Approach to Suspected Hypereosinophilic Syndrome

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Questions and Answers

What is an essential component of the diagnostic workup for patients with LHES at the time of diagnosis?

Assessment for autoimmune diseases

Assessment for occult lymphoma (correct)

Assessment for metabolic syndrome

Assessment for rheumatological disorders

Which laboratory test is suggestive but not diagnostic for Monoclonal Hypereosinophilia Syndrome (MHES)?

Complete blood count with differential and smear (correct)

Serum tryptase levels

Quantitative serum immunoglobulin levels

Liver function tests

What factors contribute to elevated IgE levels in conditions including LHES?

Parasitic infections (correct)

Viral infections

Systemic inflammation

Chronic infections

Which test is consistently elevated in PDGFRA and KIT-associated diseases?

Serum tryptase levels Signup and view all the answers

What finding on flow cytometry is characteristic of LHES?

Clonal and/or aberrant T-cell populations Signup and view all the answers

What is often present in patients with episodic angioedema and eosinophilia, besides LHES?

Elevated serum IgM levels Signup and view all the answers

Which condition is indicated by clonal B cells in diagnostic assessments?

Pre–B-cell acute lymphoblastic leukemia Signup and view all the answers

Why are liver function tests included in the diagnostic workup?

To assess end organ involvement Signup and view all the answers

What is the primary cause of mortality in patients with this condition?

Cardiac disease Signup and view all the answers

Which of the following is NOT a gastrointestinal manifestation of the condition?

Pleural effusion Signup and view all the answers

What kind of nervous system involvement may occur in this condition?

Encephalopathy Signup and view all the answers

In the classification of eosinophilic conditions, which category pertains to eosinophilic disorders linked to specific infections or neoplasms?

Associated HE/HES Signup and view all the answers

Which abnormality is associated with the myeloid variant of HE/HES?

Rearrangements of PDGFRA Signup and view all the answers

What are eosinophil mediators believed to primarily cause in affected tissues?

Tissue damage Signup and view all the answers

What is a characteristic feature of the myeloproliferative variant of hypereosinophilic syndrome (HES)?

Elevated serum tryptase Signup and view all the answers

Which variant of hypereosinophilic syndrome is associated with a FIP1L1–PDGFRA fusion gene?

Myeloproliferative variant HES Signup and view all the answers

Which of the following is a key characteristic of the familial variant of HE/HES?

Occurrence in multiple family members Signup and view all the answers

What clinical feature distinguishes lymphocytic variant HES from myeloproliferative variant HES?

Dermatologic manifestations Signup and view all the answers

Which symptom is commonly associated with skin manifestations of the condition?

Papules or plaques Signup and view all the answers

What is the gold standard for diagnosing lymphocytic variant HES?

Demonstration of a clonal T-cell population producing type 2 cytokines Signup and view all the answers

Which factor contributes to the difficulty in distinguishing lymphocytic variant HES from T-cell malignancies?

Indistinguishable surface phenotype of T-cell populations Signup and view all the answers

What should be considered when diagnosing a patient with suspected lymphocytic variant HES?

Considering other forms of malignancies and exclusions Signup and view all the answers

What should be considered early in the diagnostic process for eosinophilia?

The presence of helminth infection Signup and view all the answers

What impact does the interstitial deletion on chromosome 4q12 have on myeloproliferative variant HES?

It leads to enhanced tyrosine kinase activity Signup and view all the answers

If eosinophilia does not significantly decrease within 24 to 48 hours, what should be considered next?

Additional therapy based on clinical subtype Signup and view all the answers

In which percentage of patients does lymphocytic variant HES progress to a lymphoid malignancy?

Approximately 10% Signup and view all the answers

What role does prednisone play in the treatment of severe eosinophilia syndrome (HES)?

It is the primary therapy in acute severe cases Signup and view all the answers

Which treatment might be used for eosinophilia with suspected myeloid neoplasm?

Imatinib Signup and view all the answers

What is a common limitation of corticosteroid therapy in the treatment of symptomatic eosinophilia?

Development of toxicity and resistance Signup and view all the answers

What was the initial treatment given to the patient for presumed idiopathic thrombocytopenic purpura?

Prednisone 60 mg daily Signup and view all the answers

What defines the response to eosinophil-targeting biologics in the context of therapy?

They target pathways critical to eosinophil survival Signup and view all the answers

Which symptom did the 38-year-old woman NOT experience in her clinical case?

Skin rash Signup and view all the answers

After tapering the prednisone, which symptoms reappeared?

Eosinophilia and pruritus Signup and view all the answers

What was notable about the laboratory tests performed at the time of referral to the National Institutes of Health?

Elevated AEC and increased eosinophils Signup and view all the answers

Why might the use of eosinophil-targeting biologics in the acute setting be considered controversial?

There is limited evidence of effectiveness Signup and view all the answers

Which therapy was ineffective before the patient was referred to the National Institutes of Health?

Hydroxyurea Signup and view all the answers

Which diagnostic test revealed a clonal pattern consistent with a diagnosis of hypereosinophilic syndrome?

T-cell receptor testing by polymerase chain reaction Signup and view all the answers

What treatment led to the resolution of eosinophilia in the patient?

Interferon α therapy Signup and view all the answers

What did the repeat bone marrow show during the referral evaluation?

Increased eosinophils only Signup and view all the answers

What was a significant finding in the physical examination upon referral?

Symmetric nonpitting edema of the thighs Signup and view all the answers

Which of the following best describes the symptoms of hypereosinophilic syndromes?

Clinical manifestations vary widely, from mild fatigue to severe complications. Signup and view all the answers

What is the defining characteristic of hypereosinophilia (HE)?

Eosinophil count greater than 1.5 × 10^9 /L. Signup and view all the answers

Which of the following disorders is least likely to cause marked eosinophilia?

Acute myocardial infarction Signup and view all the answers

What is a common infectious cause of eosinophilia?

Helminth infections Signup and view all the answers

Which condition would most likely not be classified under autoimmune and immunodysregulatory disorders with marked eosinophilia?

Asthma Signup and view all the answers

The exclusion of certain conditions is necessary to define idiopathic hypereosinophilia. Which of the following must be excluded?

Drug-induced eosinophilia Signup and view all the answers

Which of the following is NOT a requirement for the WHO definition of hypereosinophilic syndrome?

Eosinophilic myeloid neoplasms present. Signup and view all the answers

Which specific neoplasia is highlighted as particularly challenging to diagnose in relation to hypereosinophilia?

Pre–B-cell acute lymphoblastic leukemia Signup and view all the answers

What is a rare but potential outcome of hypereosinophilic syndromes?

Endomyocardial fibrosis Signup and view all the answers

What type of eosinophilic condition is characterized by clonal/neoplastic processes?

Primary hypereosinophilia Signup and view all the answers

Which of the following statements about hypereosinophilia and drugs is true?

Any medication could potentially induce eosinophilia. Signup and view all the answers

What is a key feature of the consensus definition of hypereosinophilic syndrome?

Two examinations for eosinophil count must be done at least one month apart. Signup and view all the answers

In terms of helminth infections, what characteristic makes them a notable cause of eosinophilia worldwide?

They often present with tissue invasion. Signup and view all the answers

Study Notes

Approach to the Patient with Suspected Hypereosinophilic Syndrome

Hypereosinophilic syndromes (HES) are a diverse group of rare disorders.
Clinical manifestations vary from fatigue to life-threatening conditions like endomyocardial fibrosis and thromboembolic events.

Hypereosinophilic Syndromes

HES are a heterogeneous group of rare disorders.
Clinical presentations range from fatigue to life-threatening complications.

Eosinophilia and Hypereosinophilia

Eosinophilia (AEC > 0.45 x 10^9/L) is relatively common (1-2% of the general population).
Hypereosinophilia (AEC ≥ 1.5 x 10^9/L) is rare (0.315 to 6.3 per 100,000 in the United States).

Disorders Associated with Marked Eosinophilia

Atopic disorders (e.g., asthma, atopic dermatitis, chronic rhinosinusitis)
Drug hypersensitivity reactions (e.g., drug rash, eosinophilia, and systemic symptoms)
Infections and infestations (e.g., helminth, fungal, viral infections, ectoparasites, protozoa)
Autoimmune and immunodysregulatory disorders (e.g., inflammatory bowel disease, sarcoidosis, IgG4 disease)
Neoplasia (e.g. leukemia, lymphoma, solid tumors)
Inborn errors of immunity (e.g. Omenn syndrome, DOCK8 deficiency, Loeys-Dietz Syndrome)
Rare hypereosinophilic syndromes

Clinical Presentation

Patients can present with constitutional symptoms like fatigue, muscle aches, fever, pruritus, angioedema, diarrhea, and cough.
Cardiac involvement (endomyocardial fibrosis, pericarditis, myocarditis, intramural thrombus), resulting in mortality, is common.
Other organ involvement includes the central and peripheral nervous systems (mononeuritis multiplex, paraparesis, encephalopathy, dementia), pulmonary system (pulmonary infiltrates, fibrosis, pleural disease), gastrointestinal system (diarrhea, gastritis, colitis, hepatitis, Budd-Chiari syndrome) and skin (pruritus, angioedema, papules, plaques).
Kidney and bone involvement is rare.

Pathophysiology

Tissue damage in eosinophilia is secondary to eosinophil degranulation and release of mediators like cationic protein and major basic protein.
Eosinophil mediators primarily cause damage locally in infiltrated tissues.
Recent research suggests a role of other cells (e.g., mast cells) in some cases with clonal eosinophilia.

Classification of HES

Myeloid HES: suspected or proven eosinophilic myeloid neoplasm, including those with PDGFRA rearrangements.
Lymphocytic variant HES: presence of a clonal or phenotypically aberrant T-cell population producing cytokines driving eosinophilia.
Overlap HES: single-organ-restricted eosinophilic disorders overlapping with idiopathic HES (e.g. eosinophilic gastrointestinal disorders, eosinophilic granulomatosis with polyangiitis).
Associated HES: in the context of a defined disorder (e.g., helminth infection, neoplasm, immunodeficiency, hypersensitivity reaction).
Familial HES.
Idiopathic HES. (unknown cause)

Myeloproliferative Variant HES

Characterized by male predominance, end-organ damage, elevated serum tryptase, splenomegaly, anemia, thrombocytopenia, bone marrow myeloproliferation, and reticulin fibrosis.
Typically unresponsive to steroid therapy.

Molecular Abnormalities

Often associated with an interstitial deletion on chromosome 4q12, resulting in a FIP1L1–PDGFRα fusion gene.
The protein product (tyrosine kinase) has enhanced activity and particular sensitivity to low-dose imatinib therapy.

Lymphocytic Variant HES

Characterized by a large CD2+, CD3-, CD4+ T-cell population producing IL-4 and IL-5.
Typically present with dermatologic manifestations, but any organ system can be involved.
Clonal T-cell populations in asymptomatic cases can be indistinguishable from those with symptomatic cases.

Diagnostic Clues for LHES

Serum IgM, IgE, and serum and thymus and activation-regulated chemokine (TARC) levels are elevated in most patients.
Diagnosis usually relies on detecting clonal and/or aberrant T-cell populations producing type 2 cytokines using flow cytometry.
Phenotyping is often necessary to confirm the aberrant population

Clinical Evaluation and Treatment

Patients with confirmed eosinophilia undergo comprehensive history, physical examination, complete blood count differential, and routine chemistries.
Serum tryptase, immunoglobulins, and B12 levels are measured.
Additional diagnostic procedures include T- and B-cell receptor studies, flow cytometry, echocardiogram, electrocardiogram serum troponin and CT.
Biopsy of affected tissues may be necessary.
Prednisone is the mainstay of initial therapy in acute and/or life-threatening presentations. Additional therapy is selected based on clinical evaluation.
Conventional second-line agents (hydroxyurea and interferon α), and eosinophil-targeting biologics (mepolizumab and Reslizumab) are considered in more nuanced presentations and less responsive cases.
The use of eosinophil targeting biologics in the acute setting is controversial.

Diagnostic Workup (Summary)

Comprehensive clinical history and physical examination
Complete blood count with differential, routine chemistries (liver function tests)
Immunoglobulin levels
Serum tryptase and B12 levels
Further evaluation based on clinical picture.

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Description

This quiz explores the diverse and complex nature of hypereosinophilic syndromes (HES). Learn about their clinical manifestations, diagnostic criteria, and associated disorders. Ideal for medical professionals and students understanding these rare conditions.