burns 34 (2008) 98103

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Severe staphylococcal scalded skin syndrome in children

Moira Blyth *, Catalina Estela, Amber E.R. Young
South West Regional Paediatric Burns Unit, United Kingdom

article info
Article history: Accepted 22 February 2007 Keywords: Staphylococcal scalded skin syndrome Children Burns unit Critical care

abstract
Staphylococcal scalded skin syndrome (SSSS) is a rare toxin-mediated condition caused by Staphylococcus aureus, which causes blistering and desquamation of the skin. Between November 2005 and April 2006, four children were admitted to critical care beds in the South West Regional Paediatric Burns Unit because of SSSS affecting more than 50% of the body surface area. Details of these cases are presented, highlighting the potential severity of the condition. The cases also illustrate that uid overload is a common complication of the condition, despite hypovolaemia being the more obvious risk, and that both hyponatraemia and leukopenia are frequent ndings. These summaries clearly demonstrate the need for paediatric critical care in a tertiary burns unit for children with SSSS affecting a large proportion of the body surface area. The cluster of admissions prompted us to write a management protocol for children with severe SSSS and a summary of this is provided. Most children with SSSS will initially present to general paediatric units, where mild cases will be managed, but severe cases should be promptly referred to a tertiary paediatric burns unit for multi-disciplinary care in a critical care environment. # 2007 Elsevier Ltd and ISBI. All rights reserved.

1.

Introduction

Staphylococcal scalded skin syndrome (SSSS) is a rare toxinmediated condition caused by Staphylococcus aureus. This is usually a group 2 S. aureus, mainly serotypes 3A, 3B, 3C, 55 and 71 but rare cases due to MRSA (methicillin-resistant S. aureus) have been reported [13]. It is normally seen in children less than 5 years of age, who have not yet developed protective antibodies against the staphylococcal toxins, or in adults with signicant underlying morbidity. It is characterised by blistering and desquamation of the skin and Nikolskys sign (shearing of the epidermis with gentle pressure), even in areas that are not obviously affected. SSSS in children usually begins with a prodrome of pyrexia and malaise, often with signs and symptoms of an upper respiratory tract infection. Discrete erythematous areas then develop and rapidly enlarge and coalesce, leading to generalised erythema. This is often worse

in the exures with sparing of the mucous membranes. Large, fragile bullae form in the erythematous areas and then rupture. This causes large areas of epidermis to slough off resulting in the appearance of scalded skin. The main complications are hypothermia, dehydration due to uid loss through the damaged skin and secondary infection. Mortality rates of 60% in adults [4], and up to 11% in children [57] are reported. It is important that children with severe SSSS are admitted to paediatric critical care facilities for multi-disciplinary management.

2.

Case reports

Four children with SSSS affecting more than 50% of the body surface area were transferred to critical care beds in the South West Regional Paediatric Burns Unit, from four separate

* Corresponding author at: Barbara Russell Unit, Frenchay Hospital, Frenchay Park Road, Bristol BS16 1JE, United Kingdom. Tel.: +44 117 970 1212. E-mail address: drmblyth@yahoo.co.uk (M. Blyth). 0305-4179/$34.00 # 2007 Elsevier Ltd and ISBI. All rights reserved. doi:10.1016/j.burns.2007.02.006

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Table 1 Summary of length of admission/changes of dressings Case 1

Maximum affected surface area (%) Dressings change: under anaesthesia on unit with sedation Days in critical care bed Total days in unit
a

2
70 18, 10 7 12

3
5560 1, 2 3 5

4
Almost 100 19, 11, 13, 15 16, 17 15 18a

100 15, 7 8 7 12

Transferred to local burns unit as an in-patient.

district general hospitals, between November 2005 and April 2006. Their histories and relevant laboratory results are summarised below, with day 1 being the day of admission to our unit. None of these children had any signicant medical history, nor any recent medications, and all had up-to-date vaccinations. Each of them spent approximately 2 days in the local hospital before being transferred to us. Blood cultures were sterile in all cases. Each child was taken to theatre shortly after arrival, for examination under anaesthetic. The skin was cleaned and silver sulphadiazine cream applied before dressing with parafn-impregnated gauze dressings and then crepe bandage for limbs and a gauze and cotton tissue for the trunk. Central venous access was also obtained and a urinary catheter inserted if this had not been done prior to transfer. Skin biopsies were performed in all cases to conrm the diagnosis. Each child was commenced on an opiate infusion shortly after arrival in the unit and antibiotics were changed to an intravenous penicillinase-resistant penicillin alone once the diagnosis had been established. Changes of dressings under general anaesthesia were initially performed on a daily basis, and these are summarised in Table 1. In each instance, damaged skin was cleaned and covered with silver sulphadiazine cream, parafn-impregnated gauze dressings and crepe bandage for limbs and a gauze and cotton tissue for the trunk. Healing skin was covered with a hydrocolloid dressing if required, and parafn or other mild emollients, if not.

pathy. Despite the uid restriction, she also required furosemide for uid overload on day 3. By day 5, there were no new areas of blistering developing and most areas had healed by day 7. Her antibiotics were discontinued on day 10 but she was kept in hospital for another 2 days, due to poor oral intake. At review a week after discharge, her skin was healing well and she was referred back to her local hospital for further follow-up.

2.2.

Case 2

2.1.

Case 1

This 6-year-old girl presented with an erythematous rash and a few small blisters on her neck and perineum. She had been pyrexial with a cough for the preceding few days. She was commenced on intravenous antibiotics but continued to develop new areas of erythema with blistering of her back and axillae, along with increasing area of blistering on her neck and perineum. Dressings were applied under general anaesthesia at the referring hospital and the area of damaged skin was estimated at 20%. She had a urinary catheter inserted and was commenced on intravenous uids with the Parkland correction for a 20% burn. When she was transferred to our care, her uids were restricted to 80% maintenance alone due to mild uid overload. By the time of transfer, 90% of her skin showed supercial damage, with the remaining 10% having deeper damage. Fresh frozen plasma (FFP) was given for its anti-toxin properties [8] at this point and again the following day, to correct a coagulo-

This 4-year-old boy initially presented to his GP with pyrexia, sore throat and erythema on his neck. He was diagnosed with tonsillitis but presented to hospital the following day with a crusted lesion at the corner of his mouth and peeling of the peri-oral and scrotal skin. He was commenced on intravenous antibiotics but continued to develop new lesions. By the time he was transferred to us, the erythema covered his face and groin and he had developed blistering lesions on his forehead, nose, neck, axillae, abdomen, perineum and legs. His lips were crusted but there were no intra-oral lesions. His conscious level uctuated from spontaneous eye opening and obeying commands to only responding to pain. The initial estimate was that 65% of his surface area was affected and he was commenced on 100% maintenance uid plus the Parkland correction for a 65% burn. After 12 h on this regime, he was uid overloaded, with peripheral and pulmonary oedema and a positive balance of 2000 ml so the resuscitation uid was reduced by a quarter. This did not improve his clinical condition much and he required furosemide when his urine output began to tail off on day 4. The resuscitation uids were discontinued but a further dose of furosemide was required the next day. During this period, a few new blisters became apparent each day, with the area affected increasing to 70% on day 3. He was therefore given 10 ml/kg FFP on both day 4 and day 5 when uid boluses were required due to third space losses. Gabapentin was started on day 6 to decrease his itching. Between days 6 and 10, healing was noted to have started. When reviewed in clinic 4 months later, he had small areas of scarring on his chest and his right leg.

2.3.

Case 3

This 5-year-old girl was admitted with a 3-day history of being non-specically unwell with lethargy, pallor and an erythematous rash involving her face and torso. This had been preceded by 4 days of diarrhoea and pyrexia. Small blisters had appeared on her nose 2 days prior to admission and bullae

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were present on her right hand on admission. Intravenous antibiotics were started but the blistering spread rapidly. When she was transferred to us she required a uid bolus before commencing intravenous uids at 100% maintenance. At this stage, the lesions covered 5560% of her surface area, affecting face, torso, arms, buttocks and perineum but sparing the scalp and legs, so FFP was administered for its anti-toxin properties. She became systemically unwell with tachycardia, pyrexia (central temperature 40 8C) and rigors. Capillary rell time centrally was 4 s and she had a wide toe-core gap (peripheral temperature of 3132 8C), both indicators of decreased circulating blood volume and either dehydration or third space losses. This was treated with a 10 ml/kg bolus of normal saline, to improve her circulating blood volume. This, however, did not improve her urine output and her third space losses continued over the remainder of the day. A rising oxygen requirement then necessitated a dose of furosemide, which was given with good effect. The following day, her trunk, face and arms were noted to be virtually healed and her legs remained clear. She remained well post-operatively and her antibiotics were stopped the following day.

improving as fast as expected. A 5-day course of immunoglobulin was therefore given and, by day 13, only 6% of his skin had not yet healed. He developed diarrhoea and vomiting on day 10 but this resolved within a few days. Peditrace (a trace element infusion) was later given due to low copper and zinc levels. By day 18, his skin had virtually all healed, apart from deep areas on both feet and he was transferred as an inpatient to the care of his local burns team, as he had been visiting family and does not live in our area.

3.

Discussion

2.4.

Case 4

This 4-year-old boy presented with a 1-day history of peri-oral crusting and erythema in the axillae. He then developed small blistering areas on his face, neck and thorax that enlarged rapidly after admission. Intravenous antibiotics were started and he was put on intravenous uids at 100% maintenance. He had oral analgesia initially but then required a morphine infusion. Local anaesthetic gel was used to allow him to pass urine when he developed urinary retention due to pain from the blistering and desquamation of his penis. He was transferred to us after desquamation of most of his back and was taken to theatre after an initial assessment and a uid bolus. Almost 100% of his surface area was involved at this stage, with sparing only of the scalp. A naso-gastric tube was inserted and sutured into place due to the involvement of the facial epidermis. FFP and a further two uid boluses were given in theatre and his uids were restricted to 80% maintenance. Following his rst change of dressings, he became systemically unwell with rigors and peripheral vasoconstriction so he was given his second dose of FFP. On day 2, an arterial line was inserted to allow blood pressure monitoring, since non-invasive monitoring was impossible and the nasogastric tube was replaced with a naso-jejunal tube. By day 3 he was taking good volumes of water and juice orally but was still refusing food or milk and requiring naso-jejunal feeds for nutrition. He became hyponatraemic and was started on sodium supplementation but his sodium continued to fall and restriction of his oral uid intake was also required, as the uids he was consuming were all sodium-free. Albumin boluses were used to replace the large uid losses from his skin and to boost his sodium and albumin levels, while maintaining his over-all state of hydration. Gabapentin was commenced on day 4 to decrease his itching. By day 7, healing of approximately 25% was noted but his inammatory markers began to climb and he was not

SSSS cannot be diagnosed reliably in the prodromal period, as the signs and symptoms at this stage are found in many other conditions. Once the illness is established, the differential diagnoses include Kawasaki disease, toxic shock syndrome, epidermolysis bullosa and other congenital blistering disorders, graft versus host disease, scarlet fever and impetigo. All of these should be easily distinguished from SSSS on clinical grounds and the details of these conditions are beyond the scope of this article. Once blistering and desquamation is present, the main differential diagnosis is toxic epidermal necrolysis (TEN). TEN also presents with a short prodromal period, followed by blistering and skin desquamation but is caused by an immunological reaction to viral infections or drugs [9]. It almost always affects the mucous membranes [9], which are spared in SSSS, and the Nikolsky sign is only present in areas of damaged skin [10]. Where there is any doubt over the diagnosis, SSSS and TEN can be differentiated histologically on a skin biopsy. TEN causes full thickness epidermal necrosis and skin splitting at the junction between the dermis and epidermis, whereas SSSS causes splitting through the granular layer of the epidermis, without necrosis. S. aureus secretes exotoxins, known as epidermolytic toxin A (ET-A) and epidermolytic toxin B (ET-B), into the circulation from the site of primary infection. In adults, this is usually an obvious clinical infection, for example pneumonia or osteomyelitis, but in children it is normally a mild infection in the upper respiratory tract. 51% of S. aureus isolates from children with SSSS produce both epidermolytic toxins, with 30% producing ET-A alone and 19% ET-B alone [11]. The epidermolytic toxins target desmoglein 1 (Dsg1) [12], a desmosomal protein that is predominantly found in the epidermis [13] and is involved in keratinocyte adhesion in the granular layer. Binding of ET-A or ET-B to Dsg1 causes its inactivation [14], resulting in reduced cell-to-cell adhesion and splitting of the epidermis. Although Dsg1 is present in mucosal membranes, another member of the Dsg family (Dsg3) [13] predominates, explaining the mucosal sparing in this condition. These cases illustrate the potential severity of SSSS and the rapid deterioration in clinical condition that can occur with increases in the area of affected skin. They highlight the length of hospital admission and the need for multi-disciplinary paediatric critical care in a specialist unit for those with severe SSSS. This case series also illustrates that uid overload is a common complication of the condition, despite hypovolaemia

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Table 2 Sodium, CRP and leukocyte results Case 1

Sodium, minimum (mmol/l) CRP, maximum (mg/l) Total leukocyte counts (109 l1) Neutrophils, minimum (109 l1) Lymphocytes, minimum (109 l1) 132 46 2.99.9 1.2 0.4

Day
3 3 3 3

Case 2
132 102 2.310.2 0.9 0.8

Day
2 and 4 4 2 5

Case 3
134 56 4.413.4 2.5 1.1

Day
3 3 4 2

Case 4
127 224 3.017.0 0.6 1.0

Day
4 7 8 2

being the more obvious risk. It is interesting to note that all of these children became hyponatraemic at some point during their illnesses. This is not surprising, as hyponatraemia is common in severe infections [15] and inappropriate vasopressin secretion occurs in patients with burns [16], so is also likely to occur in SSSS. (Inappropriate vasopressin secretion leads to decreased urinary output, and will lead to uid overload if excessive volumes of uid are given.) Many of the children also developed neutropenia and/or lymphopenia, with every child having a total leukocyte count below the lower limit expected for their ages (5.515.5 109 per litre for children aged 47 years) at some stage. The exact values and the differential leukocyte counts are shown in Table 2. Also of note is that the rise in inammatory markers is not as marked as would have been expected with a severe systemic illness. It is important that clinicians are not falsely reassured by a CRP (C-reactive protein) that is only marginally raised and a leukocyte count that is within normal limits. It is unusual for our unit to admit four patients with SSSS in such a short period of time but there are suggestions that SSSS is becoming more prevalent [17]. Although SSSS is recognised to occur in outbreaks, these are normally due to carriers spreading the condition in one unit [2,18]. This scenario is highly unlikely in these cases as the children were transferred to our centre from four separate hospitals spread over a wide geographic area.

examination should include a search for the primary site of infection and a history of recent drug exposure should also be sought, as this may suggest that the diagnosis of TEN is more likely. The immediate investigations that we recommend are shown in Table 4. Although inammatory markers are not a reliable indicator of the severity of SSSS disease, a subsequent rise from the baseline value is a good indicator of secondary infection. A skin biopsy should also be performed in theatre as soon as possible as this will distinguish between SSSS and TEN and guide further management.

4.2.

Treatment of toxaemia

Benzylpenicillin and an intravenous penicillinase-resistant penicillin should be commenced at high doses as soon as blood cultures have been taken. (If the patient is allergic to penicillins, clarithromycin or cefuroxime would be appropriate.) This will not halt the progression of the disease until the circulating exotoxin has been neutralised by antibodies or excreted from the body by the kidneys. Pseudomonas cover is also required if there is evidence of secondary infection. Topical antibiotics should be prescribed for conjunctivitis, if present, but there is no role for topical antibiotics for the skin

Table 3 Members of our multi-disciplinary team

Burns surgeons Paediatricians Paediatric nurses experienced in burns and critical care Paediatric anaesthetists Paediatric dermatologists Microbiologists Pain team Paediatric dieticians Paediatric physiotherapists Paediatric pharmacists Play therapists Teachers Clinical psychologists

4.

Management

Most children with SSSS will initially present to a district general hospital and mild cases will be managed there. However, we would suggest that severe cases should be promptly referred to a tertiary paediatric burns unit for care in a critical care environment. This allows management by an appropriate multi-disciplinary team, including those listed below (Table 3). We have recently written a management protocol for children with severe SSSS who are admitted to our unit and this is summarised below. Some of these guidelines will also be appropriate for the management of mild cases in general paediatric units.

Table 4 Recommended initial investigations

Blood cultures Full blood count Coagulation screen Group and save serum (in case FFP is required) Urea and electrolytes C-reactive protein (or other inammatory markers, depending on availability in the laboratory) Liver function tests Calcium, magnesium and phosphate Wound swabs Nasal swabs for MRSA carriage

4.1.

Immediate assessment and investigations

The immediate management of a child with SSSS should follow basic resuscitation guidelines, with assessment of the airway, breathing and circulation taking priority. Fluid bolus(es) are likely to be required, due to toxaemia and to uid loss through the damaged skin. Both the history and

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lesions as this is not the site of primary infection and the blister uid will be sterile initially. Use of FFP (10 ml/kg) should be considered in children who are systemically unwell as this is likely to contain antibodies to the exotoxins [8]. (If a second dose is required, it should come from a different donor, as there is a possibility that the rst donor did not have antibodies against the epidermolytic toxins.) A 5-day course of pooled human immunoglobulin (0.4 g/kg each day) should also be considered if there is little, or no, improvement after two doses of FFP. This should assist in neutralisation of the exotoxins and is known to have anti-inammatory properties [19], which may be benecial.

4.3.

Analgesia

sampling. In practice, central venous access will be essential in most cases because epidermal damage will prevent secure peripheral access being obtained easily. All lines and the urinary catheter should be inserted in theatre under sterile conditions. Enteral nutrition must be commenced as soon as possible. This can be achieved with a naso-gastric tube but a nasojejunal tube is preferable as it removes the need to discontinue feeds prior to anaesthesia. Naso-jejunal (or naso-gastric) tubes are likely to require suturing into place due to epidermal damage on the face. Oral intake should be encouraged whenever possible but care should be taken that the child is not permitted excessive quantities of water or juice due to the risk of hyponatraemia.

Regular paracetamol (acetaminophen) should be commenced but many children will also require an opioid infusion, such as fentanyl (14 mg/kg/h). Non-steroidal antiinammatory drugs (NSAIDs) are contra-indicated in the acute phase as the damaged skin is already prone to bleeding and renal excretion of the exotoxins makes it important that renal function is maximised. There are also some suggestions that NSAIDs may contribute to the development of SSSS [20]. Low dose midazolam infusion (50100 mg/kg/h) may be helpful if the child is very distressed and sedation is thought to be benecial. Gabapentin is useful if itching becomes a problem (100 mg/kg once on day 1, twice on day 2 and then three times each day) and may need to be continued for a few months.

4.5.

Skin care

4.4.

Nutrition and uid balance

After the initial assessment and provision of uid boluses if required, we use a regime of intravenous uids restricted to 80% maintenance requirements of 0.45% saline with 5% dextrose plus uid boluses when required. Other standard uid for paediatric maintenance requirements can be substituted but only isotonic solutions should be used to reduce the risk of hyponatraemia. Monitoring heart rate, blood pressure, capillary rell time, core-peripheral temperature difference, urine output, base decit and lactate will give a good idea of uid status and the requirement for boluses. Fluids such as 0.9% saline, 4.5% human albumin solution, a gelatin plasma substitute or FFP should be used for boluses. Each of these solutions has a similar sodium concentration (130160 mmol l1) [2123] to the uid lost through the damaged skin (140 mmol l1) [24]. Treating with restricted uids and additional boluses makes it easier to monitor uid balance carefully and reduces the risk of uid overload and hyponatraemia. We would recommend this approach, rather than using the burns resuscitation formulae, as the size of the affected area changes and no time of injury can be identied. In our experience, using these formulae results in children receiving too much uid in the initial stages and becoming uid overloaded. In the acute period, monitoring of urea and electrolytes and arterial (or venous) blood gas analysis will be required every 8 12 h, as a minimum. A urinary catheter will be essential to allow adequate monitoring of urine output and either central venous access or arterial access will be required for blood

Sterile dressings are required and these should be applied in theatre initially to minimise the pain involved and to reduce the infection risk. Daily theatre changes of dressings will be required until recovery starts. Silver sulphadiazine creams (Flamazine or Flammacerium) have bactericidal and bacteriostatic properties and can be used with parafn-impregnated gauze dressings and then covered with a gauze and cotton tissue (for the trunk) or crepe bandaging (for limbs). Biobrane should be avoided due to the large area of potential infection/ necrotic tissue. Silver-based dressings, such as Acticoat can be substituted if there is evidence of neutropenia, as this is a potential side effect of silver sulphadiazine. Hydrocolloid dressings are helpful on small areas that are healing and mild emollients, such as parafn, may also be used when dressings are no longer required. Other dressings (for cannulae, etc.) should be avoided unless essential, as apparently undamaged skin can shear on removal. Minimal handling, basic hygiene measures and aseptic technique for procedures are essential to decrease the risk of secondary infection.

4.6.

Other issues

Suitable mattresses and bedding should be provided, as these children are likely to remain relatively immobile for a few days or even weeks. Forced-air warming blankets are useful to keep the child warm without placing heavy blankets onto the patient, and core temperature should be kept at 3738 8C. Burns units should also have the ability to heat cubicles to an appropriate ambient temperature. Physiotherapy is important to encourage mobilisation in general, and specically of the affected limbs. Since SSSS tends to affect the exures most severely, children will often limit exion of the limbs due to discomfort and physiotherapy is very helpful in preventing this. Involvement of play therapists also helps to encourage gentle mobilisation and to prevent boredom. In the initial stages, images may be projected onto the ceiling to provide entertainment but the children will be too unwell for other play activities. When the child has improved enough to leave critical care but remains on the ward, hospital schooling will also be benecial. Some children and families may also nd input from a clinical psychologist helpful.

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5.

Conclusion
[10]

We presented our experience of four cases of severe SSSS in a 6-month period. These cases illustrate the potential severity of the condition and the need to transfer these children to tertiary burns units with paediatric critical care facilities. Our unit is currently preparing referral guidelines for our region to encourage the prompt referral of these patients. We hope that our experience and newly developed guidelines will be of help to other units.

[11]

[12]

references

[13]

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