tetracycline and azelaic-acid

Rosacea is a chronic facial inflammatory dermatosis characterized by background facial erythema and flushing and may be accompanied by inflammatory papules and pustules, cutaneous fibrosis and hyperplasia known as phyma, and ocular involvement. These features can have adverse impact on quality of life, and ocular involvement can lead to visual dysfunction. The past decade has witnessed increased research into pathogenic pathways involved in rosacea and the introduction of novel treatment innovations. The objective of these guidelines is to offer evidence-based recommendations to assist Canadian health care providers in the diagnosis and management of rosacea. These guidelines were developed by an expert panel of Canadian dermatologists taking into consideration the balance of desirable and undesirable outcomes, the quality of supporting evidence, the values and preferences of patients, and the costs of treatment. The 2015 Cochrane review "Interventions in Rosacea" was used as a source of clinical trial evidence on which to base the recommendations.

Topics: Anti-Infective Agents; Consensus; Dermatologic Agents; Dicarboxylic Acids; Doxycycline; Eye Diseases; Humans; Intense Pulsed Light Therapy; Isotretinoin; Ivermectin; Laser Therapy; Metronidazole; Outliers, DRG; Practice Guidelines as Topic; Rosacea; Tetracycline

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.. To assess the efficacy and safety of treatments for rosacea.. 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.. Randomised controlled trials in people with moderate to severe rosacea.. Study selection, data extraction, risk of bias assessment and analyses were carried out independently by two authors.. 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 i. 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

Topics: Administration, Oral; Administration, Topical; Anti-Bacterial Agents; Anti-Infective Agents; Dermatologic Agents; Dicarboxylic Acids; Doxycycline; Evidence-Based Medicine; Humans; Metronidazole; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Rosacea; Tetracycline; Treatment Outcome

Rosacea is a common chronic inflammatory disease of the skin and is associated with a number of etiological causes and inciting factors. It is characterized by erythematous changes of the facial skin, and commonly presents with papules, pustules, or telangiectasias. The 4 subtypes of rosacea are categorized according to secondary symptoms, such as pain, erythema, dryness, and edema. A number of therapies are available to treat rosacea, some of which can be used in combination. The mainstays of therapy are topical metronidazole, topical azelaic acid, and oral tetracyclines. Other pharmacotherapeutic interventions have been shown to improve the signs and symptoms of rosacea, although many of these have not yet received approval by the US Food and Drug Administration for this indication.

Topics: Administration, Oral; Administration, Topical; Anti-Bacterial Agents; Anti-Infective Agents; Dermatologic Agents; Diagnosis, Differential; Dicarboxylic Acids; Humans; Laser Therapy; Metronidazole; Phytotherapy; Rosacea; Sunscreening Agents; Tetracycline

Rosacea is an extremely common chronic dermatosis affecting an estimated 14 million Americans. Rosacea is most commonly managed with topical metronidazole, sometimes in combination with oral antibiotics.. To review published studies about topical metronidazole therapy for rosacea, both as a monotherapy and in conjunction with oral antibiotics.. Medline searches were conducted for clinical trials using metronidazole, tetracycline, and doxycycline for rosacea.. Topical metronidazole has been well studied as a rosacea therapy. Twice-daily dosing of metronidazole 1.0% cream is as effective as 250 mg tetracycline twice daily. Metronidazole 1.0% gel used once daily is as effective as azelaic acid 15% gel dosed twice daily. When dosed at subantimicrobial levels, doxycycline 20 mg taken twice daily is effective in decreasing inflammatory lesions and erythema associated with rosacea. Metronidazole 0.75% lotion is more effective when used in combination with doxycycline 20 mg dosed twice daily.. Metronidazole in 0.75% strength lotion, cream, and gel and 1.0% metronidazole cream and gel are all efficacious in treating rosacea. Combination treatment with oral antibiotics at both antimicrobial and subantimicrobial doses is an efficacious means of treating rosacea. Maintenance treatment with topical metronidazole decreases relapses and allows for longer intervals between flares.

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Dermatologic Agents; Dicarboxylic Acids; Doxycycline; Drug Administration Routes; Drug Administration Schedule; Drug Therapy, Combination; Humans; Metronidazole; Rosacea; Tetracycline

Topics: Acne Vulgaris; Adapalene; Anti-Bacterial Agents; Benzoyl Peroxide; Clindamycin; Dermatologic Agents; Dicarboxylic Acids; Doxycycline; Erythromycin; Humans; Isotretinoin; Minocycline; Naphthalenes; Tetracycline; Tretinoin; Zinc

Despite its prevalence, rosacea has not received the same attention of researchers as other dermatologic disorders. Nevertheless, new pharmacologic and nonpharmacologic therapies for the condition continue to be developed. The future of rosacea treatment will probably involve a combination of drugs and devices. Certain core therapies (i.e., topical metronidazole, topical azelaic acid, oral tetracyclines, and topical sulfur/sodium sulfacetamide) are validated by the greatest amount of high-order clinical evidence and will undoubtedly remain first-line therapeutic choices. However, more research is necessary to validate the efficacy and safety of newer pharmacologic agents and light-based therapy. Because rosacea is a chronic condition, pharmacologic maintenance therapy is necessary to maintain remission.

Topics: Anti-Infective Agents; Biomedical Research; Chronic Disease; Dermatologic Agents; Dicarboxylic Acids; Forecasting; Humans; Metronidazole; Rosacea; Tetracycline

The Cochrane Collaboration is an international nonprofit organization that conducts systematic reviews of healthcare interventions. The organization has recently reviewed all studies meeting designated criteria on interventions for rosacea. To be included in the review, trials had to be randomized controlled trials (RCTs) that met the methodological criteria of the reviewers and that were conducted in an adult patient population with moderate to severe rosacea. The electronic databases searched included The Cochrane Skin Group Specialised Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, BIOSIS, and Science Citation Index. The reviewers tried to obtain details of unpublished and ongoing RCTs through correspondence with authors and pharmaceutical companies. After evaluating the included studies, the reviewers concluded there is evidence that topical metronidazole in 1% cream and 0.75% gel formulations and azelaic acid in 20% cream formulation are effective and safe. Furthermore, there is some evidence that oral metronidazole and tetracycline are effective. The reviewers also made suggestions about future rosacea research.

Topics: Anti-Infective Agents; Dermatologic Agents; Dicarboxylic Acids; Gels; Humans; Metronidazole; Randomized Controlled Trials as Topic; Rosacea; Tetracycline

Topics: Acne Vulgaris; Adapalene; Anti-Bacterial Agents; Benzoyl Peroxide; Clindamycin; Dermatologic Agents; Dicarboxylic Acids; Drug Therapy, Combination; Erythromycin; Humans; Isotretinoin; Naphthalenes; Tetracycline; Tretinoin; Zinc

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Dermatologic Agents; Diagnosis, Differential; Dicarboxylic Acids; Doxycycline; Humans; Laser Therapy; Life Style; Metronidazole; Minocycline; Patient Education as Topic; Referral and Consultation; Risk Factors; Rosacea; Tetracycline

Topics: Acne Vulgaris; Administration, Topical; Clinical Trials as Topic; Dicarboxylic Acids; Drug Tolerance; Female; Humans; Male; Random Allocation; Tetracycline

In a series of investigation using 20% azelaic acid as a therapy for acne, it was found that the treatment, compared with most common therapies (benzoylperoxide, oral tetracycline) significantly reduced inflamed lesions in papulo-pustular acne. The rates of improvement obtained indicate that topical azelaic acid treatment can be considered an effective therapy for papulo-pustular acne and it compares well with other agents. Azelaic acid cream shows a progressive and significant beneficial effect and its action is more pronounced in long-term treatment.

Topics: Acne Vulgaris; Administration, Oral; Adolescent; Benzoyl Peroxide; Clinical Trials as Topic; Dermatologic Agents; Dicarboxylic Acids; Humans; Male; Ointments; Tetracycline; Time Factors

Topical azelaic acid and oral tetracycline were compared in a 6-month double-blind study for treatment of acne vulgaris in 45 male subjects with clinical acne. Their acne was graded, inflamed or non-inflamed, lesions were counted and the density of their skin microflora was measured. Both treatments were of benefit and produced only a few minor side-effects. Although oral tetracycline was more effective than azelaic acid, the differences were only just significant. The average reduction in numbers of cutaneous micrococcaceae and Propionibacterium sp. with azelaic acid treatment was 224 and 30-fold, respectively. In a separate group of 11 male subjects with physiological acne the effect of azelaic acid on sebum excretion rate was assessed, and little change was detected.

Topics: Acne Vulgaris; Administration, Topical; Adolescent; Adult; Clinical Trials as Topic; Dicarboxylic Acids; Double-Blind Method; Humans; Male; Skin; Tetracycline

Acne pathogenesis has recently been linked to decreased nuclear FoxO1 levels and increased mTORC1 activity. This hypothesis postulates that antiacne agents either enhance nuclear FoxO activity or inhibit mTORC1. Benzoyl peroxide (BPO), by activation of oxidative stress-inducible kinases, increases nuclear FoxO levels promoting Sestrin3-mediated AMPK activation. Furthermore, BPO-derived ROS may activate AMPK via ataxia-telangiectasia mutated. Isotretinoin and all-trans retinoic acid may stimulate FoxO gene expression. Doxycycline may enhance FoxOs nuclear retention by inhibiting the expression of exportin 1. Suppression of TNFα signalling by tetracyclines, erythromycin and other macrolides may attenuate IKKβ-TSC1-mediated mTORC1 activation. Erythromycin attenuates ERK1/2 activity and thereby increases TSC2. Azelaic acid may decrease mTORC1 by inhibiting mitochondrial respiration, increasing cellular ROS and nuclear FoxO levels. Antiandrogens may attenuate mTORC1 by suppressing mTORC2-mediated Akt/TSC2 signalling. This hypothesis unmasks a common mode of action of antiacne agents as either FoxO enhancers or mTORC1 inhibitors and thus provides a rational approach for the development of new antiacne agents.

Topics: Acne Vulgaris; AMP-Activated Protein Kinases; Benzoyl Peroxide; Dermatologic Agents; Dicarboxylic Acids; Enzyme Activation; Erythromycin; Forkhead Box Protein O1; Forkhead Transcription Factors; Humans; Isotretinoin; Mechanistic Target of Rapamycin Complex 1; Multiprotein Complexes; Oxidative Stress; Tetracycline; TOR Serine-Threonine Kinases; Up-Regulation

The absence of specific histological or serological markers, the gaps in understanding the aetiology and pathophysiology of rosacea, and the broad diversity in its clinical manifestations has made it difficult to reach international consensus on therapy guidelines.. The main objective was to highlight the global diversity in current thinking about rosacea pathophysiology, classification and medical features, under particular consideration of the relevance of the findings to optimization of therapy.. The article presents findings, proposals and conclusions reached by the ROSacea International Expert group (ROSIE), comprising European and US rosacea experts.. New findings on pathogenesis provide a rationale for the development of novel therapies. Thus, recent findings suggest a central role of the antimicrobial peptide cathelicidin and its activator kallikrein-5 by eliciting an exacerbated response of the innate immune system. Cathelicidin/kallikrein-5 also provide a rationale for the effect of tetracyclines and azelaic acid against rosacea. Clinically, the ROSIE group emphasized the need for a comprehensive therapy strategy - the triad of rosacea care - that integrates patient education including psychological and social aspects, skin care with dermo-cosmetics as well as drug- and physical therapies. Classification of rosacea into stages or subgroups, with or without progression, remained controversial. However, the ROSIE group proposed that therapy decision making should be in accordance with a treatment algorithm based on the signs and symptoms of rosacea rather than on a prior classification.. The ROSIE group reviewed rosacea pathophysiology and medical features and the impact on patients and treatment options. The group suggested a rational, evidence-based approach to treatment for the various symptoms of the condition. In daily practice this approach might be more easily handled than prior subtype classification, in particular since patients often may show clinical features of more than one subtype at the same time.

Topics: Algorithms; Cosmetics; Dicarboxylic Acids; Humans; International Cooperation; Patient Education as Topic; Rosacea; Tetracycline

A range of treatment options are available in rosacea, which include several topical (mainly metronidazole, azelaic acid, other antibiotics, sulfur, retinoids) and oral drugs (mainly tetracyclines, metronidazole, macrolides). In some cases, the first choice is a systemic therapy because patients may have sensitive skin and topical medications can be irritant. Isotretinoin can be used in resistant cases of rosacea. Unfortunately, the majority of studies on rosacea treatments are at high or unclear risk of bias. A recent Cochrane review found that only topical metronidazole, azelaic acid, and oral doxycycline (40 mg) had some evidence to support their effectiveness in moderate to severe rosacea and concluded that further well-designed, adequately-powered randomised controlled trials are required. In our practice, we evaluate our patients for the presence of two possible triggers, Helicobacter pylori infection and small intestinal bacterial overgrowth. When they are present we use adapted antibiotic protocols. If not, we use oral metronidazole or oral tetracycline to treat papulopustolar rosacea. We also look for Demodex folliculorum infestation. When Demodex concentration is higher than 5/cm(2) we use topical crotamiton 10% or metronidazole.

Topics: Adapalene; Anti-Infective Agents; Cyclosporine; Dermatologic Agents; Dicarboxylic Acids; Humans; Immunosuppressive Agents; Isotretinoin; Keratolytic Agents; Metronidazole; Mite Infestations; Naphthalenes; Rosacea; Sulfacetamide; Tacrolimus; Tetracycline; Toluidines; Tretinoin

Topics: Acne Vulgaris; Administration, Oral; Adolescent; Dermatologic Agents; Dicarboxylic Acids; Drug Evaluation; Facial Dermatoses; Humans; Ointments; Skin Diseases; Tetracycline