The Experts below are selected from a list of 222 Experts worldwide ranked by ideXlab platform
Madeleine Duvic - One of the best experts on this subject based on the ideXlab platform.
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Non-Classic Signs of Sézary Syndrome: A Review
American Journal of Clinical Dermatology, 2020Co-Authors: Lisa Morris, Jessica Tran, Madeleine DuvicAbstract:The majority of patients with Sézary syndrome (SS) present with classic symptoms of erythroderma, lymphadenopathy, and pruritus. However, there have been numerous reports of patients with SS who have non-classic signs. In this review, we report the less common clinical presentations of SS and discuss their relevant treatments. Our search included all literature on SS since 2008, the year the World Health Organization (WHO) incorporated the diagnostic criteria for SS into the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. We reviewed 896 articles and identified 505 patients with non-classic presentations of SS. Of these 505 patients, the most common non-classic signs of SS were keratoderma, onychodystrophy, alopecia, Leonine Facies, and ectropion. Given the aggressive and highly symptomatic nature of SS, it is imperative that clinicians recognize the less common signs of the disease to prevent delays in diagnosis and treatment. To our knowledge, this is the first review of the clinical variations of SS with a focus on non-classic signs and symptoms.
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Non-Classic Signs of Sézary Syndrome: A Review.
American journal of clinical dermatology, 2020Co-Authors: Lisa M. Morris, Jessica Tran, Madeleine DuvicAbstract:The majority of patients with Sezary syndrome (SS) present with classic symptoms of erythroderma, lymphadenopathy, and pruritus. However, there have been numerous reports of patients with SS who have non-classic signs. In this review, we report the less common clinical presentations of SS and discuss their relevant treatments. Our search included all literature on SS since 2008, the year the World Health Organization (WHO) incorporated the diagnostic criteria for SS into the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. We reviewed 896 articles and identified 505 patients with non-classic presentations of SS. Of these 505 patients, the most common non-classic signs of SS were keratoderma, onychodystrophy, alopecia, Leonine Facies, and ectropion. Given the aggressive and highly symptomatic nature of SS, it is imperative that clinicians recognize the less common signs of the disease to prevent delays in diagnosis and treatment. To our knowledge, this is the first review of the clinical variations of SS with a focus on non-classic signs and symptoms.
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Leonine Facies (LF) and mycosis fungoides (MF): A single-center study and systematic review of the literature.
Journal of the American Academy of Dermatology, 2015Co-Authors: Danielle Nicole Brown, Iris Wieser, Casey Wang, Bouthaina S. Dabaja, Madeleine DuvicAbstract:Background Leonine Facies (LF) is defined as displaying facial features similar to that of a lion with prominent convexities and furrowed creases. LF develops in a very small population of patients with cutaneous T-cell lymphoma. Objective We aimed to study the clinicopathologic features and overall prognosis associated with LF in patients with mycosis fungoides and Sezary syndrome. Methods We conducted a single-center retrospective study, reviewing 1338 patients with mycosis fungoides seen from 1987 to 2015 at a tertiary referral center for cutaneous T-cell lymphoma, and a systematic review of 14 patients in the literature. Results We identified 10 patients with mycosis fungoides who developed LF. Folliculotropism was seen in all patients with LF who had facial biopsy specimens. Radiation was a beneficial therapy. Complete remission was achieved in 1 patient and overall 5-year survival was 26%. Systematic review of 10 additional patients showed that all patients with LF, including ours, had stage-IV disease and some degree of blood involvement, but not all met criteria for Sezary syndrome. Limitations This was a retrospective study with a small sample size. Conclusion LF is associated with stage-IV cutaneous T-cell lymphoma, is often accompanied by folliculotropism and blood involvement, and can be treated with local electron beam therapy.
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A case of indeterminate dendritic cell tumor presenting with Leonine Facies
Journal of cutaneous pathology, 2015Co-Authors: Doina Ivan, Jonathan L. Curry, Rachel M Ellis, Howard Gerber, Madeleine Duvic, Carlos A. Torres-cabalaAbstract:BACKGROUND Indeterminate dendritic cell tumor is an extremely rare neoplastic proliferation of dendritic cells that share immunophenotypic features of Langerhans cells and macrophages but lack Birbeck granules and Langerin expression. METHODS We report a 55-year-old female presenting with a Leonine Facies and generalized multiple confluent papules, nodules and plaques on neck, upper trunk, arms and thighs. Laboratory evaluations were performed including skin biopsies, peripheral blood flow cytometry and positron emission tomography-computed tomography. RESULTS The lesional skin biopsy showed a dense dermal and perifollicular infiltrate composed of histiocytoid cells with nuclear grooves lacking dendritic processes in a background of lymphocytes. Eosinophils were absent. The histiocytoid cells were CD68+CD1a+Langerin- and only focally S100+. Special stains including GMS, Gram and Fite were all negative for infectious organisms. Although an initial diagnosis suggesting Langerhans cell histiocytosis was proposed due to CD1a positivity, a diagnosis of indeterminate dendritic cell tumor was finally rendered based on the histopathological findings and the lack of expression of Langerin. CONCLUSION This case illustrates the variegated clinical presentation of indeterminate cell tumor and the necessity of appropriate immunohistochemical workup for its diagnosis.
M Jachiet - One of the best experts on this subject based on the ideXlab platform.
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plasma cell directed therapies in monoclonal gammopathy associated scleromyxedema
Blood, 2020Co-Authors: T. Mahevas, Cristina Bulai Livideanu, A Osio, Jean-david Bouaziz, Amandine Servy, Bertrand Arnulf, Bernard Cribier, Benoit Sassolas, M JachietAbstract:Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and Leonine Facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant lambda light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor beta and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
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Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.
Blood, 2020Co-Authors: T. Mahevas, Cristina Bulai Livideanu, A Osio, M Jachiet, Jean-david Bouaziz, Amandine Servy, Bertrand Arnulf, Bernard Cribier, Benoit Sassolas, Laurence MichelAbstract:Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and Leonine Facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
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Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.
Blood, 2020Co-Authors: T. Mahevas, A Osio, M Jachiet, Jean-david Bouaziz, Amandine Servy, Bertrand Arnulf, Bernard Cribier, Benoit Sassolas, Cristina Bulai Livideanu, Laurence MichelAbstract:Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French, multicenter, retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and Leonine Facies (39%). MG involved an IgG isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4/33 patients (12%) (smoldering myeloma, n=2; chronic lymphoid leukemia, n=1; and refractory cytopenia with multilineage dysplasia n=1). Carpal tunnel syndrome (33%), arthralgia (25%) and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. Intravenous immunoglobulin (HDIVig) treatment alone or in combination with steroids appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig-refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4/5 patients. Quantitative reverse transcriptase-PCR (RT-PCR) analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β (TGFβ) and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
Amandine Servy - One of the best experts on this subject based on the ideXlab platform.
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plasma cell directed therapies in monoclonal gammopathy associated scleromyxedema
Blood, 2020Co-Authors: T. Mahevas, Cristina Bulai Livideanu, A Osio, Jean-david Bouaziz, Amandine Servy, Bertrand Arnulf, Bernard Cribier, Benoit Sassolas, M JachietAbstract:Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and Leonine Facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant lambda light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor beta and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
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Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.
Blood, 2020Co-Authors: T. Mahevas, Cristina Bulai Livideanu, A Osio, M Jachiet, Jean-david Bouaziz, Amandine Servy, Bertrand Arnulf, Bernard Cribier, Benoit Sassolas, Laurence MichelAbstract:Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and Leonine Facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
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Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.
Blood, 2020Co-Authors: T. Mahevas, A Osio, M Jachiet, Jean-david Bouaziz, Amandine Servy, Bertrand Arnulf, Bernard Cribier, Benoit Sassolas, Cristina Bulai Livideanu, Laurence MichelAbstract:Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French, multicenter, retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and Leonine Facies (39%). MG involved an IgG isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4/33 patients (12%) (smoldering myeloma, n=2; chronic lymphoid leukemia, n=1; and refractory cytopenia with multilineage dysplasia n=1). Carpal tunnel syndrome (33%), arthralgia (25%) and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. Intravenous immunoglobulin (HDIVig) treatment alone or in combination with steroids appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig-refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4/5 patients. Quantitative reverse transcriptase-PCR (RT-PCR) analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β (TGFβ) and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
T. Mahevas - One of the best experts on this subject based on the ideXlab platform.
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plasma cell directed therapies in monoclonal gammopathy associated scleromyxedema
Blood, 2020Co-Authors: T. Mahevas, Cristina Bulai Livideanu, A Osio, Jean-david Bouaziz, Amandine Servy, Bertrand Arnulf, Bernard Cribier, Benoit Sassolas, M JachietAbstract:Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and Leonine Facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant lambda light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor beta and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
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Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.
Blood, 2020Co-Authors: T. Mahevas, Cristina Bulai Livideanu, A Osio, M Jachiet, Jean-david Bouaziz, Amandine Servy, Bertrand Arnulf, Bernard Cribier, Benoit Sassolas, Laurence MichelAbstract:Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and Leonine Facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
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Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.
Blood, 2020Co-Authors: T. Mahevas, A Osio, M Jachiet, Jean-david Bouaziz, Amandine Servy, Bertrand Arnulf, Bernard Cribier, Benoit Sassolas, Cristina Bulai Livideanu, Laurence MichelAbstract:Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French, multicenter, retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and Leonine Facies (39%). MG involved an IgG isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4/33 patients (12%) (smoldering myeloma, n=2; chronic lymphoid leukemia, n=1; and refractory cytopenia with multilineage dysplasia n=1). Carpal tunnel syndrome (33%), arthralgia (25%) and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. Intravenous immunoglobulin (HDIVig) treatment alone or in combination with steroids appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig-refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4/5 patients. Quantitative reverse transcriptase-PCR (RT-PCR) analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β (TGFβ) and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
Jean-david Bouaziz - One of the best experts on this subject based on the ideXlab platform.
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plasma cell directed therapies in monoclonal gammopathy associated scleromyxedema
Blood, 2020Co-Authors: T. Mahevas, Cristina Bulai Livideanu, A Osio, Jean-david Bouaziz, Amandine Servy, Bertrand Arnulf, Bernard Cribier, Benoit Sassolas, M JachietAbstract:Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and Leonine Facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant lambda light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor beta and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
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Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.
Blood, 2020Co-Authors: T. Mahevas, Cristina Bulai Livideanu, A Osio, M Jachiet, Jean-david Bouaziz, Amandine Servy, Bertrand Arnulf, Bernard Cribier, Benoit Sassolas, Laurence MichelAbstract:Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and Leonine Facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
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Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.
Blood, 2020Co-Authors: T. Mahevas, A Osio, M Jachiet, Jean-david Bouaziz, Amandine Servy, Bertrand Arnulf, Bernard Cribier, Benoit Sassolas, Cristina Bulai Livideanu, Laurence MichelAbstract:Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French, multicenter, retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and Leonine Facies (39%). MG involved an IgG isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4/33 patients (12%) (smoldering myeloma, n=2; chronic lymphoid leukemia, n=1; and refractory cytopenia with multilineage dysplasia n=1). Carpal tunnel syndrome (33%), arthralgia (25%) and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. Intravenous immunoglobulin (HDIVig) treatment alone or in combination with steroids appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig-refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4/5 patients. Quantitative reverse transcriptase-PCR (RT-PCR) analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β (TGFβ) and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.