Isotretinoin Group Research Articles

Efficacy of omega-3 fatty acids and punctal plugs in the prevention of isotretinoin-associated ocular surface disease.

To investigate the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in patients receiving systemic isotretinoin therapy. This is a prospective randomized study that included 180 eyes of 90 patients who had systemic isotretinoin therapy (120-150 mg/kg for at least 4-6 months). Exclusion criteria: DED according to the diagnostic criteria of TFOS DEWS II. Patients were assigned into three groups; (1) O3FAs/PPs group: A soft preloaded silicone plug was inserted in the inferior punctum of both eyes and received oral O3FAs two capsules twice daily total daily dose of 1040 mg/day for 6 months. (2) PPs group: A soft preloaded silicone plug was inserted in the inferior punctum of both eyes and received oral placebo. (3) Isotretinoin group: No intervention was done. At baseline, 1 week, 1, 3, and 6 months of study, Ocular surface evaluation tests were done in following order: OSDI, tear osmolarity, Schirmer's I test, TBUT, ocular surface staining score, and meibomian gland expression. The changes in measurement of ocular surface evaluation tests including ocular surface disease index (OSDI), tear film breakup time (TFBUT), corneal staining, tear osmolarity, and meibomian gland expression at 6 months. There are significant changes between all groups at 6 months follow-up. The ocular surface parameters were better for the PPs and O3FAs/PPs groups than the isotretinoin group. The isotretinoin group showed worsening of ocular surface parameters including a significant decrease of FTBUT and an increase of OSDI score, corneal staining score, tear osmolarity, and meibomian expression score. There was no significant difference in ST1 throughout the whole study in all groups. At 6 months follow-up, there were no statistically significant differences between PPs and O3FAs/PPs groups except meibomian expression score which showed a significant increase in PPs group. Our cohort highlights the beneficial effects of the combination of O3FAs supplementation with PPs in the prevention of isotretinoin-associated OSD in this sample study.

Oral isotretinoin combined with topical clobetasol 0.05% and tacrolimus 0.1% for the treatment of frontal fibrosing alopecia: a randomized controlled trial

Background Frontal fibrosing alopecia (FFA) is a scarring alopecia with no promising treatment. Objective To evaluate the additive efficacy of oral isotretinoin to topical treatments. Methods Between November 2017 and August 2018, FFA patients were randomly assigned to receive either isotretinoin (20 mg/d) plus topical treatments (clobetasol 0.05% and tacrolimus 0.1%) or monotherapy with topical treatments. Treatments’ efficacy was evaluated through Frontal Fibrosing Alopecia Severity Index (FFASI) after two and 6 months. Results From 38 participants, 28 patients completed the study. Facial papules improved after 6 months (p value < .001) in the isotretinoin group. Moreover, frontotemporal hairline (p values for frontal < .001; R lateral: 0.03; L Lateral: 0.02), total scalp margins, total additional features’ scores, and total combined (p value < .001 for all) improved more in the isotretinoin group than in the control group. Frontal band improved in the treatment group (p value: .02). Frontal margin (p value: .01), R lateral (p value: .01), total scalp (p value < .01), and combined total scores (p value: .01) worsened in the control group. Isotretinoin-related side-effects included lip dryness, telogen effluvium, and malaise. Limitations Small sample size and lost to follow-up. Conclusion Isotretinoin combined with topical treatments is more effective than monotherapy with clobetasol and tacrolimus for FFA. Clinical Trial Code (IRCT.ir) IRCT2017091736173N1.

Effects of isotretinoin on new bone formation after maxillary sutural expansion.

The aim of this study was to examine the effects of isotretinoin on new bone formation after maxillary sutural expansion in rats. A total of 32male Wistar rats were selected and randomly divided into four groups. The isotretinoin group was treated with 7.5 mg/kg isotretinoin, and the soybean group was treated with 2 ml/kg soybean oil for 57days. The substances were applied via oral gavage. The expansion-only and the control groups were not treated with any substance. In the experiment groups, expansion springs were applied on day 41 of the experiment, and after day5 of expansion, a12-day retention period was established. At the end of the experiment, all the animals were sacrificed, and their maxillae were dissected for histological evaluation. The numbers of osteoclasts, osteoblasts and formation of new bone and capillaries were evaluated on slides centered around the suture. The statistical analysis showed significant differences between the groups for the number of osteoblasts and osteoclasts (p < 0.001). In the experiment groups, higher numbers of osteoblasts and osteoclasts were detected in comparison to the control group (p < 0.001), while there was no significant difference between the experiment groups. Capillary formation and new bone formation in the isotretinoin group were found to be on ahigher level than in the other groups (p < 0.001). Isotretinoin had no negative effects on bone formation following the expansion of the maxillary suture in rats.

The effects of isotretinoin on affective and cognitive functions are disparate in adolescent acne vulgaris patients

Background: The vulnerable brain regions to isotretinoin are represented as hippocampus and prefrontal cortex, involved in mood regulation as well as coordination of cognitive functions. Adolescence is a critical period with dynamic alterations in neurocognition. Isotretinoin brought concerns about its possible effects on executive functions, attention and memory.Objective: Evaluate the impacts of isotretinoin on neurocognitive functions in adolescents with acne vulgaris and determine the emergence of psychiatric side effects.Materials and methods: Fifty-five adolescent acne vulgaris patients were assigned to either isotretinoin (n = 38) or systemic antibiotic (n = 17) groups. The neuropsychological test battery and psychometric tests were performed before treatment and during treatment with 3-months intervals.Results: Stroop-TBAG form, verbal-auditory digit span, controlled oral word association test and trail making test results improved in the isotretinoin treatment group along with stable scores in the antibiotic group. Children Depression Scale scores of the isotretinoin group showed an increase at 6th month compared to baseline. None of the patients was evaluated as depressive by the psychiatric examination.Conclusions: In a vulnerable age group, our results demonstrate an improvement for neurocognitive functions in isotretinoin patients. The conflicting results suggest distinct mechanisms to be responsible for the effects on affective and cognitive functions.

Oral Retinoidlerin İşitme Düzeyi Üzerine Olan Etkileri: Prospektif Bir Klinik Çalışma

Objective: The main purpose of this study was to analyse the effects of oral isotretinoin and acitretin, on hearing functions detected by serial odiometric examinations. Material and Methods: A total of thirty patients with moderate acne vulgaris and other thirty patients diagnosed as psoriasis vulgaris with a PASI score between 30-50% were included in this study. Isotretinoin and acitretin were prescribed for acne vulgaris and psoriasis vulgaris, respectively. The hearing of patients were tested with pure tone odiometric examination before, at the first and third months of the treatment in the remaining 55 patients (110 ears). The differences between the mean values of pretreatment and posttreatment pure tone hearing thresholds at 500, 1000, 2000, 4000, 8000 and 10000 Hz frequencies were evaluated for each group. Results: No significant difference was detected between the mean values of the pretreatment and posttreatment pure tone hearing thresholds of acitretin group (p>0.05); while in the isotretinoin group, a significant difference was detected between the pretreatment and posttreatment values at 500 Hz frequencies at first and third months of the treatment which was progressively decreasing (p<0.05).Conclusion: It can be concluded that, according to the results of our study, acitretin has no significant effect on hearing systems, while isotretinoin may lead to bilateral hearing threshold changes in a period of three months.

Oral isotretinoin for acne.

Oral isotretinoin for acne.

Effects of oral ısotretinoin on normal and wounded nasal mucosa: an experimental study.

We aimed to investigate the effect of systemic isotretinoin therapy on normal and wounded nasal septal mucosa histopathologically in an experimental rabbit model. Circular mucosal defect with a 7mm diameter was made in the left septum of 12 New Zealand white rabbits. The rabbits were divided into two groups (six rabbits in each group) oral isotretinoin was given with olive oil at the operation day to the first group. The control group was only oil given group. The harvested septum mucosas were divided into four groups (1-wounded-drug given side, 2-unwounded and drug-given side, 3-wounded-control and 4-unwounded-control side). The diameter of the defect, mucosal thickness, epithelial thickness, ciliated cell level, goblet cell level and inflammation were evaluated every week for 4weeks. At both wounded and normal side, thinning of normal respiratory ciliated epithelium was observed in the postoperative period. In study group at the wounded side; mean mucosal thickness was measured 139.66µ (± 26.24), and in the control group, mean mucosal thickness was 238.33µ (± 39.7) at the wounded side. (p < 0.001). The difference between the groups in thickness of normal septal mucosa was also statistically significant (p = 0.016) [190µ (± 14.6) and 256.66µ (± 44.66)]. The average cilia level was observed 1.16 in the wounded study group, while the average level was 2.33 in the wounded control group (p = 0.012). Average score measurements of the regenerated mucosa suggested that isotretinoin-given wounded animals have reduced goblet cell recovery, compared to the control both on the regenerated and unwounded mucosas (p = 0.007, p = 0.002, respectively). Inflammation was significantly higher in the wounded isotretinoin group (p = 0.018). Oral isotretinoin has negative effects on epithelial and ciliary regeneration, significantly reduces mucosal thickness and goblet cell counts of the normal and regenerated mucosa, causes severe inflammation and significant reactive changes.

Isotretinoin induced achilles tendinopathy: Histopathological and biomechanical evaluation on rats

ObjectiveThe aim of the present study was to evaluate histopathological and biomechanical effects of isotretinoin on Achilles tendon. Materials & methodsSixteen rats were divided into two groups including the control group (n = 8) and isotretinoin group (n = 8). The control group received 1.42 ml/kg soy oil per day whereas the isotretinoin group received 15 mg/kg/day (gavage dose 1.42 ml/kg) isotretinoin dissolved in soy oil through gavage method for 6 weeks. Achilles tendons were excised at the end of week 6. The tendon samples were evaluated by hematoxylin-eosin under a light microscope. Quantitative evaluation was performed via Movin and Bonar scoring. A computer-monitored tensile testing machine was utilised for biomechanical testing. Biomechanical characteristics of the tendon samples (elastic modulus, yield force, ultimate tensile force) were measured. ResultsHistopathological evaluation revealed a significantly higher Movin and Bonar scores in histopathological evaluation. Movin score in isotretinoin group was 4.1 ± 2.5 and it was 2.3 ± 1.0 in control group (p = 0.032). Bonar score in isotretinoin group was 2.9 ± 1.4 and it was 1.6 ± 0.7 in control group (p = 0.022). In line with histopathological evaluation, biomechanical measurements in isotretinoin group (elastic modulus, yield force, ultimate tensile force) were significantly lower than the control group. Elastic modulus in isotretinoin group was 227 ± 27.7 N/mm2 and in control group it was 281.7 ± 38.7 N/mm2 (p = 0.006). In isotretinoin group; yield force was 33.7 ± 4.3 Pa and in control group it was 40.8 ± 5.9 Pa (p = 0.021). Ultimate tensile force in isotretinoin group was 35.7 ± 4.2 Pa and in control group it was 44 ± 7 Pa (p = 0.009). ConclusionThe present study detected histopathological and biomechanical negative effect of isotretinoin on Achilles tendon. Therefore, isotretinoin should be questioned in medical history of patients with tendinopathy.

Comparison of Efficacy of Doxycycline and Isotretinoin on Cutaneous Human Beta-Defensin-1 and -2 Levels in Acne Vulgaris.

Background:Recent studies have shown that human beta-defensin-1 (hBD-1) and (human beta-defensin-2 hBD-2), which are antimicrobial peptides produced by the skin, play a role in the pathogenesis of acne vulgaris (AV).Objective:The aim of this study was to determine the role of antimicrobial peptides in the pathogenesis of AV and enlighten the effects of doxycycline and isotretinoin in the expression of these defensins in AV.Materials and Methods:A total of 44 patients (22 patients in each group) with Grade 6 and 8 AV who were indicated doxycycline or isotretinoin for their treatment, and 20 healthy volunteers were included in this study. Pretreatment cutaneous samples were obtained from pustular lesions and uninvolved skin of AV patients and were repeated after the treatment. Only one biopsy was obtained from controls.Results:Cutaneous levels of hBD-1 and hBD-2 were significantly increased in AV patients when compared with healthy controls (P<0.05). Doxycycline therapy achieved a decrease in hBD-1 levels (P<0.05), whereas isotretinoin therapy achieved a reduction in hBD-2 levels when compared with pretreatment levels (P<0.05). Posttreatment hBD-1 and hBD-2 levels were not different between doxycycline and isotretinoin groups (P>0.05).Conclusion:In the light of these results, it was reasonable to assume the role of hBD-1 and hBD-2 in the pathogenesis of AV. Our results showing a significant reduction in hBD-1 staining with doxycycline treatment and in hBD-2 with isotretinoin suggested that some part of their anti-acne effect worked through these mechanisms.

Effect of exogenous retinoic acid on tooth movement and periodontium healing following tooth extraction in a rat model.

To evaluate the effect of isotretinoin on orthodontic tooth movement (OTM) and wound healing following exodontia. Sixteen 40-day-old male Wistar rats were divided into two groups: (a) OTM and (b) tooth extraction (TE) of the upper 1st molar and OTM. The experimental animals were treated with isotretinoin (7.5mg/kg) and the control animals with oil solution for 37days. The OTM and bone volume were evaluated by the micro-CT and the periodontium healing was assessed by immunohistochemistry for VEGF-C, COX-2 and IL-1ß. The animals of both groups submitted to the TE showed a statistically significant decrease in the bone volume percentage and increase in OTM. No significant difference of OTM and bone volume was observed between the control and experimental group. However, the alveolar bone of the isotretinoin group revealed more medullary spaces with inflammatory, hematopoietic cells, blood vessels and intense immunolabeling for VEGF-C. This group also showed faster gingival regeneration. No significant difference was observed in the COX-2 and IL-1ß labelings following TE between both groups. The isotretinoin did not affect the OTM nor did it cause an alteration in maxillary bone volume. This exogenous acid may contribute to the acceleration of gingival healing.

Effect of retinoic acid on aquaporin 3 expression in keratinocytes.

To explore the possible mechanism of the third-generation retinoic acid drugs (isotretinoin, acitretin, adapalene) in inducing skin and mucosa dryness and rhagades; specifically, mechanism by which these drugs influence keratinocyte cell culture models in vitro (HaCaT) and aquaporin channel (AQP3) protein expression was investigated. Isotretinoin, acitretin, and adapalene were applied to human keratinocyte HaCaT cells. Immunohistochemistry, reverse transcriptase polymerase chain reaction, and western blotting were used to detect their effects on AQP3 expression in HaCaT cells at different concentrations (0.000, 0.001, 0.010, 0.060, and 0.100 mg/mL) or different at times (0, 6, 12, 24, and 48 h). At 0.010 mg/mL, maximal AQP3 expression was observed in HaCaT cells; this was significantly higher than the expressions at the other concentrations (P < 0.05). After treatment with isotretinoin, acitretin, or adapalene at 0.010 mg/mL for 12 h, the expression of AQP3 was the highest in the isotretinoin group, followed by the acitretin group, with the lowest expression in the adapalene group. However, the differences were not statistically significant (P > 0.05). Retinoic acid can increase AQP3 expression in HaCaT cells, with significant effects observed with 0.010 mg/mL isotretinoin treatment for 12 h. The side effects, namely skin and mucosa dryness caused by retinoic acid might be related to its effects on AQP3 expression.

Decreased ovarian reserve in female Sprague–Dawley rats induced by isotretinoin (retinoic acid) exposure

Isotretinoin is a retinoid widely used for the treatment of severe nodulocystic acne. Although it has broad side effects, there is no well-designed study about its effects on the ovary. This study investigated possible toxic effects of isotretinoin on female gonads. A total of 30 female rats were randomly divided into three equal groups according to the dose of isotretinoin they were administered: 0mg/kg/day (group 1), 7.5mg/kg/day (group 2) or 15mg/kg/day (group 3). Thirty days after the treatment, the effects of isotretinoin on the ovaries were evaluated with serum anti-Müllerian hormone (AMH) concentrations, apoptosis by TUNEL assay and immunohistochemical observations by proliferating cell nuclear antigen (PCNA). The percentage of atretic follicles was calculated for each stage of folliculogenesis. The serum AMH concentrations were found to be lower in both isotretinoin groups. The percentage of atretic follicles in both isotretinoin groups was higher than the control. The number of PCNA-positive granulosa cells was decreased in the isotretinoin groups. The number of ovarian follicles with apoptotic granulosa cells was increased in the experimental groups. These data are the first to identify that exposure of isotretinoin may be responsible for decreased ovarian reserve and toxic effects on rat ovaries.Isotretinoin (13-cis-retinoic acid) is a retinoid that is widely used for the treatment of severe acne. Although it has a broad side effects profile, no well-designed study about its effects on the ovary has been published. This study was designed to investigate possible toxic effects of isotretinoin on female gonads. A total of 30 female rats were divided into three equal groups according to the dose of isotretinoin to be administered: 0mg/kg/day (group 1), 7.5mg/kg/day (group 2) or 15mg/kg/day (group 3). Thirty days after the treatment, ovarian effects of isotretinoin were evaluated with serum anti-Müllerian hormone (AMH) concentrations and immunohistochemical examination. The percentage of atretic follicles was calculated for each stage of folliculogenesis. The serum AMH concentrations were lower in both isotretinoin groups. The percentage of atretic follicles in both isotretinoin groups was higher than the control. The number of proliferating cell nuclear antigen-positive granulosa cells was decreased in the isotretinoin groups. The number of ovarian follicles with apoptotic granulosa cells was increased in the experimental groups. These data are the first to identify that exposure of isotretinoin may be responsible for decreased ovarian reserve and toxic effect on rat ovaries.

Ocular Adverse Effects of Systemic Treatment With Isotretinoin

To examine whether isotretinoin therapy could result in deleterious ocular effects, as previously described in case report studies. Retrospective cohort study. The study was conducted using the electronic medical databases of a large health maintenance organization in Israel. The study population consisted of 14 682 adolescents and young adults who were new users of isotretinoin for acne and 2 age- and sex-matched comparison groups (isotretinoin-naive patients with acne and acne-free patients). Ocular adverse effects (AEs) or purchases of ophthalmic medications within 1 year after the first dispensed isotretinoin prescription. In total, 13.8% of the isotretinoin group experienced ocular AEs vs 9.6% of the isotretinoin-naive group and 7.1% of the acne-free group. During a 1-year follow-up period, the isotretinoin group had significantly higher risk for any ocular AEs (hazard ratio, 1.70; P.001) compared with the acne-free group. No such increased risk was observed for the isotretinoin-naive group. The isotretinoin group had higher relative risks for inflammatory and structural AEs. Isotretinoin use may be associated with short-term ocular events, especially conjunctivitis, underscoring the importance of educating patients and caregivers about these potentially important AEs of the therapy.

The effects of systemic isotretinoin and antibiotic therapy on the microbial floras in patients with acne vulgaris

Although there are several studies about the alteration in skin flora, limited number of reports about changes in the microbial contents and their resistance profile of other body sites in patients treated with isotretinoin for acne vulgaris. The aim of this study was to investigate the effects of systemic isotretinoin and antibiotic therapy on the microbial floras of oropharynx, nose and feces in acne patients. Treatment groups of isotretinoin and antibiotics consisting of 20 and 15 patients, respectively were included. Microbiological culture samples were taken at baseline and once a month during 4-6 months of treatment period. Difference in microbial flora throughout the treatment period was detected at least among one of all culture samples of 15 (75%) and 5 (33%) patients in isotretinoin and antibiotic groups. There was statistically significant difference between two groups in means of alteration of the microbial flora (P = 0.013). The difference was definitely observed among nasal cultures (65%) in isotretinoin group and fecal cultures (20%) in the other. Staphylococcus aureus colonization was prominent in the microbial floras of nose and oropharynx and 2 of 14 nasal isolates were detected to be methicilline resistant while Escherichia coli with extended spectrum beta lactamase activity was detected in fecal floras of patients in isotretinoin group. Systemic isotretinoin and antibiotic treatments in acne patients precisely caused variations in the microbial floras of several sites of the body, while isotretinoin was commonly more responsible than antibiotics. Knowing that alterations in the microbial colonization of the flora regions may preceede infectious disease and bacterial resistance, treatment options and follow-up procedures in acne vulgaris should be carefully determined to reduce the risk of destruction of the microbial flora.

Evaluation of the clinical effects of isotretinoin on chronic rhinosinusitis

This study aims to evaluate the clinical effects of isotretinoin (13-cis-retinoic acid), a derivative of retinoic acid, on the clinical features of chronic rhinosinusitis. The study group included 25 chronic rhinosinusitis patients (16 females, 9 males; mean age 25.2 ± 6.8 years; range 15 to 25 years) who were on isotretinoin for acne treatment, while the control group consisted of 25 chronic rhinosinusitis patients (15 females, 10 males; mean age 25.2 ± 6.8 years; range 15 to 25 years) who were not on isotretinoin treatment. The patients' symptom scores in visual analog scale (VAS), Lanza and Kennedy nasal endoscopic scores and Newman computed tomography (CT) scores were obtained in order to evaluate the their symptom, examination and radiological findings. These patients' symptom and examination results were evaluated first day, week two and at months 3-5 and 6-10. Paranasal sinus CT results were studied first day and at months 6-10. In the group of patients being administered isotretinoin, no significant change in the mean symptom and examination scores was detected during the acute phase (week 2), while there was a significant regression in the long-term (months 3-5 and 6-10). There was a significant regression in the mean CT score after isotretinoin therapy. In the control group no significant change was seen in any of the scores. The number of acute sinusitis attacks were significantly lower in the isotretinoin group than in the control group. No significant difference was found between the two groups in terms of the duration of the healing period of acute sinusitis attacks. We conclude that the long-term administration of isotretinoin has positive effects on the clinical results of chronic rhinosinusitis.

A prospective trial of the effects of isotretinoin on quality of life and depressive symptoms

Isotretinoin is an efficacious treatment for acne, but has been controversially linked with depression. This study aimed to examine the effects of isotretinoin on quality of life(QoL) and depression using a prospective design. The WHOQOL-BREF QoL measure and Centre for Epidemiological Studies Depression Scale were administered to consecutive outpatients with acne who were prescribed either isotretinoin (n = 65) or antibiotic treatment (n = 31).Patients and physicians rated acne severity independently. Groups were compared at baseline with a matched community sample (n = 94) and measurements repeated at 3 months for treatment groups. There were no differences between the three groups at baseline in terms of age, gender, depression or overall QoL. Acne was more severe in the treatment groups (P < 0·001). Depression was negatively correlated with QoL (P < 0·001)and hence was included as a covariate in repeated-measures analyses of QoL.Acne improved over time in both treatment groups (F = 48·2, P < 0·001). There was no detectable deterioration in depression score in either group (F = 1·1, not significant). QoL in the physical and social domains improved (P < 0·001) while psychological and environmental QoL was unchanged over time. The improvement in social QoL was greater in the isotretinoin group (P < 0·05). Those patients with higher baseline depression scores showed greater improvements in physical, psychological and social QoL (P < 0·001). Treatment of acne improves QoL, particularly in those with more depressive symptoms at the outset. Mood deterioration was not detected, but the possibility of subtle or rare mood effects of isotretinoin cannot be ruled out.

Comparison of depression, anxiety and life quality in acne vulgaris patients who were treated with either isotretinoin or topical agents

Since the introduction of isotretinoin to the market, many adverse psychiatric effects, including depression, anxiety and suicide attempts were reported. The aim of this study was to determine whether patients with acne who were treated with isotretinoin experienced significant increases in psychiatric symptoms over a 4-month period compared with patients who received topical acne therapy. Seventy-eight acne patients were allocated either to isotretinoin treatment (study group) (n = 37) or to topical treatment (control group) (n = 41). Their psychological status was evaluated at the baseline, second and fourth months of the treatment. All patients were required to complete the dermatology life quality index (DLQI), the Hospital anxiety and depression (HAD) scale, and the beck depression inventory (BDI). The two groups were not different from each other in terms of DLQI, BDI, HAD-A, HAD-D and total HAD scores at baseline. However, at the end of the second month quality of life was more impaired in the topical treatment group compared to the isotretinoin group (P < 0.05), and there were no difference between two groups in terms of BDI, HAD-A, HAD-D, and total HAD scores (P > 0.05). At the end of fourth month quality of life and all psychological test scores had improved more in the isotretinoin group compared to topical treatment group (P < 0.05). Results of the present study indicate that there is no increase in depressive and anxiety symptoms in the isotretinoin treatment group compared to that in the topical group. Instead, successful treatment of acne seems to improve both depressive and anxiety symptoms and improve quality of life.

Interventions for preventing non-melanoma skin cancers in high-risk groups.

Some groups of people have a greater risk of developing common non-melanoma skin cancers (NMSC). To evaluate interventions for preventing NMSC in people at high risk of developing NMSC. We searched the Cochrane Skin Group Specialised Register (March 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2007, MEDLINE (from 2003 to March 2007), EMBASE (from 2005 to March 2007), the metaRegister of Controlled Trials (February 2007). References from trials and reviews were also searched. Pharmaceutical companies were contacted for unpublished trials. Randomised controlled trials of adults and children at high risk of developing NMSC. Two review authors independently selected studies and assessed their methodological quality. We identified 10 trials (7,229 participants) that assessed a variety of interventions. One trial found T4N5 liposome lotion significantly reduced the rate of appearance of new BCCs in people with xeroderma pigmentosum. One of three trials of renal transplant recipients showed a significantly reduced risk of new NMSCs when acitretin was compared to placebo (relative risk (RR) 0.22 95% confidence interval (CI) 0.06 to 0.90) and no significant difference in risk of adverse events in two trials (RR 1.80, 95% CI 0.70 to 4.61). In three trials conducted in people with a history of NMSC, the evidence was inconclusive for the development of BCCs for retinol or isoretinoin. However the risk of a new SCC in one trial (HR 1.79, 95% CI 1.16 to 2.76) and adverse events in another trial (RR 1.76 95% CI 1.57 to 1.97) were significantly increased in the isotretinoin group compared with placebo. In one trial selenium showed a reduced risk of other types of cancer compared with placebo (RR 0.65, 95% CI 0.50 to 0.85) but also a significantly elevated risk of a new NMSC (HR 1.17 95% CI 1.02 to 1.34). The evidence for one trial of beta-carotene was inconclusive; and there was a trend towards fewer new NMSC in a trial of a reduced fat diet (RR 0.16, 95% CI 0.02 to 1.31), p=0.09. Some preventative treatments may benefit people at high risk of developing NMSC, but the ability to draw firm conclusions is limited by small numbers of trials, often with one trial per intervention or with inconsistent results between studies.

In vivo Porphyrin Production by P. acnes in Untreated Acne Patients and its Modulation by Acne Treatment

Propionibacterium acnes is often discussed as a contributing pathogenic factor in the aetiology of acne lesions. The aim of this study was to test which porphyrin patterns are synthesized by P. acnes in vivo in untreated acne patients and during standard acne regimens. These photosensitive compounds are potential targets for photo-dynamic therapy of acne and need to be better characterized in the skin. Using high-performance liquid chromatography coproporphyrin III was the main porphyrin identified in all patients. Coproporphyrin I and protoporphyrin were found at considerably lower concentrations. When the porphyrin concentration of individual patients receiving isotretinoin was analysed repeatedly over time, clinical improvement was associated with lowered levels of porphyrins. Statistical analysis demonstrated a significant reduction in the porphyrin fractions only in the isotretinoin group which was associated with clinical improvement 2 months after starting therapy.

Prospective, Randomized, Multicenter, Double-Blind Placebo-Controlled Trial Comparing Adjuvant Interferon Alfa and Isotretinoin With Interferon Alfa Alone in Stage IIA and IIB Melanoma: European Cooperative Adjuvant Melanoma Treatment Study Group

The combination of interferon alfa (IFNalpha) and isotretinoin has shown a direct antiproliferative effect on human melanoma cell lines, but it remained unclear whether this combination is more effective than IFNalpha alone in patients with metastatic melanoma. We evaluated safety and efficacy of IFNalpha and isotretinoin compared with IFNalpha alone as adjuvant treatment in patients with primary malignant melanoma stage IIA and IIB. In a prospective, randomized, double-blind, placebo-controlled trial, 407 melanoma patients in stage IIA (301 patients) and IIB (106 patients) were randomly assigned to either IFNalpha and isotretinoin (isotretinoin group; 206 patients) or IFNalpha and placebo (placebo group; 201 patients) after excision of the primary tumor. IFNalpha was administered three times a week at a dose of 3 million units subcutaneously for 24 months. Isotretinoin at a dose of 20 mg for patients < or = 73 kg, 30 mg for patients greater than 73 kg, or placebo daily for 24 months. A scheduled interim analysis revealed no significant differences in survival rates, with the isotretinoin group and the placebo group showing 5-year disease-free survival rates of 55% (95% CI, 46% to 65%) and 67% (95% CI, 59% to 75%), respectively, and overall 5-year survival rates of 76% (95% CI, 67% to 84%) and 81% (95% CI, 74% to 88%), respectively. The trial was stopped for futility. The addition of isotretinoin to an adjuvant treatment of low-dose IFNalpha in patients with stage IIA and IIB melanoma had no significant effect on disease-free or overall survival and is therefore not recommended.