Correction of Systemic Endotoxemia in Children with Atopic Dermatitis
B. A. Shamov, T. G. Malanicheva
Kazan State Medical University, Kazan, Russia
Lechashchiy vrach [Attending doctor]. 2010;8:108–109 (in Russian)
This controlled study has demonstrated that the plasma endotoxin levels in the children with atopic dermatitis is statistically significantly greater (up to 0.140 ± 0.071 EU/ml) than in the healthy children (0.0024 ± 0.001 EU/ml, p < 0.001). The plasma endotoxin level depends on the stage of disease, severity and activity of skin process. The presence of systemic endotoxemia upon atopic dermatitis is the indication for performing detoxification by method of gastrointestinal adsorption (enterosorption). Combination therapy with application of intestinal adsorbent Enterosgel results in 1.6-fold reduction of the exacerbation time (from 20 to 12 days), 5-fold decrease in the SCORAD index and decrease in the plasma endotoxin level.
Keywords: adsorbent, atopic dermatitis, endotoxemia, endotoxin, enterosorption, Enterosgel
The endotoxin is a biologically active compound containing the cell membrane lipopolysaccharide from Gramnegative bacteria. The endotoxin is released when Gram-negative bacteria are destroyed inside the human gut. In physiological conditions, most of the endotoxin is eliminated from the intestines with feces, while the remaining part crosses the blood-gut barrier and reaches the systemic bloodstream. The endotoxin is detoxified in the liver. Its presence in the systemic bloodstream is called “systemic endotoxemia”, which is one of the factors of antigenic stimulation of the immune system. As healthy individuals have been shown to have detectable endotoxin levels, endotoxemia may be physiological. Systemic endotoxemia develops as a result of the function of intestinal microbiota, impaired permeability of the small intestinal mucous membrane, pancreatic and biliary insufficiency, depression of the hepatic barrier, decreased portal blood flow intensity, etc. .
Normally, anti-endotoxin antibodies are produced in response to endotoxemia. Children with significant endotoxemia have decreased levels of anti-endotoxin antibodies, which reflects deteriorating adaptive capacity and body resistance [1, 3, 4]. It has also been demonstrated that this condition is accompanied by cell hypoxia, abnormal metabolic processes, activation of the sympathetic nervous system and the complement system, thus resulting in leukocyte lysis and platelet aggregation with subsequent release of biologically active substances (kinins, histamine, serotonin).
Endotoxin aggression results from the massive release of endotoxins into the bloodstream against a background of deficient eliminating systems. Endotoxin excesses released into the bloodstream over a long time lead to mobilization, and then breakdown, of the reserves of the adaptive systems and may also result in transient insufficiency of multiple organs regardless of age. Endotoxin aggression is regarded as a universal mechanism participating in the pathogenesis of the majority of infectious and non-infectious diseases .
All of the above led us to presume a possible presence of systemic endotoxemia and endotoxin aggression in children with atopic dermatitis.
The presence of systemic endotoxemia syndrome is an indication for use of intestinal adsorption and inclusion of drugs with sorptive, detoxifying, and cytoprotective activities, as well as those with a favourable effect on intestinal microflora, in combination anti-allergy treatment regimens for patients with atopic dermatitis . Enterosgel is such a medicinal product that exhibits a complex mechanism of action.
This study was conducted with the aim to determine the effect of plasma endotoxin concentrations on immune status markers in children with atopic dermatitis, as well as to evaluate the clinical effectiveness of the new-generation intestinal adsorbent Enterosgel in the treatment of atopic dermatitis.
Materials and methods
We followed up 50 children aged from 10 to 17 years. To determine both plasma endotoxin concentrations and their relationship with immune status markers, the children were divided into two groups: Group 1 comprised 30 children suffering from atopic dermatitis, while Group 2 composed 20 healthy children.
Group 1 (n = 30) had 43% of boys (n = 13) and 57% of girls (n = 17); 50% of the children (n = 15) were aged from 10 to 12 years and 50% (n = 15) were aged from 13 to 17 years. The children with erythematous-squamous atopic dermatitis with lichenification comprised 40% of the patients (n = 12), and those with the lichenoid form of atopic dermatitis 60% (n = 18). The skin process was in the second grade of activity in 40% (n = 12) of the children, and in the third grade in 60% (n = 18) of them.
Moderate atopic dermatitis was observed in 67% (n = 20) of the patients, and severe dermatitis in 33% (n = 10). All children complained of pruritus, rash, and skin dryness. Elevated total serum IgE concentrations were observed in 67% of the children (n = 20). 50% of the children had total serum IgE levels that were many times above normal, and 16% presented with insignificant elevations.
Among the children with increased total serum IgE levels (n = 20), levels up to 300 IU/ml were found in 15% (n = 3), and those above 500 IU/ml in 85% (n = 17) of them.
Specific serum IgE to food allergens was detected in 60% of the children (n = 18), that to indoor allergens in 13% (n = 4), and that to pollen allergens in 16% (n = 5) 70% (n = 21) of the patients were sensitized to all the three allergen groups.
Group 2 consisted of 40% of boys (n = 8) and 60% of girls (n = 12); 50% of the children (n = 10) were aged from 10 to 12 years and 50% (n = 10) were aged from 13 to 17 years.
To evaluate the effectiveness of method of gastrointestinal adsorption (enterosorption) with Enterosgel, the patients with atopic dermatitis (n = 30) were divided into two groups. The experimental group consisted of 16 children who received the oral adsorbent Enterosgel along with conventional anti-allergy therapy. Enterosgel was administered at the age-matched doses: 2 teaspoons 3 times a day (30 g/day) for the children aged under 14 years and 1 tablespoon 3 times a day (45 g/day) for the children aged over 14 years of age – over a 2-week course. The reference (control) group included 14 children who were administered conventional anti- -allergy therapy alone (hypoallergenic diet, antihistamine medication, topical anti- -inflammatory treatment, and therapeutic and cosmetic skin care).
Endotoxin was determined according to Levin J. and Bang F. B in an LAL (Limulus Amebocyte Lysate) test according to the instructions of the manufacturer, Sigma (USA). Results were expressed in international endotoxin units (EU/ml).
Severity of atopic dermatitis was assessed using the SCORAD scale. Statistical analyses included Student’s t-test (t) and correlation analysis (r).
Our data analysis demonstrated that Group 1 children evaluated during an exacerbation of atopic dermatitis had a mean plasma endotoxin concentration of 0.140 ± 0.071 EU/ml, whereas the respective Group 2 value was 0.0024 ± 0.001 EU/ml. During the remission, the mean plasma endotoxin concentration fell to 0.0178 ± 0.0138 EU/ml, but the endotoxin levels still exceeded the Group 2 value (р < 0.001) (Fig. 1).
In severe atopic dermatitis, the mean plasma endotoxin concentration was 0.168 ± 0.079 EU/ml, significantly exceeding the moderate disease arm level of 0.076 ± 0.023 EU/ml (р < 0.05). The children with erythematous-squamous atopic dermatitis with lichenification and those with lichenoid atopic dermatitis had practically the same endotoxin concentrations, the means being 0.123 ± 0.118 EU/ml and 0.124 ± 0.077 EU/ml, respectively. In the children with the second activity grade of the skin process, the mean plasma endotoxin concentration (0.143 ± 0.092 EU/ml) was statistically significantly higher than in those with the third grade activity (0.112 ± 0.061 EU/ml), р < 0.05.
Therefore, the plasma endotoxin concentration in exacerbated atopic dermatitis exceeded respective Group 2 (healthy children) values almost 60 times (р < 0.001), decreasing 8-fold during the remission (р < 0.05), but failing, however, to reach the healthy children levels (р < 0.001).
The overall proportion of therapeutic effect in the experimental group was found to be 87.5% (n = 14). A clinical recovery was observed in 62.5% of the patients (n = 10). Significant improvement of the skin process and reductions greater than 2.5-fold in the SCORAD index, as well as decreased intensity of pruritus and recovered night sleep, were observed in 25% (n = 4) of the patients. No effect was seen in 12.5% (n = 2) of subjects (Fig. 2). With the administered treatment, the time of exacerbation was reduced, while a complete elimination of morphological elements on the skin and achievement of a clinical remission of the disease occurred on the 12th day of treatment on the average. The SCORAD index decreased 5-fold in this group on the average, from 50 to 10 points. There was also a 12-fold decrease in the plasma endotoxin level, from 0.140 ЕU/ml to 0.012 ЕU/ml.
In the reference group, the overall proportion of therapeutic effect was 64.3% (n = 9). A clinical recovery was observed in 42.9% of subjects (n = 6). A significant improvement of the skin process was obtained in 21.4% of the patients (n = 3). No effect was achieved in 35.7% of subjects (n = 5) (Fig. 2). Against the background of the described treatment, the SCORAD index decreased 3.3-fold on the average, from 50 to 15 points.
A clinical remission of the disease was achieved by the 20th day of treatment. The plasma endotoxin reduction was half that observed in the experimental group, just 6-fold, from 0.139 ЕU/ml to 0.023 ЕU/ml, р < 0.05 (Fig. 3).
Enterosgel is very well tolerated and safe. No adverse effects were noted.
- Systemic Endotoxemia was demonstrated in children with atopic dermatitis.
- The plasma endotoxin concentration during an exacerbation of atopic dermatitis exceeded the respective levels in the healthy children group almost 60 times.
- The plasma endotoxin concentration decreases during a remission of atopic dermatitis, but does not reach the physiological endotoxemia level.
- The plasma endotoxin concentration depends on the severity and activity of the skin process.
- Enterosgel coupled with conventional anti-allergy therapy results in a 1.6-fold reduction in the duration of the exacerbation period (from 20 to 12 days) and a 5-fold decrease in the SCORAD index against a background of decreased plasma endotoxin. Therefore, the clinical effectiveness of Enterosgel in the treatment of atopic dermatitis was defined.
- Endotoxemia is an indication for use of gastrointestinal adsorbents.
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