A Clinical Study of Oral Mucous Membrane Pemphigoid
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1 The Journal of International Medical Research 2003; 31: A Clinical Study of Oral Mucous Membrane Pemphigoid A ALKAN 1, Ö GÜNHAN 3, A ALKAN 2 AND F OTAN 2 1 Department of Oral and Maxillofacial Surgery and 2 Department of Periodontology, Faculty of Dentistry, University of Ondokuz Mayis, Samsun, Turkey; 3 Department of Pathology, Gülhane Military Medical Academy, Ankara, Turkey We present 13 cases of oral mucous membrane pemphigoid (MMP) and review the literature. The cases were retrieved from the archives of Ondokuz Mayis University and Gülhane Military Medical Academy, Turkey, between 1997 and Inclusion criteria were clinical findings of oral MMP verified by histological and immunofluorescent examination. Thirteen patients (two males and 11 females), aged years, were identified. Involvement was confined to the mouth in all cases except one, in which the conjunctiva was also affected. Two individuals in the study were < 20 years old, an age group rarely affected. The oral mucosa is often the initial site of MMP lesions, so it is important that dentists as well as physicians are aware of the symptoms and signs. A swift diagnosis, made in consultation with other specialists such as ophthalmologists and dermatologists, is needed in order to prevent a delay in treatment. KEY WORDS: MUCOUS MEMBRANE PEMPHIGOID; ORAL; DIRECT IMMUNOFLUORESCENCE; CHILDHOOD Introduction Mucous membrane pemphigoid (MMP) is an autoimmune vesiculobullous disease of the mucosal tissues and, rarely, the skin. It usually affects adults over 40 years of age and occasionally children. Only 10 cases of childhood MMP affecting the oral mucosa have been reported in the English literature MMP occurs twice as often in women as in men, and no racial predilection exists. 11 Oral mucosal surfaces are the most frequently affected sites, predominantly the gingiva, where it presents as desquamative gingivitis. MMP may result in scar formation in other mucosal sites such as the conjunctiva, but oral scarring is rare. It can become life-threatening if laryngeal or oesophageal involvement lead to stenosis, and progressive ocular lesions may result in blindness. 12,13 An early and accurate diagnosis should therefore be made before these complications occur. This article presents 13 cases of oral MMP along with a review of the literature. Two of the patients were under 20 years of age, which is rare. Patients and methods A survey of the archives of the Departments of Periodontology and Maxillofacial Surgery at Ondokuz Mayis University, Turkey, and the Department of Pathology, Gülhane Military Medical Academy, Turkey, between 1997 and 2002 revealed 13 cases of oral MMP. The criteria for inclusion were the 340
2 clinical findings of oral MMP verified by histological and immunofluorescent examination. Clinical findings necessitating further laboratory investigation included the presence of persistent erythema and vesicle and ulcer formation in the oral mucosa or desquamative gingivitis (Fig. 1). Haematoxylin and eosin staining and direct immunofluorescence (Fig. 2) revealed separation of the epithelium from the basement membrane and the presence of a line of fluorescence along the basement membrane, indicating immune-complex depositions (IgG and C3). Results Patient characteristics and sites of involvement are listed in Table 1. There were two male and 11 female patients, with ages ranging from 16 to 72 years. Sites of oral involvement included keratinized gingiva, the buccal mucosa, the tonsils, the floor of the mouth, the soft palate and the tongue. Gingival involvement was typically manifested as desquamative gingivitis, with characteristic epithelial sloughing on gentle scraping with a periodontal probe (Fig. 1). One patient manifested ocular lesions in addition to the oral lesions. Strikingly, the vast majority of the patients were females of menopausal age. All the patients were adults except two, who were both under the age of 20 years. Discussion Oral MMP is a debilitating disease, its persistent character adversely affecting the patient s daily life. It usually appears as bullae or erosions on different mucosal sites of the body and/or the gingiva. Management is difficult and the possibility of recurrence is high. It is not usually lifethreatening, but its persistent nature can tax the patience of the affected individual. It mostly presents in middle-aged adults but rarely occurs in children. In our case series, FIGURE 1: Desquamative gingivitis, with epithelial sloughing on gentle scraping with a periodontal probe 341
3 FIGURE 2: (A) Photomicrograph showing separation of the epithelium from the underlying basement membrane. Haematoxylin and eosin, 200. (B) Direct immunofluorescence showing linear deposition of IgG auto-antibody along the basement membrane, 200 TABLE 1: Characteristics of 13 patients with oral mucous membrane pemphigoid from Ondokuz Mayis University, Turkey and the Department of Pathology, Gülhane Military Medical Academy, Turkey, between 1997 and 2002 Patient Age (years) Sex Site 1 63 Male Buccal mucosa 2 47 Female Gingiva 3 a 16 Female Gingiva and soft palate 4 72 Female Buccal mucosa and gingiva 5 49 Female Buccal mucosa 6 49 Female Buccal mucosa and palatine tonsil 7 50 Female Buccal mucosa 8 45 Female Buccal mucosa 9 47 Female Buccal mucosa Female Tongue and floor of mouth Male Buccal mucosa Female Buccal mucosa Female Gingiva, tonsil and conjunctiva 342
4 two of the 13 patients were young a female aged 16 years and a male aged 19 years. In both these cases, the disease was limited to the oral cavity with no other mucosal or skin lesions. There were no predisposing factors such as emotional stress, smoking, nutritional deficiency or systemic disease present in these young patients. In the literature on MMP, involvement of the skin is rare, but the conjunctiva may sometimes be affected, depending on the severity of the disease, and women are affected more frequently than men. The findings in our study are consistent with these data, since there were no skin lesions accompanying oral lesions in any of the patients, and females constituted most of the study population. The aetiology of MMP remains unclear. Severe mucosal inflammatory injury, 14 drugs, 15,16 viruses, ultraviolet light and genetic predisposition such as HLA- DQB1* are some of the suspected aetiological factors. A relationship between MMP and smoking or menopausal status has not been reported in the literature, although desquamative gingivitis, which is one of the clinical manifestations of MMP, seems to be common in post-menopausal women. 18 Since almost all the patients in our study were females of menopausal age, this specific state could be an important aetiological factor in this disease. Many diseases, including bullous pemphigoid, pemphigus vulgaris and bullous lichen planus, should be considered in the differential diagnosis of MMP. The lesions of bullous pemphigoid and MMP closely resemble each other, the main difference being in their clinical presentation. The former primarily affects the skin; the oral cavity is rarely the initial site of appearance, and scarring occurs less frequently. The latter mostly involves mucosal tissues and heals by scarring, although scarring rarely occurs in the oral mucosa. Their similarities have led some authors to suggest that they are different clinical presentations of the same disease. The vesicular lesions of MMP may also be similar to those of pemphigus vulgaris, particularly when the latter condition is confined to the oral cavity. The lesions of pemphigus vulgaris often appear first in the mouth, but soon spread widely on the skin. Acantholysis and intra-epithelial clefting are seen, and immunofluorescence reveals immunoglobulin G auto-antibody bound around the surface of the prickle cells in the epithelium, in contrast to MMP, in which it is bound along the basement membrane. 19 Clinically, bullous-type oral lichen planus may be confused with MMP. However, the histopathological subepithelial separation without oedematous degeneration of the basal layer of the epithelium seen in MMP is indicative in making the differential diagnosis. In addition, the presence of the characteristic clinical white striations at the periphery of the ulcerated areas in lichen planus helps differentiate between the two conditions. 18 There is no standard treatment protocol for the management of patients with MMP. The treatment strategy varies greatly according to the preference of the physician, the age of the patient, the severity of the disease and the site involved. Topical and systemic corticosteroids with or without immunosuppressive drugs, dapsone 20 and tetracycline 21 are some of the treatment alternatives widely used. Before choosing which medication to use, the oral hygiene of the patient should be improved, since gingival inflammation as a consequence of poor oral hygiene may aggravate the course of the disease. Good oral hygiene and use of a soft bristle toothbrush may partly alleviate 343
5 the patient s discomfort. An anti-plaque agent such as 0.2% clorhexidine mouthwash twice a day may also have beneficial effects. Systemic drugs or agents are mainly indicated when the skin or mucosal locations other than oral sites, such as the conjunctiva, are involved. Oral MMP may be more difficult to manage than other subgroups of the disease because constant trauma from chewing and the use of a toothbrush, together with the greater risk of secondary infection, prevent healing of the erosive lesions. This in turn may lead to malnutrition. 12 A pattern of remissions followed by exacerbations usually occurs, and predicting the course of the disease is not easy. Teamwork between the clinicians involved is of utmost importance in the management of this condition. Dentists should be in close contact with an ophthalmologist and dermatologist in cases with possible conjunctival or skin involvement. Received for publication 6 March 2003 Accepted subject to revision 21 March 2003 Revised accepted 15 April 2003 Copyright 2003 Cambridge Medical Publications References 1 Jolliffe DS, Sim-Davis D: Cicatricial pemphigoid in a young girl: report of a case. Clin Exp Dermatol 1977; 2: Worsaae N, Dabelsteen E: Benign mucous membrane pemphigoid in an 18-year-old woman. Arch Dermatol 1978; 114: Barnett ML, Wittwer W, Miller RL: Desquamative gingivitis in a 13-year-old male. J Periodontol 1981; 52: Rosenbaum MM, Esterly NB, Greenwald MG, Gerson QR: Cicatricial pemphigoid in a 6-year-old child: report of a case and review of literature. Pediatr Dermatol 1984; 2: Moy M, Kumar V, Friedman RP, Schaeffer M, Beutner E, Helm F: Cicatricial pemphigoid. A case of onset at age 5. J Periodontol 1986; 57: Laskaris G, Triantafyllou A, Economopoulou P: Gingival manifestation of childhood cicatricial pemphigoid. Oral Surg Oral Med Oral Pathol 1988; 66: Sklavounou A, Laskaris G: Childhood cicatricial pemphigoid with exclusive gingival involvement. J Oral Maxillofac Surg 1990; 19: Roche C, Field E: Benign mucous membrane pemphigoid presenting as desquamative gingivitis in a 14-year-old child. Pediatr Dent 1997; 7: Cheng Y, Rees T, Wright J: Oral pemphigoid in an 8-year-old girl. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000; 90: Musa NJ, Kumar V, Humphreys L, Aguirre A, Neiders ME: Oral pemphigoid masquerading as necrotizing ulcerative gingivitis in a child. J Periodontol 2002; 73: Moschella SM, Pillsbury DM, Hurley HJ, Jr (eds): Dermatology, Vol 1. Philadelphia: WB Saunders, Fleming TE, Korman NJ: Cicatricial pemphigoid. J Am Acad Dermatol 2000; 43: Nordins BJ: Cicatricial pemphigoid and erythema nodosum. Ophthalmology 1990; 97: Chan LS, Soong HK, Foster CS, Hammerberg C, Cooper KD: Ocular cicatricial pemphigoid occurring as a sequela of Stevens Johnson syndrome. JAMA 1991; 266: Vassileva S: Drug-induced pemphigoid: bullous and cicatricial. Clin Dermatol 1998; 16: Fiore PM, Jacobs IH, Goldberg DR: Drug-induced pemphigoid. Arch Ophthalmol 1987; 105: Challocombe SJ, Setterfield J, Shirlaw P, Harman K, Scully C, Black MM: Immunodiagnosis of pemphigus and mucous membrane pemphigoid. Acta Odontol Scand 2001; 59: Shklar G: Desquamative gingivitis and oral mucous membrane diseases. In: Clinical Periodontology, 8th edn (Carranza FA, Newman GM, eds). Philadelphia: WB Saunders, 1996; pp Cawson RA, Odell EW: Principals of investigation and diagnosis. In: Essentials of Oral Pathology and Oral Medicine, 6th edn. London: Churchill Livingstone, 1998; pp Rogers RS, Seehafer JR, Perry HO: Treatment of cicatricial (benign mucous membrane) pemphigoid with dapsone. J Am Acad Dermatol 1986; 6: Poskitt L, Wojnarowska F: Minimizing cicatricial pemphigoid orodynia with minocycline. Br J Dermatol 1995; 132: Address for correspondence Dr A Alkan Faculty of Dentistry, University of Ondokuz Mayis, 55139, Kurupelit, Samsun, Turkey. alpera@omu.edu.tr 344
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