Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review

JBUR 5314 No. of Pages 12

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Available online at www.sciencedirect.com

ScienceDirect journal homepage: www.elsevier.com/locate/burns

Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review Linda Gutzler a, Clemens Schiestl b , Martin Meuli b, Carol Oliveira b,c, * a

Instistute for Anaesthesiology, University Hospital Zurich, Switzerland Pediatric Burns Center, Plastic and Reconstructive Surgery, Department of Paediatric Surgery, University Children’s Hospital Zurich, Switzerland c Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada b

article info

abstract

Article history:

Background: Toxic shock syndrome (TSS) is a rare, but potentially life-threatening

Accepted 5 July 2017

complication of thermal injuries in children. The study objective was to systematically

Available online xxx

review the literature on paediatric TSS after burns or scalds, and describe our experience with this condition in Switzerland.

Keywords: Toxic shock syndrome Burns Scalds Thermal injury Children

Methods: All tertiary paediatric healthcare centres managing burns and scalds in Switzerland were inquired. A systematic literature review was performed using EMBASE (1947–2016), MEDLINE (1946–2016), Web of Science (1900–2016) and Google Scholar in October 2016. Data on patient characteristics, symptoms, laboratory parameters, management and outcome were extracted from paper and electronic patient charts. Descriptive statistics were performed. Results: The literature review revealed 25 articles describing 59 cases observed in 10 countries (UK, USA, Hungary, Austria, Sweden, Denmark, Israel, Japan, Spain, Switzerland) from 1985 to 2016. The patient age ranged from 8 months to 8 years at the time point of TSS-diagnosis. The injured total body surface area ranged from <1% to 41%. Forty-one patients suffered from scalds, 6 from burns and in 12 cases the type of injury was not specified. The TSS-diagnosis was made 1–7days after thermal injury. Nineteen children underwent admission to the Intensive Care Unit. Six children died from TSS. In Switzerland, we identified 11 consecutive cases between 07/2001 and 06/2011 (median age 15 months, range 9 months–14 years; 9 male, 2 female; 3 burns, 8 scalds; 7% median total body surface area (TBSA), range 2–30%). Diagnosis of TSS was made on day 5 after injury in median (range 3–34 days). Eight of eleven patients received intensive care. Survivors (10/11) suffered no long-term sequelae besides scars. One 13-month old boy died 3days after a 7%-TBSA scald. Conclusions: Toxic shock syndrome is an important complication of paediatric burns in Switzerland and several other countries world-wide. Diagnosis and management remain challenging. Awareness among treating clinicians is crucial for a favourable outcome. © 2017 Elsevier Ltd and ISBI. All rights reserved.

* Corresponding author at: Department of Paediatric Surgery, University Children’s Hospital, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland. Fax: +41 44 266 7171. E-mail address: [email protected] (C. Oliveira). http://dx.doi.org/10.1016/j.burns.2017.07.002 0305-4179/© 2017 Elsevier Ltd and ISBI. All rights reserved.

Please cite this article in press as: L. Gutzler, et al., Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.07.002

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1.

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Introduction

Toxic shock syndrome (TSS) in previously healthy children has first been described by Todd et al. in 1978 [1]. Seven years after the first paediatric TSS-report, TSS was observed in seven children with thermal injuries [2]. Besides these occurrences, TSS has mainly been observed in menstruating women using superabsorbent tampons [3]. Today TSS in burns is typically associated with children aged 1–4 years two days after suffering from a small burn [4]. The toxinmediated disease represents the most common cause of death in the paediatric population with small thermal injuries [4]. While diagnosis remains challenging, mortality from TSS is completely preventable by early diagnosis and aggressive treatment [4]. The diagnosis of TSS in paediatric burns is made clinically, but is challenging due to non-specific clinical signs and the disease’s ability to mimic other childhood illnesses [4]. A child with sudden deterioration after a minor thermal injury should be worked-up for TSS and a high level of suspicion should be maintained. Diagnostic criteria have been published to facilitate diagnosis [5,6]. The generic diagnostic criteria proposed by the Centers for Disease Control and Prevention (CDC) have been abbreviated and revised to make them more applicable to the paediatric burn population by Cole et al. in 1990 [5,6]: fever39  C, rash, diarrhoea vomiting, irritability and lymphopenia. Three of the 5 abbreviated, age-specific and disease-specific criteria are required for TSS-diagnosis [6]. Toxin testing is rarely useful in the acute setting as the results typically take several days to weeks to return [7]. Once TSS is suspected, treatment has to be initiated quickly due to the rapid progression of the disease. The management typically consists of four main routes: first, resuscitation and stabilization; second, inspection and cleaning of the burn wound; third, anti-staphylococcal and anti-streptococcal antibiotics; fourth, passive immunity against staphylococcal toxic shock syndrome toxin-1 (TSST-1) with fresh frozen plasma (FFP) or intravenous immunoglobulin (IVIG) [4]. Awareness of TSS in paediatric thermal injuries has been perceived as increasing among healthcare professionals. While there are multiple reports from the United Kingdom on TSS in paediatric burns, other countries explicitly report the absence of this condition in their country [8]. This uneven geographical distribution and small number of TSS-cases in paediatric burns makes continuous reporting of case series crucial to increase knowledge and evidence on this condition. An individual case of TSS in a paediatric burn has been reported in Switzerland recently [26]. However, a systematic evaluation of paediatric TSS-cases after thermal injuries in Switzerland and in the medical literature has not been performed to date. The objective of this study was to describe clinical presentation, management and outcome of children, who suffered from TSS after a thermal injury in Switzerland, and to systematically review the literature and pool the published paediatric cases of TSS after burns.

2.

Methods

2.1.

Systematic literature review

In October 2016 EMBASE (1947–2016), MEDLINE (1946–2016) and the Web of Science (1900–2016) were searched for eligible articles reporting paediatric cases of TSS after thermal injury. In addition, Google Scholar was searched for case series and case reports published in the grey literature. The references from included articles were reviewed as well. The following search terms were used: pediatric, paediatric, child, toddler, neonate, newborn, burn, scald, thermal injury, frostbite, chilblains, trench foot, frostnip, toxic shock syndrome. Reports were screened for inclusion based on title, key words and abstract review. Final inclusion was based on fulltext assessment. Inclusion criteria were individually reported cases of TSS after a thermal injury in children from zero to eighteen years of age. Data extraction was performed by one author (LG) and included study parameters (year of publication; country; sample size); patient characteristics (age; gender; injured TBSA; type of injury) and diagnostic criteria for TSS such as symptoms (symptom start; fever; rash; desquamation; hypotension; vomiting; diarrhoea; central nervous system manifestations) and laboratory parameters (lymphopenia; blood cultures; wound swabs). Surgical management (dressing type; surgical intervention); primary and secondary treatment (dressing type; systemic and topical antibiotics; FFP; IVIG); and outcome (survival; irreversible damage) were recorded as well. The yearly number of reported patients and published articles were quantified. No language restriction was adopted. One article was in Japanese so the English abstract was used to extract the data [23]. The PRISMA guidelines for systematic literature reviews were followed and a PRISMA flow chart diagram was prepared (Fig. 1).

2.2.

Case series

In a first step, all intensive care units (ICU) of hospitals managing paediatric burns in Switzerland were contacted by mail. The average yearly number of paediatric burns and the number of observed TSS in children with small to moderate thermal injuries were elucidated with a short questionnaire. None of the 7 contacted paediatric ICUs of hospitals managing paediatric burns recalled a TSS-case at the time point of the survey. Months after the questionnaire was sent out, one TSS-case in a child suffering from a scald was reported to us. Since the case was not managed at our institution and reported with a significant delay, it was not included in our case series. In a second step, consecutive paediatric patients (aged 0– 16 years) with burns or scalds who developed TSS and were treated at the Burns Center of the University Children’s Hospital Zurich, between July 2001 and June 2011 were identified and included in the current case series. Patients treated for burns or scalds were identified using two administrative databases (logbook of the burns centre, institutional administrative database). Data on patient characteristics (age, gender, injured total body surface area (TBSA), type of injury, admission type and duration), symptoms (start

Please cite this article in press as: L. Gutzler, et al., Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.07.002

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e3

Fig. 1 – PRISMA flow diagram.

of symptoms, fever, rash (non-specific), desquamation, hypotension, tachycardia, tachypnoea, vomiting, diarrhoea, myalgia, mucosal hyperaemia, disorientation, altered consciousness), laboratory parameters (lymphopenia, platelet count, blood urea, c-reactive protein (CRP), creatinine, bilirubin, alanine transaminase (ALT) and aspartate transaminase (AST), creatine kinase (CK), blood cultures, wound swabs), surgical management (surgical intervention), primary and secondary treatment (type of dressing, systemic and local antibiotics, respiratory support, inotrope administration, dialysis, administration of FFP or IVIG) and outcome (survival, irreversible damage) were extracted from paper and electronic patient charts. Non-parametric descriptive statistics were performed. The TSS-cases were identified based on the clinical diagnosis described in the patient chart. Retrospectively, the abbreviated diagnostic criteria by Cole et al. and the CDCcriteria were used to assess how well the clinical TSS-diagnosis matched with the published diagnostic criteria [5,6]. While the CDC-criteria are generic for all ages and associated condition, the abbreviated criteria are specific for a paediatric population with a thermal injury. The abbreviated, paediatric criteria consist of fever, rash, diarrhoea and/or vomiting, irritability, shock and lymphopenia [6]. Three of the six criteria are necessary to confirm a TSS-diagnosis. The CDC-criteria list major criteria such as fever, rash, desquamation, and

hypotension, and minor criteria such as vomiting/diarrhoea, severe myalgia, mucosal hyperaemia, elevated urea or creatinine, elevated bilirubin, low platelets and disorientation or altered consciousness [5]. To confirm TSS-diagnosis using the generic CDC-criteria, all 4 major and two or more minor CDCcriteria are required [5]. The diagnosis is deemed probable, when except of desquamation the major criteria fever, rash and hypotension and two or more minor criteria are present [5].

3.

Results

3.1.

Systematic literature review

The systematic literature review revealed 25 publications reporting 59 paediatric TSS-cases after thermal injury [2,6,7,9– 30]. The reports were published between 1985 and 2016, and they originated from 10 different countries. Thirty-three cases (56%) were reported from the United Kingdom, 10 (17%) from Israel, 5 (8%) from the United States and 3 from Sweden and Japan, respectively. Hungary, Austria, Switzerland, Denmark and Spain each reported one case. The yearly incidence of reports and cases is shown in Fig. 2. The TSS-diagnosis was mainly based on clinical criteria such as the CDC-criteria or the abbreviated paediatric criteria

Please cite this article in press as: L. Gutzler, et al., Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.07.002

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Fig. 2 – Reports of TSS in paediatric burns over time.

by Cole et al. [5,6]. In 7 publications, the use of CDC-criteria was mentioned explicitly [6,7,9,12,15,21,29]. The other reports did not specify the diagnosis making process.

3.1.1.

Patient characteristics

Patient characteristics of TSS-cases described in the literature are highlighted in Table 1. The age ranged from 8 months to 8 years. Seventeen patients were male (29%) [2,6,12–19,25,28] and 16 were female (27%) [2,6,9,10,20,21,23,24,27,29,30]. The affected TBSA ranged from <1% to up to 41%. Forty-one of the 59 thermal injuries (69%) were scalds [2,6,7,9,10,12–14,16–21,25– 30], six (10%) were burns [2,7,15,23,24] and for 12 cases (7%) the trauma was not further specified [11,22].

3.1.2.

Signs and symptoms

The TSS-symptoms started between the first and seventh day after injury. Fifty-three of the 59 TSS-cases (90%) developed fever [2,6,7,9,10,12–16,18–22,24,26–30], one patient remained afebrile [17] and in five cases fever was not reported [11,23,25]. A rash was described in 44 TSS-cases (75%) [2,6,7,9,10,12–30], while 12 patients (20%) did not develop a rash [2,6,7] and in 3 cases (5%) it was not reported [11,23]. developed in 19 patients (32%) Desquamation [2,7,9,10,12,14,17,18,23,24,26,29,30], while 16 children (27%) had no signs of desquamation [2,7,13,18,25,28] and 24 cases (41%) had unknown occurrence of desquamation [6,11,15,16,18– 23,27]. Thirty-six patients (61%) suffered from hypotension [2,6,7,9,10,12–14,16,19,20,22,24–26,28,30], 13 (22%) were not hypotensive [2,6,22,29] and in 10 cases (17%) the development of hypotension was not discussed [11,15,17,18,21,23,27]. Gastrointestinal symptoms like vomiting and diarrhoea were observed in 40 TSS-cases (68%) [2,6,7,9,10,12–15,17–21,23–26,28– 30]. Four children (7%) did not develop gastrointestinal symptoms [7] and in 15 (25%) cases the occurrence of such symptoms were not reported [11,16,22,23,27]. Central nervous system manifestations were observed in 34 cases (58%) [2,6,7,9,12–14,17–21,24,25,28–30]. Eight patients (14%) had no

central nervous symptoms [7,15,16,18,] and in 17 cases (29%) these symptoms were not reported [10,11,22,23,26,27]. Lymphopenia was described in ten cases (17%) [6,17,19– 21,29], while for the other 49 patients (83%) lymphopenia was not reported [2,7,9–16,18,22–28,30]. Staphylococcus aureus was found in 52 wound swabs (88%) [2,6,7,9,10,12–21,23,24,26–30]. Three wound swabs (5%) remained negative [2,22] and in the remainder 4 cases (7%) wound swab results were not reported [11,22,23,25]. Blood cultures were found positive in 7 TSS-cases (12%) [2,7,22]. Twenty-three patients (39%) had no growth of bacteria in their blood culture [7,9,12,14–16,19–21,24,26,29]. For the remainder 29 children (49%) the blood culture results were not reported [2,6,10,11,13,17,18,22–25,27,28,30]. The positive blood cultures showed growth of Pseudomonas aeruginosa [2],S. aureus [7,22] and Group A Streptococcus [22]. Eighteen cases were tested for TSST-1 production [6,10,13–18,20,21,26,27,29], twenty-four cases were not tested for TSST-1 production [2,7,9,19,24,30] and in seventeen [11,12,22,23,25,28] cases it is unclear if toxin-testing was performed. TSST-1 was positive in ten reported cases [6,13–16,18,20,21,26,29].

3.1.3.

Initial treatment

Of the 59 reported TSS-cases, only 4 children (7%) received systemic antibiotic prophylaxis [12,16,19,20]. Forty-nine patients (83%) were not treated with prophylactic antibiotics [2,6– 10,13–15,18,21,22,24,25,27–30] and for 6 (10%) cases this initial treatment was not declared [11,17,23,26].

3.1.4.

Secondary treatment

All TSS-cases in the literature received systemic antibiotics as secondary TSS-treatment, except for four cases (7%) where this aspect was not reported [11,23]. The antibiotics used were cefotaxime [7,13,15], flucloxacillin [2,6,7,13,19,20,27], penicillin [2,6,9,18,27], gentamycin [2,6,7,10,12,22], erythromycin [6], piperacillin [2], tobramycin [2], ampicillin [2,14,19], co-amoxiclav [3,7], ceftriaxone [20,30], ceftazidime [19], cefuroxime [2,18,21], metronidazole [2], clindamycin [18,26,27,28,30],

Please cite this article in press as: L. Gutzler, et al., Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.07.002

JBUR 5314 No. of Pages 12

Author

Country,

Trauma

Age

TBSA

N

Gender

Day

(%)

Fever Hypoten- Rash Lymph-

of

sion

openia

CNS manifesta-

onset Frame et al.

UK, 7

[2]

6 scalds

8m–

1 burn

6y

4–40

4M, 3F

1–3

Diarrhoea/ Desquavomiting

Wound dressing

mation

USA, 1

Scald

5y

Secondary

ICU

treatment

admission

7/7

4/7

4/7

NR

7/7

7/7

2/7

Petroleum jelly

No

tulle gras, 12

1F

2

Outcome

tions

Bactigras Farmer et al.

ABx prophylaxis

1/1

1/1

1/1

NR

1/1

1/1

1/1

[9]

ABx, fluid,

NR

inotropes

4 deaths 3 survivals

1

Fresh frozen

No

porcine xero

ABx, fluid,

No

Survival

NR

Survival

NR

NR

NR

ABx, FFP,

1/1

Survival

NR

NR

2 survivals

ABx, fluid,

NR

Survival

NR

5 survivals

ABx, steroid

1/1

Survival

ABx, fluids,

1/1

Survival

NR

Survival

inotropes 1

graft, Xeroform , 1

Kerlix Holt et al. [10] UK, 1

Scald

19m

NR

1F

3

1/1

1/1

1/1

NR

NR

1/1

1/1

NR

No

ABx, fluid, inotropes, plasma

Brain et al.

UK, 2

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

USA, 1

Scald

6y

5

1M

5

1/1

1/1

1/1

NR

1/1

1/1

1/1

Biobrane

[11] Egan and

1

Penicillin

Clark [12]

fluid, wound dressing removal

Tanaka et al.

JPN, 2

2 burns

[23]

2y,

5, 10

1F

7, NR

NR

NR

1/2

NR

NR

1/2, NR 1/2 1/2, NR

6y

Heywood and UK, 1

Scald

2y

NR

NR

NR

No

1/2 2

1M

2

1/1

1/1

1/1

NR

1/1

1/1

No

al-Essa [13] Cole and

paracetamol UK, 5

5 scalds

Shakespeare

14–

8–41

3F

1–3

5/5

4/5

2/5

5/5

5/5

5/5

NR

23m

[6]

Nitrofurazone/

No

IVIG, blood

plastic bag

transfusion,

dressing Glazowski

DNK, 1

Scald

15m

9

1M

3

1/1

1/1

1/1

NR

1/1

1/1

1/1

et al. [14] Nivenius

ABx, fluid,

Flamazine with

bicarbonate

Debridement

No

burns xxx (2017) xxx –xxx

only, no dressing SWE, 1

Burn

11m

<1

1M

3

1/1

NR

1/1

NR

No

1/1

No

NR

No

et al. [15]

albumin, ventilation, FFP, steroid

Weinzweig

USA, 1

Scald

2y

11

1M

5

1/1

1/1

1/1

NR

No

NR

NR

1

Biobrane

Penicillin

et al. [16] Maródi et al.

ABx, wound cleaning

HUN, 1

Scald

20m

NR

1M

2

No

NR

1/1

1/1

1/1

1/1

1/1

NR

UK, 1

Scald

18m

20

1M

3

1/1

1/1

1/1

1/1

1/1

1/1

NR

Flamazine

NR

ABx

NR

Survival

Ampicillin,

ABx, albu-

1/1

Survival

[17] Davis and Griffin [19]

1

Flucloxacillin min, inotropes, ventilation, FFP, fluid, blood transfusion

(continued on next page)

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Please cite this article in press as: L. Gutzler, et al., Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.07.002

Table 1 – Literature review.

Author

Country,

Trauma

Age

TBSA

N

Gender

Day

(%)

Fever Hypoten- Rash Lymph-

of

sion

openia

onset Blomquist

SWE, 2

2 Scalds

[18] Luque et al.

21m– 5, 6

CNS manifesta-

Diarrhoea/ Desquavomiting

Secondary

ICU

treatment

admission

Outcome

1F

3–4

2/2

NR

2/2

NR

1/2

2/2

1/2

1F

2

1/1

1/1

1/1

NR

1/1

1/1

1/1

OP-site

1

No

ABx, fluid

NR

2 survivals

No

Abx, fluid,

NR

Survival

6y ESP, 1

Burn

2y

NR

Compression bandage

UK, 1

Scald

7y

NR

1M

7

NR

1/1

1/1

NR

1/1

1/1

No

inotropes

Silver sulphazi-

No

ABx, fuid

NR

1 death

No

ABx, fluid,

1/1

Survival

1/1

Survival

7/13

1 death

1

[25]

dine, Tegaderm USA, 1

Scald

20m

7

1F

3

1/1

1/1

1/1

NR

1/1

1/1

1/1

Bactitracin, Biobrane

1

inotropes, ventilation

Johnson and

UK, 1

Scald

19m

2

1F

7

1/1

1/1

1/1

1/1

1/1

1/1

NR

Telfa

1

Flucloxacillin ABx, fluid,

Pathirana [20] Brown et al.

oxygen, FFP UK, 13

[7]

12 scalds 12m– 5–30 1 burn

Trop et al. [21] AUS, 1

Scald

NR

2–3

13/13 13/13

7/13

NR

8/13

9/13

6/13

5y 17m

5

1F

1

1/1

NR

1/1

1/1

1/1

1/1

NR

Silver sulphadia- No

ABx, fluid,

zine, petroleum

inotropes,

jelly

FFP 1

Omiderm ,

No

ABx, fluids,

12 survivals 1/1

polyurethane

albumin,

Silver sulphadia- No

ABx, amines, 3/10

zine, predniso-

IVIG

Survival

bicarbonate Serour et al.

ISR, 10

NR

[22]

9m–

1–14

NR

1–2

10/10 2/10

8y

10/

NR

NR

NR

NR

10

10 survivals

lone ointment, chloramphenicol Steinbrenner

CH, 1

Scald

NR

NR

NR

2

1/1

1/1

1/1

NR

NR

1/1

1/1

NR

NR

and Lucking

ABx, fluid,

NR

Survival

inotropes

[26] Fanshawe

UK, 1

Scald

13m

4

1F

6

1/1

NR

1/1

NR

NR

NR

NR

1y

20

1F

3

1/1

no

1/1

1/1

1/1

1/1

1/1

1

Mepithel

No

ABx, fluid

1/1

Survival

Unspecified

No

ABx, gabex-

NR

Survival

1/1

Survival

et al. [27] Yokochi et al. JPN, 1 [29]

ointment

ate mesilate, fluid diazepam

Garland et al. [28]

USA, 1

Scald

14m

12

1M

4

1/1

1/1

1/1

NR

1/1

1/1

No

1

Mepilex

No

ABx, fluid, inotropes, IVIG, wound cleaning

N — sample size, AUS — Austria, CH — Switzerland, ESP — Spain, DNK — Denmark, HUN — Hungary, ISR — Israel, JPN — Japan, SWE — Sweden, UK — United Kingdom, USA — United States of America, m — months, y — years, M — male, F — female, ABx — antibiotic, FFP — fresh frozen plasma, IVIG — intravenous immunoglobulins, NR — not reported.

burns xxx (2017) xxx –xxx

Shaer [30]

ABx prophylaxis

tions

[24] Money-Kyrle

Wound dressing

mation

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Please cite this article in press as: L. Gutzler, et al., Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.07.002

Table 1 (continued)

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nethylmycin [14], meropenem (26, 28), methicillin [14], nafcillin [9,12,30], lincomycin [10], cloxacillin [15,22,24], vancomycin [16,22,28,29,30] and fusidic acid [10]. Nineteen children (32%) were admitted to the ICU after TSSdiagnosis [7,12,14,15,19–22,27,28,30]. The use of inotropes and respiratory support was poorly documented. Thirty-three patients (56%) received fluid resuscitation [2,6,7,10,12,15,18– 21,24–30]. Fresh frozen plasma was administered in 11 TSScases (19%) [7,10,12,15,19,20], and IVIG was given in 4 cases [6,22,28].

3.1.5.

Outcome

Fifty-one (86%) of the 59 patients with thermal injuries complicated by TSS survived [2,6,7,9,10,12–24,26–30]. Six children (10%) died [2,7,25] and for 2 cases (3%) the outcome was not reported [11]. One child survived with permanent damage [19]. Mild spastic quadriplegia affecting the lower and upper extremities, and seizures were observed in the longterm follow-up.

3.2.

Case series

Between January 2001 and June 2011 a total of 3867 children were managed at the Burns Center of the University Children’s Hospital Zurich. The Burns Center represents a specialized surgical ward, which manages patients undergoing plastic and reconstructive surgical procedures. The patient population includes patients with acute thermal injuries and cutaneous trauma. In this cohort, 737 (19%) patients suffered from acute thermal injuries. Of these, 616 (84%) had a 10% TBSA thermal injury and 121 (16%) had >10% affected TBSA. Eleven of the 737 thermally injured patients (1.5%) were treated for TSS. Retrospectively, TSS-diagnosis was confirmed in 8 of the 11 cases (73%) as they fulfilled at least 3 of the abbreviated TSScriteria for paediatric burns [6]. A comparison between confirmed and probable TSS-cases is shown in Table 2. One child who fulfilled 3 of the 5 abbreviated diagnostic criteria (fever, rash, vomiting/diarrhoea) with a positive wound swab was treated for TSS. As symptoms of an upper respiratory tract infection developed and the fever persisted despite antibiotic therapy, the diagnosis of a viral upper airway infection was considered as alternative diagnosis. Three cases (27%) did not fulfil sufficient diagnostic criteria to confirm TSS-diagnosis. One of them presented with fever and lymphopenia, and one with diarrhoea and vomiting. In comparison to the patients with confirmed TSS-diagnosis, these two patients were similar in terms of age, gender, injured TSBA, trauma, start of TSS-symptoms and outcome. The third probable TSS-case was an older child, which presented atypically. The patient was a 14-year-old girl who developed TSS later during the hospital admission. The child suffered from a 30% TBSA burn on the face, neck, thorax, abdomen, left forearm, left hand and left leg. The patient was admitted directly to the Burns Center. Because of the extent of the burn the patient underwent escharotomy and multiple wound debridements during her hospital stay. Short systemic antibiotic prophylaxis was administered initially. Topical antibiotic (gentamicin) was applied early during the admission and continued throughout the hospital stay due to frequent debridements. Toxic Shock Syndrome symptoms started on

e7

day 34 after injury with hypotension, vomiting and diarrhoea. The child was rapidly transferred to the ICU, where she received respiratory and inotrope support for one day. Two days later desquamation of the feet was observed. The wound swab revealed Staphylococcus aureus growth and the blood culture was negative. Despite the few symptoms, TSS was suspected in these three cases and described as possible diagnosis in the patient charts. As early diagnosis is crucial for a favourable outcome in these patients, the treating clinician maintained a low level of suspicion and initiated appropriate treatment prior to full development of TSS. Neither of the cases was tested for TSST1 due to the secondary role of these test results in acute TSSmanagement.

3.2.1.

Patient characteristics

At the time point of TSS-diagnosis, the median age was 15 months with a range of 9 months to 14 years. Nine patients (82%) were male and 2 were female (18%). Seven (64%) were managed primarily at the Burns Center, while 4 (36%) were referred to the Burns Center from other hospitals prior to TSSdiagnosis. The patients suffered from 8 scalds (73%) and 3 burns (27%). The affected TBSA ranged from 2% to 30% with a median of 7%. In median, the total length of hospital stay was 10days with a range of 4–176 days. The wide range is secondary to a TSScase with a 30% TBSA burn that underwent a prolonged hospital stay for burn wound management.

3.2.2.

Signs and symptoms

The symptoms started 5days after injury in median (3–34 days). Seven (64%) of the 11 patients developed fever over 38.9  C. Six children (55%) developed a rash on day 10 after injury in median (3–36 days). There was not specific pattern to the location of the rash, as it was found on extremities, the chest and at times it was generalized. There was no correlation between the injury site and where the rash later developed. The rash was described as exanthema or maculopapular erythema with no further specifications. Desquamation was observed in 2 patients (18%) on the 7th and 36th day after injury. Both occurrences of desquamation were observed two days after TSS-symptom development. Five patients (46%) developed hypotension and tachypnea, and 6 (55%) were tachycardic. Cardiopulmonary instability was observed in close relationship with the onset of TSS. Vomiting occurred in 8 cases (73%) and 6 children (55%) suffered from diarrhoea. Myalgia and mucosal hyperaemia was not described for any of the cases. None of the children were disorientated, but 4 (36%) had an altered level of consciousness. One child (9%) suffered from a seizure. Blood cultures were drawn from 10 patients (91%), of which one (9%) was positive for coagulase negative Staphylococcus. This patient developed fever, vomiting, diarrhoea, hypotension and a rash, and died shortly after being transferred to the ICU. No wound swaps were taken for this patient. Wound swabs for the other 10 cases were positive for Staphylococcus aureus in 73% (8/10 cases). In addition to Staphylococcus aureus, one wound swab was positive for Klebsiella pneumoniae and Actinobacter, and another one was positive for

Please cite this article in press as: L. Gutzler, et al., Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.07.002

Confirmed

Confirmed

Confirmed

Confirmed

Confirmed

Confirmed

Confirmed

Confirmed a

Probable

Probable

Probable

Case

1

2

3

4

5

6

7

8

9

10

Age

12 months

15 months

19 months

11 years

13 months

17 months

13 months

2 years

15 months

9 months

14 years

Gender

Male

Male

Male

Male

Male

Male

Male

Female

Male

Male

Female

11

4

2

8

4

7

6

8

5

11

8

30

Fever > 38.9  C

No

Yes

Yes

Yes

Yes

Yes

No

Yes

Yes

No

No

Rash

Yes

Yes

Yes

Yes

Yes

No

No

Yes

No

No

No

Desquamation

No

No

Yes

No

No

No

No

No

No

No

Yes

Diarrhoea/vomiting

Yes

Yes

Yes

No

Yes

Yes

Yes

Yes

No

Yes

Yes

Hypotension/shock

No

Yes

Yes

No

Yes

No

No

Yes

No

No

Yes No

CNS manifestation

No

No

Yes

No

Yes

Yes

Yes

No

No

No

S. aureus in wound swab

Yes

Yes

Yes

Yes

Not tested

No

Yes

Yes

Yes

No

Yes

Lymphopenia

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

Yes

No

Yes

Thrombocytopenia

No

No

Yes

Yes

No

No

No

Yes

Yes

No

No

Creatinine elevation

Not tested

Yes

No

No

Not tested

Yes

No

Not tested

No

Not tested

No

BUN elevation

Not tested

No

No

No

Not tested

No

No

Not tested

No

Not tested

Yes

Bilirubin elevation

Not tested

Not tested

Yes

No

Not tested

No

Not tested

No

No

No

Yes

ALT/AST elevation

Not tested

Not tested

Yes

Yes

Not tested

Yes

No

Not tested

Not tested

Not tested

Yes

Outcome

Survival

Survival

Survival

Survival

Death

Survival

Survival

Survival

Survival

Survival

Survival

a

Bold — indicates abbreviated diagnostic criteria by Cole and Shakespeare [6]. Abbreviations: TBSA — total body surface area, % — percentage, CNS — central nervous system, BUN — blood urea nitrogen, AST — aspartate aminotransferase, ALT — alanine aminotransferase. This patient developed signs of upper respiratory tract infection after treatment initiation.

burns xxx (2017) xxx –xxx

Injured TBSA (%)

JBUR 5314 No. of Pages 12

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Please cite this article in press as: L. Gutzler, et al., Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.07.002

Table 2 – Confirmed and probable toxic shock syndrome cases.

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Bacillus species, Methicillin resistant Staphylococcus aureus (MRSA) and Streptococcus group G.

3.2.3.

Initial treatment

Initial dressing type, antibiotic prophylaxis and surgical interventions were reviewed. Primary dressings consisted of 1 Alginogel dressings (Flaminal ), sodium chloride compresses, 1 paraffin coated dressings (Jelonet ), epithelial skin replace1 1 ments (Suprathel ), silver coated dressings (Acticoat ), and 1 silicone coated dressings (Mepilex ). In one case the dressing was not specified. Systemic antibiotic prophylaxis was not administered prior to TSS-diagnosis. Three patients (27%) received topical antibiotics. Two were treated with gentamicin 1 and one with mupirocin (Bactroban ). Eight children (73%) underwent a primary surgical intervention: seven (64%) had an initial debridement, and one (9%) had a debridement and an escharotomy.

3.2.4.

Secondary treatment

After TSS-diagnosis was made the following dressings were 1 applied: paraffin coated dressings (Jelonet ) in 6 patients (55%), 1 alginogel dressing (Flaminal ) in 1 patient, silver coated 1 1 dressing (Acticoat ) and silicone coated dressing (Mepilex ) in 1 patient each, and one patient received a combination of an 1 1 epithelial skin replacement (Suprathel ) and Jelonet . Intravenous antibiotics were initiated after TSS was suspected in 10 cases (91%). For the remainder patient, specifics on secondary antibiotic therapy were not reported. Systemic antibiotics used in the case series included amoxi1 1 cillin/clavulanic acid (Augmentin ), clindamycin (Dalacin ), 1 and a combination of clindamycin (Dalacin ) and amoxicillin. 1 Topical antibiotics (gentamycin (Garamycin ), mupirocin 1 (Bactoban )) were administered in 3 patients (27%) after TSS-symptoms developed. Five (46%) of the 11 patients underwent a secondary surgical intervention: 3 patients (27%) had repeat wound debridement, and a split-thickness skin graft was performed in 3 patients (27%). Eight patients (73%) were admitted to the ICU after TSS was suspected or confirmed. Admission to the ICU was secondary to cardiopulmonary instability and rapid clinical deterioration. One patient was transferred to the ICU for better monitoring only. Four patients (36%) received respiratory support. Two of the four patients were brought ventilated to the ICU postoperatively. They were weaned from the ventilator a few hours later. The patient with a 30% TBSA burn underwent intubation for one day. The fourth patient was intubated because of rapid general deterioration. He was ventilated for a few hours only due to the fatal outcome in this case. Five patients (45%) received inotrope administration. Hemofiltration did not become necessary in any of the patients. Two children (18%) received FFP at the ICU to prevent coagulopathy. None of the other cases received blood products or IVIG to provide passive immunisation.

3.2.5.

Outcome

One patient (9%) died on the third day after injury. The oneyear old boy was referred to the Burns Center from another hospital on the day of the thermal injury. No specific treatment for the scald was initiated at the referring hospital. The initial

e9

debridement showed a 7% TBSA scald of the chin, neck, right arm and chest. On the second day after injury the boy developed fever, diarrhoea, vomiting and a skin rash. His general condition declined rapidly inducing ICU-admission. He suffered a seizure most likely due to hypoglycaemia. Despite intubation and inotrope administration the patient had a cardiac arrest and died after 30min of cardiopulmonary resuscitation. The blood culture drawn on the third day after injury was positive for coagulase negative staphylococcus. No wound swab was taken.

4.

Discussion

Although historically TSS has primarily been associated with menstruating women using superabsorbent tampons [3], there has been an increasing awareness of TSS in children with minor burns and scalds among healthcare professionals, which has particularly been fuelled by case reports from the United Kingdom [2,6,7,10,11,13,19,20,25,27]. Toxic shock syndrome is a disease most frequently caused by TSST-1 producing S. aureus [31], but also Group A Streptococcus, Pseudomonas, Klebsiella and other enterotoxin producing Staphylococcus have been isolated in patients with TSS [32]. Toxic shock syndrome toxin-1 is a superantigen, which may cause a fulminant immune system stimulation resulting in TSS-development with multi-organ failure [4]. Local factors in burns and scalds such as dysfunction of the skin barrier and the anaerobic environment in the wound are ideal for bacterial growth and TSST-1 production [4]. A factor favouring TSS-development in young children in particular is that they may not have developed antibodies against TSST-1. Quan et al. [33] showed in their study that the most vulnerable age lies between 7 months and 2 years, during which time period only approximately 35% of the children have developed TSST-1 antibodies [33]. Nine children (82%) in the present study were in this vulnerable age group, while two were older. It has been reported that between the age of eleven and fourteen, 80% of children have developed TSST-1 antibodies [33]. Toxic shock syndrome in patients with thermal injuries typically represents a complication of burns in the paediatric population. In the adult setting, TSS after a thermal injury is exceedingly rare with only one case report published in the literature [34]. This likely reflects the protective effect of the high antibody levels in 90% of the healthy adult population [35]. Nonetheless, TSS has to be considered as cause for sudden clinical deterioration of children and adults after thermal injury, particularly after a small TBSA burn or scald, which will benefit from quick decision-making and treatment initiation. Toxic shock syndrome presents itself in many ways and may lead to multi-organ failure and death. When left untreated the mortality rate has been reported as 10–15%, but up to 50% when multiple organ failure occurred [2,36]. Of the 70 TSS-cases in this case series and literature review, 6 children died indicating a lower case fatality rate of 8.5%. Early TSS is often difficult to distinguish from other infectious diseases in childhood. This is illustrated by the one case in the current series that developed signs of a viral upper respiratory tract infection, while also fulfilling diagnostic criteria for TSS. When compared to adults, children are less likely to develop all

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classic symptoms required for a TSS-diagnosis. For these reasons Cole and Shakespeare [6] published an abbreviated list of diagnostic criteria specifically for children, consisting of pyrexia, rash, diarrhoea and/or vomiting, irritability and lymphopenia. These specific paediatric diagnostic criteria are helpful to clinicians as they may enable specific and early TSS-diagnosis in children with thermal injuries, potentially resulting in more favourable outcomes. But they may also cause over-diagnosis in individual cases, as only 3 of the 5 criteria have to be fulfilled to initiate TSS-treatment. The application of clinical diagnostic scoring systems to diagnose TSS, as illustrated in the reported case series and adopted in the majority of published cases, brings the benefit of including and reviewing all potential and early TSS-cases. Given the low incidence and related paucity of medical evidence in regards to this condition, inclusion of all confirmed and potential cases in these early studies may be of benefit, as it allows for discrimination between subtypes, such as for example TSSlike syndrome or probable TSS, and more comprehensive understanding of the disease. As more studies are published and evidence grows, more stringent diagnostic tools may be developed allowing for more precise diagnosis and specific research. In the current case series, there was only one child fulfilling all CDC- and abbreviated criteria, and another one satisfying all abbreviated criteria. The patient who died presented all CDC-criteria except for desquamation, which does not occur until later in the course of the disease. In this case, the child may have died before desquamation became manifest. In other cases desquamation may not be observed as timely and aggressive treatment may prevent disease progression precluding the development of later TSS-signs. In our case series two children developed desquamation two days after TSSsymptoms became evident. The other 9 children fulfilled the abbreviated diagnostic criteria partially, with six of them displaying 3 or more signs and symptoms confirming TSSdiagnosis. With increased awareness among healthcare professionals and immediate treatment initiation, full TSSdevelopment may have been prevented in the other 3 cases of the series. These 3 patients suffered from a thermal injury and developed symptoms including vomiting, diarrhoea, rash and fever, and were treated with antibiotics to prevent a full outbreak of TSS. Two of the three cases had a negative wound swab and one patient developed signs of a co-occurring or single viral upper airway infection. This illustrates that there may be a certain amount of over-diagnosis of TSS in paediatric patients with thermal injuries. On the other hand, diagnosis based on clinical criteria alone allows for comprehensive inclusion of confirmed and potential TSS-cases. While this allows inclusion of cases that have not developed the full picture of TSS as well as such with a TSS-like disease, it comes with a risk for selection bias and over-diagnosis. However, since favourable outcome is highly time-sensitive in terms of treatment initiation and the consequences of misdiagnosed TSS are devastating, this risk is generally regarded as superior to the potential harm from TSS-treatment such as systemic antibiotic therapy, repeated wound debridement, and FFP or IVIG administration. As a discriminating diagnostic criterion or an early, readily available laboratory test allowing timely and specific TSS-diagnosis is currently warranted, treating

clinicians have to has to balance the risks and benefits of overdiagnosis and early treatment individually and in tight collaboration with the patient’s parents. Patient characteristics of the reported case series were similar to the ones reported in previously published case reports and series. One atypical case was noted, however, where the TBSA was 30% and the onset of TSS was after a month at the hospital. The 14-year old girl had burns spread over her left body side including the face. The symptoms started on day 34 with hypotension, vomiting and diarrhoea. S. aureus grew on a wound swab from the leg after showing desquamation at her feet. The reasons for delayed TSSdevelopment in this case remained unclear. Lymphopenia was present in all of the confirmed and in one of the unconfirmed TSS-cases, while only 6 authors reported on lymphopenia in a total of nine cases [6,17,19,20,21,29], A reason for this may be that lymphopenia is not part of the CDC-criteria but included in the abbreviated criteria for children only. In our case series, only one blood culture was positive and it was in the child that died from TSS. In the literature review however, seven blood cultures (Pseudomonas aeruginosa [2], S. aureus [7,22] and Streptococcus group A [22]) were found to be positive, of which one was found in a child with fatal outcome [7]. The guidelines at our institution do not favour antibiotic prophylaxis for thermal injuries. Four articles from the UK and USA report that TSS-cases developed despite antibiotic prophylaxis administration prior to symptom development [12,16,19,20]. Egan et al. and Weinzweig et al. used a combina1 tion of Biobrane and penicillin as initial treatment [12,16], 1 while Davis et al. applied Flamazine with systemic ampicillin 1 and flucloxacillin, and Johnson et al. used Telfa with gauze in combination with systemic flucloxacillin [19,20]. The dressing types used in the presented case series were very diverse and no association of dressing type and TSS-development was 1 observed. Some wound dressings such as Biobrane have been suspected to be correlated with TSS [16], but this hypothesis could not be confirmed with the reported clinical experience. Neither toxins, nor toxin antibodies were tested in the current case series as their role in the acute TSS-management is very limited and the data was derived from patient charts retrospectively. In the acute setting, the indication for such tests may be questionable, as they are costly and the test results may take several days to weeks to return. With the clinical urgency to treat rapidly deteriorating patients with a possible TSS within hours, toxin and toxin antibody testing has a limited role in the acute diagnosis-making process. While toxins and toxin antibodies may confirm the TSS-diagnosis in the long-term and be useful in prospective studies, the diagnosis and treatment initiation in the acute clinical setting has frequently to be based on clinical signs and symptoms [2,6,7,9–30]. With the majority of the treatment being in response to individual symptoms such as cardiopulmonary instability, and only a few being diseasespecific such as FFP or IVIG, the risk of adverse effects appears relatively low when compared to the potential benefits, particularly in a disease with a high risk for a rapid fatal outcome. However, as awareness for TSS increases among clinicians, toxin and toxin antibody testing may become more frequent and become a helpful parameter in retrospective studies.

Please cite this article in press as: L. Gutzler, et al., Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.07.002

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There is no evidence to explain the variable TSS-incidence among countries worldwide. Hypothetically this selective occurrence could be related to polymorphism of the immunsystem, variable wound-management protocols or different bioflora of the skin. Between 2002 and 2004, TSS was not observed in the Dutch Beverwijk Burns Centre [8]. The authors suggest that their prophylactic use of silver sulfadiazine and hydrofiber dressing may be a protective factor as TSS develops secondarily to a colonised wound [8]. After completion of this study, an information pamphlet was created and is being provided to parents of patients suffering from burns or scalds. The objective is to increase awareness of TSS among parents in addition to medical care professionals as small surface burns may be managed as outpatients. They may also be treated as sepsis and/or unspecific systemic inflammatory response syndrome (SIRS) at ICUs of non-specialized and/or non-paediatric hospitals. For these reasons, TSS may be missed in these patients particularly. In fact, the number of underreported or undetected TSScases is expected to be high, as numerous clinicians treating paediatric burns are not aware of this complication. In addition, the majority of TSS-cases may not have been published making incidence estimates difficult.

4.1.

Limitations

As with all retrospective studies, data collection may be challenging and incomplete. Due to the diagnostic challenges discussed, over-diagnosis may occur and result in selection bias. Documentation of TSS has been poor in the literature, which may be caused by the rarity of the disease and lack of knowledge among health care professionals.

4.2.

Future research

Prospective, multi-centre studies are warranted and may allow determination of risk factors, optimized diagnostic criteria, prognosis, prevention, ideal treatment and epidemiologic data (e.g. annual incidence, geographical distribution) of TSS. An international, prospective, electronic disease registry would provide a solution for research challenges related to a rare disease such as TSS in paediatric thermal injuries. Improved evidence may also provide justification of expensive diagnostic tests such as antibody testing. Potential biological and genetic factors contributing to TSS-development should be evaluated in future studies including bio-samples. Finally, future research is indicated to determine whether parental and health care provider information increases awareness and leads to earlier TSS-diagnosis and improved outcome.

5.

Conclusions

While burns and scalds in childhood are common, TSS remains a rare and life-threatening complication. Toxic shock syndrome diagnosis is challenging as it is based on clinical signs and symptoms, while rapid treatment initiation with a low level of suspicion is indicated for favourable outcomes. Due to the rarity of the disease many questions such as risk factors, prevention or genetic predisposition

e11

remain unanswered and warrant future prospective multicentre studies.

Acknowledgements This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. REFERENCES

[1] Todd J, Fishalt M, Kapral F, Welch T. Toxic shock syndrome assosiated with phage group 1 staphylococci. Lancet 1978;2: 1116–8. [2] Frame JD, Eve MD, Hackett ME, Dowsett EG, Brain AN, Gault DT, et al. The toxic shock syndrome in burned children. Burns Incl Therm Inj 1985;11(April (4)):234–41. [3] Wulff UC, Hansen HG, Marg W. Toxic shock syndrome. Dtsch Med Wochenschr 1982;107(November (46))1760–3 [German]. [4] Young AE, Thornton KL. Toxic shock syndrome in burns: diagnosis and management. Arch Dis Child Educ Pract Ed 2007;92(August (4))97–100 [Review]. [5] Davis JP, Chesney PJ, Wand PJ, LaVenture M. Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and prevention. N Engl J Med 1980;303(December (25)):1429–35. [6] Cole RP, Shakespeare PG. Toxic syndrome in scalded children. Burns 1990;16(June (3)):221–4. [7] Brown AP, Khan K, Sinclair S. Bacterial toxicosis/toxic shock syndrome as a contributor to morbidity in children with burn injuries. Burns 2003;29(November (7)):733–8. [8] Vloemans AF, Gorissen KJ. Non-existence of toxic shock syndrome in Dutch Burns Centres. Burns 2006;32(June (4)):522– 3. [9] Farmer BA, Bradley JS, Smiley PW. Toxic shock syndrome in a scald burn victim. J Trauma 1985;25(October (10)):1004–6. [10] Holt PA, Armstrong AM, Norfolk GA, Sager JM. Toxic-shock syndrome due to staphylococcal infection of a burn. Br J Clin Pract 1987;41(January (1)):582–3. [11] Brain AN, Frame JD, Eve MD. Early lymphopenia in burned children with and without the toxic shock syndrome. Burns Incl Therm Inj 1988;14(April (2)):120–4. [12] Egan WC, Clark WR. The toxic shock syndrome in a burn victim. Burns Incl Therm Inj 1988;14(April (2))135–8 [Review]. [13] Heywood AJ, al-Essa S. Toxic shock syndrome in child with only 2% burn. Lancet 1990;335(April (8693)):867. [14] Glazowski MJ, Ostergaard GZ, Arpi M, Thomsen M. Toxic shock syndrome. A case of a child with burns. Ugeskr Laeger 1992;154 (March (13))868–9 [Danish]. [15] Nivenius K, Cavell B, Gustafson I, Ljungh A. Toxic shock syndrome in a young child. A severe condition caused by a minor injury. Lakartidningen 1993;90(13)1267–8 [Swedish]. [16] Weinzweig J, Gottlieb LJ, Krizek TJ. Toxic shock syndrome associated with use of Biobrane in a scald burn victim. Burns 1994;20(April (2)):180–1. [17] Maródi L, Káposzta R, Rozgonyi F, Bergdoll MS. Staphylococcal enterotoxin A involvement in the illness of a 20-month-old burn patient. Pediatr Infect Dis J 1995;14(July (7)):632–4. [18] Blomqvist L. Toxic shock syndrome after burn injuries in children. Scand J Plast Reconstr Surg Hand Surg 1997;31(March (1)):77–81. [19] Davis TC, Griffin NK. The consequences of toxic shock syndrome in an 18-month-old boy with 20% scalds. J R Soc Med 1996;89(February (2)):115P–6P. [20] Johnson D, Pathirana PD. Toxic shock syndrome following cessation of prophylactic antibiotics in a child with a 2% scald. Burns 2002;28(March (2)):181–4.

Please cite this article in press as: L. Gutzler, et al., Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.07.002

JBUR 5314 No. of Pages 12

e12

burns xxx (2017) xxx –xxx

[21] Trop M, Zobel G, Roedl S, Grubbauer HM, Feierl G. Toxic shock syndrome in a scald burn child treated with an occlusive wound dressing. Burns 2004;30(March (2)):176–80. [22] Serour F, Stein M, Gorenstein A, Somekh E. Early burn related gram positive systemic infection in children admitted to a pediatric surgical ward. Burns 2006;32(May (3)):352–6. [23] Tanaka K, Kaji S, Onizuka K, Makino K, Fujii T. Two cases of toxic shock syndrome caused by burn. Jpn J Plast Reconstr Surg 1989;32(5)521–8 [Japanese]. [24] Luque GR, Jimenez EO, Murillo CG, Villen MN, Guerrero GC. Toxic-shock syndrome in childhood: a case report. Sindrome de shock toxico en la infancia: a proposito de un caso. Rev Esp Pediatr 1997;53(317)477–80 [Spanish]. [25] Richard Money-Kyrle. Development of toxic shock syndrome following scalding. AVMA Med Legal J 20028(March (2)) Clinical Risk. [26] Steinbrenner B, Lucking KM. Toxic shock syndrome in a toddler after scalding injury– of toxins and T cells. Swiss Med Wkly 2007137(June (37S)). [27] Fanshawe AE, Bain CJ, Williams AJ. An unusual case of Guillain–Barre syndrome following toxic shock syndrome in a burned child. Burns 2014;40(May (3)):E18–20. [28] Garland M, Zeller KA, Shetty AK. Toxic shock syndrome due to methicillin-resistant Staphylococcus aureus infection after a pediatric scald burn. Am J Emerg Med 2016;34(August (8))1735 e1-2.

[29] Yokochi T, Sakanishi S, Ishidou Y, Kawano G, Matsuishi T, Akita Y, et al. Acute encephalopathy with biphasic seizures and late reduced diffusion associated with staphylococcal toxic shock syndrome caused by burns. Brain Dev 2016;38 (October (9)):875–9. [30] Shaer J. Toxic shock syndrome in a 20-month-old boy with a 7% burn. Off Emerg Pediatr 2001;14(1):45–8. [31] Childs C, Edwards-Jones V, Heathcote DM, Dawson M, Davenport PJ. Patterns of Staphylococcus aureus colonization, toxin production, immunity and illness in burned children. Burns 1994;20(December (6)):514–21. [32] Edwards-Jones V, Greenwood JE, Manchester Burns Research Group. What’s new in burn microbiology? James Laing Memorial Prize Essay 2000. Burns 2003;29(February (1)):15–24. [33] Quan L, Morita R, Kawakami S. Toxic shock syndrome toxin-1 (TSST-1) antibody levels in Japanese children. Burns 2010;36 (August (5)):716–21. [34] Withey SJ, Carver N, Frame JD, Walker CC. Toxic shock syndrome in adult burns. Burns 1999;25(November (7)):659–62. [35] Notermans S, van Leeuwen WJ, Dufrenne J, Tips PD. Serum antibodies to enterotoxins produced by Staphylococcus aureus with special reference to enterotoxin F and toxic shock syndrome. J Clin Microbiol 1983;18(November (5)):1055–60. [36] Hardern R, Cavanagh S. Toxic shock syndrome after burns in children. J Accid Emerg Med 1995;12(March (1)):68–9.

Please cite this article in press as: L. Gutzler, et al., Toxic shock syndrome in paediatric thermal injuries: A case series and systematic literature review, Burns (2017), http://dx.doi.org/10.1016/j.burns.2017.07.002