November 2005

This 3-week-old infant presented to the emergency room with a two-day history of fever and rash. On physical exam, he had a temperature of 100.4°F and was irritable, particularly when his skin was palpated. Marked facial edema was present as well as perioral radial furrowing. A generalized erythema with a fine stippled sandpaper appearance was accentuated in the flexural folds. What’s your diagnosis?

Answer

This is staphylococcal scalded skin syndrome (SSSS), also known as Ritter’s disease. It is caused by an exfoliative toxin produced by certain strains of Staphylococcus aureus, most commonly phage group II. The elaborated S. aureus exotoxin enters the circulation, eventually reaching and binding to the mid-epidermis. It targets desmoglein-1, a desmosomal component that promotes cell-to-cell adhesion. The toxin causes disruption of these attachments, leading to a cleavage plane in the epidermis, with subsequent blistering and exfoliation of the superfi cial aspect of the skin.

SSSS typically begins with one to two days of fever and irritability followed by a generalized tender erythema. The characteristic rash is sandpaper-like, accentuated in the flexural folds and extremely tender to palpation. Fragile blisters then develop. Nikolsky’s sign is positive, which refers to the tendency toward separation of the upper epidermis with gentle pressure. Mucosal surfaces are spared, resulting in the characteristic perioral furrowing with a line of demarcation between the lips and surrounding edematous skin. There is a spectrum of disease severity, ranging from localized bullous impetigo to a generalized exfoliation of nearly the entire body surface area.

This syndrome most frequently affects neonates and children younger than 5. Various theories suggest that this is both due to a naive immune system and relatively decreased renal clearance of toxin. In the rare case that it is seen in adults, it is usually associated with a predisposition, such as immunosuppression or renal failure. Extent of disease in a given individual has been linked to the body’s ability to produce anti-toxin antibodies, the amount of toxin elaborated vs. excreted, and whether it is released locally or systemically.

Though SSSS can occur in association with a focus of infection such as conjunctivitis, pneumonia or endocarditis, it often results from colonization at sites such as the nares, umbilicus or perineum. In fact, a nosocomial outbreak has been reported which was attributed to carriage of toxin-producing S. aureus on the hands of a health care worker.

Diagnosis can often be made by clinical appearance alone, but cultures should be obtained from the blood as well as any suspected focus of infection, such as conjunctivae, nasopharynx, umbilicus, rectum or wound site. In childhood cases, a detection rate of S. aureus in blood cultures as low as a 3% has been noted. Fluid from bullae are also typically sterile. Various mechanisms for isolating the exfolative toxins exist, including polymerase chain reaction, ELISA and slide latex agglutination. A skin biopsy would reveal epidermal splitting at the granular layer without necrosis.

The differential diagnosis of SSSS primarily includes other toxin-mediated erythemas (scarlet fever), drug reactions (toxic epidermal necrolysis) and primary dermatoses (atopic dermatitis). Of note, in toxic epidermal necrolysis, the mucous membranes are involved, and biopsy would reveal a level of cleavage below the epidermis as well as full-thickness epidermal necrosis. Other less common considerations include congenital ichthyoses (bullous congenital ichthyosiform erythroderma), blistering disorders (pemphigus foliaceus), immunodeficiencies (Omenn’s syndrome), and nonaccidental injuries (scalding, chemical burn).

Source: Christine Kilcline, MD

Treatment involves antibiotics, pain control, skin care with barrier ointments and fluid and electrolyte management. An IV penicillinaseresistant penicillin, such as nafcillin, should be administered. Several cases associated with MRSA have been reported, and this should be considered if there is no response to empiric antibiotic treatment. In addition, due to the compromised barrier function of the blistered and exfoliating epidermis, one must take care to protect against hypothermia, dehydration and secondary infections, which can be fatal complications, particularly in infants.

Prognosis is generally much better for infants than adults, with a 4% mortality rate vs. at least 60% in the latter group, likely because of serious underlying comorbidities in affected adults. After appropriate antibiotic treatment is initiated, exfoliation continues for up to 48 hours. Due to the superficial nature of the skin lesions, they tend to heal rapidly within one to two weeks without scarring.

For more information:

• Ladhani S. Recent developments in staphylococcal scalded skin syndrome. Clin Microbiol Infect. 2001;7:301-307.
• Patel GK, Finlay AY. Staphylococcal scalded skin syndrome: diagnosis and management. Am J Clin Dermatol 2003;4:165-175.
• El Helali N, Carbonne A, Naas T, et al. Nosocomial outbreak of staphylococcal scalded skin syndrome in neonates: epidemiological investigation and control. J Hosp Infect. 2005;61:130-138.
• Farrell AM. Staphylococcal scalded-skin syndrome. Lancet. 1999;354:880-881.
• Hoeger PH, Harper JI. Neonatal erythroderma: differential diagnosis and management of the “red baby.” Arch Dis Child 1998;79:186-191.
• Sterry W, Muche JM. Erythroderma. Dermatology. 2005:165-174.