Young boys with desquamating skin

Case #1: Stevens-Johnson syndromeStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous diseases associated with certain groups of medications. Use of potential offender medication is reported in more than 80% of cases of TEN and in up to...

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Case #1: Stevens-Johnson syndrome

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous diseases associated with certain groups of medications. Use of potential offender medication is reported in more than 80% of cases of TEN and in up to 50% of cases of SJS, although this may be an underestimation.

SJS and TEN are diseases of unclear pathology and result in extensive keratinocyte cell death and separation of significant areas of skin and mucous membranes at the dermal-epidermal junction.^1,2 SJS and TEN are now considered to be on a spectrum. SJS is defined as <10% body surface area involvement, and TEN is defined as >30% body surface area involvement. Body surface area involvement between 10% and 30% constitutes an SJS/TEN overlap syndrome.³

Clinically, initial symptoms of SJS include fever, stinging eyes and dysphagia, all of which can precede cutaneous manifestations. Tender skin lesions appear first on the trunk before spreading to the neck, face and proximal upper extremities. While the distal extremities are often spared, the palms and soles are also a site of early involvement.^1,2 Approximately 90% of patients have erythema and painful erosions of the buccal, ocular and genital mucosa. Less commonly, the mucosa of the respiratory and GI tract are involved.⁴

Lesions first appear as an erythematous and purpuric macule with a tendency to coalesce. SJS should be suspected in any patient with these lesions plus the presence of mucosal involvement. Clinicians should look for the Nikolsky sign by applying tangential pressure with a finger on any erythematous lesions. The Nikolsky sign is positive if dermal-epidermal cleavage is seen.⁴

Within hours to days, epidermal involvement progresses towards full-thickness necrosis. The necrotic epidermis then detaches from the underlying dermis, and fluid fills the space between the dermis and the epidermis, producing blisters. The blisters are flaccid and can be extended sideways with pressure of the thumb, as more necrotic epidermis is displaced laterally (Asboe-Hansen sign). The skin resembles wet cigarette paper and reveals raw and bleeding dermis when pulled away.^1,2

Certain patient populations have an increased risk of developing SJS. Such populations include the immunocompromised and those with specific human leukocyte antigen (HLA) types. The HLA-DQB1*0601 allele is reported disproportionately in white patients with SJS and ocular complications.⁵ HLA-B*1502 in Asians and East Indians predisposes these individuals to SJS caused by carbamazepine. The FDA recently recommended genotyping all Asians for the HLA allele before administering the drug to these patients.⁶ In patients with AIDS, the risk of developing SJS is 1,000-fold higher.⁴

More than 100 drugs have been identified as being associated with SJS, the most common of which are nonsteroidal anti-inflammatory drugs, anticonvulsants, antibiotics (especially sulfonamides), and allopurinol (Aloprim, Lopurin, Zyloprim).⁴ In general, risk is highest during the initial weeks of therapy.

Because delayed withdrawal of the causative drug is associated with increased mortality, identifying the causative drug is extremely important. Currently, no reliable test for identification of the causative drug is available. Clinicians must rely on previously reported cases while taking into account the use of a given medication in relationship to the onset of SJS. SJS usually occurs seven to 21 days after initiation of the causative drug in the setting of a first exposure. In a case of re-exposure, SJS can occur as early as two days later.^1,2

Staphylococcal scalded skin syndrome (SSSS), another disease of skin desquamation, can usually be clinically distinguished from SJS. SSSS occurs in newborns and young children but can also rarely occur in adults who are in renal failure or who are immunosuppressed. SSSS tends to spare the palms, soles, and the mucous membranes, unlike SJS, in which the mucous membranes are always affected. While the Nikolsky sign may be positive, it results in a superficial subcorneal cleavage, as opposed to the dermal-epidermal separation seen in SJS. This superficial exfoliation leaves behind an intact epidermal layer instead of the wet and bright-red dermal tissue observed in SJS. Also, in SSSS, a purulent nasal discharge is frequently present. Histologically, SJS shows a full-thickness epidermal necrolysis, whereas SSSS shows a subcorneal split with a normal underlying epidermis.^1,2

Successful treatment of SJS requires early diagnosis, immediate discontinuation of the causative drug, supportive care in an intensive care unit, and specific therapy. Supportive care for SJS is similar to that of a thermal burn and is aimed at the associated complications that cause mortality (i.e., hypovolemia, electrolyte imbalance, renal insufficiency, and sepsis).^1,2

Wound care is important in the treatment of SJS. Manipulation should be kept to a minimum. Detached areas should be covered with petrolatum (Vaseline) gauze and silicone dressings.

All SJS patients should have regular ophthalmological exams. Scarring and other ocular complications are potential adverse sequelae of SJS, and the ophthalmologist is a key member of the medical team in the management of SJS.

No specific therapy for SJS has yet shown efficacy in a controlled clinical trial. High-dose systemic corticosteroids are often used, with pulse therapy proving the most successful.⁷ Recent evidence supports the use of high-dose intravenous immunoglobulin (IVIG), which has become the treatment of choice at many institutions, but this remains controversial.⁸

The patient in this case was admitted to the hospital, where the sulfamethoxazole/trimethoprim was immediately stopped. An infusion of IVIG was administered. The hospital’s wound care and ophthalmology services evaluated the patient. Two days after being admitted, the body surface area affected was up to 25%. The patient was maintained on a regimen of daily wound care. By the third day, the skin loss has stabilized. The patient remained hospitalized for 12 days. Four weeks after discharge, the boy had made a complete recovery with no anticipated long-term sequelae.

Case #2: Staphyloccal scalded skin syndrome

Formerly known in the past as Ritter’s disease or dermatitis exfoliativa neonatorum, SSSS is a generalized, confluent and superficially exfoliative disease. The syndrome triggers fever and causes the skin to exfoliate rapidly in sheets. SSSS usually occurs in neonates and in young children. Rarely, adults with chronic renal insufficiency or immune suppression are affected.⁹

SSSS is primarily attributable to hematogenous dissemination of the exfoliative toxins (ETs) type A and type B (ETA and ETB). The same toxins, when produced locally, lead to bullous impetigo. However, in SSSS, hematogenous dissemination leads to extension of the lesions beyond the area of actual staphylococcal infection.¹⁰

Staphylococcus aureus is usually transmitted through human-to-human contact. A carrier with asymptomatic colonization of the strain is responsible for the transmission. Outbreaks that occur in neonatal nurseries are usually secondary to asymptomatic carriage of a toxogenic strain of S. aureus by health-care workers or parents.

Most cases of SSSS are caused by phage-group II strains type 71 or 55 of S. aureus.¹¹ This group can be either methicillin-sensitive or methicillin-resistant, but always produces ETA or ETB. ETA (chromosomally encoded) and ETB (plasmid encoded) are serine proteases that bind and cleave desmoglein-1. This binding causes the desmosomes to split, which leads to disruption at the epidermal granular layer and blister formation.

In bullous impetigo, however, the effects of the ETs are limited to the site of infection. In contrast, the hematogenous diffusion of the ET in SSSS from a focus of infection produces widespread effects. In children, the most common infectious focus is usually in the nasopharynx or conjunctivae. In adults, SSSS is most likely due to a staphylococcal pneumonia or bacteremia.^1,2

The clinical characteristics of SSSS begin with a prodrome of malaise, fever, irritability, skin erythema and severe tenderness of the skin. The patient may have purulent rhinorrhea or conjunctivitis as a manifestation of the underlying staphylococcal infection.

Erythema typically first appears on the head with facial edema and in intertriginous sites (i.e., the groin and axilla). The erythema typically becomes diffuse within 48 hours. The skin develops a wrinkled appearance due to the formation of flaccid and sterile bullae within the superficial epidermis. As in SJS, a positive Nikolsky sign can be elicited by applying tangential pressure to bullae, which leads to subcorneal cleavage.¹

Classically, the flexural areas are the first to exfoliate, leaving behind moist skin and thin, varnish-like crusting. Patients demonstrate characteristic periorificial crusting and radial fissuring. However, unlike in SJS, intraoral lesions do not occur. Scaling and desquamation with large sheets of epidermis separating continue for the next three to five days, followed by re-epithelialization without scarring. With proper treatment, SSSS resolves in one to two weeks without sequelae. The mortality rate is only 3% in children but >50% in adults.¹²

SSSS is usually diagnosed clinically. To confirm the diagnosis or to rule out other causes, skin biopsy may be performed. Cultures taken from the intact bullae will be negative, because the skin erythema and desquamation of SSSS are caused by the distant effects of the ET. If cultures are taken, the clinician should focus on the conjunctiva, nasopharynx, feces or pyogenic foci on the skin.

Skin biopsy shows a sharply demarcated zone of cleavage at or below the stratum granulosum. There are usually no inflammatory cells in the bullae. The upper dermis also lacks an inflammatory infiltrate, and no organisms are seen on gram stain of biopsy specimens.

Individuals diagnosed with severe, generalized forms of SSSS require hospitalization and parenteral antibiotics.¹³ Initial treatment for such patients at the authors’ institution consists of intravenous clindamycin (Cleocin Phosphate IV) before transitioning to oral clindamycin (Cleocin).

The patient in this case was admitted to the hospital and started on IV clindamycin. A culture taken from the nasal passages grew methicillin-sensitive S. aureus. The patient remained stable and afebrile without any progression of skin desquamation. He was discharged after 24 hours on oral clindamycin. At the two-week follow-up, the boy had made a complete recovery.

Christopher Chu is third-year student at Baylor College of Medicine in Houston, where Adam Rees is a resident in the Department of Dermatology.

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