R.S.Soliman1,
D.Morrison3, K. Husselbee2, G.Phillips1
1Department
of Medical Microbiology, 2Department of Paediatrics, Ninewells
Hospital, Dundee.
3 MRSA
Reference Laboratory, Stobhill Hospital, Glasgow, UK
Correspondence
author:
R.S.Soliman, SPR, Department of Medical Microbiology, Level 6, Ninewells Hospital, Acute Services Division, NHS Tayside Dundee, DD1 9SY
E-mail: reham.soliman@nhs.net
SMJ 2007 52(4): 53
Abstract
A
three-year-old boy was admitted to the hospital with a three-day history of
chickenpox and a one-day history of fever and enlarging skin lesions on his
chest, trunk, and around his neck. The
lesions were enlarged and skin peeling over the chest wall was noted. Despite
starting him on Flucloxacillin/Aciclovir, new lesions were noted with blisters
over chest, legs, arms and buttocks. A clinical diagnosis of Staphylococcal
Scalded Skin Syndrome (SSSS) was made and laboratory results confirmed
Methicillin sensitive Staphylococcus aureus (MRSA) isolation. The isolates were
sent to Scottish MRSA reference lab (SMRSARL) for typing and toxin detection.
The isolate from this child was positive for the exfoliative toxin A (eta) gene
and negative for exfoliative toxin B, toxic shock syndrome toxin, panton-valentine
leukocidin and entertoxins A, B, C, D, E. By Pulse Field Gel Electrophoresis (PFGE)
this isolate was identified as MLST Type 88 clone which has been associated with
skin lesions in other countries.
Keywords
- Methicillin sensitive Staphylococcus aureus, Scalded skin Syndrome,
Exfoliative toxins, Pulse Field
Introduction
Staphylococcus
aureus is one of the major human pathogens; it causes a wide range of major and
minor infections. It produces and secretes a number of enzymes and toxins that
have been variously implicated as possible pathogenic factors. Exfoliative
toxins are a group of serologically and biologically distinct proteins
responsible for the major findings of scalded skin syndrome. ETA is heat stable
and the gene is located on chromosomes, while ETB is heat labile and plasmid
encoded.1 Recent studies suggest that the toxins may have a unique
super antigenic activity, which leads to massive, unregulated cytokine release
and the severe clinical problems.2
Scalded Skin
Syndrome (SSS) describes a spectrum of superficial blistering skin disorders
with severity varying from localised skin lesions in the form of bullous
impetigo to a more extensive generalised condition, when cutaneous erythema
occur followed by profuse peeling of the epidermal layer affecting the entire
body surface.3, 4
The
condition was first described by Baron von Rittershain, a German physician, in
1870s. However, the toxins were only identified in 1970 after Melish and Glasgow
demonstrated that injecting new born mice with S. aureus isolated from patients
with SSSS resulted in epidermal cleavage and exfoliation.5
Case
report
A three–year-old
boy was admitted to the paediatric unit with a three-day history of chickenpox
and a one-day history of intermittent pyrexia and some enlarging skin lesions on
his trunk. He was lethargic, tolerating fluids but not keen to eat. He had a
complex past medical history, which included laryngomalacia, cow’s milk
protein intolerance, mild asthma and transient hypogammaglobulinaemia for which
he was treated with immunoglobulin infusions between the ages of 6 and 12 months
under the care of a paediatric immunologist. He was also maintained on
prophylactic antibiotic therapy, initially with cotrimoxazole and later with
azithromycin, which were discontinued ten months prior to this admission. He had
had recurrent bouts of minor infections during this time but otherwise was
growing and developing normally. His only regular medications were
Beclomethasone and Salbutamol inhalers.
On admission he
was noted to have widespread Varicella lesions over the trunk, most of which
were crusted. Three lesions were enlarged, erythematous and skin peeling over
the chest wall was noted. He was otherwise well and the rest of his clinical
examination was unremarkable. Skin swabs from the enlarged lesions were taken
and initial therapy was commenced with oral flucloxacillin, aciclovir and
chlorpheniramine. Twelve hours later, new bullous lesions were noted, along with
further blistering of his neck, chest, legs, arms and buttocks. Skin peeling was
also noticed on the chest. A clinical diagnosis of Staphylococcal Scalded Skin
Syndrome (SSSS) was made and confirmed by the consulting dermatologist. He was
therefore changed to intravenous flucloxacillin, ceftriaxone and aciclovir. In
view of his past history he was given a dose of intravenous immunoglobulin. He
responded well to treatment clinically and the peripheral white blood cell count
and C-reactive protein decreased. By the third day of treatment his skin lesions
were significantly improved and he was changed to oral flucloxacillin and
aciclovir. He was discharged the following day to
complete a one-week course of flucloxacillin and aciclovir. He was
reviewed one month later in the outpatient department, where it was noted that
all his lesions had healed well. He remains under long-term immunology follow
up.
The
swabs from the primary skin lesions yielded a profuse growth of methicillin
sensitive S.aureus. sensitive to flucloxacillin, erythromycin, gentamicin,
rifampicin, vancomycin, ciprofloxacin, and fuscidic acid, resistant to
penicillin, and amoxcillin. Blood cultures were sterile.
In view of the
clinical diagnosis, the isolate was sent to the Scottish MRSA Reference
Laboratory (SMRSARL) for typing and toxin detection. The isolate was positive
for the exfoliative toxin A (eta) gene, negative for exfoliative toxin B (etb),
toxic shock syndrome (tst), panton-valentine leukocidin (lukS- luk F) and
enterotoxins A (sea), B (seb), C (sec), D (sed) and E (see). By Pulse Field Gel
Electrophoresis (PFGE) the isolate was identified as Scottish type 145,subtype
e. Subtype e differs at six band loci from subtype a, the “type strain” of
this clone (Figure). Multi-locus
Sequence Typing (MLST) identified this isolate as ST88 identical to the type
strain (145 subtype a) of this clone.
Discussion
Staphylococcal
scalded skin syndrome (SSSS) describes a spectrum of superficial blistering skin
disorders caused by the exfoliative toxins of S. aureus. In its severe form, the
exfoliation can spread to cover the entire body surface area. As in this case
report, SSSS particularly affects infants and young children. Lack of protective
antibodies and immature renal function, which impairs the ability to excrete the
toxin has been suggested as reasons for the age bias.6
Healthy adults
rarely develop SSSS.7 Reported risk factors for adult SSSS include
immunosuppression8, renal failure9 and chronic alcohol
abuse and intravenous drug addiction.
Skin
scarring is rare as the exfoliation is as a result of cleavage of the
superficial layers of the epidermis. In infants and young children, potentially
fatal complications include hypothermia, dehydration and secondary infections by
organisms such as pseudomonads.10 With appropriate management,
however, mortality due to SSSS in children remains below 5%.10 In
comparison, generalised SSSS in adults carries a mortality rate of almost 60%,
mainly because the majority of patients suffer from underlying conditions.
Two Exfoliative
Toxin serotypes affecting humans have been identified, but their purpose and
mechanism of action have remained elusive.11 Although they posses
some physicochemical differences, ETA and ETB have 40% sequence homology and
produce identical dermatological effects.6
The isolate from
this child belonged to ST 88 clone. Between 2001 and 2004, 10 isolates of this
clone were identified by SMRSARL, all with the exception of the isolate in this
report are MRSA (SCCmec type IV) and carried the sec but not the eta toxin
genes. The ST 88 clone has been reported as a cause of impetigo in two young
children in Switzerland but they were community acquired MRSA (SCC mec type IV)
and they carried the exfoliative toxin A (eta) gene.4 Liassine et al
reported that these isolates were related to an
eta-positive MRSA clone reported in Japan.12 In both these studies
the MRSA were considered to be community acquired (CA-MRSA). The emergence of
heterogeneous (low level) methicillin resistance in eta / etb- positive clones
leading to inappropriate therapy for SSSS suggests that in such cases the
antibiotic resistance of such clones should be more closely monitored.
Acknowledgement
We
thank Dr. R. Wilkie for permission to report this case.
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