Ove Bäck

Does vitamin d intake during infancy promote the development of atopic allergy

The active metabolite of vitamin D, 1,25-(OH)2D3, has immunomodulatory properties in addition to its more established action on bone and calcium metabolism. Recently vitamin D has been proposed as one of several environmental factors responsible for the increase in atopic diseases during the last decades. The objective of this study was to determine whether the estimated dose of dietary vitamin D3 during the first year of life is associated with atopic diseases up to the age of 6 years. In a prospective birth cohort study 123 six-year-old children were investigated for the cumulative incidence of atopic dermatitis, allergic rhinitis or asthma by means of a postal questionnaire. Their vitamin D3 intake during infancy was recorded in a previous study and the relationship between lower or higher vitamin D3 intake and atopic illness later in childhood was assessed. Atopic manifestations were more prevalent in the group with higher intake of vitamin D3. Although small, this study supports previous investigations suggesting a role of vitamin D intake during infancy in the development of atopic allergy later in childhood. If these findings are confirmed in prospective controlled clinical trials, prevention through modified vitamin D3 supplementation in infancy could be discussed to reduce the burden of atopic illnesses.

Pityrosporum folliculitis: A common disease of the young and middle-aged

Fifty-one patients, thirty-nine women and twelve men, with Pityrosporum folliculitis are described. This investigation clearly demonstrates that Pityrosporum folliculitis is a real entity. The diagnosis is based primarily on the clinical picture, direct microscopy, histopathology, and the effect of antimycotic treatment. The typical patient is a woman of 30 years with itching follicular papules and pustules localized to the upper trunk or upper arms. Direct microscopy reveals round yeast cells and sometimes even hyphae. In biopsy specimens, abundant round budding yeast cells and occasionally hyphae are seen in a dilated follicle. Yeast growth is obtained only on lipid-enriched media. Twenty-five patients were treated with selenium sulfide shampoo, twelve with 50% propylene glycol in water, and ten with topical econazole cream with good results. Cure or marked improvement was seen after 3 to 4 weeks, but symptoms and lesions recurred if treatment was not continued intermittently. Predisposing factors such as occlusion and greasy skin are probably important, and future studies should focus on fungal hypersensitivity, quantitative variations in the number of Pityrosporum orbiculare, lipid composition of the skin, and extended epidemiologic data.

Ketoconazole in atopic dermatitis: therapeutic response is correlated with decrease in serum IgE

The prevalence of specific IgE antibodies to the yeasts Pityrosporum orbiculare and Candida albicans was investigated in adult patients with atopic dermatitis (AD) or with seborrhoeic dermatitis and in healthy controls by means of the radioallergosorbent test (RAST). Of 63 AD patients, 28 (44%) had IgE antibodies to P. orbiculare and 21 (33%) to C. albicans. This is highly significant, since no antibodies were found in sera from other patients or controls. With the intention to treat, 20 patients with AD and a positive RAST to P. orbiculare were given ketoconazole 200 mg daily for 2 months and 200 mg twice weekly for further 3 months. The clinical scores improved during treatment with a reduction in the levels of specific IgE to P. orbiculare and total serum IgE. However, there were no correlations between clinical score and serum levels of P. orbiculare-specific IgE. C. albicans-specific IgE, on the other hand, correlated both with clinical score and with total serum IgE.

The prevalence of Malassezia yeasts in patients with atopic dermatitis, seborrhoeic dermatitis and healthy controls

Cultures for Malassezia yeasts were taken from both normal-looking skin and lesional skin in 124 patients with atopic dermatitis, 16 patients with seborrhoeic dermatitis and from normal skin of 31 healthy controls. Positive Malassezia growth was found in fewer patients with atopic dermatitis (56%) than in patients with seborrhoeic dermatitis (88%) or in healthy controls (84%, p<0.01). In the patients with atopic dermatitis, fewer positive cultures were found in lesional (28%) than in non-lesional skin (44%, p<0.05), while positive cultures were found in 75% of both lesional and non-lesional skin of patients with seborrhoeic dermatitis (not significant). M. sympodialis dominated in patients with atopic dermatitis (46%) and in healthy controls (69%). In patients with seborrhoeic dermatitis both M. sympodialis and M. obtusa were cultured in 43%. A Malassezia species extract mixture would increase the possibility of detecting IgE sensitization to Malassezia in patients with atopic dermatitis.

Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients.

Summary Background The yeast Malassezia is considered to be one of the factors that can contribute to atopic dermatitis (AD).

An immunologic and cultural study of Pityrosporum folliculitis

In patients with Pityrosporum folliculitis the mean serum antibody titer against Pityrosporum orbiculare was significantly higher than in healthy control subjects (p less than 0.01). The mean number of P. orbiculare organisms per square centimeter cultured from normal-looking skin in patients was not significantly higher than the number cultured from normal-looking skin in control subjects. Results of prick tests against P. orbiculare extract were negative or weak, indicating that patients with Pityrosporum folliculitis had no type I hypersensitivity against P. orbiculare. Immunohistochemical staining of skin lesions showed perivascular dermal cell infiltrates near the hair follicles dominated by anti-Leu 3a-reactive T lymphocytes. Human lymphocyte antigens with the DR locus, but not those with the DQ locus, on keratinocytes were observed in one case.

Serum IgE reactivity to Malassezia furfur extract and recombinant M-furfur allergens in patients with atopic dermatitis

IgE reactivity to the opportunistic yeast Malassezia furfur can be found in patients with atopic dermatitis (AD). We have previously cloned and expressed 6 recombinant allergens (rMal f 1, rMal f 5-9) from M. furfur. In the present study, we used ImmunoCAP to investigate whether these rMal f allergens can be useful in the diagnosis of M. furfur-associated AD compared with the M. furfur extract. A total of 156 adult patients with a clinical diagnosis of AD participated in the study. Sixty-four percent had increased total serum IgE levels, 79% had specific IgE antibodies to common inhalant allergens and 47% had IgE antibodies to M. furfur extract. IgE antibodies to any of the rMal f allergens were detected among 86 (55%) of the patients, 14 (16%) of whom did not react to the M. furfur extract. Any individual rMal f allergen detected between 32% and 89% of the patients ImmunoCAP-positive to the M. furfur extract, with the highest sensitivity for rMal f 9. Therefore, a couple of individual rMal f allergens can improve the diagnosis of M. furfur-associated IgE allergies in patients with AD.

Decreased Peripheral Glucocorticoid Sensitivity in Alzheimer’s Disease

Both peripheral and central glucocorticoid sensitivity was examined in patients with Alzheimers disease (AD; n = 13), glucocorticoid-treated patients (n = 8), healthy elderly controls (n = 10) and young controls (n = 9). We performed glucocorticoid receptor-mediated skin vasoconstrictor responses to clobetasol and low-dose dexamethasone suppression tests. Patients with AD showed skin blanching at a significantly higher clobetasol concentration than did healthy elderly controls (p = 0.002). There was no difference in skin blanching between patients with AD and patients treated with corticosteroids. Patients with AD had significantly higher post-dexamethasone serum cortisol levels than healthy elderly (p = 0.01). No association was found between skin blanching and dexamethasone suppressibility. Thus patients with AD have apparently independent reductions in both central nervous system and peripheral glucocorticoid sensitivity. These results predict an increase in glucocorticoid secretion in some patients, which might accelerate neuronal degeneration in the absence of features of overexposure to glucocorticoids in peripheral tissues.

Elevated plasmin-α2-antiplasmin complex levels in hereditary angioedema: Evidence for the in vivo efficiency of the intrinsic fibrinolytic system

The contact activation and fibrinolytic systems were assessed in 5 patients with hereditary angioedema (HAE). Reductions in F XII levels and increase in kallikrein-like activity in some patients indicated activation of the contact (intrinsic) system of coagulation. A great increase in plasmin-alpha 2-antiplasmin complex in all subjects indicated that in this disease, there is a constantly ongoing fibrinolysis. Since C1-inhibitor, the deficient protein in HAE, is a poor inhibitor of the well-known extrinsic (tissue-type) plasminogen activator, but the major inhibitor of the contact activation system and a related in vitro phenomenon termed intrinsic fibrinolysis, our data show that this fibrinolytic system is also sometimes operating efficiently in vivo. Furthermore, the known clinical data on HAE are compatible with a role of intrinsic fibrinolysis in the pathophysiology of this disease.

Sensitization to skin-associated microorganisms in adult patients with atopic dermatitis is of importance for disease severity.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Environmental and genetic factors, as well as microbial products from yeasts and bacteria, play a role in triggering the disease. A cohort of 619 adult patients with AD was screened for severity of AD, sensitization to Malassezia sympodialis, Candida albicans, Staphylococcus aureus enterotoxins and Dermatophagoides pteronyssinus. Serum levels of interleukin (IL)-18 were measured. Immunoglobulin E (IgE) sensitization to the combination of both yeast and mite antigens was found to be associated with more severe disease and higher levels of total IgE. AD patients with IgE sensitization to several microbial antigens had more severe disease than those with no IgE sensitization to microbial antigens. Sera from patients with IgE-associated AD showed higher levels of IL-18. Skin-associated microorganisms are exogenous factors triggering IgE-response and severity of AD. These findings are clinically important, and sensitization to these organisms should be assessed and considered in treatment strategies.