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Hervé Bachelez

Publications and source records attributed to Hervé Bachelez.

15 recordsLinked to original sources
PubMed2005

Vaccination-induced cutaneous pseudolymphoma.

BACKGROUND: Although mild early cutaneous transient reactions to vaccinations are common, late-onset chronic lesions have been scarcely reported. We report herein a series of 9 patients presenting with cutaneous and subcutaneous pseudolymphoma. OBSERVATIONS: Nine patients presenting with late-onset, chronic skin lesions occurring at the site of antihepatitis B (8 cases) and antihepatitis A (one case) vaccination were reported. Histopathologic and immunohistochemic studies, and molecular analysis of clonality of skin biopsy specimens, were performed. Furthermore, the presence of vaccine products was investigated in skin lesions by using histochemical, microanalytic, and electronic microscopy techniques. RESULTS: Histopathologic studies showed dermal and hypodermal lymphocytic follicular infiltrates with germinal center formation. The center of follicles was mostly composed of B cells without atypia, whereas CD4+ T cells were predominant at the periphery. Molecular analysis of clonality revealed a polyclonal pattern of B-cell and T-cell subsets. Aluminium deposits were evidenced in all cases by using histochemical staining in all cases, and by microanalysis and ultrastructural studies in one case. Associated manifestations were vitiligo (one case) and chronic fatigue with myalgia (two cases). CONCLUSION: Cutaneous lymphoid hyperplasia is a potential adverse effect of vaccinations including aluminium hydroxide as an adjuvant. Further prospective studies are warranted to evaluate the incidence of this complication in the immunized population.

Adolescent↗
PubMed2005

ESHAP for primary cutaneous T-cell lymphomas: efficacy and tolerance in 11 patients.

Systemic multiagent hemotherapy has been used to treat aggressive forms of primary cutaneous T-cell lymphomas (CTCL) with controversial results. Our objective was to retrospectively assess efficacy and toxicity of ESHAP (etoposide, cisplatin, high-dose aracytine, methylprednisolone) in patients with advanced CTCL. A total of 11 patients with aggressive primary CTCL, treated with the ESHAP protocol between 1995 and 2002, were studied. Two patients achieved complete remissions lasting 30+ and 6+ months, seven had partial remissions of short duration, one had stable disease and one experienced disease progression. ESHAP was poorly tolerated because of prolonged myelosuppression (91%) and infectious complications (82%). Our results suggest that ESHAP has a poor risk/benefit ratio in advanced CTCL because of the low number of complete remissions, the short duration of partial remissions and its high-grade toxicity.

Adult↗
PubMed2004

Expression and activity of IL-17 in cutaneous T-cell lymphomas (mycosis fungoides and Sezary syndrome).

Interleukin-17 (IL-17) is a proinflammatory cytokine mainly produced by activated CD4+ CD45RO T cells. In mice, we have demonstrated that, depending on the model, IL-17 may act as a tumor growth-promoting or -inhibiting factor. In order to address the relevance of these models in human tumors, we look for the natural expression and activity of IL-17 in mycosis fungoides (MF) and Sezary syndrome (SS). These cutaneous T-cell lymphomas were selected because they are usually CD3+ CD4+ CD45RO+, a phenotype similar to nontransformed T cells producing IL-17. We show that in vitro activated malignant T cells derived from MF or SS patients express IL-17 mRNA and secrete this cytokine. However, IL-17 does not act in vitro as a growth factor for MF or SS cell lines. In addition, 5 out of 10 MF/SS biopsies expressed IL-17 mRNA, while this cytokine was not detected in normal skin. IL-17 was not observed in the biopsies derived from 2 patients initially identified as MF, whereas an upregulation of this cytokine was clearly demonstrated during progression of the disease in these patients. An association between IL-17 expression and polymorphonuclear neutrophil infiltration was also recorded in this group of MF/SS patients. A more detailed analysis of 2 patients with a pustular form of MF and SS revealed that IL-17 may participate in the recruitment of polymorphonuclear neutrophils via a paracrine mechanism involving keratinocyte-released IL-8. This study is the first report demonstrating that some human tumor cells could express IL-17, a cytokine that represents an early event in the development of the inflammatory reaction within the tumor microenvironment, a process that may influence tumor phenotype and growth.

Biopsy↗
PubMed2004

Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells.

Dominant tolerance is mediated by regulatory T cells (T(reg)) that control harmful autoimmune T cells in the periphery. In this study, we investigate the implication of T(reg) in modulating infiltrating T lymphocytes in human metastatic melanoma. We found that CD4(+)CD25(high) T cells are overrepresented in metastatic lymph nodes (LNs) with a 2-fold increased frequency compared with both tumor-free LNs and autologous PBMCs. These cells express the Foxp3 transcription factor, display an activated phenotype, and display a polyclonal TCR Vbeta chain repertoire. They inhibit in vitro the proliferation and cytokine production of infiltrating CD4(+)CD25(-) and CD8(+) T cells (IL-2, IFN-gamma) through a cell-contact-dependent mechanism, thus behaving as T(reg). In some cases, the presence of T(reg) type 1/Th3-like lymphocytes could also be demonstrated. Thus, T(reg) are a major component of the immunosuppressive microenvironment of metastatic melanoma LNs. This could explain the poor clinical response of cancer patients under immunotherapeutic protocols, and provides a new basis for future immunotherapeutic strategies counteracting in vivo T(reg) to reinforce local antitumor immune responses.

CD4-Positive T-Lymphocytes↗
PubMed2004

[Prescribing immunosuppressive and immunomodulatory drugs in psoriasis].

Even though systemic immunomodulating or immunosuppressive therapies have shown efficacy in patients with psoriasis, their usage remains restricted to patients with severe, refractory forms of the disease. Indeed, the risk/benefit balance should be cautiously taken into account before prescribing such drugs. Nevertheless, risks inherent to their usage are limited by a careful knowledge of prescription rules and by a monitoring of side effects.

Adjuvants, Immunologic↗
PubMed2004

Treatment of refractory pemphigus vulgaris with rituximab (anti-CD20 monoclonal antibody).

BACKGROUND: Pemphigus vulgaris (PV) is a severe antibody-mediated autoimmune blistering disease. Because some patients with PV do not enter into remission, despite the use of high-dose corticosteroid therapy and immunosuppressive adjuvant treatments, new effective and safer agents are warranted to treat refractory PV. Rituximab, a monoclonal anti-CD20 antibody, induces depletion of B cells in vivo and has shown efficacy in patients with refractory antibody-mediated autoimmune disorders. We describe herein 3 patients treated with rituximab for severe PV. OBSERVATIONS: Three patients with refractory PV were treated with rituximab, resulting in a clinical response in all patients, which was complete in 2 patients. A decline in titers of circulating antiepidermis autoantibodies paralleled disease activity, while circulating B cells remained undetectable for 6 to 10 months. Two patients experienced bacterial infection in the weeks following the rituximab course. A clinical relapse occurred in 2 patients, at 6 and 10 months. A second course of rituximab controlled the disease in one of them. CONCLUSION: These patients' response suggests that rituximab may be a valuable treatment for refractory PV and warrants further studies to evaluate the risk-benefit ratio in patients with PV showing resistance to classic therapy.

Adult↗
PubMed2004

Prognostic value of blood eosinophilia in primary cutaneous T-cell lymphomas.

OBJECTIVE: To investigate the prognostic value of initial characteristics including blood eosinophilia in patients with primary cutaneous T-cell lymphoma. DESIGN: A retrospective inception cohort, patients included from date of diagnosis (1982-1998). SETTING: Two dermatology departments of a university hospital. Patients A total of 104 patients with cutaneous T-cell lymphoma, including patients with mycosis fungoides (n = 69), Sézary syndrome (n = 13), and nonepidermotropic cutaneous lymphoma (n = 22). The following variables were recorded: age, sex, diagnosis according to the European Organization for Research and Treatment of Cancer (EORTC) classification, type of skin involvement at the time of diagnosis, initial eosinophil absolute count, lactate dehydrogenase value, date of disease progression, and cause and date of death or date of last contact. MAIN OUTCOME MEASURES: Time from diagnosis to disease progression and to disease-specific death. RESULTS: The median follow-up was 43 months (range, 7-197 months). Estimated rates of disease progression and disease-specific death for 3 years were 19.5% (95% confidence interval [CI],11.3%-27.6%) and 9.9% (95% CI, 2.8%-13.6%), respectively. Univariable analysis of initial variables possibly influencing disease progression revealed significant prognostic value for diagnosis according to EORTC classification (hazard ratio [HR], 2.77; 95% CI, 1.04-7.41; P =.04), type of skin involvement (HR, 2.70; 95% CI, 1.00-7.25; P =.04), raised blood eosinophil absolute count (HR, 7.33; 95% CI, 2.84-18.91; P<.001), and raised serum level of lactate dehydrogenase (HR, 3.72; 95% CI, 1.58-8.78; P =.001). Concerning disease-specific death, significant prognostic indicators were diagnosis according to the EORTC classification (HR, 6.62; 95% CI, 1.68-26.12; P =.007) and a raised blood eosinophil absolute count (HR, 10.57; 95% CI, 2.28-49.0; P<.001). In multivariable analysis, only blood eosinophilia was associated with disease progression and disease-specific death. CONCLUSION: These results strongly suggest that blood eosinophilia at baseline is a prognostic factor in patients with primary cutaneous T-cell lymphoma.

Adult↗
PubMed2004

High frequency of cholestasis in generalized pustular psoriasis: Evidence for neutrophilic involvement of the biliary tract.

Generalized pustular psoriasis is a rare form of psoriasis that is sometimes associated with extracutaneous manifestations. Evidence for biliary involvement has been suggested in isolated cases. We investigated the prevalence and nature of liver abnormalities occurring in this disease. Twenty-two patients consecutively admitted for generalized pustular psoriasis who underwent liver biological tests at the time of the attack and during the following weeks were included. Twenty patients (90%) had at least one abnormal biological liver parameter. Eleven patients (50%) had pronounced abnormalities: jaundice (4/22), gammaglutamyl transferase higher than 5 times the normal value (10/22), alkaline phosphatase higher than twice the normal value (7/22), and/or aminotransferases higher than 3 times the normal value (7/22). These abnormalities returned to normal range at the time of remission of pustular psoriasis, suggesting that severe liver abnormalities could be associated with severe cutaneous disease. Neutrophilic cholangitis was observed on liver biopsy. Persistent magnetic resonance cholangiopancreatography features similar to those observed in sclerosing cholangitis were found in 3 of the 4 patients studied. No causal factor other than pustular psoriasis could be identified. In conclusion, our results demonstrate the high frequency of liver abnormalities in patients with generalized pustular psoriasis. Biliary involvement related to neutrophilic cholangitis should be added to the spectrum of extracutaneous manifestations of this disease, and physicians should be aware of such a complication.

Adult↗
PubMed2003

[Psoriasis].

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed2003

Follow-up of the T-cell clonality in Sezary patients treated by extracorporeal photopheresis using a new assay: the immunoscope technique.

Sezary syndrome is a leukemic form of epidermotropic cutaneous T-cell lymphoma related to the malignant proliferation of clonal CD4+ T-cells. Extracorporeal photochemotherapy (ECP) may induce a transient improvement of the clinical signs but it's efficiency is discussed. In order to investigate the T-cell clonality in the peripheral blood of patients with Sezary syndrome and to monitor its evolution in 8 patients treated by ECP, we used the Immunoscope technique. In one patient, we observed a decrease of the T-cell clonality from 15.6% to 0%, paralleling a complete remission of the clinical disease with a disappearance of the circulating Sezary cells. In the other cases, the evolution of the relative frequency paralleled the clinical status of the patient. In 3 cases, we observed a quick-acting direct cytotoxicity of the association 8MOP + UVA on the T-cell clone present in the cellular product. Immunoscope technique appears to be an efficient assay to appreciate the amount of tumoral cells and monitor the evolution of the clonal component in Sezary syndrome.

Aged↗
PubMed2003

Arsenic trioxide induces apoptosis of cutaneous T cell lymphoma cells: evidence for a partially caspase-independent pathway and potentiation by ascorbic acid (vitamin C).

Arsenic trioxide (As2O3) displays apoptogenic properties against various types of hematopoietic malignancies. We investigated the effects of As2O3 on the viability of the cutaneous T cell lymphoma cell lines HuT-78, SeAx, and Myla, and of peripheral blood mononuclear cells from patients with Sézary syndrome, by using propidium iodide and annexin-V staining, terminal deoxyuridine triphosphate nick end labeling (TUNEL), cell cycle analysis, mitochondrial transmembrane potential (delta psi(m)) alterations, cytochrome c release, and detection of processed caspase-3. We also report in vivo effects of As2O3 in two patients with cutaneous T cell lymphoma. The results show that As2O3 induces apoptosis of cutaneous T cell lymphoma lines and of Sézary cells from patients in a time- and concentration-dependent manner in vitro, as demonstrated by annexin-V staining, mitochondrial depolarization, and DNA fragmentation. Ascorbic acid 100 microM potentiated As2O3-induced Sézary cell death, whereas interferon-alpha had no synergistic effect. As2O3-induced Sézary cell death involves activation of caspase-3, cleavage of poly(ADP-ribose)polymerase, and cytochrome c release, but was only partially inhibited by the pancaspase inhibitor Z-VAD.fluoromethylketone. Finally, As2O3 was administered to two patients with cutaneous T cell lymphoma, allowing us to obtain a partial response in one case, whereas stability was observed in the second patient. These results demonstrate that As2O3 synergizes with ascorbic acid to induce Sézary cell death at clinically achievable concentrations, through a caspase-partially independent pathway, and provide a rationale for further in vivo studies addressing the therapeutic efficacy of As2O3 in cutaneous T cell lymphoma patients.

Aged↗
PubMed2003

Peripheral blood lymphocyte subset counts in patients with dermatomyositis: clinical correlations and changes following therapy.

Lymphocytopenia has been reported in patients with connective tissue diseases, including dermatomyositis (DM). However, the risk of infectious complications and the changes of lymphocytic subsets during treatment have been poorly investigated in these patients. We investigated the alterations of peripheral blood lymphocyte counts in patients with DM. A retrospective analysis was conducted in patients with an ascertained diagnosis of DM admitted from 1994 to 2000 in both departments of Dermatology of the Saint-Louis Hospital in Paris. All patients had a peripheral blood absolute lymphocyte count available before therapy. From an initial set of 63 patients, 47 were included in the study. The median absolute lymphocyte count was 888/mm(3) (range, 400-4,070). Low peripheral blood CD4+ and CD8+ T-cell and B-cell counts were consistent findings (median CD4+: 382/mm(3); CD8+: 211/mm(3); CD19+: 122/mm(3)). There was a significant increase in lymphocyte count after 1 month (p < 0.0001), 3-6 months (p = 0.001), and 6-12 months (p = 0.0005) of corticosteroid treatment. Infectious events, mainly pneumonia (PCP), occurred in 12 patients. Their initial lymphocyte count was lower than that of patients who did not develop infections (p = 0.0001). These results support the high prevalence of lymphocytopenia in patients with DM and emphasize the risk for opportunistic infections, mainly PCP, in these patients. Further studies are warranted to evaluate the risk/benefit balance of PCP prophylaxis in patients with DM and severe lymphocytopenia.

Adolescent↗
PubMed2002

A prospective study on the evolution of the T-cell repertoire in patients with Sézary syndrome treated by extracorporeal photopheresis.

Sézary syndrome is a leukemic form of epidermotropic cutaneous T-cell lymphoma related to the malignant proliferation of clonal CD4(+) T cells. Extracorporeal photochemotherapy may induce a transient improvement of the clinical signs, but its efficiency is discussed. To investigate the frequency of the T-cell clone in the peripheral blood of patients with Sézary syndrome and to monitor its evolution in patients treated using extracorporeal photopheresis or chemotherapy, we used the immunoscope technique. In one patient, we observed a decrease of the relative frequency of the clone from 15.6% to 0%, paralleling a complete remission of the clinical disease and a disappearance of the circulating Sézary cells. In the other cases, the evolution of the relative frequency paralleled the initial improvement of the clinical status and the absence of long-term efficiency in patients treated with extracorporeal photopheresis or chemotherapy. We observed a quick-acting direct cytotoxicity of the association 8MOP + UVA on the T-cell clone. The immunoscope technique appears to be an efficient tool to appreciate the amount of tumoral cells and to monitor the evolution of the clonal component in the Sézary syndrome.

Aged↗
PubMed2002

B-cell lymphomas involving the skin associated with hepatitis C virus infection.

BACKGROUND: A role for hepatitis C virus (HCV) infection has been suggested in the pathogenesis of non-Hodgkin lymphomas (NHL). AIM: To evaluate the characteristics of cutaneous lymphomas occurring in HCV-infected patients, and to investigate the hypothesis of a direct infection of malignant cells. METHODS: Three patients showing a positive serology for HCV and a cutaneous lymphoma were studied. Analysis of HCV replication was performed using reverse transcriptase-polymerase chain reaction. The presence of HCV RNA was also assessed in biopsies from lesional skin and in a lymph node in one case. Genotype characterization was carried out on the basis of LiPA genotyping assays using viral genomic amplification products. RESULTS: Cutaneous NHL occurred in patients with chronic and replicative HCV infection, and exhibited a B-cell phenotype (one diffuse large B-cell lymphoma, one follicular lymphoma, and one marginal zone B-cell lymphoma). All patients were male; two of them were former intravenous drug abusers, while the HCV contamination route was unknown in the third. The search for HCV RNA in the skin and in lymph nodes yielded negative results. HCV genotypes were 1b in two cases and 3a in one case. CONCLUSION: These results show that a subset of B-cell cutaneous NHL is associated with a replicative HCV infection and suggest that HCV is not involved in lymphomagenesis through a direct infection of malignant cells. The ability of HCV to trigger a chronic B-cell lymphoproliferation could represent another mechanism, while a fortuitous association cannot be excluded.

Adult↗