The management of oral mucous membrane pemphigoid with dapsone and topical corticosteroid

Statement of problem:  Mucous membrane pemphigoid (MMP) is a chronic autoimmune subepithelial disease that primarily affects the mucous membranes of patients over the age of 50 years, resulting in mucosal ulceration and subsequent scarring.
Purpose:  The purpose of this study was to investigate the efficacy of dapsone in combination with topical corticosteroids to treat the oral lesions of MMP.
Materials and methods:  Twenty-two patients who had been diagnosed with MMP were selected. The oral features were graded according to severity of disease from 1 to 3. Each patient was assigned to one of four groups according to his or her response to therapy.
Results:  Five patients with mild to moderate disease were treated with topical corticosteroids alone for the duration of the study; 15 patients with moderate to severe disease were treated by topical corticosteroid with dapsone therapy. All of 15 patients had significant benefits.
Conclusions:  The use of dapsone in combination with topical corticosteroids is one of the most useful methods for the treatment of MMP.     

Urban legend series: mucous membrane pemphigoid

Mucous membrane pemphigoid (MMP) is a heterogeneous group of autoimmune subepithelial blistering diseases affecting primarily mucous membranes showing marked degree of clinical and immunological variability. We investigated four controversial topics: (i) Does oral pemphigoid (OP) really exist as a separate entity? (ii) Is mucous membrane pemphigoid curable? (iii) What is the best therapeutic option for MMP? (iv) Does exclusive oral IgA dermatitis exist as a distinct entity from MMP? Results from extensive literature searches suggested that (i) it is still unclear whether patients with OP could be considered as a distinct subset of MMP with specific clinical and immunological features; (ii) it is uncertain whether treatment regimens that get MMP under control can be eliminated to allow patients to be in drug‐free remission or they should be continuously administered in some capacities; (iii) there is a concerning paucity of good‐quality trials on MMP and available recommendations are solely based on generally small patients' cohorts or case series. Some of the 2002 consensus experts' opinions should be possibly updated, particularly regarding the safety of sulfa drugs; (iv) we did not find any strong evidence to support an exclusive oral (and perhaps also mucosal) form of LAD as a separate entity.     

Successful treatment of mucous membrane pemphigoid with tacrolimus

Mucous membrane pemphigoid (MMP) is a heterogeneous group of autoimmune, chronic inflammatory subepithelial vesiculobullous disorders. It predominantly affects the mucous membranes of the oral cavity and eyes of the elderly population. Oral manifestations of pemphigoid include desquamative gingivitis, ulcers, erythematous patches, erosions, vesicles and bullae located on the attached gingiva, palate, buccal mucosa, labial mucosa, and tongue. Diagnosis is based on history, clinical features and a biopsy stained with hematoxylin and eosin (H&E), and also direct and indirect immunofluorescence. Topical and systemic corticosteroids are the most commonly used medications for managing pemphigoid. Recently, topical tacrolimus has been successfully used in the treatment of ocular and skin pemphigoid. In this report we present a patient with longterm recalcitrant MMP that did not respond to conventional treatment but was treated successfully with tacrolimus ointment.     

Vesiculo-bullous mucocutaneous disease: benign mucous membrane and bullous pemphigoid

Bullous pemphigoid (BP) and benign mucous membrane pemphigoid (BMMP) are autoimmune diseases characterised by subepithelial bulla formation and showing substantial overlap in clinical signs and symptoms. BP principally involves skin and BMMP the oral mucosa and eyes. The gingiva are affected in 90% of cases of BMMP and buccal mucosa and palate in up to 30%. Lesions may heal with scarring. Extension into the pharynx and esophagus causes sore throat and dysphagia. Severe ocular involvement may cause blindness. Bulla formation is attributed to complement activation, following IgG binding to the basement membrane zone, with subsequent polymorphonuclear leukocyte accumulation. The target antigen in BP is a 180-230 kD protein associated with the basilar membrane of basal keratinocytes. The gene encoding the BP antigen has been partially cloned. It is likely that the same antigen is involved in BMMP, but the mechanism of scarring is not understood. Treatment of BP and BMMP includes systemic steroid and azathioprine therapy and topical steroids.     

Periodontal status in oral mucous membrane pemphigoid: initial results of a case‐control study

Oral Diseases (2010) 17 , 90–94 Objective: To evaluate the periodontal status of mucous membrane pemphigoid (MMP) patients and compare it with that of healthy controls. Methods: A prospective study was undertaken to examine the impact of gingival MMP lesions on the human periodontium of 29 patients. Parameters evaluated included full mouth plaque score (FMPS), full mouth bleeding upon probing scores, probing depths (PD), gingival recession, clinical attachment level (CAL), mobility score, furcation involvement, number of missing teeth and Machtei criteria. Results: All periodontal parameters recorded were increased in cases when compared to controls in univariate statistics. The mean differences between groups in PD (0.8 ± 0.2 mm, 95% CI 0.3–1.3), CAL (1.3 ± 0.4 mm, 95% CI 0.4–2.2), FMPS (41.0 ± 6.2%, 95% CI 28.7–53.4), FMBS (16.2 ± 6.6%, 95% CI 3.0–29.4) and tooth loss (2 ± 1 teeth, 95% CI 1–3) were all statistically significant (P < 0.01 for all). Substantial differences in domiciliary oral hygiene routines were observed (P < 0.0001). In multivariate models when FMPS was included as covariate the difference between groups in all clinical periodontal parameters was no longer statistically significant. Conclusions: Our results showed that periodontal status is worse in MMP patients if compared with healthy controls due to a substantial difference in oral hygiene. Oral health should be promoted in MMP.     

Effect of desquamative gingivitis on periodontal status: a pilot study

Objective:  Desquamative gingivitis (DG) represents the gingival manifestation associated with several mucocutaneous disorders and systemic conditions. Little is known of whether or not DG could influence the onset or progression of plaque-related periodontitis. In this study, the potential impact of DG on plaque-related attachment loss and pocket formation has been evaluated.
Methods:  A cross-sectional evaluation of 12 patients with DG [eight oral lichen planus (OLP), four mucous membrane pemphigoid (MMP)], never treated for DG lesions or plaque-related periodontitis, was carried out. Probing depth (PD), clinical attachment loss (CAL), full-mouth plaque (FMPS), and bleeding (FMBS) scores were evaluated at six sites per tooth. Clinical parameters of sites with DG lesions were compared with that of DG unaffected sites.
Results:  Median PD and CAL, as well as FMPS and FMBS, were not significantly different ( P  > 0.05 Mann–Whitney test) for both OLP and MMP patients. However, a negative association between DG lesions and PD < 4 mm (OLP: OR = 0.26; MMP: OR = 0.47), and a positive association with PD 4–6 mm (OLP: OR = 3.76; MMP: OR = 2.68) and with PD > 6 mm (only for OLP: OR = 3.83) were found to be significant.
Conclusions:  The potential interference between DG lesions and periodontitis needs further prospective investigation; nonetheless, a higher level of attention might be prudent.     

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.     

Professional oral hygiene treatment and detailed oral hygiene instructions in patients affected by mucous membrane pemphigoid with specific gingival localization: a pilot study in 12 patients

To cite this article:
Int J Dent Hygiene 10 , 2012; 138–141
DOI: 10.1111/j.1601‐5037.2010.00527.x Arduino PG, Lopetuso E, Carcieri P, Giacometti S, Carbone M, Tanteri C, Broccoletti R. Professional oral hygiene treatment and detailed oral hygiene instructions in patients affected by mucous membrane pemphigoid with specific gingival localization: a pilot study in 12 patients. Abstract: Objectives: The aim of this prospective case series was to assess the clinical efficiency of an oral hygiene protocol in patients affected by mucous membrane pemphigoid (MMP) with specific gingival localization, before starting any medical treatment. Methods: Patients received oral hygiene instruction followed by non‐surgical periodontal therapy including oral hygiene instructions in a 3‐week cohort study. Clinical outcome variables were recorded at baseline and 5 weeks after intervention and included, as periodontal parameters, full mouth plaque (FMPS) and bleeding (FMBS) scores and patient‐related outcomes (visual analogue score of pain). Results: A total of 12 patients were recruited. The mean age at presentation was 59.5 ± 14.52 years. Five weeks after finishing the oral hygiene and periodontal therapy protocol, a statistical significant reduction was observed for FMPS (P = 0.001), FMBS (P = 0.022) and reported pain (P = 0.0028). Conclusions: Professional oral hygiene procedures and non‐surgical periodontal therapy are connected with improvement of gingival status and decrease in gingival‐related pain, in female patients affected by MMP with specific gingival localization.     

Changes in the expression of integrins and basement membrane proteins in benign mucous membrane pemphigoid

OBJECTIVE: To determine the location of the subepi-thelial split in benign mucous membrane pemphigoid (BMMP) and its relationship to the anchoring filaments and their receptors. MATERIALS AND METHODS: Frozen sections of lesional and perilesional oral mucosa from 10 cases of BMMP were stained, using an immunofluorescence method, for the β₁, β₄, α₃ and α₆ integrin subunits and for their ligands, laminin I and laminin V (kalinin). In all cases the diagnosis was confirmed by the demonstration of linear staining for IgG at the basement membrane zone. Six specimens of normal mucosa were stained for comparison. RESULTS Staining for integrins, laminin and kalinin in perilesional mucosa was similar to normals, although one case showed loss of α₆ and β₄. In lesional mucosa, laminin and kalinin showed strong linear staining localised to the floor of the bullae. The α₆ and β₄ subunits were expressed only on the roof of the bullae but staining was weak and patchy with areas of loss. In some sections a₆ showed a punctate intracellular distribution similar to IgG. The distribution of α₃ and β₁ was similar to that seen in normals. CONCLUSIONS: In all cases kalinin was found on the connective tissue side of the lesions and α₆β₄ localised to the epithelial side. This shows that the split occurs at a location which separates anchoring filaments from the hemidesmosomes. Loss of the α₆β₄ integrin in the lesions and the similar intracellular staining of α₆ and IgG, suggest that disruption of hemidesmosomes may be a key event in the immunopathogenesis of the lesions and that the α₆ integrin subunit is a potential antigen in oral mucosal BMMP.     

A review and guide to drug‐associated oral adverse effects—Oral mucosal and lichenoid reactions. Part 2

Dental practitioners and other health professionals commonly encounter and manage adverse medicine effects that manifest in the orofacial region. Numerous medicines are associated with a variety of oral adverse effects. However, due to lack of awareness and training, these side effects are not always associated with medicine use and are underreported to pharmacovigilance agencies by dentists and other health professionals. This article aims to inform health professionals about the various oral adverse effects that can occur and the most commonly implicated drugs to improve the management, recognition and reporting of adverse drug effects. This article follows on from Part 1; however, the focus here is on lichenoid reactions and oral mucosal disorders including oral aphthous‐like ulceration, mucositis and bullous disorders such as drug‐induced pemphigus, pemphigoid, Stevens‐Johnson syndrome and toxic epidermal necrolysis.     

Relationship between cancer and oral pemphigoid patients with antibodies to α6-integrin

BACKGROUND: Mucous membrane pemphigoid is an autoimmune mucocutaneous blistering disease. A subset, known as anti-epiligrin cicatricial pemphigoid is associated with a high risk for malignancy. Oral pemphigoid (OP) is limited to the oral cavity. The purpose of this study was to determine the association between malignancy and patients with OP with antibodies to alpha6-integrin subunit. METHODS: We determined the incidence of cancer in 72 patients with OP and compared it to the expected incidence using age and sex-specific rates of malignancy in the National Cancer Institute's Surveillance, Epidemiology, and End Results (NCI SEER) Registry. RESULTS: During a mean observation period of 9.1 years (range: 2.8-40), for 70, three OP patients developed malignancies. The expected number of cancers based on the NCI SEER Registry was 8.83. The relative risk for cancer in OP patients, with autoantibodies to alpha6-integrin, was 0.34 (95% CI, 0.07-0.99, P < 0.05). CONCLUSION: It appears that patients with OP, with antibodies to alpha6, may have a possible reduced relative risk for developing cancer.