1. Hypereosinophilic Syndrome & Kidney disease
Department of nephrology
R2 우용식

2. Introduction eosinophilia >600/mm3
mild 600~1600/mm3
moderat 1500~5000/mm3
severe >5000/mm3
damage to multiple organs d/t eosinophilic
infiltration & mediator
release rather than eosinophil count

3. Evaluation of eosinophilia patients
Initial interview
:allergic sx, travel history, medication history
Parasite infection
: 3 stool specimen examed for ova, parasite
serologic test in tissue or blood infection
Allergic disorder
: smear of nasal discharge – allergic rhinitis
sputum eosinophilia – asthma
Medication related
: detailed history of current or past medication
only eosinophilia not cessation but organ involvement

4. Evaluation of eosinophilia patients
Hematologic and neoplastic disorder
: hypereosinphilic syndrome
mastocytosis
leukemia (AML M4, precusor B-cell ALL)
lymphoma

5. DEFINITION of IHES eosinophilia of >1500/µL > 6 mo.
no other eti. for eosinophilia ; parasitic infection or allergic dz.
Signs & Sx of end-organ dysfunction are present

6. Pathophysiology
Defects in signal transduction from receptors to mediate eosinophilopoiesis
Overproduction of eosinophilopoietic signals (eg, interleukin (IL)-3, IL-5, GM-CSF)
Abnormalities of eosinophilopoietic cytokines
Defects in receptors for eosinophilopoietic signals
Defects in suppressive regulation of eosinophilopoiesis

7. Specific identifiable etiologies for hypereosinophilia
Variants with clonal eosinophil abnormalities
X-linked polymorphisms, limiting to women
responded to glucocorticoids alone
Atypical myeloproliferative variant
more typical of myeloproliferative disorders
often refractory to glucocorticoid
responded to tyrosine kinase inhibitor, imatinib mesylate
T cell lymphocytic variants
underlying aberrations in T lymphocytes (CD3-, CD4 +)

8. Differential diagnosis of IHES
Acute eosinophilic leukemia
marked increased immature eosinophils in the blood
> 10% blast forms in the marrow
infiltration of tissues with immature eosinophil forms
clinical course similar to other acute leukemias
Churg-Strauss syndrome
major vasculitis ass. with eosinophilia
vasculitis , not in HES but smaller vessels in CSS

9. Differential diagnosis of IHES
episodic angioedema with eosinophilia
(Gleich syndrome)
recurrent episodes of angioedema, urticaria, pruritus
elevated IgM, leukocytosis with marked blood eosinophilia
absence of end-organ involvement , episodic symptoms
may progress to HES or T lymphocytic variant HES.

10. Symptom of IHES Fatigue — 26 percent Cough — 24 percent
Breathlessness —16 percent
Muscle pains — 14 percent
Angioedema — 14 percent
Rash — 12 percent
Fever — 12 percent
Retinal lesions — 10 percent

11. Clinical manifestation
cardiac disease
: eosinophilic myocarditis , major cause of morbidity and mortality
acute necrotic stage →intermediate phase by thrombus formation damaged endocardium → fibrotic stage
neurologic disease
:cerebral thromboemboli, encephalopathy, pph neuropathy

12. other organ systems pulmonary disease
: chronic, persistent, nonproductive cough
eosinophilic infiltration of the lung with fibrosis
congestive heart failure, pulmonary emboli
ocular disease
: blurred vision, related to microemboli , local thrombosis
other organ systems
: eosinophilic gastritis, colitis
chronic active hepatitis, focal hepatic lesions,
eosinophilic cholangitis, Budd-Chiari syndrome

13. Renal involvement
Renal involvement is rare, little information on renal histopathology.
renal involvement : 36% (5/14) of IHES pts.
Chusid et al. Medicine 1975;54:1–27.
20% (12/57) have at least some renal involvement including pyuria, hematuria, modest proteinuria, cylinduria.

14. Renal involvement previously reported renal changes in IHES include:
GBM thickening , membranoproliferative GN
mesangial expansion and hypercellularity
glomerular and vascular fibrin deposits or thrombi
focal interstitial fibrosis and eosinophilic infiltration
Thickened tubular BM
nephrosclerosis, and multiple renal infarcts
Nephrol Dial Transplant 1995;10:401–403.
Medicine 1975;54:1–27.
Ann Intern Med 1968;68:1220–1229.
J Pathol 1983;140:113–122.

15. eosinophils , believed to play tissue-damaging role.
: eosinophil granules -secretory products
(major basic protein, other cationic proteins,
peroxidase, neurotoxin, cytokines, proinflammatory mediators.)
mechanism underlying tissue damage :
eosinophil cytotoxicity d/t eosinophilic infiltrates
thromboembolic events secondary to cardiac involvement

16. Treatment and prognosis of IHES
Asymptomatic patients
clinical follow-up at 6 mo. intervals
end-organ involvement insidiously ,not correlated with degree eosinophilia
Glucocorticoids
initial treatment ,end organ involvement,
(except for FIP1L1/PDGFRA mutation)
prednisone 1 mg/kg qd or 60 mg qd
slowly tapering , lowest dose to control of eosinophilia

17. Treatment and prognosis of IHES
tyrosine kinase inhibitor (imatinib mesylate)
first-line agent in FIP1L1/PDFGRA-associated HES
resolution symptoms, eosinophilia within 1~2 wk
Mepolizumab(anti-IL-5 Ab)
useful therapy for some patients
Interferon-alfa , hydroxyurea, BM transplantation

18. Treatment and prognosis of IHES
variable prognoses in HES syndromes
Mortality - cardiac complications.
prognotic factors
early diagnosis, intensive management
response to corticosteroid, IgE concentration
association with myeloproliferative disorders

19. Treatment in renal involvement
treatment of IHES is initiated with oral PDL(1 mg/kg/day).
response to steroids differs from case to case, ranging from no response to partial response or rarely complete remission.
In kidney disease
early diagnosis is essential
recovery in renal function only if management promptly.

20. Treatment in renal involvement
hydroxyurea or cyclophosphamide
: indication - rapid progression or failure to steroid therapy.
markedly improved 5-year survival rate of 70–90%, compared with early reported cases of IHES.