Drug reexposure in children with severe mucocutaneous reactions

In pediatric patients, severe cutaneous adverse reactions (SCARs) frequently occur in the course of acute illnesses, mostly infections, which are usually treated with antibiotics or analgesics. The drug provocation test (DPT) is contraindicated in such situations, due to the risk of triggering a new severe reaction. As a consequence, lifelong avoidance is recommended. However, causation is uncertain in most cases. The dilemma arises when avoiding the drug is not harmless for the patient. We have attended three patients who were referred to our pediatric allergy unit with a history of SCAR related in time to simultaneous use of paracetamol and ibuprofen. Medical records and images of the patients were reviewed with the assistance of a dermatologist, and alternative diagnoses were considered in both cases. The ALDEN score for implicated drugs was calculated. After considering a high probability of ibuprofen tolerance and obtaining informed consent from the patients, we performed a sequential allergy workup including in vitro tests, skin tests, and finally DPT in two of the patients, confirming ibuprofen tolerance. In conclusion, although generally contraindicated, DPT may be considered for some useful drugs after careful evaluation of the risk–benefit balance, preceded by a sequential study including in vitro and skin tests.

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

Current Pharmaceutical Design ◽

10.2174/1381612825666191107104126 ◽

2019 ◽

Vol 25 (36) ◽

pp. 3872-3880 ◽

Cited By ~ 3

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.

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Quinolone Allergy

Pharmacy ◽

10.3390/pharmacy7030097 ◽

2019 ◽

Vol 7 (3) ◽

pp. 97 ◽

Cited By ~ 9

Author(s):

Edoabasi U. McGee ◽

Essie Samuel ◽

Bernadett Boronea ◽

Nakoasha Dillard ◽

Madison N. Milby ◽

...

Keyword(s):

Clinical Manifestations ◽

Provocation Test ◽

Cross Reactivity ◽

Skin Tests ◽

Diagnostic Tools ◽

In Vitro Tests ◽

Allergic Reactions ◽

Drug Induced ◽

Delayed Reaction

Quinolones are the second most common antibiotic class associated with drug-induced allergic reactions, but data on quinolone allergy are scarce. This review article discusses the available evidence on quinolone allergy, including prevalence, risk factors, diagnosis, clinical manifestations, cross-reactivity, and management of allergic reactions. Although the incidence of quinolone allergy is still lower than beta-lactams, it has been increasingly reported in recent decades, most likely from its expanded use and the introduction of moxifloxacin. Thorough patient history remains essential in the evaluation of quinolone allergy. Many diagnostic tools have been investigated, but skin tests can yield false-positive results and in vitro tests have not been validated. The drug provocation test is considered the test of choice to confirm a quinolone allergy but is not without risk. Evidence regarding cross-reactivity among the quinolones is limited and conflicting. Quinolone allergy can be manifested either as an immediate or delayed reaction, but is not uniform across the class, with moxifloxacin posing the highest risk of anaphylaxis. Quinolone should be discontinued when an allergic reaction occurs and avoided in future scenarios, but desensitization may be warranted if no alternatives are available.

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Approaches to the Management of Presumed Immediate Hymenoptera Venom Allergy and Non-Detectable IgE

The Open Allergy Journal ◽

10.2174/1874838401003010016 ◽

2010 ◽

Vol 3 (1) ◽

pp. 16-23

Author(s):

Ervin Ç. Mingomataj ◽

Alketa H. Bakiri

Keyword(s):

Skin Test ◽

Case Reports ◽

Skin Tests ◽

Diagnostic Tools ◽

In Vitro Tests ◽

Insect Allergy ◽

History Of ◽

Cellular Tests

Objective: To provide a comprehensive evaluation in patients with a convincing history of immediate insect allergy but negative skin test and/or specific IgE results, adequately addressing the question of how best to manage them. Data sources: Observational peer-reviewed studies and case reports were searched on Pub-Med database from 1998 up to March 2009 using the following keywords: Hymenoptera Allergy & Negative IgE (Negative Skin Tests). Study selection: Studies on supplemental diagnostic tests that provided data from patients with immediate hymenoptera allergy but negative conventional tests results to the offending allergens were selected. In this work, we also included studies providing additional relevant information regarding this issue. Results: Among 43 identified papers only 9 of them presented relevant original data, while the other papers were reviews. In the majority of the cases, the culprit insect was identified with in vitro tests such as Basophil Activation Test, Cellular Allergen Stimulation Test or Western blot, whereas in vivo (less frequently) with sting challenge or dialyzed venom skin test. Conclusions: The management of patients with a convincing history of immediate insect allergy but negative conventional test results requires an adaption of the guidelines including an incorporation of the novel diagnostic tools. Although cellular tests represent equivalent sensitivity and superior specificity as compared with standard ones, these tests still remain supplementary diagnostic tools. In a minority of cases (especially in the developing countries where cellular tests cannot be performed), venom immunotherapy in adult subjects could be taken into account based solemnly on the history of a clear patient’s identification of the culprit insect.

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

Current Immunology Reviews ◽

10.2174/157339551101150417102232 ◽

2015 ◽

Vol 11 (1) ◽

pp. 33-42 ◽

Cited By ~ 1

Author(s):

Grzegorz Porebski ◽

Laurence Valeyrie-Allanore ◽

Francois Berrehar ◽

Sabine Gouvello

Keyword(s):

Adverse Reactions ◽

Severe Cutaneous Adverse Reactions ◽

Cutaneous Adverse Reactions ◽

Immunologic Tests

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Recombinant in vitro test T-SPOT.TB as a screening method for early diagnosis of tuberculosis infection

Tuberculosis and lung diseases ◽

10.21292/2075-1230-2020-98-4-48-52 ◽

2020 ◽

Vol 98 (4) ◽

pp. 48-52

Author(s):

E. P. Eremenko ◽

E. A. Borodulina ◽

I. A. Sergeeva ◽

D. A. Kudlay ◽

B. E. Borodulin

Keyword(s):

Screening Method ◽

Latent Tuberculosis ◽

Tuberculosis Infection ◽

Mantoux Test ◽

Skin Tests ◽

In Vitro Tests ◽

In Vitro Test ◽

Healthy Children ◽

Vitro Test

In addition to standard skin tests (Mantoux test with 2 TU PPD-L and diaskintest) for the diagnosis of tuberculosis infection, in vitro tests are used. One of these tests is T-SPOT.TB being more widely used in recent years.The objective: to evaluate the effectiveness of T-SPOT.TB test for early detection of tuberculosis infection in children and adolescents in Samara Region.Subjects and methods. From 2016 to 2019, results of T-SPOT.TB tests performed in 596 children aged 2 to 17 years inclusive were analyzed; those children had no immunodiagnosis of tuberculosis infection using skin tests since their parents refused to have it.Results. It was found out that the major reason for refusing skin tests was the “fear” of visiting a TB dispensary if the result had been positive — 38.43% (n = 229). The latent tuberculosis infection according to the results of T-SPOT.TB among children with concomitant pathology made 2.6%, among healthy children – 0.7%.Conclusion. T-SPOT.TB test may be used as an alternative method for diagnosis of tuberculosis infection, should the parent refuse to have skin tests. In children with concomitant pathology, T-SPOT.TB test can serve as a leading method for immunodiagnosis of tuberculosis.The authors state that they have no conflict of interests.

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Hypersensitivity Reactions to Monoclonal Antibodies in Children

Medicina ◽

10.3390/medicina56050232 ◽

2020 ◽

Vol 56 (5) ◽

pp. 232

Author(s):

Francesca Mori ◽

Francesca Saretta ◽

Annamaria Bianchi ◽

Giuseppe Crisafulli ◽

Silvia Caimmi ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Therapeutic Option ◽

Provocation Test ◽

Type I ◽

Hypersensitivity Reactions ◽

Biologic Drugs ◽

Type Iv ◽

Drug Provocation Test

Biologic drugs are widely used in pediatric medicine. Monoclonal antibodies (mAbs) in particular are a therapeutic option for rheumatic, autoinflammatory and oncologic diseases. Adverse drug reactions and hypersensitivity reactions (HSR) to mAbs may occur in children. Clinical presentation of HSRs to mAbs can be classified according to phenotypes in infusion-related reactions, cytokine release syndrome, both alpha type reactions and type I (IgE/non-IgE), type III, and type IV reactions, all beta-type reactions. The aim of this review is to focus on HSRs associated with the most frequent mAbs in childhood, with particular attention to beta-type reactions. When a reaction to mAbs is suspected a diagnostic work-up including in-vivo and in-vitro testing should be performed. A drug provocation test is recommended only when no alternative drugs are available. In selected patients with immediate IgE-mediated drug allergy a desensitization protocol is indicated. Despite the heavy use of mAbs in childhood, studies evaluating the reliability of diagnostic test are lacking. Although desensitization may be effective in reducing the risk of reactions in children, standardized pediatric protocols are still not available.

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Skin and In Vitro Tests are Positive in Every 10th Patient with a Plausible History of Betalactam Allergy

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2018.12.104 ◽

2019 ◽

Vol 143 (2) ◽

pp. AB33

Author(s):

Stefan Wöhrl ◽

Christian Ostermayer ◽

Gabriele Sesztak-Greinecker ◽

Wolfgang Hemmer ◽

Felix Wantke

Keyword(s):

In Vitro Tests ◽

History Of

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Resistance to Boscalid Fungicide in Alternaria alternata Isolates from Pistachio in California

Plant Disease ◽

10.1094/pdis-91-10-1345 ◽

2007 ◽

Vol 91 (10) ◽

pp. 1345-1350 ◽

Cited By ~ 105

Author(s):

Herve F. Avenot ◽

Themis J. Michailides

Keyword(s):

Spore Germination ◽

Alternaria Alternata ◽

Hyphal Growth ◽

Conidial Germination ◽

Prior History ◽

In Vitro Tests ◽

Fitness Parameters ◽

History Of ◽

The Mean

Boscalid is a new carboxamide fungicide recently introduced in a mixture with pyraclostrobin in the product Pristine for the control of Alternaria late blight of pistachio. In all, 108 isolates of Alternaria alternata were collected from pistachio orchards with (59 isolates) and without (49 isolates) prior exposure to boscalid. The sensitivity to boscalid was determined in conidial germination assays. The majority of isolates from two orchards without a prior history of boscalid usage had effective fungicide concentration to inhibit 50% of spore germination (EC50) values ranging from 0.089 to 3.435 μg/ml, and the mean EC50 was 1.515 μg/ml. Out of 59 isolates collected from an orchard with a history of boscalid usage, 52 isolates had EC50 values ranging from 0.055 to 4.222 μg/ml, and the mean EC50 was 1.214 μg/ml. However, in vitro tests for conidial germination and mycelial growth also revealed that seven A. alternata isolates, originating from the orchard exposed to boscalid were highly resistant (EC50 > 100 μg/ml) to this fungicide. Furthermore, in vitro tests showed no significant differences between wild-type and boscalid-resistant mutants in some fitness parameters such as spore germination, hyphal growth, sporulation, or virulence on pistachio leaves. Experiments on the stability of the boscalid-resistant phenotype showed no reduction of the resistance after the mutants were grown on fungicide-free medium. Preventative applications of a commercial formulation of boscalid (Endura) at a concentration which is effective against naturally sensitive isolates failed to control disease caused by the boscalid-resistant isolates in laboratory tests. To our knowledge, this is first report of field isolates of fungi resistant to boscalid.

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

Annals of the Russian academy of medical sciences ◽

10.15690/vramn583 ◽

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.

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