A Pediatric Case of Mastoiditis, Meningitis, Ventriculitis and Sinus Venous Thrombosis Due to Streptococcus pneumoniae During Tocilizumab Therapy

To the Editors: Patients receiving interleukin-6 receptor inhibitors, including tocilizumab (TCZ), have been shown to exhibit increased susceptibility to infections, including mycobacterial and opportunistic pathogens.1 To our knowledge, there are limited data regarding severe infections in patients with systemic diseases treated with TCZ, except for rheumatoid arthritis and some studies on giant cell arteritis.2 Here, we present a case of a 6-year-old girl with rituximab-refractory autoimmune encephalitis who developed mastoiditis, meningitis, ventriculitis and sinus venous thrombosis caused by Streptococcus pneumoniae while receiving TCZ therapy. A 6-year-old female presented with vomiting, fatigue, swelling and redness behind the auricle with a protrusion, which developed during treatment on amoxicillin-clavulanate for suspected otitis media. She had a history of neuroblastoma, was treated with chemotherapy and surgery and was diagnosed with paraneoplastic opsoclonus-myoclonus ataxia syndrome, anti-Hu encephalitis and epilepsia partialis continua. Despite using antiepileptics and rituximab, her seizures were uncontrolled, prompting the initiation of TCZ 2 years ago. The last dose was administered 2 weeks prior to hospitalization. The initial diagnosis included acute sinusitis, otitis and mastoiditis, but follow-up revealed altered consciousness, nuchal rigidity and positive Kernig and Brudzinski signs. Brain magnetic resonance imaging (MRI) showed auto-mastoiditis, thrombosis in the left sigmoid sinus and dense material in both lateral ventricles, suggestive of ventriculitis (Fig. 1A and D).FIGURE 1.: MRI findings of ventriculitis. A: At the diagnosis. B: The third week of treatment. C: The seventh week of treatment. D: At the diagnosis, thrombus in the left sigmoid sinus. E: The third week of treatment, regression of the thrombus and partial recanalization. F: The seventh week of treatment, regression of the thrombus and partial recanalization.Laboratory results revealed an elevated white blood cell count of 37,850/µL and a neutrophil count of 33,160/µL. C-reactive protein was measured at 17.2 mg/L and procalcitonin at 1.36 µg/L. The erythrocyte sedimentation rate was within normal limits at 19 mm/hour. Cerebrospinal fluid analysis showed purulent fluid with 6000 white blood cells/µL, 5009 neutrophils/µL, low glucose (<2 mg/dL) and high protein (286 mg/dL). Polymerase chain reaction confirmed S. pneumoniae though no growth was observed in the culture. Intravenous vancomycin (60 mg/kg/day), cefotaxime (300 mg/kg/day) and low-molecular-weight heparin were initiated. Within 3 days, meningeal signs improved, and the patient regained consciousness. During the first week, she underwent a left simple mastoidectomy and ventilation tube placement. Postoperatively, cefotaxime was replaced with cefepime (150 mg/kg/day). In the third week of follow-up, the MRI showed a 2-cm abscess-like collection extending from the mastoidectomy site, with regression of ventriculitis and meningitis, and partial recanalization of the left sigmoid sinus (Fig. 1B and E). Vancomycin was switched to linezolid (30 mg/kg/day) due to the development of an allergy. By the fourth week, a follow-up lumbar puncture revealed clear cerebrospinal fluid with normal glucose and protein levels, and no pathogens were detected in the polymerase chain reaction or culture. A comparative MRI showed complete resolution of signal enhancement in the cerebral and cerebellar sulci with no evidence of pus or hydrocephalus and a regressed abscess in the left mastoid at the seventh week (Fig. 1C and F). The patient completed 52 days of intravenous treatment and was discharged, with a plan to continue low-molecular-weight heparin therapy for a total of 3 months. Following consultation with pediatric neurology and immunology, TCZ therapy was temporarily discontinued. Her baseline immunologic tests were normal, and follow-up on the whole-exome sequencing result is ongoing. In children treated with TCZ for juvenile idiopathic arthritis, the infection rate was reported as 151.4 per 100 patient-years, with serious infections occurring at a rate of 5.2 per 100 patient-years.3 In pediatric studies, serious infections after receiving TCZ primarily involve the skin and respiratory tract.4 However, data about severe central nervous system involvement like in our case are lacking. In conclusion, close monitoring is crucial for patients receiving TCZ, especially those with significant systemic inflammation. Prophylactic vaccinations, such as pneumococcal vaccination, should be administered before starting TCZ therapy when possible.