Fulminant streptococcal infection with early immunoglobulin introduction
resulting in a favourable outcome for both mother and new-born: A case
report
Takanori Sato, Rie Oyama, Tsukasa BABA
Department of Obstetrics and Gynecology
Iwate Medical University
2-1-1 Ididori, Yaba-cho, Shiwa-gun
Iwate
Tel: 81-19-613-7111
028-3695, Japan
Co-author: Rie Oyama.
E mail:
oyamariegm@gmail.com
Running title: Successful treatment of STSS with immunoglobulin
Case report
Streptococcal toxic shock syndrome (STSS) is Group A
Streptococcus infection that causes rapidly progressive sepsis,
disseminated intravascular coagulation (DIC), and multiple organ
failure. STSS is the most common cause of sepsis-related maternal
mortality1. Early diagnosis and intervention are
important, but few reports on immunoglobulin as an adjunctive therapy.
The cytokine production is elevated during pregnancy2,
suppressing the cytokine storm is more important in sepsis caused by
STSS in pregnant women than non-pregnant women, and anti-inflammatory
immunoglobulin will likely be useful as an adjunctive therapy to improve
maternal and infant prognosis. We report a case of STSS possibility
treated using antimicrobial agents and immunoglobulin as adjuvant
therapy. This patient of case report provided informed consent. We
report a case of the potential of STSS treated with antibiotics and
immunoglobulins as adjuvant therapy, and indicate the mechanism of
effect of immunoglobulins on cytokine storm.
A 37-year-old pregnant woman (gravid 5, para3) woman with a history of
WPW syndrome and chronic thyroiditis. The patient had sore throat and
fever of 39 °C on 32 +1 weeks, who was admministred in our hospital. At
32 + 4 weeks, her blood pressure and pulse were 79/48 mmHg and 140bpm,
SpO2, 98% (oxygen mask, 6 L/min). Cardiotocography revealed delayed
transient bradycardia, and we suspected septic shock and foetal
insufficiency. Blood tests: WBC 14,740/μL, platelet 9.2 ×104/μL,
C-reactive protein 11.1 mg/dL. Her qSOFA score: 1 (respiratory rate:
>22 breaths/min), but her National Early Warning Score was
9 (respiratory rate, ≥25; oxygen demand, systolic blood pressure
101-110, heart rate ≥131/min), which is a warning value and corresponds
to symptoms of sepsis due to STSS. Therefore, the antimicrobial agent
was changed from cefepime to a combination of piperacillin and
clindamycin, and an emergency caesarean section was performed 3 houre
after admmited at our department. The baby was 2320 g, Apgar score,
1points/3 points (1 minute/5 minutes),
umbilical artery blood pH 7.28. Obstetric DIC score was 3 points.
Placental histopathology revealed stage 1 chorioamnionitis, but noGroup A streptococcal aggregation in the interchorionic space. On
the second postoperative day, we were informed that Group A
Streptococcus was detected in pharyngeal and blood cultures at the
previous hospital, and antibacterial therapy with piperacillin and
clindamycin for STSS and immunoglobulin were continued. Noradrenaline
was also started as she had trouble maintaining her blood pressure on
the first postoperative day, and dobutamine was added on the third
postoperative day. On the fourth postoperative day, her respiratory
condition worsened and bilateral diffuse frosted glass shadows were
observed on chest radiography. Bilateral pleural effusions and pleural
thickening were observed on computed tomography. Respiratory therapy
with nasal high flow (NHF) was initiated. The patient was weaned from
the NHF and switched to nasal cannula oxygenation on postoperative day
7. Oxygen administration was discontinued on postoperative day 15, and
the patient was discharged on postoperative day 21 with improved
bilateral diffuse frosted margins on chest radiography
Discussion
In this case, STSS developed during pregnancy, but early delivery of
the baby, antimicrobial therapy, and concomitant use of immunoglobulin
from the early postoperative period onward resulted in a good outcome
for both the mother and baby. In the field of obstetrics, perinatal STSS
was described as “a condition that develops in pregnant women in the
last trimester of pregnancy due to hematogenous myometrial infection
mainly originating from the upper respiratory tract that induces labour
pain and rapidly progresses to septic shock, resulting in a high rate of
foetal and maternal death” in 20013,4. There is a
trend toward poor prognosis for both the mother and new-born. In Japan,
24 (7.5%) of 317 maternal deaths were due to sepsis, and 13 (53.4%)
were due to Group A Streptococcus infection between 2010 and
2016. A 2019 proposal by the Division of Medical Safety of the Japanese
Society of Obstetricians and Gynaecologists stated that a modified
Centor score should be used for pregnant women to facilitate early
medical intervention and reduce maternal deaths due to
STSS5. Penicillin and clindamycin are the basic
antimicrobial agents of choice for STSS, and combinations containing
clindamycin effectively suppress exotoxins and TNF-α and promote
phagocytosis by inhibiting M-protein synthesis6,7.
Meta-analysis reported that adjunctive immunoglobulin administration was
associated with a significant reduction in mortality in STSS patients
treated with clindamycin in 20188.
The mechanisms of cytokine production and perinatal STSS are shown in
Figure 1. Antigens are normally absorbed by antigen-presenting cells,
fragmented into peptides, then recognised by T-cell receptors via the
major histocompatibility complex (MHC) class II, which activates T
cells. In contrast, superantigens bind directly to MHC class II and
T-cell receptors without being taken up by antigen-presenting cells and
produce numerous cytokines9,10, causing a marked
inflammatory reaction via exotoxin11 and leading to
septic shock. The production of cytokines such as TNF and IL-1β is also
elevated during pregnancy due to changes in monocyte
subsets13, and cases of perinatal STSS are prone to
cytokine storms.
Immunoglobulins exert effects similar to those of opsonin, along with
phagocytosis-promoting, superantigen-neutralizing, anti-inflammatory,
and antibody-dependent cytotoxic effects, and suppresses proinflammatory
cytokine production11,13,14. Immunoglobulins have
become a standard anti-inflammatory therapy for Kawasaki
disease15. In this case, maintaining blood pressure
became difficult on the first postoperative day, and noradrenaline was
initiated along with immunoglobulin to suppress the cytokine storm
caused by perinatal STSS. Procalcitonin levels were elevated the day
after the culture results were obtained from the previous physician
(postoperative day 3), but quickly decreased thereafter, and
immunoglobulin was discontinued on postoperative day 4. Procalcitonin is
produced by endotoxins and proinflammatory cytokines such as TNF-α,
IL-1, and IL-6 in cases of severe bacterial
infection16,17, and thus indirectly reflects the
inflammatory state in the body. Procalcitonin may be an indicator of
inflammation reflecting hypercytokinemia in cases of Kawasaki disease,
and effectively predicts immunoglobulin
refractoriness18. In this case, the reduction in
procalcitonin levels following concomitant immunoglobulin use reflected
STSS control and cytokine storm suppression, suggesting that the
concomitant use of immunoglobulin may have been effective.
In this study, we encountered a case of a mother and infant whose lives
were saved by delivering the infant early, combined with the use of
maternal antimicrobial therapy and combined immunoglobulin
administration. The usefulness of combined immunoglobulin administration
in perinatal STSS should be studied to further improve maternal and
infant prognosis.