scholarly journals T cell mediated hypersensitivity to previously tolerated iodinated contrast media precipitated by introduction of atezolizumab

2021 ◽  
Vol 9 (5) ◽  
pp. e002521
Author(s):  
Sean Hammond ◽  
Anna Olsson-Brown ◽  
Joshua Gardner ◽  
Paul Thomson ◽  
Serat-E Ali ◽  
...  
Keyword(s):  
Contrast Media ◽  
Adverse Reactions ◽  
Stevens Johnson Syndrome ◽  
Iodinated Contrast ◽  
Immune Mediated ◽  
Johnson Syndrome ◽  
Healthy Donors ◽  
Concomitant Medications

Many adverse reactions associated with immune checkpoint inhibitor (ICI) treatments are immunologically driven and may necessitate discontinuation of the ICI. Herein, we present a patient who had been administered the radio contrast media amidotrizoate multiple times without issue but who then developed a Stevens-Johnson syndrome reaction after coadministration of atezolizumab. Causality was confirmed by a positive re-challenge with amidotrizoate and laboratory investigations that implicated T cells. Importantly, the introduction of atezolizumab appears to have altered the immunologic response to amidotrizoate in terms of the tolerance–elicitation continuum. Proof of concept studies demonstrated enhancement of recall responses to a surrogate antigen panel following in-vitro (healthy donors) and in-vivo (ICI patients) administrations of ICIs. Our findings highlight the importance of considering all concomitant medications in patients on ICIs who develop immune-mediated adverse reactions. In the event of some immune-related adverse reactions, it may be critical to identify the culprit antigen-forming entity that the ICIs have altered the perception of rather than simply attribute causality to the ICI itself in order to optimize both patient safety and treatment of malignancies.

Role of in vivo and in vitro Tests in the Diagnosis of Severe Cutaneous Adverse Reactions (SCAR) to Drug

2019 ◽  
Vol 25 (36) ◽  
pp. 3872-3880 ◽  
Author(s):  
Marcel M. Bergmann ◽  
Jean-Christoph Caubet
Keyword(s):  
Adverse Reactions ◽  
Lymphocyte Transformation ◽  
Stevens Johnson Syndrome ◽  
In Vitro Tests ◽  
High Morbidity ◽  
Patch Tests ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (SCAR) are life-threatening conditions including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Diagnosis of causative underlying drug hypersensitivity (DH) is mandatory due to the high morbidity and mortality upon re-exposure with the incriminated drug. If an underlying DH is suspected, in vivo test, including patch tests (PTs), delayed-reading intradermal tests (IDTs) and in vitro tests can be performed in selected patients for which the suspected culprit drug is mandatory, or in order to find a safe alternative treatment. Positivity of in vivo and in vitro tests in SCAR to drug varies depending on the type of reaction and the incriminated drugs. Due to the severe nature of these reactions, drug provocation test (DPT) is highly contraindicated in patients who experienced SCAR. Thus, sensitivity is based on positive test results in patients with a suggestive clinical history. Patch tests still remain the first-line diagnostic tests in the majority of patients with SCAR, followed, in case of negative results, by delayed-reading IDTs, with the exception of patients with bullous diseases where IDTs are still contra-indicated. In vitro tests have shown promising results in the diagnosis of SCAR to drug. Positivity is particularly high when the lymphocyte transformation test (LTT) is combined with cytokines and cytotoxic markers measurement (cyto-LTT), but this still has to be confirmed with larger studies. Due to the rarity of SCAR, large multi-center collaborative studies are needed to better study the sensitivity and specificity of in vivo and in vitro tests.

scholarly journals Histological and SEM Assessment of Blood Stasis in Kidney Blood Vessels after Repeated Intra-Arterial Application of Radiographic Contrast Media

Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 167
Author(s):  
Philipp Lamby ◽  
Alexander Minkow ◽  
Stefan Handt ◽  
Johannes Falter ◽  
Eva-Lotte Schellenberg ◽  
...  
Keyword(s):  
Contrast Media ◽  
Blood Stasis ◽  
Resistance Index ◽  
Renal Vasculature ◽  
Usual Procedure ◽  
Iodinated Contrast ◽  
Radiographic Contrast Media ◽  
Cell Alterations

Background: After application of iodinated contrast media (CM), a pronounced deterioration of the microcirculation in skin and myocardium was reported. Clinically, the repeated application of CM, especially, led to an increase of the renal resistance index (RRI). With respect to the transiency of the RRI increase, it is reasonable to assume that the deterioration of blood flow could be due to transient blood stasis caused by reversible morphologic cell alterations due to osmotic discrepancies between CM and human blood. Therefore, the hypothesis was investigated whether CM are able to induce in vivo such blood stasis and cell deformations in the renal vasculature of well-hydrated pigs. Methods: The in vivo study was performed as a prospective randomized examination to compare the effects of two different CM in 16 pigs (German Landrace). Pigs were randomized to receive either Iodixanol (n = 8), or Iopromide (n = 8). Each animal received 10 injections separated by 5-min intervals via the suprarenal aorta at a rate of 10 mL/s according to the usual procedure during a cardiac catheter examination. Finally, the kidneys were explanted and processed for histology (H & E staining and fibrin staining according to Weigert) as well as for scanning electron microscopy (SEM) with regards to morphologic correlates explaining the changes in the microcirculation. Results: In each of the predefined four categories of vascular diameters, blood stasis were found, but clearly more often after application of Iopromide than after application of Iodixanol (p < 0.001). In addition, Iopromide induced more blood stasis in all of the examined kidney regions compared to Iodixanol (p = 0.0001). There were no obstructive events in the middle cortex following the application of Iodixanol. Except for the region around a puncture channel of a placed-in catheter probe, no fibrin was detected in Weigert’s fibrin-stained samples, neither around the histologically assessed thrombi nor in vessels with blood stasis. Complementary SEM analyses revealed in a few cases only a slight generation of fibrin and thrombi and deformations, such as echinocyte and “box-like” deformations. Conclusions: According to previous in vitro studies, pathological erythrocyte deformations, such as echinocyte and box-like formation of erythrocytes, were observed also in vivo. In addition, blood stasis and/or thrombi could be detected in histological samples from explanted kidneys from young pigs after repeated in vivo administration of CM. In only a few cases, mural platelet aggregates within minimal fibrin meshes occurred only after the application of Iopromide.

Adverse Drug Reactions to Radiographic Contrast Media in a Teaching Hospital in North India: An Observational Study

2019 ◽  
Vol 14 (2) ◽  
pp. 122-126
Author(s):  
Deepti Chopra ◽  
Abhinav Jain ◽  
Richa Garg ◽  
Shreya Dhingra
Keyword(s):  
Observational Study ◽  
Contrast Media ◽  
Adverse Drug Reactions ◽  
Teaching Hospital ◽  
Adverse Reactions ◽  
North India ◽  
Drug Reactions ◽  
Iodinated Contrast ◽  
Radiographic Contrast ◽  
Radiographic Contrast Media

Background: Radiocontrast media are used extensively nowadays to visualize internal organs. Currently, non-ionic iodinated contrast media are used which are generally considered to be safe but some adverse reactions have been reported. Thus, the present study was carried out to analyze the nature and incidence of adverse drug reactions (ADRs) to radiographic contrast media in a teaching hospital. Methods:An observational study carried out for a period of six months in a teaching hospital. Contrast media induced adverse reactions were analyzed in terms of affected organs, rate, causality assessment, severity and preventability. The treatment and outcomes of adverse events were also recorded. Naranjo Probability Scale was used to evaluate the relationship between the contrast agent used and the suspected ADR. The severity of the suspected ADRs was determined using Hartwig Scale and preventability was assessed using modified Schumock and Thornton criterion. Results:A total of 15 suspected ADRs occurred in 11 patients with an incidence of 1.4%. It included 5 (45.4%) males and 6 (54.5%) females (p < 05). The highest percentage (72.7 %) of ADRs was seen in adult patients, the mean age being 40.8 years. Vomiting (33.3%) was the most common ADR noted followed by severe nausea and rashes. 64.7 % of ADRs were categorized as probable and 35.3 % were possible. Adverse reactions required treatment in 46.6% patients. There was no fatality reported. Conclusion:The reactions observed were mild to moderate in severity and occurred within 30 minutes of the administration of the contrast.

Genetic susceptibilities and prediction modeling of carbamazepine and allopurinol-induced severe cutaneous adverse reactions in Vietnamese

2020 ◽  
Author(s):  
Dinh van Nguyen ◽  
Hieu Chi Chu ◽  
Christopher Vidal ◽  
Richard B Fulton ◽  
Nguyet Nhu Nguyen ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Surrogate Marker ◽  
Hypersensitivity Syndrome ◽  
Stevens Johnson Syndrome ◽  
Strongly Correlated ◽  
Drug Induced ◽  
Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Systemic Symptoms ◽  
Cutaneous Adverse Reactions

Aims: To determine genetic susceptibility markers for carbamazepine (CBZ) and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese. Methods: A case control study was performed involving 122 patients with CBZ or allopurinol induced SCARs and 120 drug tolerant controls. Results: HLA-B*58:01 was strongly associated with allopurinol-induced SCARs and strongly correlated with SNP rs9263726. HLA-B*15:02 was associated with CBZ-induced Stevens–Johnson syndrome/toxic epidermal necrolysis but not with drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms. No association was found between HLA-A*31:01 and CBZ-induced SCARs. HLA-B*58:01 and rs3909184 allele A with renal insufficiency were shown to increase the risk of allopurinol-induced SCARs. Conclusion: HLA-B*58:01 and HLA-B*15:02 confer susceptibility to allopurinol-induced SCARs and CBZ-induced SJS/TEN in Vietnamese. Single nucleotide polymorphism rs9263726 can be used as a surrogate marker in identifying HLA-B*58:01.

scholarly journals Neurofascin as a novel target for autoantibody-mediated axonal injury

2007 ◽  
Vol 204 (10) ◽  
pp. 2363-2372 ◽  
Author(s):  
Emily K. Mathey ◽  
Tobias Derfuss ◽  
Maria K. Storch ◽  
Kieran R. Williams ◽  
Kimberly Hales ◽  
...  
Keyword(s):  
Axonal Injury ◽  
Dependent Manner ◽  
Nodes Of Ranvier ◽  
Native Form ◽  
Neuronal Protein ◽  
Axonal Pathology ◽  
Immune Mediated ◽  
Novel Target

Axonal injury is considered the major cause of disability in patients with multiple sclerosis (MS), but the underlying effector mechanisms are poorly understood. Starting with a proteomics-based approach, we identified neurofascin-specific autoantibodies in patients with MS. These autoantibodies recognize the native form of the extracellular domains of both neurofascin 186 (NF186), a neuronal protein concentrated in myelinated fibers at nodes of Ranvier, and NF155, the oligodendrocyte-specific isoform of neurofascin. Our in vitro studies with hippocampal slice cultures indicate that neurofascin antibodies inhibit axonal conduction in a complement-dependent manner. To evaluate whether circulating antineurofascin antibodies mediate a pathogenic effect in vivo, we cotransferred these antibodies with myelin oligodendrocyte glycoprotein–specific encephalitogenic T cells to mimic the inflammatory pathology of MS and breach the blood–brain barrier. In this animal model, antibodies to neurofascin selectively targeted nodes of Ranvier, resulting in deposition of complement, axonal injury, and disease exacerbation. Collectively, these results identify a novel mechanism of immune-mediated axonal injury that can contribute to axonal pathology in MS.

In Vitro Study of Various Iodinated Contrast Media

Radiology ◽  
2006 ◽  
Vol 239 (3) ◽  
pp. 918-921
Author(s):  
Mark O. Downes
Keyword(s):  
Contrast Media ◽  
In Vitro Study ◽  
Vitro Study ◽  
Iodinated Contrast Media ◽  
Iodinated Contrast

Hypoallergenic Infant Formulas

PEDIATRICS ◽  
1989 ◽  
Vol 83 (6) ◽  
pp. 1068-1069
Author(s):  
Keyword(s):  
Adverse Reactions ◽  
Villous Atrophy ◽  
Young Infant ◽  
Specific Antigen ◽  
Double Blind ◽  
Parental History ◽  
Pulmonary Hemosiderosis ◽  
Immune Mediated ◽  
Dietary Antigens

Antigenic constituents of human milk or of alternative feedings for infants may be responsible for adverse reactions in a subset of infants with milk protein intolerance. These reactions include those commonly associated with atopy, such as angioedema, urticaria, wheezing, vomiting, and eczema. Pulmonary hemosiderosis, malabsorption with villous atrophy, and eosinophilic enterocolitis, perhaps mediated by immune complexes or T cells, have also been associated with the ingestion of cow's milk proteins and/or soy proteins in infant feedings. Colic, sleeplessness, and irritability are symptoms seen in almost all infants at some time during infancy, including those few infants with immune-mediated reactions to dietary antigens. Determining that adverse reactions are, in fact, immune mediated is often difficult and is accomplished by an in vivo challenge with the potential offending antigen, together with in vitro confirmation of immunoreactivity to the challenge antigen. Double-blind challenge with purified dietary antigens is useful in relating symptoms to a specific antigen, but the results may be difficult to interpret if the appearance of symptoms is delayed beyond several hours in a young infant. In vitro testing is compromised by the presence of some form of immunoreactivity, such as hemagglutinating antibodies, to dietary antigens in a large percentage of infants without symptoms and by lack of standardization of clinical tests for cell-mediated reactions to dietary antigens. Much effort also has been devoted to predicting in which infants immune-mediated reactions to dietary proteins will develop in advance of their introduction into the diet. Increased cord blood IgE concentrations and parental history of atopy place an infant at highest risk for atopic disease during infancy and early childhood.

scholarly journals Influence of ionic and non-ionic radiographic contrast media on leukocyte adhesion molecules

2003 ◽  
Vol 12 (5) ◽  
pp. 269-275 ◽  
Author(s):  
Guy L. J. Vermeiren ◽  
Roel Willems ◽  
Marc J. Claeys ◽  
Chris Vrints ◽  
Herman Slegers ◽  
...  
Keyword(s):  
Coronary Angiography ◽  
Contrast Media ◽  
Adhesion Molecules ◽  
Leukocyte Adhesion ◽  
Serum Samples ◽  
Cd11b Expression ◽  
Radiographic Contrast ◽  
Radiographic Contrast Media

Background:Many papers have focused on the importance of granulocytes in the process of reperfusion and ischemia. Most of the clinical studies measured several parameters of this process during and after coronary angiography, without taking into account the effect of the radiographic contrast media (RCM) used during this procedure.Materials and methods:We performed a randomized patient study(n=37)to evaluate the effect of ionic and non-ionic RCM on granulocyte adhesion during coronary angiography. We also evaluated the influence of the ionicity and osmolarity of the different substances on granulocyte adhesion molecules inin vitroexperiments.Results:The osmolarity of patient serum samples increased from 302±1 to 309±1 mOsm/kg(P<0.05)after infusion of RCM. The CD11b expression in the samples of the non-ionic RCM treated group increased from 221±21 MFI to 377±30 MFI(P<0.05)measured as the absolute mean fluorescence intensity (MFI), yet did not alter significantly in the ionic RCM group. In contrast, thein vitroexperiments showed a reduction of the CD11b expression from 360±70 MFI to 149±30 MFI(P<0.05)in the ionic RCM group.Conclusions:The upregulation of adhesion molecules was significantly reducedin vivowith ionic RCM, while ionic substances caused opposite effectsin vitro. This effect should be taken into account when performing leukocyte functional analysis of samples taken during angiography.

scholarly journals Hypotonic contrast media is more toxic than isotonic contrast media on endothelial cells in vivo and in vitro

2017 ◽  
Vol 16 (4) ◽  
pp. 4334-4340 ◽  
Author(s):  
Lihui Ren ◽  
Ping Wang ◽  
Zuoyan Wang ◽  
Yong Liu ◽  
Shuzheng Lv
Keyword(s):  
Endothelial Cells ◽  
Contrast Media
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