969VOLUME 48__DECEMBER 17, 2011
C C C C C A A A A A S S S S S E E E E E R R
R E E E E E P P P P P O O O O O R R R R R T T T T T S S S S S
Azathioprine Hypersensitivity Presenting as Sweet Syndrome in a Child
with Ulcerative Colitis
MI JIN KIM, *KEE TAEK JANG, AND YON HO CHOE
From the Departments of Pediatrics and *Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine,
Sweet syndrome is a cutaneous lesion characterized by tender, red inflammatory
nodules or papules. We describe a pediatric case of Sweet syndrome presenting
10 days after treatment with azathioprine. As azathioprine is widely used in children
with inflammatory bowel disease, clinicians should be aware of this unusual
Key words: Azathioprine, Children, Hypersensitivity, Sweet syndrome.
Yon Ho Choe, Department of Pediatrics,
Samsung Medical Center,
Sungkyunkwan University School of
Medicine, 50 Irwon-dong, Gangnam-gu,
Seoul, 135-710, South Korea.
Received: June 10, 2010;
Initial Review: July 01, 2010;
Accepted: August 05, 2010.
It can become generalized, and patients often are ill with
associated signs and symptoms, including malaise, high
fever, neutrophilia, elevated erythrocyte sedimentation
rate and C-reactive protein levels, which mimic an
infectious process. It has rarely been seen as a mani-
festation of azathioprine hypersensitivity in adults [1-4].
weet syndrome, or acute febrile neutrophilic
dermatosis, is a cutaneous lesion characterized
by tender, red inflammatory nodules or papules,
usually affecting the upper limbs, face and neck.
A nine-year-old girl was referred for management of
refractory ulcerative Colitis (UC) that had been diagnosed
one year previously. She had no history of reported drug
allergies and had been prednisolone-dependent (2 mg/kg/
day) for much of the preceding year, with her disease
flaring after attempts to reduce the prednisolone dosage.
During the hospitalization, she received mesalazine
treatment (48 mg/kg/day) without prednisolone, but it was
ineffective. She underwent azathioprine therapy (1 mg/kg/
day) and 10 days later was hospitalized for fever
(temperature of 39.2ºC), skin rash and hematochezia.
Physical examination was significant for numerous
erythematous, painful, 1-3 mm vesicular lesions with
central pustules on her face and both arms (Fig. 1).
Laboratory results showed an elevated white blood cell
count (13,470/μL) with neutrophilia, microcytic
hypochromic anemia (hemoglobin 9.2 g/dL, MCV 80.9 fl,
MCH 24.8 pg), hyponatremia (132 mmol/L), and a
markedly raised erythrocyte sedimentation rate (89 mm/
hr) and C-reactive protein level (3.13mg/dL). Anti-nuclear
antibody was negative, but c-type anti-neutrophil
cytoplasmic antibody (c-ANCA) was positive. Her
thiopurine methyltransferase (TPMT) activity was normal
(18.2 U/ml RBC, reference range: 15.1-26.4 U/mL RBC).
Blood cultures and urinalysis were obtained and the
patient was started on cefotaxime (100 mg/kg/day) for a
possible infectious etiology.
Two days after the cefotaxime treatment, the patient
still had a fever. The patient then received metronidazole
(30 mg/kg/day) for a week and prednisone (1.7 mg/kg/
day). However, she was febrile with shaking chills and
nausea. Cultures taken from blood and urine prior to
antibiotic therapy were sterile. Biopsy specimens and
tissue cultures were taken from the pustular lesions.
Pathologic evaluation of skin biopsy showed massive
neutrophilic infiltrate in the entire dermis (Fig. 1). Tissue
culture results were negative for bacterial or fungal
infection. Based on the clinical course, a diagnosis of
sweet syndrome was made. As the patient’s fever had not
subsided in spite of the administration of antibiotics and
steroid, we presumed that the sweet syndrome was caused
by the azathioprine and was not due to inflammatory bowel
disease. The azathioprine therapy was discontinued.
Within 48 hours, the patient’s fever abated and her skin
lesions improved. Following this improvement, the