Heart rate turbulence assessment in systemic sclerosis: the role for the detection of cardiac autonomic nervous system dysfunction.

OBJECTIVE: To assess the heart rate turbulence (HRT) in patients with SSc as a method of assessment for cardiac autonomic nervous function. METHODS: We prospectively studied 68 consecutive patients with SSc before inclusion in the study. After a detailed clinical evaluation, including echocardiography, 45 subjects [aged 54.6 (14.7) years; 40 women] underwent 24-h Holter monitoring for HRT and time- and frequency-domain heart rate variability (HRV) assessment. Results were compared with those in 30 age- and sex-matched healthy controls. RESULTS: As compared with controls, HRT was impaired in SSc patients: the median turbulence onset (TO) was higher (P = 0.0001) and the median turbulence slope (TS) was lower (P = 0.0003). Abnormal HRT (TO > or =0.0% and/or TS < or =2.5 ms/RR) was found in 42% of SSc patients. Moreover, SSc duration correlated negatively with values of TS (r = -0.3; P = 0.045). HRT did not differ between diffuse and limited SSc groups. All estimated time- and the majority of frequency-domain values of HRV parameters in SSc were significantly lower than in controls. Significant correlations were also demonstrated between HRT and HRV parameters. CONCLUSIONS: HRT, like HRV assessment, indicates a frequent impairment of the cardiac autonomic nervous system in SSc patients, irrespective of the SSc type.

Heart rate turbulence impairment and ventricular arrhythmias in patients with systemic sclerosis.

BACKGROUND: Arrhythmias, conduction disturbances, and cardiac autonomic nervous system dysfunction are the most frequent cardiovascular complications in systemic sclerosis (scleroderma). The aim of the study was to assess heart rate turbulence (HRT) in systemic sclerosis patients and to identify the relationship between HRT and occurrence of arrhythmias. METHODS: Forty-five patients with scleroderma (aged 54.6 +/- 14.7 years) and 30 healthy sex- and age-matched subjects were examined. In addition to routine studies, 24-hour Holter monitoring with assessment of HRT was performed. RESULTS: As compared to controls, HRT was significantly impaired in systemic sclerosis patients. Abnormal HRT defined as turbulence onset (TO) > or =0.0% and/or turbulence slope (TS) < or =2.5 ms/RR (ms/RR interval) was found in 19 (42%) scleroderma patients and in no members of the control group. Serious ventricular arrhythmias Lown class IV (VA-LownIV), for example, couplets and/or nonsustained ventricular tachycardias, were observed in 16 (36%) scleroderma patients. The median value of TS was significantly lower in systemic sclerosis patients with VA-LownIV than in patients without VA-LownIV (3.68 vs 7.00 ms/RR, P = 0.02). The area under curve of ROC analysis for prediction of VA-LownIV was 0.72 (95% confidence interval [CI] 0.56-0.87) and revealed that TS <9.0 ms/RR was associated with VA-Lown IV occurrence, with sensitivity of 93.7% and specificity of 44.8%. Univariate and multivariate analyses confirmed that lower values of TS were associated with VA-LownIV occurrence (odds ratio 1.52, 95% CI 1.09-2.12, P = 0.01). CONCLUSIONS: Patients with systemic sclerosis are characterized by significant HRT impairment. Assessment of HRT and especially TS is useful in the identification of patients at risk for ventricular arrhythmias.

Assessment of left and right ventricular diastolic function in patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease characterised by vascular changes and immunologically induced fibrosis of the skin and internal organs. Systemic sclerosis may be associated with both right (RV) and left ventricular (LV) diastolic dysfunction. AIM: To analyse RV and LV myocardial diastolic function in patients with SSc and its relation to exercise capacity. METHODS: We prospectively studied 51 consecutive patients (47 females, 4 males, age 53.3+/-15.2 years) with SSc (mean disease duration 9+/-12.4 years) and a group of 31 age-matched healthy subjects (28 females, 3 males, age 52.68+/-12.1 years). In addition to conventional investigation, transthoracic echocardiography (TTE) for assessment of RV and LV myocardial diastolic function and 6-minute walking test (6MWT) were performed. RESULTS: Abnormal LV filling, as expressed by an inverted mitral E/A ratio (Mit E/A <1), was detected in 28 (55%) SSc patients and in 8 (25%) controls (p <0.001). The mean value of Mit E/A in the SSc group was lower than in controls (1.0+/-0.3 vs. 1.2+/-0.3, p=0.04). There were no differences in pulmonary venous flow between SSc patients and controls. The mean value of Tei index for the LV was higher in SSc than in controls (0.44+/-0.08 vs. 0.38+/-0.05, p <0.001). Abnormal RV filling, as expressed by an inverted tricuspid E/A ratio (TR E/A <1), was detected in 16 (31%) SSc patients and in 5 (16%) controls (p <0.001). Patients with SSc were found to have an inverted Tr E/A ratio (Tr E/A <1), indicating abnormal RV filling. The mean value of Tr E/A in SSc was lower than in controls (1.0+/-0.2 vs. 1.2+/-0.3, p=0.04). The mean value of Tei index for the RV was higher in SSc patients than in controls (0.35+/-0.07 vs. 0.29+/-0.03, p <0.001). In multiple regression analysis Tr E/A ratio was independently correlated with Mit E/A ratio (r=0.65, p=0.01). The mean 6MWT distance was shorter in the SSc group than in controls (528+/-100.6 vs. 617.7+/-80 m, p <0.001) and the mean saturation of capillary blood after the 6-MWT was lower in SSc patients (92.7+/-4.9 vs. 97.2+/-1.2%, p <0.001). Mean desaturation after test and D sat was significantly more pronounced in the SSc group than in controls (3.4+/-3.1 vs. 0.7+/-0.9, p <0.001). The Tr E/A ratio and Mit E/A ratio correlated positively with 6MWT distance (r=0,49, p=0.01 and r=0.48, p=0.02). CONCLUSIONS: Impaired RV and LV relaxation is observed in a significant percentage of SSc patients and is associated with decreased exercise capacity.

[Allergic contact dermatitis]. / Wyprysk alergiczny.

Clinical definition of eczema is based on the presence of multiform erythematous, papular and vesicular lesions which are followed by marked desquamation. When the underlying mechanism is allergic, skin lesions are mediated by inflammatory Th1 lymphocytes recognizing hapten determinants, i.e. IVth allergic mechanism in allergic contact dermatitis. This mechanism is responsible also for allergy to bacterial proteins in nummular eczema, or to fungal and bacterial proteins, atopens and nickel in dyshidrotic eczema. Eczematous lesions can develop after damage to the skin barrier by toxic chemical or irritating substances, as non-allergic irritation eczema. These substances non-specifically stimulate the Langerhans cells and keratinocytes to produce numerous cytokines inducing expression of adhesion molecules on the endothelial cells. This is responsible for non-specific mobilization of Th1 cells to the skin. A model example is dermatitis induced by mercury salts and/or sodium lauryl sulfate. Intermediate position between allergic and non-allergic eczema is occupied by atopic dermatitis/eczema. In addition to classical IgE-dependent mechanism leading to degranulation of mast cells, there is generation of specific population of Th2 lymphocytes recognizing food and air-borne atopens. This reaction is responsible for skin inflammation in the late-phase response, in which allergic process started by Th2 cells switches to non-specific migration of Th1 cells attracted by cytokines released from eosinophils, keratinocytes and Th2 lymphocytes.

[Latent sources of contact allergy]. / Utajone zródla alergii kontaktowej.

In individuals sensitized to many contact allergens in the course of 4th immunological mechanism, in whom allergic contact dermatitis develops at the site of exposure to haptens, disseminated eczematous skin lesions might be provoked by latent source of hapten, which penetrates to the body omitting the skin. The most frequent clinical situations include: allergy to drugs, food additives, inhaled chemicals originated from plants, allergic reactions to metal endoprostheses used in orthopaedics and/or dentistry, and all conditions facilitating penetration of hapten directly to the blood through damaged skin (erosions, ulcers, etc.) and/or under occlusive dressings.

[Diagnostic, prophylactic and therapeutic guidelines in patients with atopic dermatitis. Position paper by the task force of the National Specialists on Dermatology, Venereology and Allergology]. / Postepowanie diagnostyczno-profilaktyczno-lecznicze w atopowym zapaleniu skóry. Konsensus grupy roboczej specjalistów krajowych ds. dermatologii i wenerologii oraz alergologii.

Treatment modalities of patients with atopic dermatitis (AD) are dependent on patient age, on the intensity of both skin symptoms and subjective signs of the disease i.e. itch and sleep disturbances, on the body surface involved with lesions, as well as on the type of sensitizing allergens. The characteristic of these allergens is crucial to start prophylaxis and to make decision about specific immunotherapy. In asymptomatic period of the disease the most important factor is to prevent dryness of the skin using emollients, which reconstruct integrity and continuity of stratum corneum. This procedure prevents penetration of air-borne allergens across damaged skin barrier into the skin. In mild AD cases, pimecrolimus (mainly in children) and corticosteroids of the lowest potency alternatively with their basis should be recommended. In moderate intensity AD either topical treatment with calcineurin inhibitors i.e. tacrolimus and pimecrolimus or topical corticosteroids from 4-5 group of American classification should be applied. In addition, PUVA/UVB phototherapy may be beneficial, as well as immunotherapy with specific airborne allergen/s. Coexisting bacterial skin infections should be treated with systemic antibiotics (macrolides, quinolones, and cephalosporins), viral herpes infection systemically using acyclovir for 5-7 days, and fungal infections applying ketoconazole orally, accompanied by topical treatment with miconazole or other antimycotics. Severe AD is an indication for the systemic use of cyclosporin A (rather than corticosteroids), and antibiotics as mentioned above. Prolonged 3-5 year specific immunotherapy is significant concern for selected cases. Sensitive skin areas such as face, orbicular skin, flexures should be treated with pimecrolimus and tacrolimus rather than with corticosteroids, however, topical corticosteroids are recommended on involved skin of the trunk and the extremities besides of flexures. While the improvement of severe AD is reached, the treatment modalities for benign and mild AD should be observed. In all AD patients with active skin lesions antihistaminic drugs of 2nd generation reactive with H1 receptor are a gold standard (or short treatment with these drugs of 1st generation to achieve a sedative effect, followed by the 2nd generation drug), as well as tranquilizers as the combined treatment. There is no reason for the use of anti-leukotriene drugs.

T-regulatory cells in severe atopic dermatitis: alterations related to cytokines and other lymphocyte subpopulations.

The changes in lymphocyte subpopulations in atopic dermatitis (AD) concern also T-regulatory cells. We investigated the expression of various surface receptors on CD3(+)CD4(+)CD25(high)FoxP3(+) T-regulatory cells and the activation CD28(+) receptor and the inhibitory CD152(+) receptor on helper/inducer as well as cytotoxic/suppressor T cells. Peripheral blood lymphocytes of 15 AD patients and 20 healthy subjects were analyzed by flow cytometry using monoclonal antibodies. The concentrations of IL-6, IL-10 and TGF-ß were determined in the serum and the supernatant of ConA-stimulated CD4(+) lymphocytes. In AD patients the percentage of CD4(+)CD25(high)FoxP3(+) as well as CD3(+)CD8(+) cells increased, which positively correlated with SCORAD index (r = 0.55, p = 0.03). The concentrations of IL-10 in the CD4(+) lymphocyte culture supernatants and the concentrations of TGF-ß in the sera and the supernatant negatively correlated with the severity of AD (p < 0.01, r = -0.63; p < 0.02, r = -0.64 and p < 0.03, r = -0.58, respectively), whereas the serum concentration of IL-6 correlated positively (p < 0.003, r = 0.71). The regulatory cells expressed more CD62L and CD134 surface markers but less CD95. Reduced expression of the apoptotic CD95 receptor suggests that survival time of these cells is prolonged. Since CD62L and CD134 were upregulated, the enhanced modulatory effect of CD4(+)CD25(high)FoxP3(+) cells seemed to be suggested, which may result in increased co-expression of CD28/CD152 on both CD4(+) and CD8(+) subpopulations.

Pulmonary hypertension in systemic sclerosis determines cardiac autonomic dysfunction assessed by heart rate turbulence.

There is limited data on heart rate turbulence (HRT) in systemic sclerosis (SSc) patients, potentially threatened with cardiac autonomic dysfunction. We performed 24-hour Holter monitoring for HRT assessment in 45 patients with SSc and 30 healthy controls. Abnormal HRT defined as turbulence onset (TO) >or=0.0% and/or turbulence slope (TS)