Outdated allergens are similar to unexpired extracts for the detection of allergen sensitization.

Background: Allergen extracts have relatively short shelf lives, which limits their use and increase financial loss and waste on unused extracts. It is thus important to determine if efficacy persists beyond the expiration date. Objective: To determine the in vivo efficacy and bioavailability of outdated allergen extracts for diagnosis of allergic sensitizations. Methods: We enrolled 34 participants with allergic rhinitis and 5 participants with Hymenoptera hypersensitivity. After confirming allergen sensitization with the unexpired extracts, each participant had a second skin test with the matched outdated one (up to 7 years after the expiration date). All pairs of extracts were from the same company, stored under identical conditions, and tested for microbiologic contamination. The results of 356 skin-prick tests between expired and 111 unexpired extracts were compared. Results: None of the extracts had bacterial or fungal contamination. All outdated extracts produced a positive wheal reaction, with an average of 9.4 mm, which was not significantly different than the unexpired allergens. Seven years outdated lyophilized Hymenoptera extracts showed no significant differences in the wheal's size for the intradermal test at 1 µg/mL, between 5 and 9 mm. Conclusion: Outdated allergen extracts were safe and did not seem to differ in potency and bioavailability from unexpired extracts for the detection of allergen sensitization by skin-prick testing. These results supported our hypothesis that allergen extracts have efficacy and bioavailability that extend beyond the expiry date provided by the manufacturer. For the diagnosis of aeroallergens and Hymenoptera sensitization, it seemed that allergens can be used beyond the expiration date.

Hemophagocytic lymphohistiocytosis and primary immune deficiency disorders.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled immune activation and is traditionally associated with inherited gene defects or acquired causes. In addition to abnormalities in cytotoxic granules and lysosomes, various primary immune deficiency disorders (PID) have been identified among patients suffering from HLH. Our purpose was twofold: to better characterize and detail the association between PID and HLH. We found that HLH occurs infrequently among patients with PID, particularly those suffering from abnormalities that impair T cell function. The prognosis of patients suffering from PID and HLH is poor, emphasizing the need for rapid clinical and genetic diagnosis of the PID as well as initiation of appropriate management of the HLH, including allogeneic hematopoietic stem cell transplantations. The association of HLH and PID implicates abnormal T cell function as an important factor in HLH development. It also suggests that the partition of HLH into genetic versus acquired forms might be misleading.

The Long Road of Long COVID: Specific Considerations for the Allergist/Immunologist.

Long COVID (coronavirus disease 2019) syndrome, also known as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a new disorder that can develop after an acute infection with the SARS-CoV-2 virus. The condition is characterized by multiorgan system involvement with a wide range of symptoms that can vary in severity from mild to debilitating. Some of the common symptoms associated with long COVID syndrome include cardiovascular issues such as heart palpitations and chest pain; thrombotic events (eg, blood clotting disorders); metabolic problems (eg, type 2 diabetes); dysautonomia; paroxysmal orthostatic tachycardia syndrome; myalgic encephalomyelitis/chronic fatigue syndrome; reactivation of the Epstein-Barr virus; the presence of autoantibodies; chronic spontaneous urticaria (hives); and connective tissue diseases. Whereas long COVID syndrome can affect individuals from various backgrounds, certain populations may be at higher risk such as individuals of Hispanic and Latino heritage, as well as those with low socioeconomic status, although approximately one-third of affected patients have no known risk factors or preexisting conditions. Many survivors of COVID-19 struggle with multiple symptoms, increased disability, reduced function, and poor quality of life. Whereas vaccination has been the most significant intervention able to decrease the severity of acute SARS-Cov2 infection and curtail deaths, limited data are available related to its modulating effect on long COVID necessitating the need for further investigation. Furthermore, several inflammatory pathways have been proposed for the pathogenesis of long COVID that are the targets for ongoing clinical studies evaluating novel pharmacological agents. The purpose of the present report is to review the many factors associated with long COVID with a focus on those aspects that have relevance to the allergist-immunologist.

Asthma, Family History of Drug Allergy, and Age Predict Amoxicillin Allergy in Children.

BACKGROUND: Suspected adverse reactions to amoxicillin are common, but there are no known factors that can predict amoxicillin allergy in children. In addition, methods used for the diagnosis of amoxicillin allergy are not standardized and their role in diagnosis is not clear. OBJECTIVE: To identify predictive factors and to assess the role of skin test in the diagnosis of amoxicillin allergy in children. METHODS: Children with a history of immediate (excluding anaphylaxis) or nonimmediate reactions to amoxicillin were tested by skin prick test, followed by oral graded challenge with amoxicillin. Clinical characteristics of the reaction before and after the challenge were recorded, and data of personal and relatives' drug allergies and atopy were collected for statistical analysis. RESULTS: Skin prick tests followed by an oral graded challenge with amoxicillin were performed on 133 children. The skin test result was not of clinical value because it was negative in all children. Three children (2%) had an immediate reaction and 7 children (5%) had a nonimmediate reaction. Asthma (odds ratio [OR], 0.12; 95% CI, 0.017-0.869; P = .03), family history of drug allergy (OR, 0.12; 95% CI, 0.026-0.613; P = .01), older age at reaction (OR, 0.837; 95% CI, 0.699-1; P = .05), and angioedema (OR, 0.22; 95% CI, 0.043-1.12; marginally significant at P = .069) were associated with reduced chance to pass the oral challenge. CONCLUSIONS: Skin prick test did not contribute to the diagnosis of amoxicillin allergy. The presence of asthma, family history of drug allergy, and older age at reaction can be used as predictive factors for true amoxicillin allergy in children.

Prevention of fibrosis in experimental colitis by captopril: the role of tgf-beta1.

BACKGROUND & AIMS: There is a body of evidence to suggest that the local activation of angiotensin II (ANG II) plays a pivotal role in fibrogenic response involving the kidney, heart, lung, pancreas and liver. In such conditions, fibrosis is mediated, at least partially, through ANG II induction of the cytokine transforming growth factor-beta1 (TGF-beta1). Both ANG II and TGF-beta1 also seem to be involved in intestinal fibrosis and stenosis, particularly in Crohn's disease. The aim of the present study was, firstly, to determine the effects of the angiotensin-converting enzyme inhibitor, captopril, on colonic fibrosis in experimental colitis in rats and, secondly, to check the role of TGF-beta1 on these effects. METHODS: Colitis was induced in rats by intracolonic administration of TNBS. Colonic fibrosis was assessed 21 days later by macroscopic and microscopic evaluation. Levels of collagen alpha1 gene expression, hydroxyproline, angiotensin II and TGF-beta1 proteins, and TGF-beta1 mRNA were measured on the colonic tissue. RESULTS: In chronic colitis, captopril significantly reduced the score of macroscopic and histologic lesions, as well as the colonic tissue levels of collagen alpha1, hydroxyproline, ANG II and TGF-beta1 proteins, and TGF-beta1 mRNA. CONCLUSIONS: These data demonstrate for the first time that the prophylactic administration of captopril is effective in preventing colonic fibrosis in TNBS-induced colitis. The antifibrotic action of captopril could be due to the blockade of TGFbeta-1 overexpression, and/or to a direct down-regulation of TGFbeta-1 transcript.

CD44 in cancer.

CD44 is a multistructural and multifunctional cell surface molecule involved in cell proliferation, cell differentiation, cell migration, angiogenesis, presentation of cytokines, chemokines, and growth factors to the corresponding receptors, and docking of proteases at the cell membrane, as well as in signaling for cell survival. All these biological properties are essential to the physiological activities of normal cells, but they are also associated with the pathologic activities of cancer cells. Experiments in animals have shown that targeting of CD44 by antibodies, antisense,and CD44-soluble proteins markedly reduces the malignant activities of various neoplasms, stressing the therapeutic potential of anti-CD44 agents. Furthermore, because alternative splicing and posttranslational modifications generate many different CD44 sequences, including, perhaps, tumor-specific sequences, the production of anti-CD44 tumor-specific agents may be a realistic therapeutic approach. However, in many cancers (renal cancer and non-Hodgkin's lymphomas are exceptions), a high level of CD44 expression is not always associated with an unfavorable outcome. On the contrary, in some neoplams CD44 upregulation is associated with a favorable outcome. Even worse, in many cases different research grows analyzing the same neoplastic disease reached contradictory conclusions regarding the correlation between CD44 expression and disease prognosis, possibly due to differences in methodology. These problems must be resolved before applying anti-CD44 therapy to human cancers.