斯蒂文斯-约翰逊综合征（Stevens-Johnson syndrome）和中毒性表皮坏死松解症（toxic epidermal necrolysis）患者外周血白细胞计数的变化

SJS/TEN患者外周血白细胞计数早期下降，随再上皮化显著升高，且与TNF-α、IFN-γ水平变化相关。

　　
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening drug-induced reactions characterized by widespread mucocutaneous lesions. While the pathogenesis is linked to immune dysregulation, particularly involving CD8+ T cells and cytokines like TNF-α and IFN-γ, the temporal relationship between leukocyte dynamics and disease progression remains poorly understood. This study aimed to investigate leukocyte count fluctuations in SJS/TEN patients and correlate these changes with clinical recovery and cytokine levels.

The research involved a case series of 26 patients diagnosed with SJS/TEN between 2017 and 2019 at a specialized dermatology hospital in Vietnam. Diagnostic criteria adhered to Bastuji-Garin’s classification, excluding other conditions like severe erythema multiforme or drug reaction with eosinophilia and systemic symptoms. Participants were aged 19–73 years, with a mean age of 52.5 years. Clinical management included immunosuppressive therapies: 61.5% received corticosteroids, 23.2% combined corticosteroids with cyclosporine A, and 3.8% received supportive care alone. All patients received cyclosporine A (2–3 mg/kg/day) until re-epithelialization, followed by tapering, while corticosteroids were administered at 1–2 mg/kg/day until skin healing.

Key observations included a biphasic pattern in leukocyte counts. During the initial phase (days 4–7 post-symptom onset), neutrophils and lymphocytes exhibited significant reductions, with some patients showing counts as low as 2.8×10?/L. This early leukopenia correlated with neither bone marrow dysfunction nor drug-induced suppression, suggesting instead an immune-mediated redistribution of leukocytes. Notably, 2 out of 17 TEN patients and 2 out of 9 SJS patients failed to show later-stage leukocytosis, challenging the universality of this pattern.

The subsequent leukocytosis phase (re-epithelialization period) was marked by neutrophil surges exceeding normal limits (10×10?/L). This increase coincided with declines in TNF-α and IFN-γ levels, which are implicated in keratinocyte necroptosis and tissue damage. However, the timing of leukocytosis diverged from typical corticosteroid-induced responses: Sullivan et al. reported leukocytosis peaking 2 days post-corticosteroid initiation, whereas in this study, leukocytosis emerged 5–7 days after therapy began. This discrepancy may reflect interactions between glucocorticoids and elevated macrophage migration inhibitory factor (MIF), potentially blunting the immunosuppressive effects of steroids.

The inverse correlation between leukocytosis and pro-inflammatory cytokines (TNF-α, IFN-γ) suggests a paradoxical immune response. While elevated leukocytes might indicate infection risk, the absence of bacterial sepsis in this cohort points to neutrophils playing a reparative role. This aligns with prior evidence showing neutrophil-driven epithelial regeneration in similar conditions, though the exact mechanism remains unclear. Notably, patients with persistent leukopenia (≤5 days) had extended hospital stays and higher disease severity scores, highlighting the prognostic value of early leukocyte monitoring.

Methodological considerations included the limited sample size (n=26) and single-center design, which constrained statistical power and generalizability. The study period (2017–2019) pre-dated modern advancements in immunomodulation, potentially influencing observed trends. However, the inclusion of both SJS and TEN cases provided a broader context for comparing leukocyte dynamics across different disease severities.

Limitations were acknowledged, particularly the restricted blood sampling frequency (daily for ≤3 weeks) and reliance on retrospective data collection. Despite these constraints, the study provided critical insights into the temporal dynamics of leukocytes: early leukopenia may reflect immune activation and leukocyte sequestration, while late leukocytosis correlates with tissue repair processes. This pattern was consistent across varied demographics, including 17 female and 9 male patients, and across different causative drugs.

Clinical implications include optimizing immunosuppressive timing and integrating leukocyte trends into prognosis assessment. The study suggests that initiating corticosteroids within 7 days of symptom onset, as previously recommended, may mitigate early leukopenia. Additionally, monitoring neutrophil counts during recovery phases could guide interventions, such as early granulocyte colony-stimulating factor (G-CSF) administration in refractory cases.

Future research directions include longitudinal studies with higher sample sizes to validate these patterns across diverse populations. Exploring the role of other cytokines (e.g., IL-15) and immune cell subsets (e.g., natural killer cells) could refine understanding of leukocyte dynamics. Additionally, clinical trials testing leukocyte-guided therapies, such as G-CSF supplementation during recovery phases, may yield promising outcomes.

In summary, this study elucidates a previously underappreciated temporal axis in SJS/TEN: early leukopenia reflects systemic immune activation, while subsequent leukocytosis correlates with tissue regeneration. These findings not only enhance mechanistic understanding but also provide actionable insights for optimizing immunosuppressive regimens and improving patient outcomes through early diagnostic markers and targeted therapies. The observed inverse cytokine-leukocyte relationship underscores the complexity of immune modulation in severe cutaneous adverse reactions and emphasizes the need for integrated monitoring of hematological and inflammatory parameters in clinical management.