Worsening hypereosinophilia with use of dupilumab

Eosinophils are white blood cells originating from the granulocytic lineage which mature in the bone marrow under the influence of interleukin (IL)-5, IL-3, and granulocyte-macrophage colony-stimulating factor. The eosinophils then migrate to the peripheral blood but predominantly reside in tissues such as the spleen, lymph nodes, thymus, and digestive tract. They normally account for 1% to 6% of leukocytes. An increase in eosinophils in the peripheral blood or tissues can result from pathologic conditions that vary from allergic rhinitis, asthma, and drug hypersensitivity to vasculitis, eosinophilic pneumonia, and hypereosinophilic syndrome (HES). Eosinophilia is also common in helminth infections. 1 Khoury P Akuthota P Weller PF Klion AD. Eosinophilia and eosinophil-related disorders. in: Burks AW Holgate ST Middleton's Allergy Principles and Practice. 9th ed. Elsevier, Amsterdam2020: 1197-1212 Google Scholar Eosinophilia is defined as an absolute eosinophil count (AEC) of greater than or equal to 500 eosinophils/μL, hypereosinophilia is defined as AEC greater than or equal to 1500 eosinophils/μL, and HES is defined as greater than or equal to 1500 eosinophils/μL on 2 occasions greater than or equal to 1 month apart with organ dysfunction attributable to eosinophilia or tissue eosinophilia in the setting of blood eosinophilia with evidence of organ dysfunction attributable to eosinophilia. 1 Khoury P Akuthota P Weller PF Klion AD. Eosinophilia and eosinophil-related disorders. in: Burks AW Holgate ST Middleton's Allergy Principles and Practice. 9th ed. Elsevier, Amsterdam2020: 1197-1212 Google Scholar The differential for eosinophilia is wide and can be challenging to approach. Allergic diseases and asthma are typically associated with mild eosinophilia (<1000 cells/μL of the blood). Drug hypersensitivity is another common cause of eosinophilia, and the eosinophilia in these cases can range from mild to severe. Infections can present with eosinophilia, especially parasitic infections such as strongyloidiasis, which occurs worldwide and can be present despite a lack of attributable symptoms. 1 Khoury P Akuthota P Weller PF Klion AD. Eosinophilia and eosinophil-related disorders. in: Burks AW Holgate ST Middleton's Allergy Principles and Practice. 9th ed. Elsevier, Amsterdam2020: 1197-1212 Google Scholar Eosinophilia can also be found in pulmonary diseases, cardiac diseases, skin diseases, and other processes (Table 1). 2 Gerds AT Gotlib JG Bose P Deininger MW Dunbar A Elshoury A et al. Myeloid/lymphoid neoplasms with eosinophilia and TK fusion genes, version 3.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020; 8: 1248-1269 Crossref Scopus (15) Google Scholar , 3 Valent P Gleich GJ Reiter A Roufosse F Weller PF Hellmann A et al. Pathogenesis and classification of eosinophil disorders: a review of recent developments in the field. Expert Rev Hematol. 2012; 5: 157-176 Crossref PubMed Scopus (119) Google Scholar , 4 Valent P Klion AD Rosenwasser LJ Arock M Bochner BS Butterfield JH et al. ICON: eosinophil disorders. World Allergy Organ J. 2012; 5: 174-181 Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar In contrast, blood eosinophils can be suppressed in settings of stress, fever, infections, and increased exogenous or endogenous glucocorticoid levels. 1 Khoury P Akuthota P Weller PF Klion AD. Eosinophilia and eosinophil-related disorders. in: Burks AW Holgate ST Middleton's Allergy Principles and Practice. 9th ed. Elsevier, Amsterdam2020: 1197-1212 Google Scholar Table 1Differential Diagnoses for Eosinophilia Category Examples Infections -Parasitic (strongyloidiasis, Toxocara canis, Trichinella spiralis, schistosomiasis) -Viral (HIV, HSV, HTLV-2) -Fungal (Coccidioides, Histoplasma, Cryptococcus) -Bacterial and mycobacterial Allergic and hypersensitivity diseases -Asthma -Rhinitis -Allergic rhinitis -Bronchopulmonary aspergillosis -Allergic gastroenteritis Pulmonary diseases -Bronchiectasis -Cystic fibrosis -Chronic eosinophilic pneumonia Cardiac diseases -Tropical endocardial fibrosis -Eosinophilic endomyocardial fibrosis -Myocarditis Skin diseases -Atopic dermatitis -Urticaria -Eczema -Bullous pemphigoid Connective tissue and autoimmune diseases -Inflammatory bowel disease -Celiac disease -Eosinophilic granulomatosis with polyangiitis -Rheumatoid arthritis -Systemic lupus erythematosus -IgG4-related disease Medications -Aspirin -NSAIDs -Antimicrobials -DRESS syndrome Malignancies -Solid tumors (renal, lung, breast) -Hodgkin and non-Hodgkin lymphoma -Acute lymphoblastic leukemia -Langerhans cell histiocytosis Metabolic -Adrenal insufficiency Immune system diseases -Hyper IgE syndrome -Omenn syndrome -Wiskott-Aldrich syndrome -IgA deficiency Other -Acute and chronic graft vs host disease -Solid organ rejection -Cholesterol emboli -L-tryptophan ingestion Abbreviations: DRESS, drug reaction with eosinophilia and systemic syndrome; HIV, human immunodeficiency virus; HSV, herpes simplex virus; HTLV-2, human T-lymphotropic virus 2; IgE, immunoglobulin E; NSAID, nonsteroidal anti-inflammatory drug. Open table in a new tab Abbreviations: DRESS, drug reaction with eosinophilia and systemic syndrome; HIV, human immunodeficiency virus; HSV, herpes simplex virus; HTLV-2, human T-lymphotropic virus 2; IgE, immunoglobulin E; NSAID, nonsteroidal anti-inflammatory drug.