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At present, iodinated contrast media (ICM) are mostly non-ionic, have low osmolality, and are safe. Even if adverse drug reactions (ADRs) occur, most are chemo-toxic symptoms and require only observation or H1 antihistamines. However, rare, unpredictable, and even life-threatening hypersensitivity can still occur. The aim of this review is to summarize the issues that all relevant staff need to know about and be able to respond to. The most significant risk factor for ICM hypersensitivity is a history of ICM hypersensitivity. For high-risk populations, we must cautiously weigh the advantages and disadvantages of premedication and be aware that breakthrough reactions may still occur. The best policy for patients with a history of severe ICM hypersensitivity is to avoid the same ICM. If ICM are inevitable, skin tests, in vitro tests, and drug provocation tests may help to find a feasible alternative that is safer. The severity of the hypersensitivity is correlated with the positivity rate of these tests, so there is no need for further investigations for patients with only mild reactions. We should also keep in mind that even excipients in ICM may induce hypersensitivity. Detailed, standardized documentation is essential for correct diagnosis and the prevention of future occurrence.

The causes of nonischemic dilated cardiomyopathy are classified as genetic or nongenetic, but environmental factors such as metal pollutants may interact with genetic susceptibility. The presence of metal particles has been detected in the myocardium, including in those patients with dilated cardiomyopathy. It is also known that hypersensitivity reactions can induce inflammation in tissue. The present study aimed to verify if metal-induced delayed-type hypersensitivity is present in patients with nonischemic dilated cardiomyopathy. The patient group consisted of 30 patients with newly diagnosed dilated cardiomyopathy; the control group comprised 41 healthy subjects. All patients and control subjects provided blood samples for lymphocyte transformation testing (MELISA®) to assess possible hypersensitivity to seven common metals. Specific exposure to metals was based on interview data. Results showed that exposure to cadmium and lead (p = 0.0002), aluminum (p = 0.0006), nickel (p = 0.0012), and chromium (p = 0.0065) was more often reported by patients than controls. The patients also had significantly more frequent hypersensitivity reactions to mercury (26.7% vs. 7.3%, p = 0.014624), nickel (40% vs. 12.2%, p = 0.02341), and silver (20% vs. 4.8%, p = 0.025468) than the control group. Patients with dilated cardiomyopathy had greater exposure to certain metals compared with healthy controls. Hypersensitivity to metals was more frequent in patients with dilated cardiomyopathy, suggesting a possible association that warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Furosemide is the most commonly prescribed loop diuretic worldwide. Although, its extended use, furosemide rarely induces allergic reactions. Until 2013, only 49 cases of furosemide allergy had been described. Clinical case: We have reported on a patient who developed a delayed, erythematous and pruritic skin eruption after the ingestion of furosemide. The implication of furosemide in the reaction was established by a positive lymphocyte transformation test (LTT). Conclusion: This is the first reported case of hypersensitivity to furosemide in which this drug was confirmed as the trigger by a positive LTT. LTT could become a decent diagnostic alternative for patients who experience delayed reactions to furosemide.

Background: Chemical allergies are T cell-mediated diseases that often manifest in the skin as allergic contact dermatitis (ACD). To prevent ACD on a public health scale and avoid elicitation reactions at the individual patient level, predictive and diagnostic tests, respectively, are indispensable. Currently, there is no validated in vitro T cell assay available. The main bottlenecks concern the inefficient generation of T cell epitopes and the detection of rare antigen-specific T cells. Methods: Here, we systematically review original experimental research papers describing T cell activation to chemical skin sensitizers. We focus our search on studies published in the PubMed and Scopus databases on non-metallic allergens in the last 20 years. Results: We identified 37 papers, among them 32 (86%) describing antigen-specific human T cell activation to 31 different chemical allergens. The remaining studies measured the general effects of chemical allergens on T cell function (five studies, 14%). Most antigen-specific studies used peripheral blood mononuclear cells (PBMC) as antigen-presenting cells (APC, 75%) and interrogated the blood T cell pool (91%). Depending on the individual chemical properties, T cell epitopes were generated either by direct administration into the culture medium (72%), separate modification of autologous APC (29%) or by use of hapten-modified model proteins (13%). Read-outs were mainly based on proliferation (91%), often combined with cytokine secretion (53%). The analysis of T cell clones offers additional opportunities to elucidate the mechanisms of epitope formation and cross-reactivity (13%). The best researched allergen was p-phenylenediamine (PPD, 12 studies, 38%). For this and some other allergens, stronger immune responses were observed in some allergic patients (15/31 chemicals, 48%), illustrating the in vivo relevance of the identified T cells while detection limits remain challenging in many cases. Interpretation: Our results illustrate current hardships and possible solutions to monitoring T cell responses to individual chemical skin sensitizers. The provided data can guide the further development of T cell assays to unfold their full predictive and diagnostic potential, including cross-reactivity assessments.

Copyright of Archives of Razi Institute is the property of Institut Razi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The etiology of ulcerative colitis (UC) remains elusive even though many genetic and environmental pathogenic factors have been reported. Aberrant inflammatory responses mediated by specific subsets of T cells have been observed in ulcerative lesions of UC patients. Objectives: To elucidate the involvement of a delayed-type hypersensitivity reaction in UC, we focused on dental metal hypersensitivity, a T cell-mediated, delayed-type allergic reaction that causes oral contact mucositis and systemic cutaneous inflammation. Method: We recruited 65 Japanese UC patients and 22 healthy controls (HC) and used the in vitro lymphocyte stimulation test to quantify their sensitivity to zinc, gold, nickel, and palladium – the metals that have been widely used in dentistry. All subjects were users of metallic dental implants and/or prostheses containing zinc, gold, nickel, and/or palladium as major constituents. Results: Sixty percent of the UC patients were hypersensitive to at least one metal species, whereas 32% of the HC were hypersensitive to only a single metal species. The overall incidence of metal hypersensitivity was significantly higher for UC patients than for HC. Furthermore, a significantly greater proportion of UC patients were hypersensitive to nickel or palladium. The severity of the sensitivity to nickel and palladium was also significantly greater for UC patients than for HC. Conclusions: This pilot study demonstrates that UC patients have a significantly higher incidence of hypersensitivity to nickel and palladium, suggesting the possible involvement of dental metal hypersensitivity in UC pathogenesis. [ABSTRACT FROM AUTHOR]

Although hepatitis C virus (HCV) infection is often associated with extrahepatic cutaneous manifestations such as lichen planus, it is unclear whether HCV per se or HCV-specific immune responses play a pathophysiological role in the development of HCV-related cutaneous diseases. We recently treated a patient who developed parapsoriasis en plaque-like lesions after ingestion of various drugs. She showed hypersensitivity to multiple drugs after interferon therapy. Her clinical course was complicated by flares of parapsoriasis-like lesions which returned at precisely the same sites. The flares had begun within hours of ingesting nicardipine hydrochloride, amlodipine besilate, candesartan cilexetil and atenolol for the first time despite showing a low level of HCV RNA. Interestingly, the flares gradually subsided during continued treatment with these drugs while her HCV RNA level paradoxically increased: thus, there was an inverse correlation between flares and HCV RNA level. The eruptions were eventually diagnosed as fixed drug eruption, although the clinical manifestations mimicked parapsoriasis en plaque. Our results suggest that multiple drug hypersensitivity could be induced by antiviral immune responses that are cross-reactive to multiple drugs, but not by HCV per se. [ABSTRACT FROM AUTHOR]

Previously positive lymphocyte transformation test (LTT) results changed to negative during influenza infection. As observed in the current article, results of LTT may be influenced by infection; therefore, it is crucial to consider the timing of LTT. [ABSTRACT FROM AUTHOR]

Abstract Background Toxic epidermal necrolysis (TEN) is a rare life-threatening condition almost exclusively attributed to drugs. The main etiologic factors for TEN are sulphonamides, anticonvulsants, and antibiotics; however, there are no published reports of warfarin causing TEN. Case presentation We present the case of a 3-year-old patient who developed TEN while receiving treatment for Henoch–Schönlein purpura nephritis (HSPN). With multiple-drug therapy comprising prednisolone, mizoribine, dipyridamole, and warfarin, it is difficult to detect which drug is the causative agent. While in most cases, diagnosis of the causative drug is based on clinical history without a lymphocyte transformation test (LTT), we performed the test three times and identified the causative drug as warfarin at the late phase. We continued HSPN treatment without warfarin, and results showed good renal function without life-threatening complications. Conclusion To our knowledge, this is the first report about TEN caused by warfarin. Repeated LTTs could be useful for identifying TEN-causative drugs even in the late phase.

Drug-induced liver injury (DILI) is a growing problem. Diagnostic methods to differentiate DILI caused by an adaptive immune response from liver injury of other causes or to identify the responsible drug in patients receiving multiple drugs, herbals and/or dietary supplements (polypharmacy) have not yet been established. The lymphocyte transformation test (LTT) has been proposed as a diagnostic method to determine if a subject with an apparent hypersensitivity reaction has become sensitized to a specific drug. In this test, peripheral blood mononuclear cells (PBMC) collected from a subject are incubated with drug(s) suspected of causing the reaction. Cell proliferation, measured by the incorporation of [3H]-thymidine into new DNA, is considered evidence of a drug-specific immune response. The objectives of the current studies were to: (1) develop and optimize a modified version of the LTT (mLTT) and (2) investigate the feasibility of using the mLTT for diagnosing DILI associated with an adaptive immune response and identifying the responsible drug. PBMC collected from donors with a history of drug hypersensitivity reactions to specific drugs (manifested as skin rash) were used as positive controls for assay optimization. Following optimization, samples collected from 24 subjects enrolled in the U.S. Drug-Induced Liver Injury Network (DILIN) were tested in the mLTT. Using cytokine and granzyme B production as the primary endpoints to demonstrate lymphocyte sensitization to a specific drug, most samples from the DILIN subjects failed to respond. However, robust positive mLTT responses were observed for two of four samples from three DILIN subjects with hepatitis due to isoniazid (INH). We conclude that the mLTT, as performed here on frozen and thawed PBMC, is not a reliable test for diagnosing DILI caused by all drugs, but that it may be useful for confirming the role of the adaptive immune response in DILI ascribed to INH.

Delayed type hypersensitivity (DTH) reactions are considered infrequent complications in arthroplasty, but have been recognized to be associated with devastating morbidity and substantial decrease in quality of life of affected patients. Chronic inflammation of artificial joints and associated loss of peri-implant bone often require revision surgery. Methods for the diagnosis of implant-related DTH are available but infrequently considered to the full extent. Sequential diagnostics based on exclusion of septic complications, local and systemic metal level determination, lymphocyte transformation testing (LTT), and local T cell subset analysis are required for an unequivocal DTH diagnosis. Here, we report on a patient with a history of chronic rheumatoid arthritis and an unfavorable outcome of unilateral knee arthroplasty. This case illustrates pitfalls and difficulties in the course of recurrent inflammation following joint replacement. In the early course, suspicion of low-grade bacterial infection led to three two-stage revisions. Afterwards, the joint was proven to be sterile. However, metal level quantification revealed release of especially cobalt and chromium from the joint, LTT indicated persisting cobalt and nickel sensitization and subset analysis of T cells from the synovium suggested DTH as a root cause for the inflammatory symptoms. This report aims to recommend the depicted diagnostic algorithm as an adequate tool for future DTH detection. Yet, systemic to local subset ratios for effector memory and regulatory T cells should be derived from sufficient patient numbers to establish it as a diagnostic marker. Moreover, future prospects regarding implant-related DTH diagnostics are discussed. Therapeutic options for the portrayed patient are proposed, considering pharmaceutical, cell-therapeutic and surgical aspects. Patients who experience peri-implant inflammation but do not have obvious mechanical or infectious problems remain a diagnostic challenge and are at high risk of being treated inadequately. Since potentially sensitizing materials are regularly used in arthroplasty, it is essential to detect cases of acute DTH-derived inflammation of an artificial joint at early postoperative stages. This would reduce the severity of inflammation-related long-term consequences for affected patients and may avoid unnecessary revision surgery.

Cutaneous delayed reactions to antihypertensive drugs have been described in a limited number of case reports but the mechanisms remain mostly unknown. We report the case of a 60-year-old female patient with a 3-week history of an itchy erythematous maculopapular eruption. Although the patient was polymedicated, irbesartan was the most likely culprit. Patch tests and a lymphocyte transformation test to irbesartan were both positive, which was useful for diagnosis and suggested an immunological reaction. No new lesions appeared after irbesartan was stopped or after the introduction of candesartan. Despite its similar chemical structure, candesartan may be tried in patients allergic to irbesartan.

Benznidazole (Bzn) from the nitroimidazole family and nifurtimox from nitrofurans family, are drugs used as first and second line treatment for acute and chronic phases of Chagas disease (CD). Even though skin reactions are frequent, confirmed allergy to Bzn is rare, and there are few cases reported in the literature. Since CD treatment is very restrained, the possibility of cross-reactivity between members of the same and other pharmacological families highlights the importance of an adequate diagnosis that allows alternative treatments in CD and other diseases. We report a series of 31 patients (69% women) referred to our Allergy unit with suspected hypersensitivity to Bzn, twenty three of them with mild reactions and eight of them with severe reactions. LTT with Bzn was performed in 31 patients and in 8 negative controls. LTT was also performed in 25 and 20 of these patients with nifurtimox and Mtn, respectively. Twenty-one out of thirty-one patients were Bzn prick tested, and all were negative. We obtained 2/19 positive results on patch tests to Bzn. LTT with Bzn was positive in 22/31 patients (Sensitivity 75.9% and specificity 100%). The test was considered positive with a stimulation index ≥2. There was a positive result in 7/25 patients for nifurtimox and in 7/20 patients with Mtn. After negative LTT and skin tests, oral provocation was performed in 4/9 patients, all negative. LTT is a safe test that seems to be more useful than skin tests (prick and patch test), particularly in severe reactions, in confirming delayed hypersensitivity to Bzn and detecting cross reactivity with other imidazoles such as Mtn and reactivity to other drugs like nifurtimox. Tests for these drugs need to be included in the workup of patients with hypersensitivity to Bzn in case they are needed as an alternative treatment for CD or to treat other frequent infectious diseases.

Delayed type hypersensitivity (DTH) reactions are considered infrequent complications in arthroplasty, but have been recognized to be associated with devastating morbidity and substantial decrease in quality of life of affected patients. Chronic inflammation of artificial joints and associated loss of peri-implant bone often require revision surgery. Methods for the diagnosis of implant-related DTH are available but infrequently considered to the full extent. Sequential diagnostics based on exclusion of septic complications, local and systemic metal level determination, lymphocyte transformation testing (LTT), and local T cell subset analysis are required for an unequivocal DTH diagnosis. Here, we report on a patient with a history of chronic rheumatoid arthritis and an unfavorable outcome of unilateral knee arthroplasty. This case illustrates pitfalls and difficulties in the course of recurrent inflammation following joint replacement. In the early course, suspicion of low-grade bacterial infection led to three two-stage revisions. Afterwards, the joint was proven to be sterile. However, metal level quantification revealed release of especially cobalt and chromium from the joint, LTT indicated persisting cobalt and nickel sensitization and subset analysis of T cells from the synovium suggested DTH as a root cause for the inflammatory symptoms. This report aims to recommend the depicted diagnostic algorithm as an adequate tool for future DTH detection. Yet, systemic to local subset ratios for effector memory and regulatory T cells should be derived from sufficient patient numbers to establish it as a diagnostic marker. Moreover, future prospects regarding implant-related DTH diagnostics are discussed. Therapeutic options for the portrayed patient are proposed, considering pharmaceutical, cell-therapeutic and surgical aspects. Patients who experience peri-implant inflammation but do not have obvious mechanical or infectious problems remain a diagnostic challenge and are at high risk of being treated inadequately. Since potentially sensitizing materials are regularly used in arthroplasty, it is essential to detect cases of acute DTH-derived inflammation of an artificial joint at early postoperative stages. This would reduce the severity of inflammation-related long-term consequences for affected patients and may avoid unnecessary revision surgery. [ABSTRACT FROM AUTHOR]

Background: Few studies have characterized the clinical manifestations of delayed antibiotic hypersensitivity (AH) diagnosed using objective methods. The lymphocyte transformation test (LTT) is a reproducible method to diagnose type IV hypersensitivity. The purpose of the study was to evaluate the characteristics of delayed AH diagnosed on LTT in children. Methods: We performed a retrospective analysis of patients who were evaluated for AH using LTT at National Center for Child Health and Development, Tokyo, from 2002 to 2014. We extracted patient demographics, type and duration of antibiotics, and clinical characteristics from the medical records. Clinical manifestations were compared between LTT‐positive and LTT‐negative cases. Results: Seventy‐five cases for which 101 drugs were tested were included in this study. LTT was positive against 34 drugs in 26 cases. Median age was 5 years (IQR, 1–9 years), and 49% of patients had underlying disease. LTT was performed at a median of 18 days (IQR, 4–59 days) after the suspected episode. The median number of days from the initiation of therapy to the onset of symptoms was 4. Rash was the most common manifestation (89%). Fever (>38°C) was observed in 20 cases (27%). Onset of fever preceded the rash in nine cases (45%), appeared simultaneously in five (25%), appeared afterwards in four (20%), and was unknown in two (10%). Fever was an independent factor associated with AH when comparing LTT‐positive and LTT‐negative cases (OR, 3.61; 95%CI: 1.03–12.64). Conclusions: Fever was a common presenting symptom of delayed AH in children aged ≤18 years. [ABSTRACT FROM AUTHOR]

Background: There is considerable interest in understanding the immunological variables that have the greatest influence on the effectiveness of sensitization by contact allergens, particularly in the context of developing new paradigms for risk assessment of novel compounds. Objectives: To examine the relationship between patch test score for three different contact allergens and the characteristics of T cell responses. Methods: A total of 192 patients with confirmed nickel, p‐phenylenediamine (PPD) or methylisothiazolinone (MI) allergy were recruited from the Contact Dermatitis Investigation Unit at Salford Royal Hospital. Severity of allergy was scored by the use of patch testing, peripheral blood lymphocytes were characterized for T cell phenotype by flow cytometry, and proliferative activity was characterized by radiolabelled thymidine incorporation. Comparisons were drawn with buffy coat samples from healthy volunteers. Results: Patch test positivity for nickel, PPD and MI was associated with changes in the phenotype of peripheral blood T cells: increases in naïve cells, decreases in regulatory T cell frequency and the CD4+/CD8hi ratio, and increased expression of the skin‐homing marker cutaneous lymphocyte antigen (CLA), particularly for those patients with a +++ patch test score. Conclusions: This increased understanding of the characteristics of the T cell responses to contact allergens may provide parameters with which to better measure health risks associated with skin sensitization. [ABSTRACT FROM AUTHOR]

Copyright of Gyermekgyógyászat is the property of Semmelweis Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Benznidazole (Bzn) from the nitroimidazole family and nifurtimox from nitrofurans family, are drugs used as first and second line treatment for acute and chronic phases of Chagas disease (CD). Even though skin reactions are frequent, confirmed allergy to Bzn is rare, and there are few cases reported in the literature. Since CD treatment is very restrained, the possibility of cross-reactivity between members of the same and other pharmacological families highlights the importance of an adequate diagnosis that allows alternative treatments in CD and other diseases. We report a series of 31 patients (69% women) referred to our Allergy unit with suspected hypersensitivity to Bzn, twenty three of them with mild reactions and eight of them with severe reactions. LTT with Bzn was performed in 31 patients and in 8 negative controls. LTT was also performed in 25 and 20 of these patients with nifurtimox and Mtn, respectively. Twenty-one out of thirty-one patients were Bzn prick tested, and all were negative. We obtained 2/19 positive results on patch tests to Bzn. LTT with Bzn was positive in 22/31 patients (Sensitivity 75.9% and specificity 100%). The test was considered positive with a stimulation index ≥2. There was a positive result in 7/25 patients for nifurtimox and in 7/20 patients with Mtn. After negative LTT and skin tests, oral provocation was performed in 4/9 patients, all negative. LTT is a safe test that seems to be more useful than skin tests (prick and patch test), particularly in severe reactions, in confirming delayed hypersensitivity to Bzn and detecting cross reactivity with other imidazoles such as Mtn and reactivity to other drugs like nifurtimox. Tests for these drugs need to be included in the workup of patients with hypersensitivity to Bzn in case they are needed as an alternative treatment for CD or to treat other frequent infectious diseases. [ABSTRACT FROM AUTHOR]

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse drug reactions, and SJS/TEN in infancy is rare. Here, we present a case of a 4-month-old infant with generalized exanthema, flaccid blisters, and mucosal erosions. He was diagnosed with TEN within 2 days using a granulysin quick screen test and subsequently verified with histopathologic findings. Transmission of cephalexin through breastfeeding was suspected to be a possible cause based on drug history, breastfeeding history, and lymphocyte transformation test. The patient survived with only skin hyperpigmentation remaining. [ABSTRACT FROM AUTHOR]

Growing and sustainable consumption of health‐care products raises a controversial issue underlying the reliability of an in vitro diagnostic approach for adverse skin reaction. This report aimed to: (i) discuss the causative nature of a commercial dietary supplement composed of natural ingredients, particularly an Euglena‐containing product, suspicious for erythema multiforme in our exemplified case; and (ii) to address the assay suitability of the lymphocyte transformation test (LTT) for identifying allergic reaction to any ingredient(s) of the product. A Japanese elderly man developed erythema multiforme after intake of a commercially available natural dietary product, whose LTT was positive. His clinical course and positive LTT suggested a provisional diagnosis of natural dietary product‐induced eruption. We conducted an inquiry survey for the standard LTT with any commercial products containing Euglena in three major Japanese laboratory services and identified 22 subjects, almost all of whom (21/22, 95.6%) showed a positive LTT for any Euglena‐containing products as a suspected causative. Seven normal healthy volunteers who had no intake history of Euglena‐containing products showed an equivalent LTT positivity rate with the same product taken by our case; culprit components of the product included Euglena, Angelica keiskei, Barley grass and Chlorella. A cell‐free culture system and enzyme‐linked immunoassay suggest that the high LTT positivity relies on the non‐specific lymphoproliferative activity, and not contamination of uncharacterized microorganisms and endotoxins. Because of the constitutive false positivity of LTT, this assay is unreliable for in vitro supportive diagnosis of adverse skin events caused by dietary products containing particular natural ingredients, as well as herbal materials. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) is a growing problem. Diagnostic methods to differentiate DILI caused by an adaptive immune response from liver injury of other causes or to identify the responsible drug in patients receiving multiple drugs, herbals and/or dietary supplements (polypharmacy) have not yet been established. The lymphocyte transformation test (LTT) has been proposed as a diagnostic method to determine if a subject with an apparent hypersensitivity reaction has become sensitized to a specific drug. In this test, peripheral blood mononuclear cells (PBMC) collected from a subject are incubated with drug(s) suspected of causing the reaction. Cell proliferation, measured by the incorporation of [3H]-thymidine into new DNA, is considered evidence of a drug-specific immune response. The objectives of the current studies were to: (1) develop and optimize a modified version of the LTT (mLTT) and (2) investigate the feasibility of using the mLTT for diagnosing DILI associated with an adaptive immune response and identifying the responsible drug. PBMC collected from donors with a history of drug hypersensitivity reactions to specific drugs (manifested as skin rash) were used as positive controls for assay optimization. Following optimization, samples collected from 24 subjects enrolled in the U.S. Drug-Induced Liver Injury Network (DILIN) were tested in the mLTT. Using cytokine and granzyme B production as the primary endpoints to demonstrate lymphocyte sensitization to a specific drug, most samples from the DILIN subjects failed to respond. However, robust positive mLTT responses were observed for two of four samples from three DILIN subjects with hepatitis due to isoniazid (INH). We conclude that the mLTT, as performed here on frozen and thawed PBMC, is not a reliable test for diagnosing DILI caused by all drugs, but that it may be useful for confirming the role of the adaptive immune response in DILI ascribed to INH. [ABSTRACT FROM AUTHOR]

The lymphocyte transformation test (LTT) is used for the in vitro detection of a drug sensitization in assumed drug allergic patients. It is based on the detection of antigen (drug)-specific activation of T cells indicated by e.g. proliferation or cytokine secretion. However, occasional stimulatory effects of the drug unrelated to specific drug-allergic mechanisms can only be detected if a larger number of non-drug allergic control persons are tested with this specific drug. In this respect, the overall specificity of the LTT with ELISA read-out is summarized in several review articles, but the impact of a specific drug on the specificity has not yet been analyzed in a larger set of control persons. Do amoxicillin, cefuroxime and clindamycin induce an interferon (IFN)-y or interleukin (IL)-5 secretion of PBMC from control persons using the LTT with ELISA read-out? We performed LTTs with amoxicillin, cefuroxime and clindamycin and determined drug-specific IFN-γ and IL-5 secretion measured by ELISA read-out. We included PBMC from 60 non-drug allergic control persons, who were unexposed to the tested drug at the time of blood donation. PBMC from 12 out of 23 control persons tested with amoxicillin gave a positive stimulation index (SI > 3.0) for IFN-γ resulting in a specificity of 47.8%. The corresponding specificity was 75% for cefuroxime (5/20 if SI > 3.0) and 58.8% for clindamycin (7/17, if SI > 2.0), respectively. In a next step, we calculated the Δ IFN-γ concentration by subtracting the background IFN-γ concentration in the unstimulated sample from the stimulated sample. After stimulation with amoxicillin, a mean concentration of 21.0 pg/mL IFN-γ was secreted. The less outlier prone median concentration was 7.4 pg/mL and much higher than for cefuroxime (1.7 pg/mL) and clindamycin (1.0 pg/mL). Remarkably, IL-5 concentrations were below the detection limit (< 1 pg/mL) for all drugs in all control persons who responded to TT. Consideration of these observations may be helpful since a positive LTT result in a control patient may challenge the validity of a positive LTT result in the same experiment for a patient with assumed drug allergy. [ABSTRACT FROM AUTHOR]

Background: Amlodipine is one of the third generation dihydropyridine calcium channel blockers used for hypertension. Mild, moderate and severe reactions have been reported with calcium channel blockers. Cross-reactivity among these drugs has not been established. Case report: We have presented the case of a patient who developed a delayed pruritic, and erythematous maculopapular skin exanthema after the intake of amlodipine. A positive lymphocyte transformation test (LTT) confirmed the implication of amlodipine in the reaction and showed positivity to another calcium channel blocker, nifedipine, demonstrating cross reactivity. Conclusion: This is the first reported case of hypersensitivity to amlodipine in which the involvement of the drug is confirmed by a positive TTL. TTL could become a good diagnostic alternative for patients who experience late reactions to amlodipine and possibly cross-reactivity with nifedipine. [ABSTRACT FROM AUTHOR]

Introduction: Betalactams are the most widely used drugs against infections and the primary cause of antibiotic hypersensitivity reactions. Reaction patterns for different betalactams have been changing in accordance with consumption trends, and vary among countries. As a consequence,in vivoandin vitrotests have had to change with to keep up with new tendencies. Areas covered: This review is focused on advances in betalactam hypersensitivity diagnosis. Changes inin vivomethods have been limited to the inclusion of new haptens. In contrast, major progress has been achieved forin vitrotests since the 1960s, from the first description of immunoassays, the basophil activation test and the lymphocyte transformation test, to the more sophisticated assays developed in last years. Expert commentary: Issues with diagnosis are related to test sensitivity.In vivotests show higher sensitivity, however they can be risky, especially in severe and life-threatening reactions. Therefore, we believe thatin vitrotests should be the preferred method. Current efforts are under way to enhance their sensitivity. Only multidisciplinary approaches involving immunology, proteomics, nanotechnology and chemistry can help us to fully understand conjugate structures and mechanisms involved in hypersensitivity reactions to betalactams, and consequently lead to advances inin vitromethods. [ABSTRACT FROM PUBLISHER]

Background The patch test is considered to be the gold standard for diagnosing nickel ( Ni) allergy. The lymphocyte transformation test ( LTT) can also be used to detect Ni sensitization. However, little is known about the correlation between patch test and LTT reactions to Ni. Objective To establish and validate an LTT for Ni sensitization by comparison with patch test reaction and history. Methods Fifty individuals without self-reported ' Ni allergy' (controls) and 50 patients with self-reported suspicion of Ni allergy were included. A questionnaire-aided history was taken, and patch tests with at least the baseline series and LTTs with various Ni SO4 dilutions were performed. Results In the patch tests, 2 of 50 controls and 18 of 50 patients with self-reported suspicion of Ni allergy showed positive reactions to Ni. In the LTTs, 2 of 50 controls and 26 of 50 patients with self-reported suspicion of Ni allergy showed positive reactions to Ni SO4 2.5 × 10−5 m, and 2 of 50 controls and 17 of 50 patients with self-reported suspicion of Ni allergy showed positive reactions to Ni SO4 1 × 10−5 m. Sixteen of the 18 history-positive and patch test-positive patients (i.e. 88% sensitivity) were also LTT-positive, in contrast to only 2 positive LTT reactors within the 48 PT and history negative individuals (i.e. 96% specificity). [Correction added on 16 February 2017, after first online publication: The preceding sentence has been edited for language and this has been amended in this version.] Conclusion Performing the LTT with optimized stimulating conditions might be a useful additional tool for the diagnosis of Ni allergy if non-sensitized controls are included. [ABSTRACT FROM AUTHOR]

Background: Furosemide is the most commonly prescribed loop diuretic worldwide. Although, its extended use, furosemide rarely induces allergic reactions. Until 2013, only 49 cases of furosemide allergy had been described. Clinical case: We have reported on a patient who developed a delayed, erythematous and pruritic skin eruption after the ingestion of furosemide. The implication of furosemide in the reaction was established by a positive lymphocyte transformation test (LTT). Conclusion: This is the first reported case of hypersensitivity to furosemide in which this drug was confirmed as the trigger by a positive LTT. LTT could become a decent diagnostic alternative for patients who experience delayed reactions to furosemide. [ABSTRACT FROM AUTHOR]

However, oral stomatitis induced by drug hypersensitivity could be considered within the FDE spectrum due to the shared underlying immune mechanisms and the fixed localization of the lesions. Keywords: hypersensitivity; late reactions; case report; lymphocyte transformation test; stomatitis; varenicline EN hypersensitivity late reactions case report lymphocyte transformation test stomatitis varenicline 317 318 2 03/16/22 20220401 NES 220401 CASE REPORT We present a case of erosive stomatitis as a manifestation of hypersensitivity to varenicline. Using in vitro tests in this type of reaction helps to clarify the causative drug, thereby avoiding high-risk procedures, such as oral challenge tests.6 Because this is a T cell-mediated drug hypersensitivity reaction, a differential diagnosis with fixed drug eruption (FDE) should be considered. [Extracted from the article]

The introduction of ribavirin to hepatitis C combination therapy with pegylated interferon (PEG-IFN)-α2a has improved sustained responses, but it has been accompanied by an increased incidence of cutaneous side effects. Most cases of drug eruption caused by ribavirin and PEG-IFN-α2 or IFN-α combination therapy were not severe and we progressed without discontinuation of the antiviral treatment. We describe a 59-year-old Japanese woman with a chronic hepatitis C infection who developed erythema during PEG-IFN-α2a and ribavirin combination therapy. The eruption at the injection site of IFN occurred after each injection, and then, eruption on her exposed skin was observed. Twenty milligrams of prednisolone was administered. The eruption recurred after each administration of prednisolone and ribavirin. She finally had infiltrative erythema without any mucosal symptoms on her body. It seemed to be an erythema multiforme type drug eruption of PEG-IFN-α2a, ribavirin and/or fluvastatin sodium from the clinical course. The lymphocyte transformation test (LTT) of ribavirin was positive. This is the first case of a positive result of an LTT for ribavirin. A photosensitive type drug eruption with ribavirin treatment has been reported. We should not only consider IFN, but also ribavirin in case of a generalized eruption, especially on an exposed area with combination therapy for HCV.