EOSINOPHILS are granulocyte type of WBCs. WHITE BLOOD CELLS – There are five types of white blood cell (leucocyte). These are divided into two main classes Granulocytes (includes Neutrophils, Eosinophils and Basophils) Agranulocytes (includes Lymphocytes and Monocytes). This classification depends on whether granules can be distinguished in their cytoplasm using a light microscope and conventional staining methods).

1. PRESENTATION ON
EOSINOPHILIA AND DRUG
INDUCED EOSINOPHILIA.
PRESENTEDBY:
AMEENA BEGUM, PHARM.D
SULTAN UL ULOOM
COLLEGE OF PHARMACY ,
HYDERABAD
GUIDED BY:
Dr. SRINIVAS NAYAK,
ASSISTANT PROFESSOR,
SUCP, HYD
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2. WHAT ARE EOSINOPHILS?
■ EOSINOPHILS are granulocyte type of WBCs.
WHITE BLOOD CELLS –
■ There are five types of white blood cell (leucocyte). These are divided into
two main classes
■ Granulocytes (includes Neutrophils, Eosinophils and Basophils)
■ Agranulocytes (includes Lymphocytes and Monocytes).
■ This classification depends on whether granules can be distinguished in
their cytoplasm using a light microscope and conventional staining
methods).
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5. ■ Eosinophils are also known as ACIDOPHILS.
■ In normal individuals, eosinophils make up about 1–3% of white
blood cells, and are about 12–17 micrometres in size with bilobed
nuclei.
■ They are found in the medulla and the junction between the cortex
and medulla of the thymus, and, in the lower gastrointestinal tract,
ovaries, uterus, spleen, and lymph nodes, but not in the lungs,
skin, esophagus, or some other internal organs[vague] under
normal conditions.
■ In allergic conditions, they are found in the lung, skin, and
esophagus.
■ Eosinophils persist in the circulation for 8-12 hours and can
survive in tissues for an additional 8-12 days in the absence of
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6. ■ These cells are naturally transparent but
appear brick-red when stained with a dye
called eosin using the Romanowsky
method; they are ‘eosin (or acid)-loving’
cells.
■ The red color stains small granules within
the cellular cytoplasm, which contain many
chemical mediators, such as histamine
and proteins such as eosinophil
peroxidase, Rnase, Dnases, lipase,
plasminogen, and Major Basic Protein.
■ These mediators are released by a
process called degranulation following
activation of the eosinophil, and are toxic
to both parasite and host tissues.
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7. ■ Following activation by an immune stimulus, eosinophils degranulate to release an array of
cytotoxic granule cationic proteins that are capable of inducing tissue damage and dysfunction.
These include:
■ Major basic protein (MBP)
■ Eosinophil cationic protein (ECP)
■ Eosinophil peroxidase (EPX)
■ Eosinophil-derived neurotoxin (EDN)
Major basic protein, EPX, and ECP are toxic to many tissues
ECP and EDN are ribonucleases with antiviral activity.
Major basic protein induces mast cell and basophil degranulation, and is implicated in peripheral
nerve remodelling.
Eosinophil cationic protein creates toxic pores in the membranes of target cells, allowing potential
entry of other cytotoxic molecules to the cell, can inhibit proliferation of T cells, suppress antibody
production by B cells, induce degranulation by mast cells, and stimulate fibroblast cells to secrete
mucus and glycosaminoglycan.
Eosinophil peroxidase forms reactive oxygen species and reactive nitrogen intermediates that
promote oxidative stress in the target, causing cell death by apoptosis and necrosis.
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9. EOSINOPHILS DEVELOPMENT AND MATURATION:
■ Eosinophils are granulocytes that develop in the
bone marrow from pluripotent progenitors in
response to cytokines, such as interleukin-5 (IL-5),
IL-3 and granulocyte–macrophage colony-
stimulating factor (GM-CSF)
■ Differentiation of haemato-poietic progenitors to
eosinophils in the bone marrow is governed by
SCF, IL-3, IL-4, GM-CSF and CCL11. IL-5 and
CCL11 then act in concert to drive final
differentiation, maturation and release of
eosinophils from the bone marrow into the
bloodstream.
■ Eosinophils express a range of receptors, e.g.
CCR3, the receptor for CCL11, which allow them to
respond to a multitude of cytokines, chemokines
and lipid mediators
■ Eosinophils are recruited from the blood into the
tissues at sites of inflammation. Upon activation
eosinophils can release an array of inflammatory
mediators. Dept. of pharmacy practice, SUCP, hyderabad 9

10. ROLES OF EOSINOPHILS-
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11. FUNCTIONS OF EOSINOPHILS:
■ Parasitic infections:Eosinophils are crucial for combatting parasitic infections and
inflammatory processes, such as allergic reactions. Other functions include killing cells,
anti-bacterial activity, and controlling inflammatory responses.Viral infections
■ Viral infections:Eosinophils are recruited in the lower airway epithelium during viral
infections, such as a respiratory syncytial virus (RSV). RSV can activate eosinophils
which promotes virus clearance through the production of ribonucleases and cytokines.
Eosinophils are involved in the host response to the influenza virus. They undergo
degranulation), upregulate antigen presentation, and enhance effector T-cell responses,
■ Fungal infections:Eosinophils are activated by recognizing certain antigens present in
fungi, such as β-glucan. Eosinophils release their proinflammatory and cytotoxic
granule proteins, and various chemokines in response to a fungal infection. Eosinophils
can phagocytose fungi, such as Cryptococcus neoformans and present antigens to
other immune cells. They also release cytokines, such as IL-12, IFNγ, and TNF, during
fungal infection.
■ Eosinophil in immune-mediated diseases and disorders:The increase of eosinophils
within the blood is known as eosinophilia. This can result from disorders, such as
leukemia. Dept. of pharmacy practice, SUCP, hyderabad 11

12. EOSINOPHILIA-
Eosinophilia is defined as a peripheral blood
eosinophil count > 500/mcL .
■ Peripheral eosinophilia is characterized as
■ Mild: 500 to 1500/mcL (0.5 to 1.5 × 109/L)
■ Moderate: 1500 to 5000/mcL (1.5 to 5 × 109/L)
■ Severe: > 5000/mcL (> 5 × 109/L)
■ Mild eosinophilia itself does not cause
symptoms, but levels ≥ 1500/mcL (> 1.5 ×
109/L) may cause organ damage if they persist.
Organ damage typically occurs because of
tissue inflammation and reaction to the cytokines
and chemokines released by the eosinophils as
well as to immune cells that are recruited to the
tissues. Dept. of pharmacy practice, SUCP, hyderabad 12

13. TYPES AND CAUSES OF
EOSINOPHILIA:
TYPES OF EOSINOPHILIA-
■ Primary: A clonal proliferation of eosinophils associated with hematologic
disorders such as leukemias and myeloproliferative neoplasms
■ Secondary: Caused by or associated with nonhematologic disorders
■ Idiopathic: Causes cannot be identified
ETIOLOGY: The most common cause of eosinophilia is-Allergic or atopic
disorders (typically respiratory or dermatologic)
Other common causes of eosinophilia include:-
Infections (typically parasitic)
Certain tumors (hematologic or solid, benign or malignant)
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14. ■ Hypereosinophilic syndrome is a condition characterized by peripheral
blood eosinophilia with manifestations of organ system involvement or
dysfunction directly related to eosinophilia in patients who do not have
parasitic, allergic, or other causes of eosinophilia.
■ Patients with eosinophilic drug reactions may be asymptomatic or have
various syndromes, including interstitial nephritis, serum sickness,
cholestatic jaundice, hypersensitivity vasculitis , and immunoblastic
lymphadenopathy.
■ Drug reaction with eosinophilia and systemic symptoms (DRESS) is a
rare syndrome characterized by fever, rash, eosinophilia, atypical
lymphocytosis, lymphadenopathy, and signs and symptoms related to
end-organ involvement (typically, heart, lungs, spleen, skin, nervous
system).
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16. EVALUATION AND DIAGNOSIS-
■ HISTORY CHECK-
■ The questions most likely to be helpful pertain to the following:
■ Travel (suggesting possible parasite exposure)
■ Allergies
■ Drug use
■ Use of herbal products and dietary supplements, including L-
tryptophan
■ Systemic symptoms (eg, fever, weight loss, myalgias, arthralgias,
rashes, lymphadenopathy)
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17. ■ PHYSICAL EXAMINATION-
■ General physical examination should focus on the heart, skin, and neurologic
and pulmonary systems.
■ Certain physical findings may suggest causes or associated disorders.
Examples include rash (allergic, dermatologic, or vasculitic disorders),
abnormal lung findings (asthma, lung infections, or syndromes of pulmonary
infiltration with eosinophilia), and generalized lymphadenopathy or
splenomegaly (myeloproliferative disorders or cancer).
■ TESTS-
■ Eosinophilia is typically recognized when a complete blood count (CBC) is
done for other reasons . Additional testing often includes the following -
■ *Stool ova and parasite testing
■ *other tests to detect organ damage or for specific causes based on clinical
findings
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18. DRUG RELATED EOSINOPHILIA
■ Drug reaction with eosinophilia and systemic symptoms
(DRESS), also known as drug-induced hypersensitivity syndrome
(DIHS), and DIDMOHS (drug-induced delayed multi-organ
hypersensitivity syndrome) is a delayed potentially fatal multi-
organ systemic idiosyncratic drug reaction
■ The prevalence of DHS ranges between 1 in 1000 and 1 in
10,000 exposures. It occurs more frequently in females
■ Symptoms typically develop after 2 to 6 weeks of medication use.
Re-exposure to the same drug may cause symptoms even within
24 h. The symptoms may last for weeks or even months after the
medication discontinuation .
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20. PATHOGENESIS
■ The pathogenesis of DRESS syndrome is not well understood and is
hypothesized to consist of a complex interaction between two or more of the
following-
■ DRESS induces by Th2-lymphocytes and CD8+ cells. Th2 cells probably
induce type Ivb hypersensitivity.
■ A genetic deficiency of detoxifying enzymes leading to an accumulation of drug
metabolites. The metabolites covalently bind to cell macromolecules causing
cell death or inducing secondary immunological phenomena. Eosinophilic
activation as well as activation of the inflammatory cascade may be induced by
interleukin-5 release from drug-specific T-cells.
■ Genetic associations between human leukocyte antigen (HLA) associations
and drug hypersensitivity may occur.
■ A possible virus-drug interaction associated with viral reactivation may also
exist. This phenomenon has been previously observed for herpes viruses
(notably Epstein-Barr virus [EBV]). The clinical manifestations appear to be a
result of an expansion of virus-specific and nonspecific T cells.
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22. ■ PENICILLINS-All penicillins share the same core beta-lactam and thiazolidine ring
structures but differ in their side chains. The ring structure is metabolized into major
(penicilloyl) and minor (penicillin, penicilloate, and penilloate) antigenic determinates.
Immediate reactions are the result of IgE that cross-like on mast cells when exposed
to the antigenic component.
■ The result is degranulation and release of histamine as well as other vasoactive
substances. It is the minor antigenic determinates that generate IgE specific
responses that are associated with true penicillin allergy. These minor determinates
result in immediate reactions, within minutes to 1 hour, and characterized by signs
and symptoms of acute anaphylaxis such as urticaria, flushing, dyspnea,
bronchospasm with wheezing, angioedema, hypotension, tachycardia, mental status
change or gastrointestinal (GI) upset. The major antigenic determinates more
commonly are associated with less severe urticarial reactions.
■ Delayed reactions are mediated by IgM and IgG which activates the complement
system resulting in inflammatory reactions that include Type 2 to 4 hypersensitivity
reactions. Serious hypersensitivity reactions include hemolytic anemia, toxic
epidermal necrolysis (TEN), Steven’s Johnson Syndrome (SJS), vasculitis, interstitial
nephritis, serum sickness, thrombocytopenia, and Eosinophilia.
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23. ■ Penicillins are commonly quoted as causing
eosinophilia. However, few case reports could be
found, suggesting the eosinophilia is usually mild
and transient. Penicillin-induced eosinophilia has
been reported associated with nephropathy and
interstitial nephritis. Eosinophiluria may also be
present.
■ Penicillin therapy has been reported to cause
eosinophilia with a fever and a maculopapular
rash. There has been a report of the potentially
fatal condition of toxic epidermal necrolysis.Fever
and eosinophilia were also noted.
■ Penicillins have also been implicated in causing
the potentially fatal condition of hypersensitivity
myocarditis, with presenting symptoms of fever
and rash.
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24. ■ Cephalosporins -The incidence of eosinophilic reactions in patients taking
cephalosporins is quoted as approximately 8 per cent There are, however, few
reports in the literature, suggesting, therefore, that cephalosporin-induced
eosinophilia, like penicillin-induced eosinophilia, is usually mild and transient.
■ There are two cases of a peripheral blood eosinophilia and hematuria in two
patients treated with high-dose cephalexin
■ In one case the symptoms included a fever, maculopapular pruritic discharge
and a generalised lymphadenopathy. In both cases symptoms resolved once
cephalexin was discontinued, but, unfortunately, rechallenge could not be
carried out.Cephalexin has also been reported to cause pulmonary
eosinophilia.
■ A patient developed a diffuse maculopapular rash seven days after
commencing cephalexin therapy (500mg three times a day). Eosinophilia and
diffuse consolidation of both lungs were noted. The patient made a complete
recovery after prednisolone therapy and discontinuation of cephalexin.
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25. ■ Nitrofurantoin- There are a number of reports of nitrofurantoin causing
pulmonary disease with eosinophilia.
■ Nitrofurantoin is unique among drugs causing pulmonary eosinophilia,
in that there is an acute and a chronic pattern
■ The acute episode, which tends to occur within one month of therapy,
presents as a fever with cough and pulmonary infiltrates, and there is
often a marked peripheral blood eosinophilia. These complications
usually resolve within 15 days if nitrofurantoin is discontinued,but
continued therapy may lead to a chronic disease which is characterised
by fibrosis.
■ Other symptoms of the chronic disease, which is less common and
tends to occur two months to five years after initiation of therapy,
include an exertional dyspnoea and a non-productive cough.
Nitrofurantoin should be stopped if this is suspected..
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26. ■ Tetracyclines While pulmonary
eosinophilia has been reported following
the administration of tetracycline,It is
more frequently associated with
minocycline.
■ Minocycline-induced syndrome of
pulmonary eosinophilia is characterised
by pulmonary infiltrates on the chest
roentgenogram, chest symptoms such as
dyspnoea, and eosinophilia in blood and
bronchoalveolar lavage fluids.
■ These presenting symptoms may be
severe enough to lead to transient
respiratory failure and require treatment
with steroids. The outcome after
minocycline has been discontinued is
generally good and there have been no
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27. CLINICAL PRESENTATION-
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28. MANAGEMENT-
■ If the eosinophilia is mild, transient and asymptomatic, there is no need to take action. If,
however, the eosinophilia is more severe and producing symptoms, the most important
management step is to discontinue any agent that may have caused the reaction.
■ Eosinophilia usually occurs within eight weeks of any medicine being started, so agents
started in this period should be discontinued initially. Symptoms have been reported to
develop up to five years after initiation of a medicine. Patients usually recover after the
offending drug is withdrawn. It is also important to treat any renal, hepatic, pulmonary,
CNS or any other complications of the eosinophilia.
■ Corticosteroids are often used, but there are no placebo controlled trials assessing their
effectiveness and their role is not clear. Some sources suggest they have little benefit and
no effect on outcomes,while others suggest that they produce a more rapid response.
■ Intravenous methylprednisolone at a dose of 50mg daily has been used to treat the
symptoms of eosinophilia.There is a report of high dose intravenous methylprednisolone
(125mg every four hours) being used. There is, however, no evidence that
methylprednisolone is more effective than oral corticosteroid therapy.
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