Fibrotic interstitial lung disease (fILD) is a heterogeneous group of rare diseases with a poor prognosis. Given the pro-fibrotic effects of eosinophils, we aimed to assess the distribution of blood eosinophil count (BEC) in patients with fILD and to investigate its potential association with outcomes. Single-center retrospective study of patients diagnosed with fILD between January 1, 2017 and December 31, 2022. For each patient, BECs during follow-up (except for those sampled during treatment with high-dose glucocorticoids) were pooled to assign a unique number (median). Patients' characteristics were analysed by BEC (Eo-high and Eo-low subgroups corresponding to BEC ≥75th percentile and <75th percentile, respectively). Predictors of outcomes were assessed by multivariate logistic regression. 201 patients were included. BEC's median and 75th percentile were 0.2 × 109/L and 0.3 × 109/L, respectively. Baseline BEC and median BEC during follow-up were strongly correlated (r1 = 0.66, 95 % IC 0.52-0.78, p < 0.001). Eo-high patients were significantly older (73 vs. 67 years, p = 0.014) and more likely to experience AE-ILD (36 % vs. 15 %, p = 0.002). In multivariate analysis, a diagnosis of IPF (OR 2.62, 95 % IC 1.05-7.02, p = 0.05), idiopathic NSIP (OR 3.69, 95 % IC 0.99-13.74, p = 0.05), baseline supplemental oxygen therapy (OR 4.71, 95 % IC 2.09-10.82, p < 0.001) and median BEC ≥0.3 × 109/L (OR 2.76, 95 % IC 1.25-6.14, p = 0.01) were associated with AE-ILD. BEC can be associated with AE-ILD. These findings pave the way for future research regarding the role of eosinophils in fILD.

BACKGROUND:The FIP1L1-PDFGRA (F/P)-associated hypereosinophilic syndrome (HES) is a rare condition. The F/P fusion gene testing is one of the first-line investigations in patients with unexplained eosinophilia and yields poor diagnostic performance. OBJECTIVE:To build and validate the factor interacting with PAPOLA and CPSF1 (FIP) score: a set of weighted criteria warranting testing for the F/P fusion gene. METHODS:We merged data from 151 patients with F/P-associated HES and 320 patients with either F/P-negative HES (n = 279) or hypereosinophilia of undetermined significance (n = 41). Training and validation cohorts (comprising, respectively, 90% and 10% of all patients) were randomly dichotomized. Variables with a P value less than .20 in univariate analysis were included in the multivariable forward-backward logistic regression model to assess their independent contribution to testing positive for the F/P fusion gene. Beta coefficients from multivariable logistic regression were used to assign points for the construction of the score. RESULTS:Age younger than 66 years, male sex, splenomegaly, lymphomatoid papulosis, absence of gastrointestinal involvement, high serum vitamin B12, high serum tryptase, and normal serum immunoglobulin E levels were the 8 variables retained in the model. The best cutoff value was greater than 48. The model yielded a sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve, respectively, of 88.3%, 93.7%, 87.1%, 94.4%, and 0.962 in the training dataset and of 85.7%, 97.0%, 85.7%, and 97.0%, 0.986 in the validation dataset. CONCLUSIONS:The FIP score highlights the need for closely selecting patients with hypereosinophilia for whom F/P fusion gene testing should be performed, resulting in medical time reduction and substantial cost-savings.

BACKGROUND:Hypereosinophilic syndromes (HES) are a heterogenous group of eosinophilic disorders. To date, only retrospective studies of limited sample-size and/or follow-up duration are available. METHODS:The COHESion study is a national prospective multicenter multidisciplinary cohort recruiting both adults or children with the spectrum of eosinophilic disorders (including reactive HE/HES [HE/HES-R], idiopathic HES [HES-I], lymphocytic HES [HES-L], neoplastic HE/HES [HE/HES-N], HE of unknown significance [HE-US], as well as IgG4-related disease [IgG4RD] or ANCA-negative eosinophilic granulomatosis with polyangiitis [EGPA] overlaps). Patients are followed-up yearly. All data about final diagnosis, organ involvement assessments, and outcome profiles in HES-I were captured and analyzed centrally by HES expert centers. RESULTS:From May 2019 to November 2023, 779 patients were included. For this preliminary analysis, 550 cases were available for centralized review (mean ± SD age: 56 ± 18 years, 42% of female patients). The final diagnoses were HES-I (47%), HE/HES-R (16%), HE-US (15%), HE/HES-N (7%), HE/HES-L (6%), IgG4RD (2%), and ANCA-negative EGPA (7%). In the 258 HES-I patients, outcome profiles were classified as follows: 16.3% had a "single-flare" without further relapse, 28.3% had a "relapsing-remitting" disease when there was at least a 6-month period free of symptoms between two flares, 46.1% had a "persistent disease" requiring continuous treatment to avoid relapses (9.3% remained unclassified because of insufficient follow-up). CONCLUSIONS:The COHESion cohort is the first nationwide prospective multicenter study collecting data on the full spectrum of HE/HES disorders. This preliminary analysis confirms that idiopathic HES patients have various outcome profiles, suggesting different underlying pathophysiological mechanisms and the need of patient-specific management. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT04018118.

We assess the performances of the Alinity M STI assay (Abbott Molecular) in comparison to the Xpert CT/NG assay (Cepheid). We first retrospectively used a collection of 70 frozen samples of which 33, 31, and 6 were positives for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG), and both micro-organisms respectively. The Alinity M STI and the Xpert CT/NG results were in accordance for all. The mean difference in cycle threshold values between the Xpert CT/NG and the Alinity M STI were -1.6 and 0.0 for CT and NG respectively. Then 214 fresh samples collected from 121 patients were prospectively tested with both instruments. Anal swabs, throat swabs, vaginal swabs, and urines accounted each for about 25%. Seven (3.2%) samples of which 5 anal swabs, provided inconclusive results with the Alinity M STI. In conclusion, the Alinity M STI is an accurate device for the microbiological diagnosis of NG and CT infections.

Introduction Les syndromes hyperéosinophiliques (SHE) et les hyperéosinophilies (HE) sont un groupe hétérogène de maladies, dont les étiologies peuvent être clonales, réactionnelles (secondaires) ou idiopathiques. À ce jour, seules des études rétrospectives de taille et/ou de durée de suivi limitées ont décrit les caractéristiques des patients avec les différentes formes d’HE ou SHE, et principalement dans des centres experts. Nous décrivons ici la mise en place d’une cohorte nationale associant des centres experts du CEREO, et des services de différentes spécialités au sein d’hôpitaux universitaires ou généraux, et les principales caractéristiques des patients inclus. Patients et méthodes L’étude COHESion est une cohorte nationale prospective multicentrique (n>50 centres actifs), multidisciplinaire, recrutant depuis le 1er mai 2019 à la fois des adultes et des enfants, déjà suivis dans le centre ou nouvellement diagnostiqués.Les critères d’éligibilité englobaient le spectre complet des HE/SHE, notamment les HE/SHE réactionnels (HE/SHE-R) secondaires à une infection notamment parasitaire, une hypersensibilité médicamenteuse retardée (HSR), une maladie auto-immune ou inflammatoire, un cancer solide ou une hémopathie, mais aussi le variant lymphoïde (HE/SHE-L), les HE/SHE clonaux ou « myéloïdes » (HE/SHE-M), les SHE idiopathiques (SHE-I), les HE asymptomatiques de signification indéterminée (HE-US), les situations de chevauchements entre SHE et la maladie associée aux IgG4, ou la granulomatose éosinophilique avec polyangéite (GEPA) ANCA-négative (selon les critères adaptés de la classification ACR/EULAR 2022 avec au moins un asthme, et une vascularite clinique et/ou histologiquement prouvée).Chez les patients atteints de SHE-I, les profils évolutifs ont été classés ainsi : (i) profil de « poussée unique » lorsqu’une seule poussée est survenue, traitée ou non, sans rechute ultérieure, (ii) profil de poussées récurrentes avec rémissions lorsqu’il y avait au moins une fois un intervalle de 6 mois sans symptômes entre deux poussées, et (iii) profil de « maladie chronique persistante » quand une corticothérapie au long cours était nécessaire pour éviter les rechutes précoces. Toutes les données ont été saisies et analysées de manière centralisée par les chargé(e)s de projets et attaché(e)s de recherche clinique du CEREO. Résultats Après 54 mois d’activité, 779 patients ont été inclus dans des hôpitaux généraux (20 %), des hôpitaux universitaires (46 %) ou dans un des centres experts du CEREO (34 %).Au moment de l’analyse, 550 cas étaient disponibles pour une analyse centralisée (âge moyen (±ET) : 56±18 ans, 42 % de patientes). Les diagnostics étaient les suivants : SHE idiopathiques (n=258, 47 %), HE/SHE-R (n=87, 16 %), HE-US (n=80, 15 %), HE/SHE-M (n=40, 7 %), HE/SHE-L (n=34, 6 %).Parmi les patients atteints de HE/SHE-R (n=87), les maladies sous-jacentes ou associées étaient une HSR (23 %), une parasitose (22 %), une hémopathie lymphoïde (18 %), un cancer solide (10 %), une maladie inflammatoire chronique (8 %), une mastocytose systémique (6 %) ou d’autres causes (13 %). Par ailleurs, certains patients remplissaient également les critères de la maladie associée aux IgG4 (n=13, 2 %) ou de GEPA ANCA-négative (n=38, 7 %).À la dernière visite, les profils évolutifs des 258 patients atteints de SHE-I étaient les suivants : n=42 (16 %) poussée unique, n=73 (28 %) formes récurrentes et n=119 (46 %) maladies chroniques persistantes. Enfin, 24 (9 %) cas restaient non classés en raison d’un recul insuffisant suite au diagnostic initial. Conclusion La cohorte COHESion est la première étude prospective multicentrique et multidisciplinaire de dimension nationale, collectant des données sur les patients atteints de HE et SHE. Cette cohorte permettra de décrire en détail les différentes formes de SHE, les atteintes d’organes, leur pronostic, et le bénéfice des nouvelles thérapies ciblées disponibles dans les différents variants de HE et SHE. Cette cohorte confirme déjà que les patients atteints de SHE idiopathiques présentent des profils évolutifs différents, suggérant des mécanismes physiopathologiques distincts, et la nécessité de stratégies thérapeutiques personnalisées.

Although eosinophil-induced manifestations can be life-threatening, studies focusing on the epidemiology and clinical manifestations of eosinophilia in the intensive care unit (ICU) are lacking. A retrospective, national, multicenter (14 centers) cohort study over 6 years of adult patients who presented with eosinophilia ≥ 1 × 109/L on two blood samples performed from the day before admission to the last day of an ICU stay. 620 patients (0.9

DEAR EDITOR, Hypereosinophilic syndromes (HESs) are defined by chronic blood hypereosinophilia ≥ 1 5 9 10 cells L 1 and tissue damage related to eosinophilic infiltration. This heterogeneous entity includes neoplastic HES (e.g. chronic eosinophilic leukaemia linked to the FIP1L1:PDGFRA fusion transcript) and reactive HES (parasitic infections, drug reactions and inflammatory and neoplastic diseases). Among the latter, the lymphoid-variant HES is linked to clonal circulating T helper 2 CD4 T cells, most commonly with a CD3 CD4 phenotype. Published series of lymphoid HES remain scarce. Cutaneous T-cell lymphomas (CTCLs) – mycosis fungoides (MF) and S ezary syndrome – are characterized by skin infiltration by clonal T cells. Advanced-stage CTCLs are frequently associated with eosinophilia, linked to interleukin-5 secretion. In S ezary syndrome, the immunophenotypic abnormalities of blood tumour CD4 T cells may include CD7 loss, and CD3 and/or CD4 downregulation. These abnormalities may be found in lymphoid HES. We retrieved suspicious cases of lymphoid HES from the database of the French Reference Center for Hypereosinophilic Syndromes (CEREO). The definition of HES complied with the International Cooperative Working Group on Eosinophil Disorders criteria. CD3 CD4 lymphoid HES was defined by HES and an aberrant blood CD3 CD4 lymphoid population > 0 5% T cells, without any reactive cause of HES or chronic myeloid HES. This study was approved by the local

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.

Eosinophilia-related coronary vasospasm is a diagnosis to consider in patients with chest pain and eosinophilia. Indefinite treatment aiming to normalize absolute eosinophil counts is warranted. In this setting, benralizumab is a promising steroid-free treatment regimen and deserves further investigation.

FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n = 84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99-1,03]; P = .05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; P = .004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM.

Introduction. Cases series of patients with FIP1L1-PDGFRA (F/P)-associated chronic eosinophilic leukemia (F/P+ CEL) are scarce and of small sample-size. Low-dose imatinib mesylate (IM) is highly effective in this setting. Although successful treatment discontinuation has been reported, approximately 40% of the patients subsequently relapse. To date, no predictor of relapse after IM discontinuation has yet been evidenced. Methods. We conducted a French multicentric retrospective of patients diagnosed with F/P+ CEL between 2003-2019. Weight loss was defined as a 10% weight loss over the course of the disease's history. Complete (CHR) and partial (PHR) hematological responses were defined as a normalization of the absolute eosinophil count (AEC) and as a reduction in peripheral blood eosinophilia by at least 50% from baseline, respectively. Relapses were defined as the recurrence of eosinophilia, with or without evidence of F/P-gene transcript, but without any other explanation. Complete molecular response (CMR) was defined as a negative RT-PCR and/or RQ-PCR assay for F/P rearrangement. A backward stepwise logistic regression model was used to identify factors associated with relapse after IM discontinuation. Results. One hundred and fifty F/P+ CEL patients (145 males; mean (SD) age at diagnosis: 49 (+/-12 years) were included, among which 26 (17%) did not report any symptom. The main involved organs were the spleen (n=65, 43%), skin (n=47, 31%), heart (n=27, 18%), lungs (n=36, 24%), central nervous system (n=14, 9%), and bones/joints (n=8, 5%). Four (2,6%) patients showed features of vasculitis, involving the skin (n=2) and the CNS (n=2). The mean peak AEC was 10.3 G/L (+/-6 G/l). Besides eosinophilia, the most frequent associated complete blood count (CBC) abnormalities were thrombocytopenia (n=43, 28%), anemia (n=37, 24%), hyperleukocytosis (n=33, 22%) and monocytosis (n=25, 16%). Forty-seven (31%) patients had normal CBC besides eosinophilia. Bone marrow karyotype was normal in 91% (when tested, n=94). Serum vitamin B12 and tryptase (mean: 2386 (+/-1435) pmol/L and 34 (+/-20) µg/L) levels were elevated in 74 (94%) and 44 (79%) of patients respectively, whereas CRP and IgE levels were elevated in 31 (26%) and 12 (14%) each. None of the 37 (25%) patients that received first-line glucocorticoid therapy achieved CHR. All but 3 patients received IM (daily starting dose: 100 (n= 102; 72%), 200 (n=13; 9%) or 400 mg (n=20; 14%)), of whom 100% and 99% achieved CHR and CMR (when tested: n=84), respectively. The mean follow-up (FU) was 80 (+/- 56) months, with overall survival at 1, 5 and 10 years of 99%, 95% and 84% (reaching 100%, 98% and 89% in the 147 IMB-treated patients) respectively. Overall, 8 (5%) patients died during FU, including untreated patients with acute myeloblastic leukemia transformation (n=2) and a single patient with massive cerebral infarction. Eight patients relapsed during IM tapering, all of which were successfully treated when higher doses of IM were resumed. After a median [IQR] of 44 [27-72] months of IM treatment, 46 (32%) patients eventually discontinued IM, amongst whom 19 (41%) relapsed after a median of 10[4-23] months (42% of relapses defined by PCR). In multivariate analysis, weight loss (HR: 5,02 95%CI[1,9 - 28,04]; p =0,004), the time between onset of eosinophilia and IM initiation (HR 1,02 [1,00 - 1,03]; 0,01) and duration of IM treatment prior to discontinuation (HR: 0,97 [0,95-0,99]; p=0,01) were independent factors of relapse (Table 1). Conclusion. This large cohort further confirms that F/P+ CEL almost exclusively affects male patients, with spleen, skin, heart and lung involvements being the most frequent. While glucocorticoids never lead to the normalization of CBC parameters, IM is highly effective and treated patients carry an excellent prognosis. After IM discontinuation, although 60% of patients maintain CHR overtime, 40% subsequently relapse, with weight loss, time between onset of eosinophilia and IM initiation and duration of IM treatment prior to discontinuation being significant but moderate independent factors of relapse. Disclosures Nicolini: Incyte Biosciences: Honoraria, Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Sun Pharma Ltd: Consultancy. Tavitian:Novartis: Membership on an entity's Board of Directors or advisory committees. Huguet:Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Incyte Biosciences: Honoraria; Amgen: Honoraria; Servier: Honoraria; Jazz Pharmaceuticals: Honoraria. Jardin:Servier: Honoraria; janssen: Honoraria; celgene: Honoraria; roche: Honoraria; amgen: Honoraria.