Acute Eosinophilic Pneumonia (AEP) Due to Daptomycin: Is Autoimmunity a Clinico-Pathophysiologic Bridge to AEP?

Daptomycin induced acute eosinophilic pneumonia is a rare and potentially life threatening condition characterized by rapid respiratory failure, pulmonary infiltrates and eosinophilia. Risk factors for acute eosinophilic pneumonia include smoking, environmental irritants or inhalants and certain medications such as Daptomycin [1]. In this review of literature, we aim to explore the potential triggers for developing acute eosinophilic pneumonia in patients exposed to Daptomycin. The exact immune mechanism for daptomycin induced AEP is unknown, however the current proposed mechanism describes a T helper 2 lymphocyte response to inactivated daptomycin in the pulmonary surfactant, which leads to eosinophilia. Disordered T regulatory cell function is seen in patients with certain cancers, allergies and autoimmune conditions. We propose that patients with these underlying risk factors may be at increased risk of developing AEP after becoming exposed to Daptomycin. Understanding potential risk factors is crucial for health care workers as it allows them to identify susceptible populations, explore preventative measures and treat accordingly.

Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis

BACKGROUND Eosinophilic gastroenteritis(EGE)is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract.Glucocorticoids remain the most common treatment method.However,disease relapse and glucocorticoid dependence remain notable problems.To date,few studies have illuminated the prognosis of EGE and risk factors for disease relapse.AIM To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up.METHODS This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022.Clinical records were collected and analyzed.Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival(RFS).RESULTS EGE showed a median onset age of 38 years and a slight female predominance(56.4%).The main clinical symptoms were abdominal pain(89.1%),diarrhea(61.8%),nausea(52.7%),distension(49.1%)and vomiting(47.3%).Forty-three(78.2%)patients received glucocorticoid treatment,and compared with patients without glucocorticoid treatments,they were more likely to have elevated serum immunoglobin E(IgE)(86.8%vs 50.0%,P=0.022)and descending duodenal involvement(62.8%vs 27.3%,P=0.046)at diagnosis.With a median follow-up of 67 mo,all patients survived,and 56.4%had at least one relapse.Six variables at baseline might have been associated with the overall RFS rate,including age at diagnosis<40 years[hazard ratio(HR)2.0408,95%confidence interval(CI):1.0082–4.1312,P=0.044],body mass index(BMI)>24 kg/m^(2)(HR 0.3922,95%CI:0.1916-0.8027,P=0.014),disease duration from symptom onset to diagnosis>3.5 mo(HR 2.4725,95%CI:1.220-5.0110,P=0.011),vomiting(HR 3.1259,95%CI:1.5246-6.4093,P=0.001),total serum IgE>300 KU/L at diagnosis(HR 0.2773,95%CI:0.1204-0.6384,P=0.022)and glucocorticoid treatment(HR 6.1434,95%CI:2.8446-13.2676,P=0.003).CONCLUSION In patients with EGE,younger onset age,longer disease course,vomiting and glucocorticoid treatment were risk factors for disease relapse,whereas higher BMI and total IgE level at baseline were protective.

Animal models of eosinophilic esophagitis,review and perspectives

Eosinophilic oesophagitis(EoE)is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction.Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response,the exact pathogenesis is complex,and the efficacy of existing treatments is unsatisfactory.Therefore,the study of the pathophysiological process of EOE has received increasing attention.Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents.To maximize the use of existing animal models of EOE,it is important to understand the advantages or limitations of each modeling approach.This paper systematically describes the selection of experimental animals,types of allergens,and methods of sensitization and excitation during the preparation of animal models of EoE.It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.

Chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease:Correlations with blood eosinophil level

Objective To observe the correlations of chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)with blood eosinophil(EOS)level.Methods Chest CT data of 162 AECOPD patients with elevated eosinophils were retrospectively analyzed.The patients were divided into low EOS group(n=105)and high EOS group(n=57)according to the absolute counting of blood EOS.The quantitative CT parameters,including the number of whole lung bronchi and the volume of blood vessels,low-attenuation area percentage(LAA%)of whole lung,of left/right lung and each lobe of lung,as well as the luminal diameter(LD),wall thickness(WT),wall area(WA)and WA percentage of total bronchial cross-section(WA%)of grade 3 to 8 bronchi were compared between groups.Spearman correlations were performed to analyze the correlations of quantitative CT parameters with blood EOS level.Results LAA%of the whole lung,of the left/right lung and each lobe of lung,as well as of the upper lobe of right lung LD grade 4,middle lobe of right lung WT grade 5,upper lobe of right lung WA grade 4,middle lobe of right lung WA grade 5 and lower lobe of left lung WA grade 3 in low EOS group were all higher than those in high EOS group(all P<0.05).Except for the upper lobe of right lung LD grade 4,the above quantitative CT indexes being significant different between groups were all weakly and negatively correlated with blood EOS level(r=-0.335 to-0.164,all P<0.05).Conclusion Chest CT quantitative parameters of AECOPD patients were correlated with blood EOS level,among which LAA%,a part of WT and WA were all weakly negatively correlated with blood EOS level.

Eosinophilic solid and cystic renal cell carcinoma with aggressive behavior:Two case reports

BACKGROUND Eosinophilic solid and cystic(ESC)renal cell carcinoma(RCC),a unique and emerging subtype of RCC,has an indolent nature;in some rare instances,it may exhibit metastatic potential.Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices.CASE SUMMARY Herein,we report two patients with ESC RCC.Patient 1 was a young woman with classical pathological characteristics.Patient 2 was a 52-year-old man with multifocal metastases,involving the pulmonary hilar and mediastinal lymph nodes,liver,brain,mesosternum,vertebra,rib,femur,and symphysis pubis.Awareness of ESC RCC,along with its characteristic architecture and immunophenotype,would contribute to making a definitive diagnosis,even on core biopsy samples.CONCLUSION The discovery of ESC RCC molecular signatures may provide new therapeutic strategies in the future.

Human Eosinophil Cell Manipulation by Optical Tweezers

In this work, lateral deformation of human eosinophil cell during the lateral indentation by an optically trapped microbead of diameter 4.5 µm is studied. The images were captured using a CCD camera and the Boltzmann statistics method was used for force calibration. Using the Hertz model, we calculated and compared the elastic moduli resulting from the lateral force, showing that the differences are important and the force should be considered. Besides the lateral component, the setup also allows us to examine the lateral cell-bead interaction. The mean values of the properties obtained, in particular the elastic stiffness and the shear stiffness, were Eh = (37.76 ± 2.85) µN/m and Gh = (12.57 ± 0.32) µN/m. These results show that the lateral indentation can therefore be used as a routine method for cell study, because it enabled us to manipulate the cell without contact with the laser.

Evolving strategies: Enhancements in managing eosinophilic esophagitis in pediatric patients

Eosinophilic esophagitis is a newly recognized disease first described about 50 years ago.The definition,diagnosis,and management have evolved with new published consensus guidelines and newly approved treatment available to pediatricians,enabling a better understanding of this disease and more targeted treatment for patients.We describe the definition,presentation,and diagnosis of eosinophilic esophagitis including management,challenges,and future directions in children.The definition,diagnosis,and management of eosinophilic esophagitis have evolved over the last 50 years.Consensus guidelines and newly approved biologic treatment have enabled pediatricians to better understand this disease and allow for more targeted treatment for patients.We describe the definition,presentation,diagnosis,management,and treatment in addition to the challenges and future directions of eosinophilic esophagitis management in children.

Clinical Research Progress of Peripheral Blood Eosinophils in Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease(COPD)accounts for one of the major health and economic burdens worldwide.As a heterogeneous disease,the underlying inflammatory pattern of COPD differs from the previously thought neutrophil-dominated inflammation,with eosinophilic inflammation occupying approximately one third of stable COPD.Although the eosinophil(EOS)threshold associated with clinical relevance in patients with COPD is currently debated,eosinophil count can be used as a biomarker to guide treatment and to assess the risk of acute exacerbations of COPD,the efficacy of inhaled corticosteroids,and clinical outcomes.The purpose of this review is to describe the biological characteristics of eosinophils and the related research progress as clinical biomarkers.

Development of Henoch-Schoenlein purpura in a child with idiopathic hypereosinophilia syndrome with multiple thrombotic onset: A case report

BACKGROUND The incidence of pulmonary embolism(PE) in children is low, but its mortality is high. Hypereosinophilic syndrome(HES) is a group of diseases caused by an abnormal increase in eosinophilic granulocytes resulting in multiple-organ dysfunction. The urgent event of thromboembolism in the pulmonary region provoked by eosinophils in idiopathic HES(IHES) is relatively unusual. This article reports a case of IHES with multiple PEs and left leg venous thrombosis as the first manifestation. One month later, the patient developed Henoch-Schonlein purpura(HSP), which is very rare.CASE SUMMARY We report the case of a 12-year-old boy who was admitted to the hospital with dyspnea, left leg pain, and aggravation. He had bilateral PE and left leg venous embolism with mild eosinophilia. Low-molecular-weight heparin and urokinase were given. At the same time, the interventional department was contacted about filter implantation, followed by urokinase thrombolysis. The left leg thrombus was aspirated under ultrasound guidance. He was discharged from the hospital on rivaroxaban. One month later, he developed a rash on both legs and ankle pain consistent with HSP, with severe eosinophilia and motor and sensory disturbances. The patient was diagnosed with IHES with multiple embolisms complicated by HSP after excluding other causes of the eosinophil elevation. After glucocorticoid treatment, the symptoms were relieved, but the patient later developed purpura nephritis.CONCLUSION We report a rare and life-threatening case of IHES with multiple embolisms associated with HSP.A mild elevation of eosinophils early in the disease leads to difficulties in diagnosis and delayed treatment.

Imipenem/cilastatin-induced acute eosinophilic pneumonia:A case report

Rationale:Acute eosinophilic pneumonia(AEP)is an acute pulmonary illness caused by eosinophilic infiltration of the lung parenchyma.It can happen after using drugs such as daptomycin and minocycline.AEP induced by imipenem/cilastatin is a rare condition.Patient’s Concern:A 45-year-old male patient,who previously suffered from a urinary tract infection and treated with imipenem/cilastatin antibiotic,was presented to us with acute respiratory distress,soon after the initiation of the antibiotic.Computed tomography identified pulmonary infiltrates in the upper and middle lung fields and eosinophils were found to account for 36%of differential count of the broncho-alveolar lavage fluid.He also developed peripheral eosinophilia as the disease progressed.Diagnosis:AEP,secondary to imipenem/cilastatin therapy.Interventions:Steroid therapy was administered and imipenem/cilastatin antibiotic was discontinued.Outcomes:The patient improved completely following the therapy and had clear lung fields on follow-up.Lessons:Imipenem/cilastatin is an uncommon cause of AEP and requires close monitoring during therapy.

Adult eosinophilic esophagitis and advances in its treatment

Eosinophilic esophagitis(EoE)is a chronic eosinophil inflammation that seems to be T helper type 2 antigen-driven.The disease is one of several eosinophilic gastrointestinal disorders in which there appears to be inflammation of the gastrointestinal tract without any apparent underlying causes.Differential diagnosis needs to be made with gastroesophageal reflux,which is characterized by chronic inflammation due to gastric refluxate from disorders related to motility.EoE,however,is considered a chronic allergic inflammatory disorder related to destructive tissue remodeling.There seems to be a higher prevalence of EoE in Western countries.It is typically found in atopic male individuals.Physiopathological risk factors include atopy,environmental factors,esophageal epithelial barrier dysfunctions,etc.EoE can cause several symptoms that include retrosternal burning sensation,dysphagia,food impaction,chronic reflux symptoms,nausea,and vomiting.Early diagnosis,which requires a biopsy to assess for esophageal inflammation,is essential for proper treatment.The aim of our brief overview is to summarize the current literature regarding the characteristics,diagnosis,complications,mechanisms of pathology,clinical features,influence of comorbidities,and treatment in patients with EoE.

Eosinophil disorders:an update on diagnosis and management

Eosinophilia can be seen in almost all medical subspecialty patients.Delay in diagnostic workup and treatment is associated with significant morbidity and mortality.Clinical vigilance and timely referral for diagnostic evaluation are critical.Causes of hypereosinophilia(HE)are diverse and can be grouped under 3 categories:primary(neoplastic),secondary(reactive),and idiopathic.Advances in molecular genetic diagnostics have led to elucidation of the genetic basis formany neoplastic hypereosinophilic disorders.One commonmolecular feature is formation of a fusion gene,resulting in the expression of an aberrantly activated tyrosine kinase(TK).TheWorld Health Organization endorsed a biologically oriented classification scheme and created a new major disease category,namely,myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions.Rearrangement of other TK genes and activating somatic mutation(s)in TK genes have also been reported in eosinophilic neoplasms.Diagnostic evaluation of HE involves a combination of clinical,histopathologic,and immunophenotypic analyses,as well as molecular genetic testing,including next-generation sequencing–based mutation panels.The management of primary HE is largely guided by the underlying molecular genetic abnormalities.Good knowledge of recent advances in HE is necessary to ensure timely and accurate diagnosis and to help optimize patient care.

Unusual presentations of eosinophilic gastroenteritis:Case series and review of literature

Eosinophilic gastroenteritis (EG) is an uncommon disease characterized by focal or diffuse eosinophilic infiltration of the gastrointestinal tract, and is usually associated with dyspepsia, diarrhea and peripheral eosinophilia. Diffuse gastrointestinal tract and colonic involvement are uncommon. The endoscopic appearance may vary from normal to mucosal nodularity and ulceration. Gastrointestinal obstruction is unusual and is associated with predominantly muscular disease. We present five unusual cases of EG associated with gastric outlet and duodenal obstruction. Two cases presented with acute pancreatitis and one had a history of pancreatitis. Four cases responded well to medical therapy and one had recurrent gastric outlet obstruction that required surgery. Four out of the five cases had endoscopic and histological evidence of esophagitis and two had colitis. Two patients had ascites. These cases reaffirm that EG is a disorder with protean manifestations and may involve the entire gastrointestinal tract. Gastric outlet and/or small bowel obstruction is an important though uncommon presentation of EG. It may also present as esophagitis, gastritis with polypoid lesions, ulcers or erosions, colitis and pancreatitis and may mimic malignancy.

Adult eosinophilic gastroenteritis and hypereosinophilic syndromes

Eosinophilic gastroenteritis (EGE) in the adult is a distinctive pathologically-based disorder characterized by an eosinophil-predominant mucosal inflammatory process. Most often,the disorder is detected during endoscopic investigation for abdominal pain or diarrhea. Other causes of gastric and intestinal mucosal eosinophilia require exclusion,including parasitic infections and drug-induced causes. Occasionally,the muscle wall or serosal surface may be involved. EGE appears to be more readily recognized,in large part,due to an evolution in the imaging methods used to evaluate abdominal pain and diarrhea,in particular,endoscopic imaging and mucosal biopsies. Def inition of EGE,however,may be diffi cult,as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not well standardized. Also,the eosinophilic inflammatory process may be either patchy or diffuse and the detection of the eosinophilic infiltrates may vary depending on the method of biopsy fixation. Treatment has traditionally focused on resolution of symptoms,and,in some instances,eosinophil quantification in pre-treatment and post-treatment biopsies. Future evaluation and treatment of EGE may depend on precise serological biomarkers to aid in defi nition of the long-term natural history of the disorder and its response to pharmacological or biological forms of therapy.

Eosinophilic fasciitis difficult to differentiate from scleroderma:A case report

BACKGROUND Eosinophilic fasciitis(EF)is a rare connective tissue disease that can cause swelling and sclerosis of the extremities,and special attention is needed to differentiate EF from systemic sclerosis.Misdiagnosis or omission markedly delays treatment of EF,and severe skin sclerosis in advanced stages can cause joint contracture and tendon retraction,worsening the patient's prognosis and quality of life.CASE SUMMARY We report a case of EF in a young woman diagnosed by tissue biopsy,confirming the difficulty of differential diagnosis with scleroderma.CONCLUSION Focusing on skin manifestations,completing tissue biopsy and radiography can help diagnose EF effectively.Clinicians should enhance their understanding of the differences between EF and scleroderma,and early diagnosis and standardized treatment can improve the prognosis of patients with EF.

Eosinophilic enteritis requiring differentiation from chronic enteropathy associated with SLCO2A1 gene:A case report

BACKGROUND Eosinophilic gastrointestinal disease(EGID)is a disorder characterized by infiltration of eosinophils causing mucosal damage and dysfunction of the gastrointestinal tract.The endoscopic findings of eosinophilic enteritis(EoN),an EGID variant,are nonspecific and occasionally difficult to diagnose.In contrast,chronic enteropathy associated with SLCO2A1(CEAS)is a chronic persistent small intestinal disorder characterized by endoscopic findings such as multiple oblique and circular ulcers.CASE SUMMARY We report the case of a 10-year-old boy who had suffered abdominal pain and fatigue for the preceding 6 mo.He was referred to our institute for investigation of suspected gastrointestinal bleeding because of severe anemia with hypoproteinemia and positive fecal human hemoglobin.The upper and lower gastrointestinal endoscopic findings were normal;however,double-balloon small bowel endoscopy showed multiple oblique and circular ulcers with discrete margins and mild constriction of the intestinal lumen in the ileum.The findings were highly consistent with CEAS,but urine prostaglandin metabolites were within normal limits,and no previously reported mutations in the SLCO2A1 gene were identified.Histological evaluation demonstrated moderate to severe eosinophilic infiltration localized to the small intestine suggesting a diagnosis of EoN.Clinical remission was maintained with montelukast and a partial elemental diet,but emergent surgery for bowel obstruction due to small intestinal stenosis was performed two years after the initial treatment.CONCLUSION EoN should be considered in the differential diagnosis of CEAS-like small intestinal ulcerative lesions and normal urinary prostaglandin metabolite levels.

Diagnostic role of fractional exhaled nitric oxide in pediatric eosinophilic esophagitis, relationship with gastric and duodenal eosinophils

BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.

Posterior pedicle screw fixation combined with local steroid injections for treating axial eosinophilic granulomas and atlantoaxial dislocation:A case report

BACKGROUND Eosinophilic granuloma(EG)is a proliferative condition that affects the cells of bone tissue.There are no specific clinical signs or imaging manifestations in the early stages of the disease,making it simple to overlook and misdiagnose.Because of the disease's rarity,there is presently no standardized treatment principle.There are few accounts of such occurrences affecting the axis among children.We discovered a case of a child whose EG resulted in atlantoaxial joint dislocation and destruction of the axial bone.CASE SUMMARY After having pharyngeal discomfort for more than six months without a clear explanation,a 6-year-old boy was brought to our hospital.Following a careful evaluation,the pathology indicated a strong likelihood of an axial EG.Ultimately,we decided to treat the boy with posterior pedicle screw fixation and local steroid injections.CONCLUSION EGs of the upper cervical spine are quite uncommon in children,and they are exceedingly easy to overlook or misdiagnose.Posterior pedicle screw fixation and local steroid injections are effective treatments for patients with axial EGs affecting the atlantoaxial junction.

Endoscopic Classification of Esophagic Eosinophilia

Introduction： EoE （eosinophilic esophagitis） is an inflammatory condition characterized by a dense eosinophilic infiltrate in the esophageal epithelium. In Brazil, it remains a poorly diagnosed disease due to the lack of interaction between the clinician, the endoscopist, and the pathologist. The diagnosis is performed by histological study of esophageal biopsies, with at least fifteen eosinophils per high-power field （EOS/HPF）. Some doubts remain with respect to patients with a clinical picture and symptoms compatible with the disease （EoE）, but who have a lower number of eosinophils than established. The main objective of this study was to create an endoscopic classification for EsEo （esophageal eosinophilia）, which pointed the way to the endoscopist towards the diagnosis. Methods： This study was a prospective, two-year study, at a gastrointestinal endoscopy center where all patients with endoscopic symptoms and/or endoscopic findings suggestive of EsEo were biopsied for histological examination of EOS/HPF. After the study and compilation of the results, a retrospective study was performed, based on a review of electronic medical records, where the same diagnosis was searched, although at a period when this classification was not adopted. Results： A total of 4,251 endoscopies were performed between September 2011 and September 2013. Two biopsies were performed, aimed at lesions, in 133 patients with clinical picture or imaging suggestive of EsEo. Eosinophils were found in 55 patients, corresponding to an incidence of 1.29% of the total population studied and 41.35% of the suspected cases of the disease. EoE was diagnosed in 24 patients during the period of this study. In the two-year retrospective study, only two cases of EoE were found. Conclusions： The results of this study demonstrate that the endoscopic standardization of esophageal lesions, suggestive of eosinophilia, in this case by classification, alerts the endoscopist for the diagnosis of EoE, prompting him to perform targeted biopsies. Further, it was observed that two samples of esophageal tissue were sufficient for the diagnosis. The relationship between the clinical picture, endoscopy, and histology was not evident in this study.

A Fatal Case of Chronic Eosinophilic Leukemia Not Otherwise Specified (CEL-NOS) in a 19-Year-Old Male with Acute Transformation into Blast Crisis

Chronic eosinophilic leukemia (CEL) is a rare disorder that is characterized by hypereosinophilia with increased number of blood or marrow blasts (>5% and <20%). CEL is distinguished from hypereosinophilic syndrome (HES) by the presence of eosinophilic clonality. Chronic eosinophilic leukemia not otherwise specified (CEL-NOS) diagnosis is made when no fusion genes are detected by most modern molecular testing, particularly the most common fusion gene FIP1L-1/PDGFRA (Factor Interacting with PAP like-1/Platelet-Derived Growth Factor Receptor Alpha). This disease is very rare, and its description in the literature is not well characterized. We report a fetal case of severe CEL-NOS in a 19-year-old male who presented with a plethora of clinical features consists of constitutional symptoms, pancytopenia, intravascular thrombosis, acute stroke and endomyocardial infiltrates. The course of his disease was aggressive and resistant to conventional treatment. After a short period of improvement, an acute transformation into blast crisis (BC) had occurred. The diagnosis was confirmed by morphology and immunophenotyping of bone marrow biopsy. The patient eventually died of heart failure and sepsis. To our knowledge this is the first case report of fatal CEL-NOS transforming into severe blast crisis.