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.     

Oral zinc sulfate in the treatment of rosacea: a double-blind, placebo-controlled study

BACKGROUND: Rosacea is a skin problem not uncommonly encountered world-wide. There is a need for an effective and well-tolerated treatment for this disease. OBJECTIVE: To evaluate the efficacy and side-effects of zinc sulfate in rosacea in a randomized, controlled, double-blind trial. PATIENTS AND METHODS: Patients with rosacea who attended the outpatient Clinic of Dermatology and Venereology in Baghdad Teaching Hospital were recruited into this study between October 2002 and August 2004. A disease severity score was calculated for each patient. The patients were randomly allocated to receive either zinc sulfate 100 mg or identical placebo capsules three times per day. Zinc sulfate and placebo capsules were given in a double-blind manner. Following 3 months of starting the treatment, the patients crossed over, i.e. patients on placebo crossed over to zinc sulfate and those on zinc sulfate crossed over to placebo. RESULTS: Twenty-five patients with rosacea were included in this study: 16 (64%) females and nine (36%) males. Nineteen patients completed the study: 11 (58%) females and eight (42%) males. Patient age ranged from 21 to 64 years with a mean +/- SD of 48.2 +/- 9.3 years. Duration of the disease ranged from 1 to 14 years with a mean +/- SD of 4.4 +/- 3.2 years. In the group started on zinc sulfate, the score before therapy ranged from 5 to 11 with a mean +/- SD of 8 +/- 2.0. The mean started to decrease directly after the first month of therapy with zinc sulfate to a significantly lower level. After shifting to placebo treatment, the mean started to rise gradually in the fifth month but remained significantly lower than the levels before therapy. In the group started on placebo, the score before therapy ranged from 5 to 9 with a mean +/- SD of 7 +/- 1.3. The mean remained high in the first 3 months of therapy while the patients were on placebo. After shifting to zinc sulfate, the mean started to decrease after the fourth month to significantly low levels. No important side-effects were reported apart from mild gastric upset in three (12%) patients on zinc sulfate. CONCLUSION: Zinc sulfate was found to be a good option in the treatment of rosacea, as it was safe, effective and lacking important side-effects.     

Facial Sweet's syndrome mimicking rosacea fulminans

A 36-year-old man presented with a non-pruritic, erythematous facial rash with peri-oral and peri-orbital sparing. The initial clinicopathological diagnosis was rosacea fulminans, which was treated with 25 mg oral prednisolone and cephalexin. The patient re-presented 1 week later with exacerbation of his rash in addition to constitutional symptoms of fever and malaise. A further skin biopsy was taken and the marked neutrophilic infiltrate in the absence of vasculitis made the diagnosis of Sweet's syndrome (acute febrile neutrophilic dermatosis). High-dose prednisolone (50 mg daily), topical hydrocortisone cream and ichthammol in zinc ointment were commenced with rapid clinical improvement. This case highlights the importance of considering Sweet's syndrome as a differential diagnosis when presented with a facial eruption.     

A double-blind study of 1% metronidazole cream versus systemic oxytetracycline therapy for rosacea

In a randomized double-blind trial fifty-one patients with rosacea were treated for 2 months with either 1% metronidazole cream and placebo tablets or with 250 mg oxytetracycline tablets taken twice daily, and placebo cream (the cream base). The patients were assessed before and at the end of the trial, using the following criteria: (1) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, (5) patients' opinion. An improvement was shown in 90% of the patients of both groups, and there was no significant difference between the two treatments. One per cent metronidazole cream has been shown to be significantly better than a placebo cream in the treatment of rosacea (Gamborg Nielsen, 1983a), It was therefore considered important to compare the cream with conventional therapy, and for this reason a double-blind study of 1% metronidazole cream versus a daily dose of 500 mg oxytetracycline was performed.     

Oral zinc sulfate in the treatment of Behcet's disease: a double blind cross-over study

This was a randomized, controlled, double-blind trial of zinc sulfate in the treatment of Behcet's disease. Patients with Behcet's disease were recruited in this study between November 2001 and February 2003. A clinical manifestations index (CMI) was calculated for each patient. Serum zinc was estimated in all patients both at the beginning and monthly throughout the trial. Serum zinc levels were estimated from 30 healthy normal subjects matched for age and sex as a control group. Patients were randomly allocated to receive either 100 mg zinc sulfate or identical placebo tablet three times daily in a double-blind manner. After 3 months of starting treatment, patients were crossed over, that is, patients on placebo received zinc sulfate and vice versa. Mean serum zinc level in Behcet's disease patients was statistically significantly lower than mean serum zinc levels in healthy the control. In group A (started with zinc sulfate), the mean CMI started to decline directly after the first month of therapy with zinc sulfate to significantly lower levels. After shifting to placebo treatment in the fourth month, the mean of CMI started to rise again gradually but remained significantly lower than levels before therapy for the fourth and fifth months. In group B (started with placebo), the mean of CMI remained high for the first 3 months. After crossing over to zinc sulfate in the fourth month, the mean of CMI started to decrease after the fourth month. An inverse correlation between CMI and serum zinc level was found. No side-effects were seen in either group. In conclusion, zinc sulfate was found to be a good option in the treatment of Behcet's disease.     

A double-blind study of I% metronidazole cream versus systemic oxytetracycline therapy for rosacea

In a randomized double-blind trial fifty-one patients with rosacea were treated for 2 months with either I% metronidazole cream and placebo tablets or with 250 mg oxytetracycline tablets taken twice daily, and placebo cream (the cream base). The patients were assessed before and at the end of the trial, using the following criteria: (1) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, (5) patients' opinion. An improvement was shown in 90% of the patients of both groups, and there was no significant difference between the two treatments.     

Hydroxychloroquine in polymorphic light eruption: a controlled trial with drug and visual sensitivity monitoring

A double-blind controlled trial of oral hydroxychloroquine (HC) treatment in polymorphic light eruption (PLE) was completed in 13 patients on active treatment and 15 on placebo during June, July and August 1982. HC dose was 400 mg daily for the first month and 200 mg daily thereafter. Exposure to ambient solar ultraviolet radiation (UVR) was monitored throughout the trial by polysulphone film lapel badges. Patients scored their symptoms on a visual analogue scale. Drug concentration was monitored in plasma and hair, and oculotoxicity was assessed by visual contrast sensitivity. Moderate clinical improvement occurred, associated with a statistically significant improvement in skin rash (P less than 0.01).     

Oral zinc therapy of acne. Absorption and clinical effect.

In a double-blind controlled comparison that lasted eight weeks, tablets of zinc sulfate monohydrate, 411 mg total daily dosage, and a lactose placebo were administered orally to 22 male subjects with moderate acne. At the same time, levels of zinc were determined in serum and urine. There were no statistically significant differences in the lesion counts (papules, pustules, open comedones, and closed comedones) in the zinc-treated and lactose-treated cases, despite evidence in serum and urine of absorption of zinc. The data from this study indicate that oral zinc therapy has no early clinical effect on male patients with moderate acne.     

Niacinamide-containing facial moisturizer improves skin barrier and benefits subjects with rosacea

A growing body of literature suggests that some moisturizers can improve stratum corneum barrier function, as well as ameliorate dry skin. The clinical signs and symptoms of rosacea, which include increased facial skin dryness and sensitivity, suggest a possible role for such moisturizers as an adjuvant in the management of this condition. This randomized, investigator-blind, controlled observational study (N = 50) was designed to assess whether a niacinamide-containing facial moisturizer would improve the stratum corneum barrier and thus provide a clinical benefit to subjects with rosacea. Subjects with rosacea applied the test moisturizer to their face and to one forearm twice daily for 4 weeks. The other forearm remained untreated as a control. Barrier function on the forearms was assessed instrumentally and using a dimethyl sulfoxide (DMSO) chemical probe. Stratum corneum hydration also was measured instrumentally. The dermatologist investigator evaluated each subject's rosacea condition over the course of the study, and subjects self-assessed their facial skin condition at study end. Instruments provided objective measures of stratum corneum barrier function and hydration on the face.     

A randomized, single-blind, placebo-controlled, split-face study with pimecrolimus cream 1% for papulopustular rosacea

Background Rosacea is a common inflammatory skin disorder for which the pathogenesis is unclear. Currently, there is no cure for rosacea, and it seems that standard therapies have focused mainly on minimizing inflammation. Objectives The aim of this study is to investigate the potential efficacy, tolerability and safety profile of 1% pimecrolimus cream for the treatment of rosacea. Methods Twenty‐five patients with papulopustular rosacea were enrolled to a randomized, single‐blinded, placebo‐controlled, split‐face trial of pimecrolimus cream 1% consisting 4 week treatment and 2 week follow‐up period. The patients were instructed to apply first the ‘left side cream’ labelled placebo cream (Ultrabase cream, Intendis GmbH, Berlin, Germany) to the left hemi‐face then the ‘right side cream’ labelled 1% pimecrolimus cream (Elidel; Novartis Pharma, Nuremberg, Germany) to the right hemi‐face, twice daily. They were informed to apply a standard amount of each cream with the fingertip‐unit and not allowed to use any other agent concomittantly other than sunblock. Clinical evaluation and subjective severity assessment were obtained along with photographic documentation at baseline, first, second, and fourth weeks of the therapy and at the follow‐up visit. Rosacea severity score for each sign of erythema, papules, pustules, oedema, and telengiectesia were graded from 0 to 3. Patients were questioned for the subjective symptoms, overall improvement on appearance and side‐effects. Results Twenty‐four patients completed the study with an exceptional compliance and tolerable safety profile. One patient withdrew from the study due to severe flare‐up reaction affecting both hemi‐faces. The mean baseline total rosacea severity scores were 5.06 + 1.29 for both sides and reduced to 2.5 ± 1.06 vs. 3.25 ± 1.24 on pimecrolimus vs. placebo applied sides without the significance (P = 0.06). There was not any significant difference concerning each rosacea sign scores and total rosacea severity scores except for the significant improvement in erythema score and total rosacea severity score obtained on the pimecrolimus‐applied hemi‐face at 2nd week of therapy (P =0.01 and P = 0.03, respectively). The reduction rates of the mean subjective severity scores at 4th week were 49.77% vs. 38.89% for pimecrolimus vs. placebo, respectively, without a statistical significance (P = 0.15). Subjective symptoms responded well in 54.16% of patients concerning pimecrolimus application compared with 12.50% for the placebo application. The side‐effects were mostly transient local irritations. Conclusion Our data implicated that pimecrolimus cream is not superior to placebo except for its efficacy on erythema. We believe that pimecrolimus cream can be a treatment option for rosacea patients with high erythema score for whom an initial accelerated improvement is needed. We believe further studies with topical pimecrolimus cream on larger study groups with different subtypes and severity of rosacea will clarify the potential effect of pimecrolimus cream for the treatment of 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.     

Oral zinc sulphate therapy in acne vulgaris: a double-blind trial

The effect of zinc sulphate and placebo was compared in a double-blind trial in 56 patients suffering from acne vulgaris. Serum vitamin A levels were studied in all, before and at the end of therapy, 29 patients received zinc sulphate 600 mg daily and 27 patients received placebo. Patients on placebo showed no improvement. After 12 weeks of treatment with zinc sulphate, 17 patients (58%) showed significant improvement. There was a statistically significant decrease in the number of papules, infiltrates and cysts. In zinc-treated cases there was statistically significant increase in serum vitamin A levels, while no change was found in the placebo group.     

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.     

Treatment of psoriasis with oral liarozole: a dose-ranging study

BACKGROUND: Liarozole is an inhibitor of the metabolism of all-trans-retinoic acid. Systemic administration increases tissue levels of this endogenous retinoid and has been reported to improve psoriasis in an open, uncontrolled study. OBJECTIVES: A multicentre, double-blind, placebo-controlled, dose-ranging study was therefore undertaken to determine the lowest effective oral dose of liarozole in the treatment of psoriasis vulgaris. PATIENTS/METHODS: Adult male and postmenopausal female patients requiring systemic treatment for psoriasis were randomized to receive placebo or liarozole at total daily doses of 50 mg, 75 mg or 150 mg for 12 weeks. The daily doses were each divided into two equal (morning and evening) doses. Response was assessed using an eight-point global scale to assess improvement and by monitoring the Psoriasis Area and Severity Index (PASI). The primary end-point was the proportion of subjects in each treatment group demonstrating 'marked improvement' or better as assessed on the eight-point scale. The tolerability of the treatment was assessed by recording mucocutaneous effects of retinoids and all adverse events. Biochemical and haematological monitoring were also performed. RESULTS: One hundred and thirty-nine subjects were randomized (118 male and 21 female) and 116 completed the study. A marked improvement or better response was observed in 6% of subjects on placebo, 18% on liarozole 50 mg, 11% on 75 mg and 38% on 150 mg. Only in the 150-mg group was the response rate significantly different to placebo (P < 0.001). Over the treatment period the mean PASI changed from 15.9 to 15.4 on placebo, from 17.4 to 13.8 on liarozole 50 mg, from 17.5 to 14.5 on 75 mg and from 15.8 to 8.8 on 150 mg. Again, only in the group receiving 150 mg was the response significantly better than placebo (P < 0.001). Liarozole was generally well tolerated. Mucocutaneous retinoid effects were generally infrequent and mild. Five subjects were withdrawn from treatment as a result of adverse events that may have been treatment related. These events were abnormalities of liver enzymes in two cases, an episode of erythema multiforme (in a patient receiving placebo), an allergic reaction in one and a rash accompanied by deterioration of the psoriasis in another. There was mild elevation of triglycerides in the groups receiving liarozole 75 mg and 150 mg daily. In males, the serum luteinizing hormone and testosterone levels rose significantly in all the active treatment groups. CONCLUSIONS: The data confirm that liarozole is an effective treatment for psoriasis and indicate that the lowest effective dose is 75 mg twice daily. The drug seems generally to be well tolerated.     

The effect of oral and topical tetracycline on acne severity and on surface lipid composition.

Groups of 20 males of high-school age with moderate acne were treated with oral tetracycline (500 mg/day), topical tetracycline (0.5% solution applied twice daily), or placebo for 8 weeks. The two panels treated with tetracycline showed a significant and equivalent reduction in acne severity as assessed by visual grading. The surface lipids in the panel treated with oral tetracycline showed a small but not statistically significant decrease in free fatty acid content, but the subjects receiving topical tetracycline showed no reduction in free fatty acids. Further, neither treatment was associated with a change in mass of surface lipid nor did the mass or weight percent of any component of the surface lipids change with the decrease in acne severity. These results show that acne severity can be reduced with tetracycline (both oral and topical) without any concomitant quantitative change in surface lipids.     

Alcohol-induced rosacea flushing blocked by naloxone

We evaluated the roles of endogenous opioid peptides and histamine in the pathophysiology of alcohol-induced facial flushing in rosacea. Non-diabetic patients with rosacea ingested 360 ml of 6% ethanol after receiving either subcutaneous naloxone hydrochloride or oral chloropheniramine maleate. Only pretreatment with naloxone blocked the alcohol-induced rosacea flushing (AIRF), suggesting an active role of endogenous enkephalin and/or endorphin in this vascular reactivity. In this respect, AIRF is similar to chlorpropamide alcohol flushing and menopausal flushing.     

Oral zinc sulphate therapy for acne vulgaris.

A double-blind controlled clinical trial was performed to evaluate the effect of oral zinc sulphate, 0.6 g daily, on acne vulgaris. Twenty patients received zinc sulphate tablets and 19 were given placebo tablets. Thirteen of the zinc group and 12 of the placebo group received their medication throughout a 12-week period, while the remaining patients were treated for 4 or 8 weeks. In all patients the numbers or papular and pustular acne lesions on the face and the back were significantly reduced, while larger infiltrates remained practically unaltered during the trial, which was performed from March through May 1975. No statistically significant difference in the improvement of the groups was demonstrable. Pretreatment serum zinc values, which were normal in all patients, rose significantly in the zinc group as well as in the control group, but the increase in the former was significantly higher. The negative therapeutical results might be attributable to the limited number of patients or related to the zinc dosage. Furthermore, the results might have been influenced by the unexplained rise in serum zinc values in the control group. A possible weak beneficial effect of zinc might also have been camouflaged by the seasonal variation in the severity of acne which was noted in this study.     

Short term treatment of pityrosporum folliculitis with itraconazole

We compared the efficacy and safely of short-term itraconazole with that of placebo in 26 patients of pityrosporum folliculitis. Twenty-six patients of mycologically proven pityrosporum folliculitis entered a double-blind placebo-controlled trial. Patients were randomly assigned to 7 days of treatment with either itraconazole, 200 mg once daily, or placebo. A global clinical assessment and mycological examination (KOH and smear examination) were performed at baseline and at 4 weeks after treatment. In this study, itraconazole in a dose of 200 mg for 7 days produced a distinct and statistically significant improvement over placebo (p<0.01). 84.6% of itraconazole treated patients were considered to be healed or markedly improved at the study's end point compared with 8.3% of placebo treated group (p<0.01). Eighty-four percent of patients receiving active treatment showed negative mycological examination as compared to 8.3% of placebo-treated group (p<0.01). Short-term treatment with itraconazole is effective and well tolerated in the management of pityrosporum folliculitis.     

Effects of oral zinc and vitamin A in acne.

The effects of oral zinc sulfate (corresponding to 135 mg of zinc daily) alone and in combination with vitamin A (300,000 international units) daily on acne lesions have been compared with those of vitamin A alone and of a placebo. The number of comedones, papules, pustules, and infiltrates were counted at each visit. After four weeks, there was a significant decrease in the number of papules, pustules, and infiltrates in the zinc-treated groups. The effect of zinc plus vitamin A was not better than zinc alone. After 12 weeks of treatment, the mean acne score had decreased from 100% to 15%. The mechanism for the effect of zinc therapy in acne, to our knowledge, is not presently known.?     

The link between Helicobacter pylori infection and rosacea

BACKGROUND: Rosacea is a common condition of unknown aetiology that is usually accompanied by gastrointestinal symptoms and responds favourably to treatment with antibiotics. AIMS/METHODS: This study was designed to examine the prevalence of gastric Helicobacter pylori (Hp) infection verified by 13C-UBT, CLO-test, Hp culture and serology (IgG and IgA) and the presence of Hp in the oral cavity evidenced by CLO-test, Hp culture and saliva anti-Hp antibodies (IgG and IgA). During gastroduodenoscopy antral and fundic biopsy samples were taken for histological evaluation (the Sydney system). This study was performed on 60 subjects 30-70 years old with visible cutaneous rosacea symptoms and 60 age- and gender-matched controls without skin diseases but with dyspeptic symptoms similar to those of rosacea and without endoscopic changes in gastroduodenal mucosa (non-ulcer dyspepsia--NUD). RESULTS: The Hp prevalence in rosacea patients was about 88%, compared to 65% in the NUD controls. A noticeable number of rosacea patients showed chronic active gastritis predominantly in antrum but also in the corpus while those with NUD showed only mild gastritis confined to the antrum only. Following the initial examination, a typical 1 week systemic anti-Hp therapy, induding omeprazole (2 x 30 mg), clarithromycin (2 x 500 mg) and metronidazole (2 x 500 mg), plus gargling and application of metronidazole paste in the case of Hp oral cavity infection. After the application of the systemic and local therapy in the oral cavity, Hp was eradicated from the stomach in 97% and from the oral cavity in 73% of treated patients. Within 2-4 weeks, the symptoms of rosacea disappeared or decreased markedly in 51 subjects. SUMMARY: We conclude that: (1) rosacea is a disorder with various gastrointestinal symptoms closely related to gastritis, especially involving the antrum mucosa; (2) the eradication of Hp leads to improvement of symptoms of rosacea and reduction in related gastrointestinal symptoms; (3) the lack of improvement of cutaneous symptoms in rosacea after eradication of Hp from the gastric mucosa could depend on bacteria in the oral cavity; and (4) rosacea could be considered as one of the extragastric symptoms of Hp infection probably mediated by Hp-related cytotoxins and cytokines.