PEMPix is the American Academy of Pediatrics Section on Emergency Medicine’s annual visual diagnosis competition. This year, in addition to the 10 finalists Maneesha Agarwal will be presenting at the National Conference and Exhibition we will be sharing four cases online in advance of the conference. This is the first of the four cases.

This case was submitted by…

A four-day-old, full-term, exclusively breastfed male with benign prenatal and antenatal courses, presented with one day of decreased oral intake, fussiness, and a rash. The night prior to presentation, mom noticed he was not feeding as well and seemed fussy. Overnight, she had to wake him to feed. On the morning of presentation, mom noticed his face appeared red; when she undressed him, she noted a red, blotchy rash on his chest. The rash had since evolved into full-body erythroderma sparing the palmar and plantar surfaces. He continued to have normal wet diapers and green-seedy stools without blood or mucus. There were no measured fevers at home or known sick contacts. No medication exposures. Mom was GBS negative. She did have a remote history of oral cold sores but no recent lesions. Initially in the emergency department he was generally well-appearing with normal vital signs. His rash is pictured here:

He subsequently developed a fever to 38.2C rectally, prompting a sepsis workup given his age. Labs were notable for:

  • WBC 9.1 x 10E+09/L with ANC 4.46
  • Platelets 18 (normal low 156 X10E+09/L)
  • ALT 150 (normal high 41 Int’l Unit/L)
  • Procalcitonin 6.81 (normal high <0.1 ng/mL)
  • Cerebrospinal fluid (CSF): 4 WBC/μL, protein 105 mg/dL, glucose 56 mg/dL

A. Congenital Cytomegalovirus infection
B. Neonatal Toxic Shock Syndrome
C. Staphylococcal Scalded Skin Syndrome
D. Neonatal Toxic Shock Syndrome-Like Exanthematous Disease
E. Enterovirus infection

D. Neonatal Toxic Shock Syndrome-Like Exanthematous Disease

The patient was diagnosed with Neonatal Toxic Shock Syndrome-Like Exanthematous Disease (NTED). This condition is common in Japanese NICUs, but rare in the US. This condition is Induced by the superantigen toxic shock syndrome toxin-1 (TSST-1), produced by Staphylococcus aureus. Infants with NTED generally remain well-appearing and do not meet toxic shock syndrome (TSS) criteria. Affected neonates develop systemic exanthema, thrombocytopenia, and fever during the first week of life. Suggested diagnostic criteria include skin rash with generalized macular erythema and, in the absence of another known disease process, one of the following:

  • Fever (rectal temperature of >38.0°C)
  • Thrombocytopenia (platelet count of <150 × 103 μL)
  • Low-positive C-reactive protein (CRP) level (1–5 mg/dL)

At present, there is no consensus regarding treatment. The Japanese experience has shown that overall mortality is low and that most infants do well without antibiotic treatment. However for preterm newbown with more severe illness, systemic antibiotics along with intravenous immunoglobulins may be necessary.

This patient was hospitalized for 4 days where he remained well-appearing. His rash and fever resolved, and he received platelet transfusion. He was on cefepime, ampicillin, and acyclovir until his blood, urine, and CSF cultures returned negative. He also had negative HSV PCRs, urine CMV, and respiratory viral panel. He did have an umbilicus culture positive for heavy Staphylococcus aureus (MSSA). The patient was ultimately discharged on a seven-day total course of cephalexin per Pediatric Infectious Disease recommendations.

References

Takahashi, N., Nishida, H., Kato, H., Imanishi, K., Sakata, Y., & Uchiyama, T. (1998). Exanthematous disease induced by toxic shock syndrome toxin 1 in the early neonatal period. Lancet (London, England), 351(9116), 1614–1619. https://doi.org/10.1016/S0140-6736(97)11125-4

Takahashi, N., Uehara, R., Nishida, H., Sakuma, I., Yamasaki, C., Takahashi, K., Honma, Y., Momoi, M. Y., & Uchiyama, T. (2009). Clinical features of neonatal toxic shock syndrome-like exanthematous disease emerging in Japan. The Journal of infection, 59(3), 194–200. https://doi.org/10.1016/j.jinf.2009.06.010

Takahashi N. (2003). Neonatal toxic shock syndrome-like exanthematous disease (NTED). Pediatrics international : official journal of the Japan Pediatric Society, 45(2), 233–237. https://doi.org/10.1046/j.1442-200x.2003.01703.x

Takahashi, N., Imanishi, K., & Uchiyama, T. (2013). Overall picture of an emerging neonatal infectious disease induced by a superantigenic exotoxin mainly produced by methicillin-resistant Staphylococcus aureus. Microbiology and immunology, 57(11), 737–745. https://doi.org/10.1111/1348-0421.12094

Nakano, M., Miyazawa, H., Kawano, Y., Kawagishi, M., Torii, K., Hasegawa, T., Iinuma, Y., & Ohta, M. (2002). An outbreak of neonatal toxic shock syndrome-like exanthematous disease (NTED) caused by methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal intensive care unit. Microbiology and immunology, 46(4), 277–284. https://doi.org/10.1111/j.1348-0421.2002.tb02696.x

Freeman, M. C., Mitchell, S., Ibrahim, J., & Williams, J. V. (2021). Neonatal Toxic Shock Syndrome-Like Exanthematous Disease in North America. Journal of the Pediatric Infectious Diseases Society, 10(2), 205–206. https://doi.org/10.1093/jpids/piz060

Gerard, R, Lehours, P, Boralevi, F, Sarlangue, J. Neonatal toxic shock syndrome-like exanthematous disease: A French case series. Pediatr Dermatol. 2023; 40( 2): 349- 351. doi:10.1111/pde.15165