A Rare Complication: EBV Reactivation and Secondary HLH After Teplizumab

A 44-year-old man with Down syndrome (trisomy 21) and stage 2 type 1 diabetes received a 14-day course of teplizumab—a treatment that delays progression to stage 3 type 1 diabetes. Six days after completing treatment, he developed serious complications affecting his lungs, liver, and kidneys.

Medical testing revealed his Epstein-Barr virus (EBV) had reactivated at extremely high levels—more than 2 million copies per milliliter of blood. This triggered a severe immune response called secondary hemophagocytic lymphohistiocytosis (HLH), a rare but life-threatening condition where immune cells attack the body's own tissues and organs.

Epstein-Barr virus is extremely common—most people carry it dormant in their bodies without knowing it. When the immune system is weakened or altered, the virus can reactivate. EBV reactivation after teplizumab has been observed before, but it is usually mild and goes away on its own.

In this case, the reactivation was severe enough to trigger secondary HLH, a condition where immune cells become overactive and start damaging healthy tissue. This is rare, and researchers cannot definitively say teplizumab caused it—the patient's Down syndrome and other factors may have played a role.

The patient was treated with dexamethasone (a corticosteroid) and four weekly doses of rituximab (an immunosuppressive drug). This treatment combination worked: his immune system calmed down, his viral load dropped, and his organ function improved.

At 12 months follow-up, he remained stable. Importantly, he stayed at stage 2 type 1 diabetes and did not require insulin treatment, meaning the teplizumab's effect on delaying disease progression appeared preserved despite the complications.

This case is rare—it describes a single patient, not a pattern or common side effect. However, it does raise important questions about who might be at higher risk for severe EBV reactivation after teplizumab, particularly people with Down syndrome or other conditions affecting immune function.

Researchers recommend that doctors consider checking EBV levels before teplizumab treatment and monitor patients carefully for signs of serious infection or severe immune activation after treatment, especially if they have underlying immune vulnerabilities. If a patient develops respiratory, liver, or kidney problems shortly after teplizumab, EBV testing and screening for HLH may be warranted.

Source: Diabetes care. Evidence type: PubMed indexed literature. Type1Cure is an information and intelligence hub, not a medical advice service. This article summarizes published research and does not provide diagnosis, treatment, or personal medical guidance. Always talk to your own care team before changing anything about your Type 1 diabetes management.