Noninvasive Imaging Techniques as Modern Diagnostic Tools in Desquamative Gingivitis: Focus on RCM, OCT, and LC‐OCT

ABSTRACT

Background

Desquamative gingivitis is a clinical condition characterized by erythema, blisters, and erosions within the gingiva. It may be a manifestation of oral lichen planus or autoimmune bullous diseases, such as pemphigus vulgaris and mucous membrane pemphigoid. The identification of the cause of desquamative gingivitis typically involves the analysis of clinical manifestations, histopathology, and immunopathology evaluation. This article reviews available data on the application of noninvasive imaging techniques (reflectance confocal microscopy, optical coherence tomography, and line‐field confocal optical coherence tomography) in identifying the cause of desquamative gingivitis.

Materials and Methods

The review of the literature for desquamative gingivitis was performed by searching the PubMed, Scopus, and Wiley databases up to January 2025.

Results

This study aimed to evaluate the applicability of noninvasive imaging techniques, including RCM, OCT, and LC‐OCT, in the differential diagnosis of desquamative gingivitis. Findings suggest these modalities offer characteristic diagnostic patterns across underlying diseases.

In oral lichen planus, RCM typically shows disrupted connective tissue papillae, obscured basement membranes, and inflammatory cell infiltrates. In pemphigus vulgaris, the key findings are acantholytic keratinocytes and intraepithelial clefts, while mucous membrane pemphigoid displays subepithelial clefts and signs of hemorrhage.

OCT findings in desquamative gingivitis associated with oral lichen planus include maintained epithelial thickness in the erosive forms and multilocular blisters in the bullous variants of the disease. In pemphigus vulgaris, OCT reveals intraepithelial clefts and thinning of the epithelium, while mucous membrane pemphigoid is marked by subepithelial blister formation and fluid accumulation.

Conclusion

New noninvasive imaging techniques, such as reflectance confocal microscopy and optical coherence tomography, may support clinical decision‐making, improve biopsy targeting, and enhance long‐term monitoring of desquamative gingivitis.

1. Introduction

Desquamative gingivitis is a clinical symptom characterized by erythema, desquamation, erosions, and blistering of the gingival epithelium [1]. Several diseases may present with desquamative gingivitis. The clinical criteria for diagnosing desquamative gingivitis were first established by Nisengard in 1995. These criteria included the presence of erythema not associated with plaque and desquamation of the gingiva, along with additional oral or extraoral lesions and sensations of a sore mouth, primarily triggered by spicy foods [2].

The most common causes include oral lichen planus (75%), mucous membrane pemphigoid (9%), and pemphigus vulgaris (4%) [3]. Other causes include other autoimmune blistering diseases (paraneoplastic pemphigus, epidermolysis bullosa acquisita, linear IgA bullous disease, bullous pemphigoid, dermatitis herpetiformis), connective tissue disorders (systemic lupus erythematosus, dermatomyositis, polymyositis, mixed connective tissue disease), erythema multiforme, and toxic epidermal necrolysis. Conditions similar to desquamative gingivitis that can also exacerbate and overlap with other causes of the gingival condition include infections (chronic candidiasis, histoplasmosis, SARS‐CoV‐2) and allergic contact dermatitis [4, 5, 6]. The most common contact allergens are sodium lauryl sulfate and cinnamaldehyde, which are found in toothpastes and mouthwashes. [4, 7, 8]. Plaque accumulation also leads to an exacerbation of desquamative gingivitis [9].

Recent studies have emphasized the complex interplay between local periodontal inflammation and systemic health, providing a broader context for understanding desquamative gingivitis, particularly in patients with coexisting periodontitis or peri‐implant diseases. Bibliometric analyses have highlighted a growing body of evidence linking periodontitis with systemic conditions such as cardiovascular disease, diabetes, adverse pregnancy outcomes, and autoimmune disorders, all of which may modulate gingival immune responses and exacerbate local tissue damage [10]. Moreover, successful periodontal treatment—particularly when accompanied by effective biofilm control—has been shown not only to reduce local inflammation but also to positively influence systemic inflammatory markers. In peri‐implant mucositis, for instance, nonsurgical mechanical debridement augmented with chlorhexidine protocols significantly reduced bleeding on probing and bacterial loads of key pathogens such as Porphyromonas gingivalis and Tannerella forsythia [11]. These findings are clinically relevant to desquamative gingivitis, where plaque‐induced inflammation may overlap with or mimic mucocutaneous autoimmune processes.

The diagnostic approach for desquamative gingivitis involves a combination of clinical presentation, extraoral involvement, immunopathological tests, and histopathological examinations [9, 12]. Performing biopsies on gingival tissue affected by desquamative gingivitis is particularly challenging due to the fragility and thinness of the tissues [12]. In this aspect, a real‐time, in vivo assessment of the gingiva could offer significant advantages. It would enhance the diagnostic accuracy by identifying the optimal biopsy site and enabling long‐term, noninvasive monitoring of patients with confirmed desquamative gingivitis [13]. Emerging optical imaging technologies, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), provide cross‐sectional images of tissue in a noninvasive way, providing high‐resolution microscopic images of biological tissues [14, 15]

RCM offers detailed horizontal plane visualization of tissues at cellular‐level resolution, specifically 0.5–1.0 µm horizontally and 4–5 µm axially. The system utilizes a diode laser as a source of monochromatic and coherent light, which penetrates the tissue to illuminate a small internal point. The image contrast in RCM is based on variations in the tissue's reflectivity, which depends on its chemical and molecular composition. These differences in the refractive index result in only a portion of the light being reflected, with structures possessing a higher refractive index appearing brighter in the RCM images [14].

OCT is a technique that produces optical cross‐sectional images by utilizing low‐coherence interferometry to measure both the echo time delay and the intensity of light backscattered from the surface under examination. When a light beam is directed at the surface, different structural elements reflect the light in distinct ways, generating interference patterns that are subsequently captured by a sensor. The penetration depth reaches up to 2 mm, enabling the visualization of the epidermis, dermis, skin appendages, and blood vessels. The OCT has a horizontal resolution of 7.5 µm and an axial resolution of 5 µm, with the scan covering a field of view of 6 × 6 mm. [15, 16].

Line‐field confocal optical coherence tomography (LC‐OCT) has been designed to merge the high horizontal resolution of RCM (1 µm) with the deep penetration of OCT (500 µm) [17].

This literature review examines the underlying causes of desquamative gingivitis, including oral lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris. The distribution of mucosal involvement is explored, along with emerging diagnostic techniques, such as RCM and OCT, applied to the oral cavity in relation to these conditions. Emerging diagnostic tools may hold dual value—not only for differentiating diagnoses but also for tracking therapeutic outcomes in patients at the interface of oral and systemic pathology.

A review of the literature for desquamative gingivitis was performed by searching the PubMed, Scopus and Wiley databases up to January 2025 The following search terms were used: (“oral lichen planus,” “autoimmune bullous diseases,” “autoimmune blistering diseases,” “pemphigus vulgaris,” “mucous membrane pemphigoid,”) in combination with(“desquamative gingivitis,” “mucosal involvement,” “gingiva,” “reflectance confocal microscopy,” “optical coherence tomography,” “line‐field confocal optical coherence tomography,” “review”). The reference lists of the resulting contributions were also searched for additional relevant publications. The inclusion criteria were (1) studies addressing noninvasive imaging techniques (RCM, OCT, or LC‐OCT) in the diagnosis of desquamative gingivitis; (2) studies focusing on oral lichen planus, mucous membrane pemphigoid, or pemphigus vulgaris; and (3) English‐language publications. The exclusion criteria were (1) studies focusing exclusively on therapeutic interventions; (2) animal studies; and (3) opinion articles, editorials, conference abstracts, and commentaries.

Therefore, this review aims to synthesize current evidence on the diagnostic role of RCM, OCT, and LC‐OCT in distinguishing the underlying causes of desquamative gingivitis, particularly focusing on their applicability in differentiating oral lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris.

2. Discussion

Our literature review identified consistent, disease‐specific imaging patterns across the three major etiologies of desquamative gingivitis—oral lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris—supporting the clinical utility of RCM, OCT, and LC‐OCT in differential diagnosis. The following sections summarize the findings for each condition individually.

Emerging evidence highlights the significant role of oxidative stress in the pathogenesis of periodontitis, suggesting that elevated levels of reactive oxygen species (ROS) contribute to both local tissue breakdown and systemic inflammatory burden [10, 11]. In patients with desquamative gingivitis coexisting with periodontitis, oxidative stress may act as a common pathogenic mechanism, amplifying epithelial damage and modulating immune responses. Antioxidant imbalance may also influence the severity of gingival lesions, particularly in autoimmune‐related presentations [10, 11].  Future studies should explore whether targeted antioxidant therapy could serve as an adjunct in managing desquamative manifestations associated with periodontal inflammation.

3. Oral Lichen Planus

Lichen planus is a chronic T cell‐mediated inflammatory disease of unknown etiology that causes tissue destruction through apoptosis of basal keratinocytes by Fas expression [18]. There are various clinical classifications of oral lichen planus. The first is based on six clinical types: reticular, erosive, atrophic, plaque, papular, and bullous. This classification was introduced by López‐Jornet and Bermejo‐Fenoll in 2005, categorizing oral lichen planus into these distinct forms, which may appear individually or in combination [19]. The second classification is a simplified approach, grouping oral lichen planus into three main categories: hyperkeratotic/reticular, erythematous/erosive/atrophic, and ulcerative. This version, highlighted by Hampel and Reichart, is easier to distinguish in clinical practice [20].

Patients with reticular lesions are often asymptomatic, but atrophic (erythematous) or erosive (ulcerative) oral lichen planus is associated with pain and burning sensation [21]. Oral lichen planus is typically localized on the buccal mucosa, gingiva, and tongue in a symmetric and bilateral distribution [22]. Gingival involvement is common and, in about 10% of cases, desquamative gingivitis is the only manifestation of oral lichen planus. The occurrence of desquamative gingivitis among patients with oral lichen planus varies between 10% and 25%, depending on the study [3, 22, 23, 24].

The typical clinical picture is chronic gingivitis surrounded at the periphery by Wickham's striae [20] (Figure 1). The risk of malignant transformation in oral lichen planus varies widely, with reported rates ranging from 0.3% to 14.3%, often averaging around 1% over follow‐up periods of 5–10 years. Erosive and atrophic forms are particularly at risk, as noted by Agha‐Hosseini et al., while Gandolfo et al. reported transformation rates between 0.5% and 2%, emphasizing these subtypes [25, 26]. Lodi et al. confirmed these findings, highlighting the importance of monitoring high‐risk subtypes [27].

FIGURE 1.

Desquamative gingivitis in oral lichen planus. Clinical image showing desquamative gingivitis surrounded by peripheral Wickham's striae.

Oral lichen planus has characteristic changes on histology, including hyperparakeratosis, hyperorthokeratosis, or a mix of both, with cytoid (Civatte) bodies, basal cell hydropic degeneration, and a predominantly lymphocytic band‐like infiltrate in the lamina propria [28]. This inflammatory pattern, known as interface mucositis, is also observed in oral lesions of lupus erythematosus and other oral lichenoid conditions [29]. Other notable features include saw‐tooth rete ridges, atrophy, acanthosis, eosinophilic deposits at the epithelium‐connective tissue junction, and ulceration. In contrast to skin lesions, oral lesions show less frequent saw‐tooth rete ridges and more frequent atrophy [30]. Regular follow‐up for oral lichen planus patients includes biopsies if progressive development with suspicious features is observed. If the lesions change their clinical appearance, a biopsy should be immediately considered [25].

RCM and OCT may represent promising noninvasive diagnostic tools and support tissue biopsy with increased accuracy in mucous membrane disorders. Alessi et al. compare findings in RCM in cases of desquamative gingivitis with histopathology to establish diagnostic criteria for this noninvasive technique. The authors use the term dermis for lamina propria. In our article, we will substitute dermis and dermal–epidermal junction for lamina propria in the quoted excerpts [1].

RCM has proven valuable in diagnosing and monitoring oral lichen planus. Alessi et al. [1] identified abnormal cornified and granular layers in desquamative gingivitis associated with oral lichen planus, appearing as intensely bright regions in the superficial epithelium. The spinous layer exhibited moderately bright spaces between keratinocytes, linked to inflammatory cell infiltration and a honeycomb‐like arrangement. Necrotic keratinocytes, lacking visible nuclei, appeared as isolated bright, polygonal structures, typically larger than surrounding cells. The lamina propria was challenging to discern; basal keratinocytes formed blurred, ring‐like structures without distinct edges. Sheets of bright, small inflammatory cells and melanophages—bright, reflective, plump, oval to star‐shaped cells—were present within the inflammatory infiltrate. Horizontally oriented, dilated blood vessels were also observed in the lamina propria. Histopathological examination revealed hyperkeratosis, irregular acanthosis, spongiosis, extensive erosive areas, apoptotic keratinocytes, and an inflammatory infiltrate with melanophages in the lamina propria.

Contaldo et al. further emphasized the significance of RCM in evaluating oral lichen planus, especially in the gingiva, where they observed a pronounced honeycomb pattern. Significant spongiosis and epithelial inflammatory cell infiltrates surrounded the connective tissue papillae, with horizontally oriented, dilated blood vessels identifiable within the connective tissue papillae. The reticular‐plaque pattern of oral lichen planus involving mucous membranes displayed all classical signs. RCM revealed ortho‐ and/or parakeratosis, with hypergranulosis characterized by large, polygonal keratinocytes and granules forming a crown‐like arrangement around the nuclear dark halo. Acanthosis and spongiosis in the spinous layers appeared as crowded, large keratinocytes and thickened intercellular spaces. Necrotic keratinocytes were seen as cloudy polygonal cells in the lower spinous layer. Junctional areas showed disrupted connective tissue papillae, likely due to exudate from inflammation and basal keratinocyte necrosis. In erosive‐atrophic lesions, inflammation and obscured connective tissue papillae were predominant, with hyperkeratosis, hypergranulosis, and acanthosis absent, and cells smaller than normal, revealing visible blood vessels below a few epithelial layers. Mixed forms alternated between these patterns [31].

Ardigò et al. highlighted the utility of RCM in diagnosing inflammatory oral mucosal diseases, including oral lichen planus, emphasizing its real‐time, noninvasive imaging capabilities, which facilitate differentiation of oral lichen planus from other mucosal conditions [32]. Additional studies, such as Contaldo et al. and Rajadhyaksha et al., further explored the application of RCM in identifying characteristic morphological features of oral lichen planus and its clinical relevance. Collectively, these studies underscore the importance of RCM as a noninvasive diagnostic tool, providing detailed visualization of epithelial and subepithelial changes characteristic of oral lichen planus [33, 34].

A systematic review of the literature explored the feasibility of using OCT for the initial assessment of desquamative gingivitis. OCT features of erosive oral lichen planus have been described as a normal stratified epithelial layer and epithelial thickness, an intact basal membrane and lamina propria, and the presence of intense inflammatory infiltrate. In cases of bullous oral lichen planus, OCT revealed multilocular subepithelial blisters, along with a normal stratified epithelial layer, normal epithelial thickness, an intact basal membrane, and lamina propria, as well as intense inflammatory infiltrate [35] (Figure 2).

FIGURE 2.

Desquamative gingivitis of erosive oral lichen planus in LC‐OCT: normal stratified epithelial layer (green curly bracket) and epithelial thickness, normal basal membrane (blue arrow) and lamina propria (red arrow), and the presence of intense inflammatory infiltrate (white arrows). Horizontally oriented, dilated blood vessels (pink arrows) were observed in the lamina propria.

Gambino et al. evaluated OCT as a diagnostic tool for atrophic‐erosive oral lichen planus by comparing OCT scans of healthy buccal mucosa with those of buccal mucosa affected by atrophic‐erosive oral lichen planus, using histopathology as the gold standard. En face scans, displayed in grayscale, revealed that the epithelium appeared narrower and more hyperreflective, indicating hyperorthokeratosis or hyperparakeratosis. The lamina propria exhibited an almost complete lack of distinct hyperreflectivity and an unclear transition between the epithelium and the lamina propria. Dynamic scans visualized vascularization, showing scattered red dots throughout the gray, nonhomogeneous, hyperreflective stratified squamous epithelium, which was likely due to intra‐ and inter‐cellular edema, a hallmark of acanthosis and spongiosis. Additionally, the lamina propria showed a loss of structural integrity and a denser vascular pattern, indicative of increased blood flow in chronically inflamed mucosa [36].

Panzarella et al. evaluated the diagnostic concordance between specific OCT patterns of desquamative gingivitis associated with oral lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris. Among 43 gingival lesions examined, 33 (77%) were identified as oral lichen planus by both OCT and histopathological examination. Notably, OCT identified 11 cases (33%) of bullous oral lichen planus, whereas biopsy detected only one such case [37].

Comparing OCT features of the mucous membrane across different forms of oral lichen planus (reticular, reticular‐atrophic, atrophic, atrophic‐erosive, plaque‐like) and contrasting them with leukoplakia and oral squamous cell carcinoma in a cohort of 15 patients revealed significant diagnostic patterns. Reticular oral lichen planus exhibited increased epithelial surface reflectivity, reduced lamina propria reflectivity, limited basement membrane visibility, and an inconspicuous vascular network. Atrophic oral lichen planus demonstrated a hyporeflective epithelium, absent basement membrane visibility, lack of layer differentiation, and an enhanced vascular network. Reticular‐atrophic and atrophic‐erosive oral lichen planus showed epithelial surface hyperreflectivity, reduced epithelial thickness, decreased lamina propria reflectivity, vague basement membrane visibility, reduced layer differentiation, and fewer large vessels. Additionally, reticular‐atrophic oral lichen planus displayed visibly reduced lamina propria reflectivity. Plaque‐like oral lichen planus presented a hyperreflective epithelial layer but lacked basement membrane visibility, layer differentiation, and vascular network identification. In contrast, leukoplakia exhibited a hyporeflective surface, distinct shadowing, absent basement membrane visibility, no layer differentiation, and no identifiable vascular network. Oral squamous cell carcinoma demonstrated a hyperreflective epithelial surface, significantly reduced imaging depth, a cloud‐like layered structure, distinct shadowing, an absent basement membrane and layers, and no vascular network. Diagnostic differentiation focused on epithelium integrity, epithelial thickness, the identifiability of the basement membrane and vascular network within the connective tissue, as well as the reflectivity and differentiation of the epithelium and lamina propria [38].

Additional studies have corroborated these findings. For instance, Contaldo et al. demonstrated OCT's effectiveness in identifying morphological features of oral lichen planus, facilitating noninvasive diagnosis and monitoring [39]. Rajadhyaksha et al. discussed the technical aspects of OCT and its clinical applications in dermatology, including the assessment of oral mucosal lesions, highlighting its potential for routine clinical practice [34].

Collectively, these studies affirm OCT's value as a precise and noninvasive diagnostic tool, providing detailed visualization of epithelial and subepithelial changes characteristic of oral lichen planus, thereby aiding in accurate diagnosis and effective monitoring of the disease.

4. Mucous Membrane Pemphigoid

Mucous membrane pemphigoid is a group of subepidermal bullous disorders mediated by autoantibodies against various antigens (180 kD, 230 kD, laminin 332, type VII collagen, α6 and β4 integrin subunits) and characterized by a chronic course with a predominant involvement of mucosal membranes. The severity of the disease can vary, from mild or moderate forms with slight gingival inflammation to severe cases affecting multiple mucosal areas [40].

The most commonly involved sites in mucous membrane pemphigoid are the oral mucosa (80%–85% cases), followed by conjunctiva (64%), nasal mucosa, genital mucosa, gastroesophageal mucosa, and the skin [40]. Skin involvement is observed in only 25%–30% of patients [40]. According to Sultan et al., the majority of oral mucous membrane pemphigoid cases (84%) had gingival involvement, while non‐gingival sites were less common (16%). Gingival lesions were more prevalent in mucous membrane pemphigoid patients (64%) compared to pemphigus vulgaris patients (33%). Tongue involvement was rare in mucous membrane pemphigoid patients, with only 15% showing such involvement. In mucous membrane pemphigoid, the intraoral sites most commonly involved are: the gingiva (80%), buccal mucosa (58%), palate (26%), alveolar ridge (16%), tongue (15%), and lower lip (7%) [41].

According to Bagan et al., the majority of oral mucous membrane pemphigoid lesions occurred on the gingiva (95%), followed by the palate and buccal mucosa (21% each). The lesions also affected the lips (5%), while tongue and floor of the mouth involvement were less common (3% each). Gingival mucous membrane pemphigoid typically manifests as desquamative gingivitis, with bullae present in the majority of cases, accompanied by erythematous‐erosive areas. Most cases (67%) presented with a single affected location, while a smaller proportion (15%) had three or more simultaneously affected sites [42].

As reported by Parlatescu et al., desquamative gingivitis was found in 47.72% of patients diagnosed with autoimmune blistering diseases, with 79.41% from the subepithelial group and 27.77% from the intraepithelial group. It was the only oral manifestation in 5.55% of intraepithelial disease patients and 26.47% of subepithelial disease patients. In subepithelial diseases, the buccal mucosa was the second most affected site (41.17%), followed by the soft palate (32.35%) and hard palate (17.65%). All patients with subepithelial diseases had unilateral buccal mucosa involvement. In intraepithelial diseases, the buccal mucosa was most frequently affected (83.33%), followed by the soft palate (46.29%) and tonsillar pillar (27.77%). Oral lesions were limited to a single region in 12.96% of intraepithelial patients and 32.35% of subepithelial patients [43].

Desquamative gingivitis varies from localized erythema of the gingiva to widespread inflammation with blistering or ulceration [44] (Figure 3). During the healing phase, fibrosis may occur on extra‐gingival lesions, leading to the appearance of reticulated white striations that resemble lichen planus [45, 46].

FIGURE 3.

Desquamative gingivitis in mucous membrane pemphigoid. Widespread erythema of the gingiva with blistering is visible.

In desquamative gingivitis of mucous membrane pemphigoid, RCM revealed separation in the lamina propria represented by dark spaces filled with small, bright, round‐to‐polygonal, highly refractive cells, identified as blood cells. This dark area corresponds not only to the histopathological features of mucous membrane pemphigoid but also to the clinical aspect of hemorrhagic bullae observed in some patients. These findings were confirmed by histopathological and immunofluorescence analyses [1] (Figure 4).

FIGURE 4.

Desquamative gingivitis of mucous membrane pemphigoid in RCM. Dark spaces (yellow star) filled with small, bright, round‐to‐polygonal, highly refractive cells, identified as blood cells (green arrow).

The reported OCT features for mucous membrane pemphigoid of the gingiva were the presence of multilocular subepithelial blister, a normal stratified epithelial layer and epithelial thickness, an altered/indistinguishable basal membrane and lamina propria, and the presence of inflammatory infiltrate [37]. In a documented case of desquamative gingivitis associated with mucous membrane pemphigoid, the OCT images revealed a dark region between the mucosa and submucosa. The fluid‐filled blisters appeared dark with a notable grayish hue, likely corresponding to blister fluid containing eosinophils [47, 48]. Neutrophil and eosinophil infiltration was also described as the alternation of black and gray areas [49]. The epithelial layer, measuring 300 µm and depicted as the initial horizontal band, exhibited low contrast with the underlying connective tissue and appeared to be well‐preserved [49] (Figure 5).

FIGURE 5.

Desquamative gingivitis of mucous membrane pemphigoid in LC‐OCT: presence of multilocular subepithelial blister (yellow star), normal stratified epithelial layer, altered/indistinguishable basal membrane and lamina propria (red arrow), and the presence of inflammatory infiltrate (white arrows).

5. Pemphigus vulgaris

Pemphigus vulgaris is an autoimmune bullous disorder characterized by the production of autoantibodies against desmosomal proteins, desmogleins 1 (DSG1) and 3 (DSG3), leading to acantholysis, blister formation, and subsequent erosions [50, 51]. Diagnosis of pemphigus vulgaris is based on a combination of clinical presentation, histopathology, direct immunofluorescence (DIF), and serological tests for anti‐Dsg1 and anti‐Dsg3 autoantibodies. A definitive diagnosis requires a clinical picture, histopathological evidence of suprabasal acantholysis, and positive DIF showing IgG and/or C3 deposits at the surface of epidermal keratinocytes. Additionally, serological tests, such as indirect immunofluorescence (IIF) or enzyme‐linked immunosorbent assay (ELISA), are used to detect anti‐Dsg1 and/or anti‐Dsg3 autoantibodies, which are present in more than 95% of cases and correlate with disease activity [52].

Oral lesions may appear before skin lesions or may be the sole manifestation of the disease [50]. Scully et al., discovered that only 28% of patients with pemphigus vulgaris exhibited desquamative gingivitis, while the majority, 72%, had involvement of non‐gingival sites. In a group of 55 pemphigus vulgaris patients with oral manifestations, desquamative gingivitis was present in 24% of cases and was the primary symptom in 9% of cases [53]. The pharynx was identified as the most common site of extra‐oral involvement, accounting for 38% of cases. Sultan et al., supported these findings, showing desquamative gingivitis in 28% of pemphigus vulgaris cases, with it being the sole manifestation in 6% of cases. Additionally, the pharynx was the most frequently affected extra‐oral site, observed in 55% of cases [41]. Mignogna et al., noted gingival involvement in 44% of oral pemphigus vulgaris cases, with desquamative gingivitis being the sole oral manifestation in 11% of the 18 cases studied [54]. Pemphigus vulgaris can affect any area of the oral mucosa, with a preference for the gingival papillary tips. This differs from mucous membrane pemphigoid, where there is more widespread gingival involvement [55]. Pemphigus vulgaris is characterized by extensive non‐gingival oral lesions involving most frequently on the buccal mucosa (90%) and the retromolar trigone (72.5%), and also in a high number of cases on the soft palate (60%) and the gingiva (42.5%) [56]. These results align with the findings of previous studies [52, 57]. Sultan et al., reported the following lesion distribution in oral cavity: buccal mucosa (18.4%), maxillary buccal gingiva (14.6%), lower labial mucosa (13.9%), mandibular buccal gingiva (12.7%), floor of mouth (8.8%), soft palatal mucosa (8.7%), ventral tongue (7.0%), upper labial mucosa (5.7%), dorsal tongue (3.2%), maxillary palatal gingiva (3.2%), lateral tongue (2.5%), and mandibular lingual gingiva (1.3%) [41] (Figure 3). In these cases, the oral mucosa is frequently eroded, leading to rapid rupture of superficial blisters, making intact blisters rare. Healing typically occurs without scarring. Other mucous membranes that may be involved include the less common pharyngeal and nasal mucosa, genital, ocular, laryngeal, and esophageal mucosa [56] (Figure 6).

FIGURE 6.

Clinical image of pemphigus vulgaris. Widespread oral involvement, including erosions on the buccal mucosa and palate.

The identification of acantholytic keratinocytes is essential for pemphigus vulgaris diagnosis using RCM. This is especially crucial as the gingival presentation of pemphigus vulgaris often involves extensive erosions. Acantholytic keratinocytes are readily detectable with RCM and can be observed not only within pemphigus blisters but also at the transition between eroded and apparently unaffected gingival mucosa. Additionally, RCM is beneficial for selecting biopsy sites, as specimens are often taken from areas that do not yield sufficient diagnostic material. It also aids in patient follow‐up, as some persistent lesions, especially in the gingiva, may endure despite immunosuppressive treatment and can be mistaken for periodontal disease [1].

In RCM of desquamative gingivitis in pemphigus vulgaris, an intraepithelial cleft containing rounded detached cells, which correspond with acantholytic keratinocytes, was observed, along with prominent, round or linear dark canalicular structures oriented horizontally in the lamina propria, reflecting dilated vessels. The lamina propria also showed inflammatory cells as round‐to‐polygonal, slightly refractive cells, which were smaller in size compared to melanophages and keratinocytes [1]. In the described case, a woman with pemphigus vulgaris presented with multiple erosions on the mucosa of her right cheek and the left lateral side of her tongue. RCM was used to examine the erosion on the cheek mucosa, revealing the presence of acantholytic keratinocytes and an intraepithelial cleft [32].

The OCT image of the gingiva in pemphigus vulgaris revealed dark superficial clefts within the stratified squamous epithelium. In this instance, an intraepithelial split could be clearly identified. These intraepithelial acantholytic blisters were likely fluid‐filled. The roof of these blisters appeared significantly thinner than the well‐defined epithelial layer [49]. The reported OCT features for pemphigus vulgaris involving the gingiva are: presence of unilocular intraepithelial blister, reduced stratified epithelial layer and epithelial thickness, normal basal membrane and lamina propria, and the presence of acantholytic cells in the blister [37] (Figure 7).

FIGURE 7.

LC‐OCT of desquamative gingivitis in pemphigus vulgaris: (a) Unilocular intraepithelial blister (yellow star), reduced epithelial layer and thickness, normal BM and lamina propria, with acantholytic cells in the blister. (b) Dark superficial cleft (yellow star) in the stratified squamous epithelium. (c) Intraepithelial split (yellow stars) indicates structural separation in the epithelium.

6. Conclusions

Desquamative gingivitis is a clinical manifestation of a wide range of systemic and mucocutaneous diseases, including oral lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris. An accurate diagnosis involves a combination of clinical assessment, immunopathological and histopathological examinations, and the emerging use of noninvasive imaging techniques. Noninvasive imaging techniques, particularly RCM, OCT, and LC‐OCT, have the potential to revolutionize the diagnostic approach to desquamative gingivitis by improving differential diagnosis, reducing the need for invasive biopsy, and enabling longitudinal monitoring of treatment response. Their integration into clinical practice could enhance early detection of underlying autoimmune and inflammatory conditions, contributing to improved patient outcomes.

In cases of oral lichen planus, RCM often reveals disrupted connective tissue papillae, obscured basement membranes, and inflammatory infiltrates. For pemphigus vulgaris, acantholytic keratinocytes and intraepithelial clefts are the characteristic findings, while in mucous membrane pemphigoid, subepithelial clefts and hemorrhagic features can be visualized (Table 1).

TABLE 1.

Characteristics of desquamative gingivitis in RCM for oral lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris.

Oral lichen planus	Mucous membrane pemphigoid	Pemphigus vulgaris
Focal areas of brightness at the epithelial layers as hyperkeratosis; [1] Partial to complete loss of the normal honeycombed pattern and broadened intercellular connections; [1] Necrotic keratinocytes are seen as mildly bright, polygonal structures, larger than the surrounding keratinocytes, seen as single cells at the epithelium; [1] Round‐to‐polygonal bright structures in the context of epithelial disarray and spongiosis; [1] Presence of inflammatory and bright dendritic cells within the lamina propria; [1] Papillary rims are obscured by the presence of a diffuse inflammatory cell infiltrate, almost completely involving the junction, with total or partial obliteration of the ring‐like structures around papillae that appear “non‐edged” and “non‐rimmed”; [1] Melanophage as brightly refractive, plump, oval to stellate‐shaped cells recognizable within the inflammatory infiltrates in the lamina propria; [60] Round‐to‐polygonal, mildly refractive cells, smaller in size than melanophages seen at the papillary dermis [1]	Separation in the lamina propria, visible as dark spaces filled with small, bright, round‐to‐polygonal, highly refractive cells, identified as blood cells. [1]	An intraepithelial cleft with rounded detached cells as acantholytic keratinocytes, [1] Prominent, round or linear dark, canalicular structures oriented horizontally in the lamina propria as dilated vessels. [1] Inflammatory cells as round‐to‐polygonal, slightly refractive cells, smaller in size than melanophages and keratinocytes [1]

OCT features of desquamative gingivitis in oral lichen planus include preserved epithelial thickness in erosive forms and multilocular blisters in bullous forms of the disease. In pemphigus vulgaris, OCT identifies intraepithelial clefts and thinning of the epithelium, whereas mucous membrane pemphigoid is characterized by subepithelial blistering and fluid accumulation (Table 2). Both modalities demonstrate significant alignment with histopathological findings.

TABLE 2.

Characteristics of desquamative gingivitis in OCT for oral lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris.

Oral lichen planus	Mucous membrane pemphigoid	Pemphigus vulgaris
Erosive OLP: Normal stratified epithelial layer and epithelial thickness, [35] Normal basal membrane and lamina propria, [35] The presence of an intense inflammatory infiltrate. [35] Bullous OLP: Presence of multilocular subepithelial blister, [35] Normal stratified epithelial layer and epithelial thickness, [35] Normal basal membrane and lamina propria, [35] The presence of an intense inflammatory infiltrate [35]	Multilocular subepithelial blister, [37] A dark region between the mucosa and submucosa. The fluid‐filled blisters appeared dark with a notable grayish hue, [47, 48] Normal stratified epithelial layer and epithelial thickness, [37] Altered/indistinguishable basal membrane and lamina propria, [37, 49] The presence of inflammatory infiltrate [37] is described as the alternation of black and gray areas [49]	Unilocular intraepithelial blister with dark superficial clefts, [37, 49] Reduced stratified epithelial layer and epithelial thickness, [37, 49] Normal basal membrane and lamina propria, [37] Presence of acantholytic cells in the blister [37].

LC‐OCT is an emerging new noninvasive diagnostic technique that is based on a combination of the principles of OCT and RCM with line‐field illumination.

Ethics Statement

The ethics statement is not applicable.

Conflicts of Interest

The authors declare no conflicts of interest.

Fałkowska U., Durmaj A., Szwed C., et al. “Noninvasive Imaging Techniques as Modern Diagnostic Tools in Desquamative Gingivitis: Focus on RCM, OCT, and LC‐OCT.” Skin Research and Technology 32, no. 1 (2026): e70236. 10.1111/srt.70236

Data Availability Statement

Further inquiries should be directed to the corresponding author.