Probable Dress Syndrome: A Case of Drug Hypersensitivity

in Young Man

Vera Madonna Lumbantoruan1*, Edison Harianja2

1Department of Dermato-Venereology, Faculty of Medicine, Mulawarman University, Samarinda East Kalimantan and

Samarinda Medika Citra Hospital, Samarinda East Kalimantan, Indonesia

2Department of Clinical Pathology Samarinda Medika Citra Hospital, Samarinda East Kalimantan, Indonesia

*Corresponding author

Keywords: DRESS syndrome, RegiSCAR, steroid systemic

Abstract: Drug reaction with eosinophilia and systemic symptoms (DRESS) is one of drug hypersensitivity reaction.

This condition shows a broad spectrum of clinical manifestations and severity. RegiSCAR scoring system is

one of the diagnostic criteria exist for the diagnosis DRESS syndrome. The objective of this case report is to

present a case of Probable DRESS syndrome without eosinophilia as one of Drug induced Severe Cutaneous

Adverse Reactions (SCARs) in a young man. A 23 years old man admitted to hospital with generalized

cutaneous rash and blood laboratory abnormality after consumed cefadroxyl, paracetamol and allopurinol for

2 weeks. Diagnosis Probable DRESS syndrome was made using RegiSCAR scoring system. Treatment with

prolonged steroid systemic showed good clinical and laboratory result.



1 INTRODUCTION

Drug induced Severe Cutaneous Adverse Reactions

(SCARs) include drug reaction with eosinophilia and

systemic symptoms (DRESS), Acute Generalized

Exanthematous Pustulosis (AGEP) and Stevens-

Johnson Syndrome - Toxic Epidermal Necrolisis

(SJS-TEN). DRESS syndrome is a rare case of drug

reaction, comes with extensive rash, haemotology

abnormalities and systemic involvement. This

condition could be fatal with high mortality rate if it

not handled immediately (Waseem et al, 2016;

Choudhary et al, 2013).

Clinical manifestations in DRESS Syndrome is

occuring about 2-8 weeks after introduction of the

causative drug. Pruritic maculopapular and purpura

cutaneous rash, with edema on fasial and extremities,

fever and periferal lymphadenopathies are the usual

symptoms of DRESS syndrome. Eosinophilia with

atypical lymphocytes, elevated liver enzymes and the

renal involvement were usually found in DRESS

syndrome (Choudhary et al, 2013; Watanabe, 2018).

Making diagnosis for DRESS syndrome could be a

challenging for the clinicians since the clinical

manifestations are not immediately appeared after

introduction of causative drugs (Choudhary et al,

2013). The diagnosis of DRESS syndrome is mainly

clinical and clinician must consider the latency period

and the diversity of signs and symptoms. Use of the

term DRESS has been sometimes doubtful, because

eosinophilia is not constantly found in clinical

finding and the cutaneous and systemic signs are

variable (Um et al, 2010). Making the right

differential diagnosis of the type of SCARs is

important since treatment, follow up and prognosis of

different SCARs may not be the same (Casagrada et

al, 2017). It is essential to consider this diagnosis

since the life-threatening potential of DRESS

syndrome is high and mortality is estimated as

about10 percents (Choudhary et al 2013). The

International study group investigating severe

cutaneous reactions (SCAR) has developed

RegiSCAR as one of diagnostic criteria for DRESS

syndrome (Waseem et al, 2016).

The objective of this case report is to present a case

of Probable DRESS syndrome without eosinophilia

as one of Drug induced Severe Cutaneous Adverse

Reactions (SCARs) in a young man.

Lumbantoruan, V. and Harianja, E.

Probable Dress Syndrome: A Case of Drug Hypersensitivity in Young Man.

DOI: 10.5220/0009991104410444

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 441-444

ISBN: 978-989-758-469-5

441

2 CASE

A 23 years-old man was admitted to hospital with

three days history of generalized rash, starting on the

face and then extending to the trunk and lower

extremities. He also complained of swelling and

erosion on the lips. From anamnesis there is history

of fever 3 weeks before. He went to a clinic and

doctor gave him antibiotic cefadroxyl and

paracetamol. In addition he consumed allopurinol by

himself. After 2 weeks consumed the medications, he

realized had skin rash appeared on the face. He

immediately stopped consumed all of the pills but

rash still widespread to the trunk and ekstremities,

and also he got swelling in his lips. On physical

examination he presented fever of 390C with

generalized erythema maculopapular rash, purpuric

lesions on the trunk and lower extremities, edema and

erosion on the lips. Lymphadenopathy was found on

the coli region. Laboratory examination showed a

slightly increased of Serum Glutamic Pyruvate

Transaminase (SGPT) 33 µ/L (Normal value (NV) 5-

31µ/L), blood ureum 62,2 mg/dl (NV 10-50 mg/dl)

and the presence of lymphocyte athypical. According

to RegiSCAR diagnosis criteria this patient’s score of

5 that could be classified as Probable DRESS

syndrome. Systemic corticosteroid therapy with

methylprednisolone intravenous was started from the

first day at a dose of 90mg (Body weight 85 kg) a day

and gradually decrease over a week, and supportive

local treatment for the skin and mucosal involvement.

Any other medications were also stopped. Within a

week we observed a significant improvement in

clinical condition and laboratory result showed SGPT

14µ/L. We continued therapy with

methylprednisolone oral and tappered off slowly for

2 weeks later.

Figure 1. Cutaneous rash found on the trunk and face of the patient on 1st day

Figure 2. Clinical improvement after 3 weeks followed up

3 DISCUSSION

Drug reaction with eosinophilia and systemic

symptoms (DRESS) was first defined in 1996 by

Bocquet et al, present with extensive rash, fever,

lymphadenopathy, hematologic abnormalities and

organ involvement(Waseem et al, 2016). Use of the

term DRESS has been inconsistent, since

eosinophilia is not a constant clinical finding. Some

literature use Drug-induced hypersensitivity

syndrome (DIHS)/DRESS to include both the DIHS

and DRESS syndrome. DHIS/DRESS was first

ICTROMI 2019 - The 2nd International Conference on Tropical Medicine and Infectious Disease

442

described by Chaiken et al in 1950. The most

common clinical presentation of DHIS/DRESS are

cutaneous eruption, fever and enlarged lymph nodes

RegiSCAR scoring system is one of the most

used diagnostic criteria exist for diagnosis of DRESS

syndrome.This RegiSCAR was developed by an

international study group investigating severe

cutaneous reactions (SCAR).

Table 1. RegiSCAR diagnosis score for DRESS

Features no Yes Unknown

Fever (≥ 38,5

C) -1 1 -1

Enlarged lymph nodes (≥2 sites, ≥1cm) 0 1 0

Athypical lymphocytes 0 1 0

Eosinophilia:

700-1499 or 10%-19,9%

0 1 0

≥ 1500 or ≥ 20% 0 2 0

Skin rash :

Extent >50% 0 1 0

At least 2: edema, infiltration, purpura, scalling -1 1 0

Biopsy suggesting DRESS -1 0 0

Internal organ involvement:

one 0 1 0

Two or more 0 2 0

Resolution in more than 15 days -1 0 -1

At least 3 biological inv done and negative to

exclude alternative diagnosis

0 1 0

Final score: <2 = no ; 2-3= possible; 4-5= probable; >5= definite.

According to RegiSCAR criteria this patient was

diagnosed with Probable DRESS syndrome with

score 5 for the presence of fever, athypical

lymphocyte, extent skin rash >50% with purpuric

lesions, facial edema and scalling with liver and renal

involvement.

The onset of symptoms in DRESS syndrome is

often delayed. It may took 2-8 weeks after

introduction of triggering drug. Fever and rash were

the most common symptoms. Lymphadenopathy in

more than one sites is common and may occur in 75%

cases (Choudhary et al, 2013; Corneli et al,2017). In

this case, cutaneous rash appeared after 2 weeks

consumed cefadroxyl, paracetamol and allopurinol.

There was also fever and lymphadenopathy found

only at coli region.

Systemic organ involvement was common in

DRESS syndrome and liver is the most common

organ involved. Liver failure is the most common

cause of death. Renal abnormalities may occur in

11% patients, and commonly associated with

allopurinol

(Lens et al, 2010;Alexander et al,2013). In

this case there was slightly elevated of SGPT and

blood ureum that considered as the involvement of

liver and renal organ.

Hematologic abnormalities in DRESS syndrome

present with leukocytosis or leucopenia, eosinophilia

or atypical lymphocytes. In this case there was no

eosinophilia but we found the presence of atypical

lymphocyte. The presence of atypical lymphocyte

was found in 67% cases reported by the RegiSCAR

study group, while eosinophilia was demonstrated by

95% cases (Watanabe, 2018; Corneli et al,2017).

Studies about atypical lymphocyte found that this

reactive lymphocyte have been associated with viral

infection and plays an important role in the immune

response (Cho.2017)

In this case there were some clinical entities share

same features with Stevens-Johnson syndrome (SJS),

the erosion of lip mucosal that usually found in SJS,

and eosinophil count still in normal range. But, the

delayed onset and the presence of fever and atypical

lymphocyte could be directing our diagnosis to

DRESS syndrome.

Some medicines had implicated in triggering

DRESS syndrome, there were anticonvulsants

(phenytoin,carbamazepine), antidepressants

(desipramine, amitriptiline), sulpha drugs,NSAIDS,

antibiotics (minocycline,linezolide, doxycycline,

piperacilin-tazobactam), antivirals (abacavir,

telaprevir, zalcitabine), ACE inhibitors (enalapril),

Beta blockers (atenolol) and also allopurinol

(Waseem et al, 2016). In this case we could not

identified the causal drug with certainty, since our

Probable Dress Syndrome: A Case of Drug Hypersensitivity in Young Man

443

patient consumed cefadroxyl (2

generation of

sephalosporin), paracetamol and allopurinol in the

same time period. Literatures have been reported

sefalosporine and allopurinol as potential trigger

drugs in DRESS syndrome (Corneli et al,2017;Kim et

al,2014).

The pathophysiology of DRESS is still unclear. It

is hypothesized by a complex mechanism. Genetic

factor might be plays a role in the incidence of drug

hypersensitivity, including DRESS syndrome.

Genetic deficiency of detoxifying enzymes needed to

drug metabolism, and some Human Leucocyte

Antigen (HLA) have been reported associated with

drug hypersensitivity (Choudhary et al, 2013;

Watanabe, 2018). Reactivation of Human Herpes

Virus 6 (HHV-6), Epstein-Barr virus and

cytomegalovirus have been suggested had a close

relationship with DRESS syndrome

1,6

. However, the

exactly mechanism for this viral reactivation theory is

still unclear, is it direct effect of the defect in drugs

metabolism or effect of the “cytokine storm” that

could be found in viral reactivation (Waseem et al,

2016;(Cho et al,2017)

Systemic steroids have been used in the

management of drug hypersensitivity cases, including

DRESS Syndrome. In some cases of DRESS

syndrome, relapses have been occured after

withdrawal or tappering off. Dosage, duration of

treatment and situations where steroids should be

used are not clearly defined. Some authors suggest the

use of corticosteroid systemic at a dose equivalent to

1 mg/kg/day of prednisone in case with sign severity

including liver or renal involvement, pneumonia, or

cardiac involvement. The use of systemic steroids for

a prolonged period with a gradual decrease is

important in DRESS syndrome to avoid relapses

(Silva-Feistner et al,2017). In this case, we gave

methylprednisolone intravenous at 90 mg starting

dose and tappering off over a week, then continued

with slow tappering off oral methylprednisolon. Our

patient showed good improvement and there was no

relapses after 2 weeks followed up.

4 CONCLUSION

We report here a case of Probable DRESS syndrome

in a 28 years old man, probably due to cefadroxyl

and/or allopurinol, which was diagnosed by

RegiSCAR validation scores. Our patient showed

good clinical result with steroid systemic therapy in

a slowly tappering off within 3 weeks.

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