Sample records for isotretinoin

  1. Metabolism of isotretinoin. Biliary excretion of isotretinoin glucuronide in the rat.

    PubMed

    Meloche, S; Besner, J G

    1986-01-01

    The biliary metabolites of isotretinoin were examined after iv administration of 4-20-mg/kg doses to vitamin A-normal bile duct-cannulated rats. Analysis of bile by reverse phase high performance liquid chromatography showed that injection of isotretinoin is followed by a rapid excretion of metabolites in bile. Isotretinoin glucuronide was identified as the major metabolite in bile. A specific high performance liquid chromatography method based on the assay of generated isotretinoin in beta-glucuronidase-treated bile was developed for the determination of isotretinoin glucuronide in bile samples. The excretion rate of isotretinoin glucuronide increased rapidly to reach a maximum 55 min after dosing and then declined exponentially. After 330 min of collection, biliary excretion of isotretinoin glucuronide was almost complete, and the metabolite accounted for 34.8-37.9% of the dose. These results indicate that conjugation with glucuronic acid represents a major pathway for the metabolism of pharmacological doses of isotretinoin. The maximum excretion rate of isotretinoin glucuronide in bile increased in a linear manner with the dose of isotretinoin, and no delay was observed after the larger doses. These data suggest that glucuronidation and biliary excretion are not saturated at high pharmacological doses of isotretinoin.

  2. Objective assessment of isotretinoin-associated cheilitis: Isotretinoin Cheilitis Grading Scale.

    PubMed

    Ornelas, Jennifer; Rosamilia, Lorraine; Larsen, Larissa; Foolad, Negar; Wang, Quinlu; Li, Chin-Shang; Sivamani, Raja K

    2016-01-01

    Isotretinoin remains an effective treatment for severe acne. Despite its effectiveness, it includes many side effects, of which cheilitis is the most common. To develop an objective grading scale for assessment of isotretinoin-associated cheilitis. Cross-sectional clinical grading study. UC Davis Dermatology clinic. Subjects were older than 18 years old and actively treated with oral isotretinoin. Oral Isotretinoin. We developed an Isotretinoin Cheilitis Grading Scale (ICGS) incorporating the following four characteristics: erythema, scale/crust, fissures and inflammation of the commissures. Three board-certified dermatologists independently graded photographs of the subjects. The Kendall's coefficient of concordance (KCC) for the ICGS was 0.88 (p < 0.0001). The Kendall's coefficient was ≥0.72 (p < 0.0001) for each of the four characteristics included in the grading scale. An image-based measurement for lip roughness statistically significantly correlated with the lip scale/crusting assessment (r = 0.52, p < 0.05). The ICGS is reproducible and relatively simple to use. It can be incorporated as an objective tool to aid in the assessment of isotretinoin associated cheilitis.

  3. Objective Assessment of Isotretinoin-Associated Cheilitis: Isotretinoin Cheilitis Grading Scale

    PubMed Central

    Ornelas, Jennifer; Rosamilia, Lorraine; Larsen, Larissa; Foolad, Negar; Wang, Quinlu; Li, Chin-Shang; Sivamani, Raja K.

    2016-01-01

    Importance Isotretinoin remains an effective treatment for severe acne. Despite its effectiveness, it includes many side effects, of which cheilitis is the most common. Objective To develop an objective grading scale for assessment of isotretinoin-associated cheilitis, Design Cross-sectional clinical grading study. Setting UC Davis Dermatology clinic. Participants Subjects were older than 18 years old and actively treated with oral isotretinoin. Exposures Oral Isotretinoin. Main outcomes and Measures We developed an isotretinoin cheilitis grading scale (ICGS) incorporating the following four characteristics: erythema, scale/crust, fissures, and inflammation of the commissures. Three board-certified dermatologists independently graded photographs of the subjects. Results The Kendall’s coefficient of concordance (KCC) for the ICGS was 0.88 (p<0.0001). The Kendall’s coefficient was ≥ 0.72 (p<0.0001) for each of the four characteristics included in the grading scale. An image-based measurement for lip roughness statistically significantly correlated with the lip scale/crusting assessment (r = 0.52, p <0.05). Conclusion and Relevance The ICGS is reproducible and relatively simple to use. It can be incorporated as an objective tool to aid in the assessment of isotretinoin associated cheilitis. PMID:26395167

  4. Monitoring of isotretinoin therapy by measuring the plasma levels of isotretinoin and 4-oxo-isotretinoin. A useful tool for management of severe acne.

    PubMed

    Almond-Roesler, B; Blume-Peytavi, U; Bisson, S; Krahn, M; Rohloff, E; Orfanos, C E

    1998-01-01

    Isotretinoin for oral therapy in severe acne conglobata and acne nodulocystica represents a significant achievement; however, the drug exerts several mucocutaneous and systemic adverse effects, besides its teratogenic potency. The aim of this study was to investigate the plasma levels of isotretinoin and of 4-oxo-isotretinoin over long-term treatment of severe acne and to assess any correlation with the given dose, the clinical improvement and the occurrence of side effects. Forty-one patients with severe acne and acne-related disorders were studied under long-term oral intake of isotretinoin. Therapeutic effects and side effects were evaluated prior, during and at the end of therapy. The plasma levels of isotretinoin and of its major metabolite 4-oxo-isotretinoin were measured by reversed-phase HPLC and were correlated with the administered oral dose and the number and frequency of side effects. Dose-dependent plasma levels of isotretinoin and its metabolite were observed. At a mean dosage of 0.75-1.0 mg/kg/day, 404 +/- 142 ng/ml were measured, whereas the plasma levels of 4-oxo-isotretinoin were 1-2x higher. The plasma levels correlated well with the orally administered dose of isotretinoin and the observed mucocutaneous side effects. The study demonstrates that measuring of the plasma levels may be a helpful tool to monitor the individual therapeutic dose regimen in patients with severe acne in order to minimize undesired side effects and to control oral intake.

  5. Isotretinoin in lacrimal gland fluid and tears.

    PubMed

    Rismondo, V; Ubels, J L

    1987-03-01

    Isotretinoin (13-cis-retinoic acid) is used in the treatment of severe cystic acne. Adverse ocular reactions, including blepharoconjunctivitis and dry eye symptoms, are frequent side effects of this drug. Our previous observation that retinol is present in tears and lacrimal gland fluid suggests that isotretinoin may also be secreted by the lacrimal gland. Rabbits were treated with isotretinoin, and lacrimal gland fluid was collected from the cannulated lacrimal gland duct. Tears were collected from patients who were being treated with isotretinoin. Lacrimal gland fluid and tears were analyzed by reverse-phase high-pressure liquid chromatography and a peak eluted from each sample, which was identified as isotretinoin. We conclude that the lacrimal gland is able to secrete isotretinoin in addition to retinol and that, in animals and patients treated systemically with isotretinoin, the ocular surface is exposed to the drug via the tear film.

  6. Food increases the bioavailability of isotretinoin.

    PubMed

    Colburn, W A; Gibson, D M; Wiens, R E; Hanigan, J J

    1983-01-01

    Twenty healthy male subjects received 80 mg (2 X 40 mg SEG capsules) oral isotretinoin separated by two-week washout periods in an open randomized crossover design. Isotretinoin was administered during a complete fast, 1 hour after a standard breakfast, with a standard breakfast, or 1 hour before a standard breakfast. Blood samples were obtained at specific times over a 72-hour period. Isotretinoin blood concentrations were determined by a specific HPLC method. The relative bioavailability (AUC) of isotretinoin was found to be approximately 1.5 to 2 times greater when the dose was administered 1 hour before, concomitantly with, or 1 hour after a meal than when it was given during a complete fast. In addition, because the Cmax value is lower when the dose is administered with food rather than 1 hour after a meal, coadministration of isotretinoin with food may be the best method of administration.

  7. Improving the Isotretinoin Photostability by Incorporating in Microemulsion Matrix

    PubMed Central

    Patel, Mrunali R.; Patel, Rashmin B.; Parikh, Jolly R.; Patel, Bharat G.

    2011-01-01

    The present paper demonstrates the increased photostability of isotretinoin when loaded in microemulsion. The photodegradation of isotretinoin, in methanol and microemulsion formulation was studied under direct sun light. The photodegradation process was monitored by UV spectrophotometry. In methanol solution, isotretinoin undergoes complete photodegradation just within a few minutes of light exposure. Isotretinoin incorporated in microemulsion formulation showed an increased stability in comparison to the methanol solutions. In particular for isotretinoin, a residual concentration of 75% was still present after a light irradiance versus a residual value of just 16% measured at the same time in methanol solution. Further, degradation kinetic parameters of isotretinoin-loaded microemulsion formulation were demonstrated increase isotretinoin half-life about five-times in comparison with a methanol solution under a direct sun light. PMID:22389863

  8. Isotretinoin and FoxO1

    PubMed Central

    2011-01-01

    Oral isotretinoin (13-cis retinoic acid) is the most effective drug in the treatment of acne and restores all major pathogenetic factors of acne vulgaris. isotretinoin is regarded as a prodrug which after isomerizisation to all-trans-retinoic acid (ATRA) induces apoptosis in cells cultured from human sebaceous glands, meibomian glands, neuroblastoma cells, hypothalamic cells, hippocampus cells, Dalton's lymphoma ascites cells, B16F-10 melanoma cells, and neuronal crest cells and others. By means of translational research this paper provides substantial indirect evidence for isotretinoin's mode of action by upregulation of forkhead box class O (FoxO) transcription factors. FoxOs play a pivotal role in the regulation of androgen receptor transactivation, insulin/insulin like growth factor-1 (IGF-1)-signaling, peroxisome proliferator-activated receptor-γ (PPArγ)- and liver X receptor-α (LXrα)-mediated lipogenesis, β-catenin signaling, cell proliferation, apoptosis, reactive oxygene homeostasis, innate and acquired immunity, stem cell homeostasis, as well as anti-cancer effects. An accumulating body of evidence suggests that the therapeutic, adverse, teratogenic and chemopreventive effecs of isotretinoin are all mediated by upregulation of FoxO-mediated gene transcription. These FoxO-driven transcriptional changes of the second response of retinoic acid receptor (RAR)-mediated signaling counterbalance gene expression of acne due to increased growth factor signaling with downregulated nuclear FoxO proteins. The proposed isotretinoin→ATRA→RAR→FoxO interaction offers intriguing new insights into the mode of isotretinoin action and explains most therapeutic, adverse and teratogenic effects of isotretinoin in the treatment of acne by a common mode of FoxO-mediated transcriptional regulation. PMID:22110774

  9. Occurrence of pregnancy and pregnancy outcomes during isotretinoin therapy.

    PubMed

    Henry, David; Dormuth, Colin; Winquist, Brandace; Carney, Greg; Bugden, Shawn; Teare, Gary; Lévesque, Linda E; Bérard, Anick; Paterson, J Michael; Platt, Robert W

    2016-07-12

    Isotretinoin, a teratogen, is widely used to treat cystic acne. Although the risks of pregnancy during isotretinoin therapy are well recognized, there are doubts about the level of adherence with the pregnancy prevention program in Canada. Our objective was to evaluate the effectiveness of the Canadian pregnancy prevention program in 4 provinces: British Columbia, Saskatchewan, Manitoba and Ontario. Using administrative data, we identified 4 historical cohorts of female users of isotretinoin (aged 12-48 yr) for the period 1996 to 2011. We defined pregnancy using International Statistical Classification of Diseases and billing codes. One definition included only cases with documented pregnancy outcomes (high-specificity definition); the other definition also included individuals recorded as receiving prenatal care (high-sensitivity definition). We studied new courses of isotretinoin and detected pregnancies in 2 time windows: during isotretinoin treatment only and up to 42 weeks after treatment. Live births were followed for 1 year to identify congenital malformations. A total of 59 271 female patients received 102 308 courses of isotretinoin. Between 24.3% and 32.9% of participants received prescriptions for oral contraceptives while they were taking isotretinoin, compared with 28.3% to 35.9% in the 12 months before isotretinoin was started. According to the high-specificity definition of pregnancy, there were 186 pregnancies during isotretinoin treatment (3.1/1000 isotretinoin users), compared with 367 (6.2/1000 users) according to the high-sensitivity definition. By 42 weeks after treatment, there were 1473 pregnancies (24.9/1000 users), according to the high-specificity definition. Of these, 1331 (90.4%) terminated spontaneously or were terminated by medical intervention. Among the 118 live births were 11 (9.3%) cases of congenital malformation. Pregnancy rates during isotretinoin treatment remained constant between 1996 and 2011. Adherence to the isotretinoin

  10. Occurrence of pregnancy and pregnancy outcomes during isotretinoin therapy

    PubMed Central

    Henry, David; Dormuth, Colin; Winquist, Brandace; Carney, Greg; Bugden, Shawn; Teare, Gary; Lévesque, Linda E.; Bérard, Anick; Paterson, J. Michael; Platt, Robert W.

    2016-01-01

    Background: Isotretinoin, a teratogen, is widely used to treat cystic acne. Although the risks of pregnancy during isotretinoin therapy are well recognized, there are doubts about the level of adherence with the pregnancy prevention program in Canada. Our objective was to evaluate the effectiveness of the Canadian pregnancy prevention program in 4 provinces: British Columbia, Saskatchewan, Manitoba and Ontario. Methods: Using administrative data, we identified 4 historical cohorts of female users of isotretinoin (aged 12–48 yr) for the period 1996 to 2011. We defined pregnancy using International Statistical Classification of Diseases and billing codes. One definition included only cases with documented pregnancy outcomes (high-specificity definition); the other definition also included individuals recorded as receiving prenatal care (high-sensitivity definition). We studied new courses of isotretinoin and detected pregnancies in 2 time windows: during isotretinoin treatment only and up to 42 weeks after treatment. Live births were followed for 1 year to identify congenital malformations. Results: A total of 59 271 female patients received 102 308 courses of isotretinoin. Between 24.3% and 32.9% of participants received prescriptions for oral contraceptives while they were taking isotretinoin, compared with 28.3% to 35.9% in the 12 months before isotretinoin was started. According to the high-specificity definition of pregnancy, there were 186 pregnancies during isotretinoin treatment (3.1/1000 isotretinoin users), compared with 367 (6.2/1000 users) according to the high-sensitivity definition. By 42 weeks after treatment, there were 1473 pregnancies (24.9/1000 users), according to the high-specificity definition. Of these, 1331 (90.4%) terminated spontaneously or were terminated by medical intervention. Among the 118 live births were 11 (9.3%) cases of congenital malformation. Pregnancy rates during isotretinoin treatment remained constant between 1996 and 2011

  11. Pharmacokinetics of isotretinoin during repetitive dosing to patients.

    PubMed

    Brazzell, R K; Vane, F M; Ehmann, C W; Colburn, W A

    1983-01-01

    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.

  12. Pharmaceutical quality of generic isotretinoin products, compared with Roaccutane.

    PubMed

    Taylor, Peter W; Keenan, Michael H J

    2006-03-01

    Isotretinoin is the drug of choice for the management of severe recalcitrant nodular acne. Several generic products are available. However, their pharmaceutical quality, in particular particle size distribution, which may affect safety and efficacy is unknown. Hence, prescribing of some generic products may be problematic. To assess the pharmaceutical quality of 14 generic isotretinoin products compared with Roaccutane (F. Hoffmann-La Roche Ltd). Tests were performed according to Roche standard procedures, European and US pharmacopoeia specifications. Tests included isotretinoin content, identity and amount of impurities and degradation products, effect of accelerated shelf-life studies on stability, particle size distribution and composition of non-active ingredients. The 14 isotretinoin products differed by 30-fold in median particle size and showed variation in their non-active ingredients. The average isotretinoin content of Acnotin and Acne-Tretin fell outside the 95-105% Roche specifications. Following accelerated shelf-life tests, only four products retained isotretinoin content within Roche specifications, whilst Acne-Tretin (the only powder formulation) lost 72.5% isotretinoin content. Two generic products exceeded the +/- 2% specification (Ph. Eur.) and a further three exceeded the +/- 1% (USP) for tretinoin content, eight exceeded the 2.54% specification for total impurities and six contained >or= 5 unknown impurities. Isotretinoin-5.6-epoxide content exceeded the 1.04% specification in five generic products. Thirteen generic products failed to match Roaccutane in one or more tests and 11 failed in three or more tests. It cannot be assumed that all generic isotretinoin products are as therapeutically effective or safe as Roaccutane.

  13. Successful treatment of palmoplantar pustulosis with isotretinoin.

    PubMed

    Wilken, Reason; Sharma, Ajay; Patel, Forum; Maverakis, Emanual

    2015-08-15

    Variably considered as a localized subtype of pustular psoriasis, palmoplantar pustulosis (PPP) is commonly treated with topical steroids, acitretin, and local phototherapy with oral or topical psoralen (PUVA). The utility of acitretin for PPP is limited by adverse effects such as myalgias and an extended risk of teratogenicity in female patients. Isotretinoin is a more tolerable retinoid with a shorter teratogenic window, but to date its effectiveness in PPP has not been reported. Herein we present two patients with PPP who responded well to isotretinoin treatment. Two patients with PPP refractory to topical therapies were started on acitretin. Both patients developed adverse effects (including headache, myalgias, and mood alterations) leading to acitretin discontinuation. Isotretinoin monotherapy was started in one patient resulting in significant clearing of palmar plaques and scale, and the addition of isotretinoin to UVA therapy resulted in near-complete clearing of recalcitrant plantar plaques in the second patient. Acitretin represents an important treatment for PPP, but is limited by adverse effects and extended teratogenicity. Our experience supports the utility of isotretinoin as a potential therapeutic alternative, which may be particularly beneficial in patients who are poor candidates for or unable to tolerate acitretin therapy.

  14. Isotretinoin revisited: pluripotent effects on human sebaceous gland cells.

    PubMed

    Zouboulis, Christos C

    2006-10-01

    Nelson et al. confirmed the previously described antiproliferative effect of isotretinoin on human sebocytes. They attributed a portion of this decrease to cell cycle arrest and detected sebocyte apoptosis, which was not recapitulated by alitretinoin or tretinoin. These events were specific to sebocytes, as isotretinoin failed to induce apoptosis in keratinocytes. Isotretinoin-induced apoptosis was shown to be an RAR-independent mechanism.

  15. Retinoid agonist isotretinoin ameliorates obstructive renal injury.

    PubMed

    Schaier, Matthias; Jocks, Thomas; Grone, Hermann-Josef; Ritz, Eberhard; Wagner, Juergen

    2003-10-01

    Interstitial fibrosis is a major cause of end stage renal failure. Retinoids, which are involved in tissue repair and fibrosis, inhibit inflammatory and proliferative pathways. Therefore, we studied the dose dependent effects of the retinoid receptor agonist isotretinoin 13-cis retinoic acid in the unilateral ureteral obstruction model (UUO). Sham operated control rats were compared with UUO rats treated with vehicle (UUO-Veh), or low (5 mg/kg body weight (UUO-LD) or high (25 mg/kg) (UUO-HD) dose isotretinoin. Kidneys were evaluated using reverse transcriptase-polymerase chain reaction and immunohistology 7 days after UUO. Renal injury and fibrosis were quantified by immunostaining and expression measurements of the genes involved in renal fibrosis. In UUO-Veh kidneys the interstitial area was expanded 5-fold but only 3-fold in UUO-HD and 3.5-fold in UUO-LD rats. Interstitial cell counts were 3-fold higher in UUO-Veh rats but significantly less in UUO-HD or UUO-LD animals. Tubular and interstitial cell proliferation was significantly higher in UUO-Veh rats compared with sham operated control plus vehicle animals but less so in UUO-LD and UUO-HD rats. In UUO-Veh rats interstitial infiltration by monocytes/macrophages was higher compared with unobstructed controls. It was significantly less after isotretinoin treatment. In UUO-Veh rats mRNA for procollagen I, and transforming growth factor-beta1 and II receptor was significantly increased. It was significantly less after treatment with isotretinoin. Fibronectin and collagen I immunostaining was also decreased by isotretinoin. Since isotretinoin limits proliferation, inflammation and fibrosis after UUO, retinoids should be further investigated as potentially promising therapeutic agents for renal disease.

  16. Epidermal effects of tretinoin and isotretinoin: influence of isomerism.

    PubMed

    Tadini, K A; Gaspar, L R; Maia Campos, P M B G

    2006-05-01

    The efficacy of tretinoin is well established in the treatment of acne and photoaged skin, however as a typical side effect of tretinoin treatment most patients develop a low-grade irritant dermatitis. Since isotretinoin topical treatment usually shows much lower incidence and intensity of adverse effects than tretinoin topical treatment, histological studies are needed to scientifically evaluate the effects of isotretinoin application on epidermis and also to assess if it can be used in anti-aging products as an alternative to tretinoin. Thus, the aim of this study was to compare the effects of topical use of tretinoin or isotretinoin on hairless mice epidermis, using appropriate histopathological and histometric techniques, in order to evaluate the influence of isomerism on skin effects. For this, gel cream formulations containing or not 0.05% tretinoin or 0.05% isotretinoin were applied in the dorsum of hairless mice, once a day for seven days. Histopathological evaluation, viable epidermal and horny layer thicknesses as well as the number of epidermal cell layers were determined. Our results showed that tretinoin and isotretinoin were effective in the enhancement of viable epidermis thickness and number of epidermal cell layers, suggesting that they could be used for stimulation of cellular renewal. However isomerism influenced skin effects since isotretinoin had more pronounced effects than tretinoin in viable epidermis. In addition only isotretinoin treatment enhanced horny layer thickness when compared to the gel cream treatment.

  17. [Isotretinoin embryopathy: An entity that can be avoided].

    PubMed

    Cammarata-Scalisi, Francisco; Nieves, Dairelis; Avendaño, Andrea; Lacruz-Rengel, María A; Alviárez, Karelys; Dávila, Francys; Yavuz, Izzet; Callea, Michele

    2018-04-01

    Isotretinoin is the most effective drug in the treatment of severe recalcitrant nodulocystic acne. However, treatment with this drug is associated with adverse effects, the most severe being teratogenesis. It has been estimated that 40% of pregnancies exposed to isotretinoin present spontaneous abortion and 35% develop embryopathy. We present the case of a newborn with a history of prenatal exposure to isotretinoin, a clinical entity that can be avoided, with severe congenital defects in the central nervous system and important facial dysmorphisms, with unfavorable clinical course. Sociedad Argentina de Pediatría.

  18. Isotretinoin kinetics after 80 to 320 mg oral doses.

    PubMed

    Colburn, W A; Gibson, D M

    1985-04-01

    Twelve healthy male subjects received 80, 160, 240, and 320 mg doses of oral isotretinoin as multiples of 40 mg capsules separated by 2-week washout periods in a randomized, crossover design. Blood samples were drawn at specific times over a 72-hour period after dosing. Blood concentrations of isotretinoin as well as its major metabolite, 4-oxo-isotretinoin, were determined by a specific HPLC method. In addition to the normal laboratory battery of tests, serum triglyceride levels were determined before the first dose and again 72 hours after each of the four doses. Mean (+/- SD) maximum concentrations after 80 to 320 mg doses were 366 +/- 159, 820 +/- 474, 1056 +/- 547, and 981 +/- 381 ng/ml, whereas the respective AUC0-infinity values were 3690 +/- 1280, 7030 +/- 4140, 9780 +/- 6080, and 9040 +/- 2900 ng X hr/ml. The observed apparent elimination t1/2 remained approximately the same (14.7 hours) for each dose. The maximum concentration and AUC values for isotretinoin appear to be dose proportional from 80 to 240 mg but plateau at the 320 mg dose level. Therefore, because isotretinoin blood concentrations may not increase with higher doses in the fasting state, single, oral doses in excess of 240 mg should be used with caution. The data also suggest that elevated triglyceride levels are not a simple function of isotretinoin blood concentrations across the entire study population and dose range studied, but that in subjects with triglyceride levels in excess of the normal range triglyceride levels were positively related to isotretinoin blood concentrations.

  19. Pharmacokinetics of isotretinoin and its major blood metabolite following a single oral dose to man.

    PubMed

    Colburn, W A; Vane, F M; Shorter, H J

    1983-01-01

    A pharmacokinetic profile of isotretinoin and its major dermatologically active blood metabolite, 4-oxo-isotretinoin, was developed following a single 80 mg oral suspension dose of isotretinoin to 15 normal male subjects. Blood samples were assayed for isotretinoin and 4-oxo-isotretinoin using a newly developed reverse-phase HPLC method. Following rapid absorption from the suspension formulation, isotretinoin is distributed and eliminated with harmonic mean half-lives of 1.3 and 17.4 h, respectively. Maximum concentrations of isotretinoin in blood were observed at 1 to 4 h after dosing. Maximum concentrations of the major blood metabolite of isotretinoin, 4-oxo-isotretinoin, are approximately one-half those of isotretinoin and occur at 6 to 16 h after isotretinoin dosing. The ratio of areas under the curve for metabolite and parent drug following the single dose suggests that average steady-state ratios of metabolite to parent drug during a dosing interval will be approximately 2.5. Both isotretinoin and its metabolite can be adequately described using a single linear pharmacokinetic model.

  20. Isotretinoin and mental health in adolescents: Australian consensus.

    PubMed

    Rowe, Casey; Spelman, Lynda; Oziemski, Margaret; Ryan, Alexander; Manoharan, Shobhan; Wilson, Perry; Daubney, Michael; Scott, James

    2014-05-01

    Acne is a common condition among adolescents and has the potential to negatively impact on the psychological well-being of those who suffer from it. In particular, depression and suicidal ideation are more common in adolescents with acne. Successful treatment of acne can improve the quality of life and reduce levels of anxiety and depression in these individuals. The current treatment of choice for severe or refractive acne is isotretinoin, a retinoid. While the possible causal association between isotretinoin and mental illness remains a controversial topic, a recent systematic review has presented evidence to support this relationship. In light of this evidence, a group of dermatologists and psychiatrists have collaborated to develop these recommendations to aid the safe prescribing of isotretinoin in adolescents. These clinical suggestions are aimed at practitioners in both disciplines to increase awareness of the current evidence in support of the association between isotretinoin and adolescent depression. © 2013 The Australasian College of Dermatologists.

  1. Isotretinoin therapy for acne: a population-based study.

    PubMed Central

    Hogan, D J; Strand, L M; Lane, P R

    1988-01-01

    The use of isotretinoin over a 2-year period was retrospectively studied in Saskatchewan. The database of the Saskatchewan Prescription Drug Plan was used to obtain the names of physicians who prescribed isotretinoin as well as the names of patients for whom it was prescribed. Of the 861 such patients 161 had been instructed to use the drug for at least 4 months by 42 physicians. Questionnaires were returned by 86 of the 161 patients and 22 of the 42 physicians. The responses confirmed that isotretinoin therapy is highly effective for acne. However, at least half of the patients for whom the agent was prescribed apparently did not complete a full 4- to 5-month course of treatment, and of the 34 women (average age 28 years) who responded to the questionnaire 12 (35%) did not use a method of contraception, which is a matter of concern in view of isotretinoin's teratogenic effects. PMID:2961430

  2. Recalcitrant Nodulocystic Acne in Black Americans: Treatment With Isotretinoin

    PubMed Central

    Kelly, A. Paul; Sampson, Darlene D.

    1987-01-01

    The beneficial effects of isotretinoin (Accutane) on severe nodulocystic acne and significant clinical improvement with prolonged remission are well documented in the literature; however, the subjects in these clinical studies are invariably white. The purpose of this study was to evaluate the response of black patients with recalcitrant nodulocystic acne to isotretinoin treatment. Ten black patients, ranging in age from 17 to 34 years, were treated for nodulocystic acne with 1 mg/kg/d of isotretinoin for 20 weeks and followed for an additional six months. Of the ten patients, eight adhered to the treatment regimen and were still in remission six months after completion of isotretinoin therapy. The differences and similarities seen between black patients and white patients with nodulocystic acne are discussed. ImagesFigure 1Figure 2Figure 3 PMID:2963137

  3. Effects of isotretinoin on the olfactory function in patients with acne.

    PubMed

    Kartal, Demet; Yaşar, Mehmet; Kartal, Levent; Özcan, Ibrahim; Borlu, Murat

    2017-01-01

    Isotretinoin is a synthetic analog of vitamin A. Recent studies support a role for retinoic acid in the recovery of olfactory function following injury in mice. This study aimed at determining the effect of isotretinoin on olfactory function in patients who have acne and are otherwise healthy. Forty-five patients (aged 25-40 years) with acne were included in the study. All patients underwent a rhinological examination. Olfactory function was assessed by the Sniffin' Sticks Test. The test was assessed at baseline and in the third month of isotretinoin treatment. Isotretinoin improved the performance of patients in the olfactory test. The SST score increased from 8.7±1.09 to 9.5±1.19 (p<0.001), prevalence of hyposmia decreased from 40% to 24% and normosmia increased from 60% to 75% (p=0.059). The percentage of patients whose olfactory function was categorized as "good" increased from 6% to 21.3%. This increase was statistically significant (p<0.05). Absence of a control group is one of the limitations of this study. Also, we did not evaluate patients with smell test after stopping isotretinoin treatment. We examined the effect of systemic isotretinoin on olfactory function. It can be concluded from the present investigation that isotretinoin therapy improves the sense of smell.

  4. [Clinical and monitoring experience of isotretinoin in Italy].

    PubMed

    Cavicchini, S; Bottoni, A; Caputo, R

    1989-01-01

    We report the results of a multicentric evaluation on effectiveness and safety of isotretinoin in severe acne, recalcitrant to traditional treatments. 208 patients, suffering especially from cystic acne, have been enrolled in a post-marketing clinical trial in 11 Dermatological Italian Departments. The clinical effectiveness of isotretinoin has been very good in 77% of patients, good in 16% and sufficient in 4%. The tolerability of the drug was considered good in 90% of patients. Finally, isotretinoin might be considered as one of the most effective drugs in the therapy of severe forms of acne, resistant to usual treatment, and often affecting patients on the physical and psychological side.

  5. Effects of isotretinoin on the olfactory function in patients with acne*

    PubMed Central

    Kartal, Demet; Yaşar, Mehmet; Kartal, Levent; Özcan, Ibrahim; Borlu, Murat

    2017-01-01

    Background Isotretinoin is a synthetic analog of vitamin A. Recent studies support a role for retinoic acid in the recovery of olfactory function following injury in mice. Objective This study aimed at determining the effect of isotretinoin on olfactory function in patients who have acne and are otherwise healthy. Methods Forty-five patients (aged 25-40 years) with acne were included in the study. All patients underwent a rhinological examination. Olfactory function was assessed by the Sniffin' Sticks Test. The test was assessed at baseline and in the third month of isotretinoin treatment. Results Isotretinoin improved the performance of patients in the olfactory test. The SST score increased from 8.7±1.09 to 9.5±1.19 (p<0.001), prevalence of hyposmia decreased from 40% to 24% and normosmia increased from 60% to 75% (p=0.059). The percentage of patients whose olfactory function was categorized as "good" increased from 6% to 21.3%. This increase was statistically significant (p<0.05). Study limitations Absence of a control group is one of the limitations of this study. Also, we did not evaluate patients with smell test after stopping isotretinoin treatment. Conclusion We examined the effect of systemic isotretinoin on olfactory function. It can be concluded from the present investigation that isotretinoin therapy improves the sense of smell. PMID:28538877

  6. A comparative review of the isotretinoin pregnancy risk management programs across four continents.

    PubMed

    Kovitwanichkanont, Tom; Driscoll, Tim

    2018-03-06

    Isotretinoin has revolutionized the treatment of severe acne vulgaris, a condition which if left untreated may result in significant socio-psychological implications for those affected. Timely access to isotretinoin therapy is important to avoid the risks of potential physical and emotional scarring. However, due to its high risks of teratogenicity, isotretinoin must be used with care in females of childbearing potential. Since isotretinoin's introduction, numerous risk management programs have been implemented across the world in an attempt to prevent isotretinoin use in pregnancy. This paper aims to provide an evidence-based review of the risk management programs for isotretinoin in Australia, Europe, Singapore, New Zealand, and the United States of America. The effectiveness of these programs and the factors leading to isotretinoin exposure in pregnancy are critically analyzed in an effort to inform the future direction with respect to designing the ideal regulatory program. Stringent risk management programs, such as the iPLEDGE in the US and Pregnancy Prevention Program (PPP) in Europe, may not be effective in reducing the risks of fetal exposure to isotretinoin when used alone. There is evidence that such strenuous regulation results in increased fear of teratogenic risks but does not translate into a reduced rate of pregnancies exposed to isotretinoin. A successful program must prioritize education about effective contraception, while minimizing any extraneous requirements, to ensure that women are not inadvertently undertreated for acne. © 2018 The International Society of Dermatology.

  7. Isotretinoin (Accutane) and Pregnancy

    MedlinePlus

    ... about all your breastfeeding questions. What about topical tretinoin? Topical tretinoin (Retin-A® and other brand names) is used ... skin to treat acne and other skin problems. Tretinoin is related to Vitamin A and isotretinoin. For ...

  8. A practical approach for the use of oral isotretinoin for infantile acne.

    PubMed

    Barnes, Cheryl J; Eichenfield, Lawrence F; Lee, Jungho; Cunningham, Bari B

    2005-01-01

    Infantile acne is a rare occurrence. It is more common in boys and predominately occurs on the cheeks in infants between the ages of 1 and 16 months. Clinically, the lesions range from comedones to inflammatory papulopustules to cysts. Successful therapies include topical tretinoin, benzoyl peroxide and topical and oral erythromycin. For more serious cases, oral isotretinoin (Accutane) has been reported to successfully treat recalcitrant infantile cystic acne. We describe two additional patients with infantile cystic acne treated successfully with oral isotretinoin. The dose of isotretinoin used ranged from 0.2 mg/kg/day to 1.5 mg/kg/day. The treatment duration varied from 5 to 14 months. Careful monthly monitoring is recommended because of the many side effects reported with isotretinoin. Practical tips for the administration of oral isotretinoin in infants are reviewed.

  9. Isotretinoin, depression and suicide: a review of the evidence

    PubMed Central

    Magin, Parker; Pond, Dimity; Smith, Wayne

    2005-01-01

    There is currently considerable controversy regarding a proposed causal relationship between the use of isotretinoin and depression and suicide. A search was made of the MEDLINE, EMBASE and PsychINFO databases using the search terms ‘isotretinoin’, ‘depression’ and ‘suicide’. Despite numerous case reports linking isotretinoin to depression, suicidal ideation and suicide, there is, as yet, no clear proof of an association. While isotretinoin, used to treat acne vulgaris, has not been demonstrated to be associated with depression or suicide, the possibility of a relatively rare idiosyncratic adverse effect remains. GPs have a role in the clinical application of these findings. PMID:15720936

  10. Isotretinoin therapy changes the expression of antimicrobial peptides in acne vulgaris.

    PubMed

    Borovaya, Alena; Dombrowski, Yvonne; Zwicker, Stephanie; Olisova, Olga; Ruzicka, Thomas; Wolf, Ronald; Schauber, Jürgen; Sárdy, Miklós

    2014-10-01

    In acne vulgaris, antimicrobial peptides (AMPs) could play a dual role; i.e., protective by acting against Propionibacterium acnes, pro-inflammatory by acting as signalling molecules. The cutaneous expression of 15 different AMPs was investigated in acne patients; furthermore, the impact of isotretinoin therapy on AMP expression was analysed in skin biopsies from 13 patients with acne vulgaris taken before, during and after a 6-month treatment cycle with isotretinoin using quantitative real-time polymerase chain reaction. Cutaneous expression of the AMPs cathelicidin, human β-defensin-2 (HBD-2), lactoferrin, lysozyme, psoriasin (S100A7), koebnerisin (S100A15), and RNase 7 was upregulated in untreated acne vulgaris, whereas α-defensin-1 (HNP-1) was downregulated compared to controls. While relative expression levels of cathelicidin, HBD-2, lactoferrin, psoriasin (S100A7), and koebnerisin (S100A15) decreased during isotretinoin treatment, only those of cathelicidin and koebnerisin returned to normal after 6 months of isotretinoin therapy. The increased expression of lysozyme and RNase 7 remained unaffected by isotretinoin treatment. The levels of granulysin, RANTES (CCL5), perforin, CXCL9, substance P, chromogranin B, and dermcidin were not regulated in untreated acne patients and isotretinoin had no effect on these AMPs. In conclusion, the expression of various AMPs is altered in acne vulgaris. Isotretinoin therapy normalizes the cutaneous production of distinct AMPs while the expression of others is still increased in healing acne. Considering the antimicrobial and pro-inflammatory role of AMPs, these molecules could serve as specific targets for acne therapy and maintenance of clinical remission.

  11. Steady-state pharmacokinetics of isotretinoin and its 4-oxo metabolite: implications for fetal safety.

    PubMed

    Nulman, I; Berkovitch, M; Klein, J; Pastuszak, A; Lester, R S; Shear, N; Koren, G

    1998-10-01

    Isotretinoin is the most potent human teratogen on the market. Women for whom contraception fails may conceive during or soon after discontinuing isotretinoin therapy, making its elimination kinetics a crucial determinant of fetal safety. The steady-state pharmacokinetics of isotretinoin and its major 4-oxo metabolite were studied in 16 adult patients treated for acne who were receiving doses that ranged from 0.47 to 1.7 mg/kg daily. This is the first study of the pharmacokinetics of isotretinoin in women of childbearing age (n = 11). The clinical efficacy and tolerability of isotretinoin was investigated, and the correlation between these data and steady-state serum concentrations of isotretinoin was tested. The concentration-time data best fitted a two-compartment open model with linear elimination. There was no correlation between efficacy and tolerability of isotretinoin and steady-state serum concentrations. There was no correlation between dose of isotretinoin and steady-state concentration, due to the large variability in apparent clearance. Values for elimination half-life (t1/2) of isotretinoin and its metabolite were 29+/-40 hours and 22+/-10 hours, respectively. These data suggest a longer elimination t1/2 of the parent drug than previously reported. This is probably due to the longer sampling time used in this study (as long as 28 days). This study suggests that a greater variability exists in the safe time after discontinuation of the drug for onset of conception.

  12. Updated Physician’s Guide to the Off-label Uses of Oral Isotretinoin

    PubMed Central

    Peterson, Nathan; Peterson, Michael

    2014-01-01

    While oral isotretinoin is renowned for its ability to treat acne vulgaris, many of its off-label uses continue to go underappreciated. Since the last review on the unapproved indications of isotretinoin, relevant publications have surfaced with new recommendations. This article attempts to provide physicians with the latest information regarding successful and unsuccessful use of isotretinoin as an effective treatment for dermatological conditions, such as rosacea, psoriasis, pityriasis rubra pilaris, condyloma acuminatum, granuloma annulare, Darier’s disease, systemic cutaneous lupus erythematosus, nonmelanoma skin cancer, and hidradenitis suppurativa. Variations in dosage regimens and isotretinoin viability as an alternative to other standard treatments are also discussed in relation to these conditions. PMID:24765227

  13. Affective psychosis following Accutane (isotretinoin) treatment.

    PubMed

    Barak, Yoram; Wohl, Yonit; Greenberg, Yifa; Bar Dayan, Yosefa; Friedman, Tali; Shoval, Gideon; Knobler, Haim Y

    2005-01-01

    Isotretinoin (Accutane) ranks in the top 10 of the US Food and Drug Administration's database of drugs associated with reports of depression and suicide attempts. However, this association is still controversial because up to 5.6% of patients with moderate acne may have pre-existing suicidal ideations, improvement of acne often reduces associated depression, and isotretinoin users are reportedly no more likely than those taking antibiotics for acne to have depression or commit suicide. We describe a series of cases of manic psychosis that developed in a 1-year period (2003) in association with isotretinoin treatment and resulted in suicidality and progression to long-standing psychosis. Cases were drawn from 500 soldiers who had been evaluated in a military specialists dermatology clinic for severe acne. Data were summarized from medical records of five severe acne patients treated by isotretinion during their compulsory military service. Data from their draft board examinations and service records, as well as repeated clinical assessments by certified psychiatrists at the Israel Defense Forces (IDF) Mental Health Department clinic, were evaluated. Five young adults developed manic psychosis within a mean of 7.6 months of exposure to isotretinoin. In three cases, this was accompanied by a suicide attempt, and in three cases, psychosis lasted for longer than 6 months. Either a personal history of obsessive-compulsive disorder, neurological insult or family history of a major psychiatric illness were present in all cases. The present case-series is suggestive of an increase in the likelihood of an association between exposure to isotretinion and manic psychosis. Associated risk factors were both family and personal history of psychiatric morbidity. Further studies are needed to establish our findings.

  14. The prevalence of sacroiliitis in patients with acne vulgaris using isotretinoin.

    PubMed

    Baykal Selçuk, Leyla; Aksu Arıca, Deniz; Baykal Şahin, Hanife; Yaylı, Savas; Bahadır, Sevgi

    2017-06-01

    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. 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. 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). 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.

  15. Concomitant use of isotretinoin and contraceptives before and after iPledge in the United States.

    PubMed

    Pinheiro, Simone P; Kang, Elizabeth M; Kim, Clara Y; Governale, Laura A; Zhou, Esther H; Hammad, Tarek A

    2013-12-01

    The major concern associated with isotretinoin treatment is its high teratogenic potential. Therefore, ensuring use of contraception while on therapy is an important strategy for at-risk patients and has been emphasized in all risk management programs. iPledge, the latest and most rigorous isotretinoin program, requires, among other stipulations, monthly assessments of contraceptive use for patients undergoing isotretinoin treatment. The purpose of this study is to evaluate isotretinoin usage patterns and assess concomitant use of isotretinoin and contraceptives before and after iPledge. Female patients aged 13-45 years with a new prescription for isotretinoin products during 2004-2008 were identified in the IMS Health longitudinal prescription claims database. Monthly concomitant use of isotretinoin and contraceptives was estimated. Segmented regression analysis of interrupted time series data was used to assess changes in monthly proportion of concomitant use in the 24 months preceding versus following iPledge implementation. The number of isotretinoin prescriptions decreased after iPledge implementation. A small but significant increase in monthly proportion of patients concomitantly using isotretinoin and contraceptive therapies was observed immediately after iPledge implementation (1.3%, p-value = 0.02), particularly among younger patients (2.5%, p-value < 0.01). No changes in the proportion of concomitancy over time (i.e. slope) between the periods before and after iPledge implementation were observed. The findings of this pharmacy prescription claims-based study suggest a small increase in concomitant use of isotretinoin and contraceptives coincident with the time of implementation of iPledge, particularly among younger women. Published 2013. This article is a U. S. Government work and is in the public domain in the USA. Published 2013. This article is a U. S. Government work and is in the public domain in the USA.

  16. Presumed Isotretinoin-Induced, Concomitant Autoimmune Thyroid Disease and Ocular Myasthenia Gravis: A Case Report

    PubMed Central

    Gursoy, Huseyin; Cakmak, Idil; Yildirim, Nilgun; Basmak, Hikmet

    2012-01-01

    Introduction There are many adverse effects that have been described for isotretinoin. To the best of our knowledge, this is the first report of a possible association of oral isotretinoin intake with autoimmune thyroiditis and ocular myasthenia gravis (OMG). Case Presentation A 19-year-old Caucasian male, who had used oral isotretinoin for severe acne disease for the previous six months, was referred to our clinic. He had a three-week history of diplopia and variable bilateral ptosis. Physical examination showed moderate periorbital edema and limitations of up- and down-gaze in the left eye. Laboratory findings and thyroid ultrasound were consistent with autoimmune thyroiditis. Antithyroid therapy did not relieve the clinical symptoms. Concomitant OMG was suspected. Variable ptosis and a positive response to oral prednisolone of 40 mg/day and pyridostigmine of 360 mg/day supported the diagnosis of concomitant autoimmune thyroiditis and OMG. Conclusion Autoimmune disorders may be triggered by oral isotretinoin treatment. Clinicians prescribing isotretinoin should be aware of the possible association between isotretinoin intake and concomitant autoimmune thyroiditis and OMG. PMID:23275770

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

    PubMed

    Plewig, Gerd; Dressel, Heidrun; Pfleger, Maike; Michelsen, Silke; Kligman, Albert M

    2004-01-01

    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. 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). 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%. 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.

  18. Development of a gas chromatography method for the determination of isotretinoin and its degradation products in pharmaceuticals.

    PubMed

    Lima, Eliana Martins; Diniz, Danielle G Almeida; Antoniosi-Filho, Nelson R

    2005-07-15

    This paper describes the development of a gas chromatography (GC) method used for the assay of isotretinoin in its isolated form and in pharmaceutical formulations. Isotretinoin soft and hard gelatin capsules were prepared with various excipients. The performance of the proposed gas chromatography method was compared to that of traditional high performance liquid chromatography (HPLC) systems for this substance, and the GC parameters were established based on several preliminary tests, including thermal analysis of isotretinoin. Results showed that gas chromatography-flame ionization detector (GC-FID) exhibited a separation efficiency superior to that of HPLC, particularly for separating isotretinoin degradation products. This method was proven to be effectively applicable to stability evaluation assays of isotretinoin and isotretinoin based pharmaceuticals.

  19. Isotretinoin has no negative effect on attention, executive function and mood.

    PubMed

    Ergun, T; Seckin, D; Ozaydin, N; Bakar, Ö; Comert, A; Atsu, N; Demircay, Z; Yoney, H; Zaimoglu, S

    2012-04-01

    According to some animal data, impairments in learning and memory are seen with isotretinoin. Isotretinoin has been shown to affect human brain metabolism, but the data on human neural functions is lacking. To evaluate whether isotretinoin treatment affects cognitive functions, causes depression and anxiety or alters anger level and anger expression. Neuropsychological tests of attention and executive functions, behavioural tests measuring anger and depression and measures assessing acne severity were applied to 63 severe and/or resistant acne patients from four medical centres including one primary care institute and three university hospitals at the beginning, at the end of first month, third month and at end of treatment with isotretinoin. From a total of 63 patients, 15 missed the final visit and 48 were evaluated. Overall, 11 (six women, five men) and five (all women) patients reported anger and depression, respectively, during treatment. Eleven of these 16 patients improved spontaneously. No detrimental effects of isotretinoin treatment on either executive functions or mood were found. Several executive functions and control of anger trait were found to be improved. Clearing of acne was obtained in 94.6% of patients. Improvement of several measures may be related to learning effect of repeated testing. Investigating brain functions is a complex process and various methods can be used. The test battery used in this study, which is commonly used to evaluate mental status both in adults and children, did not show any negative effect of isotretinoin on executive functional parameters in acne patients. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

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

    PubMed

    Grønhøj Larsen, F; Jakobsen, P; Grønhøj Larsen, C; Heidenheim, M; Held, E; Nielsen-Kudsk, F

    2009-09-01

    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. 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. 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. 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. The metabolism and pharmacokinetics of isotretinoin and its main metabolites are not influenced by ethanol during long-term isotretinoin treatment. After ceasing

  1. Use of isotretinoin (Accutane) in the United States: rapid increase from 1992 through 2000.

    PubMed

    Wysowski, Diane K; Swann, Joslyn; Vega, Amarilys

    2002-04-01

    Isotretinoin, a drug approved to treat severe recalcitrant nodular acne, has been marketed in the United States since 1982. The drug is an effective treatment for acne that is refractory to other therapies, but it is a teratogen and can cause serious side effects. Our purpose was to describe trends in the use of isotretinoin in the United States from marketing through year 2000 and summarize characteristics of patients and prescribers. Data from 2 pharmaceutical marketing research databases, the National Prescription Audit Plus and the National Disease and Therapeutic Index, and from 2 health plan networks were obtained and analyzed. Retail pharmacies dispensed 19.8 million outpatient prescriptions for isotretinoin from marketing in 1982 through 2000. From 1983 through 1993, the median annual number of prescriptions was just over 800,000; between 1992 and 2000, the number of prescriptions increased 2.5-fold (250%) to nearly 2 million in year 2000. The increases registered in the health plans were somewhat larger: about 275% increases from 1995 through 1999. There is no ICD-9 code for nodulocystic acne; consequently, the type of acne treated with isotretinoin is not determinable from these data. However, between 1993 and 2000, the proportion of isotretinoin treatment for severe acne declined from 63% to 46%, whereas the proportion of treatment for mild and moderate acne increased from 31% to 49%. Data also indicated that the sex distribution of patients was nearly even, and that 63% of male patients prescribed isotretinoin were 15 to 19 years old, whereas 51% of female patients were 15 to 24 years old. In the last 8 years, there has been a 2.5-fold (250%) increase in the number of dispensed prescriptions for isotretinoin in the United States. Data also reveal an increasing proportion of isotretinoin use for mild and moderate acne.

  2. Prescriptive contraceptive use among isotretinoin users in the Netherlands in comparison with non-users: a drug utilisation study.

    PubMed

    Crijns, Hubertina J M J; van Rein, Nienke; Gispen-de Wied, Christine C; Straus, Sabine M; de Jong-van den Berg, Lolkje T W

    2012-10-01

    To assess the compliance with the isotretinoin Pregnancy Prevention Programme (PPP) by evaluating the use of prescribed contraceptives among isotretinoin users. The PPP contains a requirement for the use of contraceptive methods for women of childbearing potential. A drug utilisation study was performed using data from a drug prescription database (containing Dutch community pharmacy data) covering a population of 500 000 patients. Contraceptive use in female isotretinoin users and in a reference group of female non-isotretinoin users (aged 15-49 years) was compared using data from 1999 until 2006 in 2-year periods. Descriptive statistics were used. Of the female isotretinoin users (n = 651), 52%-54% filled prescriptions on contraceptives in strict accordance to the PPP, used before, during, and after discontinuation of isotretinoin, compared with 39%-46% in the reference group. A more liberal approach of a minimum of one prescription for a contraceptive method showed 61%-64% use of contraceptives among isotretinoin users. Similar patterns were seen when data were broken down in age groups. Furthermore, a higher proportion of female patients using isotretinoin prescribed by general practitioners used prescribed contraceptives compared with those receiving isotretinoin by specialists. Compliance with the contraceptive use according to a PPP for a teratogenic drug such as isotretinoin is 52%-64%, which is lower than anticipated. Reasons for the low compliance will need to be clarified before further measures can be taken. Copyright © 2012 John Wiley & Sons, Ltd.

  3. Isotretinoin: the ups are just as troubling as the downs.

    PubMed

    Truitt, Jay M; Reichenberg, Jason S; Sharghi, Kevin G; Sampson, Shirlene M; Roenigk, Randall K; Magid, Michelle

    2018-08-01

    Isotretinoin, previously marketed as Accutane®, is an oral retinoid medication that is used to treat acne and other cutaneous disorders. Although the data is conflicting, previous reports suggest a causal relationship between isotretinoin and depression. When reviewing these previous reports, many patients who were diagnosed as "depressed" did not undergo a thorough psychiatric evaluation and/or were not diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM). These patients reported agitation, irritability, sleep disturbances, and aggression. We hypothesize that some patients previously reported as "depressed" may have been "misdiagnosed" and were actually experiencing symptoms of mania, mixed mood (depression and mania at the same time), or psychosis. An Ovid Medline and PubMed literature search of English language articles was performed using the keywords "isotretinoin", "retinoids", "mood", "psychiatric", "depression", "elevation", "bipolar", and "psychosis". Eleven case reports, three case series, three retrospective chart reviews, five drug registries, and two prospective studies were reviewed. We found that many of the patients labeled as "depressed", had signs of activation, agitation, elevated mood, and psychosis. We believe that many of these patients were most likely having manic or mixed mood episodes. These symptoms appeared to be more prevalent in patients with a personal or family history of mental illness. Isotretinoin may cause mood instability in both directions - depression and mania - especially in a predisposed population. With this in mind, we urge clinicians prescribing isotretinoin to focus on all psychiatric symptoms (not just depression) including mania, mixed mood, and psychosis, paying particular attention to individuals who have a personal or family history of psychiatric disease.

  4. Pharmacokinetics of 14C-isotretinoin in healthy volunteers and volunteers with biliary T-tube drainage.

    PubMed

    Colburn, W A; Vane, F M; Bugge, C J; Carter, D E; Bressler, R; Ehmann, C W

    1985-01-01

    The pharmacokinetics of isotretinoin and 4-oxoisotretinoin in blood, as well as the blood concentrations and urinary, biliary, and fecal excretion of carbon-14 were studied using liquid scintillation counting techniques and reverse phase HPLC methods following a single 80-mg oral suspension dose of 14C-isotretinoin to four healthy male subjects and two patients with biliary T-tube drainage. Approximately 80% of the dose was recovered as 14C in excreta during the course of the study of which about equal fractions were in the urine and feces. Secondary peaks in blood concentrations of 14C were observed in the healthy subjects whereas they were not seen in the patients with T-tubes. The harmonic mean apparent half-life for isotretinoin in the blood of the healthy subjects was 13.6 hr, whereas the corresponding value for the 14C was 90 hr. Although a rigorous comparison of pharmacokinetic parameters between healthy subjects and T-tube patients was not feasible due to the limited number of subjects studied, comparisons of certain trends in the pharmacokinetic profiles gave some possible insights into the role of biliary excretion and enterohepatic cycling on the disposition of isotretinoin. The data for isotretinoin and 4-oxoisotretinoin coupled with the total carbon-14 data suggest that the oral dose of 14C-isotretinoin is absorbed to a similar extent by the healthy subjects and T-tube patients, whereas T-tube patients clear the drug more rapidly. The biliary excretion and possible enterohepatic circulation of isotretinoin and its metabolites may have significant impact on the pharmacokinetic profile of isotretinoin in man.

  5. Topical isotretinoin for melasma in Thai patients: a vehicle-controlled clinical trial.

    PubMed

    Leenutaphong, V; Nettakul, A; Rattanasuwon, P

    1999-09-01

    Melasma is an acquired hyperpigmentary disorder commonly seen in Orientals. Recently it has been demonstrated that tretinoin (all-trans-retinoic acid) can produce significant clinical improvement of melasma. However, moderate cutaneous side effects (retinoid dermatitis) occurred in a number of patients. To investigate the efficacy of topical 0.05 per cent isotretinoin gel (Isotrex) in the treatment of melasma in Thai patients. Thirty patients with moderate to severe melasma entered a 40-week, randomized, vehicle-controlled clinical trial in which they applied either 0.05 per cent isotretinoin gel, or its vehicle base together with a broad spectrum sunscreen (SPF 28) daily to the entire face. They were evaluated clinically (using Melasma Area and Severity Index), and colorimetrically (using our Melasma Area and Melanin Index). After 40 weeks, the average MASI and MAMI scores of the isotretinoin-treated group decreased by 68.2 per cent and 47 per cent respectively, while the corresponding control scores declined 60 per cent and 34 per cent. There was no statistically significant difference between the isotretinoin and vehicle groups. When the MASI and MAMI scores of each visit were compared to their baseline data, a statistically significant reduction of the score was first noted at weeks 4 and 12 respectively. Lightening of melasma, as determined clinically (MASI score), correlated well with pigmentation measurements (MAMI score). Side effects were limited to a mild transient "retinoid dermatitis" occurring in 27 per cent of isotretinoin-treated patients. Daily use of broad spectrum sunscreen has a significant lightening effect on melasma in Thai patients. However, there was no statistically significant difference between the isotretinoin and vehicle-treated group.

  6. Improvement of cystic fibrosis during treatment with isotretinoin.

    PubMed

    Buckley, Jennifer L; Chastain, Mark A; Rietschel, Robert L

    2006-01-01

    A 15-year-old boy with a history significant for multiple respiratory infections since birth presented for evaluation of acne vulgaris. He was initially prescribed doxycycline, topical tretinoin, and topical clindamycin solution, with the later addition of a benzoyl peroxide preparation to his regimen. The patient returned 6 months later after having been diagnosed with CF (cystic fibrosis) by sweat testing and genetic testing. His skin condition had not responded adequately to prior therapy, so all acne medications were discontinued. The 84-kg patient was started on 80 mg (0.95 mg/kg/d) of isotretinoin (13-cis-retinoic acid) daily. The patient's dose was decreased to 40 mg/d 2 weeks later following an episode of blood in his stool and epistaxis. At the 1- and 2-month follow-up visits, the patient reported improvement in his acne and mentioned that his lung secretions seemed reduced. His acne cleared after 4 months of therapy, so the isotretinoin was discontinued. The patient and his mother noted that no respiratory infections had occurred during the course of therapy. The patient's acne relapsed nearly 2 years later, so isotretinoin was restarted at 60 mg/d. During the next 7 months while on the drug, he experienced no further episodes of epistaxis or bloody stools and his acne had resolved by the end of therapy. The patient and his mother again reported fewer bronchopulmonary secretions and no infections requiring antibiotics during treatment with isotretinoin. This was unusual because he had experienced numerous respiratory infections requiring antibiotics during the prior 2 years. Since discontinuing the drug, the patient has had intermittent pulmonary infections and exacerbations in the symptomatology of his CF.

  7. Assessing the availability of the teratogenic drug isotretinoin outside the pregnancy prevention programme: a survey of e-pharmacies.

    PubMed

    Lagan, Briege M; Dolk, Helen; White, Bronagh; Uges, Donald R A; Sinclair, M

    2014-04-01

    The increase in online purchasing of medications raises safety concerns regarding teratogenic drugs. The use of the teratogenic drug 'isotretinoin' for women of childbearing age requires strict adherence to the Pregnancy Prevention Programme (PPP), a risk minimisation measure imposed on prescribers and users. We sought to determine how readily consumers can purchase isotretinoin online and the associated safety procedures and information. A descriptive cross-sectional survey was conducted of 50 e-pharmacies identified from commonly used search engines. E-pharmacy characteristics and isotretinoin PPP specific criteria were evaluated. Purchases of isotretinoin from seven e-pharmacies not bearing authentication logos and not requiring a prescription were assessed for PPP policy adherence, purchasing procedures and compound quality. Forty-three (86%) of the e-pharmacies did not have an authentication seal/logo. Isotretinoin could be purchased from 42 sites without a valid prescription. Information on isotretinoin causing birth defects was lacking in 25 of the 50 sites, on not taking isotretinoin in pregnancy in 24 sites and not taking isotretinoin if planning or at risk of a pregnancy in 33 sites. Of the eight attempted purchases, seven arrived, all without any patient information leaflet. All were verified as isotretinoin. The Internet provides a loophole for purchasing of medications known to cause congenital abnormalities, which needs to be addressed by medicines regulatory agencies worldwide. The current PPP for isotretinoin may be failing to protect mothers and babies from preventable harm-clinicians need to be aware of this, and the public needs to be educated about the potential risks. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

  8. The frequency of hematuria in acne vulgaris patients during isotretinoin treatment.

    PubMed

    Yesilkaya, Burcu; Alli, Nuran; Artuz, R Ferda; Ulu, Ezgi; Kartal, Demet; Cinar, S Levent

    2017-03-01

    Systemic isotretinoin (13-cis-retinoic acid) is effective in the treatment of acne vulgaris. The most common side effects are mucocutaneous ones. Hematuria seen secondary to isotretinoin treatment is thought to be due to mucosal dryness in the urinary system. This study aims to determine the frequency of hematuria in acne vulgaris patients during isotretinoin treatment. Eighty-eight subjects aged 16-32 years were included in the study group and 52 subjects were in the control group. The subjects were treated for 6 months and were monitored monthly by complete urine analyzes. They were also examined each month in terms of cheilitis, xerosis, epistaxis, rectal bleeding, fatigue, myalgia, weight loss, dry eye, conjunctivitis, headache, dysuria and pollakiuria. In the study group, 15 subjects (17%) had hematuria at least once during the study, and in the control group, four subjects (7.7%) had hematuria. The difference was not statistically significant (p = 0.118). Among the subjects who had hematuria, 11 of them (73.3%) were female and four of them (33.3%) were male in the study group while all the subjects with hematuria in the control group were female. Hematuria and gender did not show a statistically significant correlation. Hematuria was observed in 17% of the study group; this frequency rate was not different from that of the normal population. In subjects having isotretinoin treatment, if all the other reasons or disorders are excluded, one must keep in mind that hematuria may be due to isotretinoin use.

  9. The Role of Isotretinoin Therapy for Cushing's Disease: Results of a Prospective Study

    PubMed Central

    Vilar, Lucio; Albuquerque, José Luciano; Lyra, Ruy; Trovão Diniz, Erik; Rangel Filho, Frederico; Gadelha, Patrícia; Thé, Ana Carolina; Ibiapina, George Robson; Gomes, Barbara Sales; Santos, Vera; Melo da Fonseca, Maíra; Frasão Viana, Karoline; Lopes, Isis Gabriella; Araújo, Douglas; Naves, Luciana

    2016-01-01

    Objective. This prospective open trial aimed to evaluate the efficacy and safety of isotretinoin (13-cis-retinoic acid) in patients with Cushing's disease (CD). Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism after transsphenoidal surgery were given isotretinoin orally for 6–12 months. The drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if needed and tolerated. Clinical, biochemical, and hormonal parameters were evaluated at baseline and monthly for 6–12 months. Results. Of the 16 subjects, 4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of the study. UFC reductions of up to 52.1% were found in the rest. Only patients with UFC levels below 2.5-fold of the upper limit of normal achieved sustained UFC normalization. Improvements of clinical and biochemical parameters were also noted mostly in responsive patients. Typical isotretinoin side-effects were experienced by 7 patients (43.7%), though they were mild and mostly transient. We also observed that the combination of isotretinoin with cabergoline, in relatively low doses, may occasionally be more effective than either drug alone. Conclusions. Isotretinoin may be an effective and safe therapy for some CD patients, particularly those with mild hypercortisolism. PMID:27034666

  10. Assessing the availability of the teratogenic drug isotretinoin outside the pregnancy prevention programme: a survey of e-pharmacies†

    PubMed Central

    Lagan, Briege M; Dolk, Helen; White, Bronagh; Uges, Donald R A; Sinclair, M

    2014-01-01

    Purpose The increase in online purchasing of medications raises safety concerns regarding teratogenic drugs. The use of the teratogenic drug ‘isotretinoin’ for women of childbearing age requires strict adherence to the Pregnancy Prevention Programme (PPP), a risk minimisation measure imposed on prescribers and users. We sought to determine how readily consumers can purchase isotretinoin online and the associated safety procedures and information. Methods A descriptive cross-sectional survey was conducted of 50 e-pharmacies identified from commonly used search engines. E-pharmacy characteristics and isotretinoin PPP specific criteria were evaluated. Purchases of isotretinoin from seven e-pharmacies not bearing authentication logos and not requiring a prescription were assessed for PPP policy adherence, purchasing procedures and compound quality. Results Forty-three (86%) of the e-pharmacies did not have an authentication seal/logo. Isotretinoin could be purchased from 42 sites without a valid prescription. Information on isotretinoin causing birth defects was lacking in 25 of the 50 sites, on not taking isotretinoin in pregnancy in 24 sites and not taking isotretinoin if planning or at risk of a pregnancy in 33 sites. Of the eight attempted purchases, seven arrived, all without any patient information leaflet. All were verified as isotretinoin. Conclusion The Internet provides a loophole for purchasing of medications known to cause congenital abnormalities, which needs to be addressed by medicines regulatory agencies worldwide. The current PPP for isotretinoin may be failing to protect mothers and babies from preventable harm—clinicians need to be aware of this, and the public needs to be educated about the potential risks. PMID:24493556

  11. Systemic isotretinoin therapy normalizes exaggerated TLR-2-mediated innate immune responses in acne patients

    PubMed Central

    Dispenza, Melanie C.; Wolpert, Ellen B.; Gilliland, Kathryn L.; Dai, Pingqi; Cong, Zhaoyuan; Nelson, Amanda M.; Thiboutot, Diane M.

    2012-01-01

    Retinoids are used in the treatment of inflammatory skin diseases and malignancies, but studies characterizing the in vivo actions of these drugs in humans are lacking. Isotretinoin is a pro-drug for all-trans retinoic acid that can induce long-term remissions of acne; however, its complete mechanism of action is unknown. We hypothesized that isotretinoin induces remission of acne by normalizing the innate immune response to the commensal bacterium P. acnes. Compared to normal subjects, peripheral blood monocytes from acne patients expressed significantly higher levels of TLR-2 and exhibited significantly greater induction of TLR-2 expression following P. acnes stimulation. Treatment of patients with isotretinoin significantly decreased monocyte TLR-2 expression and subsequent inflammatory cytokine response to P. acnes by one week of therapy. This effect was sustained six months following cessation of therapy, indicating that TLR-2 modulation may be involved in the durable therapeutic response to isotretinoin. This study demonstrates that isotretinoin exerts immunomodulatory effects in patients and sheds light on a potential mechanism for its long-term effects in acne. The modulation of TLR-2 expression on monocytes has important implications in other inflammatory disorders characterized by TLR-2 dysregulation. PMID:22513780

  12. Treatment of gram-negative folliculitis with isotretinoin.

    PubMed

    Neubert, U; Plewig, G; Ruhfus, A

    1986-01-01

    The clinical and bacteriological findings are reported in 13 patients with gram-negative folliculitis before, during, and after treatment with isotretinoin (13-cis-retinoic acid). Patients were treated for 14-36 weeks with a daily dose of 0.5-1.5 mg isotretinoin/kg body weight. Inflammatory lesions were counted before and during weeks 2, 4, 8, 12, 16, 20, 24, 28, and 30 of therapy and again up to 172 weeks after cessation of treatment. In all patients there was an impressive improvement in clinical symptoms, especially a decrease in seborrhea and inflammatory lesions. Simultaneously, the gram-negative bacteria disappeared from the facial skin. Full clinical bacteriological remission was achieved in 9 patients within a period of up to 43 months, with minor recurrences of the disease in the remaining 4 patients.

  13. Psychological impact of isotretinoin treatment in patients with moderate and severe acne.

    PubMed

    Simić, Dubravka; Situm, Mirna; Letica, Edita; Penavić, Jasna Zeljko; Zivković, Maja Vurnek; Tomić, Teo

    2009-12-01

    Acne patients are subject to different degree of psychosocial distress. The emotional impact of acne vulgaris due to disfigurement caused by the disease is undisputed. Most common reactions to the acne are depression and anxiety. The use of isotretinoin, one of the most effective options in acne treatment, increases depression symptoms. The aim of this study was to investigate the psychological status of the patients with moderate to severe acne and to compare patients treated with isotretinoin with patients treated with vitamin C. A total of 85 patients suffering from acne vulgaris were included in the study. The results of this study do not find a significant correlation between the use of isotretinoin and the psychological effects of the drug.

  14. The negligible systemic availability of retinoids with multiple and excessive topical application of isotretinoin 0.05% gel (Isotrex) in patients with acne vulgaris.

    PubMed

    Jensen, B K; McGann, L A; Kachevsky, V; Franz, T J

    1991-03-01

    The potential systemic availability of retinoids from topically applied isotretinoin was assessed in 12 men with acne vulgaris. Isotretinoin 0.05% gel was applied to patients at a daily dose of 20 gm (equivalent to 10 mg of isotretinoin) over a 1900 cm2 surface area of skin on the face, back, and chest for 30 days. Blood samples were collected throughout the study and up to 48 hours after the last topical application; they were assayed for isotretinoin, tretinoin, and 4-oxo-isotretinoin by specific high-performance liquid chromatography. Plasma concentrations of isotretinoin, tretinoin, and 4-oxo-isotretinoin were not measurable (less than 20 ng/ml) at any time. Most adverse experiences were cutaneous; a few systemic adverse experiences were judged to be remotely related to topical drug administration. The lack of measurable plasma concentrations of isotretinoin, tretinoin, or 4-oxo-isotretinoin and systemic adverse experiences indicates negligible systemic availability of retinoids even after multiple application of isotretinoin 0.05% gel at doses approximately 12 times greater than normal daily use.

  15. Effect of isotretinoin on tooth germ and palate development in mouse embryos.

    PubMed

    Balducci-Roslindo, E; Silvério, K G; Jorge, M A; Gonzaga, H F

    2001-01-01

    Vitamin A and its derivatives, retinoic acid, tretinoin and isotretinoin, are currently used in dermatological treatments. The administration of high doses of this vitamin provokes congenital malformations in mice: cleft palate, maxillary and mandibular hypoplasia and total or partial fusion of the maxillary incisors. This study compares the tooth germs of the first maxillary and mandibular molars of fetal mice submitted to isotretinoin during organogenesis. Twelve 60-day-old female Mus musculus were divided into two groups on the 7th day of pregnancy: treated group--1 mg isotretinoin per kg body weight, dissolved in vegetable oil, was administered from the 7th to the 13th day of pregnancy; control group--vegetable oil in equivalent volume was administered orally for the same period. On the 16th day of pregnancy, the females were sacrificed, the fetuses were removed and their heads amputated. After standard laboratory procedures, 6-micron thick serial slices were stained with hematoxylin and eosin for optical microscopy examination. The results showed that both groups had closed palates with no reminiscence of epithelial cells; however, the first molar germs of the isotretinoin-treated animals showed delayed development compared to the control animals.

  16. A comparison of the efficacy of topical tretinoin and low-dose oral isotretinoin in rosacea.

    PubMed

    Ertl, G A; Levine, N; Kligman, A M

    1994-03-01

    Twenty-two patients with severe or recalcitrant rosacea were divided into three treatment groups in a randomized, double-blind trial that compared low-dose oral isotretinoin (10 mg/d), topically applied tretinoin (0.025% cream), and the combined use of both isotretinoin and tretinoin. For the first 16 weeks of the trial, subjects received one of these three trial regimens. For the final 16 weeks, isotretinoin was withheld while tretinoin cream or a placebo cream was continued. Twenty subjects completed the trial. Each treatment produced therapeutic benefits with regard to the number of papules and pustules and erythema. Treatment with oral isotretinoin appeared to give a more rapid onset of improvement, but there were no differences between the groups after 16 weeks. This level of improvement continued during the succeeding 16 weeks of observation whether the subjects used the tretinoin or the placebo cream. Adverse events were minimal and well tolerated in all groups. Low-dose oral isotretinoin and topical tretinoin cream therapy appear to be beneficial in the treatment of severe or recalcitrant rosacea. No additive benefit is noted with the combined use of these two modalities.

  17. Evaluation of thyroid function tests of acne vulgaris patients treated with systemic isotretinoin.

    PubMed

    Yıldırım, Neslihan; Doğan, Sibel; Atakan, Nilgün

    2017-03-01

    Isotretinoin is a systemic retinoid used to treat acne and it binds receptors which are the member of steroid-thyroid hormone superfamily. Certain types of retinoids may cause abnormalities in serum thyroid function tests (sTFTs) by suppressing thyroid stimulating hormone (TSH). However, it is uncertain whether systemic isotretinoin has any effect on sTFTs. The aim of the study was to find out if there is any alteration in sTFTs of patients with acne vulgaris treated with systemic isotretinoin. A total of 51 patients (male/female: 22/29) with severe acne vulgaris treated with a total dose of 120 mg/kg isotretinoin were included into the study prospectively. Serum free T3 (fT3), free T4 (fT4) and TSH levels were measured at baseline, 3rd and 6th months of treatment. Mean serum TSH levels at baseline, 3rd and 6th months of treatment were 1.57 ± 0.67, 2.07 ± 0.88 and 2.25 ± 0.86 uIU/mL, respectively. Mean serum TSH levels increased significantly following isotretinoin therapy (p < 0.01, p = 0.007 and p < 0.01, respectively). Mean serum fT3 levels at baseline, 3rd and 6th months of treatment were 3.59 ± 0.57, 3.19 ± 0.45 and 3.09 ± 0.61 pmol/L, respectively. Mean serum fT4 levels at baseline, 3rd and 6th months of treatment were 1.21 ± 0.19, 1.09 ± 0.16 and 1.11 ± 0.19 pmol/L, respectively. Mean serum fT3 and fT4 levels decreased significantly at 3rd and 6th months compared to baseline levels (p < 0.01 and p < 0.01, p < 0.01 and p = 0.001, respectively). Systemic isotretinoin therapy causes significant alterations in sTFTs. Dose dependent or long-term effects of systemic isotretinoin on sTFTs needs further evaluation.

  18. Isotretinoin and vitiligo: can chronic cheilitis cause koebnerization?

    PubMed

    Garner, Michael L; McShane, Diana B; Burkhart, Craig N; Morrell, Dean S

    2015-01-01

    Vitiligo after trauma through koebnerization is a widely reported phenomenon. Herein we present a case of vitiligo in an area of chronic cheilitis after isotretinoin treatment. © 2015 Wiley Periodicals, Inc.

  19. Novel isotretinoin microemulsion-based gel for targeted topical therapy of acne: formulation consideration, skin retention and skin irritation studies

    NASA Astrophysics Data System (ADS)

    Patel, Mrunali R.; Patel, Rashmin B.; Parikh, Jolly R.; Patel, Bharat G.

    2016-04-01

    Isotretinoin was formulated in novel microemulsion-based gel formulation with the aim of improving its solubility, skin tolerability, therapeutic efficacy, skin-targeting efficiency and patient compliance. Microemulsion was formulated by the spontaneous microemulsification method using 8 % isopropyl myristate, 24 % Labrasol, 8 % plurol oleique and 60 % water as an external phase. All plain and isotretinoin-loaded microemulsions were clear and showed physicochemical parameters for the desired topical delivery and stability. The permeation profiles of isotretinoin through rat skin from selected microemulsion formulation followed zero-order kinetics. Microemulsion-based gel was prepared by incorporating Carbopol®971 in optimized microemulsion formulation having suitable skin permeation rate and skin uptake. Microemulsion-based gel showed desired physicochemical parameters and demonstrated advantage over marketed formulation in improving the skin tolerability of isotretinoin, indicating its potential in improving topical delivery of isotretinoin. The developed microemulsion-based gel may be a potential drug delivery vehicle for targeted topical delivery of isotretinoin in the treatment of acne.

  20. The use of isotretinoin in acne

    PubMed Central

    2009-01-01

    Systemic isotretinoin remains the most efficacious treatment for severe acne as well as many cases of more moderate disease that are unresponsive to other treatment modalities. The current chapter outlines the mechanisms behind the excellent efficacy, describes how to optimize treatment, reviews the recommended guidelines for monitoring and summarizes adverse effects. PMID:20436884

  1. Outcomes of laser in situ keratomileusis and photorefractive keratectomy in patients taking isotretinoin.

    PubMed

    Ortega-Usobiaga, Julio; Llovet-Osuna, Fernando; Djodeyre, Mohammad Reza; Bilbao-Calabuig, Rafael; González-López, Félix; Llovet-Rausell, Andrea; Druchkiv, Vasyl

    2018-05-14

    To determine the functional outcomes of laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) in patients taking isotretinoin, which is contraindicated for these procedures. Multicentre, retrospective, interventional case series METHODS: All patients taking isotretinoin who underwent LASIK or PRK from January 2003 to September 2017 were included (group 1). Patients were compared with those undergoing LASIK or PRK who had taken isotretinoin previously but not in the previous 6 months (group 2). Patients were included consecutively. A total of 113 patients (219 eyes) were included. No significant intraoperative or postoperative complications were found. There were no significant differences between the groups in terms of visual acuity, postoperative spherical equivalent, efficacy index, predictability, or safety index. When only PRK patients were taken into account, the efficacy index (p: 0.017), postoperative sphere (p: 0.041), and postoperative astigmatism (p<0.001) were better in group 2, although the difference was not clinically relevant. In our experience, LASIK and PRK can be performed effectively and safely in selected patients taking isotretinoin. The absolute exclusion of certain systemic medications should be reconsidered. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Evidence for percutaneous absorption of isotretinoin from the photo-isomerization of topical tretinoin.

    PubMed

    Lehman, P A; Malany, A M

    1989-11-01

    Tretinoin (0.1% Retin-A cream) was topically applied to human cadaver skin in vitro using Franz diffusion chambers. The photo-isomerization of tretinoin and retinoic acid percutaneous absorption in the absence of metabolic activity were assessed with and without ambient light exposure to the skin. Using HPLC, UV, and GC/MSD, a retinoid exhibiting identical chromatographic and spectral characteristics of isotretinoin was observed in the samples from the skin exposed to light, but was virtually absent in the skin samples maintained in the dark. From a single topical application of tretinoin, isotretinoin was as abundant as tretinoin in the chamber receiver solution, dermis, epidermis, and on the skin surface at 24 h after topical application. The data suggest the possibility that isotretinoin may have an important role in the pharmacology of topically applied tretinoin.

  3. Effect of route of administration and biliary excretion on the pharmacokinetics of isotretinoin in the dog.

    PubMed

    Cotler, S; Chen, S; Macasieb, T; Colburn, W A

    1984-01-01

    Oral, intraportal, iv doses of isotretinoin were administered to dogs before and after bile duct cannulation to determine the effect of route of administration and biliary excretion on the pharmacokinetics of this compound. Blood and bile samples were collected and analyzed for isotretinoin using a gradient elution high performance liquid chromatographic method. Blood concentrations were decreased after bile duct cannulation. Decreases in the area under the blood concentration-time curves were greatest following oral dosing, intermediate following intraportal dosing, and least following iv dosing. These results indicate that biliary excretion impacts on the blood profile of isotretinoin as a function of route of administration and that the differences are the result of differences in first pass clearance. In addition, the apparent bioavailability of isotretinoin was 14% in bile cannulated dogs and 54% in the intact (uncannulated) animals, suggesting that enterohepatic recycling of isotretinoin may contribute to its oral bioavailability. Isotretinoin was excreted in the bile; predominantly as a conjugate. The largest percentage (approximately 27%) of the dose was excreted in the bile following intraportal infusion, an intermediate percentage (approximately 8.5%) after iv dosing, and the smallest percentage (approximately 3.3%) after oral dosing. When the amount of drug excreted in bile as intact drug and conjugate is divided by the area under the systemic blood concentration--time curve, the resulting apparent biliary clearances following oral and intraportal administration were almost identical whereas the apparent biliary clearance after iv dosing was substantially less.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Can we ensure the safe use of known human teratogens? Introduction of generic isotretinoin in the US as an example.

    PubMed

    Honein, Margaret A; Moore, Cynthia A; Erickson, J David

    2004-01-01

    The prescription of known teratogenic medications requires a careful balance between allowing women access to medications that they might need and avoiding unnecessary exposure to these medications during pregnancy because of their devastating fetal effects. Isotretinoin, a potent human teratogen, is of particular concern because of its widespread use among reproductive-aged women and the dramatic increase in use from 1992 through 2000. A revised risk management system was implemented in 2002 because of concerns about the continued occurrence of isotretinoin-exposed pregnancies. However, the recent approval of three generic versions of isotretinoin in the US has further complicated risk management and raises concerns that use might increase further if the lower cost of generics serves to increase accessibility. There are now four separate isotretinoin risk management systems in the US, each with its own distinct packaging, though the requirements for and substance of each are identical. Some additional concrete steps could be taken to minimise any unnecessary use of isotretinoin and help allow an adequate assessment of the current risk management systems. In addition to being familiar with and following all aspects of the current risk management system, physicians could choose to limit the use of isotretinoin to those who meet the labelled indications in order to reduce the number of exposed pregnancies. All four companies currently marketing isotretinoin in the US could jointly and voluntarily establish a consolidated, mandatory registration and follow-up of all women of reproductive potential who receive an isotretinoin prescription. Mandatory registration has many challenges, but it could allow a clear accounting of the total number of women for whom follow-up information is and is not available. Although the companies cannot be legally compelled to use a consolidated approach, the use of a single registry for the originator's product and all generic brands

  5. Standard Guidelines of Care: Performing Procedures in Patients on or Recently Administered with Isotretinoin

    PubMed Central

    Mysore, Venkataram; Mahadevappa, Omprakash H.; Barua, Shyamanta; Majid, Imran; Viswanath, Vishalakshi; Bhat, Ramesh M.; Talwar, Suresh; Thurakkal, Salim; Aurangabadkar, Sanjeev J.; Chatterjee, Manas; Ganjoo, Anil

    2017-01-01

    Background: Currently, the standard protocol regarding the performance of procedures on patients receiving or having recently received isotretinoin (13-cis-retinoic acid) states that the procedures should not be performed. The recommendations in standard books and drug insert require discontinuation of isotretinoin for 6 months before performing cosmetic procedures, including waxing, dermabrasion, chemical peels, laser procedures, or incisional and excisional cold-steel surgery. These recommendations have been followed for over two decades despite little evidence for the stated increased risk of scarring. Objective: The Association of Cutaneous Surgeons (I) constituted a task force to review the evidence and to recommend consensus guidelines regarding the safety of skin procedures, including resurfacing, energy-device treatments, and dermatosurgical procedures in patients with concurrent or recent isotretinoin administration. Materials and Methods: Data were extracted from the literature through a PubMed search using the keywords “isotretinoin,” “safety,” “scarring,” “keloids,” “hypertrophic scarring,” and “pigmentation.” The evidence was then labeled and circulated to all members of task force for review. Results: The task force is of the opinion that there is insufficient evidence to support the current protocol of avoiding and delaying treatments in the patient group under consideration and recommends that the current practice should be discontinued. The task force concludes that performing procedures such as laser hair removal, fractional lasers for aging and acne scarring, lasers for pigmented skin lesions, fractional radio-frequency microneedling, superficial and medium-depth peels, microdermabrasion, dermaroller, biopsies, radio-frequency ablation, and superficial excisions is safe in patients with concurrent or recent isotretinoin administration. PMID:29491653

  6. A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne.

    PubMed

    Strauss, J S; Leyden, J J; Lucky, A W; Lookingbill, D P; Drake, L A; Hanifin, J M; Lowe, N J; Jones, T M; Stewart, D M; Jarratt, M T; Katz, I; Pariser, D M; Pariser, R J; Tschen, E; Chalker, D K; Rafal, E S; Savin, R P; Roth, H L; Chang, L K; Baginski, D J; Kempers, S; McLane, J; Eberhardt, D; Leach, E E; Bryce, G; Hong, J

    2001-08-01

    Isotretinoin is very frequently the drug of choice for the management of severe recalcitrant nodular acne. Recently, a new micronized and more bioavailable formulation of isotretinoin has been developed that permits once-daily administration in lower doses than usually used with standard isotretinoin (Accutane), regardless of whether it is taken with or without food. Our purpose was to determine whether micronized isotretinoin and standard isotretinoin are clinically equivalent. In this multicenter, double-blind, double-dummy study, 600 patients with severe recalcitrant nodular acne were treated with either 0.4 mg/kg of micronized isotretinoin once daily without food (n = 300) or 1.0 mg/kg per day of standard isotretinoin in two divided doses with food (n = 300). Lesion counts were monitored over 20 weeks. Both treatment groups in this well-controlled clinical trial experienced an equivalent reduction in the number of total nodules (facial plus truncal). In addition, an equivalent proportion of patients achieved 90% clearance of the total number of nodules. Both formulations had similar results for other efficacy variables. Once-daily use of the micronized and more bioavailable formulation of isotretinoin under fasted conditions is clinically equivalent to the standard twice-daily formulation under fed conditions in the treatment of severe recalcitrant nodular acne.

  7. Effects of isotretinoin treatment on cartilage and tendon thicknesses: an ultrasonographic study.

    PubMed

    Yıldızgören, Mustafa Turgut; Karataş Toğral, Arzu; Baki, Ali Erdem; Ekiz, Timur

    2015-07-01

    Effects of retinoic acid on collagen synthesis and cartilage have previously been shown. However, its effects on cartilage and tendons in humans have not been studied yet. Therefore, in order to provide a morphologic insight, the aim of this study was to measure femoral cartilage, Achilles and supraspinatus tendon thicknesses in patients under systemic isotretinoin treatment by using ultrasound. Fifteen patients (nine F, six M) who used isotretinoin for their acnes were included. All patients were treated with isotretinoin 0.5 mg/kg/day for the first month, and the dosage was escalated up to 1 mg/kg/day thereafter. Distal femoral cartilage, supraspinatus, and Achilles tendons thicknesses have been evaluated both before the treatment and at the end of the third month. Femoral cartilage thicknesses were assessed from three midpoints bilaterally; medial condyle, lateral condyle, and intercondylar area. Short/long-axis diameters and cross-sectional area of the Achilles tendons and axial tendon thicknesses of supraspinatus tendon were evaluated from the nondominant side. The mean age of the patients was 20.1 ± 4.9 years, and body mass index was 21.7 ± 2.5 kg/m(2). Although posttreatment cartilage measurements of 30 knees were lower for the three midpoints, it reached significance only for lateral condyle (p = 0.05). In addition, posttreatment tendon measurements were not statistically significant compared with pretreatment values (all p > 0.05). Systemic isotretinoin treatment seems to make cartilage thinner. Further studies considering histological and molecular evaluations with more sample sizes are awaited.

  8. Obsessive-compulsive disorder with bipolar diathesis following isotretinoin therapy remitting upon treatment with olanzapine and fluvoxamine

    PubMed Central

    Fornaro, Michele

    2010-01-01

    Isotretinoin, a drug used for moderate to severe acne, has been repeatedly associated with various psychiatric complications, although a definitive causal relationship has not been established to date. This case report describes a 25-year-old male who developed obsessive-compulsive disorder at the age of 23 years following isotretinoin treatment for acne (10–20 mg/day) since the age of 16 years. Although standard treatment for obsessive-compulsive disorder caused mood swings, the combination of fluvoxamine 300 mg/day and olanzapine 15 mg/day significantly improves the clinical picture. Although rare, severe adulthood psychiatric complications may occur following isotretinoin treatment, requiring management which is individually tailored to the patient. PMID:21127690

  9. Accelerated photostability study of tretinoin and isotretinoin in liposome formulations.

    PubMed

    Ioele, G; Cione, E; Risoli, A; Genchi, G; Ragno, G

    2005-04-11

    The photodegradation of retinoic acids, tretinoin and isotretinoin, in ethanol and liposomes was studied. The light irradiation was performed according to the conditions suggested by the ICH Guideline for photostability testing by using a Xenon lamp within a wavelength range of 300-800 nm. The photodegradation process was monitored by UV spectrophotometry. In ethanol solution, tretinoin and isotretinoin undergo complete isomerization just within a few seconds of light exposure to give 13-cis and 9-cis isomers, respectively. The 13-cis isomer from tretinoin undergoes in turn a slow isomerization to the same 9-cis isomer. Both retinoic acids incorporated in liposome complexes showed an increased stability in comparison to the ethanol solutions. In particular for tretinoin, a residual concentration of 60% was still present after a light irradiance of 3470 kJ/m(2), by means of a 250 W/m(2) light power for 240 min, versus a residual value of just 8% measured at the same time in ethanol solution. Moreover, the isomerization rate in liposomes resulted reduced for isotretinoin and practically irrelevant for tretinoin. The degradation rate was found to be dependent on the drug concentration. The better stability of the tretinoin in liposome complex was supposed to be related to its higher incorporation value due to the linear structure of the molecule.

  10. The efficacy of 5% dapsone gel plus oral isotretinoin versus oral isotretinoin alone in acne vulgaris: A randomized double-blind study

    PubMed Central

    Faghihi, Gita; Rakhshanpour, Mehrdad; Abtahi-Naeini, Bahareh; Nilforoushzadeh, Mohammad Ali

    2014-01-01

    Background: Acne vulgaris, a common human skin condition, is an inflammatory disease characterized by comedones, papules, nodules and possibly scarring. This study aimed to evaluate the efficacy of a combination of 5% dapsone gel plus oral isotretinoin in the treatment of acne vulgaris. Materials and Methods: A randomized, placebo-controlled, study was carried out on patients with moderate to severe acne. The patients were randomly divided in two groups: (dapsone gel and vehicle gel). All Patients were administered oral isotretinoin 20 mg daily and topical gel twice a day for 8 weeks. The Global Acne Assessment Score (GAAS), the number lesions and side-effects were documented at base line and weeks 4, 8 and 12. Results: A total of 58 patients (age range: 18-25 years) were included in our study. The number of lesions was significantly lower in the dapsone-treated group at all follow-up visits (P < 0.001). The mean GAAS score in the dapsone-treated group and in the Placebo-treated group decreased, but there was no statistical difference in two groups (P < 0.001). The side-effects on the dapsone-treated group were a mild burning sensation in 7 patients (24.13%), mild erythema of the skin and mild dryness in 4 (13.79%) and 3 (10.34%) cases respectively (P < 0.001). In our study, adverse effects were common but they were minor and tolerable. No clinically significant changes in laboratory parameters were observed (P < 0.001). Conclusions: Dapsone gel was an effective medication for patients who received isotretinoin for acne vulgaris treatment resulting in a significant reduction of the number of lesions. PMID:25250291

  11. Oral isotretinoin in photoaging: objective histological evidence of efficacy and durability*

    PubMed Central

    Bravo, Bruna Souza Felix; Azulay, David Rubem; Luiz, Ronir Raggio; Mandarim-De-Lacerda, Carlos Alberto; Cuzzi, Tullia; Azulay, Mônica Manela

    2015-01-01

    BACKGROUND The off-label use of oral isotretinoin in photoaging is a therapeutic tool that has been used by dermatologists. There are few studies to corroborate its effectiveness and durability. OBJECTIVES To assess, both clinically and histologically, the changes caused by the use of oral isotretinoin in skin photoaging as well as the duration of the effects. METHODS 20 female patients, aged 45-50 years, with phototypes II-VI, none of whom had experienced menopause, were treated with 20mg oral isotretinoin, 3 days a week, for 12 weeks. They underwent clinical analysis and skin biopsies in the pre-auricular region, while histologic cuts enabled assessment of the solar elastosis level and morphologic analysis. RESULTS Clinically, patients, as well as the researching and the assessor physicians, noticed improvement in skin quality. One patient presented severe solar elastosis, 11 manifested the moderate form, while 8 presented the discreet type. According to histological analysis, 65% of the patients revealed alteration in the distribution and thickness of the elastic fibers, which can be interpreted as a histological improvement, while 60% showed an increase in collagen density. We observed an increase in collagen density, from 51.2% to 57.4%, (p=0.004). At the end of the 12-week follow-up period, this density decreased to 54.7% (p=0.050). There was an increase in the density of elastic fibers, from 26.5% to 31.3%, (p=0.02), which had dropped to 27.5% at the end of the 12-week follow-up period. CONCLUSIONS The study confirmed the role of oral isotretinoin in remodeling the extracellular matrix against photoaging, as well as its durability after 12 weeks, especially when we consider collagen fibers. PMID:26375216

  12. Topical adapalene gel 0.1% vs. isotretinoin gel 0.05% in the treatment of acne vulgaris: a randomized open-label clinical trial.

    PubMed

    Ioannides, D; Rigopoulos, D; Katsambas, A

    2002-09-01

    Topical application of isotretinoin and adapalene has proved effective in treating acne vulgaris. Both drugs demonstrate therapeutic advantages and less irritancy over tretinoin, the most widely used treatment for acne. They both act as retinoid agonists, but differ in their affinity profile for nuclear and cytosolic retinoic acid receptors. To compare the efficacy and tolerability of adapalene gel 0.1% and isotretinoin gel 0.05% in the treatment of acne vulgaris of the face, in a randomized open-label clinical trial. Eighty patients were enrolled and were instructed to apply adapalene gel 0.1% or isotretinoin gel 0.05% once daily over a 12-week treatment period. Efficacy determination included noninflammatory and inflammatory lesion counts by the investigator and global evaluation of improvement. Cutaneous tolerance was assessed by determining erythema, scaling and burning with pruritus. Adapalene and isotretinoin gels were highly effective in treating facial acne. Adapalene gel produced greater reductions in noninflammatory and inflammatory lesion counts than did isotretinoin gel, but differences between treatments were not statistically significant. Adapalene gel was significantly better tolerated than isotretinoin gel during the whole treatment period. The two gels studied demonstrated comparable efficacy. When adapalene and isotretinoin were compared, significantly lower skin irritation was noted with adapalene, indicating that adapalene may begin a new era of treatment with low-irritant retinoids.

  13. Oral isotretinoin (13-cis-retinoic acid) therapy in severe acne: drug and vitamin A concentrations in serum and skin.

    PubMed

    Rollman, O; Vahlquist, A

    1986-04-01

    The disposition of oral isotretinoin to the skin and the effects of the drug on the vitamin A levels in serum and skin were studied in 17 patients with nodulocystic acne. All patients received 0.5 mg/kg/day for 3 months and 8 patients continued treatment with 0.75 mg/kg/day for another 3 months. The parent drug, the major metabolite (4-oxo-isotretinoin), and 2 natural retinoids (retinol and dehydroretinol) were monitored in serum and biopsies of uninvolved skin, using adsorption high-pressure liquid chromatography. During the initial 3 months of treatment the mean isotretinoin level in the serum was 145 ng/ml and in the epidermis 73 ng/g. The corresponding values for 4-oxo-isotretinoin were 615 and 113 ng/g, respectively. Even at the highest dosage there was no progressive accumulation of isotretinoin in serum, epidermis, or subcutis. After discontinuation of therapy the drug disappeared from both serum and skin within 2-4 weeks. The serum transport of vitamin A, monitored by the concentrations of retinol, retinol-binding protein, and prealbumin (transthyretin), was not affected by the treatment. By contrast, the retinol level in the epidermis increased by an average of 53% (p less than 0.01) and the dehydroretinol level decreased by 79% (p less than 0.001) as a result of 3 months of treatment. Both changes were reversible. The results suggest that isotretinoin therapy interferes with the endogenous vitamin A metabolism in the skin.

  14. Increased use of mental health services related to isotretinoin treatment: a 5-year analysis.

    PubMed

    Friedman, Tal; Wohl, Yonit; Knobler, Haim Y; Lubin, Gadi; Brenner, Sarah; Levi, Yehezkel; Barak, Yoram

    2006-08-01

    The association between exposure to Isotretinoin, the development of depression and suicide attempts is controversial. To retrospectively assess pattern of utilization of mental health services in the Israeli Defense Forces (IDF) during a 5-year period for all subjects exposed to Isotretinoin in comparison to a control group consisting of army conscripts suffering from psoriasis. All subjects were young adults (18 to 21 years old) in compulsory military service. Exposure to Isotretinoin mandates reporting and marking as a coded medical profile in the IDFs' computerized medical record of each conscript and soldier. Medical data, tracked by military medical profiles, were summarized from medical records of all subjects treated by Isotretinion during the years 1999-2003 and for the control group for the same period. Use of mental health services was the a-priori defined primary outcome measure. During the study period 1419 subjects were exposed to Isotretinoin and 1102 suffered from psoriasis. Utilization of mental health services was highest for the index group wherein 17.2% (245/1419) of subjects were evaluated or treated compared to 12.5% in the control group (psoriasis). The inter-group differences were statistically significant; Chi-square=15.9 (df=2), p=0.0003. We suggest that psychiatric evaluation be regularly undertaken prior to initiation of Isotretinion treatment in young adults at risk, as well as providing follow-up visits during and at completion of treatment.

  15. Comparison of the stability of topical isotretinoin and topical tretinoin and their efficacy in acne.

    PubMed

    Elbaum, D J

    1988-09-01

    After 4 hours of exposure to incandescent light, 80% of 0.05% topical isotretinoin and 60% of 0.05% topical tretinoin preparations remained in their original form. In contrast, after 2 hours of exposure to fluorescent light only 25% of topical tretinoin and possibly 60% of topical isotretinoin remained in their original forms. Longer exposure to fluorescent light did not result in further breakdown, and the final breakdown of both preparations was similar. A 12-week, double-blind clinical trial comparing isotretinoin (0.05%) with tretinoin (0.05%) applied topically to patients with moderate acne was carried out. Both preparations caused significant reductions in papules and pustules. However, neither treatment was significantly superior to the other in the reduction of acne lesions. This may be because both preparations are rapidly broken down to similar products when exposed to fluorescent light.

  16. Effects of isotretinoin on the platelet counts and the mean platelet volume in patients with acne vulgaris.

    PubMed

    Ataseven, Arzu; Ugur Bilgin, Aynur

    2014-01-01

    Aim. The aim of this study was to evaluate the platelet counts and the mean platelet volume in patients who received isotretinoin for the treatment of acne vulgaris. Method. A total of 110 patients were included in this retrospective study. Complete blood count parameters were recorded prior to and three-months following the treatment. Results. Both platelet counts and the mean platelet volume were significantly decreased following the treatment. No significant differences were noted on the levels of hemoglobin, hematocrit, and white blood cell count. Conclusion. Platelet counts and mean platelet volume significantly decreased following isotretinoin treatment. Since the decrease of platelet counts and the mean platelet volume was seen concomitantly, it is concluded that the effect of isotretinoin was through the suppression of bone marrow.

  17. Vitamin D levels in acne vulgaris patients treated with oral isotretinoin.

    PubMed

    El-Hamd, Mohammed Abu; El Taieb, Moustafa A; Ibrahim, Hassan M; Aly, Sanaa S

    2018-02-20

    Acne vulgaris is a common inflammatory skin disease. Vitamin D deficiency plays a role in many inflammatory skin diseases. It may play a role in pathogenesis of acne vulgaris. This study aimed to assess serum levels of 25 hydroxy vitamin D in patients with acne vulgaris before and after treatment with isotretinoin and its relation with acne vulgaris severity. Ninety patients with acne vulgaris and 60 age-sex matched healthy subject as controls have been recruited in this study. Patients were treated with 0.75 mg/kg/d isotretinoin for 3 months. Serum level of 25 hydroxy vitamin D has been measured at baseline and after treatment. Serum levels of 25 hydroxy vitamin D were significantly higher in patients with acne vulgaris than healthy controls (P = .001). There was a significant inverse relation between level of 25 hydroxy vitamin D and severity of acne vulgaris before treatment (P = .001). Serum levels of 25 hydroxy vitamin D were significantly increased after isotretinoin treatment in patients with acne vulgaris (P = .001). This study concluded that vitamin D may play a potential role in pathogenesis of acne vulgaris or acne vulgaris may have a negative effect on vitamin D synthesis. Further studies are needed to confirm these potential relations. © 2018 Wiley Periodicals, Inc.

  18. Surgical Outcome in Patients Taking Concomitant or Recent Intake of Oral Isotretinoin: A Multicentric Study-ISO-AIMS Study.

    PubMed

    Mahadevappa, Omprakash Heggadahalli; Mysore, Venkataram; Viswanath, Vishalakshi; Thurakkal, Salim; Majid, Imran; Talwar, Suresh; Aurangabadkar, Sanjeev J; Chatterjee, Manas; Bhat, M Ramesh; Barua, Shyamanta; Ganjoo, Anil

    2016-01-01

    The current standard recommendation is to avoid surgical interventions in patients taking oral isotretinoin. However, this recommendation has been questioned in several recent publications. To document the safety of cosmetic and surgical interventions, among patients receiving or recently received oral isotretinoin. Association of Cutaneous Surgeons, India, in May 2012, initiated this study, at 11 centers in different parts of India. The data of 183 cases were collected monthly, from June 2012 to May 2013. Of these 61 patients had stopped oral isotretinoin before surgery and 122 were concomitantly taking oral isotretinoin during the study period. In these 183 patients, a total of 504 interventions were performed. These included[1] 246 sessions of chemical peels such as glycolic acid, salicylic acid, trichloroacetic acid, and combination peels;[2] 158 sessions of lasers such as ablative fractional laser resurfacing with erbium-doped yttrium aluminum garnet and CO2, conventional full face CO2 laser resurfacing, laser-assisted hair reduction with long-pulsed neodymium-doped yttrium aluminum garnet, diode laser, and LASIK surgery;[3] 27 sessions of cold steel surgeries such as microneedling, skin biopsy, subcision, punch elevation of scars, excision of skin lesion, and wisdom tooth extraction;[4] 1 session of electrosurgery. No significant side effects were noted in most patients. 2 cases of keloid were documented which amounted to 0.4% of side effects in 504 interventions, with a significant P value of 0.000. Reversible transient side effects were erythema in 10 interventions and hyperpigmentation in 15. The study showed that performing dermatosurgical and laser procedures in patients receiving or recently received isotretinoin is safe, and the current guidelines of avoiding dermatosurgical and laser interventions in such patients taking isotretinoin need to be revised.

  19. Isotretinoin-induced urethritis versus non-gonococcal urethritis in a man who has sex with men: an open debate.

    PubMed

    Ballout, Rami A; Maatouk, Ismael

    2018-01-01

    This is the case of a young man presenting with urethritis despite a negative infectious work-up. Careful history taking elucidated a strong correlation between symptom onset and a recent dose escalation of isotretinoin for treatment of his refractory cystic acne. The urethral symptoms quickly resolved with dose reduction, suggesting urethritis as a rare adverse reaction of isotretinoin.

  20. Isotretinoin conundrum: a randomized, openlabel, crossover study in Mexico to evaluate the bioavailability and bioequivalence of three pharmaceutical preparations of isotretinoin in healthy participants.

    PubMed

    Piñeyro-Garza, Everardo; Gómez-Silva, Magdalena; Gamino Peña, María Elena; Palmer, Jonathan; Berber, Arturo

    2015-10-01

    The oral retinoid agent isotretinoin (13-cis-retinoic acid) is approved for the treatment of severe recalcitrant cystic acne. For registrational renewal of Oratane® in Mexico (isotretinoin; Laboratorios Dermatologicos Darier S.A. de C.V., Mexico), it was necessary to establish bioequivalence to the reference product Roaccutan® (Isotretinoin; Roche, Mannheim, Germany). Three prior studies failed to establish the bioequivalence of Oratane to Mexican-sourced Roaccutan. However, 13 studies demonstrated the bioequivalence of Oratane to Roaccutane® from multiple sources. This study compared the bioavailability of Oratane with that of Mexicansourced Roaccutan and Australian-sourced Roaccutane. Study participants received each of the three agents in a randomized, open-label, 6-sequence, 3-way crossover study with a 2-week washout period between treatments. Pharmacokinetic analysis revealed that peak plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 (dosing) to infinite time (AUC0-∞) were lower for Roaccutan than for Roaccutane and Oratane (Cmax: 1,023.35, 1,223.08, and 1,224.25 ng/mL, respectively; AUC0-∞: 13,653.65, 15,681.35 and 15,733.55 ng/mL x h, respectively). The 90% CIs (test/reference) for the ratios of the geometric means indicated that Oratane was bioequivalent to Roaccutane but not to Roaccutan. In addition, Roaccutane (R2) was not bioequivalent to Roaccutan (R1; R1/R2 90% CIs: Cmax, 76.12 - 91.04; AUC0-t, 82.19 - 91.13; AUC0-∞, 82.94 - 91.57). Oratane and Australian-sourced Roaccutane could be considered bioequivalent, but neither formulation was found to be bioequivalent to Mexican-sourced Roaccutan.

  1. Fixed-Dose Combination Gel of Adapalene and Benzoyl Peroxide plus Doxycycline 100 mg versus Oral Isotretinoin for the Treatment of Severe Acne: Efficacy and Cost Analysis.

    PubMed

    Penna, Pete; Meckfessel, Matthew H; Preston, Norman

    2014-01-01

    Acne vulgaris is a chronic skin disease with a high prevalence. Left untreated or inadequately treated, acne vulgaris can lead to psychological and physical scarring, as well as to unnecessary medical expenses. Oral isotretinoin is an effective treatment for severe resistant nodular and conglobate acne vulgaris. A regimen consisting of a fixed-dose combination of adapalene and benzoyl peroxide gel, 0.1%/2.5% (A-BPO) with oral doxycycline 100 mg (A-BPO/D) has been demonstrated to be efficacious and well tolerated in patients with severe acne and may be an alternative to oral isotretinoin for some patients with severe acne. The objective of this analysis was to compare the relative efficacy and associated costs of A-BPO/D versus oral isotretinoin. In this analysis, comparisons of relative efficacy were made using previously published studies involving similar patient populations with severe acne that warrant the use of oral isotretinoin. The pricing for oral doxycycline and oral isotretinoin was estimated based on the maximum allowable cost from 9 states, and the pricing for A-BPO was calculated as the range between the average wholesale price and the wholesale acquisition cost. For this analysis, 2 treatment models were generated to compare costs: (1) a basic treatment model that examined the costs of an initial regimen of either A-BPO/D or oral isotretinoin without considering probable outcomes, and (2) a long-term model that factored in likely treatment outcomes and subsequent treatments into associated costs. The basic treatment model assumed that patients would be prescribed a single regimen of A-BPO/D for 12 weeks or oral isotretinoin for 20 weeks. The long-term model considered the probability of each treatment successfully managing patients' acne, as well as likely additional regimens of A-BPO monotherapy or an additional regimen of oral isotretinoin. As a result of different treatment durations, the costs for each treatment were normalized to weekly cost of

  2. A rapid HPLC method for simultaneous determination of tretinoin and isotretinoin in dermatological formulations.

    PubMed

    Tashtoush, Bassam M; Jacobson, Elaine L; Jacobson, Myron K

    2007-02-19

    A rapid method using an isocratic high-pressure liquid chromatography and UV detection for determination of both all-trans retinoic acid (tretinoin) and 13-cis retinoic acid (isotretinoin) in dermatological preparations is presented. Tretinoin and isotretinoin samples were extracted with acetonitrile by a procedure that can be completed in less than 10 min. Subsequent separation and quantification of amounts as low as 10 pmol was accomplished in less than 15 min using reversed-phase HPLC with isocratic elution with 0.01% trifluoroacetic acid (TFA)/acetonitrile (15:85, v/v). Validation experiments confirmed the precision and accuracy of the method. When applied to commercial tretinoin samples, recoveries of 104.9% for cream formulations and 107.7% for gel formulations were obtained. Application of the method for analysis of a tretinoin cream exposed to solar simulated light (SSL) demonstrated detection of the major photoisomerization product isotretinoin as well as 9-cis retinoic acid, demonstrating the utility of the method for studies of tretinoin photostability. The method should also facilitate studies of the formulation compatibility and photocompatibility of tretinoin with agents that may improve its clinical tolerability.

  3. Fixed-Dose Combination Gel of Adapalene and Benzoyl Peroxide plus Doxycycline 100 mg versus Oral Isotretinoin for the Treatment of Severe Acne: Efficacy and Cost Analysis

    PubMed Central

    Penna, Pete; Meckfessel, Matthew H.; Preston, Norman

    2014-01-01

    Background Acne vulgaris is a chronic skin disease with a high prevalence. Left untreated or inadequately treated, acne vulgaris can lead to psychological and physical scarring, as well as to unnecessary medical expenses. Oral isotretinoin is an effective treatment for severe resistant nodular and conglobate acne vulgaris. A regimen consisting of a fixed-dose combination of adapalene and benzoyl peroxide gel, 0.1%/2.5% (A-BPO) with oral doxycycline 100 mg (A-BPO/D) has been demonstrated to be efficacious and well tolerated in patients with severe acne and may be an alternative to oral isotretinoin for some patients with severe acne. Objective The objective of this analysis was to compare the relative efficacy and associated costs of A-BPO/D versus oral isotretinoin. Methods In this analysis, comparisons of relative efficacy were made using previously published studies involving similar patient populations with severe acne that warrant the use of oral isotretinoin. The pricing for oral doxycycline and oral isotretinoin was estimated based on the maximum allowable cost from 9 states, and the pricing for A-BPO was calculated as the range between the average wholesale price and the wholesale acquisition cost. For this analysis, 2 treatment models were generated to compare costs: (1) a basic treatment model that examined the costs of an initial regimen of either A-BPO/D or oral isotretinoin without considering probable outcomes, and (2) a long-term model that factored in likely treatment outcomes and subsequent treatments into associated costs. The basic treatment model assumed that patients would be prescribed a single regimen of A-BPO/D for 12 weeks or oral isotretinoin for 20 weeks. The long-term model considered the probability of each treatment successfully managing patients' acne, as well as likely additional regimens of A-BPO monotherapy or an additional regimen of oral isotretinoin. As a result of different treatment durations, the costs for each treatment were

  4. A randomized comparative trial of two low-dose oral isotretinoin regimens in moderate to severe acne vulgaris

    PubMed Central

    Dhaked, Daulat Ram; Meena, Ram Singh; Maheshwari, Anshul; Agarwal, Uma Shankar; Purohit, Saroj

    2016-01-01

    Background: Oral isotretinoin is highly effective in all forms and grades of acne, even in lower dosages (<0.5 mg/kg/day). There is a paucity of comparative data on the various low-dose regimens of oral isotretinoin in the Indian literature. Objectives: To assess and compare the efficacy and tolerability of two low-dose oral isotretinoin treatment regimens (20 mg daily and 20 mg alternate days) in moderate to severe acne vulgaris. Materials and Methods: A total of 240 patients with moderate to severe acne vulgaris were selected and randomized into two groups and treated with a fixed dose of 20 mg of isotretinoin (Group A - daily and Group B - alternate days) for 24 weeks and followed up for 12 weeks post therapy. Results: A total of 234 patients completed the study. At the end of therapy, decrease in the total acne loads up to 98.99% (Group A) and 97.69% (Group B) was achieved from the baseline (P < 0.01), excellent response was observed in 98.3% (Group A) and 93.96% (Group B) patients (P = 0.166). In the severe acne, Group A performed significantly better than Group B until the end of 36 weeks. While in the moderate acne, significant difference in the response between both groups was observed only up to 12 weeks. No serious side effect was observed. Conclusion: Both isotretinoin regimens were well tolerated and found to be an effective treatment for moderate to severe acne vulgaris. However, in moderate acne 20 mg alternate day regimen may be preferred. A 20 mg daily regimen is a better choice for severe acne in terms of response. Limitation: Small sample size and short follow-up period. PMID:27730033

  5. Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study

    PubMed Central

    Alfredsson, Lars; Sjölin-Forsberg, Gunilla; Gerdén, Barbro; Bergman, Ulf; Jokinen, Jussi

    2010-01-01

    Objective To assess the risk of attempted suicide before, during, and after treatment with isotretinoin for severe acne. Design Retrospective cohort study linking a named patient register of isotretinoin users (1980-9) to hospital discharge and cause of death registers (1980-2001). Setting Sweden, 1980-2001. Population 5756 patients aged 15 to 49 years prescribed isotretinoin for severe acne observed for 17 197 person years before, 2905 person years during, and 87 120 person years after treatment. Main outcome measures Standardised incidence ratio (observed number divided by expected number of suicide attempts standardised by sex, age, and calendar year), calculated up to three years before, during, and up to 15 years after end of treatment. Results 128 patients were admitted to hospital for attempted suicide. During the year before treatment, the standardised incidence ratio for attempted suicide was raised: 1.57 (95% confidence interval 0.86 to 2.63) for all (including repeat) attempts and 1.36 (0.65 to 2.50) counting only first attempts. The standardised incidence ratio during and up to six months after treatment was 1.78 (1.04 to 2.85) for all attempts and 1.93 (1.08 to 3.18) for first attempts. Three years after treatment stopped, the observed number of attempts was close to the expected number and remained so during the 15 years of follow-up: standardised incidence ratio 1.04 (0.74 to 1.43) for all attempts and 0.97 (0.64 to 1.40) for first attempts. Twelve (38%) of 32 patients who made their first suicide attempt before treatment made a new attempt or committed suicide thereafter. In contrast, 10 (71%) of the 14 who made their first suicide attempt within six months after treatment stopped made a new attempt or committed suicide during follow-up (two sample test of proportions, P=0.034). The number needed to harm was 2300 new six month treatments per year for one additional first suicide attempt to occur and 5000 per year for one additional repeat

  6. Safety and efficacy of fixed-dose 10 mg daily isotretinoin treatment for acne vulgaris in Malaysia.

    PubMed

    Yap, Felix Boon-Bin

    2017-09-01

    Low-dose isotretinoin is used to reduce side effects albeit higher relapse. This study aimed to determine the efficacy and safety of fixed-dose 10 mg daily isotretinoin for the treatment of acne. This prospective study was performed between 2011 and 2015. All 150 patients were given 10 mg daily isotretinoin until a cumulative dose of 90-110 mg/kg. The mean age was 26.6 years with 64.7% moderate acne, 29.3% severe, and 6% very severe. The mean cumulative dose was 98.8 ± 6.05 mg/kg. All 150 patients had total clearance with a mean time to clearance of 24.0 weeks. Patients with severe/very severe acne had higher cumulative dosage (102.1 vs. 97.0, P < 0.001) and longer duration to clearance (32.9 weeks vs. 19.1 weeks, P < 0.001). Mild relapse was seen in 4%. The mean time to relapse was 32.3 weeks. Lip dryness was the commonest side effects (100%). Mild transient elevation of liver enzymes was detected in 3.3% and a slight increase of serum lipid in 2.7% with no treatment discontinuation. Fixed-dose 10 mg daily treatment with isotretinoin until a cumulative dose of 90-110 mg/kg is safe with low relapse rate. © 2016 Wiley Periodicals, Inc.

  7. Comparing the Efficacy of Low Dose and Conventional Dose of Oral Isotretinoin in Treatment of Moderate and Severe Acne Vulgaris.

    PubMed

    Faghihi, Gita; Mokhtari, Fatemeh; Fard, Nasrin Motamedi; Motamedi, Narges; Hosseini, Sayed Mohsen

    2017-01-01

    This study was conducted to compare the effect of low-dose isotretinoin with its conventional dose in patients with moderate and severe acne. This was a clinical trial conducted on 60 male and female patients with moderate and severe acne vulgaris. The patients were divided into two treatment groups: 0.5 mg/kg/day isotretinoin capsule and low-dose isotretinoin capsule (0.25 mg/kg/day). Patients in both groups received 6-month treatment. At the end of the 6 th month and 12 th month (6 months after the end of the treatment), they were examined again, and their improvement was determined and compared. The average severity of acne in the two treatment groups did not differ significantly within any of the study periods. The most common side effects were nose dryness in the low-dose group (17%) and hair thinning and loss in the conventional-dose group (33.2%), although all the patients had dry lips. According to the same severity of the acne in two groups in different study periods, as well as fewer side effects and more patients' satisfaction, the low-dose isotretinoin can be considered in the treatment of acne.

  8. A double-blind investigation of the potential systemic absorption of isotretinoin, when combined with chemical sunscreens, following topical application to patients with widespread acne of the face and trunk.

    PubMed

    Cunliffe, W J; Glass, D; Goode, K; Stables, G I; Boorman, G C

    2001-01-01

    This study assessed the systemic absorption of isotretinoin and its metabolites, during a 4-week application of a cream containing 0.1% isotretinoin and chemical sunscreens, compared with a 4% benzoyl peroxide cream, in patients with acne on the face and trunk. Blood was drawn at weeks 0, 1, 2, 3 and 4 and at 96 h post-treatment. Plasma levels of isotretinoin (13-cis-retinoic acid) and tretinoin (all-trans-retinoic acid) were quantified by liquid chromatography with tandem mass spectrometry and the presence of their combined 4-oxo metabolites were monitored from the peak area ratios observed. The isotretinoin group showed no statistically or clinically significant increases in plasma retinoid levels and mean levels did not exceed +/-2 SD of the mean pre-treatment values, indicating that endogenous levels were not being exceeded. No significant differences were detected between the isotretinoin group and the 4% benzoyl peroxide group. These findings indicated that retinoid absorption from a cream containing 0.1% isotretinoin and chemical sunscreens was clinically insignificant, when applied to patients with widespread acne.

  9. Comparing the Efficacy of Low Dose and Conventional Dose of Oral Isotretinoin in Treatment of Moderate and Severe Acne Vulgaris

    PubMed Central

    Faghihi, Gita; Mokhtari, Fatemeh; Fard, Nasrin Motamedi; Motamedi, Narges; Hosseini, Sayed Mohsen

    2017-01-01

    Objective: This study was conducted to compare the effect of low-dose isotretinoin with its conventional dose in patients with moderate and severe acne. Methods: This was a clinical trial conducted on 60 male and female patients with moderate and severe acne vulgaris. The patients were divided into two treatment groups: 0.5 mg/kg/day isotretinoin capsule and low-dose isotretinoin capsule (0.25 mg/kg/day). Patients in both groups received 6-month treatment. At the end of the 6th month and 12th month (6 months after the end of the treatment), they were examined again, and their improvement was determined and compared. Findings: The average severity of acne in the two treatment groups did not differ significantly within any of the study periods. The most common side effects were nose dryness in the low-dose group (17%) and hair thinning and loss in the conventional-dose group (33.2%), although all the patients had dry lips. Conclusion: According to the same severity of the acne in two groups in different study periods, as well as fewer side effects and more patients' satisfaction, the low-dose isotretinoin can be considered in the treatment of acne. PMID:29417084

  10. Presenile diffuse familial sebaceous hyperplasia successfully treated with low-dose isotretinoin: A report of two cases and review of the published work.

    PubMed

    Liu, You-Chen Serena; Cheng, Yu-Pin; Liu, Chuan-I; Yang, Chin-Yi; Yang, Chia-Yi

    2016-10-01

    Presenile diffuse familial sebaceous hyperplasia (PDFSH) presents as extensive yellowish papules with central umbilication on the face without involvement of periorificial regions and occurs in adolescents or young adults with a positive family history. Thirteen cases of PDFSH have been reported in the English-language published work, 10 of which responded to oral isotretinoin from 0.5 to 1 mg/kg per day but recurrences were often observed. Herein, we report two cases of PDFSH, which were successfully managed without recurrence with prolonged low-dose isotretinoin (0.2 mg/kg per day, a cumulative dose of 41 and 64 mg/kg, respectively). Treatment protocols among different published works were reviewed to verify the efficacy of isotretinoin. © 2016 Japanese Dermatological Association.

  11. The cytostatic effect of 9-cis-retinoic acid, tretinoin, and isotretinoin on three different human bladder cancer cell lines in vitro.

    PubMed

    Laaksovirta, S; Rajala, P; Nurmi, M; Tammela, T L; Laato, M

    1999-01-01

    Retinoids have been shown to have activity in both preclinical and clinical bladder cancer studies but their exact role in its treatment and prevention remains obscure. In this study cytostatic activity of a novel 9-cis-retinoic acid (9-cis-RA) was compared with two other retinoids: tretinoin and isotretinoin, in three different bladder cancer cell lines: RT4 (well differentiated), 5637 (moderately differentiated) and T24 (poorly differentiated). The three retinoids were incubated at concentrations of 0.3, 3 and 30 microg/ml with bladder cancer cells in microtitre plates for 3 and 6 days. The cytostatic effect was estimated by using luminometric measuring of ATP activity of viable cells in suspension. Compared with the older retinoids, tretinoin and isotretinoin, the highest concentration of 9-cis-RA had a cytostatic efficacy in all three bladder cancer cell lines tested. A clear dose response relationship was observed in isotretinoin-treated cultures after 6 days and in all 9-cis-RA-treated cultures. Tretinoin was either ineffective or had a stimulating effect on poorly differentiated tumour cells. To conclude, isotretinoin and 9-cis-RA had a cytostatic effect on human bladder cancer cells in vitro. However, the possibility of stimulating cancer growth at small doses, at least with tretinoin, and toxicity at high doses must be considered when planning clinical trials.

  12. ASDS Guidelines Task Force: Consensus Recommendations Regarding the Safety of Lasers, Dermabrasion, Chemical Peels, Energy Devices, and Skin Surgery During and After Isotretinoin Use.

    PubMed

    Waldman, Abigail; Bolotin, Diana; Arndt, Kenneth A; Dover, Jeffrey S; Geronemus, Roy G; Chapas, Anne; Iyengar, Sanjana; Kilmer, Suzanne L; Krakowski, Andrew C; Lawrence, Naomi; Prather, Heidi B; Rohrer, Thomas E; Schlosser, Bethanee J; Kim, John Y S; Shumaker, Peter R; Spring, Leah K; Alam, Murad

    2017-10-01

    Currently, the isotretinoin (13-cis-retinoic acid) package insert contains language advising the discontinuation of isotretinoin for 6 months before performing cosmetic procedures, including waxing, dermabrasion, chemical peels, laser procedures, or incisional and excisional cold-steel surgery. It is common practice to follow this standard because of concerns regarding reports of sporadic adverse events and increased risk of scarring. To develop expert consensus regarding the safety of skin procedures, including resurfacing, energy device treatments, and incisional and excisional procedures, in the setting of concurrent or recent isotretinoin use. The American Society for Dermatologic Surgery authorized a task force of content experts to review the evidence and provide guidance. First, data were extracted from the literature. This was followed by a clinical question review, a consensus Delphi process, and validation of the results by peer review. The task force concluded that there is insufficient evidence to justify delaying treatment with superficial chemical peels and nonablative lasers, including hair removal lasers and lights, vascular lasers, and nonablative fractional devices for patients currently or recently exposed to isotretinoin. Superficial and focal dermabrasion may also be safe when performed by a well-trained clinician.

  13. Assessment of the efficacy and safety of a combination of 2 topical retinoids (RetinSphere) in maintaining post-treatment response of acne to oral isotretinoin.

    PubMed

    Truchuelo, M T; Jiménez, N; Mavura, D; Jaén, P

    2015-03-01

    The high rate of relapse of acne lesions following oral isotretinoin treatment is a common problem which remains unsolved. To avoid or minimize relapses, topical retinoids have been used for many years as maintenance treatment. However, adverse effects frequently occur. To determine the efficacy and safety of a new retinoid combination (Retinsphere technology) in maintaining post-treatment response to oral isotretinoin. Prospective, randomized, double-blind and vehicle-controlled study of 30 patients with acne previously treated with isotretinoin. Treatment with the retinoid combination was applied to one side of the face and vehicle was applied to the other, once daily, for 3 months. Standardized photographs were taken using RBX technology at baseline, 1.5 months and 3 months. The primary efficacy endpoint was the appearance of relapse on the treated side compared to the vehicle-treated side. Other endpoints included lesion count, investigator-reported improvement, patient-reported improvement, impact on quality-of-life, and side effects. Although the majority of patients did not reach the total target dose of oral isotretinoin, the relapse rate was significantly lower on the retinoid-treated side compared to the vehicle-treated side. Likewise, improved lesion count and excellent tolerance were observed. This new retinoid combination (Retinsphere technology) were effective and safe as maintenance therapy after post-treatment response to oral isotretinoin in patients with acne. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

  14. Oral isotretinoin as the most effective treatment in folliculitis decalvans: a retrospective comparison of different treatment regimens in 28 patients.

    PubMed

    Tietze, J K; Heppt, M V; von Preußen, A; Wolf, U; Ruzicka, T; Wolff, H; Sattler, E C

    2015-09-01

    Folliculitis decalvans leads to scarring alopecia through inflammatory destruction of the hair follicle. Currently, antibiotics are most commonly used to treat this disease. However, treatment regimens with antibiotics feature a high relapse rate and encourage the development of resistant bacteria. To evaluate the outcome of different treatment options for folliculitis decalvans. Retrospective study to compare the efficacy of different treatment regimens in 28 patients with folliculitis decalvans. The success of treatment with clindamycin and rifampicin, clarithromycin, dapsone and isotretinoin was analysed. The evaluation of the combination of clindamycin and rifampicin showed the lowest success rate in achieving long-term remission, since 80% of the patients relapsed shortly after end of treatment. Clarithromycin and dapsone were more successful with long-term and stable remission rates of 33% and 43% respectively. Treatment with isotretinoin was the most successful oral treatment in our analysis with 90% of the patients experiencing stable remission during and up to two years after cessation of the treatment. The common use of antibiotics as first-line therapy in folliculitis decalvans needs to be re-evaluated critically and oral isotretinoin should be considered as valid treatment alternative. © 2015 European Academy of Dermatology and Venereology.

  15. Affective disorders as potential complication of anti-acne treatment with isotretinoin: A case series.

    PubMed

    Hanna, Karakula-Juchnowicz; Agnieszka, Kowal-Popczak; Michal, Dzikowski; Dariusz, Juchnowicz; Izabela, Dzikowska; Agata, Makarewicz; Halina, Dubas-Slemp

    2016-11-01

    To analyse cases of 9 patients (18-27 yo) who were consequently admitted to our department and treated with affective disorders (AD) while undergoing isotretinoin (INN) therapy. A semi-structured questionnaire designed by the authors was used to analyse many variables related to demographic characteristics, dermatologic and psychiatrics symptoms, AD course and treatment, family history of mental disorders, building on medical histories of patients and their families, and available medical records. Patients were diagnosed (DSM-IV-TR) with: a major depressive episode (4 patients), a recurrent major depressive episode (3), a bipolar mixed episode (1), and rapid cycling bipolar I disorder (1). The mean time from the first use of INN to: I. the onset of mental disorders was approximately 2 months (1-6 months), II. a visit with a psychiatrist was about 12 months (1-38 months). The predictors of occurrence of AD included a family history of AD and a prior episode of mental disorders. The onset of AD was in most cases preceded by prodromal symptoms such as headaches, sleep disorders, fatigue, drowsiness, or general weakness. Five patients reported suicidal ideation, four patients showed suicidal tendencies, and two persons attempted to commit suicide during the treatment. Psychiatrists should pay special attention to isotretinoin as a drug that may trigger episodes of AD, particularly in patients with a family history of AD or prior episodes of mental disorders. Isotretinoin therapy of patients with acne and a family history of AD or prior episodes of mental disorders requires special care and, if symptoms of depression develop or worsen during the INN treatment, collaboration between a dermatologist and a psychiatrist is needed. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Complete remission of recalcitrant genital warts with a combination approach of surgical debulking and oral isotretinoin in a patient with systemic lupus erythematosus.

    PubMed

    Yew, Yik Weng; Pan, Jiun Yit

    2014-01-01

    Genital warts in immunocompromised patients can be extensive and recalcitrant to treatment. We report a case of recalcitrant genital warts in a female patient with systemic lupus erythematosus (SLE), who achieved complete remission with a combination approach of surgical debulking and oral isotretinoin at an initial dose of 20 mg/day with a gradual taper of dose over 8 months. She had previously been treated with a combination of topical imiquimod cream and regular fortnightly liquid nitrogen. Although there was partial response, there was no complete clearance. Her condition worsened after topical imiquimod cream was stopped because of her pregnancy. She underwent a combination approach of surgical debulking and oral isotretinoin after her delivery and achieved full clearance for more than 2 years duration. Oral isotretinoin, especially in the treatment of recalcitrant genital warts, is a valuable and feasible option when other more conventional treatment methods have failed or are not possible. It can be used alone or in combination with other local or physical treatment methods. © 2013 Wiley Periodicals, Inc.

  17. Teratogenicity of isotretinoin revisited: species variation and the role of all-trans-retinoic acid.

    PubMed

    Nau, H

    2001-11-01

    This paper reviews the teratogenicity of isotretinoin in regard to aspects of species variation, toxicokinetics, and metabolism. Particular emphasis is given to the hypothesis that most effects of isotretinoin (13-cis-retinoic acid) are mediated by isomerization to the all-trans-retinoic acid. This mechanism of action would provide a basis for the understanding of species differences and the extrapolation of experimental results to the human situation and thus improve drug development. The insensitive species (rat, mouse) eliminate the drug rapidly through detoxification to the beta-glucuronide; also, placental transfer is limited in these species. On the other hand, in sensitive species (primates), the drug is predominantly metabolized to the active 13-cis-4-oxo-retinoic acid; placental transfer is more extensive here. The beta-glucuronides showed limited placental transfer in all species examined; these metabolites exhibited very low, if any, measurable concentrations in the human. The 13-cis-retinoic acid is not appreciably bound to cellular retinoid-binding proteins or nuclear receptors and exhibits low tissue distribution and placental transfer. Its access to the nucleus may be extensive. Because of the long half life of 13-cis-retinoic acid, continuous isomerization results in significant area under the concentration-time curve levels of all-trans-retinoic acid in the mouse, monkey and the human; the all-trans-retinoic acid formed is extensively distributed across the placenta and may be an important factor that contributes to the teratogenic potency of 13-cis-retinoic acid. Isomerization cannot explain the teratogenic effects of 13-cis-retinoic acid in the rat and rabbit. It is concluded that the high teratogenic activity of isotretinoin in sensitive species (human, monkey) is related to slow elimination of the 13-cis-isomer, to metabolism to the 4-oxo-derivative, to increased placental transfer, to continuous isomerization and significant exposure of the

  18. Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases.

    PubMed

    Healy, David; Le Noury, Joanna; Mangin, Derelie

    2018-05-01

    To investigate clinical reports of post-SSRI sexual dysfunction (PSSD), post-finasteride syndrome (PFS) and enduring sexual dysfunction following isotretinoin. Data from RxISK.org, a global adverse event reporting website, have been used to establish the clinical features, demographic details and clinical trajectories of syndromes of persistent sexual difficulties following three superficially different treatment modalities.RESULTSWe report on 300 cases of enduring sexual dysfunction from 37 countries following 14 different drugs comprised of serotonin reuptake inhibiting antidepressants, 5α-reductase inhibitors and isotretinoin. While reports of certain issues were unique to the antidepressants, such as the onset of premature ejaculation and persistent genital arousal disorder (PGAD), there was also a significant overlap in symptom profile between the drug groups, with common features including genital anaesthesia, pleasureless or weak orgasm, loss of libido and impotence. Secondary consequences included relationship breakdown and impaired quality of life.CONCLUSIONSThese data point to a legacy syndrome or syndromes comprising a range of disturbances to sexual function. More detailed studies will require developments in coding systems that recognise the condition(s). Further exploration of these tardive sexual syndromes may yield greater understanding of tardive syndromes in general.

  19. Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases

    PubMed Central

    Healy, David; Le Noury, Joanna; Mangin, Derelie

    2018-01-01

    OBJECTIVE: To investigate clinical reports of post-SSRI sexual dysfunction (PSSD), post-finasteride syndrome (PFS) and enduring sexual dysfunction following isotretinoin. METHODS: Data from RxISK.org, a global adverse event reporting website, have been used to establish the clinical features, demographic details and clinical trajectories of syndromes of persistent sexual difficulties following three superficially different treatment modalities. RESULTS We report on 300 cases of enduring sexual dysfunction from 37 countries following 14 different drugs comprised of serotonin reuptake inhibiting antidepressants, 5α-reductase inhibitors and isotretinoin. While reports of certain issues were unique to the antidepressants, such as the onset of premature ejaculation and persistent genital arousal disorder (PGAD), there was also a significant overlap in symptom profile between the drug groups, with common features including genital anaesthesia, pleasureless or weak orgasm, loss of libido and impotence. Secondary consequences included relationship breakdown and impaired quality of life. CONCLUSIONS These data point to a legacy syndrome or syndromes comprising a range of disturbances to sexual function. More detailed studies will require developments in coding systems that recognise the condition(s). Further exploration of these tardive sexual syndromes may yield greater understanding of tardive syndromes in general. PMID:29733030

  20. Topical isotretinoin vs. topical retinoic acid in the treatment of acne vulgaris.

    PubMed

    Domínguez, J; Hojyo, M T; Celayo, J L; Domínguez-Soto, L; Teixeira, F

    1998-01-01

    This is a clinical, prospective, and longitudinal study comparing the efficacy and incidence of averse effects of topical isotretinoin against those of topical retinoic acid in the treatment of acne vulgaris. The 30 participants were recruited from the patients attending the outpatient clinic of the Department of Dermatology of "Dr Manuel Gea González" General Hospital in Mexico City. They belonged to either sex and any race, their ages ranged between 13 and 30 years, and they presented with 15 to 100 facial inflammatory lesions (papulo-pustules) and/or 15 to 100 noninflammatory lesions (comedones) and no more than three nodulo-cystic lesions. The criteria of exclusion were as follows: pregnancy or lactation, systemic treatment with steroids, antibiotics, antiandrogens, or oral retinoids in the preceding 24 months, treatment with ultraviolet radiation, hypersensitivity to retinoids, or a severe systemic illness. From 44 interviewed patients, 14 were excluded. A detailed clinical history was obtained from the remaining individuals, the degree of seborrhea was recorded, and acne lesions were counted. Each patient received either isotretinoin gel 0.05% or retinoic acid cream 0.05%. The patients were instructed to wash their faces in the mornings and evenings with a neutral soap, and to apply the product after the evening cleansing. The patients were examined again after 2, 4, 8, and 12 weeks of treatment and, at each appointment, the number of lesions was recorded and the severity of acne was graded according to the classification of Plewig and Kligman. The seriousness of the adverse effects, such as stinging, pruritus, erythema, xerosis, and desquamation, was evaluated blindly by an investigator who did not know what group the patient belonged to, and graded as 1 = mild, 2 = moderate, and 3 = severe. The efficacy of each drug was determined by the reduction in the number of lesions between weeks 0 and 12 of treatment. An excellent response corresponded to a 76

  1. Analysis of clinical efficacy, side effects, and laboratory changes among patients with acne vulgaris receiving single versus twice daily dose of oral isotretinoin.

    PubMed

    Ahmad, Hesham M

    2015-01-01

    Acne vulgaris is a debilitating disorder and requires proper treatment. This work evaluates the clinical efficacy, side effects, and laboratory changes of serum lipids and liver function during oral isotretinoin therapy for acne vulgaris, comparing single versus twice daily dose. Fifty-eight patients with acne vulgaris were included and randomized into group I (26 patients), who received once daily dose, and group II (32 patients), who received twice daily dose of oral isotretinoin. Global acne scoring system was used to evaluate acne severity and post-treatment improvement. Both regimens resulted in highly significant clinical improvement of acne with no significant difference. However, side effects were significantly more common among patients of group I. Both regimens caused mild rise of serum cholesterol, alanine transaminase (ALT), and aspartate aminotransferase (AST) with more prominent rise of triglycerides especially with twice daily dose. Oral isotretinoin is a very effective treatment for acne vulgaris with no statistically significant difference in clinical efficacy between once and twice daily doses. However, dividing dose to twice per day might cause fewer incidence of side effects without reducing clinical efficacy. The drug causes mild clinically insignificant rise of serum cholesterol, triglycerides, AST, and ALT. © 2015 Wiley Periodicals, Inc.

  2. Double-blinded, vehicle-controlled proof of concept study to investigate the recurrence of inflammatory and noninflammatory acne lesions using tretinoin gel (microsphere) 0.04% in male patients after oral isotretinoin use.

    PubMed

    Vender, Reid; Vender, Ronald

    2012-01-01

    Background. Although isotretinoin orally is commonly used for moderate to severe or scarring acne, it is not a cure. Unfortunately recurrence is unpredictable and varies within the acne population. Objectives. Using a proof of concept study, determine the recurrence of acne after isotretinoin use in male patients. Methods. Twenty males aged 18-45 years old were enrolled. Subjects successfully completed a treatment of acne vulgaris with oral isotretinoin (120-150 mg/kg/course). Subjects were randomized 1 to 1. The study duration was 24 weeks. The primary endpoint measured was the absolute change in lesion counts from baseline to weeks 16 and 24. Local tolerability assessments were measured. Results. There were favorable changes in all outcomes measured. Overall, there was a 38.7% lower lesion count with tretinoin 0.04% microsphere gel use versus vehicle. The active product was well tolerated with great patient satisfaction. There were no significant safety issues. The limitations included the low number of patients enrolled, average age, and percentage of patients lost to follow-up. Conclusion. In summary, the results favored tretinoin 0.04% microsphere gel in the prevention of recurrent acne after isotretinoin use in male patients over 18 years old over a six-month period.

  3. [Severe pruriginous acne in dialysed renal failure. Diagnostic difficulties and efficacy of isotretinoin].

    PubMed

    Grange, F; Mitschler, A; Genestier, S; Guillaume, J C

    2001-11-01

    The occurrence of acne in dialysed renal failure patients has rarely been reported and the clinical characteristics and therapeutic issues rarely studied in these patients. Two men and two women, 33 to 56 years-old, with chronic renal failure and no past history of acne, developed severe acne under dialysis. The acne was excoriated in all cases and associated with prurigo-like lesions and intense pruritus, which made diagnosis difficult. Acne was profuse on the face and the trunk, but also on the neck (1 case) and the upper limbs (2 cases). No patient was taking acne-inducing substances. Various to therapies attempting to control pruritus were ineffective. However, anti-acne treatments (cyclines associated with local tretinoin in 1 case and oral isotreninoin in 3 cases) led to complete regression of the acne, pruritus and the prurigo-like lesions without relapse after a follow-up time of 4 months to 2 years. Pruritus is frequent during renal failure. However, the occurrence of unexplained acne has only rarely been reported. Our patients' clinical picture was original, characterized by the late development, under dialysis, of severe and pruriginous acne, the pathogenesis of which is unknown. Because of the clinical and therapeutic implications (impaired quality of life, pigmentation or scarring and remarkable efficacy of oral isotretinoin) this clinical picture merits more attention, and the modalities for the prescription of isotretinoin in this context should be defined.

  4. Interpretation of Biochemical Tests Using the Reference Change Value in Monitoring Adverse Effects of Oral Isotretinoin in 102 Ethnic Turkish Patients.

    PubMed

    Bugdayci, Guler; Polat, Mualla; Oguzman, Hamdi; Cinpolat, Havva Yasemin

    2016-08-01

    The aim of this study was to model the use of reference change values (RCVs) for the follow-up of 4 parameters of patients using oral isotretinoin which is gaining widespread popularity for monitoring the side effects of the treatment. 102 patients received 30 mg/day oral isotretinoin for 24 weeks for the diagnosis of acne vulgaris. Repetitive measurements of the patients were interpreted with RCVs, after comparing the first and second doses based on RCVs: TC, TG, AST and ALT results increased in 12%, 20%, 14% and 12% of the patients respectively. When the first dose was compared with the last dose, the increases were 20%, 29%, 22% and 18% respectively interpreted as significant changes based on laboratory medicine. A more sensitive follow-up is possible in the monitorization of adverse effects by using RCVs method. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Comparison of Autologous Serum Versus Preservative Free Artificial Tear in Patients with Dry Eyes Due to Systemic Isotretinoin Therapy.

    PubMed

    Yılmaz, Uğur; Küçük, Erkut; Koç, Çağdaş; Gökler, Enes

    2017-06-01

    To investigate dry eye development in the patients receiving systemic retinoic acid therapy and to compare effectiveness of Autologous Serum (AS) and preservative free artificial tear (PFAT) in the patients with dry eye disease. This prospective, crossover, double blind study was conducted on patients who have dry eyes due to systemic isotretinoin treatment for different indications. Patients detected as having dry eye during systemic isotretinoin treatment were included to our study. At baseline, 1 and 2 month of study, detailed ocular examination, best corrected visual acuity measurement, intraocular pressure measurement, and Tear Break-up Time (TBUT) and Schirmer Test (ST) without topical anesthesia were performed. We compared the efficacy of AS and PFAT. To accomplish crossover after the first month, treatment given to each patient was switched to the other treatment. Statistical analysis was measured using SPSS version 20.0. p values of < 0.05 were considered as statistically significant. At the end of the first month, there was a significant improvement for the TBUT test in both AS and PFAT groups compared to baseline (respectively p < 0.001, p < 0.001). TBUT was found to be significantly higher in the AS group compared to the PFAT group at the end of the first month (p < 0.001). At the end of the second month, TBUT was found to be significantly higher in the AS group compared to the PFAT group at the posttreatment time (p < 0.001). There was a significant OSDI score decreasing in both groups compared to that reported previously at the end of the first and second months (respectively p < 0.001, p < 0.001). OSDI score decreasing was more significant in the AS group compared to the PFAT group at both time points (respectively p < 0.001, p < 0.001). AS may be an effective alternative to PFAT in the treatment of dry eye developed during isotretinoin use.

  6. Isotretinoin Oil-Based Capsule Formulation Optimization

    PubMed Central

    Tsai, Pi-Ju; Huang, Chi-Te; Lee, Chen-Chou; Li, Chi-Lin; Huang, Yaw-Bin; Tsai, Yi-Hung; Wu, Pao-Chu

    2013-01-01

    The purpose of this study was to develop and optimize an isotretinoin oil-based capsule with specific dissolution pattern. A three-factor-constrained mixture design was used to prepare the systemic model formulations. The independent factors were the components of oil-based capsule including beeswax (X 1), hydrogenated coconut oil (X 2), and soybean oil (X 3). The drug release percentages at 10, 30, 60, and 90 min were selected as responses. The effect of formulation factors including that on responses was inspected by using response surface methodology (RSM). Multiple-response optimization was performed to search for the appropriate formulation with specific release pattern. It was found that the interaction effect of these formulation factors (X 1 X 2, X 1 X 3, and X 2 X 3) showed more potential influence than that of the main factors (X 1, X 2, and X 3). An optimal predicted formulation with Y 10 min, Y 30 min, Y 60 min, and Y 90 min release values of 12.3%, 36.7%, 73.6%, and 92.7% at X 1, X 2, and X 3 of 5.75, 15.37, and 78.88, respectively, was developed. The new formulation was prepared and performed by the dissolution test. The similarity factor f 2 was 54.8, indicating that the dissolution pattern of the new optimized formulation showed equivalence to the predicted profile. PMID:24068886

  7. Retinoic Acid 4-Hydroxylase Inducibility and Clinical Response to Isotretinoin in Acne Patients

    PubMed Central

    Wang, Frank; Kwak, Heh Shin R.; Elbuluk, Nada; Kaczmarek, Anya L.; Hamilton, Ted; Voorhees, John J.; Fisher, Gary J.; Kang, Sewon

    2011-01-01

    Background The cytochrome P450 enzyme CYP26 (retinoic acid 4-hydroxylase) initiates the catabolism of all-trans retinoic acid (tRA) and limits the effects of tRA. The CYP26 enzyme acts on tRA, but not 13-cis RA (isotretinoin), a retinoid used to treat severe acne. However, 13-cis RA can isomerize to tRA, which can then be metabolized by CYP26. Objective In healthy subjects, we assessed the variability of CYP26 enzymatic activity. We then investigated whether response to oral 13-cis RA among acne patients correlates with variability in CYP26 expression. Methods In healthy subjects, we isolated microsomal fractions from the epidermis of keratome biopsies and measured CYP26 enzymatic activity in untreated skin and skin treated with tRA. Enzymatic activity was determined based on rate of formation of 4-hydroxy RA (pg/min) per mg microsomal protein. Using real-time PCR we quantified CYP26 mRNA induction after tRA application in acne patients who responded or did not respond to one course of 13-cis RA. Results In normal skin (N=118), CYP26 enzymatic activity was widely variable (1–180 pg/min per mg microsomal fraction; mean 42.7 ± 3.5). Furthermore, CYP26 enzymatic activity was inducible in a dose-dependent manner in normal skin following tRA application, but not correlated with age or sex (N=29). In acne patients, CYP26 mRNA induction following 0.1% tRA application did not differ (P>0.05) between subjects who responded (N=8, 587±325 fold) or did not respond (N=8, 657±227 fold) to one course of 13-cis RA. Limitations The small number of acne patients treated with 13-cis RA was a major limitation. Conclusion Factors other than CYP26 activity may determine response to isotretinoin in acne. PMID:19525031

  8. Comparison of the cumulative irritation potential of adapalene gel and cream with that of erythromycin/tretinoin solution and gel and erythromycin/isotretinoin gel.

    PubMed

    Queille-Roussel, C; Poncet, M; Mesaros, S; Clucas, A; Baker, M; Soloff, A M

    2001-02-01

    Adapalene is a naphthoic acid derivative with retinoid activity that is effective in the treatment of mild to moderate acne vulgaris. This study assessed the cumulative irritation potential of adapalene gel (0.1%) and adapalene cream (0.1%) compared with that of erythromycin (4%)/tretinoin (0.025%) solution, erythromycin (4%)/tretinoin (0.025%) gel, erythromycin (2%)/isotretinoin (0.05%) gel, and white petrolatum (negative control). This was a single-center, randomized, controlled, investigator-blinded, intraindividual comparison study in healthy subjects with normal skin. The cumulative irritation assay (patch test) was used to assess the potential for irritation (including erythema) of the treatments. Each subject received all study treatments, randomly applied under occlusion (patch), to sites on either side of the midline on the mid-thoracic area of the back. All patches were applied to the same sites throughout the study, unless the degree of reaction to the treatment or adhesive necessitated removal. For 3 weeks, each test material was applied daily, Monday through Friday, for approximately 24 hours; the Friday patches were left in place over the weekend for approximately 72 hours. All 36 subjects (26 men, 10 women; age, 18-49 years [mean, 30 years]) completed the study. In the course of the study, all subjects had > or =1 application discontinued prematurely on > or =1 site due to intolerance. There were no discontinuations with white petrolatum. All erythromycin/tretinoin gel patches were discontinued at day 10; 35 of 36 erythromycin/isotretinoin gel patches were discontinued at day 9; and 35 of 36 erythromycin/tretinoin solution patches were discontinued at day 11 or day 17. The adapalene products, although slightly more irritating (mean cumulative irritation index, 0.25-1) than white petrolatum, were significantly less irritating than the erythromycin/tretinoin and erythromycin/isotretinoin products (P < 0.01). Adapalene gel and cream were well tolerated

  9. FOLLICULITIS ET PERIFOLLICULITIS CAPITIS ABSCEDENS ET SUFFODIENS CONTROLLED WITH A COMBINATION THERAPY: SYSTEMIC ANTIBIOSIS (METRONIDAZOLE PLUS CLINDAMYCIN), DERMATOSURGICAL APPROACH, AND HIGH-DOSE ISOTRETINOIN

    PubMed Central

    Tchernev, Georgi

    2011-01-01

    Folliculitis et perifolliculitis capitis abscedens et suffodiens is a rare disease of unknown etiology. It is a suppurative process that involves the scalp, eventually resulting in extensive scarring and irreversible alopecia. The condition is also known as ‘acne necrotica miliaris’ or ‘Proprionibacterium’ folliculitis. Most often the disease affects men of African-American or African-Caribbean descent between 20 and 40 years of age. The clinical picture is determined by fluctuating painful fistule-forming conglomerates of abscesses in the region of the occipital scalp. The cause of scalp folliculitis is not well understood. It is generally considered to be an inflammatory reaction to components of the hair follicle, particularly the micro-organisms. These include: bacteria (especially Propionibacterium acnes, but in severe cases, also Staphylococcus aureus), Yeasts (Malassezia species) and mites (Demodex folliculorum). The initial histopathologic finding is an exclusively neutrophilic infiltration followed by a granulomatous infiltrate. The treatment of the disease is usually difficult and often disappointing. Successful treatment with isotretinoin 1 mg/kg body mass could be achieved only after regular systematic administration in the course of 3–4 months. Here we describe a patient with eruptive purulent form of the disease, which has been controlled with combination therapy: systemic antibiosis with metronidazole and clindamycin, dermatosurgical removal of single nodular formations, and isotretinoin 1 mg/kg body mass for 3–5 months. PMID:21772598

  10. Selenium ameliorates isotretinoin-induced liver injury and dyslipidemia via antioxidant effect in rats.

    PubMed

    Saied, Nashwa Mostafa; Hamza, Alaaeldin Ahmed

    2014-09-01

    Isotretinoin (Iso) is a widely used retinoid for the treatment of dermatologic conditions. Although it has broad side effects, there is no well-designed study about preventive effects against its hepatic toxicity. This study was undertaken to evaluate the protective effect of selenium (Se) against Iso-induced hepatotoxicity in Wistar rats. Animals were divided into four groups. The first group served as control. The second, third and fourth groups received Se, Iso and Se & Iso, respectively, for 28 days. Se was administered daily orally at a dose of 50 µg / 100 g body weight. Iso was given daily orally at a dose of 0.75 mg/ 100 g /day in olive oil. Iso caused significant increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, cholesterol, triglycerides, and high-density lipids content. Animals also showed significant rise in thiobarbituric acid reacting substance and nitric oxide content with concomitant decrease in reduced glutathione content and the antioxidant enzyme activities of superoxide dismutase and catalase in liver tissue after Iso exposure. Se administration produced a significant protection against the hepatotoxic effects of Iso and markedly alleviated alterations in these parameters. The results obtained herein clearly indicate that Iso causes induction of oxidative stress and the co-administration of Iso and Se provides protection against Iso-induced liver injury.

  11. Beneficial effect of a moisturizing cream as adjunctive treatment to oral isotretinoin or topical tretinoin in the management of acne.

    PubMed

    Laquieze, Sabine; Czernielewski, Janusz; Rueda, Marie-José

    2006-01-01

    Despite their beneficial effects on the treatment of acne vulgaris, topical and oral retinoids may cause severe local irritation (retinoid dermatitis) due to their mechanism of action, thereby jeopardizing patient adherence, and thus compromising treatment efficacy. Alleviating dryness and improving skin comfort by using a moisturizer concomitantly to retinoids could enhance efficacy. In the present study, 30 subjects receiving either oral isotretinoin for at least 2 months or topical tretinoin for at least one month applied a moisturizing cream (Cetaphil Moisturizing Cream) twice daily for 15 days on one half of the face while the other side remained untreated. Clinical assessments, confirmed by biophysical measurements, showed that the moisturizer provided a significant improvement in skin dryness, roughness, and desquamation. Skin properties and skin discomfort were also greatly improved and subjects were very satisfied with the product. Retinoid-induced skin irritation can be relieved by the regular use of a gentle moisturizing cream as an adjunctive treatment.

  12. Isotretinoin was not associated with depression or anxiety: A twelve-week study

    PubMed Central

    Suarez, Bella; Serrano, Ana; Cova, Yves; Baptista, Trino

    2016-01-01

    AIM: To investigate the frequency and severity of depression and/or anxiety in isotretinoin (ITT)-treated subjects and in a non-ITT control group. METHODS: Sixty consecutively-admitted non-psychiatric outpatients with acne were assigned to either ITT at a fixed dose of 30 mg/d (n = 36) or “other treatment” group (OT; n = 24). The Zung depression or anxiety scales (with cut-off points), two locally developed scales for depression (GeDepr) and anxiety (Ansilet) (without cut-off points) and clinical global impression scales of acne severity were administered at baseline and at weeks 6 and 12 of treatment. Data was analyzed with the chi-squared test and covariance analysis. RESULTS: Gender distribution, age, marital status and education level did not differ between both treatment groups. The frequency of depression, as defined by the Zung scale cut-off points was similar in the ITT and in the non-ITT groups: Weeks 6 and 12: 8.3% in both groups, P = 0.9. The frequency of anxiety was similar in the groups as well: Week 6: ITT = 8.3%; OT = 0.0%, P > 0.05; week 12: ITT = 11.1%, OT = 4.2%, P > 0.05. The scores in both scales’ sets did not differ between the treatment groups at any evaluation time point (P > 0.05). Five ITT-treated subjects (13.8%) and two from the OT-treated group (8.3%) developed clinically significant anxiety and/or depression during treatment (P > 0.05). CONCLUSION: Our study confirms the safety of ITT regarding psychological side effects in regular dermatological patients. Susceptible subjects may exist but their identification requires additional strategies. PMID:27014604

  13. Healthcare professional surveys to investigate the implementation of the isotretinoin Pregnancy Prevention Programme: a descriptive study.

    PubMed

    Crijns, Ineke; Mantel-Teeuwisse, Aukje; Bloemberg, Rudi; Pinas, Eldridge; Straus, Sabine; de Jong-van den Berg, Lolkje

    2013-01-01

    Three online surveys explored compliance with the PPP by pharmacists and dermatologists, in the Netherlands. In 2007 and 2011, two pharmacist surveys were conducted to assess improvement over time. In 2007, survey was sent to members of the Utrecht Pharmacy Panel for Education & Research (UPPER) network (n = 1000) and in 2011, to the research group of the Dutch Association of Pharmacists (KNMP) (n = 556). In 2010, a survey was sent to 564 dermatologists of the Dutch Association of Dermatology and Venereology (NVDV). Both pharmacists' questionnaires had response rates of 20% and the dermatologist questionnaire of 28%. Pharmacists' checks on 30-day dispensing remained 82%, but a check whether the prescription is out-of-date decreased (61 to 53%). Pharmacists asked the patient for a negative pregnancy test in 15%, but use of contraception was checked by 44 - 49%. One hundred and five dermatologists (64%) always prescribe contraception; 35 (22%) occasionally. Ninety-three percent of the dermatologists were of the opinion that they performed the PPP. Analysis of different elements of the PPP showed that 41 (25%) were compliant. The observed non-adherence to the isotretinoin PPP calls for careful evaluation of risk minimisation plans and participation of all stakeholders in the development of these plans.

  14. UVA is the major contributor to the photodegradation of tretinoin and isotretinoin: implications for development of improved pharmaceutical formulations

    PubMed Central

    Tashtoush, Bassam M.; Jacobson, Elaine L.; Jacobson, Myron K.

    2008-01-01

    The chemical stability of tretinoin (RA) and isotretinoin (13RA) in ethanol and dermatological cream preparations exposed to solar simulated light (SSL), UVA, and visible light has been studied. Photostability was monitored by an HPLC method that allowed simultaneous analysis of RA and 13RA, thus allowing photodegradation due to isomerization to other retinoids and photolysis to non-retinoid products to be monitored. Both retinoids undergo both isomerization and photolysis following SSL, UVA and visible light exposure but RA is more sensitive to photodegradation than 13RA. Degradation of both retinoids by photolysis is considerably greater in cream formulations than in ethanol and the photodegradation follows second order kinetics. Rate constants and half-lives for degradation of RA and 13RA in ethanol solution and cream preparations subjected to different light sources are reported. The UVA component of SSL is the major contributor to photodegradation. Since UVA penetrates deeply into skin, our results suggest that photodegradation of RA may contribute to the photosensitivity associated with RA therapy. Our studies suggest that development of improved formulations and the use of effective UVA sunscreens may reduce the side effects of RA therapy. PMID:18093761

  15. UVA is the major contributor to the photodegradation of tretinoin and isotretinoin: Implications for development of improved pharmaceutical formulations.

    PubMed

    Tashtoush, Bassam M; Jacobson, Elaine L; Jacobson, Myron K

    2008-03-20

    The chemical stability of tretinoin (RA) and isotretinoin (13RA) in ethanol and dermatological cream preparations exposed to solar simulated light (SSL), UVA, and visible light has been studied. Photostability was monitored by an HPLC method that allowed simultaneous analysis of RA and 13RA, thus allowing photodegradation due to isomerization to other retinoids and photolysis to non-retinoid products to be monitored. Both retinoids undergo both isomerization and photolysis following SSL, UVA and visible light exposure but RA is more sensitive to photodegradation than 13RA. Degradation of both retinoids by photolysis is considerably greater in cream formulations than in ethanol and the photodegradation follows second order kinetics. Rate constants and half-lives for degradation of RA and 13RA in ethanol solution and cream preparations subjected to different light sources are reported. The UVA component of SSL is the major contributor to photodegradation. Since UVA penetrates deeply into skin, our results suggest that photodegradation of RA may contribute to the photosensitivity associated with RA therapy. Our studies suggest that development of improved formulations and the use of effective UVA sunscreens may reduce the side effects of RA therapy.

  16. Metabolic characteristics of 13-cis-retinoic acid (isotretinoin) and anti-tumour activity of the 13-cis-retinoic acid metabolite 4-oxo-13-cis-retinoic acid in neuroblastoma

    PubMed Central

    Sonawane, Poonam; Cho, Hwang Eui; Tagde, Ashujit; Verlekar, Dattesh; Yu, Alice L; Reynolds, C Patrick; Kang, Min H

    2014-01-01

    Background and Purpose Isotretinoin (13-cis-retinoic acid; 13-cRA) is a differentiation inducer used to treat minimal residual disease after myeloablative therapy for high-risk neuroblastoma. However, more than 40% of children develop recurrent disease during or after 13-cRA treatment. The plasma concentrations of 13-cRA in earlier studies were considered subtherapeutic while 4-oxo-13-cis-RA (4-oxo-13-cRA), a metabolite of 13-cRA considered by some investigators as inactive, were greater than threefold higher than 13-cRA. We sought to define the metabolic pathways of 13-cRA and investigated the anti-tumour activity of its major metabolite, 4-oxo-13-cRA. Experimental Approach Effects of 13-cRA and 4-oxo-13-cRA on human neuroblastoma cell lines were assessed by DIMSCAN and flow cytometry for cell proliferation, MYCN down-regulation by reverse transcription PCR and immunoblotting, and neurite outgrowth by confocal microscopy. 13-cRA metabolism was determined using tandem MS in human liver microsomes and in patient samples. Key Results Six major metabolites of 13-cRA were identified in patient samples. Of these, 4-oxo-13-cRA was the most abundant, and 4-oxo-13-cRA glucuronide was also detected at a higher level in patients. CYP3A4 was shown to play a major role in catalysing 13-cRA to 4-oxo-13-cRA. In human neuroblastoma cell lines, 4-oxo-13-cRA and 13-cRA were equi-effective at inducing neurite outgrowth, inhibiting proliferation, decreasing MYCN mRNA and protein, and increasing the expression of retinoic acid receptor-β mRNA and protein levels. Conclusions and Implications We showed that 4-oxo-13-cRA is as active as 13-cRA against neuroblastoma cell lines. Plasma levels of both 13-cRA and 4-oxo-13-cRA should be evaluated in pharmacokinetic studies of isotretinoin in neuroblastoma. PMID:25039756

  17. Metabolic characteristics of 13-cis-retinoic acid (isotretinoin) and anti-tumour activity of the 13-cis-retinoic acid metabolite 4-oxo-13-cis-retinoic acid in neuroblastoma.

    PubMed

    Sonawane, Poonam; Cho, Hwang Eui; Tagde, Ashujit; Verlekar, Dattesh; Yu, Alice L; Reynolds, C Patrick; Kang, Min H

    2014-12-01

    Isotretinoin (13-cis-retinoic acid; 13-cRA) is a differentiation inducer used to treat minimal residual disease after myeloablative therapy for high-risk neuroblastoma. However, more than 40% of children develop recurrent disease during or after 13-cRA treatment. The plasma concentrations of 13-cRA in earlier studies were considered subtherapeutic while 4-oxo-13-cis-RA (4-oxo-13-cRA), a metabolite of 13-cRA considered by some investigators as inactive, were greater than threefold higher than 13-cRA. We sought to define the metabolic pathways of 13-cRA and investigated the anti-tumour activity of its major metabolite, 4-oxo-13-cRA. Effects of 13-cRA and 4-oxo-13-cRA on human neuroblastoma cell lines were assessed by DIMSCAN and flow cytometry for cell proliferation, MYCN down-regulation by reverse transcription PCR and immunoblotting, and neurite outgrowth by confocal microscopy. 13-cRA metabolism was determined using tandem MS in human liver microsomes and in patient samples. Six major metabolites of 13-cRA were identified in patient samples. Of these, 4-oxo-13-cRA was the most abundant, and 4-oxo-13-cRA glucuronide was also detected at a higher level in patients. CYP3A4 was shown to play a major role in catalysing 13-cRA to 4-oxo-13-cRA. In human neuroblastoma cell lines, 4-oxo-13-cRA and 13-cRA were equi-effective at inducing neurite outgrowth, inhibiting proliferation, decreasing MYCN mRNA and protein, and increasing the expression of retinoic acid receptor-β mRNA and protein levels. We showed that 4-oxo-13-cRA is as active as 13-cRA against neuroblastoma cell lines. Plasma levels of both 13-cRA and 4-oxo-13-cRA should be evaluated in pharmacokinetic studies of isotretinoin in neuroblastoma. © 2014 The British Pharmacological Society.

  18. Low-dose oral isotretinoin versus topical retinoic acid for photoaging: a randomized, comparative study.

    PubMed

    Bagatin, Edileia; Guadanhim, Lilia R S; Enokihara, Milvia M S S; Sanudo, Adriana; Talarico, Sérgio; Miot, Helio A; Gibson, Lawrence

    2014-01-01

    Oral isotretinoin (ISO) is the only drug which promotes prolonged remission or cure of severe acne. It also has other properties, supporting its use for non-acne indications. Retinoic acid (RA) is gold standard treatment for photoaging. ISO for photoaging treatment was reported in non-controlled trials as alternative to RA, which causes skin irritation. To compare clinical, histological, and immunohistochemical effects of low-dose ISO and 0.05% topical RA to treat photoaging. Randomized, comparative, evaluator-blinded, single-center study. Twenty-four healthy, Caucasian, 50 to 75-year-old men and women (menopausal or sterilized) with advanced photoaging were included. Twelve subjects received ISO, 20 mg/day, and 12 subjects were treated with RA cream, for six months; both treatments were administered every other day, and moisturizer and sunscreen were also used. Outcome measures included patient assessments, blinded photographic evaluations, Life Quality Index, histological (HE, Verhoeff) and immunohistochemical (p53, collagen type I) evaluations, adverse events, liver function, lipid profile, and blood count. Statistical analysis with generalized estimating equations and repeated measures ANOVA tests was used. Eleven subjects in each group completed the study. Patient and photographic assessments showed overall improvement in skin appearance. Quality-of-life scores were reduced for all subjects. Histological analysis revealed corneal layer diminution, epidermal thickness increase, and elastosis reduction. Immunohistochemical findings revealed significant epidermal p53 reduction and dermal collagen 1 increase. No differences were found between groups; laboratory tests showed no significant alterations. Despite being safe and effective, low-dose ISO was not superior to 0.05% RA for advanced photoaging treatment. © 2013 The International Society of Dermatology.

  19. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Colburn, W.A.; Vane, F.M.; Bugge, C.J.

    The pharmacokinetics of isotretinoin and 4-oxoisotretinoin in blood, as well as the blood concentrations and urinary, biliary, and fecal excretion of carbon-14 were studied using liquid scintillation counting techniques and reverse phase HPLC methods following a single 80-mg oral suspension dose of UC-isotretinoin to four healthy male subjects and two patients with biliary T-tube drainage. Approximately 80% of the dose was recovered as UC in excreta during the course of the study of which about equal fractions were in the urine and feces. Secondary peaks in blood concentrations of UC were observed in the healthy subjects whereas they were notmore » seen in the patients with T-tubes. The harmonic mean apparent half-life for isotretinoin in the blood of the healthy subjects was 13.6 hr, whereas the corresponding value for the UC was 90 hr. The data for isotretinoin and 4-oxoisotretinoin coupled with the total carbon-14 data suggest that the oral dose of UC-isotretinoin is absorbed to a similar extent by the healthy subjects and T-tube patients, whereas T-tube patients clear the drug more rapidly. The biliary excretion and possible enterohepatic circulation of isotretinoin and its metabolites may have significant impact on the pharmacokinetic profile of isotretinoin in man.« less

  20. Psychiatric disorders, acne and systemic retinoids: comparison of risks.

    PubMed

    Le Moigne, M; Bulteau, S; Grall-Bronnec, Marie; Gerardin, M; Fournier, Jean-Pascal; Jonville-Bera, A P; Jolliet, Pascale; Dreno, Brigitte; Victorri-Vigneau, C

    2017-09-01

    The link between isotretinoin, treatment of a severe form of acne, and psychiatric disorders remains controversial, as acne itself could explain the occurrence of psychiatric disorders. This study aims at assessing the disproportionality of psychiatric adverse events reported with isotretinoin in the French National PharmacoVigilance Database, compared with other systemic acne treatments and systemic retinoids. Data were extracted from the French National PharmacoVigilance Database for systemic acne treatments, systemic retinoids and drugs used as comparators. Each report was subjected to double-blind analysis by two psychiatric experts. A disproportionality analysis was performed, calculating the number of psychiatric ADRs divided by the total number of notifications for each drug of interest. Concerning acne systemic treatments: all 71 reports of severe psychiatric disorders involved isotretinoin, the highest proportion of mild/moderate psychiatric adverse events was reported with isotretinoin (14.1%). Among systemic retinoids, the highest proportion of severe and mild/moderate psychiatric events occurred with isotretinoin and alitretinoin. Our study raises the hypothesis that psychiatric disorders associated with isotretinoin are related to a class effect of retinoids, as a signal emerges for alitretinoin. Complementary studies are necessary to estimate the risk and further determine at-risk populations.

  1. Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats.

    PubMed

    Ferguson, Sherry A; Cisneros, F Javier; Gough, B; Hanig, Joseph P; Berry, Kimberly J

    2005-10-01

    Oral treatment with the anti-acne drug Accutane (isotretinoin, 13-cis-retinoic acid) has been associated with suicide ideation and depression. Here, depression-like behaviors (i.e., behavioral despair and anhedonia) were quantified in adult Sprague-Dawley rats gavaged daily beginning at postnatal day (PND) 82 with 13-cis-RA (7.5 or 22.5 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg ). Tested at PND 130-131 in the Forced Swim Test, 7.5 mg/kg 13-cis-RA marginally decreased immobility and slightly increased climb/struggle durations whereas neither all-trans-retinoic acid group differed from controls. Voluntary saccharin solution (0.03%) intake at PND 102-104 and PND 151-153 was not different from controls in any treated group, although all RA-treated groups had lower intakes. Swim speed in a water maze at PND 180 was similar across groups, indicating no RA-induced differences in physical ability. Open field activity was mildly decreased at PND 91 in 7.5 mg/kg-treated males only, but it was within the control range at PND 119, 147, and 175. Thus, at serum levels similar to those in humans receiving the drug, chronic 13-cis-RA treatment did not severely affect depression-like behaviors in rats. These data do not substantiate the hypothesis of 13-cis-RA-induced depression.

  2. Quantitative analysis of retinoids in biological fluids by high-performance liquid chromatography using column switching. I. Determination of isotretinoin and tretinoin and their 4-oxo metabolites in plasma.

    PubMed

    Wyss, R; Bucheli, F

    1988-02-26

    A fully automated gradient high-performance liquid chromatographic method for the determination of isotretinoin, tretinoin and their 4-oxo metabolites in plasma was developed, using the column-switching technique. After dilution with an internal standard solution containing 20% acetonitrile, 0.5 ml of the sample was injected onto a precolumn (17 X 4.6 mm I.D.), filled with C18 Corasil 37-53 micron. Proteins and polar plasma components were washed out using 1% ammonium acetate-acetonitrile (9:1, v/v) as mobile phase 1. After valve switching, the retained components were transferred to the analytical column in the backflush mode, separated by gradient elution and detected at 360 nm by UV detection. Using two coupled reversed-phase columns (125 mm long), the separation of cis and trans isomers was possible, and all four compounds could be quantified down to 2 ng/ml of plasma. The inter-assay precision in the concentration range 20-100 ng/ml was between 1.0 and 4.7% for all compounds.

  3. Retinoic Acid and Affective Disorders: The Evidence for an Association

    PubMed Central

    Bremner, J Douglas; Shearer, Kirsty; McCaffery, Peter

    2011-01-01

    Objective Isotretinoin (13-cis-retinoic acid, or 13-cis-RA) (Accutane), approved by the FDA for the treatment of acne, carries a black box warning related to the risk of depression, suicide, and psychosis. Retinoic acid (RA), the active form of vitamin A, regulates gene expression in the brain, and isotretinoin is its 13-cis isomer. Retinoids represent a group of compounds derived from vitamin A that perform a large variety of functions in many systems, in particular the CNS, and abnormal retinoid levels can have neurological effects. Although infrequent, proper recognition and treatment of psychiatric side effects in acne patients is critical given the risk of death and disability. This paper reviews the evidence for a relationship between isotretinoin, depression and suicidality. Data Sources Evidence examined includes: 1) case reports; 2) temporal association between onset of depression and exposure to the drug; 3) challenge-rechallenge cases; 4) class effect (other compounds in the same class, like vitamin A, having similar neuropsychiatric effects); 5) dose response; and 6) biologically plausible mechanisms. Study Selection All papers in the literature related to isotretinoin, depression and suicide were reviewed, as well as papers related to class effect, dose response, and biological plausibility. Data Extraction Information from individual articles in the literature was extracted. Data Synthesis The literature reviewed is consistent with an association between isotretinoin administration, depression and suicide in some individuals. Conclusions The relationship between isotretinoin and depression may have implications for a greater understanding of the neurobiology of affective disorders. PMID:21903028

  4. Efficacy and safety of a 12-month treatment with a combination of hydroxypinacolone retinoate and retinol glycospheres as maintenance therapy in acne patients after oral isotretinoin.

    PubMed

    Bettoli, Vincenzo; Zauli, Stefania; Borghi, Alessandro; Toni, Giulia; Ricci, Michela; Bertoldi, Alberto M; Virgili, Annarosa

    2017-02-01

    A correct therapeutic management of acne should include a maintenance therapy to prevent recurrences after discontinuing a successful treatment. The aim of this study is to investigate efficacy and safety of a 12-month maintenance treatment with a product, based on Retinsphere technology that combines retinol encapsulated in glycospheres and hydroxypinacolone retinoate (Biretix gel®), to control acne relapse after a treatment with oral isotretinoin (O.I.). The study consisted of 2 phases: active treatment phase (AP) and maintenance phase (MP). In the AP, 40 consecutive patients with moderate facial acne were treated with O.I. until acne remission. Then, the patients entered in the MP and were treated with Biretix gel® once-daily for 12 months. The efficacy parameter was the relapse rate during MP. Thirty-nine patients completed the study. Relapse appeared in 6 patients (15.38%). The new product with Retinsphere technology was well tolerated and none of the subjects complained of adverse events. Our findings seems to provide favorable evidence of the efficacy and the safety of this new product in the maintenance treatment after O.I. in patient with moderate acne. The efficacy is maintain for a period as long as a year after O.I. suspension.

  5. Isotretinoin

    MedlinePlus

    ... activities you used to enjoy, poor performance at school or work, sleeping more than usual, difficulty falling asleep or staying asleep, irritability, anger, aggression, changes in appetite or weight, difficulty concentrating, withdrawing ...

  6. Effect of retinoic acid on aquaporin 3 expression in keratinocytes.

    PubMed

    Xing, F; Liao, W; Jiang, P; Xu, W; Jin, X

    2016-03-11

    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.

  7. Evaluation of compliance with isotretinoin PPP recommendations and exploration of reasons for non-compliance: Survey among French-speaking health care professionals and patients in Belgium.

    PubMed

    Lelubre, Mélanie; Hamdani, Jamila; Senterre, Christelle; Amighi, Karim; Peres, Marion; Schneider, Marie-Paule; Bugnon, Olivier; De Vriese, Carine

    2018-05-03

    To evaluate awareness of and compliance in Belgium by French-speaking health care professionals and patients with the isotretinoin safety recommendations regarding its teratogenic risk. Survey using online questionnaires, delivered from December 2014 to March 2015 for patients, pharmacists, dermatologists, and GPs and delivered again from September 2015 to October 2015 for GPs. Questionnaires were completed by 24 dermatologists, 24 GPs, 58 pharmacists, and 33 female patients. The pregnancy prevention programme was poorly known by health care professionals (23.6%) and patients (15.2%). Health care professionals informed women of childbearing age in depth about the teratogenic risk (98.3% of pharmacists and 100.0% of GPs and dermatologists) and the importance of an effective contraceptive method (87.9% and 100.0%, respectively). Patients were less informed about the pregnancy test (25.9% and 14.6%) and the need to use a second contraceptive method (29.3% and 27.1%). The low compliance with the last 2 recommendations was due to a lack of adoption by health care professionals regarding the need for these recommendations if female patients have an effective contraceptive method and the pregnancy risk is discussed in detail with them. The effectiveness of the pregnancy prevention programme recommendations should be reconsidered by an expert committee. Justifications should be added to effective recommendations to increase their adoption by health care professionals and patients. Copyright © 2018 John Wiley & Sons, Ltd.

  8. Changing the calculus of pediatric product development: narrowing the too-big gap between need and solution in a small market.

    PubMed

    Campbell, Sarah

    2015-01-01

    First, Deliece Hofen drops the pill into hot water to soften the outside coating. Then, she slices through the center of the pill with an X-ACTO knife and squeezes the isotretinoin inside into a syringe. With the drug in liquid form, she can now administer it to her ten-year-old son Brandon. ?The problem is...some of [the isotretinoin] is still left inside of the capsule and I?m not getting an exact dosage,? admits Hofen.

  9. Schools of pharmacology: retinoid update.

    PubMed

    Scheinfeld, Noah

    2006-10-01

    The most widely used retinoids include topical tretinoin (Retin-A), adapalene (Differin), topical tazarotene (Tazorac), isotretinoin (Accutane), and acitretin (Soriatane). This article will review new uses and developments in tazarotene (its failure to secure FDA approval in oral form for psoriasis), adapalene (its new 0.3% gel form and use in rosacea), alitretinoin (its use in photoaging), bexarotene (its use for psoriasis and chronic hand dermatitis), isotretinoin (the IPledge program, its use for neuroblastoma and branded formulation pharmacological superiority to generics), and retinoic acid metabolism-blocking agents (RAMBAs) (liarazole use for ichthyosis and psoriasis).

  10. Cheilitis in acne vulgaris patients with no previous use of systemic retinoid products.

    PubMed

    Balighi, Kamran; Daneshpazhooh, Maryam; Lajevardi, Vahideh; Talebi, Shahin; Azizpour, Arghavan

    2017-08-01

    Isotretinoin is commonly used in the treatment of acne vulgaris. While one of the more common side-effects is cheilitis, we have observed an increased incidence of cheilitis prior to the commencement of systemic isotretinoin. The aim of this study was to assess the prevalence of cheilitis among acne vulgaris patients. A non-interventional cross-sectional study of patients with acne vulgaris. Patients with previous use of systemic retinoids were excluded. The patients were examined for signs and symptoms of cheilitis. Of a total of 400 patients, 134 (34%) had evidence of cheilitis at initial presentation. Two-thirds (63%) were female (P < 0.001). The distribution of the cheilitis was as follows; 55% on the lower lip, 30% on both lips, and 16% on the upper lip. Over a quarter (27%) of patients with cheilitis had acne excorie, compared with only 8% of patients with no signs of cheilitis. Our findings suggest that cheilitis is quite common among acne vulgaris patients even before treatment with isotretinoin. © 2016 The Australasian College of Dermatologists.

  11. Cutaneous fungal microbiome: Malassezia yeasts in seborrheic dermatitis scalp in a randomized, comparative and therapeutic trial.

    PubMed

    Kamamoto, C S L; Nishikaku, A S; Gompertz, O F; Melo, A S; Hassun, K M; Bagatin, E

    2017-01-01

    Malassezia spp in skin microbiome scalp has been implicated in seborrheic dermatitis pathogenesis. Thus, treatment based in antifungal combined to topical keratolitic agents have been indicated as well as oral isotretinoin as it reduces the sebum production, glandular's size and possesses anti-inflammatory properties. This randomized, comparative and therapeutic trial aimed toper form the genotypic identification of Malassezia species before and after low-dose oral isotretinoin or topical antifungal treatments for moderate to severe seborrhea and/or seborrheic dermatitis on scalp. Scales and sebum of the scalp were seeded in the middle of modified Dixon and incubated at 32°C. For genotypic identification polymerase chain reaction primers for the ITS and D1/D2 ribossomal DNA were used and followed by samples sequencing. The procedure was conducted before and after therapeutic and randomized intervention for moderate to severe seborrhea/seborrheic dermatitis on the scalp, including oral isotretinoin, 10 mg, every other day and anti-seborrheic shampoo (piroctone olamine), over six months. The M. globosa and M. restricta were the most frequent species isolated on the scalp before and after both treatments. Other non- Malassezia species were also identified. The Malassezia spp. were maintained in the scalp after both treatments that were equally effective for the control of seborrhea/seborrheic dermatitis clinical signs.

  12. Acitretin

    MedlinePlus

    ... such as adapalene (Differen, in Epiduo), alitretinoin (Panretin), isotretinoin (Absorica, Accutane, Amnesteem, Claravis, Myorisan, Sotret, Zenatane), tazarotene (Avage, Fabior, Tazorac), tretinoin (Atralin, Avita, Renova, Retin-A), or any of ...

  13. Cutaneous fungal microbiome: Malassezia yeasts in seborrheic dermatitis scalp in a randomized, comparative and therapeutic trial

    PubMed Central

    Kamamoto, C. S. L.; Nishikaku, A. S.; Gompertz, O. F.; Melo, A. S.; Hassun, K. M.; Bagatin, E.

    2017-01-01

    ABSTRACT Malassezia spp in skin microbiome scalp has been implicated in seborrheic dermatitis pathogenesis. Thus, treatment based in antifungal combined to topical keratolitic agents have been indicated as well as oral isotretinoin as it reduces the sebum production, glandular's size and possesses anti-inflammatory properties. This randomized, comparative and therapeutic trial aimed toper form the genotypic identification of Malassezia species before and after low-dose oral isotretinoin or topical antifungal treatments for moderate to severe seborrhea and/or seborrheic dermatitis on scalp. Scales and sebum of the scalp were seeded in the middle of modified Dixon and incubated at 32°C. For genotypic identification polymerase chain reaction primers for the ITS and D1/D2 ribossomal DNA were used and followed by samples sequencing. The procedure was conducted before and after therapeutic and randomized intervention for moderate to severe seborrhea/seborrheic dermatitis on the scalp, including oral isotretinoin, 10 mg, every other day and anti-seborrheic shampoo (piroctone olamine), over six months. The M. globosa and M. restricta were the most frequent species isolated on the scalp before and after both treatments. Other non-Malassezia species were also identified. The Malassezia spp. were maintained in the scalp after both treatments that were equally effective for the control of seborrhea/seborrheic dermatitis clinical signs. PMID:29484095

  14. Why Do I Get Acne?

    MedlinePlus

    ... contact with oil — like in a fast-food restaurant or gas station, for example — be sure to ... medicines such as isotretinoin, or even having minor surgery. Some girls find that birth control pills help ...

  15. Determination of highly protein bound drugs in plasma using high-performance liquid chromatography and column switching, exemplified by the retinoids.

    PubMed

    Wyss, R; Bucheli, F

    1988-12-02

    During method development for the determination of either isotretinoin, tretinoin and their 4-oxo-metabolites, or etretinate, acitretin and 13-cis-acitretin in plasma using high-performance liquid chromatography and column switching, recovery problems arose, when undiluted plasma samples were injected directly onto the precolumn. These recovery problems may be due to the strong binding of the retinoids to different plasma proteins. Measures to overcome this strong protein binding, such as variation of the injection solution composition and the purge mobile phase, were systematically investigated. Best recoveries were obtained by diluting of plasma with 9 mM sodium hydroxide-acetonitrile (8:2, v/v) and protein precipitation with ethanol for the isotretinoin and etretinate series, respectively, in combination with the use of a purge mobile phase containing ammonium acetate and 10-20% acetonitrile. Less effective was the use of a longer precolumn or heating of the precolumn.

  16. A risk assessment of topical tretinoin as a potential human developmental toxin based on animal and comparative human data.

    PubMed

    Johnson, E M

    1997-03-01

    Although topically applied all-trans-retinoic acid (tretinoin) undergoes minimal absorption and adds negligibly to normal endogenous levels, its safety in humans is occasionally questioned because oral ingestion of retinoids at therapeutic levels is known to entail teratogenic risks. To assess the actual potential for developmental toxicity from treatment with topical tretinoin. Risk assessments were conducted on four known human developmental toxicants (valproic acid, methotrexate, thalidomide, and isotretinoin) and a potential developmental toxicant (acetylsalicylic acid). The margin of safety for each chemical was calculated from the ratio of animal no-observed adverse effect levels to human lowest-observed adverse effect levels or estimated exposure doses. The derived safety margin of more than 100 for topical tretinoin (with 2% absorption) contrasted sharply with the near unity values for valproic acid, methotrexate, thalidomide, and isotretinoin and was larger than that for acetylsalicylic acid. These data support other epidemiologic and animal data that topical tretinoin is not a potential human developmental toxicant.

  17. Tretinoin: a review of the nonclinical developmental toxicology experience.

    PubMed

    Kochhar, D M; Christian, M S

    1997-03-01

    Tretinoin has been thoroughly evaluated for its potential as an embryofetal developmental toxicant. Oral tretinoin produces developmental anomalies in animal models; the minimal teratogenic dose is consistently 2.5 to 10 mg/kg. In contrast, topical application does not induce developmental malformations in laboratory animals. A structurally related compound, isotretinoin, is a potent toxicant in humans and animals; the lowest systemic dose that induces fetal anomalies varies more than 100-fold depending on the model. Oral isotretinoin is a more potent developmental toxicant than oral tretinoin in monkeys. Between-drug differences in the metabolism and transplacental transfer of the two retinoids account for the differences in toxicant potency. Pharmacokinetic studies reveal that absorption of tretinoin from the skin is poor and yields maternal plasma concentrations below the developmentally toxic threshold established after oral administration. Analysis of outcomes of developmental toxicology and pharmacokinetic studies suggests that the human risk of fetal anomalies is negligible after therapeutic application of topical tretinoin.

  18. Evaluation of nasal and oropharyngeal flora in patients with acne vulgaris according to treatment options.

    PubMed

    Ozuguz, Pınar; Callioglu, Elif E; Tulaci, Kamil G; Kacar, Seval D; Balta, Ilknur; Asik, Gulsah; Karatas, Serap; Karaca, Semsettin

    2014-11-01

    The aim of this study was to evaluate changes in nasal and oropharyngeal flora in patients with acne during treatments with tetracycline and isotretinoin. Swab specimens were taken from the right and left nasal cavities and oropharynx of 55 patients with acne and 20 healthy volunteers who were admitted to the dermatology department (Etlik Educational and Research Hospital, Ankara, Turkey) before the administration of treatment and in the third month of treatment. Study participants were divided into four groups as follows: patients with acne on topical treatment only, systemic isotretinoin, and systemic tetracycline, and the control group. Of 55 patients with acne, 18 were male and 37 were female. The mean age of the patients and the control group was 22.21 ± 4.22 and 21.95 ± 7.64, respectively. Staphylococcus aureus was isolated from the nasal flora of five patients, normal flora was suppressed in the oropharyngeal cultures of seven patients, and normal flora grew in the cultures of the other 20 patients who were on tetracycline treatment. On the other hand, normal flora grew in the nasal and oropharyngeal cultures of all the patients who were on isotretinoin treatment. Treatment options and follow-up procedures for acne vulgaris may lead to the development of bacterial resistance and damage to flora. In particular, systemic tetracycline treatment leads to changes in flora of the nose and throat in patients with acne with an increased carriage of S. aureus. Therefore, careful attention should be paid to the duration of tetracycline treatment in order to not increase the risk of disturbance of microbial flora. © 2014 The International Society of Dermatology.

  19. UV-induced isomerization of oral retinoids in vitro and in vivo in hairless mice.

    PubMed

    Berne, B; Rollman, O; Vahlquist, A

    1990-08-01

    Ultraviolet (UV) irradiation causes isomerization and destruction of many vitamin A analogues (retinoids). Using high-performance liquid chromatography (HPLC), we investigated in vitro and in vivo the effects of UV irradiation on 2 all-trans aromatic retinoids (etretinate and acitretin) and on 13-cis retinoic acid (isotretinoin). When etretinate and acitretin dissolved in ethanol were irradiated with UVB (280-320 nm; 10-336 mJ/cm2) or UVA (320-400 nm; 1-5 J/cm2), extensive and reproducible cis-isomerizations occurred at the 13-position (cis/trans ratio approximately 1.6 in all experiments) but there was no progressive photodegradation of the molecules. Irradiation of isotretinoin produced only moderate trans-isomerization but the sum of HPLC peak heights fell with increasing UV doses, being 72% of the original value after 336 mJ/cm2 of UVB. Hairless mice were given etretinate (50 mg/kg bw), acitretin (200 mg/kg) or isotretinoin (50 mg/kg) on days 1, 4 and 7 and were irradiated daily for 8 d with 13 mJ/cm2 UVB plus 1 J/cm2 UVA. Samples of serum, dorsal skin and liver were collected and retinoids analyzed by HPLC. In the etretinate and acitretin-treated, irradiated animals the serum concentrations of the 13-cis isomers were 2-6 times higher than in nonirradiated controls. Irradiated epidermis also contained significantly higher concentrations of 13-cis etretinate and 13-cis acitretin than did control epidermis. The serum and epidermal concentrations of all-trans etretinate and acitretin were unchanged or even increased after irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Osteochondroma in long-term survivors of high-risk neuroblastoma.

    PubMed

    Kushner, Brian H; Roberts, Stephen S; Friedman, Danielle N; Kuk, Deborah; Ostrovnaya, Irina; Modak, Shakeel; Kramer, Kim; Basu, Ellen M; Cheung, Nai-Kong V

    2015-06-15

    Osteochondromas are benign bony protrusions that can be spontaneous or associated with radiotherapy (RT). Current treatment of high-risk neuroblastoma includes dose-intensive chemotherapy, local RT, an anti-GD2 monoclonal antibody (MoAb), and isotretinoin. Late effects are emerging. The authors examined osteochondromas in 362 patients who were aged <10 years when diagnosed with neuroblastoma, had received a MoAb plus isotretinoin since 2000, and had survived >24 months from the time of the first dose of the MoAb. The incidence rate of osteochondroma was determined using the competing risks approach, in which the primary event was osteochondroma calculated from the date of neuroblastoma diagnosis and the competing event was death without osteochondroma. A total of 21 osteochondroma cases were found among 14 patients who were aged 5.7 to 15.3 years (median, 10.4 years) and 3.1 to 11.2 years (median, 8.2 years) from the time of neuroblastoma diagnosis. The cumulative incidence rate was 0.6% at 5 years and 4.9% at 10 years from the neuroblastoma diagnosis. Nine osteochondromas were revealed incidentally during assessments of neuroblastoma disease status or bone age. Thirteen osteochondromas were detected outside RT portals and had characteristics of spontaneous forms. Complications were limited to pain necessitating surgical resection in 3 patients, but follow-up was short at 0.3 to 7.7 years (median, 3.5 years). Osteochondromas in long-term survivors of neuroblastoma should be expected because these benign growths can be related to RT and these patients undergo radiologic studies over years, are monitored for late toxicities through and beyond adolescence, and receive special attention (because of concerns about disease recurrence) if they develop a bony protuberance. A pathogenic role for chemotherapy, anti-GD2 MoAbs, or isotretinoin remains speculative. © 2015 American Cancer Society.

  1. The neurobiology of retinoic acid in affective disorders.

    PubMed

    Bremner, J Douglas; McCaffery, Peter

    2008-02-15

    Current models of affective disorders implicate alterations in norepinephrine, serotonin, dopamine, and CRF/cortisol; however treatments targeted at these neurotransmitters or hormones have led to imperfect resolution of symptoms, suggesting that the neurobiology of affective disorders is incompletely understood. Until now retinoids have not been considered as possible contributors to affective disorders. Retinoids represent a family of compounds derived from vitamin A that perform a large number of functions, many via the vitamin A product, retinoic acid. This signaling molecule binds to specific retinoic acid receptors in the brain which, like the glucocorticoid and thyroid hormone receptors, are part of the nuclear receptor superfamily and regulate gene transcription. Research in the field of retinoic acid in the CNS has focused on the developing brain, in part stimulated by the observation that isotretinoin (13-cis retinoic acid), an isomer of retinoic acid used in the treatment of acne, is highly teratogenic for the CNS. More recent work has suggested that retinoic acid may influence the adult brain; animal studies indicated that the administration of isotretinoin is associated with alterations in behavior as well as inhibition of neurogenesis in the hippocampus. Clinical evidence for an association between retinoids and depression includes case reports in the literature, studies of health care databases, and other sources. A preliminary PET study in human subjects showed that isotretinoin was associated with a decrease in orbitofrontal metabolism. Several studies have shown that the molecular components required for retinoic acid signaling are expressed in the adult brain; the overlap of brain areas implicated in retinoic acid function and stress and depression suggest that retinoids could play a role in affective disorders. This report reviews the evidence in this area and describes several systems that may be targets of retinoic acid and which contribute to

  2. The Neurobiology of Retinoic Acid in Affective Disorders

    PubMed Central

    Bremner, J Douglas; McCaffery, Peter

    2009-01-01

    Current models of affective disorders implicate alterations in norepinephrine, serotonin, dopamine, and CRF/cortisol; however treatments targeted at these neurotransmitters or hormones have led to imperfect resolution of symptoms, suggesting that the neurobiology of affective disorders is incompletely understood. Until now retinoids have not been considered as possible contributors to affective disorders. Retinoids represent a family of compounds derived from Vitamin A that perform a large number of functions, many via the vitamin A product, retinoic acid. This signaling molecule binds to specific retinoic acid receptors in the brain which, like the glucocorticoid and thyroid hormone receptors, are part of the nuclear receptor superfamily and regulate gene transcription. Research in the field of retinoic acid in the CNS has focused on the developing brain, in part stimulated by the observation that isotretinoin (13-cis retinoic acid), an isomer of retinoic acid used in the treatment of acne, is highly teratogenic for the CNS. More recent work has suggested that retinoic acid may influence the adult brain; animal studies indicated that the administration of isotretinoin is associated with alterations in behavior as well as inhibition of neurogenesis in the hippocampus. Clinical evidence for an association between retinoids and depression includes case reports in the literature, studies of health care databases, and other sources. A preliminary PET study in human subjects showed that isotretinoin was associated with a decrease in orbitofrontal metabolism. Several studies have shown that the molecular components required for retinoic acid signaling are expressed in the adult brain ; the overlap of brain areas implicated in retinoic acid function and stress and depression suggest that retinoids could play a role in affective disorders. This report reviews the evidence in this area and describes several systems that may be targets of retinoic acid and which contribute

  3. A case of refractory chronic neutrophilic pustular folliculitis treated with adalimumab.

    PubMed

    Sand, Freja Laerke; Thomsen, Simon Francis

    2015-01-01

    Neutrophilic folliculitis is an often overlooked chronic condition characterized by a monomorphic eruption of "sterile" papulopustules. Neutrophilic folliculitis is often refractory to conventional treatment with topical and systemic antibiotics or isotretinoin. We report a case of severe pustular neutrophilic folliculitis successfully treated with the tumor necrosis factor-alpha inhibitor adalimumab. © 2014 Wiley Periodicals, Inc.

  4. [Perifolliculitis capitis abscedens et suffodiens (case report)].

    PubMed

    Tsiskarishvili, N V; Katsitadze, A G; Tsiskarishvili, Ts I

    2012-04-01

    Perifolliculitis capitis abscedens et suffodiens (PCAS) is rare chronic, suppurative and inflammatory scalp disease. Its aetiology and pathogenesis is not completely understood. The treatment is usually difficult and often disappointing. We report a case of 25-year-old male who presented with tender, fluctuant nodules and abscesses, with draining pus and patchy alopecia on his scalp for 3 years. A skin biopsy from scalp lesions revealed features that are characteristic of perifolliculitis. Initially, the patient was treated with periodic incision and drainage of the scalp abscesses. The answer was very poor. When admitted to our department, isotretinoin was started at daily dose of 30 mg, because initially his cholesterol and triglyceride levels were mildly increased. When dose was reduced to 10 mg the levels of cholesterol and triglyceride remained normal. A response to treatment was excellent and rapid. The treatment of PCAS represents usually difficulties and frustration for both the patient and the physician. A long course of isotretinoin can be considered as one of the most effective treatment for PCAS.

  5. 13-cis-retinoic acid competitively inhibits 3 alpha-hydroxysteroid oxidation by retinol dehydrogenase RoDH-4: a mechanism for its anti-androgenic effects in sebaceous glands?

    PubMed

    Karlsson, Teresa; Vahlquist, Anders; Kedishvili, Natalia; Törmä, Hans

    2003-03-28

    Retinol dehydrogenase-4 (RoDH-4) converts retinol and 13-cis-retinol to corresponding aldehydes in human liver and skin in the presence of NAD(+). RoDH-4 also converts 3 alpha-androstanediol and androsterone into dihydrotestosterone and androstanedione, which may stimulate sebum secretion. This oxidative 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) activity of RoDH-4 is competitively inhibited by retinol and 13-cis-retinol. Here, we further examine the substrate specificity of RoDH-4 and the inhibition of its 3 alpha-HSD activity by retinoids. Recombinant RoDH-4 oxidized 3,4-didehydroretinol-a major form of vitamin A in the skin-to its corresponding aldehyde. 13-cis-retinoic acid (isotretinoin), 3,4-didehydroretinoic acid, and 3,4-didehydroretinol, but not all-trans-retinoic acid or the synthetic retinoids acitretin and adapalene, were potent competitive inhibitors of the oxidative 3 alpha-HSD activity of RoDH-4, i.e., reduced the formation of dihydrotestosterone and androstandione in vitro. Extrapolated to the in vivo situation, this effect might explain the unique sebosuppressive effect of isotretinoin when treating acne.

  6. Isotretinoin and Other Retinoids During Pregnancy

    MedlinePlus

    ... due date Ovulation calendar Order bereavement materials News Moms Need Blog Stories & Media News & Media News Videos ... Tools & Resources Frequently asked media questions Blog: News Moms Need Share Your Story community Join us on ...

  7. [Isotretinoin embryopathy. Report of one case].

    PubMed

    Troncoso Sch, Mónica; Rojas H, Carla; Bravo C, Eduardo

    2008-06-01

    Retinoic acid is a widely used drug in the treatment of cystic acne. It has teratogenic effects that depend on the gestational period in which it is used. We report a seven months old female whose mother was exposed to retinoic acid in both pre-gestational and gestational periods. She had a retardation of psychomotor development and a brain MRI showed frontal atrophy and a malformation of the posterior fossa. We discuss the mechanisms of the teratogenic effects of retinoic acid.

  8. Common reasons why acne patients call the office.

    PubMed

    Barnes, Lauren E; Al-Dabagh, Amir; Huang, William W; Feldman, Steven R

    2014-05-16

    Communication between physicians and patients is essential to providing proper medical care. At times, patients leave visits with insufficiently addressed questions. These questions prompt patients to call the clinic for additional information, which disrupts the flow of care, delays proper treatment, and reduces patient satisfaction. We aim to examine acne patients' post-visit questions to develop interventions to improve patient education and reduce call backs. A retrospective electronic medical record chart review was performed involving Wake Forest Baptist Health Dermatology clinic visits between October 1, 2012 and October 31, 2012. We identified acne patients using clinic visit notes and recorded their telephone calls to the clinic between October 1, 2012 and March 29, 2013. Of 315 acne patients, 31 (9.8%) called the clinic. Isotretinoin was the subject of 66.7% of the calls, half of which involved questions about potential side effects. Other calls addressed topical medications, acne symptoms, and pharmacy requests. The study involved one center and email and fax correspondence was not captured. We found gaps in communication sufficient to require patients to call in for support, specifically regarding oral isotretinoin treatment. Interventions to address these questions have the potential to improve quality of care.

  9. Determination of endogenous levels of 13-cis-retinoic acid (isotretinoin), all-trans-retinoic acid (tretinoin) and their 4-oxo metabolites in human and animal plasma by high-performance liquid chromatography with automated column switching and ultraviolet detection.

    PubMed

    Wyss, R; Bucheli, F

    1997-10-24

    A highly sensitive HPLC method with automated column switching was developed for the simultaneous determination of endogenous levels of 13-cis-retinoic acid (isotretinoin), all-trans-retinoic acid (tretinoin) and their 4-oxo metabolites in plasma samples from man, Cynomolgus monkey, rabbit, rat and mouse. Plasma (0.4 ml) was deproteinated by adding ethanol (1.5 ml) containing the internal standard acitretin. After centrifugation, 1.4 ml of the supernatant were directly injected onto the precolumn packed with LiChrospher 100 RP-18 (5 microm). 1.25% ammonium acetate and acetic acid-ethanol (8:2, v/v) was used as mobile phase during injection and 1% ammonium acetate and 2% acetic acid-ethanol (102:4, v/v) was added, on-line, to decrease the elution strength of the injection solution. After backflush purging of the precolumn, the retained components were transferred to the analytical column in the backflush mode, separated by gradient elution and detected at 360 nm. Two coupled Superspher 100 RP-18 endcapped columns (both 250x4 mm) were used for the separation, together with a mobile phase consisting of acetonitrile-water-10% ammonium acetate-acetic acid: (A) 600:300:60:10 (v/v/v/v), (B) 950:20:5:20 (v/v/v/v), and (C) 990:5:0:5 (v/v/v/v). The method was linear in the range 0.3-100 ng/ml, at least, with a quantification limit of 0.3 ng/ml. The mean recoveries from human plasma were 93.2%-94.4% and the mean inter-assay precision was 2.8%-3.2% (range 0.3-100 ng/ml). Similar results were obtained for animal plasma. The analytes were found to be stable in the plasma of all investigated species stored at -20 degrees C for 4.3 months and at -80 degrees C for 9 months, at least. At this temperature, human plasma samples were even stable for 2 years. The method was successfully applied to more than 6000 human and 1000 animal plasma samples from clinical and toxicokinetic studies. Endogenous levels determined in control patients and pregnant women were similar to published data

  10. A phase IV, open-label study evaluating the use of triple-combination therapy with minocycline HCl extended-release tablets, a topical antibiotic/retinoid preparation and benzoyl peroxide in patients with moderate to severe acne vulgaris.

    PubMed

    Zaenglein, Andrea L; Shamban, Ava; Webster, Guy; Del Rosso, James; Dover, Jeffrey S; Swinyer, Leonard; Stein, Linda; Lin, Xiaoming; Draelos, Zoe; Gold, Michael; Thiboutot, Diane

    2013-06-01

    Moderate to severe acne vulgaris is often treated with a combination of an oral antibiotic, topical antibiotic/retinoid, and benzoyl peroxide (BP), but data are limited on the efficacy of this and other combination regimens that incorporate both oral and topical therapies.
    Patients were required to be aged 12-30 years with moderate to severe acne (grades 3-4 acne on the Investigator's Global Assessment [IGA]) and deemed potential candidates for treatment with isotretinoin. Enrolled patients were given triple-combination therapy, defined in this study as oral minocycline HCl extended release 1 mg/kg QD, 6% BP foaming cloths used QD, and clindamycin phosphate 1.2%/tretinoin 0.025% gel applied QD, and were evaluated at baseline and weeks 2, 4, 8, and 12.
    A total of 97 patients were enrolled in the study. At week 12, 89% of patients had at least a one-grade improvement from baseline IGA and 96% had at least a one-grade improvement from baseline Global Aesthetic Improvement Scale score. Mean ± SD in- flammatory, non-inflammatory, and total lesion counts decreased from baseline by 61.8% ± 38.3%, 48.8% ± 34.5%, and 56.5% ± 29.9%, respectively. The percentage of patients evaluated as candidates for isotretinoin by independent photographic review was 77% (69/90) at baseline and only 16% (14/90) at week 12. Treatment-related adverse events (AEs) occurred in eight of 97 (8%) patients. Triplecombination therapy was not associated with any serious AEs or AEs leading to discontinuation.
    Triple-combination therapy was well tolerated and substantially reduced facial acne lesion counts, with 84% of patients judged to no longer be candidates for isotretinoin therapy by study end. These data support the clinical observation that a triple-combination regimen incorporating oral minocycline (dosed by patient weight), BP foaming cloths 6% QD, and clindamycin phosphate 1.2%/ tretinoin 0.025% gel QD can substantially improve moderate to severe acne vulgaris.

  11. Acne vulgaris

    PubMed Central

    2011-01-01

    Introduction Acne vulgaris affects over 80% of teenagers, and persists beyond the age of 25 years in 3% of men and 12% of women. Typical lesions of acne include comedones, inflammatory papules, and pustules. Nodules and cysts occur in more severe acne and can cause scarring and psychological distress. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of topical and oral treatments in people with acne vulgaris? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 69 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: topical treatments (adapalene, azelaic acid, benzoyl peroxide, clindamycin, erythromycin [alone or plus zinc]; isotretinoin, tetracycline, tretinoin); and oral treatments (doxycycline, isotretinoin, lymecycline, minocycline, oxytetracycline, tetracycline). PMID:21477388

  12. Acne vulgaris.

    PubMed

    Purdy, Sarah; de Berker, David

    2011-01-05

    Acne vulgaris affects over 80% of teenagers, and persists beyond the age of 25 years in 3% of men and 12% of women. Typical lesions of acne include comedones, inflammatory papules, and pustules. Nodules and cysts occur in more severe acne and can cause scarring and psychological distress. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of topical and oral treatments in people with acne vulgaris? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 69 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: topical treatments (adapalene, azelaic acid, benzoyl peroxide, clindamycin, erythromycin [alone or plus zinc]; isotretinoin, tetracycline, tretinoin); and oral treatments (doxycycline, isotretinoin, lymecycline, minocycline, oxytetracycline, tetracycline).

  13. Tretinoin overdose: a first case report.

    PubMed

    Su-Yin, Adeline; Wong, Joyce; Wiegand, Timothy; Olson, Kent

    2009-06-01

    Tretinoin (Vesanoid) is an all-trans-retinoic acid, and is related to retinol (Vitamin A). To date, there have been several case reports on overdose with its isomer isotretinoin, but none involving overdose of tretinoin. We report the first known case of a patient who ingested a massive overdose of tretinoin. A 31-year-old man ingested 1000 mg of tretinoin (100 pills of Vesanoid 10 mg) in a suicide attempt. He developed nonbloody diarrhea, but otherwise had no complaints. Clinical examination was normal. The patient was treated with activated charcoal and was hydrated. The patient's blood results did not show any deterioration on the third consecutive day. He was discharged well on the third day, but was subsequently lost to follow-up. Although there has been no reported experience with acute tretinoin overdose in humans, our patient took a dose approximately 3 times the recommended maximum tolerated daily dose in patients with myelodysplastic syndrome or solid tumors (195 mg/m2 per day). Overdose with other retinoids such as isotretinoin have been associated with only minor symptoms that resolved quickly. Our patient had diarrhea, which also resolved quickly with symptomatic treatment and hydration. We believe this to be the first case report of an acute oral overdose of tretinoin. The patient developed diarrhea, but was otherwise asymptomatic.

  14. Steatocystoma multiplex generalisata partially suppurativa--case report.

    PubMed

    Fekete, Gyula László; Fekete, Júlia Edit

    2010-01-01

    Steatocystoma multiplex is a rare inherited disorder with an autosomal dominant mode of transmission, but sometimes it may appear sporadically. Usually the onset tends to occur during adolescence or early adult life. A clinical case of a 27-year-old male patient is presented. Since the age of 8, he had been presenting with multiple, asymptomatic, round-to-oval, well-defined, smooth-surfaced, yellow to skin-colored, 5- to 22-mm diameter cysts and nodules initially scattered on the trunk and lately disseminated all over the body with less lesions on the lower extremities. At one of follow-up visits, he presented with high fever, pain with tumefaction of the small and medium size joints of the palms and soles, and deteriorated general status with polymorphous skin lesions. Based on the clinical and paraclinical features, the diagnosis of steatocystoma multiplex generalisata partially suppurativa was made. He was treated with oral isotretinoin (1 mg/kg per day) for 14 weeks, antibiotics and local treatments. The lesions healed slowly, with local disfigurement, hyperpigmentation and unpleasant scars. Isotretinoin usually does not eradicate the condition but could be effective in suppurative abscesses. Steatocystoma multiplex generalisata is considered rare; the true incidence of the disease is unknown. In the disease evolution, the severe inflammatory variant, steatocystoma multiplex suppurativa, may appear at any time.

  15. Oily Skin: A review of Treatment Options

    PubMed Central

    Miller, Richard A.

    2017-01-01

    One of the most common dermatologic concerns is oily skin, and the demand for effective treatment options is ever apparent. This review article addresses numerous topical treatment options such as retinoids, olumacostat glasaretil, and various cosmeceutical agents. several systemic and procedural techniques that incorporate isotretinoin, spironolactone, oral contraceptives, botulinum toxin, photodynamic therapy, and lasers are reviewed as well. Each treatment option is analyzed in terms of the proposed mechanism of action, efficacy reported in the literature, and potential adverse effects. PMID:28979664

  16. Which acne treatment has the best influence on health-related quality of life? Literature review by the European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes.

    PubMed

    Chernyshov, P V; Tomas-Aragones, L; Manolache, L; Svensson, A; Marron, S E; Evers, A W M; Bettoli, V; Jemec, G B; Szepietowski, J C

    2018-05-05

    According to results of a recent literature search performed by the European Academy of Dermatology and Venereology (EADV) Task Forces (TF) on Quality of Life and Patient Oriented Outcomes (QoL and PO) and Acne, Rosacea and Hidradenitis Suppurativa (ARHS) most of publications where health-related (HR) QoL of acne patients was studied were clinical trials. Members of the EADV TF on QoL and PO decided to detect which acne treatment has the best influence on HRQoL of acne patients. A new literature search was organized to find publications on acne treatment where the HRQoL of patients was assessed as an outcome measure. From 186 papers with HRQoL assessment 37 papers were included for further analysis. Our results revealed that oral isotretinoin had the best influence on HRQoL of acne patients. Several other treatment methods also showed good effects on the HRQoL of acne patients. Oral isotretinoin and norethindrone acetate/ethinyl estradiol, topical clindamycin phosphate/benzoyl peroxide and adapalene/benzoyl peroxide showed significantly better effect on HRQoL than placebo. There is limited number of the high-quality studies on acne treatment where HRQoL were assessed. Dermatology-specific and acne-specific instruments showed much better sensitivity to successful therapeutic intervention than generic HRQoL instruments. The most frequently used HRQoL instrument was the DLQI questionnaire. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Familial atrophia maculosa varioliformis cutis: first case report from the Indian subcontinent with pedigree analysis.

    PubMed

    Goyal, Tarang; Varshney, Anupam; Bakshi, S K

    2012-01-01

    Familial atrophia maculosa varioliformis cutis is a very rare disorder with less than 28 cases being reported in the literature worldwide and remains a mystery both as far as genetics and the virtue of its pathogenesis is concerned. We present a case of mother and son, both having this disorder with presentations unique in terms of sites involved and try to draw a five generations pedigree chart for the same. We further support its inheritance pattern as autosomal dominant. Also, we propose oral isotretinoin as an effective treatment modality for the same.

  18. A review of tazarotene in the treatment of photodamaged skin

    PubMed Central

    Ogden, Stephanie; Samuel, Miny; Griffiths, Christopher EM

    2008-01-01

    Chronic sun exposure leads to photodamage, which is characterized clinically by fine and coarse wrinkles, dyspigmentation, telangiectasia, laxity, roughness and a sallow appearance. Many treatments claim to reduce the signs of photodamage, however evidence from randomized controlled trials (RCT) to support these claims is limited. The use of topical retinoids, particularly tretinoin, isotretinoin and tazarotene, has been shown to significantly reduce signs of photodamage both clinically and histologically. Over recent years a number of RCTs, have affirmed that topical tazarotene is an effective and safe treatment for photodamaged skin. PMID:18488880

  19. Facial porokeratosis: A series of six patients.

    PubMed

    Gutierrez, Ericson L; Galarza, Carlos; Ramos, Willy; Tello, Mercedes; De Paz, Patricia Chávez; Bobbio, Lucia; Barquinero, Alicia; Ronceros, Gerardo; Ortega-Loayza, Alex G

    2010-08-01

    Porokeratosis is a disorder of epidermal keratinization characterized by annular plaques with an atrophic centre and hyperkeratotic edges, and includes a heterogeneous group of disorders that are mostly inherited in an autosomal dominant fashion. Facial porokeratosis is rare and is not well documented. We present six cases of facial porokeratosis seen over a period of 15 years in a hospital in Lima, Peru. In most of the cases, porokeratosis was found in younger women without any significant past medical history. Oral isotretinoin showed moderate improvement in two of our patients.

  20. The high sensitivity of the rabbit to the teratogenic effects of 13-cis-retinoic acid (isotretinoin) is a consequence of prolonged exposure of the embryo to 13-cis-retinoic acid and 13-cis-4-oxo-retinoic acid, and not of isomerization to all-trans-retinoic acid.

    PubMed

    Tzimas, G; Bürgin, H; Collins, M D; Hummler, H; Nau, H

    1994-01-01

    Previous studies suggested that the rabbit is much more susceptible to the teratogenic action of 13-cis-retinoic acid (13-cis-RA) than the mouse or the rat, while the teratogenicity of all-trans-RA was comparable in these species. In the present study we investigated if pharmacokinetics can explain these species- and structure-related differences. The embryotoxic and teratogenic potential of all-trans-retinoic acid (all-trans-RA) and 13-cis-RA were evaluated in the Swiss hare rabbit after oral administration of daily doses of the two drugs throughout organogenesis, from gestation day (GD) 6 to 18 (plug day = GD 0). All-trans-RA was given at dose levels of 0.7, 2 or 6 mg/kg body weight per day and 13-cis-RA at 3, 7.5 or 10 mg/kg per day. The doses needed to elicit a minimum teratogenic response were found to be 6 mg/kg per day for all-trans-RA and 10 mg/kg per day for 13-cis-RA. Using these doses, transplacental pharmacokinetics of all-trans- and 13-cis-RA were performed. Pregnant rabbits were treated once daily from GD 7 to 12 and plasma and embryo samples were collected for HPLC analysis at various time intervals after the final dose. The main plasma metabolites of all-trans- and 13-cis-RA were all-trans-beta-glucuronide (all-trans-RAG) and 13-cis-4-oxo-RA, respectively. The elimination of 13-cis-RA and its metabolites from maternal plasma were much slower than of all-trans-RA resulting in accumulation of the 13-cis-isomers in plasma. Marked differences in the placental transfer of the two drugs and their metabolites were observed. All-trans-RA and all-trans-4-oxo-RA were efficiently transferred to the rabbit embryo, reaching concentrations similar to the plasma levels. On the contrary, the 13-cis-isomers reached the embryo to a lesser extent. Despite its limited placental transfer, a considerable embryonic exposure to 13-cis-RA and 13-cis-4-oxo-RA was noticed after treatment with isotretinoin, as indicated by their area-under-the-concentration-time-curve (AUC

  1. The retinoids. A review of their clinical pharmacology and therapeutic use.

    PubMed

    Orfanos, C E; Ehlert, R; Gollnick, H

    1987-10-01

    With the introduction of the synthetic retinoids, oral therapy with an acceptable risk/benefit ratio became possible for a variety of skin diseases including severe acne, psoriasis and numerous genodermatoses. This article reviews the clinical pharmacology, mechanisms of action and therapeutic use of the retinoids, particularly isotretinoin (13-cis-retinoic acid) and etretinate. The free aromatic acid of etretinate, etretin, and the new polyaromatic retinoid compounds (arotinoids) are also discussed. Isotretinoin is used clinically for oral therapy of severe acne, but is also recommended for severe Gram-negative folliculitis and rosacea not responding to traditional therapy. The results of several studies have established that acne therapy should be started with 1.0 mg/kg/day for 2 to 3 months after which the daily dosage should be lowered to 0.2 to 0.5 mg/kg/day for another 2 to 3 months. This therapeutic regimen of isotretinoin has proven to be the most successful in preventing relapses. Etretinate is particularly useful for oral therapy of widespread plaque-like, pustular and erythrodermic psoriasis, and of generalised lichen planus, Darier's disease and severe congenital ichthyoses. Whereas pustular forms of psoriasis require a high daily dosage of 1.0 mg/kg/day, erythrodermic psoriasis should be treated with a lower dosage of 0.25 to 0.35 mg/kg/day. In chronic plaque-like psoriasis, a mean daily dosage of 0.5 mg/kg/day over several weeks to months, usually combined with photo(chemo)therapy, tar or dithranol, is recommended. Other indications for oral etretinate therapy are adequately treated with a moderate dosage of 0.4 to 0.75 mg/kg/day. Etretin differs from etretinate in having a much shorter elimination half-life of 2 to 3 days, in contrast to 80 to 100 days after long term administration of etretinate. Moreover, it has not been shown to increase serum cholesterol levels. However, its clinical efficacy is not yet clearly established. Among the arotinoids

  2. In vitro interaction study of retinoic acid isomers with telmisartan and amlodipine by equilibrium dialysis method using UV spectroscopy

    NASA Astrophysics Data System (ADS)

    Varghese, Susheel John; Johny, Sojimol K.; Paul, David; Ravi, Thengungal Kochupappy

    2011-07-01

    The in vitro protein binding of retinoic acid isomers (isotretinoin and tretinoin) and the antihypertensive drugs (amlodipine and telmisartan) was studied by equilibrium dialysis method. In this study, free fraction of drugs and the % of binding of drugs in the mixture to bovine serum albumin (BSA) were calculated. The influence of retinoic acid isomers on the % of protein binding of telmisartan and amlodipine at physiological pH (7.4) and temperature (37 ± 0.5 °C) was also evaluated. The in vitro displacement interaction study of drugs telmisartan and amlodipine on retinoic acid isomers and also interaction of retinoic acid isomers on telmisartan and amlodipine were carried out.

  3. Can transforming growth factor-beta1 and retinoids modify the activity of estradiol and antiestrogens in MCF-7 breast cancer cells?.

    PubMed

    Czeczuga-Semeniuk, Ewa; Anchim, Tomasz; Dziecioł, Janusz; Dabrowska, Milena; Wołczyński, Sławomir

    2004-01-01

    Retinoic acid and transforming growth factor-beta (TGF-beta) affect differentiation, proliferation and carcinogenesis of epithelial cells. The effect of both compounds on the proliferation of cells of the hormone sensitive human breast cancer cell line (ER+) MCF-7 was assessed in the presence of estradiol and tamoxifen. The assay was based on [3H]thymidine incorporation and the proliferative activity of PCNA- and Ki 67-positive cells. The apoptotic index and expression of the Bcl-2 and p53 antigens in MCF-7 cells were also determined. Exogenous TGF-beta1 added to the cell culture showed antiproliferative activity within the concentration range of 0.003-30 ng/ml. Irrespective of TGF-beta1 concentrations, a marked reduction in the stimulatory action of estradiol (10(-9) and 10(-8) M) was observed whereas in combination with tamoxifen (10(-7) and 10(-6) M) only 30 ng/ml TGF-beta1 caused a statistically significant reduction to approximately 30% of the proliferative cells. In further experiments we examined the effect of exposure of breast cancer cells to retinoids in combination with TGF-beta1. The incorporation of [3H]thymidine into MCF-7 cells was inhibited to 52 +/- 19% (control =100%) by 3 ng/ml TGF-beta1, and this dose was used throughout. It was found that addition of TGF-beta1 and isotretinoin to the culture did not decrease proliferation, while TGF-beta1 and tretinoin at low concentrations (3 x 10(-8) and 3 x 10(-7) M) reduced the percentage of proliferating cells by approximately 30% (67+/-8% and 67+/-5%, P<0.05 compared to values in the tretinoin group). Both retinoids also led to a statistically significant decrease in the stimulatory effect of 10(-9) M estradiol, attenuated by TGF-beta1. In addition, the retinoids in combination with TGF-beta1 and tamoxifen (10(-6) M) caused a further reduction in the percentage of proliferating cells. Immunocytochemical analysis showed that all the examined compounds gave a statistically significant reduction in the

  4. Memory disorders associated with consumption of drugs: updating through a case/noncase study in the French PharmacoVigilance Database.

    PubMed

    Chavant, Francois; Favrelière, Sylvie; Lafay-Chebassier, Claire; Plazanet, Caroline; Pérault-Pochat, Marie-Christine

    2011-12-01

    To investigate putative associations of reports of memory disorders and suspected drugs. We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were reports of memory loss in the FPVD between January 2000 and December 2009. Noncases were all other reports during the same period. To assess the association between memory impairment and drug intake, we calculated an odds ratio with its 95% confidence interval. Among the 188,284 adverse drug reactions recorded, we identified 519 cases of memory loss. The sex ratio was 0.6 and the median age was 54 years (range 4-93). The maximal number of cases occurred between 40-49 and 50-59 years. Evolution was favourable in 63% of the cases. We found significant odds ratios for benzodiazepines (alprazolam, bromazepam, prazepam, clonazepam etc.), benzodiazepine-like hypnotics (zolpidem and zopiclone), antidepressants (fluoxetine, paroxetine and venlafaxine), analgesics (morphine, nefopam and tramadol), anticonvulsants (topiramate, pregabalin, levetiracetam etc.), antipsychotics (aripiprazole and lithium) and other drugs, such as trihexyphenidyl, ciclosporin and isotretinoin. Our study confirmed an association between memory disorders and some drugs, such as benzodiazepines and anticonvulsants. However, other drugs, such as benzodiazepine-like hypnotics, newer anticonvulsants, serotonin reuptake inhibitor antidepressants, isotretinoin and ciclosporin were significantly associated with memory disorders, although this was not described or poorly described in the literature. Taking account of the limits of this study in the FPVD (under-reporting, notoriety bias etc.), the case/noncase method allows assessment and detection of associations between exposure to drugs and a specific adverse drug reaction, such as memory disorders, and could thus generate signals and orientate us to further prospective studies to confirm such associations. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011

  5. Embryonic subcellular distribution of 13-cis- and all-trans-retinoic acid indicates differential cytosolic/nuclear localization.

    PubMed

    Rühl, R; Plum, C; Elmazar, M M; Nau, H

    2001-09-01

    Isotretinoin (13-cis-retinoic acid [13CRA], Accutane) is used for the treatment of dermatological diseases. Isotretinoin is, however, teratogenic in animals and humans. The mechanism of action of its teratogenicity is still not clearly identified. It has little or no binding properties to cytosolic retinoid-binding proteins or nuclear retinoid receptors (RAR, RXR). One hypothesis is that the teratogenicity of 2 approximately equipotent teratogenic doses of 13CRA and all-trans-retinoic acids (ATRA) could mainly be correlated to ATRA in the nuclei, where the retinoic acid receptors (RARs) are located. To test this hypothesis, female mice at gestational day 11 were treated with approximately equipotent teratogenic doses of 13-cis-retinoic acid (100 mg/kg orally) or all-trans-retinoic acid (10 mg/kg orally) and sacrificed 1 h and 4 h after administration. Embryos were homogenized and centrifuged into 4 fractions, and the purity of the fractions was tested by quantification of marker constituents for various cell compartments. We analyzed, by RP-HPLC, nuclear, mitochondrial, microsomal, and cytosolic fractions, as well as embryo homogenate and maternal plasma. After treatment with 13-cis-retinoic acid, this substance was mainly located in the nuclear fraction of the embryo (approximately 82%), whereas all-trans-retinoic acid, after ATRA treatment, was mainly located in the cytosolic supernatant (approximately 64%). The binding to cellular retinoid-binding protein (CRABP) may limit the access of ATRA to the nucleus, in contrast to 13CRA, which does not bind to CRABP. The concentration of ATRA in the nuclear fraction was similar after administration of either 13CRA or ATRA. The teratogenic activity of 13-cis-retinoic acid could therefore be explained by its access to the nucleus and its possible conversion to all-trans-retinoic acids, which will interact with the nuclear retinoid receptors.

  6. Perception of teratogenic and foetotoxic risk by health professionals: a survey in Midi-Pyrenees area.

    PubMed

    Damase-Michel, Christine; Pichereau, Juliette; Pathak, Atul; Lacroix, Isabelle; Montastruc, Jean Louis

    2008-01-01

    Counselling or prescribing drugs during pregnancy requires health professionals to assess risk/benefit ratio for women and their baby. A misperception of the risk may lead to inappropriate decisions for pregnancy outcomes. The aim of the present study was to assess teratogenic and/or foetotoxic risk perception of common medications by general practitioners (GPs) and community pharmacists (CPs) from the Midi-Pyrenees area. 103 GPs and 104 CPs were interviewed. For 21 given drugs, a visual-analogue scale was used to evaluate the risk to give birth to a malformed infant if the mother had taken the drug during first trimester of pregnancy. For 9 drugs, health professionals had to say if they thought there was a potential foetotoxic and/or neonatal risk when drugs were administered during late pregnancy. 97% and 91% of GPs and CPs respectively thought that isotretinoin and thalidomide are teratogenic and more than 80% thought that amoxicillin and acetaminophen are safe in early pregnancy. However, 19% of the GPs and 33% of CPs answered there were no teratogenic risk for valproate. Around 11% of both GPs and CPs said that warfarin was safe during pregnancy. For 22% of GPs and for 13% and 27% of CPs respectively, ibuprofen and enalapril were safe on late pregnancy. For each drug, mean value of perceived teratogenic risk by health professionals was higher than values that can be found in scientific references. Concerning isotretinoin, thalidomide and metoclopramide, perceived teratogenic risk was higher for CPs. These data show that the potential teratogenic and foetotoxic risk of several commonly used drugs is unknown by health professionals. Conversely, GPs and CPs who think that a risk exists, overestimate it. This misperception can lead to inappropriate decisions for pregnancy outcomes.

  7. Keratosis follicularis spinulosa decalvans and acne keloidalis nuchae.

    PubMed

    Goh, Michelle S Y; Magee, Jill; Chong, Alvin H

    2005-11-01

    A 27-year-old man presented with a 10-year history of scarring alopecia on the vertex of the scalp associated with follicular crusting and pustule formation, and a papular eruption on the posterior neck. Additionally, there was keratosis pilaris on the cheeks, eyebrows and thighs. Histology from the vertex showed scarring with a mixed perifollicular inflammatory infiltrate and foci of acute suppurative folliculitis. With clinical correlation, the diagnosis of keratosis follicularis spinulosa decalvans and concurrent acne keloidalis nuchae was made. The association of keratosis follicularis spinulosa decalvans with acne keloidalis nuchae has not previously been described. The patient responded to treatment with oral isotretinoin 20 mg (0.25 mg/kg) daily for 12 months.

  8. In vitro interaction study of retinoic acid isomers with telmisartan and amlodipine by equilibrium dialysis method using UV spectroscopy.

    PubMed

    Varghese, Susheel John; Johny, Sojimol K; Paul, David; Ravi, Thengungal Kochupappy

    2011-07-01

    The in vitro protein binding of retinoic acid isomers (isotretinoin and tretinoin) and the antihypertensive drugs (amlodipine and telmisartan) was studied by equilibrium dialysis method. In this study, free fraction of drugs and the % of binding of drugs in the mixture to bovine serum albumin (BSA) were calculated. The influence of retinoic acid isomers on the % of protein binding of telmisartan and amlodipine at physiological pH (7.4) and temperature (37±0.5°C) was also evaluated. The in vitro displacement interaction study of drugs telmisartan and amlodipine on retinoic acid isomers and also interaction of retinoic acid isomers on telmisartan and amlodipine were carried out. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Vitamin A supplementation increases levels of retinoic acid compounds in human plasma: possible implications for teratogenesis.

    PubMed

    Eckhoff, C; Nau, H

    1990-01-01

    The concentrations of retinoic acid compounds were monitored by a newly developed highly sensitive HPLC procedure in plasma of six volunteers who received 833 IU vitamin A per kg body weight per day during a 20-day period. There was a significant increase of all-trans-retinoic acid (two-fold), 13-cis-retinoic acid (7-fold) and 13-cis-4-oxoretinoic acid (5-fold) over endogenous plasma levels of these retinoids. The same compounds had previously been found after treatment with the teratogenic drug isotretinoin (Roaccutan, Accutane). Our results raise the possibility that high vitamin A intake may carry a teratogenic risk attributable to increased levels of retinoic acid compounds generated from retinol by metabolic processes.

  10. Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma

    ClinicalTrials.gov

    2017-05-25

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Recurrent Adult Brain Tumor

  11. Minor malformations characteristic of the retinoic acid embryopathy and other birth outcomes in children of women exposed to topical tretinoin during early pregnancy.

    PubMed

    Loureiro, Kirsten D; Kao, Kelly K; Jones, Kenneth Lyons; Alvarado, Sonia; Chavez, Carmen; Dick, Lyn; Felix, Robert; Johnson, Diana; Chambers, Christina D

    2005-07-15

    Topical tretinoin (Retin-A) is used to treat acne and photodamaged skin. Its teratogenic potential is of concern due to its similarity to isotretinoin (Accutane), a recognized human teratogen. Through the California Teratogen Information Service and Clinical Research Program, between 1983 and 2003, 106 pregnant women with first-trimester exposure to topical tretinoin were prospectively ascertained and followed. Birth outcomes, including pregnancy loss, major structural defects, and pre- and postnatal growth were compared to 389 similarly and prospectively ascertained women with no topical tretinoin exposure during pregnancy. Because a distinct pattern of malformation had already been described for isotretinoin, we also compared exposed (n = 62) and unexposed (n = 191) infants on the prevalence of a specific subset of minor malformations selected to represent the spectrum of defects comprising the retinoic acid embyopathy. There were no significant differences between groups in the proportion of pregnancies ending in spontaneous abortion (6.6% in exposed vs. 8.5% in unexposed; P = 0.53), or infants with major structural defects (2.2% in exposed vs. 1.2% in unexposed; P = 0.62). In addition, the groups were similar in birth weight, length and head circumference, and there were no significant differences between groups in length of gestation. Furthermore, the prevalence of one or more retinoic acid-specific minor malformations did not differ significantly between groups (12.9% in exposed vs. 9.9% in unexposed; P = 0.51). First-trimester topical tretinoin exposure in this study was not associated with an increased risk of any adverse pregnancy outcome evaluated. Specifically, there was no indication that topical tretinoin is associated with an increased risk for minor malformations that are consistent with the retinoic acid embryopathy. Although it is impossible to exclude the possibility that some women/infants may be uniquely susceptible to topical tretinoin exposure

  12. Treatment of Annular Elastolytic Giant Cell Granuloma With Topical Tretinoin.

    PubMed

    Wagenseller, Aubrey; Larocca, Cecilia; Vashi, Neelam A

    2017-07-01

    Annular elastolytic giant cell granuloma, also known as actinic granuloma, is a rare skin condition with a chronic course that is often resistant to treatment. Literature is sparse, and only a handful of case reports are available to guide treatment decisions. Typical first line treatment options include topical and intralesional steroids, topical pimecrolimus, and cryotherapy. Resistant cases have been treated with cyclosporine, systemic steroids, antimalarials, and oral retinoids. In particular, acitretin and isotretinoin have shown success in three cases. However, these medications can have side effects and require frequent lab monitoring. We present a case of a 47-year-old woman with bilateral forearm lesions consistent with annular elastolytic giant cell granuloma who was successfully treated with topical tretinoin.

    J Drugs Dermatol. 2017;16(7):699-700.

    .

  13. The pivotal role of inflammation in scar/keloid formation after acne

    PubMed Central

    Shi, Chao; Zhu, Jianyu; Yang, Degang

    2017-01-01

    ABSTRACT Most keloids are clinically observed as solid nodules or claw-like extensions. However, they appear hypoechoic on ultrasound images and are therefore easily confused with liquid features such as blood or vessels. The pathological manifestations of typical keloids also include prominent, thick blood vessels. The existing classification of scars fails to reflect the natural history of keloids. The outer characteristics of a typical keloid include bright red hyperplasia with abundant vessels, suggesting the importance of vascular components in the process of scar formation and prompting consideration of the role of inflammation in the development of granular hyperplasia. Additionally, we further considered the potential effectiveness of oral isotretinoin for severe keloids secondary to severe acne. We also explored different principles and applications related to 5-fluorouracil (5-FU), pulsed dye laser (PDL), and CO2 laser treatments for scars. PMID:29707102

  14. A sensitive high-pressure liquid chromatography/particle beam/mass spectrometry assay for the determination of all-trans-retinoic acid and 13-cis-retinoic acid in human plasma.

    PubMed

    Lehman, P A; Franz, T J

    1996-03-01

    A highly sensitive assay for the measurement of all-trans-retinoic acid (tretinoin) and 13-cis-retinoic acid (isotretinoin) has been developed. Collected plasma samples were protein precipitated with 2-propanol followed by solid phase extraction. The retinoic acids were subsequently derivatized to their pentafluorobenzyl esters followed by separation and isolation by reverse phase high-pressure liquid chromatography. The HPLC eluate was directed to a mass spectrometer via a particle beam interface. Selected ion monitoring (299 m/z) for the retinoic acid's carboxylate anion produced by negative chemical ionization using methane reagent gas achieved minimum detection limits of 25 pg injected. Endogenous blood levels in 19 male and 9 female subjects were measured. It was found that females have significantly more all-trans-retinoic acid than males and that both sexes demonstrate significantly more all-trans-retinoic acid then 13-cis-retinoic acid.

  15. [A reversed-phase HPLC method for determining tretinoin].

    PubMed

    Jiang, X G; Xi, N Z

    1994-09-01

    Tretinoin (Tre) and its active stereo isomer isotretinoin (Iso) were simultaneously determined by reversed-phase high pressure liquid chromatographic method with a uv detector adjusted to 348 nm. Separation was accomplished on YWG-C18 column by using a MeOH:NH4Ac buffer (pH 6.0) 85:15 (vol:vol), chlorpromazine (Chl) being chosen as internal standard. Minimal detectable amount of Tre was 0.5 ng. Calibration curve was linear (r = 0.9999) in the concentration range of 25-2500 ng.ml-1. This method was used to determinate the transdermal amounts of Tre from three different preparations in Franz diffusion cell in vitro. The results showed that the proposed method could distinguish the transdermal differences from various formulations or different skin samples. In addition, it is able to be used in quantitative analysis of Tre and Iso.

  16. Retrospective Review of Folliculitis Decalvans in 23 Patients with Course and Treatment Analysis of Long-standing Cases.

    PubMed

    Bunagan, M J Kristine; Banka, Nusrat; Shapiro, Jerry

    2015-01-01

    To date, there is no standard treatment of folliculitis decalvans (FD), a rare type of cicatricial alopecia. The records of 23 patients with FD (1998-2012) were retrospectively analyzed, with added data review on the course and treatment of long-standing cases. Initial management consisted mostly of intralesional triamcinolone acetonide, clobetasol lotion, and either cephalexin, minocycline, doxycycline, or tetracycline. Alternatives consisted of rifampicin, clindamycin, ciprofloxacin, and isotretinoin. Remission was achieved in weeks to months in more than half of the cases, with low occurrence of relapse. The poor responders had a protracted course of temporary improvement and multiple relapses. The majority of patients showed improvement and subsequent remission with oral antibiotics. In some patients, it took years of slow taper before the antibiotic could be discontinued. Only a few patients had recalcitrant disease, with minimal response to their initial and alternative medications. © 2014 Canadian Dermatology Association.

  17. Back and face involvement in hidradenitis suppurativa.

    PubMed

    Poli, Florence; Wolkenstein, Pierre; Revuz, Jean

    2010-01-01

    Hidradenitis suppurativa (HS) may be associated with face and back lesions which are considered as acne. To describe the skin lesions of a group of patients with HS. Twelve patients were selected from a series of 648 patients on the basis of their specific skin lesions. The patients (mostly male) had typical hidradenitis. On their face or back they had one or several of the following skin lesions which are not seen in acne: hypertrophic rope-like bridged scars, raised plaques with multiple carbuncle-like openings or with ulcerations, 'worm-eaten scars' and coalescent nodules with round ulcerations. All patients had deep round scars. Several had a pilonidal cyst or large epidermal cysts. Isotretinoin had been used by 7 patients with no effect. Some HS patients have specific lesions of the face and back which are not acne and have to be treated differently. Copyright 2010 S. Karger AG, Basel.

  18. Management strategies for acne vulgaris

    PubMed Central

    Whitney, Kristen M; Ditre, Chérie M

    2011-01-01

    Clinical question: What are the most effective treatment(s) for mild, moderate, severe, and hormonally driven acne? Results: Mild acne responds favorably to topical treatments such as benzoyl peroxide, salicylic acid, and a low-dose retinoid. Moderate acne responds well to combination therapy comprising-topical benzoyl peroxide, antibiotics, and/or retinoids, as well as oral antibiotics in refractory cases and oral contraceptive pills for female acne patients. Severe nodulocystic acne vulgaris responds best to oral isotretinoin therapy. In female patients with moderate to severe acne, facial hair, loss of scalp hair and irregular periods, polycystic ovarian syndrome should be considered and appropriate treatment with hormonal modulation given. Adjunctive procedures can also be considered for all acne patients. Implementation: Pitfalls to avoid when treating acne: treatment of acne in women of child-bearing age; familiarization of all acne treatments in order to individualize management for patients; indications for specialist referral. PMID:21691566

  19. Fractional carbon dioxide (CO2) laser combined with topical tretinoin for the treatment of different forms of cystic acne.

    PubMed

    Pestoni Porvén, Carmela; Vieira Dos Santos, Vanessa; Del Pozo Losada, Jesus

    2017-12-01

    Nodulocystic acne is prone to scarring and difficult to treat with treatments other than oral isotretinoin. The aim of this article is to discuss the role of a single session of a fractional carbon dioxide (CO 2 ) laser combined with a topical treatment with a tretinoin and antibiotic gel for a month as a successful treatment to improve nodulocystic acne and chronic microcystic acne. Two cases were involved: the first with nodulocystic acne lesions that persisted after oral retinoids and the second with chronic microcystic acne resistant to topical treatments. After only one session of treatment with the CO 2 laser and the topical treatment, a complete healing of the nodulocystic acne lesions was observed with minimal secondary effects. The microcystic acne showed great improvement. No other topical or oral treatment was needed. This treatment could be a safe and effective treatment for nodulocystic acne lesions and microcystic acne when other treatments fail. More studies should be performed to confirm our results.

  20. Assessment of dermatopharmacokinetic approach in the bioequivalence determination of topical tretinoin gel products.

    PubMed

    Pershing, Lynn K; Nelson, Joel L; Corlett, Judy L; Shrivastava, Surendra P; Hare, Don B; Shah, Vinod P

    2003-05-01

    A new dermatopharmacokinetic (DPK) approach has been proposed for bioequivalence determination of topical drug products by comparing the drug content kinetics in stratum corneum. We sought to establish any correlation between clinical safety/efficacy and DPK approach in bioequivalence determination of tretinoin gel 0.025%. Tretinoin and isotretinoin were quantified in human volar forearm stratum corneum as a function of time with 3 tretinoin gel 0.025% products in 49 patients. Stratum corneum layers were harvested using multiple adhesive disks, which were subsequently extracted and quantified for both isomers by high-performance liquid chromatography. Products with similar composition and therapeutic equivalence were found bioequivalent, and products with different composition and clinical profiles were found bioinequivalent by DPK methodology. There is a direct correlation between DPK parameters in healthy patients and clinical safety/efficacy of tretinoin gel products in patients with acne. Data support the use of DPK parameters and methodology in the bioequivalence assessment of topical tretinoin gel products.

  1. 75 FR 39024 - Determination That ACCUTANE (Isotretinoin) Capsules, 10 Milligrams, 20 Milligrams, and 40...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-07

    ... Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION... safety or effectiveness. This determination means that FDA will not begin procedures to withdraw approval... or effectiveness, or if FDA determines that the listed drug was withdrawn from sale for reasons of...

  2. Dietary intervention in acne

    PubMed Central

    Melnik, Bodo

    2012-01-01

    The purpose of this paper is to highlight the endocrine signaling of Western diet, a fundamental environmental factor involved in the pathogenesis of epidemic acne. Western nutrition is characterized by high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of insulin- and IGF-1-level elevating dairy proteins. Metabolic signals of Western diet are sensed by the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), which integrates signals of cellular energy, growth factors (insulin, IGF-1) and protein-derived signals, predominantly leucine, provided in high amounts by milk proteins and meat. mTORC1 activates SREBP, the master transcription factor of lipogenesis. Leucine stimulates mTORC1-SREBP signaling and leucine is directly converted by sebocytes into fatty acids and sterols for sebaceous lipid synthesis. Over-activated mTORC1 increases androgen hormone secretion and most likely amplifies androgen-driven mTORC1 signaling of sebaceous follicles. Testosterone directly activates mTORC1. Future research should investigate the effects of isotretinoin on sebocyte mTORC1 activity. It is conceivable that isotretinoin may downregulate mTORC1 in sebocytes by upregulation of nuclear levels of FoxO1. The role of Western diet in acne can only be fully appreciated when all stimulatory inputs for maximal mTORC1 activation, i.e., glucose, insulin, IGF-1 and leucine, are adequately considered. Epidemic acne has to be recognized as an mTORC1-driven disease of civilization like obesity, type 2 diabetes, cancer and neurodegenerative diseases. These new insights into Western diet-mediated mTORC1-hyperactivity provide a rational basis for dietary intervention in acne by attenuating mTORC1 signaling by reducing (1) total energy intake, (2) hyperglycemic carbohydrates, (3) insulinotropic dairy proteins and (4) leucine-rich meat and dairy proteins. The necessary dietary changes are opposed to the evolution of

  3. Dietary intervention in acne: Attenuation of increased mTORC1 signaling promoted by Western diet.

    PubMed

    Melnik, Bodo

    2012-01-01

    The purpose of this paper is to highlight the endocrine signaling of Western diet, a fundamental environmental factor involved in the pathogenesis of epidemic acne. Western nutrition is characterized by high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of insulin- and IGF-1-level elevating dairy proteins. Metabolic signals of Western diet are sensed by the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), which integrates signals of cellular energy, growth factors (insulin, IGF-1) and protein-derived signals, predominantly leucine, provided in high amounts by milk proteins and meat. mTORC1 activates SREBP, the master transcription factor of lipogenesis. Leucine stimulates mTORC1-SREBP signaling and leucine is directly converted by sebocytes into fatty acids and sterols for sebaceous lipid synthesis. Over-activated mTORC1 increases androgen hormone secretion and most likely amplifies androgen-driven mTORC1 signaling of sebaceous follicles. Testosterone directly activates mTORC1. Future research should investigate the effects of isotretinoin on sebocyte mTORC1 activity. It is conceivable that isotretinoin may downregulate mTORC1 in sebocytes by upregulation of nuclear levels of FoxO1. The role of Western diet in acne can only be fully appreciated when all stimulatory inputs for maximal mTORC1 activation, i.e., glucose, insulin, IGF-1 and leucine, are adequately considered. Epidemic acne has to be recognized as an mTORC1-driven disease of civilization like obesity, type 2 diabetes, cancer and neurodegenerative diseases. These new insights into Western diet-mediated mTORC1-hyperactivity provide a rational basis for dietary intervention in acne by attenuating mTORC1 signaling by reducing (1) total energy intake, (2) hyperglycemic carbohydrates, (3) insulinotropic dairy proteins and (4) leucine-rich meat and dairy proteins. The necessary dietary changes are opposed to the evolution of

  4. MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas

    ClinicalTrials.gov

    2013-01-23

    Adult Grade III Lymphomatoid Granulomatosis; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  5. Body dysmorphic disorder and cosmetic dermatology: more than skin deep

    PubMed Central

    Castle, David J; Phillips, Katharine A; Dufresne, Raymond G

    2006-01-01

    Summary Body dysmorphic disorder (BDD) is relatively common in cosmetic practise, yet it remains under-recognized. BDD patients are unnaturally concerned with minimal or non-existent flaws, most commonly in the skin (e.g. facial acne or scarring) and hair (e.g. hair loss). Many patients develop social avoidance and suffer occupational or academic impairment. More severely ill patients may become housebound or even attempt suicide. Despite the minimal or non-existent nature of the perceived appearance flaws, patients with BDD may request dermatological treatments such as isotretinoin or dermabrasion. Although treatment outcome has received little investigation, it appears that most patients are dissatisfied with dermatological treatment and, even if the outcome is objectively acceptable, they do not worry any the less about their appearance afterwards. In contrast, a majority of patients respond to serotonin reuptake inhibitors or cognitive behavioural therapy. Treatment of these patients is best given by an experienced health professional. This may be a mental health professional or a dermatologist with an interest in psychological medicine. PMID:17147563

  6. Antiproliferative effect of retinoid compounds on Kaposi's sarcoma cells.

    PubMed Central

    Corbeil, J; Rapaport, E; Richman, D D; Looney, D J

    1994-01-01

    A panel of retinoid compounds (tretinoin, isotretinoin, acitretin, and RO13-1470) were tested for inhibitory activity against Kaposi's sarcoma cell (KSC) cultures in vitro. Tretinoin was found to be the most effective retinoid tested, inhibiting the growth of KSC in vitro while having no effect on the expression of interleukin-6 and basic fibroblast growth factor, two important cytokines involved in KSC growth. Tretinoin also did not appear to downregulate the expression of receptors for these two cytokines. At low concentrations (10(-9) M), acitretin and tretinoin selectively inhibited growth of early passage KSC. At higher concentrations (10(-6)-10(-5) M), retinoid treatment induced a pattern of DNA degradation and morphological changes in KSC characteristic of apoptosis (programmed cell death). The inhibitory activity of tretinoin on KSC growth was decreased if human serum (but not fetal calf serum) was present in the growth medium, and partially restored by removal of serum lipids. These data suggest that retinoids possess potential as therapeutic agents in Kaposi's sarcoma. Images PMID:8182129

  7. Xeroderma Pigmentosum: Man Deprived of His Right to Light

    PubMed Central

    Mareddy, Subhash; Reddy, Jithendra; Babu, Subhas; Balan, Preethi

    2013-01-01

    Xeroderma pigmentosum (XP) is a hereditary autosomal recessive disorder characterized by photo hypersensitivity of sun exposed tissues and subsequent several-fold increased risk for malignant changes resulting from impaired ability to repair UV-induced DNA damage. Estimated incidences vary from 1 in 20,000 in Japan to 1 in 250,000 in the USA, and approximately 2.3 per million live births in Western Europe. Diagnosis is made clinically by the presence of unusual sunburns or lentiginosis or onset of cancers at an early age. It is confirmed by cellular tests for defective DNA repair. Although there is no cure for XP as of now, skin problems can be ameliorated with the use of sunscreens, sun avoidance methods, and recurrent tumor excisions. Oral isotretinoin and topical application of 5-fluorouracil to treat actinic keratoses are other therapeutic options. T4N5 and photolyase liposomal lotions are innovations in the therapy of XP. Genetic counselling implicating the effect of consanguineous marriages should be considered in the management of XP patients. PMID:24459435

  8. Congenital oculomotor nerve synkinesis associated with fetal retinoid syndrome.

    PubMed

    Morrison, David G; Elsas, Frederick J; Descartes, Maria

    2005-04-01

    Isotretinoin (RA), used for the treatment of cystic acne, is a powerful teratogen, causing craniofacial dysmorphisms and neural tube defects. We present two patients with RA embryopathy and oculomotor nerve synkinesis. Retrospective review of patient records. Two patients presented with third nerve synkinesis and fetal RA exposure. Both had marked elevation of the upper eyelids on adduction such that the lid fissures alternately opened and closed on gaze from side to side. Both patients showed typical dysmorphisms of RA embryopathy. The first patient had complete agenesis of the cerebellar vermix and died at 2 years. The second patient had restricted extraocular muscles in one eye and was exotropic and hypotropic. Both patients demonstrated simultaneous innervation of the medial rectus and levator palpebrae muscles causing coincident lid elevation in adduction. This evidence of oculomotor nerve synkinesis is consistent with animal studies showing abnormalities in the formation of cranial nerve ganglia following fetal RA exposure. RA is a powerful teratogen. These patients provide additional clinical evidence of its influence on neural migration during early development.

  9. Topical retinoids in acne vulgaris: update on efficacy and safety.

    PubMed

    Thielitz, Anja; Gollnick, Harald

    2008-01-01

    Topical retinoids represent a mainstay of acne treatment because they expel mature comedones, reduce microcomedone formation, and exert anti-inflammatory effects. The first-generation retinoid tretinoin (all-trans retinoic acid) and the synthetic third-generation polyaromatics adapalene and tazarotene are approved for acne treatment by the US FDA, whereas topical tretinoin, isotretinoin (13-cis retinoic acid), and adapalene are accredited in Canada and Europe. Topical retinoids have a favorable safety profile distinct from the toxicity of their systemic counterparts. Local adverse effects, including erythema, dryness, itching, and stinging, occur frequently during the early treatment phase. Their impact varies with the vehicle formation, skin type, frequency and mode of application, use of moisturizers, and environmental factors such as sun exposure or temperature. The broad anti-acne activity and safety profile of topical retinoids justifies their use as first-line treatment in most types of non-inflammatory and inflammatory acne. They are also suitable as long-term medications, with no risk of inducing bacterial resistance, for maintenance of remission after cessation of initial combination therapy.

  10. Cutaneous sarcoidosis in Asians: a report of 25 patients from Singapore.

    PubMed

    Chong, W-S; Tan, H-H; Tan, S-H

    2005-03-01

    Sarcoidosis is a systemic noncaseating granulomatous disorder of unknown origin involving multiple organ systems. There has been no report so far to describe the epidemiological pattern of cutaneous involvement in sarcoidosis in South-East Asia with diverse ethnic groups. A retrospective study examining the clinicopathological features of all patients diagnosed with sarcoidosis at a tertiary dermatology centre in Singapore from 1980 to 2003 was conducted. Cutaneous sarcoidosis was diagnosed in 25 patients: 13 were Indian, 11 were Chinese and one was Eurasian. Cutaneous manifestations included papules, nodules, plaques and scarring alopecia. Extracutaneous involvement of lymph nodes (four patients), lungs (eight patients) and eyes (two patients) was seen. Eight patients had abnormal chest radiographic findings. Histopathological examination of skin lesions revealed noncaseating, epithelioid granulomatous infiltration in the dermis without evidence of mycobacterial infection, deep fungal infection or polarizable birefringent material. Treatment modalities included corticosteroids, hydroxychloroquine, isotretinoin, methotrexate and surgical excision. Five patients had complete resolution of the cutaneous lesions. Cutaneous sarcoidosis is rare in Asia and indeed in Singapore. Extracutaneous involvement is not uncommon and a thorough clinical evaluation should be undertaken.

  11. Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate.

    PubMed

    Bowers, Christian A; Kundu, Bornali; Hawryluk, Gregory W J

    2016-06-01

    Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS's status as a historical standard of care.

  12. Update on the management of rosacea

    PubMed Central

    Weinkle, Allison P; Doktor, Vladyslava; Emer, Jason

    2015-01-01

    Refining diagnostic criteria has identified key characteristics differentiating rosacea, a chronic skin disorder, from other common cutaneous inflammatory conditions. The current classification system developed by the National Rosacea Society Expert Committee consists of erythematotelangiectatic, papulopustular, phymatous, and ocular subtypes. Each subtype stands as a unique entity among a spectrum, with characteristic symptoms and physical findings, along with an intricate pathophysiology. The main treatment modalities for rosacea include topical, systemic, laser, and light therapies. Topical brimonidine tartrate gel and calcineurin inhibitors are at the forefront of topical therapies, alone or in combination with traditional therapies such as topical metronidazole or azelaic acid and oral tetracyclines or isotretinoin. Vascular laser and intense pulsed light therapies are beneficial for the erythema and telangiectasia, as well as the symptoms (itching, burning, pain, stinging, swelling) of rosacea. Injectable botulinum toxin, topical ivermectin, and microsecond long-pulsed neodymium-yttrium aluminum garnet laser are emerging therapies that may prove to be extremely beneficial in the future. Once a debilitating disorder, rosacea has become a well known and manageable entity in the setting of numerous emerging therapeutic options. Herein, we describe the treatments currently available and give our opinions regarding emerging and combination therapies. PMID:25897253

  13. Treatment of rosacea.

    PubMed

    Parodi, A; Drago, F; Paolino, S; Cozzani, E; Gallo, R

    2011-11-01

    A range of treatment options are available in rosacea, which include several topical (mainly metronidazole, azelaic acid, other antibiotics, sulfur, retinoids) and oral drugs (mainly tetracyclines, metronidazole, macrolides). In some cases, the first choice is a systemic therapy because patients may have sensitive skin and topical medications can be irritant. Isotretinoin can be used in resistant cases of rosacea. Unfortunately, the majority of studies on rosacea treatments are at high or unclear risk of bias. A recent Cochrane review found that only topical metronidazole, azelaic acid, and oral doxycycline (40 mg) had some evidence to support their effectiveness in moderate to severe rosacea and concluded that further well-designed, adequately-powered randomised controlled trials are required. In our practice, we evaluate our patients for the presence of two possible triggers, Helicobacter pylori infection and small intestinal bacterial overgrowth. When they are present we use adapted antibiotic protocols. If not, we use oral metronidazole or oral tetracycline to treat papulopustolar rosacea. We also look for Demodex folliculorum infestation. When Demodex concentration is higher than 5/cm(2) we use topical crotamiton 10% or metronidazole. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  14. [Treatment of rosacea].

    PubMed

    Parodi, A; Drago, F; Paolino, S; Cozzani, E; Gallo, R

    2011-09-01

    A range of treatment options are available in rosacea, which include several topical (mainly metronidazole, azelaic acid, other antibiotics, sulfur, retinoids) and oral drugs (mainly tetracyclines, metronidazole, macrolides). In some cases, the first choice is a systemic therapy because patients may have sensitive skin and topical medications can be irritant. Isotretinoin can be used in resistant cases of rosacea. Unfortunately, the majority of studies on rosacea treatments are at high or unclear risk of bias. A recent Cochrane review found that only topical metronidazole, azelaic acid, and oral doxycycline (40 mg) had some evidence to support their effectiveness in moderate to severe rosacea and concluded that further well-designed, adequately-powered randomised controlled trials are required. In our practice, we evaluate our patients for the presence of two possible triggers, Helicobacter pylori infection and small intestinal bacterial overgrowth. When they are present we use adapted antibiotic protocols. If not, we use oral metronidazole or oral tetracycline to treat papulopustolar rosacea. We also look for Demodex folliculorum infestation. When Demodex concentration is higher than 5/cm(2) we use topical crotamiton 10% or metronidazole. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  15. Metabolism of 13-cis-retinoic acid by a rat liver 9000g supernatant preparation.

    PubMed

    Vane, F M; Buggé, C J; Williams, T H

    1982-01-01

    The in vitro metabolites formed on incubation of 13-cis-retinoic acid (13-cis-RA, isotretinoin) with a 9000g rat liver supernatant system were isolated by HPLC and identified by their mass and NMR spectra. The major metabolic pathway was hydroxylation at C4 to give 4-hydroxy-13-cis-RA, which was rapidly oxidized to 4-oxo-13-cis-RA, the major isolated metabolite. Further metabolism of this 4-oxo metabolite led to two novel compounds, 2-hydroxy-4-oxo-13-cis-RA and 3-hydroxy-4-oxo-13-cis-RA. In addition, small amounts of 13-cis-RA and 4-oxo-13-cis-RA were enzymatically converted to their all-trans isomers. Support for these pathways was obtained by the metabolism of reference samples of 4-hydroxy-13-cis-RA, 4-oxo-13-cis-RA, all-trans-RA, and 4-oxo-all-trans-RA. The predominant formation of 4-oxo metabolites of 13-cis-RA in this in vitro rat system and the results from previously reported in vivo metabolism studies suggest that oxidation at C4 is a major metabolic pathway of 13-cis-RA in both rats and humans.

  16. Drug-induced corneal damage.

    PubMed

    2014-04-01

    Corneal damage can have a variety of causes, including infections, chemical splashes, environmental factors (radiation, trauma, contact lenses, etc.), and systemic diseases (genetic, autoimmune, inflammatory, metabolic, etc.). A wide range of drugs can also damage the cornea. The severity of drug-induced corneal changes can range from simple asymptomatic deposits to irreversible, sight-threatening damage. Several factors can influence the onset of corneal lesions. Some factors, such as the dose, are treatment-related, while others such as contact lenses, are patient-related. A variety of mechanisms may be involved, including corneal dryness, changes in the corneal epithelium, impaired wound healing and deposits. Many drugs can damage the cornea through direct contact, after intraocular injection or instillation, including VEGF inhibitors, anti-inflammatory drugs, local anaesthetics, glaucoma drugs, fluoroquinolones, and preservatives. Some systemically administered drugs can also damage the cornea, notably cancer drugs, amiodarone and isotretinoin. Vulnerable patients should be informed of this risk if they are prescribed a drug with the potential to damage the cornea so that they can identify problems in a timely manner. It may be necessary to discontinue the suspect drug when signs and symptoms of corneal damage occur.

  17. Drug safety in pregnancy: utopia or achievable prospect? Risk information, risk research and advocacy in Teratology Information Services.

    PubMed

    Schaefer, Christof

    2011-03-01

    Even though from preclinical testing to drug risk labeling, the situation with drugs in pregnancy has improved substantially since the thalidomide scandal, there is still an increasing need to provide healthcare professionals and patients with updated individualized risk information for clinical decision making. For the majority of drugs, clinical experience is still insufficient with respect to their safety in pregnancy. There is often uncertainty in how to interpret the available scientific data. Based on 20 years of experience with Teratology Information Services (TIS) cooperating in the European Network of Teratology Information Services (ENTIS) methods of risk interpretation, follow-up of exposed pregnancies through the consultation process and their evaluation is discussed. Vitamin K antagonists, isotretinoin and angiotensin (AT) II-receptor-antagonists are presented as examples of misinterpretation of drug risks and subjects of research based on observational clinical data recorded in TIS. As many TIS are poorly funded, advocacy is necessary by establishing contacts with decision makers in health politics and administration, informing them of the high return in terms of health outcomes and cost savings provided by TIS as reference institutions in clinical teratology. © 2011 The Author. Congenital Anomalies © 2011 Japanese Teratology Society.

  18. International inter-rater agreement in scoring acne severity utilizing cloud-based image sharing of mobile phone photographs.

    PubMed

    Foolad, Negar; Ornelas, Jennifer N; Clark, Ashley K; Ali, Ifrah; Sharon, Victoria R; Al Mubarak, Luluah; Lopez, Andrés; Alikhan, Ali; Al Dabagh, Bishr; Firooz, Alireza; Awasthi, Smita; Liu, Yu; Li, Chin-Shang; Sivamani, Raja K

    2017-09-01

    Cloud-based image sharing technology allows facilitated sharing of images. Cloud-based image sharing technology has not been well-studied for acne assessments or treatment preferences, among international evaluators. We evaluated inter-rater variability of acne grading and treatment recommendations among an international group of dermatologists that assessed photographs. This is a prospective, single visit photographic study to assess inter-rater agreement of acne photographs shared through an integrated mobile device, cloud-based, and HIPAA-compliant platform. Inter-rater agreements for global acne assessment and acne lesion counts were evaluated by the Kendall's coefficient of concordance while correlations between treatment recommendations and acne severity were calculated by Spearman's rank correlation coefficient. There was good agreement for the evaluation of inflammatory lesions (KCC = 0.62, P < 0.0001), noninflammatory lesions (KCC = 0.62, P < 0.0001), and the global acne grading system score (KCC = 0.69, P < 0.0001). Topical retinoid, oral antibiotic, and isotretinoin treatment preferences correlated with photographic based acne severity. Our study supports the use of mobile phone based photography and cloud-based image sharing for acne assessment. Cloud-based sharing may facilitate acne care and research among international collaborators. © 2017 The International Society of Dermatology.

  19. Interventions for photodamaged skin.

    PubMed

    Samuel, M; Brooke, R C C; Hollis, S; Griffiths, C E M

    2005-01-25

    Photodamage describes skin changes such as fine and coarse wrinkles, roughness, freckles and pigmentation changes that occur as a result of prolonged exposure to the sun. Many treatments are available to reverse the damage, but it is unclear which work and at what cost in terms of unwanted side effects. To assess the effects of topically applied treatments, tablet treatments, laser and surgical procedures for photodamaged skin. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, Issue 1 2002, MEDLINE (1966-June 2002), EMBASE (1974-June 2002), Health Periodicals (1976-June 2002). We checked references of articles and communicated with authors and the pharmaceutical industry. Randomised controlled trials which compared drug or surgical interventions with no treatment, placebo or another drug, in adults with mild, moderate or severe photodamage of the face or forearms. Two reviewers independently extracted data and assessed trial quality. Thirty studies of variable quality were included. Eight trials showed that topical tretinoin cream, in concentrations of 0.02% or higher, was superior to placebo for participants with mild to severe photodamage on the face and forearms (although losses to follow-up were relatively high in most studies). For example, the relative risk of improvement for 0.05% tretinoin cream, compared to placebo (three studies), at 24 weeks, was 1.73 (95% confidence interval 1.39 to 2.14). This effect was not seen for 0.001% topical tretinoin (one study) or 0.01% (three studies). A dose-response relationship was evident for both effectiveness and skin irritation. One small within-patient study showed benefit from topical ascorbic acid compared with placebo. Tazarotene (0.01% to 0.1%) and isotretinoin (0.1%) both showed significant improvement over placebo for moderate photodamage (one study each). There is limited evidence (one trial), to show that the effectiveness of 0.05% tretinoin, is equivalent to the

  20. Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia

    ClinicalTrials.gov

    2014-06-16

    Childhood Acute Promyelocytic Leukemia (M3); Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Juvenile Myelomonocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  1. Vorinostat Combined With Isotretinoin and Chemotherapy in Treating Younger Patients With Embryonal Tumors of the Central Nervous System

    ClinicalTrials.gov

    2018-05-16

    Medulloblastoma; Pineoblastoma; Supratentorial Embryonal Tumor, Not Otherwise Specified; Untreated Childhood Medulloblastoma; Untreated Childhood Pineoblastoma; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

  2. Oral treatment with retinoic acid decreases bone mass in rats.

    PubMed

    Hotchkiss, Charlotte E; Latendresse, John; Ferguson, Sherry A

    2006-12-01

    13-cis-retinoic acid (13-cis-RA, isotretinoin) is used to treat severe recalcitrant acne. Other retinoids have adverse effects on bone. Recent studies of human patients treated with 13-cis-RA have had varying results, perhaps because of variability among patients and the lack of control groups. The effects of retinoids have been studied in rodents, but little information is available regarding the effects of clinically relevant retinoid doses as evaluated by use of bone densitometric techniques. We treated rats for 15 or 20 wk with 13-cis-RA, all-trans-RA, or soybean oil (control) by gavage. We used dual-energy X-ray absorptiometry, histomorphometry, and histologic evaluation to evaluate effects on bone. Spontaneous long bone fractures occurred in some rats treated with 15 mg/kg all-trans-RA daily. Bone mineral density, bone mineral content, bone diameter, and cortical thickness of the femur were reduced in rats treated daily with 10 or 15 mg/kg all-trans-RA or 30 mg/kg 13-cis-RA. The lumbar spine was not affected. Although the effects of 13-cis-RA were not as dramatic as those of all-trans-RA, further study of the effects of 13-cis-RA on long bones is warranted.

  3. Wrinkles

    PubMed Central

    2008-01-01

    Introduction Skin disorders associated with photodamage from ultraviolet light include wrinkles, hyperpigmentation, tactile roughness, and telangiectasia, and are more common in people with white compared with other skin types. Wrinkles are also associated with ageing, hormonal status, smoking, and intercurrent disease. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to prevent and treat skin wrinkles? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: alpha and beta hydroxyl acids, carbon dioxide laser, chemical peel, dermabrasion, facelifts, isotretinoin, natural cartilage polysaccharides (oral or topical), retinyl esters, sunscreens, tazarotene, tretinoin, variable pulse erbium:YAG laser, and vitamin C or E (topical). PMID:19445782

  4. Wrinkles.

    PubMed

    Manríquez, Juan Jorge; Majerson Gringberg, Daniela; Nicklas Diaz, Claudia

    2008-12-16

    Skin disorders associated with photodamage from ultraviolet light include wrinkles, hyperpigmentation, tactile roughness, and telangiectasia, and are more common in people with white compared with other skin types. Wrinkles are also associated with aging, hormonal status, smoking, and intercurrent disease. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to prevent and treat skin wrinkles? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: carbon dioxide laser, chemical peel, dermabrasion, facelifts, glycolic acid, isotretinoin, lactic acid, natural cartilage polysaccharides (oral or topical), retinyl esters, sunscreens, tazarotene, tretinoin, variable pulse erbium:YAG laser, and vitamin C or E (topical).

  5. Synthetic retinoids in dermatology

    PubMed Central

    Heller, Elizabeth H.; Shiffman, Norman J.

    1985-01-01

    The potential of vitamin A, or retinol, in the treatment of a variety of skin diseases has long been recognized, but because of serious toxic effects this substance generally could not be used. The recent development and marketing of two relatively nontoxic synthetic analogues, which are known as retinoids, has made it possible to treat some of the diseases that are resistant to standard forms of therapy. Isotretinoin is very effective in cystic and conglobate acne, while etretinate is especially useful in the more severe forms of psoriasis. Good results have also been obtained in other disorders of keratinization. Vitamin A and its derivatives apparently have an antineoplastic effect as well and may come to be used in both the prevention and the treatment of epithelial cancer. In many of these diseases the retinoids act by enhancing the normal differentiation and proliferation of epidermal tissues, but the exact mechanisms are not well understood. Their influence on the intracellular polyamines that control the synthesis of nucleic acids and proteins may be an important factor. Although the retinoids have few serious systemic effects, they are teratogenic, and because they persist in the body their use in women of childbearing potential is limited. ImagesFig. 3 PMID:3158386

  6. Polar hysteria: an expression of hypervitaminosis A.

    PubMed

    O'Donnell, James

    2004-01-01

    Isotretinoin (Accutane) is a drug closely related to the chemical structure of Vitamin A. The pharmacology and toxicology of these two retinoids is similar enough to warrant comparison. Accutane is a powerful drug which its manufacturer, Roche, indicates is limited for severe recalcitrant nodular acne. This potency is also reflected in Accutane's well-known ability to produce severe birth defects if taken during pregnancy. Less well-known is the risk of this lipid soluble chemical to affect the Central Nervous System. Reports of intracranial hypertension, depression, and suicidal indeation with Accutane use have prompted an examination of this serious and life threatening potential. Though Roche has added a warning to its product label for signs of depression and suicidal ideation, this product is being overprescribed for all forms of acne, including mild cases and moderate acne that have not been treated with alternative medications, which have a lesser risk of depression and suicide. There is no contesting that this drug is effective at clearing up the most severe forms of acne, but the public must be informed of its proper, limited indication for use; depression and suicide can follow in patients with no prior history of psychiatric symptoms or suicide attempts.

  7. A Report of Two Cases of Solid Facial Edema in Acne.

    PubMed

    Kuhn-Régnier, Sarah; Mangana, Joanna; Kerl, Katrin; Kamarachev, Jivko; French, Lars E; Cozzio, Antonio; Navarini, Alexander A

    2017-03-01

    Solid facial edema (SFE) is a rare complication of acne vulgaris. To examine the clinical features of acne patients with solid facial edema, and to give an overview on the outcome of previous topical and systemic treatments in the cases so far published. We report two cases from Switzerland, both young men with initially papulopustular acne resistant to topical retinoids. Both cases responded to oral isotretinoin, in one case combined with oral steroids. Our cases show a strikingly similar clinical appearance to the cases described by Connelly and Winkelmann in 1985 (Connelly MG, Winkelmann RK. Solid facial edema as a complication of acne vulgaris. Arch Dermatol. 1985;121(1):87), as well as to cases of Morbihan's disease that occurs as a rare complication of rosacea. Even 30 years after, the cause of the edema remains unknown. In two of the original four cases, a potential triggering factor was identified such as facial trauma or insect bites; however, our two patients did not report such occurrencies. The rare cases of solid facial edema in both acne and rosacea might hold the key to understanding the specific inflammatory pattern that creates both persisting inflammation and disturbed fluid homeostasis which can occur as a slightly different presentation in dermatomyositis, angioedema, Heerfordt's syndrome and other conditions.

  8. The cost-effectiveness of rosacea treatments.

    PubMed

    Thomas, Kristen; Yelverton, Christopher B; Yentzer, Brad A; Balkrishnan, Rajesh; Fleischer, Alan B; Feldman, Steven R

    2009-01-01

    Topical and oral antibiotic/anti-inflammatory agents are mainstays of therapy for rosacea. However, costs and efficacies of these therapies vary widely. To determine relative cost-effectiveness of common therapeutic regimens using published data. Average daily costs (ADC) were determined based on treatment frequency and estimated gram usage for facial application of topical regimens of metronidazole (0.75%, 1%), azelaic acid (15%, 20%), sodium sulfacetamide and sulfur 10%/5%, and oral regimens of tetracycline, doxycycline, and isotretinoin. The ADC was compared with published efficacy rates from clinical trials, with efforts to standardize outcome measures. Based on these efficacy rates, costs per success were calculated and combined with office visit costs to estimate the total cost for each treatment for a 15-week period. The medication cost per treatment success of topical regimens ranged from $60.90 ($205.40, total, including office visits) for metronidazole 1% gel once daily, to $152.25 ($296.75, total) for azelaic acid 20% cream twice daily. Tetracycline 250 mg/day was the least costly oral agent at $6.30 per treatment success, or $150.80 total. Based on our best assessments of retrospective data from the literature, metronidazole 1% gel, once daily, was considerably less costly than several other branded and generic alternatives.

  9. An Effective Algorithm for Management of Noses with Thick Skin.

    PubMed

    Guyuron, Bahman; Lee, Michelle

    2017-04-01

    Thicker nasal skin blunts the definition of the underlying osseocartilaginous frame and the delicate topography of the nose posing additional challenges in producing desirable tip definition. Despite the recognized challenge in this patient population, there is a paucity of literature on how to overcome this problem. The goal of this article is to provide a systematic algorithm to manage patients with thick nasal skin. Approach to the thick nasal skin patient begins with an evaluation of the etiology of their skin thickness. Skin thickness secondary to sebaceous overactivity is diminished with the use of retinoic acid derivatives, lasers or isotretinoin (Accutane), commonly under the advice of the dermatologist. Rhinoplasty maneuvers include open technique, raising a healthy and reasonably thick skin flap overlying the tip, removing the remaining fat overlying and between the domes, creating a firm cartilaginous frame and eliminating dead space using the supratip suture reported by the senior author, and trimming redundant nasal skin envelope when indicated. This systematic approach has been greatly effective in achieving often predictable and aesthetically pleasing rhinoplasty results. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  10. Failure of isotretinoin and interferon-alpha combination therapy for HPV-linked severe vulvar dysplasia. A report of two cases.

    PubMed

    Vilmer, C; Havard, S; Cavelier-Balloy, B; Pelisse, M; Dubertret, L; Leibowitch, M

    1998-08-01

    Retinoids (RA) and interferon (IFN) have been reported to be active against a variety of tumors and human papillomavirus (HPV)-related lesions. Because chronic and recurrent HPV-linked vulvar intraepithelial neoplasia 3 (VIN 3) have a high risk of invasion, we evaluated combined therapy of IFN-alpha with 13-cis-retinoic acid (13 cRA) in the treatment of two VIN 3 cases of this type. Two patients with chronic and recurrent VIN 3 were treated with combined therapy of IFN-alpha (4.5 x 10(6) five times a week) and 13 cRA (1 mg/kg/d) for six months. Clinical regression was observed at the end of treatment in both cases, but histologic features of VIN 3 were still present. These data demonstrate the ineffectiveness of the combined regimen of IFN-alpha and 13 cRA with this schedule for a period of six months in recurrent and chronic VIN 3.

  11. Communication development of a young child with foetal retinoid syndrome: a seven-year follow-up study.

    PubMed

    Kritzinger, Alta; Steenkamp, Lizanne

    2006-01-01

    The aim of the article is to describe the communication development of a child with Fetal Retinoid syndrome (FRS) from six months to seven years of age. Little is known about this rare acquired syndrome and its long-term implications, especially on a child's communication development. A descriptive, ex post facto research design was used to study the participant's communication development from 1996 when the family enrolled in an early communication intervention programme. Annual serial assessments of the participant and her family were conducted and the data were stored in a research database after each assessment. The results are described according to a 4-level assessment framework and indicated consistent, but moderate to minor delays in the participant's communication development with a mild hearing loss in the right ear, associated with ear anomalies. Although prenatal exposure to isotretinoin may have serious effects on the unborn fetus and even cause death, the participant did not display all the symptoms of FRS described in the literature. The favorable family circumstances, early commencement of intervention, and supporting early educational environments were protecting factors that could have contributed positively to the participant's communication development. The importance of knowledge accumulation about rare syndromes such as FRS in Communication Pathology and Audiology is discussed and guidelines for early identification, assessment and treatment applicable to the case are proposed as an intervention option.

  12. Pharmacotherapy of retinal disease with visual cycle modulators.

    PubMed

    Hussain, Rehan M; Gregori, Ninel Z; Ciulla, Thomas A; Lam, Byron L

    2018-04-01

    Pharmacotherapy with visual cycle modulators (VCMs) is under investigation for retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), Stargardt macular dystrophy (SMD) and nonexudative age-related macular degeneration (AMD), all blinding diseases that lack effective treatment options. Areas covered: The authors review investigational VCMs, including oral retinoids, 9-cis-retinyl-acetate (zuretinol) and 9-cis-β-carotene, which restore 11-cis-retinal levels in RP and LCA caused by LRAT and RPE65 gene mutations, and may improve visual acuity and visual fields. Therapies for SMD aiming to decrease accumulation of toxic Vitamin A dimers and lipofuscin in the retina and retinal pigment epithelium (RPE) include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120. Mouse models of SMD show promising data for these treatments, though proof of efficacy in humans is currently lacking. Fenretinide and emixustat are investigational VCMs for dry AMD, though neither has been shown to reduce geographic atrophy or improve vision in human trials. A1120 prevents retinol transport into the RPE and may spare the side effects typically seen in VCMs (nyctalopia and chromatopsia) per mouse studies. Expert opinion: Oral VCMs may be feasible treatment options for degenerative retinal diseases based on pre-clinical and some early clinical studies. Further trials are warranted to assess their efficacy and safety in humans.

  13. Clindamycin phosphate/tretinoin gel formulation in the treatment of acne vulgaris.

    PubMed

    Abdel-Naser, M Badawy; Zouboulis, C C

    2008-11-01

    Clindamycin phosphate 1.2% together with tretinoin 0.025% as a gel (CTG) is a topical formulation of a fixed and stable combination approved by the FDA for the treatment of acne vulgaris in patients 12 years of age or older. The main indication of CTG is the management of moderate comedonal and mild-to-moderate papulopustular acne, an acne form which is present in more than 50% of acne patients. CTG can also be combined with systemic antiacne therapy, such as systemic isotretinoin, in nodulocystic acne. The product combines the anti-inflammatory and antibacterial properties of clindamycin with the well proven and beneficial comedolytic and anticomedogenic effects of tretinoin (all-trans retinoic acid). The addition of clindamycin to tretinoin enhances the comedolytic efficacy of tretinoin in moderate-to-severe acne of the face. The comedolytic activity of tretinoin and the anti-inflammatory efficacy of clindamycin accelerate resolution of all types of acne lesions without affecting the safety of both compounds. Discontinuation rates due to adverse events related to this formulation were found to be low (

  14. 13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes.

    PubMed

    Nelson, Amanda M; Gilliland, Kathryn L; Cong, Zhaoyuan; Thiboutot, Diane M

    2006-10-01

    Isotretinoin (13-cis retinoic acid (13-cis RA)) is the most potent inhibitor of sebum production, a key component in the pathophysiology of acne, yet its mechanism of action remains largely unknown. The effects of 13-cis RA, 9-cis retinoic acid (9-cis RA), and all-trans retinoic acid (ATRA) on cell proliferation, apoptosis, and cell cycle proteins were examined in SEB-1 sebocytes and keratinocytes. 13-cis RA causes significant dose-dependent and time-dependent decreases in viable SEB-1 sebocytes. A portion of this decrease can be attributed to cell cycle arrest as evidenced by decreased DNA synthesis, increased p21 protein expression, and decreased cyclin D1. Although not previously demonstrated in sebocytes, we report that 13-cis RA induces apoptosis in SEB-1 sebocytes as shown by increased Annexin V-FITC staining, increased TUNEL staining, and increased cleaved caspase 3 protein. Furthermore, the ability of 13-cis RA to induce apoptosis cannot be recapitulated by 9-cis RA or ATRA, and it is not inhibited by the presence of a retinoid acid receptor (RAR) pan-antagonist AGN 193109. Taken together these data indicate that 13-cis RA causes cell cycle arrest and induces apoptosis in SEB-1 sebocytes by a RAR-independent mechanism, which contributes to its sebosuppressive effect and the resolution of acne.

  15. [What's new in clinical dermatology?].

    PubMed

    Janier, M

    2013-11-01

    2013 has been the year of large genetic studies of the GWAS type (Genome wide association studies) in common diseases such as psoriasis and atopic dermatitis, aimed at localization of candidate genes. It was also the year of population-based studies from huge public or private registers. Thus, epidemiologic correlations have been put forward: psoriasis and vascular risk, psoriasis and rhinosinusitis, rosacea and migraine, acne and food habits, eczema and basal-cell carcinoma, vitiligo and lower risk of skin cancer, cutaneous Ro/SS-A pos lupus and cancer, chronic eczema and calcium-channel inhlbitors, pemphigoid and loop diuretics. Risk of IBD induced by isotretinoin has not been confirmed but risk of skin cancer under azathioprine is real. New drug reactions have appeared (pigmentation due to interferon, hypodermitis and sarcoidosis to anti-BRAF, vandetanib) and old ones are revisited (patch-testing of Severe Cutaneous adverse cutaneous reactions, pigmentation due to anti-malarial drugs, neutrophilic dermatosis due to azathioprine). Diane35(®) has been transiently withdrawn in January 2013 but tetrazepam has been withdrawn definitively in July 2013. Original aspects of cutaneous infections will be discussed along with new data on STDs (meningococcemia in MSMs, HPV, Herpes, congenital syphilis). Finally, some important papers about dermoscopy, confocal microscopy and aesthetic dermatology will be presented. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Pilosebaceous targeting by isotretenoin-loaded invasomal gel for the treatment of eosinophilic pustular folliculitis: optimization, efficacy and cellular analysis.

    PubMed

    Dwivedi, Mohit; Sharma, Vijay; Pathak, Kamla

    2017-02-01

    Eosinophilic pustular folliculitis is a secondary symptom associated with HIV infection appears as levels of CD4 lymphocyte cells and T4 lymphocyte cell. Isotretinoin, an analog of vitamin A (retinoid) alters the DNA transcription mechanism and interferes in the process of DNA formation. It also inhibits the eosinophilic chemotactic factors present in sebaceous lipids and in the stratum corneum of patients suffering from this ailment. The present research was aimed to formulate isotretenoin-loaded invasomal gel to deliver and target the drug to pilosebaceous follicular unit. Nine invasomal formulations (F1-F9) were prepared applying 3 2 factorial designs and characterized. Formulation F9 was selected as optimized formulation due to optimum results and highest %CDP of 85.94 ± 1.86% in 8 h. Transmission electron microscopy (TEM) suggested uniformity in vesicles shape and size in F9 and developed as invasomal gel (IG). Clinical phase-I, phase-II, and phase-III studies will be required before using on human patients. Confocal laser scanning microscopy (CLSM) validates that IG successfully reaches the pilosebaceous follicular unit and further studied on cell line (SZ-95) exhibited IC50 of ≤8 (25 μM of isotretenoin). Cell cycle analysis confirmed IG arrested the cell growth up to 82% with insignificant difference to pure isotretenion.

  17. Non-psychotropic medication and risk of suicide or attempted suicide: a systematic review

    PubMed Central

    Gorton, Hayley C; Webb, Roger T; Kapur, Navneet; Ashcroft, Darren M

    2016-01-01

    Objectives To establish which non-psychotropic medications have been assessed in relation to risk of suicide or attempted suicide in observational studies, document reported associations and consider study strengths and limitations. Design Systematic review. Methods Four databases (Embase, Medline, PsycINFO and International Pharmaceutical Abstracts) were searched from 1990 to June 2014, and reference lists of included articles were hand-searched. Case–control, cohort and case only studies which reported suicide or attempted suicide in association with any non-psychotropic medication were included. Outcome measures The outcomes eligible for inclusion were suicide and attempted suicide, as defined by the authors of the included study. Results Of 11 792 retrieved articles, 19 were eligible for inclusion. Five studies considered cardiovascular medication and antiepileptics; two considered leukotriene receptor antagonists, isotretinoin and corticosteroids; one assessed antibiotics and another assessed varenicline. An additional study compared multiple medications prescribed to suicide cases versus controls. There was marked heterogeneity in study design, outcome and exposure classification, and control for confounding factors; particularly comorbid mental and physical illness. No increased risk was associated with cardiovascular medications, but associations with other medications remained inconclusive and meta-analysis was inappropriate due to study heterogeneity. Conclusions Whether non-psychotropic medications are associated with increased risk of suicide or attempted suicide remains largely unknown. Robust identification of suicide outcomes and control of comorbidities could improve quantification of risk associated with non-psychotropic medication, beyond that conferred by underlying physical and mental illnesses. PMID:26769782

  18. Retinoids: fascinating up-and-coming scenario.

    PubMed

    Sardana, Kabir; Sehgal, Virendra N

    2003-05-01

    Retinoids have been in sharp focus ever since their introduction 30 years ago. They include any drug (s) that bind to retinoid receptors and elicit a biological response. Enormous information on the subject seems to embroil the recent literature. Practically it is impossible to clearly comprehend the undercurrents. The meticulously dispensing text envisages surmounting the perspective reader's predicaments. Accordingly, retinoids and their related facets namely retinoid receptors, classification, mode of action, and the pharmacological diversity have been precisely defined. Commonly used systemic retinoids too have been given a substantial fresh look along with their monitoring. Overall, adverse effects and relative and absolute contraindications have been scrupulously incorporated. Human immuno deficiency virus (HIV) and isoretinoid for acne, in particular, have been highlighted. Micronized isotretinoin formulations have also been taken care so also commonly used topical retinoids. Tretinoin and their newer formulation have also been accounted for along with tretinoin polymer cream. Adapalene, a new chemical entity possessing a unique physico-chemical activity similar to that of tretinoin has also been dealt with. Newer retinoids are likely to be a subject of intrigue. A focus on future potentials of retinoids is its special ingredient. The inclusion of details of rexinoid the most recent introduction in their purview is likely to invoke interest to further consolidate its reckoning in future. All in all the text of the paper should provide an insight into the current rumbling around retinoids.

  19. Use of topical tretinoin and the development of noncutaneous adverse events: evidence from a systematic review of the literature.

    PubMed

    Shapiro, Stanley; Heremans, Annie; Mays, David A; Martin, Amber L; Hernandez-Medina, Marisol; Lanes, Stephan

    2011-12-01

    Topical retinoids have been in clinical use for the treatment of chronic skin conditions, including acne, photodamage, and psoriasis, for 30 years. A systematic literature review was conducted to assess the incidence of noncutaneous adverse events (AE) among patients treated with topical retinoids with a focus on topical tretinoin studies reported before the Veterans Affairs Topical Tretinoin Chemoprevention trial. Electronic literature searches were conducted in Embase and MEDLINE for literature reporting development of nonteratogenic, noncutaneous AE among patients treated with topical retinoids published through September 2008. The search yielded 2778 citations, of which 20 studies met inclusion criteria. Tretinoin was used in 14 of the studies. Other retinoids assessed included isotretinoin, adapalene, alitretinoin, and tazarotene. Within patients receiving topical tretinoin, 27.9% reported the occurrence of at least one noncutaneous AE. The majority of noncutaneous AE were transient and judged not to be related to tretinoin treatment. The conclusions of this study apply largely to tretinoin compared with other topical retinoids. Many of the included trials were designed to evaluate the efficacy of topical treatment and reporting of safety events concentrated on incidence of localized AE, rather than systemic or noncutaneous events. We found no clear evidence of a relationship between the use of topical tretinoin and the development of noncutaneous AE before a recent report of excess mortality in a clinical trial. The majority of noncutaneous AE reported by patients receiving topical retinoids consisted of nonsevere, nonspecific symptoms that were judged not to be related to treatment. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  20. Hidradenitis suppurativa: A practical review of possible medical treatments based on over 350 hidradenitis patients.

    PubMed

    Scheinfeld, Noah

    2013-04-15

    Hidradenitis suppurativa (HS), a pathological follicular disease, impacts patients' lives profoundly. HS most commonly involves cutaneous intertriginous areas, such as the axilla, inner thighs, groin and buttocks, and pendulous breasts, but can appear on any follicular skin. Protean, HS manifests with variations of abscesses, folliculitis, pyogenic granulomas, scars (oval honeycombed), comedones, tracts, fistulas, and keloids. The pathophysiology might involve both defects of the innate follicular immunity and overreaction to coagulase negative Staphylococcus. Treatment depends on the morphology, extent, severity, and duration. Topical clindamycin and dapsone are often adequate for treating mild HS. For Stage 1 and 2 HS, first line treatment combines rifampin with either oral clindamycin or minocycline. Other HS treatments include: fluoroquinolones with metronidazole and rifampin, oral dapsone, zinc, acitretin, hormone blockers (oral contraceptive pills, spironolactone, finasteride, and dutasteride), and oral prednisone. For severe HS, cyclosporine, adalimumab, or infliximab (used at double psoriatic doses) and intravenous carbapenems or cephalosporins are often required. Isotretinoin, etanercept, isoniazid, lymecycline, sulfasalazine, methotrexate, metformin, colchicine, clarithromycin, IVIG, and thalidomide are less favored treatments. The role of botulinum toxin is uncertain. The most important life style modification is weight loss. De-roofing fluctuant nodules and injection of intralesional corticosteroids ameliorates the disease and perhaps, if done at regular intervals, improves HS more permanently. Surgical excision and CO2 laser ablation are more definitive treatments. The 1064 nm laser for hair removal aids in the treatment of HS. This article centers on medical therapies and will only passingly mention surgical and laser treatments. This article summarizes my treatment experience with over 350 HS patients.

  1. Identification of FDA-approved oncology drugs with selective potency in high-risk childhood ependymoma.

    PubMed

    Donson, Andrew M; Amani, Vladimir; Warner, Elliot A; Griesinger, Andrea M; Witt, Davis A; Mulcahy Levy, Jean M; Hoffman, Lindsey M; Hankinson, Todd C; Handler, Michael H; Vibhakar, Rajeev; Dorris, Kathleen; Foreman, Nicholas K

    2018-06-20

    Children with ependymoma are cured in less than 50% of cases, with little improvement in outcome over the last several decades. Chemotherapy has not impacted survival in ependymoma, due in part to a lack of preclinical models that has precluded comprehensive drug testing. We recently developed two human ependymoma cell lines harboring high-risk phenotypes which provided us with an opportunity to execute translational studies. ependymoma and other pediatric brain tumor cell lines were subject to a large-scale comparative drug screen of ependymoma -approved oncology drugs for rapid clinical application. The results of this in vitro study were combined with in silico prediction of drug sensitivity to identify ependymoma -selective compounds, which were validated by dose curve and time course modelling. Mechanisms of ependymoma -selective antitumor effect were further investigated using transcriptome and proteome analyses. We identified three classes of oncology drugs that showed ependymoma -selective anti-tumor effect, namely (i) fluorinated pyrimidines (5-fluorouracil, carmofur and floxuridine), (ii) retinoids (bexarotene, tretinoin and isotretinoin), and (iii) a subset of small-molecule multi-receptor tyrosine kinase inhibitors (axitinib, imatinib and pazopanib). Axitinib's anti-tumor mechanism in ependymoma cell lines involved inhibition of PDGFR-alpha and PDGFR-beta and was associated with reduced mitosis-related gene expression and cellular senescence. The clinically available, ependymoma -selective oncology drugs identified by our study have the potential to critically inform design of upcoming clinical studies in ependymoma, in particular for those children with recurrent ependymoma who are in the greatest need of novel therapeutic approaches. Copyright ©2018, American Association for Cancer Research.

  2. Neuroblastoma: treatment outcome after incomplete resection of primary tumors.

    PubMed

    Moon, Suk-Bae; Park, Kwi-Won; Jung, Sung-Eun; Youn, Woong-Jae

    2009-09-01

    For International Neuroblastoma Staging System (INSS) stages III or IV neuroblastoma (intermediate or high risk), complete excision of the primary tumor is not always feasible. Most current studies on the treatment outcome of these patients have reported on the complete excision status. The aim of this study is to review the treatment outcome after the incomplete resection. The medical records of 37 patients that underwent incomplete resection between January 1986 and December 2005 were reviewed retrospectively. Incomplete resection was assessed by review of the operative notes and postoperative computerized tomography. Age, gender, tumor location, INSS stage, N-myc gene copy number, pre- and postoperative therapy, and treatment outcome were reviewed. The treatment outcome was evaluated according to the postoperative treatment protocol in the high-risk group. Intermediate-risk patients were treated with conventional chemotherapy, isotretinoin (ITT) and interleukin-2 (IL-2). High-risk patients were treated with peripheral blood stem cell transplantation (PBSCT), ITT, and IL-2 (N = 11). Before the introduction of PBSCT, the high-risk patients were also treated with the conventional chemotherapy (N = 19). Intermediate-risk patients (N = 5) currently have no evidence of disease (NED). For the high-risk patients (N = 32), 19 patients were treated with chemotherapy alone; 15 patients died of their disease while four patients currently have an NED status. Eight of 11 patients that underwent PBSCT are currently alive. For intermediate risk, conventional chemotherapy appears to be acceptable treatment. However, for high-risk patients, every effort should be made to control residual disease including the use of myeloablative chemotherapy, differentiating agents and immune-modulating agents.

  3. Contraceptive Provision to Adolescent Females Prescribed Teratogenic Medications.

    PubMed

    Stancil, Stephani L; Miller, Melissa; Briggs, Holley; Lynch, Daryl; Goggin, Kathy; Kearns, Gregory

    2016-01-01

    Rates of adult women receiving contraceptive provision when simultaneously prescribed a known teratogen are alarmingly low. The prevalence of this behavior among pediatric providers and their adolescent patients is unknown. The objective of this study was to describe pediatric provider behaviors for prescribing teratogens concurrently with counseling, referral, and/or prescribing of contraception (collectively called contraceptive provision) in the adolescent population. A retrospective review was conducted examining visits in 2008-2012 by adolescents aged 14 to 25 years in which a known teratogen (US Food and Drug Administration pregnancy risk category D or X) was prescribed. The electronic medical records were queried for demographic information, evidence of contraceptive provision, and menstrual and sexual histories. The data were analyzed using standard statistical methods. Within 4172 clinic visits, 1694 females received 4506 prescriptions for teratogenic medications. The most commonly prescribed teratogens were topiramate, methotrexate, diazepam, isotretinoin, and enalapril. The subspecialties prescribing teratogens most frequently were neurology, hematology-oncology, and dermatology. Overall, contraceptive provision was documented in 28.6% of the visits. Whites versus nonwhites and older versus younger girls were more likely to receive contraceptive provision. The presence of a federal risk mitigation system for the teratogen also increased the likelihood of contraceptive provision. Our data demonstrate female adolescents prescribed teratogens receive inadequate contraception provision, which could increase their risk for negative pregnancy outcomes. Although the presence of a federal risk mitigation system appears to improve contraceptive provision, these systems are costly and, in some instances, difficult to implement. Efforts to improve provider practices are needed. Copyright © 2016 by the American Academy of Pediatrics.

  4. South-East Asia study alliance guidelines on the management of acne vulgaris in South-East Asian patients.

    PubMed

    Goh, Chee Leok; Abad-Casintahan, Flordeliz; Aw, Derrick Chen Wee; Baba, Roshidah; Chan, Lee Chin; Hung, Nguyen Thanh; Kulthanan, Kanokvalai; Leong, Hoe Nam; Medina-Oblepias, Marie Socouer; Noppakun, Nopadon; Sitohang, Irma Bernadette; Sugito, Titi Lestari; Wong, Su-Ni

    2015-10-01

    The management of acne in South-East Asia is unique, as Asian skin and local variables require a clinical approach unlike that utilized in other parts of the world. There are different treatment guidelines per country in the region, and a group of leading dermatologists from these countries convened to review these guidelines, discuss current practices and recent advances, and formulate consensus guidelines to harmonize the management of acne vulgaris in the region. Emphasis has been placed on formulating recommendations to impede the development of antibiotic resistance in Propionibacterium acnes. The group adopted the Acne Consensus Conference system for grading acne severity. The group recommends that patients may be treated with topical medications including retinoids, benzoyl peroxide (BPO), salicylic acid, a combination of retinoid and BPO, or a combination of retinoids and BPO with or without antibiotics for mild acne; topical retinoid with topical BPO and a oral antibiotic for moderate acne; and oral isotretinoin if the patient fails first-line treatment (a 6- or 8-week trial of combined oral antibiotics and topical retinoids with BPO) for severe acne. Maintenance acne treatment using topical retinoids with or without BPO is recommended. To prevent the development of antibiotic resistance, topical antibiotics should not be used as monotherapy or used simultaneously with oral antibiotics. Skin care, comprised of cleansing, moisturizing and sun protection, is likewise recommended. Patient education and good communication is recommended to improve adherence, and advice should be given about the characteristics of the skin care products patients should use. © 2015 Japanese Dermatological Association.

  5. [Case reports of drug-induced liver injury in a reference hospital of Zulia state, Venezuela].

    PubMed

    Mengual-Moreno, Edgardo; Lizarzábal-García, Maribel; Ruiz-Soler, María; Silva-Suarez, Niniveth; Andrade-Bellido, Raúl; Lucena-González, Maribel; Bessone, Fernando; Hernández, Nelia; Sánchez, Adriana; Medina-Cáliz, Inmaculada

    2015-03-01

    Drug-induced liver injury (DILI) is an important cause of morbidity and mortality worldwide, with varied geographical differences. The aim of this prospective, descriptive, cross-sectional study was to identify and characterize cases of DILI in a hospital of Zulia state, Venezuela. Thirteen patients with a presumptive diagnosis of DILI attended by the Department of Gastroenterology, Hospital Universitario, Zulia state, Venezuela, from December-2012 to December-2013 were studied. Ibuprofen (n = 3; 23.1%), acetaminophen (n = 3; 23.1), isoniazid (n = 2; 15.4%) and Herbalife products (n = 2; 15.4%) were the main drugs involved with DILI. Acetaminophen and ibuprofen showed a mixed pattern of liver injury (n = 3; 23.1%) and isoniazid presented a hepatocellular pattern (n = 2; 15.4%). The CIOMS/RUCAMS allowed the identification of possible (n = 7; 53.9%), probable (n = 4; 30.8%) and highly-probable cases (n = 2; 15.4%) of DILI. Amoxicillin/clavulanate, isoniazid, isotretinoin, methotrexate and Herbalife nutritional products were implicated as highly-probable and probable agents. The highest percentage of DILI corresponded to mild cases that recovered after the discontinuation of the agent involved (n = 9; 69.3%). The consumption of Herbalife botanical products is associated with probable causality and fatality (n = 1; 7.7%). In conclusion, the frequency of DILI cases controlled by the Department of Gastroenterology of the Hospital Universitario of Maracaibo was low, being ibuprofen, acetaminophen, isoniazid and products Herbalife the products most commonly involved. It is recommended to continue with the prospective registration of cases, with an extended follow up monitoring period and to facilitate the incorporation of other hospitals in the Zulia State and Venezuela.

  6. Vitamin D3 and its synthetic analogue secocholestra-trien-1,2, 24-triol influence the metabolism and the isomerization of retinoic acid in human keratinocytes.

    PubMed

    Jugert, F K; Roos, T C; Notzon, I; Merk, H F

    1998-01-01

    Vitamin D and vitamin A acid share metabolic pathways thereby influencing their benefit as a given drug. Little is known concerning their metabolic interactions in epidermal cells. We compared the influence of 1,25-dihydroxycholecalciferol (vitamin D3 - VD3) and its synthetic analogue secocholestra-trien-1,3,24-triol (tacalcitol - TAC) in combination with different calcium concentrations (Ca) on the metabolism and the isomerization of retinoic acid (RA) in cultured primary human keratinocytes. After preincubation with 0.09, 0.6 and 1.2 mM Ca for 24 h, followed by the addition of 10(-6), 10(-8) or 10(-10) M VD3 or TAC, we added 10(-5) M 13-cis-RA (isotretinoin). 24 h later, concentrations of RA isomers and oxidated RA metabolites were measured by RP-HPLC. VD3 (10(-6) M) inhibited the isomerization of 13-cis-RA to all-trans-RA (tretinoin) and 9-cis-RA independently from the Ca concentration in the culture medium. 10(-6)-10(-10) M TAC equally inhibit the 4-hydroxylation of all-trans-RA significantly (12.8 vs. 6.7% of total RA), thereby reducing the amount of irreversible inactivated 4-oxo-all-trans-RA, leading to a higher persistence of all-trans-RA, the active hormone. Both VD3 and its analogue TAC influence the metabolism of RA, a well-known regulator of epithelial cell proliferation and differentiation processes, in two distinct ways. Further studies are necessary to test the hypothesis that the hormone activity of RA can be increased by concomitant treatment with VD3 which prolongs the persistence of 13-cis-RA, and TAC elevating the intracellular concentration of all-trans-RA.

  7. Clinicopathological study of itchy folliculitis in HIV-infected patients.

    PubMed

    Annam, Vamseedhar; Yelikar, B R; Inamadar, Arun C; Palit, Aparna; Arathi, P

    2010-01-01

    Itchy folliculitis are pruritic, folliculo-papular lesions seen in human immunodeficiency virus (HIV)-infected patients. Previous studies have shown that it was impossible to clinically differentiate between eosinophilic folliculitis (EF) and infective folliculitis (IF). Also, attempts to suppress the intense itch of EF were ineffective. The present study is aimed at correlating clinical, histopathological and immunological features of itchy folliculitis in HIV patients along with their treatment. The present prospective study lasted for 36 months (September, 2005 to August, 2008) after informed consent, data on skin disorders, HIV status and CD4 count were obtained by physical examination, histopathological examination and laboratory methods. Of 51 HIV-positive patients with itchy folliculitis, the predominant lesion was EF in 23 (45.1%) followed by bacterial folliculitis in 21 (41.2%), Pityrosporum folliculitis in five (9.8%) and Demodex folliculitis in two (3.9%) patients. The diagnosis was based on characteristic histopathological features and was also associated with microbiology confirmation wherever required. EF was associated with a lower mean CD4 count (180.58 +/- 48.07 cells/mm3, P-value < 0.05), higher mean CD8 count (1675.42 +/- 407.62 cells/mm3) and CD8/CD4 ratio of 9.27:1. There was significant reduction in lesions following specific treatment for the specific lesion identified. Clinically, it is impossible to differentiate itchy folliculitis and therefore it requires histopathological confirmation. Appropriate antimicrobial treatment for IF can be rapidly beneficial. The highly active antiretroviral therapy along with Isotretinoin therapy has shown marked reduction in the lesions of EF. Familiarity with these lesions may help in improving the quality of lives of the patients.

  8. Large-scale survey to describe acne management in Brazilian clinical practice

    PubMed Central

    Seité, Sophie; Caixeta, Clarice; Towersey, Loan

    2015-01-01

    Background Acne is a chronic disease of the pilosebaceous unit that mainly affects adolescents. It is the most common dermatological problem, affecting approximately 80% of teenagers between 12 and 18 years of age. Diagnosis is clinical and is based on the patient’s age at the time the lesions first appear, and on its polymorphism, type of lesions, and their anatomical location. The right treatment for the right patient is key to treating acne safely. The aim of this investigational survey was to evaluate how Brazilian dermatologists in private practice currently manage acne. Materials and methods Dermatologists practicing in 12 states of Brazil were asked how they manage patients with grades I, II, III, and IV acne. Each dermatologist completed a written questionnaire about patient characteristics, acne severity, and the therapy they usually prescribe for each situation. Results In total, 596 dermatologists were interviewed. Adolescents presented as the most common acneic population received by dermatologists, and the most common acne grade was grade II. The doctors could choose more than one type of treatment for each patient, and treatment choices varied according to acne severity. A great majority of dermatologists considered treatment with drugs as the first alternative for all acne grades, choosing either topical or oral presentation depending on the pathology severity. Dermocosmetics were chosen mostly as adjunctive therapy, and their inclusion in the treatment regimen decreased as acne grades increased. Conclusion This survey illustrates that Brazilian dermatologists employ complex treatment regimens to manage acne, choosing systemic drugs, particularly isotretinoin, even in some cases of grade I acne, and heavily prescribe antibiotics. Because complex regimens are harder for patients to comply with, this result notably raises the question of adherence, which is a key factor in successful treatment. PMID:26609243

  9. Zolav®: a new antibiotic for the treatment of acne

    PubMed Central

    Dinant, Alexa; Boulos, Ramiz A

    2016-01-01

    Background Acne is a prominent skin condition affecting >80% of teenagers and young adults and ~650 million people globally. Isotretinoin, a vitamin A derivative, is currently the standard of care for treatment. However, it has a well-established teratogenic activity, a reason for the development of novel and low-risk treatment options for acne. Objective To investigate the effectiveness of Zolav®, a novel antibiotic as a treatment for acne vulgaris. Materials and methods Minimum inhibitory concentration of Zolav® against Propionibacterium acnes was determined by following a standard protocol using Mueller-Hinton broth and serial dilutions in a 96-well plate. Cytotoxicity effects on human umbilical vein endothelial cells and lung cells in the presence of Zolav® were investigated by determining the growth inhibition (GI50) concentration, total growth inhibition concentration, and the lethal concentration of 50% (LC50). The tryptophan auxotrophic mutant of Escherichia coli strain, WP2 uvrA (ATCC 49979), was used for the AMES assay with the addition of Zolav® tested for its ability to reverse the mutation and induce bacterial growth. The in vivo effectiveness of Zolav® was tested in a P. acnes mouse intradermal model where the skin at the infection site was removed, homogenized, and subjected to colony-forming unit (CFU) counts. Results Susceptibility testing of Zolav® against P. acnes showed a minimum inhibitory concentration of 2 µg/mL against three strains with no cytotoxicity and no mutagenicity observed at the highest concentrations tested, 30 µM and 1,500 µg/plate, respectively. The use of Zolav® at a concentration of 50 µg/mL (q8h) elicited a two-log difference in CFU/g between the treatment group and the control. Conclusion This study demonstrates the potential of Zolav® as a novel treatment for acne vulgaris. PMID:27042015

  10. The importance of histopathologic aspects in the diagnosis of dissecting cellulitis of the scalp.

    PubMed

    Brănişteanu, Daciana Elena; Molodoi, Andreea; Ciobanu, Delia; Bădescu, Aida; Stoica, Loredana Elena; Brănişteanu, D; Tolea, I

    2009-01-01

    Dissecting cellulitis of the scalp or dissecting folliculitis also known as "perifoliculitis capitis abscedens et suffodiens" (PCAS), is a rare, severe and distinct dermatological disease. It most probably occurs because of follicular occlusion via hyperkeratosis, having the same mechanism of acnea conglobata and hidradenitis suppurativa. These dermatoses may be associated or may have an isolated evolution. PCAS is one of the primitive cicatricial alopecia of neutrophilic type (with pustules). What is characteristic for the histopathologic picture of the disease is the deep inflammatory infiltrate, placed at the reticular derm or hypoderm level. The initial perifolliculitis evolves towards forming profound abscesses and the destruction of polysebaceous follicles because of granuloma, usually lymphoplasmocitary and with gigantic cells. Here is the case of a 24-year-old male with records of acne conglobata and cicatricial alopecia of the scalp, with relapsed inflammatory nodular lesions on the surface of the alopecic plaques and follicular pustules on their margin. The patient had followed before hospitalizing a systemic treatment with antibiotics (azithromycin, tetracycline, ciprofloxacin, in therapeutic schemes that the patient cannot mention, but anyway of short time) and after that a treatment with retinoids (isotretinoin, 20-30 mg/day, in two successive therapies of one month each). The evolution of the disease under these treatments was with outbreaks and short times of remission of the acne lesions and nodular lesions of the scalp. The clinical diagnosis of PCAS is difficult, especially in the initial stage of the disease, as it was the case of the patient presented here. We underline the importance of a correct history of the disease, of the complete clinical exams and the need of paraclinical investigations (histopathologic exam from the lesional biopsy - microscopy and immunohistochemistry) in order to come with a positive diagnosis of PCAS and a

  11. Role of UDP-glucuronosyltransferase isoforms in 13-cis retinoic acid metabolism in humans.

    PubMed

    Rowbotham, Sophie E; Illingworth, Nicola A; Daly, Ann K; Veal, Gareth J; Boddy, Alan V

    2010-07-01

    13-cis Retinoic acid (13cisRA, isotretinoin) is an important drug in both dermatology, and the treatment of high-risk neuroblastoma. 13cisRA is known to undergo cytochrome P450-mediated oxidation, mainly by CYP2C8, but phase II metabolic pathways have not been characterized. In the present study, the glucuronidation activities of human liver (HLM) and intestinal microsomes (HIM), as well as a panel of human UDP-glucuronosyltransferases (UGTs) toward both 13cisRA and the 4-oxo metabolite, 4-oxo 13cisRA, were compared using high-performance liquid chromatography. Both HLM and, to a greater extent, HIM catalyzed the glucuronidation of 13cisRA and 4-oxo 13cisRA. Based on the structures of 13cisRA and 4-oxo 13cisRA, the glucuronides formed are conjugated at the terminal carboxylic acid. Further analysis revealed that UGT1A1, UGT1A3, UGT1A7, UGT1A8, and UGT1A9 were the major isoforms responsible for the glucuronidation of both substrates. For 13cisRA, a pronounced substrate inhibition was observed with individual UGTs and with HIM. UGT1A3 exhibited the highest rate of activity toward both substrates, and a high rate of activity toward 13cisRA glucuronidation was also observed with UGT1A7. However, for both substrates, K(m) values were above concentrations reported in clinical studies. Therefore, UGT1A9 is likely to be the most important enzyme in the glucuronidation of both substrates as this enzyme had the lowest K(m) and is expressed in both the intestine and at high levels in the liver.

  12. The neurobehavioral teratology of retinoids: a 50-year history.

    PubMed

    Adams, Jane

    2010-10-01

    This review of the central nervous system (CNS) and behavioral teratology of the retinoids over the last 50 years is a commemorative retrospective organized by decade to show the prominent research focus within each period and the most salient findings. In the 1960s, research focused on the gross CNS malformations associated with exposure and the delineation of dose-response and stage-specific responses in rodent models. Relevant scientific events before and during the 1960s are also discussed to provide the zeitgeist in which the field of neurobehavioral teratology emerged in the 1970s. During this period, studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth. Work during the 1980s showed an overrepresentation of behavioral studies focused on the reliability of screening methods, while the marked effects of human exposure were illustrated in children born to women treated with isotretinoin during pregnancy. The human catastrophe invigorated research during the 1990s, a period when technological advances allowed more elegant examinations of the developing CNS, of biochemical, cellular, and molecular developmental events and regulatory actions, and of the effects of direct genetic manipulations. Likewise, research in the 1990s reflected a reinvigoration of research in neurobehavioral teratology evinced in studies that used animal models to try to better understand human vulnerability. These foci continued in the 2000-2010 period while examinations of the role of retinoids in brain development and lifelong functioning became increasingly sophisticated and broader in scope. This review of the work on retinoids also provides a lens on the more general ontogeny of the field of neurobehavioral teratology. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.

  13. [Pharmacoeconomy in acne--evaluation of benefit and economics].

    PubMed

    Radtke, Marc A; Schäfer, Ines; Augustin, Matthias

    2010-03-01

    Acne belongs to the most common skin diseases and has a prevalence in the adolescence of nearly 100% and in adults of about 4%. The quality of life indes is significantly reduced und has impact on daily activities and social life and physical and psychological well being as well. The socioeconomic relevance is based not only on its prevalence but on direct and indirect costs. For acne therapy the knowledge on therapeutic costs is of importance but the cost benefit ratio as well. Evidence of therapeutic costs in acne and economic benefit of the therapy. Systematic review of Cochrane data. Calculations reveal general costs of acne treatment in Germany over 400 Mill.Euro per year. For the treatment with topical retinoids, BPO and antibiotics as well as systemic drugs only a few studies on costeffectiveness are available. For topical treatments results are not conclusive and dependent on the different health systems. New topical combinations may have a better economic outcome, however, more studies are needed. With regard to systemic therapies of moderate to severe acne based on the international references the costbenefit ratio favours the treatment with oral isotretinoin on the longterm outcome. Superiority is based on the relationship of costs and clinical outcome and the increased quality of life as well (cost-benefit ratio). It has to be emphazised that only longterm observations over years will lead to a valid calculation of costs and benefit. FACIT: Taking the high social and quality of life impact into consideration an early, well targeted and effective therapy is prevailing. Initial higher cost are balanced by a high quality of outcome under experienced dermatological supervision. The patients benefit is ranked over the final costs because of its medical, social and ethical aspects. To sample more differentiated data on pharmacoeconomic aspects well designed new clinical studies are to be set up.

  14. Effects of topical acne treatment on the ocular surface in patients with acne vulgaris.

    PubMed

    Aslan Bayhan, Seray; Bayhan, Hasan Ali; Çölgeçen, Emine; Gürdal, Canan

    2016-12-01

    To assess the ocular side effects during topical retinoid-antibiotic combination treatment in patients with facial acne vulgaris. Forty-three patients applying topical isotretinoin+erythromycin combination (isotrexin gel, GlaxoSmithKline) once daily for the treatment of acne vulgaris were enrolled. Full ophthalmologic examination, Schirmer test (with topical anesthesia), fluorescein break-up time (BUT), corneal fluorescein staining and tear osmolarity measurement with the TearLab system (TearLab Corporation) were carried out before and at the end of the first month of the treatment. For evaluation of symptoms participants completed the ocular surface disease index (OSDI) questionnaire at each visit. The mean age of the patients was 23.16±3.03 (18-30) years. Mean tear osmolarity increased significantly from 282.09±8.95 mOsm/L at baseline to 300.39±16.65 mOsm/L after the treatment (p<0.001). BUT decreased from an average of 11.93±1.12s at baseline to 6.65±3.03s at the end of the first month (p<0.001). The OSDI score worsened significantly (5.41±3.65 vs 21.53±12.95, p<0.001) and punctate epitheliopathy was seen in 51% of eyes after the treatment. The average Schirmer values were 13.09±1.90 and 12.41±2.44mm/5min before and at the end of the first month of the treatment, respectively (p=0.117). The findings of this study indicate that topical retinoid-antibiotic combination treatment causes significant signs and symptoms of dry eye. Patients receiving topical treatment for acne should be evaluated regularly to ensure the timely detection and treatment of pathologic signs on the ocular surface. Copyright © 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  15. Zolav(®) (a p-carboethoxy-tristyrylbenzene derivative) [corrected]: a new antibiotic for the treatment of acne.

    PubMed

    Dinant, Alexa; Boulos, Ramiz A

    2016-01-01

    Acne is a prominent skin condition affecting >80% of teenagers and young adults and ~650 million people globally. Isotretinoin, a vitamin A derivative, is currently the standard of care for treatment. However, it has a well-established teratogenic activity, a reason for the development of novel and low-risk treatment options for acne. To investigate the effectiveness of Zolav(®), (a p-carboethoxy-tristyrylbenzene derivative) [corrected] a novel antibiotic as a treatment for acne vulgaris. Minimum inhibitory concentration of Zolav(®) (a p-carboethoxy-tristyrylbenzene derivative) against Propionibacterium acnes was determined by following a standard protocol using Mueller-Hinton broth and serial dilutions in a 96-well plate. Cytotoxicity effects on human umbilical vein endothelial cells and lung cells in the presence of Zolav(®) (a p-carboethoxy-tristyrylbenzene derivative) were investigated by determining the growth inhibition (GI50) concentration, total growth inhibition concentration, and the lethal concentration of 50% (LC50). The tryptophan auxotrophic mutant of Escherichia coli strain, WP2 uvrA (ATCC 49979), was used for the AMES assay with the addition of Zolav(®) (a p-carboethoxy-tristyrylbenzene derivative) tested for its ability to reverse the mutation and induce bacterial growth. The in vivo effectiveness of Zolav(®) (a p-carboethoxy-tristyrylbenzene derivative) was tested in a P. acnes mouse intradermal model where the skin at the infection site was removed, homogenized, and subjected to colony-forming unit (CFU) counts. Susceptibility testing of Zolav(®) (a p-carboethoxy-tristyrylbenzene derivative) against P. acnes showed a minimum inhibitory concentration of 2 µg/mL against three strains with no cytotoxicity and no mutagenicity observed at the highest concentrations tested, 30 µM and 1,500 µg/plate, respectively. The use of Zolav(®) (a p-carboethoxy-tristyrylbenzene derivative) at a concentration of 50 µg/mL (q8h) elicited a two

  16. [Rosacea: New data for better care].

    PubMed

    Cribier, B

    In the last 10 years, numerous studies have been published that throw new light on rosacea, in all areas of the disease. This overview summarises all the key developments, based on the indexed bibliography appearing in Medline between 2007 and 2017. Recent epidemiological data show that the prevalence of the disease is doubtless greater than estimated hitherto (more than 10% of adults in some countries) and that we should not overlook rosacea in subjects with skin phototypes V or VI, a condition that exists on all continents. A new classification of rosacea by phenotype comprising major and minor signs has been put forward; it provides a more rational approach to suitable management based upon symptoms, the severity of which may be graded into 5 classes. The treatments with the best-demonstrated efficacy (updated Cochrane study) are topical metronidazole, azelaic acid and ivermectin, and oral doxycycline; isotretinoin is effective against resistant forms but is off-label. In ocular rosacea, the reference treatment is doxycycline in combination with topical therapy of the eyelids. The physiopathology is complex and involves several factors: vascular (vasodilatation, vascular growth factors), neurovascular (hypersensitivity, neuropathic pain, neuropeptides), infectious (Demodex folliculorum and its microbiota) and inflammatory (abnormal production of pro-inflammatory peptides of the innate immune system). In addition, there is a genetic predisposition as demonstrated by the weight of familial history and comparison of homozygous and heterozygous twins. There is also activation of several genes involved in immunity, inflammation and lipid metabolism; the theory of hydrolipid film anomalies has been posited once more. There has thus been a tremendous leap forward in the field of rosacea research, with therapeutic progress and improved understanding of the underlying mechanisms, which should enable the future development of more targeted treatments as well as global

  17. Risk management strategies in the Physicians' Desk Reference product labels for pregnancy category X drugs.

    PubMed

    Uhl, Kathleen; Kennedy, Dianne L; Kweder, Sandra L

    2002-01-01

    Drugs that carry a concern for teratogenicity are often classified as pregnancy category X in the drug label and contraindicated for use during pregnancy. Many drug labels can be found in the Physicians' Desk Reference (PDR), a widely used source of drug information by American clinicians and patients. To review product labelling in the electronic PDR for the pregnancy category X products for pregnancy prevention risk management components in labelling. The electronic version of the 2001 and 2002 PDR was searched for 'pregnancy category X' products using the full text search feature. All product labels identified were retrieved and reviewed for trade name, generic name, manufacturer and indication. Product labels were manually searched for any pregnancy prevention risk management strategies included in labelling. Those labels that had specific pregnancy prevention risk management strategies were further evaluated. One hundred and seventeen pregnancy category X products were obtained from 2249 products searched in the 2001 PDR database and 124 pregnancy category X products were obtained from the 2150 products in the 2002 PDR database. All pregnancy category X products identified were drug products. The label/package insert for each drug was reviewed to identify risk management strategies for pregnancy prevention. The majority of the labels include as the sole risk management strategy either a black box warning and/or a contraindication for use in women who are or may become pregnant. Only 13 drugs contained specific pregnancy prevention risk management strategies in the label directing the clinician and/or patient, e.g. frequency of pregnancy testing, number and type of contraception methods. Two drugs, bexarotene capsules and gel, were only included in the 2001 PDR. Three drugs, isotretinoin, acitretin, and thalidomide, have formal pregnancy prevention risk management programmes. This study demonstrates the varied risk management approaches in labelling for

  18. Food-drug interactions.

    PubMed

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    Interactions between food and drugs may inadvertently reduce or increase the drug effect. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated, the bioavailability is an important pharmacokinetic effect parameter. However, in order to evaluate the clinical relevance of a food-drug interaction, the impact of food intake on the clinical effect of the drug has to be quantified as well. As a result of quality review in healthcare systems, healthcare providers are increasingly required to develop methods for identifying and preventing adverse food-drug interactions. In this review of original literature, we have tried to provide both pharmacokinetic and clinical effect parameters of clinically relevant food-drug interactions. The most important interactions are those associated with a high risk of treatment failure arising from a significantly reduced bioavailability in the fed state. Such interactions are frequently caused by chelation with components in food (as occurs with alendronic acid, clodronic acid, didanosine, etidronic acid, penicillamine and tetracycline) or dairy products (ciprofloxacin and norfloxacin), or by other direct interactions between the drug and certain food components (avitriptan, indinavir, itraconazole solution, levodopa, melphalan, mercaptopurine and perindopril). In addition, the physiological response to food intake, in particular gastric acid secretion, may reduce the bioavailability of certain drugs (ampicillin, azithromycin capsules, didanosine, erythromycin stearate or enteric coated, and isoniazid). For other drugs, concomitant food intake may result in an increase in drug bioavailability either because of a food-induced increase in drug solubility (albendazole, atovaquone, griseofulvin, isotretinoin, lovastatin, mefloquine, saquinavir and tacrolimus) or because of the secretion of

  19. Lasers for vascular lesions: standard guidelines of care.

    PubMed

    Srinivas, C R; Kumaresan, M

    2011-01-01

    Lasers are a good therapeutic tool for congenital and acquired vascular lesions. Technological advances in lasers have reduced the adverse effects and increased the efficacy. MACHINES: Among the various lasers used for treating vascular lesions, pulsed dye laser (PDL) has the best efficacy and safety data. The other machines that are widely available are Nd:YAG laser and intense pulse light (IPL). RATIONALE AND SCOPE OF GUIDELINE: Much variation exists in different machines and techniques, and therefore, establishing standard guidelines has limitations. The guidelines recommended here indicate minimum standards of care for lasers on vascular lesions based on current evidence. Laser may be administered by a dermatologist, who has received adequate background training in lasers during post-graduation or later at a center that provides education and training in lasers, or in focused workshops, which provide such trainings. He/she should have adequate knowledge of the lesions being treated, machines, parameters, cooling systems, and aftercare. The procedure may be performed in the physician's minor procedure room with adequate laser safety measures. PWS, hemangioma, facial telangiectasia, rosacea, spider angioma, pyogenic granuloma, venous lakes, leg veins. Absolute: Active local infection, photo-aggravated skin diseases, and medical conditions. Relative: Unstable vitiligo, psoriasis, keloid and keloidal tendencies, patient on isotretinoin, patient who is not cooperative or has unrealistic expectation. Patient selection should be done after detailed counseling with respect to the course of lesions, different treatment options, possible results, cost, need for multiple treatments, and possible postoperative complications. TREATMENT SESSIONS: The number of treatments per lesion varies from 2 to 12 or more at 6-8 week intervals. All lesions may not clear completely even after multiple sessions in many cases. Hence, a realistic expectation and proper counseling is very

  20. A Possible Link Between Pyriproxyfen and Microcephaly

    PubMed Central

    Parens, Raphael; Nijhout, H. Frederik; Morales, Alfredo; Xavier Costa, Felipe; Bar-Yam, Yaneer

    2017-01-01

    The Zika virus has been the primary suspect in the large increase in incidence of microcephaly in 2015-6 in Brazil. While evidence for Zika being the cause of some of the cases is strong, its role as the primary cause of the large number of cases in Brazil has not been confirmed. Recently, the disparity between the incidences in different geographic locations has led to questions about the virus's role. Here we consider the alternative possibility that the use of the insecticide pyriproxyfen for control of mosquito populations in Brazilian drinking water is the primary cause. Pyriproxifen is a juvenile hormone analog which has been shown to correspond in mammals to a number of fat soluble regulatory molecules including retinoic acid, a metabolite of vitamin A, with which it has cross-reactivity and whose application during development has been shown to cause microcephaly. Methoprene, another juvenile hormone analog that was approved as an insecticide based upon tests performed in the 1970s, has metabolites that bind to the mammalian retinoid X receptor, and has been shown to cause developmental disorders in mammals. Isotretinoin is another example of a retinoid causing microcephaly in human babies via maternal exposure and activation of the retinoid X receptor in developing fetuses. Moreover, tests of pyriproxyfen by the manufacturer, Sumitomo, widely quoted as giving no evidence for developmental toxicity, actually found some evidence for such an effect, including low brain mass and arhinencephaly—incomplete formation of the anterior cerebral hemispheres—in exposed rat pups. Finally, the pyriproxyfen use in Brazil is unprecedented—it has never before been applied to a water supply on such a scale. Claims that it is not being used in Recife, the epicenter of microcephaly cases, do not distinguish the metropolitan area of Recife, where it is widely used, and the municipality, and have not been adequately confirmed. Given this combination of information about

  1. Post-surgical treatment of thyroid carcinoma in dogs with retinoic acid 9 cis improves patient outcome

    PubMed Central

    Castillo, V.; Pessina, P.; Hall, P.; Blatter, M.F. Cabrera; Miceli, D.; Arias, E. Soler; Vidal, P.

    2016-01-01

    The objective of the present study was to compare the effects of isotretinoin 9-cis (RA9-cis) as a post-surgery treatment of thyroid carcinoma to a traditional treatment (doxorubicin) and no treatment. Owners who did not want their dogs to receive treatment were placed into the control group A (GA; n=10). The remaining dogs were randomly placed into either group B (GB; n=12) and received doxorubicin at a dose of 30 mg/m2 every three weeks, for six complete cycles or group C (GC; n=15) and treated with RA9-cis at a dose of 2 mg/kg/day for 6 months. The time of the recurrence was significantly shorter in the GA and GB compared to GC (P=0.0007; P=0.0015 respectively), while we did not detect differences between GA and GB. The hazard ratio of recurrence between GA and GB compared to GC were 7.25 and 5.60 times shorter, respectively. We did not detect any differences between the other groups. The risk ratio of recurrence was 2.0 times higher in GA compared to GC and 2.1 times higher in GB compared to GC. The type of carcinoma had an effect on time of survival with follicular carcinomas having an increased mean survival time than follicular-compact carcinomas (P<0.0001) and follicular-compact carcinomas had a longer mean survival time than compact carcinomas. The interaction among treatment and type was significant, but survival time in follicular carcinomas did not differ between treatments. In follicular-compact carcinomas the survival time of GC was greater than GB (P<0.05), but we did not detect a difference between GA and GB. In conclusion, this study shows that the use of surgery in combination with RA9-cis treatment significantly increases survival rate and decreases the time to tumor recurrence when compared to doxorubicin treated or untreated dogs. The histological type of carcinoma interacted with treatment for time to recurrence and survival time, with more undifferentiated carcinomas having a worse prognosis than differentiated carcinomas. PMID:26862515

  2. Chronic cutaneous lupus erythematosus presenting as atypical acneiform and comedonal plaque: case report and literature review.

    PubMed

    Vieira, M L; Marques, E R M C; Leda, Y L A; Noriega, L F; Bet, D L; Pereira, G A A M

    2018-04-01

    Introduction Chronic cutaneous lupus erythematosus (CCLE) usually presents as characteristic erythematous patches and infiltrated coin-shaped plaques. However, there are some atypical clinical variants that may mimic other dermatological conditions. Haroon et al. reported in 1972 an unusual presentation of CCLE with hypertrophic follicular scars seen in acne vulgaris. Acneiform presentation is one of the most rarely reported and one of the most confusing, as it resembles a very common inflammatory skin disease. A brief review of the literature using PubMed found only nine other reports. Case report A 32-year-old woman presented with two-year pruritic infiltrated acneiform and comedonal eruption on the right chin treated as acne with isotretinoin without improvement. On examination the patient presented with erythematous-infiltrated plaque, papules, open comedones, pitting scars and hypopigmented atrophic scars on the right chin area and scalp hair loss. An incisional skin biopsy on the chin and scalp lesions was performed and the anatomopathological and immunofluorescence exam showed findings that are consistent with CCLE. Additional tests ruled out systemic involvement. The patient was treated with prednisone and chloroquine diphosphate with great improvement. After four years the lesion is stable, with some scarring. Discussion In a literature review we found nine other cases of acneiform presentation of lupus erythematosus: Three cases were systemic lupus erythematosus (SLE) and seven others were diagnosed as CCLE (including our patient). All three patients who had SLE tested positive for antinuclear antibodies (ANA), and only one patient with CCLE, had a low titer of positive ANA (1:80). Ages varied from 24 to 60 years old, with a median of 32 years old, the same as our patient's age and consistent with the literature. Seven were females and three were males, with a ratio of 2.3:1. Most cases, such as our patient, showed acneiform lesions mainly on the face, a

  3. Plasma pharmacokinetics and metabolism of 13-cis- and all-trans-retinoic acid in the cynomolgus monkey and the identification of 13-cis- and all-trans-retinoyl-beta-glucuronides. A comparison to one human case study with isotretinoin.

    PubMed

    Kraft, J C; Slikker, W; Bailey, J R; Roberts, L G; Fischer, B; Wittfoht, W; Nau, H

    1991-01-01

    In order to compare the disposition and metabolism of 13-cis-retinoic acid (13-cis-RA) and all-trans-retinoic acid (all-trans-RA) in the nonpregnant female cynomolgus monkey, the plasma concentrations of the parent compound, the oxidized metabolites 4-oxo-13-cis-retinoic acid and 4-oxo-all-trans-retinoic acid, and the conjugate metabolites 13-cis-retinoyl-beta-glucuronide (13-cis-RAG) and all trans-retinoyl-beta-glucuronide (all-trans-RAG), were determined on day 1 and day 10 after oral dosing of 2 and 10 mg 13-cis- and all-trans-RA/kg/day. Both 13-cis-RAG and all-trans-RAG have been identified as major plasma metabolites in these studies using thermospray/HPLC/mass-spectrometry of the intact conjugates. AUC comparisons from 0-24 hr after administration indicated that 13-cis-RA treatment resulted in primarily cis metabolites and all-trans-RA treatment resulted in primarily trans metabolites, although low levels of isomerization products were observed. Comparison of the two doses (2 and 10 mg/kg, po) revealed that the AUCs were proportional to the dose administered. Although qualitatively similar, elimination of 13-cis-RA in the monkey was more rapid than in the human, and approximately a 10-fold greater dose of 13-cis-RA was required in the monkey to produce the AUC values comparable to the human. The elimination of all-trans-RA in monkey was faster than that of 13-cis-RA and tended to increase with repeated dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Mobile phone-based interventions for improving contraception use.

    PubMed

    Smith, Chris; Gold, Judy; Ngo, Thoai D; Sumpter, Colin; Free, Caroline

    2015-06-26

    both users and non-users of contraception. No trials were at low risk of bias in all areas assessed.One trial in the USA reported improved self reported oral contraceptive (OC) continuation at six months from an intervention comprising a range of uni-directional and interactive text messages (RR 1.19, 95% CI 1.05 to 1.35). One trial in Cambodia reported increased self reported use of effective contraception at four months post abortion from an intervention comprising automated interactive voice messages and phone counsellor support (RR 1.39, 95% CI 1.17 to 1.66).One feasibility trial in the USA reported a lower mean number of days between scheduled and completed attendance for the first but not subsequent Depo-Provera appointments using clinic records from an intervention comprising reminders and healthy self management text messages (mean difference (MD) -8.60 days, 95% CI -16.74 to -0.46). Simple text message OC reminders had no effect on missed pills as assessed by electronic medication monitoring in a small trial in the USA (MD 0.5 missed pills, 95% CI -1.08 to 2.08). No effect on self reported contraception use was noted amongst isotretinoin users from an intervention that provided health information via two uni-directional text messages and mail (RR 1.26, 95% CI 0.84 to 1.89). One trial assessed potential adverse effects of the intervention and reported no evidence of road traffic accidents or domestic abuse. Our review provides limited evidence that interventions delivered by mobile phone can improve contraception use. Whilst evidence suggests that a series of interactive voice messages and counsellor support can improve post-abortion contraception, and that a mixture of uni-directional and interactive daily educational text messages can improve OC adherence, the cost-effectiveness and long-term effects of these interventions remain unknown. Further high-quality trials are required to robustly establish the effects of interventions delivered by mobile phone to

  5. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME--PART 1.

    PubMed

    Goodman, Neil F; Cobin, Rhoda H; Futterweit, Walter; Glueck, Jennifer S; Legro, Richard S; Carmina, Enrico

    2015-11-01

    , alopecia, and acne. Cycle length >35 days suggests chronic anovulation, but cycle length slightly longer than normal (32 to 35 days) or slightly irregular (32 to 35-36 days) needs assessment for ovulatory dysfunction. Ovulatory dysfunction is associated with increased prevalence of endometrial hyperplasia and endometrial cancer, in addition to infertility. In PCOS, hirsutism develops gradually and intensifies with weight gain. In the neoplastic virilizing states, hirsutism is of rapid onset, usually associated with clitoromegaly and oligomenorrhea. Girls with severe acne or acne resistant to oral and topical agents, including isotretinoin (Accutane), may have a 40% likelihood of developing PCOS. Hair loss patterns are variable in women with hyperandrogenemia, typically the vertex, crown or diffuse pattern, whereas women with more severe hyperandrogenemia may see bitemporal hair loss and loss of the frontal hairline. Oral contraceptives (OCPs) can effectively lower androgens and block the effect of androgens via suppression of ovarian androgen production and by increasing sex hormone-binding globulin. Physiologic doses of dexamethasone or prednisone can directly lower adrenal androgen output. Anti-androgens can be used to block the effects of androgen in the pilosebaceous unit or in the hair follicle. Anti-androgen therapy works through competitive antagonism of the androgen receptor (spironolactone, cyproterone acetate, flutamide) or inhibition of 5α-reductase (finasteride) to prevent the conversion of T to its more potent form, 5α-dihydrotestosterone. The choice of antiandrogen therapy is guided by symptoms. The diagnosis of PCOS in adolescents is particularly challenging given significant age and developmental issues in this group. Management of infertility in women with PCOS requires an understanding of the pathophysiology of anovulation as well as currently available treatments. Many features of PCOS, including acne, menstrual irregularities, and hyperinsulinemia