COVID‐19‐related cutaneous manifestations associated with multiple drug sensitization as shown by lymphocyte transformation test

Abstract Background A drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe T cell mediated hypersensitivity reaction. Relapses of symptoms in the recovery phase are frequent and linked to the reduction of the corticosteroid treatment, to viral reactivations or to the exposure to new drugs. Here, we analyzed, how often the exposure to new drugs leads to new sensitization or drug-related relapses without detectable sensitization. Methods 46 patients with DRESS treated in the allergy division of the Inselspital, Bern University Hospital, were retrospectively assessed. Drug-related relapses were analyzed in terms of frequency and whether a possible sensitization evaluated by skin tests and/or lymphocyte transformation tests (LTT) to the new drugs was detectable. Furthermore, drug tolerance was evaluated in a subset of patients. Results 56 relapses were observed in 27 of 46 patients with DRESS (58.7%). 33 (58.9%) of these relapses were associated with the use of new drugs, 30 drug-related relapses were evaluated by patch test and/or lymphocyte transformation test. In 8/30 (26.7%) drug-related relapses, a sensitization to the new drug was demonstrated, suggesting the emergence of a multiple drug hypersensitivity syndrome (MDH). 14 patients experienced 22 drug-related relapses without any detectable sensitization and only 1/6 patients developed new symptoms upon reexposure. Conclusion Patients with DRESS frequently suffered from drug related relapses. Half of the patients with drug-related relapses developed a MDH with proven sensitizations not only to the DRESS inducing drugs, but also to newly applied drugs. When not sensitized, drugs involved in drug related relapses could be reintroduced, if needed. Here, we propose a procedure for drug testing and future management of drug-related relapses in DRESS.

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Diagnostic methods for confirming drug-allergy – the lymphocyte transformation test in dermatology

Orvosi Hetilap ◽

10.1556/oh.2008.28215 ◽

2008 ◽

Vol 149 (24) ◽

pp. 1107-1114

Author(s):

Sarolta Makó ◽

Réka Lepesi-Benkő ◽

Márta Marschalkó ◽

Gyöngyvér Soós ◽

Sarolta Kárpáti

Keyword(s):

Drug Allergy ◽

Lymphocyte Transformation ◽

Lymphocyte Transformation Test ◽

Diagnostic Methods

A gyógyszermellékhatások felismerése és a tüneteket kiváltó gyógyszer oki szerepének bizonyítása komoly felkészültséget igényel. E közlemény célja a gyógyszerallergiás reakciók diagnosztikai lehetőségeinek rövid áttekintése és a lymphocytatranszformációs teszt gyógyszer-hiperszenzitivitási reakciókban való bizonyító szerepének bőrgyógyászati szempontok szerinti értékelése. A lymphocytatranszformációs teszt azon a megfigyelésen alapul, hogy a gyógyszerrel való első találkozáskor kialakult antigénspecifikus T-sejtek osztódni kezdenek az antigénnel való in vitro megismételt találkozás után. A szenzibilizációt az osztódó T-sejtekbe történő 3 H-timidin-beépülés mértéke jelzi. A hatóanyag-specifikus T-sejtek szinte mindig részt vesznek a gyógyszerallergiás reakciókban, ezért a vizsgálat előnye, hogy sok gyógyszernél és különböző immunreakciók eseteiben egyaránt jól alkalmazható. Hátránya a munkaigényesség, valamint az, hogy specificitásának és szenzitivitásának bizonyításához hiányoznak a széles körű, nagy beteganyagon elvégzett tanulmányok. Emiatt a teszt nem egyértelműen elfogadott a gyógyszerallergia igazolására. Hiányosságai ellenére azonban, jobb prediktív értékű egyéb vizsgálatok hiányában, a lymphocytatranszformációs tesztnek fontos szerepe van a gyógyszerallergiák diagnosztizálása terén.

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Intradermal test and lymphocyte transformation test in guinea pigs immunized with gold compounds.

Nishi Nihon Hifuka ◽

10.2336/nishinihonhifu.47.1088 ◽

1985 ◽

Vol 47 (6) ◽

pp. 1088-1092

Author(s):

Shizuo NAITO ◽

Zenro IKEZAWA

Keyword(s):

Guinea Pigs ◽

Lymphocyte Transformation ◽

Lymphocyte Transformation Test ◽

Intradermal Test ◽

Gold Compounds

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Faculty Opinions recommendation of The lymphocyte transformation test in the diagnosis of drug hypersensitivity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.11456.468941 ◽

2006 ◽

Author(s):

Tetsuo Shiohara

Keyword(s):

Drug Hypersensitivity ◽

Lymphocyte Transformation ◽

Lymphocyte Transformation Test

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TO010A NEW IMMUN-TOXICOLOGICAL TEST TO DETECT POLYSULFONE HYPERSENSITIVITY IN HEMODIALYSIS PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa141.to010 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Joachim Beige ◽

Ralph Wendt ◽

Despina Rüssmann ◽

Karl-Peter Ringel

Keyword(s):

False Negative ◽

False Negative Rate ◽

Lymphocyte Transformation ◽

Clinical Problem ◽

Lymphocyte Transformation Test ◽

Laboratory Research ◽

Humoral Immune ◽

Before And After ◽

Positive Results

Abstract Background and Aims Incompatibility of dialysis procedure due to hypersensitivity against dialyzer material which currently is mainly based on polysulfone and derivatives can not be assessed by routine laboratory tests. Although the frequency of such symptoms is suspected to be low (below 2%) such resembles an important clinical problem because dialysis procedures are frequently accompanied by symptoms of non-tolerability with reasons not being entirely clear while circulatory reasons are suspected to play a major role. Method To enlighten the role of polysulfone hypersensitivity, we adapted known standardized material immune-toxicological tests (lymphocyte transformation test, basophil degranulation test) to the specific conditions of dialysis and polysulfone material sensitivity. We developed a method of polysulfone micronisation and measured humoral immune response of isolated patient´s lymphocytes when incubated with polysulfone dispersion. Results 39 samples from 103 patients with suspected polysulfone hypersensitivity showed positive results for type 1 (n=19), type 4 (n=18) or both type (n=2) reactions. There were no significant differences in the level of stimulation measured for DI, SI and lymphogenesis before and after dialysis (average delta -0.4; -0.28; - 1.74, p = 0.71; 0.34; 0.37) and with different dialyzer materials (Tab. 1). Patients with pos. type 4 results (LTT and lymphogenesis) showed highly correlated results in either LTT or lymphogenesis test (Fig. 1, R=0.87, p<0.0001). 8 out of 8 samples from patients with repeated test on different PS showed positive results on either PS. One patient tested positive on PS showed no hypersensitivity with another non-PS (PMMA) material. Conclusion This is the first methodological report showing plausible in-vitro results of patients samples concerning polysulfone intolerance. On the first superficial view, a “false-negative” rate of 60% looks rather disappointing, because all samples derived from patients with suspicion of PS hypersensitivity. However, due to the clinical variability of intolerance symptoms and the high prevalence of any problems after HD initiation, mainly of circulatory origin after initiating extracorporeal circuit, this rate may obviously express the true frequency of isolated PS material hypersensitivity in suspected patients. Alternative pathophysiological pathways of material sensitivity like complement activation, remain to be elucidated and incorporated into a comprehensive future testing panel. Further clinical and laboratory research is needed to define true polysulfone hypersensitivity and to enlighten the field of hypothetic subclinical material incompatibility in patients with impaired dialysis tolerability.

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