Disturbances of circadian profile and blood pressure control in patients with systemic lupus erythematosus without overt heart disease.

Introduction: Lupus erythematosus (SLE) is an autoimmune disease that causes a significantly increased risk of cardiovascular diseases. This process is underlain by the early and accelerated atherosclerosis. Aim: To assess the diurnal blood pressure profile disturbances in normotensive patients without overt cardiovascular disease and to correlate with early atherosclerotic markers. Material and methods: The study included 32 baseline normotensive women with SLE and 30 healthy control women. Each participant underwent a 24-hour automatic blood pressure measurement and an ultrasound assessment of intima media thickness (IMT) and the presence of carotid atherosclerotic plaques. Results: Atherosclerotic plaques were present in 46.9% of SLE women. They had a significantly higher IMT compared to those without atherosclerotic plaques and control group (0.833 ±0.216 vs. 0.606 ±0.121 vs. 0.66 ±0.16 mm). A significant positive correlation was found between IMT and age of patients, nocturnal systolic blood pressure (SBP), nocturnal systolic pressure (SP) load, nocturnal SBP decline and presence of atherosclerotic plaques. The plaques positively correlated with age and with ambulatory blood pressure monitoring (ABPM) parameters. Fifty percent of SLE women had an abnormal 24-hour BP profile, of which 4 had non-dipper, 8 invers, and 4 hyper-dipper profile. Based on ABPM, hypertension can be diagnosed in 14 (43.75%) initially normotensive women. Women with SLE and arterial hypertension (HA) had atherosclerotic plaques significantly more often, especially in nocturnal hypertension. Conclusions: The authors confirm the underestimation of hypertension in SLE. Most women diagnosed with hypertension by ABPM had nocturnal hypertension. We showed a more frequent disturbed BP and a significant relationship between the abnormal BP profile, especially nocturnal hypertension, and accelerated development of atherosclerosis.

The Role of Angiogenesis Factors in the Formation of Vascular Changes in Scleroderma by Assessment of the Concentrations of VEGF and sVEGFR2 in Blood Serum and Tear Fluid.

Systemic sclerosis (SSc) is a connective tissue disorder characterized by tissue hypoxia, excessive fibrosis of skin and internal organs, and angiogenesis imbalance. The aim of the study was to evaluate in SSc patients the association between the retinal microcirculation disturbances and the presence of peripheral trophic changes and to determine the role of angiogenesis factors in the formation of vascular changes in scleroderma. Twenty-five SSc patients and 25 age- and sex-matched healthy controls were included to the study. Assay of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-2 (sVEGFR-2) in blood serum and tears was done for all patients and controls using enzyme-linked immunosorbent assay. Retinal blood circulation was investigated with fluorescein angiography (FA) in the SSc patients only. In our research, proportion of mainly hypertensive patients presenting with a large spectrum of retinal microvascular lesions was 72%, while proportion of patients with skin microvascular lesions within distal phalanxes of fingers and toes was 76%. We noticed that patients with pathological changes in the FA examination had finger ulcerations significantly more often than patients without changes in the eye fundus. There were no statistically significant differences in the serum concentration of VEGF and sVEGFR2 between subjects in both analyzed groups. Analysis of lower levels of VEGF (p = <0.001) and sVEGFR-2 (p = <0.001) in blood serum accompanied by simultaneous higher levels of VEGF/sVEGFR-2 ratio in tears of SSc patients, as compared with the control group, indicates the superiority of proangiogenic factors in patients' tears.

The influence of tumour necrosis factor α inhibitors treatment - etanercept on serum concentration of biomarkers of inflammation and cartilage turnover in psoriatic arthritis patients.

INTRODUCTION: Effective treatment in psoriatic arthritis (PsA) patients can protect them from severe musculoskeletal complications. For appropriate monitoring of anti-tumour necrosis factor α (anti-TNF-α) treatment in PsA, specific biomarkers are needed. AIM: To investigate whether biological treatment with anti-TNF-α (etanercept 50 mg once a week subcutaneously) affects the activity of selected mediators of inflammation and destruction of articular cartilage: interleukin-6 (IL-6), interleukin-18 (IL-18), matrix metalloproteinases 1 and 3 (MMP-1, MMP-3), cartilage oligomeric matrix protein (COMP), human cartilage glycoprotein (YKL-40) in serum of patients with PsA. MATERIAL AND METHODS: The study included 25 patients with PsA. The concentration of IL-6, IL-18, MMP-1, MMP-3, COMP and YKL-40 in serum was determined before, and 6 and 12 weeks after the beginning of anti-TNF-α treatment. Clinical severity of the disease according to the Body Surface Area, Psoriasis Area and Severity Index and Dermatology Life Quality Index as well as tender and swollen joint count (TJC, SJC) were also evaluated. RESULTS: The study disclosed a statistically significant reduction in the serum concentration of IL-6, MMP-1 and YKL-40 in PsA patients after 6 and 12 weeks from the beginning of anti-TNF-α treatment (p = 0.00018 for IL-6; p = 0.01242 for MMP-1; p = 0.03263 for YKL-40). CONCLUSIONS: IL-6, MMP-1 and YKL-40 may be useful for monitoring the effectiveness of anti-TNF-α treatment.

Interleukin-18, interleukin-20, and matrix metalloproteinases (MMP-1, MMP-3) as markers of psoriatic arthritis disease severity and their correlations with biomarkers of inflammation and turnover of joint cartilage.

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic, seronegative spondyloarthropathy characterised by joint inflammation and psoriatic skin changes. Recent data indicate that interleukin-18 (IL-18) and interleukin-20 (IL-20) may be involved in the aetiopathogenesis of PsA. AIM: To evaluate the potential role of IL-18, IL-20, and matrix metalloproteinases (MMP-1, MMP-3) in the pathogenesis of PsA and their correlations with other markers of inflammation and destruction of joint cartilage, as well as clinical changes. MATERIAL AND METHODS: The study included 24 patients with PsA and 26 healthy volunteers as a control group. The concentration of IL-18 and IL-20, c-reactive protein (CRP), metalloproteinase-1 and -3 (MMP-1, MMP-3), cartilage oligomeric matrix protein (COMP), aggrecan (PG-AG), and human cartilage glycoprotein (YKL-40) in serum was determined. Clinical severity of the disease according to the BSA, PASI, and DLQI as well as tender and swollen joint count (TJC, SJC) were also evaluated. RESULTS: The concentration of IL-18 was statistically significantly higher in the serum of patients with PsA than in the control group (62.87 pg/ml vs. 16.73 pg/ml, p < 0.0049). Serum IL-20 levels in PsA patients were also higher than in the control group, but without statistical significance (p = 0.2939). The ROC curves showed: AUC = 0.81 for IL-18, AUC = 0.75 for IL-20, AUC = 0.96 for COMP, and AUC = 0.89 for MMP-3. CONCLUSIONS: IL-18 and IL-20 as well as MMP-3 and COMP may be sensitive markers in the diagnosis of PsA.

Abnormalities of heart rate turbulence and heart rate variability as indicators of increased cardiovascular risk in patients with systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a connective tissue disease manifested by progressive fibrosis of many internal organs including the cardiovascular system and development of autonomic disorders with sympathetic predominance. These abnormalities can increase cardiovascular mortality. AIM: To evaluate heart rate turbulence (HRT) and variability (HRV) parameters (indicator of autonomic imbalance) obtained from 24-hour ECG Holter monitoring, as predictors of the increased cardiovascular risk in patients with scleroderma. MATERIAL AND METHODS: Thirty-twoscleroderma patients and 30 healthy people were included. After clinical examination, ECG, routine laboratory tests and echocardiography, participants performed 24-hour Holter-ECG at home. For HRT assessment, turbulence onset (To) and turbulence slope (Ts) parameters were used. Both time and frequency domain analysis of HRV was used. The HRV circadian rhythm was also evaluated. RESULTS: Time domain: SDNN, SDNN-ix, SDANN and frequency domain: LF, VLF, ULF, NHF, NLF, parameters were lower, while p50NN was higher in SSc as compared to the control group. There was also a loss of the circadian rhythm for r-MSSD and p50NN present in the control group. Abnormal HRT parameters To and/or Ts occurred in the SSc group only. The median value of To = -1.24% and Ts = 11.13 ms/RR did not differ significantly as compared to the control group. CONCLUSIONS: The study confirmed the presence of HRV disturbances, including HRV circadian rhythm, as it may seem at an early stage of SSc. The HRT disorders may be characterized by the increasing changes with advancing disease. This indicates the presence of autonomic imbalance and an increased cardiovascular risk.

Correlation between IL36α and IL17 and Activity of the Disease in Selected Autoimmune Blistering Diseases.

Dermatitis herpetiformis (DH), bullous pemphigoid (BP), and pemphigus vulgaris (PV) are autoimmune bullous skin conditions with eosinophilic and neutrophilic infiltrations. While cytokines are crucial for the affinity and activation of different leukocyte cells in the inflammation and blister formation, there are no studies concerning a role of IL-36. The goal of the study was to analyze whether interleukin 36 is involved in pathogenesis of DH, BP, and PV. And the second aim of the study was the estimation of correlation between Il-36 and IL-17 and titers of specific antibodies in these diseases. Expression of IL-36 and IL-17 was detected in serum in all DH, BP, and PV samples. Serum levels of IL-36 and IL-17α were statistically higher in DH, BP, and PV groups as compared to the control group. IL-36α levels were statistically higher in DH patients, as compared to patients with PV and BP. Our results showed that IL-36 may be helpful in the diagnostic and monitoring of the activity of the disease. IL 36 may play a relevant role of enrolling eosinophils and neutrophils in DH, BP, and PV and finally provoke tissue injury.

ABCB1-Gen-Polymorphismus in einer polnischen Kohorte ist mit Risiko für bullöses Pemphigoid assoziiert.

HINTERGRUND UND ZIELE: Polymorphismen im ABCB1-Gen, das für das P-Glykoprotein kodiert, können die intrazelluläre Konzentration von Xenobiotika beeinflussen und so zur Entwicklung von Autoimmunerkrankungen, einschließlich des bullösen Pemphigoids (BP), beitragen. In der vorliegenden Studie sollte untersucht werden, ob in einer polnischen Kohorte die C3435T- und G2677T/A-Polymorphismen im ABCB1-Gen mit dem Risiko für ein BP assoziiert sind. PATIENTEN UND METHODIK: Die Studie umfasste 71 Patienten mit BP und 156 gesunde Probanden. Der C3435T-Polymorphismus wurde mittels PCR-RFLP bestimmt und der G2677T/A-Polymorphismus mittels Allel-spezifischer PCR. ERGEBNISSE: Es gab zwar keine Korrelation zwischen dem C3435-Polymorphismus und dem BP-Risiko, aber wir konnten eine derartige Assoziation hinsichtlich des G2677T/A-Polymorphismus nachweisen. Das relative Risiko eines BP war bei Personen mit dem 2677TA-Genotyp um mehr als den Faktor fünf erhöht (OR = 5,52; p = 0,0063) und bei Trägern des 2677TT-Genotyps mehr als verdoppelt (OR = 2,40; p = 0,0076). Mit 2,40 (p = 0,000018) war die OR bei Trägern des 2677T-Allels ebenfalls erhöht. Die höhere Prävalenz des 2677GG-Genotyps und des 2677G-Allels bei der Kontrollgruppe sowie eine OR < 1,0 (0,22 beziehungsweise 0,33) legen eine Schutzfunktion des 2677G-Allels hinsichtlich der Ausbildung eines BP nahe. SCHLUSSFOLGERUNGEN: Die Ergebnisse der vorliegenden Studie zeigen, dass der G2677T/A-Polymorphismus im ABCB1-Gen das Risiko für die Entstehung eines BP beeinflussen könnte.

ABCB1 gene is associated with the risk of bullous pemphigoid in a polish population.

BACKGROUND AND OBJECTIVES: Polymorphisms in the P-glycoprotein-encoding ABCB1 gene may affect the intracellular concentration of xenobiotics, and thus contribute to the development of autoimmune diseases, including bullous pemphigoid (BP). The objective of the present study was to investigate whether there is an association between the C3435T and G2677T/A polymorphisms in the ABCB1 gene and the risk of BP in a Polish population. PATIENTS AND METHODS: The study included 71 patients with BP and 156 healthy volunteers. Determination of the C3435T polymorphism was carried out using PCR-RFLP; the G2677T/A polymorphism, using allele-specific PCR. RESULTS: While there was no correlation between the C3435T polymorphism and the risk of BP, we did find such an association with respect to the G2677T/A polymorphism. The relative risk of BP was more than five times greater in individuals with the 2677TA genotype (OR = 5.52, p = 0.0063), and more than twice as high in carriers of the 2677TT genotype (OR = 2.40, p = 0.0076). At 2.40 (0.000018), the OR in carriers of the 2677T allele was also increased. The greater prevalence of the 2677GG genotype and the 2677G allele in the control group, as well as the OR < 1.0 (0.22 and 0.33, respectively), suggest a protective role of the 2677G allele with respect to the development of BP. CONCLUSIONS: The results of the present study indicate that the G2677T/A polymorphism in the ABCB1 gene may affect the risk of developing BP.

Tissue Factor in Dermatitis Herpetiformis and Bullous Pemphigoid: Link between Immune and Coagulation System in Subepidermal Autoimmune Bullous Diseases.

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although chemokines are critical for the selective accumulation and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning inflammatory cells and production of coagulation factors in blistering diseases. Skin biopsies were taken from 14 patients with DH, 27 with BP, and 20 control subjects. The localization and expression of tissue factor (TF) in skin lesions and perilesional skin were studied by immunohistochemistry and confirmed by Western Blot. Moreover the plasma concentrations of TF were measured by immunoassays. D dimers, fibrinogen, and selected coagulation parameters were measured by routine methods. Expression of TF in the epidermis and in inflammatory influxed cells in dermis was detected in skin biopsies from BP patients. Examined TF expression was detected in perilesional skin of all BP patients too. The expression of TF was not observed in biopsies from healthy people and DH patients. The findings of the study show an increased expression of tissue factor in the lesional and perilesional skin of patients with bullous pemphigoid. The difference in chemokine pattern expression and variations in the cellular infiltration in BP and DH cause variable expression of TF.

Mediators of mast cells in bullous pemphigoid and dermatitis herpetiformis.

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are skin diseases associated with inflammation. However, few findings exist concerning the role of mast cells in autoimmune blistering disease. Skin biopsies were taken from 27 BP and 14 DH patients, as well as 20 healthy individuals. Immunohistochemistry was used to identify the localization and mast cell expression of TNFα and MMP9 in skin lesions and perilesional skin. The serum concentrations of TNFα, MMP9, chymase, tryptase, PAF, and IL-4 were measured by immunoassay. TNFα and MMP9 expression in the epidermis and in inflammatory influxed cells in the dermis was detected in skin biopsies from patients. Although these mediators were found to be expressed in the perilesional skin of all patients, the level was much lower than that in lesional skin. Increased serum PAF levels were observed in BP patients. Mast cells may play an essential role in activating inflammation, which ultimately contributes to the tissue damage observed in BP and DH. Our findings suggest that differences in the pattern of cytokine expression directly contribute to variations in cellular infiltration in DH and BP.

Assessment of skin microcirculation by laser Doppler flowmetry in systemic sclerosis patients.

INTRODUCTION: First lesions to occur in the course of systemic sclerosis (SSc) involve microcirculation. AIM: The study involved assessment of the suitability of laser Doppler flowmetry (LDF) in examination of the performance of skin microcirculation in the distal portion of the upper extremity in SSc patients. MATERIAL AND METHODS: Overall the study involved 27 patients with systemic sclerosis. The control group comprised age - and gender-matched 27 healthy individuals. All the study subjects underwent microcirculation perfusion measurement at rest (rest flow - RF) as well as microcirculatory flow challenge tests - reactive hyperaemia test (RHT) and thermal stimulation test (TST). RESULTS: The study did not show any differences in the skin microcirculation perfusion at rest between the test group and the control, while reactive hyperaemia test results revealed significantly lower skin microcirculation perfusion values during the cuff inflation in SSc patients, as compared to the controls. In the test group, a lower perfusion value was observed during secondary hyperaemia following cuff release. Comparative analysis of skin microcirculation perfusion changes during the thermal stimulation test revealed a significantly lower change of the perfusion value and longer time of return to the baseline in the test group as compared to the control group. CONCLUSIONS: The study performed has shown the suitability of LDF in the assessment of the microangiopathy degree in systemic sclerosis patients. The skin perfusion value in SSc patients should be assessed on the basis of parameters obtained in microcirculation challenge tests.

IL-17 expression in dermatitis herpetiformis and bullous pemphigoid.

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although cytokines are critical for the inflammatory process, there are single findings concerning concentration of IL-17 in bullous diseases. The goal of this study was to assess IL-17 expression in DH and BP patients. Skin biopsies were taken from 10 DH, 14 BP patients and from 10 healthy subjects. The localization and expression of IL-17 was studied by immunohistochemistry and the serum concentration was measured by immunoassays. Expression of IL-17 in the epidermis and in influxed cells in dermis was detected in skin biopsies. Expression of IL-17 was statistically higher in epidermis and infiltration cells in specimens from BP than from DH patients. Examined interleukin expression was detected in perilesional skin of all patients but it was much lower than in lesional skin. The expression of IL-17 was not observed in biopsies from healthy people. Serum level of IL-17 was statistically higher in BP and DH groups as compared to control group. Our results provide the evidence that IL-17 may play an essential role in activating and recruiting eosinophils and neutrophils, which ultimately contribute to the tissue damage in DH and BP.

[Increased level of lipid peroxidation products and disturbances in oxidation-reduction balance in erythrocytes from patients suffering from systemic sclerosis, who are chronically treated with vitamin E]. / Zwiekszone stezenie produktów peroksydacji lipidów oraz zaburzenia aktywnosci enzymów antyoksydacyjnych w erytrocytach u chorych na twardzine ukladowa, przewlekle leczonych witamina E.

UNLABELLED: Systemic sclerosis is a chronic connective tissue disease of unknown pathogenesis. In view of the reports of essential role of oxidative stress in development of disease, trials with supportive care with vitamin E are undertaken. The aim of the study was to estimate parameters of oxidation-reduction balance in erythrocytes from scleroderma patients, who were chronically treated with vitamin E compared with healthy controls. MATERIAL AND METHODS: In the study there were included 14 women with systemic sclerosis (limited form - ISSc - n = 10, diffuse form - dSsc - n = 4, age 53.8 lat +/- 11.5), who were treated with vitamin E in dose 400 mg/day not shorter than in 6 months period and 23 healthy women (age 52.7 +/- 11.2) as a control group. The following measurements were done: hs CRP (immunoturbidimetic method), glutathione peroxidase activity (Gpx--method of Rice-Evans, 1991), superoxide dismutase activity (SOD--method of Misra, 1972), catalase activity (CAT--method of Aebi H, 1984), free thiol group concentration (SH--method of ElIman, 1959), level of lipid peroxidation products (TBARs--method of Stocks and Dormandy, 1971), total antioxidant capacity (TAC) depended of slow (TAC "slow") and fast (TAC "fast") antioxidants. RESULTS: . In both forms of systemic sclerosis significantly higher TBARs in comparison of healthy controls (5.81 +/- 1.57 vs 4.28 +/- 0.89 nM TBARS/gHb; p < 0.01) was observed. Patients with limited systemic sclerosis have significantly higher activity of Gpx (59.9 +/- 26.11 vs 32.19 +/- 11.67 U/mg Hb; p < 0.01), and no differences in activity of CAT and SOD. In patients with diffuse systemic sclerosis significantly lower activity of CAT (173.06 +/- 60.3 vs 284.47 +/- 43.33 U/mg Hb; p < 0.01) and SOD (2334.95 +/- 193.97 vs 3231.47 +/- 840.21 U/mg Hb; p < 0.05) was observed. There are no differences in TAC and SH between investigated groups. CONCLUSIONS: In scleroderma patients despite chronical treatment with vitamin E, oxidation-reduction balance disturbances are observed in the form of increased level of lipid peroxidation products. Besides, a lower activity of catalase and superoxide dysmutase in patients who suffer from diffuse form of systemic sclerosis is noted. Patients with limited systemic sclerosis have higher glutathione peroxidase activity.

Genetic polymorphisms of CYP2D6 oxidation in patients with autoimmune bullous diseases.

INTRODUCTION: Bullous skin diseases, which include, among others pemphigoid, pemphigus, and dermatitis herpetiformis are classified as severe autoimmune dermatoses. It has been shown that a pattern of xenobiotic metabolism may play a role in the pathogenesis of autoimmune diseases. AIM: To estimate whether the CYP2D6 genotype may be considered a predisposing factor in autoimmune bullous diseases induction. MATERIAL AND METHODS: The study included 72 patients with autoimmune bullous diseases: 37 with pemphigoid, 21 with pemphigus, and 14 with dermatitis herpetiformis (DH). The CYP2D6 genotypes were analyzed by the polymerase chain reaction fragment length polymorphism (PCR-RFLP) method. RESULTS: Relative risk of DH development for particular genotype carriers expressed by odds ratio (OR) was statistically significantly higher for subjects with CYP2D6*1/CYP2D6*4 (OR = 4.2; p = 0.0104) and 2-fold higher for subjects with CYP2D6*4 (OR = 2.3; p = 0.0351). CONCLUSIONS: The results of the present study show that the CYP2D6 oxidation polymorphism cannot be considered a risk factor for development of pemphigoid and pemphigus, however it might have an impact on dermatitis herpetiformis.

Expression of selected neuropeptides in pathogenesis of bullous pemphigoid and dermatitis herpetiformis.

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are chronic subepidermal bullous diseases, which progress together with an itch and an inflammatory reaction. These symptoms may be the cause of a phenomenon described in the literature as a neurogenic skin inflammation. Neuropeptides are one of the mediators which take part in this process. The aim of our study was to indicate the expression of selected neuropeptides - CRF (corticotropin releasing factor), CGRP (calcitonin gene-related peptide), NKB (neurokinin B), SP (substance P) and the receptor for endothelin B (ETRB) - in the skin of patients suffering from BP or DH. A significantly increased expression of CRF was found in the specimen collected from the skin lesions of patients with BP and DH as well as a significantly increased expression of receptor for endothelin B in the patients with DH by the immunohistochemical method. The results obtained give evidence of a possible participation of CRF and receptor for endothelin B in the pathogenesis of the itch in the dermatitis herpetiformis as well as CRF in bullous pemphigoid.

Hearing organ disorders in patients with systemic sclerosis.

In systemic sclerosis (SSc), there may develop hearing and balance disorders as a result of the immune-mediated vasculitis and fibrosis in the inner ear. The objective of the study was evaluation of the hearing organ function in patients with SSc with relationship to duration of the disease and Raynaud phenomenon and also to type and severity of the disease. Twenty unselected, consecutive patients with SSc diagnosed in compliance with the international diagnostic criteria of the American Rheumatism Association (1982), were enrolled into the study. The control group consisted of 26 otologically healthy persons matched to the SSc group for age and sex. Case history was recorded for all patients from questionnaire data. Otolaryngological examination and battery of audiological tests (pure tone audiometry, speech audiometry, impedance audiometry and auditory brainstem response-ABR) were performed. In the anamnesis 60% of patients reported vertigo, 55% headaches, 50% tinnitus, 40% hyperacusis, 40% hearing loss and 30% ear fullness. It was found that patients with SSc had significantly poorer mean hearing thresholds than the control group for 0.5, 1, 6 and 8 kHz. In ABR there were no differences between SSc and control groups although an increase of latency averages in the group of limited patients with SSc compared with the diffuse patients with SSc was observed. In eight patients (40%) sensorineural hearing loss, mostly bilateral and symmetrical was found. Furthermore, no relation was seen between hearing level and duration, type and severity of the disease. Ear involvement is frequent in systemic sclerosis and should be taken into consideration during diagnostic and therapeutic procedures.

[Vestibular system in patients with systemic sclerosis]. / Stan ukladu przedsionkowego u pacjentów z twardzina ukladowa.

OBJECTIVES: In systemic sclerosis (SSc) there may occur hearing and balance disorders as a result of the immune-mediated inner ear damage, the etiology being vasculitis and fibrosis. The objective is the vestibular organ evaluation in patients with SSc regarding their prevalence and relationship to duration of the disease and Raynaud phenomenon and also to type and severity of SSc. MATERIAL: Twenty unselected, consecutive patients with diagnosed SSc, complying with international diagnostic criteria of the American Rheumatism Association (1982), were enrolled into the study. The control group consisted of 26 otologically healthy persons matched to the SSc group for age and sex. METHODS: In all patients the questionnaire about audiovestibular history, otolaryngological examination, static and dynamic vestibular tests and the electronystsgmography (ENG) were performed. The patients were investigated with the electronystsgmography (ENG) for spontaneous, positional and caloric-induced nystagmus. Also visual ocular-motor tests were performer. RESULTS: In the anamnesis 65% of patients reported vertigo, 55% - headaches, 50% - tinnitus, 40% - hyperacusis, 40% - hearing loss and 30% - ear fullness. Vertigo, dizziness balance disturbance and uncorrect results of Romberg and Utenberger tests were more frequent in patients with vestibular organ lesion. Abnormalities in vestibular organ in SSc patients were fund in 14 (70%) persons - the central type of lesion - 8 (40%), mixed type in 3 (15%) and peripheral in 3 (15%). CONCLUSIONS: Ear involvement is frequent in systemic sclerosis and should be taken into consideration during diagnostic and therapeutic procedures.

Expression of selected adhesion molecules in dermatitis herpetiformis and bullous pemphigoid.

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are autoimmune diseases characterized by destruction of the basement membrane zone (BMZ) and anchoring fibres by autoantibodies and infiltration. Adhesion molecules can take part in these phenomena. Skin biopsies were taken from 13 patients with DH, 21 with BP, and from 10 healthy subjects. The localization and expression of E and L selectins and beta1, beta3, beta4 integrins were studied by immunohistochemistry. Expression of selectins was detected mainly in the skin leukocytes in all samples. Expression of beta1, beta3 integrins was detected mainly in basal keratinocytes. Expression of beta 4 integrin was irregular and detected mainly in the blister. Our results suggest that integrins and selectins may play an important role in the destruction of BMZ in DH and BP. The elucidation of the role of adhesion molecules in the pathogenesis of bullous diseases may be helpful in the development of new targeted therapies.

[Systemic sclerosis and scleroderma circumscripta--disturbances of selected serum parameters which are responsible for vascular changes and CD34 expression in involved skin]. / Twardzina ukladowa i ograniczona do skóry--zaburzenia w stezeniu wybranych czynników w surowicy odpowiedzialnych za zmiany naczyniowe i ekspresja CD34 w chorobowo zmienionej skórze.

Scleroderma is a connective tissue disease characterized by fibrosis confined only to skin (scleroderma circumscripta, morphea) or to skin and internal organs (systemic sclerosis, SSc) as a result of vascular changes, immune dysfunction and increased production of collagen and other extracellular matrix (ECM) components. Both types of scleroderma present clinical and histological similarities in skin changes but their pathogenic relationship is still not elucited. The aim of our study was to evaluate vascular changes in both types of scleroderma on the basis of: serum levels of gelatinases--MMP-2 and MMP-9, vascular endothelial growth factor (VEGF) and its soluble receptor 2 (sVEGFR2) and expression of CD34 antigen in skin changed samples. The following patients were involved in the study: 34 patients with SSc, 31 with morphea and 15 healthy controls. Serum levels of selected parameters were estimated by ELISA method; whereas CD34 antigen immunoexpression was performed by immunohistochemistry. Serum level of MMP-9 was statistically significantly higher in SSc and morphea patients compared to the control group (848.6 ng/ml; 844.4 ng/ml vs. 535.9 ng/ml; p<0.05). Statistical analysis revealed that mean serum levels of MMP-2 was significantly (p<0.05) higher in SSc group compared to morphea and control group (240.4 ng/ml vs. 208.1 ng/ml; 211.9 ng/ml) and VEGF was higher in morphea group compared to the control group (422.2 pg/ml vs. 188.7 pg/ml). Statistically significant difference between ratio VEGF/sVEGFR2 of mean serum levels in SSc patients and the control group (0.038 pg/ml vs. 0.018 pg/ml) and positive correlation between serum levels of MMP-9 and sVEGFR2 only in control group (r=0.143) were obtained. Possitive CD34 expression was found in vascular endothelial cells cytoplasm. Mean value of immunoexpression of CD34 was statistically significantly higher in the control group (2.8 +/- 0.42) compared to SSc group (1.59 +/- 0.69) and morphea (1.42 +/- 0.50) (p<0.001). There was no statistically significant difference between immunoexpression of CD34 in skin samples of both types of scleroderma (p=0.27). The obtained results seem to confirm pathogenic similarities in endothelial cells disturbances in both types of scleroderma--SSc and morphea.