What are the symptoms and treatment options for Stevens-Johnson Syndrome (SJS)?

Stevens-Johnson Syndrome: Clinical Presentation

Stevens-Johnson Syndrome presents with a characteristic triad of painful skin lesions, severe mucosal involvement, and systemic symptoms following a flu-like prodrome, typically 4-28 days after drug exposure. 1, 2

Prodromal Phase

• Fever, malaise, and upper respiratory tract symptoms precede the cutaneous eruption by several days, though this can be difficult to distinguish from a precipitating infection 1, 2
• Ocular inflammation may develop before skin signs appear 1

Cutaneous Manifestations

• Cutaneous pain is a prominent early feature and should alert clinicians to incipient epidermal necrolysis 1
• Initial presentation includes atypical target lesions, purpuric macules, and blisters 1
• Positive Nikolsky sign: minimal shearing forces cause the epidermis to peel back 1
• Flaccid bullae develop as necrotic epidermis separates from underlying dermis 1
• Extensive necrolysis results in detachment of sheets of epidermis, leaving exposed dermis that exudes serum, bleeds readily, and becomes secondarily infected 1
• Large areas of confluent erythema develop in severe cases 1

Mucosal Involvement

Ocular

• Purulent keratoconjunctivitis and eyelid edema occur early in the acute phase 1
• Persistent ocular inflammation with involvement of eyelid skin develops 1
• Ocular inflammation may precede skin manifestations 1

Oral

• Erosive and hemorrhagic mucositis affecting the mouth 1, 2
• Painful oral lesions that interfere with eating 1

Urogenital

• Mucosal erythema, blistering, and erosions 1
• Dysuria or urinary retention is common during the acute phase 1
• Genital pain is prominent 1

Other Mucosae

• Nasal involvement 1, 2
• Nasopharyngeal and esophageal involvement with blisters and erosions 3

Respiratory Manifestations

• Dyspnea and increased respiratory rate in approximately 25% of patients 1
• Bronchial hypersecretion occurs in 70% of patients with early pulmonary manifestations 1
• Cough and hemoptysis may be present 1
• Chest radiographs are typically normal on admission, with later development of diffuse pulmonary infiltrates 1
• Bronchial epithelial necrolysis can cause airway sloughing and sudden obstruction 1

Gastrointestinal Symptoms

• Diarrhea and abdominal distension indicate bowel involvement 1

Histopathological Features

• Variable epidermal damage ranging from individual cell apoptosis to confluent epidermal necrosis 1
• Basal cell vacuolar degeneration 1
• Subepidermal vesicle or bulla formation (distinguishes from staphylococcal scalded skin syndrome which has intraepidermal cleavage) 1
• Mild, predominantly perivascular infiltrate of lymphocytes and histiocytes in the dermis 1
• Occasional involvement of adnexal structures (sweat ducts, hair follicles) 1

Disease Severity Classification

• SJS: <10% body surface area involvement 3
• SJS/TEN overlap: 10-30% body surface area involvement 3
• TEN: >30% body surface area involvement 3

Common Pitfalls in Recognition

• Distinguishing from staphylococcal scalded skin syndrome (SSSS): SSSS lacks mucosal involvement and has intraepidermal rather than subepidermal cleavage 1
• Confusing the prodrome with simple upper respiratory infection, delaying recognition 1
• Failing to recognize early cutaneous pain as a warning sign before obvious skin detachment 1

---

Treatment Approach

Immediately discontinue all potential culprit drugs and transfer patients to a specialized burn unit or ICU with multidisciplinary expertise, as this is the single most critical intervention affecting mortality. 4, 5

Immediate Actions

• Calculate SCORTEN on admission to predict mortality risk and guide intensity of care 4, 5
• Transfer patients with >10% body surface area involvement to a burn center or ICU without delay 4, 5
• Early transfer reduces mortality; delays adversely affect outcomes 4
• Obtain skin biopsy to confirm diagnosis and exclude immunobullous disorders 4

Supportive Care Framework

Fluid Management

• Careful fluid resuscitation to prevent end-organ hypoperfusion while avoiding fluid overload that can lead to pulmonary, cutaneous, and intestinal edema 4, 5
• Monitor vital signs, urine output, and electrolytes regularly 4

Wound Care

• Leave detached epidermis in situ to act as a biological dressing 4, 5
• Minimize shearing forces when handling skin 4, 5
• Apply bland emollients frequently (every 4 hours) to support barrier function 4, 5
• Use nonadherent dressings (e.g., Mepitel) to denuded dermis with secondary foam or burn dressings 4, 5
• Consider high-strength topical corticosteroids on affected skin areas 4
• Gently irrigate wounds with warmed sterile water, saline, or chlorhexidine 4

Infection Management

• Do NOT use prophylactic antibiotics as they increase skin colonization with resistant organisms, particularly Candida 4, 5
• Obtain regular skin swabs for culture to detect predominant organisms 4
• Institute targeted antimicrobial therapy only when clinical signs of infection appear 4, 5
• Monitor carefully as fever from SJS/TEN itself complicates detection of secondary sepsis 4

Nutrition

• Provide continuous enteral nutrition: 20-25 kcal/kg daily during catabolic phase, 25-30 kcal/kg during recovery 4
• Consider nasogastric feeding when oral intake is precluded by buccal mucositis 4

Pain Management

• Provide adequate background simple analgesia with additional opioid analgesia for breakthrough pain 4

Mucosal Management

Ocular Care (Critical for Preventing Permanent Sequelae)

• Ophthalmology consultation within 24 hours of diagnosis with daily examinations throughout the acute phase 4, 5
• Apply preservative-free lubricant eye drops every 2 hours 4, 5
• Perform daily ocular hygiene by ophthalmologist or trained nurse to remove inflammatory debris and break down conjunctival adhesions 4, 5
• Use topical antibiotics when corneal fluorescein staining or ulceration is present 4, 5
• Consider topical corticosteroid drops under ophthalmologist supervision to reduce ocular surface damage 4
• Consider amniotic membrane transplantation in acute phase for significantly better visual outcomes 4

Oral Care

• Daily oral review during acute illness 5
• Apply white soft paraffin ointment to lips every 2 hours 4, 5
• Use anti-inflammatory oral rinse containing benzydamine hydrochloride every 3 hours, particularly before eating 4, 5
• Use antiseptic oral rinse containing chlorhexidine twice daily 4, 5
• Topical anesthetics such as viscous lidocaine 2% or cocaine mouthwashes 2-5% for severe oral discomfort 4
• Consider topical corticosteroids (clobetasol propionate 0.05% mixed with Orabase) applied to oral mucosa 4
• Treat candidal infection with nystatin oral suspension 100,000 units four times daily for 1 week 4

Urogenital Care

• Daily urogenital review during acute illness 5
• Apply white soft paraffin ointment to urogenital skin and mucosae every 4 hours 4, 5
• Catheterize all patients to prevent urethral strictures 1
• Use Mepitel dressings to eroded areas in vulva and vagina to reduce pain and prevent adhesions 1
• Insert vaginal dilator or tampon wrapped in Mepitel to prevent vaginal synechiae 1, 5
• In women, early assessment by vulval specialist for consideration of dilators 1
• Check uncircumcised males for preputial retractability 1
• Consider potent topical corticosteroid ointment once daily to involved, noneroded surfaces 4, 5

Airway Management

• Respiratory symptoms and hypoxemia on admission should prompt early ICU discussion 5
• Perform fibreoptic bronchoscopy to assess airway involvement 5
• Mechanical ventilation required in 90% of patients with early pulmonary manifestations 1

Systemic Immunomodulatory Therapy

First-Line Options

Ciclosporin (3 mg/kg daily for 10 days, tapered over 1 month) has shown benefit with reduced mortality compared to predicted rates in multiple studies. 4, 5

Systemic corticosteroids, particularly IV methylprednisolone pulse therapy (0.5-2 mg/kg depending on severity), may be beneficial if started within 72 hours of onset. 4, 5, 6

IVIG Considerations

• High-dose IVIG (2-3 g/kg over 3-5 days, typically 1 g/kg/day for 3 days) is preferred if IVIG is used 6
• Low-dose IVIG (0.4 g/kg for 4 days) shows inferior outcomes with 42% mortality 6
• No overall survival benefit demonstrated in meta-analysis comparing IVIG to supportive care alone (OR 1.00,95% CI 0.58-1.75) 6
• Pediatric patients treated with IVIG have significantly lower mortality than adults (0% vs. 21.6%) 6
• UK guidelines recommend IVIG only under specialist supervision in context of clinical research or case registry 1, 6
• Monitor for thromboembolic events, renal dysfunction, and aseptic meningitis during IVIG 6

Evidence Quality Note

• No internationally accepted consensus exists on immunomodulatory therapy 2, 7
• High-quality randomized controlled trials are still lacking 8, 7

Multidisciplinary Team Requirements

• Essential team members: dermatology, intensive care, burn surgery, ophthalmology, specialist skincare nursing 4, 5
• Additional consultations based on involvement: otolaryngology, urology/gynecology, wound care, infectious disease (especially pediatrics) 4, 6

Discharge Planning and Follow-up

• Provide written information about culprit drug(s) to avoid and potentially cross-reactive medications 4, 5
• Encourage MedicAlert bracelet bearing the name of the culprit drug 4, 5
• Document drug allergy in medical records and inform all healthcare providers 4, 5
• Report adverse drug reaction to pharmacovigilance authorities 4, 5
• Inform patients about potential fatigue and lethargy for several weeks following discharge 4
• Organize dermatology and ophthalmology outpatient appointments within weeks of discharge 5
• Consider referral to support groups (e.g., SJS Awareness UK) 4

Long-term Sequelae to Monitor

• Ocular: chronic dry eye, symblepharon, corneal scarring, vision loss 1
• Cutaneous: pigmentation changes, scarring 1
• Urogenital: urethral strictures, phimosis, vaginal synechiae, sexual dysfunction 1
• Respiratory: bronchiolitis obliterans, chronic respiratory problems 1
• Oral/dental: chronic oral problems 1
• Psychological: significant psychological sequelae 7
• Nail changes 1

Critical Pitfalls to Avoid

• Delayed discontinuation of culprit medication significantly increases mortality 5
• Delayed transfer to specialized care adversely affects outcomes 4
• Indiscriminate prophylactic antibiotics increase resistant organism colonization 4, 5
• Overaggressive fluid resuscitation leads to pulmonary, cutaneous, and intestinal edema 4, 5
• Failure to involve ophthalmology within 24 hours can lead to permanent visual sequelae 4, 5
• Inadequate pain control during acute phase 4
• Failure to prevent vaginal synechiae in female patients through early specialist involvement and dilator use 1