Management of congenital ichthyoses: European guidelines of care, part one.

These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016 and a consensus on the discussions. They summarize evidence and expert-based recommendations and are intended to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part one, covering topical therapies, systemic therapies, psychosocial management, communicating the diagnosis and genetic counselling.

Management of congenital ichthyoses: European guidelines of care, part two.

These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert-based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis.

Subcortical gray matter atrophy is associated with cognitive deficit in multiple sclerosis but not in systemic lupus erythematosus patients.

Cognitive impairment is a significant clinical problem both in multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients. In MS cognitive dysfunction has been associated with brain atrophy and total demyelinating lesion volume. In SLE cognitive impairment is much less understood, and its link to structural brain damage remains to be established. The aim of this study was to identify the relationship between subcortical gray matter volume and cognitive impairment in MS and SLE. We recruited 37 MS and 38 SLE patients matched by age, disease duration and educational level. Patients underwent magnetic resonance imaging (MRI) and a battery of psychometric tests. Severity of cognitive impairment was similar in both cohorts despite larger white matter lesion load in MS patients. Psychometric scores were associated with global and subcortical gray matter atrophy measures and lesion load in MS, but not in SLE. In SLE, the lack of a relationship between cognitive impairment and structural damage, defined either as atrophy or white matter lesions, indicates a different causal mechanism of cognitive deficit.

Distinct regional brain atrophy pattern in multiple sclerosis and neuropsychiatric systemic lupus erythematosus patients.

Differentiation of systemic lupus erythematosus (SLE) from multiple sclerosis (MS) can be challenging, especially when neuropsychiatric (NP) symptoms are accompanied by white matter lesions in the brain. Given the lack of discriminative power of currently applied tools for their differentiation, there is an unmet need for other measures that can aid in distinguishing between the two autoimmune disorders. In this study we aimed at exploring whether brain atrophy measures could serve as markers differentiating MS and SLE. Thirty-seven relapsing-remitting MS and 38 SLE patients with nervous system manifestations, matched according to age and disease duration, underwent 1.5 Tesla magnetic resonance imaging (MRI), including volumetric sequences, and clinical assessment. Voxelwise analysis was performed using ANTS-SyN elastic registration protocol, FSL Randomise and Gamma methods. Cortical and subcortical segmentation was performed with Freesurfer 5.3 pipeline using T1-weighted MPRAGE sequence data. Using MRI volumetric markers of general and subcortical gray matter atrophy and clinical variables, we built a stepwise multivariable logistic diagnostic model to identify MRI parameters that best differentiate MS and SLE patients. We found that the best volumetric predictors to distinguish them were: fourth ventricle volume (sensitivity 0.86, specificity 0.57, area under the curve, AUC 0.77), posterior corpus callosum (sensitivity 0.81, specificity 0.57, AUC 0.68), and third ventricle to thalamus ratio (sensitivity 0.42, specificity 0.84, AUC 0.65). The same classifiers were identified in a subgroup analysis that included patients with a short disease duration. In MS brain atrophy and lesion load correlated with clinical disability, while in SLE age was the main determinant of brain volume. This study proposes new imaging parameters for differential diagnosis of MS and SLE with central nervous system involvement. We show there is a different pattern of atrophy in MS and SLE, and the key structural volumes that are differentially affected include fourth ventricle and posterior section of corpus callosum, followed by third ventricle to thalamus ratio. Different correlation patterns between volumetric and clinical data may suggest that while in MS atrophy is driven mainly by disease activity, in SLE it is mostly associated with age. However, these results need further replication in a larger cohort.

Psoriasis and metabolic syndrome in children: current data.

BACKGROUND: The prevalence of cardiovascular and metabolic disorders in paediatric patients with psoriasis is not well established. AIM: To conduct a meta-analysis of previously published studies dealing with the occurrence of metabolic disorders in children with psoriasis. METHODS: Data from 7 studies with a total of 965 children with psoriasis were analysed using a random effects model. RESULTS: Prevalence of metabolic syndrome (MetS) was significantly higher in patients with psoriasis than in healthy controls (HCs). In most studies, significantly decreased levels of high-density lipoprotein (HDL) cholesterol were found in children with psoriasis. Mean level of HDL cholesterol in patients with psoriasis was 2.05 mg/dL lower than in HCs. Patients with psoriasis and HCs did not differ significantly in their mean triglyceride levels, although the difference was at a threshold of statistical significance. Mean level of fasting glucose in children with psoriasis was 5.75 mg/dL higher than in HCs (P < 0.01). The two groups did not differ significantly in mean waist circumference or in systolic and diastolic arterial pressures. CONCLUSIONS: Decreased levels of HDL cholesterol and increased concentrations of fasting glucose may represent very early stages of MetS in children with psoriasis. However, a large population-based study is needed to establish the relationship between psoriasis and MetS in children, including the environmental, genetic and immunological factors leading to their co-occurrence.

Increased serum level of N-terminal Pro-B-type natriuretic peptide as a possible biomarker of cardiovascular risk in psoriatic patients.

BACKGROUND: Apparently, these days psoriasis is regarded as a systemic disease with frequent cardiovascular comorbidities, such as hypertension, myocardial infarction, valvular defects etc., which may lead to reduced lifespan or even sudden death. Therefore, it is important that biomarkers helpful in early detection or prediction of cardiovascular complications as well as their prevention should be identified. Even though the N-terminal pro B-type natriuretic peptide (NT-proBNP) is a well-known cardiovascular predictor in cardiovascular (CV) patients and in the general population, its usefulness in detection of CV comorbidities in psoriatic patients is still unclear. OBJECTIVE: The aim of the study was to determine whether the N-terminal pro B-type natriuretic peptide (NT-proBNP) concentration was increased in psoriatic patients. METHODS: The study included 73 psoriatic patients and 45 age-matched healthy individuals. The serum NT pro-BNP concentration as well as lipid profile parameters were assessed in the study and control groups. Correlations between patients' clinical data, their serum NT-proBNP and lipid concentrations were calculated. RESULTS: The serum concentration of NT-proBNP was significantly higher in psoriatic patients (109.22 ± 172.59 pg/mL) in comparison with controls (35.82 ± 22.90 pg/mL) (P = 0.000054). In 28 (38.36%) psoriatic patients the lipid profile was within normal limits, whereas in 45 (61.64%) psoriatic patients triglyceride and/or total cholesterol were increased. Moreover, in both psoriatic groups, i.e. normo- and hyperlipidaemic, NT-proBNP concentrations were significantly higher compared to normo- and hyperlipidaemic controls, P = 0.02 and P = 0.001 respectively. A positive correlation was found between the NT-proBNP concentration and duration of psoriasis (P < 0.05). CONCLUSIONS: The study findings confirmed higher NT-proBNP concentrations in psoriatic patients, which could be a useful biomarker of CV disease in both normo- and hyperlipidaemic groups.

Cardiovascular disease in psoriatic post-menopausal women.

BACKGROUND: It is generally accepted that the risk of cardiovascular disease (CVD) in women is significantly increased after the menopause. Hormonal changes associated with the menopausal transition may also alter the course of autoimmune diseases. It has been reported that menopause may exacerbate the symptoms of rheumatoid arthritis, systemic sclerosis and giant cell arteritis, but attenuate the course of systemic lupus erythemathosus. There is a growing body of literature indicating that the course of psoriasis may be altered by menopausal hormone changes. Considering the fact that both psoriasis and menopause are independent risk factors for CVD, and that menopause may exacerbate the course of psoriasis, a possible additive effect between these two conditions may be crucial for proper monitoring and treatment of peri- and post-menopausal psoriatic patients. OBJECTIVE: The aim of this study is to analyse potential relationship between psoriasis, menopausal status and risk of CVD. MATERIALS AND METHODS: A retrospective analysis of the Clalit Health Services database was performed in an attempt to provide new data and the available literature concerning these issues was reviewed. Data on cardiovascular events in 10 872 female psoriatic patients and 19 471 controls were extracted and compared. RESULTS: In both psoriatic and control patients the association of CVD increased with age. The association of CVD was significantly greater in psoriatic patients, but no significant differences were found between any of age groups. CONCLUSIONS: The association of psoriasis and CVD in women increases with age but there is insufficient evidence to confirm that menopause increases the risk of psoriasis. Further studies directly addressing this issue are needed.

Mast cells generate cysteinyl leukotrienes and interferon-beta as well as evince impaired IgE-dependent degranulation upon TLR7 engagement.

Mast cells are numerous at anatomical sites close to external environment, virtually at the portals of infection. A few data indicated that these cells express cytoplasmic Toll-like receptors (TLRs) recognizing virus-derived molecules. Accordingly, mast cells could participate in anti-viral defense or/and in viral-related diseases. However, data concerning the influence of viruses on mast cell activity are limited. Thus, the aim of our study was to determine mast cell response to TLR7 ligand, i.e. resiquimod (R848), a synthetic mimic of viral ssRNA. Since mast cells play a central role in allergic reactions the effect of TLR7 agonist was also investigated on FcepsilonRI-dependent mast cell response. Experiments were carried out in vitro on freshly isolated fully mature rat peritoneal mast cells. Mast cells exhibit constitutive TLR7 molecule expression and its up-regulation after the agonist challenge. TLR7-mediated mast cell stimulation resulted in cysteinyl leukotriene (cysLT) and interferon (IFN)-beta synthesis, whereas no histamine and CXCL8 secretion was stated. Moreover, mast cell priming with TLR7 ligand caused the reduction in anti-IgE-induced histamine release. The results suggest that ssRNA viruses could directly activate mast cells to alter their phenotype and to release of potent proinflammatory mediators or indirectly modulate IgE-dependent allergic processes.

[Metabolic syndrome in patients with psoriasis]. / Zespól metaboliczny w luszczycy.

Psoriasis is a chronic inflammatory disease of skin, nail plates and joints, which shares similarities with other chronic inflammatory diseases such as rheumatoid arthritis and atherosclerosis. Recent studies indicated that patients with psoriasis are at greater risk for cardiovascular co-morbidities and metabolic syndrome. Published data demonstrates that there is a correlation between the severity of skin changes, cardiovascular co-morbidities and features of metabolic syndrome. Recent research showed that psoriasis plaque shares striking histological features with atherosclerotic one. Both plaques have an elevated level of activated T helper 1 and T helper 17 cells. T helper 1 cells show an overproduction of proinflammatory cytokines such as: TNF-alpha, INF-gamma IL-6 which result in endothelial dysfunction. IL-17 produced by T helper 17 cells have been known to play an important role in the pathogenesis of psoriasis and trigger inflammation in various tissues and organs. In addition, elevated level of serum IL-17 have been observed in unstable coronary artery disease (CAD) as well as in acute myocardial infarction (MI). Physical activity was proved to play a protective role in prevalence of cardiovascular co-morbidities. Recent studies showed that increased physical activity in patients with psoriasis reduce inflammation and risk of cardiometabolic co-morbidities.

Effect of scaling and root planing on interleukin-1ß, interleukin-8 and MMP-8 levels in gingival crevicular fluid from chronic periodontitis patients.

BACKGROUND AND OBJECTIVE: There are few data concerning the effect of scaling and root planing on the levels of immune and inflammatory mediators in gingival crevicular fluid from patients with chronic periodontitis. Therefore, in this study the influence of scaling and root planing was determined on amounts of interleukin (IL)-1ß, IL-8 and MMP-8 in gingival crevicular fluid from patients with chronic periodontitis, in relation to clinical parameters. MATERIAL AND METHODS: A total of 51 patients were enrolled in this study. The study population consisted of 30 patients with generalized advanced chronic periodontitis, while 21 periodontally healthy subjects were recruited for the control group. The clinical parameters included approximal plaque index, gingival index, pocket depth and clinical attachment loss. The amounts of IL-1ß, IL-8 and MMP-8 in gingival crevicular fluid were measured by ELISA. Periodontal parameters as well as gingival crevicular fluid humoral factor amounts were evaluated in the control group and in chronic periodontitis patients at baseline and at 1 and 4 wk after scaling and root planing treatment. RESULTS: At baseline, there were significant differences between control subjects and chronic periodontitis patients in terms of clinical attachment loss, pocket depth, gingival index (p < 0.001) and approximal plaque index (p < 0.01). The amounts of IL-1ß, MMP-8 (p < 0.001) and IL-8 (p < 0.01) in gingival crevicular fluid were significantly lower in healthy subjects than in chronic periodontitis patients. Scaling and root planing led to improvement in all examined clinical parameters, apart from clinical attachment loss. Periodontal treatment also resulted in a significant decrease in the amounts of IL-1ß, IL-8 and MMP-8 in comparison to baseline, especially 4 wk after scaling and root planing (p < 0.001); however, the amounts of these humoral factors were still higher than those in control group. CONCLUSION: Our observations indicated that short-term nonsurgical therapy resulted in a significant improvement in periodontal indices and in a marked decrease of IL-1ß, IL-8 and MMP-8 gingival crevicular fluid levels. Nevertheless, no significant correlations were found between clinical parameters and amounts of humoral factors after therapy.

Psoriasis and unreported excessive alcohol intake--a simple screening approach.

Psoriasis is a chronic immune-mediated skin disease of complex aetiology. Alcohol overuse has long been suspected to contribute to psoriasis pathology, and the knowledge of individual's drinking pattern may be of substantial importance for managing the disease. Unfortunately, a number of patients fail to admit to their true alcohol consumption and there is no single sign, symptom or laboratory parameter adequate for alcohol abuse diagnosis. However, there are some laboratory findings that, when present, should raise physician's suspicion that alcohol may be a problem. The aim of this article was to present simple, widely available and relatively reliable laboratory markers that might effectively assist physicians in establishing patient's drinking status. A possible screening approach is illustrated by two distinct reports of psoriatic patients who initially concealed having the problem with alcohol.

Recurrent skin eruption in patient with chronic lymphocytic leukemia and lymphocytic infiltrates of the dermis resembling Sweet's syndrome.

Sweet's syndrome (acute febrile dermatosis) is characterized by fever, peripheral neutrophil leukocytosis, acute onset of tender erythematous skin lesions (papules, nodules or plaques), and histological findings of a dense infiltrate consisting predominantly of mature neutrophils. Malignancy-associated Sweet's syndrome constitutes approximately 21% of patients, the majority of whom suffer from hematologic disorder. We report the case of patient with chronic lymphocytic leukemia with recurrent eruptions of tender, pseudovesiculated nodules and plaques with good response to corticosteroid therapy, resembling Sweet's syndrome. However, histological examination revealed lymphocytic infiltrate in the dermis, which made impossible to establish diagnosis of acute febrile dermatosis according to diagnostic criteria. Association of the skin eruptions with leukemia was implied by improvement of skin lesions after chemotherapy. We present review of the literature reporting cases with atypical histopathological presentations which preceded classical histological appearances, that were mainly associated with hematological malignancies and discuss them in the context of our patient.

The action of tumor necrosis factor-alpha on rat mast cells.

Taking into account that cytokine tumor necrosis factor-alpha (TNF-alpha) and mast cells (MC) both are involved in inflammation, it seems of great importance to recognize their relationships. Therefore, we have studied whether recombinant human TNF-alpha (rHuTNF-alpha) can cause histamine secretion from rat peritoneal MC. We have also examined the effect of this cytokine on MC reactivity. We have established that TNF-alpha stimulates rat MC to histamine release in a concentration-dependent manner. TNF-alpha-induced histamine secretion was evoked by concentrations > 10-16 M and reached the maximum rate at a concentration of 10-10 M (histamine release 17.1% +/- 1.9%, mean +/- SEM). We have also noticed that pretreatment of MC with TNF-alpha (in a concentration of 10-16 M) significantly inhibited concanavalin A (ConA)-stimulated release of histamine, with the percent release decreasing to 51% of the control value. Treatment of mast cells with TNF-alpha resulted in a decrease of compound 48/80-dependent histamine release as well (the percent released histamine fell to 85% of the control value). This altered MC responsiveness was reversible. After 120 min of resting time, the MC reactivity came back to the initial values. We have concluded that TNF-alpha appears to be a direct stimulus for MC to release histamine, and it may regulate MC secretory function.

Tumor necrosis factor alpha (TNF-alpha) activates human adenoidal and cutaneous mast cells to histamine secretion.

It is widely known that mast cells and cytokine TNF-alpha are both involved in inflammatory reactions. Therefore, we have studied whether TNF-alpha can cause histamine secretion from human adenoidal and cutaneous mast cells. The experiments were performed in vitro on mast cells isolated from tissues by enzymatic dispersion technique. The results of our experiments have clearly shown that this cytokine stimulates mast cells to histamine release. TNF-alpha-induced histamine release was concentration- and time-dependent. Moreover, the release of histamine evoked by TNF-alpha was also dependent on reaction temperature and on glycolytic and oxidative cellular metabolism. We have concluded that TNF-alpha is a potent stimulus for mast cells to release histamine and that it induces histamine release via an active, secretory process.

Functional studies of skin mast cells in lichen planus.

In order to identify possible functional differences between mast cells obtained from the skin of lichen planus (LP) patients and healthy donors, biopsies from lesional skin of 11 lichen planus patients and from normal skin of 7 healthy donors were sampled. Mast cells were obtained from the skin using an enzymatic dispersion technique. The cells were challenged in vitro with substance P (SP), tumor necrosis factor alpha (TNF-alpha) and anti-IgE. Their reactivity was estimated on the basis of histamine release. LP skin mast cells and healthy skin mast cells showed similar sensitivity to stimulation with TNF-alpha at a concentration of 10(-7) M (15.2% histamine release, as a proportion of total cellular content vs 15.9%) and to stimulation with anti-IgE at a dilution of 1:100) (38.8% vs 37.0%). Spontaneous histamine release was also very similar in both the populations of mast cells (10.2% vs 12.7%, respectively). However, LP skin mast cells showed significantly higher (P < 0.01) sensitivity towards stimulation with SP at a concentration of 10(-4) M than healthy skin mast cells (15.9% histamine release vs 7.0%). This finding could suggest that neurogenic inflammatory mechanisms contribute to the pathogenesis of LP.

Anaphylactic histamine release from human gastric and duodenal mast cells.

Mast cells from human gastric and duodenal walls were isolated using a collagenase dispersion technique. The reactivity of both mast cell populations with anti-human IgE antibodies and specific antigens was tested in an in vitro model of anaphylactic reaction. Mast cell populations were sensitive to the action of anti-IgE, and histamine release was 17.4-27.4% (duodenal) and 19.3-29.3% (gastric mast cells). No significant differences between both mast cell populations of the same individuals were observed. Gastric and duodenal mast cells obtained from patients with peptic ulcer and positive intradermal test with allergens (grass pollen, tomato, cocoa) released histamine after challenge with adequate antigens. The reaction was dose-dependent. Gastric mast cells were more reactive than duodenal cells to challenge with antigen.

[Changes in various apolipoprotein levels in psoriasis]. / Zachowanie sie niektórych apolipoprotein w luszczycy.

In 104 patients with common psoriasis the patterns of apolipoproteins A and B were studied in serum depending on the course of the disease, extent of skin changes and infection preceding the appearance of eruptions. The highest concentrations of apo A and apo B were found in the group with generalized psoriatic changes independent of the activity of the disease.