Review Article

pISSN 2288-9272 eISSN 2383-8493 J Oral Med Pain 2015;40(4):135-139 JOMP http://dx.doi.org/10.14476/jomp.2015.40.4.135 Journal of and Pain

The Correlation between Desquamative Associated-Diseases and Plaque-Induced

Hyun-Dae Lim1,3, Jin-Kyu Kang2,3, You-Mee Lee1,3, Young-Joo Shim2,3

1Department of Oral Medicine, School of , Wonkwang University, Iksan, Korea 2Department of Orofacial Pain and Oral Medicine, Wonkwang University Daejeon Dental Hospital, Daejeon, Korea 3Wonkwang Dental Research Institute, Wonkwang University, Iksan, Korea

Received November 19, 2015 (DG) is a gingival manifestation of systemic mucocutaneous disorders Revised December 1, 2015 such as mucous membrane , oral , and vulgaris. The Accepted December 2, 2015 is very painful, so affects the patient’s ability to do proper practices. This may be a potential risk factor for long-term periodontal health. However, there is some controversy about the relationship between the existence of DG and periodontal status. Although the cor- Correspondence to: Young-Joo Shim relation between DG-associated diseases and periodontal status is not to be certain, early diag- Department of Orofacial Pain and nosis and appropriate treatment including adequate plaque control and removal of local fac- Oral Medicine, Wonkwang University tors is very important for preventing the progression of diseases and destruction of periodontal Daejeon Dental Hospital, 77 Dunsan- tissues. ro, Seo-gu, Daejeon 35233, Korea Tel: +82-42-366-1128 Fax: +82-42-366-1115 E-mail: [email protected] Key Words: Desquamative gingivitis; Lichen planus, oral; Mucous membrane pemphigoid; Periodontal diseases; Plaque This study was supported by research fund from Wonkwang University, 2015.

INTRODUCTION alveolar bone destruction. The present review intends to re- flect on the most recent and relevant data concerning the Desquamative gingivitis (DG), the presence of erythema, correlation between DG-associated mucocutaneous system- desquamation, erosion, and blistering of the marginal and ic disorders and plaque-induced periodontal disease. attached gingiva, is gingival manifestation of several mu- cocutaneous disorders and systemic conditions. The DG le- DESQUAMATIVE GINGIVITIS sions may indirectly increase the long-term risk of plaque- induced periodontal disease via plaque accumulation when The gingival diseases are classified into plaque-induced pain associated with DG hinder proper oral hygiene gingival diseases and non plaque-induced gingival dis- practices. As a result, DG is usually misdiagnosed as plaque- eases in the classification system for periodontal diseases induced periodontal disease and combined with plaque- and conditions.1) Among the non plaque-induced gingi- induced gingivitis or periodontitis. However, there is some val disorder, gingival manifestation of systemic conditions controversy about the relationship between the existence includes mucocutaneous diseases, e.g., oral lichen planus of DG and periodontal status. Little is known of whether or (OLP), mucous membrane pemphigoid, not DG could influence the onset or progression of plaque- (PV), (EM), (LE), induced periodontal disease, or vice versa and there is no drug-induced lesion, and so on. These diseases are immune- evidence that DG per se can cause loss of attachment and mediated and have common clinical features, so-called

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www.journalomp.org 136 J Oral Med Pain Vol. 40 No. 4, December 2015 desquamative gingivitis (DG). DG is not a definitive diag- accumulation of . Consequent plaque accu- nosis but a descriptive term, first introduced by Prinz2) in mulation may be a long-term risk factor for periodontal 1932. Main clinical features are erythema, desquamation, disease. erosion of the gingiva, and blistering of the marginal and We reviewed studies that evaluated the periodontal status attached gingiva. In many cases, gingival lesions represent of mucocutaneous diseases confined to most common cause the onset of the disorder or appear very early during its of DG—mucous membrane pemphigoid, OLP and PV. First course, mainly in mucous membrane pemphigoid, PV, EM, of all, we reviewed studies that evaluated the periodontal and graft-versus-host disease (GVHD).3) And in many case status between affected patients and healthy controls re- of mucous membrane pemphigoid, DG is the only clinical gardless of types and extent of lesions.7-12) The results were feature. not consistent even considering the methodological differ- Mucous membrane pemphigoid, OLP, and PV are the most ences. Some reported the clinical periodontal status were common cause of DG.4) The pathogenesis of DG-associated significantly worse than in the healthy control group.7-9) diseases are cell-mediated (OLP, GVHD, and LE) and auto- Akman et al.7) evaluated the periodontal status of PV pa- -mediated (mucous membrane pemphigoid and tients and compared it with that of healthy controls. The PV). Cell-mediated diseases generally express modifications results showed that the Community Periodontal Index of of epithelial thickness—atrophic-erosive form or hyperkera- Treatment Needs (CPITN) is higher in PV patients. Lóperz- tosis. Autoantibody-mediated diseases generally express Jornet and Camacho-Alonso8) showed that the gingival in- blister formation. Mucous membrane pemphigoid which dex (GI), plaque index (PI), and CPITN is higher in OLP pa- is the most common cause of DG is autoantibody-mediat- tients than healthy controls. ed vesiculobullous lesions that typically involve gingiva. Others were reported there were no significant differences Autoantigens to the hemidesmosomal molecules or compo- between patients and healthy controls.10-12) Ertugrul et al.10) nent of the lamina lucida have been identified and result in compared OLP gingivitis or periodontitis patients with non- subepithelial split.5) OLP is a T cell-mediated responses that OLP gingivitis or periodontitis patients. It demonstrated that triggers apoptosis of oral epithelial keratinocyte via tumor clinical periodontal parameters—PI, GI, probing depth (PD) necrosis factor-alpha (TNF-α). Seven to ten percentage of and (CAL)—were slightly higher in OLP patients have lesions confined to gingiva. PV is auto- the OLP gingivitis or periodontitis patients than in the non- antibody-mediated disease typically expressing acantholy- OLP gingivitis or periodontitis patients, but did not show sis. It represents intraepithelial split because of desmosomal statistically significant. Ramón-Fluixá et al.11) revealed no damage. Involvement of the , including the gin- statistically significant differences between OLP patients giva, is observed in the early phases of PV in up to 70% of and healthy controls in relation to clinical periodontal pa- patients.6) PV initially affects the mouth and eventually af- rameters—PI, simplified index (SCI), and loss of at- fects the cutaneous lesion causing fluid loss, electrolyte im- tachment component of the periodontal disease index (PDI). balance, and septicemia. PV may be life-threatening if un- But in the case of gingival involvement, the PI and SCI are treated. Because DG can be a feature of systemic diseases, significantly higher in DG-positive OLP group than DG- early accurate clinical and histopathological diagnosis is re- negative OLP group. But the PDI was not significantly dif- quired to differentiate these DG-associated disorders, man- ferent between the groups. Furthermore, in the severity of age properly, and prevent the progression of the diseases. symptoms, the more aggressive and extensive presentations of OLP, the higher plaque and calculus deposits were exhib- EFFECTS OF DESQUAMATIVE GINGIVITIS ited. Tricamo et al.12) also showed that the gingival mucous ON PERIODONTAL STATUS membrane pemphigoid patients exhibited higher GI score than a control group, but PI and CAL were not significantly The painful gingival and oral lesions can hinder prop- different. It seems that the patients showed more gingival er oral hygiene practices, and increase the possibility of , but not periodontitis.

www.journalomp.org Hyun-Dae Lim et al. The Correlation between DG and Periodontal Disease 137

Next, there were several studies which compared the matrix in periodontal tissue. The balance between MMPs periodontal status between the DG-positive sites and DG- and MMP inhibitor (tissue inhibitor of metalloproteinases, negative sites in OLP or mucous membrane pemphigoid pa- TIMP) activity is important in the maintenance­ of many bi- tients.13,14) Lo Russo et al.13) have compared with DG-negative ologic processes, such as bone formation, wound healing, sites in the same patient who never treated for DG lesions or angiogenesis, apoptosis, immune response, and hair follicle plaque-induced periodontitis. PD, CAL, full mouth plaque cycles. If the level of MMPs is higher than TIMPs, it will score (FMPS) and full mouth bleeding score (FMBS) were cause the extracellular matrix to degrade uncontrollably, evaluated. They revealed that median PD and CAL, FMPS, which lead to pathologic lesions. Kubota et al.15) demon- and FMBS were not significantly different between the strated that increased MMP expression in inflamed gingival groups. In other study of Lo Russo et al.,14) DG-positive tissue from systemically healthy patients with chronic peri- sites only have higher FMPS compared to DG-negative sites. odontitis. One of the MMPs, MMP-1 is a key regulator of Correlations between the presence of DG lesions and clini- remodeling and exists in high concentra- cal periodontal parameters—CAL and PD—were not signifi- tions in inflamed gingiva. Up-regulation of MMP-1 is effec- cant. And no significant difference was found between DG- tive in the increase of apoptosis of the .16) positive and DG-negative sites as regards the relative per- Another one of the MMPs, MMP-9 may play a key role centage of the investigated species on the total bacterial load. in degradation of basal membrane. Zhou et al.17) reported Taken all together, first, it seems that gingival OLP and that T-cell derived MMP-9 may be involved in the patho- mucous membrane pemphigoid per se may not be able to genesis of OLP. The disrupted basal membrane can no lon- cause or increase attachment loss. We speculate that the im- ger provide a signal to maintain keratinocyte, which may portant factor which has influences on periodontal status is trigger keratinocyte apoptosis.3) Ertugrul et al.10) evaluated host, i.e., whether she or he has the disease or not, and se- the MMP-1, MMP-9, and TIMP-1 levels in the gingival cre- verity and duration of the diseases which can affect the pa- vicular fluid and gingival samples with or without DG sites tient’s oral hygiene practices. (among the enrolled OLP patients, nine patients showed Second, pain is important factor which can affect the pa- DG) between OLP gingivitis or periodontitis patients and tient’s oral hygiene practices and quality of life. But, it was non-OLP gingivitis or periodontitis. They reported that the not stated whether the included patients as study group had mean level of MMP-1 and MMP-9 is higher and the MMP subjective pain or not in the aforementioned references. inhibitor (TIMP)-1 is lower in OLP gingivitis or periodontitis Some patients may have severe pain, others may not. The patient than non-OLP gingivitis or periodontitis, although patients with painful symptoms may have impaired oral the clinical periodontal parameters—PI, GI, PD, and CAL— hygiene and result in plaque accumulation and increase did not show differences. This suggests that OLP may affect prevalence of gingivitis. This will possibly lead to periodon- periodontal status by change of enzyme levels and more tal disease and CAL in the long-term aspects, but there was breakdown of periodontal tissue could be occurring in OLP no study that demonstrated this. Therefore, it needs to be patients in the long-term course of diseases. Therefore, early further investigated of 1) correlations between the presence diagnosis and appropriate treatment of OLP is very impor- or absence of DG-associated pain and clinical periodontal tant for preventing the progression of OLP and destruction parameters; and 2) long-term follow-up evaluation under of periodontal tissues. the control of variables such as management protocol and . EFFECTS OF PERIODONTAL STATUS Meanwhile, Ertugrul et al.10) demonstrated the effect of ON DESQUAMATIVE GINGIVITIS OLP on periodontal tissue by evaluation of matrix metal- loproteinase (MMP) level. MMP, produced by fibroblast, is The dental plaque can act as an irritating factor, worsen- a zinc-containing proteolytic enzyme that responsible for ing the DG lesions and contributing to prolong the presence degradation of , a component of the extracellular of OLP lesions. Damaged oral mucosa in severe periodontal

www.journalomp.org 138 J Oral Med Pain Vol. 40 No. 4, December 2015 disease might enhance presenting antigenic determinants to manifestation of systemic conditions and it may be an ear- stimulate the autoimmune response. Periodontitis-induced ly sign of systemic conditions. Dentists should be aware of inflammatory mediators and acute-phase proteins may play signs of DG, the typical clinical features of gingival lesions. a major role in the development of a variety systemic dis- But it is almost impossible to differentiate between the dis- eases and conditions such as Behcet disease, mel- eases and disorders causing DG based only on the clinical litus and .18-20) But there was no study which features. Histopathological examination including direct concludes definitely that periodontal disease is a significant immunofluorescence testing is essential to found a defini- risk factor for the development of DG-associated diseases tive diagnosis. The painful gingival and oral lesions make such as OLP, mucous membrane pemphigoid, and PV. the patients hard to do proper oral hygiene practices and Periodontal tissue status may affect the progression of increase the possibility of accumulation of dental plaque. OLP. Salgado et al.21) evaluated the isolated effect of plaque Poor oral hygiene may lead to complications in the peri- control on the improvement of painful symptoms of OLP odontal health and periodontal tissue status may affect the with gingival involvement. It was demonstrated that plaque progression of diseases. It is very important to achieve ad- control was effective in improving the clinical features and equate plaque control and remove other local factors to painful symptoms of OLP with gingival involvement. Other maintain the gingival health and improve painful symptoms studies also reported the effect of plaque control on the and severity of DG. Previously mentioned, OLP may change improvement of OLP gingival lesions.22-24) Plaque control the enzyme levels such as MMP-1 and MMP-9 which may should be an important procedure in the management of play a role in breakdown of periodontal tissue. Therefore, OLP gingival lesion. early diagnosis and appropriate treatment including proper However, periodontal treatment failed to completely re- plaque control should be valued above everything else for solve the DG process, demonstrating that dental plaque is preventing the progression of diseases and destruction of not the prevalent etiologic factor. As for OLP, the etiology periodontal tissues. And patients must be informed about of OLP is exactly unknown to date, but it is thought that the potential risk of periodontal diseases and should be en- intrinsic or extrinsic that trigger an inflamma- couraged to maintain long-term periodontal follow-up to tory process leading to accumulation of T lymphocytes in prevent disease progression. the superficial lamina propria, liquefaction degeneration, and keratinocyte apoptosis of in the basal layer.25) In fact, CONCLUSION the pathogenesis of plaque-induced periodontal disease in- volves a local inflammatory reaction and the activation From this review, we are not able to conclude the correla- of the stimulated by bacterial factors.26) tion between DG-associated diseases and periodontal status Immune-mediated inflammatory mechanisms are also criti- definitely because it is not certain whether the differences cal for the pathogenesis of OLP.4) Both mechanisms involves of clinical parameters between patients and healthy controls common molecules like MMP-1, MMP-9, and TIMP-110) and are caused by direct effect of the diseases itself or indirect like -1 and TNF-α.27,28) Although the effect of plaque accumulation. Although the correlation be- MMP-1, MMP-9, and TIMP-1 may be involved in patho- tween DG-associated diseases and periodontal status is not genesis of OLP, the OLP is not definitely triggering by this to be certain, early diagnosis and appropriate treatment in- mechanism. Further studies are required to understand the cluding adequate plaque control and removal local factors interaction between periodontal disease and OLP, mucous is very important for preventing the progression of diseases membrane pemphigoid, and PV. and destruction of periodontal tissues.

CLINICAL CONSIDERATIONS CONFLICT OF INTEREST

Non-plaque induced gingival disorders is a gingival No potential conflict of interest relevant to this article

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