Case: TA
45F hx migraine HAs, depression and mild asthma presents to UWMC ED with CC of progressive
abdominal pain with associated nausea/vomiting and occasional diarrhea.
PE: VSS, anxious appearing. CTAB, CV wnl, diffuse abdominal tenderness, no peritoneal signs. No
palpable nodes. No rashes or skin lesions.
CT AP: Segmental wall thickening and pericolonic inflammatory changes involving the sigmoid colon,
trace ascites. No LAD or masses.
Ab US with Doppler: Nonocclusive thrombus in the superior mesenteric vein and left portal vein,
otherwise normal liver, biliary tree, GB
Labs:
Lipase/amylase: wnl
Case: TA
WBC diff:
N: 29% (4.73)
L: 15% (2.59)
M: 4% (0.59)
E: 51% (8.49)
Baso: 0% (0.05)
PBS: mild normocytic anemia, no NRBCs , rare teardrops. Platelets reduced in number, normal in
appearance.
Outline
Thrombosis in HES
Thombocytopenia in HES
Eosinophil: non-dividing, end-stage granular leukocytes derived from CD34+ marrow precursors
>100 fold higher concentration in tissue than peripheral blood (lower GI tract, spleen , LNs)
Granules contain major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase
(EPO), eosinophil derived neurotoxin (EDN)
Function/dysfunction:
Hypereosinophilia: definitions
Definitions:
infection, esp tissue invasive parasites (eg strongyloides stercoralis, schistosoma spp., toxocara spp, trichinella spp, filaria),
allergic/atopic
medication associated, DRESS (NSAIDs, PCN, cephalosporins, aspirin, allopurinol, dilantin/ AEDs)
***lymphocyte variant (clonal T-cell population evolving IL-5 with secondary eosinophilia)
Idiopathic: ???
Hypereosinophilia: etiologies
Lombardi, et al 2003
Additional history:
PMH: migraine HAs (well controlled), mild asthma (dx 20 yrs ago) has been worse lately,
depression/PTSD
Meds: No new meds. Chronic meds: clonazepam, prazosin, topiramate, rizatriptan, lunesta, albuterol
Social: US born, no recent foreign travel, no pets. Non smoker, occasional EtOH, no illicits. Sushi
aficionado.
Additional workup:
CT chest notable for left lower lobe segmental and subsegmental PEs, no LAD or pulm interstitial disease
FISH neg for FIP1L1, PDGFRA, PDGFRB, FGFR1, KIT, CBFB rearrangements
EGD/colonoscopy with mild esophagitis/gastritis, mild luminal narrowing at 23-30cm from anal
verge, otherwise normal appearing mucosa
Diagnosis?
aka
Interval worsening of the acute pulmonary thromboembolic disease. New pulmonary emboli are identified in
the left main pulmonary artery, segmental and subsegmental branches in the left upper lobe and right lower
lobe with persistent clots in the left lower lobe segmental and subsegmental branches.
Right: Non-occlusive deep venous thrombosis is present in the right proximal femoral vein. Superficial venous thrombosis is
present in the right great saphenous vein from mid calf to distal thigh.
Left: Non-occlusive deep venous thrombosis is present in the left common femoral and proximal main thigh femoral veins.
Occlusive deep venous thrombosis is present in two left gastrocnemius veins.
Compared to study of 3/7/14, evidence for progression includes new non-occlusive thrombus in the posterior branch of the
right portal vein, main portal vein, and new bidirectional flow in the left portal vein, which was previously hepatopetal.
Methylpred 1g QD initiated
Well, it happens
Approximately 25-30% of HES patients have associated thomboembolic events with approx 5-10%
associated mortality (Ogbogu, et al 2007)
Spry CJ, Davies J, Tai PC, Olsen EG, Oakley CM, Goodwin JF. Clinical features of fifteen patients with the hypereosinophilic syndrome. Q J Med. 1983;52(205):122
Elouaer-Blanc L, Zafrani ES, Farcet JP, Saint-Marc Girardin MF, Mathieu D, Dhumeaux D. Hepatic vein obstruction in idiopathic hypereosinophilic syndrome. Arch Intern
Med. 1985 Apr;145(4):751753.
Ishii T, Koide O, Hosoda Y, Takahashi R. Hypereosinophilic multiple thrombosis. A proposal of a new designation of disseminated eosinophilic collagen
disease Angiology. 1977 Jun;28(6):361375.
Kanno H, Ouchi N, Sato M, Wada T, Sawai T. Hypereosinophilia with systemic thrombophlebitis.Hum Pathol. 2005 May;36(5):585589.
Valente O, Scarpinella-Bueno MA. Deep venous thrombosis in hypereosinophilic syndrome. Am Fam Physician. 1994 Oct;50(5):921922.
Mukai HY, Ninomiya H, Mitsuhashi S, Hasegawa Y, Nagasawa T, Abe T. Thromboembolism in a patient with transient eosinophilia. Ann Hematol. 1996 Feb;72(2):9395.
Todd S1, Hemmaway C, Nagy Z. Catastrophic thrombosis in idiopathic hypereosinophilic syndrome. Br J Haematol. 2014 Jan 24. doi: 10.1111/bjh.12729. [Epub ahead of
print]
Sui T1, Li Q2, Geng L1, Xu X3, Li Y1. A case of hypereosinophilic syndrome presenting with multiorgan thromboses associated with intestinal obstruction. Turk J Haematol.
2013 Sep;30(3):311-4. doi: 10.4274/Tjh.2012.0141. Epub 2013 Sep 5.
Li Q, Sui T, Geng L. [A case of idiopathic eosinophilic syndrome complicated with multiple arterial and venousthrombosis]. Zhonghua Xue Ye Xue Za Zhi. 2012
May;33(5):377.
Sakuta R, Tomita Y, Ohashi M, Nagai T, Murakami N. Idiopathic hypereosinophilic syndrome complicated by central sinovenous thrombosis. Brain Dev. 2007 Apr;29(3):182
184
Schulman H, Hertzog L, Zirkin H, Hertzanu Y. Cerebral sinovenous thrombosis in the idiopathic hypereosinophilic syndrome in childhood. Pediatr Radiol. Aug 1999;29(8):595
597.
Narayan S, Ezughah F, Standen GR, Pawade J, Kennedy CT. Idiopathic hypereosinophilic syndrome associated with cutaneous infarction and deep venous thrombosis. Br
J Dermatol. 2003 Apr;148(4):817820.
Kikuchi K, Minami K, Miyakawa H, Ishibashi M. Portal vein thrombosis in hypereosinophilic syndrome. Am J Gastroenterol. 2002 May;97(5):1274-5.
DTI vs heparinoids for acute management (ie bival gtt vs heparin gtt)?
Meanwhile
Additional labs: Fibrinogen, PTT/PT wnl. Peripheral smear unchanged from admission (no signs of MAHA)
Well, it happens
Leon-Ferre RA, Weiler CR, Halfdanarson TR. Hypereosinophilic syndrome presenting as an unusual triad of eosinophilia,
severe thrombocytopenia, and diffuse arterial thromboses, with good response to mepolizumab. Clin Adv Hematol Oncol.
2013 May;11(5):317-9. ***Plt count of 8K on admission, inverse tracking with eosinophil count
Lim KS, Ko J, Lee SS, Shin B, Choi DC, Lee BJ. A case of idiopathic hypereosinophilic syndrome presenting with acute
respiratory distress syndrome. Allergy Asthma Immunol Res. 2014 Jan;6(1):98-101. ***plt 26 on admission
H. Liapis, A.K. Ho, D. Brown, G. Mindel, G. Gleich. Thrombotic microangiopathy associated with the hypereosinophilic
syndrome. Kidney Int, 67 (2005), pp. 18061811
Z. Al Aly, J.M. Philoctete Ashley, M.E. Gellens, E.A. Gonzalez. Thrombotic thrombocytopenic purpura in a patient treated
with imatinib mesylate: true association or mere coincidence? Am J Kidney Dis, 45 (2005), pp. 762768
Yuste C1, Quiroga B, Verde E, Barraca D, Reque JE, Perez de Jose A, Luo. The non-casual relation between eosinophilia
and thrombotic microangiopathy. J Transfus Apher Sci. 2012 Dec;47(3):365-7
Autoantibody production? (Lassalle, et al. Clin Exp Immunol. Oct 1990; 82(1): 3843)
And then
A/P
(Butterfield et al, Success of short term, higher dose imatinib mesylate to induce clincal response in FIP1L1-PDGFRa negative
hypereosinophilic syndrome. Leuk Res, 2009.)
(Ueno et al, Successful non-myeloablative allogeneic transplantation for treatment of idiopathic hypereosinophilic symdrome.
Br J Haemat, 2002)
Thank you
References
Spry CJ, Davies J, Tai PC, Olsen EG, Oakley CM, Goodwin JF. Clinical features of fifteen patients with the hypereosinophilic syndrome. Q J Med. 1983;52(205):122
Elouaer-Blanc L, Zafrani ES, Farcet JP, Saint-Marc Girardin MF, Mathieu D, Dhumeaux D. Hepatic vein obstruction in idiopathic hypereosinophilic syndrome. Arch Intern Med. 1985
Apr;145(4):751753.
Ishii T, Koide O, Hosoda Y, Takahashi R. Hypereosinophilic multiple thrombosis. A proposal of a new designation of disseminated eosinophilic collagen disease Angiology. 1977
Jun;28(6):361375.
Kanno H, Ouchi N, Sato M, Wada T, Sawai T. Hypereosinophilia with systemic thrombophlebitis.Hum Pathol. 2005 May;36(5):585589.
Valente O, Scarpinella-Bueno MA. Deep venous thrombosis in hypereosinophilic syndrome. Am Fam Physician. 1994 Oct;50(5):921922.
Mukai HY, Ninomiya H, Mitsuhashi S, Hasegawa Y, Nagasawa T, Abe T. Thromboembolism in a patient with transient eosinophilia. Ann Hematol. 1996 Feb;72(2):9395.
Todd S1, Hemmaway C, Nagy Z. Catastrophic thrombosis in idiopathic hypereosinophilic syndrome. Br J Haematol. 2014 Jan 24. doi: 10.1111/bjh.12729. [Epub ahead of print]
Sui T1, Li Q2, Geng L1, Xu X3, Li Y1. A case of hypereosinophilic syndrome presenting with multiorgan thromboses associated with intestinal obstruction. Turk J Haematol. 2013
Sep;30(3):311-4. doi: 10.4274/Tjh.2012.0141. Epub 2013 Sep 5.
Li Q, Sui T, Geng L. [A case of idiopathic eosinophilic syndrome complicated with multiple arterial and venousthrombosis]. Zhonghua Xue Ye Xue Za Zhi. 2012 May;33(5):377.
Sakuta R, Tomita Y, Ohashi M, Nagai T, Murakami N. Idiopathic hypereosinophilic syndrome complicated by central sinovenous thrombosis. Brain Dev. 2007 Apr;29(3):182184
Schulman H, Hertzog L, Zirkin H, Hertzanu Y. Cerebral sinovenous thrombosis in the idiopathic hypereosinophilic syndrome in childhood. Pediatr Radiol. Aug 1999;29(8):595597.
Narayan S, Ezughah F, Standen GR, Pawade J, Kennedy CT. Idiopathic hypereosinophilic syndrome associated with cutaneous infarction and deep venous thrombosis. Br J
Dermatol. 2003 Apr;148(4):817820.
Kikuchi K, Minami K, Miyakawa H, Ishibashi M. Portal vein thrombosis in hypereosinophilic syndrome. Am J Gastroenterol. 2002 May;97(5):1274-5.
References
Leon-Ferre RA, Weiler CR, Halfdanarson TR. Hypereosinophilic syndrome presenting as an unusual triad
of eosinophilia, severe thrombocytopenia, and diffuse arterial thromboses, with good response to mepolizumab.
Clin Adv Hematol Oncol. 2013 May;11(5):317-9. ***Plt count of 8K on admission, inverse tracking with eosinophil
count
Lim KS, Ko J, Lee SS, Shin B, Choi DC, Lee BJ. A case of idiopathic hypereosinophilic syndrome presenting with
acute respiratory distress syndrome. Allergy Asthma Immunol Res. 2014 Jan;6(1):98-101. ***plt 26 on admission
H. Liapis, A.K. Ho, D. Brown, G. Mindel, G. Gleich. Thrombotic microangiopathy associated with the
hypereosinophilic syndrome. Kidney Int, 67 (2005), pp. 18061811
Z. Al Aly, J.M. Philoctete Ashley, M.E. Gellens, E.A. Gonzalez. Thrombotic thrombocytopenic purpura in a patient
treated with imatinib mesylate: true association or mere coincidence? Am J Kidney Dis, 45 (2005), pp. 762768
Yuste C1, Quiroga B, Verde E, Barraca D, Reque JE, Perez de Jose A, Luo. The non-casual relation between
eosinophilia and thrombotic microangiopathy. J Transfus Apher Sci. 2012 Dec;47(3):365-7
Mepolizumab
Mepolizumab
Duration of remission?
Role of maintenance?