Pronounced facial flushing and persistent erythema of rosacea effectively treated by carvedilol, a nonselective β-adrenergic blocker

To the Editor: Rosacea is a common facial disorder characterized by centrofacial erythema, flushing, telangiectasia, edema, papules, and pustules.1Crawford G.H. Pelle M.T. James W.D. Rosacea, I: etiology, pathogenesis, and subtype classification.J Am Acad Dermatol. 2004; 51: 327-341Abstract Full Text Full Text PDF PubMed Scopus (456) Google Scholar, 2Wilkin J. Dahl M. Detmar M. Drake L. Liang MH. Odom R. Powell F. Standard grading system for rosacea: report of the National Rosacea Society expert committee on the classification and staging of rosacea.J Am Acad Dermatol. 2004; 50: 907-912Abstract Full Text Full Text PDF PubMed Scopus (348) Google Scholar Treatment of erythematotelangiectatic rosacea (ETR) with severe facial flushing and persistent erythema remains challenging despite some successes with β-adrenergic blockers,3Craige H. Cohen J.B. Symptomatic treatment of idiopathic and rosacea associated cutaneous flushing with propranolol.J Am Acad Dermatol. 2005; 53: 881-884Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar clonidine (α-adrenergic agonist), naloxone (opiate antagonist), ondansetron (serotonin antagonist), and endoscopic thoracic sympathectomy. Traditional β-blockers nadolol and propranolol (20-40 mg, 2-3 times a day)3Craige H. Cohen J.B. Symptomatic treatment of idiopathic and rosacea associated cutaneous flushing with propranolol.J Am Acad Dermatol. 2005; 53: 881-884Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar can suppress flushing reactions, but the side effects of hypotension and bradycardia may pose problems because most patients are normotensive. Carvedilol, a nonselective β-adrenergic blocker with α1 blocking activity and potent antioxidant activity, is indicated in treating mild to moderate congestive heart failure. We have recently reported a case of refractory ETR successfully treated with carvedilol.4Hsu C.C. Lee J.Y. Carvedilol for the treatment of refractory facial flushing and persistent erythema of rosacea.Arch Dermatol. 2011; 147: 1258-1260Crossref PubMed Scopus (37) Google Scholar In this report, we present the results of carvedilol therapy in a case series.Altogether there were 11 normotensive patients, 9 female and 2 male, ages 17 to 47 years, mean 34.5 years (clinical summary in Table I). They had been treated unsuccessfully with doxycycline, corticosteroids, propranolol, clonidine, ondansetron, metronidazole, tacrolimus and pimecrolimus, endoscopic thoracic sympathectomy, stellate ganglion block, and pulsed dye laser therapy in various combinations. Patient 6 was the subject of our earlier report.4Hsu C.C. Lee J.Y. Carvedilol for the treatment of refractory facial flushing and persistent erythema of rosacea.Arch Dermatol. 2011; 147: 1258-1260Crossref PubMed Scopus (37) Google ScholarTable IDiagnosis, treatment, efficacy, and side effects of 11 patients with erythematotelangiectatic rosacea treated with carvedilolPatient no.DiagnosisSystemic drugs before adding carvedilolCarvedilol dosageCheek/ear temperature change after carvedilol, °CFacial erythema∗Severity of facial erythema: 5+ (very severe); 4+ (severe); 3+ (moderate); 2+ (mild); 1+ (minimal); 0 (none)./VAS†10-point VAS score of patient's self-assessment of overall symptom severity (10 for maximal severity). reduction after carvedilolOnset of effect, dSide effectsTreatment duration1Rosacea with acne vulgarisDoxycycline, fexofenadine3.125 mg bid × 1 wk, then 6.25 mg bid−1.3/−0.1Erythema 4+→1+/VAS 8→47None3 mo2Rosacea, possibly with Ofuji diseaseDoxycycline, fexofenadine, prednisolone6.25 mg bid−0.6/Not doneErythema 3+→1+7None4 mo3RosaceaNone3.125 mg bid × 1 wk, then 6.25 mg bid+0.4/+0.9Erythema 2+→0/VAS 7→014None3 mo4RosaceaNone3.125 mg bid−1.9/0Erythema 4+→1+3Mild hypotension3 d, then discontinued5RosaceaDoxycycline, prednisolone6.25 mg bid−0.3/Not doneErythema 3+→1+7None1 wk6RosaceaDoxycycline, dexamethasone6.25 mg bid × 1 wk, then tid−6.9/−0.5Erythema 5+→1+/VAS 10→114None28 mo; 13.5 mg/d7RosaceaNone3.125 mg bid−2.8/+0.7Erythema 3+→1+7None1 mo8RosaceaPrednisolone, fexofenadine3.125 mg bid × 3 wk, then 6.25 mg bid−2.4/−1.2Erythema 4+→1+/VAS 10→421None3 mo9RosaceaDoxycycline, dexamethasone, ibuprofen6.25 mg bid × 1 wk, then tid × 1 wk, then gradually up to 12.5 mg, 12.5 mg, 6.25 mg tid−0.8/Not doneErythema 3+→1+/VAS 10→314None27 mo; 31.25 mg/d10RosaceaNone6.25 mg bid × 1 wk, then tid−1.2/−0.3 (Forehead)Erythema 3+→1+/VAS 8→27None5 mo; 13.5 mg/d11RosaceaDoxycycline, dexamethasone, levocetirizine3.125 mg tid × 2 wk, then 6.25 mg tid × 6 wk, then 12.5 mg, 6.25 mg, 6.25 mg tid−7.4/+0.3 (Forehead)Erythema 4+→1+/VAS 6→114None6 mo; 25 mg/dbid, Twice a day; tid, 3 times a day; VAS, visual analog scale.∗ Severity of facial erythema: 5+ (very severe); 4+ (severe); 3+ (moderate); 2+ (mild); 1+ (minimal); 0 (none).† 10-point VAS score of patient's self-assessment of overall symptom severity (10 for maximal severity). Open table in a new tab During the carvedilol therapy, we monitored the severity of facial erythema (based on clinical photographs), cheek temperature, patient's assessment of the symptom severity using a 10-point visual analog scale (score 0-10), and the side effects. Carvedilol (3.125-6.25 mg, 2-3 times a day) was added to each patient's other current medications and the daily dose was titrated gradually up to 31.25 mg/d (Table I). All patients experienced significant clinical improvement within 3 weeks (range 3-21 days, mean 10.5 days), with a mean reduction of 2.2°C of the cheek temperature and a mean reduction of 6.3 of the visual analog scale score (recorded for 7 patients). Fig 1 illustrates the clinical course of 1 patient (patient 11). Our study demonstrated that low-dose carvedilol was effective in treating ETR with rapid onset of symptom control. Moreover, it also allowed other concurrent medications to be tapered or stopped. The side effect was minimal; only 1 patient discontinued treatment because of asymptomatic hypotension. These results are encouraging, but further prospective controlled studies of carvedilol therapy for ETR are warranted to determine the optimal dosage, treatment duration, long-term therapeutic effects, and side effects.Nonselective β-blockers may cause reduction of cardiac contraction and heart rate (via blocking the β1-adrenergic receptor of the heart) as well as vasoconstriction of the cutaneous arterial blood vessels (via blocking the arterial β2-adrenergic receptor). Carvedilol and its metabolites are potent antioxidants, approximately 10 to 100 times more potent than α-tocopherol (vitamin E).5Arumanayagam M. Chan S. Tong S. Sanderson J.E. Antioxidant properties of carvedilol and metoprolol in heart failure: a double-blind randomized controlled trial.J Cardiovasc Pharmacol. 2001; 37: 48-54Crossref PubMed Scopus (79) Google Scholar Carvedilol appears special among β-blockers in its significant antioxidant and anti-inflammatory properties, which may explain its efficacy in treating ETR in the current study.Our study is a retrospective analysis and the number of patients is relatively small. More prospective studies, with larger series and comparative studies with a traditional β-blocker, such as propranolol, are necessary to evaluate the effects of carvedilol therapy in ETR. To the Editor: Rosacea is a common facial disorder characterized by centrofacial erythema, flushing, telangiectasia, edema, papules, and pustules.1Crawford G.H. Pelle M.T. James W.D. Rosacea, I: etiology, pathogenesis, and subtype classification.J Am Acad Dermatol. 2004; 51: 327-341Abstract Full Text Full Text PDF PubMed Scopus (456) Google Scholar, 2Wilkin J. Dahl M. Detmar M. Drake L. Liang MH. Odom R. Powell F. Standard grading system for rosacea: report of the National Rosacea Society expert committee on the classification and staging of rosacea.J Am Acad Dermatol. 2004; 50: 907-912Abstract Full Text Full Text PDF PubMed Scopus (348) Google Scholar Treatment of erythematotelangiectatic rosacea (ETR) with severe facial flushing and persistent erythema remains challenging despite some successes with β-adrenergic blockers,3Craige H. Cohen J.B. Symptomatic treatment of idiopathic and rosacea associated cutaneous flushing with propranolol.J Am Acad Dermatol. 2005; 53: 881-884Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar clonidine (α-adrenergic agonist), naloxone (opiate antagonist), ondansetron (serotonin antagonist), and endoscopic thoracic sympathectomy. Traditional β-blockers nadolol and propranolol (20-40 mg, 2-3 times a day)3Craige H. Cohen J.B. Symptomatic treatment of idiopathic and rosacea associated cutaneous flushing with propranolol.J Am Acad Dermatol. 2005; 53: 881-884Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar can suppress flushing reactions, but the side effects of hypotension and bradycardia may pose problems because most patients are normotensive. Carvedilol, a nonselective β-adrenergic blocker with α1 blocking activity and potent antioxidant activity, is indicated in treating mild to moderate congestive heart failure. We have recently reported a case of refractory ETR successfully treated with carvedilol.4Hsu C.C. Lee J.Y. Carvedilol for the treatment of refractory facial flushing and persistent erythema of rosacea.Arch Dermatol. 2011; 147: 1258-1260Crossref PubMed Scopus (37) Google Scholar In this report, we present the results of carvedilol therapy in a case series. Altogether there were 11 normotensive patients, 9 female and 2 male, ages 17 to 47 years, mean 34.5 years (clinical summary in Table I). They had been treated unsuccessfully with doxycycline, corticosteroids, propranolol, clonidine, ondansetron, metronidazole, tacrolimus and pimecrolimus, endoscopic thoracic sympathectomy, stellate ganglion block, and pulsed dye laser therapy in various combinations. Patient 6 was the subject of our earlier report.4Hsu C.C. Lee J.Y. Carvedilol for the treatment of refractory facial flushing and persistent erythema of rosacea.Arch Dermatol. 2011; 147: 1258-1260Crossref PubMed Scopus (37) Google Scholar bid, Twice a day; tid, 3 times a day; VAS, visual analog scale. During the carvedilol therapy, we monitored the severity of facial erythema (based on clinical photographs), cheek temperature, patient's assessment of the symptom severity using a 10-point visual analog scale (score 0-10), and the side effects. Carvedilol (3.125-6.25 mg, 2-3 times a day) was added to each patient's other current medications and the daily dose was titrated gradually up to 31.25 mg/d (Table I). All patients experienced significant clinical improvement within 3 weeks (range 3-21 days, mean 10.5 days), with a mean reduction of 2.2°C of the cheek temperature and a mean reduction of 6.3 of the visual analog scale score (recorded for 7 patients). Fig 1 illustrates the clinical course of 1 patient (patient 11). Our study demonstrated that low-dose carvedilol was effective in treating ETR with rapid onset of symptom control. Moreover, it also allowed other concurrent medications to be tapered or stopped. The side effect was minimal; only 1 patient discontinued treatment because of asymptomatic hypotension. These results are encouraging, but further prospective controlled studies of carvedilol therapy for ETR are warranted to determine the optimal dosage, treatment duration, long-term therapeutic effects, and side effects. Nonselective β-blockers may cause reduction of cardiac contraction and heart rate (via blocking the β1-adrenergic receptor of the heart) as well as vasoconstriction of the cutaneous arterial blood vessels (via blocking the arterial β2-adrenergic receptor). Carvedilol and its metabolites are potent antioxidants, approximately 10 to 100 times more potent than α-tocopherol (vitamin E).5Arumanayagam M. Chan S. Tong S. Sanderson J.E. Antioxidant properties of carvedilol and metoprolol in heart failure: a double-blind randomized controlled trial.J Cardiovasc Pharmacol. 2001; 37: 48-54Crossref PubMed Scopus (79) Google Scholar Carvedilol appears special among β-blockers in its significant antioxidant and anti-inflammatory properties, which may explain its efficacy in treating ETR in the current study. Our study is a retrospective analysis and the number of patients is relatively small. More prospective studies, with larger series and comparative studies with a traditional β-blocker, such as propranolol, are necessary to evaluate the effects of carvedilol therapy in ETR.