Systemic Lupus erythematosus complicated by thrombotic thrombocytopenic purpura

Objective. The aim of our study was to describe the clinical and pathophysiological features of Thrombotic thrombocytopenic purpura (TTP) associated with Systemic Lupus Erythematosus (SLE), in order to improve the understanding of the pathogenesis and to define a more effective treatment of this life-threatening condition. TTP is a rare syndrome, clinically characterized by a diagnostic pentad including microangiopathic hemolytic anemia, thrombocytopenia, fever, renal involvement and neurological manifestations. TTP is generally idiopathic, but can occur in association with cancer, infections, pregnancy and also autoimmune diseases, mainly SLE. Patients (pts) with SLE who develop TTP, have a significantly poorer prognosis than those with idiopathic TTP, suggesting a possible role of other pathophysiological mechanisms of microangiopathy, in addition to defective ADAMTS13 activity. Consequently, the treatment of SLE-associated TTP can be challenging and no accepted guidelines are available at present. Design and Method. We describe the clinical and laboratory features of 4 pts with a formal diagnosis of SLE, according to the 1997 revised ACR criteria, who developed severe and acute TTP, treated with different therapeutic approaches. Results. All the 4 pts had a long standing SLE, with a mean duration of 18,5 (14-24) years, when they develop TTP (Table I). At diagnosis, ANA was positive in all, pts 1 and 2 was anti-dsDNA positive, pts 1 and 3 had anti-SSA/Ro positivity. All pts were negative for anti-phospholipid antibodies. The immunological profile was unchanged in all pts when they had the first TTP episode, except for anti-dsDNA that were negative in all pts. Half of them had a single episode, while the other two had several disease flares during steroids tapering, that was very difficult to control. In both these cases, long term remission was obtained with full dose (2-3 gr daily) of mycophenolate mofetil (MMF) and flares occurred when MMF dosage was reduced. Pt 2 is now on remission on MMF 3 grams daily, while pt 4 had gastrointestinal side effects with full dose MMF; thus, belimumab and low dose cyclosporine was added to MMF 1 gr daily, without reactivation of TTP. Conclusions. TTP represents a rare but very severe complication of SLE. Even if in our cohort the pathophysiological mechanisms leading to the disease seemed to be coincident with those of classical idiopathic TTP, a complete control of the disease can be very difficult to achieve and flares of microangiopathic are not uncommon during the tapering of steroids and immunosuppressant. An aggressive therapy with multiple drugs is usually needed to maintain remission.