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.

In Vitro Immunologic Tests in Severe Cutaneous Adverse Reactions (SCARs)

2015 ◽  
Vol 11 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Grzegorz Porebski ◽  
Laurence Valeyrie-Allanore ◽  
Francois Berrehar ◽  
Sabine Gouvello
Keyword(s):  
Adverse Reactions ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions ◽  
Immunologic Tests

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 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.

The association between HLA-B*15:02 and phenytoin-induced severe cutaneous adverse reactions: a meta-analysis

2021 ◽  
Author(s):  
Thanh Huong Phung ◽  
Khanh Ngoc Cong Duong ◽  
Mac Ardy Junio Gloria ◽  
Thien Khac Nguyen
Keyword(s):  
Drug Reaction ◽  
Adverse Reactions ◽  
Meta Analysis ◽  
Stevens Johnson Syndrome ◽  
Random Effects Model ◽  
Systemic Symptom ◽  
Anticonvulsant Agent ◽  
Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

Aim: Phenytoin (PHT) is a common anticonvulsant agent known for inducing severe cutaneous adverse reactions (SCARs). HLA-B*15:02 as a risk factor of PHT-induced SCARs was reported in numerous studies with inconsistent results. This meta-analysis aimed to establish pooling evidence of this association. Materials & methods: Pooled odds ratios (ORs) with 95% CIs were estimated using a random-effects model. Results: A total of 11 studies on 1389 patients, were included for the analyses. There was a significant association between HLA-B*15:02 and PHT-induced SCAR (pooled OR = 2.29, 95% CI: 1.25–4.19, p = 0.008). Furthermore, there was a significant association regarding Stevens–Johnson syndrome/toxic epidermal necrolysis (OR = 3.63, 95% CI: 2.15–6.13, p < 0.001) but no association regarding drug reaction with eosinophilia and systemic symptom. Conclusion: The results supported the recommendations of HLA-B*15:02 screening before treatment with PHT.

scholarly journals Case Report: Suspected Case of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Overlap Due to Ursodeoxycholic Acid

2020 ◽  
pp. 96-99
Author(s):  
Shatavisa Mukherjee ◽  
Debajyoti Saha ◽  
Shreyashi Dasgupta ◽  
Santanu Kumar Tripathi
Keyword(s):  
Ursodeoxycholic Acid ◽  
Toxic Epidermal Necrolysis ◽  
Adverse Reactions ◽  
Whole Body ◽  
Stevens Johnson Syndrome ◽  
Suspected Case ◽  
Human Bile ◽  
Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

Stevens–Johnson syndrome and toxic epidermal necrolysis are well-known severe cutaneous adverse reactions, with >100 medications previously implicated, most frequently sulfonamide antibiotics. Ursodeoxycholic acid (UDCA), normally present in human bile at a low concentration, is used for the treatment of various cholestatic disorders. Reports of UDCA causing cutaneous complications are, however, rare. The present report describes a suspected case of UDCA-induced Stevens–Johnson syndrome–toxic epidermal necrolysis overlap in a 24-year-old female, admitted with a whole-body maculopapular rash with oromucocutaneous ulceration and skin desquamation. The patient was managed with supportive care, including fluid and electrolyte replacement, corticosteroids, antibiotics, antihistamines, and intravenous Ig. Early identification, prompt intervention with effective care, and support are the key action points in these severe cutaneous adverse reactions.

scholarly journals About Minimization of Expenses on Allergy Diagnosis in Children: Analysis of Consistency of in Vitro- and in Vivo-Allergic Examinations Results

2015 ◽  
Vol 70 (6) ◽  
pp. 748-755
Author(s):  
Marina Andreevna Snovskaya ◽  
Anna Sergeevna Batyrova ◽  
Leyla Seymurovna Namazova-Baranova ◽  
Anna Aleksandrovna Alekseeva ◽  
Elena Aleksandrovna Vishneva ◽  
...  
Keyword(s):  
Atopic Disease ◽  
Skin Tests ◽  
Morbidity Rate ◽  
In Vitro Tests ◽  
High Morbidity ◽  
Meadow Fescue ◽  
Ige Antibodies ◽  
High Morbidity Rate

High morbidity rate of atopic diseases among children, including high importance of grass pollen as a sensitizing agent, determine the relevance of studies on diagnostic examination systems for appointment of adequate therapy. The research of the most relevant allergens for patients to exclude of duplicating and uninformative tests became urgent after development of a new type of diagnostic tests that does not require expensive equipment. The objective of this research was to evaluate the results of in vitro- and in vivo-diagnostic examinations of children with various forms of atopic disease caused by pollen of meadow grasses, and to choose the most significant prognostic parameters for the diagnosis. Methods: 277 children aged 4–16 years with various forms of atopic disease were included in the study. There were performed skin prick tests and determination of IgE-antibodies levels to allergen extracts of cocksfoot (g3), meadow fescue (g4), timothy grass (g6). Results: In the studied group of patients 32–50% of children have antibodies to grass allergens. There was a close correlation of antibody response on the investigated allergens, quantitative coincidence of IgE-antibodies to g3 and g4 allergens levels. IgE (g6) concentration was close to the IgE(g3) and IgE(g4) levels (85,0±21,6%). Analysis of the skin tests results showed that 44% of patients have a positive response to grass allergens, and in vivo-tests results coincide with serological tests results, mostly in a qualitative sense. The most significant relationship was noted between in vivo and in vitro-tests in the results of testing the response to meadow fescue pollen.Conclusion: Based on these data IgE concentration index to meadow fescue allergens can be used as a prognostic marker to determine the sensitization of patients with different nosology forms of allergy and can help to improve allergic diagnostics.

scholarly journals The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions

2021 ◽  
Vol 13 (6) ◽  
pp. 896
Author(s):  
Jettanong Klaewsongkram ◽  
Supranee Buranapraditkun ◽  
Pattarawat Thantiworasit ◽  
Pawinee Rerknimitr ◽  
Papapit Tuchinda ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

scholarly journals In vitro detection of drug-induced granzyme B, interferon-gamma, and interleukin-22 releasing cells in different phenotypes of severe cutaneous adverse reactions

2019 ◽  
Vol 143 (2) ◽  
pp. AB208
Author(s):  
Jettanong Klaewsongkram ◽  
Supranee Buranapraditkun ◽  
Pattarawat Thantiworasit ◽  
Nithikan Suthumcha ◽  
Pawinee Rerknimitr ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Adverse Reactions ◽  
Granzyme B ◽  
Drug Induced ◽  
Interleukin 22 ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

scholarly journals Diagnostic Tools and Biomarkers for Severe Drug Eruptions

2021 ◽  
Vol 22 (14) ◽  
pp. 7527
Author(s):  
Manabu Yoshioka ◽  
Yu Sawada ◽  
Motonobu Nakamura
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Drug Eruption ◽  
Adverse Reactions ◽  
Stevens Johnson Syndrome ◽  
Diagnostic Tools ◽  
Clinical Aspects ◽  
Drug Eruptions ◽  
Johnson Syndrome ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

In accordance with the development of human technology, various medications have been speedily developed in the current decade. While they have beneficial impact on various diseases, these medications accidentally cause adverse reactions, especially drug eruption. This delayed hypersensitivity reaction in the skin sometimes causes a life-threatening adverse reaction, namely Stevens-Johnson syndrome and toxic epidermal necrolysis. Therefore, how to identify these clinical courses in early time points is a critical issue. To improve this problem, various biomarkers have been found for these severe cutaneous adverse reactions through recent research. Granulysin, Fas ligands, perforin, and granzyme B are recognized as useful biomarkers to evaluate the early onset of Stevens-Johnson syndrome and toxic epidermal necrolysis, and other biomarkers, such as miRNAs, high mobility group box 1 protein (HMGB1), and S100A2, which are also helpful to identify the severe cutaneous adverse reactions. Because these tools have been currently well developed, updates of the knowledge in this field are necessary for clinicians. In this review, we focused on the detailed biomarkers and diagnostic tools for drug eruption and we also discussed the actual usefulness of these biomarkers in the clinical aspects based on the pathogenesis of drug eruption.

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