Erythema multiforme and herpes simplex virus.

It has been suggested that herpes simplex virus (HSV) can trigger erythema multiforme (EM) at different times. One recent study showed HSV antigen in immune complexes of patients with EM. The purpose of our study was to assess a possible association between EM and HSV. Sixteen patients and 16 matched controls were studied using an enzyme-linked immunosorbent assay (ELISA) to measure antibody of the IgG, IgA, and IgM classes against HSV-1. From our study on patients with oral erythema multiforme, we found no evidence to correlate the occurrence and/or severity of EM and the HSV-1.

Expression of laminin 5, fibronectin, and epithelium-associated integrins in recurrent aphthous ulcers.

Recurrent aphthous ulceration (RAU) is characterized by an ulcerated lesion that persists longer than traumatic ulcers of similar size. This delayed healing phase of the lesion was investigated for extracellular matrix components and matrix receptors (integrins). The hypothesis tested was that aphthous ulcers may lack key extracellular matrix components, or their receptors, that are necessary for the migration of marginal keratinocytes from the ulcer edge. We immunocytochemically stained biopsy specimens of RAUs and non-involved mucosal specimens from HIV+ and non-infected individuals to investigate the presence and distribution of molecules reported to be associated with reepithelialization of mucosal and cutaneous wounds. Fibronectin, laminin type 5 (kalinin), and integrin subunits beta 1, beta 4, alpha 6, and alpha v were consistently found at the margins of RAU, as they are in traumatic ulcers. The alpha 5 and beta 6 subunits were not always present. We also found alpha v in the intact stratified squamous epithelium adjacent to ulcers. Immunohistochemical stains showed distruption in the deposition of laminin 5 and an apparent lack of fibronectin at the edges of some ulcers. Although these tissue results do not determine which integrin subunits are paired with each other, they do show some alterations in their expression in RAU. Absence of one or more of these molecules at the migrating front may contribute to delayed epithelial regeneration. It is likely that the absence or inappropriate expression of keratinocyte integrins or their extracellular matrix receptors occurs after the causative factors (currently unknown) of the lesion are gone. The reason for the altered expression of these molecules may be related to the secretory products (including lymphokines and proteinases) of the lymphocytic infiltrate.

Intralesional vinblastine vs. 3% sodium tetradecyl sulfate for the treatment of oral Kaposi's sarcoma. A double blind, randomized clinical trial.

In this double-blind, randomized trial, we compared the clinical efficacy of intralesional vinblastine (VNB) and 3% sodium tetradecyl sulfate (STS) in the treatment of oral Kaposi's sarcoma (OKS). Subjects with OKS were randomly assigned to receive a single intralesional injection of either VNB or STS, at a standard dose (0.2 mg/cm(2)). Differences were evaluated by the Mann-Whitney U and Fisher's exact tests. Sixteen HIV-infected patients were included, eight received VNB and eight received STS; clinical response was evaluated at days 7, 14, and 28 following treatment. Tumor size reduction was 0.68 and 0.61 cm in the VNB and STS groups, respectively (P=0.80). Two VNB patients had complete or partial response whereas four STS subjects had partial responses (P=0.61). Patients in both groups experienced minimal toxicity. We conclude that intralesional vinblastine or STS are adequate for the management of OKS. The benefits of STS are its low cost and ease of use.

Oral lichen planus: epidemiology, clinical characteristics, and associated diseases.

Oral lichen planus (OLP) is a chronic inflammatory disease, the cause of which remains unknown. In the last few years, significant advances have been made in understanding the mechanisms involved in the pathogenesis of the disease. Data on HLA markers for OLP vary depending on the population studied. OLP is a disease primarily of adults (50 to 55 years of age) and predominantly affects women. Any site in the oral cavity may be involved, but the buccal mucosa and gingiva are the most common sites. OLP can have different clinical presentations, with the reticular, erosive, and atrophic types being the most commonly reported. OLP has been reported to be associated with different medical conditions such as diabetes, hepatitis C infection, liver disease, and oral cancer. With the exception of oral cancer, there are not good data to support such associations. The question that remains to be answered is why we see a higher prevalence of oral carcinoma in patients with OLP. The relative prevalence from our series was 1.2%. Therefore, we believe patients with OLP have a higher risk for oral cancer and should be monitored for malignant transformation once a year.

Oral lichen planus: topical and systemic therapy.

The treatment of oral lichen planus (OLP) remains a real challenge for clinicians who deal with this patient population and thus with diagnosis of this disease. Most treatment failures are attributable to improper diagnosis. Therefore, before a patient is started on therapy, a biopsy must be done and the diagnosis established. Most patients with OLP are asymptomatic, and once the diagnosis is established, patients need to be seen once a year to monitor their disease. However, when OLP is symptomatic, it can interfere with the patient's everyday life, making it difficult to work and to eat. The most symptomatic forms of the disease are the erosive and atrophic types. Often, systemic therapy is the only way to control the acute presentation of the disease. The most effective treatment modality to control the signs and symptoms of the disease is short courses of systemic steroids (prednisone) and topical high-potency corticosteroids. Other forms of therapy include the use of cyclosporine (topical) and retinoids, both systemic (etretinate) and topical (tretinoin). However, there is no one single standard protocol proven effective with either systemic retinoids or topical cyclosporine. Results so far are controversial and not very encouraging. One aspect clinicians must remember when designing treatment protocols for erosive OLP is the chronic course of the disease and its recalcitrant nature. These factors mean that treatment has to be long, and the onset of adverse side effects from long-term therapy must be taken into account. Alternate-day treatment protocols, low doses, and adjunct therapy all should be considered when a new agent is being considered for treating erosive OLP.

Oral pemphigus vulgaris: a review of the literature and a report on the management of 12 cases.

Twelve cases of oral pemphigus vulgaris are described to illustrate the long-term behavior of the disease and the treatment challenges it presents to the oral medicine practitioner. In addition, we review the literature on oral pemphigus vulgaris with respect to clinical history, signs and symptoms, management, and treatment outcome. Pemphigus vulgaris is a chronic vesiculobullous disease with a potentially fatal outcome. Mortality from pemphigus vulgaris before the development of effective therapies was as high as 90%. Today, with treatment, it is closer to 10%. Involvement of the oral mucosa is common and in most cases precede skin lesions; in our patients, the oral lesions preceded the development of extraoral disease in 75% of cases. Pemphigus vulgaris was more frequent among women (9:3), and there was a tendency for the severity and frequency of disease to decrease with time.

Use of intralesional interferon-alpha for the treatment of recalcitrant oral warts in patients with AIDS: a report of 4 cases.

Four human immunodeficiency virus-positive homosexual men with 2- to 4.5-year histories of recurrent oral warts that had failed to respond to conventional surgical and other treatment modalities were offered treatment with interferon-alpha. All had multiple or large oral warts, 3 had skin warts, 2 had a history of anal warts, and 1 had penile lesions. All 4 patients were treated with a combination of intralesional and subcutaneous interferon-alpha. Adverse side effects were dose-related, mild, and transient; they included flulike symptoms (3 patients), hair loss and tachycardia (1 patient), and transient changes in the white blood cell count. All patients responded to therapy and remained free of disease up to 42 months. Intralesional injection with interferon-alpha appears to provide excellent clinical control for recurrent, multiple, and extensive oral warts in the human immunodeficiency virus-positive population, and is a useful adjunct to initial surgical removal of oral warts.

Heat shock (stress) proteins and gamma delta T lymphocytes in oral lichen planus.

OBJECTIVE: Heat shock proteins (Hsps), a highly conserved class of protective cellular proteins that are produced under various conditions of environmental challenge, have been implicated as the antigenic stimulus in autoimmune diseases. Because lichen planus (LP) appears to be an autoimmune or hyperimmune condition (mediated by T cells), Hsps may have a role in the pathogenesis of this disease. We believe that if keratinocyte Hsps are antigenic targets of a cellular immune response, upregulation of these proteins should be demonstrable in tissue sections. STUDY DESIGN: Immunohistochemistry was used to evaluate expression of several families of Hsps in oral lichen planus tissues. The number and distribution of gamma delta T cells, a subset of T lymphocytes with an immune surveillance function that may contribute to autoimmunity, were also evaluated. Monoclonal antibodies to Hsps 27, 60, 70, 90, gamma delta receptor, and CD3 (pan-T lymphocyte marker) were incubated with frozen sections of LP (n = 22) and normal oral mucosa (n = 17) followed by an avidin-biotin-peroxidase labeling method. Antibodies to bacterial Hsps (GroEL and DnaK) were used as negative controls, and antibody to constitutive eukaryotic Hsp (Hsc70) was used as a positive control. RESULTS: In six cases of LP, basal keratinocytes stained intensely for Hsp27, whereas controls showed only slight staining. Otherwise LP and normal tissues showed comparable positive staining of upper level keratinocytes with anti-Hsp27. Subjective increases in antibody staining were noted for Hsp60 in LP, which was due in part to staining of infiltrating lymphocytes and in part to keratinocyte expression. Normal tissues showed weak basal cell antibody staining for Hsp60. Hsp70 staining was observed at a less intense level in LP than in controls. Except for more intense basement membrane staining with anti-Hsp90 antibody in gingiva and palate, no differences in the occurrence of this protein were found. Absolute numbers of gamma delta T cells were increased in LP when compared with those in control specimens (n = 10 vs n = 1, respectively, per high-power field). However, gamma delta T cells represented less than 1% of the CD3+ lymphocytes. CONCLUSIONS: It was concluded that normal oral mucosa expresses Hsps 27, 60, 70, and 90 and contains few gamma delta T cells. Although the expression of Hsps was altered in LP, the differences demonstrated were slight and were therefore inconclusive. The Hsps expressed in LP could have contributed to the persistence or chronicity of the disease, or they could have simply reflected cellular injury.

Intraoral non-Hodgkin's lymphoma in seven patients with acquired immunodeficiency syndrome.

Since the appearance of AIDS, there has been a significant increase in the number of cases of oral non-Hodgkin's lymphoma. Rarely seen in the oral cavity before, non-Hodgkin's lymphoma is now seen with some frequency in HIV-positive patients. Oral HIV-related lymphomas exhibit an aggressive course and can mimic other oral tumors and infections, which makes early recognition and diagnosis important and difficult. We report on the clinical findings in seven homosexual men in whom the oral cavity was the first site in which non-Hodgkin's lymphoma appeared and the only site involved at the time of diagnosis. Treatment consisted of chemotherapy with or without radiation therapy. The relatively short survival in these patients averaged 8 months. All patients died of complications from their tumor.

Vascular adhesion molecules in oral lichen planus.

OBJECTIVE: Because recruitment and retention of lymphoid cells appear to be critical components of the pathogenesis of lichen planus, we have compared the expression and distribution of a panel of vascular adhesion molecules (ELAM-1, P-selectin, ICAM-1, VCAM-1, PECAM-1, CD34) and leukocyte adhesion molecule ligands (LFA-1, Mac-1, VLA4, L-selectin) in biopsies of this disease. STUDY-DESIGN: Frozen sections of 12 clinically and histologically confirmed cases of lichen planus and 9 normal control tissues were evaluated immunohistochemically with a standard 1-day avidin-biotin peroxidase technique. Staining intensity of vascular endothelium was evaluated semiquantitatively. Three microvascular zones or compartments were defined and evaluated separately. RESULTS: Generally, different staining patterns were observed in association with the various endothelium-associated adhesion molecules. In normal controls, PECAM was intensely expressed and VCAM-1 was weakly expressed. Intermediate staining was associated with ELAM-1, P-selectin, ICAM-1, and CD34. Staining within the three microvascular compartments frequently showed variations in intensity. In lichen planus, increased staining for ELAM-1, P-selectin, ICAM-1, and VCAM-1 was evident in one or more of the microvascular compartments. In the subepithelial vascular compartment where the infiltrate was the most dense, VCAM-1 appeared to show the greatest positive change. Almost all cells in the lichen planus infiltrates stained positive for ICAM-1, L-selectin, LFA-1, and VLA4, and large numbers of cells also exhibited VCAM-1, PECAM-1, and Mac-1 immunoreactivity. CONCLUSIONS: It appears that upregulation of ELAM-1, ICAM-1, and VCAM-1 (especially by endothelial cells in the subepithelial vascular plexus) could play a role in the pathogenesis of lichen planus. The expression of leukocyte receptors L-selectin, LFA-1, and VLA4 by most of the cells in the lichen planus infiltrate suggest that these molecules may be responsible for recruitment as well as retention in the active lichen planus lesion.

Leukocyte adhesion deficiency in a child with severe oral involvement.

Leukocyte adhesion deficiency is a rare inherited defect of phagocytic function resulting from a lack of leukocyte cell surface expression of beta2 integrin molecules (CD11 and CD18) that are essential for leukocyte adhesion to endothelial cells and chemotaxis. A small number of patients with leukocyte adhesion deficiency-1 have a milder defect, with residual expression of CD18. These patients tend to survive beyond infancy; they manifest progressive severe periodontitis, alveolar bone loss, periodontal pocket formation, and partial or total premature loss of the primary and permanent dentitions. We report on a 13-year-old boy with moderate leukocyte adhesion deficiency-1 and severe prepubertal periodontitis. This case illustrates the need for the dentist to work closely with the pediatrician in the prevention of premature tooth loss and control of oral infection in these patients.

Apoptosis in oral erythema multiforme.

OBJECTIVE: Cell death was evaluated in oral erythema multiforme to test the hypothesis that apoptosis may be a mechanism by which keratinocytes die in this condition. STUDY DESIGN: Ten erythema multiforme and five control oral mucosa biopsy specimens were evaluated in immunohistochemically stained sections for apoptosis-regulating proteins Bcl-2, Bcl-x, Bax, p53, Fas, and Fas-ligand. Apoptotic keratinocytes, determined by a detection method for DNA fragmentation (TUNEL) and by conventional morphologic criteria were counted per high power field. RESULTS: Keratinocyte staining for Bcl-2 protein was comparable in erythema multiforme and controls. Bcl-x expression was reduced in five erythema multiforme cases. Staining for Bax protein differed in six erythema multiforme cases and showed variable intensity in layers under the parakeratin. Only slight differences in staining patterns of Fas and Fas-ligand proteins were noted between erythema multiforme and controls. The number of apoptotic keratinocytes evaluated by morphologic examination was significantly higher in erythema multiforme (mean per high power field, 0.90 +/- 0.2; controls, 0.06 +/- 0.04; p < 0.05, Mann-Whitney test) and was limited in significance by the TUNEL method (erythema multiforme, 0.43 +/- 0.1; controls, 0.02 +/- 0.02). Overexpression of p53 protein was seen in basal keratinocytes in five erythema multiforme specimens (mean, 17.5 +/- 4.03 per high power field; controls 1.2 +/- 0.3). CONCLUSIONS: There is evidence that cell death in erythema multiforme is at least in part due to apoptosis. The apoptotic mechanism may be related to an altered expression of apoptosis-regulating proteins. Although measurable alterations in the phenotypic expression of Fas and Fas-ligand proteins were not apparent, activation of Fas/Fas-ligand system could still be involved in the induction of apoptosis in erythema multiforme.

Oral mucosal melanomas: the WESTOP Banff workshop proceedings. Western Society of Teachers of Oral Pathology.

A workshop to discuss primary oral melanomas was convened at the annual Western Society of Teachers of Oral Pathology meeting in Bannf, Alberta, Canada. Fifty oral melanomas, identified from the files of the participants, were reviewed in order to better understand the clinical features, histologic spectrum, and natural history of these perplexing lesions. Results confirmed that oral melanomas occur in adults almost three times more frequently in men than women and have a decided predilection for the palate and gingiva. Some lesions exhibit a clinically detectable and prolonged in situ growth phase, whereas others seem to lack this property and exhibit only or predominantly invasive characteristics. Recurrences, metastases, and death from tumor were characteristic of the follow-up of a limited number of patients. Until definitive prospective data are collected that elucidate natural history, oral mucosal melanomas should be tracked separately from cutaneous lesions. All oral pigmented lesions that are not clinically diagnostic should be biopsied. Lesions with equivocal histopathologic features might be referred to as "atypical melanocytic proliferation" and should be excised. Recognition of lesions in an early in situ phase and aggressive treatment should have a favorable effect on prognosis. To enhance future or prospective study of these rare neoplasms, guidelines for reporting oral melanomas are suggested.

Oral findings in people with or at high risk for AIDS: a study of 375 homosexual males.

A total of 375 homosexual males were studied to assess the dental findings, life-style, and risk factors during a 4-year period. At baseline, 136 of the patients were diagnosed as having AIDS, 116 were considered at risk for AIDS, and 123 were considered healthy. In a mean follow-up time of 23 months, nine of the patients at risk for AIDS and five of the patients considered healthy were diagnosed as having AIDS. Kaposi's sarcoma was the most common oral neoplasm, and candidiasis was the most frequent oral infection. Hairy leukoplakia was found in 28% of the patients, and periodontal disease was found in 17% of the patients. Carriers of the AIDS virus may not be identified easily and control measures in the dental office must be followed.

Oral lichen planus: patient profile, disease progression and treatment responses.

BACKGROUND: Oral lichen planus, or OLP, is a common mucocutaneous immunological disease. The objective of this study was to describe the patient profile, disease progression and treatment responses. METHODS: The authors conducted a retrospective, descriptive study using information from patient records at a tertiary referral center. The study included 229 patients with OLP who were seen in the oral medicine clinic at the University of California, San Francisco, between September 1996 and August 2000, for the first time or for a follow-up visit. Signs and symptoms at various clinic visits were quantified. Responses to treatment and disease progression were determined by comparing scores with baseline scores. RESULTS: The mean age at onset of the disease was 55 years, and 154 (67 percent) of the patients were female. Symptoms generally correlated directly with the severity of OLP forms, which ranged from reticular to erosive. Corticosteroids were effective in reducing symptoms, healing ulcers and reducing erythema. At last follow-up, 65 percent of the patients had the same type of OLP seen initially or the disease had progressed to a more severe type, while 35 percent of patients had less-severe forms than that seen at the initial visit. Four patients (1.7 percent) developed oral squamous-cell carcinoma during the follow-up period. CONCLUSIONS: OLP is a chronic disease with no known cure. Symptoms can improve with corticosteroids; however, the lack of long-term (that is, lifetime) treatment compliance and the adverse side effects of the drugs limit optimal results. CLINICAL IMPLICATIONS: Patients with OLP should be treated if symptoms are significant. Follow-up--including supervision of medication use and monitoring of side effects, as well as periodic examinations for possible malignant transformation--is necessary.

Oral hairy leukoplakia in an HIV-negative patient with systemic lupus erythematosus.

Oral hairy leukoplakia (OHL) has been reported primarily in association with HIV infection. Recently, cases have been reported in HIV-negative immunosuppressed and in immunocompetent patients. This article reports the case of an occurrence of OHL in an HIV-negative immunosuppressed patient with systemic lupus erythematosus. The case presented illustrates the importance of a thorough examination of the oral tissues in patients who are undergoing immunosuppressive therapy.