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Tidak hanya proses destruksi oleh S.mutans dan produksi membran abses saja yang terjadi pada peristiwa pembentukan abses ini, tapi juga ada pembentukan pus oleh bakteri pembuat pus (pyogenik), salah satunya juga adalah S.aureus. jadi, rongga yang terbentuk oleh sinergi dua kelompok bakteri tadi, tidak kosong, melainkan terisi oleh pus yang konsistensinya terdiri dari leukosit yang mati (oleh karena itu pus terlihat putih kekuningan), jaringan nekrotik, dan bakteri dalam jumlah besar.
Tidak hanya proses destruksi oleh S.mutans dan produksi membran abses saja yang terjadi pada peristiwa pembentukan abses ini, tapi juga ada pembentukan pus oleh bakteri pembuat pus (pyogenik), salah satunya juga adalah S.aureus. jadi, rongga yang terbentuk oleh sinergi dua kelompok bakteri tadi, tidak kosong, melainkan terisi oleh pus yang konsistensinya terdiri dari leukosit yang mati (oleh karena itu pus terlihat putih kekuningan), jaringan nekrotik, dan bakteri dalam jumlah besar.
Tidak hanya proses destruksi oleh S.mutans dan produksi membran abses saja yang terjadi pada peristiwa pembentukan abses ini, tapi juga ada pembentukan pus oleh bakteri pembuat pus (pyogenik), salah satunya juga adalah S.aureus. jadi, rongga yang terbentuk oleh sinergi dua kelompok bakteri tadi, tidak kosong, melainkan terisi oleh pus yang konsistensinya terdiri dari leukosit yang mati (oleh karena itu pus terlihat putih kekuningan), jaringan nekrotik, dan bakteri dalam jumlah besar.
Desquamative gingivitis: A clinical, histopathoiogic, and
immunologie study A- K.. Markopoulos*/D. Antoniades*/P. Papanayotou*/G. Trigonidis* Abstract Desquamative gingivitis is believed to be a clinical sign of certain mucocutaneous diseases rather than a distinct pathologic entity. The prevalence of desquamative gingivitis was studied in a group of patients with the most common mucocutaneous diseases. Of 414 patients with pemphigus vulgaris. mucous membrane pemphigoid, or oral lichen planus. 49 (1.8%) exhibited gingival lesions in the form of desquamative gingivitis. Desquamative gingivitis was most prevalent in the patients with mucous membrane pemphigoid (41.6%) followed by those with pemphigus vulgaris (9.1%). Other elinieal characteristics, as well as histo- pathoiogic and imtnunohistochemical findings, that aid in early diagnosis are presented. (Quintessence Int 996:27:763-767.') Clinical relevance Desquamative gingivitis, in most cases, represents a manifestation of systemic diseases. Because it has no specific clinical pathognomonic features, laboratory aids, such as histopathoiogic and immunohistochem- ical examination, should be used to unmask the underlying disease so that the appropriate treatment can be provided. Introduction Desquamative gingivitis (DG) is characterized by erythematous and desquamative lesions of the free and attached gingiva. The condition was first described by Tomes and Tomes' in 1894 and was further defined several years later by Prinz^ and Merrit,^ who pro- posed the term chronic diffuse desquamative gingivitis. UsuaUy the changes are confined to the labial gingival mueosa, which varies from bright to dark red and is edematous. Tbe epithelium is quite friable and can be removed easily from the underlying connective tissue, leaving a red surface that bleeds readily after minimal trauma. Other gingival sites, such as palatal and lingual surfaces, are rarely involved,"* The etiology of DG remains obscure. Early investi- gators believed that there was a single cause. McCarthy et al^ were among the first who proposed that DG is a nonspecific reaction pattern that can be associated with any one of several diseases or conditions. This group suggested that dermatologie diseases, hormonal factors, aging, metabolic disturbances, irdtational factors, and chronic infections could cause DG, However, in recent years, it has been shown that the great majority (approximateiy 75%) of cases of DG are manifestations of mucocutaneous diseases, primarily mucous membrane pemphigoid (MMP), oral lichen planus (OLP), and pemphigus vulgaris (PV).'''^"''' In the present investigation, the prevalence of DG was retrospectively studied in a large group of patients with these mucocutaneous diseases. Furthermore the clinical, histopathoiogic, and immunologie features in each disease group were analyzed. ' Department of Oral Medicine and Pathology, Aristotle University of Thessaloniki, School of Dentistry, Thessaloniki, Greece. Reprint requests: Dr A. K. Markopoulos, Department of Oral Medicine and Pathology, Aristotle University ofThessaloniki, School of Dentistry, Thessaloniki 54006, Greece. Method and materials The records of all patients with PV, MMP, and OLP who were seen during the period from Januari' 1983 to Quintessence Intemalional Volume 27, Number 11/1996 763 Markopoulos et al Fig 1 Desquamalive gingivitis in a palien! with pemphigus. Areas o erosion are seen. Fig 2 Desquamalive gingivitis in a patient with mucous membrane pemphigoid. Fig 3 Desquamalive gingivitis in a patient wiih oral lichen planus. January 1993 in the Oral Medicine Clinic were retrieved from the files ofthe Oral Pathology Depart- ment. A total of 414 cases were studied. Each file was examined carefully for documentation of DG, The final diagnosis was established on the basis of clinical, histopathologic, and immunohistochemical criteria. From the clinical point of view, only t>pical patients with severe lesions were included in the study. Typical patients were considered to be those presenting with bright to dark red, edematous, and friable gingival mucosa, Tlie patients were subjected to careflii phy- sical examination, including slit-lamp examination, laryngoscopy, and examination of the ear canal, anogenital area, and skin. The histologie slides were stained with hematoxylin and eosin. The major criteria for the histopathologic diagnosis of each mucocutaneous disease category were acantholysis and intraepithelial ciefting forma- tion for PV; subepithelial bulla formation for MMP; and hydropic degeneration of the basal layer of the epithelium with bandiike lymphocytic infiltration of the upper lamina propria for OLP. The immunohistochemical slides had been stained with a streptavidin-biotin immunoperoxidase tech- nique using polycional antibodies for the demonstra- tion of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM). and complement (C3) on paraffin-embedded tissues (Immunostain Diagnostic Products, Lianbaris), Direct immuno- fluorescence had also been performed on fresh tissues for the demonstration of fibrin-fibrinogen. The major immunologie criteria that we used were the following; intercellular deposition of IgG and IgA at the epithe- lial surface for PV; deposition of IgG and IgA in the linear basement membrane for MMP; nonspecific immunohistochemical staining of IgG and IgA for OLP; and deposition of IgM and fibrin-fibrinogen for OLP. Results An interim clinical diagnosis ofthe underlying disease in DG patients was based on the presence of erythema- tous and friable gingival mucosa or on the occasional presence of accompanying clinical matufestations of each disease in other sites of the oral mucosa; the presence of vesiculoerosive lesions and Nikolsky's sign, which are indicative of PV and MMP, or the presence of laceiike white lesions combined with erosions or atrophie mucosa, which are suggestive of erosive or atrophie OLP. 764 Quintessence International Volume 27, Number 11/1996 Markopoulos et al Table ! Prevalence of desquamative gingivitis ( DG) in 414 patients with mucosal disease Underlying disease Pemphigus vulgaris Mucous membrane pemphigoid Oral lichen plan us Idiopathic Total No. of patients 33 53 326 2 414 Patients witb DG No. 3 22 22 2 49 (%) ( 9.1) ( 41.6) { 6.8) (100,0) ( 11.8) Male No, 1 4 6 1 11 (%) (33.3) (18.2) (27.3) (50,0) (23.4) Female No. 2 18 16 1 36 (%) (66.7) (81,8) (72,7) (50.0) (76.6) Mean age of patients with DG 37.7 y 55,1 y 50,0 y 45.4 y 47.1 y No. of patients with mucosal lesions in other oral sites 1 8 12 0 21 Tabie 2 Immunohistochemical findings in biopsy specimens taken from patients with desquamative gingivitis Und e dying disease Pemphigus vulgaris Mucous membrane pemphigoid Oral lichen planus Idiopathic ' Nol performed. No. of patients 3 22 22 2 Streptavidin-biotin immunoperoxidase staining Positive IgG IgA 3 3 17 16 IgM 1 4 10 C3 3 16 IgG 5 22 2 Nei IgA 6 22 2 native IgM 2 18 12 2 C3 6 22 2 Direct immunouorescence for fibrinogen Positive Negative 19 3 The DG lesions were confined to the labial gingiva, which appeared bright to dark red and edematous (Figs 1 to 3). Accompanying lesions were found mainly in patients with OLP (12 of 22) (Table 1). Thorough physical examination oft he patients did not reveal any extraora! manifestations. Pain was a pre- dominant symptom in many patients, while the pre- sence of local factors, such as plaque or dental calculus, was evident in the majority of patients in each group. On the basis of histopathologic and immunohisto- chemical examination the 49 DG patients were divided into four categories; P y MMP. OLP, and idiopathic cases. Histopathologicaily. 47 patients ful- filled the classic criteria for PV, MMP, or OLP (Table 2). Two parients did not manifest specific microscopi- cally pathognomonic features, and therefore their cases were considered idiopathic. All the patients with PV were positive for IgG and IgA. while parients with MMP were found positive for IgG and IgA to a lesser extent (17 of 22 patients). In contrast all patients with OLP were negative for IgG and IgA. and some were posirive for IgM and fibrin-fibrinogen. The idiopathic cases were negative in all the immunohistochemical stainings that were performed. The immunohistochem- ical findings are illustrated in Figs 4 to 6. Table 1 reveals that the majority of parients with DG have MMP (41.6%). while 9.1% and 6,8% have PVand OLP, respectively. The great majority oft he patients in all disease groups were female. Discussion The clinical appearance of DG is not pathognomonic. Therefore, supplementary procedures, such as histo- pathologic examination and immunohistochemical tests of gingival biopsy specimens, are necessary for a definitive diagnosis. In the present study, one of the Quintessence Intemational Volume 27, Number 11/1996 765 Markopouios et ai Fig 4 Desquamative gingivitis m pemphigus. Intercellular deposition ol igG is apparent (Streptavidin-biotin staining, originai magnification x480.1 Fig 5 Desquamative gingivifis in mucous membrane pem- phigoid. The linear basemenf membrane exhibifs deposits of IgG (Sfreptavidin-biotin sfaining; originai magnificafion Fig 6 Desquamative gingivitis in orai lichen pianus. Direct immunofluorescence discloses the presence of fibrinogen along the basemenf membrane zone. (Original magnifica- fion x120.) few clinical characteristics beyond the erythematous atid friable gingiva was the occasional presence of accompanying lesions in other sites ofthe oral mucosa. These lesions were more frequently observed in patients with OLP. Twelve of 22 patients manifested lacelike white formations combined with erosive or atrophie lesions in other sites of their oral mucosa. The highest prevalence of DG (41.6%) was ob- served in patients with MMP. Eight of 22 of these patients had vesiculoerosive lesions in other sites of the oral mucosa. A lower prevalence of DG (9.1%) was observed in patients with PV One ofthe three DG patients in this group had vesiculoerosive lesions in other sites of his oral mucosa. Nikolsky's sign (ie, the detachment of epithelium after mild rubbing with a cotton tip) was positive in these lesions. The lowest prevalence of DG( 6.8%) was counted in the OLP group. Erosive or atrophie lesions accom- panied the gingivai desquamation in 12 of 22 patients, suggesting that erosive and atrophie forms are the most common forms of OLP to be the underlying disease in DG, Similar findings have been repotied by Daniels and Quadra-White'^ and Jadinski and Shklar.'^ No underlying disease was detected in two patients, and therefore their cases were considered idiopathic. Microscopic examination ofthe oral biopsy speci- mens revealed the classic histopathologic changes for MMP, Py and OLP, The two idiopathic cases mani- fested nonspecific histopathologic changes (nonspe- cific inflammatory reaction). The results of the immnnohistochemical tests that were performed on the gingival biopsy specimens of the patients with PV were in all cases positive, showing intercellular deposits of IgG, IgA, and complement at the spindle cell layer ofthe epithelium. Ofthe gingival specimens from patients with MMP, 77% were positive for IgG, while approxittiately 72% showed deposition of IgA and complement in the basement membrane. These findings are reasonable, because PV and MMP are autoimmune diseases in which the antigenic target of autoimmunity is believed to be located between the spindle cells of the epithehum and in the basement membrane, respectively. Similar immunohistochemi- cal findings have been reported by other investi- gators.''"^^ Results were negative in all patients with OLP for IgG and IgA; results were positive in some instances for IgM, Positive staitiing results were also seen under 766 Quintessence International Vciume 27, Number 11/1996 Mariopoulos et al the direct immunofluorescence for ftbrin-fibrinogen in the patients with OLP. It has been proposed that positive staining of IgM and fibrin-ftbrinogen are suggestive of OLP.-' The evaluation of the files of patients with muco- cutaneous diseases demonstrated that desquamative gingival lesions are not rare; they were found in 11.8% ofthe individuals in the present study. However, the prevalence of DG in patients with mucocutaneotjs diseases varies in the literature.'^*----^ Desquamative gingivitis is seen in both sexes but is more prevalent in women.-'' The present results corroborate this assumption. Before the final diagnosis of DG is made, difier- ential diagnosis should be made, especially at the hi sto patho logic level, from plasma cell gingivitis. Tlie prominent histopathologic feature of plasma cell gingivitis is the dense infiltration of lamina propria with plasma cells. Treatment of DG is symptomatic.^^ Systemic admin- istration of prednisolone may be a treatment for DG patients with PV.-'' Systemic or topical corticosteroid treatment, in the form of fluocinonitie, may be effective for DG patients with MMR-" Topical therapy with ttocinonide is also recommended for the alleviation of gingival lesions in patients with OLP.^^ Local irritating factors must always be removed. This thera- peutic measure is especiaUy recommended in patients with DG who exhibit no detectable underlying disease (idiopathic cases). Desquamative gingivitis usually represents a mani- festation of MMP, Py or OLP. Special laboratory techniques are needed to reach the correct diagnosis so that the appropriate therapy is provided. References 1. TomesJ. Tomes G. Dental Surger>',ed 4. London: Chjrchitl. 1894. 2. Prinz H. Chronic diffuse desqiiamative gingivitis. Dent Cosmos 3. Meiiit AH, Chronic desquamatiye gingivitis. J Periodontol 1933; 430-34. 4. Wood NK, Goaz PW. Differential Diagnosis of Oral Lesions, ed 4, St Louis: Mosby. 199t:93-95.97. 5. McCarthy FP, McCarthy PL. Shklar G. Chronic desquamative gingivitis, A reconsideration. Oral Surg Oral Med Oral Pathol t96O;t3:130O-13t3, 6, Shktar G. Meyer t, Lacarian S, Oral tesions in buJtous pemphigoid. Arch Dertnatol t99:99:663-67O. 7. Shklar G. McCarthy PL. Oral lesions of miicoii membrane pemphigoid. A study of 85 eases. Arch Otolaryngot t971i93:354- 364, 8. Qles RD. Chronic desquamative gingivitis, J Periodontol 967i 38:485-490. 9, Shklar G. McCarthy PL. The Oral Manifestations of Systemic Disease. London; Butterworths. 1976:136. 10. Laskaris G, Varettzidis A. Capetanakis J. A ctirucal study of pemphigus; observations on t28 patients. Mater Med Greca 197S;6r627-630. 11. Carranza FA Jr. Giiekman's Clinical PeriodunLuiogy. Philadeiphia; Saunders. t979:155-t92. 12. McCanhy PL. Shktar G. Diseases ofthe Oral Mueosa. Phitadelphia; Lea & Febiger. t980. t3. Nisengard RJ. Neiders M. Desquamative gingivitis. J Periodontol 19S1:52:500-50. t4, Sktavounou A. Laskaris G. Frequency of desquamative gingivitis in skin disease. Oral Surg Orat Med Oral Pathol 1983:56:141-144. 15. Daniels TE, Quadra White C. Direct inimunofluorescence in oral mucosal disease; A diagnostic anaiysis of 30 cases. Orat Surg Oral Med Orai Pathol 1981;5t;38-47, t6. Jadinsfci JJ, Shktar G. Lichen planus of the gingiva. J Periodontol 1976:47:724-733, t7. Williams DM. Vesicutobullous mucocutaneous disease: Pemphigus vulgaris. J Oral Pathol Med 1989;t8:544-553. 18, Bean SF. Cicatricial pemphigoid. Arch Dermatol t974;lt0:552- 555. 19, Peng T. Nisengard RJ. Levine MJ. Gingivai basement membrane antigens in desquamative lesions of the gingiva. Oral Surg Orat Med OralPathut 1986;6t:584-589. 20, Lamey PJ, Bimjje WH, Ranking KV Mucous membrane pemphi- goid. Treatment experience at two institutions. Oral Surg Oral Med Oral Pathol 1992;74:50-53. 21. Baart de al Faille-Kyper EH, Baart de ta Faille H. An immuno- fluorescent study of tichen pianus. Br J Demiatot 1974;90;365-371. 22. Rogers RS, Sheridan PJ, Jordon RE. Desquamative gingivitis: Clinical, histopathotogic and immunologie investigation. Orat Surg Oral Med Oral Pathol l976;42:3l6-327. 23, Laskaris G. Dimitriou N, Angelopoulos A. Immunofluorescent studies in desquamatjve gingivitis. J Oral Pathol 198i;10:39S-407, 24, Ghckman 1, Smulow JB, Chronic desquamative gingivitis: Its nature and treatment, J Penodontol 1964;35:397-4O5. 25. Nisengard RJ, Rogers RS, The treatment of desquamative gingival lesions. J Periodontol 1987:58:167-172. 26. KormanN. Pemphigus. J Am Acad Dermatol 1988;18:1219-1238. 27. Scully C, Mason DK. Therapeutic measures in oral medicine. In: Jones JH. Mason DK. (eds). Oral Manifestations of Systemic Disease. London- Satinders. l9S0:30-542. D Quintessence International Volutne 27, Number 11/1996 767