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The Annals of Pharmacotherapy: Vol. 37, No. 9, pp. 1228-1231. DOI 10.1345/aph.1D071
© 2003 Harvey Whitney Books Company.
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Severe Hypersensitivity Pneumonitis Associated with Anagrelide

Murugan Raghavan, MD MRCP

Postgraduate Year 2 Resident, Department of Critical Care Medicine, Conemaugh Valley Memorial Hospital, Johnstown, PA

Mark A Mazer, MD

Director of Critical Care Medicine, Conemaugh Valley Memorial Hospital

David J Brink, PharmD

Resident in Pharmacology, Conemaugh Valley Memorial Hospital

Reprints: Mark A Mazer MD, Conemaugh Valley Memorial Hospital, 1086 Franklin St., Johnstown, PA 15905-4398, FAX 814/534-3290, mmazer{at}conemaugh.org

OBJECTIVE: To report a case of severe life-threatening hypersensitivity pneumonitis temporally associated with the use of anagrelide in a patient with myeloproliferative disorder.

CASE SUMMARY: A 60-year-old white woman with chronic myeloid leukemia who had been treated with hydroxyurea for 7 years was offered anagrelide to control thrombocytosis. She developed severe hypersensitivity pneumonitis soon after the drug was initiated and required intubation and mechanical ventilation. A high-resolution computed tomography scan of the chest demonstrated extensive multifocal ground glass attenuation and patchy alveolar consolidation involving both lungs. Bronchoalveolar lavage revealed a preponderance of lymphocytes, suggesting hypersensitivity phenomenon, but was otherwise negative for malignancy and other causes of interstitial pneumonitis. An objective causality assessment revealed that an adverse drug event was probable. Discontinuation of anagrelide and hydroxyurea, and institution of corticosteroid therapy resulted in dramatic improvement.

DISCUSSION: To our knowledge, this is the first case report of severe hypersensitivity pneumonitis closely related to anagrelide therapy. Pulmonary infiltrates have rarely been noted in patients treated with anagrelide. Anagrelide does not depress white blood cell production, causes mild anemia, and is devoid of the leukemogenic potential characteristic of radioactive phosphorus and other alkylating agents. Common adverse effects to anagrelide include headache, nausea, diarrhea, peripheral edema, and palpitations. Frank congestive heart failure and cardiomyopathy have occurred in a small number of patients, but severe pulmonary adverse effects have not emerged as a frequent problem.

CONCLUSIONS: Vigilance is advised in patients who develop dyspnea while taking anagrelide and hydroxyurea. Healthcare providers need to be aware of the possibility of the development of serious life-threatening hypersensitivity pneumonitis. These patients may benefit from serial chest X-rays, pulmonary function testing, and echocardiography.

Key Words: anagrelide, hypersensitivity pneumonitis, thrombocytosis

Published Online, June 23, 2003. www.theannals.com, DOI 10.1345/aph.1D071




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