Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) - UpToDate

19/1/23, 15:27 Drug reaction with eosinophilia and systemic symptoms (DRESS) - UpToDate
Official reprint from UpToDate®

www.uptodate.com © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Drug reaction with eosinophilia and systemic

symptoms (DRESS)
Author: Haur Yueh Lee, MBBS, MRCP, M Med (Int Med), FAMS
Section Editor: Maja Mockenhaupt, MD, PhD
Deputy Editor: Rosamaria Corona, MD, DSc
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2022. | This topic last updated: Dec 08, 2020.
INTRODUCTION
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug
reaction characterized by an extensive skin rash in association with visceral organ
involvement, lymphadenopathy, eosinophilia, and atypical lymphocytosis. The clinical
presentation is heterogeneous, and the disease course is typically prolonged. Despite the
cessation of the offending drug, flares of disease may continue to occur. The latency
between drug initiation and onset of disease is prolonged, typically between two to eight
weeks. Reactivation of latent human herpesvirus infections is a common observed
phenomenon [1-4].
DRESS will be reviewed in this topic. Other types of cutaneous drug reactions, drug fever,
and drug allergy are discussed separately.
● (See "Drug eruptions".)

● (See "Exanthematous (maculopapular) drug eruption".)
● (See "Lichenoid drug eruption (drug-induced lichen planus)".)
● (See "Fixed drug eruption".)
● (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical
manifestations, and diagnosis".)
● (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Management,
prognosis, and long-term sequelae".)
● (See "Acute generalized exanthematous pustulosis (AGEP)".)
● (See "Drug hypersensitivity: Classification and clinical features".)
● (See "Drug fever".)
https://www-uptodate-com.bvcscm.a17.csinet.es/contents/drug-reaction-with-eosinophilia-and-systemic-symptoms-dress/print?search=dress&so… 1/52
TERMINOLOGY
Drug reaction with eosinophilia and systemic symptoms (DRESS) is the most widely used
term; drug-induced hypersensitivity syndrome (DIHS) is also frequently used [3]. Older terms
were previously based on the causative drug (eg, anticonvulsant hypersensitivity syndrome,
allopurinol hypersensitivity syndrome, dapsone syndrome).
EPIDEMIOLOGY
DRESS is estimated to occur in 0.9 to 2 per 100,000 patients per year [5,6]. In hospitalized
patients, DRESS accounts for 10 to 20 percent of all cutaneous adverse drug reactions [7-9].
DRESS may occur in children, although the incidence is likely to be lower than in adults [10].
The risk of developing DRESS varies from drug to drug. For high-risk, antiseizure
medications ( table 1), the incidence of DRESS is estimated to be 1 in 1000 to 1 in 10,000
exposures [11].
ETIOLOGY AND RISK FACTORS
Drug exposure — A clear drug trigger can be identified in the majority of DRESS cases
(approximately 80 percent) [4]. However, in the remaining 10 to 20 percent, the strength of
drug causality is less clear, and in 2 percent of cases, no drug exposure is present [4]. A large
proportion of cases (approximately 75 percent) are due to a few high-risk drugs ( table 1).
These include aromatic anticonvulsants (eg, carbamazepine, phenytoin, lamotrigine),
allopurinol, sulfonamide-containing antibacterials, mexiletine, minocycline, and vancomycin
[2,4,12]. In the pediatric population, antiepileptics and antibiotics account for the majority of
cases of DRESS [10].
Evolving prescription practices also impact the incidence of DRESS due to a specific drug. As
an example, the increased use of vancomycin in hospitalized patients resulted in vancomycin
being the leading cause of DRESS in certain areas of the United States [13].
There is indirect evidence that the risk of DRESS for certain drugs is dose dependent. As an
example, renal impairment has an additive effect to genetic predisposition on the risk of
allopurinol-induced DRESS and other severe cutaneous adverse reactions [14]. Similarly,
delayed drug clearance and accumulation have been found in cases of DRESS and Stevens-
Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) induced by phenytoin [15] as well as
in cases of DRESS induced by minocycline [16].
Pharmacogenetic susceptibility — Pharmacogenetic studies have found an association

between DRESS risk and several human leukocyte antigen (HLA) haplotypes and genetic
variants:
● HLA – Association of DRESS with polymorphisms in the HLA genes has been proven for
certain medications in particular at-risk ethnic populations ( table 2) [17-19]. HLA
alleles encode for the structure of the major histocompatibility complex (MHC) and may
influence the interaction between the drug or drug metabolite, T cell receptor, and
MHC proteins on antigen-presenting cells.
● Genetic polymorphisms – Polymorphisms in genes encoding drug metabolizing

enzymes (eg, cytochrome P [CYP] 450, N-acetyltransferase [NAT1, NAT2]) may result in
accumulation of the drug or its active metabolites and increased risk of hypersensitivity
reactions. As an example, Asian individuals who carry the CYP2C9*3 polymorphisms
have an increased risk of phenytoin-induced severe cutaneous adverse reactions
[15,16]. Similarly, the "slow acetylator" phenotype associated with variants in NAT genes
was found to be a risk factor for sulfonamide-related hypersensitivity reactions [20,21].
However, such pharmacogenetic associations have been found only for a limited
number of drugs and are specific to certain ethnic groups.
PATHOGENESIS
DRESS is considered a T cell-mediated hypersensitivity reaction. Although the exact

pathogenesis is not fully understood, two main pathogenetic mechanisms are thought to be
involved: a drug-specific immune response and the human Herpesviridae reactivation with a
subsequent antiviral immune response.
Drug-specific immune response — The role of drug-specific immune response in the

pathogenesis of DRESS has been proven based on the patch test positivity to some causative
drugs as well as the in vitro demonstration of drug-specific CD4+ and CD8+ T cells that
produce large amounts of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma
[22-26]. During the acute phase of the disease, there is an expansion of circulating activated
T lymphocytes of both CD4+ and CD8+ subsets that harbor activation markers and a skewed
repertoire of the antigen receptor. An expansion of regulatory T cells has also been
demonstrated in the acute phase of DRESS [26-28].
A single-cell RNA sequencing study demonstrated enhanced Janus kinase-signal transducer

and activator of transcription (JAK-STAT) signaling in activated T lymphocytes from the skin
and blood of a patient with refractory DRESS and that circulating central memory CD4+ T
cells were highly enriched in DNA from human herpesvirus (HHV) 6B [29]. This study
suggests that the JAK-STAT pathway may have a role in the pathogenesis of DRESS and may
be a potential therapeutic target.
Reactivation of Herpesviridae — Reactivation of viruses from the Herpesviridae family (eg,

HHV-6, HHV-7, Epstein-Barr virus [EBV], cytomegalovirus [CMV]) is a known phenomenon
associated with DRESS and occurs in up to 75 percent of patients [30-34]. HHV-6 is the most
common virus in the family associated with DRESS, with reactivation reported in 16 to 60
percent of cases, depending on detection methodologies [4,30-32,35]. Multiple sequential
reactivation of herpesviruses has been observed in up to 30 percent of cases [30].
Reactivation may occur in a manner similar to that observed in graft-versus-host disease
[32].
However, the mechanisms and timing of viral reactivation in relation to the drug-specific
immune response have not been clarified, and the role of virus reactivation in the
pathogenesis of DRESS remains controversial. One hypothesis is that viral reactivation
occurs as a result of an immunodeficiency state [18]. During the acute stage of DRESS, the
population of T regulatory cells is expanded, while the number of B cells and the plasma
levels of immunoglobulins are reduced, which may facilitate viral reactivation [26,36,37]. An
alternative hypothesis is that certain drugs (eg, valproic acid, amoxicillin) may directly
increase HHV-6 and CMV replication [38-40].
Since in humans latent viruses can be harbored by cells of the immune system (eg, T
lymphocytes, monocytes/macrophages), the reactivation and release of viruses may be
considered as an early marker of stimulation of these cells rather than the initiating event in
the pathogenesis of DRESS [41].
CLINICAL PRESENTATION
Latency phase — The latency phase (from drug initiation to onset of reaction) typically
ranges from two to eight weeks. However, the latency may be shorter in cases attributed to
antibiotics and iodine contrast media [42]. The prodromal phase of DRESS is often
characterized by nonspecific symptoms, such as fever, malaise, and lymphadenopathy.
Cutaneous and mucosal manifestations — The skin manifestations are the most obvious
and are often the first clue to the diagnosis. The eruption starts as a maculopapular eruption
that may progress to a coalescing erythema ( picture 1A-C). Additional findings include
purpura, infiltrated plaques, pustules, exfoliative dermatitis, and target-like lesions. Lesions
are symmetrically distributed on the trunk and extremities. Facial edema is striking and
present in the majority of cases (70 percent) [4,43]. Almost 80 percent of patients would have
a >50 percent involvement of the body surface area (BSA). In rare instances (<3 percent), the
rash may be mild or absent [4]. Pruritus may be an accompanying symptom.
Mucosal involvement can be seen in up to 50 percent of cases. However, it is typically mild, in

contrast with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and skin
detachment is rarely seen.
Systemic symptoms and laboratory abnormalities — Systemic symptoms associated with

DRESS include the following [3,4,35,43-46]:
● Fever ≥101.3°F or ≥38.5°C (75 to 90 percent)
● Lymphadenopathy (54 to 65 percent)
● Hematologic abnormalities:
• Eosinophilia >700/microL (82 to 95 percent)

• Leucocytosis (95 percent)
• Neutrophilia (78 percent)
• Lymphocytosis (25 to 52 percent)
• Monocytosis (69 percent)
• Atypical lymphocytes (35 to 67 percent)
● Symptoms and/or laboratory abnormalities related with any visceral involvement (90
percent)
Organ involvement — The extent and type of organ injury varies. Involvement of at least
one internal organ occurs in approximately 90 percent of patients. Approximately 35 percent
of patients may have two internal organs involved, and up to 20 percent of patients may
have more than two-organ involvement [4]. Internal organ involvement may precede the
development of cutaneous rash, and the clinical course of the cutaneous manifestations may
not parallel that of visceral organs [4,47].
Liver — Liver injury is the most common visceral manifestation of DRESS, occurring in 53 to
90 percent of cases [4,43-46]. The majority of liver function test abnormalities are transient
and generally mild [47,48]. Patterns of liver injury include cholestatic type (37 percent),
hepatocellular form (19 percent), and mixed (27 percent). Up to 50 percent of cases may
have elevations of liver enzymes more than 10 times the upper limit of normal [47]. Acute
liver failure is rare and may require liver transplantation. In a series of 16 patients with
DRESS and acute liver injury, nine patients recovered spontaneously and six underwent
emergency liver transplantation [49]. (See "Acute liver failure in adults: Etiology, clinical
manifestations, and diagnosis".)
Kidney — The spectrum of kidney injury associated with DRESS ranges from proteinuria to
renal failure [4,43-46]. Acute interstitial nephritis occurs in 10 to 30 percent of DRESS cases,
acute renal failure occurs in up to 8 percent of patients, and up to 3 percent of patients will
require either short- or long-term dialysis [4,43,44,50,51]. Risk factors for the development of
drug-induced kidney injury include older age and underlying renal or cardiovascular
diseases [52]. Renal involvement may be more common in DRESS cases associated with
allopurinol [53].
Pulmonary involvement — The symptoms of pulmonary involvement, which occurs in up

to 30 percent of patients with DRESS, include shortness of breath and dry cough [4,43,44].
Chest radiographs or computed tomography (CT) scans may demonstrate interstitial
infiltrates and pleural effusions. Respiratory complications may include acute interstitial
pneumonitis, lymphocytic interstitial pneumonia, pleuritis, and acute respiratory distress
syndrome [54-56].
Cardiac involvement — Cardiac involvement (2 to 20 percent of cases) is a severe

complication and poor prognostic factor [4,44,57,58]. Clinical presentations include
hypotension, tachycardia, dyspnea, and/or chest pain associated with left ventricular
dysfunction and electrocardiogram (ECG) changes [57,58]. Cardiac involvement can be
categorized into hypersensitivity myocarditis (which may be asymptomatic or associated
with nonspecific symptoms and carries a better prognosis) and acute, necrotizing,
eosinophilic myocarditis (which is the most severe form and is associated with over 50
percent mortality) [55,58]. Definitive diagnosis is based on endomyocardial biopsy.
Other organs — Central and peripheral nervous system involvement, including Bell's palsy,
peripheral neuropathy, aseptic meningitis, cerebral vasculitis, and limbic encephalitis, has
been reported in 2 to 8 percent of DRESS cases [2,4,44,50,59-62].
Gastrointestinal involvement is uncommon. It includes gastrointestinal bleeding,

esophagitis, colitis, intestinal perforation, cholecystitis, and pancreatitis [43,50,51,63,64].
Rare complications include myositis, thyroid dysfunction, uveitis, and hemophagocytic

syndrome [3,4,50,65-71].
Severe DRESS — Severe DRESS has been arbitrarily defined as DRESS cases with severe, life-
threatening organ involvement that result in intensive care unit (ICU) admission or death
[50]. No clear prognostic predictors on presentation have been determined. Reactivation of
human herpesvirus (HHV) 6 and cytomegalovirus (CMV) may be associated with severe
DRESS and poorer outcomes [31,72,73].
CLINICAL COURSE
The clinical course of DRESS is variable. There are no reliable markers at presentation to
predict outcome. However, viral reactivation and, in particular, cytomegalovirus (CMV)
reactivation, detected during the course of the disease, is associated with poorer outcomes
[50,72].
Acute phase — The cutaneous eruption and visceral involvement generally resolve
gradually after drug withdrawal. In up to 90 percent of cases, the cutaneous eruption
persists beyond 15 days and then subsides with desquamation. The average time to
recovery is approximately seven weeks, but up to 20 percent of patients may have a
prolonged course lasting more than 90 days [44,74]. Factors associated with a prolonged
course include evidence of viral reactivation, severe liver involvement, and presence of
mononucleosis-like, atypical lymphocytosis [74].
Flare-ups — Relapses or flare-ups are common after resolution of the acute disease,
occurring in up to 25 percent of cases weeks to months (median of 4.5 months) after
resolution [75]. In most cases, flare-ups are cutaneous in nature, but they may manifest as
eosinophilia or liver enzyme elevations [75]. Flare-ups tend to be more common in patients
treated with systemic corticosteroids and occur more frequently on rapid tapering of
corticosteroids [74,76]. Moreover, concurrent reactivation of human herpesvirus (HHV) 6
during flare-ups has been observed [74].
Relapses can also be triggered by medications that may be structurally different from the
initial causative drug, most commonly antibiotics given as empirical therapy for suspected
infection. The reason for the cross-reactivity to other drugs frequently shown by patients
with DRESS is incompletely understood. It may result from an immune hyperactivation
triggered by the initial episode of DRESS that leads to polysensitization to multiple drugs
[75,77,78]. As such, routine and unnecessary exposure to antibiotics and other medications
during the acute phase is discouraged [78].
Long-term outcomes — Various autoimmune sequelae have been noted in DRESS

survivors. These include autoimmune thyroiditis, vitiligo, alopecia areata/universalis,
autoimmune hemolytic anemia, lupus erythematosus, and type 1 diabetes [79-81].
Fulminant type 1 diabetes has been estimated to occur in 0.5 percent of DRESS patients and
may be related to the carriage of human leukocyte antigen (HLA) B62 in Japanese
populations [82].
DIAGNOSTIC APPROACH
When to suspect the diagnosis — DRESS should be suspected in a patient who received a
new drug treatment in the previous two to eight weeks and presents with an acute
cutaneous eruption associated with systemic involvement, such as fever, lymphadenopathy,
eosinophilia, or abnormal organ function tests. In such cases, a careful evaluation of any
exposures to new drugs and, in particular, to high-risk drugs ( table 1) in the previous two
to eight weeks is essential. (See 'Assessment of drug causality' below.)
It is important to recognize that DRESS is a dynamic process, and characteristic features are
not all present concurrently. It is also possible, though uncommon, for patients with DRESS
to have no or minimal cutaneous involvement (<5 percent), absent eosinophilia, and mild,
systemic symptoms or organ involvement [4,44]. In such cases, the diagnosis of DRESS
requires a high degree of suspicion and clinical judgment.
Assessment of drug causality — Detailed information on drug exposures in the months

preceding the illness should be obtained by the patient or caretaker. Two key considerations
in the assessment of drug causality for DRESS are:
● Prolonged latency – The latency between drug exposure and onset of disease is
prolonged. The reaction typically occurs two to eight weeks after drug exposure.
Medications that are taken for less than two weeks or more than three months before
the onset of DRESS are unlikely to be the culprit. In some cases, drugs that have been
stopped prior to onset of disease can still be suspected, if the drug or drug metabolite
is still present in the body due to a long drug half-life or impaired clearance.
● Exposure to high-risk drugs – The majority of DRESS cases are due to a limited
number of medications ( table 1).
Causality may be further supported by positive patch tests and/or in vitro tests (eg,
lymphocyte proliferation assay). (See 'Tests for delayed drug hypersensitivity reactions'
below.)
Laboratory investigations — The initial laboratory evaluation in a patient suspected to

have DRESS is aimed at confirming the diagnosis, excluding other conditions that mimic
DRESS, and evaluating the extent and severity of visceral involvement ( table 3). It
includes:
● Complete blood cell count with differential and peripheral blood smear –
Peripheral eosinophilia >700/microL and the presence of atypical mononuclear cells
support the diagnosis of DRESS. Other abnormalities in the complete blood count, such
as leukocytosis, neutrophilia, lymphocytosis, and monocytosis, may also be present [4].
● Liver function tests – Serum level of alanine aminotransferase (ALT) twice the upper
limit of normal values and/or alkaline phosphatase greater than 1.5 times the upper
limit of normal values on at least two occasions indicate liver involvement [4].
● Kidney function tests – Serum creatinine greater than 1.5 times the base value for the
patient on at least two occasions and/or proteinuria above 1 g/day, hematuria, and
decreased creatinine clearance indicate renal involvement.
● Cardiac enzymes – Cardiac enzymes are performed to exclude cardiac involvement.
● Amylase, lipase – Pancreatic involvement is considered when amylase and lipase are
≥2 times the upper limit of normal values.
● Serology for viral infection:
• HHV-6, HHV-7, Epstein-Barr virus, cytomegalovirus – Testing for human

herpesvirus (HHV) is increasingly performed in patients with suspected DRESS, as
viral reactivation is an observed phenomenon in these patients. Moreover, the
presence of viral infection may be a marker for chronicity as well as a prognostic
marker for disease severity. Testing modalities may include quantitative polymerase
chain reaction (PCR) or paired serologies [30-34]. (See "Clinical manifestations,
diagnosis, and treatment of human herpesvirus 6 infection in adults", section on
'Diagnosis' and "Human herpesvirus 7 infection", section on 'Diagnosis' and
"Infectious mononucleosis", section on 'Detection of EBV virus' and "Overview of
diagnostic tests for cytomegalovirus infection".)
• Viral hepatitis – Serology for viral hepatitis (hepatitis A immunoglobulin M [IgM]

antibody, hepatitis B surface antigen, hepatitis B core IgM antibody, hepatitis C viral
RNA) may be useful in excluding acute viral hepatitis in patients with abnormal liver
function test results. (See "Hepatitis A virus infection in adults: Epidemiology, clinical
manifestations, and diagnosis", section on 'Diagnosis' and "Hepatitis B virus:
Screening and diagnosis" and "Clinical manifestations, diagnosis, and treatment of
acute hepatitis C virus infection in adults", section on 'Diagnosis'.)
Tests for delayed drug hypersensitivity reactions
In vivo tests — Patch testing, intradermal testing, and lymphocyte activation assay may be
used to confirm drug causality:
● Patch testing – Patch testing positivity in patients with DRESS ranges from 30 to 60
percent [83,84]. Test positivity is dependent on the type of drug. It is more commonly
positive in cases due to carbamazepine, beta-blockers, and proton pump inhibitors. It is
invariably negative for allopurinol and sulfasalazine [83,84].
● Intradermal testing – Intradermal testing with a delayed reading has been utilized in
anecdotal reports. Concentrations are usually 10- to 100-fold lower than those
undertaken for immediate immunoglobulin E (IgE)-mediated reactions. Nonetheless,
there is a risk of reaction recurrence [85]. Thus, the test should only be performed in
exceptional circumstances.
In vitro tests — In vitro tests are only performed in specialized centers and largely remain
a research tool. They include:
● Lymphocyte transformation test (LTT) – It measures the proliferation of T cells after

stimulation with a drug in vitro and is best performed during the recovery stage of the
disease [86,87].
● Drug-induced cytokine assays (interferon [IFN]-gamma, tumor necrosis factor [TNF]-

alpha, upregulation of cell activation markers such as CD69).
● Analysis of cytotoxic potential of effector cells (eg, granzyme B, granulysin, CD107).
Positive LTTs have been reported in approximately 50 percent of DRESS cases [86]. The
sensitivity and specificity of the test are 73 and 82 percent, respectively [88].
Drug challenge is contraindicated in the evaluation of the causative drug, due to the
possibility of recurrence of DRESS. However, challenge has been prudently attempted in
specific situations, such as DRESS occurring in the setting of multidrug treatment for HIV
infection or tuberculosis [89].
Imaging studies — Ultrasound and computed tomography (CT) may be required to assess
for internal organ involvement. Echocardiography and cardiac magnetic resonance imaging
(MRI) might be indicated if cardiac involvement is suspected.
Biopsy — A skin biopsy for histopathologic examination should be performed in patients

with suspected DRESS. Liver or kidney biopsy may be performed in patients with severe
organ involvement. (See 'Histopathologic findings' below.)
Histopathologic findings — The cutaneous histopathologic features of DRESS are

heterogeneous and nonspecific [18]. Main histologic reaction patterns associated with
DRESS include interface dermatitis with basal vacuolization (75 percent), eczematous
(spongiotic) pattern (40 to 75 percent), and features of vascular damage with prominent
endothelial cells, perivascular lymphocytic infiltrate, red blood cells extravasation, and vessel
wall destruction (50 percent) [90-93]. Coexistence of more than one reaction is common,
occurring in more than 60 percent of cases [90].
Dermal infiltration of eosinophils is seen in 20 to 70 percent of cases and neutrophils in up to

40 percent. Atypical lymphocytes can be present in up to 30 percent of cases [90]. The
finding of extensive, necrotic keratinocytes is associated with severe disease [35,90,92,93].
Although not routinely performed, biopsy of other organs involved may show nonspecific,
inflammatory patterns:
● Lymph nodes – Histologic features of DRESS lymphadenopathy include partial or

complete effacement of nodal architecture by a polymorphous infiltrate of
immunoblasts, small lymphocytes, eosinophils, and plasma cells. Occasionally, atypical
lymphocytes mimicking lymphoma may be seen [94].
https://www-uptodate-com.bvcscm.a17.csinet.es/contents/drug-reaction-with-eosinophilia-and-systemic-symptoms-dress/print?search=dress&s… 10/52
● Liver – Liver biopsy may demonstrate an acute hepatitis injury pattern with lobular
inflammation, scattered foci of necrotic hepatocytes, and granulomatous infiltrates
containing eosinophils. Portal inflammation and cholestasis may also be seen.
Confluent hepatocyte necrosis and lobular disarray due to inflammation and
regenerative changes are seen in severe cases [95,96].
● Kidney – Renal biopsy may demonstrate tubulointerstitial nephritis with interstitial

edema and infiltrates of lymphocytes, histiocytes, eosinophils, and plasma cells [97].
● Heart – Endomyocardial biopsies are rarely performed. Two patterns may be observed:
hypersensitivity myocarditis (which shows an eosinophilic and mixed, lymphohistiocytic
infiltrate within the myocytes) and acute, necrotizing, eosinophilic myocarditis (which
demonstrates additional features of myocyte necrosis) [57].
Criteria for diagnosis confirmation — The most widely used criteria to confirm or exclude
the diagnosis of DRESS are those included in the Registry of Severe Cutaneous Adverse
Reactions (RegiSCAR) scoring system, based on the main clinical manifestations of DRESS [4]:
● Fever >101.3°F or >38.5°C (core) or >100.4°F or >38°C (axillar)

● Enlarged lymph nodes in at least two different body areas
● Eosinophilia
● Atypical lymphocytes
● Skin involvement (extent, rash suggestive of DRESS, biopsy)
● Organ involvement (eg, at least twofold elevation of liver enzymes on at least two
different days)
● Resolution >15 days
A value between -1 and 2 is assigned to each feature ( table 4). The cumulative score
ranges from -4 to 9 and defines four levels of certainty regarding the diagnosis of DRESS:
excluded, possible, probable, and definite. As some of the variables included in the RegiSCAR
DRESS score may not be available when the patient is first evaluated, the score is most
useful as a retrospective validation of suspected cases.
DIFFERENTIAL DIAGNOSIS
Due to the heterogeneity of clinical presentation, DRESS is often misdiagnosed [98]. The
differential diagnosis of DRESS includes the following:
● Other cutaneous adverse drug reactions – These include exanthematous drug

eruptions, acute generalized exanthematous pustulosis (AGEP), and Stevens-Johnson
syndrome/toxic epidermal necrolysis (SJS/TEN):
• Exanthematous drug reactions typically present with morbilliform/maculopapular

eruptions and mild, systemic symptoms (low-grade fever, pruritus, mild
eosinophilia), but visceral involvement ( picture 2A-B) is usually absent. Moreover,
the latency time between drug exposure and disease onset is usually shorter (5 to
14 days) than for DRESS. (See "Exanthematous (maculopapular) drug eruption".)
• SJS/TEN typically presents with a cutaneous eruption characterized by coalescing,

erythematous macules with atypical target lesions, blisters, erosions, and skin
detachment and is associated with severe, mucosal involvement in multiple sites in
over 90 percent of cases ( picture 3A-C). (See "Stevens-Johnson syndrome and
toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)
• AGEP presents with an extensive eruption of hundreds to thousands of pinpoint,

nonfollicular pustules ( picture 4) a few hours to a few days after the
administration of the offending drug. Systemic involvement may occur in 20 percent
of cases but is typically mild. Although pustules may be present in DRESS, they are
more commonly limited to the head and neck area. (See "Acute generalized
exanthematous pustulosis (AGEP)".)
● Lymphomas – Angioimmunoblastic T cell lymphoma typically presents with acute-

onset, systemic illness characterized by a rash (50 to 60 percent of cases), generalized
lymphadenopathy, hepatosplenomegaly, and B symptoms of fever, night sweats, or
weight loss. The cutaneous histology may not demonstrate the presence of neoplastic
cells. Diagnosis is confirmed via lymph node biopsy. (See "Clinical manifestations,
pathologic features, and diagnosis of angioimmunoblastic T cell lymphoma".)
Sézary syndrome, an aggressive, leukemic variant of cutaneous T cell lymphoma,

typically presents with erythroderma and generalized lymphadenopathy and may
occasionally mimic DRESS. The diagnosis of Sézary syndrome is based on the
evaluation of a skin biopsy for morphology, immunophenotype, and T cell receptor
gene clonality of cellular infiltrates. Evaluation of the peripheral blood with flow
cytometry and clonality studies may be needed to confirm the diagnosis. (See "Clinical
presentation, pathologic features, and diagnosis of Sézary syndrome".)
● Acute cutaneous lupus erythematosus – The acute onset of rash, especially if

widespread, and the frequent association with systemic symptoms and laboratory
abnormalities may occasionally mimic DRESS ( picture 5). The diagnosis of acute
cutaneous lupus erythematosus is confirmed by autoantibody testing and histologic
examination of skin biopsy that demonstrates interface dermatitis with increased
mucin and thickened basement membrane. Direct immunofluorescence may show a
continuous band of granular fluorescence at the dermoepidermal junction. (See
"Overview of cutaneous lupus erythematosus" and "Clinical manifestations and

diagnosis of systemic lupus erythematosus in adults".)
● Hypereosinophilic syndromes – Hypereosinophilic syndromes are characterized by

elevated, peripheral eosinophilia (>1500/microL) and involvement of multiple organs,
such as the heart, gastrointestinal tract, lungs, brain, and kidneys, without an
alternative explanation for the organ damage. Cutaneous manifestations include
eczematous eruptions, erythroderma, urticaria, and angioedema. (See
"Hypereosinophilic syndromes: Clinical manifestations, pathophysiology, and
diagnosis".)
● Viral infections – Examples of viral infections associated with generalized rash that
may mimic DRESS include infectious mononucleosis, cytomegalovirus (CMV) infection,
measles, HIV infection, viral hepatitis, and dengue.
MANAGEMENT
There are no randomized trials evaluating treatments for DRESS, and evidence-based
guidelines are lacking. Because of the high heterogeneity of the clinical manifestations of
DRESS, the approach to management is generally based on the severity of skin and organ
involvement [76,99,100]. Patients with widespread rash and severe, systemic symptoms
should be hospitalized for evaluation and treatment. Organ support and intensive care unit
(ICU) care may be needed. Patients with mild symptoms can be managed in an outpatient
setting with symptomatic treatment and close clinical and laboratory monitoring for possible
organ involvement.
Drug withdrawal, supportive treatment, and monitoring — The identification and

withdrawal of the causative medication is the mainstay of treatment for all patients with
DRESS (see 'Assessment of drug causality' above). Introducing new medications, including
empirical use of antibiotics, should be avoided, if possible. Since the cross-reactivity among
aromatic antiseizure medications is well documented, patients with DRESS triggered by
carbamazepine or other aromatic antiseizure medications should be treated with
nonaromatic agents (eg, valproic acid, topiramate, gabapentin).
Supportive care includes fluid, electrolyte, and nutritional support. Adjunctive measures
include gentle skin care with emollients and warm baths/wet dressings.
Regular clinical, laboratory, and imaging monitoring and timely consultation with specialists
(eg, hepatologist, nephrologist, pulmonologist) are warranted.
Mild disease (no organ involvement or only mild liver involvement) — Patients with
DRESS without clinical, laboratory, or imaging evidence of renal or pulmonary involvement
and those with only modest elevation of liver transaminases (<3 times the upper limit of
normal) can be treated symptomatically [101,102].
For symptomatic relief of pruritus and skin inflammation, we suggest treatment with topical
corticosteroids. High- or super high-potency topical corticosteroids (groups 1 and 2
( table 5)) are applied two to three times a day until disease resolution.
Evidence on the efficacy of topical corticosteroids for the management of DRESS without
severe or life-threatening organ involvement is limited. In small case series, patients with
DRESS without life-threatening organ involvement who were treated with topical
corticosteroids recovered and had a lower incidence of relapse, viral reactivation, and sepsis
compared with patients treated with systemic corticosteroids [76,103].
Severe disease with single or multiple organ involvement
First-line therapy
Systemic glucocorticoids — For patients with severe disease and involvement of the
lungs (dyspnea, abnormal chest radiograph, hypoxemia) or kidneys (creatinine >1.5 times
the basal level and proteinuria or hematuria), we suggest oral glucocorticoids as first-line
therapy. A moderate to high dose (0.5 to 1 mg/kg per day) of prednisone or prednisone
equivalents is given until clinical improvement and normalization of laboratory parameters
are achieved and then slowly tapered over the following 8 to 12 weeks, or longer, to avoid
relapses [101]. An alternative regimen of intravenous methylprednisolone (250 to 500 mg
per day for two to four days) followed by oral prednisolone 1 mg/kg per day tapered over 8
to 12 weeks has also been suggested for severe cases [104,105].
The benefit of systemic glucocorticoids for patients with DRESS and isolated, severe liver
involvement is unproven [49]. Patients with signs of acute liver failure (eg, hepatic
encephalopathy, coagulopathy) need prompt referral to a liver transplant specialist for
further evaluation and care. (See "Drug-induced liver injury", section on 'Management'.)
The efficacy of systemic glucocorticoids for the treatment of DRESS has not been evaluated
in randomized trials. However, there is general consensus among experts on their use for
patients with severe DRESS, particularly for those with renal and/or pulmonary involvement
[45,101,104,106].
As systemic glucocorticoids may increase the risk of cytomegalovirus (CMV) reactivation and
systemic infections, careful monitoring of infectious complications should be performed
[72,76,80,107-109]. (See "Major side effects of systemic glucocorticoids".)
Second-line therapies — Second-line therapies for patients with severe DRESS and organ
involvement include cyclosporine, intravenous immunoglobulins (IVIGs), and other
immunosuppressive agents.
Cyclosporine — Oral cyclosporine at a dose of 3 to 5 mg/kg divided twice daily for

seven days, followed by a taper over the next 7 to 14 days, may be given as a second-line
therapy for patients with DRESS and severe organ involvement who do not respond to
systemic corticosteroids or for patients in whom corticosteroids are contraindicated.
Although evidence remains limited, there are increasing reports on the rapid resolution of
symptoms with a short course of oral cyclosporine [110-113]. In a retrospective study that
included 5 patients with DRESS treated with cyclosporine and 21 patients treated with
systemic corticosteroids, treatment with cyclosporine was associated with a more rapid
resolution of fever, normalization of laboratory parameters (leukocytosis, eosinophilia, and
liver enzymes), and shorter duration of hospitalization [112].
Intravenous immunoglobulin — There is little evidence to support the use of

intravenous immunoglobulins (IVIGs) for DRESS. Although a beneficial effect of IVIG has
been reported in a few adult and pediatric patients [114-116], an open study evaluating the
efficacy of IVIG in six adult patients with DRESS was prematurely stopped due to an excess of
adverse events in five patients, four of whom needed rescue therapy with oral
glucocorticoids [117].
Other immunosuppressive agents — There are anecdotal reports of the use of the
Janus kinase (JAK) inhibitor tofacitinib at a dose of 10 mg/day for the treatment of refractory,
severe DRESS [29,118,119]. The rationale for the use of JAK inhibitors for DRESS is based on
the finding of Janus kinase-signal transducer and activator of transcription (JAK-STAT)
signaling upregulation in DRESS [29]. However, further evidence is needed before tofacitinib
can be recommended for severe DRESS.
In a few isolated case reports, cyclophosphamide has been used in patients with severe
organ involvement refractory to glucocorticoid therapy [120,121].
Antiviral therapy — The routine use of antiviral medication for DRESS is not
recommended because of the spontaneous resolution of viral reactivation in most cases and
concern about the toxicity associated with antiviral agents. However, if there is confirmation
of viral reactivation and evidence of viral-induced organ damage, or viral reactivation is
suspected to be a contributory factor to severe complications (eg, pneumonitis, colitis,
encephalitis), antiviral therapy with ganciclovir or valganciclovir is warranted. (See
"Ganciclovir and valganciclovir: An overview".)
PROGNOSIS AND FOLLOW-UP
Most patients with DRESS recover completely in weeks to months after drug
withdrawal. DRESS survivors should undergo long-term monitoring for the development of
autoimmune sequelae. (See 'Long-term outcomes' above.)
The mortality rate among patients with DRESS is estimated to be between 2 and 10 percent
[4,43-45]. A mortality rate of 3 percent has been reported in a pediatric population [10].
Severe organ involvement and multiorgan failure are the main causes of death. Viral
reactivation of cytomegalovirus (CMV) during the course of the disease and development of
CMV-related complications (eg, hepatitis, colitis) appear to be associated with poorer
outcomes [50,72,107]. (See "Epidemiology, clinical manifestations, and treatment of
cytomegalovirus infection in immunocompetent adults".)
PREVENTION
For primary prevention of DRESS, unnecessary prescribing of high-risk drugs should be

avoided ( table 1) [122]. Genetic screening for human leukocyte antigen (HLA) alleles
known to be associated with increased risk of severe drug reactions in specific populations
may reduce the risk of DRESS ( table 2) [122-124]. This was demonstrated in a Taiwanese
study that included 2926 patients who had an indication for allopurinol therapy, of whom
571 (20 percent) tested positive for HLA-B*58:01 and received an alternative drug. Among
the HLA-B*58:01-negative patients who received allopurinol, no severe cutaneous drug
reactions were reported, although seven cases were expected based on the estimated
historical incidence nationwide [123].
Patients who recover from DRESS should be educated about the need for strict avoidance of
the offending drug and cross-reacting drugs. Moreover, as DRESS survivors may have an
increased risk of reaction to structurally unrelated drugs in the months following the acute
episode, avoidance of any unnecessary drug treatments is also recommended. Drug allergy
labeling needs to be entered in the patient's medical record.
Because of pharmacogenetics susceptibility, avoidance of causative drugs should also be

recommended to family members of patients.
SOCIETY GUIDELINES
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Drug allergy and
hypersensitivity".)
SUMMARY AND RECOMMENDATIONS
● Definition, etiology, and risk factors – Drug reaction with eosinophilia and systemic
symptoms (DRESS) is a rare, potentially life-threatening, drug-induced hypersensitivity
reaction characterized by a cutaneous eruption, hematologic abnormalities,
lymphadenopathy, and/or internal organ involvement. The majority of DRESS cases are
due to antiseizure medications, allopurinol, antibacterial sulfonamides, minocycline,
and vancomycin ( table 1). Association of DRESS with polymorphisms in the HLA
genes has been proven for certain medications in particular at-risk ethnic populations
( table 2). (See 'Etiology and risk factors' above.)
● Latency and clinical presentation – In most patients, the reaction begins two to eight
weeks after the initiation of the causative drug:
• Cutaneous findings – The skin eruption starts as a maculopapular eruption that

may progress to a coalescing erythema ( picture 1A-C). Additional findings include
purpura, infiltrated plaques, pustules, exfoliative dermatitis, and target-like lesions.
• Systemic symptoms – Systemic symptoms may include fever ≥101.3°F or ≥38.5°C,

lymphadenopathy, hematologic abnormalities (eg, leukocytosis, eosinophilia,
neutrophilia, atypical lymphocytosis), and signs and symptoms related with visceral
involvement ( table 3). (See 'Clinical presentation' above.)
• Organ involvement – Involvement of one or multiple organs occurs in most

patients with DRESS. Liver injury is most common, occurring in up to 90 percent of
cases. Acute interstitial nephritis, interstitial pneumonia, and, less commonly,
myocarditis can also occur. (See 'Organ involvement' above.)
● Diagnosis – The diagnosis of DRESS is based on a combination of clinical features

(cutaneous findings ( picture 1A-C), systemic symptoms), history of exposure to
drugs and, particularly, to high-risk drugs ( table 1) in the previous two to eight
weeks, and laboratory and imaging findings ( table 3). Criteria to confirm or exclude
the diagnosis of DRESS are those included in the Registry of Severe Cutaneous Adverse
Reactions (RegiSCAR) scoring system ( table 4).
● Treatment – Identification and withdrawal of the causative drug and supportive

treatment are the mainstays of treatment for patients with DRESS. Regular monitoring
for organ involvement is warranted (see 'Drug withdrawal, supportive treatment, and
monitoring' above):
• For patients with mild disease without organ involvement or only modest elevation
of liver transaminases (<3 times the upper limit of normal), we suggest symptomatic
treatment of skin inflammation and pruritus with topical corticosteroids (Grade 2C).
High or ultra-potent topical corticosteroids (groups 1 and 2 ( table 5)) are applied
two to three times per day until resolution of the skin eruption. (See 'Mild disease
(no organ involvement or only mild liver involvement)' above.)
• For patients with severe disease and involvement of the lungs or kidneys, we
suggest oral glucocorticoids as first-line therapy (Grade 2C). A moderate to high
dose (0.5 to 1 mg/kg per day) of prednisone or prednisone equivalents is given until
clinical improvement and normalization of laboratory parameters are achieved.
Systemic glucocorticoids should be tapered slowly over 8 to 12 weeks. Oral
cyclosporine is an alternative treatment for patients with severe organ involvement
who do not respond to glucocorticoids or for patients in whom corticosteroids are
contraindicated. (See 'Severe disease with single or multiple organ involvement'
above.)
● Prognosis – Most patients with DRESS recover completely in weeks to months after
drug withdrawal. They should also undergo long-term monitoring for the development
of autoimmune sequelae. (See 'Prognosis and follow-up' above.)
● Prevention – DRESS survivors should be educated about the need for strict avoidance
of the causative drug and cross-reacting drugs. (See 'Prevention' above.)
Use of UpToDate is subject to the Terms of Use.
REFERENCES
1. Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug

hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms:
DRESS). Semin Cutan Med Surg 1996; 15:250.
2. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: Part I. Clinical perspectives. J Am
Acad Dermatol 2013; 68:693.e1.
3. Shiohara T, Inaoka M, Kano Y. Drug-induced hypersensitivity syndrome (DIHS): a

reaction induced by a complex interplay among herpesviruses and antiviral and
antidrug immune responses. Allergol Int 2006; 55:1.
4. 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; 169:1071.
5. Wolfson AR, Zhou L, Li Y, et al. Drug Reaction with Eosinophilia and Systemic Symptoms
(DRESS) Syndrome Identified in the Electronic Health Record Allergy Module. J Allergy
Clin Immunol Pract 2019; 7:633.
6. Muller P, Dubreil P, Mahé A, et al. Drug Hypersensitivity Syndrome in a West-Indian

population. Eur J Dermatol 2003; 13:478.
7. Lee HY, Tay LK, Thirumoorthy T, Pang SM. Cutaneous adverse drug reactions in
hospitalised patients. Singapore Med J 2010; 51:767.
8. Teo Y, Walsh S, Creamer D. Cutaneous adverse drug reaction referrals to a liaison
dermatology service. Br J Dermatol 2017; 177:e141.
9. Fiszenson-Albala F, Auzerie V, Mahe E, et al. A 6-month prospective survey of cutaneous

drug reactions in a hospital setting. Br J Dermatol 2003; 149:1018.
10. Kim GY, Anderson KR, Davis DMR, et al. Drug reaction with eosinophilia and systemic
symptoms (DRESS) in the pediatric population: A systematic review of the literature. J
Am Acad Dermatol 2020; 83:1323.
11. Knowles SR, Shapiro LE, Shear NH. Anticonvulsant hypersensitivity syndrome: incidence,
prevention and management. Drug Saf 1999; 21:489.
12. Kano Y, Shiohara T. The variable clinical picture of drug-induced hypersensitivity

syndrome/drug rash with eosinophilia and systemic symptoms in relation to the
eliciting drug. Immunol Allergy Clin North Am 2009; 29:481.
13. Lam BD, Miller MM, Sutton AV, et al. Vancomycin and DRESS: A retrospective chart
review of 32 cases in Los Angeles, California. J Am Acad Dermatol 2017; 77:973.
14. Ng CY, Yeh YT, Wang CW, et al. Impact of the HLA-B(*)58:01 Allele and Renal Impairment
on Allopurinol-Induced Cutaneous Adverse Reactions. J Invest Dermatol 2016; 136:1373.
15. Chung WH, Chang WC, Lee YS, et al. Genetic variants associated with phenytoin-related
severe cutaneous adverse reactions. JAMA 2014; 312:525.
16. Maubec E, Wolkenstein P, Loriot MA, et al. Minocycline-induced DRESS: evidence for
accumulation of the culprit drug. Dermatology 2008; 216:200.
17. Phillips EJ, Chung WH, Mockenhaupt M, et al. Drug hypersensitivity: pharmacogenetics
and clinical syndromes. J Allergy Clin Immunol 2011; 127:S60.
18. Cho YT, Yang CW, Chu CY. Drug Reaction with Eosinophilia and Systemic Symptoms
(DRESS): An Interplay among Drugs, Viruses, and Immune System. Int J Mol Sci 2017; 18.
19. Konvinse KC, Trubiano JA, Pavlos R, et al. HLA-A*32:01 is strongly associated with
vancomycin-induced drug reaction with eosinophilia and systemic symptoms. J Allergy
Clin Immunol 2019; 144:183.
20. Rieder MJ, Shear NH, Kanee A, et al. Prominence of slow acetylator phenotype among
patients with sulfonamide hypersensitivity reactions. Clin Pharmacol Ther 1991; 49:13.
21. Shear NH, Spielberg SP, Grant DM, et al. Differences in metabolism of sulfonamides
predisposing to idiosyncratic toxicity. Ann Intern Med 1986; 105:179.
22. Hansel K, Bellini V, Bianchi L, et al. Drug reaction with eosinophilia and systemic
symptoms from ceftriaxone confirmed by positive patch test: An immunohistochemical
study. J Allergy Clin Immunol Pract 2017; 5:808.
23. Ye YM, Hur GY, Kim SH, et al. Drug-specific CD4(+) T-cell immune responses are
responsible for antituberculosis drug-induced maculopapular exanthema and drug
reaction with eosinophilia and systemic symptoms syndrome. Br J Dermatol 2017;
176:378.
24. Chung WH, Pan RY, Chu MT, et al. Oxypurinol-Specific T Cells Possess Preferential TCR
Clonotypes and Express Granulysin in Allopurinol-Induced Severe Cutaneous Adverse
Reactions. J Invest Dermatol 2015; 135:2237.
25. Hanafusa T, Azukizawa H, Matsumura S, Katayama I. The predominant drug-specific T-

cell population may switch from cytotoxic T cells to regulatory T cells during the course
of anticonvulsant-induced hypersensitivity. J Dermatol Sci 2012; 65:213.
26. Shiohara T, Mizukawa Y. Drug-induced hypersensitivity syndrome (DiHS)/drug reaction

with eosinophilia and systemic symptoms (DRESS): An update in 2019. Allergol Int 2019;
68:301.
27. Morito H, Ogawa K, Fukumoto T, et al. Increased ratio of FoxP3+ regulatory T cells/CD3+
T cells in skin lesions in drug-induced hypersensitivity syndrome/drug rash with
eosinophilia and systemic symptoms. Clin Exp Dermatol 2014; 39:284.
28. Takahashi R, Kano Y, Yamazaki Y, et al. Defective regulatory T cells in patients with
severe drug eruptions: timing of the dysfunction is associated with the pathological
phenotype and outcome. J Immunol 2009; 182:8071.
29. Kim D, Kobayashi T, Voisin B, et al. Targeted therapy guided by single-cell transcriptomic
analysis in drug-induced hypersensitivity syndrome: a case report. Nat Med 2020;
26:236.
30. Picard D, Janela B, Descamps V, et al. Drug reaction with eosinophilia and systemic
symptoms (DRESS): a multiorgan antiviral T cell response. Sci Transl Med 2010; 2:46ra62.
31. Tohyama M, Hashimoto K, Yasukawa M, et al. Association of human herpesvirus 6
reactivation with the flaring and severity of drug-induced hypersensitivity syndrome. Br
J Dermatol 2007; 157:934.
32. Kano Y, Hiraharas K, Sakuma K, Shiohara T. Several herpesviruses can reactivate in a
severe drug-induced multiorgan reaction in the same sequential order as in graft-
versus-host disease. Br J Dermatol 2006; 155:301.
33. Descamps V, Valance A, Edlinger C, et al. Association of human herpesvirus 6 infection

with drug reaction with eosinophilia and systemic symptoms. Arch Dermatol 2001;
137:301.
34. Sekiguchi A, Kashiwagi T, Ishida-Yamamoto A, et al. Drug-induced hypersensitivity

syndrome due to mexiletine associated with human herpes virus 6 and cytomegalovirus
reactivation. J Dermatol 2005; 32:278.
35. Skowron F, Bensaid B, Balme B, et al. Drug reaction with eosinophilia and systemic
symptoms (DRESS): clinicopathological study of 45 cases. J Eur Acad Dermatol Venereol
2015; 29:2199.
36. Kano Y, Seishima M, Shiohara T. Hypogammaglobulinemia as an early sign of drug-
induced hypersensitivity syndrome. J Am Acad Dermatol 2006; 55:727.
37. Kano Y, Inaoka M, Shiohara T. Association between anticonvulsant hypersensitivity

syndrome and human herpesvirus 6 reactivation and hypogammaglobulinemia. Arch
Dermatol 2004; 140:183.
38. Mardivirin L, Lacroix A, Delebassée S, et al. Augmentation de la réplication in vitro de

l’herpèsvirus humain 6 en présence de valproate de sodium. Virologie 2007; 11:151.
39. Kuntz-Simon G, Obert G. Sodium valproate, an anticonvulsant drug, stimulates human

cytomegalovirus replication. J Gen Virol 1995; 76 ( Pt 6):1409.
40. Mardivirin L, Valeyrie-Allanore L, Branlant-Redon E, et al. Amoxicillin-induced flare in

patients with DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms): report
of seven cases and demonstration of a direct effect of amoxicillin on Human
Herpesvirus 6 replication in vitro. Eur J Dermatol 2010; 20:68.
41. Roujeau JC, Dupin N. Virus Reactivation in Drug Reaction with Eosinophilia and Systemic
Symptoms (Dress) Results from a Strong Drug-Specific Immune Response. J Allergy Clin
Immunol Pract 2017; 5:811.
42. Soria A, Bernier C, Veyrac G, et al. Drug reaction with eosinophilia and systemic
symptoms may occur within 2 weeks of drug exposure: A retrospective study. J Am Acad
Dermatol 2020; 82:606.
43. Chen YC, Chiu HC, Chu CY. Drug reaction with eosinophilia and systemic symptoms: a
retrospective study of 60 cases. Arch Dermatol 2010; 146:1373.
44. Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J
Med 2011; 124:588.
45. Chiou CC, Yang LC, Hung SI, et al. Clinicopathological features and prognosis of drug
rash with eosinophilia and systemic symptoms: a study of 30 cases in Taiwan. J Eur Acad
Dermatol Venereol 2008; 22:1044.
46. Wu X, Yang F, Chen S, et al. Clinical, Viral and Genetic Characteristics of Drug Reaction
with Eosinophilia and Systemic Symptoms (DRESS) in Shanghai, China. Acta Derm
Venereol 2018; 98:401.
47. Lin IC, Yang HC, Strong C, et al. Liver injury in patients with DRESS: A clinical study of 72
cases. J Am Acad Dermatol 2015; 72:984.

48. Lee T, Lee YS, Yoon SY, et al. Characteristics of liver injury in drug-induced systemic
hypersensitivity reactions. J Am Acad Dermatol 2013; 69:407.
49. Ichai P, Laurent-Bellue A, Saliba F, et al. Acute Liver Failure/Injury Related to Drug
Reaction With Eosinophilia and Systemic Symptoms: Outcomes and Prognostic Factors.
Transplantation 2017; 101:1830.
50. Eshki M, Allanore L, Musette P, et al. Twelve-year analysis of severe cases of drug
reaction with eosinophilia and systemic symptoms: a cause of unpredictable multiorgan
failure. Arch Dermatol 2009; 145:67.
51. Ang CC, Wang YS, Yoosuff EL, Tay YK. Retrospective analysis of drug-induced
hypersensitivity syndrome: a study of 27 patients. J Am Acad Dermatol 2010; 63:219.
52. Yang CY, Chen CH, Deng ST, et al. Allopurinol Use and Risk of Fatal Hypersensitivity
Reactions: A Nationwide Population-Based Study in Taiwan. JAMA Intern Med 2015;
175:1550.
53. Chung WH, Chang WC, Stocker SL, et al. Insights into the poor prognosis of allopurinol-
induced severe cutaneous adverse reactions: the impact of renal insufficiency, high
plasma levels of oxypurinol and granulysin. Ann Rheum Dis 2015; 74:2157.
54. Taweesedt PT, Nordstrom CW, Stoeckel J, Dumic I. Pulmonary Manifestations of Drug
Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A Systematic
Review. Biomed Res Int 2019; 2019:7863815.
55. Kano Y, Ishida T, Hirahara K, Shiohara T. Visceral involvements and long-term sequelae
in drug-induced hypersensitivity syndrome. Med Clin North Am 2010; 94:743.
56. Matsuno O. Drug-induced interstitial lung disease: mechanisms and best diagnostic
approaches. Respir Res 2012; 13:39.
57. Bourgeois GP, Cafardi JA, Groysman V, Hughey LC. A review of DRESS-associated
myocarditis. J Am Acad Dermatol 2012; 66:e229.
58. Thongsri T, Chularojanamontri L, Pichler WJ. Cardiac involvement in DRESS syndrome.

Asian Pac J Allergy Immunol 2017; 35:3.
59. Ozisik L, Tanriover MD, Saka E. Autoimmune Limbic Encephalitis and Syndrome of
Inappropriate Antidiuretic Hormone Secretion Associated with Lamotrigine-induced
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome. Intern Med
2016; 55:1393.
60. Maniyar F, Rooney C, Lily O, Bazaz R. Anticonvulsant hypersensitivity syndrome

presenting as aseptic meningitis. J Neurol 2009; 256:1190.
61. Sakuma K, Kano Y, Fukuhara M, Shiohara T. Syndrome of inappropriate secretion of

antidiuretic hormone associated with limbic encephalitis in a patient with drug-induced
hypersensitivity syndrome. Clin Exp Dermatol 2008; 33:287.
62. Gaha M, Landry D, Bélair M, et al. DRESS syndrome: cerebral vasculitic-like presentation.
Neuroradiology 2015; 57:1015.
63. Santosa A, Yang SS, Chandran NS. DRESS Masquerading as Acute Cholecystitis. Am J
Med 2020; 133:e56.
64. Do-Pham G, Charachon A, Duong TA, et al. Drug reaction with eosinophilia and systemic
symptoms and severe involvement of digestive tract: description of two cases. Br J
Dermatol 2011; 165:207.
65. Ben m'rad M, Leclerc-Mercier S, Blanche P, et al. Drug-induced hypersensitivity
syndrome: clinical and biologic disease patterns in 24 patients. Medicine (Baltimore)
2009; 88:131.
66. Karuppannasamy D, Andavar R, Arumugam J, Muthuvel K. DRESS Syndrome Secondary
to Carbamazepine Therapy Presenting with Bilateral Acute Anterior Uveitis and Angle
Closure Glaucoma. J Ophthalmic Vis Res 2019; 14:382.
67. Funck-Brentano E, Duong T, Family D, et al. [Auto-immune thyroiditis and drug reaction
with eosinophilia and systemic symptoms (DRESS) associated with HHV-6 viral
reactivation]. Ann Dermatol Venereol 2011; 138:580.
68. Cookson H, Creamer D, Walsh S. Thyroid dysfunction in drug reaction with eosinophilia
and systemic symptoms (DRESS): an unusual manifestation of systemic drug
hypersensitivity. Br J Dermatol 2013; 168:1130.
69. Descamps V. Drug reaction with eosinophilia and systemic symptoms and thyroiditis:
human herpesvirus-6, the possible common link. Br J Dermatol 2013; 169:952.
70. Carter Febres M, Abbott J, Cipriano SD, et al. Drug reaction with eosinophilia and
systemic symptoms (DRESS)-associated hemophagocytic lymphohistiocytosis (HLH), an
important and underrecognized HLH mimic: A case report. Pediatr Blood Cancer 2021;
68:e28657.
71. Massey J, Kumar K, Ng K, et al. Skeletal myositis as the sole feature of relapsing drug
reaction with eosinophilia and systemic symptoms syndrome. Ann Allergy Asthma
Immunol 2017; 118:726.
72. Mizukawa Y, Hirahara K, Kano Y, Shiohara T. Drug-induced hypersensitivity
syndrome/drug reaction with eosinophilia and systemic symptoms severity score: A
useful tool for assessing disease severity and predicting fatal cytomegalovirus disease. J
Am Acad Dermatol 2019; 80:670.
73. Asano Y, Kagawa H, Kano Y, Shiohara T. Cytomegalovirus disease during severe drug
eruptions: report of 2 cases and retrospective study of 18 patients with drug-induced
hypersensitivity syndrome. Arch Dermatol 2009; 145:1030.
74. Tetart F, Picard D, Janela B, et al. Prolonged evolution of drug reaction with eosinophilia
and systemic symptoms: clinical, virologic, and biological features. JAMA Dermatol 2014;
150:206.
75. Picard D, Vellar M, Janela B, et al. Recurrence of drug-induced reactions in DRESS
patients. J Eur Acad Dermatol Venereol 2015; 29:801.
76. Funck-Brentano E, Duong TA, Bouvresse S, et al. Therapeutic management of DRESS: a
retrospective study of 38 cases. J Am Acad Dermatol 2015; 72:246.
77. Santiago LG, Morgado FJ, Baptista MS, Gonçalo M. Hypersensitivity to antibiotics in drug
reaction with eosinophilia and systemic symptoms (DRESS) from other culprits. Contact
Dermatitis 2020; 82:290.
78. Pichler WJ, Srinoulprasert Y, Yun J, Hausmann O. Multiple Drug Hypersensitivity. Int Arch
Allergy Immunol 2017; 172:129.
79. Chen YC, Chang CY, Cho YT, et al. Long-term sequelae of drug reaction with eosinophilia
and systemic symptoms: a retrospective cohort study from Taiwan. J Am Acad Dermatol
2013; 68:459.
80. Ushigome Y, Kano Y, Ishida T, et al. Short- and long-term outcomes of 34 patients with
drug-induced hypersensitivity syndrome in a single institution. J Am Acad Dermatol
2013; 68:721.
81. Lian BS, Busmanis I, Lee HY. Relapsing Course of Sulfasalazine-Induced Drug Reaction
with Eosinophilia and Systemic Symptoms (DRESS) Complicated by Alopecia Universalis
and Vitiligo. Ann Acad Med Singap 2018; 47:492.
82. Onuma H, Tohyama M, Imagawa A, et al. High frequency of HLA B62 in fulminant type 1
diabetes with the drug-induced hypersensitivity syndrome. J Clin Endocrinol Metab
2012; 97:E2277.
83. Barbaud A, Collet E, Milpied B, et al. A multicentre study to determine the value and
safety of drug patch tests for the three main classes of severe cutaneous adverse drug
reactions. Br J Dermatol 2013; 168:555.
84. Santiago F, Gonçalo M, Vieira R, et al. Epicutaneous patch testing in drug
hypersensitivity syndrome (DRESS). Contact Dermatitis 2010; 62:47.
85. Soria A, Hamelin A, de Risi Pugliese T, et al. Are drug intradermal tests dangerous to
explore cross-reactivity and co-sensitization in DRESS? Br J Dermatol 2019; 181:611.
86. Pichler WJ, Tilch J. The lymphocyte transformation test in the diagnosis of drug
hypersensitivity. Allergy 2004; 59:809.
87. Kano Y, Hirahara K, Mitsuyama Y, et al. Utility of the lymphocyte transformation test in
the diagnosis of drug sensitivity: dependence on its timing and the type of drug
eruption. Allergy 2007; 62:1439.
88. Cabañas R, Calderón O, Ramírez E, et al. Sensitivity and specificity of the lymphocyte
transformation test in drug reaction with eosinophilia and systemic symptoms causality
assessment. Clin Exp Allergy 2018; 48:325.
89. Lehloenya RJ, Isaacs T, Nyika T, et al. Early high-dose intravenous corticosteroids rapidly
arrest Stevens Johnson syndrome and drug reaction with eosinophilia and systemic
symptoms recurrence on drug re-exposure. J Allergy Clin Immunol Pract 2021; 9:582.
90. Ortonne N, Valeyrie-Allanore L, Bastuji-Garin S, et al. Histopathology of drug rash with
eosinophilia and systemic symptoms syndrome: a morphological and phenotypical
study. Br J Dermatol 2015; 173:50.
91. Cho YT, Liau JY, Chang CY, et al. Co-existence of histopathological features is
characteristic in drug reaction with eosinophilia and systemic symptoms and correlates
with high grades of cutaneous abnormalities. J Eur Acad Dermatol Venereol 2016;
30:2077.
92. Chi MH, Hui RC, Yang CH, et al. Histopathological analysis and clinical correlation of
drug reaction with eosinophilia and systemic symptoms (DRESS). Br J Dermatol 2014;
170:866.
93. Walsh S, Diaz-Cano S, Higgins E, et al. Drug reaction with eosinophilia and systemic
symptoms: is cutaneous phenotype a prognostic marker for outcome? A review of
clinicopathological features of 27 cases. Br J Dermatol 2013; 168:391.
94. Brown JR, Skarin AT. Clinical mimics of lymphoma. Oncologist 2004; 9:406.
95. Kleiner DE. The pathology of drug-induced liver injury. Semin Liver Dis 2009; 29:364.
96. Lens S, Crespo G, Carrión JA, et al. Severe acute hepatitis in the DRESS syndrome: Report
of two cases. Ann Hepatol 2010; 9:198.
97. Praga M, González E. Acute interstitial nephritis. Kidney Int 2010; 77:956.
98. Lee HY, Walsh S, Creamer D. Initial presentation of DRESS: often misdiagnosed as
infections. Arch Dermatol 2012; 148:1085.
99. 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; 30:229.
100. Descamps V, Ben Saïd B, Sassolas B, et al. [Management of drug reaction with
eosinophilia and systemic symptoms (DRESS)]. Ann Dermatol Venereol 2010; 137:703.
101. Shiohara T, Kano Y. Drug reaction with eosinophilia and systemic symptoms (DRESS):
incidence, pathogenesis and management. Expert Opin Drug Saf 2017; 16:139.
102. Shiohara T, Kano Y, Hirahara K, Aoyama Y. Prediction and management of drug reaction
with eosinophilia and systemic symptoms (DRESS). Expert Opin Drug Metab Toxicol
2017; 13:701.
103. Uhara H, Saiki M, Kawachi S, et al. Clinical course of drug-induced hypersensitivity

syndrome treated without systemic corticosteroids. J Eur Acad Dermatol Venereol 2013;
27:722.
104. Natkunarajah J, Goolamali S, Craythorne E, et al. Ten cases of drug reaction with
eosinophilia and systemic symptoms (DRESS) treated with pulsed intravenous
methylprednisolone. Eur J Dermatol 2011; 21:385.
105. Roujeau JC, Haddad C, Paulmann M, Mockenhaupt M. Management of nonimmediate
hypersensitivity reactions to drugs. Immunol Allergy Clin North Am 2014; 34:473.
106. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: Part II. Management and
therapeutics. J Am Acad Dermatol 2013; 68:709.e1.
107. Wong YJ, Choo KJL, Soh JXJ, Tan CK. Cytomegalovirus (CMV) hepatitis: an uncommon
complication of CMV reactivation in drug reaction with eosinophilia and systemic
symptoms. Singapore Med J 2018; 59:112.
108. Tohyama M, Hashimoto K, Oda F, et al. Influence of corticosteroid therapy on viral
reactivation in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia
and systemic symptoms. J Dermatol 2020; 47:476.
109. Arakawa M, Kakuto Y, Ichikawa K, et al. Allopurinol hypersensitivity syndrome
associated with systemic cytomegalovirus infection and systemic bacteremia. Intern
Med 2001; 40:331.
110. Zuliani E, Zwahlen H, Gilliet F, Marone C. Vancomycin-induced hypersensitivity reaction
with acute renal failure: resolution following cyclosporine treatment. Clin Nephrol 2005;
64:155.
111. Kirchhof MG, Wong A, Dutz JP. Cyclosporine Treatment of Drug-Induced Hypersensitivity
Syndrome. JAMA Dermatol 2016; 152:1254.
112. Nguyen E, Yanes D, Imadojemu S, Kroshinsky D. Evaluation of Cyclosporine for the
Treatment of DRESS Syndrome. JAMA Dermatol 2020; 156:704.
113. Kuschel SL, Reedy MS. Cyclosporine treatment of drug reaction with eosinophilia and
systemic symptoms (DRESS) syndrome: a case report and brief review of the literature.
Pract Dermatol 2018; 2018:41.
114. Singer EM, Wanat KA, Rosenbach MA. A case of recalcitrant DRESS syndrome with
multiple autoimmune sequelae treated with intravenous immunoglobulins. JAMA
Dermatol 2013; 149:494.
115. Fields KS, Petersen MJ, Chiao E, Tristani-Firouzi P. Case reports: treatment of nevirapine-
associated dress syndrome with intravenous immune globulin (IVIG). J Drugs Dermatol
2005; 4:510.
116. Marcus N, Smuel K, Almog M, et al. Successful Intravenous Immunoglobulin Treatment
in Pediatric Severe DRESS Syndrome. J Allergy Clin Immunol Pract 2018; 6:1238.
117. Joly P, Janela B, Tetart F, et al. Poor benefit/risk balance of intravenous immunoglobulins
in DRESS. Arch Dermatol 2012; 148:543.
118. Damsky WE, Vesely MD, Lee AI, et al. Drug-induced hypersensitivity syndrome with
myocardial involvement treated with tofacitinib. JAAD Case Rep 2019; 5:1018.
119. Chowdhury M, Azari BM, Desai NR, Ahmad T. A Novel Treatment for a Rare Cause of
Cardiogenic Shock. JACC Case Rep 2020; 2:1461.
120. Laban E, Hainaut-Wierzbicka E, Pourreau F, et al. Cyclophosphamide therapy for

corticoresistant drug reaction with eosinophilia and systemic symptoms (DRESS)
syndrome in a patient with severe kidney and eye involvement and Epstein-Barr virus
reactivation. Am J Kidney Dis 2010; 55:e11.
121. Esposito AJ, Murphy RC, Toukatly MN, et al. Acute kidney injury in allopurinol-induced
DRESS syndrome: a case report of concurrent tubulointerstitial nephritis and kidney-
limited necrotizing vasculitis . Clin Nephrol 2017; 87:316.
122. Lee HY, Ariyasinghe JT, Thirumoorthy T. Allopurinol hypersensitivity syndrome: a
preventable severe cutaneous adverse reaction? Singapore Med J 2008; 49:384.
123. Ko TM, Tsai CY, Chen SY, et al. Use of HLA-B*58:01 genotyping to prevent allopurinol
induced severe cutaneous adverse reactions in Taiwan: national prospective cohort
study. BMJ 2015; 351:h4848.
124. Ponzo MG, Miliszewski M, Kirchhof MG, et al. HLA-B*58:01 Genotyping to Prevent Cases
of DRESS and SJS/TEN in East Asians Treated with Allopurinol-A Canadian Missed
Opportunity [Formula: see text]. J Cutan Med Surg 2019; 23:595.
Topic 16420 Version 36.0
GRAPHICS
Drugs implicated in DRESS [1-10]
High-risk drugs
Allopurinol
Aromatic antiepileptic agents:
Carbamazepine
Phenytoin
Lamotrigine
Oxcarbazepine
Phenobarbital
Sulfonamides:
Sulfasalazine
Dapsone
Trimethoprim-sulfamethoxazole
Sulfadiazine
Vancomycin
Minocycline
Nevirapine
Antituberculosis agents:
Rifampicin
Ethambutol
Isoniazid
Pyrazinamide
Mexiletine
Lower-risk drugs
Beta-lactams:
Amoxicillin
Ampicillin
Piperacillin
Others:
NSAIDs (celecoxib, ibuprofen, diclofenac)
Olanzapine
Fluoxetine
Imatinib
Sorafenib
Vemurafenib
Omeprazole
Raltegravir
DRESS: drug reaction with eosinophilia and systemic symptoms; NSAID: nonsteroidal anti-
inflammatory drug.
References:
1. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: Part I. Clinical perspectives. J Am Acad Dermatol 2013;
68:693.e1.
2. Shiohara T, Inaoka M, Kano Y. Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex
interplay among herpesviruses and antiviral and antidrug immune responses. Allergol Int 2006; 55:1.
3. 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;
169:1071.
4. Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J Med 2011; 124:588.
5. Lam BD, Miller MM, Sutton AV, et al. Vancomycin and DRESS: A retrospective chart review of 32 cases in Los
Angeles, California. J Am Acad Dermatol 2017; 77:973.
6. Coster A, Aerts O, Herman A, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome
caused by first-line antituberculosis drugs: Two case reports and a review of the literature. Contact Dermatitis
2019; 81:325.
7. Bourneau-Martin D, Leclech C, Jamet A, et al. Omeprazole-induced drug reaction with eosinophilia and systemic
symptoms (DRESS). Eur J Dermatol 2014; 24:413.
8. Peuvrel L, Quéreux G, Saint-Jean M, et al. Profile of vemurafenib-induced severe skin toxicities. J Eur Acad
Dermatol Venereol 2016; 30:250.
9. Kim DK, Lee SW, Nam HS, et al. A Case of Sorafenib-induced DRESS Syndrome in Hepatocelluar Carcinoma.
Korean J Gastroenterol 2016; 67:337.
10. Perry ME, Almaani N, Desai N, et al. Raltegravir-induced Drug Reaction with Eosinophilia and Systemic Symptoms
(DRESS) syndrome - implications for clinical practice and patient safety. Int J STD AIDS 2013; 24:639.
Graphic 129506 Version 1.0
HLA alleles associated with susceptibility to DRESS [1-5]
Drug HLA/genetic variant Population
Allopurinol B*5801 Han Chinese, European, Thai,

Korean
Carbamazepine A*3101 European, Japanese, Han

Chinese
Dapsone B*1301 Chinese
Nevirapine DRB1*01:01 African, Asian, European
CW*8, B14 European
B*35 Asian
Phenytoin B*13:01, B*51:01 Han Chinese, Thai
HLA-A*24:02 European
Vancomycin A*32:01 European
HLA: human leukocyte antigen; DRESS: drug reaction with eosinophilia and systemic symptoms.
References:
1. Phillips EJ, Chung WH, Mockenhaupt M, et al. Drug hypersensitivity: pharmacogenetics and clinical syndromes. J
Allergy Clin Immunol 2011; 127:S60.
2. Konvinse KC, Trubiano JA, Pavlos R, et al. HLA-A*32:01 is strongly associated with vancomycin-induced drug
reaction with eosinophilia and systemic symptoms. J Allergy Clin Immunol 2019; 144:183.
3. Chen CB, Abe R, Pan RY, et al. An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity. J
Immunol Res 2018; 2018:6431694.
4. Oussalah A, Yip V, Mayorga C, et al. Genetic variants associated with T cell-mediated cutaneous adverse drug
reactions: A PRISMA-compliant systematic review-An EAACI position paper. Allergy 2020; 75:1069.
5. Chang CJ, Chen CB, Hung SI, et al. Pharmacogenetic Testing for Prevention of Severe Cutaneous Adverse Drug
Reactions. Front Pharmacol 2020; 11:969.
Drug reaction with eosinophilia and systemic symptoms

(DRESS)
Confluent morbilliform skin eruption with follicular accentuation in a patient with

drug reaction with eosinophilia and systemic symptoms (DRESS).
Reproduced with permission from: www.visualdx.com. Copyright VisualDx. All rights reserved.

symptoms
Diffuse and confluent skin eruption in a patient with DRESS.
DRESS: drug reaction with eosinophilia and systemic symptoms.
Reproduced with permission from: www.visualdx.com. Copyright VisualDx. All rights

reserved.

symptoms
Diffuse, confluent, infiltrated, erythematous skin eruption in a

patient with DRESS.
DRESS: drug reaction with eosinophilia and systemic symptoms.

reserved.
Recommended laboratory and imaging investigations in patients with

suspected DRESS
Confirmation of Exclusion of alternative Assessment of organ

diagnosis diagnosis involvement
CBC with differential Blood cultures Minimal screening:

including search for Antinuclear antibodies Liver function tests
atypical lymphocytes Serology for viral hepatitis* Serum creatinine,
Inflammation markers Lymph node biopsy* urinary protein and cells
PCR for HHV-6, HHV-7, Creatine kinase,
CMV, EBV troponin
ECG
Additional investigations:
Prothrombin time/INR
CT scan*
Sonography*
Endoscopy*
Biopsy*
DRESS: drug reaction with eosinophilia and systemic symptoms; CBC: complete blood count;
PCR: polymerase chain reaction; HHV: herpesvirus; CMV: cytomegalovirus; EBV: Epstein-Barr
virus; ECG: electrocardiogram; INR: international normalized ratio; CT: computed tomography.
* Secondary investigations based upon suspected organ involvement.
Scoring system for the diagnosis of DRESS
Score
Clinical parameters Comments
–1 0 1
Fever ≥101.3°F (38.5°C) No/unknown Yes
Lymphadenopathy No/unknown Yes >1 cm, at least 2 sites
Eosinophilia ≥0.7 × 10 9 or No/unknown Yes Score 2 points of ≥1.5 ×

≥10% if leucopenia 10 9
Atypical lymphocytes No/unknown Yes
Skin rash
Rash suggestive of No Unknown Yes Suggestive features: ≥2

DRESS facial edemas, purpura,
infiltration, desquamation
Extent ≥50% of BSA No/unknown Yes
Skin biopsy suggestive of No Yes/unknown

DRESS
Organ involvement No Yes 1 point for each organ

involvement, maximum
score: 2
Disease duration ≥15 days No/unknown Yes
Exclusion of other causes No/unknown Yes 1 point if 3 of the following

tests are performed and
are negative: HAV, HBV,
HCV, mycoplasma,
chlamydia, ANA, blood
culture
Total score:
<2: Excluded
2 to 3: Possible
4 to 5: Probable
≥6: Definite
DRESS: drug reaction with eosinophilia and systemic symptoms; BSA: body surface area; HAV:
hepatitis A virus; HBV: hepatitis B virus; HCV: hepatitis C virus; ANA: antinuclear antibody.
Adapted from:
1. Kardaun SH, Sidoroff A, Valeyrie-Allanore L, et al. Variability in the clinical pattern of cutaneous side-effects of
drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol 2007; 156:609.
2. 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;
169:1071.
Exanthematous (morbilliform) drug eruption
Profuse eruption of macules and papules on the back of a patient

with exanthematous drug eruption.
Exanthematous (morbilliform) drug eruption
Numerous small, discrete papules on the back of a patient with

exanthematous drug eruption.
Toxic epidermal necrolysis
Multiple bullae and areas of denuded epidermis are present.

reserved.
Toxic epidermal necrolysis
Diffuse erythema and large areas of denuded epidermis are present.

reserved.
Mucosal changes in Stevens-Johnson syndrome/toxic

epidermal necrolysis
Changes similar to those observed in SJS/TEN can also be observed in

erythema multiforme majus.
SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis.
Acute generalized exanthematous pustulosis

(AGEP)
Confluent nonfollicular pustules superimposed on edematous

erythema in a 46-year-old woman with AGEP. A skin biopsy showed
intracorneal pustules with numerous neutrophils and neutrophilic
infiltration of the epidermis and upper dermis.
Copyright © Vincent CB Lin, MD, Dermatlas; http://www.dermatlas.org.
Systemic lupus erythematosus
Diffuse, erythematous eruption on the back of a patient with acute systemic lupus erythematosus.
Comparison of representative topical corticosteroid preparations

(classified according to the United States system)
Available
Brand names strength(s),
Potency Vehicle
Corticosteroid (United percent
group* type/form
States) (except as
noted)
Super-high Betamethasone Ointment Diprolene 0.05

potency dipropionate, (optimized)
(group 1) augmented
Gel, lotion [Generic only] 0.05
Clobetasol Cream, ointment Temovate 0.05

propionate
Gel, solution [Generic only] 0.05
(scalp)
Cream Tasoprol 0.05
Cream (emollient Temovate E ¶ 0.05

base)
Lotion, shampoo, Clobex 0.05

spray aerosol
Foam aerosol Olux, Olux-E, 0.05

Tovet
Lotion Impeklo 0.05
Ointment Clobetavix 0.05
Shampoo Clodan 0.05
Solution (scalp) Cormax ¶ 0.05
Diflucortolone Ointment, oily Nerisone Forte 0.3

valerate (not cream (United
available in Kingdom, others)
United States)
Fluocinonide Cream Vanos 0.1
Flurandrenolide Tape (roll) Cordran 4 mcg/cm 2
Halobetasol Lotion Ultravate 0.05

propionate
Cream, ointment [Generic only] 0.05
Foam Lexette 0.05
High potency Amcinonide Ointment Cyclocort ¶ , 0.1

(group 2) Amcort ¶
Betamethasone Ointment Diprosone ¶ 0.05

dipropionate
Cream, Diprolene AF 0.05
augmented
formulation (AF)
Clobetasol Cream Impoyz 0.025

propionate
Desoximetasone Cream, ointment, Topicort 0.25

spray
Gel Topicort 0.05
Diflorasone Ointment ApexiCon ¶ , 0.05

diacetate Florone ¶
Cream ApexiCon E 0.05

(emollient)
Fluocinonide Cream, gel, Lidex ¶ 0.05

ointment,
solution
Halcinonide Cream, ointment, Halog 0.1

solution
Halobetasol Lotion Bryhali 0.01

propionate
High potency Amcinonide Cream Cyclocort ¶ , 0.1

(group 3) Amcort ¶
Lotion Amcort ¶ 0.1
Betamethasone Cream Diprosone ¶ 0.05

dipropionate (hydrophilic
emollient)
Betamethasone Ointment Valisone ¶ 0.1

valerate
Foam Luxiq 0.12
Desoximetasone Cream, ointment Topicort, Topicort 0.05

LP ¶
Diflorasone Cream Florone ¶ , 0.05

diacetate Psorcon
Diflucortolone Cream, oily Nerisone (United 0.1

valerate (not cream, ointment Kingdom, others)
available in
United States)
Fluocinonide Cream (aqueous Lidex-E ¶ 0.05

emollient)
Fluticasone Ointment Cutivate ¶ 0.005

propionate
Mometasone Ointment Elocon ¶ 0.1

furoate
Triamcinolone Cream, ointment Aristocort HP ¶ , 0.5

acetonide Kenalog ¶ ,
Triderm
Medium Betamethasone Spray Sernivo 0.05

potency dipropionate
(group 4)
Clocortolone Cream Cloderm 0.1
pivalate
Fluocinolone Ointment Synalar 0.025

acetonide
Flurandrenolide Ointment Cordran 0.05
Fluticasone Cream Cutivate ¶ 0.05

propionate
Hydrocortisone Ointment Westcort ¶ 0.2

valerate
Mometasone Cream, lotion, Elocon ¶ 0.1

furoate solution
Triamcinolone Cream Kenalog ¶ , 0.1

acetonide Triderm
Ointment Kenalog ¶ 0.1
Ointment Trianex, Tritocin 0.05
Aerosol spray Kenalog 0.2 mg per 2

second spray
Dental paste Oralone 0.1
Lower-mid Betamethasone Lotion Diprosone ¶ 0.05

potency dipropionate
(group 5)
Betamethasone Cream Beta-Val ¶ , 0.1
valerate Valisone ¶
Desonide Ointment DesOwen ¶ , 0.05

Tridesilon ¶
Gel Desonate, DesRx 0.05
Fluocinolone Cream Synalar 0.025

acetonide
Flurandrenolide Cream, lotion Cordran, Nolix 0.05
Fluticasone Lotion Beser, Cutivate 0.05

propionate
Hydrocortisone Cream, lotion Locoid, Locoid 0.1

butyrate Lipocream
Ointment, [Generic only] 0.1

solution
Hydrocortisone Cream Pandel 0.1

probutate
Hydrocortisone Cream Westcort ¶ 0.2

valerate
Prednicarbate Cream Dermatop ¶ 0.1

(emollient),
ointment
Triamcinolone Lotion Kenalog ¶ 0.1

acetonide
Ointment Kenalog ¶ 0.025
Low potency Alclometasone Cream, ointment Aclovate ¶ 0.05

(group 6) dipropionate
Betamethasone Lotion Beta-Val ¶ , 0.1

valerate Valisone ¶
Desonide Cream DesOwen, 0.05

Tridesilon
Lotion DesOwen ¶ , 0.05

LoKara ¶
Foam Verdeso 0.05
Fluocinolone Cream, solution Synalar 0.01

acetonide
Shampoo Capex 0.01
Oil Δ Derma- 0.01

Smoothe/FS
Body, Derma-
Smoothe/FS
Scalp
Triamcinolone Cream, lotion Kenalog ¶ , 0.025

acetonide Aristocort ¶
Least potent Hydrocortisone Cream Ala-Cort, 2.5

(group 7) (base, ≥2%) Hytone ¶ ,
Nutracort ¶
Ointment Hytone ¶ 2.5
Lotion Hytone ¶ , Ala 2

Scalp, Scalacort
DK
Solution Texacort 2.5
Hydrocortisone Ointment Cortaid ¶ , 1

(base, <2%) Cortizone 10,
Hytone ¶ ,
Nutracort ¶
Cream Ala-Cort, 1
Cortaid ¶ ,
Cortizone 10,
Hytone ¶ ,
KeriCort,
Synacort ¶
Gel Cortizone 10 1
Lotion Aquanil HC, 1

Cortizone 10,
Sarnol-HC
Spray Cortaid ¶ 1
Solution Cortaid ¶ , 1
Noble ¶ , Scalp
Relief, Scalpicin
Cream, ointment Cortaid ¶ 0.5
Cream Instacort 0.5
Hydrocortisone Cream MiCort-HC ¶ 2.5

acetate
Cream Vanicream HC 1
Lotion Nucort 2
* Listed by potency according to the United States classification system: group 1 is the most
potent, group 7 is the least potent. Other countries use a different classification system with only
4 or 5 groups.
¶ Inactive United States brand name for specific product; brand may be available outside United
States. This product may be available generically in the United States.
Δ 48% refined peanut oil.
Data from:
1. Lexicomp Online. Copyright © 1978-2023 Lexicomp, Inc. All Rights Reserved.
2. Tadicherla S, Ross K, Shenefelt D. Topical corticosteroids in dermatology. Journal of Drugs in Dermatology 2009;
12:1093.
3. U.S. Food & Drug Administration Approved Drug Products with Therapeutic Equivalence (Orange Book). Available
at: https://www.accessdata.fda.gov/scripts/cder/ob/default.cfm (Accessed on June 18, 2017).
4. The British Association of Dermatologists' information on topical corticosteroids – established and alternative
proprietary names, potency, and discontinuation. British Association of Dermatologists. Available at:
https://www.bad.org.uk/shared/get-file.ashx?id=3427&itemtype=document (Accessed on April 26, 2021).
Contributor Disclosures
Haur Yueh Lee, MBBS, MRCP, M Med (Int Med), FAMS No relevant financial relationship(s) with
ineligible companies to disclose. Maja Mockenhaupt, MD, PhD Grant/Research/Clinical Trial Support:
Biogen [Cutaneous adverse reactions]; Boehringer Ingelheim [Severe cutaneous adverse reactions];
Janssen Pharmaceuticals [Cutaneous adverse reactions]. Consultant/Advisory Boards: Bial [Cutaneous
adverse reactions]. All of the relevant financial relationships listed have been mitigated. Rosamaria
Corona, MD, DSc No relevant financial relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) - UpToDate

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) - UpToDate

Uploaded by

Copyright:

Available Formats

19/1/23, 15:27 Drug reaction with eosinophilia and systemic symptoms (DRESS) - UpToDate

Official reprint from UpToDate®

Drug reaction with eosinophilia and systemic

● (See "Drug eruptions".)

ETIOLOGY AND RISK FACTORS

Pharmacogenetic susceptibility — Pharmacogenetic studies have found an association

● Genetic polymorphisms – Polymorphisms in genes encoding drug metabolizing

DRESS is considered a T cell-mediated hypersensitivity reaction. Although the exact

Drug-specific immune response — The role of drug-specific immune response in the

A single-cell RNA sequencing study demonstrated enhanced Janus kinase-signal transducer

Reactivation of Herpesviridae — Reactivation of viruses from the Herpesviridae family (eg,

Mucosal involvement can be seen in up to 50 percent of cases. However, it is typically mild, in

detachment is rarely seen.

Systemic symptoms and laboratory abnormalities — Systemic symptoms associated with

● Fever ≥101.3°F or ≥38.5°C (75 to 90 percent)

● Lymphadenopathy (54 to 65 percent)

• Eosinophilia >700/microL (82 to 95 percent)

Pulmonary involvement — The symptoms of pulmonary involvement, which occurs in up

Cardiac involvement — Cardiac involvement (2 to 20 percent of cases) is a severe

Gastrointestinal involvement is uncommon. It includes gastrointestinal bleeding,

Rare complications include myositis, thyroid dysfunction, uveitis, and hemophagocytic

Long-term outcomes — Various autoimmune sequelae have been noted in DRESS

Assessment of drug causality — Detailed information on drug exposures in the months

Laboratory investigations — The initial laboratory evaluation in a patient suspected to

● Cardiac enzymes – Cardiac enzymes are performed to exclude cardiac involvement.

● Serology for viral infection:

• HHV-6, HHV-7, Epstein-Barr virus, cytomegalovirus – Testing for human

• Viral hepatitis – Serology for viral hepatitis (hepatitis A immunoglobulin M [IgM]

Tests for delayed drug hypersensitivity reactions

● Lymphocyte transformation test (LTT) – It measures the proliferation of T cells after

● Drug-induced cytokine assays (interferon [IFN]-gamma, tumor necrosis factor [TNF]-

● Analysis of cytotoxic potential of effector cells (eg, granzyme B, granulysin, CD107).

Biopsy — A skin biopsy for histopathologic examination should be performed in patients

Histopathologic findings — The cutaneous histopathologic features of DRESS are

Dermal infiltration of eosinophils is seen in 20 to 70 percent of cases and neutrophils in up to

● Lymph nodes – Histologic features of DRESS lymphadenopathy include partial or

● Kidney – Renal biopsy may demonstrate tubulointerstitial nephritis with interstitial

● Fever >101.3°F or >38.5°C (core) or >100.4°F or >38°C (axillar)

● Other cutaneous adverse drug reactions – These include exanthematous drug

• Exanthematous drug reactions typically present with morbilliform/maculopapular

• SJS/TEN typically presents with a cutaneous eruption characterized by coalescing,

• AGEP presents with an extensive eruption of hundreds to thousands of pinpoint,

● Lymphomas – Angioimmunoblastic T cell lymphoma typically presents with acute-

Sézary syndrome, an aggressive, leukemic variant of cutaneous T cell lymphoma,

● Acute cutaneous lupus erythematosus – The acute onset of rash, especially if

"Overview of cutaneous lupus erythematosus" and "Clinical manifestations and

● Hypereosinophilic syndromes – Hypereosinophilic syndromes are characterized by

Drug withdrawal, supportive treatment, and monitoring — The identification and

Severe disease with single or multiple organ involvement

Cyclosporine — Oral cyclosporine at a dose of 3 to 5 mg/kg divided twice daily for

Intravenous immunoglobulin — There is little evidence to support the use of

PROGNOSIS AND FOLLOW-UP

For primary prevention of DRESS, unnecessary prescribing of high-risk drugs should be

Because of pharmacogenetics susceptibility, avoidance of causative drugs should also be

SUMMARY AND RECOMMENDATIONS

• Cutaneous findings – The skin eruption starts as a maculopapular eruption that

• Systemic symptoms – Systemic symptoms may include fever ≥101.3°F or ≥38.5°C,

• Organ involvement – Involvement of one or multiple organs occurs in most

● Diagnosis – The diagnosis of DRESS is based on a combination of clinical features

● Treatment – Identification and withdrawal of the causative drug and supportive

Use of UpToDate is subject to the Terms of Use.

1. Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug

3. Shiohara T, Inaoka M, Kano Y. Drug-induced hypersensitivity syndrome (DIHS): a

6. Muller P, Dubreil P, Mahé A, et al. Drug Hypersensitivity Syndrome in a West-Indian

Phenytoin B13:01, B51:01 Han Chinese, Thai