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Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.

Thibault Mahevas 1 Bertrand Arnulf 2 Jean-David Bouaziz 2 Cristina Bulai Livideanu 3 Amélie Osio 2 Amandine Servy 4 Bernard Cribier 5 Bruno Sassolas 6 Marie Jachiet 2 Laurence Michel 7 Pierre Aucouturier 7 Dan Lipsker 5 Camille Frances 8 Emilie Sbidian 4 Michel Rybojad 2 Vincent Descamps 9 Michel d'Incan 10, 11 Philippe Humbert 12 Marie Beylot-Barry 13 Thierry Passeron 14 Claire de Moreuil 6 Ruba Y Taha 15 Olivier Hermine 7 Alain Dupuy 16 Sébastien Barbarot 17 Sebastien Debarbieux 18 Olivier Carpentier 19 Fanny Brault 20 Jean-Luc Schmutz 20 Domitille Thomas-Beaulieu 21 Philippe Modiano 22 Charles Zarnitsky 23 François Lifermann 24 Emilie Baubion 25 Nicolas Limal 4 Fabien Le Bras 4 Marie Le Moigne 26 Marie Tauber 27 Alexis Talbot 28 Romain Prud'Homme 2 Sandy Peltier 7 Adèle de Masson 2 Maxime Battistella 2 Martine Bagot 2 Arsène Mekinian 1 Olivier Fain 1
Abstract : 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.
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Déposant : Migration Prodinra <>
Soumis le : mardi 26 mai 2020 - 06:48:34
Dernière modification le : mardi 23 février 2021 - 11:16:03

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Thibault Mahevas, Bertrand Arnulf, Jean-David Bouaziz, Cristina Bulai Livideanu, Amélie Osio, et al.. Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.. Blood, American Society of Hematology, 2020, ⟨10.1182/blood.2019002300⟩. ⟨hal-02622857⟩



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