A prospective study in children with a severe form of atopic dermatitis: clinical outcome in relation to cytokine gene polymorphisms.

BACKGROUND AND OBJECTIVE: The course of atopic dermatitis (AD) in childhood is characterized by typical changes in phenotype, including a shift from skin involvement to respiratory allergy usually around the third year of age. We thus designed a prospective study to monitor the outcome of severe AD and to investigate the association between cytokine gene polymorphisms and clinical manifestations. METHODS: Clinical and laboratory follow-up of 94 patients with severe AD and 103 healthy controls was performed using routine methodology. Allele, genotype, and haplotype frequencies of single nucleotide polymorphisms of 13 selected cytokine/receptor genes were analyzed using PCR with sequence-specific primers. RESULTS: In our study, genotypes of 7 polymorphisms--LL-4 -1098G/T and -590C/T, IL-6 -174C/G and nt565A/G, and IL-10 -1082A/G, -819C/T, and -592A/C were significantly associated with atopic AD (P < .05). A significant association was also found for TNF-alpha AA and IL-4 GC haplotypes and AD. We confirm the progressive clinical improvement of AD together with a decrease in the severity index SCORAD (SCORing atopic dermatitis) during childhood (P < .05). We found significant differences between IL-4Ralpha +1902 A/G and positivity of tree pollen-specific IgE (P < .05) in the AD group. Moreover, a weak association was also found between IL-10 -819C/T and IL-10 -590A/C and the appearance of allergic rhinitis (P < 0.1). CONCLUSIONS: We confirmed a clinical shift in allergic phenotype in the first 3 years of life, and showed an association between IL-4, IL-6, and IL-10 polymorphisms and AD. Our data indicate that IL-4alpha and IL-10 polymorphisms may be considered predictive factors of respiratory allergy in children with AD.

Selective increase in blood dendritic cell antigen-3-positive dendritic cells in bronchoalveolar lavage fluid in allergic patients.

Dendritic cells (DCs) are specific antigen-presenting cells that play critical roles in the initiation and polarization of immune responses. DCs residing in the lungs might be detected in the bronchoalveolar lavage fluid (BALF). We analysed DC compartment in the peripheral blood and BALF of patients with allergy and in controls. Plasmacytoid and four distinct subsets of myeloid DCs [characterized by the expression of blood dendritic cell antigen (BDCA)-1+ and -3+ and CD16 positivity or negativity] were detected in both tested compartments. We further evaluated the expression of C-type lectins [mannose receptor (MR), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and dendritic and epithelial cells (DEC)-205] relevant to the pathogenesis of asthma. Interestingly, we found a selective increase in the frequency of myeloid DC-expressing BDCA-3 and MR particularly in BALF from allergic patients. Specific and highly statistically significant increase in BDCA-3+ and/or MR+ DCs brings a novel characteristic to BAL analysis in allergic patients.

Serum immunoglobulin free light chains in severe forms of atopic dermatitis.

An increase in immunoglobulin free light chains (FLC) was recently described in several pathological conditions, including asthma. FLC pathology is classically associated with monoclonal gammopathies. Its association with allergic disorders is surprising and unexplained. We therefore tested a cohort of children with severe atopic dermatitis (SCORAD 50-80) to determine the serum levels of free kappa and lambda chains, and correlated the results with clinical status and relevant laboratory markers. Seventy-three patients with severe forms of AD, all children from 3 months to 3 years of age and ninety healthy age-matched controls were included in the study. Light chains in sera were tested using the Freelite assay (Binding Site, Birmingham, UK). There were highly significant differences in both kappa (mean: 7.05 and 3.22 mg/l) and lambda (mean: 10.99 and 9.8 mg/l) serum levels between patients and controls, respectively (P < 0.0001). The kappa/lambda ratio in patients with allergy (mean: 0.64) was significantly higher than in controls (0.33) (P < 0.0001). We further observed significantly increased levels of FLC and their ratio in the group of patients with severe forms of AD in comparison to the group of patients with a resting stage of the disease or healthy controls (P < 0.05 and P < 0.0001, respectively). On the other hand, we could not confirm any association of FLC levels with age or total IgE levels. In conclusion, an increase in FLC reflects disease activity in children with severe atopic dermatitis. FLC might thus represent an additional diagnostic marker independent of total IgE levels.

[Prevalence of hepatitis G virus infection (HGV) in intravenous immunoglobulin recipients in the Czech Republic]. / Výskyt infekce virem hepatitidy G (HGV) u pacientu lécených intravenózními imunoglobuliny v Ceské republice.

The prevalence of hepatitis G virus (HGV) in the serum of intravenous immunoglobulin (IVIG) recipients was studied and risk related to HGV positivity was considered. Although its pathogenicity is unclear, HGV is likely to cause liver disease or lymphoproliferation. Twenty (23%) of 86 tested MG patients were HGV RNA positive. Of the HGV positive patients, three (15%) showed mild elevation of liver enzymes and one (5%) was diagnosed with chronic lymphatic leukaemia prior to the institution of MG replacement. It can be concluded that the HGV prevalence among IVIG recipients is high but is not associated with signs of either liver disease or lymphoproliferation.

[What is Hodgkin's disease?]. / Co je Hodgkinova choroba?

The article summarizes contemporary views on the aetiology, pathogenesis, therapy and prognosis of Hodgkin's disease. The author emphasizes the necessity of intensive search for the origin of malignant cells. From the therapeutic aspect the necessity of team work and the use of a data base is emphasized which facilitates adaptation of treatment to individual patients, depending on prognostic factors.

[Prognostic factors and their importance in the modification of therapeutic approaches in patients with Hodgkin's disease]. / Prognostické faktory a jejich význam pro modifikaci lécebného postupu u nemocných s Hodgkinovou chorobou.

A prognostic study was performed in a group of 236 long-term followed patients. Eleven factors in total were included into a multivariate analysis--they were global, clinical and therapeutical factors. For complete remission, clinical stage, age at the time of diagnosis and size of affliction of mediastinum are important. Signs of poor prognosis for complete remission are "bulky" mediastinal disease, male sex and absence or reduction of chemotherapy in primary treatment. Prognostic factors as to the total survival are age at the time of diagnosis, clinical stage, total number and size of afflicted lymphatic areas and absence or reduction of chemotherapy in primary treatment. Emphasis is laid upon evaluation of the amount of individual risk to adjust therapeutic procedures to every individual patient.

[Causes of death in patients with Hodgkin's disease]. / Príciny úmrtí nemocných s morbus Hodgkin.

The authors analyze the causes of death of 52 patients from a group comprising 236 patients with Hodgkin's disease. From 51 patients 16 died within one year, with a single exception. All were in clinical stage III-IV (at the time of diagnosis). Within 5 years 40 patients died incl. 4 who the time of diagnosis belonged to clinical stage II. After more than 5 years following establishment of the diagnosis 12 patients died. Of these at the time of the diagnosis 8 were in clinical stage II, 3 in clinical stage III and one patient in clinical stage IV. In the first clinical stage and according to histological classification 10 patients survive, in clinical stage II 93 patients, in clinical stage III 105 patients and 28 patients in clinical stage IV. The mortality rate increases with the advancing clinical stage. Causes of death: progression of the basic disease in 63%, intercurrent infectious diseases in 25%, inhibition of bone marrow in 6%, same percentage for development of secondary neoplasms. The lowest mortality rate was recorded in patients treated by a combination of actino- and chemotherapy (11%), as compared with 23% treated by actinotherapy only and 41% treated by chemotherapy only.