History

Hypereosinophilia syndrome is a multisystem disease with symptoms related to eosinophil proteins and thrombotic phenomenon. Constitutional symptoms include fever, night sweats, anorexia, weight loss, fatigue, and nausea. Alcohol intolerance is occasionally noted.

Abdominal/GI symptoms include the following:

Nausea
Abdominal pain
Diarrhea
Ascites
Hepatic thrombosis (Budd-Chiari syndrome)

Pulmonary symptoms include the following:

Breathlessness
Nonproductive cough

Dermatologic symptoms include a pruritic rash.

Vascular symptoms include the following:

Raynaud phenomenon
Thrombotic phenomenon, including retinal and hepatic (Budd-Chiari syndrome) symptoms

Cardiac symptoms include cardiac phenomenon (variant angina).

Musculoskeletal symptoms include the following:

Arthralgias
Muscle pain

Neurologic symptoms include the following:

Blurred vision
Confusion
Seizures
Psychosis
Dementia

Gynecologic symptoms include mastitis.

Physical

Physical findings are those of a multisystem disease associated with thrombotic phenomenon.

Cardiac signs include the following:

Endomyocardial fibrosis with myocarditis
Arrhythmia
Heart block
Congestive heart failure (CHF)
Valvular incompetence from fibrosis of chordae tendineae
Mitral and tricuspid regurgitation
Aortic valve disease (rare)

Dermatologic signs include the following:

Vesiculobullous or petechial rash
Papulonodular
Livido reticularis
Angioedema
Blistering skin lesions
Cellulitis
Erythroderma
Erythema annulare
Ulcerating lesions of oral or nasal mucosa, genitalia, and anus
Subcutaneous nodules
Raynaud phenomenon
Subungual petechiae
Digital necrosis

Musculoskeletal signs include the following:

Effusions of large joints
Multifocal bursitis, pauciarticular arthritis, subcutaneous nodules, pseudorheumatoid arthritis, and muscle weakness or tenderness (all rare)

Vascular signs include the following:

Small-bowel necrosis
Subungual petechiae
Digital necrosis

GI signs include the following:

Esophageal and gastric ulceration
Small-bowel necrosis
Sclerosing cholangitis
Chronic active hepatitis
Eosinophilic gastritis
Enterocolitis
Colitis
Ascites
Pancreatitis
Hepatosplenomegaly

Pulmonary signs include the following:

Pulmonary infiltrates
Pleuritis
Pulmonary hypertension

Neurologic signs include the following:

Coma
Encephalopathy
Peripheral neuropathy (This may occur as symmetric or asymmetric sensory neuropathy, painful paresthesias, mixed sensory and motor neuropathy, mononeuritis multiplex, or radiculopathy.)
Intracranial hemorrhage and/or stroke

Ocular signs include the following:

Choroidal abnormalities (patchy and delayed filling, retinal vessel abnormality)
Pupillotonia
Keratoconjunctivitis sicca
Episcleritis
Retinal vein thrombosis

Causes

The cause is unknown, except in platelet-derived growth factor receptor alpha (PDGFRA)-associated hypereosinophilic syndrome. In this condition, the formation of theFLIP1L1/PDGFRA fusion gene (secondary to a 4q12 microdeletion) results in increased activity of tyrosine kinase of PDFGRA, resulting in eosinophilia or PDGFRA-associated chronic eosinophilic leukemia. Formation of the FLIP1L1/PDGFRA fusion gene is known to be found in 10-15% of patients with hypereosinophilic syndrome.

Differential Diagnoses

Kahn JE, Bletry O, Guillevin L. Hypereosinophilic syndromes. Best Pract Res Clin Rheumatol. 2008 Oct. 22(5):863-82. [QxMD MEDLINE Link].
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. 2008 May. 38(5):709-50. [QxMD MEDLINE Link].
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. 2011 Mar 10. 117(10):2935-43. [QxMD MEDLINE Link].
Rochman M, Travers J, Miracle CE, Bedard MC, Wen T, Azouz NP, et al. Profound loss of esophageal tissue differentiation in patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2017 Sep. 140 (3):738-749.e3. [QxMD MEDLINE Link].
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. 1982 Sep. 142(9):1754-5. [QxMD MEDLINE Link].
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. 2005 May. 19(5):792-8. [QxMD MEDLINE Link].
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. 2007 Jan. 85(1):5-10. [QxMD MEDLINE Link].
Roufosse F. Hypereosinophilic syndrome variants: diagnostic and therapeutic considerations. Haematologica. 2009 Sep. 94(9):1188-93. [QxMD MEDLINE Link].
Klion A. Hypereosinophilic syndrome: current approach to diagnosis and treatment. Annu Rev Med. 2009. 60:293-306. [QxMD MEDLINE Link].
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. 2009 Jan 1. 15(1):368-73. [QxMD MEDLINE Link].
Rothenberg ME, Klion AD, Roufosse FE, et al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008 Mar 20. 358(12):1215-28. [QxMD MEDLINE Link].
Adame J, Cohen PR. Eosinophilic panniculitis: diagnostic considerations and evaluation. J Am Acad Dermatol. 1996 Feb. 34(2 Pt 1):229-34. [QxMD MEDLINE Link].
Adams HW, Mainz DL. Eosinophilic ascites. A case report and review of the literature. Am J Dig Dis. 1977 Jan. 22(1):40-2. [QxMD MEDLINE Link].
Alfaham MA, Ferguson SD, Sihra B, Davies J. The idiopathic hypereosinophilic syndrome. Arch Dis Child. 1987 Jun. 62(6):601-13. [QxMD MEDLINE Link].
Anders HJ, Schattenkirchner M. Destructive joint lesions and bursitis in idiopathic hypereosinophilic syndrome. Rheumatology (Oxford). 1999 Feb. 38(2):185-6. [QxMD MEDLINE Link].
Bain BJ. Eosinophilic leukaemias and the idiopathic hypereosinophilic syndrome. Br J Haematol. 1996 Oct. 95(1):2-9. [QxMD MEDLINE Link].
Butterfield JH, Weiler CR. Use of pegylated interferon in hypereosinophilic syndrome. Leuk Res. 2012 Feb. 36(2):192-7. [QxMD MEDLINE Link].
Chaine G, Davies J, Kohner EM, Hawarth S, Spry CJ. Ophthalmologic abnormalities in the hypereosinophilic syndrome. Ophthalmology. 1982 Dec. 89(12):1348-56. [QxMD MEDLINE Link].
Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltimore). 1975 Jan. 54(1):1-27. [QxMD MEDLINE Link].
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. 1983 Winter. 52(205):23-39. [QxMD MEDLINE Link].
Flaum MA, Schooley RT, Fauci AS, Gralnick HR. A clinicopathologic correlation of the idiopathic hypereosinophilic syndrome. I. Hematologic manifestations. Blood. 1981 Nov. 58(5):1012-20. [QxMD MEDLINE Link].
Kang EY, Shim JJ, Kim JS, Kim KI. Pulmonary involvement of idiopathic hypereosinophilic syndrome: CT findings in five patients. J Comput Assist Tomogr. 1997 Jul-Aug. 21(4):612-5. [QxMD MEDLINE Link].
Katz HT, Haque SJ, Hsieh FH. Pediatric hypereosinophilic syndrome (HES) differs from adult HES. J Pediatr. 2005 Jan. 146(1):134-6. [QxMD MEDLINE Link].
Koneru S, Koshy G, Sharp C, Khalafallah AA. Hypereosinophilic syndrome associated with ulcerative colitis presenting with recurrent Loeffler's endocarditis and left ventricular thrombus treated successfully with immune suppressive therapy and anticoagulation. BMJ Case Rep. 2013 Sep 5. 2013:[QxMD MEDLINE Link].
Layzer RB, Shearn MA, Satya-Murti S. Eosinophilic polymyositis. Ann Neurol. 1977 Jan. 1(1):65-71. [QxMD MEDLINE Link].
Legrand F, Renneville A, Macintyre E, et al. The Spectrum of FIP1L1-PDGFRA-Associated Chronic Eosinophilic Leukemia: New Insights Based on a Survey of 44 Cases. Medicine (Baltimore). 2013 Aug 26. [QxMD MEDLINE Link].
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. 2006 Aug 15. 108(4):1374-6. [QxMD MEDLINE Link].
Lim J, Sternberg A, Manghat N, Ramcharitar S. Hypereosinophilic syndrome masquerading as a myocardial infarction causing decompensated heart failure. BMC Cardiovasc Disord. 2013 Sep 21. 13:75. [QxMD MEDLINE Link].
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. 1979 Oct. 67(4):572-82. [QxMD MEDLINE Link].
Podjasek JC, Butterfield JH. Mortality in hypereosinophilic syndrome: 19 years of experience at Mayo Clinic with a review of the literature. Leuk Res. 2013 Apr. 37(4):392-5. [QxMD MEDLINE Link].
Postovsky S, Daitzchman M, Dale A, Elhasid R, Ben Arush MW. Unusual presentation of mastoid eosinophilic granuloma in a young patient. Pediatr Hematol Oncol. 2001 Jun. 18(4):283-9. [QxMD MEDLINE Link].
Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol. 2006. 24:147-74. [QxMD MEDLINE Link].
Roufosse FE, Kahn JE, Gleich GJ, et al. Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes. J Allergy Clin Immunol. 2013 Feb. 131(2):461-7.e1-5. [QxMD MEDLINE Link]. [Full Text].
Shah TH, Shah S, Khan UH, et al. Idiopathic hypereosinphilic syndrome presenting as IgA nephropathy with nephrotic range proteinuria. Open J Nephrol. 2013. 2:101-3. [Full Text].
Spark RP, Gleason DM, DeBenedetti CD, Gigax JH. Is eosinophilic ureteritis an entity? 2 case reports and review. J Urol. 1991 Jun. 145(6):1256-60. [QxMD MEDLINE Link].
Strati P, Cortes J, Faderl S, Kantarjian H, Verstovsek S. Long-term follow-up of patients with hypereosinophilic syndrome treated with Alemtuzumab, an anti-CD52 antibody. Clin Lymphoma Myeloma Leuk. 2013 Jun. 13(3):287-91. [QxMD MEDLINE Link].
Tefferi A. Blood eosinophilia: a new paradigm in disease classification, diagnosis, and treatment. Mayo Clin Proc. 2005 Jan. 80(1):75-83. [QxMD MEDLINE Link].
van den Hoogenband HM. Skin lesions as the first manifestation of the hypereosinophilic syndrome. Clin Exp Dermatol. 1982 May. 7(3):267-71. [QxMD MEDLINE Link].
Wardlaw AJ, Moqbel R, Kay AB. Eosinophils: biology and role in disease. Adv Immunol. 1995. 60:151-266. [QxMD MEDLINE Link].
Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood. 1994 May 15. 83(10):2759-79. [QxMD MEDLINE Link].
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. 1981 Feb. 6(2):75-7. [QxMD MEDLINE Link].