Hypereosinophilic Syndromes Overview

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Questions and Answers

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

Dilated cardiomyopathy (correct)

Pulmonary infiltrates

Endomyocardial fibrosis

Angioedema

Which of the following is not a clinical manifestation of eosinophilia?

Pruritus

Cough

Gastrointestinal bleeding (correct)

Diarrhea

How can one define myeloid HE/HES?

Eosinophilia due to helminth infection

Suspected or proven eosinophilic myeloid neoplasm (correct)

Presence of a clonal T-cell population

Eosinophilic disorders overlapping with idiopathic HES

Which clinical involvement is unlikely to result from eosinophilia?

Bone fractures Signup and view all the answers

What is a characteristic feature of overlap HES?

Single-organ-restricted eosinophilic disorders Signup and view all the answers

Which mediator is primarily involved in local tissue damage due to eosinophilia?

Major basic protein Signup and view all the answers

Which classification of HE/HES is associated with infections or neoplasms?

Associated HE/HES Signup and view all the answers

What neurological condition can eosinophilia lead to?

Dementia Signup and view all the answers

What should patients with LHES be assessed for at diagnosis?

Occult lymphoma Signup and view all the answers

What blood test is recommended to evaluate the presence of myeloid precursors?

Complete blood count with differential Signup and view all the answers

Which test can indicate the presence of malignant hypereosinophilia syndrome (MHES)?

Dysplastic eosinophils on smear Signup and view all the answers

What is a common characteristic of clonal T-cell populations found in certain conditions?

Suggestive of LHES Signup and view all the answers

Which condition is characterized by elevated serum IgM levels?

LHES Signup and view all the answers

What condition is indicated by elevated serum tryptase levels?

PDGFRA and KIT-associated disease Signup and view all the answers

What encompasses the comprehensive history and physical examination for HE diagnosis?

Prior eosinophil counts and symptoms Signup and view all the answers

Which statement is true regarding lymphocyte phenotyping by flow cytometry?

Helps in identifying clonal T-cell populations Signup and view all the answers

What was the initial treatment administered for presumed idiopathic thrombocytopenic purpura?

Prednisone Signup and view all the answers

What was the result of the testing for FIP1L1::PDGFRA?

Negative Signup and view all the answers

During the treatment phase, what condition did the patient experience after tapering prednisone?

Increased eosinophilia and pruritus Signup and view all the answers

Which laboratory finding was NOT noted during the physical examination of the patient?

Decreased platelets Signup and view all the answers

What was the diagnosis made after T-cell receptor testing and flow cytometry?

Lymphocytic variant hypereosinophilic syndrome Signup and view all the answers

What treatment was initiated after referral to the National Institutes of Health?

Interferon α Signup and view all the answers

Which clinical symptom did the patient experience during her assessment before treatment at the National Institutes of Health?

Fatigue Signup and view all the answers

What was the peak absolute eosinophil count (AEC) recorded during the treatment?

26.0 10^9/L Signup and view all the answers

What characterizes myeloproliferative variant HES in terms of its clinical features?

Elevated serum tryptase and splenomegaly Signup and view all the answers

Which treatment option has shown effectiveness in patients with myeloproliferative variant HES due to the FIP1L1–PDGFRA fusion gene?

Low-dose imatinib therapy Signup and view all the answers

How does lymphocytic variant HES typically present in most patients?

Predominantly with dermatologic manifestations Signup and view all the answers

What is the initial therapeutic approach for a case of eosinophilia associated with a helminth infection?

Consideration of secondary causes and specific treatment Signup and view all the answers

What is the gold standard for diagnosing lymphocytic variant HES?

Identification of a clonal T-cell population Signup and view all the answers

What is the mainstay therapy for severe and/or life-threatening manifestations of Hypereosinophilia Syndrome (HES)?

Prednisone Signup and view all the answers

Which factor should be assessed to determine the urgency of intervention in eosinophilia cases?

Presence and severity of clinical manifestations Signup and view all the answers

Which statement regarding lymphocytic variant HES is accurate?

It can be indistinguishable from T-cell malignancies. Signup and view all the answers

Which of the following is NOT a feature of myeloproliferative variant HES?

Clonal aberrant T cells in peripheral blood Signup and view all the answers

In cases of hypereosinophilia where symptoms do not improve within 24 to 48 hours after starting treatment, what is the next recommended action?

Consider additional therapy based on suspected subtype Signup and view all the answers

What percentage of patients with lymphocytic variant HES may progress to a lymphoid malignancy?

Approximately 10% Signup and view all the answers

What limitation exists regarding the use of corticosteroids in the long-term treatment of symptomatic HES?

Rapid response leading to medication resistance and toxicity Signup and view all the answers

Which of the following elevates in most patients with lymphocytic variant HES?

Serum and thymus activation-regulated chemokine levels Signup and view all the answers

For which subtype of HES is imatinib specifically indicated?

Myeloid neoplasm Signup and view all the answers

How do eosinophil-targeting biologics work in the treatment of hypereosinophilia?

By reducing eosinophil levels through specific pathway targeting Signup and view all the answers

In the clinical case provided, what was the most significant blood count finding that led to the referral to hematology?

Eosinophilia Signup and view all the answers

What is defined as hypereosinophilia?

Absolute eosinophil count (AEC) > 1.5 × 10^9/L Signup and view all the answers

Which of the following is NOT typically associated with hypereosinophilic syndromes?

Chronic fatigue syndrome Signup and view all the answers

Which of these conditions can lead to significant eosinophilia?

Asthma Signup and view all the answers

What defines eosinophilia in the general population?

AEC > 0.45 × 10^9/L Signup and view all the answers

According to the WHO, how long must AEC be greater than 1.5 × 10^9/L to classify as HES?

More than 6 months Signup and view all the answers

Which of the following best describes end-organ damage as it relates to HES?

Tissue HE with evidence of organ damage Signup and view all the answers

Which neoplastic conditions are commonly associated with hypereosinophilia?

Acute myeloid leukemia Signup and view all the answers

Which of the following infections is the most common etiology for marked eosinophilia worldwide?

Helminth infection Signup and view all the answers

Which autoimmune disorder is mentioned as potentially causing eosinophilia?

Inflammatory bowel disease Signup and view all the answers

Which condition would least likely present with hypereosinophilia?

Type 2 diabetes mellitus Signup and view all the answers

What is the implication of the term 'idiopathic' in hypereosinophilic syndromes?

Exclusion of reactive causes Signup and view all the answers

Which of these conditions would most likely lead to eosinophilia as a side effect?

Administration of IL-2 Signup and view all the answers

Which of the following is classified under rare hypereosinophilic syndromes?

Eosinophilic myeloid neoplasms Signup and view all the answers

What would tissue hypereosinophilia typically indicate?

Presence of eosinophils in tissues causing damage Signup and view all the answers

Study Notes

Hypereosinophilic Syndromes (HES)

HES is a heterogeneous group of rare disorders with diverse clinical manifestations, ranging from fatigue to life-threatening conditions like endomyocardial fibrosis and thromboembolic events.

Eosinophilia

Eosinophilia, characterized by an absolute eosinophil count (AEC) greater than 0.45 x 10^9/L, is relatively common, occurring in 1% to 2% of the general population.
Hypereosinophilia (HE), with an AEC greater than 1.5 x 10^9/L, is extremely rare, with an estimated incidence of 0.315 to 6.3 per 100,000 in the United States.

Disorders Associated with Marked Eosinophilia

Atopic disorders: Asthma, atopic dermatitis, chronic rhinosinusitis
Drug hypersensitivity: Various drug reactions, including drug rash with eosinophilia and systemic symptoms (DRESS), and eosinophilia-myalgia syndrome.
Infection and infestation: Helminth infections (particularly those with a tissue invasive phase), fungal infections, viral infections (including HIV and COVID-19), ectoparasite infestations, and protozoal infections (limited to Sarcocystis and Cystoisospora).
Autoimmune and immunodysregulatory disorders: Inflammatory bowel disease, sarcoidosis, and IgG4-related disease.
Neoplasia: Leukemia, lymphoma
Inborn errors of immunity: Omenn syndrome, DOCK8 deficiency, Loeys-Dietz syndrome, eosinophilic myeloid neoplasms, lymphocytic variant HES, idiopathic HE/HES, familial HE/HES, single-organ HE/HES, etc.

Classification of HES

Myeloid HES: Suspected or proven eosinophilic myeloid neoplasm, including cases associated with rearrangements of PDGFRA.
Lymphocytic variant HE/HES: Presence of a clonal or phenotypically aberrant T-cell population that produces cytokines driving the eosinophilia.
Overlap HES: Single-organ-restricted eosinophilic disorders or eosinophilic syndromes that overlap clinically with idiopathic HES, including eosinophilic gastrointestinal disorders and eosinophilic granulomatosis with polyangiitis (EGPA).
Associated HE/HES: HES occurring in the context of a defined disorder (e.g., helminth infection, neoplasm, immunodeficiency, or hypersensitivity reaction).
Familial HE/HES: Presence in more than one family member (excluding cases with associated HE/HES).
Idiopathic HE/HES: Unknown cause, excluding other types.

CLINICAL MANIFESTATIONS

Constitutional Symptoms: fatigue, muscle aches, fevers, pruritus, angioedema, diarrhea, and cough
Cardiac involvement: endomyocardial fibrosis, pericarditis, myocarditis, and intramural thrombus formation, often leading to dilated cardiomyopathy, and is a major cause of mortality.
Involvement of the nervous system: mononeuritis multiplex, paraparesis, encephalopathy, and dementia.
Pulmonary involvement: pulmonary infiltrates, fibrosis, or pleural disease with effusions
Gastrointestinal involvement: diarrhea, gastritis, colitis, hepatitis, or Budd-Chiari syndrome
Skin involvement: pruritus, angioedema, papules, or plaques
Other tissues: rarely kidneys and bones

Pathophysiology

Tissue damage in eosinophilia is believed to be secondary to eosinophil degranulation, releasing mediators like cationic protein and major basic protein, primarily acting locally in infiltrated tissues to trigger damage.
Serum tryptase may be elevated in some cases with clonal eosinophilia, suggesting a possible role for mast cells.

Diagnositc Workup

Comprehensive History & Physical Exam
Complete Blood Count (CBC) with differential & smear
Routine Chemistries including liver function tests
Quantitative Serum Immunoglobulins (e.g., IgM, IgE)
Serum Tryptase and B12 levels
Flow cytometry for aberrant T-cells.
Bone marrow aspirate and biopsy
T- and B-cell receptor rearrangement studies

Approach to Therapy

Secondary causes (e.g., infections) should be considered and addressed early.
The presence of clinical manifestations should guide the urgency and nature of treatment.
Prednisone is the initial treatment for severe or life-threatening HES.
Alternative therapies include imatinib for myeloid neoplasms, cyclophosphamide for EGPA, hydroxyurea, and interferon-α, or specialized eosinophil-targeting biologics like mepolizumab and Reslizumab.
Patient stability should be continually monitored and additional treatments considered as needed.

Case Studies

Case studies are presented demonstrating varying approaches to diagnosis and treatment based on different presentations of clinical manifestations.
Additional tests like Bone marrow and PET/CT are crucial for the approach to the patient

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Description

Explore the complexities of Hypereosinophilic Syndromes (HES) and the various disorders associated with eosinophilia. This quiz covers clinical manifestations, prevalence, and relevant atopic disorders linked to eosinophilia. Test your knowledge on this unique group of rare disorders.