Periodontics

Desquamative : A clinical, histopathoiogic, and immunologie study

A- K.. Markopoulos*/D. Antoniades*/P. Papanayotou*/G. Trigonidis*

Abstract 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 vulgaris. mucous membrane , or oral . 49 (¡1.8%) exhibited gingival in the form of desquamative gingivitis. Desquamative gingivitis was most prevalent in the patients with mucous membrane pemphigoid (41.6%) followed by those with (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 and is edematous. Tbe is quite friable and can be removed easily from the underlying connective Desquamative gingivitis, in most cases, represents a tissue, leaving a red surface that bleeds readily after manifestation of systemic diseases. Because it has no minimal trauma. Other gingival sites, such as palatal specific clinical pathognomonic features, laboratory and lingual surfaces, are rarely involved,"* aids, such as histopathoiogic and immunohistochem- The etiology of DG remains obscure. Early investi- ical examination, should be used to unmask the gators believed that there was a single cause. McCarthy underlying disease so that the appropriate treatment et al^ were among the first who proposed that DG is a can be provided. 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, Introduction However, in recent years, it has been shown that the great majority (approximateiy 75%) of cases of DG are Desquamative gingivitis (DG) is characterized by manifestations of mucocutaneous diseases, primarily erythematous and desquamative lesions of the free and mucous membrane pemphigoid (MMP), oral lichen attached gingiva. The condition was first described by planus (OLP), and pemphigus vulgaris (PV).'''^"''' Tomes and Tomes' in 1894 and was further defined In the present investigation, the prevalence of DG several years later by Prinz^ and Merrit,^ who pro- was retrospectively studied in a large group of patients posed the term chronic diffuse desquamative gingivitis. with these mucocutaneous diseases. Furthermore the UsuaUy the changes are confined to the labial clinical, histopathoiogic, and immunologie features in gingival mueosa, which varies from bright to dark red each disease group were analyzed.

' Department of and Pathology, Aristotle University of Thessaloniki, School of , Thessaloniki, Greece. Method and materials Reprint requests: Dr A. K. Markopoulos, Department of Oral Medicine The records of all patients with PV, MMP, and OLP and Pathology, Aristotle University ofThessaloniki, School of Dentistry, Thessaloniki 54006, Greece. who were seen during the period from Januari' 1983 to

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Fig 1 Desquamalive gingivitis in a palien! with pemphigus. Fig 2 Desquamalive gingivitis in a patient with mucous Areas oí erosion are seen. membrane pemphigoid.

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 Fig 3 Desquamalive gingivitis in a patient wiih oral lichen for the demonstration of fibrin-fibrinogen. The major planus. 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 January 1993 in the Oral Medicine Clinic were immunohistochemical staining of IgG and IgA for retrieved from the files ofthe Oral Pathology Depart- OLP; and deposition of IgM and fibrin-fibrinogen for ment. A total of 414 cases were studied. Each file was OLP. examined carefully for documentation of DG, The final diagnosis was established on the basis of clinical, histopathologic, and immunohistochemical criteria. Results From the clinical point of view, only t>pical patients with severe lesions were included in the study. Typical An interim clinical diagnosis ofthe underlying disease patients were considered to be those presenting with in DG patients was based on the presence of erythema- bright to dark red, edematous, and friable gingival tous and friable gingival mucosa or on the occasional mucosa, Tlie patients were subjected to careflii phy- presence of accompanying clinical matufestations of sical examination, including slit-lamp examination, each disease in other sites of the ; the laryngoscopy, and examination of the ear canal, presence of vesiculoerosive lesions and Nikolsky's anogenital area, and skin. sign, which are indicative of PV and MMP, or the The histologie slides were stained with hematoxylin presence of laceiike white lesions combined with and eosin. The major criteria for the histopathologic erosions or atrophie mucosa, which are suggestive of diagnosis of each mucocutaneous disease category erosive or atrophie OLP.

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Table ! Prevalence of desquamative gingivitis (DG) in 414 patients with mucosal disease

No. of patients Patients Mean age of with mucosal Underlying No. of witb DG Male Female patients with lesions in other disease patients No. (%) No, (%) No. (%) DG oral sites Pemphigus vulgaris 33 3 ( 9.1) 1 (33.3) 2 (66.7) 37.7 y 1 Mucous membrane pemphigoid 53 22 ( 41.6) 4 (18.2) 18 (81,8) 55,1 y 8 Oral lichen plan us 326 22 { 6.8) 6 (27.3) 16 (72,7) 50,0 y 12 Idiopathic 2 2 (100,0) 1 (50,0) 1 (50.0) 45.4 y 0

Total 414 49 ( 11.8) 11 (23.4) 36 (76.6) 47.1 y 21

Tabie 2 Immunohistochemical findings in biopsy specimens taken from patients with desquamative gingivitis

Streptavidin-biotin immunoperoxidase staining Direct immunoñuorescence Positive Neinative for fibrinogen Und e dying No. of disease patients IgG IgA IgM C3 IgG IgA IgM C3 Positive Negative Pemphigus vulgaris 3 3 3 1 3 2 Mucous membrane pemphigoid 22 17 16 4 16 5 6 18 6 Oral lichen planus 22 10 22 22 12 22 19 3 Idiopathic 2 2 2 2 2 'Nol performed.

The DG lesions were confined to the labial gingiva, MMP were found positive for IgG and IgA to a lesser which appeared bright to dark red and edematous extent (17 of 22 patients). In contrast all patients with (Figs 1 to 3). Accompanying lesions were found OLP were negative for IgG and IgA. and some were mainly in patients with OLP (12 of 22) (Table 1). posirive for IgM and fibrin-fibrinogen. The idiopathic Thorough physical examination ofthe patients did not cases were negative in all the immunohistochemical reveal any extraora! manifestations. Pain was a pre- stainings that were performed. The immunohistochem- dominant symptom in many patients, while the pre- ical findings are illustrated in Figs 4 to 6. sence of local factors, such as plaque or dental Table 1 reveals that the majority of parients with DG , was evident in the majority of patients in each have MMP (41.6%). while 9.1% and 6,8% have PVand group. OLP, respectively. The great majority ofthe patients in On the basis of histopathologic and immunohisto- all disease groups were female. chemical examination the 49 DG patients were divided into four categories; Py MMP. OLP, and Discussion idiopathic cases. Histopathologicaily. 47 patients ful- filled the classic criteria for PV, MMP, or OLP (Table The clinical appearance of DG is not pathognomonic. 2). Two parients did not manifest specific microscopi- Therefore, supplementary procedures, such as histo- cally pathognomonic features, and therefore their pathologic examination and immunohistochemical cases were considered idiopathic. All the patients with tests of gingival biopsy specimens, are necessary for a PV were positive for IgG and IgA. while parients with definitive diagnosis. In the present study, one of the

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Fig 4 Desquamative gingivitis m pemphigus. Intercellular Fig 5 Desquamative gingivifis in mucous membrane pem- deposition ol igG is apparent (Streptavidin-biotin staining, phigoid. The linear basemenf membrane exhibifs deposits originai magnification x480.1 of IgG (Sfreptavidin-biotin sfaining; originai magnificafion

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 Fig 6 Desquamative gingivitis in orai lichen pianus. Direct immunofluorescence discloses the presence of fibrinogen MMP, Py and OLP, The two idiopathic cases mani- along the basemenf membrane zone. (Original magnifica- fested nonspecific histopathologic changes (nonspe- fion x120.) 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 few clinical characteristics beyond the erythematous intercellular deposits of IgG, IgA, and complement at atid friable gingiva was the occasional presence of the spindle cell layer ofthe epithelium. Ofthe gingival accompanying lesions in other sites ofthe oral mucosa. specimens from patients with MMP, 77% were positive These lesions were more frequently observed in for IgG, while approxittiately 72% showed deposition patients with OLP. Twelve of 22 patients manifested of IgA and complement in the basement membrane. lacelike white formations combined with erosive or These findings are reasonable, because PV and MMP atrophie lesions in other sites of their oral mucosa. are autoimmune diseases in which the antigenic target The highest prevalence of DG (41.6%) was ob- of autoimmunity is believed to be located between the served in patients with MMP. Eight of 22 of these spindle cells of the epithehum and in the basement patients had vesiculoerosive lesions in other sites of membrane, respectively. Similar immunohistochemi- the oral mucosa. cal findings have been reported by other investi- A lower prevalence of DG (9.1%) was observed in gators.''"^^ patients with PV One ofthe three DG patients in this Results were negative in all patients with OLP for group had vesiculoerosive lesions in other sites of his IgG and IgA; results were positive in some instances oral mucosa. Nikolsky's sign (ie, the detachment of for IgM, Positive staitiing results were also seen under

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the direct immunofluorescence for ftbrin-fibrinogen in 6, Shktar G. Meyer t, Lacarian S, Oral tesions in buJtous pemphigoid. the patients with OLP. It has been proposed that Arch Dertnatol t9ö9:99:663-67O. positive staining of IgM and fibrin-ftbrinogen are 7. Shklar G. McCarthy PL. Oral lesions of miicoiiä membrane pemphigoid. A study of 85 eases. Arch Otolaryngot t971i93:354- suggestive of OLP.-' 364, The evaluation of the files of patients with muco- 8. Qles RD. Chronic desquamative gingivitis, J Periodontol Í967i cutaneous diseases demonstrated that desquamative 38:485-490. gingival lesions are not rare; they were found in 11.8% 9, Shklar G. McCarthy PL. The Oral Manifestations of Systemic ofthe individuals in the present study. However, the Disease. London; Butterworths. 1976:136. prevalence of DG in patients with mucocutaneotjs 10. Laskaris G, Varettzidis A. Capetanakis J. A ctirucal study of diseases varies in the literature.'^•*----^ pemphigus; observations on t28 patients. Mater Med Greca Desquamative gingivitis is seen in both sexes but is 197S;6r627-630. more prevalent in women.-'' The present results 11. Carranza FA Jr. Giiekman's Clinical PeriodunLuiogy. Philadeiphia; corroborate this assumption. Saunders. t979:155-t92. Before the final diagnosis of DG is made, difier- 12. McCanhy PL. Shktar G. Diseases ofthe Oral Mueosa. Phitadelphia; ential diagnosis should be made, especially at the Lea & Febiger. t980. hi sto patho logic level, from . Tlie t3. Nisengard RJ. Neiders M. Desquamative gingivitis. J Periodontol 19S1:52:500-5¡0. prominent histopathologic feature of plasma cell t4, Sktavounou A. Laskaris G. Frequency of desquamative gingivitis in gingivitis is the dense infiltration of lamina propria skin disease. Oral Surg Orat Med Oral Pathol 1983:56:141-144. with plasma cells. 15. Daniels TE, Quadra White C. Direct inimunofluorescence in oral Treatment of DG is symptomatic.^^ Systemic admin- mucosal disease; A diagnostic anaiysis of Í30 cases. Orat Surg Oral istration of prednisolone may be a treatment for DG Med Orai Pathol 1981;5t;38-47, patients with PV.-'' Systemic or topical corticosteroid t6. Jadinsfci JJ, Shktar G. Lichen planus of the gingiva. J Periodontol treatment, in the form of fluocinonitie, may be effective 1976:47:724-733, for DG patients with MMR-" Topical therapy with t7. Williams DM. Vesicutobullous mucocutaneous disease: Pemphigus ñttocinonide is also recommended for the alleviation vulgaris. J Oral Pathol Med 1989;t8:544-553. of gingival lesions in patients with OLP.^^ Local 18, Bean SF. Cicatricial pemphigoid. Arch Dermatol t974;lt0:552- irritating factors must always be removed. This thera- 555. 19, Peng T. Nisengard RJ. Levine MJ. Gingivai basement membrane peutic measure is especiaUy recommended in patients antigens in desquamative lesions of the gingiva. Oral Surg Orat Med with DG who exhibit no detectable underlying disease OralPathut 1986;6t:584-589. (idiopathic cases). 20, Lamey PJ, Bimjje WH, Ranking KV Mucous membrane pemphi- Desquamative gingivitis usually represents a mani- goid. Treatment experience at two institutions. Oral Surg Oral Med festation of MMP, Py or OLP. Special laboratory Oral Pathol 1992;74:50-53. techniques are needed to reach the correct diagnosis so 21. Baart de al Faille-Kyper EH, Baart de ta Faille H. An immuno- that the appropriate therapy is provided. 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. References 23, Laskaris G. Dimitriou N, Angelopoulos A. Immunofluorescent 1. TomesJ. Tomes G. Dental Surger>',ed 4. London: Chjrchitl. 1894. studies in desquamatjve gingivitis. J Oral Pathol 198i;10:39S-407, 2. Prinz H. Chronic diffuse desqiiamative gingivitis. Dent Cosmos 24, Ghckman 1, Smulow JB, Chronic desquamative gingivitis: Its nature and treatment, J Penodontol 1964;35:397-4O5. 3. Meiiit AH, Chronic desquamatiye gingivitis. J Periodontol 1933; 25. Nisengard RJ, Rogers RS, The treatment of desquamative gingival 430-34. lesions. J Periodontol 1987:58:167-172. 4. Wood NK, Goaz PW. Differential Diagnosis of Oral Lesions, ed 4, St 26. KormanN. Pemphigus. J Am Acad Dermatol 1988;18:1219-1238. Louis: Mosby. 199t:93-95.97. 5. McCarthy FP, McCarthy PL. Shklar G. Chronic desquamative 27. Scully C, Mason DK. Therapeutic measures in oral medicine. In: gingivitis, A reconsideration. Oral Surg Oral Med Oral Pathol Jones JH. Mason DK. (eds). Oral Manifestations of Systemic t96O;t3:130O-13t3, Disease. London- Satinders. l9S0:í30-542. D

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