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.

Primary localized cutaneous amyloidosis--lichen amyloidosus. A case report.

We report a case of primary localized cutaneous amyloidosis-lichen amyloidosus in a 55-year-old man. Immunohistochemistry using antibodies against cytokeratin and AL immunoglobulins revealed the presence of both components in amyloid foci located subepidermally, mainly in dermal papillae. The results of histochemical reactions confirm the keratin-derived nature of amyloid in primary cutaneous amyloidosis.

[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.

[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.

EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivity.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common causes of adverse drug reactions. Majority of them are of the hypersensitivity type. The two frequent clinical presentations of aspirin hypersensitivity are: aspirin-induced bronchial asthma/rhinosinusitis (AIA/R) and aspirin-induced urticaria/angioedema (AIU). The decisive diagnosis is based on provocation tests with aspirin, as the in vitro test does not hold diagnostic value as yet. Detailed protocols of oral, bronchial and nasal aspirin provocation tests are presented. Indications, contraindications for the tests, the rules of drug withdrawal and equipment are reviewed. Patient supervision and interpretations of the tests are proposed.

Familial aggregation of aspirin-induced urticaria and leukotriene C synthase allelic variant.

BACKGROUND: We have reported that in patients with chronic idiopathic urticaria (CIU) who reacted adversely to aspirin, the frequency of the (-444)C allele of the leukotriene C(4) synthase gene (LTC4S) was higher than in patients who tolerated aspirin well. OBJECTIVES: To study the pattern of aspirin-induced urticaria (AIU) in two families, with special interest on the polymorphisms of LTC4S (AA, AC, CC) and the glutathione S-transferase M1 and P1 genes (GSTM1 and GSTP1). METHODS: Of 74 patients with CIU and a history of aspirin hypersensitivity studied by us, two patients (probands) gave a family history of aspirin intolerance. Oral challenge tests with aspirin were carried out in members of these families. Genomic DNA samples were obtained from peripheral blood to study the polymorphisms of LTC4S, GSTM1 and GSTP1. RESULTS: In family 1 the aspirin challenge test confirmed AIU in three of five (60%) individuals, but in family 2 only in two of seven (29%). In both families, the variant genotypes of LTC4S (AC or CC) were present in the parents, but only one of them had CIU. In family 1, with both parents healthy, the three children had AIU; in two it was associated with variant LTC4S genotype. In family 2, urticaria following aspirin ingestion was present only with variant LTC4S genotype. In patients of both families with positive aspirin challenge test, deletion of the GSTM1 gene was present. CONCLUSIONS: AIU aggregates in families inheriting the LTC4S(-444)C allele. Segregation of aspirin sensitivity in these families does not follow a clear Mendelian pattern. A common deletion of GSTM1, one of several enzymes involved in conjugation of a wide range of electrophilic substances with glutathione, was present in all individuals ascertained to have AIU.

The alpha-chain of high-affinity receptor for IgE (FcepsilonRIalpha) gene polymorphisms and serum IgE levels.

BACKGROUND: The high-affinity receptor for immunoglobulin-E (IgE) (FcepsilonRI) plays a major role in the pathogenesis of allergy, but there are only two published studies on its alpha subunit (FcepsilonRIalpha) genetic variability in allergic diseases. AIMS OF THE STUDY: Mutational screening in the region of the FcepsilonRIalpha gene promoter and the first exon with subsequent genetic variability assessment in allergic patients and a random population sample. METHODS: Allergic subjects were individuals with asthma or urticaria. Age- and sex-matched controls were randomly selected from a large population sample. Mutational screening was performed using a single-stranded conformational polymorphism and subsequent sequencing. Detected polymorphisms were genotyped by restriction fragment length polymorphism. Total serum IgE was measured in allergic subjects and controls. Skin prick tests, blood eosinophil count and aspirin challenge test were performed only in the subjects. A subgroup of the subjects was further characterized by autologous serum skin test, histamine release test, Phadiatop and IgE antibodies against staphylococcal enterotoxins. RESULTS: Two linked polymorphisms -344 C>T and -95 T>C were found within the FcepsilonRIalpha gene. The allele -344 T frequency was 0.45 vs 0.37 (P = 0.33), and the allele -95 C frequency was 0.26 in subjects vs 0.30 in controls (P = 0.62). Serum IgE was significantly higher in subjects homozygous for the -344T allele (TT genotype) than in those carrying the -344 C allele (CT or CC genotype; P = 0.003), but this association was not detectable in controls. CONCLUSIONS: Our findings of genotype-related differences in IgE levels in allergic patients suggest an impact of -344 C>T but not -95 T>C gene polymorphism of FcepsilonRIalpha on total levels of IgE. The genetic variability in FcepsilonRIalpha at the -344 nucleotide of its regulatory sequence, though not related to atopy, predicts higher levels of the immunoglobulin.