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嗜酸性粒细胞增多症最新诊疗指南

已有 2463 次阅读 2017-3-27 07:30 |个人分类:临床指南和病例解析|系统分类:观点评述| style

嗜酸性粒细胞增多症最新诊疗指南

• The underlying cause of eosinophilia should be sought and possible eosinophil-associated end-organ damage should be evaluated (Grade 1B).

Assessment of underlying cause
• A detailed medical history should be taken and a thorough physical examination should be performed (Grade 1C).

The history should include:
assessment for allergic disorders, skin rashes and cardiorespiratory, gastrointestinal and constitutional symptoms.
a detailed travel history, particularly for tropical travel; travel even in the remote past may be relevant.
a detailed drug history.

• All patients should have a full blood count, blood film examination and routine tests of renal and liver function, a bone profile, lactate dehydrogenase, erythrocyte sedimentation rate and/or C-reactive protein and vitamin B12 assay (Grade 1C).
• Patients who are otherwise well with mild to moderate eosinophilia between 0.5 and 1.5X10^9/l may not require further testing. Patients with systemic symptoms and those with persistent eosinophilia (at least 15X10^9/l), irrespective of suspected organ damage,should be considered for additional testing for an underlying cause.
• Specific causes of reactive eosinophilia, based on clinical suspicion, should be confirmed or excluded at an early stage by appropriate testing (Grade 1C).
• Patients with an eosinophil count of at least 15X10^9/l with no obvious cause should be investigated for a possible haematological neoplasm with clonal eosinophilia, initially by peripheral blood analysis for FIP1L1-PDGFRA by fluorescence in situ hybridisation (FISH) or nested reverse transcription polymerase chain reaction
(RT-PCR) (Grade 1C).
• Serum tryptase estimation should be performed if the differential diagnosis includes chronic eosinophilic leukaemia or systemic mastocytosis (Grade 1B).
• In the absence of an identifiable cause and with negative peripheral blood analysis for FIP1L1-PDGFRA by FISH or nested RT-PCR, a bone marrow aspirate, trephine biopsy and cytogenetic analysis should be performed; the possibility of an underlying lymphoma or of the lymphocytic variant of hypereosinophilic syndrome should be evaluated, including consideration of immunophenotyping of peripheral blood and bone marrow lymphocytes and analysis for T-cell receptor gene rearrangement (Grade 1C).
The possibility of systemic mastocytosis or other myeloid neoplasm should be considered.

Assessment for possible eosinophil-associated end-organ damage
• End-organ damage should be assessed using chest radiography and/or computed tomography (CT) of the thorax, echocardiography, serum troponin T and pulmonary function testing (Grade 1C).
• An unprovoked thromboembolic event should be recognised as a possible manifestation of eosinophil associated tissue damage (Grade 2C).
• In patients with end-organ damage, the frequency of further serial evaluations of organ function should be determined by the severity and extent of organ compromise and/or by worsening of the eosinophilia (Grade 2C).

Emergency treatment
• Patients requiring emergency treatment for severe or life-threatening eosinophilia should receive high-dose corticosteroids (Grade 1B).
• Patients receiving corticosteroids, in whom there is a risk of strongyloides infection, should receive concomitant ivermectin to prevent potentially fatal hyperinfection (Grade 1B)

Treatment of clonal eosinophilia
• Patients with clonal eosinophilia with FIP1L1-PDGFRA (including patients presenting with acute leukaemia), should be treated with low dose imatinib (Grade 1B).
• Patients with clonal eosinophilia with PDGFRB rearrangement or ETV6-ABL1 fusion should receive standard dose imatinib (Grade 1B).
• Patients with clonal eosinophilia with ETV6-FLT3 fusion should be considered for sunitinib or sorafenib therapy (Grade 2B)
• Patients with clonal eosinophilia with JAK2 rearrangement should be considered for ruxolitinib therapy (Grade 2B)
• Patients with acute myeloid leukaemia (AML) with clonal eosinophilia and no molecular or cytogenetic abnormality suggesting likely response to a tyrosine kinase inhibitor should be offered standard AML induction therapy (Grade 1A).
• Patients with other haematological neoplasms with clonal eosinophilia should have treatment directed at management of the neoplasm. If there is organ damage or dysfunction relating to the eosinophilia,treatment with corticosteroids should also be given (Grade 1C).

Treatment of lymphocytic variant of hypereosinophilic syndrome
• Patients with the lymphocytic variant of hypereosinophilic syndrome (HES) can be managed in the same manner as idiopathic HES (grade 2B)

Treatment of idiopathic hypereosinophilic syndrome
• Patients with idiopathic HES should be treated in the first instance with corticosteroids (see emergency treatment above).
• Patients with idiopathic HES who do not respond adequately to corticosteroids, or who require prolonged corticosteroid therapy, or who are intolerant of corticosteroids, should be considered for a short trial (4 – 6 weeks) of imatinib, immunomodulatory agents (interferon alpha, ciclosporin or azathioprine), myelosuppressive therapy (hydroxycarbamide) or monoclonal antibody therapy with mepolizumab (anti-interleukin 5), the latter preferably as part of a clinical trial (Grade 2B).
• Alemtuzumab, an anti-CD52 monoclonal antibody, should be considered for patients with severe idiopathic HES unresponsive to other therapies, and may be useful in patients with idiopathic HES-associated cardiac and cerebral dysfunction. (Grade 2B)

Role of haemopoietic stem cell transplantation (HSCT)
• HSCT should be considered for cases with clonal eosinophilia with FGFR1 rearrangement, patients with chronic eosinophilic leukaemia, not otherwise specified and those HES patients refractory to or intolerant of both conventional tyrosine kinase inhibitor (TKI) therapy and experimental medical therapy, where available, or who display progressive end-organ damage. (Grade 2C).