Fulminant toxic shock syndrome following rituximab therapy in an 11-year-old boy

Fulminant toxic shock syndrome (TSS) is a rare but severe complication of Staphylococcus aureus carriage or infection caused by TSS toxin-TSST-producing strains. Herein, we describe a fatal TSS secondary to a TSST-1 S. aureus pulmonary carriage in an 11-year-old critically ill boy following anti-CD20 monoclonal antibody, rituximab, treatment and discuss the prophylactic use of intravenous immunoglobulin (IVIG) therapy. A previously healthy boy presented with behavioral disorders and dystonic movement evolving within 3 weeks toward a pharmacoresistant status epilepticus. Five plasma exchanges were performed between day 10 and day 15 after ICU admission without improvement. Intravenous immunoglobulin supplementation was performed after the fifth plasma exchange. NMDA receptors (NMDAR) encephalitis was confirmed by antibody assay in cerebrospinal fluid and in plasma. The patient was started on an immunosuppressive treatment. On day 25, the patient received pulsed methylprednisolone intravenously with slight improvement of clinical seizures. As recently suggested in the literature [1], rituximab was then used on day 48. Within 12 days, seizures ceased and the child became markedly more alert. On day 64, he received a second dose of rituximab, and was walking on day 80 with spectacular clinical improvement. On day 88, the patient developed high fever, with biological inflammatory syndrome (Creactive protein 74 mg/L, procalcitonin 62 mg/L, leukocyte count 13,350/mm with lymphopenia 140/mm). Cutaneous inflammation was noted around the tracheostomia orifice. No bacteriological exam was immediately informative. A few hours later, he presented with massive diarrhoea, tachypnoea and diffuse cutaneous erythema. Broad spectrum antibiotherapy with meropenem and amikacin was started. Three hours later, he suddenly collapsed with cardiac arrest, unresponsive to conventional cardiopulmonary resuscitation. Intratracheal aspirates were found to be positive for methicillin-resistant S. aureus. Blood cultures were negative. TSST-1 positive S. aureus strain was confirmed by polymerase chain reaction assay. Staphylococcal TSS is described as an acute disease often leading to multiorgan failure, which is due to TSST1, a toxin which acts as a superantigen. TSST-1 is able to activate host T-cells by binding to T-cell receptors, and antigen presenting cells by binding to MHC class II molecules. Host immune cell activation by TSST-1 ultimately leads to systemic cytokines release and shock [2]. No therapeutic agent has clearly proven its efficacy. Antibiotics such as clindamycin or linezolid can be used for their in vitro reducing TSST-1 release ability [3], but no in vivo data exist to support those treatments. In a small randomized trial and short series, IVIGs were shown to improve streptococcal TSS prognosis [4, 5]. In staphylococcal TSS, there is less clinical but pathophysiological evidence for recommending IVIG. It is hypothesised that IVIG could help in neutralizing superantigens and inhibiting T-cells activation [6]. However, some recommendations for its use already exists [2, 7]. In our patient’s case, antibody deficiency secondary to B-cell depletion due to rituximab therapy could explain the severity of the fulminant TSS. The severity of his illness leads us to assume that IVIG N. Le Sache M. Afanetti L. Chevret P. Tissieres (&) Pediatric Intensive Care and Neonatal Medicine, Paris South University Hospitals AP-HP, 78, Rue du General Leclerc, 94275 Le Kremlin Bicetre, France e-mail: pierre.tissieres@bct.aphp.fr