A case of neonatal toxic shock syndrome-like exanthematous disease concurrent with maternal toxic shock syndrome

Introduction

Neonatal toxic shock syndrome-like exanthematous disease (NTED) is characterized by exanthema, fever, and thrombocytopenia. The cause of NTED is a bacterial superantigen toxic shock syndrome toxin-1 (TSST-1), which is primarily produced by methicillin-resistant Staphylococcus aureus (MRSA), and is a hospital-acquired infection in neonatal intensive care units (NICUs). In affected neonates, the proportion of Vβ2+ T cells expressing CD45RO are characteristically increased [1]. In children and adults, TSST-1 is the cause of toxic shock syndrome (TSS). To the best of our knowledge, the coincidence of NTED and maternal TSS has not yet been reported in the literature.

Presentation of the cases

Immunological analysis

We investigated the surface expressions of TCR Vβ2 and CD45RO on CD4+ T cells by flow cytometry [1]. Blood samples were obtained from the infant and the mother on days 4 and 6, respectively, following admission. The selective activation and expansion of TCR Vβ2+ CD4+ T cells were observed in both cases (Figure 1). The total expression of CD45RO was found to be higher in adults than in neonates, thus reflecting differences in immunological memory.

Figure 1:

Flowcytometric analysis of peripheral blood mononuclear cells of neonatal and maternal case and age-matched negative controls. Cells were gated by CD4 expression.

The percentage of TCR Vβ2-positive CD4 T cells expressing CD45RO were 94.5% in neonatal case and 99.3% in maternal case, respectively. In maternal case, the percentage of Vβ2-positive T cells among CD4-positive T cells was 27.3%, suggesting selective expansion of these cells.

Anti-TSST-1 IgG antibody was measured by enzyme-linked immunosorbent assay. Serum samples were obtained on days 4 and 6 following admission from the neonate and the mother, respectively. Anti-TSST-1 IgG antibodies were not detected in both cases; hence, maternal transfer of the TSST-1 producing MRSA was unlikely.

Discussion

In this report, we describe a case of concurrent NTED and maternal TSS. The neonatal case showed typical clinical course, and laboratory findings matched the diagnostic criteria for NTED. The maternal case did not meet the diagnostic criteria for TSS [2]. However, the patient was diagnosed as TSS due to the expansion of TCR Vβ2+ T cells. This is an early and definitive diagnostic marker of TSS [2] specific for TSS induced by TSST-1 [3].

Both NTED and TSS are caused by the expansion and activation of a large number of TCR Vβ2+ T cells stimulated by TSST-1 through its superantigenic activity and subsequent cytokine secretion from activated cells. However, there are significant differences in clinical features between NTED and TSS. Almost all term infants completely recover from NTED without severe complications [1]. Such complications as shock and multiple organ failure may result from TSS. Several mechanisms have been proposed to explain the reduced severity in NTED. First, the T cell response to TSST-1 between mature and newborn infants differs. Anergy is specifically induced in the expanded TSST-1 reactive T cells in patients with NTED, while T cells in healthy adults are resistant to the induction of anergy [4]. Second, the selective production of the anti-inflammatory cytokine IL-10 in neonates appears to be related to the reduced severity in NTED [5]. Third, maternally transmitted immunoglobulin against TSST-1 may have a protective role in the progression of NTED [6].

The frequency of mothers with anti-TSST-1 antibodies has been reported to be declining [7]. Furthermore, the occurrence of NTED is reportedly related to the patient’s antibody titer [6]. In our case report, the absence of the anti-TSST-1 antibody in both the mother and neonate underlies the coincidence of NTED and maternal postpartum TSS; such absence indicates the acquisition of TSST-1-producing MRSA upon delivery via cross-transmission. The development of NTED may indicate the potential development of maternal postpartum TSS, as the mother does not have protective anti-TSST-1 antibodies. Obstetricians should thus consider TSS for the differential diagnosis of puerperal fever and systemic erythema if the neonate develops NTED.

The antibiotic resistance pattern of the MRSA in our case report was nearly identical to those of the other TSST-1-producing NTED-associated MRSAs in our NICU. The patterns observed differed from those of non-NTED-associated strains isolated in our NICU, and from those of previously reported NTED-associated strains in Japan [8]. The observed differences in the antibiotic resistance pattern suggest that the MRSA isolate in this report is a locally expanded clone.

In conclusion, we report on the coincidence of NTED and maternal TSS by cross-transmission of TSST-1-producing MRSA during delivery. The demonstration of the characteristic expansion and activation of Vβ2+ CD4 T cells by flow cytometry was useful for the early and definitive diagnosis of NTED and postpartum TSS. The development of NTED also indicated the absence of protective anti-TSST-1 antibody in both mother and neonate. Hence, care should be taken in the identification of postpartum TSS.