Abstract
This retrospective cohort study examines the association of lymphocyte and neutrophil levels with treatment outcomes in 147 patients with epidermal necrolysis in France.
Epidermal necrolysis (EN, including Stevens-Johnson syndrome [SJS], overlap, and toxic epidermal necrolysis [TEN]) is a rare condition mainly induced by drugs. Overall mortality is around 15% to 20% at the acute phase, and the cornerstone of its management is supportive care.1 Mortality may be predicted by the SCORTEN, a severity score published 20 years ago,2 which includes 4 clinical and 3 biological parameters at baseline (glucose, urea, and bicarbonate levels). In a recently published study of 377 patients with EN, Wang et al3 reported that baseline leukopenia (<4000 white blood cells/mm3 at hospital admission) affected 13% of patients and was associated with higher initial body surface area involved, malignant disease, connective tissue disorder, and higher risk of infections, but without a higher rate of in-hospital mortality. However, in this study, the authors did not report differential blood leukocyte counts. We previously reported that the median blood lymphocyte counts were low in the patients with the most severe disease, whereas neutrophil counts, although lower in those with severe disease, remained in the normal range, suggesting that lymphocytes may be the most affected leukocytes.4 In the present study, we aimed to investigate the association between lymphocytes and neutrophils and outcomes of the disease.
Methods
In a retrospective cohort study of patients treated in a French reference center from January 2015 to July 2022, we calculated the prevalence of leukopenia (white blood cell counts <4000/mm3) at baseline and investigated the presentation and outcomes of patients with blood neutrophil and lymphocyte counts below the normal threshold value of our laboratory (1500/mm3 and 1000/mm3, respectively). Baseline characteristics (age, sex, cancer history, SCORTEN, initial body surface area detached) and outcomes (final body surface area detached and final diagnosis [SJS, overlap, or TEN], bloodstream infections, intensive care unit admission, and death at 6 weeks) were compared between patients with abnormal and those with normal blood neutrophil and lymphocyte counts.
Patients signed consent for the use of their data (CPP 2013/46NICB and 2018-A00371-54). Institutional review board approval was waived.
Results
Among the 147 included patients, 32 (21.8%) had leukopenia. The in-hospital mortality rate (calculated in 144 patients, 3 being lost-to-follow-up) was not significantly different between patients with (21.9%, n = 7/32) or without leukopenia (18.8%, n = 21/112; P = .69). Neutropenia was a rare feature (7.5%, n = 11/147), whereas lymphopenia was common (54.4%, n = 80/147). There were no significant differences in baseline characteristics or outcomes between patients with or without neutropenia. In contrast, patients with lymphopenia were significantly more often male, older, and had more severe disease at baseline and exhibited poorer outcomes than their counterparts, with a significantly higher mortality rate (30.0% vs 5.6%, respectively; P = .001) (Table).
Table. Characteristics and Outcomes of the 147 Patients According to the Blood Neutrophil and Lymphocyte Counts at Baseline.
| Characteristics | Neutrophils | Lymphocytes | ||||
|---|---|---|---|---|---|---|
| No. (%) | P valuea | No. (%) | P valuea | |||
| <1500 (n = 11) | ≥1500 (n = 136) | <1000 (n = 80) | ≥1000 (n = 67) | |||
| Sex | ||||||
| Female | 4 (36.4) | 91 (66.9) | .05 | 44 (55) | 51 (76) | .007 |
| Male | 7 (63.6) | 45 (33.1) | 36 (45) | 16 (24) | ||
| Age, median (IQR) | 60 (47-67) | 46 (35-64) | .11 | 52 (43-66) | 41 (31-60) | <.001 |
| Cancer history | 4 (36.4) | 21 (15.4) | .09 | 20 (25) | 5 (7.5) | .005 |
| Baseline SCORTEN, median (range) | 2 (2-3) | 2 (1-3) | .11 | 2 (2-3) | 1 (0-2) | <.001 |
| Initial BSA, median (IQR), % | 10 (5-23) | 15 (4-30) | .98 | 15 (5-36) | 10 (2-30) | .02 |
| Final maximal BSA, median (IQR), % | 25 (9-50) | 25 (5-60) | .89 | 35 (10-68) | 20 (4-55) | .02 |
| Final diagnosis | ||||||
| SJS | 3 (27.3) | 40 (29.4) | >.99 | 19 (23.7) | 24 (35.8) | .11 |
| Overlap | 3 (27.3) | 30 (22.1) | .71 | 17 (21.2) | 16 (23.9) | .70 |
| TEN | 5 (45.5) | 66 (48.5) | >.99 | 44 (55.0) | 27 (40.3) | .001 |
| Bloodstream infection | 4 (36.4) | 48 (35.3) | >.99 | 36 (45.0) | 16 (23.9) | .008 |
| Intensive care | 5 (45.5) | 44 (32.3) | .51 | 36 (45.0) | 13 (19.4) | .001 |
| Death at 6 wkb | 3 (27.3) | 25 (18.4) | .44 | 24 (30.0) | 4 (5.6) | .001 |
Abbreviations: BSA, body surface area; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis.
Mann-Whitney tests were performed for quantitative variables and Fisher exact or χ2 tests for categorical variables as appropriate.
Available for 144 participants, 3 were lost of follow-up.
Discussion
We found that 32 (21.8%) patients with EN had leukopenia at baseline, a prevalence slightly higher than described by Wang et al (13%).3 Our results are consistent with the main findings of Wang et al in a different patient population, showing that leukopenia is not associated with higher in-hospital death rates. Furthermore, we identified that, among leukocytes, lymphocyte counts at baseline seem more involved as a prognosis factor than neutrophils. Indeed, lymphopenia, which is associated with a more severe disease, a higher rate of infections and intensive care unit admission, and a higher in-hospital mortality rate, might be a better prognostic biomarker in patients with EN than the overall white blood cell counts.
Limitations of our study include its monocentric and retrospective design, with inherently associated biases, including the fact that blood cell counts were recorded at hospital admission, implying that the time lag between first symptoms and leukocytes counts varied between patients.
Conclusions
Lymphopenia, affecting more deeply CD4-positive than CD8-positive T cells, was first reported in patients with EN in 1985.5 Recent studies showed that CD8-positive lymphocytes exhibit a clonal drug-specific expansion.6 Close attention should be paid to lymphopenia in patients with EN.
Data Sharing Statement
References
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Supplementary Materials
Data Sharing Statement
