Variant Of Hypereosinophilic Syndrome Research Articles

Eosinophilic Myocarditis: From Bench to Bedside.

Myocarditis is a polymorphic and potentially life-threatening disease characterized by a large variability in clinical presentation and prognosis. Within the broad spectrum of etiology, eosinophilic myocarditis represents a rare condition characterized by eosinophilic infiltration of the myocardium, usually associated with peripheral eosinophilia. Albeit uncommon, eosinophilic myocarditis could be potentially life-threatening, ranging from mild asymptomatic disease to multifocal widespread infiltrates associated with myocardial necrosis, thrombotic complications, and endomyocardial fibrosis. Moreover, it could progress to dilated cardiomyopathy, resulting in a poor prognosis. The leading causes of eosinophilic myocarditis are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, cancer, hyper-eosinophilic syndrome variants, and infections. A thorough evaluation and accurate diagnosis are crucial to identifying the underlying cause and defining the appropriate therapeutic strategy. On these bases, this comprehensive review aims to summarize the current knowledge on eosinophilic myocarditis, providing a schematic and practical approach to diagnosing, evaluating, and treating eosinophilic myocarditis.

The Phase 3 Natron Study Evaluating Benralizumab in Patients with Hypereosinophilic Syndrome: Study Design and Patient Characteristics

Background and Significance: Hypereosinophilic syndrome (HES) is a rare, heterogeneous disorder defined by blood eosinophilia (absolute eosinophil count [AEC] >1500 cells/μL) on 2 examinations ≥1 month apart and eosinophil-mediated end-organ involvement, including dermatologic, pulmonary, gastrointestinal, and/or cardiovascular manifestations. Symptoms and health-related quality of life vary depending on the organ systems involved. HES is often treated with corticosteroids and other immunosuppressants. However, long-term use of these agents is associated with decreased efficacy and significant toxicity. Whereas anti-IL-5 antibody mepolizumab was recently approved for the treatment of HES (Roufosse, et al. J Allergy Clin Immunol. 2020;146(6):1397-1405), response is not universal and additional targeted agents are clearly warranted. Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor α monoclonal antibody that induces rapid, near-complete depletion of eosinophils through antibody-dependent, cell-mediated cytotoxicity. It is currently approved for use in patients with severe eosinophilic asthma and has demonstrated AEC-reducing effects in patients with HES (Kuang, et al. N Engl J Med. 2019;380(14):1336-46). Study Design and Methods:This phase 3, multicenter, randomized, double-blind (DB), placebo-controlled study (NATRON; NCT04191304) evaluating the efficacy of benralizumab versus placebo will enroll ~120 patients with documented HES (Figure 1A). Recruitment will stop after approximately 38 patients have had their first HES worsening/flare during the DB period, at which point the data cutoff for the primary analysis will occur. Eligible patients are ≥12 years of age with an AEC ≥1000 cells/mL at screening, have active signs/symptoms of an HES worsening/flare or a history of ≥2 HES worsening/flares within 12 months before enrollment, and have a stable treatment regimen (≥4 weeks). Patients must be FIP1L1-PDGFRA-negative and corticosteroid-responsive, defined as an AEC of <1000 cells/μL after 2 days of corticosteroid treatment. The primary endpoint is time to first HES worsening/flare during the DB period. Key secondary endpoints during the DB period include the proportion of patients who experience HES worsening/flare events, the number of HES worsening/flare events (annualized rate/year), time to first hematologic relapse, and change from baseline in fatigue at week 24 as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a. Patients who complete the 24-week DB treatment period will continue with active treatment in a ≥52-week open-label extension. We present the study design and interim baseline characteristics of patients recruited to date. Results:As of the June 6, 2023, cutoff date, 87 patients were enrolled in the full analysis set (Figure 1B). Among these patients, the mean (SD) age was 48.4 (17.79) years, 64.4% were female, and 84.3% were White. The mean (SD) time since the first appearance of HES symptoms and since HES diagnosis was 8.14 (8.12) and 4.87 (6.54) years, respectively. The proportion of patients with the lymphocytic variant HES was 14.9%. The most common primary organs involved were the lungs (35.6%), followed by the skin (25.3%) and the gastrointestinal tract (21.8%). Thirty-four (39.1%) and 32 (36.8%) patients experienced 2 and ≥3 HES worsening/flare events in the previous 12 months, respectively. The mean (SD) PROMIS Fatigue T-score was 55.0 (9.42). Mean (SD) baseline eosinophil levels were 1960 (2610) cells/µL, with median (interquartile range) levels of 1120 (60, 20910) cells/µL. Conclusions: Results from the NATRON study will provide insight into whether benralizumab is beneficial in addition to background therapy in patients with FIP1L1-PDGFRA-negative steroid-responsive HES. Funding: This study is funded by AstraZeneca (Gothenburg, Sweden). This work is funded in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Acknowledgments:Vivian H. Shih, Dianne Griffis, Himanshu Parikh, Ron A. Chen, Ying Fan, Gaëll Mayer, Rohit Katial, and Ioannis Psallidas.

Eosinophilic myocarditis: comprehensive update on pathophysiology, diagnosis, prognosis and management.

Hypereosinophilic syndromes are a group of disorders secondary to the accumulation of eosinophils leading to the injury of one or more organs. Among them, eosinophilic myocarditis (EM) is a rare form of inflammatory cardiomyopathy characterized by eosinophilic infiltration into myocardial tissue and subsequent release of substances with cell membrane damage and cell destruction. The degree of infiltration is thought to depend on the underlying condition, as well as the degree and duration of eosinophil exposure and ranges from mild localized disease to diffuse multifocal infiltrates associated with myocardial necrosis, thrombotic complications and endomyocardial fibrosis. The main causes of EM are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome variants, infections and cancer. Clinical presentation can be variable, ranging from asymptomatic forms to life-threatening conditions, to chronic heart failure due to progression to chronic restrictive cardiomyopathy. Marked eosinophilia in peripheral blood, elevated serum eosinophilic cationic protein concentration and multimodality imaging may suggest the etiology of EM, but in most cases an endomyocardial biopsy must be performed to establish a definitive diagnosis. Systemic treatment varies greatly depending on the underlying cause, however the evidence of an eosinophilic infiltrate allows initiation of immunosuppressive therapy, which is the mainstay of treatment in idiopathic and in most forms of EM. Patients with helminthic infection benefit from anti-parasitic therapy, those with myeloid clone often need a tyrosine kinase inhibitor, while anticoagulant therapy should be undertaken in case of possible thrombotic complications.

TREATMENT OF ASTHMA MIGHT HAVE DELAYED END-ORGAN DAMAGE IN THE PATIENT WITH LYMPHOCYTIC HYPEREOSINOPHILIC SYNDROME

<h3>Introduction</h3> Hypereosinophilic syndrome (HES) is characterized by an absolute eosinophil count (AEC) > 1,500 and organ damage or dysfunction attributable to tissue eosinophilia. <h3>Case Description</h3> This 71-year-old patient with a 12-year history of asthma was treated with inhaled and variable daily doses of oral corticosteroids for four years. Without the risk factors for cardiovascular disease, he suddenly developed stroke symptoms. His brain MRI revealed multiple scattered patchy foci of acute cortical matter ischemia, and he was diagnosed with an acute cerebrovascular accident. He also had elevated troponin and underwent cardiac catheterization with stent placement to a proximal LAD and mid-LAD lesion. Four months later, he came for an allergy evaluation because of "elevated white cells" and "food allergy." However, he had an increased AEC of 3,800 and clinically irrelevant IgE to the tolerated foods. His medical record revealed that over the last four years, his AEC fluctuated between 374 and 8,730. Therefore, we initiated an evaluation for suspected HES, eosinophilic granulomatosis with polyangiitis, and, less likely, parasitoses. Molecular studies revealed a clonal population of lymphocytes with T-cell receptor gene γ and β rearrangement consistent with a diagnosis of lymphoid variant HES. Other laboratory findings are in figure 1. <h3>Discussion</h3> A common occurrence of eosinophilia in the patients with asthma might lower the index of suspicion of HES. However, this patient's very high AEC should have prompted an investigation earlier. His HES presented as multifocal ischemic brain and cardiac infarcts. This presentation was likely delayed by treating the patient's asthma with systemic corticosteroids.

A SERIES OF GENETIC EVENTS: FIP1L1/PDGFR REARRANGEMENT LEADING TO EOSINOPHILIC MYOCARDITIS

A SERIES OF GENETIC EVENTS: FIP1L1/PDGFR REARRANGEMENT LEADING TO EOSINOPHILIC MYOCARDITIS

CML-216 Hypereosinophilia Syndrome With FIP1L1-PDGFRA Transcript Revealed by Cardiac Involvement

Hypereosinophilic syndrome (HES) is defined by eosinophilia greater than 1.5 G/L persisting for more than 6 months and associated with specific visceral damage (cardiac, neurological, pulmonary, etc.), after elimination of "classic" causes of hypereosinophilia. A myeloproliferative variant of HES is associated with the fusion of the FIP1L1 and PGDFRα genes, resulting in the constitutive activation of a receptor with tyrosine kinase activity. We report a case revealed unexpectedly by cardiac involvement (a mitral valve disease). A 25-year-old man with no particular history, allergies, or cardiovascular risk factors was hospitalized in the cardiology department for sudden-onset precordialgia associated with low-grade fever. The clinical examination: a general state preserved asthenic, nocturnal fever with precordialgia, and stage IV splenomegaly. ECG: unremarkable; heart echo: a thickened mitral valve with moderate mitral leakage, with rupture of the chords giving moderate grade II mitral insufficiency. Three blood cultures taken at the time of the fever peak came back sterile. FNS: anemia reduced to 9 g/dL normochromic normocytic aregenerative, activated thrombocytopenia to 124 G/L, hyperleukocytosis to 65,000/mm3, including 81% of eosinophilic polynuclear cells (52,650 elements/mm3) without myelemia. Myelogram: a very rich smear with eosinophilic hyperplasia at all stages of maturation. A thoraco-abdominopelvic CT scan showed heterogeneous splenomegaly with parenchymal involvement in centro-lobular ground glass, predominantly apical with areas of geographical somatic vertebral bone condensation staged in the dorsolumbar and pelvis. A corticosteroid test was negative, and a molecular cytogenetic study revealed the FIP1L1-PDGFRA fusion transcript in 88% of cells with a rearrangement of the locus at 4q12. The patient was put on imatinib 100 mg/day for 15 days then 200 mg/day with prophylactic anticoagulation. The evolution was favorable with a normalization of the FNS after 20 days. After 6 months of treatment, a FISH was requested, having objectified the complete disappearance of the cytogenetic anomaly. Chronic eosinophilic leukemia with FIP1L1-PDGFRA can be serious and fatal in the event of diagnostic delay and the nature of the affected organ. Patients with clinical manifestations consistent with HES should be investigated for evidence of clonality of hematopoiesis and a search for a T-lymphocyte population for treatment decisions.

Clinical Profile and Treatment in Hypereosinophilic Syndrome Variants: A Pragmatic Review

Hypereosinophilic syndrome (HES) is a group of rare hematologic disorders leading to eosinophil-driven tissue damage and dysfunction. Better understanding of HES variants may facilitate improved patient management. To describe disease characteristics, treatment, and outcomes of patients with idiopathic (I-HES), myeloproliferative (M-HES), lymphocytic (L-HES), and chronic eosinophilic leukemia, not otherwise specified (CEL-NOS) among HES case reports and aggregate data where available. Relevant articles published between January 1, 2000, and March 20, 2020, were retrieved via PubMed; those reporting secondary, associated/reactive, overlap/single-organ, or familial HES were excluded. Of 188 articles included, 171 contained data on 347 separate HES cases (152 I-HES, 121 M-HES, 62 L-HES, 12 CEL-NOS). Based on individual data, mean age at diagnosis was 43 to 48 years for patients with all HES variants. Males accounted for 90% to 91% of M-HES/CEL-NOS and 55% to 65% of I-HES/L-HES cases. Cardiac symptoms were frequently observed for all HES variants (13%-22% of patients). Respiratory symptoms (I-HES), splenomegaly (M-HES and CEL-NOS), and skin conditions (L-HES) were also frequently observed. Bone marrow, heart, lung, spleen, liver, skin, and lymph nodes were commonly involved. Most patients with I-HES, L-HES, and CEL-NOS received corticosteroids (65%-85%), whereas most with M-HES received imatinib (81%); those with CEL-NOS also received interferon alpha (42%). Collective analysis of HES case reports supports and extends current understanding of HES variants, highlighting differences in signs and symptoms, organ involvement, and treatment approaches. Improved characterization of HES variants may facilitate the development of novel treatments.

Venous thrombosis and predictors of relapse in eosinophil-related diseases

Eosinophils have widespread procoagulant effects. Eosinophilic cardiovascular toxicity mostly consists of endomyocardial damage or eosinophilic vasculitis, while reported cases of venous thrombosis (VT) are scarce. We aimed to report on the clinical features and treatment outcomes of patients with unexplained VT and eosinophilia, and to identify predictors of relapse. This retrospective, multicenter, observational study included patients aged over 15 years with VT, concomitant blood eosinophilia ≥ 1G/L and without any other moderate-to-strong contributing factors for VT. Fifty-four patients were included. VT was the initial manifestation of eosinophil-related disease in 29 (54%) patients and included pulmonary embolism (52%), deep venous thrombosis (37%), hepatic (11%) and portal vein (9%) thromboses. The median [IQR] absolute eosinophil count at VT onset was 3.3G/L [1.6–7.4]. Underlying eosinophil-related diseases included FIP1L1-PDGFRA-associated chronic myeloid neoplasm (n = 4), Eosinophilic Granulomatosis with Polyangiitis (n = 9), lymphocytic (n = 1) and idiopathic (n = 29) variants of hypereosinophilic syndrome. After a median [IQR] follow-up of 24 [10–62] months, 7 (13%) patients had a recurrence of VT. In multivariate analysis, persistent eosinophilia was the sole variable associated with a shorter time to VT relapse (HR 7.48; CI95% [1.94–29.47]; p = 0.015). Long-term normalization of eosinophil count could prevent the recurrence of VT in a subset of patients with unexplained VT and eosinophilia ≥ 1G/L.

Primary FIP1L1-PDGFR Positive Hypereosinophilic Syndrome with Unusual Rheumatic Onset

AbstractIntroduction.Hypereosinophilia (HE) is defined as an absolute eosinophil count &gt;1.5 x 109/L in the peripheral blood on two examinations separated in time by at least one monthand/orpathologic confirmation of tissue HE. A hypereosinophilic syndrome (HES) is defined by the association of HE with eosinophil-mediated organ damage and/or dysfunction if other potential causes of them have been excluded.Case report.We report a case of a 52-year-old woman admitted to Rheumatology Department for diffuse, highly intense (10/10) myalgia, associated with paravertebral, upper and lower limbs muscular edema and stiffness, having the onset of symptoms for about 4 months. During rheumatological evaluation, the patient developed posterior cervical diffuse pain with brachial irradiation associated with severe functional impotence reason for which it was indicated MRI of cervical spine. The blood count showed leucocytosis with hypereosinophilia. No evidence of Raynaud’s phenomenon, cutaneous and muscular sclerosis or visceral involvement. All muscular groups and deep fascia appeared affected on the whole-body MRI and the findings were suggestive for Shulman’s eosinophilic fasciitis or eosinophilic myopahty. All autoimmune, parasitic and allergic causes for myopathy were ruled out. Muscle tissue biopsy revealed high eosinophilic infiltrate predominantly in the deep muscular fascia, in the striated muscles and in the superficial dermis.The patient received methyl-prednisolone pulse-therapy with a low-maintenance dose of prednisone which showed clinical improvement and normalized peripheral blood eosinophilia. A hematologic evaluation revealed high percentage of bone marrow eosinophil count which harbored FIP1L1-PDGFR alpha mutation and data was suggestive for the diagnosis of myeloproliferative variant of HES syndrome along with Shulman’s eosinophilic fasciitis for which Imatinib treatment was indicated.Conclusion.The particularity of this case consists in the diagnosis of a myeloproliferative variant of HES with atypical presentation as a Shulman’s eosinophilic fasciitis, a rheumatological condition. Even though initial symptoms were suggestive for a myopathy, it was difficult to establish the positive diagnosis without any obvious paraclinical data. Further investigations such as MRI and muscle biopsy were conclusive for the diagnosis of Shulman’s eosinophilic fasciitis and clinical improvement was observed after corticosteroid treatment. Considering that after 4 months of evolution of the disease the patient did not present any atrophic lesions of the affected muscles and skin characteristic for Shulman’s eosinophilic fasciitis the patient was referred to Hematology Department with the diagnosis of HES. Advanced exams established the hematological condition as primary FIP1L1-PDGFR positive HES which could benefit from tyrosine-kinase inhibitors treatment (Imatinib) known to induce in this situation improved clinical and paraclinical status.

A case of T-cell lymphoproliferative disorder associated with hypereosinophilia with excellent response to mycophenolate mofetil

Hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by a persistent elevation of blood eosinophil count ⩾1.5×109/L and clinical manifestations attributable to eosinophilia or tissue hypereosinophilia. Lymphocytic variant of HES (HES-L) is a known subtype according to World Health Organization classification. It is well documented in the literature that patients with HES-L are predisposed to develop T-cell lymphoma. We report a case of T-cell lymphoproliferation associated with hypereosinophilia, which has been successfully treated with mycophenolate mofetil, with resolution of skin lesions and normalization of eosinophil count and immunoglobulin E level. We believe this is a clinically relevant case since this is a rare disease with little known knowledge on its best treatment modality.

Treatment of Hypereosinophilic Syndrome with Cutaneous Involvement with the JAK Inhibitors Tofacitinib and Ruxolitinib

Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders characterized by persistent peripheral blood eosinophilia, eosinophil-mediated end-organ damage, and absence of other infectious or allergic causes of eosinophilia.(Gotlib, 2014, Valent et al., 2012) Treatment of HES is challenging and usually relies on corticosteroids, which have significant adverse effects.(Klion, 2015, Klion et al., 2006) There are 3 categories of HES: primary, secondary, and idiopathic. Primary HES is a myeloproliferative disease with clonal eosinophils. In secondary HES and idiopathic HES, other cells produce Th2 cytokines that promote polyclonal expansion and activation of eosinophils.(Roufosse, Cogan and Goldman, 2007) Lymphocytic variant HES (L-HES) is a subtype of secondary HES wherein the source of Th2 cytokines is a phenotypically abnormal CD4+ T cell (typically CD3-CD4+).(Simon, Plotz, Dummer and Blaser, 1999, Walker et al., 2015) We recently demonstrated the importance of Janus kinase-Signal transducer and activation of transcription (JAK-STAT) signaling in L-HES.(Walker, et al., 2015) Specifically, we showed a gain-of-function mutation in STAT3 and overexpression of STAT3 gene targets that were necessary and sufficient for the production of eosinophil-promoting Th2 cytokines. Based on these data, we hypothesized that inhibitors of this pathway, namely the JAK inhibitors tofacitinib (JAK1/3 inhibitor) and ruxolitinib (JAK1/2 inhibitor), would be effective treatment of secondary HES.

Lymphocytic variant of Hypereosinophilic syndrome complicated by myocarditis

A 26 year-old-male with nil significant past medical history presented to us with swelling of left lower limb since 2 weeks. He has tachyapnea and tachycardia. His JVP was normal and cardiac auscultation was normal. Examination was suggestive of deep vein thrombosis (DVT) of the left lower limb. Doppler of lower limb confirmed this and patient was appropriately placed on anti-coagulation. He had persistently elevated blood eosinophil counts. Bone marrow biopsy was and mutational analysis confirmed presence of lymphocytic variant of hypereosinophilic syndrome (HES). He continued to have tachycardia and cardiac enzymes were positive. Electrocardiogram revealed sinus tachycardia and echo was normal. After ruling out the possibility of pulmonary thromboembolism with CT pulmonary angiogram, myocarditis was attributed to HES. He was promptly treated glucocorticoids which were later tapered gradually in lieu of improvement of his clinical condition and declining eosinophil counts. He was discharged and was under regular follow-up. Key words: Hypereosinophilic syndrome, Persistent eosinophilia, Deep vein thrombosis, Myocarditis.

Syndrome hyperéosinophilique d’origine myéloproliférative révélé par des ulcérations muqueuses bipolaires

Hypereosinophilic syndrome (HES) is defined as an eosinophil count equal to or greater than 1.5 G/L for more than 6 months with organ damage (heart, nervous system, lung, etc) after the exclusion of other common causes of eosinophilia. A myeloproliferative variant of HES with FIP1L1-PDGFRα fusion gene inducing constitutive activation of a tyrosine kinase receptor has been characterized. We report a case in which the diagnosis was revealed by mucosal erosions and ulcerations. A 50-year-old man reported bipolar erosions. He presented with an erosion on the glans, an ulceration on the lower lip and mild dermographism. He had an eosinophil count of 7.5 G/L (n<0.7) and raised LDH at 520 IU/L (n<480). Screening for the usual causes of eosinophilia was negative. Histology of the labial ulceration showed a polymorphous inflammatory infiltrate containing eosinophils. A chest scan demonstrated a ground glass-like pulmonary infiltrate and broncho-alveolar lavage revealed eosinophilic alveolitis. The myelogram showed rich bone marrow with eosinophils. FIP1L1-PDGFRα fusion transcript was detected in the blood. Imatinib (Glivec(®)) was initiated and a favourable outcome was achieved within a few months and maintained after one year of treatment. Cutaneous signs are frequent features of HES. They are polymorphous and include pruritis, erythematous rash and urticaria. Mucosal ulcerations are uncommon and appear more frequently with the myeloproliferative FIP1L1-PDGFRα-associated variant of HES. Early diagnosis allows the onset of a targeted treatment with imatinib that may prevent the apparition of organ damage.

Hypereosinophilic syndrome in children

Recently, according to the Hypereosinophilic Diseases Working Group of the International Eosinophil Society, six variants of hypereosinophilic syndrome have been proposed, i.e. (1) myeloproliferative, (2) lymphoproliferative, (3) idiopathic/undefined, (4) overlapping, (5) associated and (6) familial variant. Hypereosinophilic syndrome is a rare disorder in children and can occur at any age during childhood. Corticosteroids are the treatment of choice, whereas other treatment options are hydroxyurea, IFNα, imatinib, vincristine, mepolizumab. We present a fulminant fatal case of hypereosinophilic syndrome in a teenager with an initial presentation of an idiopathic thrombocytopenia (ITP) and present a narrative review of literature.

Gaining Weight And Loosing Appetite! ; A Case Of Recurrent Diffuse Angioedema, Weight Gain and Peripheral Eosinophilia Without Visceral Organ Damage

Gleich's syndrome is a variant of Hypereosinophilic syndrome (HES) presenting with episodic angioedema, urticaria, fever, anorexia and significant weight gain but lacking visceral involvement seen in classic HES. History, clinical exam, appropriate laboratory tests. Patient presented with five years of episodic generalized facial, extremities and trunk swelling accompanied by weight gain, fever, urticaria and anorexia. Each episode developed over a few days and lasted for 2-3 months, initially occurring biannually. Recent episodes have occured more frequently.Initial workup showed 16.31K/mm3 WBC with 8,644 normal appearing eosinophils. Strongyloides titer was negative. FIP1L1/PRGFR fusion by FISH was negative. C3, C4, C1 Inhibitor functional assay, metabolic profile and TSH were all normal. IgE was 804 IU/mL but other immunoglobulins were normal. ANA and ANCA were negative. CT showed esophageal, supraglottic and glottic edema. Esophagogastroduodenoscopy with biopsies showed no pathology. In absence of findings for other cause of eosinophilia and no organ involvement, a diagnosis of Gleich's syndrome was made. Patient responded to prednisone with hydorxyurea added as a steroid sparing agent. Gleich's syndrome should be considered in patients with episodic angioedema. Hypereosinophilia from other causes is associated with angioedema and should be ruled out. Lack of visceral involvement is the key to diagnosing this variant of HES.

Imatinib mesylate for lymphocytic variant of hypereosinophilic syndrome

To the editor: With a great interest I read a paper by Christoforidou et al. [1] showing the high efficacy of imatinib mesylate (IM) in a patient with L-HES and undetectable FIP1L1-PDGFRA (F/P) fusion transcript. However, after reading this case description, it seems that several issues need to be clarified and commented. The diagnosis of L-HES requires the detection of the abnormal T-cell phenotype in peripheral blood by flow cytometry and the presence of T-cell receptor clonal rearrangement [2]. It was demonstrated that clonal TCR rearrangement was detectable in patients with F/P mutation and treatment with IM resulted in disappearance of the clonal TCR pattern [3]. In this publication, the authors described a patient with lymphocytosis involving clonal but phenotypically normal CD41 cell population, but these cells were detected in marrow. I wonder if these cells were also found in peripheral blood? The presence of CD41 cells in patients with hypereosinophilic syndromes has already been demonstrated by other study groups, but it should be highlighted that this finding is extremely rare. The occurrence of such a T-cell population is usually associated with other features of T-cell mediated hypereosinophilia, e.g., increased serum IgE levels or cytokine and chemokine overproduction [4,5]. These results are needed to better characterize this variant but they are lacking in this report. Corticosteroids (CS) remain a treatment of choice for patients with L-HES [2]. The authors reported severe side effects after therapy with steroids so they were discontinued. It was demonstrated in most studies that CS resulted in decrease of blood eosinophilia and resolution of clinical symptoms but the proportion of abnormal T-cell remained unaffected [6,7]. In relation to this observation, I would expect such data from the authors of this presentation. We should keep in mind that treatment with IM, especially at a dose of 400 mg daily is expensive and associated with numerous side effects. Therefore, it seems rational to initiate IM only for patients who developed severe steroid-related complications and still require the continuation of treatment. Based on the presented case, it is difficult to judge that IM led to remission in a patient with L-HES. The therapy resulted in decrease of blood eosinophilia and withdrawal of some clinical symptoms, but in fact IM did not affect eosinophilic infiltration of the colon. The proportion of a clonal T-cell population remained intact. This case has shown that IM may remain an interesting therapeutic option but only for those patients who are resistant or intolerant to CS. As the abnormal T-cell subset remained unchanged after IM, we may expect that IM and CS will not prevent those patients from lymphoma transformation.

Imatinib mesylate for lymphocytic variant of hypereosinophilic syndrome: A response

Imatinib mesylate for lymphocytic variant of hypereosinophilic syndrome: A response

Dissection of the posterior inferior cerebellar artery in the hypereosinophilic syndrome

Dissection of the posterior inferior cerebellar artery in the hypereosinophilic syndrome

Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome

Mepolizumab, a monoclonal anti-IL-5 antibody, is an effective corticosteroid-sparing agent for patients with Fip1-like 1/platelet-derived growth factor receptor α fusion (F/P)-negative hypereosinophilic syndrome (HES). Lymphocytic variant hypereosinophilic syndrome (L-HES) is characterized by marked overproduction of IL-5 by dysregulated T cells. To determine whether patients with L-HES respond to mepolizumab in terms of corticosteroid tapering and eosinophil depletion to the same extent as corticosteroid-responsive F/P-negative patients with HES and a normal T-cell profile. Patients enrolled in the mepolizumab trial were evaluated for L-HES on the basis of T-cell phenotyping and T-cell receptor gene rearrangement patterns, and their serum thymus-and-activation-regulated chemokine (TARC) levels were measured. Response to treatment was compared in patient subgroups based on results of these analyses. Lymphocytic variant HES was diagnosed in 13 of 63 patients with HES with complete T-cell assessments. The ability to taper corticosteroids on mepolizumab was similar in patients with L-HES and those with a normal T-cell profile, although a lower proportion of patients with L-HES maintained eosinophil levels below 600/μL. Increased serum TARC levels (>1000 pg/mL) had no significant impact on the ability to reduce corticosteroid doses, but a lower proportion of patients with elevated TARC achieved eosinophil control on mepolizumab. Mepolizumab is an effective corticosteroid-sparing agent for patients with L-HES. In some cases however, eosinophil levels remain above 600/μL, suggesting incomplete neutralization of overproduced IL-5 or involvement of other eosinophilopoietic factors.

Hypereosinophilic syndrome variants: diagnostic and therapeutic considerations

Hypereosinophilic syndromes are a group of disorders characterized by persistent and marked hypereosinophilia not due to an underlying disease known to cause eosinophil expansion, and which is directly implicated in damage or dysfunction of at least one target organ or tissue. In this perspective article, Dr. Roufosse provides an updated classification of these disorders and discusses the recent advances in this field, including fascinating pathogenic mechanisms and novel targeted therapeutic approaches. See related paper on page 1236.