High frequency of upper aerodigestive tract manifestations in mucous membrane pemphigoid.

OBJECTIVE: The objective of this study was to evaluate the frequency of upper aerodigestive tract involvement in patients with mucous membrane pemphigoid associated with desquamative gingivitis. SUBJECTS AND METHODS: Data from 25 patients were collected by retrospective chart review. Their upper aerodigestive had been evaluated using a conventional flexible fiberscope. Oral disease activity was quantified on the basis of the Mucous Membrane Pemphigoid Disease Area Index activity score. RESULTS: Lesions of the upper aerodigestive tract were confirmed in nine symptomatic patients (9/25, 36%), of which five (5/25, 20%) had laryngeal involvement. No lesions were seen in the asymptomatic patients on fiberscope examination. There was a statistically significant difference in the symptoms, high oral disease activity score, and linear IgA deposition on direct immunofluorescence between patients with and without upper aerodigestive tract lesions (p = .001, .001, .002, respectively). CONCLUSION: The high frequency of considerable complications highlights the importance of confirming the presence of upper aerodigestive tract involvement in patients with mucous membrane pemphigoid having desquamative gingivitis. Signs including the presence of symptoms, high oral disease activity score, or linear IgA deposition on direct immunofluorescence might indicate a higher risk of upper aerodigestive tract involvement.

Surgical considerations and management of patients with mucocutaneous disorders.

Surgeons may be confronted with providing periodontal plastic or implant therapy for patients with gingival manifestations of systemic conditions. These conditions (often referred to as mucocutaneous disorders) commonly present with features of desquamative gingivitis, which was once believed to represent a disease entity. However, today, the term desquamative gingivitis is used to describe clinical features of various local or systemic diseases or disorders that result in chronic gingival lesions characterized by epithelial desquamation, erythema, ulceration, and/or vesiculobullous lesions of the gingiva. Often, other oral tissues also are involved. Mucocutaneous disorders include such disease entities as lichen planus, graft-versus-host disease, pemphigoid, pemphigus vulgaris, lupus erythematosus, erythema multiforme, and linear IgA disease. Surgeons should be able to recognize these disorders and have the tools necessary to treat these conditions so that they can render the appropriate surgical care. This article describes the diagnosis, etiology, and clinical manifestation of these disease entities, as well as the surgical considerations and management in providing care to these patients.

Acantholysis may precede elevation of circulating anti-desmoglein 3 antibody levels in pemphigus vulgaris presenting with desquamative gingivitis.

Pemphigus vulgaris (PV) is an autoimmune, blistering disease that affects the mucosa and skin. The current theory favors the concept that anti-desmoglein (Dsg) 3 autoimmunity is the only pathogenic event needed to induce acantholysis. However, a few cases of active PV in the oral cavity had no detectable anti-Dsg 3 antibody. The aim of this study was to evaluate the differences in clinical and laboratory findings, whether or not the anti-Dsg 3 antibodies were present. This study was based on a retrospective review of 10 PV cases. The evaluation of the circulating autoantibody titers to Dsg 3 was conducted by using enzyme-linked immunosorbent assay (ELISA). An index value of 20 or more was used as the cutoff for a positive reaction. Only five of the 10 PV cases had a positive Dsg 3 ELISA. There were no differences in clinical, cytological, histopathological, and direct immunofluorescence findings, whether or not the anti-Dsg 3 antibodies were present. Of the five patients with a negative reaction at the time of diagnosis, the Dsg 3 ELISA became positive in the follow-up period in three cases. In the remaining two cases, the Dsg 3 ELISA was consistently negative for 18 months. Dsg 3 ELISA was negative early in some PV cases. Therefore, PV acantholysis may precede the elevation of circulating anti-Dsg 3 antibody levels. The diagnosis of PV should be considered based on comprehensive clinical, histopathological, and immunofluorescent criteria.

Exophytic mass of the gingiva as the first manifestation of metastatic pulmonary adenocarcinoma.

BACKGROUND: Metastasis of a malignant tumor to the oral cavity is rare, but it can be the first manifestation of a primary tumor. METHODS: The clinicopathologic features of a gingival metastasis originating from lung adenocarcinoma in a female patient are described. A 57-year-old woman showed a rapidly growing, painless, exophytic mass in the left mandibular gingiva. The whole lesion was excised, and histologic and immunohistochemical analyses were performed. RESULTS: The histopathologic sections showed a proliferation of poorly differentiated spindle and pleomorphic cells. Because the differentiation between carcinoma and sarcoma of spindle cell tumors was difficult, additional immunohistochemical evaluation was performed. The intraoral healing after tumor removal was uneventful. The discrepancy between the histopathologic results and the clinical findings led to a thorough examination by the patient's physician. Finally, a biopsy of the lungs confirmed a poorly differentiated adenocarcinoma with multiple metastases, including the oral cavity. CONCLUSIONS: An exophytic lesion on the gingiva can be the first sign of metastatic adenocarcinoma to the oral mucosa. This case emphasizes that even apparently benign-looking gingival lesions in anamnestically healthy patients need to be examined histopathologically.

Disease progression from mucosal to mucocutaneous involvement in a patient with desquamative gingivitis associated with pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) frequently begins with oral lesions and progresses to skin lesions. A patient is described who developed skin lesions during follow-up and whose only initial symptom was desquamative gingivitis (DG). METHODS: A 31-year-old woman presented with a 2-month history of painful gingiva. The diagnosis of PV was made according to clinical, histopathological, and immunofluorescent criteria. Topical corticosteroid (0.1% triamcinolone acetonide) was provided for the treatment of DG. Evaluation of the circulating autoantibody titers to desmoglein (Dsg)1 and Dsg3 was conducted by enzyme-linked immunosorbent assay (ELISA). RESULTS: The gingival PV lesions went into remission with the use of topical corticosteroid, although the patient experienced occasional recurrent oral lesions that required retreatment. She had regular follow-ups and remained relatively stable for several months. However, relapse and worsening of the oral lesions and the onset of skin lesions occurred after 26 months. Using ELISA, a change in the autoantibody profile corresponding to the transition from mucosal PV to mucocutaneous PV was confirmed. In all ELISA studies conducted throughout the course of the patient's disease, the Dsg3 ELISA was consistently high ranging from 150 to 200. However, the Dsg1 ELISA remained low, ranging from 10 to 30. After 26 months, Dsg3 (index value of 150) and Dsg1 (index value of 114) ELISA levels were elevated, consistent with the transition to mucocutaneous PV. CONCLUSIONS: In cases in which the lesions are limited to the oral cavity, PV sometimes may be managed successfully using only topical corticosteroids. However, it may not be possible to reduce the circulating Dsg autoantibody titers without systemic immunosuppression. The sustained high Dsg3 antibody level may cause "epitope spreading" and induce skin lesions. It may be prudent to determine post-treatment levels of Dsg using ELISA and, in consultation with the physician, recommend the addition of systemic therapy if Dsg3 levels remain elevated.

Cinnamon products as a possible etiologic factor in orofacial granulomatosis.

OBJECTIVES: It has been reported that clinical changes due to hypersensitivity reactions to various foods, preservatives, and oral hygiene products may be consistent with the characteristic signs of orofacial granulomatosis (OFG). The objective of this study was to examine 37 well-documented cases of cinnamon-induced contact stomatitis for clinical and histological features consistent with a diagnosis of OFG. STUDY DESIGN: We reviewed the records of the 37 cases to screen them for the clinical and histopathologic features of OFG. RESULTS: Twelve patients showed clinical characteristics of OFG. The most commonly affected site was the gingiva. Focal non-caseating, epitheloid granulomas were observed in four histologic specimens. Multinucleated giant cells were observed in an additional four cases. CONCLUSIONS: Although OFG may have multiple etiologies, it is clear that, in some instances, a hypersensitivity reaction to cinnamon products can elicit lesions consistent with OFG.

Periodontal status in patients with gingival mucous membrane pemphigoid.

BACKGROUND: Mucous membrane pemphigoid (MMP) describes an autoimmune disease with a range of variants, including those with oral, ocular, and cutaneous lesions. Persistent oral lesions, lack of effective oral hygiene, and plaque accumulation may increase the risk of long-term periodontal disease. However, to our knowledge, no studies have evaluated the relationship between the presence of gingival MMP and periodontal health. The purpose of this study was to evaluate the possible impact of gingival pemphigoid lesions on the human periodontium. METHODS: Twenty patients with histologic confirmation of subepithelial separation with or without direct immunofluorescence testing were randomly chosen to participate in a study evaluating their periodontal status. Parameters evaluated included plaque score, gingival index, bleeding index, probing depths, recession, clinical attachment level, mobility, furcation involvement, number of missing teeth, and Machtei criteria, a previously defined criteria for periodontitis. Individuals matched with respect to age, gender, and smoking history were selected and evaluated for the same parameters. RESULTS: MMP patients had statistically significant larger mean gingival index scores than age, gender, and smoking history matched controls. Plaque scores, bleeding index, mobility, furcations, clinical attachment level, recession, and periodontal status did not show statistically significant differences between MMP and control patients. A statistically significant difference in plaque index was found when patients with MMP in treatment were compared to patients with MMP in remission. Among patients with MMP, those diagnosed >5 years in the past had statistically significantly greater Class I furcation involvement and recession on facial and lingual surfaces of teeth. CONCLUSIONS: A relationship was found to suggest that patients with MMP exhibit more gingival inflammation than a control population. Among patients with MMP, patients currently in treatment have higher plaque indices than those in remission and not receiving treatment. Furthermore, when comparing patients with MMP who received a diagnosis>5 years in the past to those with a diagnosis in the past 5 years, statistically significantly greater Class I furcation and facial and lingual recession were measured. Long-term follow-up in this population may provide additional information as to periodontal progression in MMP versus control patients.

Oral lichen planus and malignant transformation: a retrospective follow-up study of clinical and histopathologic data.

OBJECTIVE: Patients in the stomatology service of the Department of Oral Surgery and Stomatology who were clinically and histopathologically diagnosed with oral lichen planus (OLP) in the years 1995 to 2001 were examined for a possible malignant transformation of a previously biopsied OLP site. METHOD AND MATERIALS: For the 145 patients included, the recordings were searched for initial localization and type of OLP lesion, potential noxious agents, distribution between symptomatic and asymptomatic OLP types, and for a malignant transformation of a known OLP site during the follow-up period up to December 2003. RESULTS: The group comprised 47 men and 98 women with a mean age of 56.3 years. Of the 497 lesions, almost half were classified as reticular or papular, predominantly located on the buccal mucosa, gingiva, and borders of the tongue. Four patients did not adhere to their scheduled control visits and were dropped from the study. During the follow-up period 4 patients developed malignant transformation of OLP. In 3 of these cases, dysplasia was present at the initial diagnosis of OLP. This results in a malignant transformation rate of 2.84% among the remaining 141 patients; if the 3 patients with initial dysplasia are excluded, the rate drops to 0.71%. CONCLUSIONS: Until further knowledge is derived from large prospective studies, the data supporting or negating a potential malignant character of OLP lesions remains inconclusive. Special emphasis has to be directed toward unified inclusion and exclusion criteria regarding clinical and histologic findings and identifiable risk factors to allow the comparison of different studies.

Clinical features of cinnamon-induced contact stomatitis.

Cinnamon flavoring agents are known to act on the mucosa as irritants or sensitizers. The objective of this study was to report on clinical and histologic features important in the diagnosis of cinnamon-induced contact stomatitis. We examined 37 past cases of contact stomatitis and identified clinical signs and symptoms and possible causes. The most common cause in the 37 cases was toothpaste; other causes were chewing gum and foods. Although various clinical findings were observed, some characteristics were evident. The most commonly affected site was the gingiva, which showed diffuse or generalized erythema and epithelial sloughing. It is important to identify the causative agents of such a disorder by understanding characteristic signs and symptoms and conducting an appropriate inquiry.

Treatment of refractory facial pain diagnosed as atypical trigeminal neuralgia: a case report.

This case report describes an effective treatment protocol, the healing process, and the recovery of the patient to a pain-free status after more than 25 years of failed treatment for facial pain. Features of this case report include: 1. A procedure to produce a phenomenon useful as a pathognomonic sign of autonomic nervous system neuropathy, as a determination of the location of the origin of pain, and as a monitoring device for the effectiveness of treatment. 2. A digital pressure intervention procedure that appears effective as a treatment modality to relieve pain and to effect healing. 3. A method to improve posture of the body affecting the relationship of the maxilla to the mandible, the dental occlusion, and the etiology of facial pain. 4. A description of the nature and intensity of the different levels of the pain experienced in the face from the most severe state of pain to a no-pain condition. 5. A diagnosis using a diagnostic term that has developed since the initial diagnosis of atypical trigeminal neuralgia in this case.

Clinical and diagnostic features of mucous membrane pemphigoid.

The aim of this study was to characterize the clinical and diagnostic features of mucous membrane pemphigoid (MMP). Five MMP patients were evaluated, and biopsies were obtained for routine histopathology and direct immunofluorescence. Circulating autoantibodies were verified by indirect immunofluorescence. Circulating immunoglobulin G autoantibody specific for 180 kDa bullous pemphigoid antigen (BP180) was evaluated by enzyme-linked immunosorbent assay (ELISA). All 5 patients complained of erythematous gingiva. Two patients had extraoral lesions involving the nasal mucosa, eyes, and skin. Histopathological confirmation was established for 4 of the patients, while direct immunofluorescence findings were positive in all 5. Although circulating autoantibodies were not identified by indirect immunofluorescence, the BP180 ELISA was positive in 3 cases. Both histopathological and direct immunofluorescence examinations are essential to establish a definitive diagnosis. Identification of circulating BP180 specific autoantibody shows promise.

A randomized controlled trial evaluating antioxidant-essential oil gel as a treatment for gingivitis in orthodontic patients.

OBJECTIVE: To evaluate the treatment effect of an antioxidant-essential oil gel on orthodontic patients with generalized gingivitis. The gel contains the essential oils menthol and thymol and the antioxidants ferulic acid and phloretin. MATERIALS AND METHODS: Thirty patients from the university's orthodontic clinic were screened for gingivitis and randomly allocated into treatment and placebo-control groups. Each patient was evaluated at three orthodontic treatment visits (T1, T2, and T3). A periodontal examination, including probing depth (PD), bleeding on probing (BOP), gingival index (GI), and plaque index (PI) was performed at each visit. Between T1 and T2, patients were instructed to apply a topical gel (active or placebo) to their gingiva twice daily after brushing. From T2 to T3, patients were instructed to discontinue use of the gel. RESULTS: The treatment group showed statistically significant (P < .05) reductions of BOP (-13.6 percentage points) and GI (-0.14) between T1 and T2, and significant increases in BOP (13.3 percentage points) and GI (0.14) between T2 and T3. Except for an increase in the GI between T2 and T3, the control group showed no significant changes in BOP or GI over time. The only other significant changes that occurred pertained to the treatment group, which showed significant increases in PD (0.08 mm) and PI (0.18) between T2 and T3. CONCLUSION: Application of a topical antioxidant-essential oil gel is an effective means of reducing inflammation in orthodontic patients with gingivitis.

Early detection and successful management of oral pemphigus vulgaris: a case report.

BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune disease characterized by acantholysis in the epithelium. PV is often difficult to diagnose in the early stages, since the oral lesions are relatively nonspecific. We report on a case with a favorable outcome due to early diagnosis and effective treatment of oral lesions. METHODS: A 53-year-old Japanese woman presented with a month-long history of painful gingiva. PV was diagnosed using clinical, histopathological, and direct immunofluorescence criteria 1 month after the first visit. Evaluation of the circulating autoantibody titers to desmoglein (Dsg)1 and Dsg3 was conducted by enzyme-linked immunosorbent assay (ELISA). Occlusive steroid therapy (OST) using a topical corticosteroid (0.1% triamcinolone acetonide) was provided for 8 weeks. After OST was completed, a buccal frenectomy was performed to eliminate localized toothbrushing trauma. RESULTS: There were no adverse effects on wound healing after the procedure. No oral PV lesions were detectable at the 9-month reevaluation, and the patient remains in complete remission. The Dsg1 ELISA was negative while the Dsg3 ELISA was indeterminate at the first visit. The Dsg1 ELISA was also negative at reevaluation, but Dsg3 ELISA reactivity had increased 9 months after completion of treatment. CONCLUSION: Large scale clinical trials will be required to validate the clinical benefits of the OST treatment regimen, and further research is necessary to determine the importance of ELISA antibody examination in long-term management of oral PV.

A stab-and-roll biopsy technique to maintain gingival epithelium for desquamative gingivitis.

BACKGROUND: Desquamative gingivitis (DG) is a clinical manifestation common to several diseases. It is known that most cases of DG are caused by mucous membrane pemphigoid (MMP), oral lichen planus (OLP), or pemphigus vulgaris (PV). Early recognition and treatment of these diseases can improve the prognosis, but diagnostic delays are common in patients with DG because obtaining a diagnostic biopsy is technically challenging. A biopsy technique designed to maintain the gingival epithelium for patients with DG was developed. The usefulness of this technique is discussed. METHODS: This study is based on a retrospective review of 27 DG cases. A stab-and-roll technique was used to obtain gingival tissue. This technique is designed to reduce lateral forces on the epithelium during the procedure and to thereby prevent the inadvertent removal of the epithelium from the biopsy specimen. A total of 52 biopsies comprising 27 for hematoxylin and eosin (H&E)-stained samples and 25 for direct immunofluorescence (DIF) testing were reviewed. RESULTS: Fifty-one of the 52 biopsies (98.1%) maintained the epithelium. Only one biopsy (1.9%) showed that the epithelium was totally absent. Therefore, H&E and DIF features of 51 biopsies were analyzed. Definitive diagnoses of the diseases causing DG included MMP (13 cases), PV (eight cases), and OLP (six cases). CONCLUSIONS: A diagnostic biopsy was obtained from the gingiva of patients with DG using the stab-and-roll technique. The gingival epithelium was well maintained, and the relationship with the underlying connective tissue was diagnostic. In the future, this stab-and-roll biopsy technique may facilitate early diagnosis and treatment of diseases causing DG.

A comparative study of root defect coverage using an acellular dermal matrix with and without a recombinant human platelet-derived growth factor.

BACKGROUND: The objective of this case series is to compare root defect coverage results and healing responses of bilateral recession defects treated with acellular dermal matrix (ADM) with and without recombinant human platelet-derived growth factor (rhPDGF). METHODS: Seventeen patients with 40 bilateral gingival recession defects were compared. Each defect was ≥2 mm and treated with ADM and a coronally advanced flap. Using split-mouth design, the control-side ADM was hydrated in sterile saline, whereas the test-side ADM was hydrated in rhPDGF. The patients were evaluated at 1 week, 1 month, 3 months, and 6 months. Standardized measurements were taken preoperatively at 3 and 6 months. Healing was clinically assessed at 1 week and 1 month post-surgically. RESULTS: Both test and control groups showed significant gain in root defect coverage over the 6-month period for all individuals, with the test group showing a 69.0% gain and the control group showing a 76.7% gain. Patients divided into Miller Class I and Class III defects were also found to have a significant gain in root defect coverage over 6 months. The test group showed 84.1% gain, and the control group showed 84.7% gain for Miller Class I defects. For Miller Class III defects, the test group showed 51.5% gain, and the control group showed a 60.8% gain. One week after surgery, 35% of the test group showed better healing, whereas 15% of the control group showed better healing. One month after surgery, 20% of the test group showed better healing, whereas 15% of the control group showed better healing. CONCLUSION: Based on the results of this case series, there were no statistically or clinically significant differences in root defect coverage, keratinized tissue, clinical attachment level, or clinical healing for treatment of root recession with a coronally advanced flap and ADM with and without rhPDGF.

A comparison of the periodontal status in patients with mucous membrane pemphigoid: a 5-year follow-up.

BACKGROUND: Mucous membrane pemphigoid (MMP) is a heterogeneous group of blistering autoimmune disorders of unknown etiology. Intraoral manifestations of MMP feature the formation of vesiculobullous lesions that eventually rupture, leading to pseudomembrane-covered, irregularly-shaped ulcerations. The presence of these often painful oral lesions may hinder oral hygiene efforts resulting in increased plaque accumulation and may increase the risk of developing periodontal disease. The purpose of this study was to evaluate the changes in periodontal status in patients with MMP after a period of 5 years. METHODS: Twenty patients, 10 diagnosed with MMP and 10 controls matched for age, gender, and smoking history, were chosen to participate in a study evaluating their periodontal status. Parameters evaluated included the plaque index, gingival index, bleeding index, probing depths, recession, clinical attachment level, mobility, furcation involvement, number of missing teeth, and periodontitis. Data from the same MMP and control patients were available for comparison from an identical baseline evaluation performed 5 years earlier. RESULTS: Patients with MMP exhibited a statistically significant higher gingival index and amount of lingual gingival recession at both time periods compared to controls. Both groups exhibited statistically significant increases in attachment loss and facial/lingual recession, but the difference in change between groups was not statistically significant. CONCLUSIONS: The results of this study suggest that patients diagnosed with MMP appear to be no more at risk than controls matched for age, gender, and smoking history in developing or having an increased progression of periodontal disease.

Use of oral exfoliative cytology to diagnose desquamative gingivitis: a pilot study.

OBJECTIVE: To evaluate the usefulness of exfoliative cytology as a diagnostic tool for patients with clinical symptoms of desquamative gingivitis. METHOD AND MATERIALS: Fifteen patients clinically diagnosed with desquamative gingivitis were evaluated. At their first visit, a cytologic smear was performed on the gingival lesion. On their second visit, a gingival biopsy was obtained from the perilesional site. Control smears were taken from 15 patients who had no oral lesions. RESULTS: The cytologic findings showed diffuse or collective Tzanck cells in 3 of the 15 cases. The findings of the other 12 cases were nonspecific inflammatory changes compared to the control. The definitive diagnosis for each case was made according to histopathologic and direct immunofluorescence (DIF) findings. The 3 cases in which Tzanck cells were recognized in the cytologic smear were subsequently diagnosed as pemphigus vulgaris. The cases in which only nonspecific cytologic findings were obtained were later diagnosed by biopsy and DIF as mucous membrane pemphigoid or lichen planus. CONCLUSION: All the cytologic findings of the 15 patients, except for 3 cases in which Tzanck cells were found, were nondiagnostic. Therefore, the use of exfoliative cytology does not appear to be appropriate as a diagnostic tool for patients showing the clinical symptoms of desquamative gingivitis, because this technique adds to the cost and delays the definitive diagnosis. However, using the cytologic technique may occasionally be of some value as a minimally invasive screening tool when pemphigus vulgaris is suspected.