Drug-induced toxic epidermal necrolysis in children. Report of two cases

Two cases of toxic epidermal necrolysis occurring in children are presented herein. In both, multiple drugs were administered before the onset of the skin eruption. Cultures for staphylococcus were negative. Histopathologic examination of the first case revealed separations at the dermal-epidermal junction. While more commonly due to staphylococcal exfoliatoxin, a drug must be ruled out as the cause of toxic epidermal necrolysis in children.     

Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN) is a rare drug-induced disease for which the pathomechanism remains poorly understood. The effector cells of epidermal injury in TEN were studied by taking skin biopsies of early lesions in 23 TEN patients and by performing immunohistochemical tests using antibodies to factor XIIIa (type I dendrocytes), L1-protein (mainly Mac 387+ monocytes and macrophages), UCLHI (mainly CD45R0+ T-memory lymphocytes), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFalpha). Computerized image analysis was used to evaluate the cell density relative to each immunolabeling. A statistical analysis of cellular counts revealed a numeric relation between the cell types in skin with TEN. Factor XIIIa+ dendrocytes were abundant and plump in the dermis, although Mac 387+ macrophages were the most numerous inflammatory cells in the epidermis. Their numbers greatly exceeded those of CD45R0+ T lymphocytes and cells showing immunoreactivity for either IL-6 or TNFalpha. In the epidermis, IL-6+ cells were significantly less numerous than TNFalpha+ cells. No quantitative difference was found between IL-6+ and CD45R0+ cell populations. Correlations were observed between either the numbers of TNFalpha+ cells or Mac 387+ macrophages and CD45R0+ lymphocytes. In the dermis, a significant correlation was also present between the numbers of Mac 387+ and factor XIIIa+ cells. These findings highlight the complex interactions between the inflammatory cells that mediate epidermal damage in skin with TEN. The high density of factor XIIIa+ dendrocytes and Mac 387+ macrophages in lesional skin assigns these cellular populations a prominent role in the pathomechanism of TEN. Despite a lower cell density, CD45RO+ T-memory lymphocytes likely participate in TNFalpha- and IL-6-regulated processes in the epidermis of TEN. TNFalpha seems to be a major cytokine involved in TEN, although a less prominent role can be ascribed to IL-6.     

A case series of allopurinol-induced toxic epidermal necrolysis

This is a case series of allopurinol-induced toxic epidermal necrolysis. Revisiting the indications of using allopurinol in asymptomatic hyperuricemia and a critical reappraisal of the safety profile of allopurinol is done in this article. The report is based on case presented at a tertiary hospital in Singapore. The aim of this study is to highlight the fatal consequences of the indiscriminate use of allopurinol. We report four cases of toxic epidermal necrolysis from allopurinol, three of which resulted in death. Our aim is to highlight that allopurinol in all these cases was not indicated and prescribed for asymptomatic hyperuricemia. The incidence and potentially severe and lethal consequences of allopurinol hypersensitivity syndrome and toxic epidermal necrolysis could be kept to a minimum by strictly adhering to the established indications of allopurinol treatment.     

Phenytoin–induced toxic epidermal necrolysis: a case report

We present a case of phenytoin-induced toxic epidermal necrolysis resulting in 60–70% skin involvement. Systemic corticosteroids and prophylactic antibiotics used initially were discontinued, and subsequent management concentrated on intensive supportive treatment. The patient survived, but is left with disabling ocular complications.     

T-cell subsets in drug-induced toxic epidermal necrolysis. Possible pathogenic mechanism induced by CD8-positive T cells

A patient with bromisovalum-induced toxic epidermal necrolysis showed pronounced delayed hypersensitivity to bromisovalum by patch testing. Biopsy specimens from the cutaneous lesion and the site of the positive patch test reaction were analyzed and compared immunohistologically. The findings were similar: most of the mononuclear cells disposed along the dermoepidermal junction and migrating into the epidermis were CD8-positive lymphocytes, whereas the dermal inflammatory infiltrates were composed predominantly of CD4-positive lymphocytes. This case showed the potential usefulness of patch testing in evaluating cases of toxic epidermal necrolysis. We believe that delayed hypersensitivity plays a crucial role in the development of drug-induced toxic epidermal necrolysis. Furthermore, potential effector cells with phenotypic characteristics of CD8-positive lymphocytes (suppressor/cytotoxic T cells) seem to represent important mediators of the epidermal damage of the cutaneous lesion in our case.     

Acetaminophen-induced toxic epidermal necrolysis in a child

Toxic epidermal necrolysis (TEN) is a severe, life-threatening disorder that usually affects adults. It is often drug induced. We report an instance of a severe case of TEN in a 6-year-old boy, probably induced by acetaminophen, and less likely by codeine. A lymphocyte stimulation test could not identify the culprit drug. Treatment with intravenous immunoglobulin seemed to halt the disease progression.     

Plasmapheresis in toxic epidermal necrolysis

Background The treatment of toxic epidermal necrolysis (TEN) is usually based on the removal of the offending drug(s), fluid replacement, nutritional support, and local management. The mortality and morbidity, however, remain high and the death rate may be reduced to 10% only in special centers that use biologic dressings. Plasma exchange (PE) was proven efficacious in small series of patients and of no particular value in others. Methods Seven patients suffering from severe TEN covering 30%–80% of body surface area and having two or four mucous membranes involved, were included in this open study. Malignancy (Hodgkin's disease, brain tumor) and a variety of medicaments (carbamazepine, allopurinol, diphenylhydantoin, cefaclor, amoxicyllin with clavullanic acid) were considered as causally implicated. One to four PEs of 2.5 L were given on alternate days in six patients and on a daily basis in the seventh. Results All patients recovered successfully from their disease. No new lesions appeared after the first PE in four patients. Neither adverse reactions from this therapy nor sequelae from TEN were observed after a long follow-up lasting up to 8 years. Conclusions Although PE is expensive and requires easy venous access to be performed, it could be listed in the first line of TEN therapy. The method is safe and efficacious, providing prompt relief from pain and rapid cessation of necrolysis. The alternate day PEs are considered preferable to the everyday regimen.     

Abnormalities of lymphocyte function and phenotypic pattern in a case of toxic epidermal necrolysis.

We examined the blood lymphocyte function and phenotypic pattern in a patient with toxic epidermal necrolysis after taking salazopyrin. We studied cell surface markers, natural killer cell activity and mitogen-induced lymphocyte transformation. Our results point to temporary immunosuppression as evidenced by lymphopenia with a large "null cell" population, reduced natural killer cell activity, and impaired lymphocyte response to mitogens.     

纳武利尤单抗诱导的中毒性表皮坏死松解症1例

患者男,79岁,2020年4月6日因反酸20 d收入苏州大学附属第二医院肿瘤科。胃黏膜组织病理检查示低分化腺癌,诊断为胃恶性肿瘤伴淋巴结转移。联合治疗方案：静脉滴注紫杉醇脂质体150 mg每3周1次,腹腔灌注紫杉醇150 mg每3周1次,静脉滴注纳武利尤单抗200 mg每2周1次,口服替吉奥60 mg每天2次连用14 d,口服瑞戈非尼80 mg每天1次连用21 d……     

Management of toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN) is a medical emergency requiring the combined efforts of specialists from multiple disciplines. A basic guide to the management of the seriously ill patient with this disorder is provided.