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Blood, 1 July 2002, Vol. 100, No. 1, pp. 363-364
CORRESPONDENCE
To the editor:
A patient on hydroxyurea for sickle cell disease who
developed an opportunistic infection
Recent reports1-7 indicate that hydroxyurea (HU) is
safe and effective in the treatment of patients with severe sickle cell disease (SCD). In particular, there have been no reports of any patient
developing an opportunistic infection while taking this drug. Below, we
report a case of Cryptosporidium infection in a patient with
SCD on HU treatment. A 36-year-old African American woman with known sickle  +
thalassemia with past medical history significant for multiple
hospitalizations for severe pain crises was admitted to the hospital
for a severe painful episode. In addition, this time she complained of
epigastric pain with nausea, vomiting, and watery diarrhea for 2 days
prior to admission. Review of systems was negative for other symptoms. Her last blood transfusion was 6 months prior to admission, and she had
only rarely required blood transfusions in the past. Her medications
were 500 mg HU (for 20 months), acetaminophen with codeine, methadone,
folic acid, conjugated estrogens, and ranitidine. Upon physical
examination, she was afebrile and the significant findings were
tachycardia (pulse rate, 109/min) and epigastric tenderness to
palpation without guarding or rebound. Laboratory data were significant
for a low white blood cell count of 3 × 109/L
with a normal differential and hemoglobin level of 9 g/dL. Initial
stool tests for fecal leukocytes, ova and parasites, and Clostridium difficile toxin was negative. She was treated symptomatically for a presumptive diagnosis of viral
gastroenteritis. One week after admission, after she failed to respond
to treatment, she underwent colonoscopy. Colonic mucosal biopsies were
positive for Cryptosporidium. Subsequently, her stool
culture results came back as positive for Cryptosporidium as
well. Further workup revealed a negative test for the human immunodeficiency virus (HIV). But her absolute CD4 count was low at
0.234 × 109/L (normal, 0.4 to
1.77 × 109/L). She was treated with paromomycin and
octreotide. The patient required multiple subsequent admissions for
similar symptoms and was treated in similar fashion. She later
developed cholecystitis and required cholecystectomy. Pathology of the
gallbladder revealed eosinophilic cholecystitis, consistent with a
parasitic infection.8 Following removal of the
gallbladder, which can act as a reservoir of
Cryptosporidium,8 the patient's symptoms
resolved. The patient's subsequent absolute CD4 count normalized
(0.455 × 109/L) 3 months after discontinuation of HU. A
repeat value was 0.553 × 109/L 13 months after stopping HU. HU is a commonly used drug in SCD and has been reported to be safe. To
our knowledge there has been no reports of opportunistic infections
associated with HU, and it is rare to see such infections in patients
with SCD. The finding in our patient of Cryptosporidium gastroenteritis, which is an opportunistic infection, raised the question of whether there is any association between HU and such infections. Opportunistic infections are usually associated with immunosuppression
and/or low CD4 counts. We have reported that CD4 counts are normal in
sickle cell patients both during steady state and painful
crisis.9 There has been a report that HU can lower CD4
counts in HIV patients.10 Our hypothesis is that HU
lowered the CD4 count in our patient, perhaps predisposing her to
Cryptosporidium gastroenteritis. Currently we are testing
this hypothesis by checking CD4 counts in patients that are being
treated with HU and those who are not.
Pramila Venigalla, Bharat Motwani, Anitha Nallari, Sandra Allen, Manoj Agarwal, Manuel Alva, Maxwell Westerman, and Lawrence Feldman
Correspondence: Lawrence Feldman, Department of Medicine, Finch
University of Health Sciences/The Chicago Medical School at Mount Sinai
Hospital Medical Center, California Avenue at 15th Street, Chicago, IL
60608; e-mail: lef{at}sinai.org
References
1.
Ferster A, Tahriri P, Vermylen C, et al.
Five years of experience with hydroxyurea in children and young adults with sickle cell disease.
Blood.
2001;97:3628-3632[Abstract/Free Full Text].
2.
De Montalembert M, Davies SC.
Is hydroxyurea leukemogenic in children with sickle cell disease?
Blood.
2001;98:2878-2879[Free Full Text].
3.
Ware RH, Eggleston B, Redding-Lallinger R, et al.
Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy.
Blood.
2002;99:10-14[Abstract/Free Full Text].
4.
Kinney TR, Helms RW, O'Branski EE, et al.
Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial.
Blood.
1999;94:1550-1554[Abstract/Free Full Text].
5.
Steinberg MH, Barton FB, Castro O, Ramirez G, Bellevue R, Terrin M.
Hydroxyurea (HU) is associated with reduced mortality in adults with sickle cell anemia [abstract].
Blood.
2000;96:2087a.
6.
De Montalembert M, Bégué P, Bernaudin F, Thuret I, Bachir D, Micheau M.
Preliminary report of a toxicity study of hydroxyurea in sickle cell disease.
Arch Dis Child.
1999;81:437-439[Abstract/Free Full Text].
7.
Charache S, Terrin ML, Moore RD, et al.
Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia.
N Engl J Med.
1995;332:1317-1322[Abstract/Free Full Text].
8.
Ungar B.
Cryptosporidium. In:
Mandell GL,Bennett JE,Dolin R, eds.
Mandell, Douglas and Bennett's: Principles and Practice of Infectious Diseases. Vol 2. London, England: Churchill Livingston; 2000:2903-2915.
9.
Venkataraman M, Westerman MP.
B-cell changes occur in patients with sickle cell anemia.
Am J Clin Pathol.
1985;84:153-158[Medline]
[Order article via Infotrieve].
10.
Ravot E, Tambussi G, Jessen H, et al.
Effects of hydroxyurea on T-cell changes during primary HIV infection.
AIDS.
2000;14:619-621[Medline]
[Order article via Infotrieve].
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