Steven-Johns Syndrome

toxic epidermal necrolysis

blisters

bullae

Index: Wound Management & Prevention 2019;65(11):16–18

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Background

Cutaneous reactions to medications, viruses, and other agents represent a chameleon of skin eruptions, including urticarial, morbilliform, fixed, pustular, scarlatiniform, bullous, vasculitic, purpuric, phototoxic, and desquamative. They range from simple, short-lived, nonpruritic, and nonsystemic to severe, bullous, and desquamative and can manifest not only cutaneously, but also as oral, ocular, gastrointestinal, respiratory, genitourinary and systemic presentations. Uncommon but life-threatening conditions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash/eosinophilia/systemic symptoms syndrome. Drugs are the most common causes, but infection, malignancy, and vaccine response are other underlying etiologies. Most clinicians believe SJS and TEN are a continuum of one disorder, with TEN representing the more severe spectrum and featuring erythema, necrosis, and bullous detachment of the epidermis and mucous membranes, resulting in skin breakdown, erosions, and possibly sepsis. In addition, dehydration, electrolyte abnormalities, pain, and multiorgan failure can occur. When 10% of the skin is involved, SJS is considered; anything greater than 30% may be considered TEN; and 10% to 30% involvement is considered SJS/TEN overlap.1,2

SJS/TEN is a feared condition in the pediatric population because of management difficulties and the 10% to 50% mortality rate.3 The syndrome often begins with fever, headache, sore throat, malaise, and vomiting. Within days, skin becomes erythematous and painful; blisters develop and coalesce and may rupture and erode, leading to a burn-like presentation. Mucous membranes (eg, oral, airway, gastrointestinal, and genitourinary linings and ocular mucosa) are affected, causing breathing difficulty, visual deficits, feeding intolerance, urethral necrosis, and urinary failure. Systemic manifestations involve pneumonia, respiratory failure that may require intubation, hypotension, sepsis, and renal and liver failure.

Pathophysiology. TEN is believed to be an immune-related cytotoxic reaction aimed at destroying keratinocytes that express a particular antigen. Keratinocyte apoptosis leads to epidermolysis, but it also mimics a hypersensitivity reaction, with the release of destructive proteins from cytotoxic T lymphocytes and inflammatory cytokines from T cells and macrophages.1-3 The genetic variants are associated with the human leukocyte antigen complex B gene, heralding abnormal immune system reaction to an agent. Frequent offending medications include sulfonamides, macrolides, penicillins, phenobarbital, phenytoin, valproic acid, and nonsteroidal anti-inflammatory drugs, as well as viral infection, immunizations, and transplant.

Differential diagnosis is wide; biopsy maybe necessary to confirm clinical suspicion of SJS/TEN. Other entities that mimic this condition include Staphylococcal scalded skin, Kawasaki disease, toxic shock syndrome, phototoxic reaction, paraneoplastic pemphigus, burns, vasculitis, porphyria, and exfoliative dermatitis.

Presentation

Cutaneous. Erythema and macules often start on the face/chest and give way to convalescent erythroderma, pruritus, pain, and edema. Blisters that become bullae eventually rupture, causing desquamation, sheet-like epidermal detachment, erosions, and open wounds. A positive Nikolsky sign can be seen with lateral epidermal movement.

Mucous membranes. The oral cavity is the area most commonly affected, causing edema, blisters, and hemorrhagic erosions with pseudo membrane formation and subsequent patient refusal to take food. A nasogastric tube often is necessary in order to provide adequate fluid and nutrition. Hemorrhagic lip crusts and fissures complicate oral intake. Ocular manifestations vary from dry eyes to conjunctivitis, keratitis, and corneal abrasions to ulcers. Palpebral skin can be affected, causing entropion or eyelid adhesion. Respiratory epithelium involvement leads to cough, bronchitis, dyspnea, pneumonia, and respiratory failure. Genitourinary involvement includes inflammation, ulcers, and painful urination.

Management

Topical care. A large percentage of skin can be affected, with presentation and complications similar to burns. As such, patients often are managed in intensive care or burn units. If the offending agent is a drug, it should be discontinued. Careful attention to fluids and electrolyte balance is advised. Neonates can be placed in a warmed, humidified isolette; older children can be managed with nonadherent dressings to minimize contamination and evaporation. Various products are used, including petrolatum-impregnated gauze, bismuth/petrolatum combination gauze, perforated contact layers, and surfactant-impregnated and/or regular foam. Practitioners use emollients to protect skin from further fissuring, loosely covered by soft gauze or the above-mentioned dressings. I like to use a combination of spot application of petrolatum, covered by petrolatum-impregnated gauze or a contact layer and loose regular gauze. Areas of concern for infection can be treated with silver-infused foam, surfactant-impregnated foam, or polyhexamethylene-biguanide infused foam.

When significant oozing is observed, a pure or silver-impregnated hydrofiber is helpful. It is important to ensure the outer dressing is not adherent to the skin upon removal. Medical honey gel (active Leptospermum honey [ALH]) can be helpful in deeper fissures and erosions. Clinicians should be careful to look for initial discomfort because occasionally patients report mild stinging upon initial application to the raw skin. A topical antimicrobial such as Mupirocin ointment or silver sulfadiazine cream also can be used. Silver should be used cautiously in neonates and no longer than 2 weeks in pediatric cases due to its systemic effects.

Hemorrhagic erosions and crusts can be difficult to clean; concentrated surfactant gel application can make removal easier, stabilize the wound, and provide mild antimicrobial protection. Wrapping the area with dialkylcarbamoyl chloride (DACC)-coated gauze can provide both antimicrobial protection as well as denuded skin coverage. Hydrogel-infused DACC pads can offer comfort in particularly raw spots. There is no clear recommendation as to whether debridement is indicated, helpful, damaging, or safe in these wounds. I have occasionally performed a gentle debridement of desquamated skin, using scissors to cut denuded pieces. Deeper wound management may include collagen, amniotic membrane products, bilayered skin substitutes, or xenografts on a case-by-case basis.

Keeping skin clean without being overly aggressive is important; room temperature or warmed solution should be used. Normal saline is adequate in most cases. Diluted hypochlorous acid can be used in older children and likely in neonates, although supportive data are absent. Mild aqueous chlorhexidine wipes are available for spot cleaning. A solution of diluted bleach has been used in cases of significant colonization or superimposed infection.

As critical desquamation resolves, epidermal hydration, gentle physical therapy, and movement are important to avoid scarring, contractures, and depigmentation. Skin repair often is accompanied by xerosis and dryness; antihistamines can be useful for those patients.

Oral care. Chlorhexidine mouthwash can be used in older children that can manage to swish and spit. Topical anesthetic can be used for pain. Normal saline can be used in the younger population. ALH is useful in mucositis and oral sores. Petrolatum should be applied generously to dry, denuded lip areas.

Ocular care. Topical lubricant/antibiotic and steroid drops often are used. Keeping lashes clean is very important to avoid abrasion and infection.
Systemic care. Dehydration and electrolyte imbalance are common. Adequate fluids and parenteral nutrition are the mainstay of systemic support. Preventing pain during dressing changes, daily care, and simple movement is paramount. Adequate analgesia and sedation for dressing changes is key to a successful partnership with a child. Appropriate antimicrobial coverage is important, especially in neonates, because infection is a more common cause in this age group than in older children.

Corticosteroids have been used, especially in TEN, but their use is controversial and not without concern. Immunoglobulin has been used in pediatrics as well, especially if started within 48 hours of blisters and skin manifestation.2,3

Anti-tumor necrosis factor (TNF)-α can be considered in older children. There are few reports of rapid skin resolution secondary to high concentration of TNF-α in keratinocytes, macrophages, and blister fluid. Plasmapheresis and cyclosporine have been reported in adults and older children.3

Case Reports

Case 1. A 4-month-old boy was admitted with bilious vomiting. His upper gastrointestinal series study was consistent with volvulus/malrotation for which he had undergone resection. The patient was recovering on antibiotics (vancomycin/Zosyn), provided nothing by mouth, and had a peripherally inserted central catheter line and received total parenteral nutrition. He developed erythema and swelling 2 days after the procedure on his thorax (see Figure 1) and became irritable and febrile and developed mild respiratory distress. Within 2 days, he required intubation, inotropic support for hypotension, and morphine for pain.

His lips developed fissures, hemorrhagic exudatation, and aphthous ulcers (see Figure 2) and erythema continued, vesicles and blisters developed, and his skin started sloughing (see Figure 3). A biopsy of his skin was consistent with SJS. His antibiotics were discontinued; intravenous immunoglobin was administered once a day for 3 days, along with supportive care involving intravenous fluids, parenteral nutrition, and analgesics. His skin was covered with petrolatum-infused gauze. Few areas exhibited deep erosions; ALH gel covered by perforated contact layer and secondary petrolatum gauze were placed. Honey-infused lip balm was used on his lips, covered by layer of petrolatum. ALH gel was applied to aphthous ulcers. Systemic symptoms improved over 7 to 10 days. The patient’s skin healed well with a few small areas of hypopigmentation.

Case 2. An 11-month-old boy was admitted with a facial impetiginous lesion (see Figure 4), lethargy, and poor feeding. He was started on ceftriaxone. Rapid deterioration lead to multiorgan failure, including cutaneous changes. Large blisters developed on his back and upper and lower extremities (see Figure 5).

A skin biopsy was performed in order to differentiate SJS/TEN from Staphylococcal scalded skin syndrome because his wound culture grew methicillin-sensitive Staphylococcus aureus; the biopsy was consistent with TEN. He became hypercoagulable and developed a lower extremity thrombus leading to ischemia (see Figure 6) and superimposed skin slough. Eventually, he developed deeper wounds on both his wrist and foot. A dehydrated amniotic membrane allograft was used to support healing, and a concentrated surfactant gel was used for noninvasive, minimal wound debridement. The patient had a long hospital course but eventually was transferred to a rehabilitation hospital for physical therapy and feeding therapy.
 

Conclusion

Facing the challenges of medically and aesthetically frightening conditions that manifest on the skin and in mucous membranes can lead to satisfying outcomes, even in the youngest of patients. Clinicians should employ a multifaceted approach that involves treating the underlying etiology and symptomology and demonstrates an acute awareness of the effects of the conditions and their treatment.