Use of beta-blockers for rosacea-associated facial erythema and flushing: A systematic review and update on proposed mode of action.

BACKGROUND: Flushing and erythema are frequent skin symptoms in rosacea. Because their adequate treatment remains a clinical challenge, new treatment options are explored, such as oral ß-blockers. OBJECTIVES: To evaluate the efficacy of oral ß-blockers for rosacea-associated facial flushing and erythema. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were systematically searched, including studies providing original data on the efficacy of oral ß-blockers in rosacea patients with facial flushing and/or persistent erythema. Risk of bias was assessed using the Cochrane Risk of Bias tool, Newcastle-Ottawa scale, and Quality in Prognosis Studies tool. RESULTS: Nine studies evaluating the use of carvedilol, propranolol, nadolol, and ß-blockers in general were included. Articles studying carvedilol and propranolol showed a large reduction of erythema and flushing during treatment with a rapid onset of symptom control. Bradycardia and hypotension were the most commonly described adverse events. LIMITATIONS: Most studies had a retrospective design with a small sample size, and outcome measurement was often subjective. CONCLUSIONS: Oral ß-blockers could be an effective treatment option for patients with rosacea with facial erythema and flushing that does not respond to conventional therapy. Larger prospective trials with objective outcome assessment are needed to validate the promising results of these studies.

Detection of subclinical Harlequin syndrome in pediatric patients.

BACKGROUND: Harlequin syndrome presents as differences in facial coloring due to unilateral flushing. This is the result of the inability to flush on the affected side due to the disruption of vasomotor and sudomotor sympathetic activity. The neurologically intact side appears flushed. A 2°C temperature difference between the flushed and nonflushed sides of the face has been detected in patients presenting with Harlequin syndrome. This difference in temperature might be detectable even in the absence of unilateral flushing, and this subclinical manifestation of the syndrome may occur more often than realized. AIM: To measure and compare the difference in the change in temperature on both sides of the face in patients with a thoracic epidural. METHODS: Fifteen pediatric patients receiving thoracic epidurals for the correction of pectus excavatum via Nuss procedure were enrolled. Temperature measurements on each side of the face were collected at three time points: prior to epidural placement in the holding area, one hour after epidural analgesia had been instituted, and after the patient awakened in the recovery area. The primary outcome is whether or not a temperature difference occurred between the two sides of the face over time. RESULTS: Comparing the pre-op temperature change to post-op temperature change for each side of the face, patient 2 had a large increase in temperature on the left side of the face with a decrease in temperature on the right side of the face. The largest observed difference between the changes in temperature from pre-op to post-op between the right and left sides of the face was 1.85°C in patient 2. This was more than two standard deviations from the mean difference in the patient population. Patient 15 also had a large difference in change in temperature from pre-op to post-op between the right and left sides of the face with an observed difference of 1.14°C, although this was not more than two standard deviations from the mean. None of the patients had unilateral facial flushing. CONCLUSION: Asymmetric effects or distribution of local anesthetic used in thoracic epidurals may result in asymmetric blockade of efferent sympathetic nervous system activity. This may cause differences in temperature between the two sides of the face without unilateral flushing. This phenomenon has previously been termed subclinical Harlequin syndrome. Subclinical Harlequin syndrome may be more common than anticipated and may be detected by comparing temperature differences in patients.

Harlequin Syndrome in Acute Thalamic Hemorrhage.

Harlequin syndrome is a disorder of the autonomic nervous system. It clinically presents as a distinct line of hemifacial sympathetic denervation. We describe a case of Harlequin syndrome with co-existing central first-order Horner syndrome in the setting of a large thalamic hemorrhage with intraventricular extension.

[Harlequin syndrome after scoliosis surgery]. / Harlekinsyndrom nach Skoliosechirurgie.

Harlequin syndrome is a rare combination of symptoms, characterized by unilateral facial anhidrosis and paleness on the affected side, becoming obvious by contralateral flushing mainly during sports activity. The syndrome is mostly idiopathic, however it is also described as a complication of thoracic surgery, i.e. superior lobectomy. Here, we report on two cases of Harlequin syndrome following scoliosis surgery at the cervicothoracic junction.

Association Between Excessive Alcohol Consumption and Echocardiographic Parameters According to the Presence of Flushing Reaction in Korean Men: A Community-Based Study.

BACKGROUND: The objective of this study was to investigate the effect of excessive alcohol consumption on heart reflected by various echocardiographic parameters according to the presence or absence of flushing reaction that might reflect acetaldehyde metabolism. METHODS: A total of 854 Korean men without significant cardiovascular diseases who underwent echocardiography and participated in the Korean Healthy Twin Study were used as subjects of this study. These subjects were classified into 3 categories: nondrinker, moderate drinker (≤196 g/wk), and heavy drinker (>196 g/wk) within 2 strata of flushing reaction to alcohol drinking. Association between echocardiographic measurements and categories of the amount of alcohol consumption considering flushing reaction were evaluated using mixed linear regression model. RESULTS: The proportion of flushers among drinkers was 39.5% (278 of 703). In stratified analysis by flushing reaction, nonflushers showed significantly higher left ventricular mass index (ß: 4.605; 95% CI: 0.966, 8.243) and significantly lower ratio of peak early diastolic velocities (E peak) over peak late diastolic velocities of mitral inflow (ß: -0.103; 95% CI: -0.198, -0.008) in heavy drinkers compared to nondrinkers. Flushers showed significantly higher left atrial (LA) volume index (ß: 2.712; 95% CI: 0.456, 4.968) in heavy drinkers and significantly lower ratio of E peak over the peak early diastolic mitral annular velocities (ß: -0.493; 95% CI: -0.902, -0.085) in moderate drinkers compared to nondrinkers. However, the interaction according to flushing reaction was only statistically significant for the association between alcohol consumption and LA volume index (p for interaction = 0.004). CONCLUSIONS: Alcohol consumption is associated with changes in cardiac structure and function. Such association might be influenced by acetaldehyde metabolism.

Venous Cannula Positioning in Arterial Deoxygenation During Veno-Arterial Extracorporeal Membrane Oxygenation-A Simulation Study and Case Report.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is indicated in reversible life-threatening circulatory failure with or without respiratory failure. Arterial desaturation in the upper body is frequently seen in patients with peripheral arterial cannulation and severe respiratory failure. The importance of venous cannula positioning was explored in a computer simulation model and a clinical case was described. A closed-loop real-time simulation model has been developed including vascular segments, the heart with valves and pericardium. ECMO was simulated with a fixed flow pump and a selection of clinically relevant venous cannulation sites. A clinical case with no tidal volumes due to pneumonia and an arterial saturation of below 60% in the right hand despite VA-ECMO flow of 4 L/min was described. The case was compared with simulation data. Changing the venous cannulation site from the inferior to the superior caval vein increased arterial saturation in the right arm from below 60% to above 80% in the patient and from 64 to 81% in the simulation model without changing ECMO flow. The patient survived, was extubated and showed no signs of hypoxic damage. We conclude that venous drainage from the superior caval vein improves upper body arterial saturation during veno-arterial ECMO as compared with drainage solely from the inferior caval vein in patients with respiratory failure. The results from the simulation model are in agreement with the clinical scenario.

Adverse reactions to infliximab and the outcome of desensitization.

BACKGROUND: Infliximab is a highly effective monoclonal antibody against tumor necrosis factor, which is a major inflammatory mediator in certain gastrointestinal, rheumatic, and skin diseases. In some patients, infliximab infusion causes systemic adverse reactions that often lead to discontinuation of therapy even in responsive patients. OBJECTIVE: To investigate the frequency and characteristics of adverse reactions to infliximab at the authors' institution and the outcome of their management, including desensitization. METHODS: This was a single-center retrospective study of patients who were treated with infliximab, primarily for inflammatory bowel disease, from January 1, 2000 to March 31, 2014. Data included age, sex, underlying disease, infliximab therapy duration before the first reaction, manifestation of reaction, onset, and management. RESULTS: There were 336 patients with inflammatory bowel disease who were treated with infliximab during the study period. Thirty patients (8.9%) developed a systemic adverse reaction to infliximab, which was discontinued in 15 patients (50%) and was continued in 3 patients after premedication and/or decreased infusion rate. Twelve patients (40%) underwent infliximab desensitization with gradually increasing doses starting at a dilution of 0.1 mg/mL to reach the full treatment dose over approximately 4 to 6 hours. It was successful in all 12 patients, who continued to receive up to 26 infliximab infusions, mostly without premedication. CONCLUSION: Infliximab can trigger systemic reactions that hinder its administration. The present desensitization protocol appears to be safe and effective and it can be considered in patients whose inflammatory bowel disease responds well to infliximab but who develop systemic adverse reactions.

Short-lasting unilateral neuralgiform headache attacks with ispilateral facial flushing is a new variant of paroxysmal extreme pain disorder.

BACKGROUND: We encountered a 5-year-old girl who had short-lasting, severe, unilateral temporal headaches with ipsilateral lacrimation, nasal congestion and rhinorrhoea, and facial flushing after severe attacks. Family history revealed similar short-lasting, severe headaches in an older brother, younger sister, mother, maternal aunt, and maternal grandfather's brother. METHODS: We performed routine laboratory examinations and electrophysiological and radiological studies for three children, and whole-exome sequencing to determine the genetic causality in this family. RESULTS: Focal hyperperfusion of the right trigeminal root entry zone was seen during a right-sided attack in one child, while left-sided temporal headache attacks were provoked by bilateral electrical stimulation of the upper extremities in another. We identified a novel SCN9A mutation (NM_002977: c.5218G>C, p.Val1740Leu) in all affected family members, but not in any of the unaffected members. SCN9A encodes the voltage-gated sodium-channel type IX alpha subunit known as Na(v)1.7. CONCLUSIONS: Gain-of-function mutations in Na(v)1.7 are well known to cause paroxysmal extreme pain disorder (PEPD), a painful Na-channelopathy characterized by attacks of excruciating deep burning pain in the rectal, ocular, or jaw areas. The SCN9A mutation suggests that our patients had a phenotype of PEPD with a predominant symptom of short-lasting, severe, unilateral headache.

Harlequin syndrome in a pediatric population: a case series.

Harlequin syndrome is a rare condition, presenting with unilateral facial flushing and hyperhidrosis in response to physical exercise, heat or emotional stressors and has scarcely been reported in pediatric patients. It is caused by a dysfunction of vasomotor and sudomotor sympathetic fiber activity inhibiting the ability to flush on the affected side, causing the neurologically intact side to appear red. We present three pediatric cases of this uncommon syndrome, each of them of different origin and displaying distinct associated (neurological) symptoms, and review medical literature. Insight into the anatomical structure of the thoracocervical and facial sympathetic nervous system is pivotal as it dictates symptomatology. About half of Harlequin syndrome cases are complicated with ocular symptoms and a minority may be part of more extensive partial dysautonomias affecting facial sudomotor, vasomotor and pupillary responses, such as Holmes-Adie syndrome and Ross syndrome. Etiology is generally idiopathic, however, cases secondary to surgery, trauma or infection have been described. Considering its predominantly self-limiting nature, treatment is usually unnecessary and should be restricted to incapacitating cases.

The role of the flushing response in the relationship between alcohol consumption and insulin resistance.

BACKGROUND: Facial flushing responses to drinking, because of intolerance to alcohol, are observed in some people, especially Asians. This study examined the role of flushing responses in the relationship between alcohol consumption and insulin resistance (IR). METHODS: Participants in this cross-sectional analysis included 624 Korean men (80 nondrinkers, 306 nonflushing drinkers, and 238 flushing drinkers) who were free of cardiovascular disease and diabetes. Data on the flushing response to drinking and alcohol consumption were collected from medical records. IR was estimated using the Homeostasis Model Assessment (HOMA(IR) ). On the basis of comparisons with nondrinkers, the risk of IR according to the quantity of alcohol consumed per week was analyzed among nonflushers and flushers. RESULTS: After adjusting for age, exercise status, smoking status, BMI, waist circumference, blood pressure, high-density lipoprotein cholesterol, and triglycerides using a logistic regression model, we found a low risk of IR among nonflushers who consumed ≤4 drinks (1 drink = 14 g of alcohol) per week (OR = 0.3). In contrast, a higher risk of IR was associated with nonflushers who consumed >20 drinks per week (OR = 3.5). On the other hand, only a higher risk of IR was associated with flushers who consumed >12 drinks per week (>12 to 20 drinks: OR = 4.7; >20 drinks: OR = 3.5). CONCLUSIONS: The amount of drinking associated with the development of IR in flushers was lower than in nonflushers. Additionally, no positive effect of moderate drinking on IR was observed in flushers. The findings support acetaldehyde-derived mechanisms in the development of alcohol-related IR.

Symptoms and signs of syncope: a review of the link between physiology and clinical clues.

Detailed history taking is of paramount importance to establish a reliable diagnosis in patients with transient loss of consciousness. In this article the clinical symptoms and signs of the successive phases of a syncopal episode are reviewed. A failure of the systemic circulation to perfuse the brain sufficiently results in a stereotyped progression of neurological symptoms and signs culminating in loss of consciousness; when transient, this is syncope. Prior to loss of consciousness the affected individual tends to exhibit unclear thinking, followed by fixation of the eyes in the midline and a 'frozen' appearance. Narrowing of the field of vision with loss of colour vision ('greying' out) and finally a complete loss of vision (hence 'blacking' out) occurs. Hearing loss may occur following loss of vision. This process may take as little as approximately 7 s in cases of sudden complete circulatory arrest (e.g. abrupt asystole), but in other circumstances it may take longer depending on the rate and depth of cerebral hypoperfusion. Complete loss of consciousness occurs with the 'turning up' of the eyeballs. Profound cerebral hypoperfusion may be accompanied by myoclonic jerks.

Remifentanil increases the incidence of mesenteric traction syndrome: preliminary randomized controlled trial.

PURPOSE: The use of remifentanil is often associated with the observation of mesenteric traction syndrome (MTS) soon after manipulation of the intestine during abdominal surgery. MTS symptoms include facial flushing, hypotension, and tachycardia. In the study reported here, we prospectively investigated the effects of remifentanil on the incidence of MTS in abdominal surgery. METHODS: One hundred patients scheduled for abdominal surgery were randomly assigned to two groups. In one group (n = 50), fentanyl alone was used as intravenous analgesic (control, group C); in the second group (n = 50), both fentanyl and remifentanil were used (remifentanil group, group R). In all patients, anesthesia was induced with propofol and rocuronium and then maintained with sevoflurane inhalation. Remifentanil was continuously infused for patients in group R as an analgesic. Plasma concentration of 6-keto-PGF(1α) was measured before surgery and 20 min after the skin incision was made in six patients of group R and seven patients of group C. RESULTS: MTS occurred in 20 cases in group R (40.0%), but in only five cases in group C (10.0%). In both groups, the incidence of MTS was higher in laparotomy than in laparoscopic surgery. The plasma concentration of 6-keto-PGF(1α) was low in both groups before surgery and was elevated 20 min after skin incision in both groups in patients in whom MTS appeared. CONCLUSIONS: The results of this study suggest that the use of remifentanil in laparotomy facilitates MTS.

Niacin skin flush test: a research tool for studying schizophrenia.

BACKGROUND: A body of biochemical evidence suggests that abnormal phospholipid metabolism may play a role in the etiology of schizophrenia, and possibly, other psychiatric and neurological diseases. Niacin, a B-complex vitamin, induces prostaglandin synthesis, vasodilatation, and skin flushing when applied as a solution on the skin or taken orally. In schizophrenia, diminished or absent skin response to niacin represents a robust finding. RESULTS: Attenuated niacin skin-flush response has been analysed as a potential biochemical marker of impaired prostaglandin signaling in schizophrenia. Diminished skin redness after topical application of niacin might be caused by a reduced level of the precursor arachidonic acid in the peripheral membranes, increased activity of the enzyme phospholipase A2, abnormal expression of niacin or prostaglandin receptors, or poor vasomotor activity of cutaneous capillary walls. Heritability estimates established in several studies support niacin skin flush response as a vulnerability trait for the development of psychosis. However, the exact mechanism of a reduced skin flush, the possible influence of the long-term use of antipsychotics, and the usefulness of the test for diagnostic purpose are not clear yet. CONCLUSIONS: Niacin skin flush test is a simple, non-invasive and easily replicable method in the research of schizophrenia. The studies investigating niacin flushing in schizophrenia are numerous but incoherent regarding methods of niacin application and evaluation of the results. New studies, controlling adequately for age, sex, drug abuse, diet, as well as genetic factors that may influence the intensity and reaction time, are necessary to clarify the usefulness of niacin testing in psychiatry.

Idiopathic harlequin syndrome: a case report and literature review.

Harlequin's syndrome is a rare dysautonomic syndrome of the face characterized by sweating with flush of one side and anhidrosis of the contralateral side. Mostly idiopathic although several secondary cases have been reported in the literature, the purpose of the treatment is mainly aesthetic and functional. We report the case of a patient having harlequin syndrome in its idiopathic form with a literature review.

Risks of substance uses, alcohol flush response, Helicobacter pylori infection and upper digestive tract diseases-An endoscopy cross-sectional study.

This study examines the effects of environmental hazards, including tobacco, alcohol/alcohol flush response, areca nut, and Helicobacter pylori (H pylori) infection on upper digestive diseases. This is a multi-hospital-based endoscopy-survey cross-sectional study. Subjects were received upper endoscopies in outpatient clinics at four hospitals in Taiwan between 2008 and 2013. Biopsy-based methods or urea breath test were used confirm the status of H pylori infection. In total, 8135 subjects were analyzed. Higher cumulative amounts of alcohol consumption were at higher risk of Barrett's esophagus and esophageal squamous cell carcinoma (ESCC), higher cumulative amounts of tobacco consumption were at higher risk of peptic ulcer, and higher cumulative amounts of areca nut consumption were at higher risk of duodenitis. Alcohol flush response was significant risk for reflux esophagitis and Barrett's esophagus (adjusted odds ratio [aOR] = 1.18 and 1.32, 95% confidence interval [CI] = 1.07-1.31 and 1.06-1.65, respectively). H pylori infection was inversely associated with ESCC risk (aOR = 0.20, 95% CI = 0.10-0.40). In addition, H pylori infection was consistently and significantly risk factors for gastrointestinal diseases, including peptic ulcer, gastric adenocarcinoma, and duodenitis (aOR = 5.51, 1.84, and 2.10, 95% CI = 4.85-6.26, 1.03-3.26, and 1.71-2.56, respectively). Besides the cumulative risk of alcohol, tobacco, and areca nut for Barrett's esophagus, ESCC, and peptic ulcer, respectively, presence of facial flushing was the significant risk for reflux esophagitis and Barrett's esophagus. H pylori infection was positively associated with peptic ulcer, gastric adenocarcinoma, and duodenitis, but inversely associated with ESCC.

Pupillographic findings in 39 consecutive cases of harlequin syndrome.

BACKGROUND: Harlequin syndrome is a curious phenomenon in which one half of the face fails to flush during thermal or emotional stress as a result of damage to vasodilator sympathetic fibers. Anecdotal reports suggest that some of these patients have abnormal pupils. In this study we set out to systematically investigate autonomic pupil disturbances in an unselected cohort of patients with harlequin syndrome. METHODS: A consecutive series of 39 patients with harlequin syndrome who were referred to a tertiary autonomic function laboratory underwent slit-lamp examinations, testing of deep tendon reflexes, infrared video pupillography and, where needed, additional pharmacologic pupillary testing. Results were compared with a meta-analysis of all previously reported cases of harlequin syndrome (n = 39) identified from a literature search. RESULTS: In 65% of patients, no underlying causative medical disturbance could be identified. In 64% of patients, there were abnormal pupils, most commonly Horner syndrome, which was always present ipsilateral to the side of the face with impaired facial sweating and flushing. The lesion was postganglionic in 9 of 10 patients tested pharmacologically. Five (13%) patients had tonic pupils, most of whom also had tendon areflexia but no other neurologic findings, a pattern consistent with Holmes-Adie syndrome. In 2 of these patients, tonic and Horner pupils coexisted. Normal pupils were present in 36% of patients. These results are similar to those for the 39 previously reported patients with harlequin syndrome. CONCLUSIONS: The frequent coexistence of harlequin and Horner syndromes without other neurologic deficits suggests pathologic changes affecting the superior cervical ganglion. Because either syndrome may occur alone, damage is apparently selective. Among the patients with harlequin syndrome who also have tonic pupils and tendon areflexia (Holmes-Adie syndrome), we postulate a ganglionopathy affecting not merely the (sympathetic) superior cervical ganglion, but also the (parasympathetic) ciliary and dorsal root ganglia. Because we found that more than 10% of patients had an undisclosed mass lesion in the chest or neck or a generalized autonomic neuropathy, we recommend a targeted evaluation in selected patients with harlequin syndrome.