High-dose intravenuos IgG (hdIVIg) and bosentan therapy in severe scleromyxedema with pulmonary fibrosis:another chance

Aim Describe intravenous immunoglobulin (IVIg) use in scleromyxedema. Case reports Many off-label applications of IVIg are known, particularly in autoimmune diseases. IVIg mechanisms of actions include antigen neutralization, accelerated clearance and prevention of Fc? receptor involvement, idiotype–anti-idiotype binding of autoantibodies, modulation of synthesis and release of cytokines and cytokine antagonists, and immune-modulation of lymphatic cells, including regulatory T cells. In particular, clinically selected patients with autoimmune disorders not responding to conventional therapy and suffering from severe infections may be successfully treated with IVIg. Scleromyxedema, a well-defined disease characterized by waxy papules and mucin deposition, monoclonal gammopathy, increased fibroblast proliferation and fibrosis involving typical presentation on the skin (i.e. leonine face) and in internal organ (i.e. lungs, gut, heart, central nervous system) in the absence of thyroid disorder does not have convincing therapeutic options. Two patients are described here: MCT and PDC are 72- and 46-y.o. females with severe Arndt-Gottron scleromyxedema treated with IVIg after corticosteroid and disease-modifying anti-rheumatic drug (DMARD) therapy (D-penicillamine, melphalan, cyclosporin, cyclophosphamide, azatioprine, methotrexate, thalidomide) without clinical improvement. High-dose (1 g/kg body weight) IVIg (hdIVIg) was administered every 2 or 3 months. Since severe pulmonary fibrosis was described in both patients, an endothelin-receptor antagonist (bosentan) was used at a standard dose together with hdIVIg In both patients hdIVIg and bosentan resulted in a general improvement, including skin elastic condition evaluated by Rodnan skin score and reduced pulmonary pression values. On the other hand, in MCT, the clinical benefit was maintained and IVIg infusion intervals were prolonged. PDC, suffering from advanced internal organ involvement, died from central nervous system and cardiovascular complications after a 6 month treatment. IVIg was well tolerated and no side effects were reported. Conclusions Off-label use of IVIg may represent an open statement in a consistent number of rare diseases; nevertheless, some institutional difficulties may result from both economic and legal point of view when hdIVIg is adopted. Further studies are needed to better understand usefulness of IVIg in clinical conditions. We suggest that hdIVIg in combination with bosentan may represent a valuable approach to treat critical conditions such as scleromyxedema. Interaction of hdIVIg with over-stimulated fibroblasts may also affect the evolution of fibrosis significantly. According to our limited experience, it would be critical to start such a treatment in an early stage of the disease