What are the symptoms, diagnosis, and treatment options for Steven Johnson's syndrome?

Stevens-Johnson Syndrome: Symptoms, Diagnosis, and Treatment

Clinical Presentation and Symptoms

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) present with a characteristic prodromal phase followed by painful mucocutaneous involvement, requiring immediate recognition and intervention. 1

Prodromal Phase

• Fever, malaise, and upper respiratory tract symptoms typically occur 4-28 days after drug exposure 1, 2, 3
• Patients report sore throat, general unwellness, and anorexia before skin manifestations appear 1, 3

Cutaneous Manifestations

• Painful rash initially appearing on the face and chest, rapidly progressing to other areas 1
• Atypical target lesions, purpuric macules, and flaccid blisters that coalesce 1
• Positive Nikolsky sign (epidermis detaches with gentle lateral pressure) 1, 4
• Confluent erythema with sheets of epidermal detachment and denuded dermis 1
• Disease severity classification based on body surface area (BSA) involvement: SJS (<10% BSA), SJS/TEN overlap (10-30% BSA), TEN (>30% BSA) 2, 3

Mucosal Involvement

• All mucosal sites must be examined: eyes, mouth, nose, and genitalia 1
• Purulent keratoconjunctivitis with eyelid edema and ocular inflammation 1
• Oral mucositis with blisters and painful erosions 1
• Genital and perianal involvement with erosions 1

Systemic Symptoms

• Respiratory involvement: cough, dyspnea, bronchial hypersecretion, hemoptysis 1
• Gastrointestinal symptoms: diarrhea, abdominal distension 1
• Skin pain is a prominent and distressing feature 1, 3

Diagnostic Approach

Immediate Clinical Assessment

When SJS/TEN is suspected, immediately discontinue all potential culprit drugs before completing the diagnostic workup. 1, 5

History Taking

• Document the index date (first symptom onset) and progression timeline 1
• Record all medications taken in the preceding 2 months, including over-the-counter and complementary therapies, with exact start and stop dates 1
• Most common culprit drugs: sulfonamides (especially trimethoprim-sulfamethoxazole), anticonvulsants (carbamazepine, lamotrigine, phenytoin), allopurinol, NSAIDs (oxicam type), and nevirapine 1, 2, 6
• Ask about previous drug allergies and recurrent herpes simplex virus infections 1
• In children, investigate infectious triggers including HSV, Mycoplasma pneumoniae, and Chlamydia pneumoniae 1

Physical Examination

• Record vital signs, oxygen saturation, and baseline body weight 1
• Assess airway patency immediately—involve anesthesia if any concerns about need for intubation 1
• Map extent of erythema and epidermal detachment separately using Lund and Browder chart 1
• The percentage of detached/detachable epidermis (not erythema) has prognostic value 1

Laboratory Investigations

• Full blood count, C-reactive protein, erythrocyte sedimentation rate 1
• Urea and electrolytes, magnesium, phosphate, bicarbonate, glucose 1
• Liver function tests and coagulation studies 1
• Mycoplasma and chlamydia serology 1
• Chest X-ray 1
• Bacterial swabs from lesional skin and conjunctival swabs for HSV PCR 1

Histopathology

• Skin biopsy from lesional skin adjacent to a blister for routine histopathology 1, 5
• Second biopsy from perilesional skin sent unfixed for direct immunofluorescence to exclude immunobullous disorders 1, 5
• Expected findings: variable epidermal damage ranging from individual cell apoptosis to confluent epidermal necrosis, basal cell vacuolar degeneration, subepidermal vesicle formation, and mild perivascular lymphocytic infiltrate 1, 2

Prognostic Assessment

• Calculate SCORTEN within the first 24 hours to predict mortality risk 1, 5
• SCORTEN uses seven parameters: age >40 years, malignancy, heart rate >120/min, initial BSA detachment >10%, serum urea >10 mmol/L, serum glucose >14 mmol/L, and serum bicarbonate <20 mmol/L 1

Differential Diagnosis to Exclude

• Erythema multiforme major, pemphigus vulgaris, mucous membrane pemphigoid, bullous pemphigoid, staphylococcal scalded skin syndrome, acute generalized exanthematous pustulosis, and acute graft-versus-host disease 1

Treatment and Management

Immediate Actions

Transfer patients with >10% BSA epidermal detachment to a specialized burn unit or intensive care unit immediately, as delayed transfer increases mortality. 1, 5

Multidisciplinary Team Coordination

• Care should be coordinated by a specialist in skin failure (dermatology/plastic surgery) 1, 5
• Include intensive care physicians, ophthalmologists, and specialist skincare nurses 1, 5
• Additional specialists as needed: respiratory medicine, gastroenterology, gynecology, urology, oral medicine, microbiology, pain team, dietetics, physiotherapy, and pharmacy 1, 5

Environmental and Supportive Care

• Barrier-nurse in a side room with controlled humidity on a pressure-relieving mattress 1, 5
• Raise ambient temperature to 25-28°C to prevent hypothermia 1, 5
• Establish peripheral venous access through non-lesional skin if possible 1, 5
• Initiate appropriate intravenous fluid resuscitation guided by urine output 5
• Avoid overaggressive fluid resuscitation which causes pulmonary, cutaneous, and intestinal edema 5

Wound Care

• Handle skin carefully to minimize shearing forces and further detachment 5
• Regularly cleanse wounds by gently irrigating with warmed sterile water, saline, or chlorhexidine (1:5000) 5
• Apply greasy emollient (50% white soft paraffin with 50% liquid paraffin) over the whole epidermis 5
• Apply non-adherent dressings (Mepitel™ or Telfa™) to denuded dermis with secondary foam dressings to collect exudate 5
• Take swabs for bacterial and candidal culture from lesional skin 5

Pain Management

• Use validated pain assessment tools at least once daily 5
• Administer adequate analgesia using intravenous opioid infusions for those not tolerating oral medication 5
• Consider patient-controlled analgesia where appropriate 5
• Consider sedation or general anesthesia for patient handling and dressing changes 5

Infection Prevention

• Do NOT administer prophylactic systemic antibiotics as this increases skin colonization, particularly with Candida albicans 5
• Only institute antimicrobial therapy if clinical signs of infection develop (confusion, hypotension, reduced urine output, reduced oxygen saturation) 5
• Monitor for monoculture of organisms on swabs from multiple sites, indicating increased likelihood of invasive infection 5

Ophthalmologic Care

• Arrange examination by an ophthalmologist experienced in ocular surface diseases within 24 hours of diagnosis 1, 5
• This is critical as ocular complications are common and early intervention improves long-term outcomes 1, 5

Pharmacologic Therapy

While no single pharmacologic agent has proven superior for all patients, available evidence supports several treatment options that may halt disease progression. 7, 6

The most frequently used treatments include:

• Systemic corticosteroids: Used in 42.5% of treated patients in a large US cohort 6
• Intravenous immunoglobulin (IVIG): Used in 35.3% of treated patients 6
• Combined corticosteroids and IVIG: Associated with the lowest standardized mortality ratio (0.52) in one large study 6
• Cyclosporine A: Considered as a potential treatment option under specialist supervision 5, 2

Important caveat: The controversy over systemic corticosteroids remains unresolved—while they may suppress progression, they also enhance infection risk, which is the most common cause of death 4. If used, administer only during the progression phase and withdraw as soon as possible 4.

Respiratory Management

• Assess for respiratory symptoms and involve pediatric/adult intensivists early 1
• Consider fiber-optic bronchoscopy if respiratory symptoms are present 1
• Rapid transfer to ICU if airway compromise is suspected 1, 5

Monitoring

• Daily assessment of vital signs and organ function 5
• Regular monitoring for infection, the most common cause of mortality 5, 2
• Daily review of all mucosal sites (oral, ocular, urogenital) 5

Critical Pitfalls to Avoid

• Delayed transfer to specialized care significantly increases mortality 1, 5
• Failure to discontinue the culprit drug immediately worsens prognosis 1
• Indiscriminate use of prophylactic antibiotics increases colonization risk 5
• Neglecting ophthalmologic care results in permanent visual impairment 5
• Overaggressive fluid resuscitation causes complications 5
• Overlooking infectious causes (particularly Mycoplasma in children) worsens outcomes 1

Discharge Planning and Follow-up

• Provide written information about drugs to avoid and encourage wearing a MedicAlert bracelet 5
• Document drug allergy in patient's notes and inform all healthcare providers 5
• Report the episode to pharmacovigilance authorities 5
• Arrange follow-up with dermatology and ophthalmology within weeks of discharge 5
• Monitor for long-term sequelae including ocular complications, cutaneous scarring, and fatigue 1