Highlight
Nearly one in five hospitalized adults with Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) required intensive care in this multicentre Paris cohort.
Hospital-acquired DRESS was independently associated with ICU admission, with an adjusted odds ratio of 5.21, suggesting that inpatient onset may be a clinically meaningful warning signal.
Clinical severity at presentation was strongly linked to escalation of care: moderate DRESS carried an adjusted odds ratio of 3.74 for ICU admission, while severe disease carried an adjusted odds ratio of 12.5 versus mild forms.
Mortality remained substantial in critically ill patients, with in-hospital death in 20% of ICU cases compared with 4.8% overall.
Background
DRESS is a severe T-cell-mediated drug hypersensitivity reaction characterized by a delayed-onset eruption accompanied by hematologic abnormalities, especially eosinophilia, and involvement of internal organs. Although uncommon, it is among the most clinically consequential severe cutaneous adverse reactions because it can progress rapidly from a dermatologic presentation to multiorgan dysfunction. The syndrome is classically associated with anticonvulsants, allopurinol, sulfonamides, and several other agents, but contemporary pharmacovigilance has expanded the list of implicated drugs considerably.
From a practical bedside perspective, one of the major challenges in DRESS is early risk stratification. Some patients have limited disease that responds to drug withdrawal and supportive care, whereas others develop fulminant hepatitis, renal failure, myocarditis, hemodynamic instability, or respiratory compromise requiring critical care. Yet clinicians often lack robust data to identify, early in the hospital course, which patients are most likely to deteriorate.
This question has direct implications for triage, monitoring intensity, corticosteroid strategy, and specialist involvement. It also matters for inpatient safety: when DRESS develops during hospitalization, the diagnosis may be delayed because the rash and eosinophilia emerge in complex, medically fragile patients already receiving multiple drugs. The study by Gaillet and colleagues addresses this gap by focusing specifically on predictors of DRESS-related ICU admission in a large real-world hospitalized cohort.
Study Design
This was a multicentre retrospective cohort study conducted across 39 hospitals in the Greater Paris area using the Assistance Publique-Hôpitaux de Paris Health Data Warehouse. The investigators included adult patients hospitalized between July 2017 and January 2023 with probable or definite DRESS, defined by a RegiSCAR score of 4 or higher. Using a structured multicentre data source is an important strength, as DRESS is rare and single-centre studies are often underpowered for clinically meaningful subgroup analysis.
The primary endpoint was DRESS-related ICU admission. Secondary endpoints included in-hospital mortality and management patterns both inside and outside the ICU. The study therefore addressed not only prognostic factors but also treatment practices in routine care. This dual focus is valuable because management of severe DRESS remains heterogeneous, especially regarding the threshold for systemic corticosteroids and adjunctive immunomodulatory therapy.
The cohort comprised 207 cases. Median age was 58 years, with an interquartile range of 41 to 72 years. Women represented 62% of patients, and the median Charlson comorbidity score was 3, indicating a population with substantial baseline medical complexity. Anti-epileptic drugs were the most frequently implicated agents, accounting for 22% of cases.
Clinical Profile of the Cohort
Visceral involvement was common, underlining that hospitalized DRESS is usually more than a skin-limited syndrome. Hepatic involvement occurred in 70% of cases and was the dominant organ manifestation. Renal involvement was present in 30%. Less frequent but clinically ominous complications included hemodynamic involvement in 6.3%, cardiac involvement in 5.3%, and pulmonary involvement in 1.9%.
The distribution of disease severity is also informative. Mild disease accounted for 40% of cases, moderate disease for 35%, and severe disease for 25%. This means that 60% of hospitalized patients had at least moderate DRESS, which helps explain the relatively high ICU utilization observed. It also suggests that hospital-based cohorts may differ substantially from ambulatory or referral-center dermatology cohorts, where case mix may be skewed in other directions.
Corticosteroids were used in nearly all patients. Topical corticosteroids predominated in mild to moderate forms, while systemic corticosteroids were used mainly in severe disease. Although this pattern aligns with common clinical reasoning, it also highlights the limited standardization in DRESS treatment. Current practice is still guided more by expert opinion, pathophysiologic rationale, and observational evidence than by randomized comparative trials.
Key Results
ICU utilization and mortality
Among 207 hospitalized adults with probable or definite DRESS, 35 patients, or 17%, required ICU admission. This figure is clinically important because it quantifies the burden of critical illness in contemporary inpatient DRESS care. In-hospital mortality for the entire cohort was 4.8% (10 deaths), but mortality rose sharply to 20% among ICU patients (7 deaths). This gap underscores that ICU admission in DRESS is not simply a marker of cautious monitoring; it identifies a subgroup with materially worse prognosis.
Predictors of ICU admission
In multivariable analysis, two factors emerged as independent predictors of ICU admission.
First, hospital-acquired DRESS was strongly associated with critical care requirement, with an adjusted odds ratio of 5.21 and a 95% confidence interval of 1.96 to 14.1 (p = 0.001). This is one of the most clinically actionable findings in the study. It suggests that when DRESS begins during an existing hospitalization, clinicians should assume a higher risk trajectory. Several explanations are plausible. Inpatients often have greater comorbidity burden, more severe underlying illness, polypharmacy, greater exposure to high-risk agents such as anticonvulsants and antibiotics, and a higher likelihood that early symptoms will be attributed to competing diagnoses such as sepsis or drug fever.
Second, DRESS severity was independently associated with ICU admission. Compared with mild forms, moderate DRESS had an adjusted odds ratio of 3.74 for ICU admission, while severe DRESS had an adjusted odds ratio of 12.5. The 95% confidence intervals were 1.13 to 14.9 for moderate disease and 3.79 to 51.3 for severe disease, with an overall p value below 0.001. The stepwise increase in risk across severity strata strengthens the biological and clinical plausibility of the findings.
Together, these results support a pragmatic risk model: patients with more severe systemic involvement and those whose DRESS develops in hospital are the individuals most likely to need escalation to critical care.
Management patterns
The study also provides a useful snapshot of therapeutic practice. Nearly all patients received corticosteroids, but route and intensity varied by severity. Topical corticosteroids were used predominantly in milder disease, whereas systemic corticosteroids were favored in severe cases. This is broadly consistent with the traditional management principle that cutaneous disease without major organ injury may be approached more conservatively, while clinically significant organ involvement usually prompts systemic immunosuppression.
The paper is especially relevant to intensivists because DRESS management in ICU settings often requires balancing immunosuppression against diagnostic uncertainty. Critically ill patients may simultaneously carry infectious concerns, drug-induced liver injury, hemodynamic instability, or acute kidney injury from multiple causes. In this context, recognizing DRESS early and discontinuing culprit drugs remains the most important intervention, while corticosteroid initiation and dose escalation depend on organ involvement and competing risks.
Clinical Interpretation
This study adds practical value because it does not merely reaffirm that DRESS can be severe; it identifies specific, independently validated markers associated with ICU use in a large hospital network. The finding that hospital-acquired DRESS carries a fivefold increase in adjusted odds of ICU admission deserves particular attention. In many hospitals, inpatient drug eruptions are initially evaluated as benign exanthems, especially when fever, laboratory abnormalities, and organ dysfunction are attributed to the primary admission diagnosis. This study argues against complacency in that setting.
For dermatologists, internists, hospitalists, and intensivists, the message is straightforward: a new rash with eosinophilia or organ dysfunction in an inpatient receiving multiple medications should trigger early consideration of DRESS and prompt use of structured diagnostic tools such as RegiSCAR. For patients already categorized as moderate or severe, lower thresholds for high-acuity monitoring may be justified.
The organ involvement profile is also clinically instructive. Hepatic injury was far more common than cardiac or pulmonary complications, but the latter, although less frequent, likely contribute disproportionately to ICU admission and mortality. DRESS-associated myocarditis in particular is rare but feared because it can deteriorate abruptly. The relatively low percentage of documented cardiac involvement should not lead clinicians to underestimate it; instead, it reinforces the need for vigilance, electrocardiography, cardiac biomarkers when clinically indicated, and imaging in selected high-risk patients.
Strengths and Limitations
The study has several strengths. It leverages a large multicentre health system dataset covering 39 centres, uses a recognized diagnostic framework through RegiSCAR scoring, and focuses on a clinically meaningful endpoint rather than solely descriptive epidemiology. The sample size is substantial for a rare syndrome, and the multicentre design improves real-world relevance.
At the same time, the retrospective design introduces the usual limitations. Case identification and severity classification depend on documentation quality, and residual confounding is unavoidable. Because treatment was not protocolized, management-outcome associations cannot be interpreted causally. The study also reflects hospitalized adults in the Greater Paris area, so extrapolation to pediatric populations, outpatient settings, or health systems with different ICU triage practices should be cautious.
Another limitation is that the summary data do not provide detailed timing information on drug exposure, onset of organ dysfunction, steroid initiation, ICU transfer triggers, or specific causes of death. Such temporal granularity would be valuable in future studies because DRESS often evolves over days, and early recognition may alter outcomes. Similarly, while anti-epileptic drugs were the most common implicated class, a more granular analysis by culprit drug could help refine preventive strategies.
Implications for Practice
Several practical takeaways emerge from this cohort.
First, DRESS in hospitalized adults should be treated as a syndrome with meaningful critical care risk, not simply a severe rash. With 17% of patients requiring ICU admission, clinicians should monitor for evolving organ dysfunction from the outset.
Second, hospital-acquired DRESS appears to define a particularly vulnerable subgroup. Inpatient onset should prompt rapid multidisciplinary review involving dermatology, the primary team, pharmacy, and, when organ failure is present or imminent, critical care specialists.
Third, severity stratification matters. The adjusted odds ratios for moderate and severe disease suggest that even moderate DRESS cannot be assumed to be stable. If these findings are validated externally, they may support escalation pathways based on standardized severity scoring.
Fourth, the mortality differential between ICU and non-ICU patients highlights the need for earlier recognition rather than delayed rescue. By the time DRESS reaches a stage requiring intensive care, prognosis worsens substantially.
Finally, corticosteroid use was nearly universal in this cohort, but evidence-based consensus on optimal dose, duration, and taper remains incomplete. Clinicians should continue to individualize therapy according to organ involvement, infectious risk, and relapse potential, while recognizing that abrupt tapering can precipitate recurrence.
Future Directions
Prospective studies are needed to validate hospital-acquired onset and severity as triage markers, ideally with time-stamped clinical and laboratory trajectories. Future research should also determine whether early specialist review, standardized monitoring bundles, or treatment algorithms can reduce ICU transfer or mortality. Biomarkers that improve distinction between DRESS, sepsis, and other causes of inpatient rash would be especially valuable.
Interventional evidence is another unmet need. Systemic corticosteroids remain standard practice for severe disease, but comparative data on dosing strategy, pulse therapy, and steroid-sparing options are limited. Because DRESS is immunologically complex and may involve viral reactivation in some patients, more mechanistically informed treatment studies are warranted.
Funding and ClinicalTrials.gov
No ClinicalTrials.gov registration number is provided in the source summary. Specific funding information is not reported in the material provided and should be verified from the full published article.
Conclusion
This multicentre retrospective cohort provides one of the clearest contemporary signals that ICU admission in DRESS is both common and clinically predictable. Seventeen percent of hospitalized adults required intensive care, and one in five ICU patients died during hospitalization. Among the variables examined, hospital-acquired DRESS and baseline disease severity were the major independent determinants of ICU admission. For frontline clinicians, the message is practical: inpatient-onset DRESS and moderate-to-severe disease should trigger early escalation of surveillance, rapid culprit-drug withdrawal, and low thresholds for multidisciplinary management. In a syndrome where delay can be dangerous, these data offer a more actionable framework for identifying the patients most likely to deteriorate.
Citation
Gaillet A, Layese R, Oubaya N, Sbidian E, Descamps V, Azoulay E, Bouaziz JD, Touron M, Dupin N, Dessap AM, Ingen-Housz-Oro S, de Prost N; ICUDRESS study group. Management and predictors of ICU admission in DRESS: A multicentre retrospective cohort study. J Eur Acad Dermatol Venereol. 2026 May 16. doi: 10.1111/jdv.70505. Epub ahead of print. PMID: 42141852.
Kardaun SH, Sekula P, Valeyrie-Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169(5):1071-1080.
Cabañas R, Ramírez E, Sendagorta E, et al. Spanish Guidelines for Diagnosis, Management, Treatment, and Prevention of DRESS Syndrome. J Investig Allergol Clin Immunol. 2020;30(4):229-253.
