The CD40/CD40 ligand system is expressed in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum

Caproni, Marzia; Torchia, Daniele; Schincaglia, Emiliano; Volpi, Walter; Frezzolini, Alessandra; Schena, Donatella; Marzano, Angelo Valerio; Quaglino, Pietro; Simone, Clara De; Parodi, Aurora; Barletta, Emanuela; Fabbri, Paolo

doi:10.1111/j.1365-2133.2005.07023.x

Cited by 50 publications

(58 citation statements)

References 40 publications

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“…By contrast, the role of macrophages is generally neglected. However, the present study confirms previous findings [12,13] showing that CD68+ macrophages are numerous in most TEN blisters. Their number was not correlated to the timing of the skin biopsies since they were sometimes more numerous in early than in late biopsies.…”

Section: Discussionsupporting

confidence: 82%

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Functionally Active Macrophage-Derived Myeloperoxidase in the Skin of Drug-Induced Toxic Epidermal Necrolysis

Paquet

Groote²,

Pierard

2010

Dermatology

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Background: Drug-induced toxic epidermal necrolysis (TEN) probably results from a complex and specific immune cell reaction involving lymphocytes and macrophages. Objective: To assess the functional role of macrophages in TEN. Methods: Immunohistochemistry was performed on biopsies from early blisters developed in 9 TEN patients. The amount of extracellular myeloperoxidase (MPO) was measured by ELISA in TEN blister fluid and serum. Controls were blister fluids taken from 9 second-degree burns. In addition, 3-chlorotyrosine (a specific marker of MPO activity) was searched for using liquid mass chromatography both in TEN and burn blister fluids. Results: Immunohistochemistry revealed numerous CD68+ macrophages in 8/9 TEN patients; 5–20% of these cells and rare CD15+ neutrophils exhibited MPO immunoreactivity, while keratinocytes were negative. The amount of MPO was significantly higher in TEN blister fluid than in TEN serum, suggesting macrophage production of MPO in the skin. In addition, MPO was significantly more abundant in TEN blister fluid than in burn blister fluid. 3-Chlorotyrosine was detected in 7/9 TEN blister fluids, but in only 2/9 burn blister fluids. Discussion: MPO produced by macrophages was functionally active in most TEN patients, leading to the production of hypochlorous acid, a potent oxidative compound that alters keratinocytes.

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Section: Discussionsupporting

confidence: 82%

“…Compared to T lymphocytes, the role of macrophages in TEN epidermal destruction has rarely been emphasized [12,13]. In the present study, we show using dual immunohistochemistry that macrophages are the main producers of the strong oxidative enzyme MPO in TEN skin.…”

Section: Introductionmentioning

confidence: 60%

Functionally Active Macrophage-Derived Myeloperoxidase in the Skin of Drug-Induced Toxic Epidermal Necrolysis

Paquet

Groote²,

Pierard

2010

Dermatology

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“…IL-12 is a key cytokine of cell-mediated immune responses, released predominantly by antigen presenting cells able to induce a potent promotion of IFN-γ production by T and NK cells, enhancement of antigen-specific T-cell proliferation and differentiation of naive T cells toward the Th1 phenotype [35]. The IL-12 overexpression could be related to the enhanced expression of the CD40/CD40 ligand system recently demonstrated by our group in the cutaneous lesions [36] and sera [37] of EM and SJS/TEN patients. Indeed, previous in vitro studies demonstrated that the ligation between cell-surface CD40 and its ligand CD154 on T cells enhances the synthesis of IL-12 [38], which, in turn, up-regulates the CD154 expression on T helper cells [39], thus indicating the presence of a positive feedback loop between these cells.…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of the Th1 Promoter IL-12 and the Th2 Chemokine TARC Are Elevated in Erythema Multiforme and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis and Correlate with Soluble Fas Ligand Expression

et al. 2007

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Background: No data exist as to Th2 chemokines in erythema multiforme (EM) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Objective: To evaluate thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and regulated upon activation, normal T-lymphocyte-expressed and secreted chemokine (RANTES) expression in EM and SJS/TEN and to correlate with the serum levels of the Th1 promoter interleukin (IL)-12 and soluble Fas ligand (sFasL). Materials and Methods: IL-12, sFasL, TARC, MDC and RANTES expression were analyzed by ELISA techniques in 31 untreated EM (n = 24) or SJS/TEN (n = 7) patients and in 28 healthy donors (HD). Results: EM and SJS/TEN exhibited significantly higher levels of TARC, IL-12 and sFasL with respect to HD. TARC upregulation paralleled both the IL-12 (p = 0.0225) and sFasL increase (p = 0.0194). Conclusions: Our results support a role of TARC in the pathophysiology of EM/SJS/TEN and confirm the coexistence of a Th2 response in addition to the predominant Th1 profile.

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“…These presentations differ from erythematous multiforme majus (EMM) which is related to infection and features only target-like exanthemas. SJS/TEN (denotes both SJS and TEN) and EMM are currently considered as cell-mediated reactions aimed at the destruction of keratinocytes expressing drug-related or herpes-related antigens, respectively [6]. Besides, more than 65% of SJS/TEN cases are induced by drugs including antibiotics, nonsteroid anti-inflammatory drugs (NSAIDs) and anticonvulsants [5].…”

Section: Introductionmentioning

confidence: 99%

Acute Renal Failure and Its Risk Factors in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Hung¹,

Liu²,

Kuo³

et al. 2009

Am J Nephrol

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Background: Skin lesion is the most frequent manifestation of adverse drug reactions. Drug-induced cutaneous hypersensitivity and drug-induced acute interstitial nephritis might share a similar mechanism involving drug-specific T cells. We thus investigated the renal outcome of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), the most severe drug-induced cutaneous hypersensitivity, and hypothesize that skin detachment in SJS/TEN might be associated with acute renal failure (ARF). Methods: 234 hospitalized patients were retrospectively classified into an SJS/TEN group (skin detachment) or an erythematous multiforme majus group (target-like exanthema alone). Results: Both drugs and chronic kidney disease (CKD) are associated with SJS/TEN. The SJS/TEN group was more likely to develop ARF than the erythematous multiforme majus group (18.8 vs. 4.3%, p < 0.05) despite similar initial creatinine clearance. In the ARF patients, RIFLE-F class, dialysis and long-term dialysis were 25, 15 and 5%, respectively. The offending drugs in ARF were also associated with CKD. Hyponatremia and late hypokalemia were more frequently in the SJS/TEN group (15.6 vs. 2.9%, 7.3 vs. 0.7%, respectively, p < 0.05). Sepsis, allopurinol, antibiotics, NSAIDs, CKD and hypoalbuminemia (OR: 18.8, 9.8, 10.1, 9.0, 5.3 and 3.3, respectively, p < 0.05) were the risk factors of developing ARF. Conclusion: ARF, the need for dialysis, and late hypokalemia could be the consequences of SJS/TEN. Skin detachment after certain medication might implicate the associated ARF, especially in CKD patients.

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The CD40/CD40 ligand system is expressed in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum

Cited by 50 publications

References 40 publications

Functionally Active Macrophage-Derived Myeloperoxidase in the Skin of Drug-Induced Toxic Epidermal Necrolysis

Functionally Active Macrophage-Derived Myeloperoxidase in the Skin of Drug-Induced Toxic Epidermal Necrolysis

Serum Levels of the Th1 Promoter IL-12 and the Th2 Chemokine TARC Are Elevated in Erythema Multiforme and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis and Correlate with Soluble Fas Ligand Expression

Acute Renal Failure and Its Risk Factors in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

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