Low-dose schema of isotretinoin in acne vulgaris

In severe papulopustular and in nodulocystic/conglobate acne, oral isotretinoin is the treatment of choice. It is also required for patients with moderate to severe acne, especially when acne scars start to occur A new therapeutic approach consists of a low-dose regimen of isotretinoin. We performed a comparative study of high- and low-dose schemas of isotretinoin per os for the treatment of acne. The purpose of this study was to assess the therapeutic effect and tolerability of low doses of isotretinoin in the treatment of acne vulgaris and compare low-dose with high-dose regimens. Sixty-four patients (35 women and 29 men) with different types and grades of acne vulgaris were divided into two treatment groups of 32 patients, in a trial that compared a low dose of 0.15-0.40 mg/kg per day with a high dose of 0.5-1.0 mg/kg per day. These regimens were analyzed with reference to clinical history of acne, baseline investigations, dose and response to isotretinoin, clinical and laboratory adverse effects, relapses and cost of therapy. The mean success rate of the low-dose schema was 69%. The total dose up to 120 mg/kg should be followed for optimal results (success rate of 91%) and avoidance of relapses. The low-dose schema produced fewer adverse effects and offered a very beneficial effect on pre-existing scarring. Our results confirm the beneficial effect of the low-dose schema. We recommend a total dose > or = 120 mg/kg, as this therapeutic regimen of isotretinoin has proven to be the most successful in preventing relapses and scarring.     

Evaluation of ovarian reserve and function in female patients treated with oral isotretinoin for severe acne: an exploratory study

Background: Isotretinoin affects the levels of female hormones and ovaries in patients with severe acne.

Objective: This study evaluated the effects of isotretinoin on the ovarian reserve and levels of female hormones in patients with severe acne.

Methods: Thirty-two female patients with severe acne were enrolled. All the patients were treated with oral isotretinoin 0.5–2?mg/kg/d. The total cumulative dose for a full course was 120–135?mg/kg. The treatment duration ranged from 5 to 8 months. The serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels and antral follicle count (AFC) and ovarian volume (OV) were evaluated before and after treatment.

Results: After treatment, the mean FSH, LH, and E2 levels were significantly lower than before treatment. In addition, the mean AFC and OV decreased after treatment, although the difference was not significant.

Conclusion: The results of this exploratory study do not demonstrate that oral isotretinoin has an impact in ovarian function. In contrast, isotretinoin affects levels of female hormones in patients with severe acne.     

Systemic treatment of severe acne with a retinoic acid derivative, isotretinoin

Twenty-eight patients with severe acne and one with hidradenitis suppurativa and acne were treated for 12 to 16 weeks with a new synthetic retinoid, isotretinoin (Roaccutane). The average dose was 0.56 mg/kg/day. Patients were seen weekly for four weeks and then fortnightly for the remaining treatment period, being evaluated both qualitatively and quantitatively. Twenty-five patients had an excellent response. Two to five months after the end of treatment no patient had relapsed. No patient withdrew because of side effects, but all suffered dry lips. This study confirms the potential of isotretinoin in the treatment of severe acne.     

The prevalence of sacroiliitis in patients with acne vulgaris using isotretinoin

Background/Objective: Acne vulgaris is a chronic inflammatory disease affecting the pilosebaceous unit in the skin. Isotretinoin is a synthetic vitamin A derivative regarded as the most effective agent in the treatment of acne. There have recently been increasing reports of adverse effects of isotretinoin on the skeletal system. Our aim in this study was to evaluate the rheumatic side-effects triggered by this drug, and particularly the prevalence of sacroiliitis.

Materials and methods: A total of 73 patients receiving isotretinoin due to moderate or severe acne vulgaris were included. All patients were questioned about inflammatory low back pain and musculoskeletal pains during the treatment process. Inflammatory low back pain was evaluated using Assessment of Spondyloarthritis International Society (ASAS) criteria. Patients meeting ASAS criteria were evaluated with radiography and when necessary with sacroiliac magnetic resonance.

Results: The dose range for isotretinoin was between 0.4 and 0.8?mg/kg/day (mean 0.53?mg/kg/day). Treatment lasted for 6–8 months (mean 6.8 months). Lethargy was determined in 37 (50.7%) patients, myalgia in 31 (42.5%) and low back pain in 36 (49.3%). Mechanical low back pain symptoms were present in 20 of the patients describing low back pain and inflammatory low back pain in 16. Acute sacroiliitis was determined in six patients (8.2%) following a sacroiliac magnetic resonance imaging (MRI). Five (83.3%) of the patients with sacroiliitis were female and one (16.7%) was male. No statistically significant difference was determined between male and female patients in terms of prevalence of sacroiliitis (p =?0.392).

Conclusion: The incidence of sacroiliitis in patients using isotretinoin is quite high. Patients using isotretinoin must be questioned about sacroiliitis findings and must be subjected to advanced assessment when necessary. Further studies regarding the development of sacroiliitis under isotretinoin therapy are now needed.     

异维A酸治疗痤疮及对女性血清性激素的影响

目的：观察异维Ａ酸治疗痤疮的疗效及其对血清内性激素水平的影响。方法：痤疮病人５０例，单纯口服异维Ａ酸胶丸１０ｍｇ，ｔｉｄ×８ｗｋ，然后改为１０ｍｇ，ｑｄ×４ｗｋ。另用放射免疫法测定７例女性治疗前及治疗后血清黄体生成素、卵泡刺激素、雌二醇、睾酮及孕酮水平。结果：总有效率为９６％，显效率为６４％。无严重毒副作用。治疗前后血清性激素水平差异不显著（Ｐ＞０．０５）。结论：异维Ａ酸为痤疮治疗的优选药物，对病人的血清性激素水平无影响。     

维胺酯2种给药方案治疗寻常痤疮44例

目的 :观察维胺酯不同剂量治疗痤疮的疗效和安全性 ,探索有效治疗方案。方法 :将 4 4例中、重度寻常痤疮病人分为 2组 ,A组 2 4例 ,总疗程 6mo ,分别在mo 1～ 2按 1mg·kg- 1·d- 1;在mo 3～ 4按 2 5mg ,qd ;在mo 5～ 6按 2 5mg ,qod的剂量口服。B组 2 0例 ,5 0mg ,tid ,总疗程 6wk。结果 :2组总累积量A组为 (6 14 3±s 5 71)mg ,B组为 6 30 0mg ;治疗后临床评分分别为 (7.7± 1.7)分vs(7.7±1.6 )分 ;基本痊愈率分别为 5 4%vs 5 0 % ,差异均无显著意义 (P >0 .0 5 )。日剂量分别为 (0 .5 3±0 .0 3)mg·kg- 1·d- 1vs (2 .4± 0 .3)mg·kg- 1·d- 1、不良反应率为 8%vs 4 0 % ;复发率 12 %vs4 5 % ,差异均有显著意义 (P <0 .0 5或P <0 .0 1)。结论 :应用维胺酯低剂量长疗程治疗寻常痤疮 ,疗效好 ,安全性高 ,复发率低。     

Facial edema induced by isotretinoin use: a case and a review of the side effects of isotretinoin

Isotretinoin (13-cis-retinoic acid) is a retinoid that is used to treat cystic acne, comedonal acne, and other diseases. For the treatment of acne, isotretinoin is dosed at 0.5 to 2 mg/kg daily for 5 months with a target total dose of approximately 120 mg/kg. Its most common side effects are mucocutaneous and ocular in nature (ie, cheilitis, ocular sicca, and decreased dark adaptation). It can also cause xerosis. Patients should be made aware of these side effects before taking isotretinoin and also that utilization of moisturizers and eye drops can help to mitigate such side effects. Sometimes, however, the dose of isotretinoin needs to be decreased to reduce the induction of side effects. Isotretinoin's most significant side effect is the induction of birth defects if a fetus is exposed to isotretinoin, which is pregnancy category X. Isotretinoin should be used with 2 forms of birth control by fecund women. It can rarely increase serum levels of triglycerides, which can, if very elevated, be related to the development of pancreatitis and xanthomas. Isotretinoin's well-documented but rarer side effects include intracranial hypertension. It can induce bony changes. A review of the literature demonstrates that isotretinoin is not linked to depression and suicide. Facial swelling has been linked to isotretinoin use in 3 previous case reports. We note herein the first case of facial swelling that occurred in an acne patient being treated with isotretinoin who at the time the swelling developed had no cysts, comedones, pustules, or evidence of bacterial infection. Possible reasons for the patient's facial swelling include some type of retinoid induced angioedema, exacerbation of inflammation by isotretinoin, and isotretinoin induced capillary leak syndrome.     

Evaluation of sequential effect of isotretinoin on the haematological parameters in patients with acne vulgaris

Purpose: Isotretinoin is the most effective drug for acne with some side effects. Few studies exist regarding the effects of isotretinoin on haematological parameters with different results. Mostly, baseline values with a single value during or at the end of the treatment were compared. In this study, we aimed to determine the differences in haematological parameters during isotretinoin treatment until reaching the cumulative dose of 120?mg/kg.

Materials and methods: The study included 118 patients with moderate-to-severe acne vulgaris. Patients with preexisting liver disease, anaemia, iron deficiency, abnormal liver function tests, thrombocytopenia/thrombocytosis or hyperlipidaemia were excluded. Laboratory monitoring for haematological parameters was performed at baseline and monthly during treatment. Parameters at the baseline, at the first and second months and at the end of the therapy were taken into account.

Results: According to general linear model analysis, platelets and plateletcrit increased at the first month of the treatment and then decreased to baseline. White blood cells and neutrophils decreased at the first month, then increased to baseline value at the second month, and were found to be decreased again at the end of the treatment. Mean corpuscle volume was found to be increased at the end of the treatment. Other parameters in CBC did not show statistically significant differences.

Conclusions: Although some changes occur in haematological parameters during isotretinoin therapy, all of these changes remain within the normal range. Evaluating the spot values at any time during treatment may cause misinterpretations.     

Isotretinoin in acne vulgaris: a prospective analysis of 160 cases from Kuwait

A total of 160 patients (59 male and 101 female) ages varying from 13 to 28 years (mean age 20 years) with moderate to severe acne were treated with isotretinoin in the doses ranging from 0.5 mg/kg/day to 1 mg/kg/day. The drug was given for a period ranging from 6 to 28 weeks. The patients were followed up regularly for a period of 12 months after stoppage of isotretinoin for any evidence of relapse. In the event of a recurrence greater than mild acne after 8 weeks of stoppage of isotretinoin therapy, the patients were given another course of the drug. Patients were considered to be non-relapsing if they had no evidence of recurrence after 12 months of follow-up. Twenty seven patients were excluded from the study. Of the remaining 133 patients (51 male and 82 female) only 117 patients (36 male and 81 female) could follow up for at least 12 months after stopping therapy. Of the 133 patients, a total of 127 patients (95.5%) achieved complete or partial clearance. Forty two percent (total 49 patients: 20 male and 29 female) experienced relapse after stopping therapy. Of these, 21 (42.85%) were given a second course of the drug. None of the patients developed a rise in lipids levels significant enough to warrant stoppage of the drug.     

异维A酸红霉素凝胶联合过氧苯甲酰凝胶治疗中、重度痤疮

目的观察异维A酸红霉素凝胶联合过氧苯甲酰凝胶治疗中、重度痤疮的疗效。方法将201例Ⅱ～Ⅳ度寻常痤疮患者随机分为2组,治疗组106例,对照组95例。治疗组予异维A酸红霉素凝胶联合过氧苯甲酰凝胶,对照组给予异维A酸红霉素凝胶治疗。每2周随访1次,观察疗效及不良反应,8周后进行治疗评定。结果治疗组痊愈率和有效率(58.49%、96.23%)高于对照组(36.84%、88.42%)。结论异维A酸红霉素凝胶联合过氧苯甲酰凝胶治疗中、重度痤疮较单纯外用异维A酸红霉素凝胶疗效好。     

Effects of isotretinoin on the inflammatory markers and the platelet counts in patients with acne vulgaris

Objective: Oral isotretinoin is an efficient treatment used commonly in treating the moderate and severe acne. It has various side effects that affect many systems in the body. In this study, we are planning to examine the possible effects of the oral isotretinoin on platelet density, mean platelet volume, neutrophil lymphocyte rate, platelet lymphocyte rate, and red-blood-cell distribution width level.

Methods: Twenty-eight males and 84 females, 112 patients in total, diagnosed with acne vulgaris and receiving oral isotretinoin treatment were examined retrospectively. The full blood parameters of the patients before the treatment and in the third month of the treatment were recorded.

Results: A statistically meaningful increase was observed in the platelet density, hemoglobin levels. And a statistically significant decrease has been determined in the red-blood-cell distribution width level while no meaningful differences were detected in the mean platelet volume, neutrophil lymphocyte rate, platelet lymphocyte rate, and white blood cell count.

Conclusions: The oral isotretinoin treatment has been demonstrated as having increased the platelet density, hemoglobin levels and having decreased red-blood-cell distribution width level significantly.     

The new therapy schema of the various kinds of acne based on the mucosa-skin side effects of the retinoids

The most common adverse effects of oral isotretinoin (>1/10) are: cheilitis, skin dryness, erythema, itching, scaling, bruising, skin atopy, conjunctivitis, dry eyes and eyelid inflammation. The aim of this work was to define an optimal dose regime of the oral isotretinoin allowing for effective reduction of sebum production and minimalization of adverse effects such as decreased skin moisturization, increase in TEWL and intensified erythema. The skin parameters were assessed using the MPA 5 diagnostic apparatus. Moisturization together with an increase in TEWL and erythema during treatment with isotretinoin seem to be crucial factors responsible for patient discomfort. The decrease in the pigment content in the skin during retinoid treatment is a favourable symptom, due to the frequent tendency of skin pigmentation disturbances in the sites after acne changes. On the basis of performed analyses it was concluded that the new therapy schema is the most advantageous form of isotretinoin dosing and it involves the use of a constant drug dose - 0.4-1.0 mg/kg body mass/day without modification during treatment.     

The effect of systemic isotretinoin on male fertility

Background/objective: Acne vulgaris is one of the most common diseases of the youth. Systemic isotretinoin is the only drug which acts on all of the etiopathogenic mechanisms of acne. Isotretinoin has some well-known side effects. Besides these, there is a suspicion whether it causes infertility or not. In this study, we aimed to evaluate the effects of systemic isotretinoin on male fertility.

Methods: Eighty one male patients, who were older than 18 years of age, and had severe or refractory acne vulgaris were included in the study. They were given a total dose of 120 mg/kg of systemic isotretinoin over a period of six months. Before and after the study, the spermiogram parameters of the patients were evaluated to show any possible effect on male fertility. The patients’ total testosterone, follicle stimulating hormone and luteinizing hormone levels were also evaluated.

Results: All of the spermiogram parameters changed positively (p?<?0.05). There was no significant change in the hormone levels.

Conclusion: Systemic isotretinoin has a positive effect on male fertility. Since the hormone levels did not change significantly, this positive effect of isotretinoin is not via the hypothalamic–pituitary–gonadal axis but can be due to its regenerative and proliferative effects on the testes.     

异维A酸联合克林霉素凝胶治疗痤疮的疗效观察

目的：观察口服异维A酸与外用克林霉素磷酸酯凝胶联合治疗面部中度寻常痤疮的疗效。方法：将136例中度痤疮患者随机分为两组,治疗组70例采用口服异维A酸联合外用克林霉素磷酸酯凝胶治疗8wk;对照组单用克林霉素磷酸酯凝胶治疗8wk。结果：治疗组的总有效率为84．29％;对照组的总有效率为39．39％。经卡方检验,两组有极显著性差异（P〈0．01）。结论：口服异维A酸联合外用克林霉素磷酸酯凝胶是治疗中度寻常痤疮的有效方法。     

The new therapy schema of the various kinds of acne based on the mucosa-skin side effects of the retinoids

The most common adverse effects of oral isotretinoin (>1/10) are: cheilitis, skin dryness, erythema, itching, scaling, bruising, skin atopy, conjunctivitis, dry eyes and eyelid inflammation. The aim of this work was to define an optimal dose regime of the oral isotretinoin allowing for effective reduction of sebum production and minimalization of adverse effects such as decreased skin moisturization, increase in TEWL and intensified erythema. The skin parameters were assessed using the MPA 5 diagnostic apparatus. Moisturization together with an increase in TEWL and erythema during treatment with isotretinoin seem to be crucial factors responsible for patient discomfort. The decrease in the pigment content in the skin during retinoid treatment is a favourable symptom, due to the frequent tendency of skin pigmentation disturbances in the sites after acne changes. On the basis of performed analyses it was concluded that the new therapy schema is the most advantageous form of isotretinoin dosing and it involves the use of a constant drug dose – 0.4–1.0?mg/kg body mass/day without modification during treatment.     

Use of gamma distributed residence times in pharmacokinetics

The multiple dose pharmacokinetics of isotretinoin and its major blood metabolite, 4-oxo-isotretinoin, were studied in 10 patients with cystic acne and 11 patients with various keratinization disorders. Blood samples were obtained at predetermined times following the first dose, interim doses and the final dose. Blood concentrations of isotretinoin and 4-oxo-isotretinoin were measured by a specific and sensitive HPLC method. A lag time was usually observed prior to the onset of absorption following oral administration of the drug in a soft elastic gelatin capsule. Absorption then proceeded rapidly and maximum blood concentrations usually occurred within 4 h of drug administration. The harmonic mean half-life for the elimination of isotretinoin by the cystic acne patients was approximately 10 h after the initial dose and did not change significantly following 25 days of 40 mg b.i.d. dosing. Steady-state blood concentrations remained relatively constant after the fifth day of dosing. The harmonic mean elimination half-life in the patients with various disorders of keratinization was about 16 h. The results of the 2 studies suggest that no significant changes in the pharmacokinetics of isotretinoin occur during multiple dosing and that the multiple dose pharmacokinetic profile is predictable and can be described using a linear pharmacokinetic model. This suggests that the steady-state concentrations of isotretinoin can be predicted from single dose data.     

口服异维A酸治疗扁平疣疗效观察

目的：观察异维A酸治疗扁平疣的疗效、副作用。方法：口服异维A酸10mg，3次／d，两周后改用10mg，2次／d。结果：总有效率88，4％。结论：异维A酸是治疗扁平疣的有效药物，且药量小，副作用小。     

Long-pulsed dye laser-mediated photodynamic therapy combined with topical therapy for mild to severe comedonal, inflammatory, or cystic acne

BACKGROUND: Acne patients who fail to respond to conventional treatments have been treated with isotretinoin, an effective treatment coming under strict regulation due to the risk of significant side effects. Photodynamic therapy (PDT) may be a viable alternative treatment for recalcitrant acne of various types and levels of severity. OBJECTIVE: To determine the safety and efficacy of combination PDT with topical 5-aminolevulinic acid (ALA) and activation by long-pulsed, pulsed dye laser (LP PDL, 595 nm) energy with topical therapy in patients with mild to severe acne. METHODS: A prospective, controlled pilot, proof-of-principle study of 19 consecutive patients (aged 16-47 years, Fitzpatrick skin types I-VI) with mild to severe cystic, inflammatory, or comedonal acne of the face was conducted. All patients had failed conventional therapy, including oral antibiotics, topical treatments, hormonal therapy, laser procedures (without ALA), and/or oral isotretinoin. Fifteen patients were treated with ALA PDT and 4 patients served as controls; all were continued on topical medications. Patients undergoing PDT were initially randomized to receive either blue light or laser energy. Because recrudescence occurred in 1 patient while undergoing multiple treatments with ALA and blue light, all subsequent patients were treated with ALA and laser energy. The total number of patients treated with LP PDL-mediated ALA PDT was 14. ALA was applied for a short 45-minute incubation followed by 1 minimally overlapping pass with the LP PDL (595 nm, 7.0-7.5 J/cm2 fluence, 10-ms pulse duration, 10-mm spot size, and dynamic cooling spray of 30 ms with a 30-ms delay). Patients treated with conventional therapy (oral antibiotics, oral contraceptives, and topical medications) or laser energy without ALA PDT served as control groups. Patients were followed monthly for up to 13 months. RESULTS: Complete clearance was achieved in 100% (14 out of 14) patients in the LP PDL PDT-treated group. A mean of 2.9 treatments (range 1-6; 2.0-3.7, 95% CI; n=14) was required to achieve complete clearance for a mean follow-up time of 6.4 months (range 1-13; 3.8-8.9 95% CI; n=14). The patient mean percent lesional clearance rate per treatment was 77% (64%-90%, 95% CI; n=14). Improvement in acne lesions became apparent within 1 to 2 weeks after the first treatment. Clearance in the LP PDL PDT group was superior to control groups. In the LP PDL-only control group (n=2), the patient mean percent lesional clearance rate per treatment was 32% without complete clearance after 3 to 4 treatments. In the oral antibiotics, oral contraceptives, and topicals control group (n=2), the clearance rate per treatment was 20%, the mean clearance rate per month was 4%, and complete clearance was not achieved after 6 to 10 months. In the LP PDL-mediated PDT group, treatments were well-tolerated with minimal erythema lasting 1 to 2 days. No cases of crusting, blistering, purpura, scarring, or dyspigmentation occurred. A reduction in the erythema in erythematous acne scars was observed. CONCLUSION: For teenage to adult patients with recalcitrant comedonal, inflammatory, or cystic acne of various degrees of severity, ALA PDT with activation by LP PDL appears to be a safe and effective treatment with minimal side effects. LP PDL-mediated PDT may serve as an important alternative to isotretinoin. Cosmetically well-accepted, LP PDL PDT combined with topical therapy is the first PDT modality to achieve complete clearance with long-term follow-up as compared to controls.     

异维A酸红霉素凝胶配合痤疮挤压法治疗痤疮疗效观察

目的分析对痤疮患者实施痤疮挤压法配合异维A酸红霉素凝胶治疗的临床疗效。方法112例痤疮患者,依据数字编号的奇偶性质将患者分为观察组与对照组,各56例。对照组患者应用单一的痤疮挤压法治疗,观察组患者执行痤疮挤压法配合使用异维A酸红霉素凝胶治疗。对比两组患者临床疗效及皮疹消退情况。结果观察组治疗总有效率为92.86%高于对照组的78.57%,差异具有统计学意义(P<0.05)。治疗后,观察组丘疹、黑头粉刺、皮脂溢出、白头粉刺消退率分别为90.00%、91.49%、90.24%、92.86%均高于对照组的55.17%、47.91%、47.62%、46.15%,差异具有统计学意义(P<0.05)。结论利用痤疮挤压法对痤疮患者实施基本治疗的同时配合使用异维A酸红霉素凝胶对患处进行外擦,能实现疾病疗效的提升,帮助患者改善皮疹症状,实现皮肤的好转与恢复,值得临床拓展推广。