[Staphylococcal scalded skin syndrom: a case report]. / Syndrome de Lyell staphylococcique: à propos d'un cas.

Staphylococcal scalded skin syndrom is a bullous dermatosis induced by exfoliating staphylococcal exotoxins. Children are most often affected. We report the case of a 6-month-old infant who had angina in the few days before leading up to bullous erythroderma and whose skin biopsy showed characteristic appearance of staphylococcal scalded skin syndrom. The development was rapidly unfavourable and the infant died in a refractory septic shock chart, despite the introduction of norepinephrine and anti-SAMR antibiotic therapy. The term staphylococcal scalded skin syndrome (SSSS) was separated from the toxic or allergic epidermal necrolysis by Lyell into the opposite anatomical aspect of these two entities: in scalded skin syndrome, Skin detachment is done by cleavage of the superficial part of the epidermis at the granular layer, while in toxic Lyell syndrome, the cleavage sits deeper at the level of the mucous body.

Staphylococcal Scalded Skin Syndrome: A Case Review.

Staphylococcal scalded skin syndrome (SSSS) is a rare yet well-known exfoliative skin syndrome. It involves extensive desquamated areas caused by an exfoliative toxin from Staphylococcus aureus. The typical presentation of SSSS allows for early diagnosis and treatment of the disease. Knowing and understanding the prevalence, pathophysiology, risk factors, and diagnosis of SSSS will ensure that infants being treated and cared for by neonatal nurses and neonatal nurse practitioners will receive appropriate, comprehensive, and multidisciplinary care while in the NICU. The purpose of this case review is to inform neonatal nurses and practitioners of the current literature that focuses on the diagnosis and management of SSSS.

Escarlatina estafilocócica como manifestación atenuada del síndrome de escaldadura estafilocócica / Staphylococcal scarlet fever as a mild manifestation of Staphylococcal Scalded Skin Syndrome

Se presenta el caso de un niño de cuatro años con fiebre, adenopatías y faringoamigdalitis con exantema escarlatiniforme. Se trató con amoxicilina/ácido clavulánico y evolucionó favorablemente. Se aisló Staphylococcus aureus en la faringe y dos semanas después presentó descamación en dedo de guante. Parece tratarse de una forma abortada del síndrome de escaldadura estafilocócica (AU)

We report the case of a four years old child with fever, adenopathies, pharyngitis and scarlet micropapular exanthema. He was treated with amoxicillin/clavulanic acid and he had a favourable outcome. Staphylococcus aureus was isolated from his throat. Two weeks later he presented exfoliation. It seems to be an abortive form of Staphylococcal Scalded Skin Syndrome (AU)

Neonate twin with staphylococcal scalded skin syndrome from a renal source.

OBJECTIVE: To understand the underlying mechanism of exfoliative toxins causing staphylococcal scalded skin syndrome or Ritter's Disease that predominantly affects newborns and infants, although it is sometimes found in adults. Staphylococcal scalded skin syndrome is typically diagnosed by the characteristic fluid-filled bullae together with superficial skin loss. A histopathological diagnosis may be made by looking for subcorneal acantholytic cleavage with minimal inflammation on biopsy, although this is not normally required. Exfoliative toxin A and B are both responsible for the "acantholytic" infection of Staphylococcus aureus as they target desmoglein-1 leading to loss of cell-to-cell cohesion and subsequent spread of infection. Other factors produced by S. aureus can cause a myriad of other problems including neutralization of antimicrobial peptides, inactivation of neutrophils, proteolysis, T-cell anergy, and immunosuppression. DESIGN: Individual care report. SETTING: Pediatric intensive care unit. PATIENT: We describe a normal male infant who was born at term and developed 100% total body surface area staphylococcal scalded skin syndrome on the 14 day of life with associated renal sepsis. INTERVENTIONS: After cultures from the lesions, bloodstream, and urine were obtained, intravenous Vancomycin and Ceftriaxone were commenced. The initial lesions increased in size over a 36-hr period to cover the entire body surface; this was associated with a decline in hemodynamic status. MEASUREMENTS AND MAIN RESULTS: Cultures from the urine and blood grew coagulase-positive S. aureus. An ultrasound scan revealed bilateral pyonephroses, which necessitated the placement of percutaneous nephrostomies with subsequent decompression of the collecting system. CONCLUSIONS: After the decompression hemodynamic status stabilized and over the ensuing 10 days, the patient made a full recovery with no scarring. No similar lesions were noticed on the infant's twin brother. We discuss the recent developments in understanding the underlying mechanism of exfoliative toxins causing staphylococcal scalded skin syndrome, review current treatment guidelines, and outline the need for new therapeutic options.

Exfoliative toxins of Staphylococcus aureus.

Staphylococcus aureus is an important pathogen of humans and livestock. It causes a diverse array of diseases, ranging from relatively harmless localized skin infections to life-threatening systemic conditions. Among multiple virulence factors, staphylococci secrete several exotoxins directly associated with particular disease symptoms. These include toxic shock syndrome toxin 1 (TSST-1), enterotoxins, and exfoliative toxins (ETs). The latter are particularly interesting as the sole agents responsible for staphylococcal scalded skin syndrome (SSSS), a disease predominantly affecting infants and characterized by the loss of superficial skin layers, dehydration, and secondary infections. The molecular basis of the clinical symptoms of SSSS is well understood. ETs are serine proteases with high substrate specificity, which selectively recognize and hydrolyze desmosomal proteins in the skin. The fascinating road leading to the discovery of ETs as the agents responsible for SSSS and the characterization of the molecular mechanism of their action, including recent advances in the field, are reviewed in this article.

The molecular logic of pemphigus and impetigo: the desmoglein story.

Desmosomes are intercellular adhesive junctions of epithelial cells that contain two major transmembrane components, desmogleins (Dsg) and desmocollins; these are both cadherin-type cell-cell adhesion molecules. Pemphigus is an autoimmune blistering disease caused by IgG autoantibodies that target Dsg1 and Dsg3 in pemphigus foliaceus and pemphigus vulgaris respectively. Bullous impetigo is a common and highly contagious superficial skin infection caused by Staphylococcus aureus. Staphylococcal scalded skin syndrome (SSSS) is a generalized form of bullous impetigo. The blisters in bullous impetigo and SSSS are induced by exfoliative toxin that specifically cleaves Dsg1. Clinical and microscopic localization of blisters in pemphigus, bullous impetigo and SSSS are logically explained at the molecular level by the desmoglein compensation theory; the similarity of lesions among these diseases is underscored by a similar pathogenesis.

Molluscum contagiosum prevents progression of staphylococcal scalded skin syndrome.

Prevention of progression of staphylococcal scalded skin syndrome by molluscum contagiosum indicated a possible interference by viral anti-cytokine molecule such as interleukin-18 binding protein.

Clinical manifestations of staphylococcal scalded-skin syndrome depend on serotypes of exfoliative toxins.

We sought a possible correlation between the clinical manifestations of staphylococcal scalded-skin syndrome (SSSS) and the serotype of exfoliative toxins (ET) by PCR screening of the eta and etb genes in Staphylococcus aureus strains isolated from 103 patients with generalized SSSS and 95 patients with bullous impetigo. The eta gene and the etb gene were detected in, respectively, 31 (30%) and 20 (19%) episodes of generalized SSSS and 57 (60%) and 5 (5%) episodes of bullous impetigo. Both genes were detected in 52 (50%) episodes of generalized SSS and 33 (35%) episodes of bullous impetigo. To explain this link between etb and generalized SSSS, we examined the distribution of ETA- and ETB-specific antibodies in the healthy population (n = 175) and found that the anti-ETB antibody titer was lower than the anti-ETA titer. Thus, ETA is associated with bullous impetigo and ETB is associated with generalized SSSS, possibly owing to a lower titer of anti-ETB neutralizing antibodies in the general population.

The management of staphylococcal scalded skin syndrome in infants.

Staphylococcal scalded skin syndrome (SSSS) is a disease that usually affects infants and young children who lack the antibodies to Staphylococcus aureus toxins that adults have. It is caused by bacterial infection by group II S. aureus that produces toxins that cause exfoliation, bullae (blister) formation and redness of skin. In children mortality is low, but can be high in adults, who will usually have a serious underlying disease that makes them susceptible to infection (Kim, 2002; Ladhani and Joannu, 2000).

Understanding the mechanism of action of the exfoliative toxins of Staphylococcus aureus.

The exfoliative toxins of Staphylococcus aureus are responsible for the staphylococcal scalded skin syndrome, a blistering skin disorder that particularly affects infants and young children, as well as adults with underlying disease. Their three-dimensional structure is similar to other glutamate-specific trypsin-like serine proteases with two substrate-binding domains and a serine-histidine-aspartate catalytic triad that forms the active site. However, unlike other serine proteases, the exfoliative toxins possess a highly charged N-terminal alpha-helix and a unique orientation of a critical peptide bond, which blocks the active site of the toxins so that, in their native state, they do not possess any significant enzymatic activity. The target for the toxins has recently been identified as desmoglein-1, a desmosomal glycoprotein which plays an important role in maintaining cell-to-cell adhesion in the superficial epidermis. It is speculated that binding of the N-terminal alpha-helix to desmoglein-1 results in a conformation change that opens the active site of the toxin to cleave the extracellular domain of desmoglein-1 between the third and fourth domains, resulting in disruption of intercellular adhesion and formation of superficial blisters. Elucidating the mechanism of action of the toxins and identifying desmoglein-1 as their specific epidermal substrate has not only given us an insight into the pathogenesis of the staphylococcal scalded skin syndrome, but also provided us with useful information on normal skin physiology and the pathogenesis of other toxin-mediated diseases. It is hoped that this knowledge will lead to development of rapid screening and diagnostic tests, and new antitoxin strategies for the treatment and prevention of the staphylococcal scalded skin syndrome in the near future.

Staphylococcal epidermolysins.

PURPOSE OF REVIEW: Staphylococcal epidermolysins are the major causative toxins of bullous impetigo and staphylococcal scalded skin syndrome. This disease is characterized by the splitting of the epidermis between two cell layers resulting in exfoliation. It predominantly affects newborn babies and exposes them to secondary infections. This leads to the risk of epidemics, especially in nurseries. With only an experimental model which consists of skin injections in newborn mice and the recent determination of three-dimensional structures, the essential function of these toxins remained controversial, split between that of specific proteases and that of superantigens. RECENT FINDINGS: Staphylococcal epidermolysins now constitute a family of toxins, with the recent characterizations of two new serotypes: ETC and ETD. They may be secreted by sensitive or methicillin-resistant strains. Four molecules were also identified in Staphylococcus hyicus responsible for exudative epidermitis in swine. While different observations suggested a proteolytic action to these toxins, the histological parallel made with pemphigus foliaceus greatly helped in the characterization of the targets for epidermolysins ETA, ETB, ETD: desmoglein-1, a desmosome-constitutive protein, and incidentally melanocyte-stimulating hormones, which accounts for the blisters observed clinically. SUMMARY: The growing complexity in staphylococcal toxins has to be taken into account both for their association with diseases and for diagnosis purposes. Even though cases of staphylococcal scalded skin syndrome in adults are rare, they raise further questions about the pathogenic features of the disease such as individual sensitivity and distribution of the toxins into the body.

Toxin levels in serum correlate with the development of staphylococcal scalded skin syndrome in a murine model.

Staphylococcal scalded skin syndrome (SSSS) is an exfoliative dermatitis that results from infection with exfoliative toxin-producing Staphylococcus aureus. SSSS is seen primarily in infants and children. Here we ask if there is a specific maturation process that protects healthy adults from this syndrome. For these studies, an active recombinant exfoliative toxin A (rETA) was used in a neonatal mouse model. A time course generated on the susceptibility to the toxin as a function of mouse age indicated that BALB/c mice developed the characteristic symptoms of SSSS until day 7 of life. Between day 7 and day 8 of life there was a dramatic decrease in susceptibility, such that mice at day 9 of life were resistant to the effects of the toxin. This time course corresponds approximately to the time needed for maturation of the adaptive immune response, and SSSS in adults is often identified with immunocompromised states. Therefore, mice deficient in this response were examined. Adult mice thymectomized at birth and adult SCID mice did not develop the symptoms of SSSS after injection with the toxin, indicating that the adaptive immune response is not responsible for the lack of susceptibility observed in the older mice. SSSS in adults is also associated with renal disorders, suggesting that levels of toxin in serum are important in the development of the disease. rETA was not cleared as efficiently from the serum of 1-day-old mice compared to clearance from 10-day-old mice. Ten-day-old mice were given repeated injections of toxin so that the maximal level of toxin was maintained for a sustained period of time, and exfoliation occurred in these mice. Thus, whereas the adaptive immune response is not needed for protection of adult mice from SSSS, efficient clearance of the toxin from the bloodstream is a critical factor.

Toxin in bullous impetigo and staphylococcal scalded-skin syndrome targets desmoglein 1.

Exfoliative toxin A, produced by Staphylococcus aureus, causes blisters in bullous impetigo and its more generalized form, staphylococcal scalded-skin syndrome. The toxin shows exquisite specificity in causing loss of cell adhesion only in the superficial epidermis. Although exfoliative toxin A has the structure of a serine protease, a target protein has not been identified. Desmoglein (Dsg) 1, a desmosomal cadherin that mediates cell-cell adhesion, may be the target of exfoliative toxin A, because it is the target of autoantibodies in pemphigus foliaceus, in which blisters form with identical tissue specificity and histology. We show here that exfoliative toxin A cleaved mouse and human Dsg1, but not closely related cadherins such as Dsg3. We demonstrate this specific cleavage in cell culture, in neonatal mouse skin and with recombinant Dsg1, and conclude that Dsg1 is the specific receptor for exfoliative toxin A cleavage. This unique proteolytic attack on the desmosome causes a blister just below the stratum corneum, which forms the epidermal barrier, presumably allowing the bacteria in bullous impetigo to proliferate and spread beneath this barrier.

Recombinant Staphylococcus aureus exfoliative toxins are not bacterial superantigens.

Staphylococcal scalded-skin syndrome is an exfoliative dermatitis characterized by the separation of the epidermis at the stratum granulosum. This disruption is mediated by one of two Staphylococcus aureus exotoxins, exfoliative toxins A and B (ETA and ETB). Both ETA and ETB have been reported to be bacterial superantigens. A controversy exists, however, as other data indicate that these exotoxins are not superantigens. Here we demonstrate that recombinant exfoliative toxins produced in Escherichia coli do not act as T-cell mitogens and thus are not bacterial superantigens. These data fit the clinical profile of the disease, which is not associated with the classic symptoms of a superantigen-mediated syndrome.