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Severe Periorbital Edema Secondary to Imatinib Mesylate for Chronic Myelogenous Leukemia
Jill S. Melicher Larson, MD;
Lance K. Bergstrom, MD;
J. Douglas Cameron, MD, MBA;
Lori A. Erickson, MD;
Terrence E. Grimm, MD
Arch Ophthalmol. 2007;125(7):985-986.
A 70-year-old man developed severe periorbital edema secondary to imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp, East Hanover, NJ). Imatinib mesylate is a tyrosine kinase inhibitor with a high degree of specificity for the BCR-ABL, KIT, and platelet-derived growth factor receptor β tyrosine kinases. It is thought that inhibition of platelet-derived growth factor receptor β results in disruption of fluid homeostasis in the eyelids, resulting in the development of periorbital edema.
Report of a Case
A 70-year-old man developed mild periorbital edema within 2 weeks of starting imatinib mesylate at 400 mg perday for treatment of BCR-ABL–positive chronicmyelogenous leukemia. Three months later, the patient developed accelerated-phase chronic myelogenous leukemia and his imatinib mesylate dose was increased to 600 mg per day. His periorbital edema became significantly worse and visually disrupting. The patient was unresponsive to conservative therapy, including following a low-salt diet, restricting fluid intake, elevating the head of his bed, and using hydrocortisone cream, and was subsequently referred for bilateral upper and lower eyelid blepharoplasty.
At the time of his first examination, his visual acuity was 20/25 OD and 20/40 OS. His intraocular pressure was 18 mm Hg bilaterally. There was no clinical evidence of intraocular involvement by his leukemia. The anterior septal tissue of the upper and lower eyelids was markedly distended bilaterally (Figure 1A). There was a visually disrupting superior field defect that disappeared with taping of the eyelid bilaterally. The patient illustrated a functional field defect that was treated definitively with bilateral upper and lower eyelid blepharoplasty. Postoperative bleeding was extensive, requiring blood transfusion, and was attributed to thrombocytopenia secondary to his leukemia.
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Figure 1. Frontal photographs of the patient. A, Markedly distended anterior septal tissue of the upper and lower eyelids. B, At the 17-month postoperative follow-up, his facial appearance returned to normal.
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By light microscopy, the lower eyelid skin was edematous (Figure 2 and Figure 3). There was a mild increase in dermal epithelioid histiocytic cells and dermal dendrocytes. Immunoperoxidase studies were performed on paraffin-embedded tissue sections with antibodies to KIT (Dako, Carpinteria, CA), S100 (Dako), and CD1a (Immuntech, Marseille, France). The dermal dendrocytes were immunoreactive with antibodies to KIT. S100 immunostainhighlighted dermal nerve twigs. CD1a immunostain highlighted Langerhans cells. The diagnosis was marked periorbital edema associated with the use of imatinib mesylate.
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Figure 2. Light microscopic section of eyelid skin removed during blepharoplasty. The surface epithelium is intact with moderate swelling of all dermal tissues. The skin adnexa is spared. Procedure-related extravasation of blood is present at the surgical margin (original magnification x20, hematoxylin-eosin).
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Figure 3. Light microscopic section of excised eyelid tissue. All of the structural elements of the cutaneous tissue are separated by edema. There is mild infiltrate of plasma cells and acute inflammatory cells (original magnification x400, hematoxylin-eosin).
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Treatment with imatinib mesylate for BCR-ABL–positive chronic myelogenous leukemia was continued following blepharoplasty. Seventeen months following blepharoplasty, the patient continued treatment with imatinib mesylate at 600 mg per day. There has been no recurrence of periorbital edema (Figure 1B).
Comment
Imatinib mesylate is a selective signal transduction inhibitor showing a high degree of specificity to the pathologic BCR-ABL tyrosine kinase as well as normal KIT and the platelet-derived growth factor receptor tyrosine kinase family. This drug inhibits proliferation and promotes apoptosis in BCR-ABL cell lines.1 A promising treatment for chronic myelogenous leukemia and gastrointestinal stromal tumors, imatinib mesylate is generally well tolerated. Fluid retention, superficial and periorbital edema, nausea, vomiting, myalgia, fatigue, skin rashes, diarrhea, and hepatotoxicity are reported as the most common clinical adverse effects of imatinib mesylate.1-2 Periorbital edema has been reported in up to 70% of patients treated with imatinib mesylate.3
Platelet-derived growth factor receptor β is thought to regulate tissue fluid properties and is avidly expressed on the dermal dendrocytes of periorbital tissue. Studies have shown that inhibition of platelet-derived growth factor receptor β in dermal dendrocytes by imatinib mesylate increases interstitial fluid pressure in the dermis, predisposing to edema.3-4 The lack of structural support in periorbital tissue, particularly the lower eyelids, makes it exceptionally vulnerable to localized edema.
Our patient was treated definitively with bilateral blepharoplasty, rather than biopsy, because of a significant field defect.5 Immunohistochemical studies showed that dermal dendrocytes were positive for KIT, suggesting the periorbital edema in this patient was secondary to imatinib mesylate.
AUTHOR INFORMATION
Correspondence: Dr Melicher Larson, Department of Ophthalmology, University of Minnesota, 420 Delaware St SE, MMC 493, Minneapolis, MN 55455 (melic014{at}umn.edu).
Financial Disclosure: None reported.
REFERENCES
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1. Druker BJ, Talpaz M, Resta DJ; et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344(14):1031-1037.
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2. Gleevec [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2003.3. Fraunfelder FW, Solomon J, Druker BJ, Esmaeli B, Kuyl J. Ocular side-effects associated with imatinib mesylate (Gleevec). J Ocul Pharmacol Ther. 2003;19(4):371-375.
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4. Esmaeli B, Prieto VG, Butler CE; et al. Severe periorbital edema secondary to STI571 (Gleevec). Cancer. 2002;95(4):881-887.
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5. Maalouf T, Angioi K, Champigneulle J, Guerci A, George JL. Palpebral edema secondary to treatment by a specific inhibitor of tyrosine kinase, Glivec: a case report [in French]. J Fr Ophtalmol. 2004;27(1):107-109.
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SECTION EDITOR: W. RICHARD GREEN, MD
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