French guidelines for the management of oral lichen planus (excluding pharmacological therapy).

INTRODUCTION: Oral lichen is a chronic inflammatory disease for which diagnostic management and follow-up are heterogeneous given the absence of specific guidelines in France. Our objective was to develop French multidisciplinary guidelines for the management of oral lichen. MATERIALS AND METHODS: Working groups from the Groupe d'Etude de la Muqueuse Buccale (GEMUB) formulated a list of research questions and the corresponding recommendations according to the "formal consensus" method for developing practice guidelines. These recommendations were submitted to a group of experts and the degree of agreement for each recommendation was assessed by a scoring group. RESULTS: Twenty-two research questions, divided into 3 themes (nosological classification and initial assessment, induced oral lichenoid lesions, and follow-up) resulted in 22 recommendations. Initial biopsy for histology is recommended in the absence of reticulated lesions. Biopsy for direct immunofluorescence is recommended for ulcerated, erosive, bullous types and for diffuse erythematous gingivitis. Management should include a periodontal and dental check-up, and investigation for extra-oral lesions. Hepatitis C testing is recommended only if risk factors are present. Definitions, triggering factors and the management of "induced oral lichenoid lesions" were clarified. Oral lichen must be monitored by a practitioner familiar with the disease at least once a year, using objective tools. CONCLUSION: This formalised consensus of multidisciplinary experts provides clinical practice guidelines on the management and monitoring of oral lichen.

[CLOVES syndrome: a malformational syndrome closely resembling Proteus syndrome]. / Syndrome CLOVES: un syndrome malformatif proche du syndrome de Protée.

BACKGROUND: CLOVES syndrome (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined-type Vascular malformations, Epidermal nevi, Skeletal anomalies) is a sporadic malformational syndrome that has recently been described (mutation of PIK3CA), with asymmetric body hypertrophy, lipomatous hamartoma of the trunk and numerous malformations. PATIENTS AND METHODS: We report a case of CLOVES syndrome initially diagnosed as Proteus syndrome, revealed by infection of a dorsal lipomatous hamartoma. The patient presented with both right lower limb hypertrophy and capillary and venous-lymphatic malformations, associated with dorsal capillary malformations, left cervico-facial hypertrophy, and cervical epidermal hamartoma, all of which are consistent with Proteus syndrome. Imaging of the dorsal lipomatous hamartoma associated with capillary as well as underlying venous-lymphatic malformations and syringomyelia resulted in subsequent correction of the earlier diagnosis of Proteus syndrome to that of CLOVES syndrome. DISCUSSION: Several malformational syndromes are associated with tissue hypertrophy, hamartoma and vascular malformations. Diagnosis of CLOVES syndrome may be delayed due to its fairly close phenotypic similarity to Proteus syndrome. Nevertheless, the prognosis and complications differ. Our case underlines the importance of considering a diagnosis of CLOVES syndrome in the presence of lipomatous hamartoma with hemi-hypertrophy and epidermal hamartoma, in order to enable adequate follow-up with specific monitoring for the possible complications associated with this disease.

Amlodipine-induced gingival enlargement: A case report.

Gingival enlargements (GEs) can be caused by local, systemic diseases or drugs. Three molecules can be responsible of GEs: ciclosporin, phenytoin and calcium channel blockers (CCBs). We report the case of a 56-year-old male treated by Amlodipine, a CCB, for hypertension for many years and who recently developed a severe GE affecting both mandibular and maxillary arches inducing dental malposition. The histological examination showed non-specific inflammation with a predominance of lymphocytes. Amlodipine was suspected and suspended in agreement with his physician. One month later, the enlargement significantly reduced but GE was so severe and dental malposition so marked that all the teeth but the canines were extracted. No recurrence was noted one year later. This exceptional case should encourage every practitioner to be vigilant with patient treated with CCBs and their potential side effects and consequences.

[Pyodermatitis-pyostomatitis vegetans with nasal involvement]. / Pyostomatite-pyodermatite végétante avec atteinte nasale.

BACKGROUND: Pyodermatitis-pyostomatitis vegetans (PPV) is a rare chronic disorder often associated with inflammatory bowel disease. We report an isolated case involving the oral, labial and nasal mucosa. PATIENTS AND METHODS: A 28-year-old man, in good general condition, presented with a 2-year history of painless stomatitis. The physical examination revealed pustular and exophytic lesions of the jugal, gingival and palatine mucosa on an erythematous background, as well as some pustular and crusted lesions of the lower lip and nostrils. Histopathological analysis revealed epithelial hyperplasia and a suprabasal cleft with some signs of acantholysis and numerous neutrophils and eosinophils. Direct and indirect immunofluorescence assay was negative. There was no associated bowel disease. We concluded on a diagnosis of PPV of younger subjects. The lesions disappeared with oral corticosteroids but with steroid dependency. DISCUSSION: PPV is a rare dermatosis associated in more than 75% of cases with inflammatory bowel disease, usually ulcerative colitis. Lesions of the oral mucosa are a constant finding and are characterised by aseptic pustules on an erythematous background. Skin lesions are pustular and more or less exophytic. To our knowledge, there have been no reports to date of intranasal lesions of PPV.

[Combination of dacarbazine, cisplatin and interferon alpha in the treatment of metastatic melanoma]. / Association dacarbazine, cisplatinium et interféron alpha dans le traitement du mélanome métastatique.

INTRODUCTION: The aim of this work was to study the effectiveness and safety of a combined therapy with dacarbazine, cisplatin and interferon alpha in the treatment of metastatic melanoma. PATIENTS AND METHODS: Sixteen patients, including 15 with one or more visceral metastases, were treated with dacarbazin 400 mg/m2, cisplatin 100 mg/m2 repeated every 28-day and interferon alpha-2a 3.10(6) IU subcutaneously 3 times weekly. Fifty percent of patients had at least 3 different sites of metastases. Ten patients had previously received one or more specific treatment for their melanoma. RESULTS: The overall response was 25 p. 100 (2 complete responses and 2 partial responses). The two complete responses were obtained on liver, lung and cutaneous metastases and remain in sustained, unmaintained remission for 22 and 24 months. Administration of this treatment was well tolerated, the most prevalent toxicity being hematologic. At present, responding patients have a median survival of 26 months+ since the beginning of the treatment, compared to 7 months for non responding patients. DISCUSSION: Dacarbazine and cisplatin combined chemotherapy has been used at various doses with an overall response rate of 14 to 37 p. 100, similar to our results. However, duration of complete response in our study (22 months+ and 24 months+) seem more prolonged than in studies using dacarbazine and cisplatin at dose of 100 mg/m2/21 d (7 to 9 months) and comparable to studies using dacarbazine and cisplatin at dose of 150 mg/m2/28 d or more (15 months+ to 19 months+ and 24 months+) but with less toxicity. Therefore addition of interferon alpha might be of interest in the maintain of complete remissions and perhaps in the prolongation of survival of responding patients as it has already been suggested with the dacarbazine-interferon alpha combination.

[Detection of circulating neoplastic cells by reverse transcriptase and polymerase chain reaction in melanoma]. / Détection de cellules mélaniques circulantes par transcription inverse et réaction de polymérisation en chaîne dans les mélanomes.

BACKGROUND: Circulating melanocytes can be detected in peripheral blood of patients with malignant melanoma by means of tyrosinase messenger RNA amplification. In this study we especially examined peripheral blood from patients with stage II melanoma before and after lymph node dissection for the detection of these circulating melanoma cells. Indeed the presence of regional nodal metastasis is one of the most important prognostic factors in patients with cutaneous melanoma. PATIENTS AND METHODS: Blood samples were collected from 20 normal patients, 42 patients with stage I melanoma and 23 patients with stage III melanoma. Twenty patients with stage II melanoma were tested 3 days before lymph node dissection and 2 à 8 weeks after. To identify circulating melanocytes, we used coupled reverse-transcription and polymerase chain reaction to target tyrosinase messenger RNA. RESULTS: None of the 20 patients with stage II melanoma had detectable circulating melanocytes before lymph node dissection. By contrast, 7 of them became transiently PCR positive in the 8 weeks following surgery. We observed no evidence of correlation between the presence of circulating melanocytes after lymph node dissection and the risk of relapse within 6 months after surgery or the presence of capsule breaking or the number of involved lymph nodes. Sixty-nine percent of stage III patients and none of stage I patients were found to have circulating melanocytes. DISCUSSION: Our study suggests that melanoma cells could circulate transiently after lymph node dissection. Confrontation of our results with literature data, despite important discrepancies related in part to sensibility technique, shows that the presence of circulating melanoma cells is correlated to the clinical stage. Prognostic value of these circulating cells need to be further assessed by prospective studies with large number of patients and long follow-up.

[Gingival lichen planus]. / Le lichen plan gingival.

Lichen planus (LP) is a chronic inflammatory disease of uncertain etiology. When the gingiva is affected, the LP can appear under several clinical forms. The diagnosis of the gingival lichen planus is based on the anamnesis, the clinical observation and the histological analysis. Various medicamentous and non medicamentous treatments are used to treat gingival LP with random results, due to the lack of knowledge on the etiology and the recidiving character of the lesions. The risk of malignant transformation of gingival LP is weak but it depends on clinical forms, justifying a periodic follow-up of all patients.

[Desquamative gingivitis]. / La gingivite desquamative.

The desquamative gingivitis is the clinical term given to the gingival manifestation of mucocutaneous diseases. It is characterized by an erythematous, glazed, friable and hemorrhagic gingiva, which can be accompanied by pains. Except the gingiva, the lesions can be localised on other oral mucous membranes or on the skin. The three principal diseases at the origin of the desquamative gingivitis are by order of frequency: the cicatricial pemphigoïd, erosive lichen planus and pemphigus. The knowledge of the clinical, histological and immunohistochemical characteristics of these three affections is essential for the diagnosis and the suitable treatment of the desquamative gingivitis.

Primary cutaneous B-cell lymphomas of the lower limbs: a study of integrin expression in 11 cases.

Primary cutaneous B-cell lymphoma is a rare disease. Among the cutaneous B lymphomas, B-cell lymphomas of the lower limbs appear as a special subgroup with a prognosis that is possibly worse than that of primary cutaneous B-cell lymphomas located on the trunk, arms or head, with more frequent relapses. In addition, some recent studies indicate that the level of expression of integrins on tumour cells could be related to the clinical course of the disease. This study reports on 14 cases of primary cutaneous B-cell lymphomas of the lower limbs and their clinical course. A study of integrin expression by tumour cells was performed in 11 of these cases. With a mean follow-up of 31 months, the study confirmed the worse prognosis of lymphomas with a predominance of centroblasts and immunoblasts (3 deaths) compared with lymphomas with a predominance of centrocytes, as well as their higher rate of recurrence (7/11). A correlation was confirmed between the course of the disease and the level of expression of lymphocyte function-associated antigen-1, intercellular adhesion molecule-1 and very late antigen-4 by tumour cells.

Long-term follow-up in 51 patients with mycosis fungoides and Sézary syndrome treated by interferon-alfa.

Although interferon-alfa (IFN-alpha) has proved effective in treating epidermotropic cutaneous T-cell lymphoma (ECTL), few studies have considered the follow-up of treated patients and whether complete remission was maintained. We studied 51 patients (one stage Ia, seven stage Ib, one stage IIa, 30 stage IIb, 11 stage III (Sézary syndrome) and one stage IV) who received low-dose IFN-alpha as monotherapy for ECTL (mean daily dose of IFN-alpha 2.7 x 106 units for 14.9 months), giving special consideration to the significance of My7 (CD13) antigen expression by epidermal basal cells in predicting the maintenance of complete remission. For a mean follow-up period of 43.4 months, the results showed 21 complete remissions, 13 partial remissions and 17 patients with stable or progressive disease. Twelve patients died during the follow-up (3-52 months). IFN-alpha led to an improved response in the early stages, with a greater number of complete remissions (P = 0.03) and partial remissions (P = 0.01). The mean time to complete remission was 4 months, regardless of clinical stage (P = 0.1). Of 21 patients in complete remission, 57% had a relapse within a mean period of 7.5 months. For patients maintained in complete remission, the mean period of response was 31 months. The length of complete remission was independent of clinical stage, and My7 antigen expression was not predictive of complete remission.

High-scale expansion of melanoma-reactive TIL by a polyclonal stimulus: predictability and relation with disease advancement.

The rationale of treating melanoma patients by infusion with tumor-infiltrating leukocytes (TIL) is to perform an adoptive therapy through injection of tumor-specific T cells. Nonetheless, methods currently used for ex vivo TIL expansion have not been evaluated for their efficacy to expand TAA-specific T cells. We have addressed this question here, using a culture method in which high TIL growth was induced by a polyclonal T cell stimulus. Intracellular cytokine assays were performed to measure the proportion of T cells responding to autologous tumor cells among the lymphocytes from lymph node biopsies (TIL) of 26 patients with stage III melanoma. The data show that TIL from 18 of these patients contained detectable amounts of tumor-specific T cells before expansion. Although they decreased somewhat in percent abundance during expansion, they were still present afterwards, ranging from 0.3 to 13.8%. Since a median number of 1.7 x 10(10) TIL was obtained from these patients (starting from 3.6 x 10(6) TIL), a total amount of tumor-reactive cytokine-secreting TIL of between 2.8 x 10(6) and 1.12 x 10(9) was obtained in each case from 18 patients. The TIL populations from 8 patients did not contain tumor-reactive T cells: neither before expansion, nor after expansion. Lack of tumor-reactive TIL only occurs for patients bearing several tumor-invaded lymph nodes (40%), but not for those having a single invaded lymph node. Therefore, high numbers of tumor-reactive T cells can be produced, through a polyclonal TIL stimulation, from most early stage III melanoma patients but from only about half of the patients with a more disseminated disease. For this last group, the possibility of getting tumor-reactive TIL can be predicted by checking the presence of these cells before expansion.

Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1.

Thirty-nine tumor-bearing patients with metastatic melanoma were treated with 3 subcutaneous injections of the MAGE-3.A1 peptide at monthly intervals. No significant toxicity was observed. Of the 25 patients who received the complete treatment, 7 displayed significant tumor regressions. All but one of these regressions involved cutaneous metastases. Three regressions were complete and 2 of these led to a disease-free state, which persisted for more than 2 years after the beginning of treatment. No evidence for a cytolytic T lymphocyte (CTL) response was found in the blood of the 4 patients who were analyzed, including 2 who displayed complete tumor regression. Our results suggest that injection of the MAGE-3.A1 peptide induced tumor regression in a significant number of the patients, even though no massive CTL response was produced.