How should I manage Stevens‑Johnson syndrome that developed after influenza and initiation of oseltamivir (Tamiflu)?

Management of Stevens-Johnson Syndrome After Influenza and Oseltamivir

Immediate Critical Actions

Discontinue oseltamivir immediately and transfer the patient to a specialized burn unit or ICU with multidisciplinary expertise in managing Stevens-Johnson syndrome, as this is a life-threatening medical emergency requiring urgent specialized care. 1, 2

While oseltamivir (Tamiflu) is listed as a very rare cause of Stevens-Johnson syndrome in guidelines, the temporal relationship between drug initiation and symptom onset makes it the most likely culprit drug that must be stopped immediately. 3 The influenza infection itself could theoretically trigger SJS, but drug-induced SJS is far more common and oseltamivir must be presumed guilty until proven otherwise. 4, 5

Initial Assessment Within First 24 Hours

• Calculate SCORTEN immediately upon admission to predict mortality risk, with scores ranging from 0-7 correlating with mortality from 1% to 99%. 1, 2

• Document the exact date of rash onset, progression pattern, and create a detailed timeline of all medications taken in the preceding 2 months, including the start date of oseltamivir. 1

• Measure body surface area (BSA) of epidermal detachment using a Lund and Browder chart—patients with >10% BSA detachment require immediate transfer to a burn center or ICU. 1, 2

• Obtain skin biopsy from lesional skin adjacent to a blister for histopathology showing full-thickness epidermal necrolysis with keratinocyte apoptosis, and a second periblister biopsy for direct immunofluorescence to exclude autoimmune bullous disorders. 1, 6

• Arrange ophthalmology consultation within 24 hours of diagnosis with daily reviews throughout the acute illness, as ocular complications are among the most common long-term sequelae. 1, 2

Specialized Care Environment

• Barrier-nurse the patient in a temperature-controlled side room (25-28°C) on a pressure-relieving mattress with humidity control to prevent hypothermia and reduce infection risk. 1, 2

• Assemble a multidisciplinary team led by a dermatologist or plastic surgeon experienced in skin failure, including intensive care physicians, ophthalmologists, specialist skincare nurses, and additional consultants as needed based on organ involvement. 1, 2

Comprehensive Supportive Care Protocol

Fluid Management

• Establish adequate intravenous fluid replacement guided by urine output, vital signs, and hemodynamic parameters, monitoring carefully to prevent end-organ hypoperfusion. 1, 2

• Avoid overaggressive fluid resuscitation, which leads to pulmonary, cutaneous, and intestinal edema—this is a critical pitfall that worsens outcomes. 1, 2

• Insert urinary catheter when clinically indicated for accurate fluid balance monitoring. 1, 2

Wound Care Protocol

• Handle skin with extreme care to minimize shearing forces that cause further epidermal detachment—every touch can worsen the condition. 1, 2

• Leave detached epidermis in situ to act as a biological dressing rather than removing it. 1, 2

• Irrigate wounds gently using warmed sterile water, saline, or chlorhexidine (1:5000 dilution) regularly. 1, 2

• Apply greasy emollient (50% white soft paraffin with 50% liquid paraffin) over the entire epidermis including denuded areas every few hours. 1, 2

• Use nonadherent dressings (such as Mepitel or Telfa) on denuded dermis with secondary foam or burn dressings to collect exudate. 1, 2

• Consider high-strength topical corticosteroids on affected skin areas. 1

Infection Prevention and Management

Do not administer prophylactic systemic antibiotics—this is a critical error that increases skin colonization with resistant organisms, particularly Candida albicans. 1, 2

• Take swabs for bacterial and candidal culture from three lesional areas on alternate days to monitor for colonization patterns. 1, 2

• Monitor for clinical signs of systemic infection including confusion, hypotension, reduced urine output, reduced oxygen saturation, rising C-reactive protein, and neutrophilia. 1, 2

• Institute targeted antimicrobial therapy only when clinical signs of infection appear—monoculture of organisms on swabs from multiple sites indicates increased likelihood of invasive infection requiring treatment. 1, 2

• Recognize that septicemia is the leading cause of death in SJS/TEN, so vigilant monitoring is essential. 6

Mucosal Management

Ocular Care (Critical for Preventing Permanent Vision Loss)

• Apply preservative-free lubricant eye drops every 2 hours throughout the acute illness. 1, 2

• Perform daily ocular hygiene by an ophthalmologist or ophthalmically trained nurse to remove inflammatory debris and break down conjunctival adhesions. 1

• Use topical antibiotics when corneal fluorescein staining or ulceration is present. 1

• Consider topical corticosteroid drops under ophthalmologist supervision to reduce ocular surface damage. 1

• Consider amniotic membrane transplantation in the acute phase, which demonstrates significantly better visual outcomes compared to medical management alone. 1

Oral Care

• Apply white soft paraffin ointment to the lips immediately, then every 2 hours throughout the acute illness to reduce risk of fibrotic scars. 1

• Use anti-inflammatory oral rinse containing benzydamine hydrochloride every 3 hours, particularly before eating. 1

• Use antiseptic oral rinse twice daily to reduce bacterial colonization. 1

• Apply topical anesthetics such as viscous lidocaine 2% or cocaine mouthwashes 2-5% for severe oral discomfort. 1

• Treat candidal infection with nystatin oral suspension 100,000 units four times daily for 1 week, or miconazole. 1

Urogenital Care

• Examine the urogenital tract regularly during acute illness. 1

• Apply white soft paraffin ointment to urogenital skin and mucosae every 4 hours. 1

• Consider vaginal dilators or tampons wrapped in Mepitel to prevent vaginal synechiae formation. 1

Nutrition Support

• Deliver continuous enteral nutrition throughout the acute phase, providing 20-25 kcal/kg daily during the catabolic phase and 25-30 kcal/kg during recovery. 1

• Consider nasogastric feeding when oral intake is precluded by buccal mucositis. 1

Pain Management

• Use validated pain assessment tools at least once daily. 1, 2

• Provide adequate background simple analgesia with additional opioid analgesia for breakthrough pain. 1

• Consider patient-controlled analgesia where appropriate. 2

• Consider sedation or general anesthesia for patient handling, repositioning, and dressing changes. 2

Additional Supportive Measures

• Administer low molecular weight heparin as prophylactic anticoagulation for immobile patients. 1

• Provide proton pump inhibitor if enteral nutrition cannot be established. 1

• Consider recombinant human G-CSF for neutropenic patients. 1

Systemic Immunomodulatory Therapy

• Consider cyclosporine (3 mg/kg daily for 10 days, tapered over 1 month) as it has shown benefit in multiple studies with reduced mortality compared to predicted rates. 1

• Consider systemic corticosteroids, particularly early IV methylprednisolone pulse therapy, if started within 72 hours of onset—the evidence is mixed but early initiation may be beneficial. 1

• Intravenous immunoglobulin (IVIg) has equivocal evidence—pooled analysis showed no mortality benefit (OR 1.00,95% CI 0.58-1.75), so it should not be considered first-line therapy. 1

• Never use thalidomide—it was associated with excess deaths in one randomized trial and should be avoided. 1

Respiratory Management

• If respiratory symptoms and hypoxemia are present on admission, arrange urgent discussion with an intensivist and rapid transfer to ICU or burn center. 1

• Perform fibreoptic bronchoscopy to identify bronchial involvement, evaluate prognosis, investigate pneumonitis, and mechanically remove sloughed bronchial epithelium. 1

Discharge Planning and Long-Term Follow-Up

• Provide written information about oseltamivir and any potentially cross-reactive medications to avoid. 1

• Encourage the patient to wear a MedicAlert bracelet bearing the name of oseltamivir. 1

• Document the drug allergy prominently in the patient's medical records and inform all healthcare providers involved in their care. 1

• Report the adverse drug reaction to pharmacovigilance authorities. 1

• Inform patients about potential fatigue and lethargy for several weeks following discharge and the need for convalescence. 1

• Arrange follow-up with dermatology and ophthalmology within weeks of discharge. 2

• Consider referral to support groups such as SJS Awareness U.K. 1

Common Pitfalls to Avoid

• Delayed transfer to a specialized unit significantly increases mortality risk—this must happen within hours, not days. 1, 2

• Continuing oseltamivir or any other suspected culprit medication will worsen the condition and increase mortality. 1

• Indiscriminate use of prophylactic antibiotics increases skin colonization with resistant organisms. 1, 2

• Failure to involve ophthalmology early leads to permanent visual impairment in over 50% of survivors. 1

• Overaggressive fluid resuscitation causes pulmonary and cutaneous edema. 1, 2

• Waiting for laboratory confirmation before discontinuing suspected drugs delays critical intervention. 1

Prognosis

The mortality rate for SJS is 1-5%, but can be higher in elderly patients and those with extensive skin involvement. 4, 7 More than 50% of patients surviving SJS suffer from long-term sequelae including ocular complications, cutaneous scarring, and mucosal strictures. 4, 6 Early recognition, immediate drug discontinuation, and prompt transfer to specialized care are the most important determinants of survival. 1, 5