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.     

Rosacea treatment with intermediate-dose isotretinoin: follow-up with erythema and sebum measurements

Isotretinoin is one of the therapeutic options for rosacea. However, the response of erythema to treatment with isotretinoin is usually slow and incomplete with common (0.5-1 mg/kg/day) or low (10 mg/day) doses. This study investigated the efficacy of, and relapse on, 20 mg/day isotretinoin treatment in rosacea, with the aid of instrumental measurement of facial erythema and sebum levels. A 20 mg/day dose of isotretinoin was given for 4 months, and then the dose was tapered off within the following 6 months. A total of 25 patients were included in the study. Papule and pustule counts, erythema index, sebum level, dermatologist's and patient's erythema scores, and dermatologist's sebum scores were significantly lower in the first month of therapy compared with pre-treatment values (p < 0.05). Within a median follow-up of 11 months (95% confidence interval: 8.4-13.5 months) 45% of patients had a relapse. In conclusion, 20 mg/day isotretinoin was rapidly efficient for reducing both inflammatory lesions and erythema in rosacea.     

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.     

The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol

Background Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4‐oxo‐isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids also containing a carboxylic acid moiety are capable of undergoing an ethyl esterification with the metabolic formation of more lipophilic compounds with a much longer terminal half‐life. Objectives To determine if isotretinoin (13‐cis‐RA), its main metabolite 4‐oxo‐isotretinoin (4‐oxo‐13‐cis‐RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4‐oxo metabolite were determined. Patients/methods Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple self‐administered questionnaire and by measuring serum ethanol levels during treatment. The concentrations of isotretinoin, 4‐oxo‐isotretinoin and possible ethylated and nonethylated metabolites were measured by reverse‐phase high‐performance liquid chromatography. Results Although seven of 11 patients had a considerable weekly alcohol intake, no endogenous synthesis of ethyl derivatives of isotretinoin, the main 4‐oxo metabolite or the all‐trans compounds was chromatographically detectable in any of the patients’ plasma samples during the treatment period. Multiple dose pharmacokinetic data for the parent drug and its main metabolite were comparable to previous studies. Conclusions The metabolism and pharmacokinetics of isotretinoin and its main metabolites are not influenced by ethanol during long‐term isotretinoin treatment. After ceasing long‐term isotretinoin therapy the recommended period of 1 month for using anticonceptive measures in fertile women seems adequate.     

Roaccutan in acne and rosacea

Isotretinoin (Accutane) is a lately developed synthetic oral retinoid for treatment of severe forms of cystic acne resistant to therapy. Its pharmacological effect principally consists in decreased size of the sebaceous glands, reduced sebum production, as well as alteration of the bacterial micropopulation. At a dosage of 0.5 mg up to 1.0 mg/kg body weight daily, isotretinoin led to significant reduction of the inflammatory skin eruptions and long-lasting remission after discontinuation of the drug. With regard to 18 patients suffering from rosacea, the application of Accutane brought about satisfactory results, as well. Mucocutaneous side-effects were almost compulsory, but did never lead to discontinuation of the treatment. Because of its teratogenity, isotretinoin must not be applied in case of gravidity. Accutane offers new modes of therapy with respect to patients suffering from nodulocystic acne or severe rosacea which did not respond to common forms of treatment.     

Low‐cumulative dose isotretinoin treatment in mild‐to‐moderate acne: efficacy in achieving stable remission

Background Aimed at the reduction of post‐treatment relapse of severe acne, the cumulative dose of oral isotretinoin should be ≥120 mg/kg. However, data on the appropriate oral isotretinoin treatment regimen in mild and moderate acne are lacking. Objective The purpose of this study was to determine the efficacy of an isotretinoin‐sparing protocol in inducing permanent remission of mild and moderate acne. Methods In this open, prospective, non‐comparative study, 150 patients affected with mild‐to‐moderate acne were treated with isotretinoin until complete recovery and for a further month of treatment, independent of the total cumulative dose reached. Patients then underwent a 1‐year maintenance therapy with adapalene 0.1% cream. Patients were followed up for a further year, without any treatment. Results A total of 139 patients completed the study. Overall, patients received a mean of 80.92 mg/kg cumulative dose of isotretinoin. In the 2‐year follow‐up, relapse only appeared in 13 patients (9.35%). Conclusion Comparing our findings with published data, this isotretinoin‐sparing regimen was shown to be effective in inducing stable remission and preventing acne relapses in patients with mild‐to‐moderate acne. Low‐cumulative dose regimens may potentially lead to a lower incidence of side‐effects and to lower costs than higher doses.     

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.     

High-dose isotretinoin in acne vulgaris: improved treatment outcomes and quality of life

Background Isotretinoin, for acne treatment, is associated with high rates of permanent remission. However, at recommended doses of 0.5-1.0 mg/kg/day for 5-6 months [average cumulative dose: 120-150 mg/kg], more than 20% of patients experience a relapse within two years that requires further medical management. Objective To examine outcomes of high-dose isotretinoin in a cohort with cystic acne, as well as measuring its impact on quality of life (QOL). Methods A single dermatologist, single institution investigation within an academic tertiary care center in Bronx, NY. Eighty patients with nodulocystic acne, maintained on oral isotretinoin at a dose of 1.3 mg/kg/day or greater, were studied from 2006-2009 while additionally participating in a QOL survey. Main outcome measures included documented events, acne clearance, presence of relapse, and quality of life parameters. Results The mean daily dose of isotretinoin was 1.6 mg/kg/day for an average time course of 178 days [cumulative dose: 290 mg/kg]. No side effects or laboratory abnormalities led to discontinuation of treatment. There were no psychiatric symptoms. One-hundred percent (100%) of patients were disease-free upon completion of treatment. During the three-year study period, 10 patients (12.5%) developed a relapse that required an additional course of isotretinoin. Analysis of QOL domains (self-perception, role-social, symptoms) revealed significant improvement following isotretinoin therapy (p = 0.0124, p = 0.0066, p = 0.0265, respectively). Conclusions Isotretinoin prescribed at 1.5 mg/kg/day or greater for 5-6 months [cumulative total dose of 290 mg/kg] is safe and effective compared to current standard dosing practices. We propose the use of high-dose isotretinoin (>1.3 mg/kg/day) as a treatment option in severe nodulocystic acne and encourage larger, prospective, multicenter studies into this therapeutic approach.     

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.     

Short‐term isotretinoin treatment decreases insulin‐like growth factor‐1 and insulin‐like growth factor binding protein‐3 levels: does isotretinoin affect growth hormone physiology?

Summary Background Isotretinoin is an effective treatment for acne vulgaris. However, it has numerous side‐effects. It was previously reported that serum growth hormone (GH) levels decreased with isotretinoin treament. Objectives To analyse whether isotretinoin has any effects on insulin‐like growth factor‐1 (IGF‐1), insulin‐like growth factor binding protein‐3 (IGFBP3) and GH levels. Methods Forty‐seven patients aged 21·5 ± 5·1 years (mean ± SD) with acne vulgaris were included in this study. Isotretinoin therapy was initiated at a dose of 0·5–0·75 mg kg^?1 daily and then adjusted to 0·88 mg kg^?1 daily as maintenance dosage after 1 month. Screening for biochemical and hormonal parameters was performed just before initiation and after 3 months of isotretinoin treatment. Results IGF‐1 and IGFBP3 levels decreased significantly after treatment (P < 0·01), while GH levels did not change. Post‐treatment, significant increases were seen in aspartate aminotransferase, total cholesterol, low‐density lipoprotein cholesterol, triglycerides and low‐density lipoprotein cholesterol/high‐density lipoprotein cholesterol ratio (P < 0·0001) while high‐density lipoprotein cholesterol levels were significantly decreased (P < 0·0001). Conclusions Isotretinoin therapy may have an effect on GH physiology, and further studies are needed to understand this association.     

Low dose isotretinoin combined with tretinoin is effective to correct abnormalities of acne

Background: Isotretinoin is well known in the therapy of acne papulopustulosa and acne conglobata. No study has investigated the pathophysiological changes of the skin of acne patients, especially when low dose oral isotretinoin is given in combination with topical tretinoin. Patients and methods: 28 patients were treated for 6 months with oral isotretinoin. In the acne conglobata group (A – C) patients were treated with 10 mg (Group A) or 20 mg isotretinoin (Groups B, C) in combination with topical 0.05 % tretinoin cream. Group C was treated the first 2 weeks with 0.05 % betamethasone valerate cream instead of tretinoin cream. In the acne papulopustulosa group, the patients received 0.5 mg isotretinoin/kg bodyweight and 0.05 % tretinoin cream, either alone (Group E), or with oral methylprednisolone during induction (Group D). Results: Acne conglobata – A reduction of inflammatory lesion by 87 – 94 % and of non‐inflammatory lesions by 81 – 88 % was achieved (Groups A – C). A reduction of sebaceous gland size by 35 – 58 %, sebum production by 90 – 95 %, follicular keratinization by 55 – 70 % and Propionibacteria by 33 – 73 % was seen (Groups B and C better than Group A). In Group A the amount of lipids was only reduced by 6 %, in Group B by 35 % and in Group C by 40 %. Acne papulopustulosa – Sebum excretion rate and follicular keratinization were reduced in Group D by 89 % and 50 % respectively, with isotretinoin alone by 94 % and 53 %. The amount of lipids was reduced in Group D by 40 % and in Group E by 21 %. Conclusions: Because of the efficacy and cost‐benefit relationship of isotretinoin in the treatment of acne compared to other therapeutic approaches, further use low dose isotretinoin in the described settings seems to justified.     

Prognosis of 234 rosacea patients according to clinical subtype: The significance of central facial erythema in the prognosis of rosacea

Rosacea has a wide spectrum of clinical features, which include persistent facial redness, flushing, telangiectasia, inflammatory papules/pustules, hypertrophy and/or ocular features. The prognosis of rosacea according to clinical subtype has not been evaluated. We analyzed the prognosis of rosacea in 234 patients, which included 120 patients with mixed subtype, 75 with the erythematotelangiectatic rosacea subtype and 39 with the papulopustular rosacea (PPR) subtype. The prognosis of rosacea was classified as: (i) no improvement; (ii) partial remission; and (iii) complete remission. The frequencies of complete remission, time to complete remission and 1‐year complete remission rate were compared between subtypes. Follow‐up periods ranged 2–72 months (median follow‐up, 17.5). Aggravation of the disease was found in 50.4% of patients during follow up. Partial or complete remission was noted in 61.5% and 20.9% of patients, respectively. The median time to complete remission was 56.0 months. The prognosis of disease was more favorable for patients with the PPR subtype than for patients with other subtypes with respect to the frequency of complete remission, median time to complete remission and the 2‐year complete remission rate. In conclusion, papulopustular rosacea without remarkable centrofacial erythema showed a more favorable prognosis than other subtypes. Erythematotelangiectatic lesions in rosacea patients present a challenge for the treatment of rosacea.     

Response of rosacea to isotretinoin

We have treated seven patients with severe rosacea with 1 mg kg^?1 day^?1 isotretinoin for 12 weeks. There were large reductions in numbers of papules and pustules (P < 0.001) small decreases in measurements of erythema (P < 0.01) and median values for severity were lower during and after treatment. There was evidence of relapse by 8 weeks after stopping isotretinoin. Side-effects were well tolerated and increases in serum lipids and indices of liver function had reversed by 4 weeks after treatment. We conclude that isotretinoin is effective in rosacea.     

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.     

Adverse effects of isotretinoin: A retrospective review of 1743 patients started on isotretinoin

Background/Objectives: Isotretinoin has revolutionized the management of acne vulgaris. However, concerns continue regarding the adverse effect profile of isotretinoin. This study aims to review the adverse effects experienced by patients started on isotretinoin by a single dermatologist. Methods: Retrospective chart review of 1743 patients started on isotretinoin for various dermatological conditions over a 6‐year period. Details of the dose of isotretinoin used, concomitant medications, adverse effects and outcome were recorded. Results: One‐fifth (18.5%) of patients reported no adverse effects during the study period. Cheilitis was the most commonly reported adverse effect, affecting 78% of users, followed by eczema and tiredness, seen in 12% each. However, these were clearly dose‐dependent, as the group treated with doses of isotretinoin under 0.25 mg/kg/day only reported cheilitis in 47%, eczema in 7% and tiredness in 5%, compared with 96%, 16% and 18%, respectively, in those treated with more than 0.75 mg/gm/day. Twenty‐four patients (1.4%) stopped isotretinoin because of adverse effects; a further three patients complained of severe adverse effects on at least one occasion, but continued taking the medication. The adverse effect(s) that led to patients stopping isotretinoin were cheilitis (22 patients), mood change (13), tiredness (12), eczema (6) and pregnancy (2). There were no reported instances of suicidal ideation or attempted suicide. Conclusions: Other than the two oral contraceptive failures, there were no serious adverse events recorded during this review period. Isotretinoin is a very effective medication with a low adverse‐effect profile when used at lower doses.     

ISOTRETINOIN FOR ACNE VULGARIS

Background. The clinical efficacy of oral isotretinoin in the treatment of severe acne is now well established and so are the clinical and laboratory adverse effects of the drug. Isotretinoin was first introduced in Saudi Arabia late in 1987. In this 7-year retrospective study, efficacy and side effects of isotretinoin are reviewed in Saudi patients with acne vulgaris seen in a university skin clinic in Riyadh, Saudi Arabia. Materials and Methods. A total of 262 patients had been treated with isotretinoin. Their case records were studied with reference to demographic data, clinical findings, dosage of isotretinoin, response to the drug, and the prevalence and severity of clinical and laboratory adverse effects. Results. Only 156 case records (69.9% women) could be evaluated. Most patients received 0.60 to 0.75 mg of isotretinoin per kg per day for a period ranging from 16 to 35 weeks (mean ± SD: 21.2 ± 3.3 weeks); a total cumulative dose of 75 to 146 mg per kg (mean ± SD: 104 ± 10.6 mg per kg). Approximately 56% of the patients had therapy-resistant moderate acne and only 14% had nodulocystic acne. Of the patients, 90.4% had an excellent response and 3.8% were poor responders. Adverse effects occurred in 99% of the patients, but in no case did they lead to discontinuation of the drug. Except for minor differences in prevalence, the clinical side effects were similar to those reported in the literature. Elevation of plasma triglyceride levels was the most significant laboratory adverse effect. Conclusions. This is the first report on the experience with isotretinoin in the treatment of acne in the Middle East. Moderate doses of isotretinoin are well tolerated and produce excellent results in Saudi patients with acne.     

The use and long-term benefit of isotretinoin

Isotretinoin is effective in the treatment of acne, but at low doses (0·1 mg/kg) many patients relapse. Over the past 5 years we have treated 250 patients with either 0·5 mg/kg or 1·0 mg/kg of isotretinoin and have followed them up for up to 3 years to determine the relapse rate. All patients in each dose group responded well, with a 90% improvement in acne grade. The majority (86%) needed only 4 months'treatment, but 13% needed 6 months, and two patients required 9 months of continuous therapy. Patients with marked mucous membrane side-effects tended to respond better than those without such side-effects.
The relapse rate in the 0·5 mg/kg group was significantly greater (42%) than in the 1·0 mg/kg group (13%) (P < 0·01); relapse was defined as the need for further oral therapy—either antibiotics or isotretinoin. Truncal acne was more likely to relapse than facial acne (P < 0·05). Younger patients relapsed more quickly than older patients (P < 0·05). Patients treated with isotretinoin fell into one of five categories: (i) severe acne with isotretinoin as first-line therapy (18%); (2) failure to improve on conventional antibiotic therapy (55%); (3) rapid relapse after two courses of conventional antibiotic therapy (21%); (4) Gram-negative folliculitis (3%); and (5) severe psychological disturbance about minor degrees of acne that normally would not require isotretinoin (3%).
We thus recommend 1·0 mg/kg as the best dose of isotretinoin for long-term benefit in acne, and that isotretinoin should now be considered as part of the treatment for less severe types of acne.     

A single blind randomized clinical study: the efficacy of isotretinoin plus narrow band ultraviolet B in the treatment of psoriasis vulgaris

In this randomized clinical trial, 39 patients with psoriasis vulgaris were randomized in two groups. Intervention group received narrow band ultraviolet B (NBUVB)+isotretinoin (0.5 mg/kg/day), control group received NBUVB+placebo. Psoriasis Area Severity Index (PASI) scoring was recorded at baseline and weeks 4, 10, and 14. Thirty‐seven patients completed the study. According to recorded PASI scores the difference between efficacies of two treatments was not significant. Complete clearing was noticed in 14 and 13 patients in intervention group and controls. The mean cumulative NBUVB dose in intervention group and controls was 29.95 ± 16.11 vs. 45.77 ± 7.72 J/cm² (P=0.004). Isotretinoin+NBUVB can reduce number of phototherapy sessions and cumulative NBUVB dose.     

ISOTRETINOIN THERAPY IN ACNE VULGARIS: A 10-YEAR RETROSPECTIVE STUDY IN SINGAPORE

Background. The use of isotretinoin, a first generation synthetic retinoid, in the treatment of patients with severe acne vulgaris was a major therapeutic advance in dermatology. This 10–year retrospective study reviews the effectiveness of isotretinoin in patients with acne vulgaris seen in a skin clinic in Singapore. Methods. The case records of 250 cases of severe inflammatory and nodulocystic acne treated with isotretinoin were analyzed with reference to the demographic data, response to isotretinoin, dosage and cost of isotretinoin used, adverse effects, clinical follow-up, and relapse. Results. Two hundred and fifty patients, 171 men (68.4%) and 79 women (31.6%), with different types and grades of acne vulgaris were studied. The dose of isotretinoin used ranged from 0.33 to 1.0 mg/kg/day (median 0.5 mg/kg/day) for a period ranging from 1 to 12 months (median 4 months). Response was excellent in 127 (50.8%) patients, good in 86 (34.4%), fair in 30 (12.0%) and poor in 7 (2.8%). Relapse occurred in 14 (5.6%) patients over a 6–month follow-up period. Adverse effects were noted in 140 (56.0%) patients and were mild in most cases. Eighteen (7.2%) patients had to discontinue the drug due to significant side effects. Conclusion. This study confirms that isotretinoin is very effective for severe acne, and complete remission can be induced in more than 90% of cases even with lower dosage regimens. Significant clinical improvement can be achieved with the use of lower doses (mean 0.5 mg/kg/day) for an average of 4 months of treatment with lower risk of adverse effects.     

Real‐life experience on effectiveness and tolerability of topical ivermectin in papulopustular rosacea and antiparasitic effect on Demodex mites

Ivermectin is a drug approved for the treatment of papulopustular rosacea (PPR). Although clinical guidelines recommend the use of ivermectin as the first‐line treatment in patients with almost clear and mild rosacea, studies concerning its use on them are lacking. This study investigated the effectiveness and the tolerability of ivermectin in almost clear to severe rosacea and assessed the antiparasitic effect on Demodex mites. This is a retrospective study based on 50 patients affected by PPR and treated with topical ivermectin 1% once daily over 16 weeks. The disease severity, the patient‐examined improvement, and the safety assessment of patients were evaluated. Demodex mites were studied with the standardized skin surface biopsy. PPR to all severity achieved a therapeutic success. The number of inflammatory lesions was significantly decreased in almost clear (p < .0001), mild, moderate, and severe (p < .001) forms. A complete remission of inflammatory lesions was achieved by almost clear (p < .001) and mild (p = .005) with 82% with none‐to‐mild cutaneous adverse events. Thirty‐two percent were positive for Demodex mites, and all of them turned negative after 16 weeks. Ivermectin is an effective treatment not only in moderate to severe PPR but also in almost clear/mild rosacea.