, FDSRCPS, PhD, FRCPath. Bristol, England CENTRE SURGERY,
FOR THE AND
STUDY
PATHOLOGY,
OF ORAL
DISEASES,
BRISTOL
DENTAL
UNIVERSITY HOSPITAL
DEPARTMENT AND
OF ORAL
MEDICINE,
SCHOOL
Desquamative gingivitis is a manifestation of various dermatoses, particularly lichen planus and mucous membrane pemphigoid. A rare example of adult linear immunoglobulin A disease manifesting as desquamative gingivitis is presented. Although the initial clinical features were typical of desquamative gingivitis, the persistence of ulceration after dental extractions was unusual, and the management of the oral lesions proved difficult. The clinical, immunopathologic, and therapeutic aspects of linear immunoglobulin A dermatoses are reviewed.
(ORALSURCORALMEDORALP~~~0~1990;70:450-3)
D
esquamative gingivitis (DG) is a common oral disorder clinically characterized by diffuse erythematous desquamation, ulceration, and possible bulla formation affecting the free and attached maxillary and mandibular gingivae. DG most frequently occurs in the sixth and seventh decades; there is a female predisposition. DG is usually a manifestation of lichen planus or mucous membrane pemphigoid and may be the only or initial clinical presentation of these disorders.‘-l4 A variety of other less common mucocutaneous diseasescan also give rise to DG (Table I). This report appearsto be the first detailed report of adult linear immunoglobulin A (Ig A) disease(LAD) manifesting as desquamative gingivitis.
Fig. 1. Severeulceration of attached and marginal labial gingivae about lower teeth of present patient.
CASEREPORT
A 69-year-old white man sought treatment in October 1981 with a complaint of gingival sorenessand blistering of 6 months’ duration. This was the first episode, and no precipitating, perpetuating, or relieving factors were identified. The patient had no notable medical problems, although in 1982 he had an episodeof optic neuritis due to the onset of multiple sclerosis. He had no cutaneous, genital, or other ocular symptoms. Examination revealed erythema and ulceration of the attached and marginal gingiva about all surfaces of all teeth 87~~: i ::li568 (Fig. 1). 7/13/16830 450
The only other oral problem was plaque-associatedadult periodontitis affecting all teeth. There were no other mucosal or cutaneous lesions. Biopsy of the perilesional tissue of an ulcer revealed a split at the epitheliomesenchymal junction (Fig. 2), and direct immunofluorescencedemonstrated homogeneouslinear deposits of IgA and C3 at the epitheliomesenchymal junction. Although the patient had no cutaneous lesions, a biopsy of skin was undertaken, but immune deposits were not detected. Hematology (hemoglobin concentration, red cell indexes, white cell total and differential counts, and red cell folate) and serology (serum ferritin, vitamin Br2, and immunoglobulins) were normal, and there were no circulating an-
Volume 70 Number 4
Adult linear IgA disease manifesting as gingivitis
451
Fig. 2. Histology of bullous gingival area-note subepithelial bulla, split at epitheliomesenchymal junction, and intense inflammatory infiltrate within corium.
tibodies to nuclear components, smooth muscle, mitochondria, thyroid colloid, or squamous epithelium. The linear deposits of IgA and C3 and the split at the epitheliomesenchymal junction indicated a diagnosis of adult linear IgA disease. Initial treatment with betamethasone valerate mouthrinses (2.5 mg four times daily) had little effect. Systemic prednisolone (15 mg daily) did produce some clinical improvement, but the gingival lesions did not resolve completely. Dapsone (50 mg daily) failed to produce any improvement, and in view of the poor periodontal status, all the remaining teeth were extracted in October 1985. Surprisingly, ulceration of the alveolar mucosain the maxillary and mandibular areas persisted for the next 4 years, symptoms being managed throughout this period with betamethasone spray (100 gm, six times daily) and benzydamine hydrochloride mouthrinses with a slow but obvious decreasein ulceration. DISCUSSION
Desquamative gingivitis usually occurs as persistent sorenessof the gingiva without frank ulceration. Edentulous areasare typically lessaffected. The cause is usually lichen planus or mucous membrane pemphigoid. The present case of desquamative gingivitis is clinically notable becauseof the frank gingival ulceration and persistence of ulceration of the alveolar mucosa after extraction of the teeth. This latter observation is a rare clinical feature that hasonly been mentioned in a few early reviews of desquamative gingivitis.15, l6 The persistence of oral lesions may reflect the underlying pathology; certainly other workers have noted that (ill-defined) gingival lesions in adult linear IgA disease can respond poorly to systemic therapies.17
Although the patient did not have IgA deposits in
Table
I. Underlying pathologies of DG Lichen planus Mucous membrane pemphigoid Bullous pemphigoid Pemphigus vulgaris Dermatitis herpetiformis LAD Drug reactions (e.g., chlorhexidine Other
gluconate)
uninvolved skin, the prominent homogeneous linear deposits of IgA and C3 suggested the diagnosis of LAD, rather than any of the other bullous dermatoses,was most appropriate. Oral ulceration, erythematous patches, and bullae have previously been observed in some patients with LAD17M24; however, this appears to be the first case of LAD described manifesting solely as desquamative gingivitis. In view of the few reports of linear IgA dermatoses in the oral medicine or oral pathology literature, a review of the major features of these diseasesis detailed below. Adult linear IgA disease (linear IgA bullous dermatosis; linear dermatitis herpetiformis; LAD) is an uncommon mucocutaneousbullous disorder that usually gives rise to a rash of variable presentation. An eruption of vesiclesand bullae, usually in clusters, can develop on the lower trunk, groin, lower extremities, and periorally. There may be an associated pruritus. LAD more frequently affects females and has a mean age of presentation in the fifth decade.i7,23-28 The lesions of LAD are subepithelial vesicles or bullae; microabscessesare present in 50% of specimens and an infiltrate of eosinophils may be present in some lesions.22,24The site of bulla formation is at
452
Porter et al.
the basement membrane zone (BMZ), occurring either below the basal lamina (as in dermatitis herpetiformis2g) or between the basal lamina and the basal cell membranes (as in bullous pemphigoid27). Homogeneousdeposits of IgA have consistently been detected at the basement membrane zone in perilesional and uninvolved skin and mucosaeof affected persons. Deposits of IgG, IgM, and C3 are less frequently found. 17,25Circulating IgA and IgG antibodies to BMZ antigens are present in a minority of patients; titers are generally low and they do not correlate with diseaseactivity. 17*25However, the low detection of circulating antibodies may reflect the choice of tissue substrate since circulating antibodies to human bulbar conjunctiva, as opposedto intact or split skin or oral mucosa, have been detected in patients with LAD.23 Previous reports have suggested that IgA antibodies can be deposited either immediately below the epithelial basal lamina or in the lamina lucida20,30-32; however, recent immunoelectron microscopic analysis of uninvolved skin of patients with LAD has consistently found IgA deposits to be located below the lamina lucida whereas a mirror image pattern has beendemonstrated in somepatients having depositsin both the lamina lucida and below the lamina densa. The target antigen may lie in the sublamina densa in a different site to the antigen of epidermolysis bullosa acquisita (EBA) .33,34 It is probable that the LAD antigen has an intracellular location and that splitting of the BMZ in vitro exposes the antibody binding sites, which are otherwise inaccessible. Fifty percent of personswith LAD have circulating autoantibodies to a variety of antigens,17y25and some patients may have other autoimmune disorders.35,36 Circulating immune complexes, especially IgA type, can be present, although their pathogenic importance is not clear.25 Unlike in dermatitis herpetiformis, gluten-sensitive enteropathy (GSE) is not a frequent feature of LAD, only 25% to 33% of patients having clinical evidence of GSE, and few others have histologic evidenceof gut disease17,30;antiendomysium antibody is infrequent in patients with LAD.37 The low incidence of GSE in LAD may be reflected by the predominance of IgAl subclass in the immune deposits of perilesional tissue.38The association between LAD and HLA-B8 may not be as strong as that of dermatitis herpetiformis and HLA-B8.17q25,3o Lesions spontaneously remit in up to 48% of patients with LAD, and most other patients can be successfully treated with long-term sulfone therapy sometimes complemented with systemic corticosteroids.r7,25,27 Chronic bullous diseaseof childhood (CBDC) has previously been considered to be clinically distinct
ORAL SURGORAL MED ORAL PATHOL October 1990
from LAD, since there may be a predisposition for facial and perineal cutaneous involvement in the latter and CBDC was thought to spontaneously remit by puberty.26,3gHowever, more detailed investigations of substantial numbers of affected patients suggest that CBDC may be an earlier manifestation of LAD.17 Cutaneous lesions of CBDC are identical to those of LAD and although the perioral and perineal surfaces are usually affected, up to 96% of groups of patients with CBDC have lesions involving the trunk and limbs. The conjunctivae are the most frequently affected mucosaein CBDC, although oral lesions can also occur. There are linear deposits of IgA at the BMZ of perilesional and uninvolved skin in CBDC in the same location as those of LAD,17*40-43and they can persist for several years after remission.43However, the frequency and titer of circulating IgA antiBMZ antibodies is higher in CBDC compared with LAD, possibly reflecting the higher frequency of HLA-B8 in CBDC.17 Gluten-sensitive enteropathy is infrequent in CBDC and antiendomysium antibodies are not present.44 Spontaneous remission is more common in CBDC than in LAD, although some patients do require sulfone therapy. Childhood cicatricial pemphigoid is a very rare linear IgA dermatosis that has previously beenclinically distinguished from CBDC by the high frequency of ocular scarring. 17,45 Recent evidence has suggested that there may be marked clinical and immunopathologic overlap between childhood cicatricial pemphigoid and CBDC, but the small number of cases reported precludes any detailed analysis of the precise relationship of these disorders. REFERENCES
1. Rogers RS, Sheridan PJ, Jordon RE. Desquamative gingivitis. Clinical, histopathologic, and immunopathologic investigations. ORAL SURGORAL MED ORAL PATHOL1976;42:316-20. 2. Forman L, Nally FF. Oral nondystrophic bullous eruption mainly limited to the gingivae: a mechanobullous response.A variant of cicatricial mucous membrane pemphigoid? Br J Dermatol 1977;96:111. 3. Person JR, Rogers RS III. Bullous and cicatricial pemphigoid: clinical histopathologic and immunopathologic correlations. Mayo Clin Proc 1977;52:54-66. 4. Rivers EP, Hoover D, Dunlap C, Gier R, Alms T. An immunologic investigation of atypical gingivostomatitis. J Periodontol 1978;49:301-6. 5. Fine RM, Weathers DR. Desquamative gingivitis: a form of cicatricial pemphigoid? Br J Dermatol 1980;102:393-9. 6. Laskaris G, Nicolis G. Immunopathology of oral mucosa in bullous pemphigoid. ORAL SURGORAL MED ORAL PATHOL 1980;50:340-5. 7. Laskaris Cl, Demetriou N, Angelopoulos A. Immunofluorescent studies in desquamative gingivitis. J Oral Path01 1981; 10:398-407. 8. Nisengard RJ, Neiders M. Desquamative lesions of the gingiva. J Periodontol 1981;52:500-10. 9. Laskaris G, Sklavounou A, Stratigos J. Bullous pemphigoid: cicatricial pemphigoid, and pemphigus vulgaris. A comparative clinical survey of 278 cases.ORALSURGORAL MED ORAL PATHOL1982;54:656-62. 10. Rogers RS, Sheridan PJ, Nightingale SH. Desquamative gin-
Volume 70 Number 4 givitis: clinical histopathologic, immunopathologic, and therapeutic observations. J Am Acad Dermatol 1982;7:729-35. 11. Sklavounou A, Laskaris G. Frequency of desquamative gingivitis in skin disease. ORAL SURC ORAL MED ORAL PATHOL 1983;56:141-4. 12. JensenGL, Correll RW, Wescott WB. Desquamative gingivitis and extragingival collapsed bulla. J Am Dent Assoc 1984;109:753-5. 13. Silverman S, Gorsky M, Lozada-Nur F, Liu A. Oral mucous membrane pemphigoid. A study of sixty-five patients. ORAL SURF ORAL MED ORAL PATHOL 1986;61:233-7.
14. Porter SR, Malamos D, Smith RG, Scully C. Desquamative gingivitis: clinical and immunopathological features. (Submitted for publication). 15. Scopp IW. Desquamative gingivitis. J Periodontol 1984; 35:149-54. 16. Otes RD. Chronic desquamative gingivitis. J Periodontol 1967;38:485-90. 17. Wojnarowska F, Marsden RA, Bhogal B, Black MM. Chronic bullous disease of childhood, childhood cicatricial pemphigoid, and linear IgA disease of adults. A comparative study demonstrating clinical and immunopathologic overlap. J Am Acad Dermatol 1988;19:792-804. 18. Wiesenfeld D, Martin A, Scully C, Thomson J. Oral manifestations in linear IgA disease. Br Dent J 1982;153:398-9. 19. Hietanen J, Reunala T. IgA deposits in the oral mucosa of patients with dermatitis herpetiformis and linear IgA disease. Stand J Dent Res 1984;92:230-4. 20. Williams DM, Leonard JN, Wright P, et al. Benign mucous membrane (cicatricial) pemphigoid revisited: a clinical and immunological reanuraisal. Br Dent J 1984:157:313-6. 21. Leonard JN, Wrighi P, Williams DM, et all The relationship between linear IgA disease and benign mucous membrane pemphigoid. Br J Dermatol 1984;110:307-14. 22. Rantala I, Hietanen J, Soidinmaki H, Reunala T. Immunoelectron microscopic findings in oral mucosa of patients with dermatitis herpetiformis and linear IgA disease.Stand J Dent Res 1985;93:239-43. 23. Kelly S, Frith PA, Millard PR, Wojnarowska F, Black MM. A clinicopathological study of mucosal involvement in linear IgA disease. Br J Dermatol 1988;119:161-70. 24. Prost C, Colonna A, Combemale P, et al. Diagnosis of adult linear IgA dermatosis by immunoelectronmicroscopy in 16 patients with linear IgA deposits. J Invest Dermatol 1989; 92:39-45. 25. Leonard JN, Haffenden GP, Ring NP, et al. Linear IgA disease in adults. Br J Dermatol 1982;107:301-6. 26. Marsden RA, McKee PH, Bhogal B, et al. A study of benign chronic bullous dermatosis of childhood and linear IgA dermatosis of adults. Br. J Dermatol 1985;113:17-9. 27. Chorzelski T, Jablonska S. Evolving concept of IgA linear dermatosis. Semin Dermatol 1988;7:225-32. 28. Verhelst F, Demedts M, Verschakelen J, Verbeken D, Marien K, Peeters C. Adult linear IgA bullous dermatosis with bronchial involvement. Br J Dermatol 1987;116:587-90. 29. Yaoita H, Katz SI. Immunoelectron microscopic localization of IgA in skin of patients with dermatitis herpetiformis. J Invest Dermatol 1976;67:502-6. 30. Lawley TJ, Strober W, Yaoita H, Katz SI. Small intestinal biopsies and HLA types in dermatitis herpetiformis patients with granular and linear IgA skin deposits. J Invest Dermatol 1980;74:9-12.
Adult linear IgA disease manifesting as gingivitis
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31. Haffenden GP, Ring NP, Leonard JN, Fry L. Immunoelectron microscopical studies in patients with linear IgA deposits. J Invest Dermatol 1983;80:363. 32. Yamasaki Y, Hashimoto T, Nishikawa T. Dermatitis herpetiformis with linear IgA deposition: ultrastructural localisation of in vivo bound IgA. Acta Derm Venereol (Stockh) 1982; 62:401-5. 33. Bhogal B, Wojnarowska F, Marsden RA, Das A, Black MM, McKee PH. Linear IgA bullous dermatosis of adults and children: an immunoelectron microscopic study. Br J Dermatol 1987;117:289-96. 34. Pothupitiya GM, Wojnarowska F, Bhogal BS, et al. Comparison of the antigen in linear IgA bullous dermatosis (LABD) with the antigens in epidermolysis bullosa. Br J Dermatol 1984;116:443. 35. Davies MG, Marks R, Nuki G. Dermatitis herpetiformis-a skin manifestation of a generalised disturbance in immunity. Q J Med 1978;47:221-48. 36. Oranje AP, Vuzevski VD, Bouquet J, Sinaasapel M, Van Hoost T, Stolz E. Linear IgA diseaseand chronic active hepatitis-a coincidence or not? Acta Derm Venereol (Stockh) 1985;65:440-2. 37. Chorzelski TP, Beutner EH, Sule J, et al. IgA anti-endomysium antibody. A new immunological marker of dermatitis herpetiformisandcoeliacdisease. Br J Dermatol1984;111:395402. 38. Flotte TJ, Olbricht SM, Collins B, Harrist TJ. Immunopathologic studies of adult linear IgA bullous dermatosis. Arch Path01 Lab Med 1985;109:457-9. 39. Marsden RA, Skeete MVH, Black MM. The chronic acquired bullous diseasesof childhood. Clin Exp Dermatol 1979;4:22740. 40. Horiguchi Y, Toda K, Okamoto H, et al. Immunoelectronmicroscopic observations in a case of linear IgA bullous dermatosis of childhood. J Am Acad Dermatol 1986;14:593-9. 41. Roberts LJ, Sontheimer RD. Chronic bullous dermatosis of childhood. Immunopathologic studies. Pediatr Dermatol 1987;4:10-6. 42. Dabrowski J, Chorzelski TP, Jablonska S, et al. The ultrastructural localisation of IgA deposits in chronic bullous diseaseof childhood (CBDC). J Invest Dermatol 1979;72:291-5. 43. Larreque M, Bressieux JM, Laidet B, et al. Erytheme annulaire centrifuge revelateur d’une dermatite a IgA lineaire de l’enfant. Ann Dermatol Venereol 1986;113:1213-22. 44. Chorzleski TP, Jablonska S, Chadzynska M, et al. IgA endomysium antibody in children with dermatitis herpetiformis treated with gluten-free diet. Pediatr Dermatol 1986;3:291-4. 45. Langeland T. Childhood cicatricial pemphigoid with linear IgA deposits. Acta Derm Venereol (Stockh) 1985;65:354-5. Reprint requests to:
Dr. Stephen R. Porter Centre for the Study of Oral Diseases University Department of Oral Medicine, Surgery, and Pathology Bristol Dental Hospital and School Lower Maudlin St. Bristol BSl 2LY England, U.K.
FOR THE AND
STUDY
PATHOLOGY,
OF ORAL
DISEASES,
BRISTOL
DENTAL
UNIVERSITY HOSPITAL
DEPARTMENT AND
OF ORAL
MEDICINE,
SCHOOL
Desquamative gingivitis is a manifestation of various dermatoses, particularly lichen planus and mucous membrane pemphigoid. A rare example of adult linear immunoglobulin A disease manifesting as desquamative gingivitis is presented. Although the initial clinical features were typical of desquamative gingivitis, the persistence of ulceration after dental extractions was unusual, and the management of the oral lesions proved difficult. The clinical, immunopathologic, and therapeutic aspects of linear immunoglobulin A dermatoses are reviewed.
(ORALSURCORALMEDORALP~~~0~1990;70:450-3)
D
esquamative gingivitis (DG) is a common oral disorder clinically characterized by diffuse erythematous desquamation, ulceration, and possible bulla formation affecting the free and attached maxillary and mandibular gingivae. DG most frequently occurs in the sixth and seventh decades; there is a female predisposition. DG is usually a manifestation of lichen planus or mucous membrane pemphigoid and may be the only or initial clinical presentation of these disorders.‘-l4 A variety of other less common mucocutaneous diseasescan also give rise to DG (Table I). This report appearsto be the first detailed report of adult linear immunoglobulin A (Ig A) disease(LAD) manifesting as desquamative gingivitis.
Fig. 1. Severeulceration of attached and marginal labial gingivae about lower teeth of present patient.
CASEREPORT
A 69-year-old white man sought treatment in October 1981 with a complaint of gingival sorenessand blistering of 6 months’ duration. This was the first episode, and no precipitating, perpetuating, or relieving factors were identified. The patient had no notable medical problems, although in 1982 he had an episodeof optic neuritis due to the onset of multiple sclerosis. He had no cutaneous, genital, or other ocular symptoms. Examination revealed erythema and ulceration of the attached and marginal gingiva about all surfaces of all teeth 87~~: i ::li568 (Fig. 1). 7/13/16830 450
The only other oral problem was plaque-associatedadult periodontitis affecting all teeth. There were no other mucosal or cutaneous lesions. Biopsy of the perilesional tissue of an ulcer revealed a split at the epitheliomesenchymal junction (Fig. 2), and direct immunofluorescencedemonstrated homogeneouslinear deposits of IgA and C3 at the epitheliomesenchymal junction. Although the patient had no cutaneous lesions, a biopsy of skin was undertaken, but immune deposits were not detected. Hematology (hemoglobin concentration, red cell indexes, white cell total and differential counts, and red cell folate) and serology (serum ferritin, vitamin Br2, and immunoglobulins) were normal, and there were no circulating an-
Volume 70 Number 4
Adult linear IgA disease manifesting as gingivitis
451
Fig. 2. Histology of bullous gingival area-note subepithelial bulla, split at epitheliomesenchymal junction, and intense inflammatory infiltrate within corium.
tibodies to nuclear components, smooth muscle, mitochondria, thyroid colloid, or squamous epithelium. The linear deposits of IgA and C3 and the split at the epitheliomesenchymal junction indicated a diagnosis of adult linear IgA disease. Initial treatment with betamethasone valerate mouthrinses (2.5 mg four times daily) had little effect. Systemic prednisolone (15 mg daily) did produce some clinical improvement, but the gingival lesions did not resolve completely. Dapsone (50 mg daily) failed to produce any improvement, and in view of the poor periodontal status, all the remaining teeth were extracted in October 1985. Surprisingly, ulceration of the alveolar mucosain the maxillary and mandibular areas persisted for the next 4 years, symptoms being managed throughout this period with betamethasone spray (100 gm, six times daily) and benzydamine hydrochloride mouthrinses with a slow but obvious decreasein ulceration. DISCUSSION
Desquamative gingivitis usually occurs as persistent sorenessof the gingiva without frank ulceration. Edentulous areasare typically lessaffected. The cause is usually lichen planus or mucous membrane pemphigoid. The present case of desquamative gingivitis is clinically notable becauseof the frank gingival ulceration and persistence of ulceration of the alveolar mucosa after extraction of the teeth. This latter observation is a rare clinical feature that hasonly been mentioned in a few early reviews of desquamative gingivitis.15, l6 The persistence of oral lesions may reflect the underlying pathology; certainly other workers have noted that (ill-defined) gingival lesions in adult linear IgA disease can respond poorly to systemic therapies.17
Although the patient did not have IgA deposits in
Table
I. Underlying pathologies of DG Lichen planus Mucous membrane pemphigoid Bullous pemphigoid Pemphigus vulgaris Dermatitis herpetiformis LAD Drug reactions (e.g., chlorhexidine Other
gluconate)
uninvolved skin, the prominent homogeneous linear deposits of IgA and C3 suggested the diagnosis of LAD, rather than any of the other bullous dermatoses,was most appropriate. Oral ulceration, erythematous patches, and bullae have previously been observed in some patients with LAD17M24; however, this appears to be the first case of LAD described manifesting solely as desquamative gingivitis. In view of the few reports of linear IgA dermatoses in the oral medicine or oral pathology literature, a review of the major features of these diseasesis detailed below. Adult linear IgA disease (linear IgA bullous dermatosis; linear dermatitis herpetiformis; LAD) is an uncommon mucocutaneousbullous disorder that usually gives rise to a rash of variable presentation. An eruption of vesiclesand bullae, usually in clusters, can develop on the lower trunk, groin, lower extremities, and periorally. There may be an associated pruritus. LAD more frequently affects females and has a mean age of presentation in the fifth decade.i7,23-28 The lesions of LAD are subepithelial vesicles or bullae; microabscessesare present in 50% of specimens and an infiltrate of eosinophils may be present in some lesions.22,24The site of bulla formation is at
452
Porter et al.
the basement membrane zone (BMZ), occurring either below the basal lamina (as in dermatitis herpetiformis2g) or between the basal lamina and the basal cell membranes (as in bullous pemphigoid27). Homogeneousdeposits of IgA have consistently been detected at the basement membrane zone in perilesional and uninvolved skin and mucosaeof affected persons. Deposits of IgG, IgM, and C3 are less frequently found. 17,25Circulating IgA and IgG antibodies to BMZ antigens are present in a minority of patients; titers are generally low and they do not correlate with diseaseactivity. 17*25However, the low detection of circulating antibodies may reflect the choice of tissue substrate since circulating antibodies to human bulbar conjunctiva, as opposedto intact or split skin or oral mucosa, have been detected in patients with LAD.23 Previous reports have suggested that IgA antibodies can be deposited either immediately below the epithelial basal lamina or in the lamina lucida20,30-32; however, recent immunoelectron microscopic analysis of uninvolved skin of patients with LAD has consistently found IgA deposits to be located below the lamina lucida whereas a mirror image pattern has beendemonstrated in somepatients having depositsin both the lamina lucida and below the lamina densa. The target antigen may lie in the sublamina densa in a different site to the antigen of epidermolysis bullosa acquisita (EBA) .33,34 It is probable that the LAD antigen has an intracellular location and that splitting of the BMZ in vitro exposes the antibody binding sites, which are otherwise inaccessible. Fifty percent of personswith LAD have circulating autoantibodies to a variety of antigens,17y25and some patients may have other autoimmune disorders.35,36 Circulating immune complexes, especially IgA type, can be present, although their pathogenic importance is not clear.25 Unlike in dermatitis herpetiformis, gluten-sensitive enteropathy (GSE) is not a frequent feature of LAD, only 25% to 33% of patients having clinical evidence of GSE, and few others have histologic evidenceof gut disease17,30;antiendomysium antibody is infrequent in patients with LAD.37 The low incidence of GSE in LAD may be reflected by the predominance of IgAl subclass in the immune deposits of perilesional tissue.38The association between LAD and HLA-B8 may not be as strong as that of dermatitis herpetiformis and HLA-B8.17q25,3o Lesions spontaneously remit in up to 48% of patients with LAD, and most other patients can be successfully treated with long-term sulfone therapy sometimes complemented with systemic corticosteroids.r7,25,27 Chronic bullous diseaseof childhood (CBDC) has previously been considered to be clinically distinct
ORAL SURGORAL MED ORAL PATHOL October 1990
from LAD, since there may be a predisposition for facial and perineal cutaneous involvement in the latter and CBDC was thought to spontaneously remit by puberty.26,3gHowever, more detailed investigations of substantial numbers of affected patients suggest that CBDC may be an earlier manifestation of LAD.17 Cutaneous lesions of CBDC are identical to those of LAD and although the perioral and perineal surfaces are usually affected, up to 96% of groups of patients with CBDC have lesions involving the trunk and limbs. The conjunctivae are the most frequently affected mucosaein CBDC, although oral lesions can also occur. There are linear deposits of IgA at the BMZ of perilesional and uninvolved skin in CBDC in the same location as those of LAD,17*40-43and they can persist for several years after remission.43However, the frequency and titer of circulating IgA antiBMZ antibodies is higher in CBDC compared with LAD, possibly reflecting the higher frequency of HLA-B8 in CBDC.17 Gluten-sensitive enteropathy is infrequent in CBDC and antiendomysium antibodies are not present.44 Spontaneous remission is more common in CBDC than in LAD, although some patients do require sulfone therapy. Childhood cicatricial pemphigoid is a very rare linear IgA dermatosis that has previously beenclinically distinguished from CBDC by the high frequency of ocular scarring. 17,45 Recent evidence has suggested that there may be marked clinical and immunopathologic overlap between childhood cicatricial pemphigoid and CBDC, but the small number of cases reported precludes any detailed analysis of the precise relationship of these disorders. REFERENCES
1. Rogers RS, Sheridan PJ, Jordon RE. Desquamative gingivitis. Clinical, histopathologic, and immunopathologic investigations. ORAL SURGORAL MED ORAL PATHOL1976;42:316-20. 2. Forman L, Nally FF. Oral nondystrophic bullous eruption mainly limited to the gingivae: a mechanobullous response.A variant of cicatricial mucous membrane pemphigoid? Br J Dermatol 1977;96:111. 3. Person JR, Rogers RS III. Bullous and cicatricial pemphigoid: clinical histopathologic and immunopathologic correlations. Mayo Clin Proc 1977;52:54-66. 4. Rivers EP, Hoover D, Dunlap C, Gier R, Alms T. An immunologic investigation of atypical gingivostomatitis. J Periodontol 1978;49:301-6. 5. Fine RM, Weathers DR. Desquamative gingivitis: a form of cicatricial pemphigoid? Br J Dermatol 1980;102:393-9. 6. Laskaris G, Nicolis G. Immunopathology of oral mucosa in bullous pemphigoid. ORAL SURGORAL MED ORAL PATHOL 1980;50:340-5. 7. Laskaris Cl, Demetriou N, Angelopoulos A. Immunofluorescent studies in desquamative gingivitis. J Oral Path01 1981; 10:398-407. 8. Nisengard RJ, Neiders M. Desquamative lesions of the gingiva. J Periodontol 1981;52:500-10. 9. Laskaris G, Sklavounou A, Stratigos J. Bullous pemphigoid: cicatricial pemphigoid, and pemphigus vulgaris. A comparative clinical survey of 278 cases.ORALSURGORAL MED ORAL PATHOL1982;54:656-62. 10. Rogers RS, Sheridan PJ, Nightingale SH. Desquamative gin-
Volume 70 Number 4 givitis: clinical histopathologic, immunopathologic, and therapeutic observations. J Am Acad Dermatol 1982;7:729-35. 11. Sklavounou A, Laskaris G. Frequency of desquamative gingivitis in skin disease. ORAL SURC ORAL MED ORAL PATHOL 1983;56:141-4. 12. JensenGL, Correll RW, Wescott WB. Desquamative gingivitis and extragingival collapsed bulla. J Am Dent Assoc 1984;109:753-5. 13. Silverman S, Gorsky M, Lozada-Nur F, Liu A. Oral mucous membrane pemphigoid. A study of sixty-five patients. ORAL SURF ORAL MED ORAL PATHOL 1986;61:233-7.
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Dr. Stephen R. Porter Centre for the Study of Oral Diseases University Department of Oral Medicine, Surgery, and Pathology Bristol Dental Hospital and School Lower Maudlin St. Bristol BSl 2LY England, U.K.