Melkersson-Rosenthal syndrome and acquired C1 inhibitor deficiency.

BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare disease whose full-blown form is characterized by orofacial swelling, facial palsy and lingua plicata. OBJECTIVE: To investigate the complement system as well as its role in patients with MRS. METHODS: Seven patients presenting at this hospital between November 2002 and May 2003 and meeting the diagnostic criteria according to Hornstein were evaluated retrospectively. The investigations included clinical signs, an analysis of the complement system including levels of CH50, C3, C4, C1 inhibitor (INH) functions and C1-INH antigen detection. RESULTS: Two female patients showed isolated low levels of functional C1-INH as determined by duplicate tests. Both patients took estrogen-progestin contraceptives. CONCLUSION: Since deficiency in plasma protease C1-INH is known to lead to recurrent angioedema, we hypothesize that low levels of functional C1-INH may have contributed to the orofacial swelling in the 2 patients.

[Cicatricial pemphigoid: management in stomatology]. / Pemphigoïde cicatricielle: prise en charge en stomatologie.

BACKGROUND: Cicatricial pemphigoid is a subepidermal disease of the mucous membranes. In some patients blisters involving the oral cavity may be the only manifestation. The purpose of this work was to detail the clinical features and biological findings, highlighting the diagnostic and therapeutic difficulties. MATERIAL AND METHODS: Seventeen patients, nine women (mean age 59.6 years) and eight men (mean age 67.8 years) managed between 1990 and 2000 were reviewed retrospectively. RESULTS: Mucous membranes of the mouth were the only localization in six of the seventeen patients. Other localizations (skin, eye, nose, anus) were associated, alone or in combination, in the other eleven patients. The gingivae were involved in 15/17 patients and constituted the only localization in six. Skin lesions (sometimes involving the lower limb) were variable and found in 6/17 patients. Ocular lesions were present at diagnosis in six patients, including two with severe lesions at onset. Nasal and/or laryngeal involvement was found in 6/17 patients. These lesions were often severe with major functional impact. ENT localizations were found in patients with at least three localizations and lesions extending to mucous membranes distant from the oral cavity. A biopsy was obtained from all patients and demonstrated subepidermal detachment in eleven. Direct immunofluorescence was positive in eleven. Indirect immunofluorescence, performed in twelve patients, was negative. In two patients, both histology and immunofluorescence were negative. Electron immunomicroscopy was performed in four patients and confirmed the diagnosis. Five out of six isolated oral manifestations were treated with topical steroids alone. Multiple lesions were treated case by case using daprosone and/or systemic corticosteroids associated with topical steroids in 16/17 patients. A bolus of cyclophosphamid was given for four patients with very severe lesions which did not respond to other treatments. At last follow-up (22 +/- 17 months), none of the patients was considered cured. DISCUSSION: Cicatricial pemphigoid is a complex chronic disease. Oral manifestations may be isolated or associated with lesions of the skin or other mucous membranes. The painful aspect of oral lesions explains why the diagnosis is often made in stomatology. Careful evaluation at diagnosis is essential and requires a multidisciplinary approach. Certain diagnosis can be provided by immunohistology, particularly electron immunomicroscopy which enables distinguishing cicatricial pemphigoid from other autoimmune diseases of the dermo-epidermal junction. Treatment depends on disease severity. Isolated oral manifestations are generally well controlled by topical corticosteroids which ocular, nasal, and laryngeal localizations often require more extensive treatment.

Topical retinaldehyde treatment in oral lichen planus and leukoplakia.

The aim of this exploratory study was to assess the efficacy of a natural metabolite of vitamin A, retinaldehyde 0.1%, vehicled in a gel in 17 patients with oral lichen planus and in 13 patients with oral leukoplakia, twice daily for 2 months. Our investigation was clinical, histological, immunohistochemical through the expression of markers of cell terminal differentiation and biochemical by using two-dimensional gel electrophoresis of cytokeratins (CK). In addition, the activity of retinaldehyde was studied ex vivo on surviving buccal mucosa. Retinaldehyde gel 0.1% showed good clinical efficacy, resulting in 6% disappearance and 82% improvement of the lesions in lichen planus and 17% disappearance and 75% improvement in leukoplakia. This was confirmed with immunohistochemistry, which revealed down-regulation of filaggrin and CK-10 as markers of terminal differentiation in both diseases. The effects of retinaldehyde in these two diseases were further demonstrated in the ex vivo surviving mucosal model, resulting in histological disappearance of keratinization in 80% of the lichen planus fragments and 40% of the leukoplakia fragments, associated with down-regulation of filaggrin and CK-10.

Phase III trial of modulation of cisplatin/fluorouracil chemotherapy by interferon alfa-2b in patients with recurrent or metastatic head and neck cancer. Head and Neck Interferon Cooperative Study Group.

PURPOSE: In preclinical experiments, interferon alfa modulates the anticancer activity of fluorouracil (5-FU) and cisplatin (CDDP). To test this effect clinically in patients with recurrent or metastatic head and neck cancer (RMHNC), a multicenter randomized controlled trial with CDDP and 5-FU with or without interferon alfa-2b (IFNalpha) was performed. PATIENTS AND METHODS: Eligible patients had histologically confirmed RMHNC; a good performance status; measurable disease; adequate bone marrow, hepatic, and renal function; no prior chemotherapy for recurrent or metastatic disease; only one chemotherapy regimen administered with previous local therapy; and a treatment-free interval of at least 3 months following previous local therapy. Patients were randomized and stratified according to treatment center, and prior radiotherapy and chemotherapy. The treatment regimen consisted of CDDP 100 mg/m2 on day 1 and 5-FU 1,000 mg/m2/d by continuous infusion for 96 hours (days 1 to 4), without (arm A) or with (arm B) IFNg alpha 3 x 10(6) U/d subcutaneously on days 1 to 5. Cycles were repeated every 21 days. RESULTS: One hundred twenty-two patients were entered on each arm. The response rate (RR) was similar in both arms (arm A: complete response [CR] 10.7%, partial response [PR] 36.4%; arm B: CR 6.8%, PR 31.6%) (.70 < P < .50). There was no difference in median survival between the two arms (arm A 6.3 months v arm B 6.0 months; P = .49). Anorexia, fever, leukopenia, and thrombocytopenia grade III to IV were significantly more frequent in the IFNalpha arm. CONCLUSION: Modulation of CDDP and 5-FU with IFNalpha as used in this study does not improve the RR or the median survival in patients with RMHNC. Patients on both study arms had a poor prognosis, which indicates the need for novel therapies.

Nodal failures in patients with NO N+ oral squamous cell carcinoma without capsular rupture.

BACKGROUND: The efficacy of postoperative irradiation of the neck after lymph node dissection in terms of prevention of cervical node recurrence (NR) has not been demonstrated in patients with NO squamous cell carcinoma of the oral cavity. METHODS: This multicenter retrospective analysis comprises 826 patients with squamous cell carcinoma of the oral cavity, all clinically NO. The primary tumor was treated by resection or brachytherapy. All patients underwent cervical dissection adapted to the site of the tumor. Fourty seven N+ patients with capsular rupture were excluded; 160 patients were N+ without capsular rupture (N+ CR-), and 619 were N-. Postoperative cervical irradiation was performed in 67 of 160 N+ CR- patients and in 49 of 619 N- patients. RESULTS: NR developed in 78 patients, associated with local recurrence in 33 cases and isolated in 45 cases. Twenty-six of the 45 cases of isolated NR occurred in the 619 N- patients (4%), and 19 occurred in the 160 N+ CR- patients (12%, p = .001). The 26 NR observed in the N- patients occurred in nonirradiated patients. Among the 19 NR observed in the N+ CR- patients, the incidence of recurrence was not significantly different between irradiated patients (6 NR of 67.9%) and nonirradiated patients (13 NR of 93, 14%). NR rates also did not differ according to the number of lymph nodes invaded nor according to the level of the positive nodes; 14 of 45 isolated NR occurred in a nondissected suprahyoid region. Of 779 patients, 255 (33%) subsequently developed a metachronous cancer; 153 upper respiratory and digestive tract tumors, 37 lung tumors, 33 esophageal tumors, and 32 other tumors. Isolated cervical failure was responsible for 40 deaths. CONCLUSION: The low NR rate in NO N+ CR- patients means that postoperative irradiation can be confined to N+ CR+ patients and, as a precautionary measure, to patients with more than 3 N+ CR-. Keeping irradiation in reserve allows the treatment of metachronous cancers, which are particularly frequent in these patients, in whom the 5-year survival rate is 54% in N+ CR- and 69% in N-.

[Detection of oral cancers and current conception of precancerous conditions]. / Détection des cancers buccaux et conception actuelle des états précancéreux.

Detection and early diagnosis of oral cancers are conducted by general practitioners and dentists. Oral examination is particularly simple: it must be conducted methodically, helped with a good topographical knowledge. Oral examination allows to recognize cancers among tumorous oral lesions based on characteristic criteria. Precancerous lesions, like leucoplakias and lichen planus need a special attention; they must be treated to prevent cancers or strictly followed to catch up a possible worsening. The same physicians can help all along the treatment of oral cancers but their contribution is of major importance in prevention mostly against tobacco smoking.

Alteration of cytokeratin expression in oral lichen planus.

The purpose of this investigation is to examine the possible biochemical and topographic cytokeratin alterations in lichen planus of oral mucosa. Biopsy samples of clinically normal buccal mucosa (n = 5), normal gingiva (n = 5), lichen planus from buccal mucosa (n = 5), and lichen planus from gingiva (n = 5) were obtained from patients of both sexes. Cytokeratin expression was determined by means of immunohistochemical labeling with use of a battery of monoclonal antibodies against cytokeratins and filaggrin and two-dimensional gel electrophoresis. In buccal mucosa, which is not keratinized cytokeratins 4 and 13 are expressed in the majority. In buccal mucosa lichen planus, the appearance of cytokeratins 1, 2, 10, and 11 coincides with a decrease in cytokeratins 4 and 13 and a moderate increase in cytokeratins 6, 16, 17, and 19. In normal gingiva, which is normally keratinized, the main cytokeratins are 1, 2, 10, and 11. In gingival lichen planus, a slight decrease in these cytokeratins and in cytokeratin 13 expression was noted. Finally, alterations in cytokeratins 5 and 14, explained by marked alterations of basal cells, were observed. The battery of antibodies used in this study, in correlation with two-dimensional gel electrophoresis, could represent useful diagnostic tools that enable the distinction between inflammatory keratosis and so-called quiescent lichen planus. Moreover, this work showed that cytokeratins 1, 2, 10, and 11 and filaggrin are sensitive tools that may help detect early relapse before clinical exacerbation. Finally, these biochemical techniques may be useful to follow the evolution of lichen planus under treatment.

[Topical tretinoin in the treatment of lichen planus and leukoplakia of the oral mucosa. A biochemical evaluation of the keratinization]. / Trétinoïne topique dans le traitement des lichens plans et des leucoplasies de la muqueuse buccale. Evaluation biochimique de la kératinisation.

In earlier work, we demonstrated that 0.1 p. 100 topical tretinoin is clinically effective and well tolerated compared with placebo for the treatment of oral leukoplakia and oral keratosic or erythematous lichen planus. Here we aimed to complete this clinical protocol with histological and biochemical analyses comparing the biopsy specimens collected at inclusion and those collected after 4 months of treatment. Histological results were based on changes in keratinization observed between onset of treatment and 4 months treatment. Biochemical studies included the use of antibodies (anti-cytokeratins 10-11, anti-filaggrine) for the immunohistochemical evaluation of keratinization and 2-dimensional gel electrophoresis for measuring cytokeratins. In patients with lichen planus, histological changes during treatment showed that, in the 10 patients in the tretinoin group, keratinization disappeared in 6 and decreased significantly in 3. Immunohistochemistry revealed that cytokeratins 10-11 and filaggrin disappeared in 57 p. 100 of the patients treated with tretinoin versus 25 p. 100 in the patients given placebo. Bidimensional gel electrophoresis showed that cytokeratins 1, 2, 10 and 11 disappeared only in the tretinoin group (60 p. 100 of the cases). In patients with leukoplakia, histological changes during treatment showed that, in the tretinoin group, keratinization disappeared in 5 cases and decreased in 5 others. Immunohistochemistry revealed that cytokeratins 10-11 disappeared in 30 p. 100 of the patients treated with tretinoin versus 25 p. 100 in the placebo group. Bidimensional electrophoresis demonstrated that cytokeratins 1, 2, 10 and 11 disappeared in 43 p. 100 of the patients treated with tretinoin.

[Topical tretinoin in the treatment of lichen planus and leukoplakia of the mouth mucosa. A clinical evaluation]. / Trétinoïne topique dans le traitement des lichens plans et des leucoplasies de la muqueuse buccale. Evaluation clinique.

A randomized study was conducted to evaluate the effect of tretinoin and patient tolerance to treatment with topical applications in series of 20 cases of smoking-related or traumatic oral keratoses leukoplakia and of 20 cases of lichen planus. In each group, patients applied the topical ointment containing tretinoin (10 patients) or placebo (10 patients) twice daily. Clinical outcome was evaluated on the basis of the surface area of the lesion, measured monthly during treatment, as compared with the area observed at treatment onset. After 4 months treatment, there was a significant decrease in the surface area of the lesion in the patients with lichen planus (p < 0.02): 94 p. 100 in the tretinoin group versus 21.4 p. 100 in the placebo group. In patients with leukoplakias, there was also a very significant reduction in the surface area of the lesion after 4 months of treatment (p < 0.001): 80 p. 100 in the tretinoin group and 16 p. 100 in the placebo group. Tolerance to treatment was generally good despite a few complaints of quite temporary burning sensation at application rapidly resolutive.

[Sarcoid granuloma of the accessory salivary glands. An anatomic study and anatomo-clinical correlations: apropos of 17 cases]. / Granulomes sarcoïdosiques des glandes salivaires accessoires. Etude anatomique et corrélations anatomo-cliniques: à propos de 17 observations.

From 228 clinical files of cases with suspected sarcoidosis who had had a biopsy of the accessory salivary glands, 17 cases with both a final diagnosis of sarcoidosis and one or more tuberculoid granulomas. There were 12 women (mean age: 30 years) and 5 men (mean age: 28.5 years) including 3 of Caribbean or African descent. The histopathological examination was performed to determine: 1) the number of granulomas per biopsy, divided into 3 groups: group I, 1 granuloma (n = 1); group II, 2 to 5 granulomas, mean 3.5 (n = 6); group III more than 5 granulomas, mean 12.5 (n = 5); 2) the diffusion of the granulomas within the lobules: 17% of the lobules were involved in groups I and II vs 47% in group III; 3) the size of the granulomas "minimal" (barely identifiable in 3 of 6 patients in group I; rather easily identifiable in all the other patients; 4) the presence of "non-specific" lesions including lymphoid infiltration, epithelial changes. In addition correlations with other clinical parameters of severity and/or duration were evaluated including: involvement of the main salivary glands and/or non-secretory syndrome. The following conclusions were drawn: 1) lesions of the accessory salivary glands is a sign of sarcoid lesions outside the thorax since 16 of the 17 patients had extra-thoracic clinical, biological or anatomic manifestations; 2) there is not however any significant difference in clinical severity between the 3 anatomic "intensity" groups (number of follicules in the accessory salivary glands); 3) both cases of sarcoidosis of recent onset (< 3 months) with Loefgren's syndrome were in group I; 4) the intensity of the specific lesions in the accessory salivary glands was similar to that of the non-specific lesions and can be correlated with the intensity of the main salivary gland involvement, with or without a non-secretory syndrome.

[Biopsy of the accessory salivary glands. 5 years' experience]. / Biopsie des glandes salivaires accessoires. Bilan de 5 ans.

Biopsy of the minor salivary glands has become a routine examination ordered by physicians working in a wide range of disciplines in order to search for or eliminate the diagnosis of Gougerot Sjögren's disease or another systemic disease. We emphasize the need to use this examinations as a part of a complete work-up of the buccal cavity and the salivary glands. We reviewed our experience with 1,500 biopsies. The glands biopsied were normal in 56% of the cases and led to the diagnosis of Gougerot Sjögren's disease in 24%, chronic sialadenitis in 10% and diverse trophic problems in 5%. The clinical stage of Gougerot Sjögren's disease is usually proposed according to the Chisholm classification which we propose to compare with the Chomette classification. Finally, we described the technique of minor salivary gland biopsy.

[Histopathologic lesions of the accessory salivary glands in Gougerot-Sjögren syndrome: re-evaluation of the diagnostic criteria of Chisholm and Mason and of Chometter et al]. / Lésions histopathologiques des glandes salivaires accessoires (G.S.A.) au cours du syndrome de Gougerot-Sjögren: réévaluation des critères diagnostiques de Chisholm et Mason et de Chomette et coll.

In a retrospective study, we used a series of 29 patients with Sjögren's Syndrome diagnosed according to the new European criteria (Cl. Vitali, S. Bombardieri, H. M. Moutsopoulos et al.) (8). (Arthritis Rheum 1993; 36:340-7). A labial biopsy technique allowed to classify these patients into the anatomical "scores" formerly related by Chisholm and Mason and Chomette et al. Referring to these criteria, only 45% of patients presented a characteristic histopathological pattern. If another complementary criterium, i.e. ductal tropism of lymphoid infiltrates, was added, that percentage remained low (50% only). Thus, these results would suggest the following considerations: the classical histopathological criteria do not seem sufficiently specific; other histological criteria such as ductal lesions previously noted by Leroy et al. must in addition be looked for; thus it would seem to be of considerable value to use in the future complementary quantitative studies by means of morphometric methods.

[Maxillary ameloblastoma. Apropos of a case and review of the literature]. / Améloblastome maxillaire. A propos d'un cas et revue de la littérature.

Although ameloblastoma is one of the benign odontogenic tumors, the maxillary localisations often grow more infiltratively and show higher recurrency than the mandibular localisations. The authors report a case of ameloblastoma in maxillary sinus and sketch out the operative methods with a literature review.