Ocular Manifestations and Management of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis

Felon Mahrous

Introduction

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) represent a rare but potentially life-threatening immune-complex-mediated hypersensitivity reaction that predominantly affects the skin and mucous membranes (1). Characterized by widespread epidermal necrosis and detachment, these syndromes also involve significant mucosal inflammation, including oral, ophthalmic, and urological surfaces (2). Initial symptoms often mimic a viral prodrome, presenting as flu-like malaise and fever, which rapidly progress to painful blistering and erosions. Given the acute and systemic nature of SJS/TEN, early recognition and urgent multidisciplinary intervention are crucial to mitigate morbidity and mortality.

Prevalence and Incidence

The global incidence of SJS is estimated at approximately 1 to 6 cases per million individuals annually, though regional variations exist due to differences in genetic predisposition, environmental factors, and medication usage patterns (3). Accurate epidemiological data on ocular involvement remains limited; however, studies report ocular manifestations in 80–90% of SJS/TEN cases, with a wide spectrum of clinical severity (4). This high prevalence underscores the importance of ophthalmic evaluation as a standard component of care.

Causes and Risk Factors for SJS/TEN

Medications are the primary triggers for SJS/TEN, especially those that induce delayed-type hypersensitivity reactions. Common culprits include anticonvulsants (e.g., carbamazepine, phenytoin), sulfonamide antibiotics, antiviral agents, and non-steroidal anti-inflammatory drugs (NSAIDs) (5). Infectious agents, particularly Mycoplasma pneumoniae, account for a significant proportion of non-drug-induced SJS cases, with herpes simplex virus, cytomegalovirus, and streptococcal infections also implicated (6).

Genetic predisposition plays a critical role in susceptibility. Specific human leukocyte antigen (HLA) alleles, such as HLA-A0206 and HLA-DQB10601, have been associated with increased risk of ocular complications in SJS, highlighting the importance of genetic screening in at-risk populations (7).

Diagnostic Approaches and Assessment Tools

SJS and TEN are considered part of a disease spectrum distinguished by the extent of epidermal detachment. SJS involves less than 10% of the body surface area (BSA), whereas TEN involves more than 30%, with overlap syndrome involving 10–30% (3). Clinical diagnosis is supported by a positive Nikolsky sign – detachment of the epidermis upon gentle pressure – and confirmed via skin biopsy demonstrating full-thickness epidermal necrosis with minimal dermal inflammation (8). Comprehensive ophthalmic assessment, including slit-lamp examination and fluorescein staining, is critical to evaluate conjunctival and corneal involvement. It is also essential for the ophthalmology team to have a low threshold for reviewing these patients whenever the parent team looking after them are concerned, due to the rapid escalation of ocular manifestations.

There are several grading systems that exist to classify ocular involvement in SJS/TEN, including the acute-phase classification proposed by Power et al., and the widely used chronic ocular severity grading system developed by Sotozono et al., which evaluates corneal, conjunctival, eyelid, and tear-film abnormalities (9). This can then provide further guidance on the required aggressiveness of treatment.

Acute Ophthalmic Manifestations of SJS/TEN

Ocular involvement in the acute phase is frequent and varies from mild irritation to severe inflammation with potentially sight-threatening complications. Early findings include conjunctival hyperemia, chemosis, and pseudomembrane formation, often progressing to symblepharon (adhesions between the palpebral and bulbar conjunctiva), conjunctival epithelial defects, and corneal epithelial ulcerations (10). Corneal involvement may escalate to stromal ulceration, thinning, and in severe cases, perforation, risking endophthalmitis and permanent vision loss. Prompt identification and treatment during this stage are paramount to prevent chronic sequelae.

Long-Term Ophthalmic Complications

Chronic ocular sequelae develop in up to 90% of SJS/TEN survivors, often resulting in significant morbidity (11). Classification systems for chronic ocular involvement vary, but complications commonly include:

  • Tear film dysfunction: Superficial punctate keratopathy and dry eye syndrome arise due to lacrimal gland damage and conjunctival scarring, related to aqueous tear deficiency (12)
  • Conjunctival and eyelid changes: Chronic conjunctival inflammation, symblepharon, and mucocutaneous junction abnormalities; eyelid malposition such as entropion and trichiasis are frequent and cause further corneal irritation (13)
  • Corneal abnormalities: limbal stem cell deficiency, corneal neovascularisation and opacification, and persistent epithelial defects (14)

The pathogenesis of chronic ocular complications remains unclear. Notably, there is poor correlation between the severity of acute ocular symptoms and long-term outcomes, with some patients developing significant chronic sequelae despite mild acute involvement. Moreover, patients with non-pharmaceutical triggers tend to have more severe chronic visual impairment.

Current Management Approaches and UK Guidelines

SJS/TEN management demands a multidisciplinary approach involving dermatology, ophthalmology, critical care, and other specialties. The primary therapeutic goals are to halt disease progression, control inflammation, prevent infection, and preserve visual function.

Acute phase management includes:

  • Ocular lubrication: Frequent and intensive use of preservative-free artificial tears to maintain ocular surface hydration (15)
  • Sytemic and Topical corticosteroids: To reduce inflammation, with great importance in reducing risk of progression of ocular symptoms and chronic sequelae (16)
  • Broad-spectrum antibiotics: Prophylactic use to prevent secondary infections (15)
  • Immunomodulatory therapy: Emerging evidence supports agents such as IVIG therapy (17) whilst other agents such as cyclosporin which was historically used more is now less used
  • Surgical intervention: Early amniotic membrane transplantation can promote epithelial healing and reduce scarring (18)

Long-term management focuses on:

  • Maintenance of ocular surface integrity through continued lubrication and interventions such as punctul plugs when appropriate and repeated AMT as required
  • Management of eyelid malposition and symblepharon via surgical correction.

Psychosocial support is also vital given the chronic nature of the disease and its impact on quality of life and visual acuity.

Conclusion

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis are complex multisystem disorders with significant acute and chronic ophthalmic morbidity. Early recognition and aggressive multidisciplinary management are essential to mitigate devastating ocular complications. Ongoing research into genetic risk factors, and optimal treatment strategies is critical to improve visual outcomes and patient quality of life.

References

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