**1. Introduction**

Autoimmune bullous diseases are a group of rare, chronic blistering diseases that affect the skin and mucous membranes. Mucous membrane pemphigoid (MMP) is the most frequently occurring autoimmune bullous disease in the oral cavity, followed by pemphigus vulgaris (PV) [1–3]. Other diseases include bullous pemphigoid, lichen planus pemphigoides, paraneoplastic pemphigus, and chronic ulcerative stomatitis [4, 5]. The primary lesions of MMP or PV often develop in the oral cavity, and patients may complain of oral symptoms and visit their dental clinic first before seeking medical consultation [6, 7]. Therefore, oral healthcare providers need to have some current knowledge about autoimmune bullous diseases and have a great responsibility to achieve early detection, diagnosis, and treatment of the diseases or to refer the patients to other medical or dental specialists as soon as possible.

The gingiva is one of the target tissues of autoimmune bullous diseases. Patients often complain of uncomfortable or painful gingiva or other oral pathologic tissues and usually seek care from their general dentist or periodontist. Desquamative gingivitis (DG) characterized by gingival desquamation, erosion, ulceration, erythematous gingiva, and hemorrhage is a clinical term used to describe some pathologic changes that are common to a variety of gingival diseases or disorders [1–3, 8, 9]. **Table 1** summarizes the clinical appearance of DG. It is important to remember that DG is a general descriptive term rather than a diagnosis (**Table 2**). Therefore, diagnosis of the specific disease or disorder causing DG is important to provide proper treatment. Biopsy evaluation is often required for definitive diagnosis. Especially, histopathological examination and direct immunofluorescence (DIF) testing are critical to establish the final diagnosis for MMP or PV [3, 10–12].

MMP is a group of rare, autoimmune bullous disease that can primarily affect mucous membranes. Various components in the basement membrane zone (BMZ) have been recognized as the target antigens of MMP [13–16]. The major autoantigens in MMP are BP180 C-terminal domain and laminin-332 [15, 16]. In more than 90% of MMP patients, lesions are found in the oral mucosa [14, 17, 18]. DG lesions are usually present. Most MMP patients are in their fifth decade of life, and majority of them are females [13, 14, 17, 18]. Scar formation and an associated loss of function are the most serious complications of some forms of MMP. Sight-threatening ocular scarring and life-threatening airway obstruction have been reported although the scarring is rarely seen in the oral mucosa [17, 19–22]. Early diagnosis of MMP is critical, and immunosuppressive therapy may prevent scarring in mucous membranes. Histopathologically, subepithelial blister formation is characteristic, but it is not always seen in biopsy specimens [3, 10, 12, 13]. However, this is a nondiagnostic finding since it is also found in other vesiculobullous diseases. In DIF testing, a linear pattern of C3, IgG, or other immunoglobulin, fibrin, or fibrinogen is present along the BMZ [3, 10, 12, 13].

PV is a rare, autoimmune bullous disease that is characterized by intraepithelial acantholysis. PV can develop at any age but most commonly occurs in middle-aged and elderly patients [2, 23, 24]. PV affects both males and females equally [2, 23, 24]. PV is a rare, but serious and potentially life-threatening condition if left untreated [25]. Oral lesions are the first site of PV involvement in most patients. The oral lesions of PV are usually multiple, typically involving the buccal mucosa and soft palate [24, 26]. On

**59**

cavity.

*Gingival Nikolsky's Sign: A Valuable Tool in Identifying Oral Manifestations of Mucous…*

Hypersensitivity reactions to dental hygiene products, food flavorings, or preservatives

*desquamative gingivitis. Modified from Endo et al. [2, 6], Rees & Burkhart [3].*

*Diseases or disorders that are associated with desquamative gingivitis.*

occasion, the gingiva is the only site involved, and DG is a relatively common clinical manifestation of the disease [27, 28]. It has been determined that the principal autoantigens in pemphigus patients are desmogleins (Dsgs), which are the components of desmosomes in the epidermis and mucous membranes [29, 30]. The main target antigen of PV is Dsg 3 [29, 30]. Most patients with PV lesions limited to the oral mucosa have only anti-Dsg 3 antibody in the serum, whereas patients involving both the oral mucosa and skin may have both anti-Dsg 3 and anti-Dsg 1 antibodies [28, 31]. In a histopathologic examination, PV is characterized by acantholysis and suprabasilar blister formation in the epithelium [3, 10, 12]. In the DIF testing of PV patients, deposition of IgG and C3 is often found between the epithelial cells and is characterized by a "fishnet" or "chicken-

*\*A variety of other potential causes such as lupus erythematosus, mixed connective tissue disease, graft versus host disease, erythema multiforme, epidermolysis bullosa, epidermolysis bullosa acquisita, Kindler syndrome, chronic ulcerative stomatitis, lichen planus pemphigoides, plasmacytosis, plasma cell gingivitis, orofacial granulomatosis, foreign body granulomas, candidal infection and linear IgA disease, factitious injury of the gingiva, Crohn's disease, psoriasis, sarcoidosis, and adverse drug reactions may possess some but usually not all of the clinical features of* 

In addition to the classic DG lesions, clinical diagnosis for MMP or PV may be supported by the presence of extragingival lesions including the buccal mucosa, the soft palate or tongue, or the presence of extraoral lesions including the eyes, upper respiratory tract, genitals, anus, or skin [3, 17, 31]. However, the patients often had lesions confined only to the gingiva [27]. In such a case, early diagnosis of autoimmune bullous diseases in the oral cavity may become more difficult. Diagnosis delays of more than 6 months were experienced by 30.8% of this group of PV patients and 54.2% of the MMP patients [27]. 16.7% of patients with MMP were

Epithelial desquamation of the gingiva is a prominent clinical feature that supports early clinical diagnosis of autoimmune bullous diseases in the oral cavity [6]. Some of the patients with MMP or PV were aware of painful epithelial desquamation of the gingiva during meals or oral hygiene practices, and the patients complained it to the dental practitioners. However, due to the limited understanding of oral healthcare providers for autoimmune bullous diseases, MMP or PV was not included in the differential diagnosis [6]. For that reason, many patients are not diagnosed until lesions have become severe. Early diagnosis of MMP or PV is critical for proper management and prevention of potential serious complications. Nikolsky's sign is a phenomenon characterized by epithelial desquamation as a result of slight pressure or rubbing the skin or oral mucosa [32]. This sign is a simple test that can confirm the existence of gingival desquamation. In the dental clinic, the presence of Nikolsky's sign can be evaluated by the application of a firm sliding or rubbing force to the mucosal surface using a dental instrument [3, 32]. In an attempt to facilitate the recognition of the early symptoms of autoimmune bullous diseases, the purpose of this study was to examine the frequency of positive Nikolsky's sign at the first visit in patients with MMP or PV. Results of this study may expedite the diagnosis of autoimmune bullous diseases developing in the oral

delayed for more than 12 months from onset to diagnosis [27].

*DOI: http://dx.doi.org/10.5772/intechopen.82582*

The most frequent diseases or disorders

Mucous membrane pemphigoid

Oral lichen planus

Pemphigus vulgaris

Other rare conditions\*

**Table 2.**

wire" pattern [3, 10, 12].


#### **Table 1.** *Clinical appearance of desquamative gingivitis.*


*\*A variety of other potential causes such as lupus erythematosus, mixed connective tissue disease, graft versus host disease, erythema multiforme, epidermolysis bullosa, epidermolysis bullosa acquisita, Kindler syndrome, chronic ulcerative stomatitis, lichen planus pemphigoides, plasmacytosis, plasma cell gingivitis, orofacial granulomatosis, foreign body granulomas, candidal infection and linear IgA disease, factitious injury of the gingiva, Crohn's disease, psoriasis, sarcoidosis, and adverse drug reactions may possess some but usually not all of the clinical features of desquamative gingivitis. Modified from Endo et al. [2, 6], Rees & Burkhart [3].*

#### **Table 2.**

*Gingival Disease - A Professional Approach for Treatment and Prevention*

as possible.

ulcerative stomatitis [4, 5]. The primary lesions of MMP or PV often develop in the oral cavity, and patients may complain of oral symptoms and visit their dental clinic first before seeking medical consultation [6, 7]. Therefore, oral healthcare providers need to have some current knowledge about autoimmune bullous diseases and have a great responsibility to achieve early detection, diagnosis, and treatment of the diseases or to refer the patients to other medical or dental specialists as soon

The gingiva is one of the target tissues of autoimmune bullous diseases. Patients often complain of uncomfortable or painful gingiva or other oral pathologic tissues and usually seek care from their general dentist or periodontist. Desquamative gingivitis (DG) characterized by gingival desquamation, erosion, ulceration, erythematous gingiva, and hemorrhage is a clinical term used to describe some pathologic changes that are common to a variety of gingival diseases or disorders [1–3, 8, 9]. **Table 1** summarizes the clinical appearance of DG. It is important to remember that DG is a general descriptive term rather than a diagnosis (**Table 2**). Therefore, diagnosis of the specific disease or disorder causing DG is important to provide proper treatment. Biopsy evaluation is often required for definitive diagnosis. Especially, histopathological examination and direct immunofluorescence (DIF) testing are critical to establish the final diagnosis for MMP or PV [3, 10–12]. MMP is a group of rare, autoimmune bullous disease that can primarily affect mucous membranes. Various components in the basement membrane zone (BMZ) have been recognized as the target antigens of MMP [13–16]. The major autoantigens in MMP are BP180 C-terminal domain and laminin-332 [15, 16]. In more than 90% of MMP patients, lesions are found in the oral mucosa [14, 17, 18]. DG lesions are usually present. Most MMP patients are in their fifth decade of life, and majority of them are females [13, 14, 17, 18]. Scar formation and an associated loss of function are the most serious complications of some forms of MMP. Sight-threatening ocular scarring and life-threatening airway obstruction have been reported

although the scarring is rarely seen in the oral mucosa [17, 19–22]. Early diagnosis of MMP is critical, and immunosuppressive therapy may prevent scarring in mucous membranes. Histopathologically, subepithelial blister formation is characteristic, but it is not always seen in biopsy specimens [3, 10, 12, 13]. However, this is a nondiagnostic finding since it is also found in other vesiculobullous diseases. In DIF testing, a linear pattern of C3, IgG, or other immunoglobulin, fibrin, or fibrinogen

PV is a rare, autoimmune bullous disease that is characterized by intraepithelial acantholysis. PV can develop at any age but most commonly occurs in middle-aged and elderly patients [2, 23, 24]. PV affects both males and females equally [2, 23, 24]. PV is a rare, but serious and potentially life-threatening condition if left untreated [25]. Oral lesions are the first site of PV involvement in most patients. The oral lesions of PV are usually multiple, typically involving the buccal mucosa and soft palate [24, 26]. On

is present along the BMZ [3, 10, 12, 13].

Gingival erythema not resulting from dental plaque accumulation

Desquamation, erosion, and ulceration of the gingiva

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**Table 1.**

Painful gingiva Burning sensation Gingival bleeding

Blister formation on the gingiva Other intraoral and/or extraoral lesions Possible positive Nikolsky's sign of the gingiva *Modified from Endo et al. [6, 17], Rees & Burkhart [3].*

*Clinical appearance of desquamative gingivitis.*

*Diseases or disorders that are associated with desquamative gingivitis.*

occasion, the gingiva is the only site involved, and DG is a relatively common clinical manifestation of the disease [27, 28]. It has been determined that the principal autoantigens in pemphigus patients are desmogleins (Dsgs), which are the components of desmosomes in the epidermis and mucous membranes [29, 30]. The main target antigen of PV is Dsg 3 [29, 30]. Most patients with PV lesions limited to the oral mucosa have only anti-Dsg 3 antibody in the serum, whereas patients involving both the oral mucosa and skin may have both anti-Dsg 3 and anti-Dsg 1 antibodies [28, 31]. In a histopathologic examination, PV is characterized by acantholysis and suprabasilar blister formation in the epithelium [3, 10, 12]. In the DIF testing of PV patients, deposition of IgG and C3 is often found between the epithelial cells and is characterized by a "fishnet" or "chickenwire" pattern [3, 10, 12].

In addition to the classic DG lesions, clinical diagnosis for MMP or PV may be supported by the presence of extragingival lesions including the buccal mucosa, the soft palate or tongue, or the presence of extraoral lesions including the eyes, upper respiratory tract, genitals, anus, or skin [3, 17, 31]. However, the patients often had lesions confined only to the gingiva [27]. In such a case, early diagnosis of autoimmune bullous diseases in the oral cavity may become more difficult. Diagnosis delays of more than 6 months were experienced by 30.8% of this group of PV patients and 54.2% of the MMP patients [27]. 16.7% of patients with MMP were delayed for more than 12 months from onset to diagnosis [27].

Epithelial desquamation of the gingiva is a prominent clinical feature that supports early clinical diagnosis of autoimmune bullous diseases in the oral cavity [6]. Some of the patients with MMP or PV were aware of painful epithelial desquamation of the gingiva during meals or oral hygiene practices, and the patients complained it to the dental practitioners. However, due to the limited understanding of oral healthcare providers for autoimmune bullous diseases, MMP or PV was not included in the differential diagnosis [6]. For that reason, many patients are not diagnosed until lesions have become severe. Early diagnosis of MMP or PV is critical for proper management and prevention of potential serious complications. Nikolsky's sign is a phenomenon characterized by epithelial desquamation as a result of slight pressure or rubbing the skin or oral mucosa [32]. This sign is a simple test that can confirm the existence of gingival desquamation. In the dental clinic, the presence of Nikolsky's sign can be evaluated by the application of a firm sliding or rubbing force to the mucosal surface using a dental instrument [3, 32]. In an attempt to facilitate the recognition of the early symptoms of autoimmune bullous diseases, the purpose of this study was to examine the frequency of positive Nikolsky's sign at the first visit in patients with MMP or PV. Results of this study may expedite the diagnosis of autoimmune bullous diseases developing in the oral cavity.
