Anticonvulsant-induced toxic epidermal necrolysis: Monitoring the immunologic response Laura Leyva, MD, PhDa, Maria José Torres, MD, PhDa, Sinforiano.

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Presentation transcript:

Anticonvulsant-induced toxic epidermal necrolysis: Monitoring the immunologic response Laura Leyva, MD, PhDa, Maria José Torres, MD, PhDa, Sinforiano Posadas, BSa, Miguel Blanca, MD, PhDa, Guillermo Besso, MDc, Francisco O’Valle, MD, PhDe, Raimundo García del Moral, MD, PhDe, Luis F. Santamaría, PhDd, Carlos Juárez, MD, PhDb Journal of Allergy and Clinical Immunology Volume 105, Issue 1, Pages 157-165 (January 2000) DOI: 10.1016/S0091-6749(00)90191-X Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 1 Serial expression of homing receptors in T lymphocytes (CD3+) from PBMCs at different time intervals after admission in 3 patients. A, Expression of skin homing receptor CLA. B, Expression of secondary lymphoid tissue homing receptor L-selectin. Journal of Allergy and Clinical Immunology 2000 105, 157-165DOI: (10.1016/S0091-6749(00)90191-X) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 2 Serial expression of skin homing receptor CLA in T-lymphocyte subsets (CD4+ and CD8+) from PBMCs at different time intervals after admission in 3 patients. Journal of Allergy and Clinical Immunology 2000 105, 157-165DOI: (10.1016/S0091-6749(00)90191-X) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 3 Serial expression of activation markers (CD25, CD69, and HLA-DR) in T-lymphocyte subsets (CD4+ and CD8+) from PBMCs at different time intervals after admission in 3 patients. Values are expressed as percentages. Journal of Allergy and Clinical Immunology 2000 105, 157-165DOI: (10.1016/S0091-6749(00)90191-X) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 4 Histopathologic evolution of skin lesion in case 2. (Hematoxylin-eosin stain, original magnification ×200.) A, Subepidermal blister with inflammatory infiltrate in dermoepidermal junction on day 5. B, Epithelial confluent necrosis of blister roof on day 12. C, Complete re-epithelialization with evident dermoepidermal lymphocytic and macrophagic infiltrate on day 90. Journal of Allergy and Clinical Immunology 2000 105, 157-165DOI: (10.1016/S0091-6749(00)90191-X) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 5 A, Skin biopsy specimen of case 3 on day 5. (Mayer’s hematoxylin, original magnification ×20). B, Isotype control for CLA on day 5. (SBAP, original magnification × 100.) C, No positive staining for CLA can be observed on day 5. (SBAP, original magnificaiton × 100.) D, Day 12. Presence of CD3+CLA+ cells is marked by arrow. (SBAP, ×100.) Journal of Allergy and Clinical Immunology 2000 105, 157-165DOI: (10.1016/S0091-6749(00)90191-X) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 6 Proposed mechanism for anticonvulsant-induced TEN. An immunologic reaction originating in skin enables CLA+ T cells to migrate toward cutaneous areas by a multistep adhesion mechanism involving CLA/E-selectin, very late activation antigen-4 (VLA-4) /VCAM-1 and lymphocyte function-associated antigen-1 (LFA-1) /ICAM-1 interactions. After activation by Langerhans cells (Lc) in the skin, T cells can release TNF-α and IFN-γ, leading to the necrosis of epidermal cells. Journal of Allergy and Clinical Immunology 2000 105, 157-165DOI: (10.1016/S0091-6749(00)90191-X) Copyright © 2000 Mosby, Inc. Terms and Conditions