Immunoelectron microscopic findings in oral mucosa of patients with dermatitis herpetiformis and linear IgA disease

Abstract – Two patients with dermatitis herpetiformis and one with linear IgA disease were examined. Two of the patients had oral lesions and all three showed IgA deposits detected by direct immunofluorescence in apparently normal buccal mucosa. To localize the target structures for IgA deposition, biopsy specimens were taken from normal appearing buccal mucosa for immunoelectron microscopy. The patients with dermatitis herpetiformis had distinct IgA deposits in the upper connective tissue. These were often associated with elastic fibers and occasionally also with capillary walls. In contrast, the patient with linear IgA disease had IgA deposition at the subbasal lamina. Though the clinical expressions may be similar the present immunoelectron microscopic fmdings in oral mucosa clearly differentiate dermatitis herpetiformis from linear IgA disease.     

IgA deposits in the oral mucosa of patients with dermatitis herpetiformis and linear IgA disease

The oral mucosa of seven patients with dermatitis herpetiformis (DH) and one with linear IgA disease was studied. None of the patients with DH showed any macroscopic oral lesions, but direct immunofluorescence (IFL) examination of the buccal mucosa revealed granular IgA deposits in all patients. IgA deposits were found just below the basement membrane zone or slightly deeper in the connective tissue, i.e. a deposition pattern which is pathognomonic to DH. In three patients C3 deposits occurred in the same area as IgA. The patient with linear IgA disease had small white erythematous patches, nonspecific both clinically and histologically, on the palatal mucosa. However, oral IFL specimens showed heavy linear IgA deposits in the basement membrane zone, indicating that the oral mucosa is also involved in this rare disease. Buccal mucosal biopsy specimens were stained with four FITC-conjugated lectins (Ulex europaeus I, soybean, peanut and lentil). The lectin staining was similar in patients with DH and linear IgA disease and did not markedly differ from normal oral mucosa. Our results show that buccal IFL examination is a useful diagnostic aid in both DH and linear IgA disease.     

IgA deposits in the oral mucosa of patients with dermatitis herpetiformis and linear IgA disease

Abstract – The oral mucosa of seven patients with dermatitis herpetiformis (DH) and one with linear IgA disease was studied. None of the patients with DH showed any macroscopic oral lesions, but direct immunofluorescence (IFL) examination of the buccal mucosa revealed granular IgA deposits in all patients. IgA deposits were found just below the basement membrane zone or slightly deeper in the connective tissue, i.e. a deposition pattern which is pathognomonic to DH. In three patients C3 deposits occurred in the same area as IgA. The patient with linear IgA disease had small white erythematous patches, nonspecific both clinically and histologically, on the palatal mucosa. However, oral IFL specimens showed heavy linear IgA deposits in the basement membrane zone, indicating that the oral mucosa is also involved in this rare disease. Buccal mucosal biopsy specimens were stained with four FITC-conjugated lectins (Ulex europaeus I, soybean, peanut and lentil). The lectin staining was similar in patients with DH and linear IgA disease and did not markedly differ from normal oral mucosa. Our results show that buccal IFL examination is a useful diagnostic aid in both DH and linear IgA disease.     

Dermatitis herpetiformis: IgA deposits in gingiva, buccal mucosa, and skin

Fourteen patients who had dermatitis herpetiformis of the skin with no gingival lesions were studied. In each patient biopsy specimens of normal gingiva, buccal mucosa, and perilesional skin were examined for IgA and IgG deposits. Depending on the method of handling biopsy specimens for immunofluorescence, IgA deposits were detected in 21 to 25 percent of gingival specimens, 27 to 46 percent of buccal mucosal specimens, and 64 to 76 percent of skin specimens. The occurrence of IgA deposits in the gingival papillae, a site where lesions of DH have not been reported in the past or observed in this study, suggests that these IgA deposits alone may not play a primary role in the pathogenesis of this disease. Similar immunofluorescent findings of IgA deposits were observed in both quick-frozen biopsy specimens and those placed in holding solution, indicating the suitability of the holding solution for transporting suggested DH biopsy material.     

Benign mucous membrane pemphigoid with linear IgA deposits in oral mucosa

Two patients with severe oral ulcerations and concomitant lesions in the nose, eyes and genitals were examined. The immunofluorescence (IFL) studies of buccal and genital mucosa revealed that the only deposited immunoglobulin was IgA. Immunoelectron microscopy confirmed the linear pattern of IgA deposition and localized IgA in lamina lucida in both patients. Dapsone 50 mg daily was effective in controlling the disease activity partially in the first and completely in the second patient. The results suggest that our patients had benign mucous membrane pemphigoid (BMMP) with linear IgA deposition but do not exclude a mucosal form of a newly recognized bullous skin disease termed linear IgA disease.     

Benign mucous membrane pemphigoid with linear IgA deposits in oral mucosa

Two patients with severe oral ulcerations and concomitant lesions in the nose, eyes and genitals were examined. The immunofluorescence (IFL) studies of buccal and genital mucosa revealed that the only deposited immunoglobulin was IgA. Immunoelectron microscopy confirmed the linear pattern of IgA deposition and localized IgA in lamina lucida in both patients. Dapsone 50 mg daily was effective in controlling the disease activity partially in the first and completely in the second patient. The results suggest that our patients had benign mucous membrane pemphigoid (BMMP) was linear IgA deposition but do not exclude a mucosal form of a newly recognized bullous skin disease termed linear IgA disease.     

Oral acantholytic itching disease responding to dapsone. Dermatitis herpetiformis, pemphigus, or a new disease?

A patient had a blistering and severely itching disease confined solely to the oral cavity. The histopathologic findings had the features of both pemphigus and dermatitis herpetiformis. There were no gastrointestinal symptoms, no IgA could be found in uninvolved skin, and no intercellular or basement membrane antibodies were present in the serum or epidermis. The disease responded favorable to dapsone (diaminodiphenylsulfone), which could be discontinued after 2 1/2 years. The literature is briefly reviewed, and there is a discussion of whether the patient was suffering from pemphigus or dermatitis herpetiformis. The conclusion is drawn that the diagnosis cannot be established with certainty and that we are perhaps dealing with a new disease. It is stressed that in such aberrant cases a therapeutic trial with dapsone should be made.     

Linear IgA disease (LAD): immunoglobulin deposition in oral and colonic lesions

Two cases of adult linear IgA disease (LAD) with oral and colonic involvement are presented. Oral findings, for both patients, were of widespread painful ulceration present for two to three months and diagnosis was confirmed by biopsy and direct immunofluorescence. Colonic symptoms preceded oral symptoms in both cases and a number of investigations were undertaken, including routine histological examination, which suggested either lymphocytic colitis or Crohn's disease. Immunofluorescence studies showed linear IgA deposition confined to the distal colon. These cases highlight that large bowel involvement can be a feature of linear IgA disease and for the first time demonstrate IgA deposition at that site.     

Intraepithelial lymphocytes bearing the γ/δ receptor in the oral and jejunal mucosa in patients with dermatitis herpetiformis

Lymphocytes bearing T cell receptor (TcR) γ/δ are increased in the jejunal mucosa of patients with dermatitis herpetiformis (DH) and coeliac disease. In this study, we examined whether increased numbers of γ/δ TcR positive lymphocytes occur in the oral mucosa of patients with DH. Oral and jejunal rnucosal biopsies were taken from 13 newly diagnosed and 13 gluten free diet (GFD)-treated patients with DH. Monoclonal antibodies and avidin-biotin peroxidase method was used for staining, and TcR positive cells were counted from the buccal and jejunal epithelium. Very few γ/δ TcR positive lymphocytes were seen in the buccal epithelium of untreated or GFD-treated DH patients (median 0.4 and 0.3 cells/mm²), whereas α/β TcR positive lymphocytes were frequent in both groups of DH patients (154 and 250 cells/mm²) and healthy controls (135 cells/mm²). The numbers of γ/δ TcR positive intraepithelial lymphocytes were significantly increased in the jejunum of both untreated (43 cells/mm) and GFD-treated (27 cells/mm) DH patients compared to control patients (2.2 cells/mm). The present study did not, therefore, disclose any evidence for active recruitment of γ/δ TcR positive lymphocytes in the oral epithelium, but showed substantial amounts of intraepithelial γ/β TcR positive lymphocytes both in DH patients and healthy controls.     

Circulating antibodies and immune complexes in oral mucosal diseases

This paper reviews the use of measurement of circulating auto-antibodies and antibodies to food proteins, and of circulating immune complexes (CIC) for diagnosis of various systemic diseases with oral involvement. Results of a study of 29 patients suffering from chronic oral mucosal disease, in which such methods were applied are reported. Auto-antibodies against epithelial intercellular substance (AICSA) were found in three patients, two of whom had pemphigus. Only one of the two patients diagnosed as having pemphigoid had circulating antibodies to basement membrane zone (ABMZA). Auto-antibodies to reticulin (IgA-ARA) were found in one patient in whom a diagnosis of coeliac disease (CD) was confirmed by intestinal biopsy. In addition to the patient with CD, another patient had IgA class antibodies against gliadin (IgA-AGA). IgG-AGA were found in five other patients, in one of whom dermatitis herpetiformis (DH) was diagnosed. Antibodies to cow's milk (ACMA) were detected in 10 patients and CIC in 4 patients. Case reports are given to illustrate the important role of antibody determination coupled with histopathological and immunofluorescence examination of tissue biopsy material in the diagnosis of serious oral disease.     

Anti-BP180-type mucous membrane pemphigoid: report of two cases

We describe two patients with anti-BP180-type mucous membrane pemphigoid (MMP), who were correctly diagnosed and treated in early stages through the cooperation of dentists and dermatologists. Patient 1 was a 74-year-old woman who visited our dental department due to blisters over the oral mucosa and eruptions on the skin. She had also experienced bleeding of the gingiva and palate mucosa. Biopsy specimens from the oral mucosa revealed detachment of epithelial basement membrane and subepithelial lamina propria with slight chronic inflammation. Direct immunofluorescence (DIF) revealed linear IgG and IgA deposits along the basement membrane zone (BMZ). Indirect immunofluorescence (IIF) using 1 M-NaCl split normal human skin showed binding of IgG and IgA on the epidermal side. On immunoblot analysis, IgG and IgA autoantibodies reacted with the C-terminal protein of BP180. These findings indicated a diagnosis of anti-BP180-type MMP. Patient 2 was a 59-year-old woman who was referred to our dental department with a history of blisters and large erosions on the gingiva. Biopsy specimens from the oral mucosa revealed partial junctional separation at the level of the basement membrane. DIF showed linear depositions of IgG and C3 along the BMZ. IIF, using 1 M-NaCl split normal human skin, revealed circulating anti-BMZ-IgG antibodies bound to the epidermal side. These findings indicated a diagnosis of anti-BP180-type MMP. Both patients were treated successfully with systemic or topical steroids and oral health care. In conclusion, appropriate clinical examination and cooperation among medical specialists are important for the early diagnosis and treatment of patients with recurrent and chronic stomatitis and for their good prognosis.     

Asymptomatic oral human papillomavirus (HPV) infection in women with a histopathologic diagnosis of genital HPV

The oral route of human papillomavirus (HPV) transmission is not fully understood. It has been suggested that genital infection can act as a reservoir for oral HPV infection. We investigated the presence of oral HPV DNA and anti-HPV IgA in the buccal cavity of patients with a histopathologic diagnosis of cervical HPV infection. One hundred women underwent oral clinical examinations to detect HPV-DNA by polymerase chain reaction and salivary anti-HPV IgA by indirect immunofluorescence. Information on the personal habits of all the women was collected in personal interviews. Our results showed that 99% of the patients had no clinical manifestations of oral HPV. However, HPV DNA was detected in 81% of oral mucosa samples, and anti-HPV IgA was detected in the saliva of 44% of the patients. Consumption of alcoholic beverages was significantly associated with detection of oral HPV DNA and salivary anti-HPV IgA. Other behavioral risk factors associated with oral HPV and anti-HPV IgA are also discussed. In conclusion, patients with genital HPV infection are at risk for subclinical oral HPV infection. Thus, a molecular assay might be necessary to diagnose such infections.     

Prevention of cancer of the buccal mucosa

Cancer of the buccal mucosa ranks fourth in the structure of cancers. Pretumor processes of the buccal mucosa are Bouin's disease, leukoplakia verrucosa, papillomatosis, erosive ulcerative and hyperkeratotic lupus erythematosus and lichen planus, and postradiation stomatitis. Two clinical cases of cancer of the tongue in young men aged 27 years are described. Preventive measures are treatment of pretumor processes in the buccal mucosa, absolute refusal from caustics and from dentures made of different materials, regular check-ups of patients, consultations at specialized oncological institutions with cytological and morphological studies, thorough sanitation of the oral cavity including therapy, surgery, and orthodontic treatment.     

The clinical and cytological characteristics of the oral mucosa in Sj?gren's disease and chronic parotitis]

Clinical stomatologic and cytologic studies were carried out in 31 patients with Sjogren's disease, 12 ones with chronic parotitis, and 5 normal subjects. Patients with Sjogren's disease, in contrast to those with chronic parotitis, develop clinically manifest signs of dry exfoliative cheilitis, xerostomia, atrophic changes in the buccal mucosa; this condition is associated with a very high caries intensity and no clinical manifestations of periodontitis or tartar. Elevated leukocyte levels in oral washings and oral fluid of patients with Sjogren's disease and chronic parotitis point to inflammations in the salivary glands, buccal mucosa, and periodontal tissues. Assessment of the leukocyte levels may be used for monitoring the disease course and treatment efficacy. A 3-5-fold enlargement of the deep-layer epitheliocytes, seen on the cytogram of oral washings, is characteristic of patients with Sjogren's disease, in contrast to those with chronic parotitis or normal subjects. A differentiated estimation of the epitheliocyte types in the cytogram of oral washings may be used in the diagnosis of Sjogren's disease along with the criteria suggested before.     

Study of the oral mucosa in 200 consecutive patients with psoriasis

Abstract – The oral cavities of 200 consecutive psoriasis patients, most of them with widespread disease on the skin, were examined (man/woman ratio 1.63:1, mean age of the patients 43.7 yr). The average duration of the disease at time of examination was 15.8 yr. When questioned, 16% of the patients reported changes in the joints, which, according to them, had been verified by radiography. 72.5% of the patients reported on nail involvement at some time during their disease. Fissured tongue was present in 9.5% of the patients, and geographic tongue and smooth tongue each in 1 % of the patients. Angular cheilitis was found in 3.5% of the patients. In 20 out of 200 cases, the oral mucosa showed changes and biopsy was taken. Four out of 20 patients showed histologic features typical of psoriasis, including accumulations of leukocytes in the upper layers of the epithelium, all with widespread psoriasis skin involvement. Areas of oral mucosa were most often deep red in color, the buccal mucosa and tongue being the two most common sites. Two out of these four patients had a fissured tongue and one had a geographic tongue.     

Castleman's disease of the buccal mucosa: report of a case and review of the literature of head and neck cases

A case of Castleman's disease occurring in the buccal mucosa is described. An 84-year-old woman noticed that a mass in the left buccal mucosa that had been present for half a year. Computed tomography revealed a well-demarcated submucosal tumor, measuring 4.0 x 3.0 x 2.0 cm. The patient received no treatment at this time, and continued growth of the mass was observed. After incisional biopsy, the lesion was surgically removed. Histologically, the tumor consisted of an enlarged lymph node with conspicuous lymph follicles, in which vascular channels and deposits of eosinophilic material were noted. Laboratory examination showed an increase of serum antibody level of cytomegalovirus but of no other viruses. The patient was followed up for 1(1/2) years, with no clinical evidence of recurrence. This is the first report of Castleman's disease presenting in an oral site.     

Angina bullosa haemorrhagica: a case report and a concise review

Various differential diagnoses pertaining to angina bullosa haemorrhagica (ABH) have been reported in the dental literature; these differential diagnoses include mucous membrane pemphigoid, bullous pemphigoid, bullous lichen planus, epidermolysis bullosa, dermatitis herpetiformis, linear IgA disease, and oral amyloidosis. ABH is characterized by a solitary blood blister in the palate and may worsen progressively, leading to multiple lesions in other areas. The bullae usually rupture spontaneously and the sites heal uneventfully. Possible etiological factors include trauma, long-term use of steroids, diabetes, and hereditary predilection. Pathological studies have yielded nonspecific findings and the underlying etiopathology remains ill-defined. This article describes a case of ABH following the use of a 0.12% chlorhexidine gluconate mouthrinse and presents a concise review of the literature pertaining to ABH and differential diagnoses.     

Human papilloma virus types in the oral and cervical mucosa of HIV‐positive South African women prior to antiretroviral therapy

Background: To evaluate the prevalence of human papilloma virus (HPV) infection and types in the oral and cervix mucosa of treatment‐naïve HIV‐1‐positive women with CD4 counts less than 300 cells per ml with no HPV‐associated oral lesions. Methods: Oral epithelium was harvested from the buccal mucosa and lateral borders of the tongue and cervical samples were collected from the endocervical area of 30 women, 22–64 years old. Cytobrush Plus cell collectors were used for sampling both anatomical areas. Genital pathology, obstetric and gynaecological history, co‐morbid disease, hormone therapy, sexual behavior and smoking history were assessed via physical examination and clinical interviews. Special investigations included cervical Papanicolau smears, CD4 counts and HIV‐1 viral loads. The linear array HPV test was used to determine HPV genotypes present in the specimens. Results: Oral HPV were identified in 20% (n = 6) of the patients, of which two had infection with two HPV types. Genital HPV was found in 96.7% (n = 29) of the women, of which only 14 had cytological abnormalities on Papanicolau smear. Infection with multiple HPV types were present in 93.1% (n = 27) of the patients, with an average of four HPV types per individual. Conclusions: South African HIV‐positive women with CD4 counts less than 300 cells per ml have a significant risk of cervical HPV strains and multiple strain infection of the cervix. The prevalence of HPV in normal oral mucosa was low but high‐risk types were present. Limited correlation between oral HPV types and those identified in the cervical mucosa was found.     

LncRNA H19与OSF发生及癌变的关系

目的:探讨lncRNA H19在口腔黏膜下纤维性变(OSF)发生及癌变过程中的表达变化及其意义.方法:实时荧光定量PCR技术分别检测12例正常颊黏膜组织、33例OSF颊黏膜组织、31例伴OSF颊癌组织中的LncRNA H19的表达水平.结果:LncRNA H19在颊黏膜组织、OSF颊黏膜组织、伴OSF颊癌组织中的相对表达量分别为1.17±0.37、3.44±1.08、8.88±1.78,组间两两之间比较,P＜0.01.结论:LncRNA H19可能参与OSF的发生及癌变.     

Two cases of linear IgA disease with clinical manifestations limited to the gingiva

Linear IgA disease (LAD) is a chronic, subepithelial blistering disease that is associated with the presence of linear deposits of IgA along the basement membrane zone. Etiopathogenic aspects of LAD are only partially known. LAD is clinically characterized by vesiculobullous skin and mucous lesions. Although more than half of LAD patients present oral mucosal lesions, there are only a few cases reported of oral lesions as the only manifestation of LAD. This study presents 2 of these uncommon cases.