Lymphocyte-variant hypereosinophilia
These aberrant lymphocytes function abnormally by stimulating the proliferation and maturation of bone marrow eosinophil-precursor cells termed colony forming unit-eosinophils or CFU-Eos.
[1] The overly stimulated CFU-Eos cells mature to apparently normal appearing but possibly overactive eosinophils which enter the circulation and may accumulate in and damage various tissues.
[1] The disorder merits therapeutic intervention to avoid or reduce eosinophil-induced tissue injury and treat its leukemic phase.
[3][2] The symptom of episodic angioedema (i.e. soft tissue swelling of the face, tongue, larynx, abdomen, arms, or legs) in lymphocyte-variant hypereosinophilia resembles that occurring in Gleich's syndrome, a rare disease that is accompanied by secondary hypereosinophilia plus a sub-population of CD3(-), CD4(+) T cells; this involvement of the latter cell types supports the notion that Gleich's syndrome is a subtype of lymphocyte-variant hypereosiophilia.
[3] Following the historical findings cited above, studies identified the cytokine, interleukin 5 (IL5), as the eosinophil growth-stimulating CFU made by T cells from patients suffering the idiopathic hypereosinophilic syndrome.
[2] The underlying cause(s) for the origination and expansion of the phenotypically and clonally aberrant T cells in lymphocyte-variant hypereosinophilia remains unclear.
Criteria for the diagnosis include findings of: a) long term hypereosinophilia (i.e. eosinophil blood counts >1,500/microliter) plus physical findings and symptoms associated with the disease; b) bone marrow analysis showing abnormally high levels of eosinophils; c) elevated serum levels of Immunoglobulin E, other immunoglobulins, and CCL17; d) eosinophil infiltrates in afflicted tissues; e) increased numbers of blood and/or bone marrow T cells bearing abnormal immunophenotype cluster of differentiation markers as defined by fluorescence-activated cell sorting (see above section on Pathogenesis); f) abnormal T cell receptor arrangements as defined by polymerase chain reaction methods (see above section on Pathogenesis); and g) evidence of excessive IL-5 secretion by lymphocytes (see above section on Pathogenesis).
Alternate treatments used to treat corticosteroid resistant disease or for use as corticosteroid-sparing substitutes include interferon-α or its analog, peginterferon alfa-2a, mepolizumab (an antibody directed against IL-5), ciclosporin (an immunosuppressive drug), imatinib (an inhibitor of tyrosine kinases; numerous tyrosine kinase cell signaling proteins are responsible for the growth and proliferation of eosinophils (see clonal eosinophilia}), methotrexate and hydroxycarbamide (both are chemotherapy and immunosuppressant drugs), and alemtuzumab (an antibody that binds to the CD52 antigen on mature lymphocytes thereby marking them for destruction by the body).
Reslizumab, a newly developed antibody directed against interleukin 5 that has been successfully used to treat 4 patients with the hypereosinophilic syndrome, may also be of use for lymphocyte-variant eosinophilia.
[3] In 1987, however, a 42-year-old male patient was described who presented with cardiac failure, mitral heart valve regurgitation, pericardial effusion, splenomegaly, kidney dysfunction, non-specific skin lesions, a six-year history of eosinophilia, and, on admission, an eosinophil blood count of 7,150 per microliter (normal <500/microliter), a level that was 50% of total white blood cells (normal <5%).
Cell cultures from the patient's bone morrow grew an abnormally high percentage (52%) of eosinophil colony-forming units (CFUs).
