Lymphocyte-variant hypereosinophilia is a rare disorder in which eosinophilia or hypereosinophilia (i.e. a large or extremely large increase in the number of eosinophils in the blood circulation) is caused by an aberrant population of lymphocytes. 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. 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. The disorder is usually indolent or slowly progressive but may proceed to a leukemic phase sometimes classified as acute eosinophilic leukemia. Lymphocyte-variant hypereosinophilia can therefore be regarded as a precancerous disorder. The disorder merits therapeutic intervention to avoid or reduce eosinophil-induced tissue injury and treat its leukemic phase. The latter phase is aggressive and typically responds relatively poorly to anti-leukemia chemotherapeutic drug regimens.
Presentation
The typical patient with lymphocyte-variant hypereosinophilia presents with an extended history of hypereosinophilia and cutaneous allergy-like symptoms. Skin symptoms, which occur in >75% of patients, include erythroderma, pruritus, eczema, poikiloderma, urticarial, and episodic angioedema. 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. Biopsies of skin lesions commonly find prominent accumulations of eosinophils. Other presentations include:
a) lymphadenopathy occurring in ~60% of patients; b) eosinophil infiltrations in lung similar to, and often diagnosed as, eosinophilic pneumonia, occurring in ~20% of patients; c) episodic angioedema-related gastrointestinal symptoms that are sometimes similar to symptoms of the irritable bowel syndrome occurring in ~20% of patients; d) rheumatologic manifestations of inflammatory arthralgias in ~20% of patients; and e) splenomegaly occurring in ~10% of patients. Cardiovascular complications such as various types of heart damage due to eosinophilic myocarditis and vascular disorders due to eosinophil infiltration of the vascular wall that lead to vascular thrombosis are often critical components of persistent hypereosinophilia syndromes; These complications are not a prominent component of lymphocyte-variant hypereosionophilia, occurring in <10% of patients.
Other lymphoid disorders associated with eosinophilia Lymphoid neoplasms can be associated with eosinophilia presumably because of the secretion of eosinophil/eosinophil precursor cell-stimulating cytokines by the malignant lymphoid cells. Most commonly, this is seen in cutaneous T cell lymphoma, adult T-cell leukemia/lymphoma, and angioimmunoblastic T cell lymphoma. Less often, it is seen in B cell neoplasms such as Hodgkin's lymphoma, and B cell acute lymphoblastic leukemia, particularly forms of the latter disease associated with the t(5;9)(q31;p24) translocation creating gene fusion between the IL3 (at chromosome 5q31) and the JAK2 (at chromosome 9p24). The JAK2-IL3 fusion gene associated disease is accompanied by the overproduction of IL3, a simulator of eosinophil and eosinophil precursor cell growth.
… excerpt ends here. Continue reading the full article.
