Increased soluble Fas ligand levels in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis preceding skin detachment  Junko Murata,

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Increased soluble Fas ligand levels in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis preceding skin detachment  Junko Murata, MD, Riichiro Abe, MD, PhD, Hiroshi Shimizu, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 122, Issue 5, Pages 992-1000 (November 2008) DOI: 10.1016/j.jaci.2008.06.013 Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Increased serum sFasL levels of patients with SJS/TEN. A, sFasL levels of healthy control subjects, patients with ODSRs, and patients with SJS/TEN, with disease courses. In patients with SJS/TEN, we examined concentrations of serum sFasL at 5 times: day −4 to day −2, day −1 to day 2, day 3 to day 5, day 6 to day 10, and after day 11. sFasL levels were significantly increased before onset of disease, day −4 to day −2, compared with those in patients with ODSRs and healthy control subjects (∗P < .05). B, Time course of serum sFasL levels in patients with SJS/TEN. Increased sFasL levels in patients with SJS/TEN rapidly decreased to the normal range within 5 days after onset. Journal of Allergy and Clinical Immunology 2008 122, 992-1000DOI: (10.1016/j.jaci.2008.06.013) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Serum levels of TNF-α, IFN-γ, IL-6, and sCD40L. A, TNF-α levels in sera of healthy control subjects, patients with ODSRs, and patients with SJS/TEN, with disease courses. High TNF-α concentrations were detected in sera of 25.0% of patients with SJS/TEN before onset (ND, approximately 33.8 pg/mL; mean, 20.2 ± 9.1 pg/mL) and 20.0% of patients with ODSRs (ND, approximately 411.9 pg/mL; mean 40.6 ± 89.7 pg/mL). There was no significant difference between patients with SJS/TEN and patients with ODSRs. B, In 20.0% of samples from patients with ODSRs, IFN-γ levels were increased (ND, approximately 778.7 pg/mL; mean, 68.5 ± 176.8 pg/mL). From day −4 to day −2, 75.0% of samples showed high IFN-γ levels (ND, approximately 57.6 pg/mL; mean, 31.4 ± 18.6pg/mL) in patients with SJS/TEN. There was no significant difference between patients with ODSRs and patients with SJS/TEN between day −4 and day −2. C, In 65.0% of samples of patients with ODSRs, IL-6 levels were increased (ND, approximately 202.9 pg/mL; mean, 41.1 ± 63.5 pg/mL) and significantly increased compared with those seen in healthy control subjects (∗∗P < .01). Before onset, day −4 to day −2, the IL-6 level increased in all samples (approximately 11.9-139.6 pg/mL; mean, 64.7 ± 53.7 pg/mL), whereas they did not significantly increase compared with those of patients with ODSRs. D, In 20.0% of samples from patients with ODSRs, sCD40L levels were increased (approximately 314-18424 pg/mL; mean, 6955 ± 5092 pg/mL). sCD40L concentrations in patients with SJS/TEN taken before onset, from day −4 to day −2, were not increased (ND, approximately 10,197 pg/mL; mean, 2559 ± 3525 pg/mL) and were lower than those of patients with ODSRs (∗∗∗P < .05). Journal of Allergy and Clinical Immunology 2008 122, 992-1000DOI: (10.1016/j.jaci.2008.06.013) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Case 1 (patient 6). A, clinical presentation of the patient at day −4 and day 1. B, sFasL levels of sera with disease course. sFasL levels were increased up to 232 pg/mL on day −4 when she presented with only erythema without oral lesions and skin detachment. When an oral lesion developed (day 1), sFasL levels had already decreased to normal levels and remained at these levels until her eruption was cured (day 11). C-F, TNF-α, IFN-γ, IL-6, and sCD40L levels of sera with disease course. In her serum IFN-γ and IL-6 levels increased on day −4 and day 1 and then decreased to within normal levels. Journal of Allergy and Clinical Immunology 2008 122, 992-1000DOI: (10.1016/j.jaci.2008.06.013) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Case 2 (patient 20). A, clinical presentation of the patient at day 12. B, sFasL level of sera with disease course. Although increased sFasL levels were detected on day −3 (126 pg/mL), they decreased to normal ranges on day 20 and after healing. C-F, TNF-α, IFN-γ, IL-6, and sCD40L levels in sera with disease course. The peak of TNF-α was 25.4 pg/mL on day 20, that of IL-6 was 72.1 pg/mL on day 20, and that of sCD40L was 14,424 pg/mL on day 5. IFN-γ levels were slightly increased on day −3 (21.5 pg/mL) and soon decreased. Journal of Allergy and Clinical Immunology 2008 122, 992-1000DOI: (10.1016/j.jaci.2008.06.013) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Case 3 (patient 27). A, Clinical presentation of the patient at day −3 and day 1. B, sFasL level of sera with disease course. Increased sFasL levels were detected on day −3 (127 pg/mL) and were decreased on day 2 and day 5 to less than 100 pg/mL. C-F, TNF-α, IFN-γ, IL-6, and sCD40L levels in sera with disease course. TNF-α increased on day 5 (24.8 pg/mL), and IFN-γ levels increased before onset at day −3 (30.7 pg/mL). sCD40L levels were not increased in any samples. IL-6 concentrations were considerably increased on day 2 (825.2 pg/mL). Journal of Allergy and Clinical Immunology 2008 122, 992-1000DOI: (10.1016/j.jaci.2008.06.013) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions