Immune globulin/immunosuppressants

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 6-year-old girl developed cranial polyneuropathy during treatment with antithymocyte globulin, cyclophosphamide, busulfan, methotrexate, ciclosporin and rituximab. Additionally, she exhibited no improvement during treatment with immune globulin for the cranial polyneuropathy [not all dosages and routes stated].

The girl presented with sickle cell anaemia complicated by cerebral vasculopathy. She underwent haematopoietic stem cell transplantation (HSCT) following myeloablative conditioning regimen with cyclophosphamide, busulfan and antithymocyte globulin [anti-T-lymphocyte globulin]. She also received treatment with methotrexate and ciclosporin [cyclosporine] as prophylaxis for graft-versus host disease. However, around the time of transplant (day 0), various infectious complications occurred including asymptomatic Epstein-Barr virus replication, which was treated with one rituximab infusion. She additionally developed severe mucositis, which was aggravated by the concomitant herpes simplex virus-1 (HSV-1) reactivation, early after conditioning, which was treated with aciclovir [acyclovir]. She also developed febrile neutropenia during HSV-1 reactivation. Therefore, she was treated with piperacillin/tazobactam, ciprofloxacin and vancomycin [vancomycine] from day 0−day 20. On day 20, neutrophil engraftment was achieved, mucositis/HSV lesions healed. As a result, antibiotics (piperacillin/tazobactam, ciprofloxacin and vancomycin) were stopped, and aciclovir therapy was switched to prophylactic doses. On day 21, she presented with left trigeminal hypoesthesia, bilateral facial palsy and voice alteration followed 24h later by swallowing impairment. A few hours after the symptoms onset, cerebral MRI showed T2-fluid-attenuated inversion recovery hypersignals of the intracranial and meatal segments of the two facial nerves as well as the left hypoglossal nerve with T1 gadolinium enhancement. Based on the clinical presentation, cranial polyneuropathy secondary to the immunosuppressants (antithymocyte globulin, cyclophosphamide, busulfan, methotrexate, ciclosporin and rituximab) was considered.

The girl was hospitalised, and she received IV immune globulin [immunoglobulin] 1 g/kg infusion on day 22 and day 23 for the cranial polyneuropathy; however, no improvement was noted. On day 25, fever and respiratory symptoms (productive cough) appeared. The laboratory findings showed pulmonary COVID-19. After that, she developed acute respiratory distress syndrome, and was transferred to the ICU on day 29. She then received protective mechanical ventilation for 17 days. Additionally, she received off-label treatment with remdesivir [remdesevir] for 10 days and two infusions of tocilizumab for the COVID-19 infection. On day 51 and day 52, she received second course of IV immune globulin. Despite treatment, facial diplegia persisted beyond mechanical ventilation. Significant clinical improvement was noted in her condition around day 60.