CS4-11) Desquamative Gingivitis PDF

Prof. Dr. TOLGA TOZUM YAKINDOĞU ÜNİVERSİTESİ DİŞHEKİMLİĞİ FAKÜLTESİ Learning outcomes: 1- Will be able to describes diseases and conditions that are seen in with desquamative gingivitis. 2- Will be able to distinguish clinnically diseases and conditions that are seen in with desquamative gingivitis...

Prof. Dr. TOLGA TOZUM YAKINDOĞU ÜNİVERSİTESİ DİŞHEKİMLİĞİ FAKÜLTESİ Learning outcomes: 1- Will be able to describes diseases and conditions that are seen in with desquamative gingivitis. 2- Will be able to distinguish clinnically diseases and conditions that are seen in with desquamative gingivitis. 3- Will be able to refer her to a physician for a biopsy to be taken or evaluated for dermatological or autoimmune diseases. Desquamative Gingivitis Chronic Desquamative Gingivitis Although first recognized and reported in 1894,157 the term chronic desquamative gingivitis was coined in 1932 by Prinz122 to describe a peculiar condition characterized by intense erythema, desquamation, and ulceration of the free and attached gingiva. Patients may be asymptomatic; when symptomatic, however, their complaints range from a mild burning sensation to an intense pain. Approximately 50% of desquamative gingivitis cases are localized to the gingiva, although patients can have involvement of the gingiva plus other intraoral and even extraoral sites.Initially, the cause of this condition was unclear, with a variety of possibilities suggested. Because most cases were diagnosed in women during the fourth and fifth decades of life (although desquamative gingivitis may occur as early as puberty or as late as the seventh or eighth decade), a hormonal derangement was suspected. In 1960, however, McCarthy and colleagues suggested that desquamative gingivitis was not a specific disease entity but rather a gingival response associated with a variety of conditions. This concept has been further supported by numerous immunopathologic studies.The use of clinical and laboratory parameters has revealed that approximately 75% of desquamative gingivitis cases have a dermatologic genesis. Cicatricial pemphigoid and lichen planus account for more than 95% of the dermatologic cases.However, many other mucocutaneous autoimmune conditions (e.g., bullous pemphigoid, pemphigus vulgaris, linear immunoglobulin A [IgA] disease, dermatitis herpetiformis, lupus erythematosus, chronic ulcerative stomatitis) can clinically manifest as desquamative gingivitis.Other conditions that must be considered in the differential diagnosis of desquamative gingivitis include chronic bacterial, fungal, and viral infections as well as reactions to medications, mouthwashes, and chewing gum. Although less common, Crohn’s disease, sarcoidosis, some leukemias, and even factitious lesions have also been reported to present clinically as desquamative gingivitis. Diagnosis of Desquamative Gingivitis: A Systematic Approach Desquamative gingivitis is only a clinical term and not a diagnosis per se. Once the presence of this condition is determined, a serie of laboratory procedures should be used to arrive at a final diagnosis. Thus, the success of any given therapeutic approach depends on the establishment of an accurate final diagnosis. The following discussion represents a systematic approach to elucidate the disease that is triggering desquamative gingivitis. Clinical History A thorough clinical history is mandatory to begin the assessment of desquamative gingivitis. Data regarding the symptomatology associated with this condition as well as its historical aspects (i.e., when the lesion started, whether it has worsened, if there is a habit that exacerbates the condition) provide the foundation for a thorough examination. Information regarding previous therapy to alleviate the condition should also be documented. Clinical Examination Recognition of the pattern of distribution of the lesions (i.e., focal or multifocal, with or without confinement to the gingival tissues) provides leading information to begin the formulation of a differential diagnosis. In addition, a simple clinical maneuver such as Nikolsky’s sign offers insight into the plausibility of the presence of a vesiculobullous disorder. Biopsy Given the extent and number of lesions that may be present in an individual, an incisional biopsy is the best alternative to use to begin the microscopic and immunologic evaluation. An important consideration is the selection of the biopsy site. Microscopic Examination. Sections of approximately 5 μm of formalin-fixed, paraffin-embedded tissue stained with conventional H&E are obtained for light microscopy examination. Immunofluorescence. For direct immunofluorescence, unfixed frozen sections are incubated with a variety of fluoresceinlabeled, antihuman serum (i.e., anti-IgG, anti-IgA, anti-IgM, antifibrin, and anti-C3). With indirect immunofluorescence, unfixed frozen sections of oral or esophageal mucosa from an animal such as a monkey are first incubated with the patient’s serum to allow for the attachment of any serum antibodies to the mucosal tissue. The tissue is then incubated with fluorescein-labeled antihuman serum. Immunofluorescence tests are positive if a fluorescent signal is observed in the epithelium, its associated basement membrane, or the underlying connective tissue Management After the diagnosis is established, the dentist must choose the optimum management for the patient. This is accomplished in accordance with three factors: (1) the practitioner’s experience; (2) the systemic impact of the disease; and (3) the systemic complications of the medications. A detailed consideration of these three factors dictates three different scenarios. In the first scenario, the dental practitioner takes direct and exclusive responsibility for the treatment of the patient; this occurs with conditions such as erosive lichen planus, which is responsive to topical steroids In the second scenario, the dentist collaborates with another health care provider to evaluate and treat a patient concurrently. The classic example is seen with cicatricial pemphigoid, in which dentists and ophthalmologists work together . Although the dentist addresses the oral lesions, the ophthalmologist monitors the integrity of the ocular conjunctiva. In the third scenario, the patient is immediately referred to a dermatologist for further evaluation and treatment. This occurs with conditions in which the systemic impact of the disease transcends the boundaries of the oral cavity and results in significant morbidity and even mortality. Pemphigus vulgaris is a clear example of a condition that, after diagnosis by the dentist, requires immediate referral to a dermatologist Diseases that Present Clinically as Desquamative Gingivitis Lichen Planus Lichen planus is an inflammatory mucocutaneous disorder that may involve the mucosal surfaces (e.g., oral cavity, genital tract, other mucosae) and the skin (including the scalp and the nails).Current evidence suggests that lichen planus is an immunologically mediated mucocutaneous disorder in which host T lymphocytes play a central role.Although the oral cavity may present lichen planus lesions with a distinct clinical configuration and distribution, the clinical presentation may sometimes simulate other mucocutaneous disorders. Therefore, a clinical diagnosis of oral lichen planus should be accompanied by a broad differential diagnosis. Numerous epidemiologic studies have shown that oral lichen planus presents in 0.1% to 4% of the population. Oral Lesions. Although there are several clinical forms of oral lichen planus (i.e., reticular, patch, atrophic, erosive, and bullous), the most common are the reticular and erosive subtypes. The typical reticular lesions are asymptomatic and bilateral, and they consist of interlacing white lines on the posterior region of the buccal mucosa. The lateral border and dorsum of the tongue, the hard palate, the alveolar ridge, and the gingiva may also be affected. In addition, the reticular lesions may have an erythematous background, which is a feature that is associated with coexisting candidiasis. Oral lichen planus lesions follow a chronic course and have alternating, unpredictable periods of quiescence and flare-ups. bordering the atrophic and ulcerated zones. These areas may be sensitive to heat, acid, and spicy foods . Gingival Lesions. Approximately 7% to 10% of patients with oral lichen planus have lesions restricted to the gingival tissue. These may occur as one or more types of the following four distinctive patterns: 1. Keratotic lesions. These raised white lesions may present as groups of individual papules, linear or reticular lesions, or plaquelike configurations. 2. Erosive or ulcerative lesions. These extensive erythematous areas with a patchy distribution may present as focal or diffuse hemorrhagic areas. These lesions are exacerbated by slight trauma (e.g., toothbrushing). 3. Vesicular or bullous lesions. These raised, fluid-filled lesions are uncommon and short lived on the gingiva, quickly rupturing and leaving ulcerations. 4. Atrophic lesions. Atrophy of the gingival tissues with ensuing epithelial thinning results in erythema that is confined to the gingiva. Immunopathology. Direct immunofluorescence of both lesional and perilesional oral lichen planus biopsy specimens reveals linear fibrillar (“shaggy”) deposits of fibrin in the basement membrane zone , along with scattered immunoglobulin staining cytoid bodies in the upper areas of the lamina propria. Serum tests involving the use of indirect immunofluorescence are negative in patients with lichen planus Differential Diagnosis. The classic clinical presentation of oral lichen planus can be simulated by other conditions and mainly by lichenoid mucositis. If oral lichen planus is confined to the gingival tissues (i.e., erosive oral lichen planus), then the identification of fine white radiating striations bordering the erosive areas support a clinical diagnosis of oral lichen planus. If the white striations are absent, the differential diagnosis should primarily include mucous membrane pemphigoid and pemphigus vulgaris. Other, less common possibilities include linear IgA disease (LAD) and chronic ulcerative stomatitis. Treatment. The keratotic lesions of oral lichen planus are asymptomatic and do not require treatment after the microscopic diagnosis has been established. Pemphigoid The term pemphigoid applies to a number of cutaneous, immune mediated, subepithelial bullous diseases that are characterized by a separation of the basement membrane zone, including bullous pemphigoid, mucous membrane pemphigoid, and pemphigoid (herpes) gestationis. Among these conditions, bullous pemphi goid and mucous membrane pemphigoid (also known as benign mucous membrane pemphigoid and cicatricial pemphigoid), have received considerable attention. Current molecular findings involving these two diseases clearly indicate that they are separate entities. However, considerable histologic and immunopathologic overlap exists between the two diseases, so their differentiation may be impossible on the basis of these two criteria. In many cases, the clinical findings are probably the best cognitive element to use to discriminate between them. Accordingly, the term bullous pemphigoid is preferred when the disease is nonscarring and mainly affects the skin. The term cicatricial pemphigoid is favored Bullous Pemphigoid. Bullous pemphigoid is a chronic, autoimmune, subepidermal bullous disease with tense cutaneous bullae that rupture and become flaccid Oral involvement occurs in about a third of affected patients.Although the skin lesions of bullous pemphigoid clinically resemble those of pemphigus, the microscopic picture is quite distinct. Immunofluorescence. Immunologically, bullous pemphigoid is characterized by immunoglobulin G (IgG) and complement (C3) immune deposits along the epithelial basement membranes and circulating IgG antibodies to the epithelial basement membrane. Oral Lesions. Oral lesions have been reported to occur second- arily in up to 40% of cases. There is an erosive or desquamative gingivitis presentation and occasional vesicular or bullous lesions. Treatment. Because its etiologic factors are unknown, the treatment of bullous pemphigoid is designed to control its signs and symptoms. The primary treatment is a moderate dose of systemic prednisone. Steroid-sparing strategies (i.e., prednisone plus other immunomodulatory drugs) are used when high doses of steroids are needed or when the steroid alone fails to control the disease. Mucous Membrane Pemphigoid (Cicatricial Pemphigoid). Mucous membrane pemphigoid, which is also known as cicatricial pemphigoid, is a chronic vesiculobullous autoimmune disorder of unknown cause that predominantly affects women during the fifth decade of life. It has also rarely been reported in young children.Cicatricial pemphigoid involves the oral cavity, the conjunctiva, and the mucosa of the nose, vagina, rectum, esophagus, and urethra. In about 20% of patients, however, the skin may also be involved. Recent investigations suggest that cicatricial pemphigoid encom passes a group of heterogeneous conditions with distinct clinical and molecular features. An elaborate cascade of events is involved in the pathogenesis of cicatricial pemphigoid. Initially, antigen–antibody complexing occurs at the basement membrane zone, and this is followed by complement activation and subsequent leukocyte recruitment. Next, proteolytic enzymes are released and dissolve or cleave the basement membrane zone, usually at the level of the lamina lucida. The two major antigenic determinants for cicatricial pemphigoid are bullous pemphigoid 1 and 2 (BP1 and BP2). Most cases of cicatricial pemphigoid are the result of an immune response directed against BP2; less often, this response is mounted against BP1, epiligrin (laminin-5, a lamina lucida protein in basement membrane of stratified epithelium), and β4 integrins Oral Lesions. The most characteristic feature of oral involvement is the presence of desquamative gingivitis, typically with areas of erythema, desquamation, ulceration, and vesiculation of the attached gingiva. Vesiculobullous lesions may occur elsewhere in the mouth. The bullae tend to have a relatively thick roof and to rupture within 2 to 3 days, leaving irregularly shaped areas of ulceration. Healing of these lesions may take 3 weeks or more. Immunofluorescence. Positive findings along the basement membrane area have been reported with the use of both direct and indirect immunofluorescence. In biopsy tests by direct immunofluorescence, the main immunoreactants are IgG and C3, which are confined to the basement membrane Differential Diagnosis. Several disease entities present with similar clinical and histologic (subepithelial bulla) features. These include bullous pemphigoid, bullous lichen planus, dermatitis herpetiformis, LAD, erythema multiforme, herpes gestationis,and epidermolysis bullosa acquisita.Treatment. Topical steroids are the mainstay of treatment for mucous membrane pemphigoid, particularly when localized lesions are present. Fluocinonide (0.05%) and clobetasol propionate (0.05%) in an adhesive vehicle can be used three times a day for up to 6 months. Pemphigus Vulgaris The pemphigus diseases are a group of autoimmune bullous disorders that produce cutaneous and mucous membranes blisters. Pemphigus vulgaris is the most common of the pemphigus diseases, which also include pemphigus foliaceus, pemphigus vegetans, and pemphigus erythematosus.Pemphigus vulgaris is a potentially lethal chronic condition with a 10% mortality rate and a worldwide incidence of 0.1 to 0.5 cases per year per 100,000 individuals. A predilection in women, usually after the fourth decade of life, has been observed.However, pemphigus vulgaris has also been reported in unusually young children and even in newborns.The epidermal and mucous membrane blisters occur when the cell-to-cell adhesion structures are damaged by the action of circulating autoantibodies and by the in vivo binding of these autoanti bodies to the pemphigus vulgaris antigens, which are cell-surface glycoproteins that are present in keratinocytes. These pemphigus vulgaris glycoproteins are members of the desmoglein (DSG) subfamily of the cadherin superfamily of cell–cell adhesion molecules, which are present in desmosomes.78 Whereas high levels of desmoglein 3 (Dsg3) autoantibodies correlate with the severity of oral disease in patients with pemphigus vulgaris, elevated levels of desmoglein 1 (Dsg1) autoantibodies are associated with severity of cutaneous disease.60 Recent evidence suggests that DSG3, which is the gene that codes for pemphigus vulgaris, is located in chromosome. Oral Lesions. Oral lesions can range from small vesicles to large bullae. When the bullae rupture, they leave extensive areas of ulceration Virtually any region of the oral cavity can be involved, but multiple lesions often develop at sites of irritation or trauma. The soft palate is most often involved (80%), and this is followed by the buccal mucosa (46%), the ventral aspect or dorsum of the tongue (20%), and the lower labial mucosa (10%). Oral lesions of pemphigus vulgaris are confined less often to the gingival tissues. In these patients, a clinical diagnosis of erosive gingivitis or desquamative gingivitis is seen as the sole manifestation of oral pemphigus. Immunofluorescence. The presence of autoantibodies can be demonstrated in the oral mucosa of patients with oral pemphigus with the use of immunofluorescence techniques. For direct immunofluorescence, perilesional unfixed frozen sections are incubated with fluorescein-labeled human anti-IgG. With indirect immunofluorescence, unfixed frozen sections of oral or esophageal mucosa from an animal such as a monkey are first incubated with the patient’s serum to allow for the attachment of any serum antibodies to the mucosal tissue. The tissue is then incubated with fluorescein labeled antihuman IgG serum. Differential Diagnosis. The oral lesions of pemphigus vulgaris may be similar to those seen with erythema multiforme. In patients with erythema multiforme, however, recurrent active episodes of comparatively short duration are followed by long intervals that are free of skin or oral lesions. Erythema multiforme affects the lips with considerable severity. Microscopic examination with conventional H&E and direct immunofluorescence can discriminate between the oral lesions of pemphigus and those of erythema multiforme. Pemphigus vulgaris will show characteristic intraepithelial clefting at the basal–spinous cell layers and interface with acantholysis, whereas erythema multiforme shows microvesiculation of the superficial epithelial layers and numerous necrotic keratinocytes. Pemphigus vulgaris shows an intercellular and intraepithelial signal with direct immunofluorescence. By contrast, erythema multiforme exhibits negative immunofluorescence. Treatment. The main therapy for pemphigus vulgaris is systemic corticosteroids with or without the addition of other immunosuppressive agents. If the patient responds well to corticosteroids, the dosage can be gradually reduced, but a low maintenance dosage is usually necessary to prevent or minimize the recurrence of lesions. Many dermatologists monitor the dose of steroids via the periodic evaluation of the titers of DsG3 and DsG1 antibodies. Increasing titers are often associated with an impending exacerbation and warrant an increase of the steroid dose. A decrease in titer justifies a reduction of the steroid dose. In patients who are not responsive to corticosteroids or who gradually adapt to them, “steroid-sparing” therapies are used; these consist of combinations of steroids plus other medications (e.g., azathioprine, cyclophosphamide, cyclosporine, dapsone, gold, methotrexate) as well as photoplasmapheresis and plasmapheresis. Rituximab is an anti-CD20 monoclonal antibody that is aimed at the removal of desmoglein-reactive autoantibodies and that is currently being evaluated as an adjunct to treat pemphigus vulgaris. Chronic Ulcerative Stomatitis Chronic ulcerative stomatitis, which was first reported in 1990,clinically presents with chronic oral ulcerations and has a predilection for women during their fourth decade of life. The erosions and ulcerations present predominantly in the oral cavity, with only a few cases exhibiting cutaneous lesions. Oral Lesions. Painful solitary small blisters and erosions with surrounding erythema are present mainly on the gingiva and the lateral border of the tongue. Because of the magnitude and clinical features of the gingival lesions, a diagnosis of desquamative gingivitis is considered. The buccal mucosae and hard palate may also present similar lesions. Immunofluorescence. The direct immunofluorescence of normal and perilesional tissues reveals typical strat ified epithelium specific antinuclear antibodies. These are nuclear deposits of IgGDiagnosis. Chronic ulcerative stomatitis is clinically similar to erosive lichen planus. In addition, pemphigus vulgaris, mucous membrane pemphigoid, LAD, bullous pemphigoid, and lupus erythematosus have to be included in the clinical differential diagnosis. Microscopic examination usually reduces the number of possibilities to chronic ulcerative stomatitis, LAD, and erosive lichen planus. Direct and indirect immunofluorescence studies are needed to arrive at the correct diagnosis. Treatment. For mild cases, topical steroids (e.g., fluocinonide clobetasol propionate) and topical tetracycline may produce clinical improvement; however, recurrences are common.For severe cases, a high dose of systemic corticosteroids is needed to achieve remission. Unfortunately, the reduction of the corticosteroid dose results in relapse of the lesions. Linear Immunoglobulin A Disease (Linear Immunoglobulin A Dermatosis) LAD, which is also known as linear IgA dermatosis, is an uncommon mucocutaneous disorder with a predilection for women. The etiopathogenic aspects of LAD are not fully understood, although drug-induced LAD triggered by angiotensin-converting enzyme inhibitors has been reported.LAD clinically presents as a pruritic vesiculobullous rash, usually during middle age and later, although younger individuals may be affected. Characteristic plaques or crops with an annular presentation surrounded by a peripheral rim of blisters affect the skin of the upper and lower trunk, the shoulders, the groin, and the lower limbs. The face and perineum may also be affected. Mucosal involvement, including that of the oral mucosa, ranges from 50% to 100% of the cases published.LAD may mimic lichen planus both clinically and histologically. Immunofluorescence studies are needed to establish the correct diagnosis. Oral Lesions. Oral manifestations of LAD consist of vesicles,painful ulcerations or erosions, and erosive gingivitis or cheilitis. The hard and soft palates are affected more often; the tonsillar pillars, the buccal mucosa, the tongue, and the gingiva follow in frequency. Rarely, oral lesions may be the only manifestation of LAD for several years before the presentation of cutaneous lesions. In addition, oral lesions of LAD have been clinically reported as desquamative gingivitis Immunofluorescence. Linear deposits of IgA are observed at the epithelial tissue–connective tissue interface. They differ from the granular pattern that is observed with dermatitis herpetiformis. Differential Diagnosis. The differential diagnosis of LAD includes erosive lichen planus, chronic ulcerative stomatitis, pemphigus vulgaris, bullous pemphigoid, and lupus erythematosus. Microscopic examination and immunofluorescence studies are necessary to establish the correct diagnosis. Treatment. The primary treatment of LAD involves a combination of sulfones and dapsone. Small amounts of prednisone(10 mg/day to 30 mg/day) can be added if the initial response is inadequate. Alternatively, tetracycline (2 g/day) in combination with nicotinamide (1.5 g/day) has shown promising results.Recently, mycophenolate (1 g twice daily) in combination with prednisolone (30 mg daily) resulted in the resolution of the refractory ulcerations associated with LAD.83 Dermatitis Herpetiformis Dermatitis herpetiformis is a chronic condition that usually develops in young adults between the ages of 20 and 30 years, and it has a slight predilection for men.39 Currently, evidence indicates that dermatitis herpetiformis is a cutaneous manifestation of celiac disease. Approximately 25% of patients with celiac disease have dermatitis herpetiformis. The etiology of celiac disease is obscure; however, tissue transglutaminase seems to be the predominant autoantigen in the intestine, the skin, and sometimes the mucosae.Gluten enteropathy can be severe in about two thirds of patients, and it is mild or subclinical in the remaining third. In severe cases, patients may complain of dysphagia, weakness, diarrhea, and weight loss. Immunofluorescence. Direct immunofluorescence shows that IgA and C3 are present at the dermal papillary apices. These findings are present in both perilesional tissue as well as normal, uninvolved tissue. By contrast, biopsies taken from lesional sites may fail to exhibit IgA or C3, thereby resulting in false-negative results. Although no circulating autoantibodies to epithelial base- ment membrane are present in dermatitis herpetiformis, almost 80% of patients have anti-endomysial and gliadin antibodies. Treatment. A gluten-free diet is essential for the treatment of celiac disease and dermatitis herpetiformis. Oral dapsone is usually needed for patients with newly detected dermatitis herpetiformis to alleviate symptoms promptly. Lupus Erythematosus Lupus erythematosus is an autoimmune disease with three different clinical presentations: systemic, chronic cutaneous, and subacute cutaneous. Systemic Lupus Erythematosus. Systemic lupus erythematosus (SLE) is a severe disease with a 10:1 predilection for women as compared with men. SLE affects vital organs such as the kidneys and heart as well as the skin and mucosa. The classic cutaneous lesions characterized by the presence of a rash on the malar area with a butterfly distribution are actually uncommon Chronic Cutaneous Lupus Erythematosus. Chronic cutaneous lupus erythematosus usually has no systemic signs or symptoms, with lesions being limited to the skin or the mucosal surfaces. The skin lesions are referred to as discoid lupus erythematosus (DLE). DLE merely describes the chronic scarring, atrophy-producing lesion that may develop into hyperpigmentation or hypopigmentation of the healing area Subacute Cutaneous Lupus Erythematosus. Patients with subacute cutaneous lupus erythematosus present cutaneous lesions that are similar to DLE but that lack the development of scarring and atrophy. In addition, arthritis and arthralgia, low- grade fever, malaise, and myalgia may present in up to 50% of patients with subacute cutaneous lupus erythematosus. Differential Diagnosis. Erosive lichen planus, erythema multiforme, and pemphigus vulgaris may sometimes simulate the lesions observed in patients with lupus erythematosus. The diagnosis of DLE confined to the oral cavity is difficult to make, but microscopic studies may suggest the characteristic histopathology. Biopsy studies (i.e., H&E and direct immunofluorescence) help with differentiation between lupus erythematosus and other erosive diseases. Treatment. The therapy for SLE depends on the severity and extent of the disease; it may range from topical steroids to nonsteroidal anti-inflammatory drugs to, for severe systemic organ involvement, moderate to high doses of prednisone. Immunosuppressive drugs (e.g., cytotoxic agents such as cyclophosphamide and azathioprine) and plasmapheresis alone or with steroids can be useful. Erythema Multiforme Erythema multiforme is an acute bullous and macular inflammatory mucocutaneous disease that affects mainly young adults between the ages of 20 and 40 years; it is rarely seen in children (≤20%).134 The genesis of the mucocutaneous lesions is believed to reside in the development of immune complex vasculitis. This is followed by complement fixation that leads to the leukocytoclastic destruction of vascular walls and small vessel occlusion. The culmination of these events produces ischemic necrosis of the epithelium and underlying connective tissue. Target or “iris’ lesions with central clearing are the hallmark of erythema multiforme. It may be a mild condition (erythema multiforme minor) or a severe and possibly life-threatening condition (erythema multiforme major or Stevens–Johnson syndrome). An underdiagnosed type of erythema multiforme is the oral form, with which most patients have chronic or recurrent oral lesions only. Immunofluorescence. Immunofluorescence examination is negative in patients with erythema multiforme. Its value resides in ruling out other vesiculobullous and ulcerative disorders. Treatment. There is no specific treatment for erythema multiforme. For mild symptoms, systemic and local antihistamines together with topical anesthetics and the debridement of lesions with an oxygenating agent are adequate. In patients with bullous or ulcerative lesions and severe symptoms, corticosteroids are considered the drug of choice, although their use is controversial and not completely accepted Drug Eruptions An increase in the incidence of skin and oral manifestations of hypersensitivity to drugs has been noted since the advent of sulfonamides, barbiturates, and various antibiotics. The cutaneous and oral lesions are attributed to the drug acting as an allergen that sensitizes the tissues. Eruptions in the oral cavity that result from sensitivity to drugs that have been taken by mouth or parenterally are called stomatitis medicamentosa. The local reaction from the use of a medicament in the oral cavity (e.g., stomatitis as a result of topical penicillin use) is referred to as stomatitis venenata or contact stomatitis. In many cases, skin eruptions may accompany the oral lesions. In general, drug eruptions in the oral cavity are multiform. Vesicular and bullous lesions occur most often, but pigmented or nonpigmented macular lesions are also frequently observed. Erosions, which are often followed by deep ulceration with purpuric lesions, may also occur. The lesions are seen in different areas of the oral cavity, with the gingiva often being affected.Miscellaneous Conditions that Mimic Desquamative Gingivitis Another group of heterogeneous conditions may masquerade as desquamative gingivitis. Factitious lesions, candidiasis, graftversus-host disease, Wegener’s granulomatosis, foreign body gingivitis, Kindler syndrome, and even squamous cell carcinoma can divert the attention of the clinician and result in a diagnostic challenge. Factitious lesions are injuries that are consciously and intentionally produced without a clear motive, although guilt, the seeking of sympathy, or monetary compensation may be the driving forces behind this abnormal behavior. Factitious desquamative gingivitis has been reported in the literature; it may be difficult to diagnose, and it may become apparent only after extensive and costly laboratory tests fail to reveal the genesis of the lesions.Candidiasis may rarely be limited to the gingival tissues, and it may simulate desquamative gingivitis. Linear gingival erythema is a Candida-associated lesion in individuals who are infected with human immunodeficiency virus in which a ribbonlike red band of the gingival margins is present and reminiscent of desquamative gingivitis. 1-Newman M, Takei H, Klokkevold P, Carranza F. Newman and Carranza (2019); Clinical Periodontology, 13th Ed., Elsevier.