DOI: 10.1111/jdv.

12346 JEADV

SHORT REPORT

Dress syndrome induced by levetiracetam

K. Eleni*
Department of Dermatology, Thriassio General Hospital, Athens, Greece
*Correspondence: K. Eleni. E-mail: klimi1961@hotmail.com

Abstract
Background The tremendous increase in the use of drugs has considerably increased their side effects.
Objectives The aim of this work is to demonstrate Dress syndrome induced by levetiracetam an anti-epileptic drug.
Methods We describe a skin eruption observed in an-hospitalized in an intensive care unit patient who received leveti-
racetam.
Results According to morphology of the rash and the laboratory findings the rash fulfills the criteria for Dress syn-
drome.
Conclusion Levetiracetam may induce Dress syndrome.
Received: 23 September 2013; Accepted: 13 November 2013

Conflict of interest
None declared.

Funding sources
None declared.

A 53-year-old man was admitted in the Intensive care Unit of
our Hospital for severe cerebral haemorrhage due to uncon-
trolled hypertension. The day of the admission (14-08-2013) lev-
etiracetam 500 mg twice daily was started. Sixteen days after
initiation of the drug (30-08-2013), the patient developed a skin
rash on his face, back, upper arms and abdomen. The rash con-
sisted of erythematous plaques separated by areas of healthy skin
(Figs 1,2). Neither detachment of the epidermis was noticed
nor lesions on mucous membranes. Fever (38.2 °C) and severe
rectal haemorrhage accompanied the rash (Fig. 3). The patient
necessitated two blood transfusions although no predisposing
factors such as haemorrhoids were present on rectal examina-
tion. Significant leucocytosis (28 000 mm³) with marked eosin-
ophilia – eosinophils 50% of the total blood count
(14 860 mm³) were present from the first day of the appearance
of the rash. Liver enzymes were also elevated SGOT = 101 IU,
SGPT = 172 IU. These clinical and laboratory findings were
suggestive of Dress syndrome. Steroid therapy was started at a
dose of 1 mg methylprednisolone per kilogramme. This led to
complete regression of the rectal haemorrhage 4 days later

Figure 1 Rash on the abdomen. Figure 2 Rash on the right thigh.

JEADV 2015, 29, 377–378 © 2014 European Academy of Dermatology and Venereology
378
Figure 3 Detail of the rash.
followed by complete resolution of the rash 10 days after cessa-
tion of the drug. No flares during the steroid tapering period
were noted. The eosinophilic blood count and liver enzymes
returned to normal 9 days following cessation of the drug dur-
ing the steroid tapering period. Detection of Herpes Virus 6
reactivation was not performed due to lack of reagent.
Discussion
Dress syndrome is a skin eruption induced mainly by antiepilep-
tic drugs such as phenytoin, phenobarbital and carbamazepine
and aromatic structure containing anticonvulsants while
non-aromatic antiepileptics appear to be safe. Dress syndrome
may be also induced by allopurinol, non-steroidal anti-inflam-
matory drugs, angiotensin enzyme inhibitors and antibiotics
such as tetracyclines or rarely b – lactams derivatives.1 Reactiva-
tion of Herpes Virus 6 following administration of the responsi-
ble drug plays a major role in the pathogenesis of the
syndrome.1 Immunosuppression also favours the appearance of
the syndrome as in the case of our patient hospitalized in an
Intensive care unit. The immunologic mechanism consists of
diminution of circulating immunoglobulins and expansion of a
clonal population of stimulated lymphocytes that are seques-
trated in the skin and are responsible for the clinical aspect of
JEADV 2015, 29, 377–378
Eleni
the syndrome. HLAb1301 and HLA-A3201 have also been found
to be related with Dress syndrome in Japan.1
The diagnostic criteria for Dress syndrome are the following:1
1 Maculopapular rash developing 3 days after starting therapy
with a limited number of drugs.
2 Rersistent clinical findings after drug withdrawal.
3 Fever (>38 °C).
4 Hepatic abnormalities,
5 Leucocyte abnormalities (at least one present) (i) Leucocyto-
sis (>11 000/mm³), (ii) atypical lymphocytosis (5%), (iii)
Eosinophilia (>1500/mm³).
6 HHV-6 reactivation.
The treatment of choice consists of intravenous administra-
tion of steroids at a dose of 1–1.5 mg/kg of prednisone or equiv-
alent maintained until complete resolution of the rash then
tapered slowly. Alternatively, immunoglobulins can be used to
compensate for the immunosuppression accompanying the syn-
drome and also for their anti-inflammatory effect. Our patient
fulfils four of the criteria of Dress Syndrome as maculopapular
rash, hepatic and leucocytic abnormalities as well as eosinophilia
are present 16 days after introduction of levetiracetam. To our
knowledge this is the second case of Dress syndrome induced by
levetiracetam, the first being that of G

omez-Zorrilla S and others
published in the Ann of Pharmacotherapy.2 In addition rectal
haemorrhage – a very rare complication of Dress syndrome as it
has been described within colitis by Kano3 and others – has
responded to steroid therapy and totally regressed the fourth day
following initiation of steroids.
References
1 Criado PR, Criado RFJ, Avancini JM, Santi CG. Drug reaction with Eosin-
ophilia and Systemic Symptoms (DRESS)/Drug-induced Hypersensitivity
Syndrome (DIHS): a review of current concepts. An Bras Dermatol 2012;
87: 435–449.
2 G
omez-Zorrilla S, Ferraz AV, Pedr

os C, Lemus M, Pe~ na C. Levetiracetam-
induced drug reaction with eosinophilia and systemic symptoms syn-
drome. Ann Pharmacother 2012; 46: 7–8.
3 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: 743–759.
© 2014 European Academy of Dermatology and Venereology