Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening, drug-induced adverse reaction characterized by skin eruptions, lymphadenopathy, fever, and a broad range of other bodily manifestations. The spectrum of histopathologic and clinical presentations is wide; therefore, DRESS syndrome can mimic other diseases. Case Presentation: We present a case of a 4-year-old male patient who started chemotherapy with vincristine, cytarabine, and etoposide. The first clinical signs were fever, hemodynamic in-stability, and maculopapular erythema. Biopsies of skin lesions were taken, and hyperkeratosis, focal parakeratosis, acanthosis with slight spongiosis, and intraepithelial dyskeratotic cells were observed. There was a perivascular lymphoid infiltrate with abundant eosinophils in the dermis, and eosinophil permeations to the acrosyringium and epithelium were found. Conclusion: DRESS syndrome is a drug-induced reaction that shares histopathological findings in skin biopsies with those seen in graft-versus-host disease. Although the histological findings are non-pathognomonic, they were characteristic enough to be of importance in the differential diagnosis.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a serious and potentially fatal adverse reaction to drugs [1]. Its incidence ranges from 1 in 1,000 to 1 in 10,000, varying among different populations, as it is believed to have a marked genetic component associated with the major histocompatibility complex [2].

The most common clinical manifestations of this syndrome include rash, facial edema, fever, lymphadenopathy, and eosinophilia. Additionally, it can involve various organs such as the liver, lungs, kidneys, pancreas, or heart [3, 4]. Mortality rates are approximately 10% in adults and 5.4% in children [5]. These rates increase with late diagnosis, which is common due to the disease's long latency period and clinical similarities with other pathologies [6].

DRESS syndrome is nicknamed “the great imitator” because its presentation is highly heterogeneous, allowing it to mimic the semiology of many diseases with dermatologic involvement [6, 7]. The most common differential diagnoses are pathologies, such as infectious mononucleosis, parvovirus B19 infection, measles, dengue virus infection, Kawasaki disease, and Kikuchi–Fujimoto disease [8], making its identification a challenge, especially in children. Due to this heterogeneity, a scoring scale known as RegiSCAR was introduced in the early 2010s to diagnose clinical entities more accurately, including DRESS syndrome [4].

The drugs most commonly associated with the development of DRESS syndrome are anticonvulsants and antibiotics, accounting for 50% and 31% of cases, respectively [8]. Currently, there are reports of cases of DRESS syndrome caused by chemotherapy agents. However, no studies relate DRESS syndrome to chemotherapeutics, such as vincristine or etoposide.

The most frequently reported histopathological changes are keratinocyte damage, dermal edema, erythrocyte extravasation, superficial perivascular inflammation, and spongiform dermatitis [9‒11]. Contrary to what the disease name suggests, in skin biopsies, eosinophil infiltration was only seen in approximately 20% of the specimens examined compared to neutrophil infiltration, seen in about 50% [12, 13].

A 4-year-old male diagnosed with juvenile myelomonocytic leukemia is undergoing chemotherapy with vincristine, cytarabine, and etoposide. He presented to the emergency room with a 2-day history of fever, hypotension, and pruritic lesions on his inner thighs, which progressively spread to cover his entire body surface. Physical examination revealed multiple erythematous papules, some non-responsive to acupressure. On the elbows and knees, they formed large purple plaques, with few papules on the soles and palms and no oral mucosal involvement (Fig. 1a, b). Additionally, facial edema was noted. The patient was hospitalized 15 days prior for severe thrombocytopenia (platelets <6,000) and received a platelet transfusion. He was subsequently diagnosed with juvenile myelomonocytic leukemia and started chemotherapy 10 days before admission.

Fig. 1.

a, b Skin with generalized erythema with desquamation in flaps. Congruence of erythematous-violaceous macules is seen to form plaques. c, d HE ×10–×40. Skin with discrete hyperkeratosis, acanthosis with slight spongiosis, and frequent intraepithelial dyskeratotic cells. In the dermis, perivascular lymphoid infiltrate, surface with eosinophils permeating the acrosyringium and eccrine ducts. There is no vasculitis.

Fig. 1.

a, b Skin with generalized erythema with desquamation in flaps. Congruence of erythematous-violaceous macules is seen to form plaques. c, d HE ×10–×40. Skin with discrete hyperkeratosis, acanthosis with slight spongiosis, and frequent intraepithelial dyskeratotic cells. In the dermis, perivascular lymphoid infiltrate, surface with eosinophils permeating the acrosyringium and eccrine ducts. There is no vasculitis.

Close modal

The patient's diagnostic tests revealed significant abnormalities in the blood count: white blood cell count of 1,100, with an absolute neutrophil count of 50, absolute lymphocyte count of 840, absolute monocyte count of 150, and absolute eosinophil count of 50. Hemoglobin level was measured at 7.6 g/dL, hematocrit at 22.8%, and platelet count at 23,000 per microliter. Additionally, the C-reactive protein level was elevated at 2.67 mg/L. Liver function tests returned within normal ranges, as did the lactate dehydrogenase test, which showed a value of 245 U/L.

Based on the low-output clinical symptoms, it was decided to start volume expansion with crystalloids and to initiate intravenous immunoglobulin support. In addition, albumin replacement associated with diuretic infusion was started, in search of physiological dialysis. With worsening symptoms and suspicion of a hypersensitivity reaction, a biopsy of the skin lesions was taken for histopathological study. The dermatopathological changes observed were hyperkeratosis, focal parakeratosis, acanthosis with slight spongiosis, and frequent intraepithelial dyskeratotic cells, and there was involvement of the dermis by perivascular lymphoid infiltrates with abundant eosinophils. In addition, eosinophils permeated the acrosyringium, eccrine ducts, and epithelium (Fig. 1c, d). This skin biopsy report was compatible with drug-induced toxicoderma. According to the RegiSCAR scale for DRESS, the total score is 5, which classifies it as a probable case.

With the definitive diagnosis and given the continued progression of the lesions and lack of response to immunoglobulin, bolus methylprednisolone (30 mg/kg per day) was started. Five doses were administered without clinical relapses. After 2 days, the patient showed a better hemodynamic evolution, though with initial progress of the extension and intensity of cutaneous erythematous involvement, which resolved during the week. Given the patient's progression, a modification of the chemotherapeutic regimen is undertaken, with mercaptopurine being administered.

Finally, the management of this syndrome involves early elimination of the causative agent and treatment with antihistamines in their mild form, corticosteroids in their moderate form, and plasmapheresis in the more severe forms [1‒7]. Healthcare professionals should be more attentive to the early manifestations of this syndrome, as early diagnosis and treatment improve outcomes significantly.

The clinical and physical examination features in this patient are consistent with the most frequent findings reported in the literature, including fever, lymphadenopathy, and eosinophilia. Generally, there is also involvement of such organs as the liver, lungs, kidneys, pancreas, or heart [3, 4], but in this patient, despite laboratory findings, no organ involvement was evident.

DRESS syndrome, also known as the great imitator, presents a complex diagnosis, especially in pediatrics, as most differential diagnoses are diseases that peak in the first and second decades of life. The diagnosis also becomes more complex when there is a patient history that guides the physician to consider a wider variety of differential diagnoses. Cases have been reported in the literature in which DRESS syndrome mimicked autoimmune diseases or hematologic malignancies, such as lymphomas [14, 15]. Another differential diagnosis may be exanthematous eruptions, also common in the pediatric population, and which affect the face, neck and upper part of the trunk, and which can extend symmetrically towards the extremities [16].

In the present case, the patient has a history of having received a unit of platelets before the onset of symptoms, which led to the consideration of transfusion-associated GvHD. Thus, the histopathological study has become the gold standard diagnostic tool, as it allowed us to confirm drug-induced toxicoderma. Early differentiation of this entity using biopsies plays a fundamental role, as studies show higher morbimortality rates following late diagnosis [9].

Concerning the observations in histological slides, it can be affirmed that the report is compatible with the details in the literature. This mainly shows damage from keratinocytes, dermal edema, spongiform dermatitis, and superficial perivascular inflammation [17]. In this case, the biopsies revealed abundant eosinophils in the dermis, which in turn permeated the acrosyringium; however, these findings are only observed in approximately 20% of the samples examined, as reported in the literature [11, 12].

In conclusion, DRESS syndrome is a drug-induced reaction that shares clinical and histopathological findings with those observed in GvHD. Although such histologic findings are not pathognomonic, they are sufficient to establish a definitive diagnosis. Systemic immunoglobulin (IgA, IgM, IgG) levels, particularly the early decrease in total IgG levels, have been documented as a valuable indicator to support clinical suspicion of DRESS [18].

The present case report can serve as a reference for decision-making concerning patients with a similar clinical course; however, due to the level of evidence, general recommendations and a confirmed cause-effect relationship between drugs and disease development cannot be established. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material at https://doi.org/10.1159/000541046.

This study protocol was reviewed and approved by the Institutional Ethics Commit-tee of University Hospital, Fundación Santa Fe de Bogotá (review CCEI-14943-2022 and date of review December 16, 2022). Written informed consent was obtained from the parent/legal guardian of the patient for publication of the details of their medical case and any accompanying images.

The authors declare no conflicts of interest.

This research received no external funding.

Conceptualization, formal analysis, and investigation, Marian Rolón, Mateo Barros, Clara Ortiz, and Johanna Álvarez. Writing – original draft preparation, writing – review and editing, and visualization: Marian Rolón, Mateo Barros, Clara Ortiz, Sergio Cruz, and Johanna Álvarez. Supervision: Marian Rolón, Clara Ortiz, and Johanna Álvarez.

The research data are not publicly available, for ethical reasons, to protect the patient's identity. Further inquiries can be directed to the corresponding author.

1.
Behera
S
,
Das
S
,
Xavier
AS
,
Selvarajan
S
.
DRESS syndrome: a detailed insight
.
Hosp Pract
.
2018
;
46
(
3
):
152
62
.
2.
Quach
C
,
Galen
BT
.
HLA-B* 5801 testing to prevent allopurinol hypersensitivity syndrome: a teachable moment
.
JAMA Intern Med
.
2018
;
178
(
9
):
1260
1
.
3.
Isaacs
M
,
Cardones
AR
,
Rahnama-Moghadam
S
.
DRESS syndrome: clinical myths and pearls
.
Cutis
.
2018
;
102
(
5
):
322
6
.
4.
Kim
G
,
Anderson
KR
,
Davis
DMR
,
Hand
J
,
Tollefson
MM
.
Drug reaction with eosinophilia and systemic symptoms (DRESS) in the pediatric population: a systematic review of the literature
.
J Am Acad Dermatol
.
2020
;
83
(
5
):
1323
30
.
5.
Metterle
L
,
Hatch
L
,
Seminario-Vidal
L
.
Pediatric drug reaction with eosinophilia and systemic symptoms: a systematic review of the literature
.
Pediatr Dermatol
.
2020
;
37
(
1
):
124
9
.
6.
Taweesedt
TT
,
Dumic
I
,
Stoeckel
J
.
Pulmonary manifestations of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a systematic review
.
BioMed Res Int
.
2019
;
20
(
4
):
786
.
7.
Fleming
P
,
Marik
E
.
The DRESS syndrome: the great clinical mimicker
.
Pharmacotherapy
.
2011
;
31
(
3
):
332
.
8.
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
(
3
):
301
8
.
9.
Wegner
A
.
Enfermedad injerto contra huésped asociada a transfusión
.
Rev Chil de Ped
.
2007
;
15
:
500
10
.
10.
Skowron
F
,
Bensaid
B
,
Balme
B
,
Depaepe
L
,
Kanitakis
J
,
Nosbaum
A
, et al
.
Drug reaction with eosinophilia and systemic symptoms (DRESS): clinicopathological study of 45 cases
.
J Eur Acad Dermatol Venereol
.
2015
;
29
(
11
):
2199
205
.
11.
Gonçalo
MM
,
Cardoso
JC
,
Gouveia
MP
,
Coutinho
I
,
Gameiro
AR
,
Brites
MM
, et al
.
Histopathology of the exanthema in DRESS is not specific but may indicate severity of systemic involvement
.
Am J Dermatopathol
.
2016
;
38
(
6
):
423
33
.
12.
Ortonne
N
,
Valeyrie-Allanore
L
,
Bastuji-Garin
S
,
Wechsler
J
,
de Feraudy
S
,
Duong
TA
, et al
.
Histopathology of drug rash with eosinophilia and systemic symptoms syndrome: a morphological and phenotypical study
.
Br J Dermatol
.
2015
;
173
(
1
):
50
8
.
13.
Sasidharanpillai
S
,
Govindan
A
,
Riyaz
N
,
Binitha
MP
,
Muhammed
K
,
Khader
A
, et al
.
Drug reaction with eosinophilia and systemic symptoms (DRESS): a histopathology based analysis
.
Indian J Dermatol Venereol Leprol
.
2016
;
82
(
1
):
28
36
.
14.
Besli
GE
,
Yildirim
S
,
Yilmaz
K
,
Yuksel
E
.
DRESS syndrome or hematologic malignancy
.
Pediatr Emerg Care
.
2017
;
33
(
7
):
494
6
.
15.
Johnson
S
,
Mathews
S
,
Hudnall
SD
.
Human herpesvirus 6 lymphadenitis in drug rash with eosinophilia and systemic symptoms syndrome: a lymphoma mimic
.
Histopathology
.
2017
;
70
(
7
):
1166
70
.
16.
Crisafulli
G
,
Franceschini
F
,
Caimmi
S
,
Bottau
P
,
Liotti
L
,
Saretta
F
, et al
.
Mild cutaneous reactions to drugs
.
Acta Biomed
.
2019
;
90
(
3-S
):
36
43
.
17.
Weyers
W
,
Metze
D
.
Histopathology of drug eruptions–general criteria, common patterns, and differential diagnosis
.
Dermatol Pract Concept
.
2011
;
1
(
1
):
33
47
.
18.
Ramirez
GA
,
Ripa
M
,
Burastero
S
,
Benanti
G
,
Bagnasco
D
,
Nannipieri
S
, et al
.
Drug reaction with eosinophilia and systemic symptoms (DRESS): focus on the pathophysiological and diagnostic role of viruses
.
Microorganisms
.
2023
;
11
(
2
):
346
.