Quantification of Demodex folliculorum by PCR in rosacea and its relationship to skin innate immune activation

The aim of this study is to quantify D. folliculorum colonisation in rosacea subtypes and age‐matched controls and to determine the relationship between D. folliculorum load, rosacea subtype and skin innate immune system activation markers. We set up a multicentre, cross‐sectional, prospective study in which 98 adults were included: 50 with facial rosacea, including 18 with erythematotelangiectatic rosacea (ETR), and 32 with papulopustular rosacea (PPR) and 48 age‐ and sex‐matched healthy volunteers. Non‐invasive facial samples were taken to quantify D. folliculorum infestation by quantitative PCR and evaluate inflammatory and immune markers. Analysis of the skin samples show that D. folliculorum was detected more frequently in rosacea patients than age‐matched controls (96% vs 74%, P < 0.01). D. folliculorum density was 5.7 times higher in rosacea patients than in healthy volunteers. Skin sample analysis showed a higher expression of genes encoding pro‐inflammatory cytokines (Il‐8, Il‐1b, TNF‐a) and inflammasome‐related genes (NALP‐3 and CASP‐1) in rosacea, especially PPR. Overexpression of LL‐37 and VEGF, as well as CD45RO, MPO and CD163, was observed, indicating broad immune system activation in patients with rosacea. In conclusion, D. folliculorum density is highly increased in patients with rosacea, irrespective of rosacea subtype. There appears to be an inverse relationship between D. folliculorum density and inflammation markers in the skin of rosacea patients, with clear differences between rosacea subtypes.     

Density of Demodex folliculorum in rosacea: a case-control study using standardized skin-surface biopsy

A standardized skin-surface biopsy (1 cm²) of the cheek was performed in 49 patients with rosacea [13 with erythematotelangiectatic rosacea (ETR). three with squamous rosacea (SR), 33 with papulopustular rosacea (PPR)], and 45 controls. A mean density of 0.7 Demodex folliculorum/cm² was found in controls, 98% of whom had less than five Demodex/cm². When all clinical types of rosacea were considered collectively, the density of Demodex was significantly higher in patients with rosacea than in controls (mean=10.8/cm²: P<0.001). When the various clinical types of rosacea were considered separately. Demodex density was statistically significantly higher than in controls only in the PPR patients (mean=12.8/cm²; P<0.001). The same type of comparison was also made for three other groups of subjects—patients with isolated inflammatory papules (n=4). rhinophyma (n=3), and HIV infection (n=21), respectively: in these groups, the Demodex density did not differ significantly from controls. The present study demonstrates a high density of D. folliculorum in PPR, and supports its pathogenic role in the papulopustular phase of rosacea. The study suggests that standardized surface biopsy could be a useful diagnostic tool for PPR, with a 98% specificity when Demodex density is higher than 5/cm².     

Comparative efficacy of intense pulsed light for different erythema associated with rosacea

Abstract

Objective: To compare the efficacy of intense pulsed light (IPL) (540–950nm) in treating different erythema associated with rosacea. Methods: Thirty-two patients with erythematotelangiectatic rosacea (ETR) (n = 16) and papulopustular rosacea (PPR, n = 16) were recruited. Three treatments of IPL (540–950nm) were administered on the face at 3-week intervals. Clinical improvement in erythema was independently assessed by two dermatologists using a quartile grading scale [0, ≤ 25% improvement (poor); 1, 26–50% improvement (fair); 2, 51–75% improvement (good); and 3, 76–100% improvement (excellent)]. Patient satisfaction was evaluated using a 10-point visual analog scale (VAS: 0, lowest; and 10, highest). Results: Thirty patients were involved in this study. All patients showed improvement in erythema after three sessions of IPL (540–950nm) treatment. Based on physician's assessment, the overall clinical improvement in PPR group was significantly higher (mean ± SD of PPR group, 2.167 ± 0.748 vs. ETR group, 1.400 ± 0.541; P = 0.003) and patient satisfaction was also higher in PPR group (mean ± SD of PPR group, 6.867 ± 1.457 vs. ETR group, 5.600 ± 1.502; P = 0.026). The proportion of patients showing > 75% clinical improvement among PPR group was also higher than that among ETR group (5/15 and 0/15, respectively; P = 0.021). Side effects were minimal and transient (erythema and/or edema) for patients. Conclusions: IPL (540–950nm) is a safe and effective treatment for rosacea-associated erythema, especially for perilesional erythema.     

Effects of Helicobacter pylori treatment on rosacea: A single‐arm clinical trial study

Rosacea is a chronic dermatological disease. Helicobacter pylori has been discussed as one of its causative factors. In this clinical trial study, we attempted to evaluate the effect of H. pylori standard eradication protocol on the rosacea clinical course. In this single‐arm clinical trial, patients ascertained to have H. pylori infection based on serological studies were assessed to examine existence of rosacea. Patients with concurrent rosacea and H. pylori infection were included in the study and underwent standard H. pylori eradication therapy. Rosacea was evaluated using the Duluth rosacea grading score at the beginning, 2 months later and at the end of the trial (day 180). Of 872 patients positive for H. pylori, 167 patients (19.15%) manifested the clinical features of rosacea. The patients with concurrent rosacea were younger (P < 0.001) and with a female sex predominance (P = 0.03) when compared with rosacea‐free patients. Of 167 patients, 150 received H. pylori eradication therapy, demonstrating a 92% (138/150) cure rate. The rosacea Duluth score grading on day 0, 60 and 180 among 138 patients significantly decreased in most of the criteria except for telangiectasias (P = 0.712), phymatous changes (P = 0.535) and the existence of peripheral involvement (P = 0.431). The present study concluded that H. pylori eradication leads to improvement of rosacea.     

Risk factors associated with rosacea

Background Although rosacea is a common disease, the cause of disease is still a mystery –Helicobacter pylori infection, genetic predisposition, climatic factors, and detrimental habits are implicated as triggers of rosacea. Objective The aim of current study is to evaluate several suspected risk factors coincidently. Methods Patients with rosacea from a dermatology clinic and skin‐healthy controls from an randomly selected employees' population enrolled the study. Skin status were evaluated by one and same dermatologist. Participants were queried for age, gender, sun‐reactive skin type, and detrimental habits using a questionnaire; blood samples for detecting Helicobacter pylori serostatus were collected. Results Totally 145 skin‐healthy controls and 172 subjects either with flushing episodes or established rosacea included the study. In multivariate analysis, rosacea patients had significantly higher chance to have photosensitive skin types (OR 1.75; 95% CI 1.01–3.04; P < 0.05), positive family history to rosacea (OR 4.31; 95% CI 2.34–7.92; P < 0.0001) or previous smoking status (OR 2.01; 95% CI 1.07–3.80; P < 0.05) comparing with skin‐healthy controls. There were no statistically significant differences either in gender, Helicobacter pylori serostatus, caffeine intake, alcohol consumption, occupational environment, or education level between rosacea patients and controls. Conclusion Rosacea is foremost associated with familial predisposition. There is no association between Helicobacter pylori infection and rosacea in current study.     

Association of rs3783641 single‐nucleotide polymorphism in GTP cyclohydrolase 1 gene with post‐herpetic neuralgia

Post‐herpetic neuralgia (PHN) is a well‐established clinical problem with potential severe personal and socioeconomic implications. GTP cyclohydrolase 1 (GCH1) gene, which encodes the rate‐limiting enzyme in tetrahydrobiopterin synthesis, has been strongly implicated to be associated with neuropathic pain in previous animal and human studies. The rs3783641 (T > A) single‐nucleotide polymorphism (SNP) in the GCH1 gene is functional. Here we examine the association between rs3783641 and PHN. A total of 292 subjects including 103 PHN patients, 87 herpes zoster (HZ) patients and 102 healthy controls were enrolled in this study. The rs3783641 polymorphisms were detected via the high‐resolution melting curve (HRM) method. There were statistical differences between PHN group and the other two groups in genotype distribution (P = 0.029 and 0.017, respectively) and allele frequency (P = 0.032 and 0.005, respectively) of rs3783641. The proportion of subjects with AA genotype in the PHN group was significantly lower compared to HZ group and control group (P = 0.026 and 0.016, respectively). The frequency of A allele was lower in the PHN group than in control group (P = 0.005), and the frequency of T allele in the PHN group was higher than in HZ group and control group (P = 0.001 and 0.003, respectively). The results of this study suggest that the rs3783641 SNP in the GCH1 gene is associated with PHN, and the AA genotype showed a protective effect in PHN.     

Clinical and laboratory study of rosacea in northern Greece

Background Numerous factors have been implicated in the pathogenesis of rosacea, which remains obscure. Objectives To examine the epidemiological characteristics of rosacea patients, the histopathological alterations, the prevalence of gastric Helicobacter pylori infection and the role of ultraviolet radiation, to detect the presence of Demodex folliculorum on affected skin and to elucidate the immunological nature of this disorder. Methods The study included 100 patients with rosacea. Each patient was assessed with a clinical, haematological, biochemical and histological examination; serology test for the detection of antibodies against H. pylori; direct immunofluorescence on perilesional, sun exposed skin and indirect immunofluorescence with monkey oesophagus as a substrate; antinuclear antibody titre and a skin surface biopsy to search for Demodex folliculorum. Results Women were more frequently affected. Half of our patients were 51–70 years old. About two‐thirds were phototypes I and II and 73% complained of worsening of conditions after sun exposure. An almost permanent histopathological feature was solar elastosis. Higher prevalence of H. pylori was not established. Prevalence and mean density of Demodex folliculorum were significantly increased in rosacea patients. Direct and indirect immunofluorescence tests were positive in 6.4% and 6.7% respectively. Antinuclear antibody titres were found in 21.1%. Conclusions Our results suggest the pivotal role of chronic sun exposure in the pathogenesis of rosacea. Demodex folliculorum represents a significant cofactor that may contribute to the transition of the disease from a vascular to an inflammatory stage. The low positive results of direct and indirect immunofluorescence do not support a potential autoimmune role in the development of rosacea.     

Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis

Psoriasis is characterized by keratinocyte proliferation and chronic inflammation, but the pathogenesis is still unclear. Dysregulated mitochondria (mt) could lead to reduced apoptosis and extracellular secretion of mtDNA, acting as “innate pathogen” triggering inflammation. Serum was obtained from healthy volunteers and psoriatic patients. Mitochondrial DNA was extracted from the serum and amplified with quantitative PCR (qPCR). Punch biopsies were obtained from lesional and non‐lesional psoriatic skin (10 cm apart) and from healthy volunteers, were placed in RNA later and were stored at ?80°C until RNA was extracted and cDNA was synthesized; gene expression of uncoupling protein 2 (UCP2), Dynamin‐related protein 1 (Drp1) and calcineurin, involved in the regulation of mitochondria function, was detected with qPCR. Mitochondrial DNA was significantly increased (7s, P = 0.0496 and Cytochrome B, CytB, P = 0.0403) in the serum of psoriatic patients (n = 63) as compared to controls (n = 27). Gene expression was significantly reduced for UCP2 (P = 0.0218), Drp1 (P = 0.0001) and calcineurin (P = 0.0001) in lesional psoriatic skin, as compared to non‐lesional or control skin. Increased serum extracellular mtDNA in psoriatic patients and decreased expression of mitochondrial regulatory proteins in psoriatic skin suggest increased inflammation and reduced keratinocyte apoptosis, respectively. Inhibitors of mtDNA secretion and/or UCP2 stimulants may be potential treatment options.     

In situ assessment of PI3K and PTEN alterations in mycosis fungoides: correlation with clinicopathological features

Deregulated signalling through phosphatidylinositol 3‐kinase (PI3K) pathway plays a critical role in tumour initiation and progression. We have already shown that AKT is activated in skin lesions in Mycosis Fungoides (MF) and we herein further investigate the frequency and clinical significance of PTEN and PI3K at the protein and at the DNA level as well as the presence of AKT1 mutations in skin lesions from 50 patients with MF clinical stages I‐IV in relation to clinicopathological features. Increased p‐AKT expression correlated with poor prognosis in plaques (P = 0.0198), whereas p‐AKT was an independent predictor of poor survival in the entire cohort (P = 0.017, HR = 1.012). PTEN cytoplasmic expression was found low or absent in all 77.3% of cases and inversely correlated with advanced clinical stages (P = 0.0744). Molecular analysis showed no AKT1 mutation, no PI3KCA copy number gain, only 1 case with PI3KCA mutation in exon 9 and 3 cases with PTEN mutations (7%) in exons 7, 8 and 5. The latter correlated with disease (P = 0.0253) and progression (P < 0.0001) free survival in tumour stage. Although activation of PI3K/AKT signalling pathway due to PTEN alterations is rarely attributed to abnormalities in PTEN, PI3K, and AKT1 genes, PTEN mutations exert a negative effect on patients’ prognosis with tumours.     

Role of CPI‐17 in restoring skin homoeostasis in cutaneous field of cancerization: effects of topical application of a film‐forming medical device containing photolyase and UV filters

Cutaneous field of cancerization (CFC) is caused in part by the carcinogenic effect of the cyclobutane pyrimidine dimers CPD and 6‐4 photoproducts (6‐4PPs). Photoreactivation is carried out by photolyases which specifically recognize and repair both photoproducts. The study evaluates the molecular effects of topical application of a film‐forming medical device containing photolyase and UV filters on the precancerous field in AK from seven patients. Skin improvement after treatment was confirmed in all patients by histopathological and molecular assessment. A gene set analysis showed that skin recovery was associated with biological processes involved in tissue homoeostasis and cell maintenance. The CFC response was associated with over‐expression of the CPI‐17 gene, and a dependence on the initial expression level was observed (P = 0.001). Low CPI‐17 levels were directly associated with pro‐inflammatory genes such as TNF (P = 0.012) and IL‐1B (P = 0.07). Our results suggest a role for CPI‐17 in restoring skin homoeostasis in CFC lesions.     

Characteristics of cutaneous adverse drug reactions caused by triple-combination drug therapy used for Helicobacter pylori eradication

Cutaneous adverse drug reactions (cADR) should be appropriately managed in drug administration. LANSAP^®, Rabecure^® and VONOSAP^® are currently used for Helicobacter pylori eradication therapy. Here, we examined the characteristics of cADR caused by these drugs using data from the Pharmaceuticals and Medical Devices Agency (PMDA). Periods subject to analyses were set according to the year of release of these drugs: (i) from 2008 to 2017 for LANSAP; (ii) from 2014 to 2017 for Rabecure; and (iii) 2017 for VONOSAP. Among all cADR reported to the PMDA, those attributed to LANSAP, Rabecure and VONOSAP accounted for 2.3%, 1.0% and 3.6% of cases, respectively. cADR occurred in patients aged in their 20s or older, with the oldest patients aged in their 60s. Numbers of male and female patients were 28 and 70 for LANSAP, eight and 14 for Rabecure and three and 16 for VONOSAP, respectively. Statistical analyses revealed significant sex differences for LANSAP (P = 0.022) and VONOSAP (P = 0.012), but not for Rabecure (P = 0.729). LANSAP, Rabecure or VONOSAP caused erythema multiforme in the largest population of patients and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in three patients. Ratios of SJS/TEN were 0.0–5.3% for LANSAP, Rabecure or VONOSAP, but 11.5–44.8% for the corresponding single constituent drugs other than vonoprazan. In conclusion, female sex appears to represent a risk factor for cADR attributed to H. pylori eradication therapy using LANSAP or VONOSAP, although H. pylori eradication therapy without these drugs rarely causes severe cADR.     

Risk of psychiatric disorders in rosacea: A nationwide,population‐based,cohort study in Taiwan

Rosacea has been reported to be associated with psychiatric disorders. Nevertheless, a nationwide study of the relationship between rosacea and comorbid psychiatric diseases in an Asian population has not been conducted. The aim of this study was to clarify the role of rosacea in the various psychiatric disorders by using a nationwide database in Taiwan. Data were obtained from the National Health Insurance Research Database of Taiwan from 2000 to 2013. In total, 7881 patients with rosacea and 31 524 age‐ and sex‐matched controls were enrolled. Patients with rosacea tended to have more coexisting psychiatric disorders. After adjusting for age, sex, comorbidity and residence/regions, the adjusted hazard ratio (HR) of psychiatric disorders for patients with rosacea was 2.761 (95% CI = 2.650–2.877, P < 0.001). Among them, the highest adjusted HR are phobic disorder and obsessive–compulsive disorder of 7.841 (95% CI = 7.526–8.170, P < 0.001) and 6.389 (95% CI = 6.132–6.657, P < 0.001), respectively. The National Health Insurance Research Database of Taiwan does not include the information about rosacea subtypes, severity and laboratory parameters. In conclusion, rosacea is related to various psychiatric disorders. In addition to anxiety and depression, patients are also at increased risk of phobic disorder and obsessive–compulsive disorder.     

Identification of PTPN22, ST6GAL1 and JAZF1 as psoriasis risk genes demonstrates shared pathogenesis between psoriasis and diabetes

The biological connections between psoriasis and diabetes have been suggested by epidemiological, immunological and genetic studies. To identify additional shared susceptibility loci and investigate shared pathogenesis between these two diseases, we genotyped 89 reported diabetes susceptibility loci in 4456 psoriasis cases and 6027 controls of Chinese population using the MassARRAY system from Sequenom. We discovered three significant associations at rs6679677 on 1p13.2 (P=6.15×10^?5, OR=5.07), rs16861329 on 3q27.3 (P=2.02×10^?4, OR=0.87) and rs849135 on 7p15.1 (P=6.59×10^?9, OR=1.78), which suggested PTPN22, ST6GAL1 and JAZF1 as novel susceptibility genes for psoriasis in Chinese population. Our findings implicated the involvement of T‐cell receptor signalling pathway in the pathogenesis of psoriasis and further confirmed the shared genetic susceptibility between psoriasis and diabetes.     

Assessment of thyroid disorders in patients with rosacea: a large case-control study

BackgroundThe frequency of autoimmune diseases and thyroid cancer has been increasingly reported in association with rosacea. However, studies investigating thyroid diseases in rosacea are scarce with conflicting results.ObjectiveTo investigate the relationship between thyroid disorders and rosacea.MethodsA large case-control study on age- and gender-matched 2091 rosacea patients and 9572 controls was conducted. Rosacea patients using the rosacea-specific ICD codes were compiled from the hospital records. Additionally, all participants were evaluated in terms of the presence of hypothyroidism and hyperthyroidism. Conditional logistic regression analysis was used to compute case-control odds ratios (OR) with 95% confidence intervals.ResultsThe analysis comprehended 2091 rosacea patients (1546 female, 545 male; mean 48.73 ± 14.53 years) and 9572 controls (7009 female, 2563 male; mean 48.73 ± 15.1 years). Whereas the rate of hypothyroidism was significantly higher in rosacea patients (OR = 1.3, 95% CI 1.13–1.49, p < 0.001), there was no significant difference in the rate of hyperthyroidism between the groups (OR = 1.12, 95% CI 0.81–1.53, p = 0.497). Stratification for gender revealed a significant association between hypothyroidism and rosacea in females (OR = 1.27, 95% CI 1.1–1.47, p = 0.002) and males (OR = 1.58, 95% CI 1.04–2.4, p = 0.032). The frequency of hypothyroidism in rosacea patients increased towards the age range of 40–49 and then decreased, parallel with the hypothyroidism frequency of the study population.Study limitationsDifferent subtypes and severities of rosacea were not distinguished.ConclusionsHypothyroidism may be a comorbidity of rosacea and investigation for hypothyroidism may be appropriate when evaluating rosacea patients.     

Upper gastrointestinal findings and detection of Helicobacter pylori in patients with oral lichen planus

Background. Lichen planus (LP) is a mucocutaneous disease of unknown aetiology, which may involve the gastrointestinal (GI) mucosa. The association of Helicobacter pylori with LP has been a subject of debate. Aim. To investigate upper GI findings and the presence of H. pylori in GI mucosa and oral LP (OLP). Methods. Oral biopsies from 20 patients with erosive OLP and 20 with non‐erosive OLP were investigated for the presence of H. pylori by histopathological examination and PCR. Upper GI endoscopy and GI mucosal biopsies were examined for LP lesions and/or H. pylori. Results. The endoscopic findings of both groups were oesophagitis, antral gastritis and duodenitis. No LP or LP‐like changes were found in the upper GI mucosa. H. pylori was found by histopathological examination in the gastric mucosa of 18 patients (45%), with equal distribution in both the control and study groups. Positive PCR results were obtained from biopsy specimens of oral lesions in all patients with erosive OLP and presence of H. pylori in the stomach (9 patients), but in none of the patients with non‐erosive OLP (P = 0.001). Conclusion. We did not find any difference in symptoms, endoscopic findings and histopathological results between patients with erosive and non‐erosive OLP. However, the concomitant presence of erosive OLP, of H. pylori nucleic acid in erosive OLP and the H. pylori organisms in gastric mucosa implies a possible pathogenic connection between this bacterium and erosive OLP.     

Claudin reduction may relate to an impaired skin barrier in rosacea

Rosacea is a chronic inflammatory skin disorder whose pathophysiological mechanism remains largely unknown. Although recent studies have revealed the hypersensitivity of the skin towards chemical, thermal and biological stimuli, there is no direct molecular evidence suggesting the skin barrier is impaired in rosacea. In this study, we demonstrated that the mRNA levels of most claudins (CLDN), the main components of tight junctions determining the major barrier of the paracellular pathway between epithelial cells, were lowered in lesional skin of rosacea patients, especially with erythematotelangiectatic (ETR) and papulopustular (PPR) subtypes. Immunohistochemical analysis showed a significant decrease in the expression of CLDN1, CLDN3, CLDN4 and CLDN5 in the epidermis of ETR and PPR patients. However, the expression of other skin barrier genes, such as filaggrin, loricrin and keratin 10, was not altered. In vitro, various rosacea trigger factors reduced the protein levels of CLDN1, CLDN3 and CLDN5 in keratinocytes. Taken together, our results demonstrate a significant decrease in the expression of CLDN rather than other skin barrier genes, which may be associated with an impaired skin barrier responsible for the development of rosacea.     

Clinical and bacteriological evaluation of adapalene 0.1% gel plus nadifloxacin 1% cream versus adapalene 0.1% gel in patients with acne vulgaris

This multicenter, randomized parallel group study investigated the efficacy and tolerability of adapalene 0.1% gel plus nadifloxacin 1% cream (combination therapy) compared with adapalene gel (monotherapy) during 12‐week treatment of acne vulgaris. A total of 184 Japanese patients aged above 12 years with moderate to severe acne as indicated by the Japanese severity grading criteria were randomized to combination therapy (n = 84) and monotherapy (n = 100) groups, both having comparable demographic and baseline characteristics. Adapalene was applied only to inflammatory acne lesions in order to minimize skin irritation and ensure the treatment results. Efficacy and safety evaluations, treatment compliance and satisfaction with drug application were periodically monitored. The combination therapy provided a significantly greater efficacy than adapalene in decrement of inflammatory papulopustular lesions at 4 weeks and thereafter (P = 0.0056). The overall judgment of the therapeutic efficacy by the physician at the end of study revealed a significant difference (P = 0.02496) between the groups in favor of combination therapy. Dryness was reported in a greater proportion of patients undergoing monotherapy than combination therapy at weeks 2 and 4 (P = 0.04652). The patient self‐assessment in satisfaction with the drug application at the end of study revealed a significant difference (P = 0.00268) between the groups in favor of combination therapy. Among 76 strains of Propionibacterium acnes isolated from 87 patients, no strain was resistant to nadifloxacin. Thus, the simultaneous use of adapalene and nadifloxacin may provide an additive and complementary effect, resulting in clinical superiority and greater patient adherence compared to adapalene monotherapy.     

Relationship between rosacea and sleep

Rosacea is a chronic facial skin disease involved in neurovascular dysregulation and neurogenic inflammation. Behavioral factors such as stress, anxiety, depression and sleep were identified to be associated with other inflammatory skin diseases. Few studies have reported sleep status in rosacea. Aiming to investigate the relationship between rosacea and sleep, a case–control survey was conducted, enrolling 608 rosacea patients and 608 sex- and age-matched healthy controls. Sleep quality was assessed through the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Diagnosis and severity grading of rosacea were evaluated under the standard guidelines of the National Rosacea Society. More rosacea patients (52.3%, n = 318) suffered poor sleep quality (PSQI, >5) than the healthy controls (24.0%, n = 146), displaying a much higher PSQI score (rosacea vs control, 6.20 vs 3.95). There was a strong association between sleep quality and rosacea (odds ratio [OR], 3.525; 95% confidence interval [CI], 2.759–4.519). Moreover, the severity of rosacea was also associated with sleep quality (OR, 1.847; 95% CI, 1.332–2.570). Single nucleotide polymorphisms in hydroxytryptamine receptor 2A and adrenoceptor-β1 genes, which are associated with sleep behaviour, were detected and revealed to be associated with rosacea. Furthermore, the LL-37-induced rosacea-like phenotype and sleep-deprivation mice models were applied, revealing that sleep deprivation aggravated the rosacea-like phenotype in mice, with higher expression of matrix metallopeptidase 9, Toll-like receptor 2, cathelicidin antimicrobial peptide and vascular endothelial growth factor. In conclusion, rosacea patients presented poorer sleep quality, as well as a higher propability of genetic background with sleep disturbance. In addition, poor sleep might aggravate rosacea through regulating inflammatory factors, contributing to a vicious cycle in the progression of disease.     

Real‐life experience on effectiveness and tolerability of topical ivermectin in papulopustular rosacea and antiparasitic effect on Demodex mites

Ivermectin is a drug approved for the treatment of papulopustular rosacea (PPR). Although clinical guidelines recommend the use of ivermectin as the first‐line treatment in patients with almost clear and mild rosacea, studies concerning its use on them are lacking. This study investigated the effectiveness and the tolerability of ivermectin in almost clear to severe rosacea and assessed the antiparasitic effect on Demodex mites. This is a retrospective study based on 50 patients affected by PPR and treated with topical ivermectin 1% once daily over 16 weeks. The disease severity, the patient‐examined improvement, and the safety assessment of patients were evaluated. Demodex mites were studied with the standardized skin surface biopsy. PPR to all severity achieved a therapeutic success. The number of inflammatory lesions was significantly decreased in almost clear (p < .0001), mild, moderate, and severe (p < .001) forms. A complete remission of inflammatory lesions was achieved by almost clear (p < .001) and mild (p = .005) with 82% with none‐to‐mild cutaneous adverse events. Thirty‐two percent were positive for Demodex mites, and all of them turned negative after 16 weeks. Ivermectin is an effective treatment not only in moderate to severe PPR but also in almost clear/mild rosacea.