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Dermatology Online Journal Jul 2021Exacerbation of rosacea may occur during pregnancy and there are multiple associated cases of rosacea fulminans (RF). Treatment during pregnancy poses a significant... (Review)
Review
BACKGROUND
Exacerbation of rosacea may occur during pregnancy and there are multiple associated cases of rosacea fulminans (RF). Treatment during pregnancy poses a significant challenge as many rosacea treatments are contraindicated or have limited evidence regarding potential adverse fetal effects.
OBJECTIVE
Review the pregnancy categories of various treatments and develop algorithms for treating pregnant patients with rosacea and RF.
METHODS
Rosacea treatments showing efficacy in randomized controlled trials were searched through DailyMed to review pregnancy labelling. Searching the PubMed/MEDLINE database for English articles using keywords "rosacea fulminans AND pregnancy" without publishing-time restrictions yielded 8 articles. We summarized treatments used in cases of RF during pregnancy.
RESULTS
Topical ivermectin was more effective than metronidazole, but has a more concerning pregnancy category. Three pregnant women with RF were treated successfully with topical metronidazole in combination with other therapies. Azithromycin is the only oral rosacea therapy that is considered safe for pregnant patients and it has been used to treat RF.
CONCLUSIONS
This review highlights the challenging aspects of treating pregnant patients with rosacea, as there is limited pregnancy-related treatment efficacy and safety data. The pregnancy categories of therapeutic options are summarized. Further studies are needed to learn which therapies are effective and safe for use during pregnancy.
Topics: Adult; Algorithms; Animals; Anti-Bacterial Agents; Azithromycin; Brimonidine Tartrate; Dermatologic Agents; Dicarboxylic Acids; Doxycycline; Female; Humans; Isotretinoin; Ivermectin; Metronidazole; Mice; Minocycline; Phototherapy; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Rosacea; Tetracyclines; Treatment Outcome
PubMed: 34391325
DOI: 10.5070/D327754360 -
Skin Therapy Letter Jul 2021The diagnosis and classification of rosacea has been modified to reflect presenting features. On exclusion of differentials, the diagnosis of rosacea is based on the...
The diagnosis and classification of rosacea has been modified to reflect presenting features. On exclusion of differentials, the diagnosis of rosacea is based on the presence of either (1) phymatous changes, or (2) centrofacial persistent erythema. In their absence, diagnosis can be established by presence of any two of: flushing/transient erythema, papules and pustules, telangiectases, or ocular manifestations. Management of rosacea depends on presenting feature(s), their severity, and impact. General management includes gentle skin care, sun protection, and trigger avoidance. Evidence-based treatment recommendations include topical brimonidine and oxymetazoline for persistent erythema; topical azelaic acid, ivermectin, metronidazole, minocycline and oral doxycycline, tetracycline and isotretinoin for papules and pustules; vascular lasers and light devices for telangiectases; and omega-3 fatty acids and cyclosporine ophthalmic emulsion for ocular rosacea. While surgical or laser therapy can be considered for clinically noninflamed phyma, there are no trials on their utility. Combination therapies include topical brimonidine with topical ivermectin, or topical metronidazole with oral doxycycline. Topical metronidazole, topical ivermectin, and topical azelaic acid are appropriate for maintenance therapy. In conclusion, the updated phenotype approach, based on presenting clinical features, is the foundation for current diagnosis, classification, and treatment of rosacea.
Topics: Brimonidine Tartrate; Dermatologic Agents; Doxycycline; Humans; Metronidazole; Rosacea
PubMed: 34347259
DOI: No ID Found -
The Cochrane Database of Systematic... Apr 2015Rosacea is a common chronic skin condition affecting the face, characterised by flushing, redness, pimples, pustules and dilated blood vessels. The eyes are often... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rosacea is a common chronic skin condition affecting the face, characterised by flushing, redness, pimples, pustules and dilated blood vessels. The eyes are often involved and thickening of the skin with enlargement (phymas), especially of the nose, can occur in some people. A range of treatment options are available but it is unclear which are most effective.
OBJECTIVES
To assess the efficacy and safety of treatments for rosacea.
SEARCH METHODS
We updated our searches, to July 2014, of: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974) and Science Citation Index (from 1988). We searched five trials registers and checked reference lists for further relevant studies.
SELECTION CRITERIA
Randomised controlled trials in people with moderate to severe rosacea.
DATA COLLECTION AND ANALYSIS
Study selection, data extraction, risk of bias assessment and analyses were carried out independently by two authors.
MAIN RESULTS
We included 106 studies, comprising 13,631 participants. Sample sizes of 30-100 and study duration of two to three months were most common. More women than men were included, mean age of 48.6 years, and the majority had papulopustular rosacea, followed by erythematotelangiectatic rosacea.A wide range of comparisons (67) were evaluated. Topical interventions: metronidazole, azelaic acid, ivermectin, brimonidine or other topical treatments. Systemic interventions: oral antibiotics, combinations with topical treatments or other systemic treatments, i.e. isotretinoin. Several studies evaluated laser or light-based treatment.The majority of studies (57/106) were assessed as 'unclear risk of bias', 37 'high risk ' and 12 'low risk'. Twenty-two studies provided no usable or retrievable data i.e. none of our outcomes were addressed, no separate data reported for rosacea or limited data in abstracts.Eleven studies assessed our primary outcome 'change in quality of life', 52 studies participant-assessed changes in rosacea severity and almost all studies addressed adverse events, although often only limited data were provided. In most comparisons there were no statistically significant differences in number of adverse events, most were mild and transient. Physician assessments including investigators' global assessments, lesion counts and erythema were evaluated in three-quarters of the studies, but time needed for improvement and duration of remission were incompletely or not reported.The quality of the body of evidence was rated moderate to high for most outcomes, but for some outcomes low to very low.Data for several outcomes could only be pooled for topical metronidazole and azelaic acid. Both were shown to be more effective than placebo in papulopustular rosacea (moderate quality evidence for metronidazole and high for azelaic acid). Pooled data from physician assessments in three trials demonstrated that metronidazole was more effective compared to placebo (risk ratio (RR) 1.98, 95% confidence interval (CI) 1.29 to 3.02). Four trials provided data on participants' assessments, illustrating that azelaic acid was more effective than placebo (RR 1.46, 95% CI 1.30 to 1.63). The results from three studies were contradictory on which of these two treatments was most effective.Two studies showed a statistically significant and clinically important improvement in favour of topical ivermectin when compared to placebo (high quality evidence). Participants' assessments in these studies showed a RR of 1.78 (95% CI 1.50 to 2.11) and RR of 1.92 (95% CI 1.59 to 2.32),which were supported by physicians' assessments. Topical ivermectin appeared to be slightly more effective than topical metronidazole for papulopustular rosacea, based on one study, for improving quality of life and participant and physician assessed outcomes (high quality evidence for these outcomes).Topical brimonidine in two studies was more effective than vehicle in reducing erythema in rosacea at all time points over 12 hours (high quality evidence). At three hours the participants' assessments had a RR of 2.21 (95% CI 1.52 to 3.22) and RR of 2.00 (95% CI 1.33 to 3.01) in favour of brimonidine. Physicians' assessments confirmed these data. There was no rebound or worsening of erythema after treatment cessation.Topical clindamycin phosphate combined with tretinoin was not considered to be effective compared to placebo (moderate quality evidence).Topical ciclosporin ophthalmic emulsion demonstrated effectiveness and improved quality of life for people with ocular rosacea (low quality evidence).Of the comparisons assessing oral treatments for papulopustular rosacea there was moderate quality evidence that tetracycline was effective but this was based on two old studies of short duration. Physician-based assessments in two trials indicated that doxycycline appeared to be significantly more effective than placebo (RR 1.59, 95% CI 1.02 to 2.47 and RR 2.37, 95% CI 1.12 to 4.99) (high quality evidence). There was no statistically significant difference in effectiveness between 100 mg and 40 mg doxycycline, but there was evidence of fewer adverse effects with the lower dose (RR 0.25, 95% CI 0.11 to 0.54) (low quality evidence). There was very low quality evidence from one study (assessed at high risk of bias) that doxycycline 100 mg was as effective as azithromycin. Low dose minocycline (45 mg) was effective for papulopustular rosacea (low quality evidence).Oral tetracycline was compared with topical metronidazole in four studies and showed no statistically significant difference between the two treatments for any outcome (low to moderate quality evidence).Low dose isotretinoin was considered by both the participants (RR 1.23, 95% CI 1.05 to 1.43) and physicians (RR 1.18, 95% CI 1.03 to 1.36) to be slightly more effective than doxycycline 50-100 mg (high quality evidence).Pulsed dye laser was more effective than yttrium-aluminium-garnet (Nd:YAG) laser based on one study, and it appeared to be as effective as intense pulsed light therapy (both low quality evidence).
AUTHORS' CONCLUSIONS
There was high quality evidence to support the effectiveness of topical azelaic acid, topical ivermectin, brimonidine, doxycycline and isotretinoin for rosacea. Moderate quality evidence was available for topical metronidazole and oral tetracycline. There was low quality evidence for low dose minocycline, laser and intense pulsed light therapy and ciclosporin ophthalmic emulsion for ocular rosacea. Time needed to response and response duration should be addressed more completely, with more rigorous reporting of adverse events. Further studies on treatment of ocular rosacea are warranted.
Topics: Anti-Infective Agents; Brimonidine Tartrate; Cyclosporine; Dermatologic Agents; Dicarboxylic Acids; Doxycycline; Female; Humans; Ivermectin; Male; Metronidazole; Middle Aged; Ophthalmic Solutions; Quinoxalines; Randomized Controlled Trials as Topic; Rosacea; Tetracycline
PubMed: 25919144
DOI: 10.1002/14651858.CD003262.pub5 -
The British Journal of Dermatology Jul 2019Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping.
BACKGROUND
Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping.
OBJECTIVES
To update our systematic review on interventions for rosacea.
METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index and ongoing trials registers (March 2018) for randomized controlled trials. Study selection, data extraction, risk-of-bias assessment and analyses were carried out independently by two authors. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess certainty of evidence.
RESULTS
We included 152 studies (46 were new), comprising 20 944 participants. Topical interventions included brimonidine, oxymetazoline, metronidazole, azelaic acid, ivermectin and other topical treatments. Systemic interventions included oral antibiotics, combinations with topical treatments or other systemic treatments. Several studies evaluated laser or light-based treatment. We present the most current evidence for rosacea management based on a phenotype-led approach.
CONCLUSIONS
For reducing temporarily persistent erythema there was high-certainty evidence for topical brimonidine and moderate certainty for topical oxymetazoline; for erythema and mainly telangiectasia there was low-to-moderate-certainty evidence for laser and intense pulsed light therapy. For reducing papules/pustules there was high-certainty evidence for topical azelaic acid and topical ivermectin; moderate-to-high-certainty evidence for doxycycline 40 mg modified release (MR) and isotretinoin; and moderate-certainty evidence for topical metronidazole, and topical minocycline and oral minocycline being equally effective as doxycycline 40 mg MR. There was low-certainty evidence for tetracycline and low-dose minocycline. For ocular rosacea, there was moderate-certainty evidence that oral omega-3 fatty acids were effective and low-certainty evidence for ciclosporin ophthalmic emulsion and doxycycline.
Topics: Administration, Cutaneous; Administration, Oral; Anti-Bacterial Agents; Brimonidine Tartrate; Combined Modality Therapy; Dermatologic Agents; Dermatology; Drug Therapy, Combination; Evidence-Based Medicine; Facial Dermatoses; Humans; Intense Pulsed Light Therapy; Low-Level Light Therapy; Oxymetazoline; Randomized Controlled Trials as Topic; Rosacea; Severity of Illness Index; Treatment Outcome
PubMed: 30585305
DOI: 10.1111/bjd.17590 -
Scientific Reports Apr 2023This multicenter (four institutions), randomized, investigator-masked, parallel-group clinical trial evaluated and compared the efficacy and safety of preservative-free... (Randomized Controlled Trial)
Randomized Controlled Trial
This multicenter (four institutions), randomized, investigator-masked, parallel-group clinical trial evaluated and compared the efficacy and safety of preservative-free and preserved brimonidine tartrate 0.15% in open-angle glaucoma and ocular hypertension. Sixty eyes of 60 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomized to preserved (n = 31) and preservative-free (n = 29) brimonidine groups. The enrolled eyes received brimonidine monotherapy three times daily. Main outcome measures were corneal/conjunctival staining score, ocular surface disease index, patient satisfaction score, drug tolerance, and drug adherence rate 12 weeks post first administration. Secondary outcome measurements included visual acuity, IOP, drug tolerance, tear-film break-up time, hemodynamic changes including blood pressure and heart rates, and ocular adverse events. After 12 weeks, both preserved and preservative-free groups showed similar IOP reduction, corneal and conjunctival staining scores, drug tolerance, and adherence rates. The preservative-free group showed significantly better tear-film break-up time and higher patient satisfaction regarding drug use and management. Systolic and diastolic blood pressure reductions during the 12 weeks were significantly lower in the preserved group than in the preservative-free group. Preservative-free brimonidine tartrate showed comparable efficacy and safety, better corneal tear film stability, and patient satisfaction than preserved brimonidine.
Topics: Humans; Brimonidine Tartrate; Glaucoma, Open-Angle; Quinoxalines; Glaucoma; Ocular Hypertension; Intraocular Pressure; Preservatives, Pharmaceutical; Treatment Outcome; Antihypertensive Agents; Double-Blind Method; Ophthalmic Solutions
PubMed: 37029145
DOI: 10.1038/s41598-023-31726-1 -
Australian Family Physician 2017Rosacea is a chronic and common cutaneous condition characterised by symptoms of facial flushing and a broad spectrum of clinical signs. The clinical presentation for...
BACKGROUND
Rosacea is a chronic and common cutaneous condition characterised by symptoms of facial flushing and a broad spectrum of clinical signs. The clinical presentation for rosacea is varied, and there are four primary subtypes, which may overlap - erythrotelangiectatic, inflammatory, phymatous and ocular. It is important to recognise the different subtypes because of the differences in therapy.
OBJECTIVE
The objective of this article is to provide evidence-based clinical updates to clinicians, specifically general practitioners (GPs), to assist with their everyday practice, and effective assessment and treatment of rosacea.
DISCUSSION
Therapeutic modalities are chosen on the basis of the subtypes and clinical features identified; often a combination of these therapies is required.
Topics: Anti-Bacterial Agents; Brimonidine Tartrate; Diagnosis, Differential; Doxycycline; Humans; Isotretinoin; Ivermectin; Laser Therapy; Metronidazole; Rosacea
PubMed: 28472572
DOI: No ID Found -
Skin Appendage Disorders Sep 2016Rosacea is a chronic inflammatory skin condition associated with four distinct subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. (Review)
Review
BACKGROUND
Rosacea is a chronic inflammatory skin condition associated with four distinct subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular.
PURPOSE
To review the different kinds of management for all subtypes.
METHODS
We divided rosacea management into three main categories: patient education, skin care, and pharmacological/procedural interventions.
RESULTS
Flushing is better prevented rather than treated, by avoiding specific triggers, decreasing transepidermal water loss by moisturizers, and blocking ultraviolet light. Nonselective β-blockers and α-adrenergic agonists decrease erythema and flushing. The topical α-adrenergic receptor agonist brimonidine tartrate 0.5% reduces persistent facial erythema. Intradermal botulinum toxin injection is almost safe and effective for the erythema and flushing. Flashlamp-pumped dye, potassium-titanyl-phosphate and pulsed-dye laser, and intense pulsed light are used for telangiectasias. Metronidazole 1% and azelaic acid 15% cream reduce the severity of erythema. Both systemic and topical remedies treat papulopustules. Systemic remedies include metronidazole, doxycycline, minocycline, clarithromycin and isotretinoin, while topical remedies are based on metronidazole 0.75%, azelaic acid 15 or 20%, sodium sulfacetamide, ivermectin 1%, permethrin 5%, and retinoid. Ocular involvement can be treated with oral or topical antibacterial. Rhinophyma can be corrected by dermatosurgical procedures, decortication, and various types of lasers.
CONCLUSION
There are many options for rosacea management. Patients may have multiple subtypes, and each phase has its own treatment.
PubMed: 27843919
DOI: 10.1159/000446215 -
Clinical, Cosmetic and Investigational... 2015Rosacea is a chronic cutaneous condition with a prevalence rate ranging from 9.6% to 22% in recent studies. Facial erythema (transient and permanent) is considered a... (Review)
Review
Rosacea is a chronic cutaneous condition with a prevalence rate ranging from 9.6% to 22% in recent studies. Facial erythema (transient and permanent) is considered a common denominator that is frequently observed in all subtypes of rosacea and is estimated to affect more than 40 million people worldwide. Brimonidine tartrate is a selective α2-adrenergic receptor agonist and is the first topical treatment approved for facial erythema of rosacea. Clinical trials have demonstrated that brimonidine tartrate provided significantly greater efficacy, compared to vehicle, for the treatment of moderate to severe erythema of rosacea. In addition, brimonidine tartrate has demonstrated a rapid onset of effect, duration of action throughout the day, and good safety profile in studies of up to 1 year. This review critically discusses the role of brimonidine tartrate for the treatment of facial erythema of rosacea by examining both clinical study data and real-world dermatologist experiences across a wide spectrum of treated patients, and concludes that it is a significant therapeutic option in the management of an unmet need of this chronic condition.
PubMed: 26566370
DOI: 10.2147/CCID.S58920 -
Pharmaceuticals (Basel, Switzerland) Jan 2023Brimonidine tartrate (BRT) is a highly selective α2 adrenergic receptor agonist as treatment for patients with open angle glaucoma and high intraocular pressure. The...
Brimonidine tartrate (BRT) is a highly selective α2 adrenergic receptor agonist as treatment for patients with open angle glaucoma and high intraocular pressure. The objective of this study was to formulate an ophthalmic ion-sensitive in situ gel (ISG) of BRT to increase the retention time of the drug and its bioavailability. The optimum formulation of 2 mg/mL BRT-ISG was obtained with 0.45% gellan gum as the gel matrix. In vitro release results showed that the water-soluble drug bromonidine tartrate in ocular in situ gels exhibited a high burst effect and fast release in solution. The results of dialysis membrane permeation showed that there was a significant difference between the commercially available and BRT-ISG groups after 45 min. The results of the pre-corneal retention study indicated that gellan gum can effectively prolong ocular surface retention. Preliminary stability results showed that it should be stored in a cool and dark place, and the formulation under long-term preservation can be basically stable. The pharmacokinetic study of the BRT-ISG in the anterior chamber of the rabbit eye was studied by microdialysis technique, and microdialysis samples were analyzed by LC-MS/MS. The pharmacokinetic study showed that the BRT-ISG reached Cmax (8.16 mg/L) at 93 min after administration, which was 2.7 times that of the BRT eye drops, and the AUC(0-t) (1397.08 mg·min/L) was 3.4 times that of the BRT eye drops. The optimal prescription can prolong the retention time of BRT in front of the cornea and significantly improve the bioavailability of BRT in the eye. Combined with the results of in vitro release, permeation and pre-corneal retention studies, the improvement of BRT-ISG bioavailability in rabbit eyes was found to be mainly due to the retention effect after the mixture of ISG and tears.
PubMed: 36678587
DOI: 10.3390/ph16010090 -
American Journal of Ophthalmology Apr 2023To confirm the superiority of the intraocular pressure (IOP)-lowering effect of the ripasudil-brimonidine fixed-dose combination (RBFC, K-232) to ripasudil 0.4% or...
PURPOSE
To confirm the superiority of the intraocular pressure (IOP)-lowering effect of the ripasudil-brimonidine fixed-dose combination (RBFC, K-232) to ripasudil 0.4% or brimonidine 0.1% ophthalmic solution.
DESIGN
Two prospective multicenter, randomized, double- or single-masked, active-controlled, phase 3 trials.
METHODS
Patients with primary open-angle glaucoma or ocular hypertension whose IOP level was ≥18 mm Hg during treatment with ripasudil or brimonidine alone were randomized to 2 groups (RBFC and ripasudil) in a 1:1 ratio in the ripasudil-controlled trial and to 3 groups (RBFC, brimonidine, and ripasudil-brimonidine combination) in a 2:2:1 ratio in the brimonidine-controlled trial. The allocated study drugs were instilled twice daily for 8 weeks. The primary efficacy endpoint was the change in IOP 2 hours after instillation (11 AM) from the baseline to weeks 4, 6, and 8.
RESULTS
There were 206 patients randomized in the ripasudil-controlled trial. Changes in IOP were -2.6 and -1.2 mm Hg in the RBFC and ripasudil groups, respectively, with a difference of -1.4 mm Hg (95% CI = -1.8 to -1.0 mm Hg; P < .001). There were 282 randomized patients in the brimonidine-controlled trial. Changes in IOP were -3.4 and -1.5 mm Hg in the RBFC and brimonidine groups, respectively, with a difference of -1.8 mm Hg (95% CI = -2.3 to -1.4 mm Hg; P < .001). The most frequent adverse event was conjunctival hyperemia.
CONCLUSIONS
The IOP-lowering effect of RBFC was superior to that of ripasudil or brimonidine.
Topics: Humans; Brimonidine Tartrate; Glaucoma, Open-Angle; Prospective Studies; Antihypertensive Agents; Quinoxalines; Treatment Outcome; Randomized Controlled Trials as Topic; Ocular Hypertension; Intraocular Pressure; Double-Blind Method
PubMed: 36410471
DOI: 10.1016/j.ajo.2022.11.017