Pediatric Hypereosinophilic Syndrome Medication
- Author: Bruce M Rothschild, MD; Chief Editor: Harumi Jyonouchi, MD more...
Medication Summary
No therapy is indicated in the absence of organ damage. Treatment is directed at organ system involvement and at reducing the eosinophil load and perhaps the eosinophil effect.
A small experimental study found that alemtuzumab was helpful in advanced hypereosinophilic syndrome refractory to other standard therapies. Escalating doses of 5 mg, 10 mg, and 30 mg IV on days 1-3, and then at tolerated dose 3 times per week for 3 weeks, were suggested. If a full response is seen, consider weekly administration. The authors suggest clinical evaluation of alemtuzumab in a larger clinical trial is warranted.[12]
Corticosteroids
Class Summary
These agents interfere with eosinophilopoiesis by antagonizing IL-5, IL-3, and granulocyte/monocyte cell–stimulating factor. They also suppress eosinophilia; however, discontinue corticosteroids if eosinophilia is not suppressed. Response to steroids is considered a good prognostic indicator.
Prednisone (Deltasone, Meticorten, Orasone, Sterapred)
Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.
Immunosuppressant and immunomodulator agents
Class Summary
These drugs are used to inhibit DNA synthesis, but only case reports of their effectiveness are available.
Hydroxyurea (Hydrea)
Interferes with DNA synthesis. Used to reduce total leukocyte count to < 10,000/µL. Requires 7-14 d for effectiveness.
Vincristine (Oncovin)
Used to reduce total leukocyte count to < 10,000/µL. Effective in 1-3 d and spares bone marrow toxicity but may cause paresthesias.
Cyclophosphamide (Cytoxan)
Used to reduce total leukocyte count to < 10,000/µL.
Busulfan (Myleran)
Used to reduce total leukocyte count to < 10,000/µL.
Methotrexate (Rheumatrex)
Used to reduce total leukocyte count to < 10,000/µL.
Chlorambucil (Leukeran)
Used to reduce total leukocyte count to < 10,000/µL.
Etoposide (VP16-213, VePesid)
Podophyllotoxin derivative that acts as topoisomerase II inhibitor to cause DNA damage.
Interferon alfa 2a or 2b (Roferon-A, Intron-A)
Empirically applied to many diseases as immunomodulator. Acts at biologically active sites in eosinophil action.
Cyclosporine (Sandimmune, Neoral)
Inhibits T-cell clonal release of eosinophilopoietin cytokines.
Sorafenib (Nexavar)
Multikinase inhibitor that targets serine/threonine and tyrosine receptor kinases in both the tumor cell and the tumor vasculature. Targets kinases involved in tumor cell proliferation and angiogenesis, thereby decreasing tumor cell proliferation. These kinases include RAF kinase, VEGFR-2, VEGFR-3, PDGFR-beta, KIT, and FLT-3.
Imatinib mesylate (Gleevec)
Specifically designed to inhibit tyrosine kinase activity of the bcr-abl kinase in Ph+ leukemic chronic myeloid leukemia (CML) cell lines. Well absorbed after PO administration, with maximum concentrations achieved within 2-4 hours. Elimination is primarily in feces in form of metabolites. FDA-approved for chronic hypereosinophilic syndrome in adults. Also indicated to treat pediatric patients with Ph+ chronic phase CML whose disease has recurred after stem cell transplant, or have demonstrated interferon alpha resistance.
Anti-inflammatory agents
Class Summary
Dapsone is a sulfone antimicrobial. Its anti-inflammatory action, which enables its use for dermatologic conditions, is not fully understood but does not appear to be associated with its antibacterial action.
Dapsone (Avlosulfon)
Sulfone specifically useful for skin involvement.
Anticoagulant and antiplatelet agents
Class Summary
These agents are used in an effort to reduce frequency of thrombotic events. Warfarin and aspirin have well-established roles in preventing thrombosis. Warfarin acts as an anticoagulant by antagonizing vitamin K in its role as a cofactor in the carboxylation process of coagulation factors II, VII, IX, and X. Aspirin possess antiplatelet ability by permanently inactivating cyclooxygenase (COX) activity of prostaglandin synthase-1 and prostaglandin synthase-2 (ie, COX-1 and COX-2).
Thromboxane A2 (TXA2) induces platelet aggregation and vasoconstriction. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit TXA2 by reversible inhibition of COX-1. The level of reversible inhibition provided by NSAIDS may be inadequate to effectively block platelet aggregation in vivo. However, the NSAID indobufen, which is not available in the United States, is a potent inhibitor and has biochemical activity comparable to aspirin. Further investigation of effective antiplatelet drugs is essential to overcome obstacles associated with aspirin (eg, toxicity, resistance).
Warfarin (Coumadin)
Used to achieve sufficient anticoagulation to prevent thrombotic events. Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Adjust dose to maintain INR of 2-3 in absence of associated anticardiolipin syndrome.
Aspirin (Anacin, Ascriptin, Bayer)
Inhibits prostaglandin synthesis, preventing formation of platelet-aggregating TXA2. May be used in low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis.
Interleukin inhibitor
Class Summary
Results from a Phase III study demonstrate significantly more patients who received mepolizumab for treatment of hypereosinophilic syndrome were able to maintain disease control with reduced corticosteroid use (84% vs 43%, p< 0.001).[13]
Mepolizumab (Bosatria)
Humanized anti-interleukin-5 monoclonal immunoglobulin G1 antibody. Orphan drug status in the United States and the European Union.
Kahn JE, Bletry O, Guillevin L. Hypereosinophilic syndromes. Best Pract Res Clin Rheumatol. Oct 2008;22(5):863-82. [Medline].
Martinelli G, Rondoni M, Ottaviani E, Paolini S, Baccarani M. Hypereosinophilic syndrome and molecularly targeted therapy. Semin Hematol. 2007;44(Suppl 2):S4-S16.
Hogan SP, Rosenberg HF, Moqbel R, Phipps S, Foster PS, Lacy P. Eosinophils: biological properties and role in health and disease. Clin Exp Allergy. May 2008;38(5):709-50. [Medline].
Elling C, Erben P, Walz C, Frickenhaus M, Schemionek M, Stehling M. Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease. Blood. Mar 10 2011;117(10):2935-43. [Medline].
James J. Pediatric hypereosinophilic syndrome (HES) differs from adult HES. Pediatrics. 2006;118:S49-S50. [Full Text].
Carey JP, Burke AC. Transient hypereosinophilia in the infant of a mother with hypereosinophilic syndrome. Arch Intern Med. Sep 1982;142(9):1754-5. [Medline].
Roche-Lestienne C, Lepers S, Soenen-Cornu V, et al. Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics. Leukemia. May 2005;19(5):792-8. [Medline].
Schoch C, Reiter A, Bursch S, et al. Chromosome binding analysis, FISH and RT-PCR performed in parallel in hyperesosinophilic syndrome establishes the diagnosis of chronic eosinophilic leukemia in 22% of cases: A study of 40 patients. Blood. 2004;104:2444.
Miyazawa K, Kakazu N, Ohyashiki K. Clinical features of hypereosinophilic syndrome: FIP1L1-PDGFRA fusion gene-positive disease is a distinct clinical entity with myeloproliferative features and a poor response to corticosteroid. Int J Hematol. Jan 2007;85(1):5-10. [Medline].
Klion A. Hypereosinophilic syndrome: current approach to diagnosis and treatment. Annu Rev Med. 2009;60:293-306. [Medline].
Roufosse F. Hypereosinophilic syndrome variants: diagnostic and therapeutic considerations. Haematologica. Sep 2009;94(9):1188-93. [Medline].
Verstovsek S, Tefferi A, Kantarjian H, Manshouri T, Luthra R, Pardanani A, et al. Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic leukemia. Clin Cancer Res. Jan 1 2009;15(1):368-73. [Medline].
[Best Evidence] Rothenberg ME, Klion AD, Roufosse FE, et al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. Mar 20 2008;358(12):1215-28. [Medline].
Adame J, Cohen PR. Eosinophilic panniculitis: diagnostic considerations and evaluation. J Am Acad Dermatol. Feb 1996;34(2 Pt 1):229-34. [Medline].
Adams HW, Mainz DL. Eosinophilic ascites. A case report and review of the literature. Am J Dig Dis. Jan 1977;22(1):40-2. [Medline].
Alfaham MA, Ferguson SD, Sihra B, Davies J. The idiopathic hypereosinophilic syndrome. Arch Dis Child. Jun 1987;62(6):601-13. [Medline].
Anders HJ, Schattenkirchner M. Destructive joint lesions and bursitis in idiopathic hypereosinophilic syndrome. Rheumatology (Oxford). Feb 1999;38(2):185-6. [Medline].
Bain BJ. Eosinophilic leukaemias and the idiopathic hypereosinophilic syndrome. Br J Haematol. Oct 1996;95(1):2-9. [Medline].
Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltimore). Jan 1975;54(1):1-27. [Medline].
Cryer PE, Kissane J. Hypereosinophilic syndrome with pulmonary hypertension. 1976;60:239-247.
Davies J, Spry CJ, Sapsford R, et al. Cardiovascular features of 11 patients with eosinophilic endomyocardial disease. Q J Med. Winter 1983;52(205):23-39. [Medline].
Flaum MA, Schooley RT, Fauci AS, Gralnick HR. A clinicopathologic correlation of the idiopathic hypereosinophilic syndrome. I. Hematologic manifestations. Blood. Nov 1981;58(5):1012-20. [Medline].
Kang EY, Shim JJ, Kim JS, Kim KI. Pulmonary involvement of idiopathic hypereosinophilic syndrome: CT findings in five patients. J Comput Assist Tomogr. Jul-Aug 1997;21(4):612-5. [Medline].
Katz HT, Haque SJ, Hsieh FH. Pediatric hypereosinophilic syndrome (HES) differs from adult HES. J Pediatr. Jan 2005;146(1):134-6. [Medline].
Layzer RB, Shearn MA, Satya-Murti S. Eosinophilic polymyositis. Ann Neurol. Jan 1977;1(1):65-71. [Medline].
Lierman E, Folens C, Stover EH, et al. Sorafenib is a potent inhibitor of FIP1L1-PDGFRalpha and the imatinib-resistant FIP1L1-PDGFRalpha T674I mutant. Blood. Aug 15 2006;108(4):1374-6. [Medline].
Parrillo JE, Borer JS, Henry WL, et al. The cardiovascular manifestations of the hypereosinophilic syndrome. Prospective study of 26 patients, with review of the literature. Am J Med. Oct 1979;67(4):572-82. [Medline].
Postovsky S, Daitzchman M, Dale A, Elhasid R, Ben Arush MW. Unusual presentation of mastoid eosinophilic granuloma in a young patient. Pediatr Hematol Oncol. Jun 2001;18(4):283-9. [Medline].
Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol. 2006;24:147-74. [Medline].
Spark RP, Gleason DM, DeBenedetti CD, Gigax JH. Is eosinophilic ureteritis an entity? 2 case reports and review. J Urol. Jun 1991;145(6):1256-60. [Medline].
Tefferi A. Blood eosinophilia: a new paradigm in disease classification, diagnosis, and treatment. Mayo Clin Proc. Jan 2005;80(1):75-83. [Medline].
van den Hoogenband HM. Skin lesions as the first manifestation of the hypereosinophilic syndrome. Clin Exp Dermatol. May 1982;7(3):267-71. [Medline].
Wardlaw AJ, Moqbel R, Kay AB. Eosinophils: biology and role in disease. Adv Immunol. 1995;60:151-266. [Medline].
Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood. May 15 1994;83(10):2759-79. [Medline].
White WL, Wahner HW, Brown ML, James EM. Sequential liver imaging in the hypereosinophilic syndrome: discordant images with scintigraphy, ultrasound, and computed tomography. Clin Nucl Med. Feb 1981;6(2):75-7. [Medline].
Print
