Clinical and pathogenic aspects of the severe cutaneous adverse reaction epidermal necrolysis (EN).

The severe cutaneous adverse reaction epidermal necrolysis (EN) which includes toxic epidermal necrolysis and the milder Stevens-Johnson syndrome is characterized by epidermal loss due to massive keratinocyte apoptosis and/or necroptosis. EN is often caused by a drug mediating a specific TCR-HLA interaction via the (pro)hapten, pharmacological interaction or altered peptide loading mechanism involving a self-peptide presented by keratinocytes. (Memory) CD8 + T cells are activated and exhibit cytotoxicity against keratinocytes via the perforin/granzyme B and granulysin pathway and Fas/FasL interaction. Alternatively drug-induced annexin release by CD14 + monocytes can induce formyl peptide receptor 1 death of keratinocytes by necroptosis. Subsequent keratinocyte death stimulates local inflammation, activating other immune cells producing pro-inflammatory molecules and downregulating regulatory T cells. Widespread epidermal necrolysis and inflammation can induce life-threatening systemic effects, leading to high mortality rates. Research into genetic susceptibility aims to identify risk factors for eventual prevention of EN. Specific HLA class I alleles show the strongest association with EN, but risk variants have also been identified in genes involved in drug metabolism, cellular drug uptake, peptide presentation and function of CD8 + T cells and other immune cells involved in cytotoxic responses. After the acute phase of EN, long-term symptoms can remain or arise mainly affecting the skin and eyes. Mucosal sequelae are characterized by occlusions and strictures due to adherence of denuded surfaces and fibrosis following mucosal inflammation. In addition, systemic pathology can cause acute and chronic hepatic and renal symptoms. EN has a large psychological impact and strongly affects health-related quality of life among EN survivors.

Epidemiology of children admitted to the Dutch burn centres. Changes in referral influence admittance rates in burn centres.

BACKGROUND: In the Beverwijk Burn Centre a remarkable rise has been noted in the number of paediatric admissions since 2000. To investigate if this is a national trend and, if so, what may have caused it, a retrospective epidemiological study has been undertaken. MATERIALS AND METHODS: The databases of the three Dutch burn centres were combined. Data on the population at risk for admission in a burn centre and data on burns related hospital admissions were added. Two age groups, 0-4 years and 5-17 years and two time periods, 1995-1999 and 2000-2007, were compared. RESULTS: The mean number of paediatric admissions in the Dutch burn centres per year increased by 44.0% and 44.3% for the younger children (0-4 years) and the older children (5-17 years), respectively, whereas the number of paediatric burn admissions in other hospitals in the Netherlands decreased. The percentage of children that was referred from other hospitals increased in both age groups, and for the younger children this was significant. CONCLUSION: There has been a shift in paediatric burn care towards a greater volume of admissions in specialized burn care of especially young children with less severe burns. A possible explanation for the increased number of referred children may be the introduction of the EMSB course in 1998, since EMSB guidelines dictate stricter and generally accepted referral criteria.

Increasing the daily water intake for the prophylactic treatment of headache: a pilot trial.

Dehydration is commonly believed to result in headache, but the effectiveness of increasing the water intake in patients who frequently suffer from headaches has not been studied thus far. In a pilot study, we examined the possible effects and feasibility of increased water intake in headache patients. Eighteen headache patients (all had migraine, two also had tension-type headache) were randomly allocated to placebo medication, or the advice to additionally drink 1.5 l of water per day, for a period of 12 weeks. Effect measurements consisted of a 2 weeks headache diary and the Migraine Specific Quality of Life (MSQOL) questionnaire. The advice to increase the daily fluid intake by 1.5 l increased the fluid intake in the intervention group by approximately 1 l. This reduced the total hours of headache in 2 weeks by 21 h (95% CI: -48 to 5). Mean headache intensity decreased by 13 mm (95% CI: -32 to 5) on a visual analogue scale (VAS). The effects on MSQOL, number of headache episodes, and medication seemed to be small. The data of the present study suggest a reduction in the total number of hours and intensity of headache episodes after increased water intake. Our results seem to justify larger scaled research on the effectiveness of increased water intake in headache patients.

Seven-year experience with a 'quarantine and isolation unit' for patients with burns. A retrospective analysis.

In the burns unit of the Red Cross Hospital, Beverwijk. The Netherlands we performed a retrospective analysis to evaluate whether the spread of multi-resistant micro-organisms (MRMO) in burn victims with a high risk of contamination can be prevented by isolation in a quarantine and isolation unit (QIU). We analysed 1006 patients who where consecutively admitted to the burns unit between 26-03-1985 and 31-12-1992. The age TBSA, and the bacteriological status of all patients were recorded. With regard to the stay in the QIU we recorded the actual number of days between the accident and the time of admission, the duration of the stay, and the therapy given. Of 1006 patients, 72 met the criteria of the Dutch Health Inspectorate for classification as high risk of MRMO contamination. Sixty-one of these 72 patients were treated in the QIU. The mean duration of stay in the QIU was 8.2 days, admission was at 10.2 days postburn, and 20 patients did harbour MRMO. There was no report of any cross-contamination. Since the QIU became operational there have been no outbreaks of MRMO in our burns unit. In our opinion this shows the effectiveness of the QIU.

Reduction in Staphylococcus aureus wound colonization using nasal mupirocin and selective decontamination of the digestive tract in extensive burns.

Following the introduction in 1988 of a regimen of selective decontamination of the digestive tract (SDD) for extensively injured patients in our burns centre, colonization rates with Gram-negative organisms declined significantly, but colonization with Staphylococcus aureus was unaffected. In an effort to reduce staphylococcal colonization, the SDD regimen has been supplemented with intranasal mupirocin since 1991. In this paper, 33 consecutive patients with burns of > 30 per cent TBSA who were treated with the supplemental regimen (SDD + M) in 1991 and 1992, were compared with 34 consecutive patients admitted in the previous 2 years who were treated with SDD only. Staph. aureus colonization of wounds, sputum and gastric aspirates was significantly reduced in the SDD + M group. Gram-negative colonization rates and the incidence of clinical infections remained low in both groups. Our experience suggests that decontamination of endogenous bacterial reservoirs, in combination with isolation measures to prevent exogenous colonization, effectively prevents infectious complications in patients with severe burns.

Prevention of infection in burns: preliminary experience with selective decontamination of the digestive tract in patients with extensive injuries.

Evidence from studies of trauma patients suggests that selective decontamination of the digestive tract (SDD) might also be of value in preventing colonization and infection by enteric organisms in burn patients. In a retrospective study, 31 consecutive patients with burns of greater than 30% of total body surface area, admitted over a 2-year period, who were treated with an SDD regimen, were compared with a similar group of 33 consecutive patients admitted in the 2 years immediately preceding the introduction of SDD. Fewer SDD-treated patients developed wound colonization with Pseudomonas species (29% vs. 61%), or with Enterobacteriaceae (10% vs. 73%). Similar reductions in colonization with gram-negative organisms were found in urine and gastric aspirates. There were fewer respiratory infections in the SDD group (6.5% vs. 27.3%), and only one patient developed septicemia, compared with eight in the control group (3.2% vs. 24.2%). Fewer SDD-treated patients died (one death, compared with seven in the non-SDD group). These results suggest that SDD may be of value in the management of patients with severe burn injuries, but further studies are required to test the validity of this conclusion.