Erenumab for Treatment of Persistent Erythema and Flushing in Rosacea: A Nonrandomized Controlled Trial.

Importance: Treatment of erythema and flushing in rosacea is challenging. Calcitonin gene-related peptide (CGRP) has been associated with the pathogenesis of rosacea, raising the possibility that inhibition of the CGRP pathway might improve certain features of the disease. Objective: To examine the effectiveness, tolerability, and safety of erenumab, an anti-CGRP-receptor monoclonal antibody, for the treatment of rosacea-associated erythema and flushing. Design, Setting, and Participants: This single-center, open-label, single-group, nonrandomized controlled trial was conducted between June 9, 2020, and May 11, 2021. Eligible participants included adults with rosacea with at least 15 days of either moderate to severe erythema and/or moderate to extreme flushing. No concomitant rosacea treatment was allowed throughout the study period. Visits took place at the Danish Headache Center, Copenhagen University Hospital, Rigshospitalet in Copenhagen, Denmark. Participants received 140 mg of erenumab subcutaneously every 4 weeks for 12 weeks. A safety follow-up visit was performed at week 20. Data analysis occurred from January 2023 to January 2024. Intervention: 140 mg of erenumab every 4 weeks for 12 weeks. Main Outcomes and Measures: The primary outcome was mean change in the number of days with moderate to extreme flushing during weeks 9 through 12, compared with the 4-week run-in period (baseline). The mean change in number of days with moderate to severe erythema was a secondary outcome. Adverse events were recorded for participants who received at least 1 dose of erenumab. Differences in means were calculated with a paired t test. Results: A total of 30 participants (mean [SD] age, 38.8 [13.1] years; 23 female [77%]; 7 male [23%]) were included, of whom 27 completed the 12-week study. The mean (SD) number of days with moderate to extreme flushing was reduced by -6.9 days (95% CI, -10.4 to -3.4 days; P < .001) from 23.6 (5.8) days at baseline. The mean (SD) number of days with moderate to severe erythema was reduced by -8.1 days (95% CI, -12.5 to -3.7 days; P < .001) from 15.2 (9.1) days at baseline. Adverse events included transient mild to moderate constipation (10 participants [33%]), transient worsening of flushing (4 participants [13%]), bloating (3 participants [10%]), and upper respiratory tract infections (3 participants [10%]), consistent with previous data. One participant discontinued the study due to a serious adverse event (hospital admission due to gallstones deemed unrelated to the study), and 2 participants withdrew consent due to lack of time. Conclusions and Relevance: These findings suggest that erenumab might be effective in reducing rosacea-associated flushing and chronic erythema (participants generally tolerated the treatment well, which was consistent with previous data), and that CGRP-receptor inhibition holds potential in the treatment of erythema and flushing associated with rosacea. Larger randomized clinical trials are needed to confirm this finding. Trial Registration: ClinicalTrials.gov Identifier: NCT04419259.

A randomized, controlled, split-face study of botulinum toxin and broadband light for the treatment of erythematotelangiectatic rosacea.

To study the efficacy and safety of botulinum toxin (BTX) combined with broadband light (BBL) in the treatment of rosacea-related erythema and flushing. A randomized, single-blind, split-face controlled study including 22 patients with erythemato telangiectatic rosacea were enrolled. Both cheeks were randomly divided into experimental group and control group. They were treated three times with an interval of 1 month. In the first treatment, the experimental group received BBL treatment and intradermal injection of BTX, and the control group received BBL treatment and intradermal injection of the same amount of normal saline; in the second and third treatments were both groups received the same BBL treatment. The patients were evaluated before the first treatment and 1, 2, 3, and 6 months after the treatment. Compared with the control group, the hydration in the experimental group increased and the global flushing symptom score (GFSS), VISIA red value, erythema index, transepidermal water loss, and sebum secretion decreased. The differences were statistically significant (p < 0.05). In the experimental group, at 3 months after the first treatment, compared with before treatment, the GFSS, VISIA red value, erythema index, transepidermal water loss and sebum secretion decreased the hydration increased. The sebum secretion returned to the pretreatment level in 6 months after treatment, and the other indexes maintained the level in 3 months after treatment. One patient had a slight lifting limitation of the corners of his mouth after 10 days of BTX injection, without special treatment, and recovered after 1 month. BTX intradermal injection combined with BBL has a definite therapeutic effect on the improvement of rosacea related erythema and flushing, which is better than simple BBL, and has high safety. It is worthy of clinical promotion.

Successful treatment of idiopathic Harlequin Syndrome with oxybutynin and propranolol.

Harlequin syndrome (HS) is a rare entity derived from the dysfunction of the sympathetic nervous system. It is characterised by unilateral facial flushing and sweating induced by exercise, heat and emotion. Most cases are primary with an unknown pathogenic mechanism. In these cases, the prognosis is favourable. Medical or surgical treatments are not usually required for idiopathic HS. However, symptomatic treatment may be indicated when symptoms affect the quality of life of patients. We present the case of a patient with idiopathic HS successfully treated with oxybutynin and propranolol. In this patient, a marked improvement in both hyperhidrosis and facial erythema was noted with this combined therapy. We consider it of interest to highlight the response of our patient to the treatment employed, which may be advantageous in future cases of this rare disorder.

Infusion of Pituitary Adenylate Cyclase-Activating Polypeptide-38 in Patients with Rosacea Induces Flushing and Facial Edema that Can Be Attenuated by Sumatriptan.

BACKGROUND: The pathogenesis of rosacea is incompletely understood. Signaling neuropeptides, including PACAP, a regulator of vasodilation and edema, are upregulated in rosacea skin. Here, we evaluated PACAP38-induced rosacea features and examined whether a 5-HT1B/1D receptor agonist could reduce these features. METHODS: A total of 35 patients with erythematotelangiectatic rosacea received an intravenous infusion of 10 pmol/kg/minute of PACAP38 followed by an intravenous infusion of 4 mg sumatriptan or placebo (saline) on two study days in a double-blind, randomized, placebo-controlled, and cross-over trial. RESULTS: PACAP38 increased facial skin blood flow by 90%, dilated the superficial temporal artery by 56%, and induced prolonged flushing and facial edema. Compared with placebo, sumatriptan reduced PACAP38-induced facial skin blood flow for 50 minutes (P = 0.023), constricted the superficial temporal artery for 80 minutes (P = 0.010), and reduced duration of flushing (P = 0.001) and facial edema (P < 0.001). CONCLUSIONS: We established a clinical experimental model of rosacea features and showed that sumatriptan was able to attenuate PACAP38-induced rosacea flushing and edema. Findings support a key role of PACAP38 in rosacea flushing pathogenesis. It remains unknown whether PACAP38 inhibition can improve rosacea. TRIAL REGISTER: The trial was registered at ClinicalTrials.govNCT03878784 in March 2019.

Facial flushing and erythema of rosacea improved by carvedilol.

Flushing and erythema are the most common symptoms of rosacea; however, management of these symptoms remains challenging. Recent case studies suggest that treatment with carvedilol may reduce facial flushing and persistent erythema in the pathogenesis of rosacea. To find the effect of carvedilol in the treatment of facial flushing and erythema in rosacea. Twenty-four rosacea patients treated with carvedilol for facial flushing and erythema were retrospectively reviewed. All patients were prescribed carvedilol 6.25 mg either once or twice per day, and the daily dose was gradually titrated up to 12.5 mg. Clinical erythema severity was assessed by the Clinician's Erythema Assessment (CEA) and Patient's Self-Assessment (PSA) scales. Improvement of CEA and PSA scores compared to the baseline were assessed. The proportion of patients with improvement of two or more points from baseline in CEA score was analyzed by sex, previous treatment exposure, disease duration, and subtypes. The mean change of -1.6 in the CEA score and of -1.8 in the PSA score showed significant improvement from baseline. Erythematotelangiectatic rosacea (ETR) patients achieved more than 2-points improvement in the CEA score, compared with non-ETR patients (53.8% vs 16.7% [P = .035]). No statistically significant differences were observed by sex, disease duration, or previous treatment exposure. No serious adverse event was observed. Carvedilol can be an effective and safe treatment option for rosacea patients suffering from facial flushing and erythema.

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.

Clinical Benefits of Telotristat Ethyl in Patients With Neuroendocrine Tumors and Low Bowel Movement Frequency: An Observational Patient-Reported Outcomes Study.

OBJECTIVES: We evaluated carcinoid syndrome (CS) symptoms and the real-world effectiveness of telotristat ethyl (TE) among patients with ≤3 bowel movements (BM) per day. METHODS: Patients with CS initiating TE between March and November 2017 could participate in a nurse support program collecting demographic and CS symptom data before TE initiation (baseline) and during ≥1 monthly follow-up within 3 months. Symptoms for patients averaging ≤3 BM/d at baseline were evaluated using pre/post-Student t tests. RESULTS: Sixty-eight patients reported ≤3 BM/d at baseline. Symptom burden was high and similar to participants with higher daily BM frequency. After 3 months of TE, most patients reported stable or improved symptoms with significant improvements in urgency (88%; mean [SD], -13.2 [32.2]), stool consistency (88%; -1.3 [2.0]), BMs per day (81%; -0.2 [1.2]), abdominal pain (86%; -13.7 [25.8]), nausea (85%; -30.9 [35.7]), and daily flushing episodes (83%; -1.7 [4.4]; all except BMs per day, P < 0.05). CONCLUSIONS: This analysis illustrates high CS symptom burden among patients with relatively low daily BM frequency. After initiating TE, patients reported significant improvements in urgency, stool consistency, abdominal pain, nausea, and flushing episodes. Clinicians and population health managers should consider CS symptom burden beyond daily BM frequency when evaluating treatment selection.

College students' use of strategies to hide facial flushing: A target for alcohol education.

OBJECTIVE: Alcohol-related facial flushing occurs in individuals who are unable to metabolize ethanol effectively and is associated with increased cancer risk. This study describes college students' understanding of the meaning of flushing for how much alcohol a person should drink and their use of over-the-counter medications and other strategies to reduce its visible effects. Participants: The sample includes 335 White and Asian college students who reported facial flushing after an alcoholic drink. Methods: Students completed an online survey in the spring of their junior year. Results: Most students reported that flushing had no special meaning for drinking or that they did not know what it meant. Six percent reported ever using strategies to hide facial flushing; they were mostly Asian, and those using these strategies drank more alcohol. Conclusions: Findings identify a need for targeted alcohol education with Asian college students who drink alcohol despite experiencing the flushing response.

The toxic edge-A novel treatment for refractory erythema and flushing of rosacea.

PURPOSE: Rosacea is a common, chronic facial skin disease that affects the quality of life. Treatment of facial erythema with intradermal botulinum toxin injection has previously been reported. The primary objective of the study was the safety and efficacy of thermal decomposition of the stratum corneum using a novel non-laser thermomechanical system (Tixel, Novoxel, Israel) to increase skin permeability for Botulinum toxin in the treatment of facial flushing of rosacea. METHODS: A retrospective review of16 patients aged 23-45 years with Fitzpatrick Skin Types II to IV and facial erythematotelangiectatic rosacea treated by Tixel followed by topical application of 100 U of abobotulinumtoxin. A standardized high-definition digital camera photographed the patients at baseline and 1, 3, and 6 months after the last treatment. Objective and subjective assessments of the patients were done via Mexameter, the Clinicians Erythema Assessment (CEA), and Patients self-assessment (PSA) scores and the dermatology life quality index (DLQI) validated instrument. RESULTS: The average Maxameter, CEA, and PSA scores at 1, 3, and 6 months were significantly improved compared with baseline (all had a P-value <0.001). DLQI scores significantly improved with an average score of 18.6 at baseline at 6 months after treatment (P < 0.001). Self-rated patient satisfaction was high. There were no motor function side-effects or drooping. CONCLUSION: Thermal breakage of the stratum corneum using the device to increase skin permeability for botulinum toxin type A in the treatment of facial flushing of rosacea seems both effective and safe. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Long-term management of distinct facial flushing and persistent erythema of rosacea by treatment with carvedilol.

BACKGROUND: The treatment of persistent erythema and flushing episodes in patients with rosacea remains a clinical challenge. A possible therapeutic option could be the use of antihypertensive drugs. OBJECTIVES: We therefore evaluated the effect of the non-selective ß-blocker carvedilol in five Caucasian patients. METHODS: In a monocentric retrospective case study, the patients were treated with carvedilol titrated up to 12.5 mg twice a day over at least six months. Patients self assessment (PSA), clinicians erythema assessment (CEA), and the patients levels of embarrassment and satisfaction were performed by questionaires. RESULTS: The CEA grade description as well as the PSA grade description decreased remarkably in all five patients. Furthermore, all patients reported to have a major improvement of their level of satisfaction and no feelings of embarrassment anymore. CONCLUSIONS: These findings demonstrate that facial flushing and persistent erythema can be effectively treated by carvedilol long-term with a fast onset of improvement in a dose well tolerated.

Therapeutic effects of flurbiprofen axetil on mesenteric traction syndrome: randomized clinical trial.

BACKGROUND: This study aimed to reveal the appropriate timing for the intravenous administration of flurbiprofen axetil for preventing mesenteric traction syndrome (MTS), caused by prostacyclin release. METHODS: In this prospective, randomized, clinical study, forty-five patients who were undergoing elective surgery for colorectal cancer via laparotomy were enrolled. Patients were randomly divided into 3 groups: a preoperative group (n = 16) receiving flurbiprofen axetil directly before surgery; a post-MTS group (n = 14) receiving following MTS onset; and a control group (n = 15) who were not administered flurbiprofen axetil. 6-keto-PGF1α, a stable metabolite of prostacyclin, levels were measured and mean blood pressures were recorded. RESULTS: In the preoperative group, 6-keto-PGF1α levels did not increase, blood pressure levels did not decrease, and no facial flushing was observed. In both the post-MTS and control groups, 6-keto-PGF1α levels increased markedly after mesenteric traction and blood pressure decreased significantly. The post-MTS group exhibited a faster decreasing trend in 6-keto-PGF1α levels and quick restore of the mean blood pressure, and the use of vasopressors and phenylephrine were lower than that in the control group. CONCLUSIONS: Even therapeutic administration of flurbiprofen axetil after the onset of MTS has also effects on MTS by suppressing prostacyclin production. TRIAL REGISTRATION: Clinical trial number: UMIN000009111 . (Registered 14 October 2012).

Cost reduction from resolution/improvement of carcinoid syndrome symptoms following treatment with above-standard dose of octreotide LAR.

AIMS: To calculate the cost reduction associated with diarrhea/flushing symptom resolution/improvement following treatment with above-standard dose octreotide-LAR from the commercial payor's perspective. MATERIALS AND METHODS: Diarrhea and flushing are two major carcinoid syndrome symptoms of neuroendocrine tumor (NET). Previously, a study of NET patients from three US tertiary oncology centers (NET 3-Center Study) demonstrated that dose escalation of octreotide LAR to above-standard dose resolved/improved diarrhea/flushing in 79% of the patients within 1 year. Time course of diarrhea/flushing symptom data were collected from the NET 3-Center Study. Daily healthcare costs were calculated from a commercial claims database analysis. For the patient cohort experiencing any diarrhea/flushing symptom resolution/improvement, their observation period was divided into days of symptom resolution/improvement or no improvement, which were then multiplied by the respective daily healthcare cost and summed over 1 year to yield the blended mean annual cost per patient. For patients who experienced no diarrhea/flushing symptom improvement, mean annual daily healthcare cost of diarrhea/flushing over a 1-year period was calculated. RESULTS: The economic model found that 108 NET patients who experienced diarrhea/flushing symptom resolution/improvement within 1 year had statistically significantly lower mean annual healthcare cost/patient than patients with no symptom improvement, by $14,766 (p = .03). For the sub-set of 85 patients experiencing resolution/improvement of diarrhea, their cost reduction was more pronounced, at $18,740 (p = .01), statistically significantly lower than those with no improvement; outpatient costs accounted for 56% of the cost reduction (p = .02); inpatient costs, emergency department costs, and pharmacy costs accounted for the remaining 44%. LIMITATIONS: The economic model relied on two different sources of data, with some heterogeneity in the prior treatment and disease status of patients. CONCLUSIONS: Symptom resolution/improvement of diarrhea/flushing after treatment with an above-standard dose of octreotide-LAR in NET was associated with a statistically significant healthcare cost decrease compared to a scenario of no symptom improvement.

Efficacy and safety of APT198K for the treatment of infantile colic: a pilot study.

AIM: Comparing efficacy and safety of APT198K (xyloglucan plus heat-killed Lactobacillus reuteri SGL01 and Bifidobacterium brevis SGB01) versus a lactase dietary supplement as first-line treatment of infantile colic. METHODS: Randomized, multicenter, open-label, parallel group, active-controlled study, in 46 infants aged 3-16 weeks with infantile colic, receiving APT198K or a lactase dietary supplement for 10 days. RESULTS: Number and duration of crying episodes decreased significantly versus baseline in both groups. On day 8, the mean duration of crying per episode was significantly shorter in the APT198K group compared with the lactase group (9.14 ± 5.34 vs 13.22 ± 5.29 min; p = 0.014) and remained so up to day 11. CONCLUSION: APT198K decreased the mean duration per crying episode significantly more than a lactase dietary supplement in infants with colic. Further evaluation in larger studies is warranted. Clinical trial registry: EudraCT number 2014-002860-334; https://eudract.ema.europa.eu .

Botulinum Toxin A in Treatment of Facial Flushing.

Flushing is a condition with episodic attacks of redness of the skin with a sensation of warmth or burning, this disease causes emotional and functional problems in patients. There is various treatments for this condition; one of them is the use of botulinum toxin-A (BTA). In this prospective pilot study we studied the effect of Botulinum toxin-A (BTA) effect on DLQI of patients with facial flushing, we compared the DLQI before and after treatment. The number of 24 women with facial flushing admitted to the department of dermatology of Hamadan Farshchian Hospital, with the age range of 18 to 60 was enrolled in the study. Patients completed Dermatology Quality of life Index questionnaire before and one month after treatment. In our study 1 unit of BTA was injected intracutaneously per square cm in both sides of cheeks, to a total dose of 30 units per session. All of 24 patients completed the study. The mean age was 37.79±13.13. In all patients, DLQI decreased, and in two months follow up, the mean of DLQI improved from 8.08±1.17 to 4.5±1.21 (P.value<0.005). Based on this study BTA is an effective and safe treatment for facial flushing.

The efficacy of oral anticholinergics for sympathetic overactivity in a thoracic surgery clinic.

OBJECTIVE: Little is known of the success rates of oral anticholinergics for the treatment of primary hyperhidrosis and facial blushing as alternatives to surgical intervention. We examine predictors of success with these medications. METHODS: A retrospective review was performed at a single institution, including all patients presenting with symptoms of primary hyperhidrosis, facial blushing, or both from 2004 to 2015. All patients were offered a trial of oral anticholinergics. If oral anticholinergic therapy was not successful, patients were offered surgery. Statistical analyses were performed to compare patients who declined surgery given the trial of oral anticholinergics with those who proceeded with surgery. RESULTS: A total of 381 patients presented with symptoms of primary hyperhidrosis (86.6%), facial blushing (2.4%), or both (11.0%). A total of 230 patients (60.4%) declined surgery after using oral anticholinergics, and 151 patients (39.6%) chose surgery. Patients who declined surgery were more likely to have symptoms of primary hyperhidrosis without facial blushing (89.6% vs 82.1%; P = .02) or have primary symptoms involving the axilla, torso, scalp, or groin. Patients who proceeded with surgery had higher rates of palmar symptoms as a primary site (77.6% vs 61.1%; P = .01) and were more likely to have facial blushing alone or in combination with primary hyperhidrosis. Presentation with palmar symptoms and greater number of prior therapy attempts were independent predictors of proceeding with surgery after controlling for concomitant symptom type and location (P = .01 and P < .0001, respectively). CONCLUSIONS: The majority of patients presenting with sympathetic overactivity decline surgery when a trial of oral anticholinergics is included in the treatment algorithm. Facial blushing and palmar symptoms were each associated with choosing surgery.

Pharmacologic Therapies in Women's Health: Contraception and Menopause Treatment.

Female hormones play a significant role in the etiology and treatment of many women's health conditions. This article focuses on the common uses of hormonal therapy. When prescribing estrogen-containing regimens throughout the span of a woman's life, the risks are similar (ie, cardiovascular risk and venous thromboembolism), but the degree of risk varies significantly depending on a woman's particular set of risk factors and the details of the hormone regimen. In addition to estrogens and progestogens, this article also touches on the use of selective steroid receptor modulators in emergency contraception and in treatment of menopause symptoms.