Therapeutic management of DRESS: A retrospective study of 38 cases

doi:10.1016/j.jaad.2014.10.032

Journal of the American Academy of Dermatology

Volume 72, Issue 2, February 2015, Pages 246-252

Presented at the Journées Dermatologiques de Paris, December 2009.

https://doi.org/10.1016/j.jaad.2014.10.032 Get rights and content

Background

There is no consensus regarding treatment for drug reaction with eosinophilia and systemic symptoms (DRESS).

Objectives

We report a single-center observational series of therapeutic management of DRESS.

Methods

We examined data for 50 consecutive patients admitted from March 2005 to June 2009 with a discharge diagnosis of DRESS (RegiSCAR score).

Results

For the 38 patients with a DRESS score of 4 or more, topical steroid treatment alone was initiated in 66% of cases. On admission, 13 patients received systemic steroids; in 7 of them, systemic steroid treatment was initiated or maintained for life-threatening organ failure, with kidney, lung, and/or nervous system involvement. Complications of DRESS, such as relapse, viral reactivation, and sepsis, were less frequent with topical steroid than with systemic steroids. None of the patients died during their stay in hospital.

Limitations

Retrospective nonblinded design and dermatologic recruitment are limitations. The variables underlying the choice of treatment study were not analyzed.

Conclusions

Systemic steroids may not be required for the management of mild forms of DRESS, and may thus be reserved for more severe cases. Prospective studies are required to evaluate strategies for treating DRESS.

Section snippets

Patients

We retrospectively screened all consecutive patients admitted to our department from March 2005 to June 2009 who received steroids and had a discharge diagnosis of DRESS. The final diagnosis was validated by a review committee (J-C. R., L. V-A., S. B.), using the RegiSCAR DRESS score,⁶ with blinding to any risk factors. Each case was scored (4-5 = probable case; >5 = definite case); we considered only cases with a score of 4 or more.

We collected clinical and epidemiologic data, including

Description of the population

We analyzed data for 50 consecutive patients with a discharge diagnosis of DRESS; 38 patients had a RegiSCAR score of 4 or more, indicating probable DRESS, and were included in the study (Fig 1). The patients treated with topical and systemic steroids did not differ in age (median age: 49 ± 22 years [range: 16-87 years] vs 54 ± 22 years [range: 20-88 years], respectively, P = .66) or sex (number of female: n = 14/25 [56%] vs n = 5/13 [38%], respectively, P = .2) (data not shown).

The drugs

Discussion

Published guidelines for the treatment of DRESS are currently lacking. Only a few observational series have focused on the therapeutic management of this syndrome.14, 17 Systemic corticosteroids have long been considered the mainstay treatment for DRESS.⁸ Intravenous and oral pulse strategies are currently proposed.18, 19, 20, 21 Topical corticosteroids are effective alternative treatments for dermatologic diseases, such as bullous pemphigoid,²² decreasing the number of severe adverse events.

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Cited by (107)

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part II diagnosis and management
2024, Journal of the American Academy of Dermatology
Drug-induced hypersensitivity syndrome, also known as drug reaction with eosinophilia and systemic symptoms, is a severe cutaneous adverse reaction characterized by an exanthem, fever, and hematologic and visceral organ involvement. The differential diagnosis includes other cutaneous adverse reactions, infections, inflammatory and autoimmune diseases, and neoplastic disorders. Three sets of diagnostic criteria have been proposed; however, consensus is lacking. The cornerstone of management is immediate discontinuation of the suspected drug culprit. Systemic corticosteroids remain first-line therapy, but the literature on steroid-sparing agents is expanding. Longitudinal evaluation for sequelae is recommended. Adjunctive tests for risk stratification and drug culprit identification remain under investigation. Part II of this continuing medical education activity begins by exploring the differential diagnosis and diagnosis of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms and concludes with an evidence-based overview of evaluation and treatment.
Drug-Induced Hypersensitivity Syndrome/Drug Reaction With Eosinophilia and Systemic Symptoms: Predictive Score and Outcomes
2023, Journal of Allergy and Clinical Immunology: In Practice
We previously developed a drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) severity (DDS) score that may predict DIHS/DRESS-associated complications (DACs), including myocarditis, gastrointestinal bleeding, and autoimmune diseases.
To externally confirm the predictive accuracy of the DDS score, clarify its ability to identify patients at high risk of DACs and fatal outcome, and determine which treatments might reduce or increase the risk.
We conducted a nationwide multicenter retrospective study in which we followed 48 patients with DIHS/DRESS at 5 university hospitals in Japan for 1 year after onset. Patients were divided into mild, moderate, and severe DIHS/DRESS groups depending on their early DDS score.
Eight cases had DACs in the severe group (n = 17); no DACs were observed in the mild group (n = 12). Receiver-operating characteristic curve analysis showed that a cutoff DDS score of ≥4.0 and ≤2.0 could differentiate patients who would and would not develop DACs, respectively. In the moderate-to-severe disease groups, DACs occurred only in patients who received corticosteroids and not in those who received supportive care. None of the patients who received early treatment for cytomegalovirus developed DACs. Autoimmune DACs were significantly more common in patients who received pulse corticosteroid therapy. Four deaths occurred within the 1-year follow-up; all were in patients with infectious DACs who received systemic corticosteroids.
Our scoring system allows early identification of patients at increased risk for DACs. Risk factors for DACs include systemic or pulse corticosteroid therapy.
Clinical features and prognostic factors of severe cutaneous adverse drug reactions: A single-center retrospective study of 209 cases in China
2023, International Immunopharmacology
Citation Excerpt :
For DRESS, allopurinol, TCM, NSAIDs, and sulfasalazine were the most common causative drugs in our and other studies [8,17]. The difference is that antiepileptic drugs (carbamazepine, oxcarbazepine, and phenobarbital) are relatively infrequent in our study compared to other studies [27–30]. For SJS/TEN, antibiotics and anticonvulsants were the most frequent causative drugs in our study, which was similar to multicenter studies in European [23,31]and research in China [32,33].
Severe cutaneous adverse drug reactions (SCAR) are life-threatening and contain drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP).
We aimed to evaluate clinical features and prognostic factors for SCAR patients. From January 2010 to April 2022, 209 patients with SCAR (DRESS, n = 46, SJS/TEN, n = 128, AGEP, n = 35) were included in this study. Clinical symptoms, laboratory tests, causative drugs, disease courses, treatments, and outcomes were investigated.
Antibiotics ranked first (35.9 %) followed by traditional Chinese medicine (15.8 %) and antiepileptic drugs (14.8 %) among causative drugs of SCAR. One patient (2.2 %) with DRESS and seven patients (5.5 %) with SJS/TEN died in the hospital, while there was no AGEP-related mortality. The multivariate logistic regression analysis showed that high Registry of Severe Cutaneous Adverse Reactions score (OR = 2.340, 95 % CI = 1.192–4.591) and hemoglobin < 100 g/L (OR = 0.126, 95 % CI = 0.016–0.983) were independent risk factors of DRESS. Anemia (OR = 0.191, 95 % CI = 0.037–0.984) and body surface area detached involved at day 1 (OR = 2.749, 95 % CI = 1.115–6.778) were independent risk factors of SJS/TEN for severe acute complications and hospital death (P < 0.05). Lymphocytopenia (OR = 0.004, 95 % CI = 0.000–0.553) was a risk factor of AGEP for acute complications (P = 0.028).
This study reveals the clinical features and independent prognostic factors for SCAR, which may be helpful in the clinical management for SCAR patients.
Clinical aspects and therapeutic approach of drug-induced adverse skin reactions in a quaternary hospital: a retrospective study with 219 cases
2022, Anais Brasileiros de Dermatologia
Adverse drug reactions are frequent, with cutaneous manifestations being the most common. In the hospital environment, the incidence of cutaneous drug reactions varies from 2% to 3%.
To analyze the profile of cutaneous drug reactions, relating clinical forms, suspected medications, histopathological alterations, systemic repercussions, treatment and course.
Clinical, retrospective and observational study of patients seen by the Dermatology Interconsultation team from January 2013 to December 2016.
The frequency of cutaneous drug reactions among the evaluated patients was 13.6%, with 219 cases diagnosed. In 65.7%, the reaction was considered mild, of which the most common was exanthema, while in 34.2%, the reaction was considered severe, with DRESS being the main form of reaction(18.2%). Antibiotics (36.5%) and anticonvulsants (10%) were the most involved drugs. In addition to drug discontinuation, systemic corticosteroids were prescribed in 47% of cases and intravenous immunoglobulin (IVIg) in 4.5%. Of the mild forms, in 62%, expectant management and/or exclusive use of symptomatic treatment was used.
Retrospective study, with limitations inherent to this type of investigation; lack of some information in medical records; long evaluation period, with a possible change in external validity.
The most frequently identified clinical form was exanthema, and antibiotics and anticonvulsants were the most frequently involved drug classes. About one-third of the patients had severe cutaneous drug reactions, with DRESS being the main one. Cutaneous drug reactions are frequent in clinical practice, and the dermatologist should be called in as soon as possible to assist in the diagnosis and management of these cases.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Series of 49 French Pediatric Cases
2022, Journal of Allergy and Clinical Immunology: In Practice
Citation Excerpt :
Furthermore, the rash appears to resolve more rapidly (16 vs 23.5 days). These results are consistent with those of Funck-Brentano et al33 and Uhara et al,34 who suggested that TS can be used in patients with nonsevere DRESS. Treatment with SC might favor relapse30; it is often prolonged and carries an infection risk.35,36
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and potentially fatal adverse reaction. It can be difficult to diagnose, even more so among children, because symptoms may mimic other commonly encountered pediatric conditions.
To describe clinical and laboratory features of DRESS syndrome in the pediatric population (age ≤18 years) and establish causative agents and treatment modalities.
This was a multicenter retrospective study of probable and definite DRESS cases (Registry of Sever Cutaneous Adverse Reaction score ≥ 4) in children hospitalized in 15 French university hospitals between 2000 and 2020.
We included 49 cases. All children had fever and rash, 69.4% had lymphadenopathy, and 65.3% had facial edema. The most common organ affected was the liver (83.7%). Treatment consisted of topical corticosteroid in only 30.6% and systemic corticosteroid in 55.1%; 12.2% received intravenous immunoglobulin. Among probable and likely culprit drugs, 65% were antibiotics and 27.5% were antiepileptics, median time to DRESS symptom onset after initiation of 15 days (13 days with antibiotics and 21 days with antiepileptics). Twenty-seven children had allergy assessment for causative agents, 65.4% of whom had positive tests.
Culprit drugs are frequently antibiotics and antiepileptic drugs, and onset is often less than 2 weeks after treatment starts, especially with antibiotics. Treatment with topical corticosteroids appears to be sufficient in the least severe cases. Treatment by systemic corticosteroid therapy remains the reference treatment in case of severe organ damage.
Successful treatment of corticosteroid-dependent drug reaction with eosinophilia and systemic symptoms with cyclosporine
2021, Annals of Allergy, Asthma and Immunology
Drug reaction with eosinophilia and systemic symptoms (DRESS) is an intractable drug hypersensitivity disease with high mortality. The current standard treatment requires high-dose and long-term systemic corticosteroids, which may lead to adverse effects and intolerability of patients.
To evaluate the efficacy and safety of cyclosporine in patients with corticosteroid-dependent DRESS or intolerance to systemic corticosteroids.
A retrospective review of 8 patients with corticosteroid-dependent DRESS who were treated with cyclosporine as an alternative treatment owing to suboptimal response to regular doses of systemic corticosteroids for at least 3 weeks, flare-ups when tapering corticosteroids, or experiencing intolerable adverse effects of corticosteroids.
In all 8 patients (4 women and 4 men; age range, 15-75 years), either intractable skin eruptions, persistent eosinophilia, or elevated liver function was noted after at least 3 weeks of treatment with systemic corticosteroids. The patients had marked cutaneous improvement and normalization of liver function and eosinophil count after adding cyclosporine, and the systemic corticosteroid treatment was smoothly tapered down. The mean dosage of cyclosporine was 1.68 ± 0.73 mg/kg/d, and the mean duration of cyclosporine treatment was 76.13 ± 35.64 days. Their serum eosinophil counts, serum alanine aminotransferase levels, and serum thymus and activation-regulated chemokine levels were all elevated at baseline and then significantly decreased during the recovery stage after cyclosporine therapy (P < .05). No adverse events were reported after adding cyclosporine.
Cyclosporine is an effective and safe therapeutic alternative as a steroid-sparing agent for corticosteroid-dependent DRESS. Further prospective randomized controlled studies are required to confirm these preliminary results.

View all citing articles on Scopus

: Dr Funck-Brentano is currently affiliated with the Department of Dermatology, Hôpital Ambroise Paré, Boulogne-Billancourt, France.

: Funding sources: None.

: Conflicts of interest: None declared.

View full text

Original articleTherapeutic management of DRESS: A retrospective study of 38 cases

Background

Objectives

Methods

Results

Limitations

Conclusions

Section snippets

Patients

Description of the population

Discussion

Toxicology

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

Ann Dermatol Venereol

Toxicology

J Am Acad Dermatol

Drug-induced pseudolymphoma and drug hypersensitivity syndrome (drug rash with eosinophilia and systemic symptoms: DRESS)

Semin Cutan Med Surg

Anticonvulsant hypersensitivity syndrome

Arch Intern Med

Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: a record linkage study

Neurology

The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations

Br J Dermatol

Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist?

Br J Dermatol

Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study

Br J Dermatol

Severe adverse cutaneous reactions to drugs

N Engl J Med

Drug rash with eosinophilia and systemic symptoms induced by valproate and carbamazepine: formation of circulating auto-antibody against 190-kDa antigen

Acta Derm Venereol

Minocycline hypersensitivity syndrome with hypotension mimicking septic shock

Pediatr Dermatol

Drug-induced hepatitis with autoimmune features during minocycline therapy

Intern Med

Original article
Therapeutic management of DRESS: A retrospective study of 38 cases