Anabolic androgen use in the management of hereditary angioedema: Not so cheap after all.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (HAE) is a rare, life-threatening disease that imposes a significant burden on affected patients. 17α-alkylated androgens (anabolic androgens) decrease attack frequency and severity but carry the risk of potentially serious dose-related adverse effects. Despite the emergence of targeted therapies for HAE, continued anabolic androgen use has been driven in part by their low cost. OBJECTIVE: To examine the hidden cost of anabolic androgen use related to the risk of developing non-HAE comorbidities. METHODS: Patients with HAE were identified in the Southern California Kaiser Permanente database using clinical and laboratory findings compatible with HAE. These patients were stratified into anabolic androgen exposed and nonexposed groups. Matched controls were selected from the Kaiser database who did not have HAE or anabolic androgen exposure. Using multivariate analysis, we determined the number of non-HAE comorbidities linked to anabolic androgen use. We next determined the association between dosing and increasing exposure to anabolic androgens and the likelihood of having various comorbidities. RESULTS: Patients with HAE exposed to anabolic androgens had a 28% increase (P = .04) in non-HAE comorbidities when compared with their matched (nonexposed) controls. With each gram per month increase in exposure, a 12% increase in non-HAE comorbidities is observed (P < .01). The most commonly occurring non-HAE comorbidities were psychiatric, muscle cramps, obesity, and hyperlipidemia. CONCLUSION: Our data suggest that long-term anabolic androgen use enhances the risk of developing comorbid health conditions, thus amplifying the cost of care. Our report provides additional support for the preferred use of newer, targeted therapies for the management of HAE.

The Utility of the Reflux Symptom Index for Diagnosis of Laryngopharyngeal Reflux in an Allergy Patient Population.

BACKGROUND: Laryngopharyngeal reflux (LPR) is associated with asthma, vocal cord dysfunction, cough, postnasal drainage, and throat irritation. The Reflux Symptom Index (RSI) is a clinical tool to predict the presence of LPR, but a threshold RSI score has never been validated for the diagnosis of LPR in an allergic patient population. OBJECTIVE: To identify the optimal threshold RSI score predictive of LPR in an allergy clinic population. METHODS: The 9-question RSI questionnaire was administered to 84 patients in the Kaiser Permanente San Diego Allergy Department. The patient's allergist (who was blinded to the patient's RSI responses) was asked to determine whether the patient had symptoms consistent with LPR. Each subject's RSI score was then compared with a corresponding physician-based diagnosis. After determining the correlation between the subject's RSI score and physician-diagnosed LPR/supraesophageal reflux, a cutoff level above which LPR/supraesophageal reflux would be highly suspected was calculated on the basis of most optimal balance of sensitivity and specificity determined via a receiver-operating curve analysis. RESULTS: Thirty of the 84 patients (36%) were diagnosed with LPR. The mean RSI score for the group without LPR was 18.3 ± 9.8 (out of 45 possible), while the LPR group's mean was 25.0 ± 8.3 (P < .01). The optimal RSI score cutoff was determined to be 19. An abbreviated questionnaire was also generated using 6 of the RSI questions found to be significantly different between patients with and without LPR. CONCLUSIONS: An RSI score of 19 appears to represent the best threshold for predicting LPR in an allergy clinic patient population.

T-Cells Specific for a Self-Peptide of ApoB-100 Exacerbate Aortic Atheroma in Murine Atherosclerosis.

On the basis of mouse I-Ab-binding motifs, two sequences of the murine apolipoprotein B-100 (mApoB-100), mApoB-1003501-3515 (designated P3) and mApoB-100978-992 (designated P6), were found to be immunogenic. In this report, we show that P6 is also atherogenic. Immunization of Apoe-/- mice fed a high-fat diet (HFD) with P6 resulted in enhanced development of aortic atheroma as compared to control mice immunized with an irrelevant peptide MOG35-55 or with complete Freund's adjuvant alone. Adoptive transfer of lymph node cells from P6-immunized donor mice to recipients fed an HFD caused exacerbated aortic atheromas, correlating P6-primed cells with disease development. Finally, P6-specific T cell clones were generated and adoptive transfer of T cell clones into recipients fed an HFD led to significant increase in aortic plaque coverage when compared to control animals receiving a MOG35-55-specific T cell line. Recipient mice not fed an HFD, however, did not exhibit such enhancement, indicating that an inflammatory environment facilitated the atherogenic activity of P6-specific T cells. That P6 is identical to or cross-reacts with a naturally processed peptide of ApoB-100 is evidenced by the ability of P6 to stimulate the proliferation of T cells in the lymph node of mice primed by full-length human ApoB-100. By identifying an atherogenic T cell epitope of ApoB-100 and establishing specific T cell clones, our studies open up new and hitherto unavailable avenues to study the nature of atherogenic T cells and their functions in the atherosclerotic disease process.

Eosinophilic gastroenteritis due to egg allergy presenting as acute pancreatitis.

We describe a case of a 25-year-old female with newly diagnosed egg allergy, presenting with both peripheral and duodenal eosinophilia suspicious for eosinophilic gastroenteritis (EG). The EG was severe enough to have likely caused acute pancreatitis. Cessation of all egg products lead to resolution of all symptoms. This represents the first report of EG manifesting as pancreatitis due to egg ingestion.

Heritability of bone density: regional and gender differences in monozygotic twins.

Bone mineral density (BMD) is a measure of a person's skeletal mineral content, and assessing BMD by dual x-ray absorptiometry (DEXA) can help to diagnose diseases of low bone density. In this study, we determine the heritability of BMD in male and female monozygotic twin subjects using DEXA in 13 specific anatomical regions. In an attempt to quantify the genetic contribution of gender and skeletal region to BMD heritability, we scanned 14 pairs of identical twins using DEXA and calculated the broad-sense heritability coefficient (H(2)) in each of the 13 different body regions. The region of the body that was most heritable for both genders was the head (H(2) >or= 95%). When males were compared to females, H(2) values for male hip (H(2) = 87%) and lower extremities (H(2) = 90%) were higher than those in females (H(2) = 49% and 56%, respectively). Conversely, H(2) value for the female pelvis (H(2) = 68%) was higher than that for males (H(2) = 26%). These data show that different regions of the skeleton exhibit different degrees of heritability, and that the variation depends on gender.

Subversion of T lineage commitment by PU.1 in a clonal cell line system.

Specification of mammalian T lymphocytes involves prolonged developmental plasticity even after lineage-specific gene expression begins. Expression of transcription factor PU.1 may maintain some myeloid-like developmental alternatives until commitment. Commitment could reflect PU.1 shutoff, resistance to PU.1 effects, and/or imposition of a suicide penalty for diversion. Here, we describe subclones from the SCID.adh murine thymic lymphoma, adh.2C2 and adh.6D4, that represent a new tool for probing these mechanisms. PU.1 can induce many adh.2C2 cells to undergo diversion to a myeloid-like phenotype, in an all-or-none fashion with multiple, coordinate gene expression changes; adh.6D4 cells resist diversion, and most die. Diversion depends on the PU.1 Ets domain but not on known interactions in the PEST or Q-rich domains, although the Q-rich domain enhances diversion frequency. Protein kinase C/MAP kinase stimulation can make adh.6D4 cells permissive for diversion without protecting from suicide. These results show distinct roles for regulated cell death and another stimulation-sensitive function that establishes a threshold for diversion competence. PU.1 also diverts normal T-cell precursors from wild type or Bcl2-transgenic mice to a myeloid-like phenotype, upon transduction in short-term culture. The adh.2C2 and adh.6D4 clones thus provide an accessible system for defining mechanisms controlling developmental plasticity in early T-cell development.