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, 8) , Pierre Aucouturier (7) , Dan Lipsker (5) , Camille Frances (9) , Emilie Sbidian (4) , Michel Rybojad (10) , Vincent Descamps (11) , Michel d'Incan (12, 13) , Philippe Humbert (14) , Marie Beylot-Barry (15) , Thierry Passeron (16) , Claire de Moreuil (6) , Ruba y Taha (17) , Olivier Hermine (7, 18) , Alain Dupuy (19) , Sébastien Barbarot (20) , Sebastien Debarbieux (21) , Olivier Carpentier (22) , Fanny Brault (23) , Jean-Luc Schmutz (23) , Domitille Thomas-Beaulieu (24) , Philippe Modiano (25) , Charles Zarnitsky (26) , François Lifermann (27) , Emilie Baubion (28) , Nicolas Limal (4) , Fabien Le Bras (4) , Marie Le Moigne (29) , Marie Tauber (30) , Alexis Talbot (31) , Romain Prud'Homme (2) , Sandy Peltier (7, 8) , Adèle de Masson (2) , Maxime Battistella (8, 2) , Martine Bagot (2) , Arsène Mekinian (1) , Olivier Fain (1)

1 SU - Sorbonne Université
2 AP-HP - Hopital Saint-Louis [AP-HP]
3 UT3 - Université Toulouse III - Paul Sabatier
4 CHU Henri Mondor [Créteil]
5 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
6 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
7 INSERM - Institut National de la Santé et de la Recherche Médicale
8 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie
9 CHU Tenon [AP-HP]
10 Hôpital Saint-Louis
11 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
12 CHU Clermont-Ferrand
13 IMoST - Imagerie Moléculaire et Stratégies Théranostiques
14 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
15 CHU Bordeaux
16 CHU Nice - Centre Hospitalier Universitaire de Nice
17 NCCCR - DOHA - QATAR - National Center for Cancer Care and Research
18 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
19 Centre Hospitalier Universitaire [Rennes]
20 PhAN - Physiopathologie des Adaptations Nutritionnelles
21 Centre Hospitalier Universitaire de Lyon
22 Centre Hospitalier de Roubaix
23 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
24 CHI Poissy-Saint-Germain
25 Hôpital Saint-Vincent de Paul
26 Centre Hospitalier
27 Centre Hospitalier de Dax
28 CHU - Centre Hospitalier Universitaire
29 CHU Nantes - Centre Hospitalier Universitaire de Nantes
30 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
31 CHU Limoges

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.

Domaines: Dermatologie

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