Initial diagnostic testing in the patient with presumed HES
| Test . | Comment . |
|---|---|
| All patients with presumed HES | |
| Complete blood count* | |
| Routine chemistries, including liver function tests* | |
| Quantitative serum immunoglobulin levels, including IgE | IgE levels are typically elevated in LHES, EGPA and some immunodeficiencies associated with eosinophilia (eg, DOCK8, hyper-IgE syndrome) |
| Serum troponin,* echocardiogram, electrocardiogram | If abnormal, cardiac MRI should be considered, because this may show characteristic features of eosinophilic involvement; tissue involvement may be patchy, limiting the utility of biopsy |
| Pulmonary function tests* | |
| Chest/abdomen/pelvis CT* | To assess for splenomegaly, lymphadenopathy, and occult neoplasms |
| Bone marrow biopsy, including cytogenetics* | Recommended in all patients with AEC > 5000/μL and if the clinical picture is suggestive of MHES or LHES; should be considered in other patients |
| Biopsies of affected tissues (if possible) * | Eosinophilic infiltration in endomyocardial fibrosis tends to be patchy and occur early in disease, limiting the value of biopsy |
| Other testing for secondary causes | As indicated by history and clinical manifestations; may include serology or stool examination for diagnosis of parasitic infection, HIV testing, antineutrophil antibodies (ANCA) |
| Serum tryptase and B12 levels | Elevated serum B12 levels are common in all forms of MHES; serum tryptase is typically elevated in the setting of mutations in PDGFRA and KIT |
| FIP1L1/PDGFRA analysis by FISH or RT-PCR | Testing of peripheral blood has comparable sensitivity to bone marrow; false negative results can occur, especially with FISH testing |
| T- and B-cell receptor rearrangement studies | Clonal patterns are typical (but not diagnostic) of LHES |
| Lymphocyte phenotyping by flow cytometry* | At a minimum, CD3, CD4, CD8, and CD19 or CD20 staining should be performed to assess for aberrant CD3−CD4+, CD3+CD4+CD8+, and CD3+CD4−CD8− populations and B-cell lymphoproliferative disorders† |
| Patients with features of MHES | |
| Additional testing for BCR-ABL1, PDGFRB, JAK2, FGFR1, and KIT mutations by PCR, FISH, or other methods as appropriate | Testing should be guided by bone marrow findings |
| Myeloid mutation panel testing | Consider if BCR-ABL1, PDGFRB, JAK2, FGFR1, and KIT testing is negative |
| Patients with evidence of LHES | |
| Consider PET scan,* lymph node biopsy* | For exclusion of lymphoma |
| EBV viral load |
| Test . | Comment . |
|---|---|
| All patients with presumed HES | |
| Complete blood count* | |
| Routine chemistries, including liver function tests* | |
| Quantitative serum immunoglobulin levels, including IgE | IgE levels are typically elevated in LHES, EGPA and some immunodeficiencies associated with eosinophilia (eg, DOCK8, hyper-IgE syndrome) |
| Serum troponin,* echocardiogram, electrocardiogram | If abnormal, cardiac MRI should be considered, because this may show characteristic features of eosinophilic involvement; tissue involvement may be patchy, limiting the utility of biopsy |
| Pulmonary function tests* | |
| Chest/abdomen/pelvis CT* | To assess for splenomegaly, lymphadenopathy, and occult neoplasms |
| Bone marrow biopsy, including cytogenetics* | Recommended in all patients with AEC > 5000/μL and if the clinical picture is suggestive of MHES or LHES; should be considered in other patients |
| Biopsies of affected tissues (if possible) * | Eosinophilic infiltration in endomyocardial fibrosis tends to be patchy and occur early in disease, limiting the value of biopsy |
| Other testing for secondary causes | As indicated by history and clinical manifestations; may include serology or stool examination for diagnosis of parasitic infection, HIV testing, antineutrophil antibodies (ANCA) |
| Serum tryptase and B12 levels | Elevated serum B12 levels are common in all forms of MHES; serum tryptase is typically elevated in the setting of mutations in PDGFRA and KIT |
| FIP1L1/PDGFRA analysis by FISH or RT-PCR | Testing of peripheral blood has comparable sensitivity to bone marrow; false negative results can occur, especially with FISH testing |
| T- and B-cell receptor rearrangement studies | Clonal patterns are typical (but not diagnostic) of LHES |
| Lymphocyte phenotyping by flow cytometry* | At a minimum, CD3, CD4, CD8, and CD19 or CD20 staining should be performed to assess for aberrant CD3−CD4+, CD3+CD4+CD8+, and CD3+CD4−CD8− populations and B-cell lymphoproliferative disorders† |
| Patients with features of MHES | |
| Additional testing for BCR-ABL1, PDGFRB, JAK2, FGFR1, and KIT mutations by PCR, FISH, or other methods as appropriate | Testing should be guided by bone marrow findings |
| Myeloid mutation panel testing | Consider if BCR-ABL1, PDGFRB, JAK2, FGFR1, and KIT testing is negative |
| Patients with evidence of LHES | |
| Consider PET scan,* lymph node biopsy* | For exclusion of lymphoma |
| EBV viral load |
ANCA, anti-nuclear cytoplasmic antibody; CT, computed tomography; DOCK8, dedicator of cytokinesis 8; EBV, Epstein-Barr virus; FISH, fluorescence in situ hybridization; IgE, immunoglobulin E; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; PET, positron emission tomography; RT-PCR, reverse transcription polymerase chain reaction; TARC, thymus and activation regulated chemokine.
Substantially affected by glucocorticoid therapy.
Not all patients with LHES will have an aberrant T-cell population detectable by flow cytometry or a clonal population identified by PCR. Clinical and laboratory findings suggestive, but not diagnostic, of LHES include skin and soft tissue manifestations, elevated serum IgE, and TARC levels.