Hypereosinophilic Syndromes Overview
54 Questions
1 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

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?

<p>Bone fractures (B)</p> Signup and view all the answers

What is a characteristic feature of overlap HES?

<p>Single-organ-restricted eosinophilic disorders (D)</p> Signup and view all the answers

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

<p>Major basic protein (B)</p> Signup and view all the answers

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

<p>Associated HE/HES (C)</p> Signup and view all the answers

What neurological condition can eosinophilia lead to?

<p>Dementia (A)</p> Signup and view all the answers

What should patients with LHES be assessed for at diagnosis?

<p>Occult lymphoma (C)</p> Signup and view all the answers

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

<p>Complete blood count with differential (A)</p> Signup and view all the answers

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

<p>Dysplastic eosinophils on smear (D)</p> Signup and view all the answers

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

<p>Suggestive of LHES (A)</p> Signup and view all the answers

Which condition is characterized by elevated serum IgM levels?

<p>LHES (B)</p> Signup and view all the answers

What condition is indicated by elevated serum tryptase levels?

<p>PDGFRA and KIT-associated disease (C)</p> Signup and view all the answers

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

<p>Prior eosinophil counts and symptoms (A)</p> Signup and view all the answers

Which statement is true regarding lymphocyte phenotyping by flow cytometry?

<p>Helps in identifying clonal T-cell populations (D)</p> Signup and view all the answers

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

<p>Prednisone (A)</p> Signup and view all the answers

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

<p>Negative (D)</p> Signup and view all the answers

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

<p>Increased eosinophilia and pruritus (A)</p> Signup and view all the answers

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

<p>Decreased platelets (A)</p> Signup and view all the answers

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

<p>Lymphocytic variant hypereosinophilic syndrome (A)</p> Signup and view all the answers

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

<p>Interferon α (A)</p> Signup and view all the answers

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

<p>Fatigue (A)</p> Signup and view all the answers

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

<p>26.0 10^9/L (D)</p> Signup and view all the answers

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

<p>Elevated serum tryptase and splenomegaly (C)</p> 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?

<p>Low-dose imatinib therapy (C)</p> Signup and view all the answers

How does lymphocytic variant HES typically present in most patients?

<p>Predominantly with dermatologic manifestations (D)</p> Signup and view all the answers

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

<p>Consideration of secondary causes and specific treatment (D)</p> Signup and view all the answers

What is the gold standard for diagnosing lymphocytic variant HES?

<p>Identification of a clonal T-cell population (B)</p> Signup and view all the answers

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

<p>Prednisone (D)</p> Signup and view all the answers

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

<p>Presence and severity of clinical manifestations (A)</p> Signup and view all the answers

Which statement regarding lymphocytic variant HES is accurate?

<p>It can be indistinguishable from T-cell malignancies. (B)</p> Signup and view all the answers

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

<p>Clonal aberrant T cells in peripheral blood (A)</p> 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?

<p>Consider additional therapy based on suspected subtype (D)</p> Signup and view all the answers

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

<p>Approximately 10% (A)</p> Signup and view all the answers

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

<p>Rapid response leading to medication resistance and toxicity (A)</p> Signup and view all the answers

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

<p>Serum and thymus activation-regulated chemokine levels (B)</p> Signup and view all the answers

For which subtype of HES is imatinib specifically indicated?

<p>Myeloid neoplasm (C)</p> Signup and view all the answers

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

<p>By reducing eosinophil levels through specific pathway targeting (A)</p> 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?

<p>Eosinophilia (B)</p> Signup and view all the answers

What is defined as hypereosinophilia?

<p>Absolute eosinophil count (AEC) &gt; 1.5 × 10^9/L (C)</p> Signup and view all the answers

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

<p>Chronic fatigue syndrome (A)</p> Signup and view all the answers

Which of these conditions can lead to significant eosinophilia?

<p>Asthma (A)</p> Signup and view all the answers

What defines eosinophilia in the general population?

<p>AEC &gt; 0.45 × 10^9/L (B)</p> 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?

<p>More than 6 months (C)</p> Signup and view all the answers

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

<p>Tissue HE with evidence of organ damage (A)</p> Signup and view all the answers

Which neoplastic conditions are commonly associated with hypereosinophilia?

<p>Acute myeloid leukemia (A)</p> Signup and view all the answers

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

<p>Helminth infection (C)</p> Signup and view all the answers

Which autoimmune disorder is mentioned as potentially causing eosinophilia?

<p>Inflammatory bowel disease (B)</p> Signup and view all the answers

Which condition would least likely present with hypereosinophilia?

<p>Type 2 diabetes mellitus (D)</p> Signup and view all the answers

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

<p>Exclusion of reactive causes (C)</p> Signup and view all the answers

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

<p>Administration of IL-2 (C)</p> Signup and view all the answers

Which of the following is classified under rare hypereosinophilic syndromes?

<p>Eosinophilic myeloid neoplasms (C)</p> Signup and view all the answers

What would tissue hypereosinophilia typically indicate?

<p>Presence of eosinophils in tissues causing damage (C)</p> Signup and view all the answers

Flashcards

Hypereosinophilic Syndrome (HES)

A condition characterized by an abnormally high number of eosinophils in the blood and tissues. It can affect various organs, leading to diverse symptoms and potentially severe complications.

Cardiac involvement in HES

The most common cause of death in HES. It can manifest as endomyocardial fibrosis, pericarditis, myocarditis, and intramural thrombus formation, often leading to dilated cardiomyopathy.

Neurological involvement in HES

Infiltration and damage caused by HES in the central and peripheral nervous systems. This can lead to a variety of neurological symptoms.

Idiopathic HES

A type of HES where the cause is unknown, and other subtypes have been excluded. This is often the most challenging type to diagnose and manage.

Signup and view all the flashcards

Lymphocytic Variant HES

A type of HES where a clonal population of T cells produces cytokines that drive the eosinophilia. This suggests an underlying immune system dysfunction.

Signup and view all the flashcards

Myeloid HES

A type of HES where a specific type of myeloid neoplasm (cancer) occurs, often with genetic abnormalities like PDGFRA rearrangements.

Signup and view all the flashcards

Familial HES

A type of HES where the condition is present in multiple members of a family, excluding cases associated with other factors like infections or allergies.

Signup and view all the flashcards

Associated HES

A type of HES where the condition is associated with a known factor like a parasite infection, allergy, or other medical condition.

Signup and view all the flashcards

Myeloproliferative variant HES

A subtype of HES characterized by male predominance, end organ damage, elevated serum tryptase, splenomegaly, anaemia, thrombocytopenia, and bone marrow myeloproliferation with reticulin fibrosis.

Signup and view all the flashcards

FIP1L1–PDGFRA fusion gene

A chromosomal abnormality, specifically an interstitial deletion on chromosome 4q12, leading to the fusion of FIP1L1 and PDGFRA genes.

Signup and view all the flashcards

FIP1L1–PDGFRA fusion protein

A tyrosine kinase with increased activity due to the FIP1L1–PDGFRA fusion gene, highly sensitive to low-dose imatinib therapy.

Signup and view all the flashcards

Interleukin-4 (IL-4)

A cytokine involved in the development of allergies and other immune responses, produced by T-cells in LHES.

Signup and view all the flashcards

Interleukin-5 (IL-5)

Another cytokine produced by T-cells in LHES, involved in the growth and differentiation of eosinophils.

Signup and view all the flashcards

Angioimmunoblastic T-cell lymphoma

A type of cancer affecting the immune system's T-cells, which can sometimes resemble the aberrant T-cell population found in LHES.

Signup and view all the flashcards

Cutaneous T-cell lymphoma

A subtype of T-cell lymphoma that affects the skin, having some overlap in T-cell phenotype with LHES.

Signup and view all the flashcards

Eosinophilia

The presence of high levels of eosinophils in the blood.

Signup and view all the flashcards

Eosinophil-targeting biologics

A type of therapy that targets the eosinophils directly, aiming to reduce their numbers and activity.

Signup and view all the flashcards

Prednisone

The most commonly used drug for acute cases of HES, effective in reducing eosinophil levels.

Signup and view all the flashcards

Eosinophilic granulomatosis with polyangiitis (EGPA)

A condition characterized by inflammation and tissue damage caused by the infiltration of eosinophils.

Signup and view all the flashcards

Approach to HES treatment

A primary approach in treating HES involves first identifying any underlying cause, such as parasitic infections, and then considering the severity of symptoms to determine the urgency and type of treatment.

Signup and view all the flashcards

Eosinophil

A type of blood cell that plays a role in fighting parasites and allergic reactions.

Signup and view all the flashcards

Pruritus

A common symptom of HES, often characterized by intense itching.

Signup and view all the flashcards

Löffler's Endomyocardial Fibrosis (LEMF)

A type of HES that involves the lungs and other organs like the heart and skin, causing damage and inflammation.

Signup and view all the flashcards

Idiopathic Hypereosinophilic Syndrome (IHES)

HES that is caused by an unknown factor and is not related to any specific cause or underlying condition.

Signup and view all the flashcards

PDGFRα and KIT-associated HES

A type of HES that is caused by a specific group of genes known as PDGFRα and KIT.

Signup and view all the flashcards

Lymphoma-associated Hypereosinophilic Syndrome (LHES)

A type of HES that is associated with a specific type of lymphoma, a type of cancer affecting the lymphatic system.

Signup and view all the flashcards

Eosinophil count

A blood test to determine the number of eosinophils in the blood.

Signup and view all the flashcards

Blood smear

A diagnostic tool that analyzes the structure of the cells, looking for abnormalities that may suggest HES.

Signup and view all the flashcards

Genetic testing (PDGFRα and KIT genes)

A type of blood test examining the genes responsible for cell growth, looking for mutations associated with HES.

Signup and view all the flashcards

What are Hypereosinophilic Syndromes (HES)?

A group of rare disorders characterized by high eosinophil counts in the blood, often leading to organ damage and complications like heart problems and blood clots.

Signup and view all the flashcards

What is the definition of hypereosinophilia?

Absolute Eosinophil Count (AEC) greater than or equal to 1.5 x 10^9/L

Signup and view all the flashcards

How common is hypereosinophilia?

Hypereosinophilia is a rare condition, affecting approximately 0.315 to 6.3 out of every 100,000 people in the United States.

Signup and view all the flashcards

What are some atopic disorders associated with mild eosinophilia?

Allergic conditions like asthma, eczema, and chronic sinus infections.

Signup and view all the flashcards

What is drug hypersensitivity and its relation to eosinophilia?

Drug reactions that can cause skin rashes, eosinophilia, and even systemic symptoms (affecting the entire body).

Signup and view all the flashcards

What are some infectious causes of hypereosinophilia?

Infections caused by parasites (like worms), fungi, viruses, or bacteria.

Signup and view all the flashcards

What autoimmune disorders can be associated with eosinophilia?

Autoimmune diseases like inflammatory bowel disease, sarcoidosis, and IgG4 disease.

Signup and view all the flashcards

What types of cancers can be associated with hypereosinophilia?

Cancers, including leukemia, lymphoma, and solid tumors.

Signup and view all the flashcards

What are some inborn errors of immunity associated with eosinophilia?

Rare genetic disorders that affect the immune system like Omenn syndrome, DOCK8 deficiency, and Loeys-Dietz syndrome.

Signup and view all the flashcards

What are some rare hypereosinophilic syndromes?

A broad category that includes eosinophilic myeloid neoplasms, idiopathic HES, familial HES, and single-organ HES.

Signup and view all the flashcards

What are some other miscellaneous causes of hypereosinophilia?

Exposure to radiation, hormone deficiencies, cholesterol emboli, and certain medications.

Signup and view all the flashcards

What is the WHO definition of hypereosinophilic syndrome?

The World Health Organization (WHO) definition requires an AEC greater than 1.5 x 10^9/L for at least six months, evidence of end-organ damage, and exclusion of reactive causes.

Signup and view all the flashcards

What is the consensus definition of hypereosinophilic syndrome?

This definition focuses on an AEC greater than 1.5 x 10^9/L on two separate occasions at least one month apart, documented tissue eosinophilia, and evidence of organ damage caused by eosinophils.

Signup and view all the flashcards

What is Idiopathic Hypereosinophilic Syndrome?

This refers to the type of HES where the cause is unknown, and other potential causes have been ruled out.

Signup and view all the flashcards

What is primary (clonal/neoplastic) hypereosinophilic syndrome?

This type of HES is believed to be caused by the uncontrolled growth of eosinophil precursors.

Signup and view all the flashcards

Serologic Test

A blood test that looks for the presence of specific antibodies in the blood. These antibodies can indicate the presence of a particular infection or disease.

Signup and view all the flashcards

Hydroxyurea

A cancer drug that helps control the growth of cells, including blood cells.

Signup and view all the flashcards

Interferon α

A type of protein found in the body that plays a role in the immune response and fighting infection.

Signup and view all the flashcards

Absolute Eosinophil Count (AEC)

The count of eosinophils (a type of white blood cell) in the blood.

Signup and view all the flashcards

Computed Tomography (CT) Scan

A type of imaging test that uses X-rays to create detailed images of the inside of the body.

Signup and view all the flashcards

Bone Marrow Biopsy

A test used to identify and analyze the cells present in the bone marrow.

Signup and view all the flashcards

Splenomegaly

The enlargement of the spleen, an organ that filters blood and fights infection.

Signup and view all the flashcards

T-cell

A type of immune cell that plays a role in protecting the body from infections and other threats.

Signup and view all the flashcards

B-cell

A type of immune cell that plays a crucial role in the immune system's response to infection.

Signup and view all the flashcards

Ultrasound

An imaging test that uses sound waves to create detailed images of the inside of the body, particularly organs and tissues.

Signup and view all the flashcards

Immunoglobulin

A type of protein found in the body that plays a role in the immune system's response to infection.

Signup and view all the flashcards

IgE

A type of protein found in the body that plays a role in the immune system's response to infection.

Signup and view all the flashcards

MRI (Magnetic Resonance Imaging)

An imaging test used to detect abnormalities in the brain and other parts of the nervous system.

Signup and view all the flashcards

IgG

A type of protein found in the body that plays a role in the immune system's response to infection.

Signup and view all the flashcards

IgM

A type of protein found in the body that plays a role in the immune system's response to infection.

Signup and view all the flashcards

Ivermectin

A medication used to treat certain types of infections, particularly those caused by worms.

Signup and view all the flashcards

Albendazole

A type of medication used to treat certain types of infections, particularly those caused by worms.

Signup and view all the flashcards

Tryptase

A type of protein found in the body that can trigger allergic reactions.

Signup and view all the flashcards

Cytokine

A type of protein found in the body that plays a role in the immune system's response to infection.

Signup and view all the flashcards

Edema

A condition that involves persistent swelling, often in the ankles and legs.

Signup and view all the flashcards

FIP1L1::PDGFRA

A specific type of gene abnormality. FIP1L1 and PDGFRA are two genes involved in this abnormality.

Signup and view all the flashcards

KIT

A gene that plays a role in the development and function of certain cells, particularly those involved in the immune system.

Signup and view all the flashcards

D816V KIT

A type of gene abnormality that can lead to certain types of cancers.

Signup and view all the flashcards

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

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Related Documents

Approach to Hypereosinophilic Syndrome (PDF)

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.

More Like This

Use Quizgecko on...
Browser
Open
Browser
Browser