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Evidence for histamine-mediated inhibition of monocyte chemotaxis in atopic dermatitis.

Leukocyte chemotaxis was studied in 11 patients with severe childhood onset atopic dermatitis at a time when their disease was relatively quiescent. Pyoderma had been an important complication of the dermatitis in these patients. The chemotactic responsiveness of patient neutrophils and monocytes was on the average not significantly different from that of healthy control subjects, although three patients were identified who had significantly impaired responses. No correlation between IgE levels and leukocyte chemotaxis was observed. Because excessive amounts of histamine have been recovered from the skin of patients with atopic dermatitis, we evaluated the effects of histamine on the chemotactic responsiveness of leukocytes from these patients. Histamine caused a small dose-related increase in chemotaxis of neutrophils from both patients and control subjects (10(-7)M to 10(-5)M histamine). In contrast, histamine had no effect on the chemotaxis of monocytes from control subjects but inhibited the chemotactic responsiveness of monocytes from atopic dermatitis patients. These findings suggest that an abnormal sensitivity of monocytes to histamine is an intrinsic feature of atopic dermatitis that may be detectable when the disease is quiescent. Furthermore, this abnormality may contribute to the impairment of monocyte chemotaxis that has been previously observed in patients with active atopic dermatitis.

Chemotaxis↗

Evolution of atopic dermatitis.

A follow-up study was done in 50 patients with atopic dermatitis over a time lapse of approximately 20 years. 31 patients (62%) continued to have atopic dermatitis, although usually in a less severe form. Severe atopic dermatitis in childhood, association with asthma and hay fever, presence of atopy in the family seem to indicate that atopic dermatitis will continue in adult age. Hay fever and a familial history of atopy are statistically significant risk factors.

Adolescent↗

Bronchial hyperresponsiveness in children with atopic dermatitis.

Using histamine provocation tests, bronchial responsiveness was measured in 43 children with atopic dermatitis, aged 7 to 15 years, who had attended pediatric dermatology clinics within the past 5 years. The children were divided into two groups, one group of 21 children in whom asthma had been previously diagnosed and in whom symptoms of asthma had occurred in the preceding year, and the other comprising 22 children who denied any such symptoms. Bronchial hyperresponsiveness (as defined by a 20% fall in forced expiratory volume in 1 second at a provoking dose of histamine of 7.8 mumol or less [PD20]) was demonstrated in all but 1 of the children with atopic dermatitis and asthma, in 18 of the 22 children with atopic dermatitis alone, but in only 3 of a control group of 18 children without atopic dermatitis or asthma. The asthmatic subjects (median PD20 = 0.22 mumol) had more severe bronchial hyperresponsiveness than the nonasthmatic subjects (median PD20 = 2.10 mumol). This study confirms the strong association between atopic dermatitis and bronchial hyperresponsiveness, even in the absence of overt asthmatic symptoms.

Adolescent↗

The relationship between the psychological and immunological state in patients with atopic dermatitis.

The relationship between the psychological and immunological state in patients with atopic dermatitis was investigated. It was found that patients with atopic dermatitis are significantly more depressive and scored higher for state anxiety (P < 0.05) than the normal control group. They also tended to be more psychosomatic symptom-prone and to score higher for trait anxiety. NK activity in patients with atopic dermatitis was significantly lower than in normal controls (P < 0.01), while serum IFN-gamma levels tended to be slightly higher and serum IL-4 levels somewhat lower. No significant correlation was detected between any pair of psychological test/immunological examination for either patients or normal controls. However, in the examination of path analyses, psychological variables affect serum levels of IFN-gamma and IL-4 more in the patients than the normal controls. Only STAI(T) and (S) affect NK activity in atopic dermatitis patients. By a discriminant analysis, NK cell activity and serum IFN-gamma appeared statistically significant. We conclude that the psychological state is to some extent related to the immunological state.

Adolescent↗

Association between atopic dermatitis and insulin-dependent diabetes mellitus: a case-control study.

BACKGROUND: Up to two-thirds of children with atopic dermatitis have IgE-mediated allergic reactions and a Th2 immune reactivity pattern with low production of interferon gamma and high production of interleukin 4 after allergen stimulation of T lymphocytes. Insulin-dependent diabetes mellitus (IDDM) seems to be associated with a Th1 immune reactivity pattern. We therefore postulated that these diseases may be inversely associated. METHODS: We designed a case-control study including 920 children with IDDM, registered in the Danish Registry for Childhood Diabetes, and a sample of 9732 non-diabetic children registered in the Danish Medical Birth Registry. The children were aged 3-15 years. Information on atopic dermatitis was obtained by questionnaires. FINDINGS: The cumulative incidence of atopic dermatitis up to age 15 years was 13.1% among children with IDDM and 19.8% in non-diabetic children (p<0.0001). Among children who developed IDDM, the incidence of atopic dermatitis was significantly lower than in the controls before onset of IDDM (73 cases in 5314 person-months vs 1375 in 57432 person-months; odds ratio 0.49 [0.39-0.63]). After onset of IDDM, diabetic and non-diabetic groups did not differ in incidence of atopic dermatitis (1.36 [0.89-2.07]). INTERPRETATION: Our findings may be explained by different acquired or inherited reactivity patterns associated with atopic dermatitis (Th2) and IDDM (Th1). The results do not allow us to find out whether early development of atopic dermatitis reduces the risk of IDDM, or a propensity for IDDM reduces the risk of early-onset atopic dermatitis.

Adolescent↗

Mast cell density and subtypes in the skin of dogs with atopic dermatitis.

Skin biopsies from seven dogs with atopic dermatitis and 13 dogs with no clinical or histological evidence of skin diseases were examined. The study of the atopic dogs included 11 biopsy samples of nonlesional skin and 15 samples of lesional skin. One section of each tissue sample was stained with haematoxylin and eosin and another with toluidine blue to demonstrate the sulphated acid glycosaminoglycans in mast cell (MC) granules. To investigate MC subtypes, the MC-specific proteases tryptase and chymase were examined by a double enzyme-immunohistochemical staining technique. With the double labelling technique a significantly lower mast cell density was demonstrated in lesional (P = 0.0023) and nonlesional (P = 0.0004) skin samples of the atopic dogs than in the skin of control dogs. In the dermis of control dogs, a median mast cell density of 31.2 MC/mm2 was detected with the toluidine blue staining method and of 27.5 MC/mm2 with the double labelling technique. In lesional dermis of atopic dogs 29.8 MC/mm2 were seen with toluidine blue while only 12.4 MC/mm2 were stained with the double labelling method (P = 0.0027). A similar difference was observed in nonlesional dermis samples, in which a mast cell density of 23.3 MC/mm2 was detected with toluidine blue but only 6.4 MC/mm2 with the double labelling method (P = 0.0127). The data provide evidence that mast cell granule heterogeneity exists in the dog and suggests that degranulation occurs selectively, depending on the pathological condition of the canine skin. Further investigations on the pathophysiological role of mast cell subtypes may help to elucidate the pathogenesis of atopic dermatitis.

Animals↗

Dermal deposition of eosinophil-granule major basic protein in atopic dermatitis. Comparison with onchocerciasis.

Although blood eosinophilia is commonly present in atopic dermatitis, accumulation of tissue eosinophils is not prominent. To determine whether eosinophil degranulation occurs in lesions of atopic dermatitis, we analyzed tissues by immunofluorescence for the presence of the eosinophil-granule major basic protein. Twenty biopsy specimens from 18 patients with atopic dermatitis were studied, and all showed major basic protein staining outside eosinophils. In 18 specimens, the staining was fibrillar, was located in the upper half of the dermis, and was similar to the distribution of elastic fibers. Twelve specimens with fibrillar staining also showed major basic protein staining in the form of extracellular granules. One specimen from unaffected skin showed minimal faint, fine, fluorescing fibrils, but there was marked deposition of the protein in affected skin. The fibrillar pattern of major basic protein staining in atopic dermatitis was very similar to that seen in lichenified lesions of untreated onchocerciasis. These results suggest that eosinophils commonly release granule proteins in the dermis and that assessment of eosinophil involvement in disease cannot be based simply on numbers of eosinophils in tissue.

Adolescent↗

Gamma-linolenic acid supplementation for prophylaxis of atopic dermatitis--a randomized controlled trial in infants at high familial risk.

BACKGROUND: Studies suggest that low concentrations of n-6 long-chain polyenes in early life are correlated to atopic disease in later life. OBJECTIVE: The purpose of the study was to investigate the possible preventive effect of gamma-linolenic acid (GLA) supplementation on the development of atopic dermatitis in infants at risk. DESIGN: In a double-blind, randomized, placebo-controlled trial, formula-fed infants (n = 118) with a maternal history of atopic disease received borage oil supplement (containing 100 mg GLA) or sunflower oil supplement as a placebo daily for the first 6 mo of life. Main outcome measures were the incidence of atopic dermatitis in the first year of life (by UK Working Party criteria), the severity of atopic dermatitis (SCORing Atopic Dermatitis; SCORAD), and the total serum immunoglobulin E (IgE) concentration at the age of 1 y. RESULTS: The intention-to-treat analysis showed a favorable trend for severity of atopic dermatitis associated with GLA supplementation ( x+/- SD SCORAD: 6.32 +/- 5.32) in the GLA-supplemented group as compared with 8.28 +/- 6.54 in the placebo group (P = 0.09; P = 0.06 after adjustment for total serum IgE at baseline, age 1 wk), but no significant effects on the other atopic outcomes. The increase in GLA concentrations in plasma phospholipids between baseline and 3 mo was negatively associated with the severity of atopic dermatitis at 1 y (Spearman's correlation coefficient = -0.233, P = 0.013). There was no significant effect on total serum IgE concentration. CONCLUSION: Early supplementation with GLA in children at high familial risk does not prevent the expression of atopy as reflected by total serum IgE, but it tends to alleviate the severity of atopic dermatitis in later infancy in these children.

Dermatitis, Atopic↗

[ATOPIC DERMATITIS].

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Adrenal Cortex Hormones↗

Fungal flora of human faeces in psoriasis and atopic dermatitis.

Faeces samples taken from 343 patients with psoriasis and 581 patients with atopic dermatitis were subjected to mycological examination. Yeasts were detected in 68% of the psoriatics and in 70% of the patients with atopic dermatitis but in only 54% of the controls (n = 50). Qualitative analysis revealed a predominance of Candida albicans. Non-pathogenic yeasts constituted only 1% in each of these groups. Of the hyphomycetes, Geotrichum candidum occurred in 22% of the psoriatics, in 10% of the atopic dermatitis patients and in 3% of the controls. Aspergillus species were found in 1% of the patients but not in the controls. Stool samples collected on three consecutive days from 141 patients were examined for yeasts. Qualitative correlation between all three samples was shown in 95% of the patients and quantitative correlation in 38%. Deviations were mainly of exponential magnitude. Germ cell concentration of 10(4) cells per ml and above were measured in 38% of the psoriatics and in 28% of the atopic dermatitis patients but in only 22% of the test subjects with healthy skin. There was no correlation between the concentration levels of yeasts in the faeces and the extent of psoriasis or atopic dermatitis.

Aspergillus↗

Bicentre experience in the treatment of severe generalised atopic dermatitis with extracorporeal photochemotherapy.

Pilot studies have shown an improvement of atopic dermatitis in approximately 65% of patients during extracorporeal photopheresis (ExP) therapy. The purpose of the present clinical trial was to investigate the response to ExP by controlling clinical and laboratory parameters during short term ExP therapy in patients with severe generalised atopic dermatitis. Thirty-five patients with severe, therapy-resistant atopic dermatitis were treated with ExP in an open clinical trial at two week intervals over a period of 6 to 10 cycles. Disease activity was measured before each cycle by SCORAD index together with a standardized protocol for blood samples. ExP led to a significant decrease (p < 0.05) in SCORAD from 74.4 +/- 15.5 before to 36.8 +/- 16.8 after ExP therapy (mean 10 cycles). Approximately 70% (24/33 patients = responder) of patients had a favourable response to ExP requiring at least 6 cycles. The decrease in SCORAD was accompanied by a significant decrease of eosinophil cationic protein (27%), sE-selectin (37%) and sIL-2R (53%) levels in serum (p < 0.05). No significant correlation between a decrease in these levels and values of blood eosinophils or lymphocytes was found (p > 0.05). In comparison to responders, most non-responders were characterised by very high levels of total IgE before and during therapy (p < 0.05). The present clinical trial confirms that short term ExP is an effective treatment for certain patients with severe atopic dermatitis based on anti-inflammatory mechanisms. Total IgE could be a predictor of outcome in ExP treatment.

Administration, Oral↗