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PubMed1993

[Rosacea].

Rosacea is a frequent disease which occurs mostly in women with dry skin and much more rarely in men with greasy skin. In women, rosacea is heralded, around the age of 20 years, by intermittent facial erythema, and this is followed by the gradual development of permanent erythema (erythrosis) with telangiectasia (couperose) and later on, around the age of 40, very unsightly papulo-pustules (papular rosacea, improperly called acne rosacea). In men, these successive stages are less frequent, but progressive dilatation of the nose due to sebaceous gland overgrowth may occur (rhinophyma). Rosacea is caused by vascular abnormalities not completely determined, and also, at the papulo-pustural stage, by a small parasite called Demodex folliculorum. Treatment rests on hygienic and dietary rules and vasoconstrictor drugs at the erythema stage, then on fine electrocoagulation or pulsed dye laser to suppress couperose and on the prescription of long-term low-dose tetracycline, sometimes preceded by a 2-month course of metronidazole to remove the papulo-pustules. Rhinophyma is treated by surgery. The results obtained are remarkable, at least on couperose, papulo-pustules and rhinophyma.

Adult↗
PubMed1993

[Double-blind study versus excipient of 0.75% metronidazole gel in the treatment of rosacea].

INTRODUCTION: The proven value of tetracyclines and metronidazole administered orally in the treatment of the chronic and recurrent disease that is rosacea is tempered by the important undesirable effects observed in long-term therapy. The purpose of this study was to test the effectiveness of an 0.75 p. 100 metronidazole gel in the treatment of rosacea. PATIENTS AND METHODS: The study involved two groups of patients: one received the metronidazole gel and the other the vehicle of the gel used as placebo. The multicentre randomized trial was conducted in the double-blind fashion by 18 private dermatologists working in the Paris region. Fifty one patients who, since more than 3 months, had been presenting with rosacea, defined as at least 4 papulopustules associated with erythema and/or telangiectasia, entered the trial. Topical treatments and systemic treatments which had shown some activity against rosacea had been interrupted for 15 days or 2 months respectively. The product (or the placebo) was applied a.m. and p.m. on the whole dry face. The patients were seen on days 0, 21 and 42. The evaluation was purely clinical, and the principal criterion of judgement was a change in the number of papulopustules between days 0 and 42. RESULTS: The metronidazole gel reduced the number of papulopustules between day 0 and day 42, and this reduction was significantly greater than that observed with the excipient alone. The active product began to be effective during the third week and remained so during the next three weeks. Both the metronidazole gel and its excipient seemed to be poorly tolerated, with frequent complaints of dry skin, but in 5 women of the metronidazole group this dryness was alleviated by application of moisturizers. CONCLUSION: This study has demonstrated that the 0.75 p. 100 metronidazole gel is effective in the treatment of the papulopustular component of rosacea.

Administration, Topical↗
PubMed1997

Rosacea: recognition and management for the primary care provider.

Rosacea is a common facial dermatitis that currently affects an estimated 13 million Americans. It is a chronic and progressive cutaneous vascular disorder, primarily involving the malar and nasal areas of the face. Rosacea is characterized by flushing, erythema, papules, pustules, telanglectasia, facial edema, ocular lesions, and, in its most advanced and severe form, rhinophyma. Ocular lesions are common, including mild conjunctivitis, burning, and grittiness. Blepharitis, the most common ocular manifestation, is a nonulcerative condition of the lid margins. Rosacea most commonly occurs between the ages of 30 to 60, and may be seen in women experiencing hormonal changes associated with menopause. Women are more frequently affected than men; the most severe cases, however, are seen in men. Fair complexioned individuals of Northern European descent are most likely to be at risk for rosacea; most appear to be pre-disposed to flushing and blushing. Alcohol, stress, spicy foods, and extremes of temperature have all been implicated, but have not been found to actually cause rosacea. Early diagnosis by the primary care practitioner, management with systemic antibiotics such as tetracycline, and topical agents such as metronidazole, in conjunction with patient education and lifestyle modifications, can achieve remission in most instances.

Acne Vulgaris↗
PubMed1997

[Rilmenidine in rosacea: a double-blind study versus placebo].

INTRODUCTION: The usual treatments of rosacea (cyclines and metronidazole) are mainly effective on reducing the number of papules and pustules. Clonidine only was employed in order to treat flushes observed in rosacea. Rilmenidine is a central hypotensive drug which acts more specifically than clonidine on imidazoline receptors and which has no sedative side effects. The purpose of this study was to evaluate the efficacy of rilmenidine 1 mg/d in the treatment of rosacea. PATIENTS AND METHODS: A total of 41 patients suffering from typical rosacea were selected in this randomised double blind study rilmenidine versus placebo. The study comprised an 1-month observation period without treatment followed by 3 months of treatment. The major assessment criteria was the proportion of responders at the end of the treatment period. Responders were defined as patients showing a decrease of more than 50 p. 100 in the count of papules and pustules. Minor criterias were the variation of the number of flushes, self-evaluated by the patient and the variation of the redness of the face, noted by the investigator on a scale from 0 to 5. RESULTS: Fifteen patients treated by rilmenidine (R) and 19 patients receiving the placebo (P) were evaluated. The proportion of responders was 69.2 p. 100 in group R and 57.1 p. 100 in group P (p = 0.69). The variations of the number of papules and pustules and of the redness of the face were not significantly different in the two groups. The decrease in the number of flushes was higher in group R (around -13) than in group P (around -5), but the difference was not really significant (p = 0.076). Arterial pressure decreased in 3 patients in group R and in 2 patients in group P. Minor side effects were noted in a similar proportion of patients in the two groups. DISCUSSION: Rilmenidine is not efficient in reducing the number of papules and pustules but could decrease the number of flushes. Nevertheless, many patients were lost for follow-up and because of a major placebo effect, the conclusions of this study are not strong enough. Another study including more patients and using evaluation criteria based on the vascular components of rosacea could perhaps confirm this hypothesis.

Adrenergic alpha-Agonists↗
PubMed1996

Self-incompatibility (S) alleles of the Rosaceae encode members of a distinct class of the T2/S ribonuclease superfamily.

Stylar ribonucleases (RNases) are associated with gametophytic self-incompatibility in two plant families, the Solanaceae and the Rosaceae. The self-incompatibility-associated RNases (S-RNases) of both the Solanaceae and the Rosaceae were recently reported to belong to the T2 RNase gene family, based on the presence of two well-conserved sequence motifs. Here, the cloning and characterization of S-RNase genes from two species of Rosaceae, apple (Malus x domestica) and Japanese pear (Pyrus serotina) is described and these sequences are compared with those of other T2-type RNases. The S-RNases of apple specifically accumulated in styles following maturation of the flower bud. Two cDNA clones for S-RNases from apple, and PCR clones encoding a further two apple S-RNases as well as two Japanese pear S-RNases were isolated and sequenced. The deduced amino acid sequences of the rosaceous S-RNases contained two conserved regions characteristic of the T2/S-type RNases. The sequences showed a high degree of diversity, with similarities ranging from 60.4% to 69.2%. Interestingly, some interspecific sequence similarities were higher than those within a species, possibly indicating that diversification of S-RNase alleles predated speciation in the Rosaceae. A phylogenetic tree of members of the T2/S-RNase superfamily in plants was obtained. The rosaceous S-RNases formed a new lineage in the tree that was distinct from those of the solanaceous S-RNases and the S-like RNases. The findings suggested that self-incompatibility mechanisms in Rosaceae and Solanaceae are similar but arose independently in the course of evolution.

Alleles↗
PubMed2005

Frequency, type, distribution and annotation of simple sequence repeats in Rosaceae ESTs.

Genomic resources for peach, a model species for Rosaceae, are being developed to accelerate gene discovery in other Rosaceae species by comparative mapping. Simple sequence repeats (SSRs) are an important tool for comparative mapping because of their high polymorphism and transportability. To accelerate the development of SSR markers, we analyzed publicly available Rosaceae expressed sequence tags (ESTs) for SSRs. A total of 17,284 ESTs from almond, peach and rose were assembled into putatively non-redundant EST sets. For comparison, 179,099 ESTs from Arabidopsis were also used in the analysis. About 4% of the assembled ESTs contained SSRs in Rosaceae, which was higher than the 2.4% found in Arabidopsis. About half of the SSRs were found in the putative UTR, and the estimated average distance between SSRs in the UTR was 5.5 kb in rose, 5.1 kb in almond, 7 kb in peach and 13 kb in Arabidopsis. In the putative coding region, the estimated average distance was two to four times longer than in the UTR. Rosaceae ESTs containing SSRs were functionally annotated using the GenBank nr database and further classified using the gene ontology terms associated with the matching sequences in the SwissProt database. The detailed data including the sequences and annotation results are available from http://www.genome.clemson.edu/gdr/rosaceaessr/.

Arabidopsis↗
PubMed2024

Construction of a molecular diagnostic system for neurogenic rosacea by combining transcriptome sequencing and machine learning.

Patients with neurogenic rosacea (NR) frequently demonstrate pronounced neurological manifestations, often unresponsive to conventional therapeutic approaches. A molecular-level understanding and diagnosis of this patient cohort could significantly guide clinical interventions. In this study, we amalgamated our sequencing data (n = 46) with a publicly accessible database (n = 38) to perform an unsupervised cluster analysis of the integrated dataset. The eighty-four rosacea patients were partitioned into two distinct clusters. Neurovascular biomarkers were found to be elevated in cluster 1 compared to cluster 2. Pathways in cluster 1 were predominantly involved in neurotransmitter synthesis, transmission, and functionality, whereas cluster 2 pathways were centered on inflammation-related processes. Differential gene expression analysis and WGCNA were employed to delineate the characteristic gene sets of the two clusters. Subsequently, a diagnostic model was constructed from the identified gene sets using linear regression methodologies. The model's C index, comprising genes PNPLA3, CUX2, PLIN2, and HMGCR, achieved a remarkable value of 0.9683, with an area under the curve (AUC) for the training cohort's nomogram of 0.9376. Clinical characteristics from our dataset (n = 46) were assessed by three seasoned dermatologists, forming the NR validation cohort (NR, n = 18; non-neurogenic rosacea, n = 28). Upon application of our model to NR diagnosis, the model's AUC value reached 0.9023. Finally, potential therapeutic candidates for both patient groups were predicted via the Connectivity Map. In summation, this study unveiled two clusters with unique molecular phenotypes within rosacea, leading to the development of a precise diagnostic model instrumental in NR diagnosis.

Humans↗
PubMed2003

A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial.

OBJECTIVE: To compare the efficacy and safety of a novel formulation of 15% azelaic acid gel (Finacea; Berlex Laboratories, Inc, Montville, NJ) with 0.75% metronidazole gel (MetroGel; Galderma Laboratories LP, Fort Worth, Tex) as topical therapy for moderate, papulopustular facial rosacea. DESIGN: Multicenter, double-blind, randomized, parallel-group study. SETTING: Thirteen US centers. PATIENTS: A total of 251 patients with papulopustular rosacea with persistent erythema and telangiectasia. INTERVENTIONS: Patients were randomized to receive azelaic acid gel or metronidazole gel twice daily for 15 weeks. MAIN OUTCOME MEASURES: Nominal and percent change in inflammatory lesion count, change in erythema and telangiectasia severity ratings, investigator's global assessment of rosacea, and investigator's and patient's overall improvement ratings. RESULTS: Azelaic acid gel was superior to metronidazole gel in reduction of mean nominal lesion count (-12.9 vs -10.7, respectively) (P =.003) and mean percent decrease in inflammatory lesions (-72.7% vs -55.8%, respectively) (P<.001). With respect to erythema severity, 56% of azelaic acid gel-treated patients were rated improved vs 42% of metronidazole gel-treated patients (P =.02). The effectiveness of metronidazole gel on these variables seemed to plateau after week 8, whereas azelaic acid gel demonstrated progressive improvement through week 15. Neither treatment had a clinically appreciable effect on telangiectasia. Both the investigator's global assessment (P =.02) and overall assessment of improvement (P =.005) showed a significant therapeutic advantage for azelaic acid gel. Azelaic acid gel also scored higher on the patient's overall assessment of efficacy. Both treatments were rated as having high cosmetic acceptability. No serious or systemic treatment-related adverse events were reported in either group. CONCLUSION: Use of 15% azelaic acid gel twice daily for 15 weeks demonstrated significant superiority over using 0.75% metronidazole gel in improving principal signs of rosacea (inflammatory lesions and erythema).

Administration, Topical↗
PubMed2006

Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials.

OBJECTIVE: To evaluate the clinical efficacy of topical 20% azelaic acid cream and 15% azelaic acid gel compared with their respective vehicles and metronidazole gel in the treatment of papulopustular rosacea. DATA SOURCES: Electronic searches of MEDLINE, EMBASE, BIOSIS, and SciSearch through July or August 2004 and the Cochrane Central Register of Controlled Trials through 2004 (issue 3). We performed hand searches of reference lists, conference proceedings, and clinical trial databases. Experts in rosacea and azelaic acid were contacted. STUDY SELECTION: Randomized controlled trials involving topical azelaic acid (cream or gel) for the treatment of rosacea compared with placebo or other topical treatments. Two authors independently examined the studies identified by the searches. Ten studies were identified, of which 5 were included (873 patients). DATA EXTRACTION: Two authors independently extracted data from the included studies, then jointly assessed methodological quality using a quality assessment scale. DATA SYNTHESIS: Because standard deviation data were not available for 4 of the 5 studies, a meta-analysis could not be conducted. Four of the 5 studies demonstrated significant decreases in mean inflammatory lesion count and erythema severity after treatment with azelaic acid compared with vehicle. None of the studies showed any significant decrease in telangiectasia severity. CONCLUSIONS: Azelaic acid in 20% cream and 15% gel formulations appears to be effective in the treatment of papulopustular rosacea, particularly in regard to decreases in mean inflammatory lesion count and erythema severity. Compared with metronidazole, azelaic acid appears to be an equally effective, if not better, treatment option.

Administration, Cutaneous↗
PubMed1984

Association of rosacea and keratoconjunctivitis sicca.

Sixty consecutive patients with active ocular rosacea underwent Schirmer's test without anesthesia. A randomly selected group of 120 patients without rosacea, matched for age and sex, served as controls. The prevalence of dry eyes was significantly greater in the patients with rosacea. The coexistence of keratoconjunctivitis sicca and ocular rosacea probably causes a high level of symptoms that lead patients to examination and recognition.

Adult↗
PubMed2004

Flashlamp pulsed dye laser (FPDL) did not cure papulopustular rosacea.

BACKGROUND AND OBJECTIVES: Pharmacological treatment has a fairly good effect on the papulopustular lesions in rosacea, but not as good an effect on the erythema and telangiectases. The aim was to treat rosacea patients with both erythematotelangiectatic and papulopustular lesions with flashlamp pulsed dye laser (FPDL) until telangiectases/erythema disappeared, and to evaluate whether the treatment might also be effective on papulopustular lesions. STUDY DESIGN/MATERIALS AND METHODS: Ten patients were treated on one side of the face with FPDL. The final examination was blinded and performed on the average 10 months after the last treatment. RESULTS: Two of the patients had more lesions after treatment, three were unchanged, three had only slightly less, and two had markedly less papulopustular lesions. CONCLUSION: Our conclusion from this small sample of patients is that FPDL probably has limited value on papulopustular lesions in rosacea. This indicates that the origin of rosacea may not be only vascular.

Female↗
PubMedDate not supplied

Potential antioxidant mechanism of action for metronidazole: implications for rosacea management.

Chronic inflammation is believed to account for some symptoms of rosacea. The efficacy of topical metronidazole in the treatment of rosacea may be due to its antimicrobial as well as anti-inflammatory activity. Neutrophils release potent inflammatory mediators, including reactive oxygen species (ROS), and intrafollicular neutrophils have been observed in stage II disease. ROS and other free radicals may contribute to intrinsic and extrinsic aging, both of which accentuate clinical manifestations of rosacea. If, as in vitro data suggest, metronidazole has antioxidant activity, it may help subdue the oxidative tissue damage of intrinsic and extrinsic aging as well as prevent and treat rosacea symptoms.

Aging↗
PubMedDate not supplied

Ocular rosacea.

The demographic, clinical, and histopathologic characteristics of ocular rosacea are reviewed, with emphasis on examination of the skin in patients with external ocular disease. Since no single clinical or pathological hallmark of rosacea exists, a proposed point system for diagnosis is presented. Studies of pathogenesis reveal that no single unifying hypothesis accounts for all the expressions of ocular rosacea. Reports of treatment with tetracycline and other antibiotics demonstrate efficacy, although the mechanisms of action of these drugs are not known. More recently, other classes of drugs, including isotretinoin and hexachlorocyclohexane, have proven to be effective in dermatologic manifestations of rosacea, but effects on ocular manifestations are unknown.

Adolescent↗
PubMed2004

Pulsed dye laser therapy for rosacea.

Rosacea is a chronic and progressive inflammatory skin disorder affecting the facial convexities for which no curative measure is currently available. Forty consecutive patients with rosacea were treated with the Cynosure PhotoGenica V pulsed dye laser. The improvement following laser therapy was assessed according to a sliding scale: 1 (worse after treatment), 2 (no improvement), 3 (slight improvement), 4 (moderate improvement), 5 (marked improvement). Following an average of 2.4 (range 1-10) laser treatments, a mean score of 4.4 and 4.3 for overall improvement was achieved as judged by the patients and independently assessed by a family member or a close friend of the patients, respectively. The response of erythema and telangiectasia to laser therapy, evaluated by an independent panel of 10 members, showed a mean score of 3.7. Three patients experienced an exacerbation of rosacea during the treatment period requiring antibiotic therapy. During the follow-up period of 6.0-55.5 (mean, 23.3) months after completion of laser therapy, no patient (including 13 patients in whom papulation and pustulation which were amongst the presenting symptoms) required medical treatment. Six patients developed post-inflammatory hyper-pigmentation necessitating skin bleach but no other complication such as scarring was observed. Three patients reported that the residual erythema had progressed after an initial improvement during follow-up periods of 52.4, 15.8 and 6.0 months. All patients felt that laser therapy was worthwhile. We conclude that pulsed dye laser therapy is a useful treatment for rosacea.

Adolescent↗
PubMed2005

Molecular evidence of sorbitol dehydrogenase in tomato, a non-Rosaceae plant.

The enzyme NAD-dependent sorbitol dehydrogenase (SDH) is well characterized in the Rosaceae family of fruit trees, which synthesizes sorbitol as a translocatable photosynthate. Expressed sequence tags of SDH-like sequences have also been generated from various non-Rosaceae species that do not synthesize sorbitol as a primary photosynthetic product, but the physiological roles of the encoded proteins in non-Rosaceae plants are unknown. Therefore, we isolated an SDH-like cDNA (SDL) from tomato (Lycopersicon esculentum Mill.). Genomic Southern blot analysis suggested that SDL exists in the tomato genome as a single-copy gene. Northern blot analysis showed that SDL is ubiquitously expressed in tomato plants. Recombinant SDL protein was produced and purified for enzymatic characterization. SDL catalyzed the interconversion of sorbitol and fructose with NAD (H). SDL showed highest activity for sorbitol among the several substrates tested. SDL showed no activity with NADP+. Thus, SDL was identified as a SDH, although the Km values and substrate specificity of SDL were significantly different from those of SDH purified from the Japanese pear (Pyrus pyrifolia), a Rosaceae fruit tree. In addition, tomato was transformed with antisense SDL to evaluate the contribution of SDL to SDH activity in tomato. The transformation decreased SDH activity to approximately 50% on average. Taken together, these results provide molecular evidence of SDH in tomato, and SDL was renamed LeSDH.

Amino Acid Sequence↗
PubMed2000

Flow cytometric analysis of conjunctival epithelium in ocular rosacea and keratoconjunctivitis sicca.

PURPOSE: To investigate by flow cytometry and impression cytology (IC) specimens the inflammatory status of the conjunctival epithelium and goblet cell density in two series of patients with rosacea and dry eye syndrome compared with a population of healthy subjects. DESIGN: Nonrandomized, prospective, comparative case series. PARTICIPANTS: Twenty-six eyes of 13 patients with rosacea, 26 eyes of 13 patients with dry eye syndrome, and 24 eyes of 12 control subjects were included in this study. METHODS: IC specimens were collected after clinical examination of the ocular surface and analyzed by flow cytometry, using antibodies directed to human lymphocyte antigen-DR (HLA-DR), intercellular adhesion molecule-1 (ICAM-1) (CD 54), and the peptidic core of the conjunctival mucin (M1/MUC5AC). The percentage of positive cells was calculated and levels of fluorescence expression quantified and compared with those obtained in a series of 12 healthy subjects. MAIN OUTCOME MEASURES: Tear break-up time (TBUT), Schirmer test, fluorescein and lissamin green stainings, and IC were realized in this study. RESULTS: A significant increase of HLA-DR and ICAM-1 expressions by epithelial cells was consistently found in the two pathologic groups compared with levels calculated in normal eyes. The two markers were well correlated with each other and inversely with TBUT and Schirmer test. The percentage of goblet cells was significantly decreased in rosacea patients and in dry eye patients compared with the normal group with a significant negative correlation with both HLA DR and ICAM-1 markers. CONCLUSIONS: Ocular rosacea and keratoconjunctivitis sicca were associated with severe ocular surface changes, such as an overexpression of inflammatory markers and a significant decrease in the number of goblet cells.

Adult↗
PubMed2000

Chronic eyelid lymphedema and acne rosacea. Report of two cases.

OBJECTIVE: The authors describe the clinical findings and surgical treatment of two patients affected by chronic eyelid lymphedema associated with facial acne rosacea. DESIGN: Two interventional case reports. METHODS AND INTERVENTION: The clinical diagnosis of acne rosacea was based on the physical examination and confirmed by the histopathologic findings obtained from biopsy of the involved tissue. Surgical treatment was required to address the disfiguring chronic eyelid lymphedema and to correct the resultant mechanical lower eyelid ectropion in both patients. RESULTS: Surgical debulking of the affected soft tissue resulted in very satisfactory cosmetic and functional improvement in both patients. CONCLUSIONS: To our knowledge, this is the first series of cases of chronic eyelid lymphedema secondary to acne rosacea reported in the ophthalmic literature. Six similar cases have been described previously in the dermatologic literature; all of which had been treated medically without satisfactory results. Surgical debulking of the involved eyelids should be considered in patients affected by persistent symptomatic rosacea lymphedema.

Aged↗
PubMed1999

A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea.

BACKGROUND: Although it is important for physicians to have sufficient clinical data on which to base treatment decisions, little comparative data exist regarding newer treatment modalities for rosacea. OBJECTIVE: The goal of the study was to compare the efficacy and safety of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. Parameters of patient satisfaction to treatment were also assessed. METHODS: Forty patients with the clinical manifestation of symmetric facial rosacea were investigated in this single-center, double-blind, randomized, contralateral split-face comparison clinical trial. RESULTS: After 15 weeks of treatment, both azelaic acid and metronidazole induced significant, albeit equal reductions in the number of inflammatory lesions (pustules and papules). A significantly higher physician rating of global improvement was achieved with azelaic acid. Changes in the rosacea signs and symptoms of dryness, burning, telangiectasia, and itching were equal between treatments. A reduction in erythema tended toward significance with azelaic acid at week 15. A trace amount of stinging on application was noted with azelaic acid; however, such discomfort did not appear to concern patients because their overall impression of azelaic acid was superior to that of metronidazole. CONCLUSION: Azelaic acid 20% cream provides an effective and safe alternative to metronidazole 0.75% cream with the added benefit of increased patient satisfaction.

Administration, Topical↗