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Sample records for isotretinoin

  1. Isotretinoin (Accutane) and Pregnancy

    MedlinePlus

    ... been no studies looking at taking isotretinoin during breastfeeding. It is not known if isotretinoin can get into breast milk but other similar medications can. We do not know what effect exposure to isotretinoin through the breast milk can ...

  2. Improving bioavailability with a novel isotretinoin formulation (isotretinoin-Lidose).

    PubMed

    Tan, Jerry; Knezevic, Sanja

    2013-01-01

    Current practice guidelines recommend administration of oral isotretinoin with high-fat meals, which may pose issues with patient compliance. Isotretinoin-Lidose (Epuris™), approved by Health Canada in November 2012 and scheduled for commercial release June 2013, is based on novel lipid encapsulation technology (Lidose®) to enclose isotretinoin, thereby increasing drug absorption during fasted states. An open label, single dose randomized crossover study demonstrated pharmacokinetic bioequivalence of isotretinoin-Lidose to standard isotretinoin formulations during fed states, with significantly greater absorption during fasting. Isotretinoin-Lidose, may lead to more consistent plasma levels of isotretinoin during variable dietary conditions, providing the potential for enhanced patient outcomes.

  3. [Isotretinoin, depression and medias].

    PubMed

    Wolkenstein, P

    2010-11-01

    Acne is a frequent disease with a strong impact upon quality of life. The most effective treatment of severe acne is isotretinoin. Cases of suicid have been reported during isotretinoin treatments in adolescents and were mediatised. Now a day, the link between isotretinoin intake and psychiatric troubles is not established at populational level. The pressure of public and medias led the French Drug Agency to send a letter to health professionals to summarize the scientific question. An explanative video is on line on the website of the French Society of Dermatology www.dermato-info.fr. This video summarizes the state of the art concerning the context of isotretinoin for public, dermatologists and other physicians To summarize isotretinoin is the drug for severe acne in case of failure of first line classical treatment. Dermatologists must stay the first line prescribers reminding that adolescence is a fragile period.

  4. Isotretinoin: update on controversial issues.

    PubMed

    Prevost, Noel; English, Joseph C

    2013-10-01

    Acne vulgaris is a commonly seen dermatologic condition that plagues millions and can be very psychosocially disabling. Severe and recalcitrant acne is typically treated with isotretinoin. Isotretinoin is a synthetic vitamin A derivative that has been available since 1982.This therapeutic option has been the most effective at putting severe and recalcitrant acne vulgaris into remission. Despite its effectiveness,it has been associated with inflammatory bowel disease, depression, suicidality, and teratogenicity. We review the current literature on isotretinoin's role in inflammatory bowel disease, depression, and suicidality. In addition, we review whether or not the iPledge program has been successful at reducing pregnancy rates while on isotretinoin.

  5. Isotretinoin and Other Retinoids During Pregnancy

    MedlinePlus

    ... virus and pregnancy Microcephaly Medicine safety and pregnancy Birth defects prevention Learn how to help reduce your risk ... the body from infection. How can you prevent birth defects from isotretinoin? Because isotretinoin can be so harmful ...

  6. Isotretinoin induced rhabdomyolysis? A case report.

    PubMed

    Trauner, M A; Ruben, B S

    1999-11-01

    Isotretinoin, an effective therapy for nodulocystic acne and dissecting cellulitis of the scalp, has many known side effects. However, its association with elevated creatine kinase levels and its potential to cause rhabdomyolysis is not well established. We describe a patient with a significant elevation in creatine kinase after beginning therapy with isotretinoin for dissecting cellulitis of the scalp. The implications of isotretinoin causing rhabdomyolysis are discussed. PMID:10673455

  7. Isotretinoin Exposure and Risk of Celiac Disease

    PubMed Central

    Rashtak, Shadi; Khaleghi, Shahryar; Marietta, Eric V.; Pittelkow, Mark R.; Larson, Joseph J.; Lahr, Brian D.; Murray, Joseph A.

    2015-01-01

    Background Isotretinoin (13-cis retinoic acid) is a metabolite of vitamin A and has anti-inflammatory and immunoregulatory effects; however, a recent publication by DePaolo et al. demonstrated that in the presence of IL-15, retinoic acid can act as an adjuvant and promote inflammation against dietary proteins. Objective To evaluate the risk of overt and latent celiac disease (CD) among users of isotretinoin. Material and Methods Medical records of patients from 1995 to 2011 who had a mention of isotretinoin in their records (N = 8393) were searched for CD diagnosis using ICD-09CM codes. Isotretinoin exposure was compared across overt CD patients and their age- and gender-matched controls from the same pool. To evaluate the risk of latent CD with isotretinoin exposure, patients were overlapped with a community-based list of patients with waste serum samples that were tested for CD serology, excluding those with overt CD (2006–2011). Isotretinoin exposure was defined as the use of isotretinoin prior to CD diagnosis or serology. Results Of 8393 patients, 25 had a confirmed CD diagnosis. Compared to matched controls (N = 75), isotretinoin exposure was not significantly different between overt CD patients versus controls (36% versus 39%, respectively; P = 0.712). Likewise, latent CD defined as positive serology was not statistically different between isotretinoin exposed (N = 506) versus non-exposed (N = 571) groups (1.8% versus 1.4%, respectively; P = 0.474). Conclusions There was no association between isotretinoin use and risk of either overt or latent CD. PMID:26287738

  8. Sebaceous hyperplasia: systemic treatment with isotretinoin.

    PubMed

    Tagliolatto, Sandra; Santos Neto, Octavio de Oliveira; Alchorne, Maurício Mota de Avelar; Enokihara, Mauro Yoshiaki

    2015-01-01

    The study aimed to verify the therapeutic action of isotretinoin in the treatment of sebaceous hyperplasia. During two months, 20 patients with sebaceous hyperplasia took isotretinoin at a dosage of 1mg/kg per day. Their skin lesions were counted and photographed before and after treatment and re-evaluated two years later. The average number of sebaceous hyperplasia lesions before treatment was 24 per patient. At the end of two months of therapy, the number of lesions decreased to 2 per patient. The statistically analyzed data showed a reduction in the number of lesions following isotretinoin use (p < 0.05). Two years after the end of the treatment, the average number of sebaceous hyperplasia lesions was 4 per patient. There were no severe side effects. Thus, the data analysis suggests that isotretinoin is a safe and effective drug for treating the disease under study.

  9. Isotretinoin for acne and rosacea.

    PubMed

    Watson, Kendra D; Miest, Rachel Y; Tollefson, Megha M

    2016-06-01

    Isotretinoin is a revolutionary medicine for the treatment of acne vulgaris, with new studies showing evidence of excellent clinical outcomes in treating rosacea. After 30 years of clinical experience, new insights are being gained into dosing strategies, recurrence prevention, and dose-related side effects. Previous controversial associations with inflammatory bowel diseases and mood disorders have hampered the use of this medication in some clinical situations, with new evidence disproving these claims. The teratogenicity of this medication mandates iPLEDGE compliance with government regulations. Clinicians should be knowledgeable about this medication including its side effects, teratogenicity, and its controversies in order to adequately counsel patients, dissuade fears, and obtain the best clinical outcome when treating acne and rosacea. PMID:27416313

  10. Isotretinoin

    MedlinePlus

    ... operate machinery at night.plan to avoid hair removal by waxing, laser skin treatments, and dermabrasion (surgical ... room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication ...

  11. Isotretinoin, tetracycline and circulating hormones in acne.

    PubMed

    Palatsi, R; Ruokonen, A; Oikarinen, A

    1997-09-01

    Isotretinoin, used to treat severe acne, has been shown to induce hormonal changes, especially to reduce 5 alpha-reductase in the production of the tissue-derived dihydrotestosterone (DHT) metabolite 3 alpha-Adiol G. However, the effects of isotretinoin on other pituitary, adrenal or gonadal hormones have not been thoroughly elucidated. In the present study, isotretinoin administered at a dose of 0.5 mg/kg/day for 4 weeks caused no marked changes in the serum levels of pituitary, adrenal or gonadal hormones or 3 alpha-Adiol G in patients with severe papulopustulotic acne (n = 19). After 12 weeks of therapy, there was a decrease in the levels of the precursor androgens androstenedione, testosterone and 3 alpha-Adiol G in 6/9 patients. Acne improved after 4.5 months in all but 2 male patients, who had very low serum hormone binding globulins (SHBG) and a high free androgen index (FAI). Isotretinoin did not affect the elevated LH/FSH ratio in a patient with the polycystic ovarian syndrome (PCOS); nor did it change the high FAI or low SHBG in the male patients. For comparison, tetracycline had no effects on the serum hormonal levels of patients with mild acne (n = 19) after 7 days of treatment. This study confirms that the effects of isotretinoin on the serum hormone levels are small and unlikely to be of relevance for the resolution of acne or the suppression of sebum excretion. PMID:9298137

  12. Managing nonteratogenic adverse reactions to isotretinoin treatment for acne vulgaris.

    PubMed

    Reilly, Bridget K; Ritsema, Tamara S

    2015-07-01

    Isotretinoin is the strongest, most effective oral treatment for patients with severe acne vulgaris, with remission rates of 89% and higher. Because of its potency, isotretinoin causes many adverse reactions. This article reviews common and severe adverse reactions to isotretinoin and how providers can best manage these reactions. Because of inconclusive research on the correlation between isotretinoin and depression and irritable bowel syndrome, providers should ask patients about symptoms monthly. Prescribing micronized isotretinoin and starting at the lowest dose with gradual upward titration also can help reduce the incidence of adverse reactions.

  13. 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

  14. 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

  15. 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.

  16. Effects of Isotretinoin on Meibomian Glands.

    PubMed

    Moy, Allison; McNamara, Nancy A; Lin, Meng C

    2015-09-01

    The authors have reviewed the potential etiology and long-standing consequences of isotretinoin use in the development of dry eye symptoms in the absence of significant clinical findings. Despite the normal appearance of meibomian gland structure on meibography and minimal signs of eyelid margin inflammation, the secretory function of these glands is reduced and symptoms of dryness can greatly impact a patient's quality of life. The available literature indicates that isotretinoin's effect on the meibomian glands likely mimics its effects on the sebaceous glands of the skin in the treatment of acne. Several representative cases seen at the University of California Berkeley School of Optometry Dry Eye Clinic provide a clinical paradigm with the goal of raising awareness of the potential prevalence of this disease in patients who experience symptoms of dry eye. These cases highlight the importance of meibomian gland expression in determining whether there is poor quality and/or quantity of meibum secondary to reduced gland function. Currently, there is no definitive method to restore the structure and function of damaged meibomian glands; thus, treatment options for isotretinoin-associated meibomian gland dysfunction are primarily palliative to manage patient symptoms. PMID:26154692

  17. Effects of Isotretinoin on Meibomian Glands.

    PubMed

    Moy, Allison; McNamara, Nancy A; Lin, Meng C

    2015-09-01

    The authors have reviewed the potential etiology and long-standing consequences of isotretinoin use in the development of dry eye symptoms in the absence of significant clinical findings. Despite the normal appearance of meibomian gland structure on meibography and minimal signs of eyelid margin inflammation, the secretory function of these glands is reduced and symptoms of dryness can greatly impact a patient's quality of life. The available literature indicates that isotretinoin's effect on the meibomian glands likely mimics its effects on the sebaceous glands of the skin in the treatment of acne. Several representative cases seen at the University of California Berkeley School of Optometry Dry Eye Clinic provide a clinical paradigm with the goal of raising awareness of the potential prevalence of this disease in patients who experience symptoms of dry eye. These cases highlight the importance of meibomian gland expression in determining whether there is poor quality and/or quantity of meibum secondary to reduced gland function. Currently, there is no definitive method to restore the structure and function of damaged meibomian glands; thus, treatment options for isotretinoin-associated meibomian gland dysfunction are primarily palliative to manage patient symptoms.

  18. Acute myocardial infarction in a young woman on isotretinoin treatment.

    PubMed

    Lorenzo, Natalia; Antuña, Paula; Dominguez, Lourdes; Rivero, Fernando; Bastante, Teresa; Alfonso, Fernando

    2015-02-15

    The use of isotretinoin has been associated with mild changes in the metabolic profile of adolescents. In very rare cases, a possible association with myocardial infarction, stroke and thromboembolic events has been reported. In this report we describe the potential association of isotretinoin with the occurrence of an acute myocardial infarction in a very young girl. OCT provided unique visualization of the culprit lesion.

  19. Isotretinoin exposure and risk of inflammatory bowel disease.

    PubMed

    Rashtak, Shadi; Khaleghi, Shahryar; Pittelkow, Mark R; Larson, Joseph J; Lahr, Brian D; Murray, Joseph A

    2014-12-01

    IMPORTANCE Isotretinoin is the standard treatment for refractory severe nodulocystic acne.A true association between prior isotretinoin use and development of inflammatory bowel disease (IBD) is uncertain. Addressing the reality of this association is important in decision making for both the clinician and the patient when isotretinoin treatment is indicated.OBJECTIVE To assess the risk of IBD mainly in patients with acne with and without isotretinoin exposure.DESIGN, SETTING, AND PARTICIPANTS In this retrospective, single-center study, the electronic medical records of patients who were primarily seeking acne treatment were reviewed for isotretinoin exposure. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to search for IBD diagnosis. participants included 1078 patients from 1995 to 2011,with isotretinoin referenced in their medical records, and who had ongoing local medical care defined as having had a serum sample collected between 2006 to 2011 for any reason while an Olmsted County, Minnesota, resident at the time of serum sample collection.EXPOSURES The exposed group included the patients with confirmed prior isotretinoin exposure (n = 576), and the nonexposed group were defined as patients who never received isotretinoin or received it after the diagnosis of IBD (n = 502).MAIN OUTCOMES AND MEASURES Risk of IBD among isotretinoin-exposed vs non exposed patients.RESULTS Both groups were comparable by race, prior systemic antibiotic use, and systemic tetracycline use. Inflammatory bowel disease developed less frequently in the isotretinoin-exposed group vs the nonexposed group (0.9%vs 2.6%; P = .03; unadjusted odds ratio [OR], 0.33; 95%CI, 0.12-0.93; P = .04). The negative association between isotretinoin exposure and IBD remained after adjusting for sex (OR, 0.28; 95%CI, 0.10-0.80;P = .02) and for sex and non acne indication (OR, 0.28; 95%CI, 0.10-0.79; P = .02).CONCLUSIONS AND RELEVANCE Our study did not show an increased risk

  20. Isotretinoin exposure and risk of inflammatory bowel disease.

    PubMed

    Rashtak, Shadi; Khaleghi, Shahryar; Pittelkow, Mark R; Larson, Joseph J; Lahr, Brian D; Murray, Joseph A

    2014-12-01

    IMPORTANCE Isotretinoin is the standard treatment for refractory severe nodulocystic acne.A true association between prior isotretinoin use and development of inflammatory bowel disease (IBD) is uncertain. Addressing the reality of this association is important in decision making for both the clinician and the patient when isotretinoin treatment is indicated.OBJECTIVE To assess the risk of IBD mainly in patients with acne with and without isotretinoin exposure.DESIGN, SETTING, AND PARTICIPANTS In this retrospective, single-center study, the electronic medical records of patients who were primarily seeking acne treatment were reviewed for isotretinoin exposure. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to search for IBD diagnosis. participants included 1078 patients from 1995 to 2011,with isotretinoin referenced in their medical records, and who had ongoing local medical care defined as having had a serum sample collected between 2006 to 2011 for any reason while an Olmsted County, Minnesota, resident at the time of serum sample collection.EXPOSURES The exposed group included the patients with confirmed prior isotretinoin exposure (n = 576), and the nonexposed group were defined as patients who never received isotretinoin or received it after the diagnosis of IBD (n = 502).MAIN OUTCOMES AND MEASURES Risk of IBD among isotretinoin-exposed vs non exposed patients.RESULTS Both groups were comparable by race, prior systemic antibiotic use, and systemic tetracycline use. Inflammatory bowel disease developed less frequently in the isotretinoin-exposed group vs the nonexposed group (0.9%vs 2.6%; P = .03; unadjusted odds ratio [OR], 0.33; 95%CI, 0.12-0.93; P = .04). The negative association between isotretinoin exposure and IBD remained after adjusting for sex (OR, 0.28; 95%CI, 0.10-0.80;P = .02) and for sex and non acne indication (OR, 0.28; 95%CI, 0.10-0.79; P = .02).CONCLUSIONS AND RELEVANCE Our study did not show an increased risk

  1. Important controversies associated with isotretinoin therapy for acne.

    PubMed

    Wolverton, Stephen E; Harper, Julie C

    2013-04-01

    Isotretinoin is a remarkably effective drug for severe, recalcitrant acne vulgaris. Soon after the drug's release in the early 1980s, a number of important adverse effects were reported subsequently leading to a variety of medical and medicolegal controversies. Three of these controversies will be highlighted concerning the putative role of isotretinoin in (1) depression and suicide, (2) inflammatory bowel disease, and (3) iPledge and pregnancy prevention programs. It appears that a very small subset of patients receiving isotretinoin for acne are at risk for depression, which is very manageable provided there is adequate patient awareness of the possibility, maximum communication between the patient and physician, and cessation of therapy if clinically important depression occurs (after which the depression rapidly resolves in a week or less). Multiple controlled studies actually suggest a very favorable effect of isotretinoin on depression and anxiety common in the population requiring isotretinoin. With regard to inflammatory bowel disease, in just one study, only ulcerative colitis association with isotretinoin reached statistical significance. The actual incidence of this association is strikingly low. Finally, it is clear that even the most recent pregnancy prevention program (iPledge) is no more successful than prior programs; there will likely always be a small number of female patients becoming pregnant while receiving isotretinoin for acne vulgaris.

  2. Does isotretinoin therapy of acne cure or cause depression?

    PubMed

    Borovaya, Alena; Olisova, Olga; Ruzicka, Thomas; Sárdy, Miklós

    2013-09-01

    Cosmetic defects in acne may provoke a wide range of mental disorders (depressive, social-phobic, etc.). Isotretinoin is a very effective acne treatment; hence, it usually resolves the associated mental disorders. However, more available data show the possible association of taking isotretinoin and the onset of a depressive syndrome that includes frank depression and even suicidal ideation. The frequency of depressive disorders during isotretinoin treatment varies from 1% to 11% in different studies, and it is unclear whether this is a consequence of isotretinoin therapy. Since it crosses the blood-brain barrier, isotretinoin affects the expression of a broad spectrum of genes in the limbic structures, thus affecting the function of the dopaminergic, serotonergic, and noradrenergic neurons involved in the regulation of mood and emotion. It was suggested that isotretinoin in high concentrations inhibits hippocampal neurogenesis and induces apoptosis of hippocampal cells. However, some studies do not confirm this pathogenic role, and isotretinoin was even reported to have a therapeutic effect in acne-associated depression. In this review, we highlight epidemiological data, the underlying molecular pathogenesis, and the aspects of prevention concerning retinoid-induced depression in acne from the practical point of view of a dermatologist.

  3. 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.

  4. [Isotretinoin and exercise: can the two walk together?].

    PubMed

    Dalal, Adam; Ben-Barak, Shira; Zlotogorski, Abraham; Constantini, Naama

    2014-02-01

    Since its introduction in 1982, isotretinoin has revolutionized acne treatment, targeting the underlying mechanism of the disease, with effective and long-lasting results. During the first decade of its marketing, several cases of hyperCKemia and rhabdomyolysis were linked to isotretinon therapy. A special concern was given to the possible triggering of muscle toxicity by vigorous exercise. These potential effects discouraged the prescription of isotretinoin to physically active patients or required them to abstain from exercise during treatment. Common musculoskeletal adverse effects of isotretinoin include muscle or joint pains. HyperCKemia is frequently found in patients receiving treatment for rare cases of rhabdomyolysis. Isotretinoin-associated muscle toxicity is usually detected in asymptomatic patients, even though symptoms can appear without hyperCKemia. A possible synergistic effect of isotretinoin and exercise is plausible, although supported by weak evidence and mediated by an unknown mechanism. There are only two reports of myoglobinuria and no reports of decreased renal function in exercising patient under treatment. In conclusion, we believe that current data should not deter physicians from offering isotretinoin to physically active patients nor require them to abstain from exercise. Physicians must explain to patients the possible side effects of treatment, ask them to refrain from an unusual change in their exercise regimen and advise them to avoid other triggers of rhabdomyolysis. Patients should be aware of possible signs of muscle toxicity and inform their doctors about any relevant symptoms.

  5. Isotretinoin-induced arthritis mimicking both rheumatoid arthritis and axial spondyloarthritis.

    PubMed

    Yilmaz Tasdelen, Ozlem; Yurdakul, Fatma Gul; Duran, Semra; Bodur, Hatice

    2015-05-01

    Isotretinoin is used for the treatment of various acne lesions that are resistant to other treatments. The most frequent rheumatologic side effect of isotretinoin is transient muscle and/or joint pains. Here, we report a case with bilateral wrist and metacarpophalangeal joint arthritis and unilateral sacroiliitis associated with isotretinoin usage to attract attention, particularly from physiatrists, rheumatologists and dermatologists, to this rare adverse effect of isotretinoin.

  6. Drug-induced ocular side-effects with isotretinoin.

    PubMed

    Santodomingo-Rubido, Jacinto; Barrado-Navascués, Eva; Rubido-Crespo, María-José

    2008-09-01

    Whereas there are numerous reported ocular side-effects from isotretinoin medication, we present the first case report of corneal steepening after systemic treatment with isotretinoin for seven and a half weeks. The case was associated with a significant drop in visual acuity which could not be explained from the refractive error change. All signs and symptoms were absent seven and a half weeks after the medication was withdrawn. The case indicates that eye care professionals need to be vigilant about the possibility of adverse ocular manifestations associated with the use of systemic medications.

  7. Are we underdosing acne patients with generic isotretinoin?

    PubMed

    Mutizwa, Misha M; Sheinbein, David M

    2013-01-15

    With Roche's withdrawl of Accutane from the U.S. market in 2009, isotretinoin has only been available in its generic form. Many clinicians fail to realize that for approval by the U.S. Food and Drug Administration, a generic medication must have a bioequivalence between 80 percent and 125 percent of that of the innovator product. This potential variability in bioavailability between branded and generic medications is important to keep in mind with isotretinoin, given the implications for achieving a sustained remission in acne patients.

  8. Use of Oral Isotretinoin in the Management of Rosacea

    PubMed Central

    Park, Hyunhee; Del Rosso, James Q.

    2011-01-01

    Rosacea is a chronic inflammatory disease affecting roughly 16 million Americans. Topical and oral antibiotic/anti-inflammatory agents are currently the mainstay of therapy and are often used in combination. In this article, the authors discuss the use of oral isotretinoin in the management of rosacea, exploring dosage, comparable efficacy, safety, and cost. PMID:21938271

  9. Use of oral isotretinoin in the management of rosacea.

    PubMed

    Park, Hyunhee; Del Rosso, James Q

    2011-09-01

    Rosacea is a chronic inflammatory disease affecting roughly 16 million Americans. Topical and oral antibiotic/anti-inflammatory agents are currently the mainstay of therapy and are often used in combination. In this article, the authors discuss the use of oral isotretinoin in the management of rosacea, exploring dosage, comparable efficacy, safety, and cost. PMID:21938271

  10. Dissecting cellulitis of the scalp: response to isotretinoin.

    PubMed

    Scerri, L; Williams, H C; Allen, B R

    1996-06-01

    We report three patients with dissecting cellulitis of the scalp. Prolonged treatment with oral isotretinoin was highly effective in all three patients. Furthermore, long-term post-treatment follow-up in two of the patients has shown a sustained therapeutic benefit. PMID:8763434

  11. 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

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

    PubMed

    Nickle, Steven Brandon; Peterson, Nathan; Peterson, Michael

    2014-04-01

    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.

  13. Dermatologists' attitudes, prescription, and counseling patterns for isotretinoin: a questionnaire-based study.

    PubMed

    Nagler, Arielle R; Orlow, Seth J

    2015-02-01

    Isotretinoin, the most effective therapy for severe acne, has engendered controversy. These controversies impact dermatologists' opinions of isotretinoin and prescription behaviors. This study was designed to characterize dermatologists' opinions of controversies surrounding isotretinoin, as well as counseling and prescribing practices. A 25-question survey was emailed to 7,013 dermatologists included in a proprietary database (MBD, Inc.) and anonymous responses were collected. 591 board-certified dermatologists participated. Thirty-seven percent of the responding dermatologists believe that isotretinoin may cause psychiatric disturbances. Dermatologists' opinions on this relationship did not significantly impact prescription practices in patients with history of depression (P=0.056) or in patients being treated with an antidepressant (P=0.118). A larger percentage of dermatologists surveyed believe there is a causal relationship between isotretinoin and psychiatric disturbances than isotretinoin and IBD. Of the surveyed dermatologists, 2.7% believe there is a causal association between isotretinoin and inflammatory bowel disease IBD. In addition, physicians with 20 or fewer years of experience, which included 50% of the responding dermatologists, were significantly less likely to have read the patient brochure (P=0.004), and more likely to prescribe isotretinoin to patients who had not failed systemic antibiotics (P=0.015). This questionnaire also may highlight a practice gap, as more recently trained dermatologists appear less likely to require failure of systemic antibiotics prior to initiating isotretinoin.

  14. Paronychia and granulation tissue formation during treatment with isotretinoin*

    PubMed Central

    Figueiras, Daniela de Almeida; Ramos, Ticiana Batista; Marinho, Ayana Karla de Oliveira Ferreira; Bezerra, Milena Soneley Mendonça; Cauas, Renata Cavalcanti

    2016-01-01

    This paper describes the association of two unusual side effects of treatment with isotretinoin for severe acne: paronychia and excess granulation tissue in the nails furrows. We report a case of male patient aged 19 years, who in the course of the 36th week of treatment with isotretinoin for acne grade III showed erythema, edema, excess granulation tissue and onychocryptosis in various nail beds of hands and feet, with no history of trauma associated. A literature review revealed few reports of these adverse events, and two clinical patterns of exuberant granulation tissue has been described: one in periungual location and other in lesions of previous acne. The rarity and lack of knowledge on the best treatment for granuloma-like reactions make this theme a considerable challenge. PMID:27192525

  15. Perifolliculitis capitis abscedens et suffodiens successfully controlled with topical isotretinoin.

    PubMed

    Karpouzis, Anthony; Giatromanolaki, Alexandra; Sivridis, Efthymios; Kouskoukis, Constantin

    2003-01-01

    Perifolliculitis capitis abscedens et suffodiens (or dissecting folliculitis of the scalp or dissecting cellulitis of the scalp or dissecting perifolliculitis of the scalp) is a rare entity and constitutes the equivalent over the scalp, of hidradenitis suppurativa and acne conglobata. Etiologic factors are unknown. Diagnosis is proven histologically. Management is very difficult and consists in systemic administration or intralesional injection of several drugs or in surgical manipulations. An 18 year-old white patient with cystic infiltrations, alopecia plaques, pustules and other inflammatory elements (clinicohistological features consistent with dissecting folliculitis of the scalp), is presented. Isotretinoin topical application assured successful control of the disease and averted the evolution of the clinical aspect to scarring alopecia and nodule formation. Topical isotretinoin exercises a curative, inhibitory and antiproliferative action, in perifolliculitis capitis abscedens et suffodiens. PMID:12695138

  16. Oral isotretinoin. How can we treat difficult acne patients?

    PubMed

    Leyden, J J

    1997-01-01

    Isotretinoin (Roaccutane/Accutane) therapy (120 mg/kg) normally results in complete clearing of nodulocystic acne followed by prolonged remission, and many patients remain free of disease. Four groups of patients respond poorly or have a high rate of relapse. Preteens and young teenagers show a high rate of relapse and several courses of treatment are usually needed; 14 of 20 under the age of 12 years, 21 of 47 aged 12-14 and 23 of 66 aged 14-16 relapsed within 1 year. Individuals with linear lesions consisting of undermining tracks of follicular epithelium often show only a partial response. These individuals typically have a history of other 'sinus track' disease such as pilonidial sinus and hidradenitis, either themselves or other family members. Hemorrhagic or crusted lesions can be exacerbated by full doses of isotretinoin and patients develop pyrogenic-granuloma-type lesions and even acne-fulminans-like eruptions. Women with adrenal or ovarian syndrome associated with elevated androgens commonly relapse with 6-12 months after isotretinoin therapy.

  17. Oral isotretinoin. How can we treat difficult acne patients?

    PubMed

    Leyden, J J

    1997-01-01

    Isotretinoin (Roaccutane/Accutane) therapy (120 mg/kg) normally results in complete clearing of nodulocystic acne followed by prolonged remission, and many patients remain free of disease. Four groups of patients respond poorly or have a high rate of relapse. Preteens and young teenagers show a high rate of relapse and several courses of treatment are usually needed; 14 of 20 under the age of 12 years, 21 of 47 aged 12-14 and 23 of 66 aged 14-16 relapsed within 1 year. Individuals with linear lesions consisting of undermining tracks of follicular epithelium often show only a partial response. These individuals typically have a history of other 'sinus track' disease such as pilonidial sinus and hidradenitis, either themselves or other family members. Hemorrhagic or crusted lesions can be exacerbated by full doses of isotretinoin and patients develop pyrogenic-granuloma-type lesions and even acne-fulminans-like eruptions. Women with adrenal or ovarian syndrome associated with elevated androgens commonly relapse with 6-12 months after isotretinoin therapy. PMID:9310743

  18. Isotretinoin-induced acute severe myopathy involving pelvic girdle muscles: A case report

    PubMed Central

    Sameem, Farah; Semira

    2016-01-01

    Oral isotretinoin has been in widespread use for more than three decades. It causes numerous side effects; skin and mucous membrane being commonly involved. Musculoskeletal adverse effects are also known to occur, but pelvic girdle myopathy is rarely reported. We report myopathy involving pelvic girdle muscles in a young male who received oral isotretinoin for folliculitis decalvans. PMID:27721552

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

    PubMed

    Abali, Remzi; Yuksel, Mehmet Aytac; Aktas, Cevat; Celik, Cem; Guzel, Savas; Erfan, Gamze; Sahin, Onder

    2013-08-01

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

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-07

    ... HUMAN SERVICES> Food and Drug Administration Determination That ACCUTANE (Isotretinoin) Capsules, 10... Administration (FDA) is announcing its determination that ACCUTANE (isotretinoin) Capsules, 10 milligrams (mg... approved. FDA may not approve an ANDA that does not refer to a listed drug. ACCUTANE...

  1. A novel patient support program to address isotretinoin adherence: proof-of-concept analysis.

    PubMed

    Eichenfield, Lawrence F; Krakowski, Andrew C

    2015-04-01

    The iPLEDGE protocol for isotretinoin treatment requires multiple steps to be completed within strict timing windows, resulting in many interruptions or discontinuations of treatment. The US Food and Drug Administration has indicated that approximately 40% of isotretinoin prescriptions written over the course of one year of the iPLEDGE program were denied due to failure to comply with iPLEDGE. Insurance restrictions add to the likelihood of prescriptions not being filled. Here, we describe a novel program implemented specifically to assist patients and providers with improving isotretinoin therapy adherence. This innovative isotretinoin support program provides assistance with insurance questions and hurdles, an uninterrupted treatment supply, educational support, reminder communications, and an indigent patient assistance program. Proof-of-concept analysis shows that 17 months after implementation of the program, 93% of prescriptions received have been filled. Utilization of the program appears to improve adherence to an isotretinoin treatment regimen, with fewer interruptions due directly to unfilled prescriptions.

  2. Isotretinoin-induced skin fragility in a teenaged athlete: a case report.

    PubMed

    Pavlis, Michelle B; Lieblich, Lawrence

    2013-07-01

    Isotretinoin is approved by the US Food and Drug Administration for the treatment of severe recalcitrant nodular acne. Mucocutaneous toxicity is the most commonly observed side effect of isotretinoin use. Because atrophy and skin fragility may occur while taking isotretinoin, most warnings recommend avoidance of cosmetic procedures, such as dermabrasion, laser treatments, waxing, and chemical peels. We report a case of isotretinoin-induced skin fragility in a 16-year-old adolescent boy who presented with an unusual amount of skin erosions and excoriations on his face during wrestling season. We propose that it may be prudent to advise athletes who are involved in contact sports that skin fragility and increased erosions may occur during or after their course of treatment with isotretinoin.

  3. Effects of isotretinoin on serum vitamin E levels in patients with acne.

    PubMed

    Aktürk, Aysun Şikar; Güzel, Savaş; Bulca, Songül; Demirsoy, Evren Odyakmaz; Bayramgürler, Dilek; Bilen, Nilgün; Kıran, Rebiay

    2013-03-01

    Anecdotal reports suggest that using retinoids with vitamin E leads to improvements of some side effects due to isotretinoin. However, vitamin E blood levels have not been reported previously in patients with acne treated with isotretinoin. We aimed to investigate the serum vitamin E levels before and after isotretinoin therapy in patients with acne. A total of 70 patients treated with isotretinoin for acne in our dermatology department were included in this study. The serum vitamin E levels were measured as baseline before isotretinoin treatment. All patients received 0.6-0.8 mg/kg/d isotretinoin. The treatment was finished within 5-7 months while ensuring that the cumulative dose was 120 mg/kg. Serum vitamin E levels were measured again in the last month of treatment. The mean serum vitamin E levels before and after treatment were compared. Forty-six patients completed the study. It was detected that the mean serum vitamin E level was 20.22 mg/dl before isotretinoin treatment. In the last month of treatment, the mean serum vitamin E level was 16.24 mg/dl. Serum vitamin E levels decreased in all patients except three. The mean serum vitamin E level after treatment was statistically decreased in comparison with the mean serum vitamin E level before treatment. Our results showed that vitamin E levels decreased during isotretinoin treatment. We considered that some of the side effects due to isotretinoin treatment might be related to this, and supplementation vitamin E may be useful during isotretinoin treatment.

  4. Isotretinoin use and the risk of inflammatory bowel disease: a population-based cohort study.

    PubMed

    Alhusayen, Raed O; Juurlink, David N; Mamdani, Muhammad M; Morrow, Richard L; Shear, Neil H; Dormuth, Colin R

    2013-04-01

    Limited evidence suggests that isotretinoin may be associated with inflammatory bowel disease (IBD). To explore this association, we conducted a retrospective population-based cohort study in British Columbia, Canada, among participants who were newly treated with isotretinoin or topical acne medications. The entire population of untreated provincial residents aged 12-29 years served as the reference group. During the 12-year study period, we identified 46,922 participants treated with isotretinoin, 184,824 treated with a topical acne medication, and 1,526,946 untreated individuals. Compared with untreated individuals, we observed no significant association between isotretinoin use and IBD (rate ratio (RR) 1.14; 95% confidence interval (CI) 0.92-1.41). As expected, we found no association with topical acne medications (RR 1.11; 95% CI 0.99-1.24). In prespecified secondary analyses, isotretinoin was associated with IBD among individuals aged 12-19 years (RR 1.39; 95% CI 1.03-1.87) and topical acne medications were associated with ulcerative colitis (RR 1.19; 95% CI 1.00-1.42). Our primary analyses found no association between isotretinoin and IBD. In prespecified secondary analyses, some evidence was found of associations with isotretinoin as well as topical acne medications, suggesting a possible association between IBD and acne itself. Additional research is needed to explore this possibility.

  5. Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients

    PubMed Central

    Ayvaz, Havva Hilal; Ozturk, Gulfer; Ergin, Can; Akıs, Havva Kaya; Gonul, Muzeyyen; Arzuhal, Ercan

    2016-01-01

    Introduction Isotretinoin has been successfully used for the treatment of acne vulgaris. Aim To investigate the effects of isotretinoin on body mass index (BMI), to determine whether isotretinoin causes any changes in serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients, and to correlate variables. Material and methods Thirty-two patients were included in this study. Oral isotretinoin was begun at a dose of 0.5–0.6 mg/kg and raised to 0.6–0.75 mg/kg. Pretreatment and posttreatment third-month BMI and adiponectin, leptin, and ghrelin serum levels were measured. Results The pre- and posttreatment BMI values were not significantly different. In addition, serum adiponectin and leptin levels were significantly increased following isotretinoin therapy while serum ghrelin levels were not different. Conclusions Isotretinoin may exert its anti-inflammatory activity by increasing leptin and adiponectin levels.

  6. Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients

    PubMed Central

    Ayvaz, Havva Hilal; Ozturk, Gulfer; Ergin, Can; Akıs, Havva Kaya; Gonul, Muzeyyen; Arzuhal, Ercan

    2016-01-01

    Introduction Isotretinoin has been successfully used for the treatment of acne vulgaris. Aim To investigate the effects of isotretinoin on body mass index (BMI), to determine whether isotretinoin causes any changes in serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients, and to correlate variables. Material and methods Thirty-two patients were included in this study. Oral isotretinoin was begun at a dose of 0.5–0.6 mg/kg and raised to 0.6–0.75 mg/kg. Pretreatment and posttreatment third-month BMI and adiponectin, leptin, and ghrelin serum levels were measured. Results The pre- and posttreatment BMI values were not significantly different. In addition, serum adiponectin and leptin levels were significantly increased following isotretinoin therapy while serum ghrelin levels were not different. Conclusions Isotretinoin may exert its anti-inflammatory activity by increasing leptin and adiponectin levels. PMID:27605902

  7. Isotretinoin treatment in patients with acne vulgaris: does it impact muscle strength, fatigue, and endurance?

    PubMed

    Yıldızgören, Mustafa Turgut; Rifaioğlu, Emine Nur; Demirkapı, Musa; Ekiz, Timur; Micooğulları, Ahmet; Şen, Tuğba; Turhanoğlu, Ayşe Dicle

    2015-07-01

    The objective of this study was to evaluate the effects of isotretinoin on muscle strength, fatigue, and endurance in patients with acne vulgaris. The study included 27 patients with acne vulgaris who underwent treatment with isotretinoin as well as 26 control patients for comparison. Participants in the treatment group received oral isotretinoin 0.5 mg/kg once daily for 1 month followed by an increased dose of 1 mg/kg once daily for 2 months. Isokinetic measurements were obtained from the hamstrings and quadriceps on the nondominant side of the body at baseline and 3-month follow-up using an isokinetic dynamometer. Results indicated that systemic isotretinoin did not significantly alter muscle strength, fatigue, and endurance.

  8. Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration.

    PubMed

    Radu, Roxana A; Mata, Nathan L; Nusinowitz, Steven; Liu, Xinran; Sieving, Paul A; Travis, Gabriel H

    2003-04-15

    Recessive Stargardt's macular degeneration is an inherited blinding disease of children caused by mutations in the ABCR gene. The primary pathologic defect in Stargardt's disease is accumulation of toxic lipofuscin pigments such as N-retinylidene-N-retinylethanolamine (A2E) in cells of the retinal pigment epithelium. This accumulation appears to be responsible for the photoreceptor death and severe visual loss in Stargardt's patients. Here, we tested a therapeutic strategy to inhibit lipofuscin accumulation in a mouse model of recessive Stargardt's disease. Isotretinoin (Accutane) has been shown to slow the synthesis of 11-cis-retinaldehyde and regeneration of rhodopsin by inhibiting 11-cis-retinol dehydrogenase in the visual cycle. Light activation of rhodopsin results in its release of all-trans-retinaldehyde, which constitutes the first reactant in A2E biosynthesis. Accordingly, we tested the effects of isotretinoin on lipofuscin accumulation in abcr(-/-) knockout mice. Isotretinoin blocked the formation of A2E biochemically and the accumulation of lipofuscin pigments by electron microscopy. We observed no significant visual loss in treated abcr(-/-) mice by electroretinography. Isotretinoin also blocked the slower, age-dependent accumulation of lipofuscin in wild-type mice. These results corroborate the proposed mechanism of A2E biogenesis. Further, they suggest that treatment with isotretinoin may inhibit lipofuscin accumulation and thus delay the onset of visual loss in Stargardt's patients. Finally, the results suggest that isotretinoin may be an effective treatment for other forms of retinal or macular degeneration associated with lipofuscin accumulation.

  9. Effects of oral isotretinoin on lipids and liver enzymes in acne patients.

    PubMed

    Kızılyel, Okan; Metin, Mahmut S; Elmas, Ömer F; Çayır, Yasemin; Aktaş, Akın

    2014-11-01

    Isotretinoin has been used to treat severe inflammatory acne that is resistant to antibiotics or topical agents; however, it also may cause alterations in lipids and liver enzymes. In this retrospective study, we evaluated changes in lipids and liver enzymes in 322 acne patients who had been treated with oral isotretinoin at our institution over a 3-year period. Each patient's medical records were evaluated to determine baseline triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels compared to levels recorded at 3 and 6 months following initiation of treatment with oral isotretinoin. Overall, statistically significant increases in TG and LDL levels were noted following treatment with isotretinoin (P<.001, respectively), while HDL levels were shown to decrease (P=.016). Although ALT levels also increased, the changes were not statistically significant increases in AST levels also were noted (P=.72). In our study, isotretinoin appeared to have a greater effect on lipids than liver enzymes. Dermatologists should not avoid isotretinoin use for appropriate indications, but close follow-up is important.

  10. The antiestrogen 4-hydroxytamoxifen protects against isotretinoin-induced permeability transition and bioenergetic dysfunction of liver mitochondria: comparison with tamoxifen.

    PubMed

    Silva, Filomena S G; Ribeiro, Mariana P C; Santos, Maria S; Rocha-Pereira, Petronila; Santos-Silva, Alice; Custódio, José B A

    2013-08-01

    The combination of isotretinoin (13-cis-retinoic acid) with antiestrogens seems to be a promising strategy for cancer chemotherapy. The aim of the study was to evaluate the effects of isotretinoin alone or in combination with 4-hydroxytamoxifen (OHTAM) and with its prodrug tamoxifen (TAM), on the functions of rat liver mitochondria, i.e., mitochondrial permeability transition (MPT), bioenergetic functions and adenine nucleotide translocase (ANT). Isotretinoin (5 nmol/mg protein) induced the Ca²⁺-dependent MPT pore opening in mitochondria energized with succinate, which was prevented by OHTAM, cyclosporine A, TAM and ANT ligands. When mitochondria were energized with glutamate/malate and in the absence of added Ca²⁺ isotretinoin decreased the state 3 respiration, the ATP levels, the active ANT content and increased the lag phase of the phosphorylation cycle, demonstrating that isotretinoin decreased the mitochondrial phosphorylation efficiency. These changes of isotretinoin in bioenergetic parameters were not significant in the presence of succinate. The effects of isotretinoin at 5 nmol/mg protein on the Ca²⁺-dependent MPT and phosphorylative efficacy may be related with interactions with the ANT. Above 10 nmol/mg protein isotretinoin strongly diminished the active ANT content, decreased the Δψ, inhibited the complex I and induced proton leak through the Fo fraction of complex V. The combination of OHTAM with isotretinoin only induced significant changes in the energy production systems at concentrations ≥5 nmol isotretinoin/mg protein. Therefore, our results suggest that isotretinoin-associated liver toxicity is possibly related with mitochondrial dysfunctions and that the combination with OHTAM may contribute to decrease its toxicity.

  11. 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.

  12. The in vitro and in vivo genotoxicity of isotretinoin assessed by cytokinesis blocked micronucleus assay and comet assay.

    PubMed

    Silva, F S G; Oliveira, H; Moreiras, A; Fernandes, J C; Bronze-da-Rocha, E; Figueiredo, A; Custódio, J B A; Rocha-Pereira, P; Santos-Silva, A

    2013-03-01

    Isotretinoin is a retinoic acid frequently used in monotherapy or combined with narrow-band ultraviolet B (NBUVB) irradiation to treat patients with acne and psoriasis vulgaris. As both diseases need frequent and/or prolonged therapeutic interventions, the study of the genotoxicity of retinoids becomes important. Our aim was to study the genotoxic effects of isotretinoin alone or combined with NBUVB. In vitro studies were performed in the absence of S9 metabolic activation using blood from five healthy volunteers, incubated 72 h with isotretinoin (1.2-20 μM) (i.e., at concentrations usually achieved in blood with therapeutic doses as well as at higher concentrations). In vivo studies were also performed using blood from two patients with acne and three patients with psoriasis vulgaris treated with isotretinoin in monotherapy (8 or 20mg/day) or combined with NBUVB (20mg isotretinoin/day+NBUVB). The genotoxic effect was evaluated by the cytokinesis-blocked micronucleus and the comet assays. Our studies showed that isotretinoin alone was not genotoxic when tested in human lymphocytes in vitro and in vivo. There was no clear genotoxic effect in psoriatic patients treated with isotretinoin and NBUVB. The in vitro studies showed that isotretinoin induced apoptosis and necrosis in human lymphocytes at higher doses.

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

    PubMed

    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

  14. Effect of isotretinoin on serum levels of precursor and peripherally derived androgens in patients with acne.

    PubMed

    Lookingbill, D P; Demers, L M; Tigelaar, R E; Shalita, A R

    1988-04-01

    Sebaceous glands are stimulated by androgens and can convert them to more active forms. Isotretinoin, however, has a profound inhibitory effect on sebaceous gland size and function. This study evaluated the effect of isotretinoin on serum levels of precursor and tissue-derived androgens. Twenty-four subjects (15 men and nine women) were treated for 20 weeks with 1 mg/kg/d of isotretinoin. Serum samples were obtained at baseline, 8, 16, and 24 weeks, and assayed for precursor androgens--total testosterone (TT), free testosterone (free T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S); and tissue androgens--dihydrotestosterone (DHT), and its metabolite, 3 alpha-androstanediol glucuronide (3 alpha-diol G). Isotretinoin had no meaningful effects on precursor androgens, except for producing an elevation of free T in women. In contrast, isotretinoin produced depressions in the serum levels of DHT and 3 alpha-diol G in women and in 3 alpha-diol G in men. These decreases are believed to be the result, rather than the cause, of a reduction in the size of the sebaceous glands: The magnitude of the observed decreases may represent the amount of tissue-derived androgens that sebaceous glands normally contribute to the circulating pool. PMID:2965551

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

    PubMed

    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.

  16. The effects of isotretinoin on the ovarian reserve of females with acne.

    PubMed

    Sikar Aktürk, Aysun; Abalı, Remzi; Yüksel, Mehmet Aytaç; Güzel, Eda Çelik; Güzel, Savaş; Kıran, Rebiay

    2014-01-01

    There are some side effects of isotretinoin in many organs. However, a study investigating the effects of isotretinoin on the human ovarian reserve has not been reported previously. The study was conducted to investigate possible effects of isotretinoin on ovarian reserve. Serum anti-Müllerian hormone (AMH) levels were measured at the beginning and at the end of isotretinoin treatment in 22 patients with acne and in 22 women without. The mean AMH level before treatment was 5.77 ng/mL in the study group and 3.79 ng/mL in the control group (p = 0.008). Following treatment, the mean AMH level was 4.69 ng/mL in the study group. This mean AMH level after treatment was statistically lower than the AMH level before treatment (p = 0.012). There was no significant difference between the mean AMH level at the end of treatment and that of the control group (p = 0.20). The high level of pre-treatment AMH levels could be an evidence of hyperandrogenism in women with acne, even if they are not identified as having polycystic ovary syndrome (PCOS) or hyperandrogenism. Decrease in AMH levels following exposure to isotretinoin may suggest that it has a detrimental effect on the ovaries.

  17. 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

  18. A case of isotretinoin-induced purpura annularis telangiectodes of Majocchi and review of substance-induced pigmented purpuric dermatosis.

    PubMed

    Kaplan, Rachel; Meehan, Shane A; Leger, Marie

    2014-02-01

    IMPORTANCE Medications as well as chemical and food exposures have been causally linked to the development of pigmented purpuric dermatosis (PPD). We describe herein what is to our knowledge the first reported case of isotretinoin-induced PPD. OBSERVATIONS A woman in her 30s presented with purpura annularis telangiectodes of Majocchi on the lower extremities 2 months after initiating isotretinoin for the treatment of refractory nodulocystic acne. CONCLUSIONS AND RELEVANCE We believe isotretinoin was the most likely causative agent in this case because the lesions began after initiation of isotretinoin treatment and resolved shortly after its termination, and the pathologic findings were consistent with other described cases of drug-induced PPD. The lesions have continued to fade, and no new lesions have developed in a 3-month follow-up period. Drug-induced PPD is distinct from idiopathic PPD, and it is important to consider isotretinoin as a potential inciting agent.

  19. Congenital microtia in a neonate due to maternal isotretinoin exposure 1 month before pregnancy: Case Report.

    PubMed

    Shirazi, Mahboobeh; Abbariki, Ezzat; Pirjani, Reihaneh; Akhavan, Setareh; Dastgerdy, Ebrahim

    2015-06-01

    Isotretinoin is a drug used for treating severe cystic/nodular acne. Severe malformations have been documented in neonates whose mothers had taken isotretinoin during pregnancy. Women who became pregnant one cycle after completing therapy are believed to be at teratogenic risk not higher than baseline. We describe the case of a newborn whose mother had taken the drug for 4 weeks. The woman then had contraception for 4 weeks (after the drug treatment had finished), and became pregnant after that period. The newborn had isolated bilateral microtia due to suspected isotretinoin exposure. His mother also had a history of urine tract infection in the second week of pregnancy that was treated with cephalexin. The parents were not from a consanguineous marriage and had no family history of congenital malformations. To reduce the risk, effective contraception should be continued in fertile women more than 1 month after completing therapy. PMID:25773513

  20. Isotretinoin treatment inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration.

    PubMed

    Radu, Roxana A; Mata, Nathan L; Nusinowitz, Steven; Liu, Xinran; Travis, Gabriel H

    2004-01-01

    Recessive Stargardt's macular degeneration is an inherited blinding disease of children caused by mutations in the ABCR gene. The primary pathologic defect in Stargardt's discase is accumulation of toxic lipofuscin pigments such as N-retinylidene-N-retinylethanolamine (A2E) in cells of the retinal pigment epithelium (RPE). This accumulation appears to be responsible for the photoreceptor death and severe visual loss in Stargardt's patients. Here, we tested a novel therapeutic strategy to inhibit lipofuscin accumulation in a mouse model of recessive Stargardt's disease. Isotretinoin (Accutane) has been shown to slow the synthesis of 11-cis-retinaldehyde (11cRAL) and regeneration of rhodopsin by inhibiting 11-cis-retinol dehydrogenase (11cRDH) in the visual cycle. Light activation of rhodopsin results in its release of all-trans-retinaldehyde (atRAL), which constitutes the first reactant in A2E biosynthesis. Accordingly, we tested the effects of isotretinoin on lipofuscin accumulation in abcr-/- knockout mice. Isotretinoin blocked the formation of A2E biochemically and the accumulation of lipofuscin pigments by electron microscopy. We observed no significant visual loss in treated abcr-/- mice by electroretinography. Isotretinoin also blocked the slower, age-dependent accumulation of lipofuscin in wild-type mice. These results corroborate the proposed mechanism of A2E biogenesis. Further, they suggest that treatment with isotretinoin may inhibit lipofuscin accumulation and thus delay the onset of visual loss in Stargardt's patients. Finally, the results suggest that isotretinoin may be an effective treatment for other forms of retinal or macular degeneration associated with lipofuscin accumulation.

  1. Generation of radical oxygen species by neural crest cells treated in vitro with isotretinoin and 4-oxo-isotretinoin.

    PubMed

    Davis, W L; Crawford, L A; Cooper, O J; Farmer, G R; Thomas, D; Freeman, B L

    1990-01-01

    The effects of isotretinoin (IR) and its primary metabolite (in the human), 4-oxo-isotretinoin (4-OIR or OIR), on isolated chick neural crest cells (NCC's) in culture were studied. NCC's were found to be deficient in both superoxide dismutase (SOD) and catalase, two of the enzymes known to function in the "scavenging" (dismutation) of toxic radical oxygen species (ROS) such as the superoxide anion and hydrogen peroxide. The addition of IR or OIR to the culture medium significantly depressed the viability of the NCC's when compared to untreated cells. OIR was more potent in this regard than IR. In the presence of either IR or OIR, NCC's generated superoxide anions (O2.), hydrogen peroxide (H2O2), and hydroxyl anions (OH.). OIR was again more potent. The cytotoxicity of IR or OIR was demonstrated by the "leakage" of radioactive chromium from prelabeled cells. The latter is suggestive of a primary surface membrane defect, most logically via the induction of lipid peroxides by the retinoids. The latter is accompanied by an increase in membrane permeability and porosity as evidenced by the fact that various fluorescently labeled molecules, including BSA-FITC (MW 69,000), gain entrance into the cytoplasm of the retinoid treated cells. No label was seen in the cytoplasm of similarly treated control cells. When SOD (200 units/ml) or catalase (400 units/ml) was added to the culture media of IR- or OIR-treated NCCs, cell viability was increased and the concentration of the various ROS generated was decreased. Membrane leakiness to chromium and FITC-BSA was also decreased in the presence of these enzymes. Free radicals, when not inactivated (dismutated), are known to be pathobiotic to most cells. Cell membranes are at a particular high risk from ROS which induce structural, physiological, and biochemical alterations in the cell membrane. The latter can have a negative effect on cell permeability, maintenance of normal ionic gradients, membrane enzyme activity, cell

  2. Dissecting cellulitis of the scalp treated with rifampicin and isotretinoin: case reports.

    PubMed

    Georgala, Sofia; Korfitis, Chrysovalantis; Ioannidou, Dikaia; Alestas, Theodosis; Kylafis, Georgios; Georgala, Caterina

    2008-09-01

    Dissecting cellulitis of the scalp, or perifolliculitis capitis abscedens et suffodiens, is an uncommon chronic suppurative disease of the scalp manifested by follicular and perifollicular inflammatory nodules that suppurate and undermine, forming intercommunicating sinuses, and leading to scarring alopecia. Treatment generally fails to obtain a permanently successful result; thus, many therapeutic options have been proposed. We report 4 cases of dissecting cellulitis of the scalp successfully treated with oral rifampicin and oral isotretinoin. To our knowledge, this is the first report of oral rifampicin used concomitantly with oral isotretinoin in this disease entity. We also present a brief review of the literature on the topic. PMID:18856159

  3. Severe Facial Hirsutism Following Isotretinoin Therapy: An Under-reported Entity.

    PubMed

    Ramot, Yuval; Sheffer, Sivan; Zlotogorski, Abraham

    2015-01-01

    Hirsutism is usually a manifestation of hyperandrogenism, and iatrogenic causes for excess hair growth are uncommon. Here, we report on a 48-year-old female patient, who developed severe excess facial hair following treatment with isotretinoin for papulopustular rosacea. To the best of our knowledge, only one case has been reported before, and not in the dermatology literature. Taking into consideration the fact that isotretinoin is a widely prescribed medication in the dermatology practice, information on its possible adverse effects is of major importance for the treating dermatologist. PMID:26622158

  4. Severe Facial Hirsutism Following Isotretinoin Therapy: An Under-reported Entity

    PubMed Central

    Ramot, Yuval; Sheffer, Sivan; Zlotogorski, Abraham

    2015-01-01

    Hirsutism is usually a manifestation of hyperandrogenism, and iatrogenic causes for excess hair growth are uncommon. Here, we report on a 48-year-old female patient, who developed severe excess facial hair following treatment with isotretinoin for papulopustular rosacea. To the best of our knowledge, only one case has been reported before, and not in the dermatology literature. Taking into consideration the fact that isotretinoin is a widely prescribed medication in the dermatology practice, information on its possible adverse effects is of major importance for the treating dermatologist. PMID:26622158

  5. Tolerance to systemic isotretinoin therapy in two patients using highly wettable contact lenses.

    PubMed

    Arman, Ayşegül; Demirseren, D Deniz; Akoglu, Gulsen

    2014-01-01

    Purpose. Numerous ocular side effects have been reported with the use of systemic isotretinoin therapy. Herein, we presented two contact lens user patients who did not have contact lens intolerance during systemic isotretinoin therapy. Methods. 25-year-old male and 20-year-old female patients with severe acne vulgaris who were using highly wettable silicone hydrogel contact lenses which increase tear film stability were examined. Tear film function tests including Schirmer tests and tear break up time (TBUT) test and ocular surface staining with fluorescein were done. Subjective ocular complaints were scored with ocular surface disease index (OSDI) questionnaire. Patients were followed up monthly and examinations were repeated at each visit. Results. Both patients completed the therapy after a cumulative dose of 140 mg/kg isotretinoin in 6 months. The OSDI score and tear film function tests before and after treatment were all within normal limits. Discussion. Highly wettable contact lenses that provide increase in the tear film stability may be used during systemic retinoid therapy under close followups. Although isotretinoin affects ocular glands, the differences between tolerances to this retinoid therapy need to be investigated in larger patient groups using contact lenses.

  6. Tolerance to Systemic Isotretinoin Therapy in Two Patients Using Highly Wettable Contact Lenses

    PubMed Central

    Arman, Ayşegül; Demirseren, D. Deniz

    2014-01-01

    Purpose. Numerous ocular side effects have been reported with the use of systemic isotretinoin therapy. Herein, we presented two contact lens user patients who did not have contact lens intolerance during systemic isotretinoin therapy. Methods. 25-year-old male and 20-year-old female patients with severe acne vulgaris who were using highly wettable silicone hydrogel contact lenses which increase tear film stability were examined. Tear film function tests including Schirmer tests and tear break up time (TBUT) test and ocular surface staining with fluorescein were done. Subjective ocular complaints were scored with ocular surface disease index (OSDI) questionnaire. Patients were followed up monthly and examinations were repeated at each visit. Results. Both patients completed the therapy after a cumulative dose of 140 mg/kg isotretinoin in 6 months. The OSDI score and tear film function tests before and after treatment were all within normal limits. Discussion. Highly wettable contact lenses that provide increase in the tear film stability may be used during systemic retinoid therapy under close followups. Although isotretinoin affects ocular glands, the differences between tolerances to this retinoid therapy need to be investigated in larger patient groups using contact lenses. PMID:24707422

  7. [Exposure to isotretinoin during pregnancy in France: 25 years of follow-up].

    PubMed

    Rouzès, Agnès; Jonville-Béra, Annie-Pierre

    2014-01-01

    Because of its teratogenicity, isotretinoin is contraindicated in pregnant women and also among women of childbearing age in the absence of effective contraception. The objective of this work is to summarize the results of studies assessing the effects of regulatory measures successively implemented in France since 1996 to prevent foetal exposure to isotretinoin. The five pharmacovigilance studies have shown persistence of pregnancies exposed to isotretinoin, with an estimated incidence in the latter study, between 0.32 and 0.95 per 1000 treated women of childbearing age. The strengthening of the prevention plan of pregnancies, established in France in March 2010, seems to have resulted in a decrease in the incidence of pregnancies exposed, but this trend needs to be confirmed. However, these pregnancies are almost preventable, because most of them are explained by the non-compliance with the conditions of prescribing and dispensing. Then it seems mandatory to not deliver oral isotretinoin if it is not prescribed in accordance with the prescription laid down by the authorities.

  8. Retinal nerve fiber layer and ganglion cell layer thickness in patients receiving systemic isotretinoin therapy.

    PubMed

    Sekeryapan, Berrak; Dılek, Nursel; Oner, Veysi; Turkyılmaz, Kemal; Aslan, Mehmet Gokhan

    2013-10-01

    To evaluate the effect of oral isotretinoin therapy on retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness by spectral domain optical coherence tomography (OCT). This prospective study included newly diagnosed nodulocystic acne patients about to receive isotretinoin treatment. Macular average GCL thickness and peripapillary average, temporal, nasal, inferior, and superior quadrant RNFL thickness were measured by OCT before and after isotretinoin treatment. Pre- and post-treatment measurements were compared with paired t test. Fifty-six eyes of 28 patients were included. The mean duration of the treatment was 6.5 ± 1.3 months. The mean average GCL thickness was 90.04 ± 5.87 (80-96) μm at baseline and 90.75 ± 6.34 (81-96) μm after treatment. The mean average RNFL thickness was 93.25 ± 6.06 μm (84-107) before treatment and 93.05 ± 5.54 μm (82-106) after treatment. There were no statistically significant differences between pre- and post-treatment values (all p > 0.05). A 6-month course of systemic isotretinoin therapy seems to have no unfavorable effect on retinal ganglion cells; however, larger studies with longer follow-up periods are needed to be conclusive.

  9. A randomized and controlled trial about the use of oral isotretinoin for photoaging.

    PubMed

    Bagatin, Ediléia; Parada, Meire O B; Miot, Hélio A; Hassun, Karime M; Michalany, Nilceo; Talarico, Sergio

    2010-02-01

    Topical retinoids are used to treat photoaging; oral isotretinoin is gold standard for acne; "off label" indications, including photoaging, have been reported with insufficient evidence of efficacy. This is a randomized controlled phase II trial with clinical and histological assessment to evaluate efficacy and safety of oral isotretinoin for photoaging. Study population was comprised of 32 menopausal or sterilized women, aged 40-55, divided in 2 groups: A (21) received 20mg isotretinoin, 3 times per week, nightly moisturizer, and daily sunscreen, for three months; B (11) just moisturizer/sunscreen. Main outcome measures were: overall clinical assessment; profilometry, corneometer and elasticity tests in periocular regions and left forearm; before/after biopsies from left forearm in patients of B and in 10 randomly selected of A. Microscopic blinded evaluation of epidermal thickness, dermal elastosis, new collagen, p53 epidermal expression was performed by quantitative digital image analysis. All data were submitted to statistical analysis. Clinical evaluation showed slight improvement; profilometry, corneometer and skin elasticity tests presented significant difference in pre/post values (P = 0.001 to 0.028), but no differences between A/B. Histological findings and p53 expression were comparable between groups before treatment (P > 0.1); microscopic analysis showed no differences between groups for most variables, after treatment. Slight but significant difference between A/B for p53 with major reduction post isotretinoin [0.66+/-0.31 vs. 0.94+/-0.34 respectively (P = 0.04) was observed. There were minor side effects and no significant laboratory test alterations. We concluded that no significant clinical, microscopic changes but p53 epidermal expression reduction were observed. The role of ultra-violet induced p53 mutation in skin carcinogenesis reinforces retinoids chemoprevention. Oral isotretinoin seemed safe but not effective to treat photoaging. Caution

  10. 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.

  11. Colloidal carriers of isotretinoin for topical acne treatment: skin uptake, ATR-FTIR and in vitro cytotoxicity studies.

    PubMed

    Gürbüz, Aslı; Özhan, Gül; Güngör, Sevgi; Erdal, M Sedef

    2015-09-01

    Acne vulgaris is the chronical, multifactorial and complex disease of the pilosebaceous unit in the skin. The main goal of the topical therapy in acne is to target the drug to epidermal and deep dermal regions by minimizing systemic absorption . Isotretinoin, a retinoic acid derivative, is the most effective drug in acne pathogenesis. Because systemic treatment may cause many side effects, topical isotretinoin treatment is an option in the management of acne. However, due to its high lipophilic character, isotretinoin tends to accumulate in the upper stratum corneum, thus its penetration into the lower layers is limited, which restricts the efficiency of topical treatment. Microemulsions are fluid, isotropic, colloidal drug carriers that have been widely studied as drug delivery systems. The percutaneous transport of active agents can be enhanced by microemulsions when compared with their conventional formulations. The purpose of this study was to evaluate microemulsions as alternative topical carriers for isotretinoin with an objective to improve its skin uptake. After in vitro permeation studies, the dermal penetration of isotretinoin from microemulsions was investigated by tape stripping procedure. Confocal laser scanning microscopy provided insight about the localization of the drug in the skin. The interaction between the microemulsion components and stratum corneum lipids is studied by ATR-FTIR spectroscopy. The relative safety of the microemulsions was assessed in mouse embryonic fibroblasts using MTT viability test. The results indicate that microemulsion-based novel colloidal carriers have a potential for enhanced skin delivery and localization of isotretinoin.

  12. A Randomized-Controlled Trial of Oral Low-Dose Isotretinoin for Difficult-To-Treat Papulopustular Rosacea.

    PubMed

    Sbidian, Emilie; Vicaut, Éric; Chidiack, Henri; Anselin, Elie; Cribier, Bernard; Dréno, Brigitte; Chosidow, Olivier

    2016-06-01

    Rosacea is a chronic inflammatory facial skin disease with psychosocial impact. Oral cyclines are recommended for moderate-to-severe papulopustular rosacea. Oral isotretinoin was found valuable for difficult-to-treat cases in several reports. This multicenter, double-blind, randomized-placebo-controlled trial compared oral isotretinoin (0.25 mg/kg/day) with placebo (2:1 ratio) for difficult-to-treat papulopustular rosacea. Included patients had at least eight papulopustular lesions. The primary endpoint after the 4-month treatment period was the response rate: at least 90% reduction of the number of papules/pustules compared with baseline. Secondary outcomes included measures on quality of life (Skindex score). Between February 2007 and August 2009, 156 patients were randomized to receive either isotretinoin (n = 108) or placebo (n = 48). In the intention-to-treat population, 57.4% of isotretinoin recipients reached the primary endpoint, compared with 10.4% of those taking the placebo (absolute difference, 47 percentage points; 95% confidence interval, 34.3-59.7; P < 0.0001). To consider therapy successful, 2.1 (95% confidence interval 1.7-2.9) patients had to be treated. Skindex scores had improved significantly more for isotretinoin- than placebo-treated patients. Rosacea relapsed in 27 (58.3%) of 51 patients who accepted 4 months of continued follow-up, with a median of 15 weeks to recurrence. The percentages of patients in each arm who stopped their treatment because of adverse event(s) did not differ. Low-dose isotretinoin was an effective therapeutic option for difficult-to-treat papulopustular rosacea. Further studies should investigate the value of a minimal effective isotretinoin dose to maintain these remissions. PMID:26854486

  13. [Folliculitis nuchae scleroticans--successful treatment with 13-cis-retinoic acid (isotretinoin)].

    PubMed

    Stieler, W; Senff, H; Jänner, M

    1988-11-01

    Acne keloidalis nuchae is characterized by keloidal papules and plaques. The lesions are located on the occipital scalp and posterior neck. This rare therapy-resistant condition is nearly always seen in men, particularly in negroes. Advanced stages of the disease require surgical excision with split-thickness skin grafts or treatment with a CO2 laser. Oral therapy with 13-cis-retinoic acid (isotretinoin) in a 23-year-old white man resulted in remarkable improvement within a few weeks.

  14. 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

  15. 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. PMID:24985041

  16. Isotretinoin: dose, duration and relapse. What does 30 years of usage tell us?

    PubMed

    Rademaker, Marius

    2013-08-01

    With 30 years of clinical use, it is appropriate to review the use of isotretinoin. We now understand that retinoids influence cellular growth, differentiation, morphogenesis and apoptosis, inhibit tumour promotion and malignant cell growth, exert immuno-modulatory actions and alter cellular cohesiveness. This has expanded the indications of isotretinoin from just acne and rosacea to a wide range of inflammatory and malignant skin disorders. While the standard dose of 0.5 to 1 mg/kg per day for 4 months to a cumulative dose of 120-140 mg/kg per day has served us well in the management of acne vulgaris, there is emerging evidence that much lower dosages (as low as 5 mg/day) are just as effective but have significantly fewer adverse effects. Relapse of acne vulgaris continues to be a problem but we are beginning to recognise that this is related less to the cumulative dose and more to the length of sebaceous gland suppression. Other factors important for relapse include a macrocomedonal pattern of acne, smoking and age, both younger (under 14 years) and older (over 25 years). After 30 years of use, we now understand why isotretinoin is such an effective drug. Not only does it clear acne in almost all patients, long-term remission can be achieved in 70-80% of patients with a single course. Important changes in the use of isotretinoin include using a lower daily dose for a longer period of time. New indications continue to emerge, particularly as a potential treatment for both intrinsic and extrinsic (photo) aging. Teratogenicity however, remains a very significant concern.

  17. 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.

  18. Low-Dose Isotretinoin: An Option for Difficult-to-Treat Papulopustular Rosacea.

    PubMed

    van Zuuren, Esther J; Fedorowicz, Zbys

    2016-06-01

    Rosacea is a chronic disease with a profound impact on quality of life. Although there are a range of treatments for its many manifestations, some cases are difficult to treat. Sbidian et al. show in this double-blind, randomized, placebo-controlled trial that low-dose isotretinoin can be effective in treating difficult-to-treat and frequently relapsing papulopustular rosacea. PMID:27212646

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

    PubMed Central

    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

    Background: The current standard recommendation is to avoid surgical interventions in patients taking oral isotretinoin. However, this recommendation has been questioned in several recent publications. Aim: To document the safety of cosmetic and surgical interventions, among patients receiving or recently received oral isotretinoin. Materials and Methods: 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. Results: 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. Conclusion: 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. PMID:27398012

  20. Hepatotoxicity of isotretinoin in patients with acne and Gilbert's syndrome: a comparative study

    PubMed Central

    Fernández-Crehuet, Pablo; Fernández-Crehuet, José Luis; Allam, Mohamed Farouk; Fernández-Crehuet Navajas, Rafael

    2014-01-01

    Objectives The objective of our follow-up study is to evaluate liver function tests (LFTs) and lipid profiles in patients with Gilbert's syndrome treated with isotretinoin because of severe acne. Setting Dermatology outpatient clinics of three regional hospitals of Jaén (Spain). Participants Over 4 years, we included all patients diagnosed with severe acne. Only 37 patients were identified, of which 11 had Gilbert's syndrome. Interventions All patients were treated with isotretinoin and followed-up in our outpatient clinics after 10 and 20 weeks. Patients were subjected to an interview questionnaire which included data on age, gender, complete blood count, coagulation profile, fasting blood glucose, LFTs and lipid profiles. Data and results of patients with severe acne and Gilbert's syndrome were compared with those of 26 patients with only severe acne (control group). Primary outcome Blood analyses were repeated in the follow-up visits. Results In patients with Gilbert's syndrome, bilirubin levels showed substantial decrease over the 20-week follow-up, with more decrease after 10 weeks. None of the control group patients had significant increase in total bilirubin levels after 10 and 20 weeks of follow-up. Liver enzymes were maintained within normal levels in both groups. Both study groups did not show significant pathological increase in lipid profile levels. LDL levels were increased in the two study groups, but this increase was less substantial in patients with Gilbert's syndrome. Conclusions Our preliminary results suggest that oral isotretinoin could be an effective, safe treatment for patients with Gilbert's syndrome, and may lower bilirubin levels in the first 10 weeks of treatment. Limitations of the study include the small numbers of participants and the fact that it is restricted to one region of Spain. PMID:24650805

  1. Isotretinoin treatment of autosomal recessive congenital ichthyosis complicated by coexisting dysferlinopathy.

    PubMed

    Mashiah, J; Harel, A; Bitterman, O; Sagi, L; Gat, A; Fellig, Y; Ben-Shachar, S; Sprecher, E

    2016-06-01

    Consanguinity is known to be associated with an increase in the prevalence of autosomal recessive disorders such as autosomal recessive congenital ichthyosis (ARCI). ARCI often responds well to retinoid treatment. We describe a patient with ARCI who improved under isotretinoin treatment. The patient subsequently developed elevated levels of serum creatinine phosphokinase (CPK), which led to the diagnosis of a second autosomal recessive disorder, dysferlinopathy, a rare myopathy characterized by muscle weakness, decreased tendon reflexes and marked elevation of CPK levels. This report demonstrates the need for physicians to remain alert to the possible coexistence of rare and mutually relevant disorders in populations with a high rate of consanguinity. PMID:26620441

  2. 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

  3. The Effect of Evening Primrose Oil for the Prevention of Xerotic Cheilitis in Acne Patients Being Treated with Isotretinoin: A Pilot Study

    PubMed Central

    Park, Kui Young; Ko, Eun Jung; Kim, In Su; Li, Kapsok; Kim, Beom Joon; Seo, Seong Jun; Kim, Myeung Nam

    2014-01-01

    Background The most common adverse effects of oral isotretinoin are cheilitis, skin dryness, dry eyes, and conjunctivitis, whereas evening primrose oil (EPO) is known to improve skin moisture and transepidermal water loss (TEWL) in healthy adults and atopic patients. Objective To evaluate the clinical efficacy and safety of EPO in preventing xerotic cheilitis in acne patients being treated with oral isotretinoin. Methods Forty Korean volunteers of Fitzpatrick skin types III and IV, having moderate acne, were enrolled and randomized to receive either isotretinoin with or without EPO for 8 weeks. The efficacy of treatment was evaluated on the basis of global acne grading system scores, number of inflammatory and noninflammatory lesions, TEWL, corneometry, physician's global assessment, and patient satisfaction. Results The results after 8 weeks of treatment showed that the TEWL of the lip increased significantly during isotretinoin treatment, whereas the TEWL of the hand dorsum showed no significant change. The increase of the TEWL of the lip was more definite in the control group than in the experimental group. The number of acne lesions decreased significantly in both groups, and there were no differences between them. Conclusion Our study suggests that the addition of EPO improved xerotic cheilitis in acne patients being treated with oral isotretinoin. However, besides TEWL and corneometry assessments, additional studies are required for a complete understanding of the role of EPO in xerotic cheilitis in acne patients being treated with oral isotretinoin. PMID:25473222

  4. Matrix based system of isotretinoin as nail lacquer to enhance transungal delivery across human nail plate.

    PubMed

    Joshi, Monika; Sharma, Vijay; Pathak, Kamla

    2015-01-15

    The project was aimed at development of isotretinoin nail lacquer and assessment of its penetration efficiency across human nail plate. Preliminary studies (hydration enhancement factor and SEM) aided the selection of thioglycolic acid as permeation and eugenol was selected as local anesthetic in the formulation. The nail lacquer was optimized by 3(2) factorial design and a total of nine formulations were prepared and screened. In vitro adhesion and ex vivo permeation (cumulative drug permeation per unit area (CDP/A) = 6.61 ± 0.57 mg/cm(2)) across bovine hoof guided the selection of F3 as optimized formulation that was improvised. Viscosity adjustments to improve handling characteristics were affected by incorporation of ethyl cellulose (6%; F3M1) that scaled the viscosity to 312.681 cp and insignificantly (p > 0.05) affected CDP/A (6.32 ± 0.45 mg/cm(2)). In comparison to marketed preparation (Retino-A cream) F3M1 afforded two fold increase in CDP/A. The permeation characteristics were defined by Higuchi model (r(2) = 0.964) and flux value of 176 μg/cm(2)/h. Confocal laser scanning microscopy, after 72 h of nail lacquer application, revealed extensive distribution of the fluorescent tracer across the human nail plate in comparison to control that was confined to the top layer. Conclusively, an efficacious and stable nail lacquer of isotretinoin was developed for potential clinical topical use to target the drug to nail bed in treatment of nail psoriasis. PMID:25445993

  5. Matrix based system of isotretinoin as nail lacquer to enhance transungal delivery across human nail plate.

    PubMed

    Joshi, Monika; Sharma, Vijay; Pathak, Kamla

    2015-01-15

    The project was aimed at development of isotretinoin nail lacquer and assessment of its penetration efficiency across human nail plate. Preliminary studies (hydration enhancement factor and SEM) aided the selection of thioglycolic acid as permeation and eugenol was selected as local anesthetic in the formulation. The nail lacquer was optimized by 3(2) factorial design and a total of nine formulations were prepared and screened. In vitro adhesion and ex vivo permeation (cumulative drug permeation per unit area (CDP/A) = 6.61 ± 0.57 mg/cm(2)) across bovine hoof guided the selection of F3 as optimized formulation that was improvised. Viscosity adjustments to improve handling characteristics were affected by incorporation of ethyl cellulose (6%; F3M1) that scaled the viscosity to 312.681 cp and insignificantly (p > 0.05) affected CDP/A (6.32 ± 0.45 mg/cm(2)). In comparison to marketed preparation (Retino-A cream) F3M1 afforded two fold increase in CDP/A. The permeation characteristics were defined by Higuchi model (r(2) = 0.964) and flux value of 176 μg/cm(2)/h. Confocal laser scanning microscopy, after 72 h of nail lacquer application, revealed extensive distribution of the fluorescent tracer across the human nail plate in comparison to control that was confined to the top layer. Conclusively, an efficacious and stable nail lacquer of isotretinoin was developed for potential clinical topical use to target the drug to nail bed in treatment of nail psoriasis.

  6. 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

  7. Multi-drugs resistant acne rosacea in a child affected by Ataxia-Telangiectasia: successful treatment with Isotretinoin.

    PubMed

    Cantarutti, Nicoletta; Claps, Alessia; Angelino, Giulia; Chessa, Luciana; Callea, Francesco; El Hachem, May; Diociaiuti, Andrea; Finocchi, Andrea

    2015-03-28

    Ataxia-Telangiectasia is a rare multisystem autosomal recessive disorder [OMIM 208900], caused by mutations in Ataxia-Telangiectasia Mutated gene. It is characterized by neurological, immunological and cutaneous involvement. Granulomas have been previously reported in Ataxia-Telangiectasia patients, even if acne rosacea has not been described.We report a case of a young Ataxia-Telangiectasia patient with a severe immunological and neurological involvement, who developed granulomatous skin lesions diagnosed by skin biopsy as acne rosacea. Considering the severe clinical picture and the lack of improvement to multiple topic and systemic therapies, treatment with Isotretinoin was started and the skin lesions disappeared after five months. However the therapy was stopped due to drug-hepatotoxicity.Systemic treatment with Isotretinoin should be carefully considered in patient with Ataxia-Telangiectasia for the treatment of multi-drug resistant acne rosacea, however its toxicity may limit long-term use and the risk/benefit ratio of the treatment should be evaluated.

  8. Inhibition of the visual cycle in vivo by 13-cis retinoic acid protects from light damage and provides a mechanism for night blindness in isotretinoin therapy.

    PubMed

    Sieving, P A; Chaudhry, P; Kondo, M; Provenzano, M; Wu, D; Carlson, T J; Bush, R A; Thompson, D A

    2001-02-13

    Isotretinoin (13-cis retinoic acid) is frequently prescribed for severe acne [Peck, G. L., Olsen, T. G., Yoder, F. W., Strauss, J. S., Downing, D. T., Pandya, M., Butkus, D. & Arnaud-Battandier, J. (1979) N. Engl. J. Med. 300, 329-333] but can impair night vision [Fraunfelder, F. T., LaBraico, J. M. & Meyer, S. M. (1985) Am. J. Ophthalmol. 100, 534-537] shortly after the beginning of therapy [Shulman, S. R. (1989) Am. J. Public Health 79, 1565-1568]. As rod photoreceptors are responsible for night vision, we administered isotretinoin to rats to learn whether night blindness resulted from rod cell death or from rod functional impairment. High-dose isotretinoin was given daily for 2 months and produced systemic toxicity, but this caused no histological loss of rod photoreceptors, and rod-driven electroretinogram amplitudes were normal after prolonged dark adaptation. Additional studies showed, however, that even a single dose of isotretinoin slowed the recovery of rod signaling after exposure to an intense bleaching light, and that rhodopsin regeneration was markedly slowed. When only a single dose was given, rod function recovered to normal within several days. Rods and cones both showed slow recovery from bleach after isotretinoin in rats and in mice. HPLC analysis of ocular retinoids after isotretinoin and an intense bleach showed decreased levels of rhodopsin chromophore, 11-cis retinal, and the accumulation of the biosynthetic intermediates, 11-cis and all-trans retinyl esters. Isotretinoin was also found to protect rat photoreceptors from light-induced damage, suggesting that strategies of altering retinoid cycling may have therapeutic implications for some forms of retinal and macular degeneration. PMID:11172037

  9. Overview of existing research and information linking isotretinoin (accutane), depression, psychosis, and suicide.

    PubMed

    O'Donnell, James

    2003-01-01

    Isotretinoin (Accutane; Hoffmann-La Roche, Nutley, NJ) is a drug closely related to the chemical structure of vitamin A. The pharmacology and toxicology of these two retinoids are similar enough to warrant comparison. Accutane is a powerful drug that 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 ideation with Accutane use have prompted an examination of its serious and life-threatening potential. Although Roche has added a warning to its product label for signs of depression, and suicidal ideation, this product is overprescribed for all forms of acne, including mild and moderate cases that have not been treated with alternative medications with less 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 the proper limited indication for its use, because depression and suicide can follow in patients with no prior history of psychiatric symptoms or suicide attempts.

  10. 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

  11. The role of transcription factor FoxO1 in the pathogenesis of acne vulgaris and the mode of isotretinoin action.

    PubMed

    Melnik, B C

    2010-10-01

    It is the purpose of this review to demonstrate that oral isotretinoin treatment restores all major pathogenetic factors of acne vulgaris by upregulation of the nuclear transcription factor FoxO1, which will be shown to be the major target of retinoid action. Nuclear FoxO1 deficiency is the result of increased growth factor signaling with activated phosphoinositol-3-kinase (PI3K) and Akt kinase during growth hormone signaling of puberty and increased insulin/IGF-1 signaling due to consumption of insulinotropic milk/dairy products as well as hyperglycemic carbohydrates of Western diet. Nuclear FoxO1 deficiency increases androgen receptor transactivation and modifies the activity of important nuclear receptors and key genes involved in pilosebaceous keratinocyte proliferation, sebaceous lipogenesis and expression of perifollicular inflammatory cytokines. Isotretinoin-induced upregulation of nuclear FoxO1 is proposed to be responsible for the mode of action of isotretinoin on all major pathogenetic factors in acne. Acne pathogenesis can be explained at the genomic level of transcriptional regulation. All major events in acne pathogenesis as well as all major effects of isotretinoin treatment appear to be related to modifications of the PI3K/Akt/FoxO1 signaling pathway, the well-known oncogenic pathway. These insights extend our understanding of FoxO1-mediated retinoid action in acne and other hyperproliferative skin diseases, cancer chemoprevention and cutaneous immune regulation. Understanding FoxO´s pivotal regulatory role in acne allows the development of novel treatment strategies and dietary interventions in acne which focus on the restoration of growth factor- and diet-induced imbalances of nuclear FoxO protein levels.

  12. 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.

  13. 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.

  14. Lack of survival advantage with autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy and isotretinoin.

    PubMed

    Kushner, Brian H; Ostrovnaya, Irina; Cheung, Irene Y; Kuk, Deborah; Modak, Shakeel; Kramer, Kim; Roberts, Stephen S; Basu, Ellen M; Yataghene, Karima; Cheung, Nai-Kong V

    2016-01-26

    Since 2003, high-risk neuroblastoma (HR-NB) patients at our center received anti-GD2 antibody 3F8/GM-CSF + isotretinoin - but not myeloablative therapy with autologous stem-cell transplantation (ASCT). Post-ASCT patients referred from elsewhere also received 3F8/GM-CSF + isotretinoin. We therefore accrued a study population of two groups treated during the same period and whose consolidative therapy, aside from ASCT, was identical. We analyzed patients enrolled in 1st complete/very good partial remission (CR/VGPR). Their event-free survival (EFS) and overall survival (OS) were calculated from study entry. Large study size allowed robust statistical analyses of key prognosticators including MYCN amplification, minimal residual disease (MRD), FCGR2A polymorphisms, and killer immunoglobulin-like receptor genotypes of natural killer cells. The 170 study patients included 60 enrolled following ASCT and 110 following conventional chemotherapy. The two cohorts had similar clinical and biological features. Five-year rates for ASCT and non-ASCT patients were, respectively: EFS 65% vs. 51% (p = .128), and OS 76% vs. 75% (p = .975). In multivariate analysis, ASCT was not prognostic and only MRD-negativity after two cycles of 3F8/GM-CSF correlated with significantly improved EFS and OS. Although a trend towards better EFS is seen with ASCT, OS is near identical. Cure rates may be similar, as close surveillance detects localized relapse and effective salvage treatments are applied. ASCT may not be needed to improve outcome when anti-GD2 immunotherapy is used for consolidation after dose-intensive conventional chemotherapy.

  15. Lack of survival advantage with autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy and isotretinoin.

    PubMed

    Kushner, Brian H; Ostrovnaya, Irina; Cheung, Irene Y; Kuk, Deborah; Modak, Shakeel; Kramer, Kim; Roberts, Stephen S; Basu, Ellen M; Yataghene, Karima; Cheung, Nai-Kong V

    2016-01-26

    Since 2003, high-risk neuroblastoma (HR-NB) patients at our center received anti-GD2 antibody 3F8/GM-CSF + isotretinoin - but not myeloablative therapy with autologous stem-cell transplantation (ASCT). Post-ASCT patients referred from elsewhere also received 3F8/GM-CSF + isotretinoin. We therefore accrued a study population of two groups treated during the same period and whose consolidative therapy, aside from ASCT, was identical. We analyzed patients enrolled in 1st complete/very good partial remission (CR/VGPR). Their event-free survival (EFS) and overall survival (OS) were calculated from study entry. Large study size allowed robust statistical analyses of key prognosticators including MYCN amplification, minimal residual disease (MRD), FCGR2A polymorphisms, and killer immunoglobulin-like receptor genotypes of natural killer cells. The 170 study patients included 60 enrolled following ASCT and 110 following conventional chemotherapy. The two cohorts had similar clinical and biological features. Five-year rates for ASCT and non-ASCT patients were, respectively: EFS 65% vs. 51% (p = .128), and OS 76% vs. 75% (p = .975). In multivariate analysis, ASCT was not prognostic and only MRD-negativity after two cycles of 3F8/GM-CSF correlated with significantly improved EFS and OS. Although a trend towards better EFS is seen with ASCT, OS is near identical. Cure rates may be similar, as close surveillance detects localized relapse and effective salvage treatments are applied. ASCT may not be needed to improve outcome when anti-GD2 immunotherapy is used for consolidation after dose-intensive conventional chemotherapy. PMID:26623730

  16. 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.

  17. Cross-sectional Pilot Study of Antibiotic Resistance in Propionibacterium Acnes Strains in Indian Acne Patients Using 16S-RNA Polymerase Chain Reaction: A Comparison Among Treatment Modalities Including Antibiotics, Benzoyl Peroxide, and Isotretinoin

    PubMed Central

    Sardana, Kabir; Gupta, Tanvi; Kumar, Bipul; Gautam, Hemant K; Garg, Vijay K

    2016-01-01

    Background: Antibiotic resistance is a worldwide problem in acne patients due to regional prescription practices, patient compliance, and genomic variability in Propionibacterium acnes, though the effect of treatment on the resistance has not been comprehensively analyzed. Aims: Our primary objective was to assess the level of antibiotic resistance in the Indian patients and to assess whether there was a difference in the resistance across common treatment groups. Subjects and Methods: A cross-sectional, institutional based study was undertaken and three groups of patients were analyzed, treatment naïve, those on antibiotics and patients on benzoyl peroxide (BPO) and/isotretinoin. The follicular content was sampled and the culture was verified with 16S rRNA polymerase chain reaction, genomic sequencing, and pulsed-field gel electrophoresis. Minimum inhibitory concentration (MIC) assessment was done for erythromycin (ERY), azithromycin (AZI), clindamycin (CL), tetracycline (TET), doxycycline (DOX), minocycline (MINO), and levofloxacin (LEVO). The four groups of patients were compared for any difference in the resistant strains. Results: Of the 52 P. acnes strains isolated (80 patients), high resistance was observed to AZI (100%), ERY (98%), CL (90.4%), DOX (44.2%), and TETs (30.8%). Low resistance was observed to MINO (1.9%) and LEVO (9.6%). Statistical difference was seen in the resistance between CL and TETs; DOX/LEVO and DOX/MINO (P < 0.001). High MIC90 (≥256 μg/ml) was seen with CL, macrolides, and TETs; moreover, low MIC90 was observed to DOX (16 μg/ml), MINO (8 μg/ml), and LEVO (4 μg/ml). Though the treatment group with isotretinoin/BPO had the least number of resistant strains there was no statistical difference in the antibiotic resistance among the various groups of patients. Conclusions: High resistance was seen among the P. acnes strains to macrolides-lincosamides (AZI and CL) while MINO and LEVO resistance was low. PMID:26955094

  18. 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

  19. Isotretinoin (Ro-Accutane) teratogenesis. A case report.

    PubMed

    Giannoulis, C H; Papathanasiou, K; Tantanasis, T H; Vaitsi, V; Tzafettas, I

    2005-01-01

    A case of teratogenesis in a 16-year-old pregnant patient is described. She had been using 60 mg Ro-Accutane daily till the 16th week of gestation. Sonography showed no cephalic skull up to the frontal bone of the fetus. A central lagostroma was also detected.

  20. [Isotretinoin and depressive symptoms in patiens with severe and recurrent acne].

    PubMed

    Rubio-García, Leticia; Pulido-Díaz, Nancy; Jímenez-López, José Luis

    2015-01-01

    Introducción: a partir del uso de isotretinoína para el manejo del acné, se han publicado resultados controversiales en torno a una probable asociación entre esta y depresión. El objetivo de este estudio fue conocer si el uso de isotretinoína en pacientes con acné severo y recurrente (ASR) se asocia a depresión.Métodos: se incluyeron 22 pacientes con diagnóstico de ASR pertenecientes a la clínica de acné del Centro Médico Nacional La Raza. Se les aplicó el inventario de depresión de Beck (IDB-II) antes, durante (2 meses) y después del tratamiento con isotretinoína (4 meses), calculada a 0.5 mg/kg.Resultados: en las primeras mediciones se reportaron puntuaciones bajas de síntomas depresivos que disminuyeron aún más al final del tratamiento (mediana = 6.5 antes del tratamiento, 3 a los dos meses y 0 al final, con una p < 0.001).Conclusiones: el tratamiento con isotretinoína en esta muestra de pacientes con acné severo y recurrente no produjo aumento de síntomas depresivos, por el contrario los redujo de manera indirecta al mejorar su imagen corporal.

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

    ClinicalTrials.gov

    2015-07-27

    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

  2. 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

  3. 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

  4. Adaptive dosing approaches to the individualization of 13-cis-retinoic acid (isotretinoin) treatment for children with high-risk neuroblastoma

    PubMed Central

    Veal, Gareth J.; Errington, Julie; Rowbotham, Sophie E.; Illingworth, Nicola A.; Malik, Ghada; Cole, Michael; Daly, Ann K.; Pearson, Andrew D.J.; Boddy, Alan V.

    2012-01-01

    Purpose To investigate the feasibility of adaptive dosing and the impact of pharmacogenetic variation on 13-cisRA disposition in high-risk neuroblastoma patients. Experimental Design 13cisRA (160mg/m2 or 5.33mg/kg/day) was administered to 103 patients ≤21 years and plasma concentrations of 13-cisRA and 4-oxo-13-cisRA quantitated on day 14 of treatment. 71 patients were recruited to a dose adjustment group, targeting a 13-cisRA Cmax of 2μM, with dose increases of 25-50% implemented for patients with Cmax values <2μM. A population pharmacokinetic model was applied and polymorphisms in relevant cytochrome P450 genes analyzed. Results 13-cisRA Cmax values ranged from 0.42–11.2μM, with 34/103 (33%) patients failing to achieve a Cmax >2μM. Dose increases carried out in 20 patients in the dose adjustment study group led to concentrations >2μM in 18 patients (90%). 8/11 (73%) patients <12kg, receiving a dose of 5.33mg/kg, failed to achieve a Cmax ≥2μM. Significantly lower Cmax values were observed for patients treated with 5.33mg/kg versus 160mg/m2 (1.9±1.2 versus 3.1±2.0μM; mean±SD; P=0.023). Cmax was higher in patients who swallowed 13-cisRA capsules as compared to receiving the drug extracted from capsules (4.0±2.2 versus 2.6±1.8μM; P=0.0012). The target Cmax was achieved by 93% (25/27) versus 55% (42/76) of patients in these two groups respectively. No clear relationships were found between genetic variants and 13-cisRA pharmacokinetic parameters. Conclusions Dosing regimen and method of administration have a marked influence on 13-cisRA plasma concentrations. Body weight-based dosing should not be implemented for children <12kg and pharmacological data support higher doses for children unable to swallow 13-cisRA capsules. PMID:23087409

  5. 75 FR 71135 - Hoffmann-La Roche Inc.; Withdrawal of Approval of a New Drug Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-22

    ..., 2010 (75 FR 39024), FDA issued a notice announcing its determination that ACCUTANE (isotretinoin... Administration (FDA) is withdrawing approval of a new drug application (NDA) for ACCUTANE (isotretinoin) Capsules... INFORMATION: Hoffmann-La Roche Inc. has requested that FDA withdraw approval of NDA 18-662,...

  6. Acne

    MedlinePlus

    ... acne and scarring may try a medicine called isotretinoin (Accutane). You will be watched closely when taking this ... its side effects. Pregnant women should NOT take Accutane, because it causes severe birth defects. Women taking ...

  7. Management of severe acne.

    PubMed

    Zouboulis, C C; Bettoli, V

    2015-07-01

    Acne is the most common skin disease, affecting up to 95% of adolescents. Severe episodes of acne can cause considerable physical and psychological scarring, and overexpression of transforming growth factor-β can lead to formation of hypertrophic scars and keloids. The severity of acne in adolescence is associated with a positive history of severe acne in first-degree relatives, especially the mother. In most cases acne is a chronic disease, and it is often a component of systemic diseases or syndromes. All forms of severe acne require systemic treatment. The available options include oral antibiotics, hormonal antiandrogens for female patients and oral isotretinoin, as well as other combination treatments. Oral isotretinoin is the only drug available that affects all four pathogenic factors of acne. However, due to possible serious side-effects, a European directive states that oral isotretinoin should be used only as a second-line therapy in cases of severe, nodular and conglobate acne. The pharmaceutical quality of generic isotretinoin products and the obtainability of isotretinoin through e-pharmacies without prescription raise new therapeutic problems. New anti-inflammatory compounds, such as the 5-lipoxygenase inhibitor zileuton, may replace systemic antibiotics in the future, especially under the scope of antibiotic resistance prevention. This review looks into the various options and latest approaches, and factors to consider, when combating severe acne.

  8. What's new in acne and rosacea?

    PubMed

    Keri, Jonette

    2016-06-01

    Acne and rosacea are common conditions seen every day by dermatologists. This review will discuss the most recent therapeutic options for patients with these conditions. Specifically, for acne, there will be a discussion of the use of isotretinoin at higher cumulative doses as well as a new formulation of isotretinoin, isotretinoin-lidose. Adult women with acne represent a growing population of patients who present for treatment of acne; the use of hormonal therapies as well as topical dapsone gel will be reviewed for these patients. For rosacea patients, the new topical agents - brimonidine gel and ivermectin cream - will be reviewed, with a discussion on possible rebound phenomenon from brimonidine. Finally, future treatments in the pipeline will be discussed. PMID:27416316

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

    PubMed

    Bergler-Czop, Beata; Brzezińska-Wcisło, Ligia

    2012-09-01

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

  10. Epidermolytic variant of hereditary palmoplantar keratoderma.

    PubMed

    Camisa, C; Williams, H

    1985-02-01

    The seventh family with autosomal dominant epidermolytic palmoplantar keratoderma is reported. The lesions are clinically indistinguishable from Unna-Thost disease but resemble epidermolytic hyperkeratosis (bullous ichthyosiform erythroderma) histopathologically. A skin biopsy is essential for making the correct diagnosis. One of our patients was treated with isotretinoin for 13 weeks without significant improvement.

  11. To dispense or not to dispense? Ethical case decision-making in pharmacy practice.

    PubMed

    Bolt, Ineke; van den Hoven, Mariëtte; Blom, Lyda; Bouvy, Marcel

    2015-12-01

    In daily practice, pharmacists are regularly confronted with moral problems in which deciding what to do is not always a straightforward decision. In this contribution we show how the use of a specific method for moral deliberation can (in retrospect or prospective) aid moral judgements. We use the case of dispensing isotretinoin to demonstrate one ethical reflection method, namely the Utrecht Method.

  12. Sudden Appearance of Indurated Erythematous Plaques on a Man's Face

    PubMed Central

    Carter, A.; Shulman, K.

    2016-01-01

    Rosacea fulminans (RF), previously known as pyoderma faciale, is a rare presentation of rosacea mostly seen in young women. RF is seen very rarely in men. We present below a case of a fifty-year-old male who presented with RF and was successfully treated with a combination of corticosteroids and isotretinoin. PMID:27703816

  13. Newer approaches to the treatment of acne vulgaris.

    PubMed

    Simonart, Thierry

    2012-12-01

    The multifactorial etiology of acne vulgaris makes it challenging to treat. Current treatments include topical retinoids, benzoyl peroxide, topical and systemic antibiotics, azelaic acid, and systemic isotretinoin. Adjunctive and/or emerging approaches include topical dapsone, taurine bromamine, resveratrol, chemical peels, optical treatments, as well as complementary and alternative medications. The purpose of this paper is to discuss the therapies available for acne and their latest developments, including new treatment strategies (i.e. re-evaluation of the use of oral antibiotics and avoidance of topical antibiotic monotherapy, use of subantimicrobial antibiotic dosing, use of low-dose isotretinoin, optical treatments), new formulations (microsponges, liposomes, nanoemulsions, aerosol foams), new combinations (fixed-combination products of topical retinoids and topical antibiotics [essentially clindamycin] or benzoyl peroxide), new agents (topical dapsone, taurine bromamine, resveratrol) and their rationale and likely place in treatment. Acne vaccines, topical natural antimicrobial peptides, and lauric acid represent other promising therapies. PMID:22920095

  14. DTB Select: 7 | July 2016.

    PubMed

    2016-07-01

    MHRA: avoid live vaccines in immunosuppressed patients ● Topical NSAIDs for musculoskeletal pain in adults ● Adherence to pregnancy prevention measures during isotretinoin treatment ● Impact of the NHS Health Check programme ● Ibuprofen: first choice for migraine in young people? ● Neuropsychiatric safety of ▼ varenicline and bupropion ● Effects of anticholinergic medication in cognitively normal older adults ● New NICE guidance for controlled drugs. PMID:27364828

  15. Hormonal Treatment of Acne in Women

    PubMed Central

    Ebede, Tobechi L.; Arch, Emily L.

    2009-01-01

    Acne vulgaris is a common and chronic disorder of the pilosebaceous unit. Standard treatment protocols include topical retinoids, topical and oral antimicrobials, and isotretinoin. Hormonal therapies can be added to the regimen in some patients. This article will review the hormonal pathogenesis of acne, discuss the basics of an endocrine evaluation, and provide an overview of the current hormonal treatment options in women. PMID:20725580

  16. Dissecting cellulitis in a white male: a case report and review of the literature.

    PubMed

    Stites, P C; Boyd, A S

    2001-01-01

    Dissecting cellulitis is an uncommon, chronic, progressive suppurative disease of unknown etiology. It is characterized by painful papules and nodules, interconnecting sinus tracts, purulent drainage, and scarring alopecia. This disease predominately affects young black men, but is rarely reported in white males. The refractory nature of this process makes treatment difficult. We report a case of dissecting cellulitis in a white male, which responded to oral isotretinoin. PMID:11204602

  17. Refractory dissecting cellulitis of the scalp treated with adalimumab.

    PubMed

    Sukhatme, Smita V; Lenzy, Yolanda M; Gottlieb, Alice B

    2008-10-01

    Dissecting cellulitis of the scalp (DCS) is a suppurative, neutrophillic dermatosis. Therapies typically provide short-term improvement and include antibiotics, prednisone, and isotretinoin, as well as radiation, surgical excision, and laser ablation. The authors report the use of the tumor necrosis factor (TNF) blocker, adalimumab, to successfully treat a 39-year-old male with a long-standing history of DCS. PMID:19112766

  18. Dissecting cellulitis of the scalp.

    PubMed

    Mundi, Jyoti P; Marmon, Shoshana; Fischer, Max; Kamino, Hideko; Patel, Rishi; Shapiro, Jerry

    2012-12-01

    Dissecting cellulitis of the scalp is a chronic, relapsing, inflammatory disease of the scalp that results in scarring alopecia. We present a case of a 32-year-old man with recalcitrant disease who is now responding to treatment with isotretinoin. The pathogenesis, clinical presentation, disease associations, and histopathological findings are reviewed. Treatment can be challenging. The literature on medical and surgical therapeutic options is reviewed. PMID:23286798

  19. Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society

    PubMed Central

    Gallo, Richard L.; Thiboutot, Diane; Webster, Guy F.; Rosen, Ted; Leyden, James J.; Walker, Clay; Zhanel, George; Eichenfield, Lawrence

    2016-01-01

    In this second part of a three-part series addressing several issues related to antibiotic use in dermatology, potential effects of antibiotic use on the human microbiota and microbiome are reviewed. Data from available literature on the microbiologic effects of specific therapeutic agents commonly used in dermatology, including oral isotretinoin, tetracycline agents, and sub-antimicrobial (sub-antibiotic) dose doxycycline, are also discussed.

  20. Hepatitis B, interferon, and acne fulminans in a young girl.

    PubMed

    Arora, Sandeep; Malik, Ajay; Kumar, Dharmendra; Sodhi, Neha

    2016-01-01

    Acne fulminans (AF) is a very rare severe form of acne seen in young males, characterized by a sudden and explosive onset of hemorrhagic pustules and ulceration on the trunk, systemic features in the form of fever, polyarthropathy, malaise, erythema nodosum and painful osteolytic bone involvement with leukocytosis, and an elevated erythrocyte sedimentation rate. Conventional treatment of AF includes corticosteroids or immunosuppressive agents for the initial phase followed by isotretinoin. Active hepatitis B infection with a high viral load precludes the administration of any immunosuppressive drugs. We present the case of an 18-year-old girl with a history of occasional acne who presented with AF of sudden onset following administration of interferon-alpha-2a for her recently detected hepatitis B infection. Management of hepatitis B was withheld in view of her general condition. The patient was managed with low dose isotretinoin with subsidence of lesions. AF in a young female precipitated by interferon and its management with isotretinoin in the presence of active hepatitis B infection make the case unique. PMID:27057488

  1. Hepatitis B, interferon, and acne fulminans in a young girl.

    PubMed

    Arora, Sandeep; Malik, Ajay; Kumar, Dharmendra; Sodhi, Neha

    2016-01-01

    Acne fulminans (AF) is a very rare severe form of acne seen in young males, characterized by a sudden and explosive onset of hemorrhagic pustules and ulceration on the trunk, systemic features in the form of fever, polyarthropathy, malaise, erythema nodosum and painful osteolytic bone involvement with leukocytosis, and an elevated erythrocyte sedimentation rate. Conventional treatment of AF includes corticosteroids or immunosuppressive agents for the initial phase followed by isotretinoin. Active hepatitis B infection with a high viral load precludes the administration of any immunosuppressive drugs. We present the case of an 18-year-old girl with a history of occasional acne who presented with AF of sudden onset following administration of interferon-alpha-2a for her recently detected hepatitis B infection. Management of hepatitis B was withheld in view of her general condition. The patient was managed with low dose isotretinoin with subsidence of lesions. AF in a young female precipitated by interferon and its management with isotretinoin in the presence of active hepatitis B infection make the case unique.

  2. Hepatitis B, interferon, and acne fulminans in a young girl

    PubMed Central

    Arora, Sandeep; Malik, Ajay; Kumar, Dharmendra; Sodhi, Neha

    2016-01-01

    Acne fulminans (AF) is a very rare severe form of acne seen in young males, characterized by a sudden and explosive onset of hemorrhagic pustules and ulceration on the trunk, systemic features in the form of fever, polyarthropathy, malaise, erythema nodosum and painful osteolytic bone involvement with leukocytosis, and an elevated erythrocyte sedimentation rate. Conventional treatment of AF includes corticosteroids or immunosuppressive agents for the initial phase followed by isotretinoin. Active hepatitis B infection with a high viral load precludes the administration of any immunosuppressive drugs. We present the case of an 18-year-old girl with a history of occasional acne who presented with AF of sudden onset following administration of interferon-alpha-2a for her recently detected hepatitis B infection. Management of hepatitis B was withheld in view of her general condition. The patient was managed with low dose isotretinoin with subsidence of lesions. AF in a young female precipitated by interferon and its management with isotretinoin in the presence of active hepatitis B infection make the case unique. PMID:27057488

  3. Neuromuscular adverse effects associated with systemic retinoid dermatotherapy: monitoring and treatment algorithm for clinicians.

    PubMed

    Chroni, Elisabeth; Monastirli, Alexandra; Tsambaos, Dionysios

    2010-01-01

    Although neuromuscular adverse effects represent significant clinical manifestations of hypervitaminosis A syndrome, surprisingly little attention has been paid to the potential neuromuscular toxicity of vitamin A derivatives (retinoids). Since isotretinoin and acitretin are currently the two most commonly used oral retinoids in systemic dermatotherapy, this review focuses exclusively on their neuromuscular adverse effects and proposes a neuromuscular algorithm for appropriate monitoring of patients treated with these two compounds. The most frequent CNS adverse effect associated with oral isotretinoin is headache, either as an independent adverse effect or as part of benign intracranial hypertension, which is additionally characterized by nausea and visual changes. Isolated cases of stiff-person-like syndrome, epileptic seizures and generalized muscle stiffness syndrome, possibly or probably related to oral treatment with isotretinoin, have also been reported. In addition, oral isotretinoin has reportedly been associated with muscular adverse effects that most frequently manifest as myalgia and stiffness and, in rare cases, as true myopathy or rhabdomyolysis. Creatine phosphokinase, a specific marker of muscle destruction, has been found to be elevated, occasionally by up to 100 times the normal value (with or without muscular symptoms and signs), in a variable percentage of patients receiving isotretinoin treatment and particularly in those undergoing vigorous physical exercise. Oral acitretin has been found to cause peripheral nerve dysfunction, particularly of sensory fibres, which in rare cases leads to clinically evident sensory disturbances. Less clear is the causal relationship between acitretin and benign intracranial hypertension or myopathy, whereas an isolated case of cranial nerve IV (oculomotor) palsy and a further case of thrombotic stroke during treatment with oral acitretin have been reported. Systemic diseases with involvement of nervous and

  4. Osteochondroma in Long-Term Survivors of High-Risk Neuroblastoma

    PubMed Central

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

    2016-01-01

    Background Osteochondromas are benign bony protrusions that can be spontaneous or associated with radiation therapy (RT). Current treatment of high-risk neuroblastoma includes dose-intensive chemotherapy, local RT, anti-GD2 monoclonal antibody (MAb), and isotretinoin. Late effects are emerging. Methods We studied osteochondromas in 362 patients who were <10 years old when diagnosed with neuroblastoma; received MAb+isotretinoin since 2000; and survived ≥24 months from the first dose of MAb. The incidence rate of osteochondromas was determined using the competing risks approach where the primary event was osteochondroma calculated from the date of neuroblastoma diagnosis and the competing event was death without osteochondroma. Results Twenty-one osteochondromas were found in 14 patients who were 5.7-15.3 (median 10.4) years of age and 3.1-11.2 (median 8.2) years from neuroblastoma diagnosis. The cumulative incidence rate was 0.6% at five years and 4.9% at 10 years from neuroblastoma diagnosis. Nine osteochondromas were revealed incidentally during assessments of neuroblastoma disease status or bone age. Thirteen osteochondromas were outside RT portals and had characteristics of spontaneous forms. Complications were limited to pain necessitating resection in three patients, but follow-up is short at 0.3-7.7 (median 3.5) years. Conclusions Osteochondromas in long-term survivors of neuroblastoma should be expected because these benign growths can be RT-related and these patients undergo radiologic studies over years, are monitored for late toxicities through and beyond adolescence, and receive special attention (because of concern about relapse) if they develop a bony protuberance. A pathogenic role for chemotherapy, anti-GD2 MAb, or isotretinoin remains speculative. PMID:25728463

  5. 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.

  6. 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

  7. General Medical Drugs Associated with Depression

    PubMed Central

    2008-01-01

    Drug-induced depression has been the focus of intense scrutiny by the US Food and Drug Administration and has serious clinical and medicolegal implications. “Gold standard” studies of drug-induced depression—involving randomized, placebo-controlled design and direct assessment of depressive symptoms—are lacking. Based on the available literature, our review suggests that only a few types of drugs are strongly linked with induction of depression. However, the potential for idiosyncratic reactions—not necessarily detected in large-scale studies—suggests that particular caution and careful monitoring are warranted with several types of drugs, including isotretinoin, rimonabant, and alpha interferons. PMID:19724774

  8. Treatment of nevus comedonicus with ammonium lactate lotion.

    PubMed

    Milton, G P; DiGiovanna, J J; Peck, G L

    1989-02-01

    A patient with an extensive nevus comedonicus, which is associated frequently with the development of large inflammatory cysts and abscesses within the nevus, responded dramatically within 1 month to a once-daily application of 12% ammonium lactate lotion. A marked beneficial effect on the comedonal component of the nevus was noted. One inflammatory cyst has developed in an area left untreated by the patient, but none have occurred in treated areas since therapy with ammonium lactate lotion was begun. Previous treatments, which were either ineffective or of minimal effectiveness, included oral isotretinoin, topical tretinoin, salicylic acid, lactic acid, and d-tartaric acid creams.

  9. Blood donors on teratogenic drugs and donor deferral periods in a clinical situation.

    PubMed

    Shin, S Y; Shin, Y H; Lee, S W; Shin, J Y; Kim, C H

    2012-05-01

    Deferral of blood donors taking teratogenic drugs is critical. From March 2008 to January 2009, we analysed stored blood specimens from donors who had taken teratogenic drugs and whose blood was transfused to women of childbearing age to determine the plasma concentration at the time of donation using high-performance liquid chromatography. In total, 167 specimens were examined. The numbers of specimens exceeding the quantification limit were 7, 39, 4, 2 and 1 for finasteride, isotretinoin, acitretin, etretinate and dutasteride, respectively. Finasteride was beyond the recommended drug deferral period in one specimen. These results may help create practical deferral policies. PMID:22211799

  10. Revealed: The spy who regulates neuroblastoma stem cells.

    PubMed

    Vora, Parvez; Venugopal, Chitra; Singh, Sheila K

    2014-11-30

    Neuroblastoma (NB), an embryonal tumour of the sympathetic nervous system, is thought to originate from undifferentiated neural crest cells and is known to exhibit extremely heterogeneous biological and clinical behaviors. Occurring in very young children, the median age at diagnosis is 17 months and it accounts for 10% of all pediatric cancer mortalities. The standard treatment regimen for patients with high-risk NB includes induction and surgery followed by isotretinoin or Accutane (13-cis retinoic acid) treatment, which is shown to induce terminal differentiation of NB cells. However, molecular regulators that maintain an undifferentiated phenotype in NB cells are still poorly understood. PMID:25483101

  11. Dissecting Cellulitis of the Scalp Responding to Intravenous Tumor Necrosis Factor-alpha Antagonist.

    PubMed

    Wollina, Uwe; Gemmeke, Astrid; Koch, André

    2012-04-01

    The authors present the case of a 30-year-old male patient with a severe and long-standing dissecting cellulitis of the scalp. The disease did not respond to conventional treatment, including oral antibiotics, isotretinoin, and prednisolone. Quality of life was significantly impaired. After introduction of anti-tumor necrosis factor-alpha treatment (infliximab), the malodorous discharge stopped, inflammation was reduced significantly, nodules became flat, and pain decreased. The treatment was well tolerated although he developed a temporary psoriasiform rash after the second intravenous infusion. In conclusion, anti-tumor necrosis factor-alpha treatment is a new therapeutic option in this severe and recalcitrant disorder. PMID:22708007

  12. Surgical Management and Reconstruction of Hoffman's Disease (Dissecting Cellulitis of the Scalp).

    PubMed

    Hintze, Justin M; Howard, Brittany E; Donald, Carrlene B; Hayden, Richard E

    2016-01-01

    Dissecting cellulitis of the scalp, or Hoffman's disease, is a rare dermatologic condition characterized by recurrent pustules and sinus tract formation leading to scarring and alopecia. Medical management includes the use of corticosteroids, antibiotics, isotretinoin, and adalimumab. In cases where the disease is severe, refractory, and intractable, surgery is an option. We report two cases of Hoffman's disease, where medical management failed to achieve remission. Surgical treatment was undertaken with complete resection of the affected scalp in staged procedures with subsequent split-thickness skin grafting for reconstruction. Surgery achieved both disease remission and excellent aesthetic outcomes in both patients. PMID:26966606

  13. Dissecting Cellulitis of the Scalp Responding to Intravenous Tumor Necrosis Factor-alpha Antagonist

    PubMed Central

    Wollina, Uwe; Gemmeke, Astrid; Koch, André

    2012-01-01

    The authors present the case of a 30-year-old male patient with a severe and long-standing dissecting cellulitis of the scalp. The disease did not respond to conventional treatment, including oral antibiotics, isotretinoin, and prednisolone. Quality of life was significantly impaired. After introduction of anti-tumor necrosis factor-alpha treatment (infliximab), the malodorous discharge stopped, inflammation was reduced significantly, nodules became flat, and pain decreased. The treatment was well tolerated although he developed a temporary psoriasiform rash after the second intravenous infusion. In conclusion, anti-tumor necrosis factor-alpha treatment is a new therapeutic option in this severe and recalcitrant disorder. PMID:22708007

  14. Dissecting cellulitis (Perifolliculitis Capitis Abscedens et Suffodiens): a comprehensive review focusing on new treatments and findings of the last decade with commentary comparing the therapies and causes of dissecting cellulitis to hidradenitis suppurativa.

    PubMed

    Scheinfeld, Noah

    2014-05-01

    Dissecting cellulitis (DC) also referred to as to as perifolliculitis capitis abscedens et suffodiens (Hoffman) manifests with perifollicular pustules, nodules, abscesses and sinuses that evolve into scarring alopecia. In the U.S., it predominantly occurs in African American men between 20-40 years of age. DC also occurs in other races and women more rarely. DC has been reported worldwide. Older therapies reported effective include: low dose oral zinc, isotretinoin, minocycline, sulfa drugs, tetracycline, prednisone, intralesional triamcinolone, incision and drainage, dapsone, antiandrogens (in women), topical clindamycin, topical isotretinoin, X-ray epilation and ablation, ablative C02 lasers, hair removal lasers (800nm and 694nm), and surgical excision. Newer treatments reported include tumor necrosis factor blockers (TNFB), quinolones, macrolide antibiotics, rifampin, alitretinoin, metronidazole, and high dose zinc sulphate (135-220 mg TID). Isotretinoin seems to provide the best chance at remission, but the number of reports is small, dosing schedules variable, and the long term follow up beyond a year is negligible; treatment failures have been reported. TNFB can succeed when isotretinoin fails, either as monotherapy, or as a bridge to aggressive surgical treatment, but long term data is lacking. Non-medical therapies noted in the last decade include: the 1064 nm laser, ALA-PDT, and modern external beam radiation therapy. Studies that span more than 1 year are lacking. Newer pathologic hair findings include: pigmented casts, black dots, and "3D" yellow dots. Newer associations include: keratitis-ichthyosis-deafness syndrome, Crohn disease and pyoderma gangrenosum. Older associations include arthritis and keratitis. DC is likely a reaction pattern, as is shown by its varied therapeutic successes and failures. The etiology of DC remains enigmatic and DC is distinct from hidradenitis suppurativa, which is shown by their varied responses to therapies and their

  15. Surgical Management and Reconstruction of Hoffman's Disease (Dissecting Cellulitis of the Scalp)

    PubMed Central

    Hintze, Justin M.; Howard, Brittany E.; Donald, Carrlene B.; Hayden, Richard E.

    2016-01-01

    Dissecting cellulitis of the scalp, or Hoffman's disease, is a rare dermatologic condition characterized by recurrent pustules and sinus tract formation leading to scarring and alopecia. Medical management includes the use of corticosteroids, antibiotics, isotretinoin, and adalimumab. In cases where the disease is severe, refractory, and intractable, surgery is an option. We report two cases of Hoffman's disease, where medical management failed to achieve remission. Surgical treatment was undertaken with complete resection of the affected scalp in staged procedures with subsequent split-thickness skin grafting for reconstruction. Surgery achieved both disease remission and excellent aesthetic outcomes in both patients. PMID:26966606

  16. Management of cutaneous human papillomavirus infection in immunocompromised patients.

    PubMed

    Varada, Sowmya; Posnick, Mark; Alessa, Dana; Ramírez-Fort, Marigdalia K

    2014-01-01

    Individuals with inherited immunodeficiencies, autoimmune disorders, organ or bone marrow transplantation and with human immunodeficiency virus are particularly susceptible to developing severe, persistent and extensive manifestations of cutaneous human papillomavirus (HPV) disease. These complex cases require a unique and often multimodal approach to management. In this chapter, we discuss several states of immune compromise with increased susceptibility to HPV disease and review the literature on available management strategies including acitretin, cidofovir, Candida antigen, cimetidine, imiquimod, isotretinoin, fluorouracil, selenium, podophyllotoxin, photodynamic therapy, mammalian target of rapamycin inhibitors and the quadrivalent HPV vaccine.

  17. Atypical rosacea in a male patient: case study.

    PubMed

    Debroy Kidambi, A; Tiffin, N J; Ramsay, H M

    2016-01-01

    Rosacea fulminans is a rare disorder of unknown cause, almost exclusively affecting women. There are only a few reported cases in men. The condition is characterized by the abrupt onset of pustules and nodules predominantly affecting the cheeks or chin without any systemic upset. We report the case of a 37-year-old man who presented with papulopustules, predominantly localized to his nose. Histopathological features were consistent with rosacea fulminans. The patient was managed with treatments including oral prednisolone, isotretinoin, and trimethioprim. PMID:27267199

  18. Systemic therapy with immunosuppressive agents and retinoids in hidradenitis suppurativa: a systematic review.

    PubMed

    Blok, J L; van Hattem, S; Jonkman, M F; Horváth, B

    2013-02-01

    Hidradenitis suppurativa (HS) is a difficult disease to treat. Although the pathogenesis of this inflammatory skin disease is largely unknown, the important role of the immune system has been demonstrated in both experimental and clinical studies. Clinicians are therefore increasingly prescribing systemic treatments with immunosuppressive agents, but the more traditionally used systemic retinoids, especially isotretinoin, also remain relatively common therapies. In order to provide an overview of all currently available systemic immunosuppressive agents and retinoids for the treatment of HS, a systematic search was performed using the Medline and Embase databases. All published papers concerning systemic retinoids or immunosuppressive treatments for HS in adults were included. The primary endpoints were the percentages of significant responders, moderate responders and nonresponders. Other endpoints were the relapse rate and adverse events. In total 87 papers were included, comprising 518 patients with HS who were treated with systemic retinoids, biological agents or another immunosuppressive agents, including colchicine, ciclosporin, dapsone or methotrexate. The highest response rates were observed with infliximab, adalimumab and acitretin. Overall, the quality of evidence was low and differed between the agents, making direct comparisons difficult. However, based on the amount of evidence, infliximab and adalimumab were the most effective agents. Acitretin was also effective in HS, although the quality of the evidence was low. The therapeutic effect of isotretinoin is questionable. Randomized controlled trials are needed to confirm the effectiveness of acitretin, and to identify the most effective immunosuppressive agents in HS.

  19. Developmental Neurotoxic Effects of Percutaneous Drug Delivery: Behavior and Neurochemical Studies in C57BL/6 Mice.

    PubMed

    Wu, Huali; Feng, Junyi; Lv, Wenting; Huang, Qiaoling; Fu, Mengsi; Cai, Minxuan; He, Qiangqiang; Shang, Jing

    2016-01-01

    Dermatosis often as a chronic disease requires effective long-term treatment; a comprehensive evaluation of mental health of dermatology drug does not receive enough attention. An interaction between dermatology and psychiatry has been increasingly described. Substantial evidence has accumulated that psychological stress can be associated with pigmentation, endocrine and immune systems in skin to create the optimal responses against pathogens and other physicochemical stressors to maintain or restore internal homeostasis. Additionally, given the common ectodermal origin shared by the brain and skin, we are interested in assessing how disruption of skin systems (pigmentary, endocrine and immune systems) may play a key role in brain functions. Thus, we selected three drugs (hydroquinone, isotretinoin, tacrolimus) with percutaneous excessive delivery to respectively intervene in these systems and then evaluate the potential neurotoxic effects. Firstly, C57BL/6 mice were administrated a dermal dose of hydroquinone cream, isotretinoin gel or tacrolimus ointment (2%, 0.05%, 0.1%, respectively, 5 times of the clinical dose). Behavioral testing was performed and levels of proteins were measured in the hippocampus. It was found that mice treated with isotretinoin or tacrolimus, presented a lower activity in open-field test and obvious depressive-like behavior in tail suspension test. Besides, they damaged cytoarchitecture, reduced the level of 5-HT-5-HT1A/1B system and increased the expression of apoptosis-related proteins in the hippocampus. To enable sensitive monitoring the dose-response characteristics of the consecutive neurobehavioral disorders, mice received gradient concentrations of hydroquinone (2%, 4%, 6%). Subsequently, hydroquinone induced behavioral disorders and hippocampal dysfunction in a dose-dependent response. When doses were high as 6% which was 3 times higher than 2% dose, then 100% of mice exhibited depressive-like behavior. Certainly, 6% hydroquinone

  20. Developmental Neurotoxic Effects of Percutaneous Drug Delivery: Behavior and Neurochemical Studies in C57BL/6 Mice

    PubMed Central

    Lv, Wenting; Huang, Qiaoling; Fu, Mengsi; Cai, Minxuan; He, Qiangqiang

    2016-01-01

    Dermatosis often as a chronic disease requires effective long-term treatment; a comprehensive evaluation of mental health of dermatology drug does not receive enough attention. An interaction between dermatology and psychiatry has been increasingly described. Substantial evidence has accumulated that psychological stress can be associated with pigmentation, endocrine and immune systems in skin to create the optimal responses against pathogens and other physicochemical stressors to maintain or restore internal homeostasis. Additionally, given the common ectodermal origin shared by the brain and skin, we are interested in assessing how disruption of skin systems (pigmentary, endocrine and immune systems) may play a key role in brain functions. Thus, we selected three drugs (hydroquinone, isotretinoin, tacrolimus) with percutaneous excessive delivery to respectively intervene in these systems and then evaluate the potential neurotoxic effects. Firstly, C57BL/6 mice were administrated a dermal dose of hydroquinone cream, isotretinoin gel or tacrolimus ointment (2%, 0.05%, 0.1%, respectively, 5 times of the clinical dose). Behavioral testing was performed and levels of proteins were measured in the hippocampus. It was found that mice treated with isotretinoin or tacrolimus, presented a lower activity in open-field test and obvious depressive-like behavior in tail suspension test. Besides, they damaged cytoarchitecture, reduced the level of 5-HT-5-HT1A/1B system and increased the expression of apoptosis-related proteins in the hippocampus. To enable sensitive monitoring the dose-response characteristics of the consecutive neurobehavioral disorders, mice received gradient concentrations of hydroquinone (2%, 4%, 6%). Subsequently, hydroquinone induced behavioral disorders and hippocampal dysfunction in a dose-dependent response. When doses were high as 6% which was 3 times higher than 2% dose, then 100% of mice exhibited depressive-like behavior. Certainly, 6% hydroquinone

  1. Structural changes of β-carotene and some retinoid pharmaceuticals induced by environmental factors

    NASA Astrophysics Data System (ADS)

    Roman, Maciej; Kaczor, Agnieszka; Dobrowolski, Jan Cz.; Baranska, Malgorzata

    2013-04-01

    Four pharmaceuticals (β-carotene (1), retinoic acid (2), isotretinoin (3), and etretinate (4)) were analyzed using Raman spectroscopy and quantum-chemical calculations followed by potential energy distribution (PED) analysis to gain deeper insight into the experimental vibrational spectra. Small shifts of characteristic bands of (4) upon change of solvent and pH were interpreted as a result of molecular aggregation. Temperature-dependent studies on the Raman spectrum of (1) were performed in the temperature region of -150 °C to +150 °C. The observed small shifts in the experimental spectra upon heating were explained by increase of the high-energy conformers (of the trans type) in the population of (1) related to weakening of the intermolecular interactions that enables rotation of the terminal rings with respect to the polyene chain. Deconvolution of the ν1 band showed changes in intensity and position of the deconvoluted bands with the increase of temperature.

  2. Clinical Effects of Topical Tacrolimus on Fox-Fordyce Disease

    PubMed Central

    Kaya Erdoğan, Hilal; Bulur, Işıl; Kaya, Zeliha

    2015-01-01

    Fox-Fordyce Disease (FFD) is a rare, chronic, pruritic, inflammatory disorder of apocrine glands. It is characterized by dome-shaped, firm, discrete, skin-colored, and monomorphic perifollicular papules. The most common sites of involvement are axillae and anogenital and periareolar regions which are rich in apocrine sweat glands. Treatment is difficult. Topical, intralesional steroids, topical tretinoin, adapalene, clindamycin, benzoyl peroxide, oral contraceptives, isotretinoin, phototherapy, electrocauterisation, excision-liposuction and curettage, and fractional carbon dioxide laser are among the treatment options. In the literature, there are articles reporting beneficial effects of pimecrolimus in FFD. Nevertheless, there have not been any reports about the use of tacrolimus in FFD. We report two patients diagnosed with FFD by clinical and histopathologic examination and discussed therapeutic effects of topical tacrolimus on FFD in the light of literature. PMID:26171257

  3. 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

  4. Acne pathogenesis: history of concepts.

    PubMed

    Tilles, Gérard

    2014-01-01

    From the first reliable descriptions of acne in the early 19th century, dermatologists recognized it as a disease of the pilosebaceous follicle. Until the middle of the 20th century, they hypothesized that seborrhoea, follicular keratosis and microorganisms could be individually responsible for the acne lesions. Inflammation was only regarded as the final and inescapable step of the acne process. Although the importance of these factors has been reevaluated, recent works still regarded them as mandatory. In the 1970s, the onset of isotretinoin dramatically improved acne management. It also provided great opportunities for a better understanding of the pathogenic factors of acne. This study analyzes their genesis and development from the seminal contributions until recent advances.

  5. Rosacea and rhinophyma.

    PubMed

    Tüzün, Yalçın; Wolf, Ronni; Kutlubay, Zekayi; Karakuş, Ozge; Engin, Burhan

    2014-01-01

    Rosacea is a common and chronic inflammatory cutaneous disease with unknown etiology. The pathophysiology of rosacea is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been detected yet. Recent molecular studies propose that an altered innate immune response is involved in the pathogenesis of the rosacea disease. Signs of rosacea are indicated by the presence of characteristic facial or ocular inflammation involving both the vascular and tissue stroma. A wide range of drug options is available for the treatment of rosacea, including several topical ones (metronidazole, antibiotics, azelaic acid, benzoyl peroxide, sulfacetamide/sulfur, retinoids) and oral ones (mainly tetracyclines, metronidazole, macrolides, isotretinoin). This review highlights the recent clinical and pathophysiological developments concerning rosacea.

  6. [Systemic therapy of rosacea].

    PubMed

    Schaller, M; Belge, K

    2013-07-01

    The only medication which is authorized for therapy of rosacea is doxycycline. It is usually administered at a dose of 40-100 mg daily for 3-6 months. In case of a lack of efficacy or in case of contraindications (e.g. pregnancy, children below 8 years), azithromycin or metronidazole are alternative systemic therapies. Those forms of rosacea which involve hyperplasia of sebaceous glands respond well to retinoids such as isotretinoin. Dapsone has been successfully used for the treatment of granulomatous rosacea and rosacea fulminans. Erythema can be reduced by use of beta blockers. If patients do not respond to various therapies or if they are immunocompromised, the differential diagnosis of demodicosis should be considered; here the treatment is oral ivermectin. Some forms of rosacea (rosacea fulminans and granulomatous rosacea) may be treated initially with oral corticosteroids. Ophthalmic rosacea is treated topically as well as with tetracyclines or macrolides.

  7. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 3: a status report on systemic therapies.

    PubMed

    Del Rosso, James Q; Thiboutot, Diane; Gallo, Richard; Webster, Guy; Tanghetti, Emil; Eichenfield, Lawrence F; Stein-Gold, Linda; Berson, Diane; Zaenglein, Andrea

    2014-01-01

    The third article in this 5-part series reviews systemic therapies used to treat cutaneous rosacea based on consensus recommendations from the American Acne & Rosacea Society (AARS) on the management of the common presentations of cutaneous rosacea. The consensus recommendations are based on current understanding of research that describes pathophysiologic mechanisms that appear to be operative in rosacea, correlation of these underlying pathophysiologic mechanisms with specific clinical manifestations of rosacea, and outcomes from clinical trials that evaluate therapies for rosacea both as monotherapy and in combination with other agents. Systemic agents used for treatment of rosacea have been administered as oral formulations (ie, tablets, capsules). The only oral agent for rosacea approved by the US Food and Drug Administration (FDA) is a modified-release doxycycline 40-mg capsule. Other non-FDA-approved oral agents also are discussed including other tetracyclines, macrolides, metronidazole, and isotretinoin.

  8. A case of dissecting cellulitis and a review of the literature.

    PubMed

    Scheinfeld, Noah S

    2003-02-01

    Dissecting cellulitis (also called perifolliculitis capitis abscedens et suffodiens) manifests with perifollicular pustules, nodules, abscesses and sinuses that evolve into scarring alopecia. It predominantly occurs in African American men between 20-40 years of age, but can occasionally affect other races and women too. Associated musculoskeletal findings are sometimes reported. When it occurs with acne conglobata, hidradenitis suppurativa, and pilonidal cysts, the syndrome is referred to as the follicular occlusion triad or tetrad. Its course is chronic and relapsing, and treatment is often difficult. Medical therapies include isotretinoin, antibiotics, and prednisone. Destructive therapies include X-ray therapy, surgical excision, and skin grafting. Laser epilation of hair follicles is a promising new therapy for dissecting cellulitis. PMID:12639466

  9. Postimplantation embryo culture for the assessment of the teratogenic potential and potency of compounds.

    PubMed

    Cicurel, L; Schmid, B P

    1988-10-15

    Whole rat embryos cultured during the early stages of organogenesis were subjected to a panel of selected chemicals. Of seventeen known in vivo teratogens, seventeen also induced specific malformations in embryos grown in culture. Of ten chemicals which were reported to be negative in in vivo rat teratogenicity studies, eight also did not provoke dysmorphogenic effects in vitro. Of five additionally tested retinoids, all induced multiple malformations. However, concentrations used to induce these effects varied considerably, isotretinoin inducing malformations at 10(-5) M and arotinoid at 10(-11) M. The results indicate qualitatively as well as quantitatively a high predictability of this in vitro system and suggest that the postimplantation embryo culture system may also be useful in the prospective testing of new drugs and environmental chemicals.

  10. Olmsted Syndrome: Rare Occurrence in Four Siblings

    PubMed Central

    Bukharia, Atishay; Komal, Sweta; Sudhanan, V Madhu; Chaudhary, Shyam Sundar

    2016-01-01

    Olmsted syndrome is a very rare and severe cicatrizing keratoderma associated with periorificial lesion. Most cases are sporadic but familial occurrence has been also seen. Till now around 73 cases have been reported and none of the reported cases have 4 siblings affected from this disease. We are reporting cases of 4 siblings of age 30 year female, 26 year female, 20 year male and 10 year male who were born to a third degree consangueinous marriage and presented with palmoplantar keratoderma, periorificial hyperkeratosis, flexion deformity, pseudoainhum and contracture of digits. There was no cardiac involvement. Hence, the diagnosis of Olmsted syndrome was made and all four patients were non responsive to treatment which included topical corticosteroid, topical salicylic acid, systemic isotretinoin, systemic acitretin and oral zinc in child. PMID:27293270

  11. Oral Accutane (13-cis-retinoic acid) has no effects on spatial learning and memory in male and female Sprague-Dawley rats.

    PubMed

    Ferguson, Sherry A; Berry, Kimberly J

    2007-01-01

    Descriptions of psychiatric effects with Accutane (13-cis-retinoic acid (13-cis-RA)) use prompted a series of studies in a rodent model to ascertain its cognitive effects. Previously, we reported no effects on measures of anhedonia and depression in rats treated with 7.5, 22.5, or 30 mg/kg 13-cis-RA [S.A. Ferguson, F.J. Cisneros, B. Gough, J.P. Hanig, K.J. Berry, Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats, Toxicol. Sci. 87 (2005) 451-459 [16]; S.A. Ferguson, F.J., Cisneros, J.P. Hanig, K.J. Berry, Chronic oral treatment with Accutane (13-cis-retinoic acid) does not increase measures of anhedonia or depression in male and female Sprague-Dawley rats, (in preparation) [19

  12. Rosacea fulminans or acute rosacea? Report of 5 cases and review of the literature.

    PubMed

    Mantovani, Lucia; Zauli, Stefania; Virgili, Annarosa; Bettoli, Vincenzo

    2016-10-01

    Rosacea fulminans, previously called pyoderma faciale, is an inflammatory disease considered a dramatic form of rosacea rather than of acne. Typical features are: exclusive facial involvement of young women, sudden onset of large nodules without other signs of acne, remission without scarring or with minimal scars, no recurrences or systemic symptoms. Oral isotretinoin associated with a short course of systemic and topical corticosteroids represent the recommended treatment. Personal observation of 5 cases has induced us to make a review of worldwide literature in order to better define this clinical entity. In our opinion, rosacea fulminans is a valid diagnosis, but clinical criteria should be rigorously respected to fully exclude rosacea conglobata and acne fulminans. PMID:27595202

  13. Retinoic acid inhibits migration of cranial neural crest cells in the cultured mouse embryo.

    PubMed

    Pratt, R M; Goulding, E H; Abbott, B D

    1987-01-01

    Clinical observations have demonstrated that isotretinoin (13-cis-retinoic acid; cis-RA) is a human teratogen causing primarily heart and craniofacial malformations. Isotretinoin exposure to the early postimplantation mouse embryo in culture results in specific defects in craniofacial development that may be due to an interference in the early migration of cranial neural crest (CNC) cells [Goulding and Pratt, 1986]. The present study was designed to test this hypothesis by examining the migration of these cells in whole embryo culture. Day 8 CD-1 mouse embryos were cultured for 6-48 hr in the presence or absence of cis-RA at 2 X 10(-6) to 2 X 10(-5) M. Embryos either were fixed for light microscopy using Nichols' method for localization of CNC cells or were processed for scanning and transmission electron microscopy. At the light microscopic level, CNC cells in the mid-brain region of control embryos had migrated to the region of the first and second visceral arches after 6 hr in culture. Cis-RA interfered with this migration; CNC cells in treated embryos either did not leave the neuroepithelium (NE) or were aggregated near the NE. Autoradiographic studies indicated that cis-RA did not affect the overall viability or DNA synthesis of the CNC cells. However, at the TEM level, there was a dramatic increase in the number of cellular blebs in the CNC cells. Our results demonstrate a direct effect of 13-cis-RA on the CNC cells and suggest that this effect is due to alterations in the cell surface.

  14. Systematic review on the rapidity of the onset of action of topical treatments in the therapy of mild-to-moderate acne vulgaris.

    PubMed

    Jacobs, A; Starke, G; Rosumeck, S; Nast, A

    2014-03-01

    The time until a patient achieves a relevant improvement during the treatment of a skin disease is important for selecting a therapy, but has been largely neglected in reviews and guidelines. The aim of this systematic review was to determine the time until the onset of action (TOA) of topical acne treatments. The primary outcome was the TOA defined as the time until a 25% reduction in the mean number of inflammatory lesions had been achieved. A systematic literature search in Medline and Embase was carried out. Clinical trials that evaluated head-to-head comparisons of treatments in patients suffering from mild-to-moderate papulopustular acne were included. Abstract and full-text screening and data extraction were done independently by two investigators. With respect to inflammatory lesions, different concentrations of benzoyl peroxide (BPO) or adapalene did not seem to influence the TOA. BPO seemed to act more quickly than isotretinoin and tretinoin. Adapalene showed a shorter TOA than isotretinoin. Conflicting results were seen when comparing adapalene with tretinoin, with a tendency for adapalene to be faster. Clindamycin/BPO seemed to act more quickly than adapalene. Inconsistent results were seen for the comparison of clindamycin/BPO and BPO alone with a slight indication of a shorter TOA for clindamycin/BPO. Adapalene/BPO and clindamycin/BPO showed comparable TOA. When interpreting the data, the different study designs and the limited study quality need to be taken into account. Further research is needed to identify treatments that offer an early onset of action and possibly help to optimize patients' adherence. TOA should be considered as an additional outcome in acne trials.

  15. Reporting of drug induced depression and fatal and non-fatal suicidal behaviour in the UK from 1998 to 2011

    PubMed Central

    2014-01-01

    Background Psychiatric adverse drug reactions (ADRs) are distressing for patients and have important public health implications. We identified the drugs with the most frequent spontaneous reports of depression, and fatal and non-fatal suicidal behaviour to the UK’s Yellow Card Scheme from 1998 to 2011. Methods We obtained Yellow Card data from the Medicines and Healthcare products Regulatory Agency for the drugs with the most frequent spontaneous reports of depression and suicidal behaviour from 1964 onwards. Prescribing data were obtained from the NHS Information Centre and the Department of Health. We examined the frequency of reports for drugs and estimated rates of reporting of psychiatric ADRs using prescribing data as proxy denominators from 1998 to 2011, as prescribing data were not available prior to 1998. Results There were 110 different drugs with ≥ 20 reports of depression, 58 with ≥10 reports of non-fatal suicidal behaviour and 33 with ≥5 reports of fatal suicidal behaviour in the time period. The top five drugs with the most frequent reports of depression were the smoking cessation medicines varenicline and bupropion, followed by paroxetine (a selective serotonin reuptake inhibitor), isotretinoin (used in acne treatment) and rimonabant (a weight loss drug). Selective serotonin reuptake inhibitors, varenicline and the antipsychotic medicine clozapine were included in the top five medicines with the most frequent reports of fatal and non-fatal suicidal behaviour. Medicines with the highest reliably measured reporting rates of psychiatric ADRs per million prescriptions dispensed in the community included rimonabant, isotretinoin, mefloquine (an antimalarial), varenicline and bupropion. Robust denominators for community prescribing were not available for two drugs with five or more suicide reports, efavirenz (an antiretroviral medicine) and clozapine. Conclusions Depression and suicide-related ADRs are reported for many nervous system and non

  16. 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

  17. 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

  18. Management of EGFR-inhibitor associated rash: a retrospective study in 49 patients

    PubMed Central

    2012-01-01

    Background In recent years inhibitors directed against the epidermal growth factor receptor (EGFR) have evolved as effective targeting cancer drugs. Characteristic papulopustular exanthemas, often described as acneiform rashes, are the most frequent adverse effect associated with this class of novel cancer drugs and develop in > 90% of patients. Notably, the rash may significantly compromise the patients' quality of life, thereby potentially leading to incompliance as well as dose reduction or even termination of the anti-EGFR therapy. Yet, an effective dermatologic management of cutaneous adverse effects can be achieved. Whereas various case reports, case series or expert opinions on the management of EGFR-inhibitor (EGFRI) induced rashes have been published, data on systematic management studies are sparse. Methods Here, we present a retrospective, uncontrolled, comparative study in 49 patients on three established regimens for the management of EGFRI-associated rashes. Results Strikingly, patients' rash severity improved significantly over three weeks of treatment with topical mometason furoate cream, topical prednicarbate cream plus nadifloxacin cream, as well as topical prednicarbate cream plus nadifloxacin cream plus systemic isotretinoin. Conclusions In summary our results demonstrate that EGFRI-associated rashes can be effectively managed by specific dermatologic interventions. Whereas mild to moderate rashes should be treated with basic measures in combination with topical glucocorticosteroids or combined regiments using glucocorticosteroids and antiseptics/antibiotics, more severe or therapy-resistant rashes are likely to respond with the addition of systemic retinoids. PMID:22472354

  19. 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

  20. Assessment of BMI, Serum Leptin Levels and Lipid Profile in Patients with Skin Tags

    PubMed Central

    Sunitha, S

    2014-01-01

    Background: Skin tags (ST) are benign lesions composed of loose fibrous tissue, associated with obesity and atherogenic profile. Thus help in the follow up by considering ST as a useful cutaneous sign for the risk factor of atherosclerosis. Aim: To evaluate the association of skin tags with BMI, serum leptin and lipid profile. Materials and Methods: The study was carried out in 40 cases with ST and 40 age and gender matched controls. Subjects on oral contraceptives and systemic drugs especially lipid lowering agents, pregnant women, cases with medical history of endocrine disease, acute infection, erythroderma and psoriasis, cases with a drug history of isotretinoin use in last six months were excluded from the study. Blood samples were collected. Serum lipids and serum leptin were estimated. Result: The acrochordons group showed significantly higher values of BMI, total cholesterol (TC) and TC/HDL ratio. 60% of the patients with ST were overweight and 10% were obese. There was no statistical significant difference in leptin levels between the groups. Leptin showed a positive significant correlation with BMI in the acrochordons group. Conclusion: All the above derangements confirm that ST is cutaneous findings frequently associated with obesity and dyslipidemia. Thus follow-up of these patients with regard to the development of diseases associated with atherosclerosis may be beneficial. PMID:25386426

  1. Vaccination Targeting a Surface Sialidase of P. acnes: Implication for New Treatment of Acne Vulgaris

    PubMed Central

    Nakatsuji, Teruaki; Liu, Yu-Tsueng; Huang, Cheng-Po; Gallo, Richard L.; Huang, Chun-Ming

    2008-01-01

    Background Acne vulgaris afflicts more than fifty million people in the United State and the severity of this disorder is associated with the immune response to Propionibacterium acnes (P. acnes). Systemic therapies for acne target P. acnes using antibiotics, or target the follicle with retinoids such as isotretinoin. The latter systemic treatment is highly effective but also carries a risk of side effects including immune imbalance, hyperlipidemia, and teratogenicity. Despite substantial research into potential new therapies for this common disease, vaccines against acne vulgaris are not yet available. Methods and Findings Here we create an acne vaccine targeting a cell wall-anchored sialidase of P. acnes. The importance of sialidase to disease pathogenesis is shown by treatment of a human sebocyte cell line with recombinant sialidase that increased susceptibility to P. acnes cytotoxicity and adhesion. Mice immunized with sialidase elicit a detectable antibody; the anti-sialidase serum effectively neutralized the cytotoxicity of P. acnes in vitro and P. acnes-induced interleukin-8 (IL-8) production in human sebocytes. Furthermore, the sialidase-immunized mice provided protective immunity against P. acnes in vivo as this treatment blocked an increase in ear thickness and release of pro-inflammatory macrophage inflammatory protein (MIP-2) cytokine. Conclusions Results indicated that acne vaccines open novel therapeutic avenues for acne vulgaris and other P. acnes-associated diseases. PMID:18253498

  2. [Chemoprevention of oral cancer--clinical and experimental studies].

    PubMed

    Szumiło, Justyna; Podlodowska, Justyna; Podlodowski, Wiktor; Starosławska, Elzbieta; Burdan, Franciszek

    2012-02-01

    Chemoprevention is one of the cancer prevention methods, applied for the oral squamous cell carcinoma and its main precursor lesions--leukoplakia and erythroplakia. Presently, the most extensive clinically studied group used in such cases are retinoids: vitamin A (retinol), 13-cis-retinic acid (isotretinoin), N-(4-hydroxyphenyl)retinamide (fenretinide) and precursor of vitamin A--beta-carotene. However, despite good short-time effectiveness, retinoids do not prevent recurrences of the lesions and insignificantly increase cancer-free survival. Moreover, they are also characterized by relatively high toxicity. Vitamin E, Bowman-Birkprotease inhibitor, Spirulina fusiformis and green tee extracts as well as traditional Chinese herbs known as ZengShengPing were also found as effective agents. Lack of activity was reported for cyclooxygenase inhibitors--ketorolac and celecoxib. More promising data was collected from animal experimental studies with chemically induced oral squamous cell carcinoma. Chemopreventive activity was revealed for various agents including plant-derived compounds like resveratrol, green and black tee polyphenols, as well as protocatechuic, ellagic and caffeic acids. PMID:22590920

  3. 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

  4. Oral trimethoprim as a third-line antibiotic in the management of acne vulgaris.

    PubMed

    Bottomley, W W; Cunliffe, W J

    1993-01-01

    Acne vulgaris usually improves with long-term oral antibiotic therapy; however, some patients fail or only partially respond to the commonly prescribed antibiotics. Only a proportion of these patients warrants treatment with isotretinoin suggesting a need for additional therapeutic options. We have therefore performed an open retrospective study of the efficacy of trimethoprim as a third-line antibiotic in the treatment of patients whose acne vulgaris failed to respond to at least 2 courses of antibiotics. A total of 56 patients were reviewed, who had all failed to respond adequately to a minimum of 2 courses of antibiotics. All patients received trimethoprim in a dosage of 300 mg twice daily for at least 4 months, unless it had been withdrawn due to side effects. Topically they were given 1% clindamycin lotion twice daily to the affected areas. The severity of the patient's acne was graded on the face, back and chest. The changes in acne grades were evaluated using non-parametric statistics (Wilcoxon matched pairs). At 4 months there were significant improvements from the grades at initiation in all three sites (p = 0.005 or less). Twenty-one patients remained on the treatment for 8 months, and a significant improvement in the changes of the acne grades remained (p = 0.02 or less). Two patients had the trimethoprim stopped due to side effects. We can therefore recommend this regime as a third-line treatment in the management of acne.

  5. Dermatitis artefacta as a symptom of schizophrenia?

    PubMed Central

    Majtyka, Magdalena; Kowman, Maciej; Kłoszewska, Iwona; Kwiecińska, Ewa; Zalewska-Janowska, Anna

    2014-01-01

    Dermatitis artefacta is a disease that occurs as a result of a self-inflicted injury of the skin. The skin lesions are most often located on the areas within easy reach of the patient's dominant hand sparing the middle part of the back. Dermatitis artefacta may coexist with psychiatric disorders and imitate many dermatologic diseases. As most of the patients with self-inflicted dermatoses usually initially deny any psychiatric problems, what delays psychiatric intervention, they are typically first seen by dermatologists. We are reporting a case of a 35-year-old man with a 3-year-long history of schizophrenia who has been treated at a dermatologist's office sequentially with acne, bacterial lesions, suspected tuberculosis. However, the treatment was ineffective. He was diagnosed with dermatitis artefacta after 7 years of disease duration. During this time he was treated with many medicines e.g. isotretinoin, which is contraindicated in psychosis as it worsens the course of disease. After establishing the correct diagnosis and antipsychotic treatment, a significant improvement was obtained in both skin condition and mental state. These are the reasons why we would like to recommend close cooperation between dermatologists and psychiatrists. PMID:25254016

  6. Acne vulgaris.

    PubMed

    Aydemir, Ertuğrul H

    2014-03-01

    Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit and it is observed equally in both sexes and nearly all races. It generally begins at puberty, but the healing period is variable. There is no known etiological factor, except genetic tendency. Androgens play a very limited role in some female patients. The effects of cosmetics, foods and drinks are also discussible and too limited. There are four factors in acne pathogenesis: Increase of the sebum excretionKeratinization of infrainfundibulumBacterial colonization of the follicleInflammation It is mainly observed on the face and back, shoulders and chest. Initial lesions are comedons. Papules, pustules and cysts of severe types follow it. The most important factor in treatment is a very good patient-physician communication. Topical or systemic treatment or both can be used depending on the severity of acne. Benzoyl peroxyde, azelaic acid, AHA's antibiotics, retinoic acid and derivatives are the topical choices. For systemic treatment antibiotics are the most commonly used medicines, but isotretinoine has a very spesific place with the possibility of permanent healing. All kind of treatments need approximately six months for a good result.

  7. [Acne vulgaris].

    PubMed

    Zouboulis, C C

    2014-08-01

    Acne vulgaris is worldwide the most common skin disease. Acne is an inflammatory disorder in whose emergence androgens, PPAR ligands, the IGF-1 signaling pathway, regulating neuropeptides and environmental factors are probably involved. These factors interrupt the natural cycling process in the sebaceous gland follicle and support the transition of microcomedones to comedones and inflammatory lesions. Proinflammatory lipids and cytokines are mediators for the development of acne lesions. Bacterial antigens can potentate the inflammatory phenomena. Acne is predominantly treated with combination therapy. Selecting a treatment regimen depends on the exact classification of acne type and severity. The development of scars is the main criterion for the choice of systemic therapy. Retinoids for mild comedonal acne and the combination of retinoids with antibiotics and/or benzoyl peroxide for mild to moderate papulopustular acne are the drugs of first choice for topical treatment. The use of topical antibiotics is not recommended any more because of the development of resistant bacterial strains. Systemic antibiotics, in combination with topical retinoids and/or benzoyl peroxide, for moderate papular/nodular acne and isotretinoin for severe nodular/conglobate acne are the columns of systemic acne treatment. Systemic anti-androgens are used in women against moderate papulopustular acne. Due to advances in the understanding of the underlying inflammatory mechanisms in recent years the development of new therapeutic agents with good efficacy and better side effect profile should be expected in the future.

  8. Clinical practice guidelines for treatment of acne vulgaris: a critical appraisal using the AGREE II instrument.

    PubMed

    Sanclemente, Gloria; Acosta, Jorge-Luis; Tamayo, Maria-Eulalia; Bonfill, Xavier; Alonso-Coello, Pablo

    2014-04-01

    A significant number of clinical practice guidelines (CPGs) about the treatment of acne vulgaris in adolescents and adults have been published worldwide. However, little is known about the quality of CPGs in this field. The aim of this study was to appraise the methodological quality of published acne vulgaris CPGs. We performed a systematic review of published CPGs on acne vulgaris therapy from July 2002 to July 2012. Three reviewers independently assessed each CPG using the AGREE II instrument. A standardized score was calculated for each of the six domains. Our search strategy identified 103 citations but just six met our inclusion criteria. Agreement among reviewers was very good: 0.981. The domains that scored better were: "scope and purpose" and "clarity and presentation". Those that scored worse were "stakeholder involvement", "rigor of development", and "applicability". The European and the Malaysian CPGs were the only recommended with no further modifications. In addition, the Mexican, Colombian and the United States guidelines were recommended with provisos, with lower scores regarding stakeholder involvement, rigor of development and applicability. Only two guidelines clearly reported outcome measures for evaluating efficacy or included quality of life outcomes. CPGs varied regarding the consideration of light/laser therapy or consideration of complementary/alternative medicines. None of them included cost considerations of drugs such as systemic isotretinoin. In conclusion, published acne vulgaris CPGs for acne therapy vary in quality with a clear need to improve their methodological rigor. This could be achieved with the adherence to current CPGs development standards.

  9. 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

  10. Meibomian gland morphology and tear osmolarity: changes with Accutane therapy.

    PubMed

    Mathers, W D; Shields, W J; Sachdev, M S; Petroll, W M; Jester, J V

    1991-07-01

    We evaluated the meibomian gland function of 11 patients before and during treatment with isotretinoin (Accutane) by assessing tear osmolarity, meibomian gland morphology, tear production, rose bengal staining, and meibomian gland excreta. We found, during Accutane use, that meibomian glands appeared significantly less dense and atrophic by meibography. Excreta thickness increased from 1.7 +/- 0.9 to 3.1 +/- 1.2 (p less than 0.005), and expressible excreta volume decreased from 1.52 +/- 0.68 to 1.10 +/- 0.3 (p less than 0.05) (scale 1-4). We also found a significant increase in tear osmolarity from 304.9 +/- 11 to 316.3 +/- 10 mosmol/L (p less than 0.005). There was no significant change in the Schirmer test during treatment. We suggest that the clinical symptoms of blepharitis during Accutane therapy are related to decreased meibomian gland function and consequent increased tear evaporation and tear osmolarity.

  11. [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. PMID:24365496

  12. Ligand-specific and non-specific in vivo modulation of human epidermal cellular retinoic acid binding protein (CRABP).

    PubMed

    Hirschel-Scholz, S; Siegenthaler, G; Saurat, J H

    1989-04-01

    Retinoic acid (RA) is bound intracellularly by a specific, low molecular weight protein (CRABP), that is unrelated to its nuclear receptor and whose function and regulation are still unknown. In the present study we were able to obtain an in vivo modulation of CRABP by different stimuli in one of the major target organs of RA: the human skin. We found increased CRABP after daily application during 4 days of natural or synthetic retinoids (RA, acitretin, isotretinoin, Ro137410, retinol), that have either a high affinity to CRABP or can be transformed into RA. Only Ro150778 with no affinity and no reported transformation had no effect. No macro- or microscopical changes could be observed with any of the tested compounds. Induction of inflammatory and hyperproliferative changes in the skin by topical dithranol treatment, UVB irradiation or scotch tape stripping also induced a significant increase of CRABP 3 days after exposure. Topical diflucortolone showed not only a tendancy to decrease intrinsic CRABP levels, but significantly reduced the retinoid stimulated rise of CRABP. Thus we conclude that the increase of CRABP in a fully differentiated adult tissue seems to be a biological phenomenon following processes of inflammation and proliferation with a lag of several days, while retinoids seem to be able to induce such a rise independently of, or before, the appearance of such processes. Corticosteroids seem to be inhibitors of this reaction. We discuss the hypothesis that CRABP might function as an intracellular 'buffer' in the case of RA overload. PMID:2543582

  13. Update on the Management of Rosacea.

    PubMed

    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.

  14. Update on the management of rosacea.

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27482201

  16. Treatment of generalized granuloma annulare - a systematic review.

    PubMed

    Lukács, J; Schliemann, S; Elsner, P

    2015-08-01

    Granuloma annulare (GA) is a benign inflammatory skin disease. Localized GA is likely to resolve spontaneously, while generalized GA (GGA) is rare and may persist for decades. GGA usually is resistant to a variety of therapeutic modalities and takes a chronic course. The objective of this study was to summarize all reported treatments of generalized granuloma annulare. This is a systematic review based on MEDLINE, Embase and Cochrane Central Register search of articles in English and German and a manual search, between 1980 and 2013, to summarize the treatment of generalized granuloma annulare. Most medical literature on treatment of GGA is limited to individual case reports and small series of patients treated without a control group. Randomized controlled clinical studies are missing. Multiple treatment modalities for GGA were reported including topical and systemic steroids, PUVA, isotretinoin, dapsone, pentoxifylline, hydroxychloroquine, cyclosporine, IFN-γ, potassium iodide, nicotinamide, niacinamide, salicylic acid, dipyridamole, PDT, fumaric acid ester, etanercept, infliximab, adalimumab. While there are numerous case reports of successful treatments in the literature including surgical, medical and phototherapy options, well-designed, randomized, controlled clinical trials are required for an evidence-based treatment of GGA. PMID:25651003

  17. Perifolliculitis capitis abscedens et suffodiens in a caucasian: diagnostic and therapeutic challenge.

    PubMed

    Mihić, Liborija Lugović; Tomas, Davor; Situm, Mirna; Krolo, Iva; Sebetić, Klaudija; Sjerobabski-Masnec, Ines; Barišić, Freja

    2011-01-01

    Perifolliculitis capitis abscedens et suffodiens or dissecting cellulitis of the scalp is a rare, chronic destructive folliculitis of the scalp, characterized by painful nodules, purulent drainage, sinus tracts, keloid formation and cicatricial alopecia. The cause of the disease is unknown, but it is similar in many features to hidradenitis suppurativa and acne conglobata. In our case report, the patient's dermatologic appearance included one slightly erythematous, infiltrated alopecic area with draining lesions in the right parietal part of the scalp with a few alopecic areas in other parts of the scalp. The identification of the infectious agent, repeated swabs and KOH examination/or fungal cultures and tissue sampling for histopathologic analysis were necessary to confirm the diagnosis of perifolliculitis capitis abscedens et suffodiens. The patient received systemic antibiotics (azithromycin and amoxicillin-clavulanate) and oral antimycotic therapy (fluconazole), followed by a long period of oral isotretinoin with local skin care, which led to resolution and thus inhibited the evolution to scarring and nodular stage of the disease. Thus, such combined approach could be useful for other patients with these dermatologic problems. PMID:21703156

  18. Update on the Management of Rosacea.

    PubMed

    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:26605825

  19. Clinical, ultrasound and hormonal markers of androgenicity in acne vulgaris.

    PubMed

    Walton, S; Cunliffe, W J; Keczkes, K; Early, A S; McGarrigle, H H; Katz, M; Reese, R A

    1995-08-01

    Androgenic stimulation of sebaceous glands is an important factor in the development of acne. We examined 36 females (aged 14-34 years), selected because none had received oral contraceptives, anti-androgen therapy, or systemic antibiotics during the previous year, or isotretinoin therapy, prior to their participation in the study. Subjects were divided into groups on the basis of acne severity, as follows: physiological, mild and moderate. Only two patients had polycystic ovaries on ultrasound examination. Seven patients had irregular menses; none had evidence of hirsutism. We found that the severity of acne, based on the acne grade, was highly correlated with the inflammatory lesion count, and less correlated with the sebum excretion rate. Either acne grade or inflammatory lesion count could be related to some of the five androgenic hormone determinants; free testosterone (TESTOS), delta 4 androstenedione (DELTA 4), sex hormone binding globulin (SHBG), dehydroepiandrostenedione sulphate (DHEAS) and dihydrotestosterone (DHT). Multiple linear regression analysis determined the best model for predicting ACNE scores as involving DELTA 4 and DHEAS (positive effects), and SHBG (negative effect), P < 0.005, R2 = 0.36). In none of the patients were the levels of DHEAS or SHBG outside the normal range. The findings in the two patients with polycystic ovaries did not differ significantly from those in the remainder of the patients. PMID:7547392

  20. Off the beaten renin-angiotensin-aldosterone system pathway: new perspectives on antiproteinuric therapy.

    PubMed

    Gordon, Judit; Kopp, Jeffrey B

    2011-07-01

    CKD is a major public health problem in the developed and the developing world. The degree of proteinuria associated with renal failure is a generally well accepted marker of disease severity. Agents with direct antiproteinuric effects are highly desirable therapeutic strategies for slowing, or even halting, progressive loss of kidney function. We review progress on therapies acting further downstream of the renin-angiotensin-aldosterone system pathway (e.g., transforming growth factor-beta antagonism, endothelin antagonism) and on those acting independent of the renin-angiotensin-aldosterone system pathway. In all, we discuss 26 therapeutic targets or compounds and 2 lifestyle changes (dietary modification and weight loss) that have been used clinically for diabetic or nondiabetic kidney disease. These therapies include endogenous molecules (estrogens, isotretinoin), biologic antagonists (monoclonal antibodies, soluble receptors), and small molecules. Where mechanistic data are available, these therapies have been shown to exert favorable effects on glomerular cell phenotype. In some cases, recent work has indicated surprising new molecular pathways for some therapies, such as direct effects on the podocyte by glucocorticoids, rituximab, and erythropoietin. It is hoped that recent advances in the basic science of kidney injury will prompt development of more effective pharmaceutical and biologic therapies for proteinuria.

  1. 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.

  2. How Much Do We Know about Maintaining Treatment Response after Successful Acne Therapy? Systematic Review on the Efficacy and Safety of Acne Maintenance Therapy.

    PubMed

    Dressler, Corinna; Rosumeck, Stefanie; Nast, Alexander

    2016-01-01

    After cessation of successful initial acne therapy, patients often experience flares. Consecutive maintenance treatment after successful induction therapy is promoted by guidelines; however, little is known about the efficacy/safety of different maintenance regimens. A systematic review on acne maintenance treatments was conducted. We identified 5 randomized controlled trials [RCTs; adapalene vs. vehicle or vs. no treatment (3 RCTs), adapalene/benzoyl peroxide (BPO) vs. vehicle, combination/monotherapy of minocycline (systemic)/tazarotene/placebo] and 3 non-RCTs on systemic isotretinoin, adapalene/BPO and azelaic acid. The results of adapalene versus vehicle/no treatment varied depending on the reported outcome. The 'number of patients maintaining at least 50% improvement' counting inflammatory lesions/non-inflammatory lesions with adapalene was superior to vehicle (risk ratio, RR 1.24, 95% confidence interval, CI 1.08-1.43/RR 1.34, 95% CI 1.18-1.59). However, no significant differences were found in 2 of 3 RCTs for maintaining 'clear/almost clear' or 'mild acne' or on the global grading score. For the combination regimens of minocycline/tazarotene/placebo, no significant differences were found. Adapalene/BPO was superior to vehicle counting inflammatory lesions/non-inflammatory lesions (RR 1.61, 95% CI 1.31-1.99; RR 1.80, 95% CI 1.44-2.26). Due to the scarcity of studies, few conclusions can be drawn. More homogeneous outcome measures and specific maintenance study designs may lead to more robust findings.

  3. Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain

    PubMed Central

    He, Shuning; Mansour, Marc R; Zimmerman, Mark W; Ki, Dong Hyuk; Layden, Hillary M; Akahane, Koshi; Gjini, Evisa; de Groh, Eric D; Perez-Atayde, Antonio R; Zhu, Shizhen; Epstein, Jonathan A; Look, A Thomas

    2016-01-01

    Earlier reports showed that hyperplasia of sympathoadrenal cell precursors during embryogenesis in Nf1-deficient mice is independent of Nf1’s role in down-modulating RAS-MAPK signaling. We demonstrate in zebrafish that nf1 loss leads to aberrant activation of RAS signaling in MYCN-induced neuroblastomas that arise in these precursors, and that the GTPase-activating protein (GAP)-related domain (GRD) is sufficient to suppress the acceleration of neuroblastoma in nf1-deficient fish, but not the hypertrophy of sympathoadrenal cells in nf1 mutant embryos. Thus, even though neuroblastoma is a classical “developmental tumor”, NF1 relies on a very different mechanism to suppress malignant transformation than it does to modulate normal neural crest cell growth. We also show marked synergy in tumor cell killing between MEK inhibitors (trametinib) and retinoids (isotretinoin) in primary nf1a-/- zebrafish neuroblastomas. Thus, our model system has considerable translational potential for investigating new strategies to improve the treatment of very high-risk neuroblastomas with aberrant RAS-MAPK activation. DOI: http://dx.doi.org/10.7554/eLife.14713.001 PMID:27130733

  4. 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

  5. Hidradenitis Suppurativa Management in the United States: An Analysis of the National Ambulatory Medical Care Survey and MarketScan Medicaid Databases

    PubMed Central

    Davis, Scott A.; Lin, Hsien-Chang; Balkrishnan, Rajesh; Feldman, Steven R.

    2015-01-01

    Purpose To present nationally representative data demonstrating how frequently hidradenitis suppurativa (HS) occurs in specific groups and how it is currently managed. Methods We analyzed data from the 1990–2009 National Ambulatory Medical Care Survey (NAMCS) and the 2003–2007 MarketScan Medicaid databases for patients with a diagnosis of HS (ICD-9-CM code 705.83). Visits per 100,000 population of each race and ethnicity were calculated using the 2000 US Census data for specific demographics. Results There were 164,000 patient visits (95% CI: 128,000–200,000) annually with a diagnosis of HS in the NAMCS, and 17,270 HS patients were found in the MarketScan Medicaid over the 5-year period. Antibiotics were the most common treatment, followed by pain medications, topical steroids, and isotretinoin. Prescriptions of biologics and systemic methotrexate, cyclosporine, and acitretin were not observed in the NAMCS. Physicians prescribed medications in 74% of visits and used procedures in 11% of visits. African Americans, females, and young adults had higher numbers of visits for HS. Conclusions Our data showing a maximum of 0.06% of the population being treated for HS in a given year are consistent with the low estimates of HS prevalence. Compared to the current prescribing patterns, the more frequent prescription of biologics and systemic treatments may yield better outcomes. PMID:27172455

  6. 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.

  7. On the ability of birth defects monitoring to detect new teratogens.

    PubMed

    Khoury, M J; Holtzman, N A

    1987-07-01

    Recent concerns have been raised about the ability of birth defects monitoring programs to detect increases in the incidence of birth defects following the introduction of new teratogens. The authors illustrate how most monitoring programs in the United States and Europe are limited in their ability to detect new teratogens because of a combination of parameters: the small population size, the low population frequency of exposure to the new teratogen, the weakness of many suspected teratogens (measured in terms of relative risk R), the low background rate, and the etiologic heterogeneity in the measured defects. In a system that monitors 25,000 births per year, it can be shown that although a new teratogen such as thalidomide (R = 175) can lead to a significant increase in the number of observed cases in 1-2 weeks of monitoring, even strong teratogens such as valproic acid and isotretinoin (R = 20-25) require more than 20 years of monitoring to show a significant increase in the number of cases because of low exposure frequency. Also, most mild to moderate teratogens (R = 2-5) can be totally missed. To improve the ability of birth defects monitoring programs to detect new teratogens, it is suggested that surveillance systems ought to examine subsegments of the population with maximal exposure potential, classify birth defects into more etiologically homogeneous groups, and expand the sample size of the monitored population.

  8. 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.

  9. SAPHO syndrome with acne fulminans and severe polyosteitis involving axial skeleton

    PubMed Central

    Divya, B Lakshmi; Rao, P Narasimha

    2016-01-01

    SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis), a rare inflammatory disorder, is an association of distinct skin disorders with pustules with osteoarticular inflammation. Its etiology remains unclear, and various treatment regimens frequently fail to control the disease. An 18-year-old male patient presented to the outpatient department with severe nodulocystic acne on the face with pain at both the wrists and lower back associated with high-grade fever and chills. On physical examination, he had severe tenderness at both wrist joints and lower back, along with swelling of right wrist. Magnetic resonance imaging revealed osteitis of the distal end of the right radius. Technetium-99m-MDP Whole Body Bone Scan revealed increased metaphyseal uptake in distal radius on both sides and prominent uptake at the sacroiliac joints, vertebral end plate, left 7th costo-vertebral joint and bilateral sternoclavicular joints and manubrium sternum (resulting in “bull's head” sign, which is characteristic of SAPHO syndrome). He responded very well to a combination therapy of nonsteroid anti-inflammatory drugs, antibiotics, colchicine, and isotretinoin over a 12-week period. PMID:27730042

  10. Treatment of adult female acne: a new challenge.

    PubMed

    Dréno, B

    2015-06-01

    Acne is affecting an increasing number of adult females and so can no longer be considered as a disease of adolescence. The disease has a greater negative impact on the quality of life of adult females than their younger counterparts. Adult female acne may persist from adolescence or may have its first occurrence once adulthood has been reached. The clinical presentation and pathogenesis of adult female acne may be somewhat different to that of adolescent acne and this may require a different treatment approach. Genetic and hormonal factors are thought to play key roles in the pathogenesis of adult female acne and the disease is characterized by a chronic evolution with frequent relapses requiring long-term maintenance therapy. Fixed-dose retinoid/antimicrobial combinations may be of interest for the treatment of adult female acne given that subgroup analysis of clinical trials has indicated that they are effective against both inflammatory and non-inflammatory lesions in these patients. These treatments may also be of interest, given the chronic course of the disease in adult females, the high likelihood of the presence of antibiotic-resistant P. acnes and the poor adherence of patients to other long-term therapies. Oral hormonal treatment or isotretinoin may be required in patients with severe acne or disease that is refractory to other treatments. Additional clinical studies of acne treatments specifically conducted in adult female patients are required to increase the evidence base on which future treatment recommendations can be based.

  11. Infantile acne: a retrospective study of 16 cases.

    PubMed

    Hello, Muriel; Prey, Sorilla; Léauté-Labrèze, Christine; Khammari, Amir; Dreno, Brigitte; Stalder, Jean-François; Barbarot, Sébastien

    2008-01-01

    Infantile acne is a rare and poorly understood disorder. The objective of this study was to improve our knowledge about the epidemiology and clinical course of infantile acne, and evaluate approaches to treatment. This two-center retrospective study covered the period between 1985 and 2007. Inclusion criteria were: (i) age less than 24 months when lesions appeared; (ii) presence of both inflammatory and noninflammatory lesions; (iii) persistence of lesions for at least 2 months. The data were drawn from clinical and photographic records, followed by administration of a telephone questionnaire to parents. It was proposed that each case be reviewed on the basis of the child's appearance and score on an acne scar clinical grading scale. Sixteen children were included. Nine had a family history of severe adolescent acne. The average duration of disease was 22 months. Two patients had been effectively treated with oral isotretinoin. More than half of the patients exhibited scars. We re-examined five children (average acne scar clinical grading scale score = 12/540). On the basis of the frequency of scarring, and the severity and average duration of lesions, the use of oral retinoids in severe infantile acne warrants evaluation.

  12. 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. PMID:27482201

  13. [Autoimmune hepatitis induced by isotretionine].

    PubMed

    Guzman Rojas, Patricia; Gallegos Lopez, Roxana; Ciliotta Chehade, Alessandra; Scavino, Yolanda; Morales, Alejandro; Tagle, Martín

    2016-01-01

    We describe a case of a teenage patient with the diagnosis of drug induced autoimmune hepatitis. The patient is a 16 years old female, with the past medical history of Hashimoto’s hypothyroidism controlled with levothyroxine, who started treatment with Isotretionin (®Accutane) 20 mg q/12 hours for a total of 3 months for the treatment of severe acne. The physical examination was within normal limits and the results of the laboratory exams are: Baseline values of ALT 28 U/L, AST 28 U/L. Three months later: AST 756 U/L, ALT 1199U/L, alkaline phosphatase 114 U/L, with normal bilirrubin levels throughout the process. The serology studies were negative for all viral hepatitis; ANA titers were positive (1/160) and igG levels were also elevated. A liver biopsy was performed, and was compatible with the diagnosis of autoimmune hepatitis. Corticosteroid therapy was started with Prednisone 40 mg per day one week after stopping the treatment with isotretionin, observing an improvement in the laboratory values. We describe this case and review the world literature since there are no reported cases of Isotretinoin-induced autoimmune hepatitis. PMID:27131947

  14. Teratogenicity of benzoic acid derivatives of retinoic acid in cultured mouse embryos.

    PubMed

    Goulding, E H; Jetten, A M; Abbott, B D; Pratt, R M

    1988-01-01

    Isotretinoin (13-cis-RA) is a human teratogen and mouse embryos exposed to 13-cis-RA in vivo exhibit many of the same defects as humans. Early postimplantation mouse embryos exposed to 13-cis-RA in culture exhibit developmental alterations of the visceral arches, similar to those seen after in vivo exposure. Certain benzoic acid derivatives of retinoic acid have been shown to possess activity equal to or greater than retinoic acid in several in vitro systems. This study examines the teratogenic effects of some of these retinoids on mouse embryos in vitro. Day 8 CD-1 mouse embryos were cultured for 48 hours in the presence of these benzoic acid derivatives. With the exception of Ro-15-0778, all compounds produced visceral arch malformations similar to those seen in embryos exposed to 13-cis-RA, but at dramatically different effective concentrations. Extremely low concentrations of the retinoic acid-related compounds tested appear to have detrimental effects on embryonic development and these compounds may be poor candidates for therapeutic use.

  15. 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.

  16. Recent advances in the use of adapalene 0.1%/benzoyl peroxide 2.5% to treat patients with moderate to severe acne.

    PubMed

    Leyden, James

    2016-01-01

    The central role of inflammation in acne is now more clearly understood. Adapalene, a third-generation topical retinoid, down-regulates toll-like receptor 2 expression and inhibits activator protein-1 activity. In a fixed-dose combination, adapalene and benzoyl peroxide (BPO) act synergistically on inflammatory patterns through regulation of innate immunity. In addition to reducing inflammatory and non-inflammatory lesions, adapalene/BPO helps prevent lesion and microcomedone formation. The combination of a topical retinoid and antimicrobial agent remains the preferred approach for almost all patients with acne. In cases of more severe disease, there is a clinical benefit in combining adapalene/BPO with an oral antibiotic for 12 weeks. Most recently, adapalene/BPO plus doxycycline 200 mg was found to be highly effective when compared with isotretinoin in the treatment of patients with severe acne with nodules. Long-term maintenance therapy is needed for most patients. Retinoids are the preferred agents, with BPO added in patients with more severe disease if needed. Adapalene is anticomedogenic, reduces comedones and has anti-inflammatory properties, while BPO is a unique antimicrobial agent not shown to induce microbial resistance after more than 50 years of use. Maintenance therapy for 6 months with adapalene/BPO prevents relapse among patients with severe acne and continues to reduce disease symptoms.

  17. Selective induction of apoptosis in the hamster flank sebaceous gland organ by a topical liposome 5-alpha-reductase inhibitor: a treatment strategy for acne.

    PubMed

    Li, Lingna; Tang, Li; Baranov, Eugene; Yang, Meng; Amoh, Yasuyuki; Katsuoka, Kensei; Hoffman, Robert M

    2010-02-01

    Acne is a very widespread cosmesis problem. Isotretinoin, a synthetic oral retinoid is used to treat acne, which is androgen dependent. Numerous side-effects occur from this treatment. 5-alpha-Reductase plays a critical role in normal and pathological androgen-dependent processes. We have taken the approach to develop a selective, effective, topically-applied 5-alpha-reductase inhibitor to modify unwanted or pathological processes in the pilosebaceous unit such as acne. Toward this goal, we have previously developed a selective liposome hair follicle targeting system. We demonstrate in this report that the 5-alpha-reductase inhibitor N,N-diethyl-4-methyl-3-oxo-4-aza-5alpha-androstane-17beta-carboxamide (4-MA) incorporated into liposomes induces apoptosis and inhibits growth of the dihydrotestosterone (DHT)-dependent hamster flank organ sebaceous gland. We have compared topical application of liposome 4-MA and solvent-formulated 4-MA and observed selective efficacy of topical application of liposome 4-MA by the reduction of size and induction of apoptosis only in the treated hamster flank organ. Apoptosis induced by liposome 4-MA in the treated flank organ sebaceous gland cells was observed both by assays for DNA fragments (transferase deoxytidyl uridine end labeling) and by observation of condensed and fragmented nuclei. When 4-MA was topically applied formulated in ethanol and glycerol without liposomes, the selective efficacy was lost. Liposome 4-MA did not significantly affect prostate weight, testosterone/DHT ratios or bodyweight gain compared to controls indicating safety as well as efficacy of topical application of liposome 4-MA for pathological processes such as acne. PMID:20175850

  18. 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

  19. What's new in acne? An analysis of systematic reviews published in 2011-2012.

    PubMed

    Bhate, K; Williams, H C

    2014-04-01

    This review summarizes important clinical developments in acne vulgaris identified from 17 systematic reviews published between February 2011 and August 2012. Regarding causes, Demodex mites have been shown to be associated with both acne vulgaris and rosacea, although it is unclear if their eradication improves either disease. Some weak evidence has emerged that suggests a possible link between dairy produce and acne, which warrants further research. With reference to the effects of acne, there is good evidence that acne negatively affects quality of life, self-esteem and mood in adolescents. Acne is also associated with an increased risk of anxiety, depression and suicidal ideation, highlighting the importance of asking patients with acne directly about psychological issues in order to identify those who might benefit from early psychiatric support. Regarding treatment, there seems to be no additional benefit to using higher strengths of benzoyl peroxide, and lower strengths such as 2.5% have fewer side effects. Despite earlier concerns of increased mortality in those using topical tretinoin for skin cancer prevention, a systematic review on this topic has not found any convincing evidence of a link between such non-cutaneous events and once-daily application of 0.02-0.05% tretinoin. Combined oral contraceptives are of benefit in both inflammatory and non-inflammatory acne. Current surveys suggest that implementation of the pregnancy prevention programme for isotretinoin may not be stringent, and a high level of monitoring and audit is recommended. Ablative and non-ablative laser resurfacing for the treatment of acne scars may be beneficial, but further studies with a longer follow-up period are required.

  20. Promising therapeutic targets in neuroblastoma.

    PubMed

    Matthay, Katherine K; George, Rani E; Yu, Alice L

    2012-05-15

    Neuroblastoma, the most common extracranial solid tumor in children, is derived from neural crest cells. Nearly half of patients present with metastatic disease and have a 5-year event-free survival of <50%. New approaches with targeted therapy may improve efficacy without increased toxicity. In this review we evaluate 3 promising targeted therapies: (i) (131)I-metaiodobenzylguanidine (MIBG), a radiopharmaceutical that is taken up by human norepinephrine transporter (hNET), which is expressed in 90% of neuroblastomas; (ii) immunotherapy with monoclonal antibodies targeting the GD2 ganglioside, which is expressed on 98% of neuroblastoma cells; and (iii) inhibitors of anaplastic lymphoma kinase (ALK), a tyrosine kinase that is mutated or amplified in ~10% of neuroblastomas and expressed on the surface of most neuroblastoma cells. Early-phase trials have confirmed the activity of (131)I-MIBG in relapsed neuroblastoma, with response rates of ~30%, but the technical aspects of administering large amounts of radioactivity in young children and limited access to this agent have hindered its incorporation into treatment of newly diagnosed patients. Anti-GD2 antibodies have also shown activity in relapsed disease, and a recent phase III randomized trial showed a significant improvement in event-free survival for patients receiving chimeric anti-GD2 (ch14.18) combined with cytokines and isotretinoin after myeloablative consolidation therapy. A recently approved small-molecule inhibitor of ALK has shown promising preclinical activity for neuroblastoma and is currently in phase I and II trials. This is the first agent directed to a specific mutation in neuroblastoma, and marks a new step toward personalized therapy for neuroblastoma. Further clinical development of targeted treatments offers new hope for children with neuroblastoma.

  1. Interventions for rosacea: abridged updated Cochrane systematic review including GRADE assessments.

    PubMed

    van Zuuren, E J; Fedorowicz, Z

    2015-09-01

    Rosacea is a common chronic facial dermatosis. This update of our Cochrane review on interventions for rosacea summarizes the evidence, including Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group assessments, of the effects of the currently available treatments. Searches included the following: Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE, EMBASE, LILACS and the Science Citation Index, and ongoing trials registries (July 2014). We included 106 randomized controlled trials (RCTs) with 13 631 participants, a more than 80% increase since the last update in 2011. Pooling of data was feasible for a few outcomes, for topical metronidazole and azelaic acid and both appeared to be more effective than placebo (moderate and high-quality evidence, respectively). Topical ivermectin was more effective than placebo based on two studies (high-quality evidence), and slightly more effective than metronidazole in one study. Brimonidine was more effective than vehicle in reducing erythema in rosacea (high-quality evidence). Ciclosporin ophthalmic emulsion was effective for ocular rosacea (low-quality evidence). For oral treatments there was moderate-quality evidence for the effectiveness of tetracycline based on two old studies, and high-quality evidence for doxycycline 40 mg compared with placebo according to physician assessments. One study at high risk of bias demonstrated equivalent effectiveness for azithromycin and doxycycline 100 mg. Minocycline 45 mg may be effective for papulopustular rosacea (low-quality evidence). Low-dose isotretinoin appeared to be slightly more effective than doxycycline 50-100 mg (high-quality evidence). Laser and light-based therapies for erythema in rosacea were effective (low-quality evidence). Further RCTs are required for ocular rosacea.

  2. [Signs and symptoms of rosacea].

    PubMed

    Schmutz, J-L

    2014-09-01

    Rosacea is a chronic inflammatory dermatosis characterized by outbreaks of exacerbation and remission. The diagnosis of rosacea based on specific clinical criteria, mainly centrofacial erythema occurring between 30 and 50 years. The disease predominates in women, in light phototype, especially from Northern Europe. Several classifications of the disease exist. In France, Edouard Grosshans described four stages. Stage I is that of flushing, stage II is that of erythrocouperosis, stage III papules and pustules and stage IV rhinophyma. German schools described only 3 stages, like experts from the National Rosacea Society (NRS), who described four subtypes: • 1. erythematotelangiectatic rosacea; • 2. papulopustular rosacea; • 3. phymas; • 4. ocular rosacea. The patient can enter the disease at any stage. CLINICAL ASPECTS OF ROSACEA: Stage I (flushes) sometimes starts very early at the age of 20 years by the occurrence of paroxysmal facial erythema that might be associated with conjunctival hyperemia. Flushes occur after meals, sudden change in temperature or absorption of alcohol or hot drinks. Stage II or erythrocouperosis comprises permanent facial erythema with telangiectasia. Stage III is the most characteric of the disease. On the erythematous background patient develop outbreak of papules and pustules. Stage IV is mainly observed in males and is characterized mainly by rhinophyma. There is no consensus regarding the description of the other variants. NRS describe a particular subtype, granulomatous or lupoid rosacea, characterized by yellowish or brownish papules of the cheeks and peri-orificial areas. Ocular rosacea is common and should be systematically looked for in all patients with rosacea. Steroid rosacea is a complication of topical corticosteroids use on the face. Fulminant rosacea occurs abruptly in young women, who develop papules, pustules and deep purulent sinuses. Treatment includes the combination of systemic corticosteroids and isotretinoin

  3. 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

  4. Drug-induced Depression: a Case/Non Case Study in the French Pharmacovigilance Database.

    PubMed

    Lafay-Chebassier, Claire; Chavant, François; Favrelière, Sylvie; Pizzoglio, Véronique; Pérault-Pochat, Marie-Christine

    2015-01-01

    Depression is a complex disorder with heterogeneous clinical anomalies whose neurobiological understanding still remains unclear. Medications have been implicated as potential causes of depression but for many of them, data are controversial. The present study aims to investigate association bet ween drugs and reports of depression. We used the case/non case method in the French pharmacovigilance database (FPVD) to identify drugs associated with depression. Cases were reports of depression in the FPVD between January 2007 and December 2011. Non cases were all other reports during the same period. Data were expressed as reporting odds ratio (ROR) with their 95% confidence interval. Of the 114,692 reports recorded in the FPVD during the studied period, we identified 474 cases of depression. For the majority of the patients, they were considered as "non serious" (56%) and evolution was favorable (64%). Significant RORs were found for antiepileptics (topiramate, levetiracetam), anti-infective and especially anti-retroviral drugs (efavirenz, emtricitabine, tenofovir, etravirine, raltegravir), interferons and other agents including isotretinoin, methylphenidate, sodium oxybate, varenicline, montelukast, flunarizine, adalimumab, anastrozole. Taking into account the limits of the methodology, the present study described associations with mainly expected drugs belonging to various therapeutic classes but it also found a signal with some anti-retrovirals. On the contrary, we did not find some assumed associations like cardiovascular medications, antimalarial. For most of the drugs, one or more mechanisms were found to explain these depressogenic effects on the basis of animal and human literature. Even if such associations need to be confirmed by further prospective studies, cautions are necessary for many drugs to early detect depressive symptoms. PMID:26056040

  5. Promising therapeutic targets in neuroblastoma

    PubMed Central

    Matthay, Katherine K.; George, Rani E.; Yu, Alice L.

    2012-01-01

    Neuroblastoma, the most common extra- cranial solid tumor in children, is derived from neural crest cells. Nearly half of patients present with metastatic disease, and have 5-year EFS of less than 50%. New approaches with targeted therapy may improve efficacy without increased toxicity. The current review will evaluate three promising targeted therapies, including 131I-metaiodobenzylguanidine (MIBG), a radiopharmaceutical taken up by the human norepinephrine transporter expressed in 90% of neuroblastomas, immunotherapy with monoclonal antibodies targeting the GD2 ganglioside, expressed on 98% of neuroblastoma cells, and inhibitors of ALK, a tyrosine kinase which is mutated or amplified in approximately 10% of neuroblastoma and expressed on the surface of most neuroblastoma cells. Early phase trials have confirmed the activity of 131I-MIBG in relapsed neuroblastoma, with response rates of about 30%, but the technical aspects of administration of large amounts of radioactivity in young children and the limited access have hindered incorporation into treatment of newly diagnosed patients. Anti-GD2 antibodies have also demonstrated activity in relapsed disease, and a recent phase III randomized trial showed a significant improvement in event-free survival for patients receiving chimeric anti-GD2 (ch14.18) combined with cytokines and isotretinoin after myeloablative consolidation therapy. A recently approved small molecule inhibitor of ALK has promising pre-clinical activity for neuroblastoma, and is currently in phase I and II trials. This is the first agent directed to a specific mutation in neuroblastoma, and marks a new step toward personalized therapy for neuroblastoma. Further clinical development of targeted treatments offers new hope for children with neuroblastoma. PMID:22589483

  6. 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

  7. 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.

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

    PubMed

    Scheinfeld, Noah

    2013-01-01

    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. PMID:24021361

  9. PERIORAL DERMATITIS: STILL A THERAPEUTIC CHALLENGE.

    PubMed

    Mokos, Zrinka Bukvić; Kummer, Ana; Mosler, Elvira Lazić; Čeović, Romana; Basta-Juzbašić, Aleksandra

    2015-06-01

    Perioral dermatitis is a common and often chronic dermatosis. In its classic form, it primarily affects women aged 15 to 45 years, but there are also variants including lupus-like and granulomatous perioral dermatitis, where granulomatous form is more common in childhood and affects mostly prepubescent boys. The etiopathogenesis of the disease remains unclear, but there is a frequent finding of prolonged use of topical products, especially corticosteroids, in the treatment of rosacea and seborrheic dermatitis, preceding the clinical manifestation of perioral dermatitis. Other causes important for the occurrence of the disease include various skin irritants, as well as other physical and hormonal factors, which all share the epidermal barrier dysfunction as an underlying main pathogenic factor. Clinical presentation of papulovesicular eruption in the perioral region with a typical narrow spared zone around the edge of the lips is characteristic. Therapeutic approach should be individually addressed, depending on the severity of clinical presentation and patient's age, with special attention to patient's education and continuous psychological support. In mild forms of perioral dermatitis, 'zero therapy' is the treatment of choice. In the initial treatment period, patients with steroid-induced perioral dermatitis should be closely followed up because the rebound phenomenon usually develops after cessation of previous topical treatment. In moderate disease, treatment includes topical metronidazole, erythromycin, and pimecrolimus, whereas in more severe cases the best validated choice is oral tetracycline in a subantimicrobial dose until complete remission is achieved. Systemic isotretinoin should be considered as a therapeutic option for patients refractory to all standard therapies. PMID:26415314

  10. 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

  11. A case of a patient with stage III familial hidradenitis suppurativa treated with 3 courses of infliximab and died of metastatic squamous cell carcinoma.

    PubMed

    Scheinfeld, Noah

    2014-03-01

    had also taken isotretinoin years before without substantial long-term benefit. The various treatments were palliative but the HS always returned. He expressed that the pain from his HS was not bearable. He decided in consultations with his doctors to try infliximab owing to the positive clinical data for its efficacy in HS. He took 3 courses of infliximab 500mg, each of which was followed by surgical debridement of the perineal and anal areas. At the 3rd surgical debridement his physician noted the presence of squamous cell carcinoma (SCC) on July 28, 2008. The infliximab was stopped. However, the patient developed the patient underwent scanning soon after that showed soon after that the SCC had metastasized. He expired in June of 2009. PMID:24656278

  12. Refractory Hailey-Hailey disease successfully treated with sandpaper dermabrasion.

    PubMed

    LeBlanc, Keith G; Wharton, Joshua B; Sheehan, Daniel J

    2011-01-01

    A 53-year-old woman presented with a 20-year history of pruritic dermatitis on the groin, axillae, inframammary folds, posterior aspect of the neck, and popliteal fossae. She was referred to our clinic by an outside facility after results from a punch biopsy diagnosed Hailey-Hailey disease (HHD). The patient had previously attempted treatment with many traditional noninvasive options with no success. Topical treatment modalities included corticosteroids, immunomodulators, antifungals, retinoids, and antibiotic preparations. Intralesional corticosteroids, as well as botulinum toxin and carbon dioxide laser, were also unsuccessful. Failed systemic treatment modalities included antibiotics, antihistamines, prednisone, azathioprine, mycophenolate mofetil, acitretin, isotretinoin, adalimumab, and etanercept. Of note, cyclosporine was successful in clearing the cutaneous involvement in our patient, but elevation ofcreatinine and exacerbated hypertension precluded continued use. The decision was made to treat the patient by dermabrasion with sandpaper. The patient was prepped in a sterile fashion, and a field block with 1% lidocaine with epinephrine was performed. This was followed by abrasion down to the superficial dermis with 3M Sandblaster fine sandpaper (3M, St. Paul, MN) and hyfrecation between rounds ofdermabrasion. The treated areas were then covered with petrolatum and sterile gauze, and antibiotics and pain medication were prescribed. This treatment was initially performed on the patient's posterior aspect of the neck and later to the bilateral popliteal fossae and axillae. Three months post-treatment, desirable functional and cosmetic results of the treated areas had been achieved (Figure 1 and Figure 2). While no recurrence of clinically active HHD has been seen in the dermabraded areas of the neck and popliteal fossae, the patient continues to have active disease in the axillae despite sandpaper dermabrasion. To quantify our results, we performed two biopsies

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

    PubMed

    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/m(2) 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.

  14. Prolonged Inner Retinal Photoreception Depends on the Visual Retinoid Cycle

    PubMed Central

    Zhao, Xiwu; Pack, Weston; Khan, Naheed W.

    2016-01-01

    In addition to rods and cones, mammals have inner retinal photoreceptors called intrinsically photosensitive retinal ganglion cells (ipRGCs), which use the photopigment melanopsin and mediate nonimage-forming visual responses, such as pupil reflexes and circadian entrainment. After photic activation, photopigments must be reverted to their dark state to be light-sensitive again. For rods and to some extent cones, photopigment regeneration depends on the retinoid cycle in the adjacent retinal pigment epithelium (RPE). By contrast, ipRGCs are far from the RPE, and previous work suggests that melanopsin is capable of light-dependent self-regeneration. Here, we used in vitro ipRGC recording and in vivo pupillometry to show that the RPE is required for normal melanopsin-based responses to prolonged light, especially at high stimulus intensities. Melanopsin-based photoresponses of rat ipRGCs were remarkably sustained when a functional RPE was attached to the retina, but became far more transient if the RPE was removed, or if the retinoid cycle was inhibited, or when Müller glia were poisoned. Similarly, retinoid cycle inhibition markedly reduced the steady-state amplitude of melanopsin-driven pupil reflexes in both mice and rats. However, melanopsin photoresponses in RPE-separated rat retinas became more sustained in the presence of an 11-cis-retinal analog. In conclusion, during prolonged illumination, melanopsin regeneration depends partly on 11-cis-retinal from the RPE, possibly imported via Müller cells. Implications for RPE-related eye diseases and the acne drug isotretinoin (a retinoid cycle inhibitor) are discussed. SIGNIFICANCE STATEMENT Intrinsically photosensitive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin and drive subconscious physiological responses to light, e.g., pupillary constriction and neuroendocrine regulation. In darkness, each photopigment molecule in ipRGCs, as well as rod/cone photoreceptors, contains 11-cis-retinal (a

  15. Oral treatment with ACCUTANE does not increase measures of anhedonia or depression in rats.

    PubMed

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

    2007-01-01

    Reports of depression and/or suicide with ACCUTANE (13-cis-retinoic acid (13-cis-RA)) use prompted studies in a rodent model to ascertain its potential effects. Previously, there were no effects on measures of anhedonia (intake of a saccharin-flavored solution) and depression (forced swim test (FST) behaviors) in rats treated with 7.5 or 22.5 mg/kg 13-cis-RA [S.A. Ferguson, F.J. Cisneros, B. Gough, J.P. Hanig, K.J. Berry, Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats, Toxicol. Sci. 87 (2005) 451-459.]. Here, dose and temporal thresholds were investigated by increasing the maximum 13-cis-RA dose to 30 mg/kg, extending treatment duration, and measuring behaviors repeatedly. Beginning on post-natal day 59, male and female Sprague-Dawley rats were gavaged with soybean oil, 7.5 or 30 mg/kg/day of 13-cis-RA for approximately 19 weeks. FST behaviors were measured after 24, 82, and 131 treatment days and saccharin intake (0.03% solution) was measured at baseline and after 14, 35, 56, and 112 treatment days. Body weight and food intake were not altered by treatment. FST durations of swim, climb/struggle, and immobility were unaffected by 13-cis-RA at any time during treatment. More males than females required "rescue" in the FST but there was no treatment effect on number of rats requiring early removal. 13-cis-RA treatment had no effects on saccharin intake at any time. Given that the 7.5 mg/kg dose produces serum levels which parallel those of humans [S.A. Ferguson, P.H. Siitonen, F.J. Cisneros, B. Gough, J.F. Young, Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats, Basic Clin. Pharmacol. Toxicol 98 (2006) 582-587.], these results are quite relevant. Combined with previous results, these results provide further evidence that 13-cis-RA does not produce behavioral alterations indicative of depression

  16. 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

  17. 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