Periodontics

Desquamative gingivitis: A clinical, histopathoiogic, andimmunologie studyA- K.. Markopoulos*/D. Antoniades*/P. Papanayotou*/G. Trigonidis*

Abstract Desquamative gingivitis is believed to be a clinical sign of certain mucocutaneousdiseases rather than a distinct pathologic entity. The prevalence of desquamativegingivitis was studied in a group of patients with the most common mucocutaneousdiseases. Of 414 patients with pemphigus vulgaris. mucous membranepemphigoid, or oral lichen planus. 49 (1.8%) exhibited gingival lesions in theform of desquamative gingivitis. Desquamative gingivitis was most prevalent in thepatients with mucous membrane pemphigoid (41.6%) followed by those withpemphigus vulgaris (9.1%). Other elinieal characteristics, as well as histo-pathoiogic and imtnunohistochemical findings, that aid in early diagnosis arepresented. (Quintessence Int 996:27:763-767.')

Clinical relevance

Desquamative gingivitis, in most cases, represents amanifestation of systemic diseases. Because it has nospecific clinical pathognomonic features, laboratoryaids, such as histopathoiogic and immunohistochem-ical examination, should be used to unmask theunderlying disease so that the appropriate treatmentcan be provided.

Introduction

Desquamative gingivitis (DG) is characterized byerythematous and desquamative lesions of the free andattached gingiva. The condition was first described byTomes and Tomes' in 1894 and was further definedseveral years later by Prinz^ and Merrit,^ who pro-posed the term chronic diffuse desquamative gingivitis.

UsuaUy the changes are confined to the labialgingival mueosa, which varies from bright to dark red

and is edematous. Tbe epithelium is quite friable andcan be removed easily from the underlying connectivetissue, leaving a red surface that bleeds readily afterminimal trauma. Other gingival sites, such as palataland lingual surfaces, are rarely involved,"*

The etiology of DG remains obscure. Early investi-gators believed that there was a single cause. McCarthyet al^ were among the first who proposed that DG is anonspecific reaction pattern that can be associatedwith any one of several diseases or conditions. Thisgroup suggested that dermatologie diseases, hormonalfactors, aging, metabolic disturbances, irdtationalfactors, and chronic infections could cause DG,However, in recent years, it has been shown that thegreat majority (approximateiy 75%) of cases of DG aremanifestations of mucocutaneous diseases, primarilymucous membrane pemphigoid (MMP), oral lichenplanus (OLP), and pemphigus vulgaris (PV).'''^"'''

In the present investigation, the prevalence of DGwas retrospectively studied in a large group of patientswith these mucocutaneous diseases. Furthermore theclinical, histopathoiogic, and immunologie features ineach disease group were analyzed.

' Department of Oral Medicine and Pathology, Aristotle University ofThessaloniki, School of Dentistry, Thessaloniki, Greece.

Reprint requests: Dr A. K. Markopoulos, Department of Oral Medicineand Pathology, Aristotle University ofThessaloniki, School of Dentistry,Thessaloniki 54006, Greece.

Method and materialsThe records of all patients with PV, MMP, and OLPwho 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 mucousmembrane pemphigoid.

Fig 3 Desquamalive gingivitis in a patient wiih oral lichenplanus.

January 1993 in the Oral Medicine Clinic wereretrieved from the files ofthe Oral Pathology Depart-ment. A total of 414 cases were studied. Each file wasexamined carefully for documentation of DG, Thefinal diagnosis was established on the basis of clinical,histopathologic, and immunohistochemical criteria.

From the clinical point of view, only t>pical patientswith severe lesions were included in the study. Typicalpatients were considered to be those presenting withbright to dark red, edematous, and friable gingivalmucosa, 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 hematoxylinand eosin. The major criteria for the histopathologicdiagnosis 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 theepithelium with bandiike lymphocytic infiltration ofthe upper lamina propria for OLP.

The immunohistochemical slides had been stainedwith 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 (ImmunostainDiagnostic Products, Lianbaris), Direct immuno-fluorescence had also been performed on fresh tissuesfor the demonstration of fibrin-fibrinogen. The majorimmunologie 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 thelinear basement membrane for MMP; nonspecificimmunohistochemical staining of IgG and IgA forOLP; and deposition of IgM and fibrin-fibrinogen forOLP.

ResultsAn interim clinical diagnosis ofthe underlying diseasein DG patients was based on the presence of erythema-tous and friable gingival mucosa or on the occasionalpresence of accompanying clinical matufestations ofeach disease in other sites of the oral mucosa; thepresence of vesiculoerosive lesions and Nikolsky'ssign, which are indicative of PV and MMP, or thepresence of laceiike white lesions combined witherosions or atrophie mucosa, which are suggestive oferosive 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

Underlyingdisease

Pemphigus vulgarisMucous membranepemphigoid

Oral lichenplan us

Idiopathic

Total

No. ofpatients

33

53

3262

414

Patientswitb DG

No.

3

22

222

49

(%)( 9.1)

( 41.6)

{ 6.8)(100,0)

( 11.8)

MaleNo,

1

4

61

11

(%)(33.3)

(18.2)

(27.3)(50,0)

(23.4)

FemaleNo.

2

18

161

36

(%)(66.7)

(81,8)

(72,7)(50.0)

(76.6)

Mean age ofpatients with

DG

37.7 y

55,1 y

50,0 y45.4 y

47.1 y

No. of patientswith mucosal

lesions in otheroral sites

1

8

120

21

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

Und e dyingdisease

Pemphigus vulgarisMucous membranepemphigoid

Oral lichenplanus

Idiopathic

'Nol performed.

No. ofpatients

3

22

222

Streptavidin-biotin immunoperoxidasestaining

Positive

IgG IgA

3 3

17 16

IgM

1

4

10

C3

3

16

IgG

5

222

Nei

IgA

6

222

native

IgM

2

18

122

C3

6

222

Direct immunouorescencefor 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 foundmainly in patients with OLP (12 of 22) (Table 1).Thorough physical examination ofthe patients did notreveal any extraora! manifestations. Pain was a pre-dominant symptom in many patients, while the pre-sence of local factors, such as plaque or dentalcalculus, was evident in the majority of patients in eachgroup.

On the basis of histopathologic and immunohisto-chemical examination the 49 D G patients weredivided into four categories; P y MMP. OLP, andidiopathic cases. Histopathologicaily. 47 patients ful-filled the classic criteria for PV, MMP, or OLP (Table2). Two parients did not manifest specific microscopi-cally pathognomonic features, and therefore theircases were considered idiopathic. All the patients withPV were positive for IgG and IgA. while parients with

MMP were found positive for IgG and IgA to a lesserextent (17 of 22 patients). In contrast all patients withOLP were negative for IgG and IgA. and some wereposirive for IgM and fibrin-fibrinogen. The idiopathiccases were negative in all the immunohistochemicalstainings that were performed. The immunohistochem-ical findings are illustrated in Figs 4 to 6.

Table 1 reveals that the majority of parients with D Ghave MMP (41.6%). while 9.1% and 6,8% have PVandOLP, respectively. The great majority ofthe patients inall disease groups were female.

Discussion

The clinical appearance of DG is not pathognomonic.Therefore, supplementary procedures, such as histo-pathologic examination and immunohistochemicaltests of gingival biopsy specimens, are necessary for adefinitive 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. Intercellulardeposition 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 depositsof IgG (Sfreptavidin-biotin sfaining; originai magnificafion

Fig 6 Desquamative gingivitis in orai lichen pianus. Directimmunofluorescence discloses the presence of fibrinogenalong the basemenf membrane zone. (Original magnifica-fion x120.)

few clinical characteristics beyond the erythematousatid friable gingiva was the occasional presence ofaccompanying lesions in other sites ofthe oral mucosa.These lesions were more frequently observed inpatients with OLP. Twelve of 22 patients manifestedlacelike white formations combined with erosive oratrophie 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 thesepatients had vesiculoerosive lesions in other sites ofthe oral mucosa.

A lower prevalence of DG (9.1%) was observed inpatients with PV One ofthe three DG patients in thisgroup had vesiculoerosive lesions in other sites of hisoral mucosa. Nikolsky's sign (ie, the detachment of

epithelium after mild rubbing with a cotton tip) waspositive in these lesions.

The lowest prevalence of DG( 6.8%) was counted inthe OLP group. Erosive or atrophie lesions accom-panied the gingivai desquamation in 12 of 22 patients,suggesting that erosive and atrophie forms are the mostcommon forms of OLP to be the underlying disease inDG, Similar findings have been repotied by Danielsand 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 forMMP, Py and OLP, The two idiopathic cases mani-fested nonspecific histopathologic changes (nonspe-cific inflammatory reaction).

The results of the immnnohistochemical tests thatwere performed on the gingival biopsy specimens ofthe patients with PV were in all cases positive, showingintercellular deposits of IgG, IgA, and complement atthe spindle cell layer ofthe epithelium. Ofthe gingivalspecimens from patients with MMP, 77% were positivefor IgG, while approxittiately 72% showed depositionof IgA and complement in the basement membrane.These findings are reasonable, because PV and MMPare autoimmune diseases in which the antigenic targetof autoimmunity is believed to be located between thespindle cells of the epithehum and in the basementmembrane, respectively. Similar immunohistochemi-cal findings have been reported by other investi-gators.''"^^

Results were negative in all patients with OLP forIgG and IgA; results were positive in some instancesfor 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 inthe patients with OLP. It has been proposed thatpositive staining of IgM and fibrin-ftbrinogen aresuggestive of OLP.-'

The evaluation of the files of patients with muco-cutaneous diseases demonstrated that desquamativegingival lesions are not rare; they were found in 11.8%ofthe individuals in the present study. However, theprevalence of DG in patients with mucocutaneotjsdiseases varies in the literature.'^ *----^

Desquamative gingivitis is seen in both sexes but ismore prevalent in women.-'' The present resultscorroborate this assumption.

Before the final diagnosis of DG is made, difier-ential diagnosis should be made, especially at thehi sto patho logic level, from plasma cell gingivitis. Tlieprominent histopathologic feature of plasma cellgingivitis is the dense infiltration of lamina propriawith plasma cells.

Treatment of DG is symptomatic.^^ Systemic admin-istration of prednisolone may be a treatment for DGpatients with PV.-'' Systemic or topical corticosteroidtreatment, in the form of fluocinonitie, may be effectivefor DG patients with MMR-" Topical therapy withttocinonide is also recommended for the alleviationof gingival lesions in patients with OLP.^ ^ Localirritating factors must always be removed. This thera-peutic measure is especiaUy recommended in patientswith DG who exhibit no detectable underlying disease(idiopathic cases).

Desquamative gingivitis usually represents a mani-festation of MMP, Py or OLP. Special laboratorytechniques are needed to reach the correct diagnosis sothat the appropriate therapy is provided.

References1. 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, StLouis: Mosby. 199t:93-95.97.

5. McCarthy FP, McCarthy PL. Shklar G. Chronic desquamativegingivitis, A reconsideration. Oral Surg Oral Med Oral Patholt96O;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 membranepemphigoid. A study of 85 eases. Arch Otolaryngot t971i93:354-364,

8. Qles RD. Chronic desquamative gingivitis, J Periodontol 967i38:485-490.

9, Shklar G. McCarthy PL. The Oral Manifestations of SystemicDisease. London; Butterworths. 1976:136.

10. Laskaris G, Varettzidis A. Capetanakis J. A ctirucal study ofpemphigus; observations on t28 patients. Mater Med Greca197S;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 Periodontol19S1:52:500-50.

t4, Sktavounou A. Laskaris G. Frequency of desquamative gingivitis inskin disease. Oral Surg Orat Med Oral Pathol 1983:56:141-144.

15. Daniels TE, Quadra White C. Direct inimunofluorescence in oralmucosal disease; A diagnostic anaiysis of 30 cases. Orat Surg OralMed Orai Pathol 1981;5t;38-47,

t6. Jadinsfci JJ, Shktar G. Lichen planus of the gingiva. J Periodontol1976:47:724-733,

t7. Williams DM. Vesicutobullous mucocutaneous disease: Pemphigusvulgaris. 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 membraneantigens in desquamative lesions of the gingiva. Oral Surg Orat MedOralPathut 1986;6t:584-589.

20, Lamey PJ, Bimjje WH, Ranking KV Mucous membrane pemphi-goid. Treatment experience at two institutions. Oral Surg Oral MedOral 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 SurgOral Med Oral Pathol l976;42:3l6-327.

23, Laskaris G. Dimitriou N, Angelopoulos A. Immunofluorescentstudies in desquamatjve gingivitis. J Oral Pathol 198i;10:39S-407,

24, Ghckman 1, Smulow JB, Chronic desquamative gingivitis: Its natureand treatment, J Penodontol 1964;35:397-4O5.

25. Nisengard RJ, Rogers RS, The treatment of desquamative gingivallesions. 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 SystemicDisease. London- Satinders. l9S0:30-542. D

Quintessence International Volutne 27, Number 11/1996 767