Acute pancreatic injuries: A complication of Stevens-Johnson syndrome/toxic epidermal necrolysis associated with cytotoxic immunocell activation

Abstract

Background: Complications involving internal organs are usually present in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, pancreatic complications are rarely reported and studied.

Objective: To summarize clinical characteristics of SJS/TEN-associated acute pancreatic injuries and to investigate underlying inflammatory mechanisms.

Methods: Clinical records of 124 inpatients with SJS/TEN were reviewed. Serum levels of tumor necrosis factor α, interleukin (IL) 6, IL-18, IL-15, IL-12p70, and soluble CD56 were determined in 18 healthy donors and 17 patients with SJS/TEN, including 3 with acute pancreatic injuries.

Results: Acute pancreatic injury was diagnosed in 7.3% of patients (9/124) in the SJS/TEN cohort. Elevation of serum transaminase level and hypoalbuminemia occurred more frequently in patients with acute pancreatic injuries compared with those without pancreatic symptoms (P = .004 and <.001, respectively). Although acute pancreatic injury did not alter mortality rate of SJS/TEN, it was associated with longer hospitalization stays (P = .008). Within the serum cytokines whose levels were elevated in SJS/TEN, only IL-18 was found to be selectively increased in patients with acute pancreatic injuries compared with those without them (P = .03).

Limitations: Cohort was small.

Conclusion: Acute pancreatic injury is a gastrointestinal complication of SJS/TEN in which hepatotoxicity is more likely to occur. Overexpression of IL-18 might be involved in this unique entity.

Keywords: Stevens-Johnson syndrome; complication; cytokine storm; interleukin 18; liver dysfunction; pancreatitis; toxic epidermal necrolysis.

Graphical abstract

Fig 1

Incidence rate and distribution of acute pancreatic injuries in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis. A, Acute pancreatic injuries and nonpancreatitis in the subtypes of Stevens-Johnson syndrome. Patient numbers are shown at the top of the bar. B, Incidence of acute pancreatic injuries in Stevens-Johnson syndrome patients, patients with Stevens-Johnson syndrome/toxic epidermal necrolysis overlap, and in the toxic epidermal necrolysis cohort. P values are determined by Fisher's exact test. API, Acute pancreatic injury; NP, nonpancreatitis; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis.

Fig 2

Comparison of disease triggers, laboratory test results, and prognosis between the acute pancreatic injuries group and nonpancreatitis group in the context of Stevens-Johnson syndrome/toxic epidermal necrolysis. No significant difference was revealed in biliary history (A), alcohol abuse (B), kidney dysfunction (D), positive autoantibody results (E), and mortality rate (F) between the 2 groups. C, A higher incidence rate of liver dysfunction was shown in patients with acute pancreatic injuries than in the nonpancreatitis cohort. G, The average hospitalization stay was much greater when patients developed acute pancreatic injuries. Fisher's exact test was applied for comparison (A-F); the P value was determined by Student t test (G).API, Acute pancreatic injury; NP, nonpancreatitis.

Fig 3

Comparison of serum cytokine levels. None of cytokines, including tumor necrosis factor α (A), IL-6 (B), IL-15 (D), IL-12p70 (E), and soluble CD56 (F), has significantly different levels between the nonpancreatitis group (n = 14) and acute pancreatic injuries group (n = 3). IL-18 levels were significantly increased in the acute pancreatic injuries group compared with those in nonpancreatitis patients (C). Symbols represent individuals. P values were determined by Mann-Whitney-Wilcoxon test. API, Acute pancreatic injury; IL, interleukin; NP, nonpancreatitis; TNF, tumor necrosis factor.