Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in relapsing-remitting multiple sclerosis patients on high-dose interferon β

Abstract

Three women aged 34-47 years old, on high dose interferon beta-1a for relapsing-remitting multiple sclerosis, were hospitalized between 2009-2012 for thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Patients sought medical attention for neurological symptoms including cephalalgia, blurred vision, confusion, focal deficits and seizures. All patients presented thrombocytopenia, hemolytic anemia and arterial hypertension. Despite plasma exchanges, corticosteroids and anti-CD20 treatments, all patients progressed towards severe renal insufficiency and one patient died of hemorrhagic shock. In this report we identify a rare but morbid complication of interferon beta-1a treatment associated with female gender, Caucasian background and low body mass index.

Thrombotic microangiopathy caused by interferon β-1b for multiple sclerosis: a case report

“…Cessation of interferon might resolve TMA in some patients, and PE has been effective in controlling TMA in other patients. Serious cases might require continuation of dialysis therapy [6][7][8][9]. Similar clinical courses have also been reported for tacrolimus in patients with organ transplantation [19,20].…”

“…A renal biopsy was not performed. Along with his clinical course, we concluded that this patient had possible TMA that was triggered by interferon b-1b administrated to treat MS, which was complicated by PRES through significant amplification of RAS by TMA in the kidney [6].…”

“…Nevertheless, we concluded that his TMA have been triggered by interferon b-1b that was administered as a treatment for MS. Indeed, interferon b-1a has been shown to cause TMA [6][7][8][9]. The difference between interferon b-1a and interferon b-1b is the presence (1a) or absence (1b) of glycosylation.…”

“…For TMA, the glycosylation is likely not associated with the pathogenicity of interferon b. It remains unclear why interferon causes TMA [6,8,10,11]. Interferon has been reported to cause endothelial cell damage directly through a decrease in vascular endothelial growth factor production, or to generate ADAMTS-13 inhibitor through T cell activation [12][13][14].…”

“…In our patient, severe hypertension had emerged before admission probably as a result of RAS activation induced by TMA in the kidney. Because severe hypertension can also accelerate endothelial damage, such as malignant hypertension, it is important to treat hypertension by inhibiting RAS system activation [6]. PE might also help to control the TMA activity and organ damage [4].…”