This case report describes a 24-year-old man who presented with fever, rash, abdominal pain, and vomiting. He had been taking carbamazepine for seizures. His symptoms and lab results met the criteria for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as drug hypersensitivity syndrome. DRESS is caused by certain drugs and is characterized by fever, rash, eosinophilia, and involvement of internal organs like the liver or lungs. Carbamazepine was withdrawn and steroids were started, leading to improvement. The report reviews the characteristics, diagnosis, and treatment of DRESS, noting it is important to identify the causative drug and avoid re-

1. Drug Reaction with Eosinophilia and Systemic Symptoms
(DRESS)

2. Case Report
CASE REPORT
A twenty-four year old man presented with complaints
of high grade fever for 10 days associated with an
erythematous rash all over the body for 7 days. He also had
recurrent abdominal pain and vomitings, but no history of
hematemesis, malena, constipation, loose stools, urinary
symptoms or joint pains. He was managed at a local
hospital initially and treated on the lines of abdominal
infection with I/V antibiotics but there was no relief and he
was subsequently brought to IAH for further management.
Past history was significant for an episode of
generalised tonic clonic seizure one month prior to the
present illness and a neurological assessment was done at
that time. MRI head had revealed a granulomatous lesion,
probably neurocysticercosis. He was started on Tab.
Carbamazepine thereafter.
On presentation,the patient was conscious,looked
toxic, dehydrated, Temp.101ºF, pulse 112/min, reg, BP
130/80 mm Hg, Resp 20/min, SPo2 94% on room air.
Icterus was present and he had a diffusely erythematous
maculopapular rash all over the body with areas of
desquamation.There were no oral ulcers, no pallor,
cyanosis, clubbing or palpable lymph nodes. Pitting edema
was present at the ankle. The systemic examination
revealed absent breath sounds at bases, hepatomegaly and
free fluid in the abdomen with generalised tenderness, the
bowel sounds were sluggish.
The patient was started on supportive treatment with I/
V fluids to maintain hydration, PPIs, antiemetics and Vit
K. Preliminary investigations revealed eosinophilic
leucocytosis-TLC 27000 /cumm, with 24% eosinophils,
deranged liver function tests-conjugated hyper-
bilirubinemia, Total bil. 19.35mg/dL, direct bil 17.29 mg/
dL, AST 535 IU/L, ALT 656 IU/L, ALP 458 IU/L, GGTP
484 IU/L, Total prot. 4.1gm/dL, Alb 2.3 gm/dL, A/G ratio
1.3, INR was 2.6. The renal profile revealed pre renal
azotemia with hyperuricemia and hypocalcemia-urea 125
mg/dL, creat. 0.9 mg/dL, uric acid 13.6 mg/dL, S.calcium
6.8 mg/dL. The chest X ray and 2D Echo were normal,
ultrasound abdomen revealed hepatosplenomegaly,
ascites but no collaterals or pancreatic pathology. Ascitic
fluid analysis revealed a transudative fluid and X-ray
abdomen was non contributory. Cultures were
unremarkable as were viral hepatitis markers, Dengue,
malaria Leptospira and typhoid tests. The serial LFTs
showed a worsening trend with continuous spiking fever.
Dermatology opinion was taken and a suspicion of
drug related rash was thought of. Carbamazepine was
gradually withdrawn and Levetiracetam was started. A
repeat HEV serology was weakly positive, hence
initiation of steroids was withheld. A bone marrow
aspiration and biopsy ruled out eosinophilic
leukemia.Vasculitic markers and a skin biopsy were non
contributory.
There was a gradual improvement in the patient’s
condition with settling of fever, rash, decrease in
leucocytosis and hepatic enzymes, and he was sent home.
77 Apollo Medicine, Vol. 7, No. 1, March 2010
DRUG REACTION WITH EOSINOPHILIAAND SYSTEMIC SYMPTOMS (DRESS)
Vijay Kumar Aneja*, Gitanjali Kochar** and Neelam Bisht***
*Senior Consultant, **Attending Physician, ***Associate Consultant, Department of Internal Medicine,
Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India.
Correspondence to: Dr Vijay Kumar Aneja, Senior Consultant Internal Medicine, Indraprastha Apollo Hospitals,
Sarita Vihar, New Delhi 110076, India.
Severe skin adverse drug reactions can result in death. Toxic epidermal necrolysis (TEN) has the highest
mortality (30-35%); Stevens-Johnson syndrome and transitional forms correspond to the same syndrome, but
with less extensive skin detachment and a lower mortality (5-15%). Hypersensitivity syndrome, sometimes
called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), has a mortality rate evaluated at
about 10%. It is characterised by fever, rash and internal organ involvement. Prompt diagnosis is vital, along
with identification and early withdrawal of suspect medicines and avoidance of re-exposure to the responsible
agent is essential. Cross-reactivity to structurally-related syndrome caused by Carbamazepine medicines is
common, thus first-degree relatives may be predisposed to developing this syndrome.We report a case of
DRESS secondary to use of Carbamazepine.
Key words: Drug reaction with eosinophilia and systemic symptoms.

3. Apollo Medicine, Vol. 7, No. 1, March 2010 78
Case Report
However on follow up, the bilirubin continued to rise with
intermittent spikes of fever, a repeat HEV serology was
negative and oral prednisolone was started. Following this
intervention, the patient became afebrile and liver
functions normalised. The steroid was tapered over a
period of 4 weeks.
This patient’s clinical picture satisfies the criteria for
the diagnosis of DRESS syndrome (Drug rash with
eosinophilia and systemic symptoms). The symptoms
began more than 3 weeks after starting the offending drug-
Carbamazepine, in our patient, with persistence of
symptoms 2 weeks after discontinuing it,associated with
fever, rash, leucocytosis, eosinophilia and deranged liver
function tests.
REVIEW OF LITERATURE
A systemic allergic reaction to anticonvulsant therapy
was first described in 1950 and was named anticonvulsant
hypersensitivity syndrome when associated with
phenytoin therapy. It has since been known as drug
hypersensitivity syndrome, and is now more often referred
to as DRESS syndrome, when it involves a case of “drug
rash with eosinophilia and systemic symptoms” [1,2].
DRESS syndrome is a specific, severe, idiosyncratic
drug reaction characterized by a skin rash with fever,
facial edema, lymphadenopathy, and visceral involvement
(hepatitis, pneumonitis, myocarditis, nephritis, and
colitis). The diagnosis can be difficult, because many of
the clinical features can be nonspecific, and the syndrome
often mimics infectious, neoplastic, or rheumatologic
conditions [3-6].
The diagnosis of DRESS syndrome involves 3 criteria:
(i) Drug-induced skin eruption, (ii) Eosinophilia 1.5
×109/L, or atypical lymphocytes, and (iii) At least 1 of the
following systemic abnormalities: enlarged lymph nodes
at least 2 cm in diameter, hepatitis, interstitial
nephropathy, interstitial lung disease, or myocardial
involvement.
A variety of hypersensitivity responses are responsible
for most cutaneous reactions to drugs. The term DRESS
syndrome usually refers to a specific, severe, idiosyncratic
reaction, defined by a widespread and long-lasting
papulopustular or erythematous skin eruption often
progressing to exfoliative dermatitis, with fever,
lymphadenopathy, and visceral involvement (hepatitis,
pneumonitis, myocarditis, periarditis, nephritis). Blood
alterations are also rather characteristic with eosinophilia
in about 90% and mononucleosis in about 40% of cases.
The symptoms of DRESS syndrome usually begin 1 to 8
weeks after exposure to the offending drug.
Approximately 50% of patients will have hepatitis, 30%
will have eosinophilia, 10% will have nephritis and 10%
will have pneumonitis. Drugs that commonly induce
DRESS syndrome include phenobarbitol, carbamazepine,
phenytoin, lamotrigine, minocycline, sulfonamides,
allopurinol, modafinil and dapsone [6].
Incidence/prevalence
For phenytoin, carbamazepine, and phenobarbital, the
incidence of DRESS has been estimated to 1 reaction per
5,000 to 10,000 exposures.
Etiology/risk factors
By definition, drugs are the causal agent.
Anticonvulsants, sulfonamides, dapsone, allopurinol,
minocycline and gold salts are among the most frequent
culprit drugs.
Medicines more often reported to cause drug
hypersensitivity syndrome
Abacavir Dapsone Nevirapine
Allopurinol Diltiazem Oxicam NSAIAs
Atenolol Gold salts Phenobarbitone
Azathioprine Isoniazid Phenytoin
Captopril Lamotrogine Sulphasalazine
Carbamazepine Mexiletine Sulphonamides
Clomipramine Minocycline Trimethoprim
Detoxification defects have been implicated in the
pathophysiology of this syndrome, with an inherited
component. Slow acetylation is probably one of the risk
factors. A role of viral co-infection is also suspected
(specifically, a reactivation of the herpes virus HHV6) [8-
10].
Diagnosis
DRESS syndrome is a clinical diagnosis and there is
some controversy in the literature on what criteria should
be used to diagnose it. Some dermatologists believe it
would better be called Drug-induced Hypersensitivity
Syndrome (DIH).
SA Japanese consensus group developed criteria for
what they call DIHS which includes:
• Maculopapular rash that occurs more than 3 weeks
after starting certain drugs (Fig.1).
• Prolonged clinical symptoms 2 weeks after stopping
the drug.

4. Case Report
79 Apollo Medicine, Vol. 7, No. 1, March 2010
• Fever more than 38° C.
• Liver enzyme abnormalities (alanine amino-
transferase >100 U/ L), or other organ involvement.
• At least one leukocyte abnormality = leukocytosis >
11 × 1000/mm2, atypical leukocytosis >5%, or
eosinophilia >1.5 × 1000/mm2
• Lymphadenopathy
• HHV-6 reactivitation
Prognosis
DRESS is potentially life-threatening. The mortality
rate is estimated at near 10%. In other cases, recovery is
usually total. Rash and hepatitis may persist for weeks;
some cases persist for months.
TREATMENT
Acute period
DRESS syndrome must be promptly recognized and
all potential culprit drugs withdrawn. The typical delay
between beginning the administration of a drug and the
onset of the reaction is two to six weeks.
Systemic corticosteroids are often used (0.5 to 1 mg/
kg). This therapy rapidly improves symptoms and
laboratory measurements, but its impact on the long term
disease course is not known. Controlled clinical trials are
lacking. Relapses of rash and hepatitis may occur as
corticosteroids are tapered. A chronic HHV6 activation
promoted by systemic steroids could explain these
relapses [10,11].
Systemic steroids are used only for patients with life-
threatening visceral manifestations such as insterstitial
pneumonitis or nephrirtis. In milder cases, topical steroids
improve the skin manifestations. Interferon has been used
in a few cases of long-lasting DRESS. This is not enough
to allow appropriate evaluation. Successful use of IV
immune globulin in nevirapine-induced DRESS
syndrome has been reported, as well as N-acetylcysteine
(Acetadote, Mucomyst) in a patient with sulfasalazine-
induced DRESS syndrome [12,13].
When the skin rash results in exfoliative dermatitis,
supportive care consists of warming the environmental
temperature and using local antiseptics and topical
corticosteroids. If the erythroderma is severe, the
cutaneous blood flow is significantly increased; cardiac
failure may occur in elderly patients or those with prior
cardiac disease and should be carefully monitored and
treated. Oral antipyretics and topical corticosteroids are
helpful to decrease this risk.
Prevention of recurrence
To distinguish the culprit drug among several
suspected drugs, drug administration timing and its
temporal relationship to the onset of the syndrome must be
evaluated in detail. Patch tests and in-vitro lymphocyte
tests have been used, but the sensitivity and specificity of
these tests are variable, depending on the drug.
Cross-reactions are frequent between the three main
aromatic anticonvulsants (phenytoin, carbamazepine,
phenobarbital), and all three must be avoided by the
patient if one has been causative. It may be difficult to find
a safe alternative anticonvulsant therapy.
As for TEN/SJS, first-degree relatives should be
alerted to their elevated risk of such reactions to the same
drug(s).
CONCLUSION
DRESS syndrome is a multisystem, potentially life-
threatening condition associated with certain drugs and
infectious agents in predisposed individuals. It is
imperative to discontinue the causative medication and
avoid reexposure. If an anticonvulsant is the etiology, it is
important to avoid exposure to other aromatic
anticonvulsants.
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Fig.1. Maculopapular rash in DRESS

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Case Report
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