1. By
Nehal Hamdy

2. Introduction about eosinophil.
What is eosinophilia?
Work up of eosinophilia.
 Hypereosinophilic syndrome.
Definition
Clinical presentation
Diagnosis
Treatment

3. Eosinophil granulocytes:- are white blood cell
develop and mature in the bone marrow from myeloid
precursor cells.

4. Marrow
production
IL3,IL5,
GM-CSF
Tissue
migration to
site of
parasitic
infection
TH2 cell
cytokines:
IL3,IL4
GM-CSF
IL5
LTB4
Eotaxin
1 &2
cationic
granule
Proteins
eosinophil
perioxidase
neurotoxin
Organ damage

5.  In normal individuals, eosinophils make up about 1-6% of white
blood cells.
 They are found in
 but not in the lung, skin, esophagus. The presence of eosinophils in
these latter organs is associated with disease.
 Eosinophils persist in the circulation for 8–12 hours, and can
survive in tissue for an additional 8–12 days in the absence of
stimulation..

6. Normal:<500/mm3
Eosinophilia can be categorized:-
Mild (500 to 1500 cells/microL).
moderate (1500 to 5000 cells/microL).
severe (>5000 cells/microL).

7. Primary(clonal):
eosinophils are clonally derived from an
underlying hematologic neoplasm
Secondary(reactive)
Hyperesnophilic
syndromes

8.  Chronic eosinophilic leukemia
 Certain subtypes of ALL and ML.
 Myelodysplastic syndrome.
 Systemic mastocytosis.
 Stem cell myeloproliferative syndrome.
 Chronic myeloproliferative syndrome.

9.  Infectious diseases:
parasitic, viral, bacterial and fungal
 Allergic disorders:
Eosinophilia commonly results from atopic conditions asthma, and various forms of
rhinitis, as well as allergic drug reactions.
 Rheumatic disease:
Eosinophilia-myalgia syndrome and toxic oil syndrome-Idiopathic eosinophilic
synovitis- Churg-Strauss ,wegener,sarcoidosis ,RA and SLE.
 Dermatologic:
atopic dermatitis,urticaria,eczema and dermatitis herpetiformis.
 Pulmonary:
cystic fibrosis-esnophilic granuloma-bronchiectasis
 GIT:
esnophilic gastroenteritis and celiac disease
 Cardiac:
Tropical endocardial fibrosis –endomyocardial fibrosis.
 Malignancy:
Breast, lung and renal cancer.
 Metabolic: adernal insufficiency.
 Immunodeficiency states: hyper-IgE syndrome

10.  History ,PE and laboratory studies directed toward
possible reactive causes(travel, medications and systemic
disease).
 Stool O and P or serologic studies for parasites.
 CXR, CTscan,Echocardiography.
 Biopsy of involved organs.
 Bone marrow biopsy with cytogenetic.

11.  Blood eosinophilia of ≥1500/microliter, present for
more than six months.
 No other apparent etiologies for eosinophilia, such
as parasitic infection or allergic disease.
 Signs and/or symptoms of eosinophil-mediated
end-organ dysfunction.
Some HES patients require therapeutic interventions well before the six
month period specified in the first criterion, in order to treat or prevent
potentially life-threatening complications of sustained hypereosinophilia.
The third criterion excludes patients with early HES, who have not yet
developed signs and symptoms of disease

12.  Blood eosinophilia of ≥1500/microliter, present on
at least two occasion.
 No other apparent etiologies for this degree of
eosinophilia.

13. • Clonal eosinophilic proliferation as a result of a primary
molecular defect involving hematopoietic stem cells
• Overproduction of eosinophilopoietic cytokines, such as
IL-5
• Functional abnormalities of the eosinophilopoietic
cytokines
• Defects in the normal suppressive regulation of
eosinophil survival and activation

14.  Myeloproliferative variants of HES.
 HES T-lymphocytic variants (L-HES).
 Familial HES.
 Undefined HES.
 Overlap HES.
 Associated HES.

16.  A subgroup of patients with:-
 Anemia.
 Thrombocytopenia.
 Splenomegaly.
 Hepatomegaly.
 Increased serum level of vitamin B 12.
Clonal DNA analysis of some HES
patients: mutation in FIP gene( FIP1L1-
PDGFRA chromosomal fusion)

17. Fip gene: factor interacting polymerase alpha.
What is the normal function of the
FIP1L1 gene?
•The FIP1L1 gene provides instructions for making part of a protein
complex named cleavage and polyadenylation specificity factor (CPSF).
•The CPSF protein complex helps add a string of the RNA building
block adenine to the mRNA, creating a polyadenine tail or poly(A) tail.
The poly(A) tail is important for stability of the mRNA.

18.  The FIP1L1 gene is located on the long (q)
arm of chromosome 4 at position 12.

19.  PDGFRA: Platelet-derived growth factor receptor, alpha
polypeptide gene.
 This gene encodes a cell surface tyrosine kinase receptor.
which stimulates signaling pathways inside the cell that
control cell growth and division (proliferation) and cell
survival.

20. Unlike the normal PDGFRA protein, the FIP1L1-PDGFRA protein is
constantly turned on (constitutively activated), which means the cells
are always receiving signals to proliferate.
The FIP1L1-PDGFRA protein produced from the fusion gene has the function
of the normal PDGFRA protein, which stimulates signaling pathways inside
the cell that control cell growth and division (proliferation) and cell survival.
A deletion of genetic material from chromosome 4 brings together part of the
FIP1L1 gene and part of another gene called PDGFRA, creating the FIP1L1-
PDGFRA fusion gene.

21. When the FIP1L1-PDGFRA fusion gene occurs in
blood cell precursors, the growth of eosinophils (and
occasionally other blood cells) is poorly controlled. It is
unclear why eosinophils in particular is affected by
this genetic change.

22. The same gene mutation found in patients
with CEL.
CEL: blast cells in peripheral blood(>2%).
Increased blast cells in bone marrow(>5%).

23.  Serum tryptase is elevated in myeloproliferative type.
 Tryptase is an enzyme found in mast cells, released
during anaphylactic reaction
 Used as a marker of mast cell activation.
 Myeloproliferative variant associated with hyperplasia of
mast cells and therefore elevation in serum tryptase level.

24. Worse prognosis.
Poor response to steroids.
More liable to develop acute myeloid
leukemia.

25.  Predominance of skin.
 Soft tissue involvement.
 Increased serum level of IGE and IL5 by the
abnormal T cells.
 Better prognosis
 Respond well to steroids.

26.  Autosomal dominant transmission of marked
eosinophilia has been reported.
 Eosinophilia begins at birth and most family
members have remained asymptomatic, although
progression, with fatal endomyocardial fibrosis,
has occurred in a few individuals.

27.  Up to 75 percent of patients with HES remain
undefined.
 Three clinical subtypes of undefined HES are
currently recognized:
1. Benign HES (asymptomatic eosinophilia
≥1500/microliter).
2. Complex HES (multisystem involvement).
3. Episodic HES (including episodic angioedema
and eosinophilia).

28.  Overlap disorders are disorders with blood eosinophilia
≥1500/microliter in the setting of single organ
involvement.
 Overlap disorders include eosinophilic gastrointestinal
disorders, chronic eosinophilic pneumonia.
Churg Strauss syndrome :- Churg Strauss syndrome (CSS) is particularly difficult
to categorize. However it is considered as an overlap disorder.
Sometimes it is difficult to differentiate between CSS and HES especially in cases
of ANCA negative and before development of vasculitis.
Histopathological assesment of vasculitis is mandatory to decide 2nd line of
treatment as both of them will respond intially to steroids.

29.  Eosinophilia ≥1500/microliter can be seen at times
in a variety of conditions associated with
immunodysregulation. Examples include collagen
vascular diseases, sarcoid, ulcerative colitis and
HIV infection.
 The etiology of the eosinophilia in such cases is
unknown.

30. Cardiac
5%
Gastrointestinal
- 14 percent
Pulmonary
(cough and
breathlessness)
- 25 percent
Dermatologic
(eg, rash) –
37 percent

31.  Eosinophilic myocarditis is a major cause of morbidity and
mortality among patients with HES.
 Eosinophil-mediated heart damage evolves through three
stages
 An acute necrotic stage.
 An intermediate phase characterized by thrombus
formation along the damaged endocardium.
 A fibrotic stage.
The acute necrotic stage:
The disease is clinically silent
with normal physical examination.
Echogradiography: normal.
Elevations in serum troponin
levels can be indicator of early
myocardial damage
Cardiac MRI:
can detect early inflammatory
changes:subendothelial fibrosis
The thrombotic and fibrotic
Stage:
The patient will present by dyspnea, chest pain,
signs of left and/or right ventricular failure, mitral
or tricuspid regurgitation
Cardiac MRI and Echo:
demonstrate intracardiac thrombi , restrictive
cardiomyopathy, TR and MR ,thickening of
posterior wall and increased cardiac echodenisty in
the fibrotic stage

32.  Pulmonary involvement is common in HES and may
result from eosinophilic infiltration of the lung with
subsequent fibrosis, heart failure, or pulmonary emboli.
 The most common presenting symptoms were:
 Dyspnea.
 Cough.
 Wheezing.
 Chest radiography:
 parenchymal infiltrates and they were most commonly
patchy ground glass infiltrates.
 pleural effusion.
 intrathoracic lymphadenopathy.
 and pulmonary emboli.

34.  Eosinophilic gastritis &enteritis may occur
secondary to HES causing :-
 weight loss
 abdominal pain, vomiting
 diarrhea
 Hepatic involvement :-
 active hepatitis,
 focal hepatic lesions,
 eosinophilic cholangitis
 The Budd-Chiari syndrome

35.  Patients have been reported to develop:-
 femoral artery occlusion .
 intracranial sinus thrombosis.
 digital gangrene in the setting of progressive
Raynaud's phenomenon.
Eosinophil-related damage to endothelium
combined with activation of the coagulation system

36.  HES may be complicated by
Cerebral thromboemboli
Encephalopathy.
Peripheral neuropathy
 Longitudinal and/or transverse
sinus thrombosis.

37.  Common skin manifestations of HES:-
 Eczema (involving hands, flexural areas, or
dispersed plaques).
 Erythroderma.
 Generalized thickening of the skin.
 Recurrent urticaria .
 Angioedema.
 Mucosal ulcers, which often develop in the
mouth, nose, pharynx, esophagus, and stomach.

39.  30 yrs old female patient diagnosed at our outpatient
clinic as a case of 1ry sjogren in 2003 by:
 Sicca symptoms(dry eyes, dry mouth).
 Non erosive symmetrical polyarthritis.
 Anti RO>200.
 Anti la >200.
 Generalized lymphadenopathy &parotid gland
enlargement
 We started methotrexate 25mg/week for arthritis with
improvement.
 During course of the disease the patient was irregular
on ttt(due to improvement).

40.  The patient presented
with angioedema.
 Generalized papular
and pustular
eruptions.
 The patient was
admitted at
dermatology
department

41.  ESR 1st hour:130
 CBC
HB:8.2g%.
WBC:4.000/ul
Platelet:361000/ul
 Differential WC count
Neutrophils:42%
Lymphocytes:50%.
Esoinphils:45%.
Basophils:3%.
Serial CBC showed persistent esnophilia

42.  Sgpt:32u/l.
 Sgot:22u/l.
 Creatinine:0.28 mg/dl.
 Urea:38 mg/dl.
 ANA:negative.
 DNA:negative
 RF:negative.
 ANCA P & C: negative.
 ACL IGM & IGG: negative.
 HCV ab & HBSag: negative.
 Urine analysis:free.
 Stool analysis for ova & parasite:free.
 Anti bilharzial ab: negative.
 Serum IGE:9980 IU/ml(up to 100).
 B2 microglobulin:3951 IU/ml.

43.  Chest xray:normal study.
 Abdominal and pelvic ultrasound: hepatosplenpmegaly.
 Echo cradiography :normal study.
 Other investigations:
Skin biopsy:- showed perivascular eosinophilic infilitration
with no evidence of vasculitis.
Bone marrow biopsy: normocellular bone marrow with
eosinophils and areas of fibrosis with no lymphoid
infiltrate.

44.  So the patient was diagnosed as a case of HES
based on :
 hypereosinphilia on 2 occasions.
 Skin biopsy.
 Mostly T Lymphocytic type based on:
 Predominance of skin involvement
 Elevation of serum IGE.

45.  The patient was treated by pulse of methylperdinsolone
followed by oral steroids
 Hydrea was added (1×2) with improvement of her
condition.

47.  Step1:clincal signs and symptoms.
 Step2: peripheral blood analysis for esnophils and blast cells,
serum tryptase and vitamin B 12.
 Step 3: Bone marrow examination for esnophils and blast cells
 Step 4: chromosomal testing to detect FIP1L1/PDGFRA
mutation.

48. HES is diagnosis of exclusion

50.  is a cytogenetic technique used to detect and localize the
presence or absence of specific DNA sequences
on chromosomes.
 Can be performed on peripheral blood and/or bone marrow.
 In HES (absence of cysteine rich hydropic domain 2 (CHIC2
locus) considered a marker for presence of the F/P fusion.
 FISH uses fluorescent probes that bind to only those parts of
the chromosome with which they show a high degree of
sequence complementarity

52.  The reference range is < 11.4 ng/mL.
 Tryptase can also be elevated with:-
 Asthma.
 Myelodysplastic syndrome.
 Acute myelocytic leukemia.
 Systemic mastocytosis
Detection of KIT gene mutation. Normally gene
encode Mast cell growth factor receptor:- protein
found on surface of mast cell, work as tyrosine
kinase receptor.

53.  Normal:110–1500 picograms per milliliter
(pg/mL).
 High Vitamin B12
 Liver disease.
 Kidney failure.
 Blood cancers :-myeloproliferative disorders,
which includes myelocytic leukemia.
 polycythemia vera.
 Hypereosinophilic syndrome.

54. Why vitamin b12 level increased in
myeloproliferative disorder?
Vitamin
b12
Transcobalamin
(TC) ssential for the transport of
vitamin B12 from ileum into the blood
and then into most cells, only vitamin
b12 bound to TC aviable for cellular
uptake
Haptocorrin
(HC) produced by myeloid
cells, binds to 80% of
plasma vitamin b12 ,
largely saturated by B12
In myeloproliferative disorder up regulation of HC
with increase in level of vitamin b12

55. The pathogenic T cells display an aberrant surface
phenotype in all reported cases, and while CD3-CD4+cells
represent the most frequently encountered subset in this
setting, CD3+CD4-CD8-, CD4+CD7- and other populations
have also been reported

56.  The effect of Th 2 cytokines on antigen presenting
cells lead to high-level production of thymus
activation-regulated chemokine (TARC) which is
increased in serum from such patients.

57.  As result of B cell stimulation by TH 2 cytokines.
Causes of elevated IgE
Common
 Allergic disease (eg, atopic dermatitis/eczema, asthma, allergic rhinitis,
 food allergy, eosinophilic esophagitis, urticaria, drug allergy)
 Parasitic worm infestation (eg, helminth infection).
Uncommon
 Malignancy (eg, IgE myeloma, Hodgkin's lymphoma)
 Primary and secondary immunodeficiencies (eg, Hyper-IgE syndrome,
Wiskott-Aldrich syndrome, Nezelof syndrome, AIDS, GVHD)
 Infectious diseases (eg, allergic bronchopulmonary aspergillosis, leprosy)
 Inflammatory diseases (eg, Churg-Strauss syndrome, Kawasaki disease)
 Drug effect ( penicillin G).

58.  Serum tropnin, ECG, echo and CMR.
 Chest xray,CT chest pulmonary function test ,
bronchoalveolar lavage.
 Abdominal us ,CT abdomen.
 Biopsy from the affected organ.

59.  ECG findings(not specific)
 T wave inversions.
 left atrial enlargement.
 left ventricular hypertrophy.
 incomplete right bundle branch block.
Electrocardiography is a screening tool that detects
changes related to the underlying cardiac pathology in
HES, especially left ventricular hypertrophy, but does
not reveal any abnormalities that are specific for HES.

60.  The classic echocardiographic findings in HES
include :-
 Endomyocardial thickening.
 left and right ventricular apical thrombus
formation.
 posterior mitral leaflet involvement.
 restrictive cardiomyopathy with regurgitation of
the atrioventricular valves secondary to
subvalvular damage

61.  CMR imaging is more sensitive to and specific for the
than echocardiography in detection of ventricular
thrombi
 Overlying thrombus is identifiable as a low signal mass
on the delayed enhancement images

62.  T2-weighted image:- Hyperintense myocardial area is
suggestive of increased free-water content due to
myocardial oedema and/or necrosis particularly seen in
ventricular apex
 T1-weighted images sequencing after the intravenous
administration of gadolinium demonstrates nonviable
tissue as delayed enhancement .
 Delayed enhancement resulting from fibrosis is more
intense than delayed enhancement due to inflammation.
 Regional areas of hypokinesia or akinesia and findings of
restrictive cardiomyopathy (diastolic dysfunction with atrial
enlargement and valvular regurgitation) can be visualised.

63.  Endomyocardial biopsy is the gold standard diagnostic
tool in HES.
 The histopathologic features of HES endomyocardial
diseases include:-
 Fibrotic thickening of the endocardium, mural
thrombosis, and fibrinoid change, thrombosis.
 Inflammation of the small intramural coronary vessels.
 Infiltration of eosinophils into the myocardium and
sometimes endocardium.

65.  Radiological features in pulmonary involvement are non
specific so bronchoalveolar lavage and some times
surgical lung biopsy is recommended to detect
eosinophilic infiltration.

66. Abdominal Ultrasonography and CT
Thickening of the intestinal wall, intestinal wall edema
Barium studies
 Mucosal edema and/or thickening of the small intestinal
wall.
 Partial gastric outlet obstruction.
 Narrowing of lumen of the terminal ileum.

67. Endoscopy
 Endoscopically the gastrointestinal mucosa may vary in
appearance from normal to ulcerated, hemorrhagic or
nodular.
 In cases of eosinophilic esophagitis pseudomembranes,
marked mucosal friability, as well as narrowing of the
esophageal lumen can be seen.
 In the stomach, when the mucosa is involved nodularity
and ulceration are present.

68. The eosinophilic infiltration tends to affect specific layers
of the gastric or intestinal wall. Lesions are usually
multiple and patchy.
Mucosa
Edema, lymphatic dilatation as well
as an intense eosinophilic infiltrate,
epithelial cell necrosis, pit or crypt
abscesses, erosions, shallow ulcers,
or villous atrophy.
Submucosa
edema is more common and
destruction of the wall and fibrosis

69.  The pathology of skin lesions in HES is in general non-
specific with variable eosinophilic infiltration and
cutaneous microthrombi(Beritand Michael.,2013)
 2o% infiltration with eosinophilis is highly suggestive
of HES.

71. Reduction of eosinophil level.
Prevent irreversible organ
damage(cardiac).

72.  All F/P-positive patients regardless of the demonstration
of eosinophil-mediated tissue damage.
 In other non-M-HES patients, the major indication for
specific treatment is the demonstration of eosinophil-
mediated tissue injury.
 Asymptomatic patients with chronic eosinophilia,
regardless of their eosinophil counts, could be left
untreated with regular follow up every 6 month for organ
damage.

73. Is the patient requires urgent intervention or
no?
Patients presenting with potentially life-
threatening complications, including cardiac or
neurologic involvement, and marked
eosinophilia(above 100,000 cells/microliter)

74.  In these situations, hypercellularity should be
rapidly reduced. High dose intravenous
glucocorticoids (eg, at a dose equivalent to 15
mg/kg of prednisone.
 In response to high dose glucocorticoids, the
eosinophil count typically drops dramatically (eg,
by more than 50 percent of the original value).
 If a significant reduction is not observed after 24
hours, then glucocorticoids alone are unlikely to be
effective for that patient.

75.  2nd line agent should be used:-
 vincristine has been administered at doses of 1 to
2 mg/m2 intravenously, weekly to monthly. In
responsive patients, eosinophil counts begin to fall
within hours.
 Imatinib therapy (400 mg daily) may be effective
in steroid-refractory patients with extremely high
counts, since these patients are more likely to have
FIP1L1/PDGFRA-positive disease. it takes longer
time (two to four weeks) to reduce counts.
Once the patient is clinically stable,
treatment will be according to HES
specific variant

77. First-line therapy for all patients with FIP1L1- and
PDGFRA-positive disease is the tyrosine kinase
inhibitor, imatinib mesylate

78.  2-phenylamino pyrimidine derivative that functions
as a specific competitive inhibitor of a number of
tyrosine kinase enzymes. It occupies the TK active
site, leading to a decrease in activity.

79. • Oral dose100 -400 mg daily.
• Typically, symptoms improve and eosinophil counts
normalize within one to two weeks after initiation of
imatinib.
• Imatinib therapy is alife long treatment .
• stopping imatinib in patients with the
FIP1L1/PDGFRA mutation has resulted in a rapid
return of FIP1L1/PDGFRA transcripts, detected by
polymerase chain reaction (PCR) .

80.  Efficacy of the drug should be monitored with
monthly eosinophil counts and regular assessment of
organ involvement.
 F/P-positive patients should be tested for the presence
of the fusion gene every 3 to 6 months. Because
molecular relapse typically occurs before the
recurrence of eosinophilia and clinical manifestations
 A positive test should raise concern for drug
resistance and prompt an increase in imatinib dose.

81.  Persistent eosinophilia of 1.5 109/L or higher after
1 month of treatment .
 Consider shifting to other tyrosine kinase inhibitor
or bone marrow transplantation.

82.  Bone marrow suppression: May cause bone marrow
suppression (anemia, neutropenia, and thrombocytopenia)..
 Opportunistic infections: Has been associated with
development of opportunistic.
 GI irritation: May cause GI irritation; take with food and
water to minimize irritation. There have been rare reports
(including fatalities) of GI perforation.
 Hepatotoxicity: Hepatotoxicity may occur (may be severe);
monitor; therapy interruption or dose reduction may be
necessary. Transaminase and bilirubin elevations, and acute
liver failure .
 Dermatologic reactions: Severe bullous dermatologic
reactions, including erythema multiforme and Stevens-Johnson
syndrome, have been reported.

83.  Fluid retention/edema: Often associated with
fluid retention, weight gain, and edema
(probability increases with higher doses and age
>65 years).
 Cardiovascular effects: Severe heart failure (HF)
and left ventricular dysfunction (LVD) have been
reported .This can be explained by massive
release of eosinophil granule proteins and
subsequent damage to the myocardium.

84.  When imatinib is initiated in patients with cardiac
disease. Concomitant treatment with systemic
glucocorticoids (1 to 2 mg/kg daily) for one to two
weeks is recommended.

85. Glucocorticoids
 Prednisone at doses of 1 mg/kg daily or 60 mg once daily for
one to two weeks is the primary therapy for FIP1L1-
PDGFRA-negative HES.
 If the eosinophil count does not respond to this initial dose,
even higher doses (eg, methylprednisolone, 1 gram daily or
15 mg/kg/day) could be administered for a few days.
 Once blood eosinophilia is suppressed and symptoms are
controlled, daily doses are gradually tapered to lowest dose
that maintains control of the eosinophil count and clinical
manifestations.during tapering steroid sparing agent is used.

86.  Hydroxyurea
 Interferon-alfa.
 Anti-IL-5.
 Anti-CD52.
In combination with steroids as
steroid sparing agent.
2nd line monotherapy for FIP
negative patients who didn’t respond
initially to steroids.

87.  Is an antineoplastic agent available for oral
use as capsules providing 500 mg
hydroxyurea.
 Hydroxyurea causes an immediate inhibition
of DNA synthesis by acting as a ribonucleotide
reductase inhibitor .

88.  500-2000mg daily as tolerated.
 In renal impairment:-Clcr 10-50 mL/minute: Administer
50% of dose.
 Clcr <10 mL/minute: Administer 20% of dose.
 Hemodialysis: Administer dose after dialysis on dialysis
days.

89.  Category D: highly teratogenic so a contraception
should be used.
 Breast feeding not allowed during treatment.

90.  Gastrointestinal: Anorexia, constipation, diarrhea
nausea, pancreatitis, stomatitis, vomiting.
 Hematologic: Myelosuppression (anemia, leukopenia ,
thrombocytopenia).
 Hydroxyurea is contraindicated in patients with marked
bone marrow suppression, i.e., leukopenia (<2500 WBC)
or thrombocytopenia (<100,000).

91.  Dermatological :-maculopapular rash, skin ulceration,
dermatomyositis-like skin changes, peripheral and facial
erythema. Hyperpigmentation, atrophy of skin and nail.
Cutaneous vasculitic toxicities, including vasculitic
ulcerations and gangrene.
 Neurological:-headache, dizziness, disorientation,
hallucinations, and convulsion
 Renal:Temporary impairment of renal tubular function
accompanied by elevations in serum uric acid, blood urea
nitrogen (BUN), and creatinine levels.
 Hepatic: Hepatotoxicity.

92.  Low doses of IFN-α (1-2 million U/m2/d) are often
effective but the response usually become evident after
several weeks of treatment .
 Low-dose hydroxyurea (500 mgdaily) potentiates the
effect of IFN-α .
 Monotherapy with IFN-α should be avoided in
lymphocytic HES; in vitro data have demonstrated an
inhibitory effect of IFN-α on spontaneous apoptosis of
clonal CD3−CD4+ T cells.
 In this setting a corticosteroid should be addedbecause of
its proapoptotic effect on the clonal T cells

93.  IFN-α treatment may be used in pregnancy .
 Side effects: myelosuppression, flu-like symptoms,
depression orfatigue, increased liver transaminases,
gastrointestinal discomfort.

94.  Mepolizumab, a humanized anti-IL-5 antibody.
Have shown promising results in the treatment of
FIP1L1/PDGFRA-negative HES patients, but are
available only in clinical trials .
 Alemtuzumab
It is a monoclonal antibody that binds to CD52, a protein
present on the surface of mature lymphocytes and
Eosinophils .
A trial of alemtuzumab in patients with FIP1L1/PDGFRA-
negative HES reported that eosinophil counts normalized
at a median time of two weeks (range: 0.5 to 5 weeks) in
10 of 11 patients refractory to various therapies.

95.  Campath®: 30 mg/mL (1 mL).
B-cell CLL:
I.V. infusion: Initial: 3 mg/day beginning on day 1; if
tolerated), increase to 10 mg/day; if tolerated, increase to
maintenance of 30 mg/dose 3 times/week on alternate
days for a total duration of therapy of up to 12 weeks.

96.  Alemtuzumab has been associated with infusion-related
events including hypotension, rigors, fever, shortness of
breath, bronchospasm, chills, and/or rash.
 It can also precipitate autoimmune disease through the
suppression of suppressor T cell populations and/or the
emergence of autoreactive B-cells.

97.  This intervention may be useful in patients with
treatment-refractory HES, particularly those
with imatinib-resistant PDGFRA-associated disease.
 Transplantation should also be considered for patients
with L-HES who develop T cell lymphoma, which may
be resistant to classical chemotherapeutic regimens.

98. Fish for fip gene
FIP -ve
Symptoms
Organ damage
Yes:
Steroids high
dose.
Hydroxy urea
IFalpha
NO: observeation
Fip +ve
Gleevec
1oomg
Another TKI
Bone marrow
transplant