Mycophenolate Mofetil in Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune/connective tissue disease with complex
pathogenesis involving immune system dysregulation, leading to fibrosis. Inflammatory and
autoimmune aspects of this disease overlap systemic lupus erythematosus (SLE), a disease
shown clearly to respond to MMF. Activated T-cells, the probable target of MMF in SLE,
likely also play an important role in SSc pathogenesis. Evidence for this includes the
similarity of SSc skin disease to chronic graft versus host disease, a disease in which
T-cells play a critical role. MMF has proven one of the most effective medications to date
for SLE and associated nephritis [1]. It also appears to be active in polymyositis and
dermatomyositis, disease that also show significant overlap with SSc [2]. Myositis can also
be a feature of SSc, suggesting that his disease manifestation might be particularly likely
to respond to MMF. MMF inhibits inosine monophosphate dehydrogenase, the rate-limiting
enzyme in synthesis of guanosine nucleotides. It blocks the type II isoform found in
activated lymphocytes more potently than the type I isoform inhibiting both T- and
B-lymphocytes [3]. In SSc, mycophenolate has been tried after anti-thymocyte globulin in one
small open label study with efficacy with a significant improvement in skin score [4].
However, MMF has not been tried alone inSSc and has not been tried in muscle disease
associated with SSc. In this study, we will test the safety and efficacy of MMF in SSc. In
this study all study patients will receive the medication.