University of Pennsylvania ScholarlyCommons

Departmental Papers (Dental) Penn Dental Medicine

2003

Desquamative Gingivitis: Early Presenting Symptom of Mucocutaneous Disease

Eric T. Stoopler University of Pennsylvania, [email protected]

Thomas P. Sollecito University of Pennsylvania, [email protected]

Scott S. DeRossi University of Pennsylvania

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Recommended Citation Stoopler, E. T., Sollecito, T. P., & DeRossi, S. S. (2003). Desquamative Gingivitis: Early Presenting Symptom of Mucocutaneous Disease. Quintessence International, 34 (8), 582-586. Retrieved from https://repository.upenn.edu/dental_papers/40

This paper is posted at ScholarlyCommons. https://repository.upenn.edu/dental_papers/40 For more information, please contact [email protected]. Desquamative Gingivitis: Early Presenting Symptom of Mucocutaneous Disease

Abstract Desquamation of the gingiva is a sign that may be encountered in clinical practice. Various diseases can affect the gingival tissues. Mild desquamation that is localized may be associated with mechanical irritation or induced by trauma. Moderate to severe generalized desquamation associated with ulceration and erythema may be indicative of a more serious systemic condition. Although often overlooked, mucocutaneous diseases frequently present with gingival desquamation as an early presenting symptom. The most common mucocutaneous diseases that affect the oral cavity are lichen planus, pemphigus, and mucous membrane pemphigoid. This article reviews the etiology, signs and symptoms, and therapies for these disorders. Increased knowledge of mucocutaneous diseases can help the clinician recognize these disorders and enable the patient to receive appropriate therapy.

Keywords desquamative gingivitis, erosive lichen planus, mucous membrane pemphigoid, pemphigus vulgaris, reticular lichen planus

Disciplines Dental Public Health and Education | Dentistry | Oral Biology and Oral Pathology | Pathological Conditions, Signs and Symptoms

This journal article is available at ScholarlyCommons: https://repository.upenn.edu/dental_papers/40 Desquamative gingivitis: Early presenting symptom of mucocutaneous disease

Eric T. Stoopler, DMD'fThomas P. Soll ecito, DMD2/Scott S. DeRossi, DMD'

Desquamation of the gingiva is a sign that may be encountered in clinical practice. Various diseases can affect the gingival tissues. Mild desquamation th at is localized may be associated with mechanical irritation or induced by trauma. Moderate to severe generalized desquamation associated with ulceration and ery­ thema may be indicative of a more serious systemic condition. Although chen overlooked, mucocutaneous diseases frequently present with gingival desquamation as an early presenting symptom. The most com­ mon mucocutaneous diseases that affect the oral cavity are lichen planus, pemphigus, and mucous mem­ brane pemphigoid. This article reviews the etiology, signs and symptoms, and therapies for these disor­ ders. Increased knowledge of mucocutaneous diseases can help the clin ician recognize these disorders and enable the patient to receive appropriate therapy. (Quintessence lnt 2003;34:582-586)

Key words: desquamative gingivitis, erosive lichen planus, mucous membrane pemphigoid, pemphigus vulgaris, reticular lichen planus

ingival tissue can be differentiated based on its may be attributed to mechanical abrasion or irritation. Ganatomic position. The free gingiva comprises the Aggressive toothbrushing or parafunctional habits may gingival tissue at the vestibular and lingual/palatal as­ cause these localized forms of gingival desquamation. pects of the teeth and in health, is coral pink and has Various oral hygiene products may also cause a mild a dull surface and firm consistency.' The attached gin­ superficial peeling of the gingiva. Toothpaste hyper­ giva extends apically from the free gingiva to the sensitivity, especially to tartar-control products, has mucogingival junction, where it becomes contiguous been reported as an etiology of desquamative gingivi­ with the darker red alveolar mucosa. The alveolar mu­ tis.2 The patient should be educated on proper tooth­ cosa is loosely bound to the underlying bone and is brushing techniques and encouraged to discontinue relatively mobile. The attached gi ngiva is firm ly adher­ parafunctional habits if these are the suspected etiolo­ ent to the underlying alveolar bone and in health, is gies. More severe desquamation may be generalized coral pink and often shows a fine, surface stippling, and accompanied by intense erythema and ulcerations giving it the appearance of an orange peel. ' on the free and attached gingiva, as well as the alveo­ Desquamation or peeling of the epithelial tissue lar mucosa. When local factors cannot be attributed to usually occurs mainly on the free and attached gin­ the etiology of the desquamation, systemic conditions giva. Mild cases that are localized and display minimal must be considered. Three common mucocutaneous loss of tissue with mild erythema and no ulceration diseases that can present with initial symptoms of desquamative gingivitis (peeling of the gi ngival tissue usually accompanied by erythema, ulceration, and pain) are lichen planus, pemphigus, and mucous mem­ 1Assistant Professor, Department of Oral Medtcme, University of brane pemphigoid. These conditions are immune me­ Pennsytvama School of Dental Medic ine, Phtladelphta, Pennsylvania. diated and are managed via topical and/or systemic ZAssociate Professor, Department of Oral Medtcine, University of medications. Knowledge of the etiology, signs and Pennsytvanta School of Dental Med!Ctne, Phtladelptua, Pennsytvama. symptoms, and therapies for these diseases will enable Reprint requests: Dr Enc T. Stoopler. Department of Oral Medicme. umverstty ol Pennsylvanta School of Dental Medte•ne. 240 South 401h the clinician to more effectively recognize and diag­ Slreet. Philadelphia, PA 19104. E· mail: etsOpobox.upenn.edu nose these conditions.

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LICHEN PLANUS

Lichen planu s (LP) is a relatively common dermato­ logic disorder that occurs on the skin and oral mucous membranes. There are several forms of this disease, in­ cluding reticular, papular, atrophic, bullous, and ero­ sive patterns. This discussion will focus on the reticu­ lar and erosive forms of LP. The reticular form of LP is the most common and most readily recognized form of the disease. It consists of slightly elevated. fine, whitish lines (Wickham's striae) that produce a lacelike lesion.' Reticular LP is most commonly seen bilaterally on the cheeks and is usually asymptomatic requiring no treatment. Fig 1 Generalized desquamation and erythema in the maxillary Erosive LP presents as chronic multiple oral mu­ and mandibular ging1vae of a pat1ent d1agnosed with erosive cosal ulcers. A significant number of cases of erosive lichen planus LP presents with an initial sign of erythema and/ or desquamative gingivitis' Figure 1 demonstrates gener­ alized desquamative gingivitis in a patient diagnosed with erosive LP. In some cases, the lesions start as vesicles or bullae (bullous LP), and in others, the dis­ Treatment of LP/ lichenoid reactions can be wide ease is characterized solely by erythema or ulcers (ero­ ranging. If the patient has been using navori ng agents, sive LP). The etiology of LP is idiopathic, which distin­ they should be advised to discontinue the use of such guishes itself from lichenoid reactions. Li chenoid products. If the patient has started a new medication reactions have a similar clinical presentation to LP but that correlates to the onset of LP, they should discuss are differentiated on the basis of the association of the changing classes of medication with their physician. reactions \vith administration of a drug, systemic dis­ The erosive type of LP should be managed more ag­ ease, or contact allergy, and they may slowly resolve gressively with the use of high potency (fluocinonide) when the allergen is discontinued or the disease is and ultra high potency (clobetasol) topical steroid treated. Drugs that have been reported to induce gels. These agents may be placed in an occlusive den­ lichenoid reactions are penicillamine, ACE inhibitors, tal splint that covers the affected area of the gi ngiva to and nonsteroidal anti-inflammatory drugs (NSA!Ds), increase healing time and decrease pain. Topical although, less commonly, numerous other drugs have steroid rinses and topical steroids applied to gauze been implicated.' Contact allergens such as cinnamon pads are other methods of administering medication. and peppermint, as well as mercury and gold in select Intralesional steroid injections may be necessary to d ental ma te rials have been reported to cause a treat lesions that are recalcitrant to conventional ther­ lichenoid reaction due to contact allergy.' Hepatitis C apy; however, this may be difficult for gingival lesions. is a systemic condition that has been implicated with A short course of systemic steroids may be considered induction of LP-Iike lesions• for extremely indolent lesions• Recently, several re­ The diagnosis of LP and lichenoid reactions is ports have been published regarding the use of topical made by biopsy. Three characteristic features of LP are tacrolimus in treating oral lichen planus. Tacrolimus is seen histologically: a dense subepithelial band of lym­ an immunosuppressive agent used in the prevention of phocytes; liquefactive degeneration of the basal cell solid organ transplant rejection, and several reports layer; and areas of hyperorthokeratosis and hyper­ have been published demonstrating the effectiveness parakeratosis with a saw tooth appearance to the rete of the topical formulation in managing oral LP, espe­ pegs.1• Lichenoid reactions cannot always be distin­ cially lesions recalcitrant to conventional therapyiD- 13 guished from LP but may show deep, as well as super­ There is evidence that suggests that patients with ero­ ficial lymphocytic infiltrates, rather than the classic sive LP are of a higher risk for developing squamous bandlike infiltrate of LP, as well as eosinophils, neu­ cell carcinoma. Therefore, it is important to evaluate trophils, and plasma cells. Direct immunofluorescence these patients on a standard recall basis. This recall can be performed mainly to rule out other mucocuta­ should be based on the patient's response to treat­ neous diseases, such as pemphigus or mucous mem­ ment. Areas unresponsive to treatment should be re­ brane pemphigoid. Subepithelial deposits of fibrinogen biopsied to rule out dysplasia. Often, the recall will be are the most consistent feature of LPa when nalyzed more frequent than that usually performed for perio­ via immunofluorescence. dontal disease, usually every 1 to 3 months.

Quintessence International 583 --Stoopler et at

Once desmoglein 3 is bound by the autoantibody, there is loss of cell-to-cell adhesion and blister forma­ tion begins. As blister formation p~ogresses, it results in a suprabasilar bulla, which can involve loss of large areas of skin and mucosal> Initial signs of PV may include generalized desqua­ mative gingivitis, as seen in Fig 2. The classical oral le­ sion of pemphigus is a thin-walled bulla with associ­ ated erythema. The lesions are commonly seen on the gingival and buccal mucosa, and the edges of the le­ sion can continue to extend peripherally until they in­ volve large areas of the oral mucosa. It is common for the oral lesions to present up to 4 months before the Fig 2 Genera lized 1ntense erythema and areas of desquamation skin lesions appear. If treatment is instituted during m the max1llary and man dibular gingivae of a pat1ent diagnosed this time, the disease will be easier to control, and the w1th pemphigus vulgaris chance for early remission is enhanced15 Biopsy is the standard for diagnosing PV. Ideally, the biopsy specimen should be taken from an intact vesicle less than 24 hours old. Since these types of le­ sions are rarely present in the mouth, the biopsy An important aspect of LP that must be appreciated should be taken from the advancing edge of the lesion by the clinician is the chronic nature of this disease. where the characteristic suprabasilar splitting of the Lichen planus, when properly managed, can undergo epithelium may be observed. A second biopsy speci­ periods of quiescence where the patient does not ex­ men should be taken from clinically normal-appearing perience any symptoms. When the condition becomes intact perilesional mucosa and sent fo r direct im­ exacerbated, it can cause desquamation of the gingiva, munofluorescene studies (DIP). Direct immunofluo­ which may lead to severe and painful gingivitis. This rescene is performed by placing fluorescene-labeled may cause the patient to neglect daily oral hygiene due antihuman immunoglobulins over the patient's tissue to the painful nature of these symptoms and may, in specimen in order to detect antibodies bound to the turn, lead to an increase in gingival infl ammation and surface of keratinocytes. If the patient is positive for periodontal disease. More frequent professional pro­ PV, the immunofluorescence pattern will reveal a lace­ phylaxis may be indicated. Due to the chronic nature like pattern around the epithelial cells of the tissue of LP, periodontal therapy becomes more integral in specimen. the maintenance of oral health in these patients, as The mainstay of treatment is high doses of systemic poor periodontal health makes the management of corticosteroids. Prednisone is initially used to bring erosive LP extremely difficult. the disease under control and once this is achieved, the dose of prednisone is decreased to the lowest pos­ sible maintenance level. A critical aspect of patient PEMPHIGUS management is early diagnosis; this allows the clini­ cian to use lower doses of medication for shorter peri­ Pemphigus is an autoimmune disease characterized by ods of time to control the disease. Azathioprine and blisters, peeling, and erosions of the skin and mucous cyclophosphamide are immunosuppressive drugs used membranes. The highest incidence of the disease occurs as adjuvant therapies in conjunction with prednisone in the fifth and sixth decades of li fe." This discussion to reduce side effects of the steroid 16 by allowing the will be limited to the most common fonn of the disease, clinician to administer lower doses of systemic steroid. pemphigus vulgaris (PV), which accounts for over 80% Studies have shown that adjuvant therapy decreases of cases. The other fonns of pemphigus are pemphigus mortality when used with systemic corticosteroids. ~ 18 vegetans, pemphigus foliaceus, pemphigus erythemato­ Mycophenolate mofetil, a newer immunosuppressive sus, paraneoplastic pemphigus (a condition where pa­ drug, has been effective in managing patients resistant tients with neoplasms, such as lymphoma, present wtth to other adjuvants1 9 Current studies have demon­ 15 pemphigus), and drug-related pemphigus . . strated the effectiveness of mycophenolate in combi­ Lesions associated with PV are mtraeptthehal, and nation with prednisone to successfully manage PV blister formation is initiated by the binding of IgG au­ while managing adverse side effects of medication.2o toantibodies to desmoglein 3, a transmembrane glyco­ protein adhesion molecule present on desmosomes.

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MUCOUS MEMBRANE PEMPHIGOID

Mucous membrane pemphigoid (MMP), also com­ monly referred to as cicatricial pemphigoid, is a chronic, autoimmune disease that results in mucosal ulceration and subsequent scarring. It primarily affects the mucous membranes of patients over the age of 50 and is considered a subepithelial disease'' Auto­ antibodies, usually of the lgG class, cause subepithelial blistering by cleaving fibrils in the basement mem­ brane zone, as well as activating complement and re­ cruiting neutrophils.21 Subsets of MMP have been identified using sophisticated immunology testing and salt-split skin. These subsets are based on the location Fig 3 Area of hemorrhage and 1ntense erythema m the maxtllary and molecular weight of the antigens involved in ging1va of a pat1ent d1agnosed w1th mucous membrane pem­ M MP , and the majority of cases have antigens on the phiQOid. epidermal side of salt-split skin.22 Today, MMP is con­ sidered a family of closely related autoimmune disor­ ders in which the various autoantigens are found in the BMZ and are involved in the attachment of basal epithelial cells to the underlying connective tissue. have demonstrated its effectiveness in treating mucous Oral manifestations of M MP include desquamative membrane pemphigoid.2124 The major adverse effect of gingivitis and erosion or ulcerations of buccal and dapsone is hemolysis, and prior to initiating therapy, labial mucosa, palate, and tongue. Figure 3 demon­ patients should be screened for glucose-6-phosphate strates intense erythema and an area of hemorrhage in dehydrogenase (G6PD) deficiency. This is a key en­ the gingiva of a patient with MMP. Extraoral manifes­ zyme that prevents oxidation of hemoglobin to methe­ tations include ulceration and scarring of the conjunc­ moglobin, and individuals who are G6PD deficient tiva, corneal damage, and mucosal lesions of the geni­ may develop extensive hemolysis.25 Minocycline, a tals, esophagus, larynx, and trachea."' Skin involvement member of the tetracycline family of antibiotics, also is seen in a low percentage of patients with MMP'' has been shown to be effective in treating MMP.2• Any patient suspected of having MMP must have Reported adverse effects include nausea, vomiting, two biopsy specimens taken for both routine histology dizziness, photosensitivity, and hyperpigmentation." and direct immunofluorescence study. Routine Combination therapies consisting of nicotinamide and histopathology will demonstrate sub-basilar cleavage tetracycline also have been reponed as effective ther­ and immunofluorescence will show positive fluores­ apy for MMP. 27 It is very important for the clinician to cence for immunoglobulin and complement in the thoroughly examine all skin surfaces and the patient's basement membrane zone in 50% to 80% of patients." eyes to determine the extent of the M MP. If extraoral Clinical correlation with routine and immunofluores­ manifestations are observed, it is imperative that the cence studies should be interpreted together to arrive patient be referred to the appropriate specialist for fur­ at a diagnosis of MMP. ther evaluation. It is important to remember that ap­ Management of MMP depends on the severity of proximately 10% of patients with MMP will develop symptoms. Patients with mild oral disease may be eye lesions which often result in scarring and can lead managed by topical and intralesional steroids. to blindness. Desquamative gingivitis is often managed with topical steroids in a soft occlusive splint that covers the gin­ giva. An adverse sequela of chronic topical steroid use CONCLUSION is candida! infection, and the clinician must closely monitor the patient for development of infection. Gingival desquamation can be indicative of local If topical therapies prove ineffective, systemic medi­ trauma/ irritation or systemic disease. Lichen planus, cations may be used for treatment. Like PV, systemic pemphigus, and mucous membrane pemphigoid are steroids are often effective. Dapsone is a synthetic sul­ three mucocutaneous diseases that can present with fone with anti-inflammatory properties that is found gingival desquamation as their initial symptom. With a to be most effective in diseases associated with signifi­ comprehensive history and physical exam, as well as cant neutrophil infiltration. It has been in clinical use the use of gingival biopsy, diagnosis of these disorders for many years to treat leprosy and malaria. Studies will not be delayed.

Quintessence International 585 ---Stoopter e t a t

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