CASE REPORT

DOI: 10.4274/ejgg.galenos.2019.131
Eur J Geriatr Gerontol 2019;1(3):107-111

Approach to DRESS Syndrome Associated with Allopurinol Use in

a Geriatric Patient
Can Sevinç1, Pınar Tosun Taşar2, Elif Büyükkurt3
1Erzurum Atatürk University Faculty of Medicine, Department of Nephrology, Erzurum, Turkey
2Erzurum Atatürk University Faculty of Medicine, Department of Geriatrics, Erzurum, Turkey
3Erzurum Atatürk University Faculty of Medicine, Department of Internal Medicine, Erzurum, Turkey

Abstract
Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a rare and life-threatening drug-induced hypersensitivity reaction. Here,
we present the case of an old man diagnosed with DRESS syndrome after allopurinol therapy. This case highlights the importance of being vigilant
for drug toxicity reactions due to allopurinol use that may occur in older adults.
Keywords: Allopurinol, drug toxicity, hypereosinophilia

Introduction onset of pruritus, he had developed a fever of 39°C and rashes

had started on his extremities and spread over the entire body.
Drug rash with eosinophilia and systemic symptoms (DRESS
Facial edema was developed and erythematous maculopapular
syndrome) is a rare and life-threatening drug-induced
rashes were observed on his back, trunk, and bilateral upper and
hypersensitivity reaction that presents with skin rashes,
lower extremities (Figures 1, 2, and 3). There was no oral mucosal
hematological abnormalities such as eosinophilia and
involvement. Other system examinations were normal. The
atypical lymphocytosis, lymphadenopathy, and involvement
patient’s medical history included no known diseases, but the
of internal organs such as the liver, kidney, and lung. Here, we
patient reported that he had started allopurinol therapy (300
present the case of a 65-year-old man diagnosed with DRESS
mg/day) due to hyperuricemia 1 month before the admission.
syndrome after allopurinol therapy. This case highlights the
There was no other medication than allopurinol. His family
importance of being vigilant for drug toxicity reactions that
history was unremarkable.
may occur in older adults due to allopurinol use.
At the time of presentation to the emergency department, his
Case Presentation creatinine level was 6.59 mg/dL (0.67-1.17 mg/dL), white blood
cell count was 23,000/μL (3,900-10,800/μL), neutrophil count
A 65-year-old man presented to the emergency department
was 16,300 (2,300-7,600), eosinophil count was 3000 (10-500),
with complaints of generalized itching, low-grade fever, and
and leukocytosis, eosinophilia (13%), and atypical lymphocytes
rash covering his body. He reported that the pruritus started
were detected in peripheral blood smear. Complete urinalysis
10 days before the admission. Three days after the onset of
revealed leukocyturia (53; 0-4), hematuria (32; 0-3), and no
pruritus, he had also developed a fever of 39°C and rashes
proteinuria. On abdominal ultrasound, kidney size, parenchymal
starting on the extremities and spreading over his entire body.
echo, and collecting systems were normal bilaterally.
Systemic inquiry revealed the additional complaint of reduced
urine output. On physical examination, his general condition The patient was admitted to our ward with a preliminary
was fair, body temperature was 38.7°C. Three days after the diagnosis of renal failure and DRESS syndrome due to allopurinol

Address for Correspondence: Pınar Tosun Taşar, Erzurum Atatürk University Faculty of Medicine, Department of Geriatrics, Erzurum, Turkey
E-mail: [email protected] ORCID: orcid.org/0000-0002-2617-4610
Received: Aug 17, 2019 Accepted: Oct 23, 2019
Our case will be presented as an oral presentation in 5th Drug and Treatment Congress 2019.
Cite this article as: Sevinç C, Tosun Taşar P, Büyükkurt E. Approach to DRESS Syndrome Associated with Allopurinol Use in a Geriatric Patient.
Eur J Geriatr Gerontol 2019;1(3):107-111

©Copyright 2019 by the Academic Geriatrics Society / European Journal of Geriatrics and Gerontology published by Galenos Publishing House.

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Sevinç et al. Approach to DRESS Syndrome Associated with Allopurinol Use in a Geriatric Patient Eur J Geriatr Gerontol 2019;1(3):107-111

use. The patient was started on intravenous hydration, 40 mg/ syndrome is about one in 260 patients treated with this drug (3).
day methylprednisolone, and oral antihistamine therapy. The Genetic associations between human leukocyte antigen (HLA)
patient’s skin lesions began to regress during follow-up and associations and drug hypersensitivity may occur. HLA-B*1508,
dose of steroid was tapered. The patient received the steroid associated with allopurinol induced Stevens-Johnson syndrome
therapy for a total of 9 days, during this time itchy skin lesions and toxic epidermal necrolysis (4,5).
and facial edema and leukocytosis were regressed. C-reactive
protein and alanine aminotransferase levels decreased to In most patients, the reaction begins 2-6 weeks after initiation
within normal reference range and the patient’s creatinine of the inducing drug (3). In our patient, the most likely cause of
level decreased to 1.24 mg/dL. Following steroid therapy, the DRESS syndrome was allopurinol, which the patient had started
patient’s fever gradually fell. The patient’s pre-treatment and taking 1 month earlier for hyperuricemia.
post-treatment values are summarized in Table 1. Currently, the indications for allopurinol therapy are
hyperuricemia (gouty arthritis, urate nephropathy,
Discussion
nephrolithiasis) and prophylaxis against urate nephropathy
DRESS syndrome is a type IV hypersensitivity reaction. It is during chemotherapy for neoplastic diseases. Allopurinol
characterized by severe skin rashes, fever, lymphadenopathy,
hematological abnormalities (eosinophilia or atypical
lymphocytes), and internal organ involvement. Although
the pathogenesis of DRESS syndrome is not fully known,
immunological factors, genetic factors, and factors involved in
drug detoxification pathways have been implicated (1). Aromatic
anticonvulsants (phenytoin, phenobarbital, carbamazepine) and
sulfonamides are the most common causes of DRESS syndrome.
Lamotrigine, allopurinol, nonsteroidal anti-inflammatory drugs,
captopril, calcium channel blockers, terbinafine, metronidazole,
minocycline, and antiretroviral drugs may also cause DRESS
syndrome (2). The frequency of allopurinol-induced DRESS

Figure 2. Erythematous maculopapular rashes on both of the patient’s

lower extremities

Figure 1. Widespread erythematous maculopapular rashes on the abdomen Figure 3. Erythematous maculopapular rash on the patient’s upper
and chest extremity

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Eur J Geriatr Gerontol 2019;1(3):107-111 Sevinç et al. Approach to DRESS Syndrome Associated with Allopurinol Use in a Geriatric Patient

should be used only in these cases and at the appropriate most cases, over 50% of the body surface area is erythematous
dose. The likely mechanism underlying the development of (9). Our patient also had marked facial edema and diffuse
DRESS syndrome due to allopurinol use is hypersensitivity to erythema on his body (Figures 1, 2, and 3).
allopurinol or oxipurinol (the main metabolite of allopurinol) At least one internal organ is involved in approximately 90%
and immune complex formation with subsequent vasculitis (6). of the patients. Two or more organs are involved in 50-60% of
Oxipurinol accumulation, especially in patients with reduced cases, most commonly the liver, kidney, and lung (9-11).
renal clearance, increases the risk of developing DRESS Renal involvement manifests as acute interstitial nephritis and
syndrome. Numerous studies have shown that advanced occurs in 10-30% of DRESS cases, most frequently in those
age, comorbid kidney disease, high-dose drug use, and associated with allopurinol (12,13). Renal abnormalities include
concomitant use of thiazide diuretics constitute a potential a moderate increase in creatinine level, low-grade proteinuria,
risk for allopurinol-induced DRESS syndrome (7). Fever, and in rare cases, abnormal urinary sediment containing
malaise, lymphadenopathy, and skin eruptions are the most eosinophils. He had no sign or symptom of other systems
common symptoms (8). involvement.
The rash usually presents in the form of facial and periorbital To help clinicians confirm or exclude the diagnosis of DRESS
edema with widespread erythematous eruptions on the trunk syndrome, the European Registry of Severe Cutaneous
and upper extremities. About half of all cases exhibit facial Adverse Reactions (RegiSCAR) developed a scoring system
edema (9). Body surface area demonstrates degree of disease based on clinical features, degree of skin involvement, organ
involvement and is an important indicator of disease severity. In involvement, and clinical course (8). According to this scoring
Table 1. Comparison of the patient’s laboratory values at presentation with post-steroid therapy
Laboratory variables Pre-treatment values Post-treatment values Reference range
White blood cell count (x103/µL) 23.02 11.26 3.9-10.8
% Eosinophil 13.4 13 0.1-6.3
Hemoglobin (g/dL) 12.4 9.9 14.4-18.3
Erythrocyte sedimentation rate 4 5 0-20
C-reactive protein (mg/L) 48.1 6.89 0-5
Urea (mg/dL) 142 77 17-43
Blood urea nitrogen (mg/dL) 66.36 35.98 6-22
Alanine aminotransferase (U/L) 69 30 1-50
Aspartate aminotransferase (U/L) 37 24 1-50
Gamma-glutamyl transferase (U/L) 51 40 1-55
Creatinine (mg/dL) 6.59 1.24 0.67-1.17
Albumin (g/dL) 2.51 2.69 3.5-5.2

Table 2. RegiSCAR DRESS syndrome scoring system

Present Absent
Fever ≥38.5°C 0 -1
Enlarged lymph nodes (>1 cm in size, at least 2 regions) 1 0
Eosinophilia: ≥700 or ≥10% (leukopenia) ≥1500 or ≥20% (leukopenia) 1 2 0
Atypical lymphocytes 1 0
Rash covering ≥50% of body surface area 1 0
Suspicious rash (≥2 facial edema, purpura, infiltration, desquamation) 1 0
Skin biopsy suggesting an alternative diagnosis -1 0
Organ involvement: 1 2 or more 1 2 0
Disease duration >15 days 0 -1
Investigation of 3 or more alternative causes (blood cultures, anti-nuclear antibody, serology for hepatitis 1 0
viruses, Mycoplasma, Chlamydia) with negative results
Total score <2: impossible; 2–3: possible; 4–5: probable; ≥6: definite
RegiSCAR: The European Registry of Severe Cutaneous Adverse Reactions, DRESS: Drug rash with eosinophilia and systemic symptoms

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system, DRESS syndrome is classified as definite, probable, or Ethics

possible (Table 2). Our patient received a RegiSCAR score of
Informed Consent: Informed consent was obtained from the
7 (fever, eosinophilia, atypical lymphocytes, involvement of
patient.
more than 50% of the body surface area, facial edema, kidney
and liver involvement), resulting in a definite diagnosis of Peer-review: Externally and internally peer-reviewed.
DRESS syndrome.
Authorship Contributions
There is no standard treatment for DRESS syndrome. The
Concept: C.S., Design: C.S., P.T.T., Data Collection or Processing:
first step in treatment is to discontinue the suspected drugs.
C.S., P.T.T., Analysis or Interpretation: E.B., Literature Search:
Corticosteroids can dramatically improve clinical condition (14-
P.T.T., Writing: C.S., P.T.T., E.B.
17). Early discontinuation of the drug causing DRESS syndrome
will lead to better outcomes. DRESS syndrome can cause life- Conflict of Interest: No conflict of interest was declared by
threatening multiple organ failure (18,19). The mortality rate the authors
is 10% (16). Intravenous immunoglobulins, plasmapheresis, or Financial Disclosure: The authors declared that this study
a combination of these treatments can be used if symptoms
received no financial support.
worsen (20).
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