The causal relationship between blood metabolites and rosacea: A Mendelian randomization.

BACKGROUND: An increasing amount of research demonstrates that metabolic disorders are related to rosacea. However, the correlations and causal relationships among them remain unknown. METHODS: We conducted not only forward 2-sample MR (Mendelian randomization) analyses but also reverse MR analyses which showed positive results in the forward MR analysis. In the forward MR analyses, inverse-variance weighted (IVW) and MR-Egger were performed as MR analyses. Cochran's Q test and the MR-Egger Intercept were used for sensitivity analyses. Concerning reverse MR analyses, IVW, MR-Egger, weighted median, simple mode, and weighted mode were applied. Cochran's Q test, MR-Egger Intercept, and MR pleiotropy residual sum and outlier (MR-PRESSO) outlier test were applied as sensitivity analyses. RESULTS: A total of 24 metabolites and 1 metabolite ratio were shown to have a causal effect on rosacea. N-lactoyl phenylalanine (N-Lac-Phe) was estimated as statistically significant by Bonferroni correction. Interestingly, we found three metabolites that were negatively associated with rosacea, especially caffeine, which are in line with the results of a large cohort study of females. For reverse MR analysis, we revealed that rosacea could potentially decrease the generation of two metabolites: octadecenedioate (C18:1-DC) and methyl vanillate sulfate. CONCLUSION: This study identified blood metabolites that may be associated with the development of rosacea. However, the exact mechanism by which these positive metabolites influence rosacea remains uncertain due to the paucity of experimental investigations. The combination of genetics and metabolomics offers novel viewpoints on the research of underlying mechanisms of rosacea and has significant value in screening and prevention of rosacea.

Hematological parameters as diagnostic biomarkers for patients with rosacea.

Rosacea is a chronic inflammatory skin disease. Systemic inflammation plays a vital role in the pathogenesis of rosacea. Many studies have reported hematological parameters as biomarkers for diseases with inflammatory processes. However, the diagnostic value of hematological parameters in rosacea remains a puzzle. This study involved 462 patients with rosacea, including erythematotelangiectatic rosacea (ETR, n = 179), papulopustular rosacea (PPR, n = 250), and phymatous rosacea (PhR, n = 33), and 924 healthy control subjects. Demographic, clinical, and laboratory information was collected and compared between rosacea subtypes. The hematological parameters of the patients and the healthy controls were compared retrospectively. The platelet volume (MPV) and platelet crit (PCT) were significantly upregulated, and the lower red cell distribution width (RDW) was significantly downregulated in rosacea compared to healthy controls, and they were identified as the diagnostic biomarkers for rosacea with area under the curve values of 0.828, 0.742, and 0.787, respectively. Comparing the hematological parameters among the three rosacea subtypes, we found that platelet-to-lymphocyte ratio and platelet-to-neutrophil ratio values in the ETR group were significantly higher than those in the PPR and PhR groups. The correlation between hematological parameters and clinical scores showed that RDW was negatively correlated with the Clinician Erythema Assessment score. However, there was no significant correlation between the Investigator Global Assessment score and hematological parameters. In conclusion, PCT, MPV, and RDW have diagnostic value for rosacea, and RDW is correlated with the severity of rosacea erythema, implying the potential applications of PCT, MPV, and RDW in the diagnosis and monitoring of rosacea.

Association between Rosacea and Cardiovascular Diseases and Related Risk Factors: A Systematic Review and Meta-Analysis.

BACKGROUND: Rosacea is a common inflammatory skin disorder. Several studies, but not all, have suggested a high prevalence of cardiovascular diseases (CVDs) in rosacea patients. This study is aimed at investigating the association between rosacea and CVDs and related risk factors. METHODS: We performed a literature search through PubMed, Embase, and Web of Science databases, from their respective inception to December 21, 2019. Two reviewers independently screened the articles, extracted data, and performed analysis, following the PRISMA guidelines. Odds ratios (OR) or standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes. The included studies' quality was evaluated using the Newcastle Ottawa Scale (NOS). RESULTS: The final meta-analysis included ten studies. The pooled analysis found no association between rosacea prevalence and the incidence of CVDs (OR 0.97; 95% CI 0.86-1.10). Rosacea was found to be significantly associated with several risk factors for CVDs (OR 1.17; 95% CI 1.05-1.31), including hypertension (OR 1.17; 95% CI 1.02-1.35), dyslipidemia (OR 1.34; 95% CI 1.00-1.79), and metabolic syndrome (OR 1.72; 95% CI 1.09-2.72). However, no association was found between rosacea and diabetes mellitus (OR 0.98; 95% CI 0.82-1.16). Among the biological parameters, a significant association was found between rosacea and total cholesterol (SMD = 0.40; 95% CI = -0.00, 0.81; p < 0.05), low-density lipoprotein cholesterol (SMD = 0.28; 95% CI = 0.01, 0.56; p < 0.05), and C-reactive protein (CRP) (SMD = 0.25; 95% CI = 0.10, 0.41; p < 0.05). We found no association between rosacea and high-density lipoprotein cholesterol (SMD = 0.00; 95% CI = -0.18, 0.18; p = 0.968) or triglycerides (SMD = 0.10; 95% CI = -0.04, 0.24; p = 0.171). CONCLUSIONS: Although no significant association was found between rosacea and CVDs, rosacea was found to be associated with several of related risk factors. Patients with rosacea should pay more attention to identifiable CVD risk factors, especially those related to inflammatory and metabolic disorders.

Do blood groups play a role in etiology of rosacea?

BACKGROUND: The pathogenesis of rosacea is not fully understood. The innate immune system is impaired in patients with rosacea. This leads to abnormal inflammatory cytokine release. It has been proposed that the molecular mechanism for the role of the ABO antigenic system in human diseases may arise from its relationship with the von Willebrand factor and several pro-inflammatory and adhesion molecules. To our knowledge, the relationship between ABO-Rh groups and rosacea has not been investigated previously. MATERIALS AND METHODS: One hundred and fourteen patients with rosacea and 258 healthy individuals who had blood group record were included in this study. The results were analyzed statistically. RESULTS: In terms of ABO blood groups, 54 (47.4%) patients had A, 14 (12.3%) patients had B, 7 (6.1%) patients had AB, and 39 (34.2%) patients had O blood groups in the patient group. In the control group, 109 (42.2%) individuals had A, 45 (17.5%) individuals had B, 29 (11.2%) individuals had AB, and 75 (29.1%) individuals had O blood group. There was no significant difference between the groups (P > .05). In terms of Rh groups, 103 (90.4%) patients were Rh (+) and 11 (9.6%) patients were Rh (-). In the control group, 220 (85.3%) individuals were Rh (+) and 38 (14.7%) were Rh (-). There was no significant difference between the groups (P > .05). CONCLUSION: We did not find a relationship between blood groups and rosacea. But, we think this is an interesting hypothesis. To clarify this possible relationship, comprehensive and further studies are needed in different races and geographic regions.

Vascular endothelial growth factor gene polymorphisms in patients with rosacea: A case-control study.

BACKGROUND: Rosacea is a chronic disease that is characterized by facial skin inflammation and vascular abnormality. Vascular endothelial growth factor (VEGF) is a potent mediator of vascular permeability and inflammation that might play a role in the pathogenesis of rosacea. OBJECTIVE: This study aimed to determine the association between VEGF gene polymorphisms and rosacea. METHODS: A case-control study design was used to compare 100 patients with rosacea and 100 age- and gender-matched control subjects in terms of VEGF polymorphisms based on polymerase chain reaction and the serum level of VEGF and VEGF receptors based on enzyme-linked immunosorbent assay. RESULTS: Heterozygous and homozygous +405C/G polymorphism of the VEGF gene was observed to increase the risk of rosacea 1.7-fold (95% confidence interval 1.2-4.2) and 2.3-fold (95% confidence interval 1.2-4.2), respectively. There was a significant positive correlation between the severity of rosacea and +405C/G polymorphism of the VEGF gene in patients with erythematotelangiectatic rosacea. LIMITATIONS: Serum VEGF and VEGF receptor levels were measured in the limited number of patients. CONCLUSION: The present findings indicate that +405C/G polymorphism of the VEGF gene increases the risk of rosacea.

Thiol/disulfide homeostasis as a marker of oxidative stress in rosacea: a controlled spectrophotometric study.

BACKGROUND: Rosacea is the chronic inflammatory disease of the facial skin. Although its aetiology is not clear yet, inflammatory processes triggered by oxidative stress and oxidation of lipids have been suggested to play a role. While studies on the relationship between inflammation and oxidative stress are ongoing, thiol metabolism and its role in oxidative stress have also begun to be investigated. Thiols are among the key molecules of protein metabolism in the organism and they are the firstly consumed antioxidants in case of oxidative stress. Thiols regulate intracellular redox metabolism and protect keratinocytes against the results of oxidative alterations in the stratum corneum. There is a balance known as dynamic thiol/disulfide homeostasis between thiols and their oxidized forms; disulfides. AIM: This study aimed to determine the effects of oxidative stress on protein metabolism in rosacea patients by investigating thiol/disulfide homeostasis using a newly developed and fully automated method. Determination of plasma thiol levels provides important clues regarding the extent of free radical-mediated oxidation of proteins causing damage in rosacea. METHODS: The study included 50 rosacea patients who were diagnosed clinically or histopathologically with rosacea and 42 age- and gender-matched healthy controls. Plasma levels of native thiol, total thiol, and disulfide were determined. The following ratios were calculated: disulfide/native thiol ratio, disulfide/total thiol ratio, and native thiol/total thiol ratio. RESULTS: The mean age was 41.8 ± 10.5 in the rosacea patients (35 females) and 42.5 ± 10.3 years in the control group (33 females). The mean disulfide level was found to be significantly higher in the rosacea patients than in the control group (23.4 ± 5.5 µM/L and 17.3 ± 6.2µM/L, respectively; p < 0.001). The mean disulfide/native thiol ratio (0.055 ± 0.016 vs. 0.041 ± 0.017) and the mean disulfide/total thiol ratio (0.049 ± 0.012 vs.0.037 ± 0.013) were significantly higher and the mean native thiol/total thiol ratio (0.884 ± 0.118 vs. 0.923 ± 0.027) was significantly lower in the patients as compared with the controls (p < 0.05 for all). CONCLUSION: In rosacea patients, the thiol/disulfide balance was observed to shift towards disulfides, which could be considered an indicator of oxidative stress in rosacea.

[FEATURES OF ROSACEA PATHOGENESIS IN PERIMENOPAUSAL WOMEN].

In patients with rosacea, the monitoring of blood melatonin in the menopausal period, as one of the criteria for assessing the severity of the disease, seems appropriate and pathogenetically justified. The aim of this study was determination of blood melatonin, VEGF, IL-8 concentration in perimenopausal period of women suffering by rosacea. 43 to 65 years old 15 women with various clinical manifestations of rosacea, and severe climacteric syndrome were under observation. The control group consisted of 15 female patients with rosacea but without climacteric syndrome. Melatonin, VEGF,IL-8 level in serum were determined by ELISA (IBL - international - reagent), the results were expressed in pg/ml).As the results of the study showed, the concentration of vasoactive peptides in patients with rosacea differes significantly from those in the control group. Increase the concentration of cytokinesin in the blood of patients with rosacea indicate that they are playing significant role in the pathogenesis of rosaceaAccording to the results of the study, the concentration of melatonin was reduced in all patients with rosacea (the main group). The degree of reduction was in direct correlation with the severity of climacteric syndrome (11,6÷1,5 pg/ml at a rate of ≥ 20,0 pg/ml). In the control group, the melatonin concentration was approaching to the norm (19.1 pg/ml). Statistical analysis of received data revealed the correlation in between of the severity of dermatosis and changes in lipid metabolism and concentration of melatonin (R = 0,91; p <0,05) in the main group of patients (with rosacea and climacteric period). Thus, on the basis of the obtained results it can be concluded that the inclusion of melatonin-containing preparations in prescription for rosacea patients having climacteric syndrome pathogenetically is justified.

[THE ROLE OF SOME VAZOACTIVE PEPTIDES IN THE PATHOGENESIS OF EARLY FORMES OF ROSACEA AND THE HEMOSTASIS SYSTEM].

Recently, the role of vasoactive peptides has been increasingly discussed in the pathogenesis of rosacea. The most attention is paid to the growth factor of the vascular endothelium (VEGF). VEGF affects angiogenesis and survival of immature blood vessels. Cytokine contributes to an increase in the level of IL-8, which plays a role in the development of inflammation. VEGF is synthesized by activated keratinocytes as a result of various factors. In particular, after exposure to ultraviolet irradiation, the production of cytokines-IL-1 and TNF-α-is provoced, which stimulate keratinocytes to synthesize of VEGF. The latest data on the state of the coagulation system in rosacea patients indicate a shift in the functional activity of the hemostasis system toward hypercoagulability. The aim of the study was to study the relationship between changes in the concentration of certain vasoactive peptides and the parameters of the hemostasis system in patients with rosacea. The state of the hemostasis system was assessed by prothrombin and thrombin time. The content of fibrinogen, fibrinolytic activity of blood, and also prothrombin index were determined as well. The concentration of free VEGF, IL-8 in the serum was determined by the method of enzyme immunoassay In the study, patients with rosacea, according to their age, were divided into 2 groups: -I group - patients aged 35 to 45 years, II group - patients aged 45 to 65 years. As the results of the study showed, the concentration of vasoactive peptides in patients with various clinical forms of rosacea differs significantly from those in the control group. In patients with various clinical forms of rosacea, the tendency of changes in all parameters (thrombin time, prothrombin time, fibrinogen, prothrombinic index) of the state of the coagulating system of blood with the manifestation of hypercoagulability is traced. And if the change in the content of cytokines was observed equally often in all observed patients, the manifestations of hypercoagulability were most pronounced in the second group of patients (aged 45 to 65 years) Thus, the results of the study allow us to conclude that an increase in the concentration of cytokines (which are a potent provoker of changes in permeability, atony and brittleness of the vessel walls), as well as hypercoagulable phenomena, indicative of ongoing microcracking processes, are the leading links in the pathogenesis of early forms of rosacea.

Can Hematologic Parameters be an Indicator of Metabolic Disorders Accompanying Rosacea?

Recently, diverse hematologic parameters have been used as an indicator of the presence or severity of inflammatory and cardiovascular diseases. Our aim was to investigate the ratios of neutrophils to lymphocytes (NL), monocytes to high-density lipoprotein (HDL) cholesterol (MHC), and platelets to lymphocytes (PL) in patients with rosacea in comparison with the control group and determine whether there was a correlation between these ratios and metabolic disorders in patients with rosacea. We conducted a case-control study on 61 patients with rosacea and 60 healthy controls between January 2015 and January 2016 at the Dermatology Outpatient Clinic, Mugla, Turkey. Demographic data, biochemical parameters, hematologic parameters and ratios, the presence of metabolic syndrome (MS), and the presence of insulin resistance (IR) in the participants were recorded. Sixty one patients with rosacea (16 men, 45 women) and 60 controls (13 men, 47 women) were included in the study. The NL ratio, mean levels of low-density lipoprotein (LDL) and total cholesterol, triglyceride, C-reactive protein (CRP), systolic and diastolic blood pressures, and the presence of IR were significantly higher in patients with rosacea than in controls. In the rosacea group, the MHC ratio was significantly higher in patients with rosacea with IR and MS. Moreover, only the MHC ratio was an independent predictor of MS according to univariate logistic regression analysis. The cutoff value of MHC on admission for predicting MS in patients with rosacea was 0.013.The higher levels of NL ratio and IR in the rosacea group corroborate the previous studies demonstrating a high level of cardiovascular risk factors in patients with rosacea. The MHC ratio may be used as a simple and inexpensive method to predict metabolic disorders in patients with rosacea.

[RISK-FSCTORS OF CARDIOVASCULAR DISEASE IN PATIENTS WITH ROSACEA].

The purpose of the research was to study the lipid profile, some indices of hemostasis and cytokine status of rosacea patients with severe climacteric syndrome. Serum lipid profile was studied by means of the following parameters: total cholesterol, high density lipoproteins (HDL), low density lipoproteins (LDL), triglycerides (the study of lipid profile was performed by the device "INTEGRAM +400" (Company "ROSH¼). Haemostatic system was evaluated in terms of prothrombin, thrombin time. Content of fibrinogen, fibrinolytic activity, and prothrombin index were determined. The concentration of free VEGF (vascular endothelial growth factor) and IL-8 were measured by ELISA. The results of these studies suggest that the phenomenon of hyper coagulation and disorders in lipid profile of blood serum in patients with rosacea with climacteric syndrome can be considered as risk factors of cardiovascular disease. From the other side, as a powerful provocateur of increased permeability, atony and fragility of vessel walls, VEGF, IL-2, IL-8 may be directly related to the mechanism of the development of cardiovascular disease in rosacea patients.

Improved clinical outcome and biomarkers in adults with papulopustular rosacea treated with doxycycline modified-release capsules in a randomized trial.

BACKGROUND: Patients with rosacea have increased amounts of cathelicidin and protease activity but their usefulness as disease biomarkers is unclear. OBJECTIVE: We sought to evaluate the effect of doxycycline treatment on cathelicidin expression, protease activity, and clinical response in rosacea. METHODS: In all, 170 adults with papulopustular rosacea were treated for 12 weeks with doxycycline 40-mg modified-release capsules or placebo in a multicenter, randomized, double-blind, placebo-controlled study. Clinical response was compared with cathelicidin and protease activity in stratum corneum samples obtained by tape strip and in skin biopsy specimens obtained from a random subset of patients. RESULTS: Treatment with doxycycline significantly reduced inflammatory lesions and improved investigator global assessment scores compared with placebo. Cathelicidin expression and protein levels decreased over the course of 12 weeks in patients treated with doxycycline. Low levels of protease activity and cathelicidin expression at 12 weeks correlated with treatment success. Low protease activity at baseline was a predictor of clinical response in the doxycycline treatment group. LIMITATIONS: Healthy control subjects were not studied. CONCLUSIONS: Improved clinical outcome correlated with reduced cathelicidin and protease activity, supporting both the mechanism of doxycycline and the potential of these molecules as biomarkers for rosacea.

[Capillary fragility and some hemostatic parameters in patients with rosacea].

The aim of the study was to investigate the association between capillary fragility and some hemostatic parameters, lipid profile in patients with rosacea. 50 patients (30 women and 20 men) aged 35 to 65 years were under observation. Control group consisted of 50 healthy persons, adequate to comparison group by sex and age. To determine the resistance of the capillary, Rumpel-Leede cuff (tourniquet test) was used which consists in determining the formation of petechial hemorrhages on the skin in the area of ​​short-term increase in venous pressure. The hemostatic system was evaluated in terms of prothrombin and thrombin time. Content of fibrinogen and fibrinolytic activity of blood were determined also. The serum lipid profile was studied by means of the following parameters: total cholesterol, triglycerides, HDL (high density lipoprotein), LDL (low density lipoproteins). The survey revealed that in 25 patients the arm cuff test was positive, whereas in the control group, only 2 cases it was weakly positive. Manifestations of hypercoagulation were found in half of patients with a positive cuff test, almost in half of the patients an increased level of fibrinogen and the reduced fibrinolytic activity in blood serum has been revealed. Significant correlation with lipid metabolism have not been identified. Phenomenon of hypercoagulation in rosacea patients on the one hand suggests the existence of processes of microcoagulation, on the other hand the connection with the results of a cuff test can be used to predict the severity of the dermatosis and the possible risk for developing of cardiovascular disease.

Multi-drugs resistant acne rosacea in a child affected by Ataxia-Telangiectasia: successful treatment with Isotretinoin.

Ataxia-Telangiectasia is a rare multisystem autosomal recessive disorder [OMIM 208900], caused by mutations in Ataxia-Telangiectasia Mutated gene. It is characterized by neurological, immunological and cutaneous involvement. Granulomas have been previously reported in Ataxia-Telangiectasia patients, even if acne rosacea has not been described.We report a case of a young Ataxia-Telangiectasia patient with a severe immunological and neurological involvement, who developed granulomatous skin lesions diagnosed by skin biopsy as acne rosacea. Considering the severe clinical picture and the lack of improvement to multiple topic and systemic therapies, treatment with Isotretinoin was started and the skin lesions disappeared after five months. However the therapy was stopped due to drug-hepatotoxicity.Systemic treatment with Isotretinoin should be carefully considered in patient with Ataxia-Telangiectasia for the treatment of multi-drug resistant acne rosacea, however its toxicity may limit long-term use and the risk/benefit ratio of the treatment should be evaluated.

Decreased serum paraoxonase and arylesterase activities in patients with rosacea.

BACKGROUND: Recent evidence suggests that oxidative stress may be an important phenomenon in the pathophysiology of rosacea. Paraoxonase-1 (PON1) is an antioxidant enzyme with three activities: paraoxonase, arylesterase and dyazoxonase. In this study, we evaluated serum paraoxonase and arylesterase activities, and serum lipid hydroperoxide (LOOH) levels in patients with rosacea in comparison to healthy controls. MATERIAL AND METHOD: The study included 39 rosacea patients and healthy controls, consisting of 40 age- and sex-matched healthy volunteers. Serum paraoxonase and arylesterase activities were measured using paraoxon and phenylacetate substrates. Serum LOOH levels were measured with the ferrous ion oxidation-xylenol orange assay. RESULTS: In rosacea group mean serum paraoxonase and arylesterase activities were 74.54 ± 38.30 U L(-1) and 141.29 ± 22.27 kU L(-1) respectively, which were significantly lower than controls (P = 0.010, 0.005; respectively). Mean serum LOOH level of rosacea group was 8.17 ± 1.91 µmol L(-1) which was significantly higher than controls (P = 0.009). There were no statistically significant differences between the clinical subtypes of the disease, menopause situation or ocular involvement with the respect to the serum paraoxonase and arylesterase activities and LOOH levels (all; P > 0.05). CONCLUSIONS: Serum PON1 enzyme activities have decreased significantly in rosacea. These findings support that decreased PON1 activity and increased oxidative stress may play a role in the pathogenesis of rosacea. Further studies are needed to elucidate the role of PON1 activity in the pathophysiology of rosacea.

Vitamin D status in patients with rosacea.

BACKGROUND: Rosacea is a common chronic skin condition affecting the face. In recent years, significant evidence shows that vitamin D plays an important role in modulating the immune system. Vitamin D and its analogues via these mechanisms are playing an increasing role in the management of atopic dermatitis, psoriasis, vitiligo, acne and rosacea. OBJECTIVES: In our study, we aimed to investigate the relationship between serum vitamin D levels in patients with rosacea and analyze the association of vitamin D with clinical features. METHODS: Forty-four rosacea patients and 32 healthy control subjects were included into the study. 25-hydroxyvitamin D (25(OH)D), calcium and intact parathyroid hormone were measured. Deficiency of vitamin D is defined as the level of 25(OH)D being less than 20 ng/ml. RESULTS: Thirty-three female and 11 male patients were included in the study. The mean age of patients was 48.6 ± 11.5. The mean levels of vitamin D levels were found as 21.4 ± 9.9 and 17.1 ± 7.9 in patients and controls, respectively. The difference was statistically significant (p = 0.04). The prevalence of vitamin D deficiency in patients with rosacea was 38.6% and 28.1% in healthy controls (p = 0.34). CONCLUSIONS: To the best of our knowledge, our study is the first study for evaluating serum vitamin D levels of patients with rosacea in the literature. Patients with rosacea have relatively high serum vitamin D levels compared to control groups. The result of our study suggests that increased vitamin D levels may lead to the development of rosacea. To confirm status of vitamin D levels in patients with rosacea, larger epidemiological studies are needed.

Determination of tear and serum inflammatory cytokines in patients with rosacea using multiplex bead technology.

PURPOSE: To compare serum and tear inflammatory and anti-inflammatory cytokine levels of rosacea patients with the healthy controls and evaluate the correlation of tear cytokine levels with tear function parameters. METHODS: Tear and serum interleukin (IL)-1α, IL-6, IL-8, IL-10, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) levels were measured using multiplex bead (Luminex) technology in 12 rosacea patients without ocular involvement (group 1), 20 rosacea patients with ocular involvement (group 2), and 22 healthy subjects (group 3). The correlation of the cytokines with tear function parameters was analyzed using Spearman correlation test. RESULTS: Tear IL-10 and VEGF levels were significantly lower in group 1 (median: 35.78 pg/mL and 427.29, respectively) and group 2 (median: 26.25 pg/mL and 348.31, respectively) than in group 3 (median: 75.96 pg/mL and 480.12, respectively) (p < 0.05). Mean serum IL-8 level was significantly lower in group 2 (median = 0) compared to group 3 (median = 3.98) (p = 0.02). Tear breakup time was found to be positively correlated with IL-10 (r = 0.46, p = 0.013) and inversely correlated with MCP-1 (r = -0.52, p = 0.004). CONCLUSIONS: Tear and serum levels of cytokines and growth factors measured with Luminex technology showed a large variation in rosacea and healthy subjects. Decreased levels of tear IL-10, an anti-inflammatory cytokine, may lead to an inflammatory ocular surface environment, exacerbate ocular surface inflammation, and deteriorate tear function tests. A bigger sample size, including rosacea patients with corneal involvement, is needed to confirm the role of cytokines in the pathogenesis of rosacea-associated ocular inflammation.

Randomized, double-blind trial of 220 mg zinc sulfate twice daily in the treatment of rosacea.

A 2006 article published in the International Journal of Dermatology reported that oral zinc sulfate 100 mg three times daily was associated with improvement in the severity of facial rosacea (Sharquie et al. 2006; 45: 857-861). The current study was undertaken to further assess the role of zinc in the management of rosacea. This was a randomized, double-blind trial of 220 mg of zinc sulfate twice daily for 90 days in patients with moderately severe facial rosacea at baseline. Subjects were recruited in the Upper Midwest USA between August 2006 and April 2008, and followed until July 2008. Forty-four subjects completed the trial (22 in each arm). Rosacea improved in both groups. There were no differences in magnitude of improvement based on rosacea severity scores between subjects receiving zinc sulfate and subjects receiving placebo (P=0.284). Serum zinc levels were higher in subjects receiving zinc (P<0.001). Oral zinc sulfate was not associated with greater improvement in rosacea severity compared with placebo in this study. Additional studies are needed to determine what role oral zinc may have in the management of rosacea.

[Oxidative stress level in patients with rosacea and a rationale for the therapeutic use of an ozone-oxygen mixture].

The paper gives information on the possible involvement of pro- and antioxidant imbalance in the pathogenesis of rosacea. Eighty patients with different clinical types of rosacea were examined; the parameters of primary and intermediate products of lipid peroxidation, superoxide dismutase, plasma total antioxidative activity, and protein oxidative modification were studied. Based on the findings, oxidative therapy options for rosacea, treatment with an ozone-oxygen mixture in particular, are proposed.

Correlation between ocular Demodex infestation and serum immunoreactivity to Bacillus proteins in patients with Facial rosacea.

PURPOSE: To investigate correlation between ocular Demodex infestation and serum. DESIGN: A prospective study to correlate clinical findings with laboratory data. PARTICIPANTS: We consecutively enrolled 59 patients: 34 men and 25 women with a mean age of 60.4+/-17.6 years (range, 17-93). METHODS: Demodex counting was performed based on lash sampling. Serum immunoreactivity to two 62-kDa and 83-kDa proteins derived from B oleronius was determined by Western blot analysis. Facial rosacea, lid margin, and ocular surface inflammation were documented by photography and graded in a masked fashion. MAIN OUTCOME MEASURES: Statistical significance based on correlative analyses of clinical and laboratory data. RESULTS: These 59 patients were age matched, but not gender matched, regarding serum immunoreactivity, ocular Demodex infestation, or facial rosacea. There was a significant correlation between serum immunoreactivity and facial rosacea (P = 0.009), lid margin inflammation (P = 0.040), and ocular Demodex infestation (P = 0.048), but not inferior bulbar conjunctival inflammation (P = 0.573). The Demodex count was significantly higher in patients with positive facial rosacea (6.6+/-9.0 vs. 1.9+/-2.2; P = 0.014). There was a significant correlation of facial rosacea with lid margin inflammation (P = 0.016), but not with inferior bulbar conjunctival inflammation (P = 0.728). Ocular Demodex infestation was less prevalent in patients with aqueous tear-deficiency dry eye than those without (7/38 vs. 12/21; P = 0.002). CONCLUSIONS: The strong correlation provides a better understanding of comorbidity between Demodex mites and their symbiotic B oleronius in facial rosacea and blepharitis. Treatments directed to both warrant future investigation.