**4. Discussion**

In this study, 39 DG patients with autoimmune bullous diseases diagnosed as MMP or PV participated. All the patients complained of gingival soreness, bleeding, and/or swelling (**Table 4**). A positive reaction showing Nikolsky's sign was confirmed in 38 patients (97.4%) at their first visit (**Table 6**). This result indicates that it is important to evaluate the presence of gingival Nikolsky's sign in DG patients. Patients showing positive Nikolsky's sign should have MMP or PV included in the differential diagnosis when DG is identified. However, it should be noted that it is critical to conduct DIF biopsy testing in addition to histopathological examination. By doing this, the oral healthcare providers can contribute to the early diagnosis and treatment for MMP or PV lesions in the oral cavity. It is

important to note, however, that DG sites should not be selected for biopsy diagnosis since intact epithelium is necessary to confirm the diagnosis of these autoimmune disorders [3, 10]. This retrospective study was limited to those who exhibited autoimmune bullous diseases, and consequently we do not know the nature or number of diseases causing DG in individuals with other disorders. Another limitation of this study is that it does not include a control group. Future controlled clinical studies, including the test in non-autoimmune diseases groups, are needed to establish the validity of the results of the present study.

This study found that the gingiva is a preferable site for performing a test for Nikolsky's sign. The site where DG lesions were frequently found was the anterior area of 35 patients (89.7%), while 37 patients (94.7%) were identified to have DG on either labial or buccal gingiva (**Table 5**). This indicates that direct access to the gingival surface to be examined is easy. The most suitable site for a test for Nikolsky's sign would be the labial gingiva of the anterior area of the upper and lower jaws. In evaluating Nikolsky's sign, the presence of bleeding from the gingiva roughly guess which epithelial cleavage level is occurring (subepithelial separation or intraepithelial separation). If the gingival bleeding occurred after performing a Nikolsky's sign, this would imply a subepithelial separation such as MMP. In contrast, if the gingival bleeding was unlikely to occur, this would imply an intraepithelial separation such as PV. In this study, 16 patients (42.1%) had bleeding after application of a sliding or rubbing force on the gingiva, and all of 16 patients diagnosed as having MMP (**Table 7**). It should be noted, however, that the presence of gingival bleeding is also affected by the magnitude of the sliding or rubbing force to the gingival surface and the degree of gingival inflammation caused by concomitant dental plaque-induced gingivitis.

The classic Nikolsky's sign seen on the skin was first described by Piotr Vasiliyevich Nikolskiy who was a Russian dermatologist [33]. Presently, "Nikolskiy" and "Nikolsky" are synonyms in the English literature [32, 33]. Nikolsky's sign that was originally defined by Nikolskiy is a characteristic of skin lesions in pemphigus foliaceus [34]. Many experts, however, now agree that Nikolsky's sign is elicited by several mucocutaneous disorders, as well as the pemphigus group [32–37]. Grando et al. [33] described two modifications of Nikolsky's sign, the "marginal" method that is performed on the edge of an active skin lesion and the "direct" method that is on an area of apparently unaffected skin distant from the lesions. The "direct" Nikolsky's sign is a phenomenon that occurs when an immunological disorder has been implicated such as in pemphigus [38]. This finding supports the concept that immune deposits in autoimmune bullous diseases may be present in outwardly normal-appearing tissue. Sheklakov, another Russian dermatologist, first reported the ability to elicit Nikolsky's sign in the oral mucosa [33]. This phenomenon is very common in MMP or PV patients with lesions in the oral mucosa as shown in this study. Other autoimmune bullous diseases such as bullous pemphigoid, lichen planus pemphigoides, and paraneoplastic pemphigus show a positive Nikolsky's sign in the mouth although the number of patients is small [32, 39]. In addition, there are a number of other non-autoimmune diseases or disorders associated with positive Nikolsky's sign on the oral mucosa [32, 35]. Oral lichen planus is a chronic inflammatory mucocutaneous disease caused by an unknown etiology. A possible autoimmune etiology has been suggested but not yet confirmed in lichen planus. Nonetheless, a positive Nikolsky's sign sometimes was identified in patients with erosive oral lichen planus (**Figure 7**) [40, 41]. Histopathologically, oral lichen planus is characterized by band-like lymphocyte infiltration below the epithelium and basal cell liquefaction [40, 42]. The basal cell liquefaction may cause the epithelial separation from underlying connective tissue, especially if traumatic forces are present [3]. Positive DIF findings are only considered to be

**65**

**Figure 9.**

*treatment.*

**Figure 7.**

**Figure 8.**

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

supportive but not diagnostic for oral lichen planus [3]. Erythema multiforme is a rare, acute reactive disorder that can affect the skin and mucous membranes. The clinical appearance of oral lesions may present as diffuse erythema, bulla, erosions, and ulcerations with or without pseudomembrane [43, 44]. The vermilion border of the lips is often involved. Nikolsky's sign of the gingiva has occasionally been described (**Figure 8**) [32]. The diagnosis of oral erythema multiforme is often difficult because the clinical features may mimic other oral inflammatory and vesiculobullous diseases or disorders. The diagnosis is usually supported by biopsy and exclusion of other causes [43, 44]. On rare occasions, gingival lesions caused by

*Desquamative gingivitis in erosive oral lichen planus. Localized erythematous lesions were found in the attached gingiva. The "marginal" Nikolsky's sign showed a positive reaction. The histopathological findings* 

*Erythema multiforme with epithelial desquamation. The clinical manifestations of severe oral ulceration can be difficult to differentiate from autoimmune bullous diseases. Histopathological and direct immunofluorescence findings were nonspecific. The "marginal" Nikolsky's sign of the gingiva showed a positive reaction.*

*Gingival injuries caused by excessive toothbrushing. Sharply demarcated abrasions of the gingiva were seen and may mimic the "marginal" Nikolsky's sign elicited by autoimmune bullous diseases. The gingival trauma was arrested quickly by making the patients aware that it was caused by incorrect toothbrushing and that it could be alleviated by learning correct oral hygiene practices. Their gingival trauma has not recurred since their* 

*indicated band-like lymphocyte infiltration below the epithelium and basal cell liquefaction.*

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

*Gingival Nikolsky's Sign: A Valuable Tool in Identifying Oral Manifestations of Mucous… DOI: http://dx.doi.org/10.5772/intechopen.82582*

supportive but not diagnostic for oral lichen planus [3]. Erythema multiforme is a rare, acute reactive disorder that can affect the skin and mucous membranes. The clinical appearance of oral lesions may present as diffuse erythema, bulla, erosions, and ulcerations with or without pseudomembrane [43, 44]. The vermilion border of the lips is often involved. Nikolsky's sign of the gingiva has occasionally been described (**Figure 8**) [32]. The diagnosis of oral erythema multiforme is often difficult because the clinical features may mimic other oral inflammatory and vesiculobullous diseases or disorders. The diagnosis is usually supported by biopsy and exclusion of other causes [43, 44]. On rare occasions, gingival lesions caused by

#### **Figure 7.**

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

to establish the validity of the results of the present study.

plaque-induced gingivitis.

important to note, however, that DG sites should not be selected for biopsy diagnosis since intact epithelium is necessary to confirm the diagnosis of these autoimmune disorders [3, 10]. This retrospective study was limited to those who exhibited autoimmune bullous diseases, and consequently we do not know the nature or number of diseases causing DG in individuals with other disorders. Another limitation of this study is that it does not include a control group. Future controlled clinical studies, including the test in non-autoimmune diseases groups, are needed

This study found that the gingiva is a preferable site for performing a test for Nikolsky's sign. The site where DG lesions were frequently found was the anterior area of 35 patients (89.7%), while 37 patients (94.7%) were identified to have DG on either labial or buccal gingiva (**Table 5**). This indicates that direct access to the gingival surface to be examined is easy. The most suitable site for a test for Nikolsky's sign would be the labial gingiva of the anterior area of the upper and lower jaws. In evaluating Nikolsky's sign, the presence of bleeding from the gingiva roughly guess which epithelial cleavage level is occurring (subepithelial separation or intraepithelial separation). If the gingival bleeding occurred after performing a Nikolsky's sign, this would imply a subepithelial separation such as MMP. In contrast, if the gingival bleeding was unlikely to occur, this would imply an intraepithelial separation such as PV. In this study, 16 patients (42.1%) had bleeding after application of a sliding or rubbing force on the gingiva, and all of 16 patients diagnosed as having MMP (**Table 7**). It should be noted, however, that the presence of gingival bleeding is also affected by the magnitude of the sliding or rubbing force to the gingival surface and the degree of gingival inflammation caused by concomitant dental

The classic Nikolsky's sign seen on the skin was first described by Piotr Vasiliyevich Nikolskiy who was a Russian dermatologist [33]. Presently, "Nikolskiy" and "Nikolsky" are synonyms in the English literature [32, 33]. Nikolsky's sign that was originally defined by Nikolskiy is a characteristic of skin lesions in pemphigus foliaceus [34]. Many experts, however, now agree that Nikolsky's sign is elicited by several mucocutaneous disorders, as well as the pemphigus group [32–37]. Grando et al. [33] described two modifications of Nikolsky's sign, the "marginal" method that is performed on the edge of an active skin lesion and the "direct" method that is on an area of apparently unaffected skin distant from the lesions. The "direct" Nikolsky's sign is a phenomenon that occurs when an immunological disorder has been implicated such as in pemphigus [38]. This finding supports the concept that immune deposits in autoimmune bullous diseases may be present in outwardly normal-appearing tissue. Sheklakov, another Russian dermatologist, first reported the ability to elicit Nikolsky's sign in the oral mucosa [33]. This phenomenon is very common in MMP or PV patients with lesions in the oral mucosa as shown in this study. Other autoimmune bullous diseases such as bullous pemphigoid, lichen planus pemphigoides, and paraneoplastic pemphigus show a positive Nikolsky's sign in the mouth although the number of patients is small [32, 39]. In addition, there are a number of other non-autoimmune diseases or disorders associated with positive Nikolsky's sign on the oral mucosa [32, 35]. Oral lichen planus is a chronic inflammatory mucocutaneous disease caused by an unknown etiology. A possible autoimmune etiology has been suggested but not yet confirmed in lichen planus. Nonetheless, a positive Nikolsky's sign sometimes was identified in patients with erosive oral lichen planus (**Figure 7**) [40, 41]. Histopathologically, oral lichen planus is characterized by band-like lymphocyte infiltration below the epithelium and basal cell liquefaction [40, 42]. The basal cell liquefaction may cause the epithelial separation from underlying connective tissue, especially if traumatic forces are present [3]. Positive DIF findings are only considered to be

**64**

*Desquamative gingivitis in erosive oral lichen planus. Localized erythematous lesions were found in the attached gingiva. The "marginal" Nikolsky's sign showed a positive reaction. The histopathological findings indicated band-like lymphocyte infiltration below the epithelium and basal cell liquefaction.*

#### **Figure 8.**

*Erythema multiforme with epithelial desquamation. The clinical manifestations of severe oral ulceration can be difficult to differentiate from autoimmune bullous diseases. Histopathological and direct immunofluorescence findings were nonspecific. The "marginal" Nikolsky's sign of the gingiva showed a positive reaction.*

#### **Figure 9.**

*Gingival injuries caused by excessive toothbrushing. Sharply demarcated abrasions of the gingiva were seen and may mimic the "marginal" Nikolsky's sign elicited by autoimmune bullous diseases. The gingival trauma was arrested quickly by making the patients aware that it was caused by incorrect toothbrushing and that it could be alleviated by learning correct oral hygiene practices. Their gingival trauma has not recurred since their treatment.*

excessive or improper oral hygiene practices or by hypersensitivity reactions to oral hygiene products such as toothpaste or mouth rinses may mimic positive Nikolsky's sign elicited by autoimmune bullous diseases (**Figure 9**) [45–47]. Biopsy may provide histopathologic evidence supporting the diagnosis, but DIF is often not indicated because it is routinely negative since intact epithelium may be required to validate the diagnosis. Eliminating causative agents leads to disappearance of gingival involvement in most patients with hypersensitivity reactions to dental or dental hygiene products.

After the diagnosis of MMP or PV, patients often require an extraoral examination by medical specialists including a dermatologist, an ophthalmologist, and an otolaryngologist. All patients with extraoral involvement should be managed by medical specialists using systemic treatment with or without hospitalization. Patients with exclusively oral lesions may be managed using moderate to very-highpotency topical corticosteroid therapy often combined with effective dental plaque control. The therapeutic goal for DG lesions is the remission or suppression of the clinical signs and symptoms such as gingival soreness, bleeding, and swelling as shown in **Table 4**. Response to therapy can be assessed to determine whether or not the patient exhibits a positive Nikolsky's sign or other evidence of ongoing disease. The disappearance of lesions and of Nikolsky's sign may indicate a favorable treatment outcome.
