Interleukin 25, thymic stromal lymphopoietin and house dust mites in pathogenesis of atopic dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the world. It is characterized by recurrent eczematous skin lesions, fluctuating course and chronic pruritus. Increasing evidence suggest that AD is more common in adults than previously thought. The disease is characterized by an impaired skin barrier, aberrant Th2-type cytokine production and intensive pruritus. Epithelial keratinocytes constitute the first physical, chemical and immunological barrier, classified as a part of the innate defense system. These keratinocytes secrete various factors, e.g. alarmins such as thymic stromal lymphopoietin (TSLP) and interleukin 25 (IL-25). Serum levels of substance P (SP) have been reported to be increased in patients with AD and correlated with itch intensity. Several previous studies reported a positive association between AD severity and house dust mites (HDM) sensitization. The aim of the study was to analyze IL-25, TSLP and SP concentrations in blood serum of adult patients with severe AD, depending on the degree of allergy to HDM. There were 31 adult AD patients enrolled into the study and a control group that consisted of 20 healthy subjects. AD was diagnosed on the basis of Hanifin and Rajka criteria. SCORing Atopic Dermatitis (SCORAD) and visual analogue (VAS) scores were used to assess the intensity of pruritus and blood content of specific IgE to HDM, as well as TSLP, IL-25 cytokines and SP was measured. Our study presents the evidence that IL-25 serum concentration is increased in patients with atopic dermatitis and this cytokine plays an important role in pathogenesis of this disease. HDM could stimulate the release of IL-25 which aggravates the disease severity. Our results corroborate previous findings on the role of TSLP in atopic dermatitis.

Lack of association of ALOX12 and ALOX15B polymorphisms with psoriasis despite altered urinary excretion of 12(S)-hydroxyeicosatetraenoic acid.

BACKGROUND: Pro- and anti-inflammatory metabolites of arachidonic acid - eicosanoids - participate in skin homeostasis, affecting the growth and differentiation of keratinocytes. Alterations of 12-lipoxygenase (LOX) and 15-LOX and their metabolites have been described in the epidermis of patients with psoriasis, but systemic production of 12-LOX and 15-LOX eicosanoids has not been studied in the disease. OBJECTIVES: To ascertain the frequencies of the genetic variants ALOX12 rs1126667 and ALOX15 rs11568070 in cases and controls, and to compare urinary metabolites of 12(S)-hydroxyeicosatetraenoic acid (HETE) between patients with psoriasis and healthy controls. METHODS: Patients with psoriasis (n = 200) were stratified depending on the severity of their dermal lesions. Genotyping was performed using a 5'-nuclease real-time assay. The concentrations of 12(S)-HETE, its metabolites and 15(S)-HETE were determined in urine samples using high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Tetranor-12(S)-HETE metabolite excretion was significantly higher in urine of patients with psoriasis, while excretion of 12(S)-HETE was decreased. Neither 12(S)-HETE nor tetranor-12(S)-HETE correlated with the type of disease or severity score. No difference in urinary 15(S)-HETE was found between the study groups. Genotype distribution of the ALOX12 rs1126667 or ALOX15 rs11568070 polymorphisms did not discriminate for the disease or its severity. CONCLUSIONS: Systemic metabolism of 12(S)-HETE is accelerated in psoriasis because excretion of the tetranor-12(S)-HETE inactivation product is elevated. No correlation with the severity or extent of psoriasis is detectable. We propose that in patients with psoriasis, 12(S)-HETE to tetranor-12(S)-HETE conversion could be at least a marker for this disease, in which inflammation of the skin can induce microsomal beta-oxidation of this eicosanoid.

An association of TLR2­16934A >T polymorphism and severity/phenotype of atopic dermatitis.

BACKGROUND: Toll-like receptor 2 gene (TLR2) ­16934A>T polymorphism has been shown to be associated with severity of atopic dermatitis (AD) as measured using severity scoring of atopic dermatitis (SCORAD) index. Moreover, TLR2­16934A>T polymorphism has been associated with atopy and allergic disorders in farmers' children. OBJECTIVE: The aim of this study was to evaluate an association between TLR2­16934A>T polymorphism and AD phenotype, including disease severity and concomitant atopic diseases, or potential serum markers of AD severity and also to find a molecular background of the clinical associations. METHODS: Genotyping for TLR2­16934A>T polymorphism was performed in 130 consecutive adult ambulatory patients with AD. Total serum (TS) IgE levels, serum tryptase, plasma interleukin-6 and C-reactive protein were measured. In addition, luciferase assay and electrophoretic-mobility shift assay were conducted to assess the effect of ­16934A>T polymorphism on transcriptional activity. RESULTS: There was an inverse association of TLR2­16934TT genotype and/or ­16934T allele with SCORAD, but not with TS IgE, tryptase or inflammatory markers. Interestingly, ­16934AA genotype and/or ­16934A allele were overrepresented in AD patients with concomitant asthma or a family history of atopy. In a subgroup analysis, TLR2­16934A>T polymorphism was associated with SCORAD, asthma, allergic conjunctivitis or family history of atopy in AD patients with TS IgE ≥106 IU/mL but not in those having TS IgE <106 IU/mL. Functional analyses showed that TLR2­16934T allele is associated with higher luciferase activity in human monocytic THP-1 cells and preferential binding of the THP-1-derived nuclear protein. CONCLUSION: TLR2­16934A>T polymorphism could be a genetic predictor of AD severity, the coexistence of asthma or atopic conjunctivitis as well as a family history of atopic diseases, especially in subjects having higher TS IgE. TLR2­16934A>T polymorphism affects transcriptional activity, which may at least in part account for the clinical associations observed for the ­16934A>T polymorphism.

Association of polymorphic sites in the OCA2 gene with eye colour using the tree scanning method.

A number of genes are considered to affect normal variation in human pigmentation. Recent studies have indicated that OCA2 is the crucial gene involved in the high variation of iris colour present among populations of European descent. In this study, eleven polymorphisms of the OCA2 gene were examined in search of their association with different pigment traits. The evolutionary tree scanning method indicated that the strongest phenotypic eye colour variation is associated with the branch defined by nonsynonymous change rs1800407, which refers to amino acid causing change Arg419Gln located in exon 13. Single SNP analysis indicated that allele 419Gln is associated with green/hazel iris colour (p < 0.001). According to tree scanning analysis, the proportion of eye colour variation explained by this nucleotide position is merely 4%. Thus, additional variation present in the OCA2 gene and perhaps some other pigment related genes must be taken into account in order to explain the high phenotypic variation in iris colour.

Tumorous variant of scleromyxedema. Successful therapy with intravenous immunoglobulins.

We present an unusual tumorous variety of scleromyxedema mimicking facies leonina in lymphoma. In spite of pronounced and widespread cutaneous changes, hypergammaglobulinaemia and paraproteinaemia, the general condition of the patient was satisfactory, there was no internal involvement and no symptoms of any malignancy. Initially, melphalan and corticosteroids were applied but were not effective. High-dose intravenous immunoglobulin (IVIG) therapy had dramatic effect, and after five 5-day monthly courses the tumours almost regressed and the skin became less hard. After a further five courses in the following year there was complete clearance, which was sustained without any therapy for 1 year (until now). IVIG appears to be the therapy of choice for scleromyxedema. We stress, however, that at the start of therapy, IVIG applications should be supplemented with small doses of melphalan and/or corticosteroids.

[Ulcerative colitis concomitant with pyoderma gangrenosum and erythema nodosum--presentation of two cases]. / Wrzodziejace zapalenie jelit towarzyszace piodermii zgorzelinowej i rumieniowi guzowatemu--pokaz dwóch przypadków.

Authors present case of a 28-year old woman with skin symptoms of pyoderma gangrenosum and ulcerative colitis seriously advanced. The patient benefited from wide resection of the colon and steroid therapy. The other patient was 23-year old woman with ulcerative colitis concomitant with skin changes of erythema nodosum. In this case steroid therapy gave also a very good effect. We tried to find pathogenetic connection between these diseases based on the reports from the medical literature.

[Changes in lymphocyte subsets in bronchoalveolar lavage fluid in patients with systemic sclerosis]. / Zmiany w subpopulacjach limfocytów w plynie z plukania oskrzelowo-pecherzykowego u chorych na twardzine ukladowa.

The aim of this study was to estimate if alterations of lymphocyte subsets obtained by broncholaveolar lavage (BAL) were related to clinical data observed in nonsmoking patients with systemic sclerosis (SSc). Clinical examination included chest X-rays, spirometry and arterial blood gasometry. Patients were divided into group A (pulmonary changes present, n = 15) and B (without any changes, n = 7). Healthy subjects constituted the control group (n = 10). BAL lymphocytes were phenotyped using monoclonal antibodies coupling CD4, CD8 (both in coexpression with CD25), CD19 and HLA-DR human antigens and flow cytometer FACStar (Becton-Dickinson). Parallel staining was performed in peripheral blood. BAL lymphocyte typing was completed by BAL routine cytology. In SSc patients we found increased BAL total cell number, percentage of neutrophils, eosinophils and macrophage giant cells, as well as high percent of CD25+ and HLA-DR+ lymphocytes. In the group A neutrophilic alveolitis was observed in nearly half of cases: total lymphocyte number (per 1 ml of BAL fluid) and significantly reduced CD4/CD8 ratio were found. In the group B, as compared with controls, we found significantly elevated lymphocyte total cell number per 1 ml of BAL fluid (including particular subsets: CD3+, CD4+, CD8+). Also significantly high CD4+25+ lymphocyte percent was observed. Summing up, cytological and/or immunological alterations were observed in all examined SSc patients. The intensity of these alterations seems to be related to the clinical data. A decreased value of CD4/CD8 ratio may play a role in the local appearance of pulmonary changes in the course of systemic sclerosis.

[Sarcoidosis--a diagnostic and therapeutic problem]. / Sarkoidoza--problem diagnostyczny i terapeutyczny.

Sarcoidosis is a multi-organ granulomatous disorder of an unknown cause. Skin sarcoidosis occurs in about 20-35% of patients with systemic disease and may also arise in isolation. A wide range of clinical presentations of cutaneous sarcoidosis is recognised. The diagnosis rests on the presence of non-caseating granulomas on skin biopsy. Treatment and overall prognosis of cutaneous sarcoidosis is primarily dependent on the degree of systemic involvement.

Serum levels of soluble TNF alpha receptor type I and the severity of systemic sclerosis.

Several abnormalities of cytokines have been shown to occur in systemic scleroderma; however their correlation with clinical parameters is controversial. Since serum concentrations of cytokine receptors have been shown to correlate with inflammatory processes, including systemic sclerosis, the aim of our study was to compare serum concentrations of TNF alpha receptor type 1 with the concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble interleukin-2 receptor (sIL-2R) and aminoterminal propeptide of procollagen type III (PIII NP). The findings were correlated with the clinical parameters and antibody patterns, and with the disease severity. Serum samples were studied with the use of enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) for sTNF alpha R1, sICAM-1, sIL-2R and PIII NP. The series comprised 36 patients with systemic scleroderma: 13 with diffuse variety and 23 with limited variety, and 7 with Raynaud's disease. Healthy volunteers (n = 25) were chosen from doctors and/or other laboratory staff. Increased levels of sTNF alpha-receptor type 1 were found in 77% of patients with diffuse variety and in only 30% of patients with limited form. Increased serum concentrations in patients with diffuse scleroderma and limited variety were found for sICAM-1 54% and 65%, for sIL-2R 46% and 15%, and for PIIINP 77% and 50%, respectively. There were significant correlations between serum levels of sTNF alpha-receptor type 1 and PIIINP (r = 0.653, p < 0.0001), and sTNF alpha-receptor type 1 and sIL-2R (r = 0.625, p < 0.0001), but not between sTNF alpha-receptor type 1 and sICAM-1 (r = 0.127, p < 0.526). Clinical analysis revealed that serum concentrations of sTNF alpha-RI seem to correlate best with the severity of the disease and, as the only parameter, correlated with lung involvement. The study showed that, in addition to recognized parameters of scleroderma severity (IL-2R, PIIINP), a new important marker appears to be sTNF alpha-receptor type 1.