Increased Hazard Risk of First Malignancy in Adults with Undetectable Serum IgE: a Retrospective Cohort Study.

PURPOSE: The clinical relevance of IgE-deficiency is not established. Previous studies have postulated a relationship between absent serum IgE and the incidence of specific malignancies. We sought to examine the relationship between undetectable total serum IgE (< 3 IU/mL) and first malignancy, considering both general all-cause malignancy risk and risk of specific malignancy subtypes in adult subjects. METHODS: Retrospective cohort study at a single center of 39,965 adults aged 18 or older (median age 51, 65.1% female) with at least one serum total IgE measurement from 1998 to 2020. Analytics included chi2 table and logistic regression modeling of the main outcome measures, which include diagnosis of first malignancy and first diagnosis of specific malignancy subtype. RESULTS: Of the entire cohort, 2584 subjects (6.5%) developed a first malignancy and 2516 (6.3%) had an undetectable IgE. Of those with undetectable IgE levels, 8.9% developed a first malignancy versus 6.3% with detectable IgE measurements. After adjusting for risk factors, there was a significant association between undetectable IgE and risk/hazard of first malignancy (relative risk 1.49, 95% confidence interval (CI) 1.27-1.75) (hazard ratio 1.28, 95% CI 1.08-1.52). Results were similar in multiple sensitivity analyses. For type of malignancy developed, undetectable IgE was associated with increased risk of hematologic malignancy (relative risk 2.07, 95% CI 1.29-3.30) and skin malignancy (relative risk 1.52, 95% CI 1.13-2.05). CONCLUSION: Compared to individuals with detectable IgE levels, patients with undetectable total serum IgE had increased risk and hazard of first malignancy in general, and increased risk of hematologic malignancy in particular.

Anaphylaxis: Highlights from the practice parameter update.

The practice parameter update on anaphylaxis from the Joint Task Force on Practice Parameters, with the collaboration of the American Academy of Allergy, Asthma, and Immunology and the American College of Allergy, Asthma, and Immunology, addresses key issues in the management and prevention of anaphylaxis. The updated guidelines define diagnostic criteria for anaphylaxis; therapeutic use of epinephrine, antihistamines, and glucocorticoids; prevention of recurrent anaphylaxis; and follow-up care that includes education on trigger avoidance and use of self-injectable epinephrine.

Suspected food allergies in a septuagenarian with recurrent anaphylaxis.

Anaphylaxis is an acute, life-threatening reaction that can occur due to a variety of triggers. It is often associated with allergen exposure, such as food, venom, or medications; however, there are other less-common causes, and many patients are ultimately classified as idiopathic. In this report, we described a patient with recurrent reactions attributed to food exposure. Further evaluation revealed an alternative, less common diagnosis.

Gastrointestinal Involvement in Mast Cell Activation Disorders.

Gastrointestinal (GI) symptoms are commonly reported in patients with mast cell disease. GI involvement in systemic mastocytosis is heterogeneous and symptoms may be caused by infiltration of abnormal mast cells in the GI tract and/or by the downstream effect of mast cell mediators on GI tissues. GI symptoms described the monoclonal mast cell activation syndrome are best characterized in the context of acute anaphylaxis. The presence of GI symptoms and a subjective response of symptoms to anti-mast cell mediator therapy are considered qualifying criteria in the diagnosis of the idiopathic mast cell activation syndrome. Antimediator therapy may help alleviate GI symptoms in mast cell disease.

Mast cell phenotypes in the allograft after lung transplantation.

BACKGROUND: The burden of mast cell (MC) infiltration and their phenotypes, MC-tryptase (MCT ) and MC-tryptase/chymase (MCTC ), after lung transplantation (LT) has not been evaluated in human studies. METHODS: We reviewed 20 transbronchial lung biopsy (TBLB) specimen from patients with early normal allograft (<6 months post-LT, n=5), late normal allograft (>6 months, n=5), A2 or worse acute cellular rejection (ACR, n=5), and chronic lung allograft dysfunction (CLAD, n=5). Slides were immunostained for tryptase and chymase. Total MC, MCT , MCTC and MCTC to-MCT ratio were compared between the four groups using a generalized linear mixed model. RESULTS: Irrespective of clinicopathologic diagnosis, MC burden tends to increase with time (r(2) =.56, P=.009). MCTC phenotype was significantly increased in the CLAD group (8.2±4.9 cells per HPF) in comparison with the other three groups (early normal: 1.6±1.7, P=.0026; late normal: 2.5±2.3, P=.048; ACR: 2.7±3.5, P=.021). Further, the ratio of MCTC to MCT was significantly increased in CLAD group as compared to the other three groups (P<.001 for all comparisons). CONCLUSIONS: The burden of MC may increase in the allograft as function of time. Patients with CLAD have an increased relative and absolute burden of MCTC phenotype MC. Future studies are needed to confirm these findings and evaluate the potential pathologic role of MCTC in allograft dysfunction.

Osteogenic differentiation of late-outgrowth CD45-negative endothelial progenitor cells.

BACKGROUND/AIMS: Late-outgrowth CD45-negative endothelial colony-forming cells are implicated to be circulating endothelial progenitor cells (EPCs), as they express endothelial cell markers and can directly form blood vessels. As these cells share characteristics of other progenitor cell phenotypes, late-outgrowth EPCs were assayed for both multilineage differentiation capability and for markers of pluripotency. METHODS: Clonal single-colony late-outgrowth EPCs were derived from human cord blood and assayed both for multilineage differentiation capability in vitro and for markers of pluripotency by qPCR. RESULTS: Under osteogenic growth conditions, these EPCs expressed the osteogenic markers RUNX2, COL1A1, ALPL, and osteocalcin and demonstrated calcium deposition and bone mineralization. Endothelial colony-forming cells expressed markers associated with induced pluripotent stem cells, including SOX2, POU5F1, c-MYC, and KLF4. CONCLUSIONS: Late-outgrowth EPCs express markers associated with pluripotency and can directly express an osteogenic phenotype under bone differentiation conditions in vitro.

Hypereosinophilic syndrome.

OBJECTIVE: To summarize the identified molecular and cellular mechanisms relevant to clinicians evaluating patients with hypereosinophilic syndrome (HES). DATA SOURCES: Review of relevant peer-reviewed literature. STUDY SELECTIONS: Studies on the pathogenesis of HES in relation to consensus definitions, disease classification, mechanisms of disease, and diagnosis and treatment are included. RESULTS: Changes to the definition of HES have been proposed based on recent studies identifying specific cellular and molecular disease phenotypes. Identification of specific mechanisms of disease may have clinical and therapeutic significance. Despite recent advances, in most cases the molecular pathogenesis of HES remains unknown. CONCLUSION: Identification of specific HES disease mechanisms empowers the practicing clinician to offer specific mechanism-based treatment options to patients with HES in their clinical practice.

Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis.

We hypothesized that analysis of single nucleotide polymorphism arrays (SNP-A) and new molecular defects may provide new insight in the pathogenesis of systemic mastocytosis (SM). SNP-A karyotyping was applied to identify recurrent areas of loss of heterozygosity and bidirectional sequencing was performed to evaluate the mutational status of TET2, DNMT3A, ASXL1, EZH2, IDH1/IDH2 and the CBL gene family. Overall survival (OS) was analyzed using the Kaplan-Meier method. We studied a total of 26 patients with SM. In 67% of SM patients, SNP-A karyotyping showed new chromosomal abnormalities including uniparental disomy of 4q and 2p spanning TET2/KIT and DNMT3A. Mutations in TET2, DNMT3A, ASXL1 and CBL were found in 23%, 12%, 12%, and 4% of SM patients, respectively. No mutations were observed in EZH2 and IDH1/IDH2. Significant differences in OS were observed for SM mutated patients grouped based on the presence of combined TET2/DNMT3A/ASXL1 mutations independent of KIT (P = 0.04) and sole TET2 mutations (P<0.001). In conclusion, TET2, DNMT3A and ASXL1 mutations are also present in mastocytosis and these mutations may affect prognosis, as demonstrated by worse OS in mutated patients.

Allergy blood testing: A practical guide for clinicians.

Blood tests are available that measure levels of immunoglobulin E (IgE) against specific allergens such as foods, inhalants, medications, latex, and venoms. These tests can confirm the diagnosis of an allergic disorder, supplementing a clinical history consistent with an immediate allergic reaction. They are particularly useful when skin testing cannot or should not be performed.

Glatiramer acetate: successful desensitization for treatment of multiple sclerosis.

BACKGROUND: Glatiramer acetate is an immunomodulatory drug that is widely prescribed for the treatment of multiple sclerosis. It is frequently associated with local injection site reactions and generalized urticaria. It is also associated with immediate postinjection systemic reactions in approximately 10% of patients. To our knowledge, no desensitization protocols for glatiramer acetate have been published to date. OBJECTIVES: To evaluate the safety and efficacy of glatiramer acetate desensitization in a series of patients with multiple sclerosis. METHODS: Six patients with multiple sclerosis and glatiramer acetate-associated local or systemic reactions underwent a 4-hour outpatient desensitization procedure at Cleveland Clinic between 2003 and 2008. Beginning with 20 ng, we administered subcutaneous glatiramer acetate suspension in increasing dosages every 15 minutes. Patient outcomes were monitored by return clinic visit and telephone follow-up. RESULTS: No episodes of anaphylaxis or serious adverse reactions occurred during or immediately after desensitization. One patient suspended therapy after 14 months due to persistent local injection site reactions. All other patients successfully continued glatiramer acetate therapy. CONCLUSION: Glatiramer acetate offers significant benefit to patients with multiple sclerosis. Our experience suggests that patients who suspend its use owing to local or systemic reactions can be successfully and safely desensitized and can resume medication use. To our knowledge, this is the first report of successful desensitization to glatiramer acetate in patients with multiple sclerosis.