Hospital Pharmacy - April 2018 - 93

756666
research-article2018

HPXXXX10.1177/0018578718756666Hospital PharmacyMancano

ISMP Adverse Drug Reactions
Hospital Pharmacy
2018, Vol. 53(2) 93-95
© The Author(s) 2018
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https://doi.org/10.1177/0018578718756666
DOI: 10.1177/0018578718756666
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ISMP Adverse Drug Reactions:
Minocycline-Induced Drug Fever Without Skin Rash
Lupus Erythematosus-Like Eruption Induced by Hydroxyurea
Cardiotoxicity and Fever Induced by Clozapine
Denosumab-Induced Hepatotoxicity
Severe Cardiotoxicity Induced by Bevacizumab
Michael A. Mancano1

Minocycline-Induced Drug Fever
Without Skin Rash
A 24-year-old female had been receiving minocycline 100
mg daily for 6 days for the treatment of acne. The patient
reported a fever of 39.2°C (102.6°F), dizziness, chest tightness, and eye pain. Her physician diagnosed her with a cold
and she was treated. Minocycline therapy was stopped at this
time. The patient's fever and malaise lasted 5 days. Three
days later, the patient was restarted on minocycline for her
acne. Within 3 hours of minocycline administration, she
again developed a high fever of 39.2°C with dizziness, chest
tightness, and eye pain.
The patient was initiated on 30 mg of prednisone. She
was examined and her blood pressure, respiratory rate, and
heart rate were normal. She did not exhibit any throat swelling, enlarged lymph nodes, or rash. Magnetic resonance
imaging of the brain revealed no abnormalities and a computed tomographic scan of the chest also was negative. The
patient did have an eosinophilia with a white blood cell
count (WBC) of 7.5 × 109/L (normal range, 4.5-11 × 109/L)
and eosinophils of 1.2 × 109/L (normal range, 0.1-0.6 ×
109/L). Her renal and liver function tests were normal as
well as blood cultures for bacteria and testing for the antihuman herpes virus-6 IgG were also negative.
The authors1 note that there have been rare reports of
minocycline-induced drug fever and the consequences can
be serious. In prior cases, minocycline has been overlooked
as a potential cause because the patient did not have a skin
rash. The authors state,
"The diagnosis of drug fever is often difficult, and a careful
review of the clinical presentation and medication history can
confirm the diagnosis. Although this patient had severe
symptoms, the diagnostic criteria for drug reaction with
eosinophilia and systemic symptoms (DRESS) were not
fulfilled because of the absence of skins rash and other
systemic features."

The authors warn that clinicians should be alert for
unusual drug-induced fever, especially in patients without
apparent skin rashes.

Lupus Erythematosus-Like Eruption
Induced by Hydroxyurea
A 14-year-old female had been receiving hydroxyurea 1500
mg daily for the past 5 years for the management of her
sickle cell anemia. The patient developed a hyperpigmented
rash and plaques on her bilateral upper arms, back, and right
conical bowl as well as pruritus. She also exhibited scattered
discrete erythematous, hypopigmented, hyperkeratotic papules across her back, left malar cheek, and bilateral upper
extremities. The patient had tried to self-treat the condition
with clotrimazole cream with no effect.
The patient had biopsy specimens taken from the lesions
and the results pointed to a possible collagen vascular disorder-like eruption and hydroxyurea dermopathy. The patient
was subsequently started on fluocinonide 0.05% cream for
the lesions; however, she did not experience significant
improvement. Additional testing pointed to a possible discoid lupus with a positive antinuclear antibody (ANA) titer
of 1:160 and a high antihistone immunoglobulin G (IgG)
level of 4.5 U (reference range, <1 U).
The patient's hydroxyurea was then stopped, and treatment with fluocinonide cream was continued. The patient
began to experience significant improvement in her rash, and
her antihistone IgG level fell gradually. One year after stopping the hydroxyurea, the patient noted minimal hyperpigmentation with no new lesions.
1

Temple University, Philadelphia, PA, USA

Corresponding Author:
Michael A. Mancano, Chair and Clinical Professor, Department of
Pharmacy Practice, Temple University School of Pharmacy, Philadelphia,
PA 19019, USA.
Email: michael.mancano@temple.edu

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