Epithelial hyperproliferation and transglutaminase 1 gene expression in Stevens-Johnson syndrome conjunctiva.
In Stevens-Johnson syndrome, pathological keratinization of the ordinarily nonkeratinized corneal and conjunctival mucosal epithelia results in severe visual loss. We examined conjunctiva covering cornea in five eyes in the chronic cicatricial phase of Stevens-Johnson syndrome. Normal conjunctiva from five age-matched individuals was studied also. The number of epithelial cells in Stevens-Johnson syndrome conjunctiva that were immunoreactive with a monoclonal antibody, Ki-67, to a nuclear antigen found only in proliferating cells was greater than normal (93.8+/-19.8 cells above 100 basal cells versus 12.8+/-0.5 cells above 100 basal cells; P = 0.009). In addition, although clinical inflammation was mild, massive lymphocytic infiltration was seen in the substantia propria of conjunctiva covering cornea. In situ hybridization documented transglutaminase 1 (keratinocyte transglutaminase) mRNA in suprabasal cells of the abnormally thickened conjunctival epithelium in all Stevens-Johnson syndrome patients. In contrast, no message was detected in normal conjunctival or corneal epithelia. Transglutaminase 1 is expressed during the terminal differentiation of keratinocytes where it helps synthesize cornified cell envelopes. We speculate that in Stevens-Johnson syndrome, epithelial hyperproliferation, and transglutaminase 1 gene expression lead to the pathological keratinization of ocular surface mucosal epithelia. (+info)
Blister fluid T lymphocytes during toxic epidermal necrolysis are functional cytotoxic cells which express human natural killer (NK) inhibitory receptors.
Toxic epidermal necrolysis (TEN) is a rare life-threatening adverse drug reaction characterized by a massive destruction of the epidermis. Immunohistological studies of skin biopsies of TEN showed infiltrates of predominantly CD8+ T lymphocytes even though other authors reported a prominent involvement of cells of the monocyte-macrophage lineage. The aim of this study was to characterize phenotypically and functionally the cells present in the cutaneous blister fluid of four patients with TEN. We first determined that lymphocytes were predominant in blister fluid obtained early, while monocytes/macrophages later became the most important population. We then showed that this lymphocyte population, mainly CD3+CD8+, corresponded to a peculiar cell subset as they expressed cutaneous leucocyte antigen, killer inhibitory receptors KIR/KAR and failed to express CD28 molecule. Functionally, we determined that blister T lymphocytes had a cytotoxic T lymphocyte (CTL)- and NK-like cytotoxicity. The role of this cytotoxic lymphocyte population present at the site of lesions during TEN remains to be understood. (+info)
Nitric oxide synthase in toxic epidermal necrolysis and Stevens-Johnson syndrome.
Toxic epidermal necrolysis and Stevens-Johnson syndrome are severe cutaneous drug reactions of unknown mechanism. Nitric oxide can cause apoptosis and necrosis. The inducible form of nitric oxide synthase generates large amounts of nitric oxide and has been described in human skin. We propose that a large burst of nitric oxide in toxic epidermal necrolysis and Stevens-Johnson syndrome may cause the epidermal apoptosis and necrosis. Skin biopsies were taken from seven patients with actively progressing Stevens-Johnson syndrome or toxic epidermal necrolysis. Expression of inducible nitric oxide synthase was examined by reverse transcription-polymerase chain reaction and by immunoperoxidase staining for inducible nitric oxide synthase protein. Messenger RNA for inducible nitric oxide synthase was detected by reverse transcription-polymerase chain reaction and confirmed by the sequencing of polymerase chain reaction products. Strong staining for inducible nitric oxide synthase was observed in inflammatory cells in the lower epidermis and upper dermis. Diffuse, weaker staining was observed in keratinocytes. Expression of inducible nitric oxide synthase is consistent with the hypothesis that nitric oxide mediates the epidermal necrosis in toxic epidermal necrolysis and provides a potential target for therapeutic intervention. (+info)
SCORTEN: a severity-of-illness score for toxic epidermal necrolysis.
The mortality of toxic epidermal necrolysis is about 30%. Our purpose was to develop and validate a specific severity-of-illness score for cases of toxic epidermal necrolysis admitted to a specialized unit and to compare it with the Simplified Acute Physiology Score and a burn scoring system. A sample of 165 patients was used to develop the toxic epidermal necrolysis-specific severity-of-illness score and evaluate the other scores, a sample of 75 for validation. Model development used logistic regression equations that were translated into probability of hospital mortality; validation used measures of calibration and discrimination. We identified seven independent risk factors for death and constituted the toxic epidermal necrolysis-specific severity-of-illness score: age above 40 y, malignancy, tachycardia above 120 per min, initial percentage of epidermal detachment above 10%, serum urea above 10 mmol per liter, serum glucose above 14 mmol per liter, and bicarbonate below 20 mmol per liter. For each toxic epidermal necrolysis-specific severity-of-illness score point the odds ratio was 3.45 (confidence interval 2.26-5.25). Probability of death was: P(death) = elogit/1 + elogit with logit = -4.448 + 1.237 (toxic epidermal nec-rolysis-specific severity-of-illness score). Calibration demonstrated excellent agreement between expected (19. 6%) and actual (20%) mortality; discrimination was also excellent with a receiver operating characteristic area of 82%. The Simplified Acute Physiology Score and the burn score were also associated with mortality. The discriminatory powers were poorer (receiver operating characteristic area: 72 and 75%) and calibration of the Simplified Acute Physiology Score indicated a poor agreement between expected (9.1%) and actual (26.7%) mortality. This study demonstrates that the risk of death of toxic epidermal necrolysis patients can be accurately predicted by the toxic epidermal necrolysis-specific severity-of-illness score. The Simplified Acute Physiology Score and burn score appear to be less adequate. (+info)
Diagnosis, classification, and management of erythema multiforme and Stevens-Johnson syndrome.
BACKGROUND: In adults, erythema multiforme (EM) is thought to be mainly related to herpes infection and Stevens-Johnson syndrome (SJS) to drug reactions. AIMS: To investigate this hypothesis in children, and to review our experience in the management of these patients. METHODS: A retrospective analysis of 77 paediatric cases of EM or SJS admitted to the Children's Hospital in Bordeaux between 1974 and 1998. RESULTS: Thirty five cases, inadequately documented or misdiagnosed mostly as urticarias or non-EM drug reactions were excluded. Among the remaining 42 patients (14 girls and 28 boys), 22 had EM (11 EM minor and 11 EM major), 17 had SJS, and three had isolated mucous membrane involvement and were classified separately. Childhood EM was mostly related to herpes infection and SJS to infectious agents, especially Mycoplasma pneumoniae. Only two cases were firmly attributed to drugs (antibiotics). No patient died. EM and SJS sequelae were minor and steroids were of no overall benefit. CONCLUSION: In paediatric practice EM is frequently misdiagnosed. The proposal that SJS is drug related in adults does not apply to children, and in our recruitment EM and SJS are mostly triggered by infectious agents. The course of both diseases, even though dramatic at onset, leads to low morbidity and mortality when appropriate symptomatic treatment is given. (+info)
Conjunctival inflammation in the chronic phase of Stevens-Johnson syndrome.
AIMS: To understand the immunopathogenesis of the corneal conjunctivalisation in Stevens-Johnson syndrome. METHODS: Conjunctivalised corneas from five patients with Stevens-Johnson syndrome were studied immunohistochemically for several cell surface antigens and two cytokines. Chemical injury specimens were also studied. RESULTS: In all cases, immunohistochemistry revealed LFA-1, CD4, CD8, and CD68 on subepithelial infiltrating cells. Also, HLA-DR and ICAM-1 were found on the surfaces of epithelial cells, subepithelial infiltrating cells, subepithelial fibroblasts, and endothelial cells in blood vessels. IFN-gamma was found in basal epithelial cells; subepithelial cells and subepithelial extracellular matrix CD19 and IL4 were not detected. CONCLUSIONS: The infiltrating cell population in the Stevens-Johnson syndrome samples includes macrophages, CD4 positive T cells, and CD8 positive T cells. The cytokine expression pattern suggests CD4 positive T cells are Th1 cells. The infiltrating cell population is similar in Stevens-Johnson syndrome and chemical injury conjunctivalised corneas. (+info)
Toxic epidermal necrolysis in a monkey (Macaca fascicularis).
An adult male Macaca fascicularis monkey developed toxic epidermal necrolysis after ingestion of methylmercury. The clinical picture was characterized by the development of large cutaneous bullae with subsequent full-thickness epidermal exfoliation. Areas of sparse pelage were most affected, with the most severe exfoliation occurring on the palms, soles, face and ears. Erosions also developed within the oral mucosa and conjunctivae. (+info)
Patients with acute skin loss: are they best managed on a burns unit?
Patients who are critically ill and have large areas of skin loss or breakdown present a difficult management problem. They require the combination of intensive therapy facilities to support failing organs and specialized skin care, sometimes including extensive debridement and reconstruction. The expertise required for both aspects of treatment are found uniquely on a burns unit. We present five patients with large areas of cutaneous loss or damage secondary to a variety of non-burn aetiologies who were managed on a burns unit. We suggest that a burns unit may be the most appropriate place for such patients to be treated during both the acute phase of their illness and the later stages of surgical reconstruction and physical rehabilitation. (+info)