Case Report of Chronic Eosinophilic Leukemia Associated with Long-Term Use of Infliximab

Article Information

William Morse; MD1*, Haroon Nawaz; MD2, Cynthia Lopez; MD3, Farhad Sanati; MD3

1Palmetto General Hospital, Hialeah, Florida, USA

2Westside Regional Medical Center, Plantation, Florida, USA

3Larkin Community Hospital, Florida, USA

*Corresponding Author: William Morse, Palmetto General Hospital, 2001 W 68th St, Hialeah, FL 33016, USA

Received: 15 December 2023; Accepted: 03 January 2024; Published: 15 January 2024

Citation: William Morse, Haroon Nawaz, Cynthia Lopez, Farhad Sanati. Case Report of Chronic Eosinophilic Leukemia Associated with Long-Term Use of Infliximab. Archives of Clinical and Medical Case Reports 8 (2024): 10-12.

View / Download Pdf Share at Facebook

Abstract

Hypereosinophilic syndrome (HES) is a rare condition in which the quantity of eosinophils in the body’s blood and tissues increases substantially. Hypereosinophilic syndrome can often go underdiagnosed as the symptoms such as cough, malaise, chills, night sweat, and flulike symptoms can often be attributed to allergic causes. We present a patient who has been diagnosed with Hypereosinophilic syndrome, later determined to be chronic eosinophilic leukemia, after long-term treatment with infliximab for ulcerative colitis. Follow-up immunochemistry showed that discontinuation of infliximab improved the polyclonality of eosinophils in our patient. Further research and reported cases will help us better understand this relationship.

Keywords

Hypereosinophilic Syndrome; Chronic Eosinophilic Leukemia; Infliximab; imatinib; Bone Marrow Biopsy; Diagnosis; Epidemiology; Chemotherapy.

Hypereosinophilic Syndrome articles; Chronic Eosinophilic Leukemia articles; Infliximab articles; imatinib articles; Bone Marrow Biopsy articles; Diagnosis articles; Epidemiology articles; Chemotherapy articles.

Hypereosinophilic Syndrome articles Hypereosinophilic Syndrome Research articles Hypereosinophilic Syndrome review articles Hypereosinophilic Syndrome PubMed articles Hypereosinophilic Syndrome PubMed Central articles Hypereosinophilic Syndrome 2023 articles Hypereosinophilic Syndrome 2024 articles Hypereosinophilic Syndrome Scopus articles Hypereosinophilic Syndrome impact factor journals Hypereosinophilic Syndrome Scopus journals Hypereosinophilic Syndrome PubMed journals Hypereosinophilic Syndrome medical journals Hypereosinophilic Syndrome free journals Hypereosinophilic Syndrome best journals Hypereosinophilic Syndrome top journals Hypereosinophilic Syndrome free medical journals Hypereosinophilic Syndrome famous journals Hypereosinophilic Syndrome Google Scholar indexed journals Syndrome articles Syndrome Research articles Syndrome review articles Syndrome PubMed articles Syndrome PubMed Central articles Syndrome 2023 articles Syndrome 2024 articles Syndrome Scopus articles Syndrome impact factor journals Syndrome Scopus journals Syndrome PubMed journals Syndrome medical journals Syndrome free journals Syndrome best journals Syndrome top journals Syndrome free medical journals Syndrome famous journals Syndrome Google Scholar indexed journals Chronic Eosinophilic Leukemia articles Chronic Eosinophilic Leukemia Research articles Chronic Eosinophilic Leukemia review articles Chronic Eosinophilic Leukemia PubMed articles Chronic Eosinophilic Leukemia PubMed Central articles Chronic Eosinophilic Leukemia 2023 articles Chronic Eosinophilic Leukemia 2024 articles Chronic Eosinophilic Leukemia Scopus articles Chronic Eosinophilic Leukemia impact factor journals Chronic Eosinophilic Leukemia Scopus journals Chronic Eosinophilic Leukemia PubMed journals Chronic Eosinophilic Leukemia medical journals Chronic Eosinophilic Leukemia free journals Chronic Eosinophilic Leukemia best journals Chronic Eosinophilic Leukemia top journals Chronic Eosinophilic Leukemia free medical journals Chronic Eosinophilic Leukemia famous journals Chronic Eosinophilic Leukemia Google Scholar indexed journals Leukemia articles Leukemia Research articles Leukemia review articles Leukemia PubMed articles Leukemia PubMed Central articles Leukemia 2023 articles Leukemia 2024 articles Leukemia Scopus articles Leukemia impact factor journals Leukemia Scopus journals Leukemia PubMed journals Leukemia medical journals Leukemia free journals Leukemia best journals Leukemia top journals Leukemia free medical journals Leukemia famous journals Leukemia Google Scholar indexed journals Infliximab articles Infliximab Research articles Infliximab review articles Infliximab PubMed articles Infliximab PubMed Central articles Infliximab 2023 articles Infliximab 2024 articles Infliximab Scopus articles Infliximab impact factor journals Infliximab Scopus journals Infliximab PubMed journals Infliximab medical journals Infliximab free journals Infliximab best journals Infliximab top journals Infliximab free medical journals Infliximab famous journals Infliximab Google Scholar indexed journals treatment articles treatment Research articles treatment review articles treatment PubMed articles treatment PubMed Central articles treatment 2023 articles treatment 2024 articles treatment Scopus articles treatment impact factor journals treatment Scopus journals treatment PubMed journals treatment medical journals treatment free journals treatment best journals treatment top journals treatment free medical journals treatment famous journals treatment Google Scholar indexed journals CT articles CT Research articles CT review articles CT PubMed articles CT PubMed Central articles CT 2023 articles CT 2024 articles CT Scopus articles CT impact factor journals CT Scopus journals CT PubMed journals CT medical journals CT free journals CT best journals CT top journals CT free medical journals CT famous journals CT Google Scholar indexed journals surgery articles surgery Research articles surgery review articles surgery PubMed articles surgery PubMed Central articles surgery 2023 articles surgery 2024 articles surgery Scopus articles surgery impact factor journals surgery Scopus journals surgery PubMed journals surgery medical journals surgery free journals surgery best journals surgery top journals surgery free medical journals surgery famous journals surgery Google Scholar indexed journals Bone Marrow Biopsy articles Bone Marrow Biopsy Research articles Bone Marrow Biopsy review articles Bone Marrow Biopsy PubMed articles Bone Marrow Biopsy PubMed Central articles Bone Marrow Biopsy 2023 articles Bone Marrow Biopsy 2024 articles Bone Marrow Biopsy Scopus articles Bone Marrow Biopsy impact factor journals Bone Marrow Biopsy Scopus journals Bone Marrow Biopsy PubMed journals Bone Marrow Biopsy medical journals Bone Marrow Biopsy free journals Bone Marrow Biopsy best journals Bone Marrow Biopsy top journals Bone Marrow Biopsy free medical journals Bone Marrow Biopsy famous journals Bone Marrow Biopsy Google Scholar indexed journals Epidemiology articles Epidemiology Research articles Epidemiology review articles Epidemiology PubMed articles Epidemiology PubMed Central articles Epidemiology 2023 articles Epidemiology 2024 articles Epidemiology Scopus articles Epidemiology impact factor journals Epidemiology Scopus journals Epidemiology PubMed journals Epidemiology medical journals Epidemiology free journals Epidemiology best journals Epidemiology top journals Epidemiology free medical journals Epidemiology famous journals Epidemiology Google Scholar indexed journals

Article Details

1. Introduction

Hypereosinophilic syndrome (HES) is a rare disorder in which there is an unidentified increase in the number of eosinophils in the blood and tissues throughout the body. The criteria to determine this syndrome include eosinophilia (≥1500/mm3) in the blood for greater than six months, no evidence indicating there may be a parasitic infection, allergic reaction, or any other common cause of eosinophilia, and signs that systemic organs may be involved depending on the patients presenting symptoms [1]. Two variants of Hypereosinophilic syndrome have been identified with varying underlying etiology. These subtypes are known as the lymphocytic variant and the myeloproliferative variant of chronic eosinophilic leukemia [2]. Hypereosinophilic syndrome primarily occurs in persons between the ages of 20 and 50, more often in males than females, though cases have been rising in the children and infant population [3]. Though, there is a lack of population-based data, the incidence of Hypereosinophilic syndrome reported by the Surveillance, Epidemiology, and End Results (SEER) database is known to range from 0.3 to 6.3 per 100,000 [4]. Clinical manifestations of the syndrome present similarly in all ages, with the most common presenting symptoms including rash, myalgias, fatigue, cough, dyspnea, and retinal lesions [5]. We present a patient diagnosed with Hypereosinophilic syndrome, later determined to be chronic eosinophilic leukemia, after long-term treatment with infliximab for ulcerative colitis.

2. Case Presentation

A 44-year-old male presents to the office with a past medical history of ulcerative colitis for seven years. The patient was actively treated with infliximab and mercaptopurine for the past seven years. The patient presented with a cough, malaise, chills, night sweat, and flu-like symptoms. Initially, the patient was treated for possible allergic bronchitis as he has a history of allergies without any improvement. On lab results, complete blood count was increased. White blood cell count was increased to 30,000 with predominant eosinophilia. Computerized Tomography (CT) scan of the chest with contrast showed bilateral apical infiltrates with no adenopathy or mass. Computerized Tomography scan of abdomen and pelvis did not show any hepatosplenomegaly. Bone marrow biopsy showed hypercellular bone marrow with trilineage hematopoiesis and markedly increased eosinophils. The blast cells were less than 1 percent. Surprisingly, a peripheral molecular panel of myeloproliferative disease showed positive platelet-derived growth factor receptor A (PDGFRA), and myeloproliferative leukemia mutation (MPL) was positive, suggesting a diagnosis of chronic eosinophilic leukemia. The patient was receiving infliximab every two months for several years and was suspected as the cause of leukemia. After stopping infliximab and initiating the treatment with imatinib, the patient’s condition improved significantly. A follow up immunohistochemistry was performed and showed polyclonal plasma cells rather than monoclonal. This confirmed our suspicion that the chronic eosinophilic leukemia in our patient was associated with chronic use of infliximab.

3. Discussion

According to the World Health Organization (WHO), the clinical course of Hypereosinophilic syndrome may affect various organs, with dermatologic involvement reported being the highest (69%), followed by pulmonary (44%), gastrointestinal (38%), and cardiac-related issues (20%) respectively [6]. Eosinophils are known to develop from CD34+ hematopoietic stem cells along the myeloid lineage. The cytokine network typically controls the eosinophil levels throughout the body’s tissues and organs. When there is an imbalance, T-cells, mast cells, and stromal cells are triggered to release cytokines such as Interleukin-5, Interleukin-3, and granulocyte-macrophage-colony-stimulating factor, and platelet-derived growth factor (PDGF), resulting in exponential growth and activation of eosinophils. This results in a vicious cycle as the activated eosinophils release their own mediators stored in granules to promote growth, negatively influencing homeostasis. The active molecules can damage the surrounding environment leading to fibrosis and thrombosis in various organs [7]. Since there is a likelihood that hypereosinophilic syndrome can affect many organ systems, the diagnostic workup should be thorough and catered to the presenting symptoms of the patient. After taking a careful history and physical exam, a complete blood count with differentials, routine chemistries, electrocardiogram, echocardiogram, pulmonary function tests, chest X-ray, ultrasound or computed tomography, bone marrow aspirate, and tissue biopsies may be ordered. Given the other known causes of an increased number of eosinophils, tests can also be ordered to rule out infection by blood culture, stool culture, serological studies (for human immunodeficiency virus, cytomegalovirus, Epstein barre virus, hepatitis B virus, hepatitis C virus), and imaging studies if necessary [8]. For acute intervention in severe cases, it is essential to treat with a single stat dose of a high-dose glucocorticoid such as prednisone or methylprednisolone once the possibility of a parasitic infection has been ruled out. If unable to rule out a parasitic infection, ivermectin should be administered along with the steroid to prevent possible strongyloides hyper-infection syndrome. After two days, if no sufficient improvement is seen in the hypereosinophilic syndrome or clinical symptoms, second-line treatment should be added to the patient's regimen, such as imatinib for the myeloproliferative variant, until their absolute eosinophil counts have improved. Studies have shown that imatinib, a tyrosine kinase receptor inhibitor, has high efficacy for hypereosinophilic syndrome and other related chronic myeloid disorders [9]. Though asymptomatic patients do not require treatment, they must be closely monitored to avoid organ damage [10].

4. Conclusion

We report a severely underreported association between infliximab and monoclonal proliferation, leading to, in our case, chronic eosinophilic leukemia. We recommend clinicians remain vigilant regarding symptoms of hypereosinophilic syndrome in long-term users of infliximab. Depending on lab results, additional immunochemistry workup may be necessary to determine monoclonality if leukemia is suspected. Following discontinuation of infliximab and appropriate treatment initiation, an increase in polyclonality may substantiate the suspicion of leukemia secondary to infliximab. We hope that further research and cases are reported in the literature to understand this relationship better.

Funding:

None

Competing interests: None

Ethics approval and consent to participate: Approved informed consent.

Consent for publication: Approved verbal informed consent. Approved by Westside Regional Medical Center and Northwest Medical Center. All authors approved manuscript.

Availability of data and material: The datasets generated and/or analyzed during the current study are not publicly available due to HIPAA but are available from the corresponding author on reasonable request, if permissible by patient.

Authors' contributions:

‘WM’ was a major contributor in the writing of the manuscript. ‘HN’ oversaw the patient with the attending physician and contributed to the editing of the paper. ‘A.A.C’ helped with the interpretation of the patient data. All authors approved the final manuscript.

Acknowledgements:

Not applicable

References

  1. Alan Paul Knutsen, James Temprano, Deepika Bhatla, et al. Hypersensitivity Pneumonitis and Eosinophilic Lung Diseases, Kendig's Disorders of the Respiratory Tract in Children, Elsevier (2019): 944-967.
  2. Alan P Knutsen, James Temprano, Jamie L Wooldridge, et al. Deterding, Felix Ratjen, Kendig & Chernick's Disorders of the Respiratory Tract in Children, W.B. Saunders (2012): 858-876.
  3. Animesh Pardanani, Terra Reeder, Luis Porrata F, Chin-Yang Li, Henry Tazelaar D, et al. Ayalew Tefferi; Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders. Blood 101 (2003): 3391-3397.
  4. Crane MM, Chang CM, Kobayashi MG, Weller PF. Incidence of myeloproliferative hypereosinophilic syndrome in the United States and an estimate of all hypereosinophilic syndrome incidence. J Allergy Clin Immunol 126 (2010): 179-181.
  5. Helbig G, Wieczorkiewicz A, Dziaczkowska-Suszek J, Majewski M, Kyrcz-Krzemien S. T-cell abnormalities are present at high frequencies in patients with hypereosinophilic syndrome. Haematol 94 (2009): 1236-1241.
  6. Ogbogu PU, Bochner BS, Butterfield JH, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol 124 (2006): 1319-25.
  7. Schuster B, Zink A, Eyerich K. Medical algorithm: Diagnosis and treatment of hypereosinophilic syndrome. Allergy 75 (2020): 3003-3006.
  8. Shomali W, Gotlib J. World Health Organization-defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management. Am J Hematol 94 (2019): 1149-1167.
  9. Simon H-U, Rothenberg ME, Bochner BS, et al. Refining the definition of hypereosinophilic syndrome. J Allergy Clin Immun 126 (2010): 45-49.
  10. Valent P, Klion AD, Horny H-P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immun 130 (2012): 607-612.

© 2016-2024, Copyrights Fortune Journals. All Rights Reserved