CD8+ Lymphocytes in the Blister Fluid of Severe Acute Cutaneous Graft-versus-Host Disease: Further Similarities with Toxic Epidermal Necrolysis

Correia, Osvaldo; Delgado, Luís; Barbosa, I.L.; Domingues, José Carlos; Azevedo, Rita I.; Cp, Vaz; Pimentel, Pedro

doi:10.1159/000051751

Cited by 28 publications

(18 citation statements)

References 19 publications

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“…Cytotoxic CD8+ T lymphocytes may represent major effector cells responsible for the TEN epidermal necrosis [11, 12], even if only rare inflammatory cells are present in the necrotic epidermis. As DCs may present antigens to CD8+ T cells [23], the low number of factor-XIIIa-positive DCs in TEN LNs could participate in the low densities in the skin infiltrating CD8+ cells.…”

Section: Discussionmentioning

confidence: 99%

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Factor-XIIIa-Positive Dendrocytes in Drug-Induced Toxic Epidermal Necrolysis (Lyell’s Syndrome): Paradoxical Activation in Skin and Rarefaction in Lymph Nodes

Paquet¹,

Quatresooz²,

Pierard³

2003

Dermatology

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Background: Drug-induced toxic epidermal necrolysis (TEN) is a rare life-threatening disease characterized by the extensive destruction of the epidermis contrasting with the discreteness of lymphoid cell infiltration. The precise pathomechanism of the disease remains unclear. Methods: Skin specimens and peripheral and thoracic lymph nodes (LNs) were collected from 2 TEN patients. They were examined by conventional histology and immunohistochemistry using antibodies directed to factor XIIIa (dermal dendrocytes), CD1a (Langerhans cells), CD15 (granulocytes), CD20 (B lymphocytes), CD45RO (activated T lymphocytes), CD68 (macrophages) and the proliferation marker Ki-67. LNs from patients with mycosis fungoides, from subjects dead from acute cardiac failure or traumatic injuries, as well as metastasis-free sentinel LNs of cutaneous melanoma served as positive and negative controls. Results: TEN LNs showed absence of germinal centers but a moderate hyperplasia of the paracortical T cell zone. Immunohistochemistry did not reveal any distinctive aspect in LN cellular densities between TEN and other control conditions except for the factor-XIIIa+ dendritic cells which were dramatically reduced in numbers in TEN LNs. This rarefaction in LNs contrasted with the great number of these cells in the skin of the same patients. Conclusion: The structure of TEN LNs rules out the involvement of an antibody-mediated response. As dendritic factor-XIIIa+ cells are involved in most cutaneous T-cell-mediated responses, their depletion in TEN LNs could explain the sparse lymphoid cell infiltrate in lesional TEN skin.

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Section: Discussionmentioning

confidence: 99%

“…Indeed, an active role was ascribed to T lymphocytes, particularly CD4+ cells in the dermis and CD8+ cells in the epidermis [11, 12]. Calprotectin-enriched macrophages and factor-XIIIa+ dermal dendrocytes also appear to play a prominent pathogenic role in the epidermis and dermis, respectively [9, 10, 13, 14].…”

Section: Introductionmentioning

confidence: 99%

Factor-XIIIa-Positive Dendrocytes in Drug-Induced Toxic Epidermal Necrolysis (Lyell’s Syndrome): Paradoxical Activation in Skin and Rarefaction in Lymph Nodes

Paquet¹,

Quatresooz²,

Pierard³

2003

Dermatology

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“…Lymphocyte populations present in TEN blister fluid showed mainly a peculiar CD3+ CD8+ T cell subset expressing both cutaneous leukocyte antigen and killer inhibitory receptor KIR/KAR without CD28 expression [27, 28]. Blister T lymphocytes express functional properties of cytotoxic T lymphocytes and natural killer (NK)-like cells [28].…”

Section: Immunohistochemical and Functional Aspectsmentioning

confidence: 99%

Novel Treatments for Drug-Induced Toxic Epidermal Necrolysis (Lyell’s Syndrome)

Paquet

Pierard

Quatresooz³

2005

Int Arch Allergy Immunol

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Drug-induced toxic epidermal necrolysis (TEN) is a life-threatening disease characterized by extensive destruction of the epidermis. It apparently results from the formation of specific toxic drug metabolites by the keratinocytes. The mortality rate which averages 25–30% is mainly due to secondary septicemia, and to ionic and metabolic disturbances following loss of epidermal integrity. Apoptosis is the likely mechanism leading to massive keratinocyte death in TEN. Dysregulations in the tumor necrosis factor-α (TNF-α) pathway, CD95 system (Fas ligand, CD95L; Fas receptor, CD95R) and calcium homeostasis in the epidermis are involved in this apoptotic process. An active role has also been ascribed to T lymphocytes, macrophages and factor XIIIa-positive dermal dendrocytes. Despite progress, treatment of TEN remains controversial. In the past, systemic glucocorticoids were used in order to target the inflammatory reaction in TEN. However, there was no evidence for improvement of the healing process, while corticosteroids worsened the prognosis by increasing the risk of septicemia. Only a few cases have been treated with other drugs including cyclophosphamide, pentoxyfilline, thalidomide, anti-TNF-α antibodies and cyclosporin A. In the recent past, some TEN patients were treated with intravenous human immunoglobulins (IVIG). The rationale for such a treatment was to block the CD95 system on keratinocytes. The early promising clinical results of IVIG treatment in TEN were subsequently challenged. This review compares the effectiveness and drawbacks of the major drugs presently used in TEN treatment. Some future prospects in TEN management are also discussed.

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“…The pathogenesis of TEN remains essentially unknown, but the clinical and histological similarities with severe cutaneous acute graft-versus-host disease suggest a common pathogenic pathway [2]. The presence, in both diseases, of a high number of CD8+ T lymphocytes in the blister fluid supports the intervention of cell-mediated cytotoxicity in keratinocyte apoptosis [3, 4]. Recent results suggest a major role for keratinocyte Fas ligand (CD95L) in the apoptosis observed in TEN [5], and intravenous immunoglobulin containing specific anti-Fas antibodies seems to be useful in these patients [5, 6], although this effectiveness should be confirmed in a controlled study.…”

Section: Introductionmentioning

confidence: 99%

Dermatological and Ophthalmological Sequels in Toxic Epidermal Necrolysis

Magina¹,

Lisboa²,

Leal³

et al. 2003

Dermatology

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Background: Toxic epidermal necrolysis (TEN) is a rare, drug-induced disease characterized by epidermal detachment and mucosal involvement. After an acute period, potentially disabling cutaneous and ocular sequels may appear. Although long-term complications are not rare, only few outcome studies are published. Objective: To evaluate the incidence of dermatological and ophthalmological sequels following TEN, to describe its clinical aspects and correlation with acute involvement. Patients and Methods: Eight patients surviving to TEN were submitted to dermatological and ophthalmological observation ranging from 0.5 to 8 years after hospitalization. Cutaneous and ocular involvement, during the acute phase, was retrospectively analysed. Results: Dermatological sequels were observed in 6 patients (75%) corresponding to those with more extensive skin involvement in the acute phase. The most frequent complications were cutaneous dyschromia (62.5%) and nail dystrophies (37.5%). Six patients (75%) had ocular complications with tarsal conjunctiva keratinization in 5 (62.5%) and keratoconjunctivitis sicca in 4 of them (50%). Trichiasis, corneal neovascularization and symblepharon were observed in 1 case. There was no correlation between the severity of acute ocular involvement and long-term complications. Conclusion: Following TEN, most patients have dermatological and ophthalmological sequels that persist for several years.

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CD8+ Lymphocytes in the Blister Fluid of Severe Acute Cutaneous Graft-versus-Host Disease: Further Similarities with Toxic Epidermal Necrolysis

Cited by 28 publications

References 19 publications

Factor-XIIIa-Positive Dendrocytes in Drug-Induced Toxic Epidermal Necrolysis (Lyell’s Syndrome): Paradoxical Activation in Skin and Rarefaction in Lymph Nodes

Factor-XIIIa-Positive Dendrocytes in Drug-Induced Toxic Epidermal Necrolysis (Lyell’s Syndrome): Paradoxical Activation in Skin and Rarefaction in Lymph Nodes

Novel Treatments for Drug-Induced Toxic Epidermal Necrolysis (Lyell’s Syndrome)

Dermatological and Ophthalmological Sequels in Toxic Epidermal Necrolysis

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