Local IgE production and positive nasal provocation test in patients with persistent nonallergic rhinitis

BACKGROUND: Allergic rhinitis is an IgE-mediated inflammatory disease of the nasal mucosa, which is usually diagnosed by typical symptoms, positive skin tests, and/or serum specific IgE antibodies to allergens. Despite suggestive symptoms of allergic rhinitis, some patients have a negative diagnostic test for atopy. OBJECTIVE: To evaluate in the nose the inflammatory response, specific IgE to Dermatophagoides pteronyssinus (DP), and the response to a nasal allergen provocation test with DP (NAPT-DP), in patients with persistent nonallergic rhinitis (PNAR) compared with patients with persistent allergic rhinitis (PAR) and healthy controls. METHODS: Fifty patients with PNAR, 30 with PAR to DP, and 30 healthy controls were studied by determining the nasal leukocyte-lymphocyte phenotype by flow cytometry (CD16, CD8, CD4, CD33, CD3, and CD45), nasal eosinophil cationic protein (ECP), albumin, total and specific IgE to DP, and NAPT-DP. RESULTS: The PNAR patients showed a similar leukocyte-lymphocyte phenotype in nasal lavage to the PAR patients and was different to the healthy controls. Within the PNAR group, 54% showed a positive NAPT-DP, with 22% of these having nasal specific IgE to DP. CONCLUSION: These data support the hypothesis that in persistent nonallergic rhinitis some patients may have local inflammation, nasal IgE production, and a positive response to a nasal allergen provocation test despite no evidence of systemic atopy. Further research is needed to evaluate the influence of other perennial allergens and/or immunologic mechanisms. CLINICAL IMPLICATIONS: The local production of IgE antibodies without systemic detection is a condition that should be considered in patients with PNAR.     

JAK2V617F monitoring in polycythemia vera and essential thrombocythemia: Clinical usefulness for predicting myelofibrotic transformation and thrombotic events

The JAK2V617F allele burden has been identified as a risk factor for vascular events and myelofibrotic transformation in polycythemia vera (PV) and essential thrombocythemia (ET). However, all previous studies have evaluated a single time point JAK2V617F measurement. Therefore, the frequency and the clinical significance of changes in the JAK2V617F mutant load occurring during the disease evolution remain unknown. In the present study, JAK2V617F monitoring was performed during the follow‐up of 347 patients (PV = 163, ET = 184). According to their JAK2V617F evolutionary patterns, patients were stratified as stable < 50% (n = 261), stable ≥50% (n = 52), progressive increase (n = 24) and unexplained decrease (n = 10). After a 2,453 person‐years follow‐up, a total of 59 thrombotic events, 16 major hemorrhages, and 27 cases of myelofibrotic transformations were registered. At multivariate analyses, patients with a persistently high (≥50%) or unsteady JAK2V617F load during follow‐up had an increased risk of myelofibrotic transformation (Incidence rate ratio [IRR]: 20.7, 95% CI: 6.5–65.4; P < 0.001) and a trend for a higher incidence of thrombosis (IRR: 1.7, 1–3.3; P = 0.05) than patients with a stable allele burden below 50%. In conclusion, JAK2V617F monitoring could be useful in patients with PV and ET for predicting disease's complications, especially myelofibrotic transformation. Am. J. Hematol. 89:517–523, 2014. © 2014 Wiley Periodicals, Inc.     

Outcome and management of pregnancies in severe chronic neutropenia patients by the European Branch of the Severe Chronic Neutropenia International Registry

Long-term granulocyte-colony stimulating factor treatment has been shown to be safe and effective in severe chronic neutropenia patients. However, data on its use during pregnancy are limited. To address this issue, we analyzed all pregnancies reported to the European branch of the Severe Chronic Neutropenia International Registry since 1994. A total of 38 pregnancies in 21 women with chronic neutropenia (16 pregnancies in 10 women with congenital, 10 in 6 women with cyclic, 12 in 5 women with idiopathic neutropenia) were reported. Granulocyte-colony stimulating factor was administered throughout pregnancy in 16 women and for at least one trimester in a further 5 women. No major differences were seen between treated and untreated women with respect to pregnancy outcome, newborn complications and infections. In addition, we evaluated the genetic transmission of known or suspected genetic defects in 16 mothers having 22 newborns as well as in 8 men fathering 15 children. As a proof of inheritance, neutropenia was passed on to the newborn in 58% from female and in 62% from male patients with ELANE mutations, but also to some newborns from parents with unknown gene mutation. Based on our results, granulocyte-colony stimulating factor therapy has been shown to be safe for mothers throughout pregnancies and for newborns without any signs of teratogenicity. With an increasing number of adult patients, genetic counseling prior to conception and supportive care of mothers during pregnancy are crucial. The acceptance of having affected children may reflect the high quality of life obtained due to this treatment.