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Hypereosinophilic Syndrome Last Updated: April 14, 2004 |
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| Synonyms and related keywords: idiopathic hypereosinophilic syndrome, HES, IHS, IHES, eosinophilia, eosinophilic leukemia, acute eosinophilic leukemia, chronic eosinophilic leukemia, CEL, overproduction of eosinophils |
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AUTHOR INFORMATION
| Section 1 of 11   |
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| Author: Vincent E Herrin, MD, Associate Professor of Medicine, Divisions of Hematology and Oncology, University of Mississippi School of Medicine Coauthor(s): Joe C Files, MD, Director, Division of Hematology, Associate Chairman, Professor, Department of Internal Medicine, University of Mississippi Medical Center; Youwen Zhou, MD, PhD, FRCPC, Assistant Professor, Department of Medicine, Division of Dermatology, University of British Columbia, Vancouver, Canada; Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Department of Internal Medicine, Drexel University College of Medicine |
| Vincent E Herrin, MD, is a member of the following medical societies:
American College of Physicians-American Society of Internal Medicine, and
American Society of Hematology |
| Editor(s): Antoni Ribas, MD, Assistant Professor of Medicine, Department of Medicine, Division of Hematology-Oncology, University of California at Los Angeles Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine;
Ronald A Sacher, MD, Director of the Hoxworth Blood Center, Professor, Departments of Internal Medicine and Pathology, University of Cincinnati Medical Center;
Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems;
and Emmanuel C Besa, MD, Professor of Medicine, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University |
Disclosure
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INTRODUCTION
| Section 2 of 11   |
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Background: Idiopathic hypereosinophilic syndrome (HES) refers to a group of leukoproliferative disorders characterized by an overproduction of eosinophils that results in organ damage. Peripheral eosinophilia with tissue damage has been noted for approximately 80 years, but Hardy and Anderson first described the specific syndrome in 1968. In 1975, Chusid et al defined the 3 features required for a diagnosis of HES. First, a sustained eosinophil count of greater than >1500 cells/mL should persist for more than 6 months. Second, no other etiologies for eosinophilia are present. Finally, patients must have signs and symptoms of organ involvement. This last requirement excludes benign eosinophilia, which may exist for years with no associated pathology.
HES is likely a collection of several similar entities, but the important commonality is the disseminated nature of tissue involvement and damage. If blood eosinophilia is associated with other disorders, such as allergic diseases, parasitic infections, eosinophilia-myalgia syndrome, Churg-Strauss syndrome, or malignancy, then, by definition, idiopathic HES is not present.
Eosinophil production is governed by several cytokines, including interleukin 3 (IL-3), interleukin 5 (IL-5), and granulocyte-macrophage colony-stimulating factor (GM-CSF). IL-5 appears to be the most important and specific cytokine and is responsible for differentiation of the eosinophil line. The difference between the mechanisms of eosinophil production in HES and in secondary eosinophilic syndromes is not known. An association between T-cell clonal proliferation and hypereosinophilia has been reported. In these cases, the T cells were responsible for the hypersecretion of IL-5.
Some cases previously diagnosed as HES involved malignant transformation of eosinophils, but these constitute a minority. Most patients with HES do not have a subsequently identified neoplastic association to explain the disorder. The overlap between diseases referred to as eosinophilic leukemia and those called HES is confusing, and both groups of patients may initially appear to meet the criteria for HES. However, most patients with HES have a normal karyotype, though some series have identified clonal abnormalities. A US National Institutes of Health (NIH) study reported abnormalities in 8 of 33 patients. The patients with chromosomal abnormalities (rarely including Philadelphia chromosome) seem to fit a neoplastic profile, with a myeloproliferativelike picture. Patients may have anemia at diagnosis.
Most reviews of HES include discussions of both malignant disease and nonmalignant disease. However, recent papers propose that patients with severe hematologic manifestations or clonal chromosomal abnormalities have chronic eosinophilic leukemia, which is distinct from HES. This approach is supported by long-established factors associated with the poorest prognoses, including a peripheral leukocyte count of greater than 90,000 cells/mL and the presence of myeloblasts in the periphery.
Eosinophilic leukemia
Some patients with HES have acute or chronic eosinophilic leukemia (CEL). Distinguishing eosinophilic leukemias from HES is often difficult because the clinical presentations of CEL and HES share common features. Both commonly demonstrate eosinophilia of more than >1500 cells/mL for more than 6 months and varying degrees of organ involvement. Thus, patients with eosinophilic leukemia as well as those with HES can present with mural thrombosis and endocardial fibrosis, thromboembolic events, pulmonary impairment, and neurologic signs.
Criteria proposed to identify eosinophilic leukemia include (1) clonality, (2) an increase of more than 25% in immature eosinophils in peripheral blood or in bone marrow, and (3) more than 5% myeloblasts in bone marrow. Cytochemical positivity for naphthol chloroacetate esterase, a criterion that is more likely to be positive in patients with neoplastic eosinophilia than with reactive eosinophilia, supports an eosinophilic leukemia diagnosis. However, morphologic features in reactive eosinophilia may be similar to those observed in eosinophilic leukemia. The following 3 steps are used in diagnosing eosinophilic leukemia:
- First, the causes for secondary eosinophilia must be excluded. The most common cause of secondary eosinophilia is parasitic disease.
- Next, excluding chronic myelogenous leukemia, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML-M4EO), and myelodysplastic syndromes that manifest with significant eosinophilia is important. The presence of a Philadelphia chromosome or BCR/ABL suggests myelogenous leukemia. The presence of a t(5;14)(q31;q32) translocation indicates ALL with eosinophilia. The finding of inv(16)(p13q22) indicates AML-M4EO.
- Finally, establishing clonality and the presence of chromosomal abnormalities consistent with eosinophilic leukemia is important in determining the diagnosis of this entity. Unfortunately, this can be difficult because most patients with CEL have normal karyotypes.
Clonality can be demonstrated in females with eosinophilic leukemia by the investigation of X-linked polymorphism, the phosphoglycerate kinase gene, and the human androgen receptor gene (HUMARA). However, this approach is limited because approximately 90% of patients with eosinophilic leukemia are males.
A number of abnormal karyotypes reportedly occur in eosinophilic leukemia. In acute eosinophilia, translocation (10;11)(p12;q14) has been noted in a number of case reports. Translocation (8;13)(p11;q12) and related translocations have often been detected in CEL. Other common abnormalities in CEL are breaks in the q31-35 region of chromosome 5, where genes encoding for IL-3, IL-5, and GM-CSF (cytokines involved in promoting eosinophilia) are located. Translocation (3;9;5)(q25;q34;q33) has been detected in a patient with CEL with an elevated blood IL-5 level. A hyperdiploid karyotype with trisomy 18 has been reported in this disorder. Oliver et al have reviewed a number of abnormal karyotypes found in CEL.
In summary, acute eosinophilic leukemia and CEL are rare neoplastic disorders that primarily occur in males (>90%). Distinguishing eosinophilic leukemias from HES is often difficult. The prognosis is guarded, and to predict the severity and the progression of the leukemia in a patient who is newly diagnosed is difficult. Some patients with CEL enter a blast crisis. Patients have been treated with corticosteroids, busulfan, and hydroxyurea, with variable success. The results of using imatinib and bone marrow transplantation have not yet been reported. Pathophysiology: Under usual circumstances, eosinophils arrive at an area of inflammation and quickly undergo apoptosis after degranulation, though normal eosinophils live longer than neutrophils and can recirculate from the tissues. In HES, the cells stimulated by the above-mentioned cytokines may survive in the tissues for longer periods of time, thus increasing the amount of damage they can inflict.
Eosinophils contain granules that store toxic cationic proteins, which are the primary mediators of tissue damage. These toxins include major basic protein, eosinophil peroxidase, eosinophil-derived neurotoxin, and eosinophil cationic protein. Eosinophils also release specific cytokines that recruit additional eosinophils and advance the cycle of tissue damage and the modulation of the immune response. Oxidative products produced by the respiratory burst pathway of the infiltrating eosinophils add more damage. Precisely how or why circulating eosinophils degranulate in HES remains unknown, but it seems to account for the organ toxicity associated with the disease.
The most serious complication of HES is cardiac involvement that leads to myocardial fibrosis, congestive heart failure (CHF), and death. The mechanisms of cardiac damage are not entirely understood, but the damage is marked by severe endocardial fibrotic thickening of either ventricle or both ventricles resulting in restrictive cardiomyopathy due to inflow obstruction. Hypereosinophilia alone is not sufficient to cause cardiac damage. Frequency:
- In the US: Various sources indicate that the prevalence of true HES is rare. The most common cause of eosinophilia in the United States is allergic reaction or allergic disease, but the prevalence of HES is far less.
- Internationally: The most common cause of eosinophilia worldwide is parasitosis. The prevalence of HES is far less.
Mortality/Morbidity: While often progressive and rapidly fatal if untreated, HES may also take a much more indolent course. Patients with characteristics suggestive of a myeloproliferative/neoplastic disorder and those who manifest CHF have a worse prognosis.
- An older review of 57 patients with advanced disease reported a mean survival of 9 months and a 3-year survival rate of 12%.
- A more recent analysis from France noted an 80% 5-year survival rate and a 42% 10-year survival rate among 40 patients.
Race: No racial predilection is reported.
Sex: A 9:1 male-to-female predominance exists. The reason for this difference is not known.
Age: HES is most commonly diagnosed in patients aged 20-50 years.
- The incidence of HES seems to decrease in the elderly population.
History: HES is a heterogeneous disease process; thus, multiple manifestations may occur simultaneously or individually. The presenting symptoms can be sudden and dramatic, which sometimes occur with cardiac, neurologic, or thrombotic complications, but, more often, the onset is insidious. In one series, 12% of patients with HES discovered it as an incidental finding. Virtually any organ system may be involved. Major symptoms include the following:- The cardiac system is one of the most frequently involved systems, and cardiac complications are a leading cause of mortality.
- Damage typically occurs in 3 stages: (1) initial acute necrosis early in the disease process that typically has no clinical manifestations but may occasionally be severe enough to cause symptoms, (2) thrombotic phase, and (3) endomyocardial fibrosis. Common symptoms in these phases include chest pain, dyspnea, or orthopnea.
- Symptoms are largely nonspecific and may include fatigue, which may be due to the anemia that is occasionally observed with HES.
- Left upper quadrant pain may indicate splenomegaly, which occurs in about 40% of patients.
- Thrombotic episodes occur frequently and often present as neurologic symptoms. The thrombotic events may occur solely due to cardiac disease, or they may be caused by hypercoagulability. The mechanism of hypercoagulability is unknown.
- Embolic or thrombotic strokes or transient ischemic episodes may occur and are often the initial manifestations of disease.
- Some patients experience an encephalopathy caused by CNS dysfunction.
- Blurred vision and slurred speech have been reported.
- Peripheral neuropathies account for about 50% of all neurologic symptoms. Their etiology is poorly understood, but the symptoms may present as symmetric or asymmetric sensory changes, pure motor deficits, or mixed sensory and motor complaints.
- The most benign variant of HES involves eosinophilic infiltrates in the bases and periphery of the lungs, according to one source.
- Patients often have recurrent angioedema.
- A chronic, persistent cough, usually nonproductive, is the most common respiratory symptom reported.
- Dyspnea may occur due to CHF or pleural effusions (which are not always secondary to CHF).
- Less frequently, pulmonary fibrosis occurs after prolonged disease and often accompanies cardiac fibrosis.
- Bronchospasm and asthmatic symptoms are infrequent.
- Rhinitis is sometimes a presenting symptom.
- Arthralgias and myalgias are frequent complaints.
- Raynaud phenomenon occurs but is infrequent.
- Skin involvement is common and nonspecific.
- The most common symptom is pruritus.
- Dermatographism and angioedema are also frequently present.
- Gastrointestinal symptoms
- Diarrhea is a relatively common complaint, occurring in approximately 20% of patients.
- Nausea and abdominal pain are also common complaints.
- Occasionally, small bowel necrosis due to microthrombi can occur.
- Many patients experience fever and night sweats.
- Some sources identify anorexia and weight loss as common presenting symptoms; however, other sources report that these symptoms do not usually occur unless underlying cardiac disease is present.
Physical: The physical findings are varied and parallel the clinical history. - Evidence of CHF becomes prominent with advanced HES and is an ominous sign.
- Various murmurs may be heard, especially mitral or tricuspid regurgitation.
- Splinter hemorrhages are often observed with cardiac involvement.
- Physical findings typical of restrictive heart disease can be expected.
- Hematologic findings include splenomegaly in approximately 40% of patients.
- Physical findings associated with stroke and transient ischemic attacks can be observed.
- When peripheral neuropathy is present, findings may be purely sensory, entirely motor, or a combination of both.
- Deficits are often symmetric.
- Mononeuritis multiplex and muscle atrophy due to radiculopathy are sometimes encountered.
- Generalized weakness is observed but is less specific.
- Rales may accompany infiltrates and fibrosis.
- Findings typical of CHF with effusion may also be encountered.
- Angioedema is often a prominent feature associated with pulmonary involvement.
- Large joint effusions can occur.
- Digital necrosis is rare but sometimes observed with associated Raynaud phenomenon.
- Dermatologic findings
- The skin is among the most common organ systems involved; more than half of all patients have cutaneous involvement. In a minority of reports, skin involvement is the only manifestation.
- Most skin eruptions fall into 2 patterns. One pattern is angioedematous or urticarial. This pattern is associated with a benign prognosis. The other pattern is erythematous, pruritic papules, plaques, and nodules, with or without ulceration.
- A special form of urticaria is dermatographism, which occurs in up to 75% of affected patients.
- Other less common cutaneous manifestations include erythroderma, erythema annulare centrifugum, erythema gyratum repens, and mucosal ulcerations.
- Gastrointestinal findings
- Hepatomegaly may occur with chronic active hepatitis due to HES.
- Hepatomegaly may also occur with Budd-Chiari syndrome, which may infrequently be a thrombotic complication of HES.
Causes: - HES likely represents a variety of similar disorders, and the underlying cause of eosinophil overproduction is not well understood.
- Eosinophilia due to some other disorder is not HES.
- Cytokine overproduction may account for some cases of HES.
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DIFFERENTIALS
| Section 4 of 11 |
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Asthma
Chronic Myelogenous Leukemia
Churg-Strauss Syndrome
Eosinophilia
Eosinophilia-Myalgia Syndrome
Eosinophilic Fasciitis
Eosinophilic Gastroenteritis
Eosinophilic Pneumonia
Hodgkin Disease
Meckel Diverticulum
Strongyloidiasis
Other Problems to be Considered:
Angiolymphoid hyperplasia with eosinophilia
Dermatitis, Atopic
Asthma
Allergic diseases
Collagen vascular diseases
Drug reactions
Eosinophilic toxocariasis
Episodic angioedema with eosinophilia
Hypersensitivity diseases
Malignancy with secondary eosinophilia (eg, Hodgkin disease, AML-M4EO)
Parasitic infections |
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Patient Education
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Click here for patient education.
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Lab Studies:
- Eosinophilia is present (>1500 cells/mL).
- The overall neutrophil count may be normal but is often elevated. Many patients have absolute neutrophilia.
- Infrequently, bands and other immature forms may be present. Mild basophilia may be observed. Increased numbers of eosinophilic or neutrophilic precursors may be indicative of neoplastic disease. Teardrops and nucleated red blood cells are common.
- Approximately 50% of patients are anemic on presentation, often because of chronic disease. Platelet counts are most often normal but may be high or low.
- The eosinophils as observed on the peripheral smear may be normal in appearance, but often some morphologic abnormalities, such as a decrease in granule number and size, are observed.
- Vacuoles may be prominent in some patients, and nuclear hypersegmentation may also be observed.
- The NIH series indicated that the presence of eosinophils with vacuolization and hypogranularity is more commonly associated with cardiac disease.
- Serum vitamin B-12 levels may be elevated in some patients. This typically indicates the presence of a myeloproliferativelike picture.
- Immunoglobulin E (IgE) levels may be elevated, and hypergammaglobulinemia is common.
- Other expected blood chemistry abnormalities may accompany renal involvement, heart failure, liver involvement, or thrombotic insult to various tissues.
Imaging Studies:
- In the initial phase of endocardial damage, usually no echocardiographic or angiographic abnormalities are present. If HES is strongly suspected, right ventricular biopsy can be performed to evaluate for endomyocardial involvement. If successful treatment can be initiated during this early period of cardiac damage, the later thrombotic and fibrotic stages might be avoided or delayed.
- In the later phases, which are usually symptomatic, echocardiography (ECHO) is helpful. Intracardiac thrombi may be detected, as well as the fibrosis that appears not only as areas of increased echogenicity but often as posterior mitral valve leaflet thickening. Because the papillary muscles are often involved in HES, mitral and tricuspid dysfunction may also be detected by ECHO. On electrocardiography (ECG), T-wave inversion is a common finding, but, more often, no abnormalities are present in the early stages of disease.
- CT scanning may be helpful for evaluating suspected thrombotic or embolic complications.
Procedures:
- An endocardial biopsy may be performed via cardiac catheterization if any question about the diagnosis exists.
- Perform bone marrow aspiration and biopsy, and submit samples for cytogenetics.
- Occasionally, the findings may suggest an atypical presentation of chronic myelogenous leukemia.
- Cytogenetic abnormalities or the presence of a myeloproliferative picture in the bone marrow may be indicative of more aggressive disease.
- If cutaneous involvement is present, skin biopsies may be performed to rule out other diagnoses that have similar skin presentations, such as drug eruptions, cutaneous T-cell lymphoma, Wells syndrome, immunobullous diseases, and vasculitis.
Histologic Findings: Eosinophil infiltrates are present in affected tissues. Cutaneous histologic features vary with the pattern of presentation. In patients with papular or nodular lesions, perivascular mixed cellular infiltrates (eosinophils and other cell types) are present. However, vasculitis is not present. See Lab Studies.
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TREATMENT
| Section 6 of 11 |
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Medical Care: Direct treatment toward suppressing organ damage and eradicating eosinophilia. The disease is often chronic, but sometimes resolution occurs. More often, periods of increased disease activity are followed by periods of moderate improvement. Cardiac damage does not seem to correlate with the levels or the duration of eosinophilia. Some patients with very mild disease and no evidence of cardiac involvement may be monitored closely without treatment. - Medical therapy
- Institute medical therapy for symptomatic disease. Therapy can range from corticosteroids to chemotherapeutic agents to biologic agents. Corticosteroids are the first line of therapy.
- If no appreciable organ involvement is present (diagnosis is in doubt, but eosinophilia is persistent), a short trial of steroids can be administered simply to ascertain future responsiveness to therapy.
- Anticoagulation
- Because thrombotic and embolic complications are relatively common and contribute substantially to morbidity, anticoagulants or antiplatelet agents have been administered to some patients.
- No data exist that show whether this approach has any benefit.
- Many patients continue to form clots despite anticoagulation therapy.
- Symptomatic therapies should include treating associated entities, such as CHF, just as they are treated if associated with another etiology.
- Antihistamines: Hydroxyzine or doxepin can be used to control pruritus.
- Leukapheresis
- Attempts that use apheresis to remove eosinophils from the peripheral blood have mostly been unsuccessful. This therapy does not have a defined role in treatment.
- Although eosinophils can often be rapidly removed from the periphery, the effects of removal are short lived.
- Psoralen and ultraviolet A (PUVA): For patients with prominent skin eruption and pruritus, symptomatic control can be achieved with PUVA therapy.
Surgical Care: - If medical management does not ameliorate the symptoms of heart involvement, a definite role exists for valve replacement. Some authors even suggest that endocardectomy may be beneficial in refractory cases of fibrosis.
- A splenectomy may be useful for patients with chronic pain or thrombocytopenia due to hypersplenism, but it has no established role in the treatment of HES.
- A bone marrow transplantation is rarely used to treat HES, and the toxicity of transplantation is probably not justified for any but the most aggressive cases.
Consultations: Consult a hematologist to assist with diagnosis, management, and follow-up care of unexplained eosinophilia. Diet: No special diet modifications are required. Activity: No special modifications in activity are required.
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MEDICATION
| Section 7 of 11 |
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Corticosteroids are the mainstays of initial treatment. Prednisone is the prototypical drug in this category. Once the eosinophils are suppressed, steroids may be slowly tapered to an every-other-day dosage regimen for long-term suppression. Patients who respond to steroids tend to have a better prognosis. The NIH study showed that about 66% of patients had at least a partial response to prednisone. Patients responsive to steroids should demonstrate a significant reduction in the number of circulating eosinophils within 24-48 hours.
Toxic overtreatment of a chronic disease should be avoided, but some patients have aggressive disease that causes significant end-organ impairment. For patients who have a more aggressive course but are unresponsive to prednisone, a few chemotherapeutic and some newer biologic agents can be considered.
Drug Category: Corticosteroids -- These agents often cause a rapid reduction in level of the eosinophilia. The mechanisms for this are not entirely clear. Drug Name
| Prednisone (Deltasone, Meticorten, Orasone) -- Initial DOC. Once eosinophils are suppressed, dose may be slowly tapered. Patients responding to steroids tend to have a better prognosis. |
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| Adult Dose | Initially: 1 mg/kg/d PO or 60 mg/d PO
With response, may taper dose and may ultimately be administered qod for long-term suppression| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; viral, fungal, connective tissue, or tubercular skin infections; peptic ulcer disease; hepatic dysfunction; GI disease |
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| Interactions | Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
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| Precautions | Dose should be lowered by tapering; may have increased adverse effects in hypertension, diabetes, hypothyroidism, cirrhosis, and CHF and in patients at high risk for peptic ulcer disease |
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Drug Category: Antineoplastic agents -- Chemotherapeutic agents may be used in patients who are refractory to steroid treatment. As a group, these drugs interfere with the production of eosinophils, but they may also cause toxicity to normal tissues, especially the bone marrow.Drug Name
| Hydroxyurea (Hydrea) -- Second line of treatment. Goal is to reduce total WBC count to <10,000 cells/mL. One week of therapy may be required before a reduction of the eosinophil count is observed. Anemia and thrombocytopenia are common complications associated with this drug. |
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| Adult Dose | 1-2 g PO qd; adjust dose as WBC count decreases |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; severe anemia or bone marrow suppression |
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| Interactions | Coadministration with fluorouracil or cytarabine can increase neurotoxicity |
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| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | Caution in renal failure or history of radiation therapy; monitor blood counts in patients on chemotherapeutic agents |
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Drug Name
| Vincristine (Oncovin, Vincasar) -- May be instituted in patients who fail or are only partially responsive to hydroxyurea. A response is often observed within 1-3 d. Marrow suppression is less common than with hydroxyurea, but occurrence of neurologic toxicity may limit treatment and closely resemble neurologic symptoms of HES. |
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| Adult Dose | 1-2 mg IV q2wk |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Acute pulmonary reaction may occur when taken concurrently with mitomycin-C |
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| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | Dose adjustments may be required in preexisting neuromuscular disease or hepatic impairment; caution in patients with severe cardiopulmonary or hepatic impairment and in patients with preexisting neuromuscular disease; monitor blood counts in patients taking chemotherapeutic agents |
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Drug Name
| Chlorambucil (Leukeran) -- Primary alkylating agent used in patients in whom prednisone fails and in those who cannot tolerate hydroxyurea or vincristine. A reasonable alternative for long-term treatment. Bone marrow suppression may be a problem. |
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| Adult Dose | A pulse of 4-10 mg/m2/d PO for 4 d every other mo |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; previous resistance; bone marrow suppression |
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| Interactions | Increases toxicity of barbiturates |
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| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | Monitor blood counts; risk for secondary leukemia in patients on long-term treatment with alkylating agents |
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Drug Category: Immunomodulators -- These agents are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha, beta, and gamma interferons may be given topically, systemically, and intralesionally. They have demonstrated efficacy in small trials.Drug Name
| Interferon alfa-2a (Roferon-A) -- Has been reported to effectively suppress eosinophilia in several different patients using several different doses. Some patients have had progression of disease despite therapy. |
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| Adult Dose | Initial doses as high as 8 million U/d IM/SC followed by maintenance doses of 2 million U/d used successfully
Lower doses, such as 3 million U 3 times/wk, also used with success| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; uncontrolled thyroid disease; autoimmune hepatitis; patients who are diabetic and prone to DKA |
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| Interactions | Theophylline may increase toxicity of interferon alpha by reducing clearance; cimetidine may increase antitumor effects of interferon alpha; zidovudine and vinblastine may increase toxicity of interferon alpha |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Depression and suicidal ideation may be adverse effects of treatment; infrequently, severe or fatal GI hemorrhage reported in association with alpha interferon therapy; in bone marrow suppression, prior to initiation of therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cell, and bone marrow hairy cells; monitor patient periodically (eg, monthly) during treatment to determine response to treatment; if patient does not respond within 6 mo, discontinue treatment; if response occurs, continue treatment until no further improvement observed (not known whether continued treatment after that time is beneficial) |
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Drug Name
| Interferon alfa-2b (Intron A) -- Has been reported to effectively suppress eosinophilia in several different patients using several different doses. Some patients have had progression of disease despite therapy. |
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| Adult Dose | Initial doses as high as 8 million U/d IM/SC followed by maintenance doses of 2 million U/d used successfully
Lower doses, such as 3 million U 3 times/wk, also used with success| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; uncontrolled thyroid disease; autoimmune hepatitis; patients who are diabetic and prone to DKA |
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| Interactions | Theophylline may increase toxicity of interferon alpha by reducing clearance; cimetidine may increase antitumor effects of interferon alpha; zidovudine and vinblastine may increase toxicity of interferon alpha |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Depression and suicidal ideation may be adverse effects of treatment; infrequently, severe or fatal GI hemorrhage reported in association with alpha interferon therapy; prior to initiation of therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cell, and bone marrow hairy cells; monitor periodically (eg, monthly) during treatment to determine response to treatment; if patient does not respond within 6 mo, discontinue treatment; if response occurs, continue treatment until no further improvement observed; not known whether continued treatment after that time is beneficial |
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FOLLOW-UP
| Section 8 of 11 |
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Further Outpatient Care:
- Observe patients periodically to confirm that the eosinophilia is controlled and that no evidence of new or worsening organ involvement exists.
- For patients with cardiac involvement, periodic ECGs may be useful for monitoring the disease progression.
- In patients who have not manifested cardiac disease, less frequent ECGs may be useful for identifying the early, potentially treatable stages of cardiac involvement.
Deterrence/Prevention:
- No known method of prevention exists.
Complications:
- Many, varied complications depend entirely on the organ systems involved in the disease process (see Clinical and Pathophysiology).
- The most serious complication of HES is cardiac involvement that leads to myocardial fibrosis, CHF, and death (see Pathophysiology).
Prognosis:
- The course of HES may be aggressive or rather benign.
- In more aggressive cases of disease, patients who respond to corticosteroid therapy generally have a better prognosis.
- Patients who appear to have a myeloproliferative disorder often have a worse prognosis, and some of these patients actually enter a blast crisis.
- Survival and complications do not appear to be directly related to the level of eosinophilia, except that patients with an extremely high WBC count on presentation (>90,000 cells/mL) do worse.
- Patients who manifest CHF have a worse prognosis.
Patient Education:
- Report any new or worsening symptoms.
- The disease process may involve almost any organ system, and the prognosis is variable.
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MISCELLANEOUS
| Section 9 of 11 |
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Medical/Legal Pitfalls:
- Failure to make the diagnosis is a pitfall. Because the onset of HES is often insidious, the diagnosis may be overlooked until significant end-organ impairment has occurred.
- Failure to distinguish HES from other diseases is a pitfall. Because the etiology of many eosinophilic syndromes is unknown, and no definitive test for HES exists, distinctions between the following diseases must be made based on clinical presentation and available pathologic evidence:
- Malignancy with secondary eosinophilia (eg, Hodgkin disease, AML-M4)
- Angiolymphoid hyperplasia with eosinophilia
- Episodic angioedema with eosinophilia
- Parasitic infections (numerous causes)
- Collagen vascular diseases
- Asthma and other allergic or hypersensitivity diseases
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PICTURES
| Section 10 of 11 |
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| Caption: Picture 1. Hypereosinophilic syndrome. Indurated edematous plaques on the legs.
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Picture Type: Photo |
| Caption: Picture 2. Hypereosinophilic syndrome. Erythroderma.
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Picture Type: Photo |
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BIBLIOGRAPHY
| Section 11 of 11 |
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Bain BJ: Hypereosinophilia. Curr Opin Hematol 2000 Jan; 7(1): 21-5[Medline].
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Broustet A, Bernard P, Dachary D, et al: Acute eosinophilic leukemia with a translocation (10p+;11q-). Cancer Genet Cytogenet 1986 Apr 15; 21(4): 327-33[Medline].
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Brugnoni D, Airó P, Rossi G, et al: A case of hypereosinophilic syndrome is associated with the expansion of a CD3-CD4+ T-cell population able to secrete large amounts of interleukin-5. Blood 1996 Feb 15; 87(4): 1416-22[Medline].
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Hypereosinophilic Syndrome excerpt |
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