**3. Hematologic and neoplastic diseases**

*Cells of the Immune System*

below 1500/mm3

resistance to treatment (**Figure 2**) [11].

**2.3 Treatment of HES and CEL-NOS**

HES or CEL-NOS (**Figure 2**) [10, 12, 14].

Severe primary (IL-5) and secondary immunodeficiencies (HIV) are associated with eosinophilia when there is polarization of TH2 by the immunogen (allergen) or drug (antiretroviral); infections such as tuberculosis are the cause of infections and

Corticosteroids should be considered a first-line treatment, which are potent anti-eosinophil agents, effective in producing rapid reductions. Maximal dose was 1 mg × kg 2 months, with symptom control and reduction of the eosinophil count to

Hydroxyurea is an effective first-line agent for HES which may be used in conjunction with corticosteroids or in steroid nonresponders. A typical starting dose is 500–1000 mg daily which can serve as effective palliative to control leukocytosis and eosinophilia but with no proven role in favorably altering the natural history of

IFN-a has demonstrated hematologic responses and reversion of organ injury in patients with HES and CEL-NOS refractory to therapies including prednisone and/or hydroxyurea. Remissions have been associated with improvement in clinical symptoms and organ disease, including hepatosplenomegaly, cardiac and thrombo-

embolic complications, mucosal ulcers, and skin involvement [5, 10–12].

*Diagnostic and treatment algorithm based on revised 2016 WHO classification of eosinophilic disorders. According to the algorithm, the type of eosinophilia can be monitored according to the cases where other drugs other than imatinib should be used, with three pathological options being present: chronic leukemia with eosinophilia, idiopathic hypereosinophilia, and lymphocyte variant, all share the administration of imatinib* 

*and corticosteroids (idiopathic hypereosinophilia and lymphocyte variant) [10].*

after 1 month of treatment.

**158**

**Figure 3.**

Mastocytosis: Develops from a neoplastic proliferation of mast cells. It develops from a neoplastic clonal proliferation of mastocytes that accumulate in one or more organ systems and are organize as compact cohesive aggregate groups or multifocal groups of abnormal mastocytes. This disorder is diverse; it can be found as cutaneous lesions that may naturally recede, to highly aggressive neoplasias related with multiple organ failure and short outliving. Mastocytosis subtypes are principally characterized by the clinical manifestations and the spread of the disease. When cutaneous mastocytosis (CM) occurs, mastocyte infiltration is restricted to the skin, whereas systemic mastocytosis (SM) includes at least one extracutaneous organ, with or without skin lesions. Mastocytosis must be distinguished from mastocyte hyperplasia or from the mastocyte activation states, without the morphological or molecular abnormalities that characterize neoplastic proliferation [15]. The WHO classification includes seven types:


Hypereosinophilic syndrome (HES): It has been described as a condition associated with persistent eosinophilia in the peripheral blood, organ damage, and exclusion of any other underlying disease or condition that may explain eosinophilia or organ damage [4, 16–18]. The diagnostic algorithm must begin with the evaluation of peripheral blood hypereosinophilia (HE), defined as a persistent increase of blood eosinophils, above 1.5 X 109/L blood [4, 16–18]. The term "tissue HE" has also been proposed, and it may be useful in the evaluation and the classification of the disorders related to HES [16, 19]. The establishment of an HES diagnosis must be

considered: (a) the existence of an underlying disease or condition and (b) the presence of clinical signs and symptoms or laboratory abnormalities that show organ damage induced by HE (HES) [19]. There are four important groups of underlying disorders in patients with documented HES:


Lymphoid and myeloid leukemias: Many hematologic disorders may present eosinophilia, but only a few present clonal (primary) neoplasias, and just a small number of neoplasms present HE and organ damage. Myeloid neoplasias that present HE include rare acute eosinophilic leukemia types. The most common type of chronic leukemia is chronic eosinophilic leukemia (CEL), which is frequently associated with the FIP1L1-PDGFRA rearrangement in endomyocardial fibrosis/ thrombosis and other myeloid neoplasias with rearrangements, such as the 8p11 syndrome [19, 20]. Clonal eosinophilia is frequently observed in advanced cases of systemic mastocytosis [19, 21, 22].

Lymphoid neoplasms may present HE, and in most cases, a T cell lymphoma is diagnosed. Nevertheless, in such patients with 8p11 syndrome and other rare entities, both eosinophils and lymphocytes may be involved in the neoplastic clonal processes [19, 21].

Paraneoplastic conditions associated with hypereosinophilia. Different types of cancers may be preceded or accompanied by eosinophilia. Cancers associated with HE include lung, gastrointestinal tract, pancreas, and thyroid adenocarcinomas, gynecologic tumors, and skin cancer. Although pathogenesis is unclear, there is a widely accepted hypothesis stating that carcinogenic cells or cancer or the cancer microenvironment around fibroblasts produce eosinophilopoietic cytokines [19, 23].

Identification and quantification.

Classic methodology: Clinical manifestations and diagnosis depend on the type of disease and other factors, where different organs may be involved in patients with HES, for example, skin, gastrointestinal tract, heart, and central nervous system.

In order to establish an HES diagnosis, it is recommended to include clinical and laboratory parameters, such as:


**161**

CPA-MHC.

*Eosinophilic Disorders: Extrinsic and Intrinsic Immune Response, New Diagnostic Perspectives…*

Immunoglobulins rearrangements are detected by real-time polymerase chain reaction with TaqMan molecular probes, such as TCR, BCR/ABL1, JAK2 V617F, KITD816V, PDGFRA/PDGFRB, and FGR1. The most recommended bone marrow exams are cytogenetic assays and fluorescence in situ hybridization (FISH)—other studies which do not include molecular detection are tissue immunohistochemistry

*Flow diagram to perform real-time PCR. In a simplified way, the preparation of the sample with its corresponding primer and the distribution of the samples for its reaction are shown, which can be seen in real* 

The WHO defines an ADR to any predictable noxious reaction that appears at therapeutic doses, depends on the doses, and is related to pharmacological actions. Other unpredictable reactions: hypersensitivity or allergic (DHRs) associated with immunological mechanisms, susceptibility (atopy), and polymorphism (pharmaco-

It is considered as a public health problem due to its high morbidity and mortality being 20%; hence, the importance of its clinical diagnosis and laboratory tests is being considered at all stages of life (prenatal, postnatal, childhood, adolescence,

Pro-haptens. Drugs are generally non-immunogenic haptens of different types: Pro-haptens (non-active reagents) low molecular weight chemicals of less than 1000 D; examples aromatic, heterocyclic, sulfonamides, OH, halogens, resonance, and beta-lactam are processed and presented in the CPA-MHC context and produce

Active reagents: aromatic, polar, with nitrogen, to induce an immune response

**4.1 Immune response to drugs in DHRs: haptens, pro-haptens, and TCR pi**

Medications are usually non-immunogenic haptens of different types:

*DOI: http://dx.doi.org/10.5772/intechopen.89229*

**3.1 Laboratory diagnosis by molecular parameters**

*time by monitoring the amplification as the cycles in the thermal cycler pass.*

**4. Allergy and hypersensitivity to drugs (DHRs)**

a humoral response, IgE, IgG and IgM or cellular.

and histology (**Figure 4**) [16].

**Figure 4.**

genetic, MHC-HLA) [24–27].

adult, and older adult).

*Eosinophilic Disorders: Extrinsic and Intrinsic Immune Response, New Diagnostic Perspectives… DOI: http://dx.doi.org/10.5772/intechopen.89229*

#### **Figure 4.**

*Cells of the Immune System*

disorders in patients with documented HES:

1.Hematopoietic neoplasias

systemic mastocytosis [19, 21, 22].

Identification and quantification.

a.Physical exam of organs and body systems

ultrasound, and normal endoscopic study [19]

V617F, KITD816V, PDGFRA/PDGFRB, and FGR1

laboratory parameters, such as:

tests, and urinalysis

processes [19, 21].

system.

disorders [19]

considered: (a) the existence of an underlying disease or condition and (b) the presence of clinical signs and symptoms or laboratory abnormalities that show organ damage induced by HE (HES) [19]. There are four important groups of underlying

4.Infrequent clinical syndromes that present HE, including rare hereditary

Lymphoid and myeloid leukemias: Many hematologic disorders may present eosinophilia, but only a few present clonal (primary) neoplasias, and just a small number of neoplasms present HE and organ damage. Myeloid neoplasias that present HE include rare acute eosinophilic leukemia types. The most common type of chronic leukemia is chronic eosinophilic leukemia (CEL), which is frequently associated with the FIP1L1-PDGFRA rearrangement in endomyocardial fibrosis/ thrombosis and other myeloid neoplasias with rearrangements, such as the 8p11 syndrome [19, 20]. Clonal eosinophilia is frequently observed in advanced cases of

Lymphoid neoplasms may present HE, and in most cases, a T cell lymphoma is diagnosed. Nevertheless, in such patients with 8p11 syndrome and other rare entities, both eosinophils and lymphocytes may be involved in the neoplastic clonal

Paraneoplastic conditions associated with hypereosinophilia. Different types of cancers may be preceded or accompanied by eosinophilia. Cancers associated with HE include lung, gastrointestinal tract, pancreas, and thyroid adenocarcinomas, gynecologic tumors, and skin cancer. Although pathogenesis is unclear, there is a widely accepted hypothesis stating that carcinogenic cells or cancer or the cancer microenvironment around fibroblasts produce eosinophilopoietic cytokines [19, 23].

Classic methodology: Clinical manifestations and diagnosis depend on the type of disease and other factors, where different organs may be involved in patients with HES, for example, skin, gastrointestinal tract, heart, and central nervous

In order to establish an HES diagnosis, it is recommended to include clinical and

b.Laboratory exams: white blood cell count (eosinophils, basophils, neutrophils), hemoglobin, platelet count, B12 vitamin, hepatic enzymes, kidney function

c.Organic functional tests: electrocardiogram, echocardiogram, pulmonary function tests, chest computed tomography and radiography, abdominal

d.Molecular detection of some translocations, such as TCR, BCR/ABL1, JAK2

2.Other neoplasias (non-hematopoietic) (paraneoplastic HE)

3.Common allergic, reactive, or immunological conditions

**160**

*Flow diagram to perform real-time PCR. In a simplified way, the preparation of the sample with its corresponding primer and the distribution of the samples for its reaction are shown, which can be seen in real time by monitoring the amplification as the cycles in the thermal cycler pass.*

#### **3.1 Laboratory diagnosis by molecular parameters**

Immunoglobulins rearrangements are detected by real-time polymerase chain reaction with TaqMan molecular probes, such as TCR, BCR/ABL1, JAK2 V617F, KITD816V, PDGFRA/PDGFRB, and FGR1. The most recommended bone marrow exams are cytogenetic assays and fluorescence in situ hybridization (FISH)—other studies which do not include molecular detection are tissue immunohistochemistry and histology (**Figure 4**) [16].

### **4. Allergy and hypersensitivity to drugs (DHRs)**

The WHO defines an ADR to any predictable noxious reaction that appears at therapeutic doses, depends on the doses, and is related to pharmacological actions. Other unpredictable reactions: hypersensitivity or allergic (DHRs) associated with immunological mechanisms, susceptibility (atopy), and polymorphism (pharmacogenetic, MHC-HLA) [24–27].

It is considered as a public health problem due to its high morbidity and mortality being 20%; hence, the importance of its clinical diagnosis and laboratory tests is being considered at all stages of life (prenatal, postnatal, childhood, adolescence, adult, and older adult).

#### **4.1 Immune response to drugs in DHRs: haptens, pro-haptens, and TCR pi**

Medications are usually non-immunogenic haptens of different types:

Pro-haptens. Drugs are generally non-immunogenic haptens of different types: Pro-haptens (non-active reagents) low molecular weight chemicals of less than 1000 D; examples aromatic, heterocyclic, sulfonamides, OH, halogens, resonance, and beta-lactam are processed and presented in the CPA-MHC context and produce a humoral response, IgE, IgG and IgM or cellular.

Active reagents: aromatic, polar, with nitrogen, to induce an immune response CPA-MHC.

Inert TCR pi (pharmacological interaction with immune receptors): Some drugs are able to bind non-covalently to TCR pi receptors pre-developed by a previous immune response to a non-covalently reversible drug and signaling toward a response of hypersensitivity and explain the rapid appearance of symptoms, some cross reactions to the drug, or its metabolites.

Pi concept and HLA restriction in hypersensitivity: In the pi concept, drugs primarily activate TCR, for example, abacavir associated with the HLA-B \* 5701 allele in whites, Stevens-Johnson syndrome (SJS) with carbamazepine treatment in Chinese associated in patients with the HLA-B \* 1502, and HLA-B \* 5801 allele in allopurinolinduced adverse reactions such as SJS and toxic epidermal necrolysis (TEN) [28–31].

#### **4.2 Hypersensitivity and diagnosis**

Hypersensitivity is an exacerbated immune response, which produces a clinical picture with dermal, systemic disorders, and sometimes sudden death. In 1930 Coombs systematized these reactions according to the period of time in which the symptoms appear, and the dose of challenge has been fundamental to guide the diagnosis, treatment, and monitoring. It has many points in common with autoimmunity, where the antigens are their own; in the case of allergies to medications, the antigens are allergens: drugs or metabolic derivatives. Hypersensitivity reactions require that the individual has been previously sensitized or exposed to at least the antigens in question. The classification of allergic or hypersensitivity reactions into four types (I, II, III, and IV) and subsequently Pichler in 2003 proposed the subdivision of type IV into IVa, IVb, IVc, and IVd (**Table 1**) [28, 29].

### **4.3 In vitro tests associated with drug and drug eosinophilia: antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs) anticonvulsants, and antidiuretics**

Modified basophil degranulation (MBD): The test is a basophil activation test (BAT) which consists of incubating the basophils in vitro with the suspected drug to be carried out: epitope-paratope binding, activating the basophils and causing degranulation and release of the aforementioned content (specificity 100%, sensitivity 84.0%) [28, 29].

CD63 flow cytometry: Basophils with specific IgE when incubated with the suspected drug are activated by Fcε I receptors; high affinity and low affinity cause crosslinking and protein kinase signal transduction (MAP, PKC) that stimulate expression of the receptor (CD63) -gp53 (lysosomal-transmembrane protein tetraspanin LAMP-31) on the surface of the basophil while the eosinophilic expresses CD23 [30].

Modified leukocyte migration inhibition factor (MLIF) type IV a, b, and c. Associated with anaphylactic degranulation: It has been reported that leukocytes including basophils (BAT-Chemotaxis) also play a role in directional chemotaxis; therefore, when microhematocrits are incubated in Bloom chambers with medications in two dilutions (1 and 0.1 mg/mL) in an RPMI medium, with negative and positive controls, at 37°C, the first (20 min at 2 hours) and delayed migration can be measured (4, 6, and 18 hours); the % of MLIF can also be calculated against the negative control, as well as the reference values (RV) for MLIF (0–25% inhibition of leukocyte migration) [29].

Eosinophilia in the peripheral blood is a common cause in patients who consume medications, especially in developed countries, who are monitored and can restrict their consumption without changes. However, for the doctor, concern may arise in cases of impending hypersensitivity reaction (HSR). Severe HSRs associated with peripheral blood may include specific reactions of organs (heart, kidney, liver,

**163**

**Table 1.**

*Eosinophilic Disorders: Extrinsic and Intrinsic Immune Response, New Diagnostic Perspectives…*

lungs, joints, central nervous system, and skin) and adverse skin reactions (SCAR)

**Clinical symptoms In vitro** 

Contact dermatitis Lymphocyte

Urticaria Angioedema Rhinitis Bronchospasm Anaphylaxis

Hemolytic Anemia

Thrombocytopenia Neutropenia Autoimmunity

Serum disease Vasculitis, LES-like by medications Glomerulonephritis

Maculopapular eruptions (MPE) with eosinophilia (DRESS)

Contact dermatitis, maculopapular, and bullous diseases(SJS), TEN

Acute generalized exanthemic pustulosis (AGEP) pharmacodermias associated with neutrophilia

*subsequently Pichler in 2003 proposed the subdivision of type IV into IVa, IVb, IVc, and IVd [27–29].*

*Hypersensitivity classification according to the Gell and Coombs modified by Sell, Pichler, and ICON.*

*Hypersensitivity reactions require that the individual has been previously sensitized or exposed at least once to the antigens in question. The classification of allergic or hypersensitivity reactions into four types (I, II, III, and IV) and* 

drug

**diagnostics**

IgE specific Serum tryptase Cell stimulation test (CAST) BAT(MDB, CD63)

Coombs test Ab vs. platelets Ab vs. neutrophils

C3, C4, ANA, ANCA, CCP, antithyroid, etc. Liver and kidney function tests Pathological anatomy

transformation test (LT or BT), MLIF, cytotoxic T lymphocyte precursors (CTLp), cytokines (ELISA, PCR)

CBC with check eosinophil cellularity, atypical lymphocytes MLIF, BT, LT

MLIF, liver function tests, CD4/CD8 (death keratinocytes) Activity of IgM vs. herpes virus, Epstein-Barr, and cytomegalovirus (CMV)

CBC T cells CD4/

CD8

**In vivo diagnostics**

Only challenges to the drug can make diagnosis but are high risk [Coombs]

Biopsies with immunofluorescence

Patch tests [Pichler]

Patch tests [Pichler]

Patch tests [Pichler]

Patch tests [Pichler]

[Coombs]

Cutaneous tests (prick, intradermal) Challenge tests Proving tests [Coombs]

*DOI: http://dx.doi.org/10.5772/intechopen.89229*

**Type Type of immune response**

I Measured by IgE

II Cytotoxicity

III Deposit of

FcR

IVa TH1 (IFNγ),

IVb TH2 (IL-4, IL5,

IVc CLT, CD4/

eosinophils, mast cells, and basophils (immediate)

dependent on IgG and IGM antibodies (not immediate) and complement

immunocomplexes [IgG and IgM] (not immediate) Complement or

TNFα, IL12, and macrophages (late)

IL13) eosinophils

CD8 (perforin, granzyme B, Fas L)

IVd T cells, IL8, CXCL8 cells Neutrophils Inflammation

where SJS, TEN, and DRESS are included [32, 33].

*Eosinophilic Disorders: Extrinsic and Intrinsic Immune Response, New Diagnostic Perspectives… DOI: http://dx.doi.org/10.5772/intechopen.89229*

lungs, joints, central nervous system, and skin) and adverse skin reactions (SCAR) where SJS, TEN, and DRESS are included [32, 33].


*Hypersensitivity reactions require that the individual has been previously sensitized or exposed at least once to the antigens in question. The classification of allergic or hypersensitivity reactions into four types (I, II, III, and IV) and subsequently Pichler in 2003 proposed the subdivision of type IV into IVa, IVb, IVc, and IVd [27–29].*

#### **Table 1.**

*Cells of the Immune System*

cross reactions to the drug, or its metabolites.

**4.2 Hypersensitivity and diagnosis**

**antidiuretics**

sensitivity 84.0%) [28, 29].

leukocyte migration) [29].

Inert TCR pi (pharmacological interaction with immune receptors): Some drugs

Pi concept and HLA restriction in hypersensitivity: In the pi concept, drugs primarily activate TCR, for example, abacavir associated with the HLA-B \* 5701 allele in whites, Stevens-Johnson syndrome (SJS) with carbamazepine treatment in Chinese associated in patients with the HLA-B \* 1502, and HLA-B \* 5801 allele in allopurinolinduced adverse reactions such as SJS and toxic epidermal necrolysis (TEN) [28–31].

Hypersensitivity is an exacerbated immune response, which produces a clinical picture with dermal, systemic disorders, and sometimes sudden death. In 1930 Coombs systematized these reactions according to the period of time in which the symptoms appear, and the dose of challenge has been fundamental to guide the diagnosis, treatment, and monitoring. It has many points in common with autoimmunity, where the antigens are their own; in the case of allergies to medications, the antigens are allergens: drugs or metabolic derivatives. Hypersensitivity reactions require that the individual has been previously sensitized or exposed to at least the antigens in question. The classification of allergic or hypersensitivity reactions into four types (I, II, III, and IV) and subsequently Pichler in 2003 proposed the subdi-

vision of type IV into IVa, IVb, IVc, and IVd (**Table 1**) [28, 29].

**4.3 In vitro tests associated with drug and drug eosinophilia: antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs) anticonvulsants, and** 

Modified basophil degranulation (MBD): The test is a basophil activation test (BAT) which consists of incubating the basophils in vitro with the suspected drug to be carried out: epitope-paratope binding, activating the basophils and causing degranulation and release of the aforementioned content (specificity 100%,

CD63 flow cytometry: Basophils with specific IgE when incubated with the suspected drug are activated by Fcε I receptors; high affinity and low affinity cause crosslinking and protein kinase signal transduction (MAP, PKC) that stimulate expression of the receptor (CD63) -gp53 (lysosomal-transmembrane protein tetraspanin LAMP-

Eosinophilia in the peripheral blood is a common cause in patients who consume medications, especially in developed countries, who are monitored and can restrict their consumption without changes. However, for the doctor, concern may arise in cases of impending hypersensitivity reaction (HSR). Severe HSRs associated with peripheral blood may include specific reactions of organs (heart, kidney, liver,

31) on the surface of the basophil while the eosinophilic expresses CD23 [30]. Modified leukocyte migration inhibition factor (MLIF) type IV a, b, and c. Associated with anaphylactic degranulation: It has been reported that leukocytes including basophils (BAT-Chemotaxis) also play a role in directional chemotaxis; therefore, when microhematocrits are incubated in Bloom chambers with medications in two dilutions (1 and 0.1 mg/mL) in an RPMI medium, with negative and positive controls, at 37°C, the first (20 min at 2 hours) and delayed migration can be measured (4, 6, and 18 hours); the % of MLIF can also be calculated against the negative control, as well as the reference values (RV) for MLIF (0–25% inhibition of

are able to bind non-covalently to TCR pi receptors pre-developed by a previous immune response to a non-covalently reversible drug and signaling toward a response of hypersensitivity and explain the rapid appearance of symptoms, some

**162**

*Hypersensitivity classification according to the Gell and Coombs modified by Sell, Pichler, and ICON.*

The prolongation of eosinophilia can cause tissue damage, although without being clarified specifically, adding to the condition infections as another factor that preserves eosinophilia (parasitic and fungal infestations) or decreases (eosinopenia due to bacterial and viral infections). The diagnosis can be complicated because of the presence of the drug which worsens a preexisting eosinophilia, particularly in atopic patients [33].

DRESS is more common in adult patients than in children, with approximately 50 drugs being described, highlighting anticonvulsants (phenytoin, phenobarbital, and carbamazepine) and antibiotics as the main causes of the syndrome and, to a lesser extent, sulfate derivatives, antidepressants, NSAIDs, and antidiuretics [34]. There is no clear association between variability of the type of drug and the affected organ with the degree of eosinophilia, which can be mild or self-limited and severe when multisystemic complications are generated due to the presence of symptoms that are not appreciated in the mild form [32, 33].

Other proposals that lead to the pathogenesis of DRESS include detoxification defects at the time of the formation of reactive metabolites, slow acetylation, and reactivation of the human herpes virus (HHV-6-7) or EBV [34].

In general, the diagnostic algorithm for eosinophilia linked to SCAR can be visualized as a hypersensitivity response type IVb (SJS and NET) and type IVc (DRESS), which in some way can highlight the pathogenesis proposals previously mentioned not only by DRESS but identify an atopic patient (**Table 1**).

### **5. Conclusions**

Eosinophils are leukocytes (white blood cells) found in the peripheral blood, hematopoietic, lymphatic organs, thymus, connective tissue, and digestive tract. They are identified and quantified by manual counting (Neubauer chamber), automated count with autoanalyzer hemocytometers (impedance, colorimetry, and differential in optical microscope), flow cytometry after the advent of monoclonal antibodies, currently the most used to identify surface markers and immunoenzymatic methods (ELISA, RAST, IMMUNOCAP) for cytoplasmic granules.

The classification of eosinophilic diseases "eosinophilic disorders" was revised in 2008 and confirmed in 2016; its study focused on external (extrinsic) and internal (intrinsic) causes (optimized) and optimized and failed diagnosis by precise and timely diagnosis. The algorithms are used and started with the main pillar: The clinical history (clinical criteria, anamnesis, and exploitative maneuvers leading to clinical laboratory algorithms, with initial, basic, and special tests including imaging, tomography, and X-rays to finally improve the prognosis and modify the natural history. The intrinsic and extrinsic disorder algorithm planting is different; this is due to the recognition of molecular altered T cell clones, bone marrow studies, and markers of apoptotic genes, PCM1-JAK2, Fas L, and bcl2.

Some allergies to medications with symptomatology related to specific organ and severe cutaneous against antiepileptics (phenytoin, phenobarbital, carbamazepine) as well as other medications (antibiotics, NSAIDs, antidiuretics) can be related, which rethinks the proposed immunological response algorithm not only in basophil evaluation but also the search for eosinophils in flow cytometry or optical microscopy to assess not only damage but neutralization (eosinophil histaminase).

Corticosteroids are considered the first line of treatment because of their potent anti-eosinophilic effect for disease control, prognosis, and prevention. So the new

**165**

*Eosinophilic Disorders: Extrinsic and Intrinsic Immune Response, New Diagnostic Perspectives…*

treatment alternatives could displace steroids with monoclonal antibodies such as

Thanks to the headquarters and staff of the Department of Allergy and Immunology of the Juarez Hospital of Mexico, Dr. Ruben Humberto Meyer Gomez of the Angeles Hospital, and the laboratory technician Isabel Guerrero Vargas of the

*DOI: http://dx.doi.org/10.5772/intechopen.89229*

**Acknowledgements**

LCEIL Laus Deo.

**Conflict of interest**

There is no conflict of interest.

**Appendices and nomenclature**

AEC absolute eosinophil count HSR hypersensitivity reaction

CBC complete blood count

SCAR severe cutaneous adverse reaction SJS Stevens-Johnson's syndrome TEN toxic epidermal necrolysis

DHRs drug hypersensitivity reaction

DRESS drug rash eosinophilia and systemic symptoms

the IL-5 inhibitor that show less long-term toxicity.

*Eosinophilic Disorders: Extrinsic and Intrinsic Immune Response, New Diagnostic Perspectives… DOI: http://dx.doi.org/10.5772/intechopen.89229*

treatment alternatives could displace steroids with monoclonal antibodies such as the IL-5 inhibitor that show less long-term toxicity.
