Yun-Yun K Chen, Paneez Khoury, JeanAnne M Ware, Nicole C Holland-Thomas, Jennifer L Stoddard, Shakuntala Gurprasad, Amy J Waldner, Amy D Klion
Marked and persistent eosinophilia in the absence of clinical manifestations.
J Allergy Clin Immunol. 2014 Apr;133(4):1195-202. doi: 10.1016/j.jaci.2013.06.037. Epub 2013 Aug 26.
Abstract/Text
BACKGROUND: Although most patients with hypereosinophilic syndromes (HES) present with clinical signs and symptoms attributable to eosinophilic tissue infiltration, some untreated patients remain asymptomatic or have signs and symptoms, such as allergic rhinitis, for which the relationship to peripheral eosinophilia is unclear (hypereosinophilia of unknown significance [HEUS]).
OBJECTIVE: To identify and characterize subjects with HEUS of 5 years duration or more as compared to untreated patients with symptomatic HES and healthy normal volunteers.
METHODS: All subjects with eosinophilia underwent yearly evaluation, including a standardized clinical evaluation, whole blood flow cytometry to assess lymphocyte subsets and eosinophil activation, and serum collection. Peripheral blood mononuclear cells were cultured overnight with and without phorbol 12-myristate 13-acetate/ionomycin. Cytokines and chemokines were measured in serum and cell supernatants, and mRNA expression was assessed by using quantitative real-time PCR.
RESULTS: Eight of the 210 subjects referred for the evaluation of eosinophilia (absolute eosinophil count [AEC] > 1500/μL) met the criteria for HEUS of 5 years duration or more (range, 7-29 years). Peak eosinophil count and surface expression of eosinophil activation markers were similar in subjects with HEUS and in untreated subjects with platelet-derived growth factor alpha-negative HES (n = 28). Aberrant or clonal T-cell populations were identified in 50% of the subjects with HEUS as compared to 29% of the subjects with HES (P = .12). Increased levels of IL-5, GM-CSF, IL-9, and IL-17A were also comparable in subjects with HEUS and HES. Serum levels of IgE and IL-13 were significantly increased only in subjects with HES.
CONCLUSIONS: A small number of patients with persistent peripheral eosinophilia (AEC > 1500/μL) appear to have clinically benign disease.
Published by Mosby, Inc.
Ole Weis Bjerrum, Volkert Siersma, Hans Carl Hasselbalch, Bent Lind, Christen Lykkegaard Andersen
Association of the blood eosinophil count with end-organ symptoms.
Ann Med Surg (Lond). 2019 Sep;45:11-18. doi: 10.1016/j.amsu.2019.06.015. Epub 2019 Jul 9.
Abstract/Text
Introduction: Eosinophilia may cause organ dysfunction, but an exact relation between eosinophil blood counts and adverse outcomes has not been described. The aim of the study is to associate in one model both normal and increased blood eosinophil counts to the subsequent development of common conditions in internal medicine, in which eosinophil granulocytes may play a role for the symptoms.
Methods: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 359,950 individuals with at least one differential cell count (DIFF) during 2000-2007. From these, one DIFF was randomly chosen. From the Danish National Patient Register we ascertained organ damage, within four years following the DIFF. Using multivariable logistic regression, odds ratios were calculated and adjusted for previous eosinophilia, sex, age, year, month, CRP and comorbid conditions.
Results: Risks for skin- and respiratory disease were increased from above the median eosinophil count of 0.16 × 109/l and reached a plateau around 1.0 × 109/l. Furthermore, risks of most outcomes also increased when the eosinophil count approached zero.
Conclusions: The observed U-shaped association with a plateau of risks around 1 × 109/l indicates that the risk for symptoms due to eosinophilia do not increase proportionate at higher counts. This study demonstrates for the first time that there is indeed an increased risk below median count of 0.16 × 109/l for an increased risk for the same manifestations. Clinically, it means that a normal or even low count of eosinophils do not rule out a risk for organ affection by eosinophils, and may contribute to explain, why patients may have normal eosinophil counts in e.g. asthma or allergy and still have symptoms from the lungs and skin, most likely explained by the extravasation of eosinophils.
Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, Leiferman KM, Nutman TB, Pfab F, Ring J, Rothenberg ME, Roufosse F, Sajous M-H, Sheikh J, Simon D, Simon H-U, Stein ML, Wardlaw A, Weller PF, Klion AD. Hypereosinophilic syndrome: A multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol [Internet]. 2009 Dec [cited 2019 Feb 26];124(6):1319-1325.e3. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0091674909014109
Grzegorz Helbig, Katarzyna Wiśniewska-Piąty, Tomasz Francuz, Joanna Dziaczkowska-Suszek, Sławomira Kyrcz-Krzemień
Diversity of clinical manifestations and response to corticosteroids for idiopathic hypereosinophilic syndrome: retrospective study in 33 patients.
Leuk Lymphoma. 2013 Apr;54(4):807-11. doi: 10.3109/10428194.2012.731602. Epub 2012 Oct 5.
Abstract/Text
Idiopathic hypereosinophilic syndrome (IHES) is characterized by blood hypereosinophilia with no underlying cause and eosinophilia-associated organ dysfunction. Thirty-three patients, 20 female (61%) and 13 male (29%), with a median age of 56 years at diagnosis (range 16-77 years) were included in the study. The median blood eosinophilia at diagnosis was 7.6 × 10(9)/L and the median percentage of eosinophils in the bone marrow was 39.5%. The most common clinical manifestations were splenomegaly and cardiac involvement. Corticosteroids (CS) as monotherapy were initiated in all study patients. The median starting dose of prednisone was 30 mg daily (range 5-85 mg), and the maintenance dose varied from 5 mg twice weekly to 60 mg daily. Overall, 21 patients (64%) responded to CS within a week. Seven patients (21%) were resistant or intolerant to CS. Five patients (15%) achieved a 50% reduction of blood eosinophilia. In conclusion, CS were found to be highly effective in IHES with manageable side effects.
Sa A Wang, Robert P Hasserjian, Wayne Tam, Albert G Tsai, Julia T Geyer, Tracy I George, Kathryn Foucar, Heesun J Rogers, Eric D Hsi, Bryan A Rea, Adam Bagg, Carlos E Bueso-Ramos, Daniel A Arber, Srdan Verstovsek, Attilio Orazi
Bone marrow morphology is a strong discriminator between chronic eosinophilic leukemia, not otherwise specified and reactive idiopathic hypereosinophilic syndrome.
Haematologica. 2017 Aug;102(8):1352-1360. doi: 10.3324/haematol.2017.165340. Epub 2017 May 11.
Abstract/Text
Chronic eosinophilic leukemia, not otherwise specified can be difficult to distinguish from idiopathic hypereosinophilic syndrome according to the current World Health Organization guideline. To examine whether the morphological features of bone marrow might aid in the differential diagnosis of these two entities, we studied a total of 139 patients with a diagnosis of chronic eosinophilic leukemia, not otherwise specified (n=17) or idiopathic hypereosinophilic syndrome (n=122). As a group, abnormal bone marrow morphological features, resembling myelodysplastic syndromes, myeloproliferative neoplasm or myelodysplastic/myeloproliferative neoplasm, were identified in 40/139 (27%) patients: 16 (94%) of those with chronic eosinophilic leukemia and 24 (20%) of those with hypereosinophilic syndrome. Abnormal bone marrow correlated with older age (P<0.001), constitutional symptoms (P<0.001), anemia (P=0.041), abnormal platelet count (P=0.002), organomegaly (P=0.008), elevated lactate dehydrogenase concentration (P=0.005), abnormal karyotype (P<0.001), as well as the presence of myeloid neoplasm-related mutations (P<0.001). Patients with abnormal bone marrow had shorter survival (48.1 months versus not reached, P<0.001), a finding which was independent of other confounding factors (P<0.001). The association between abnormal bone marrow and shorter survival was also observed in hypereosinophilic syndrome patients alone. In summary, most patients with chronic eosinophilic leukemia, not otherwise specified and a proportion of those with idiopathic hypereosinophilic syndrome show abnormal bone marrow features similar to the ones encountered in patients with myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasm or BCR-ABL1-negative myeloproliferative neoplasm. Among patients who are currently considered to have idiopathic hypereosinophilic syndrome, abnormal bone marrow is a strong indicator of clonal hematopoiesis. Similar to other myeloid neoplasms, bone marrow morphology should be one of the major criteria to distinguish patients with chronic eosinophilic leukemia, not otherwise specified or clonal hypereosinophilic syndrome from those with truly reactive idiopathic hypereosinophilic syndrome.
Copyright© 2017 Ferrata Storti Foundation.
Grzegorz Helbig, Agata Wieczorkiewicz, Joanna Dziaczkowska-Suszek, Miroslaw Majewski, Slawomira Kyrcz-Krzemien
T-cell abnormalities are present at high frequencies in patients with hypereosinophilic syndrome.
Haematologica. 2009 Sep;94(9):1236-41. doi: 10.3324/haematol.2008.005447.
Abstract/Text
BACKGROUND: A T-cell clone, thought to be the source of eosinophilopoietic cytokines, identified by clonal rearrangement of the T-cell receptor and by the presence of aberrant T-cell immunophenotype in peripheral blood defines lymphocytic variant of hypereosinophilic syndrome (L-HES).
DESIGN AND METHODS: Peripheral blood samples from 42 patients who satisfied the diagnostic criteria for HES were studied for T-cell receptor clonal rearrangement by polymerase chain reaction according to BIOMED-2. The T-cell immunophenotype population was assessed in peripheral blood by flow cytometry. The FIP1L1-PDGFRA fusion gene was detected by nested polymerase chain reaction.
RESULTS: Forty-two HES patients (18 males and 24 females) with a median age at diagnosis of 56 years (range 17-84) were examined in this study. Their median white blood cell count was 12.9 x 10(9)/L (range 5.3-121), with an absolute eosinophil count of 4.5 x 10(9)/L (range 1.5-99) and a median eosinophilic bone marrow infiltration of 30% (range 11-64). Among the 42 patients, clonal T-cell receptor rearrangements were detected in 18 patients (42.8%). Patients with T-cell receptor clonality included: T-cell receptor beta in 15 patients (35%), T-cell receptor gamma in 9 (21%) and T-cell receptor delta in 9 (21%) patients, respectively. Clonality was detected in all three T-cell receptor loci in 4 cases, in two loci in 7 patients and in one T-cell receptor locus in the remaining 7 patients. The FIP1L1-PDGFRA fusion transcript was absent in all but 2 patients with T-cell receptor clonality. Three patients out of 42 revealed an aberrant T-cell immunophenotype. In some patients, an abnormal CD4:CD8 ratio was demonstrated.
CONCLUSIONS: T-cell abnormalities are present at high frequencies in patients with HES.
Georgia Metzgeroth, Christoph Walz, Philipp Erben, Helena Popp, Annette Schmitt-Graeff, Claudia Haferlach, Alice Fabarius, Susanne Schnittger, David Grimwade, Nicholas C P Cross, Rüdiger Hehlmann, Andreas Hochhaus, Andreas Reiter
Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hypereosinophilic syndrome: a phase-II study.
Br J Haematol. 2008 Dec;143(5):707-15. doi: 10.1111/j.1365-2141.2008.07294.x. Epub 2008 Oct 17.
Abstract/Text
This study evaluated the efficacy and safety of imatinib in chronic eosinophilic leukaemia (CEL, n = 23) and hypereosinophilic syndrome (HES, n = 13). In CEL with FIP1L1-PDGFRA (n = 16) or various PDGFRB fusion genes (n = 5), complete haematological remission (CHR) was achieved in 95% (20/21) after 3 months. Complete molecular remission (CMR) was seen in 75% (12/16) of cases with FIP1L1-PDGFRA positive CEL by 6 months, and in 87% (13/15) after 12 months. CMR was achieved in three of five PDGFRB fusion positive patients after 3, 9 and 18 months respectively. All patients are currently on imatinib (100 mg; n = 13, 400 mg; n = 8) and no molecular relapse has yet been observed (median 26.7 months; range, 6.9-39.9). Imatinib was less effective in HES and CEL without known molecular aberration (n = 15); CHR was observed in 40% (6/15) of patients, two patients relapsed after 4.8 and 24.5 months. Three patients died due to imatinib-resistant progressive CEL (n = 2) or myocardial infarction (n = 1) unrelated to study treatment. Overall, imatinib was well tolerated with a low incidence of grade III/IV toxicities. These data confirmed the long-term efficacy of imatinib for PDGFR-rearranged CEL patients, and also showed that a minority of HES cases without known molecular aberrations may benefit from imatinib.
Sa A Wang, Wayne Tam, Albert G Tsai, Daniel A Arber, Robert P Hasserjian, Julia T Geyer, Tracy I George, David R Czuchlewski, Kathryn Foucar, Heesun J Rogers, Eric D Hsi, B Bryan Rea, Adam Bagg, Paola Dal Cin, Chong Zhao, Todd W Kelley, Srdan Verstovsek, Carlos Bueso-Ramos, Attilio Orazi
Targeted next-generation sequencing identifies a subset of idiopathic hypereosinophilic syndrome with features similar to chronic eosinophilic leukemia, not otherwise specified.
Mod Pathol. 2016 Aug;29(8):854-64. doi: 10.1038/modpathol.2016.75. Epub 2016 May 13.
Abstract/Text
The distinction between chronic eosinophilic leukemia, not otherwise specified and idiopathic hypereosinophilic syndrome largely relies on clonality assessment. Prior to the advent of next-generation sequencing, clonality was usually determined by cytogenetic analysis. We applied targeted next-generation sequencing panels designed for myeloid neoplasms to bone marrow specimens from a cohort of idiopathic hypereosinophilic syndrome patients (n=51), and assessed the significance of mutations in conjunction with clinicopathological features. The findings were further compared with those of 17 chronic eosinophilic leukemia, not otherwise specified patients defined by their abnormal cytogenetics and/or increased blasts. Mutations were detected in 14/51 idiopathic hypereosinophilic syndrome patients (idiopathic hypereosinophilic syndrome/next-generation sequencing-positive) (28%), involving single gene in 7 and ≥2 in 7 patients. The more frequently mutated genes included ASXL1 (43%), TET2 (36%), EZH2 (29%), SETBP1 (22%), CBL (14%), and NOTCH1 (14%). Idiopathic hypereosinophilic syndrome/next-generation sequencing-positive patients showed a number of clinical features and bone marrow findings resembling chronic eosinophilic leukemia, not otherwise specified. Chronic eosinophilic leukemia, not otherwise specified patients showed a disease-specific survival of 14.4 months, markedly inferior to idiopathic hypereosinophilic syndrome/next-generation sequencing-negative (P<0.001), but not significantly different from idiopathic hypereosinophilic syndrome/next-generation sequencing-positive (P=0.117). These data suggest that targeted next-generation sequencing helps to establish clonality in a subset of patients with hypereosinophilia that would otherwise be classified as idiopathic hypereosinophilic syndrome. In conjunction with other diagnostic features, mutation data can be used to establish a diagnosis of chronic eosinophilic leukemia, not otherwise specified in patients presenting with hypereosinophilia.
K Leder, P F Weller
Eosinophilia and helminthic infections.
Baillieres Best Pract Res Clin Haematol. 2000 Jun;13(2):301-17. doi: 10.1053/beha.1999.0074.
Abstract/Text
Among microbial agents, helminths are the most common cause of eosinophilia. An approach to the evaluation of a patient with eosinophilia is outlined, with particular emphasis on clues in the history, examination and routine laboratory data that can help with the diagnosis. Multiple helminthic infections have been associated with eosinophilia, and the characteristic modes of spread, clinical manifestations, diagnostic tests and therapeutic considerations of these infections are discussed.
Copyright 2000 Harcourt Publishers Ltd.
Friedrich Wimazal, Ulrich Germing, Michael Kundi, Thomas Noesslinger, Sabine Blum, Philipp Geissler, Christian Baumgartner, Michael Pfeilstoecker, Peter Valent, Wolfgang R Sperr
Evaluation of the prognostic significance of eosinophilia and basophilia in a larger cohort of patients with myelodysplastic syndromes.
Cancer. 2010 May 15;116(10):2372-81. doi: 10.1002/cncr.25036.
Abstract/Text
BACKGROUND: Lineage involvement and maturation arrest are considered to have prognostic significance in patients with myelodysplastic syndromes (MDS). However, although the prognostic value of neutropenia, thrombocytopenia, and monocytosis have been documented, little is known about the impact of eosinophils and basophils.
METHODS: The authors examined the prognostic significance of eosinophils and basophils in 1008 patients with de novo MDS. Patients were enrolled from 3 centers of the Austrian-German MDS Working Group and were analyzed retrospectively. Blood eosinophils and basophils were quantified by light microscopy, and their impact on survival and leukemia-free survival was calculated by using Cox regression.
RESULTS: Eosinophilia (eosinophils >350/microL) and basophilia (basophils >250/microL) predicted a significantly reduced survival (P < .05) without having a significant impact on leukemia-free survival. In multivariate analysis, eosinophilia and basophilia were identified as lactate dehydrogenase (LDH)-independent prognostic variables with International Prognostic Scoring System (IPSS)-specific impact. Although elevated LDH was identified as a major prognostic determinant in IPSS low-risk, intermediate-1 risk, and high-risk subgroups, the condition "eosinophilia and/or basophilia" was identified as a superior prognostic indicator in the IPSS intermediate-2 risk subgroup.
CONCLUSIONS: The evaluation of eosinophils and basophils in patients with MDS was helpful and may complement the spectrum of variables to optimize prognostication in MDS.
(c) 2010 American Cancer Society.
Grzegorz Helbig, Anna Soja, Aleksandra Bartkowska-Chrobok, Sławomira Kyrcz-Krzemień
Chronic eosinophilic leukemia-not otherwise specified has a poor prognosis with unresponsiveness to conventional treatment and high risk of acute transformation.
Am J Hematol. 2012 Jun;87(6):643-5. doi: 10.1002/ajh.23193. Epub 2012 Mar 31.
Abstract/Text
Chronic eosinophilic leukemia-not otherwise specified (CEL-NOS) is a rare disorder with hypereosinophilia and an increased number of blood or marrow blast (<20%) or an evidence of eosinophil clonality.We evaluated the clinical outcome of 10 patients with CEL-NOS. Seven males and three females at a median age of 62 years (range, 23–73) were included. The median leukocyte count at diagnosis was 33.4 3109/l (range, 9.3–175.0) with a median eosinophil count of 15.6 3 109/l (range, 1.5–136.0). Median hemoglobin and platelets were 11.0 g/dl (range, 8.3–13.3) and 158 3 109/l (range, 31.0–891.0), respectively. Clinical manifestations included splenomegaly (n 5 7), hepatomegaly (n 56), cardiac failure (n 5 2), and lung infiltrations (n 5 1). Median survival from diagnosis to death for entire cohort was 22.2 months (range,2.2–186.2). Five of the 10 studied patients developed acute transformation(AT) after median of 20 months from diagnosis (range, 1.6–41.9).None of patients with AT is alive at the time of last follow-up. Median time from AT to death was 2 months (range, 1.0–6.1). Among five patients who did not develop AT, three died in active disease. Two patients are alive in complete remission; first underwent allogeneic stem-cell transplantation preceding by intensive induction chemotherapy;the second remains on imatinib with hydroxyurea. Except the latter patient, imatinib was ineffective in our study population. CEL-NOS is a rare and aggressive disease with high rate of AT and resistance to conventional treatment.
Xia Zhang, Panpan Zhang, Jieqiong Li, Yujie He, Yunyun Fei, Linyi Peng, Qun Shi, Wen Zhang, Yan Zhao
Different clinical patterns of IgG4-RD patients with and without eosinophilia.
Sci Rep. 2019 Nov 11;9(1):16483. doi: 10.1038/s41598-019-52847-6. Epub 2019 Nov 11.
Abstract/Text
It has been reported that patients with IgG4-related disease (IgG4-RD) showed an elevated incidence of eosinophilia. We aim to explore the clinical patterns of IgG4-RD patients with and without eosinophilia. Four hundred and twenty-five IgG4-RD patients referred to Peking Union Medical College Hospital were enrolled. Blood eosinophil count higher than 0.5 × 109/L was defined as eosinophilia. Clinical features of all the participants were collected and analyzed statistically. Eighty-seven patients (20%) with eosinophilia were found. As compared to those with a normal range of blood eosinophil count, male predominance, longer disease duration, increased prevalence of dacryoadenitis, sialadenitis, lymphadenopathy, and skin rash, higher IgG4-RD responder index, more organ involvement and higher levels of serum IgG4 (17.0 g/L vs 6.5 g/L, P < 0.001) was found in patients with eosinophilia. There was no significant difference in the incidence of allergic disease between the two groups. Peripheral eosinophil counts were positively correlated with disease duration, the number of involved organs, IgG4-RD responder index, and serum IgG4. Higher recurrence rate during follow-up period was found in patients with eosinophilia [28.6% (20/70) vs 17.1% (42/245), P = 0.034]. IgG4-RD patients with eosinophilia exhibited different clinical patterns from patients without. Eosinophilia appeared independent of allergies in IgG4-RD.
Tara E Ness, Timothy A Erickson, Veronica Diaz, Amanda B Grimes, Ryan Rochat, Sara Anvari, Joud Hajjar, Jill Weatherhead
Pediatric Eosinophilia: A Review and Multiyear Investigation into Etiologies.
J Pediatr. 2023 Feb;253:232-237.e1. doi: 10.1016/j.jpeds.2022.09.048. Epub 2022 Oct 3.
Abstract/Text
OBJECTIVES: To identify the etiology of peripheral eosinophilia in a large pediatric population and to develop a diagnostic algorithm to help guide diagnosis and management of peripheral eosinophilia in the outpatient pediatric population.
STUDY DESIGN: We performed a retrospective chart review of children presenting to Texas Children's Hospital in Houston with peripheral eosinophilia between January 1, 2011 and December 31, 2019. Eosinophilia was classified as mild (absolute eosinophil count [AEC] >500 and <1500 cells/μL), moderate (AEC >1500 and <4500 cells/μL), or severe (AEC >4500 cells/μL). Demographic information and diagnostic workup data were collected.
RESULTS: A total of 771 patients aged <18 years were evaluated. The most common cause of eosinophilia was allergy (n = 357; 46%), with atopy (n = 296) and drug reaction (n = 54) the most common subcauses. This was followed by unknown etiology (n = 274; 36%), infectious causes (n = 72; 9%), and eosinophilic disorders (n = 47; 6%). Many patients with an unknown cause (n = 202; 74%) had limited or no follow-up testing.
CONCLUSIONS: More information on the etiology of pediatric eosinophilia and workup data could help identify the causes. This study provides important information on the evaluation of eosinophilia in the US pediatric population, including a diagnostic algorithm to guide primary care pediatricians.
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
