Immunopathology of toxic epidermal necrolysis. Keratinocytes, HLA-DR expression, Langerhans cells, and mononuclear cells: an immunopathologic study of five cases

Villada, Gabriel; Roujeau, Jean‐Claude; Clérici, T.; Bourgault, I.; Revuz, J.

doi:10.1001/archderm.128.1.50

Cited by 63 publications

(18 citation statements)

References 14 publications

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“…Immunohistological studies have recently shed some light on the biological factors. An active role has been ascribed to T lymphocytes, particularly CD4+ cells in the dermis and CD8+ cells in the epidermis [18, 19, 20, 21]. L1-protein-rich macrophages and factor-XIIIa-positive dendrocytes appear to have significant pathogenic roles in the epidermis and dermis, respectively [22].…”

Section: Ten Pathomechanismsmentioning

confidence: 99%

Would Cyclosporin A Be Beneficial to Mitigate Drug-Induced Toxic Epidermal Necrolysis?

Paquet¹,

Pierard²

1999

Dermatology

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Drug-induced toxic epidermal necrolysis (TEN) is a rare life-threatening disease whose mortality remains high. The treatment of the disease is badly settled. Several kinds of drugs have been tested, including systemic corticosteroids, cyclophosphamide, pentoxifylline and thalidomide, but without any clear-cut outcome. Cyclosporin A (CsA) has many inhibitory effects on the main cell populations involved in TEN (T lymphocytes, macrophages and keratinocytes). CsA could also act on tumor necrosis factor α metabolism, a cytokine which is important in TEN epidermal destruction. Moreover, apoptosis is the mechanism leading to keratinocyte death and CsA has antiapoptotic properties. CsA has already been used successfully on a limited series of TEN patients. We have reviewed the potential theoretical useful effects of CsA in TEN. We conclude that CsA could be a good candidate to reverse TEN progression.

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Section: Ten Pathomechanismsmentioning

confidence: 99%

Would Cyclosporin A Be Beneficial to Mitigate Drug-Induced Toxic Epidermal Necrolysis?

Paquet¹,

Pierard²

1999

Dermatology

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“…In pathological reports, accumulated CD 8+ T lymphocytes and macrophages (eg, Langerhans cells) in the epidermis23,24 and TNF-α elevated by macrophages25 might cause a cytotoxic cellular immune reaction and apoptosis in the epidermis and result in the clinical presentation of SJS 9. Clozapine actually is believed to elevate plasma TNF-α levels 26,27.…”

Section: Resultsmentioning

confidence: 99%

The severe complication of Stevens–Johnson syndrome induced by long-term clozapine treatment in a male schizophrenia patient: a case report

Wu¹,

Chung²,

Wu³

et al. 2015

NDT

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Introduction:Stevens–Johnson syndrome (SJS) is a severe adverse drug reaction that can result in disability and mortality. SJS is defined as having a widespread distribution throughout the whole body surface area with <10% extent of skin detachment and skin lesions. Some drugs, such as carbamazepine, have been reported to have a greater correlation to SJS. Although clozapine use has been mentioned as a risk factor for development of SJS, no report has clearly described the features of SJS as a reaction to clozapine use. Herein, we report the case of a patient presenting SJS after long-term clozapine treatment.Case report:Mr A was a 54-year-old male with a diagnosis of chronic schizophrenia. He was hospitalized in a mental institute and received clozapine 200 mg/day for 2 years, without discomfort or drug side effects. He developed acute-onset mouth edema, multiple oral and ocular ulcers, oral and ocular mucosa swelling, and multiple erythematous skin rashes over his entire body and extremities with hypertension and high fever. SJS was diagnosed after referral to a general hospital.ResultsThe SJS subsided under supportive treatment.ConclusionAccumulated lymphocytes and macrophages in the epidermis and elevated TNF-α might cause an immune reaction and apoptosis and result in the clinical presentation of SJS. Clozapine is believed to modulate the immunologic reaction, and therefore might induce SJS through immunomodulation. This case highlights the importance of considering the possibility of SJS resulting from the use of drugs for which there are no reports of such a severe complication.

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“…Chronic biopsies show acanthosis, hyperkeratosis, hypergranulosis and infiltration of melanophages in dermis [20,110] Erythema multiforme/ SJS and TEN Infiltration of inflammatory cells at the dermal region along with discrete regions of epidermal necrosis SJS and TEN show widespread epidermal necrosis, reduction in Langerhans cells, keratinocyte expression of HLA-DR [20,112] CLA and resolve rapidly once the drug is removed, often leaving a postinflammatory hyperpigmented patch, although nonpigmenting fixed reactions have also been reported [23]. Limbs, extremities, genitalia and face are commonly affected sites, although the affected site may be drug dependent; for example, tetracycline and ampicillin elicit FDE on the genitalia, whereas aspirin usually causes eruptions on the trunk, face and limbs [24].…”

Section: Exanthemamentioning

confidence: 99%

Immune response to xenobiotics in the skin: from contact sensitivity to drug allergy

Khan

Roychowdhury

Gaspari

et al. 2006

Expert Opinion on Drug Metabolism & Toxicology

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Skin is the most frequent target of adverse drug reactions. These cutaneous drug reactions (CDRs) show varied clinical manifestations ranging from mildly discomforting rashes to life-threatening Stevens-Johnson syndrome or toxic epidermal necrolysis. Most CDRs appear to be immune mediated, although the mechanism by which they are initiated remains unclear. In this review, current knowledge of the mechanisms by which xenobiotics provoke immune responses in the skin after epicutaneous administration and how similar reactions may occur after systemic routes are summarised. This review also discusses a variety of genetic or environmental factors that may determine the susceptibility of individuals towards immune responses in skin following drug exposure.

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Immunopathology of toxic epidermal necrolysis. Keratinocytes, HLA-DR expression, Langerhans cells, and mononuclear cells: an immunopathologic study of five cases

Cited by 63 publications

References 14 publications

Would Cyclosporin A Be Beneficial to Mitigate Drug-Induced Toxic Epidermal Necrolysis?

Would Cyclosporin A Be Beneficial to Mitigate Drug-Induced Toxic Epidermal Necrolysis?

The severe complication of Stevens–Johnson syndrome induced by long-term clozapine treatment in a male schizophrenia patient: a case report

Immune response to xenobiotics in the skin: from contact sensitivity to drug allergy

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Immunopathology of toxic epidermal necrolysis. Keratinocytes, HLA-DR expression, Langerhans cells, and mononuclear cells: an immunopathologic study of five cases

Cited by 63 publications

References 14 publications

Would Cyclosporin A Be Beneficial to Mitigate Drug-Induced Toxic Epidermal Necrolysis?

Would Cyclosporin A Be Beneficial to Mitigate Drug-Induced Toxic Epidermal Necrolysis?

The severe complication of Stevens&ndash;Johnson syndrome induced by long-term clozapine treatment in a male schizophrenia patient: a&nbsp;case&nbsp;report

Immune response to xenobiotics in the skin: from contact sensitivity to drug allergy

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The severe complication of Stevens–Johnson syndrome induced by long-term clozapine treatment in a male schizophrenia patient: a case report