Anticonvulsant-induced toxic epidermal necrolysis: Monitoring the immunologic response
Background: Toxic epidermal necrolysis is a severe reaction with skin involvement induced by different drugs and other agents. The mechanisms implicated in the induction of the reaction are poorly understood. Objective: Our purpose was to study the involvement of T lymphocytes and other immunocompet...
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description | Background: Toxic epidermal necrolysis is a severe reaction with skin involvement induced by different drugs and other agents. The mechanisms implicated in the induction of the reaction are poorly understood. Objective: Our purpose was to study the involvement of T lymphocytes and other immunocompetent cells in the peripheral blood, blister fluid, and affected skin of 3 patients who had a severe reaction after receiving anticonvulsant medication. Methods: Quantification of T lymphocytes expressing the skin-homing receptor (cutaneous lymphocyte-associated antigen [CLA]) in peripheral blood, skin, and skin blister fluid and assessment of other adhesion molecules, activation markers, and inflammatory interleukins by flow cytometry, immunohistochemistry, and reverse transcription–PCR. Results: An increase in CD3+CLA+ cells paralleling the severity of the disease was observed in both peripheral blood and skin, tending to normalize as soon as patient’s conditions improved. E-selectin was detected in endothelial vessels in parallel with CLA expression on lymphocytes. An overexpression of TNFα, IFN-γ, and IL-2 was also observed in PBMCs. The expression of the different markers changed over the course of the disease. Conclusions: These data show an increase in activated T cells expressing the skin-homing receptor in both tissue and peripheral blood accompanying clinical symptoms, with a recruitment of macrophages and an overexpression of cytokines. All these results suggest an important role for T cells in the production of toxic epidermal necrolysis. (J Allergy Clin Immunol 2000;105:157-65.) |
doi_str_mv | 10.1016/S0091-6749(00)90191-X |
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The mechanisms implicated in the induction of the reaction are poorly understood. Objective: Our purpose was to study the involvement of T lymphocytes and other immunocompetent cells in the peripheral blood, blister fluid, and affected skin of 3 patients who had a severe reaction after receiving anticonvulsant medication. Methods: Quantification of T lymphocytes expressing the skin-homing receptor (cutaneous lymphocyte-associated antigen [CLA]) in peripheral blood, skin, and skin blister fluid and assessment of other adhesion molecules, activation markers, and inflammatory interleukins by flow cytometry, immunohistochemistry, and reverse transcription–PCR. Results: An increase in CD3+CLA+ cells paralleling the severity of the disease was observed in both peripheral blood and skin, tending to normalize as soon as patient’s conditions improved. E-selectin was detected in endothelial vessels in parallel with CLA expression on lymphocytes. An overexpression of TNFα, IFN-γ, and IL-2 was also observed in PBMCs. The expression of the different markers changed over the course of the disease. Conclusions: These data show an increase in activated T cells expressing the skin-homing receptor in both tissue and peripheral blood accompanying clinical symptoms, with a recruitment of macrophages and an overexpression of cytokines. All these results suggest an important role for T cells in the production of toxic epidermal necrolysis. (J Allergy Clin Immunol 2000;105:157-65.)</description><identifier>ISSN: 0091-6749</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1016/S0091-6749(00)90191-X</identifier><identifier>PMID: 10629466</identifier><identifier>CODEN: JACIBY</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Adult ; Antibody Formation ; anticonvulsant ; Anticonvulsants - adverse effects ; Biological and medical sciences ; Blood Cells - metabolism ; Blood Cells - pathology ; Carbamazepine - adverse effects ; CD3 Complex - analysis ; cutaneous lymphocyte-associated antigen ; cytokines ; Cytokines - metabolism ; Drug toxicity and drugs side effects treatment ; E-Selectin - metabolism ; Endothelium - metabolism ; Female ; homing ; Humans ; Male ; Medical sciences ; Middle Aged ; Miscellaneous (drug allergy, mutagens, teratogens...) ; Pharmacology. Drug treatments ; Phenytoin - adverse effects ; Receptors, Lymphocyte Homing - metabolism ; severe skin reactions ; Skin - metabolism ; Skin - pathology ; Stevens-Johnson Syndrome - immunology ; Stevens-Johnson Syndrome - metabolism ; Stevens-Johnson Syndrome - pathology ; Stevens-Johnson Syndrome - physiopathology ; T lymphocytes ; Toxic epidermal necrolysis</subject><ispartof>Journal of allergy and clinical immunology, 2000-01, Vol.105 (1), p.157-165</ispartof><rights>2000 Mosby, Inc.</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-bcb53c70f83ffe84d8d27924c44d917098c2b0b9ab144e88ba4f469ea3a41c3d3</citedby><cites>FETCH-LOGICAL-c534t-bcb53c70f83ffe84d8d27924c44d917098c2b0b9ab144e88ba4f469ea3a41c3d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0091-6749(00)90191-X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,4010,27904,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1263989$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10629466$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leyva, Laura</creatorcontrib><creatorcontrib>Torres, Maria José</creatorcontrib><creatorcontrib>Posadas, Sinforiano</creatorcontrib><creatorcontrib>Blanca, Miguel</creatorcontrib><creatorcontrib>Besso, Guillermo</creatorcontrib><creatorcontrib>O’Valle, Francisco</creatorcontrib><creatorcontrib>del Moral, Raimundo García</creatorcontrib><creatorcontrib>Santamaría, Luis F.</creatorcontrib><creatorcontrib>Juárez, Carlos</creatorcontrib><title>Anticonvulsant-induced toxic epidermal necrolysis: Monitoring the immunologic response</title><title>Journal of allergy and clinical immunology</title><addtitle>J Allergy Clin Immunol</addtitle><description>Background: Toxic epidermal necrolysis is a severe reaction with skin involvement induced by different drugs and other agents. The mechanisms implicated in the induction of the reaction are poorly understood. Objective: Our purpose was to study the involvement of T lymphocytes and other immunocompetent cells in the peripheral blood, blister fluid, and affected skin of 3 patients who had a severe reaction after receiving anticonvulsant medication. Methods: Quantification of T lymphocytes expressing the skin-homing receptor (cutaneous lymphocyte-associated antigen [CLA]) in peripheral blood, skin, and skin blister fluid and assessment of other adhesion molecules, activation markers, and inflammatory interleukins by flow cytometry, immunohistochemistry, and reverse transcription–PCR. Results: An increase in CD3+CLA+ cells paralleling the severity of the disease was observed in both peripheral blood and skin, tending to normalize as soon as patient’s conditions improved. E-selectin was detected in endothelial vessels in parallel with CLA expression on lymphocytes. An overexpression of TNFα, IFN-γ, and IL-2 was also observed in PBMCs. The expression of the different markers changed over the course of the disease. Conclusions: These data show an increase in activated T cells expressing the skin-homing receptor in both tissue and peripheral blood accompanying clinical symptoms, with a recruitment of macrophages and an overexpression of cytokines. All these results suggest an important role for T cells in the production of toxic epidermal necrolysis. (J Allergy Clin Immunol 2000;105:157-65.)</description><subject>Adult</subject><subject>Antibody Formation</subject><subject>anticonvulsant</subject><subject>Anticonvulsants - adverse effects</subject><subject>Biological and medical sciences</subject><subject>Blood Cells - metabolism</subject><subject>Blood Cells - pathology</subject><subject>Carbamazepine - adverse effects</subject><subject>CD3 Complex - analysis</subject><subject>cutaneous lymphocyte-associated antigen</subject><subject>cytokines</subject><subject>Cytokines - metabolism</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>E-Selectin - metabolism</subject><subject>Endothelium - metabolism</subject><subject>Female</subject><subject>homing</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Miscellaneous (drug allergy, mutagens, teratogens...)</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenytoin - adverse effects</subject><subject>Receptors, Lymphocyte Homing - metabolism</subject><subject>severe skin reactions</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><subject>Stevens-Johnson Syndrome - immunology</subject><subject>Stevens-Johnson Syndrome - metabolism</subject><subject>Stevens-Johnson Syndrome - pathology</subject><subject>Stevens-Johnson Syndrome - physiopathology</subject><subject>T lymphocytes</subject><subject>Toxic epidermal necrolysis</subject><issn>0091-6749</issn><issn>1097-6825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1O3TAQRq0KVC6UR2iVBaroIu04dhKbDUIIChKoi7aIneXYEzBK7IudoPL2GO4VsOtqNNL55ucQ8pnCdwq0-fEbQNKyabncB_gmgebu-gNZUJBt2Yiq3iCLV2SLbKd0B7lnQn4kWxSaSvKmWZCrIz85E_zDPCTtp9J5Oxu0xRT-OVPg0lmMox4KjyaG4TG5dFBcBu-mEJ2_KaZbLNw4zj4M4SYHIqZl8Ak_kc1eDwl313WH_D09-XN8Vl78-nl-fHRRmprxqexMVzPTQi9Y36PgVtiqlRU3nFtJW5DCVB10UneUcxSi07znjUTNNKeGWbZDvq7mLmO4nzFNanTJ4DBoj2FOira1bBm0GaxXYH4jpYi9WkY36vioKKhnoepFqHq2pQDUi1B1nXNf1gvmbkT7LrUymIG9NaCT0UMftTcuvXFVw6SQGTtcYZhtPDiMKhmHPqt2Ec2kbHD_ueQJ0t-UhA</recordid><startdate>200001</startdate><enddate>200001</enddate><creator>Leyva, Laura</creator><creator>Torres, Maria José</creator><creator>Posadas, Sinforiano</creator><creator>Blanca, Miguel</creator><creator>Besso, Guillermo</creator><creator>O’Valle, Francisco</creator><creator>del Moral, Raimundo García</creator><creator>Santamaría, Luis F.</creator><creator>Juárez, Carlos</creator><general>Mosby, Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>200001</creationdate><title>Anticonvulsant-induced toxic epidermal necrolysis: Monitoring the immunologic response</title><author>Leyva, Laura ; Torres, Maria José ; Posadas, Sinforiano ; Blanca, Miguel ; Besso, Guillermo ; O’Valle, Francisco ; del Moral, Raimundo García ; Santamaría, Luis F. ; Juárez, Carlos</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-bcb53c70f83ffe84d8d27924c44d917098c2b0b9ab144e88ba4f469ea3a41c3d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adult</topic><topic>Antibody Formation</topic><topic>anticonvulsant</topic><topic>Anticonvulsants - adverse effects</topic><topic>Biological and medical sciences</topic><topic>Blood Cells - metabolism</topic><topic>Blood Cells - pathology</topic><topic>Carbamazepine - adverse effects</topic><topic>CD3 Complex - analysis</topic><topic>cutaneous lymphocyte-associated antigen</topic><topic>cytokines</topic><topic>Cytokines - metabolism</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>E-Selectin - metabolism</topic><topic>Endothelium - metabolism</topic><topic>Female</topic><topic>homing</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Miscellaneous (drug allergy, mutagens, teratogens...)</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenytoin - adverse effects</topic><topic>Receptors, Lymphocyte Homing - metabolism</topic><topic>severe skin reactions</topic><topic>Skin - metabolism</topic><topic>Skin - pathology</topic><topic>Stevens-Johnson Syndrome - immunology</topic><topic>Stevens-Johnson Syndrome - metabolism</topic><topic>Stevens-Johnson Syndrome - pathology</topic><topic>Stevens-Johnson Syndrome - physiopathology</topic><topic>T lymphocytes</topic><topic>Toxic epidermal necrolysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leyva, Laura</creatorcontrib><creatorcontrib>Torres, Maria José</creatorcontrib><creatorcontrib>Posadas, Sinforiano</creatorcontrib><creatorcontrib>Blanca, Miguel</creatorcontrib><creatorcontrib>Besso, Guillermo</creatorcontrib><creatorcontrib>O’Valle, Francisco</creatorcontrib><creatorcontrib>del Moral, Raimundo García</creatorcontrib><creatorcontrib>Santamaría, Luis F.</creatorcontrib><creatorcontrib>Juárez, Carlos</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of allergy and clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leyva, Laura</au><au>Torres, Maria José</au><au>Posadas, Sinforiano</au><au>Blanca, Miguel</au><au>Besso, Guillermo</au><au>O’Valle, Francisco</au><au>del Moral, Raimundo García</au><au>Santamaría, Luis F.</au><au>Juárez, Carlos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anticonvulsant-induced toxic epidermal necrolysis: Monitoring the immunologic response</atitle><jtitle>Journal of allergy and clinical immunology</jtitle><addtitle>J Allergy Clin Immunol</addtitle><date>2000-01</date><risdate>2000</risdate><volume>105</volume><issue>1</issue><spage>157</spage><epage>165</epage><pages>157-165</pages><issn>0091-6749</issn><eissn>1097-6825</eissn><coden>JACIBY</coden><abstract>Background: Toxic epidermal necrolysis is a severe reaction with skin involvement induced by different drugs and other agents. The mechanisms implicated in the induction of the reaction are poorly understood. Objective: Our purpose was to study the involvement of T lymphocytes and other immunocompetent cells in the peripheral blood, blister fluid, and affected skin of 3 patients who had a severe reaction after receiving anticonvulsant medication. Methods: Quantification of T lymphocytes expressing the skin-homing receptor (cutaneous lymphocyte-associated antigen [CLA]) in peripheral blood, skin, and skin blister fluid and assessment of other adhesion molecules, activation markers, and inflammatory interleukins by flow cytometry, immunohistochemistry, and reverse transcription–PCR. Results: An increase in CD3+CLA+ cells paralleling the severity of the disease was observed in both peripheral blood and skin, tending to normalize as soon as patient’s conditions improved. E-selectin was detected in endothelial vessels in parallel with CLA expression on lymphocytes. An overexpression of TNFα, IFN-γ, and IL-2 was also observed in PBMCs. The expression of the different markers changed over the course of the disease. Conclusions: These data show an increase in activated T cells expressing the skin-homing receptor in both tissue and peripheral blood accompanying clinical symptoms, with a recruitment of macrophages and an overexpression of cytokines. All these results suggest an important role for T cells in the production of toxic epidermal necrolysis. (J Allergy Clin Immunol 2000;105:157-65.)</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>10629466</pmid><doi>10.1016/S0091-6749(00)90191-X</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Antibody Formation anticonvulsant Anticonvulsants - adverse effects Biological and medical sciences Blood Cells - metabolism Blood Cells - pathology Carbamazepine - adverse effects CD3 Complex - analysis cutaneous lymphocyte-associated antigen cytokines Cytokines - metabolism Drug toxicity and drugs side effects treatment E-Selectin - metabolism Endothelium - metabolism Female homing Humans Male Medical sciences Middle Aged Miscellaneous (drug allergy, mutagens, teratogens...) Pharmacology. Drug treatments Phenytoin - adverse effects Receptors, Lymphocyte Homing - metabolism severe skin reactions Skin - metabolism Skin - pathology Stevens-Johnson Syndrome - immunology Stevens-Johnson Syndrome - metabolism Stevens-Johnson Syndrome - pathology Stevens-Johnson Syndrome - physiopathology T lymphocytes Toxic epidermal necrolysis |
title | Anticonvulsant-induced toxic epidermal necrolysis: Monitoring the immunologic response |
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