Immunopathological diagnosis of cicatricial pemphigoid with desquamative gingivitis. A case report

Cicatricial pemphigoid (CP) is a chronic subepidermal bullous dermatosis which primarily involves the mucous membranes. The oral cavity and the eye are most frequently involved. Since extension of the lesion into the pharynx and esophagus causes sore throat and dysphagia and progressive ocular lesions may cause blindness, early and valid diagnosis is very important. Here we present a case of cicatricial pemphigoid with onset at age 45 in a patient who manifested severe periodontal disease and showed the lesion on the mucous membranes of the mouth (desquamative gingivitis), skin, and eyes. Since definite diagnosis is very important, we describe how we made a differential diagnosis from other diseases which also accompany desquamative gingivitis. We examined the clinical manifestations, blood test results, HLA-genotype, histopathologic findings of the affected tissue, and immunological findings in relation to autoimmunity. Since many of the CP cases are first referred to periodontists or dentists, we believe that the diagnostic strategy described in the present study will be quite informative for making rapid and definite diagnoses of similar cases.     

Subgingival Microbiota in White Patients With Desquamative Gingivitis: A Cross‐Sectional Study

Background: Presence of epithelial desquamation, erythema, and erosions on gingival tissue is usually described in the literature as desquamative gingivitis (DG). A wide range of autoimmune/dermatologic disorders can manifest as DG, although the two more common are oral lichen planus and mucous membrane pemphigoid. The aim of this study is to investigate prevalence of 11 periodontopathogenic microorganisms in patients with DG and to compare it with the microbiologic status of individuals affected by plaque‐induced gingivitis (pGI). Methods: Cross‐sectional clinical and microbiologic data were obtained from 66 patients (33 in each group). Subgingival plaque samples were analyzed using semiquantitative polymerase chain reaction analysis. Results: Statistically significant difference, but with little clinical significance, was observed in gingival conditions between the two groups, probably due to the worse home control hygiene of patients with DG. Prevalence and levels of Aggregatibacter actinomycetemcomitans, Eikenella corrodens, and Fusobacterium nucleatum/periodonticum were statistically higher in samples from patients with DG than in those with pGI. In multivariate regression models, subgingival colonization of A. actinomycetemcomitans and F. nucleatum/periodonticum was not statistically associated with DG, whereas, high levels of E. corrodens were associated with 13‐fold increased odds for DG. Conclusions: Microbiologic differences were found in subgingival plaque for patients with DG and pGI. This may suggest possible association between periodontal pathogens and DG.     

Cicatricial pemphigoid with severe gingival and laryngeal involvement in an 18-year-old female

Cicatricial pemphigoid (CP), also known as mucous membrane pemphigoid, is an autoimmune vesiculobullous disease occurring mostly in elderly people and seldom occurring in individuals under the age of 20 years. It predominantly affects the mucosal surfaces, primarily the oral and conjunctival mucosa. Uncommonly, the upper aerodigestive tract is involved, which can lead to life-threatening complications. We present the case of an 18-year-old girl with desquamative gingivitis and severe laryngeal webbing and stenosis, caused by cicatricial pemphigoid. Airway management necessitated a tracheostomy and additional surgical procedure. The clinical, diagnostic, and therapeutic features of this disease are discussed, focusing on the oral and unique laryngeal manifestations.     

Microorganism presence in desquamative gingivitis

Histologic tissue analysis was retrospectively performed on 19 cases which met the diagnostic criteria of desquamative gingivitis (DG) or benign mucous membrane pemphigoid (BMMP) to determine whether microorganisms were present. Original paraffin blocks were resectioned and tissue specimens were stained with hematoxylin and eosin and with Brown and Brenn solutions. The presence of microorganisms at specific sites was recorded and identification of gram type and histomorphology was made. Bacteria were seen in hematoxylin and eosin and Brown and Brenn stained specimens on the epithelial surface in 31.6% and 68.4% of cases, within the epithelium in 0% and 57.9% of cases, within the subbasilar cleft in 52.6% and 94.7% of cases, and within the submucosa in 5.3% and 57.9% of cases respectively. The epithelial surface was colonized primarily by gram positive cocci (47.4%) and gram negative bacilli (42.1%), which also were the most common types of bacteria seen within the epithelium (26.3% each). 94.7% of specimens examined demonstrated gram negative bacilli within the subepithelial cleft. The predominate form of bacteria found in the submucosa was gram negative cocci (42.1%). Results of this study show that colonization of desquamative gingivitis/benign mucous membrane pemphigoid tissue samples occurs.     

Gingival manifestations of childhood cicatricial pemphigoid

Cicatricial pemphigoid (CP) is found almost exclusively among middle-aged and elderly persons. This article describes a rare case of CP in a 14-year-old girl; it appeared on the mandibular anterior gingiva as desquamative gingivitis. Histologic examination of the lesions showed a subepithelial bulla. Immunofluorescence of gingival biopsy revealed immunoglobulin G, protein C3, and faint immunoglobulin A deposition along the basement membrane zone; results for normal skin were negative. Indirect immunofluorescence produced negative results. There are only six documented cases of childhood CP previously reported in the literature. The clinical and immunologic features of these cases are reviewed.     

Oral mucous membrane pemphigoid in a 6-year-old boy: diagnosis, treatment and 4 years follow-up

Background.  Childhood oral pemphigoid is extremely rare and usually takes the form of desquamative gingivitis.
Case report.  We describe a 6-year-old boy who presented with gingival bleeding, pain, eating difficulty, and peeling of the gums. Clinical examination revealed desquamative gingivitis with no extra-oral involvement. The diagnosis was established as oral pemphigoid based on the clinical, histological, and immunofluorescence findings. Symptoms resolved on treatment with occlusive topical corticosteroids. The patient was a carrier of the HLA-DQB₁*0301 allele.
Conclusion.  Mucous membrane pemphigoid should be considered in the differential diagnosis of chronic desquamative gingivitis in childhood. Occlusive therapy with topical fluocinonide may alleviate the symptoms.     

Expression of estrogen receptors in desquamative gingivitis

BACKGROUND: Most cases of chronic desquamative gingivitis (CDG) are shown by direct immunofluorescence (DIF) to be immune mediated diseases. Some patients present with similar clinical and microscopic findings as CDG but DIF staining is negative. It has been suggested that those cases of CDG may be hormone (estrogen) mediated and may be treated with estrogens with favorable results. METHODS: Gingival tissue from 24 cases of CDG and one case of ordinary gingivitis were studied for estrogen receptor (ER) expression using immunohistochemical techniques. Twenty-four of the 25 cases were female. Using standard DIF analysis, 11 of the CDG cases were diagnosed as benign mucous membrane pemphigoid, 10 as lichen planus or lichenoid mucositis (LP), and one as pemphigus. The remaining 3 cases were not diagnostic for a specific disorder (idiopathic). Five of the females had a history of estrogen substitute therapy. RESULTS: Twenty-two of 23 female CDG cases were positive for ER, although the degree of staining varied. A 32-year-old female with ordinary gingivitis, whose gingivitis varied with her menstrual cycle, did not stain for ER. A 50-year-old male and a 76-year-old female, both with gingival LP, also had negative staining for ER. CONCLUSIONS: There appears to be no correlation between diagnosed diseases (immunological versus idiopathic) and expression of ER in CDG gingiva. ER expression in the gingiva is probably not related to the presence or absence of estrogen supplementation. The results of this study do not support the use of estrogen in the treatment of idiopathic CDG.     

Adult linear immunoglobulin A disease manifesting as desquamative gingivitis

Desquamative gingivitis is a manifestation of various dermatoses, particularly lichen planus and mucous membrane pemphigoid. A rare example of adult linear immunoglobulin A disease manifesting as desquamative gingivitis is presented. Although the initial clinical features were typical of desquamative gingivitis, the persistence of ulceration after dental extractions was unusual, and the management of the oral lesions proved difficult. The clinical, immunopathologic, and therapeutic aspects of linear immunoglobulin A dermatoses are reviewed.     

Mucous membrane pemphigoid: a disease of the elderly

Mucous membrane pemphigoid (MMP) is a vesiculo-bullous, mucocu-taneous disease that generally affects elderly people. The diagnosis of mucous membrane pemphigoid may be overlooked since the disease is often confined to the mouth and desquamative gingivitis may be the only symptom. Gerodontic patients with this condition are often diagnosed as having "desquamative gingivitis" without obtaining the proper therapy to control chronic pain and effect disease remission. The discomfort associated with eating may prevent many elderly patients from obtaining adequate nutrition. Topical and/or systemic corticosteroid therapy are the only available methods of managing this condition. Immu-nologic studies support the autoimmune nature of MMP and infer that it may be a variant of bullous pemphigoid .     

Diagnostic pathways and clinical significance of desquamative gingivitis

The term desquamative gingivitis (DG) refers to a clinical manifestation that can be caused by several disorders. Many of them are immunologically mediated; in addition to the oral cavity, they can affect extraoral mucocutaneous sites, e.g., larynx, conjunctiva, esophagus, nasal and genital mucosa, and the skin. The degree of oral, periodontal, and systemic involvement determines the overall morbidity and, sometimes, the mortality of these disorders. We comprehensively review disorders commonly associated with DG and highlight diagnostic pathways, guidelines for differential diagnosis, and oral, periodontal, and systemic implications. More rare conditions are reviewed as well. Mucous membrane pemphigoid, oral lichen planus, and pemphigus vulgaris are responsible for the majority of cases of DG. In addition, other uncommon disorders should be considered. Accurate clinical, histologic, and serologic investigations are often required to differentiate among DG-associated disorders, provide adequate therapy, and improve the prognosis of patients.     

The management of intransigent desquamative gingivitis with Dapsone

Fifteen patients suffering from intransigent desquamative gingivitis due to lichen planus or benign mucous membrane pemphigoid were treated with dapsone (diphenylsulphapyridine) over a 3-month period. Twelve patients completed the trial. Therapeutic benefit was estimated clinically with the aid of 35mm color transparencies taken at 4-week intervals; and subjectively by the patients estimating their progress as worse, no change, some improvement or complete recovery. Taken as a whole, some 58% of patients had some benefit from therapy. Of the 7 patients with lichen planus, 1 showed complete recovery and 3 showed some improvement. In the 5 patients with desquamative gingivitis due to mucous membrane pemphigoid, 3 showed some improvement and 2 received no benefit. Three patients withdrew from the trial due to side effects of the dapsone such as headaches and nausea. It is concluded that dapsone therapy may be of some use in the management of desquamative gingivitis when traditional treatments have failed. Patients should be warned of the possibility of side effects.     

Desquamative gingivitis associated with IgG/IgA pemphigoid presents a challenging diagnosis and treatment: a case report

BACKGROUND: Mucous membrane pemphigoid (MMP) is a heterogeneous group of autoimmune blistering disorders characterized by subepithelial separation and the deposition of immunoglobulins and complement along the basement membrane zone (BMZ). This disease is diagnosed with direct immunofluorescence testing showing a linear deposition of immunoglobulins and/or complement along the BMZ and indirect immunofluorescence testing showing circulating IgG (and sometimes IgA) autoantibodies along the BMZ. In this case report we describe desquamative gingivitis secondary to IgG/IgA pemphigoid and the management of this challenging variant of MMP. METHODS: Routine histology, direct immunofluorescence testing, and indirect immunofluorescence testing were utilized and correlated to the clinical findings to diagnose this unusual immunobullous disease. RESULTS: Direct and indirect immunofluorescence testing confirmed the clinical diagnosis of IgG/IgA pemphigoid as the cause of desquamative gingivitis and the other mucosal findings in this patient. A treatment program including dapsone and other drugs completely resolved the oral lesions after 14 months of therapy. CONCLUSIONS: Desquamative gingivitis associated with IgG/IgA pemphigoid can be challenging to diagnose and treat. After 14 months of treatment, a combination therapy consisting of dapsone with cimetidine and vitamin E to enhance drug efficacy and frequent intramuscular administrations of triamcinolone achieved control of both the oral and genital elements of IgG/IgA pemphigoid in this patient.     

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.     

Clinical features of gingival pemphigus vulgaris

BACKGROUND: Pemphigus vulgaris (PV) is a rare, chronic, intraepithelial bullous disease with a potentially fatal outcome. Oral lesions are a hallmark of PV and occur in almost all cases, and represent the preliminary symptom in more than half of the patients. Gingival lesions are very common and, when solitary, often first recognized by periodontist. METHOD: In the literature, gingival localization of PV are usually described as desquamative gingivitis (DG) and/or as vesiculobullous lesions of the free and attached gingiva; in our experience, early lesions only rarely appears as extensive erythema and erosions. CONCLUSIONS: PV at the onset may frequently appear on gingiva as isolated blisters and/or erosions mainly located to the free gingiva, very little in extension and hardly to recognize as bullous lesions.     

Plurimucosal cicatricial pemphigoid. A case with involvement of the gingival, vulval and vaginal mucosa

We have studied a 62 years old woman with the infrequent involvement of the gingiva (desquamative gingivitis), vulvar and vaginal mucouses in benign mucosal pemphigoid. The clinical features and pathology are exposed and we debate differential diagnosis principally with pemphigus and lichen planus.     

Immunofluorescent studies in desquamative gingivitis

Twenty-seven patients (19 females and 8 males) with a clinically diagnosed desquamative gingivitis were used in this study. Twenty-seven additional patients with oral and skin diseases and with gingival involvement other than that of the de-squamative gingivitis type served as controls. Biopsy gingival specimens were sectioned and stained with H and E. The rest of the tissue specimen was cut with a cryostat and used for immunofluorescent assays of the tissue-bound antibodies (IgG, IgA, IgM, C3 and fibrin). Circulating antibodies were determined by using the indirect immunofluorescence method in serum samples. Normal human oral mucosa and several animal epithelial tissues were used as substrates. The immunopathologic findings suggest the diagnosis of lichen planus in the presence of linear or granular fibrin deposition at the basement membrane zone/mucosal submucosal interface with or without cytoid bodies and cicalricial pemphigoid, in the presence of circulating and/or tissue-bound immunoglobulins and C3 in a linear continuous pattern along the BMZ. It is suggested that an accurate diagnosis of the underlying disease of the desquamative gingivitis can be made on the basis of the clinical, histopalhologie, immunopathologic and follow-up findings.     

Childhood cicatricial pemphigoid with exclusive gingival involvement

A case of cicatricial pemphigoid in a 13-year-old boy presenting in the form of desquamative gingivitis is described. There are only 7 documented cases of childhood cicatricial pemphigoid reported in the literature.     

Gingival lesions diagnosed as pemphigus vulgaris in an adolescent. Case report.

Desquamative gingivitis (DG) is a fairly common disorder in which the gingivae show chronic desquamation. Originally considered to be related to hormonal changes at menopause, since many of the patients are middle-aged women, DG is now recognized to be mainly a manifestation of a number of disorders ranging from vesiculobullous diseases to adverse reactions to a variety of chemicals or allergens. Desquamative gingivitis can be an important early clinical manifestation of serious systemic diseases such as pemphigus vulgaris. The authors present a case that illustrates the importance of a specific diagnosis in patients with desquamative gingival lesions previously treated for 6 months as classical gingivitis. Gingival biopsy showed histologic patterns typical of pemphigus vulgaris. The patient was treated with systemic and topical corticosteroids in association with miconazole. The patient is now under control with low-dose systemic corticosteroids. Proper recognition of lesions in the oral mucosa leads, in several situations, to an early diagnosis of a systemic disease.     

Periodontal clinical and microbiological data in desquamative gingivitis patients

Objectives

A series of patients affected by desquamative gingivitis (DG) was investigated in order to evaluate relation patterns among clinical parameters relevant to plaque-induced periodontitis, periodontal microbiological data and the presence of DG lesions.

Patients and methods

Eight oral lichen planus (OLP) and four mucous membrane pemphigoid (MMP) patients were examined. Periodontal measurements (performed at six sites per tooth on all teeth) included probing depth (PD), gingival recession (REC), clinical attachment loss (CAL) and full-mouth plaque (FMPS) and bleeding (FMBS) scores; the presence and the exact location (site by site) of DG lesions were carefully recorded. Sub-gingival plaque samples were collected and examined by means of real-time PCR for the quantitative determination of the six most important marker organisms of periodontitis. Statistically significant differences and correlation of studied variables between DG-positive and DG-negative sites were investigated in MMP and OLP cases using Mann–Whitney test (p?<?0.05) and the Spearman rank correlation coefficient, respectively.

Results

OLP gingival lesions do not significantly affect CAL, although the presence of such lesions may reduce REC and increase PD and FMPS. MMP gingival lesions significantly worsened CAL and increased REC and FMPS. In both OLP and MMP cases, no significant difference was found between DG-positive and DG-negative sites as regards the relative percentage of the investigated species on the total bacterial load. Correlations between the presence of DG lesions and clinical parameters (CAL, PD, REC) were not significant (p?<?0.05). Significant correlations were found for the presence of gingival OLP lesions and Aggregatibacter actinomycetemcomitans (AA) and for the absence of gingival MMP lesions and AA.

Conclusions

These findings are not definitive, but highlight the need for further investigations of periodontal clinical and microbiological aspects of disorders causing DG in order to clarify their potential interference with plaque-related periodontitis.