Comparison of efficacy of azithromycin vs. doxycycline in the treatment of acne vulgaris

Acne vulgaris is a common inflammatory disorder of the skin. Oral antibiotics are known to be effective in its treatment. A randomized, investigator-blinded study was performed to compare the efficacy of azithromycin with doxycycline. Fifty-one patients were randomized to receive either azithromycin 500 mg/day on 3 consecutive days per week in the first, on 2 consecutive days per week in the second, and on 1 day per week in the third month. The other group was given doxycycline twice a day for the first month and once a day for the second and third months. Clinical assessment was made at baseline, at the end of first, second, third, and post-treatment first and second months. Side effects were recorded. Statistically significant improvement for the facial lesions were obtained with both drugs. Neither drug was shown to be more effective than the other. The beneficial effect continued until 2 months after treatment. In the azithromycin group three patients had diarrohea, while photosensitivity was seen in two patients using doxycycline. This study indicates that azithromycin is at least as effective as doxycycline in the treatment of acne.     

Doxycycline 40 mg Capsules (30 mg Immediate-Release/10 mg Delayed-Release Beads)

Anti-inflammatory dose doxycycline 40 mg capsules (30 mg immediate-release and 10 mg delayed-release beads) provide a sub-antimicrobial dose that reduces the inflammatory response in patients with rosacea without producing drug concentrations required to treat bacterial diseases. The efficacy of oral, anti-inflammatory dose doxycycline 40 mg capsules once daily in the treatment of adults with rosacea was demonstrated in two pivotal large, randomized, double-blind, placebo-controlled, multicenter trials. After 16 weeks’ therapy, anti-inflammatory dose doxycycline 40 mg was significantly more effective in improving rosacea than placebo, providing a greater reduction in the total inflammatory lesion count (primary endpoint) than placebo. Anti-inflammatory dose doxycycline 40 mg was associated with a rapid onset of action, achieving a significantly greater decrease in total inflammatory lesion count than placebo by the first follow-up visit at week 3 in both studies. Maximum anti-inflammatory efficacy appears to be achieved with doxycycline 40 mg capsules once daily, as no additional improvement in rosacea symptoms was achieved with oral doxycycline 100 mg once daily (usual antibacterial dosage) in a small, randomized, double-blind trial. Anti-inflammatory dose doxycycline 40 mg was generally well tolerated in clinical trials, with most adverse events being of mild to moderate intensity.     

The role of Chlamydia pneumoniae in the etiology of acne rosacea: response to the use of oral azithromycin

Acne rosacea is a chronic skin disorder that requires long-term therapy. Oral azithromycin has been used successfully to treat acne vulgaris. an observation that suggested an infectious agent may play an active role in the etiology of this disorder. Ten adults (not previously reported) with acne rosacea were selected to be treated with oral azithromycin. Nine of the 10 subjects received 250 mg 3 times weekly for periods ranging from 5 to 19 weeks, at which time follow-up examinations were performed on 8 of the 9 treated subjects: 1 subject was lost to follow-up. Prior to therapy. C pneumoniae antigen was detected in malar biopsy specimens in 4 of 10 subjects by immunoperoxidase technique (using monoclonal antibody to C pneumoniae). Serum antibodies against C pneumoniae were detected in 8 of 10 intent-to-treat subjects. Using polymerase chain reaction, C pneumoniae was not detected in peripheral blood mononuclear cells. The inflammatory response in tissues was characterized by a widespread infiltration of polymorphonuclear neutrophil cells, lymphocytes, and plasma cells, which support the clinical diagnosis of acne rosacea. Nine of 10 subjects treated with azithromycin showed moderate to marked improvement of their acne rosacea. No adverse reactions to azithromycin occurred. and the drug appeared to be safe and effective. These preliminary data suggest the need for further investigation with clinical trials to study long-term tolerability and efficacy and also strongly implicate C pneumoniae in the pathogenesis of acne rosacea.     

Interventions for rosacea: abridged updated Cochrane systematic review including GRADE assessments

Rosacea is a common chronic facial dermatosis. This update of our Cochrane review on interventions for rosacea summarizes the evidence, including Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group assessments, of the effects of the currently available treatments. Searches included the following: Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE, EMBASE, LILACS and the Science Citation Index, and ongoing trials registries (July 2014). We included 106 randomized controlled trials (RCTs) with 13 631 participants, a more than 80% increase since the last update in 2011. Pooling of data was feasible for a few outcomes, for topical metronidazole and azelaic acid and both appeared to be more effective than placebo (moderate and high‐quality evidence, respectively). Topical ivermectin was more effective than placebo based on two studies (high‐quality evidence), and slightly more effective than metronidazole in one study. Brimonidine was more effective than vehicle in reducing erythema in rosacea (high‐quality evidence). Ciclosporin ophthalmic emulsion was effective for ocular rosacea (low‐quality evidence). For oral treatments there was moderate‐quality evidence for the effectiveness of tetracycline based on two old studies, and high‐quality evidence for doxycycline 40 mg compared with placebo according to physician assessments. One study at high risk of bias demonstrated equivalent effectiveness for azithromycin and doxycycline 100 mg. Minocycline 45 mg may be effective for papulopustular rosacea (low‐quality evidence). Low‐dose isotretinoin appeared to be slightly more effective than doxycycline 50–100 mg (high‐quality evidence). Laser and light‐based therapies for erythema in rosacea were effective (low‐quality evidence). Further RCTs are required for ocular rosacea.     

Moderate acne vulgaris: efficacy, tolerance and compliance of oral azithromycin thrice weekly for

The aim of the study was to investigate the efficacy, safety and compliance of 500 mg azithromycin thrice weekly for 12 weeks in moderate inflammatory acne vulgaris. An open-label, noncomparative study was carried out for 12 weeks at Department of Dermatology and Plastic Surgery, La Sapienza University in Rome. Fifty-seven patients (20 male and 37 female) between 13 and 41 years of age, affected by moderate papulopustular and nodular acne vulgaris, were enrolled in the study. Azithromycin 500 mg was administered orally thrice weekly for 12 weeks. Patients were examined at baseline, 4 weeks, 8 weeks and 12 weeks (completion of treatment), evaluating both clinical (Global Acne Grading System, GAGS) and quality of life (Acne Quality of Life Questionnaire, AQoL) improvements. Forty-six patients completed the study and showed significant improvement. Six patients interrupted their treatment, while five patients did not complete the study for unknown reasons. Side effects (diarrhea and abdominal pain) were recorded in eight patients. Azithromycin, 500 mg thrice weekly for 12 weeks, is a safe and effective treatment for moderate acne vulgaris with excellent patient compliance.     

The effect of azithromycin on reactive oxygen species in rosacea

BACKGROUND: Recent evidence suggests that inflammation in rosacea is associated with generation of reactive oxygen species (ROS) that are released by inflammatory cells. The efficacy of current therapeutic agents for rosacea such as tetracyclines and metronidazole has also been attributed to their antioxidant properties. Recently, a macrolide antibiotic, azithromycin, has been found to be an effective alternative in the treatment of rosacea. AIM: We planned a study to evaluate the antioxidant effects of azithromycin on ROS in rosacea. We compared basal ROS concentrations measured in the facial skin of patients with rosacea with the post-treatment levels and with those of healthy controls. METHODS: Facial skin biopsies of 17 papulopustular patients with rosacea and 25 healthy controls were taken. Rosacea patients were assigned to receive oral azithromycin 500 mg on three consecutive days each week for 4 weeks. The total number of inflammatory lesions (the sum of papules and pustules) on the face of each patient with rosacea was counted at each visit. The luminol- and lucigenin-enhanced chemiluminescence (CL) levels of patients with rosacea were measured before and after 4 weeks of treatment and compared with those of healthy controls. RESULTS: Rosacea patients had higher ROS levels than healthy controls (P < 0.001). A statistically significant decrease of both luminol- and lucigenin-enhanced CL levels were observed in patients with rosacea after treatment with azithromycin (t = 4.602, P < 0.001; vs. t = 4.634, P < 0.001, respectively). CONCLUSION: Rosacea patients have higher ROS levels than healthy controls. The results of our study support the antioxidant properties of azithromycin in rosacea.     

Effective and evidence-based management strategies for rosacea: summary of a Cochrane systematic review

Rosacea is a common chronic skin disease affecting the face. There are numerous treatment options, but it is unclear which are the most effective. The aim of this review was to assess the evidence for the efficacy and safety of treatments for rosacea. Searches included the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index, and Ongoing Trials Registers (updated February 2011). Randomized controlled trials in people with moderate to severe rosacea were included. Fifty-eight trials, including 27 from the original review, comprising 6633 participants were included in this updated review. Interventions included topical metronidazole, oral antibiotics, topical azelaic cream or gel, topical benzoyl peroxide and/or combined with topical antibiotics, sulphacetamide/sulphur, and others. There was some evidence that topical metronidazole and azelaic acid were more effective than placebo. Two trials indicated that doxycycline 40mg was more effective than placebo. There was no statistically significant difference in effectiveness between doxycycline 40mg and 100mg but there were fewer adverse effects. One study reported that ciclosporin ophthalmic emulsion was significantly more effective than artificial tears for treating ocular rosacea. Although the majority of included studies were assessed as being at high or unclear risk of bias, there was some evidence to support the effectiveness of topical metronidazole, azelaic acid and doxycycline (40mg) in the treatment of moderate to severe rosacea, and ciclosporin 0·05% ophthalmic emulsion for ocular rosacea. Further well-designed, adequately powered randomized controlled trials are required.     

Systemic isotretinoin in the treatment of rosacea – doxycycline‐ and placebo‐controlled,randomized clinical study

Background: Systemic isotretinoin has been known for decades to be effective in the treatment of severe forms of rosacea, but it must be used off‐label because of the lack of evidence‐based data. Patients and Methods: 573 patients with rosacea subtype II and III received one of three different dosages of isotretinoin (0.1 mg, 0.3 mg, or 0.5 mg per kg body weight), doxycycline (100 mg daily for 14 days, then 50 mg daily) or placebo in a double‐blinded, randomized way for 12 weeks in 35 German centers. Results: Isotretinoin 0.3 mg/kg proved to be the most effective dose with significant superiority versus placebo. Isotretinoin 0.3 mg/kg showed also significant non‐inferiority versus doxycycline with reduction of lesions of 90 % compared to 83 % with doxycycline. Investigators diagnosed complete remission in 24 % and marked improvement in further 57 % of patients with isotretinoin treatment, in contrast to remission in 14 % and marked improvement in 55 % of patients treated with doxycycline. Isotretinoin 0.3 mg/kg revealed a similar safety profile as for the treatment of acne. Isotretinoin 0.5 mg/kg showed more dermatitis facialis as compared to 0.3 mg/kg. Conclusions: Isotretinoin 0.3 mg/kg is an effective and well‐tolerated therapy option for the treatment of rosacea subtype II and III and can therefore be used successfully as an alternative to therapy with oral antibiotics.     

Systemische Therapie der Rosazea

The only medication which is authorized for therapy of rosacea is doxycycline. It is usually administered at a dose of 40–100 mg daily for 3–6 months. In case of a lack of efficacy or in case of contraindications (e.g. pregnancy, children below 8 years), azithromycin or metronidazole are alternative systemic therapies. Those forms of rosacea which involve hyperplasia of sebaceous glands respond well to retinoids such as isotretinoin. Dapsone has been successfully used for the treatment of granulomatous rosacea and rosacea fulminans. Erythema can be reduced by use of beta blockers. If patients do not respond to various therapies or if they are immunocompromised, the differential diagnosis of demodicosis should be considered; here the treatment is oral ivermectin. Some forms of rosacea (rosacea fulminans and granulomatous rosacea) may be treated initially with oral corticosteroids. Ophthalmic rosacea is treated topically as well as with tetracyclines or macrolides.     

Treatment of ocular rosacea with 40 mg doxycycline in a slow release form

Background: About 30–50 % of rosacea patients have ocular involvement. The symptoms range from a foreign‐body sensation to conjunctivitis or blepharitis and may even include severe corneal ulcerations. Systemic treatment is generally with tetracycline. Side effects can occur with the usual antimicrobial dose. Patients and Methods: In a retrospective study, seven patients were evaluated who had been treated for ocular rosacea with a sub‐antimicrobial dose of doxycycline 40 mg in a slow‐release form (Oraycea^®). The responses were evaluated on the basis of clinical findings. Results: Seven patients with an average age of 63 took slow release doxycycline 40 mg every day for at least two months. In five patients, other systemic drugs had already failed. All patients experienced a clear improvement in their ocular rosacea after an average of 2.29 months of treatment. One patient had complete clearance and another had almost complete clearance. None of the patients experienced side effects. Conclusions: A sub‐antimicrobial dose of slow release doxycycline 40 mg daily is an effective long‐term therapy for ocular rosacea. It is not associated with the side effects of long‐term antibiotic therapy or the risk of resistance.     

Azithromycin monthly pulse vs daily doxycycline in the treatment of acne vulgaris

Acne vulgaris is a common skin disease seen primarily in adolescent and young adults. As the treatment involves long term therapy with antibiotics, an agent with a long half life can be very useful in increasing the compliance. To evaluate the role of a monthly dose of azithromycin and compare it with daily doxycycline, we conducted this randomized comparative study. Sixty patients with moderate to severe acne were randomly assigned to two treatment groups, A & B. Patients in group A received 100 mg doxycycline daily in addition to topical 0.05% tretinoin cream, whereas patients in group B were given 500 mg azithromycin once a day for four days per month along with 0.05% topical tretinoin for a total of 12 weeks. Of the 60 patients, 22 in group A and 28 in group B were evaluated. The monthly dose of azithromycin was found to be as effective as daily doxycycline on a pure protocol basis and statistically significantly better than doxycycline by intention to treat analysis.     

Therapeutic potential of azithromycin in rosacea

BACKGROUND: Systemic antibiotics currently used in the treatment of rosacea are sometimes associated with uncomfortable side-effects. Therefore, a need for an effective agent with few side-effects and good patient compliance exists. Azithromycin, a macrolide antibiotic with prolonged mode of action, has recently been found to be an effective alternative in the treatment of inflammatory acne. We planned a study to evaluate the efficacy and safety of azithromycin in rosacea. METHODS: An open-labeled study was performed in a population of 18 patients, with Plewig-Kligman stage 2 rosacea. Patients were given oral azithromycin for 12 weeks in decreasing doses. RESULTS: Fourteen subjects completed the trial. The treatment produced therapeutic benefits with regard to total scores as well as inflammatory lesion scores. At the end of 12 weeks, there was a 75% decrease in total scores (P < 0.001) and an 89% decrease in inflammatory lesion scores compared with basal values. Improvement continued during the 4 weeks after treatment. Adverse effects were minimal and well tolerated in most patients. CONCLUSION: Azithromycin is a promising agent in the treatment of rosacea with its few side-effects and good patient compliance.     

Clarithromycin versus doxycycline in the treatment of rosacea

Forty patients with rosacea were entered into a study comparing clarithromycin with doxycycline in the systemic treatment of mild and severe rosacea. The patients, 25 women and 15 men, aged from 26 to 62 years, were subdivided into two homogeneous groups with regard to age, sex, and disease seventy. The first group of 23 patients, 14 women and 9 men, was treated with 250 mg of clarithromycin for 4 weeks twice daily, and then with 250 mg once daily for the following 4 weeks. The second group of 17 patients, 11 women and 6 men was treated with 100 mg of doxycycline for 4 weeks twice daily, and then with 100 mg once a day for the following 4 weeks. Both objective and subjective evaluations of the dermatosis were performed prior to therapy and after 4, 6, and 8 weeks of treatment.     

Ocular signs, symptoms and tear function tests of papulopustular rosacea patients receiving azithromycin

Background  Tetracycline derivatives provide moderate benefit in the treatment of ocular rosacea. Recently, azithromycin has been found to be an effective alternative in the treatment of cutaneous papulopustular rosacea.
Objective  We planned a study to evaluate the effects of azithromycin on ocular symptoms, signs and tear function tests of papulopustular rosacea patients.
Methods  An open-labelled study was performed in a population of 20 papulopustular rosacea patients.
Results  Eighteen subjects completed the trial. Significant improvement was seen in ocular symptoms, eyelid findings and conjunctival hyperaemia scores ( P  = 0.002, P <  0.0001, and P  = 0.005, respectively). Therapeutic benefit was not observed in ocular surface staining scores. Baseline values of Schirmer test results were within normal limits. No significant side-effects were observed.
Limitations  The study population is limited to dermatology patients who had been referred to the ophthalmology clinic.
Conclusion  Azithromycin may be a new promising therapeutic alternative in ocular rosacea.

Conflicts of interest

None declared.     

Current topical and systemic approaches to treatment of rosacea

Rosacea is a common, often overlooked, chronic facial dermatosis characterized by intermittent periods of exacerbation and remission. Clinical subtypes and grading of the disease have been defined in the literature. On the basis of a genetic predisposition, there are several intrinsic and extrinsic factors possibly correlating with the phenotypic expression of the disease. Although rosacea cannot be cured, there are several recommended treatment strategies appropriate to control the corresponding symptoms/signs. In addition to adequate skin care, these include topical and systemic medications particularly suitable for the papulopustular subtype of rosacea with moderate to severe intensity. The most commonly used and most established therapeutic regimens are topical metronidazole and topical azelaic acid as well as oral doxycycline. Conventionally, 100–200 mg per day have been used. Today also a controlled release formulation is available, delivering 40 mg per day using non-antibiotic, anti-inflammatory activities of the drug. Anti-inflammatory dose doxycycline in particular allows for a safe and effective short- and long-term therapy of rosacea. Topical metronidazole and topical azelaic acid also appear to be safe and effective for short-term use. There are indications that a combined therapy of anti-inflammatory dose doxycycline and topical metronidazole could possibly have synergy effects. Further interesting therapy options for the short- and long-term therapy of rosacea could be low-dose minocycline and isotretinoin; however, too little data are available with regard to the effectiveness, safety, optimal dosage and appropriate length of treatment for these medications to draw final conclusions.

Conflicts of interest

None declared.     

Rosazea

Systemic isotretinoin has been known for decades as an effective and safe therapeutic option in the treatment of severe and refractory forms of rosacea. It can also be used in special treatment-resistant forms of rosacea, e.g. granulomatous rosacea, as efficacious second-line therapy. Previously, the effect of isotretinoin in rosacea has been mainly studied in small cohorts or anecdotal reports. Recently, a big randomized double-blind dose-response and comparative study revealed that an optimized dosage of 0,3 mg/kg was superior to other dosages and non-inferior to doxycycline as gold standard of systemic rosacea treatment and proved effective and safe in papulopustular and phymatous subtypes. However, the substance is still not licensed for this indication The efficacy of isotretinoin in rosacea is probably mainly related to anti-inflammatory mechanisms as well as anti-oxidative, anti-angiogenic and antifibrotic properties. The classical antiseborrheic effect of isotretinoin might play a role in special subtypes like the phymatous type or rosacea fulminans.     

A randomized,observer-blinded trial of twice vs. three times weekly narrowband ultraviolet B phototherapy for chronic plaque psoriasis

BACKGROUND: The optimum treatment frequency for narrowband (TL-01) ultraviolet B (NB-UVB) in psoriasis is not yet known. We have previously found three times weekly to be preferable to five times weekly treatment in our population. OBJECTIVES: To compare twice weekly with three times weekly NB-UVB phototherapy in chronic plaque psoriasis. METHODS: In an observer-blinded, randomized comparison, patients with chronic plaque psoriasis referred from dermatology out-patient clinics in Tayside for NB-UVB phototherapy received either twice weekly (Monday and Friday) or three times weekly (Monday, Wednesday and Friday) whole-body NB-UVB phototherapy following our standard departmental treatment protocol. Treatment was continued to clearance or until the fourth treatment after minimal residual activity (MRA) was first documented. Number of days in treatment, number of treatments, total dose and time to relapse were recorded. RESULTS: In total, 113 patients were recruited, skin phototypes I-III: 58 in the twice weekly and 55 in the three times weekly group. Forty patients in the twice weekly group reached clearance/MRA, as did 44 in the three times weekly group. It took 1.5 (95% confidence interval 1.3-1.7) times longer to reach clearance/MRA with twice weekly therapy, a geometric mean of 88 vs. 58 days (P < 0.0001). Small differences in numbers of treatments and total dose to reach clearance tended to favour three times weekly therapy, but these were not significant. CONCLUSIONS: Three times weekly NB-UVB clears psoriasis significantly faster than twice weekly treatment, and therefore is preferable for most patients.     

The Role of Tetracyclines in Rosacea

There is a great deal of evidence to support the use of tetracycline and doxycycline in the treatment of papulopustular rosacea. Nevertheless, these agents have shared and unique adverse effects and relative contraindications. Recently, subantimicrobial-dose doxycycline was demonstrated to be an effective treatment for rosacea, due to its inherent anti-inflammatory properties. Furthermore, subantimicrobial-dose doxycycline has a more preferable tolerability profile and a lower occurrence of bacterial resistance than traditional-dose doxycycline. To further elucidate the role of tetracycline agents in rosacea, clinical trials that compare these agents with each other as well as with other effective rosacea treatments are called for. Adherence studies comparing oral tetracycline treatment with topical metronidazole treatment may also enhance clinical decision making.     

Acne treated successfully with azithromycin

AIM: To study the efficacy, safety, and compliance of 500 mg azithromycin thrice weekly for 12 weeks in acne vulgaris. METHODS: An open-label, noncomparative study was carried out for 12 weeks at the outpatient clinics of Aga Khan University Hospital, Abassi Shaheed Hospital, and Burhani Community Hospital in Karachi, Pakistan. Thirty-five adolescent and postadolescent patients with moderate to severe papulopustular acne vulgaris were enrolled. All patients completed the study. Azithromycin, 500 mg orally thrice weekly for 12 weeks, was used. After the baseline visit, patients were scheduled to return at four-weekly intervals for 12 weeks. Efficacy was gauged by the percentage clearance of papulopustular acne lesions. Safety assessments included the monitoring of adverse events, and compliance was checked at the four-weekly regular visits up to 12 weeks. RESULTS: Twenty-nine patients (82.9%) showed remarkable improvement in the first 4 weeks with 60% reduction of their inflammatory papulopustular lesions. Maximum clearance (80%) was observed at 12 weeks. Residual postinflammatory pigmentation and pitted and linear scarring represented the aftermath of the relapsing pattern of acne. Six patients (17.1%) showed slow clearance with eruptions of new lesions. Adverse events, such as heartburn and nausea, were reported by four patients (11.4%). All patients completed the 12-week study period. CONCLUSION: Azithromycin, 500 mg thrice weekly for 12 weeks, is a safe and effective treatment of acne vulgaris with excellent patient compliance.     

Interventions for rosacea based on the phenotype approach: an updated systematic review including GRADE assessments

Rosacea is a common, chronic skin condition causing flushing, redness, red pimples and pus-filled spots (pustules) on the face. It affects about 1-20% of people worldwide. Rosacea can also cause inflammation of the eyes/eyelids (ocular rosacea) and thickening of the skin, especially the nose (rhinophyma). Although the cause of rosacea is unclear, treatments are available for this distressing disease. This review from the Netherlands, U.K. and Canada aimed to find out which treatments are effective for rosacea. The authors included data from 152 studies. For reducing redness, brimonidine and oxymetazoline worked from three up to 12 hours after being applied. For reducing pimples and pustules with topical (applied to the skin) treatments, azelaic acid, ivermectin and metronidazole were effective and safe. Ivermectin was slightly more effective than metronidazole. Minocycline foam also showed a large reduction in pimples and pustules. With oral (taken by mouth) antibiotics, tetracycline, doxycycline 40 mg or minocycline 45 mg reduced the number of pimples and pustules. Doxycycline 40 mg was likely as effective as 100 mg, with fewer side effects like diarrhoea and nausea. Oral minocycline 100 mg was as effective as doxycycline 40 mg. Azithromycin may be as effective as 100 mg doxycycline. Isotretinoin 0.25 mg/kg decreased pimples and pustules by 90%, and increased quality of life and patients’ satisfaction. Isotretinoin 0.3 mg/kg appeared to be slightly more effective than 50-100 mg doxycycline. However, isotretinoin is known to cause serious birth defects, so pregnancy must be avoided when using it. For treating dilated blood vessels, laser therapy and intense pulsed light therapy were both effective, but these studies had limited data. In ocular rosacea, ciclosporin 0.05% ophthalmic emulsion increased quality of life and improved the amount/quality of tears, and was slightly more effective than oral doxycycline. Omega-3 fatty acids likely improve dry eyes and tear gland function.