Systemic Immunomodulating Therapies for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in a COVID-19 Patient: A Case Report

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis lie on a spectrum of severe cutaneous adverse reactions characterized by extensive epidermal detachment and mucosal involvement. Mortality in TEN may reach 40%–50% and is increased by the presence of comorbidities such as COVID-19^[1][2]. The mainstay of management remains immediate withdrawal of the causative agent and prompt supportive care, but systemic immunomodulating therapies are increasingly employed in severe cases. The context of COVID-19 presents additional immunological challenges, requiring careful consideration of therapeutic approaches.

Clinical Summary

A 47-year-old male, with no significant prior medical history, presented with fever, malaise, sore throat, and widespread erythematous maculopapular rash involving >30% of total body surface area. Three days prior, he had been prescribed paracetamol and azithromycin for symptoms suggestive of upper respiratory tract infection. On admission, he was febrile, tachypneic, with oxygen saturation dropping to 91% on room air. RT-PCR for SARS-CoV-2 returned positive.

On examination, targetoid lesions were present on trunk, limbs, face, and genitals. Oral, ocular, and genital mucosae were severely affected. Histopathological examination confirmed full-thickness epidermal necrosis, compatible with SJS/TEN overlap.

Laboratory Findings

·        Hemoglobin: 13.5g/dl

·        Leukocyte count: 6,200/mm³

·        Liver function: Mild elevation of transaminases

·        C-reactive protein: 52mg/L

Management

Supportive Measures

·        Immediate withdrawal of all non-essential drugs

·        High-flow oxygen and careful fluid management

·        Analgesia and nutritional support

·        Strict temperature and hemodynamic monitoring

·        Wound care in a negative pressure isolation room^[3][4]

Systemic Immunomodulating Therapy

Given the severity and rapid progression, the following regimen was initiated:

·        IV Methylprednisolone: 1.5mg/kg/day for 5 days, tapered gradually

·        Intravenous Immunoglobulin (IVIG): 2g/kg over 3 days^[5][6]

·        Empiric antibiotics (pending cultures)

Clinical Course

Within 48 hours, progression of skin lesions stabilized. Mucosal involvement improved within 10 days, with gradual re-epithelialization. The patient’s COVID-19 pneumonia remained mild, and oxygen was weaned off by day 7. No secondary infections occurred.

Pathogenesis

Both SJS/TEN and severe COVID-19 manifest as immune-mediated damage via cytokine storm—overproduction of TNF-α and other pro-inflammatory mediators. This common pathogenesis provides rationale for the use of systemic immunomodulation in both diseases^[7][1].

Therapeutic Options

Figure: Immunopathogenesis and therapy targets in SJS/TEN and COVID-19 overlap

[Immunopathogenesis diagram or illustration of cross-talk between SJS/TEN and COVID-19 cytokine storm, showing therapeutic intervention sites.]

Literature Review of SJS/TEN in COVID-19 Patients

Several reports confirm that COVID-19 and drug exposures synergistically increase the risk or severity of SJS/TEN. The most common medications implicated include antibiotics (azithromycin), NSAIDs (naproxen), and paracetamol^[2][11].

Case Outcomes Overview:

·        Most reported cases used systemic corticosteroids as first-line therapy^[2][11].

·        IVIG was added in rapidly progressing or severe cases; clinical improvement usually occurred within 7–10 days^[12][5].

·        Some reports detail cyclosporine or TNF-α blockers as rescue therapies, but data remain limited.

·        Concerns persist regarding the risk of secondary infections and delayed viral clearance.

Incidence of SJS/TEN in the Setting of COVID-19

Combined immune activation due to SARS-CoV-2 and drug hypersensitivity increases risk for SJS/TEN. The rate of cutaneous drug reactions in COVID-19–positive patients has been reported as up to 2–3% in some cohorts, with SJS/TEN remaining rare but severe.

Outcome and Prognosis

This patient’s rapid stabilization and recovery support early and aggressive systemic immunomodulation in severe SJS/TEN, even in the presence of COVID-19, provided infection control and close monitoring are implemented. Long-term sequelae for SJS/TEN may include ocular scarring and pigmentation changes^[2]; in this case, only minimal sequelae were observed.

Review of Key Evidence

Comparative Efficacy: Systemic Therapies

Odds Ratios for Mortality in SJS/TEN by Therapy:

SJS/TEN in the context of COVID-19 presents unique challenges but can be treated effectively with systemic immunomodulating therapies. Corticosteroids and IVIG remain the mainstays, with cyclosporine and TNF-α antagonists as promising adjuncts, especially in refractory cases. Supportive care measures and interdisciplinary management are essential for optimal outcomes.

Graphs & Figures

Figure 1: Mechanism of Action—Systemic Immunomodulators in SJS/TEN

A schematic illustration would show pathways for corticosteroids (inhibition of pro-inflammatory cytokines), IVIG (Fas-FasL blockade), and cyclosporine (T-cell suppression).

Figure 2: Recovery Timeline of Patient Treated with Systemic Immunomodulation

| Day 0   | Day 2      | Day 5      | Day 10 | Day 14 |
|---------|------------|------------|--------|--------|
| Admission, Initial    | Lesion progression  | Stabilization, IVIG complete | Partial re-epithelization | Full recovery, discharge |
| symptoms, therapy started | slows                  | Improvement visible        |                          |                        |

1.      Chang, H.C., et al. "A Review of the Systemic Treatment of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis." Biomedicines, vol. 10, no. 9, 2022.

2.      Tsai, Tsung-Yu, et al. "Treating toxic epidermal necrolysis with systemic immunomodulating therapies: A systematic review and network meta-analysis." Journal of the American Academy of Dermatology, 2020.

3.      Mojtaba, Ahangarkani, et al. "Corona virus disease 2019-associated Stevens-Johnson syndrome: a case report." American Journal of Ophthalmology Case Reports, 2021.