isotretinoin and Hyperlipidemias

A case of acquired perforating dermatosis associated with diabetic nephropathy is described. The case is unusual in that the dermatosis first developed approximately 1 year after renal transplantation rather than at a time when renal function was more severely impaired or during haemodialysis. There was a partial response to treatment with isotretinoin but the use of this drug was limited by the development of hyperlipidaemia. The relevant literature is reviewed.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Hyperlipidemias; Isotretinoin; Keratolytic Agents; Kidney Failure, Chronic; Male; Skin Diseases

Topics: Animals; Humans; Hyperlipidemias; Isotretinoin; Lipoproteins; Retinoids; Triglycerides

Topics: Etretinate; Humans; Hyperlipidemias; Isotretinoin; Kinetics; Lipid Metabolism; Lipoproteins; Pancreatitis; Retinoids

Topics: Adult; Cholesterol; Coronary Disease; Etretinate; Humans; Hyperlipidemias; Isotretinoin; Lipids; Lipoproteins; Liver; Male; Tretinoin; Triglycerides

Sebum production is key in the pathophysiology of acne, an extremely common condition, which when severe, may require treatment with isotretinoin, a known teratogen. Apart from isotretinoin and hormonal therapy, no agents are available to reduce sebum. Increasing our understanding of the regulation of sebum production is a milestone in identifying alternative therapeutic targets. Studies in sebocytes and human sebaceous glands indicate that agonists of peroxisome proliferator-activated receptors (PPARs) alter sebaceous lipid production. The goal of this study is to verify the expression and activity of PPARs in human skin and SEB-1 sebocytes and to assess the effects of PPAR ligands on sebum production in patients. To investigate the contribution of each receptor subtype to sebum production, lipogenesis assays were performed in SEB-1 sebocytes that were treated with PPAR ligands and isotretinoin. Isotretinoin significantly decreased lipogenesis, while the PPARalpha agonist-GW7647, PPARdelta agonist-GW0742, PPARalpha/delta agonist-GW2433, PPARgamma agonist rosiglitazone, and the pan-agonist-GW4148, increased lipogenesis. Patients treated with thiazolidinediones or fibrates had significant increases in sebum production (37 and 77%, respectively) when compared to age-, disease-, and sex-matched controls. These data indicate that PPARs play a role in regulating sebum production and that selective modulation of their activity may represent a novel therapeutic strategy for the treatment of acne.

Topics: Adult; Cell Line, Transformed; Diabetes Mellitus; Female; Fenofibrate; Gemfibrozil; Humans; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; Isotretinoin; Ligands; Lipogenesis; Male; Middle Aged; Pioglitazone; PPAR alpha; PPAR gamma; Rosiglitazone; Sebaceous Glands; Sebum; Thiazolidinediones

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

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Disease-Free Survival; Double-Blind Method; Europe; Female; Head and Neck Neoplasms; Humans; Hyperlipidemias; Interferon-alpha; Isotretinoin; Male; Melanoma; Middle Aged; Multivariate Analysis; Neoplasm Staging; Prognosis; Prospective Studies; Quality of Life; Skin Diseases; Treatment Outcome

As a result of concerns about hypertriglyceridemia, liver enzyme abnormalities, and leukopenia during isotretinoin therapy for acne, patients are often monitored closely with routine laboratory assessments, although the value of this practice has been questioned.. We conducted a cohort study of patients receiving isotretinoin for acne between January 1, 2008, and June 30, 2017, using the OptumInsights Electronic Health Record Database (Optum, Eden Prairie, MN) to evaluate the frequency of laboratory abnormalities. Poisson regression was used to evaluate for changes to the frequency of routine laboratory monitoring over time.. Among 1863 patients treated with isotretinoin, grade 3 or greater triglyceride and liver function testing abnormalities were noted in fewer than 1% and 0.5% of patients screened, respectively. No grade 3 or greater cholesterol or complete blood count abnormalities were observed. There were no meaningful changes in the frequency of laboratory monitoring over time.. Limitations include that we are unable to evaluate the clinical notes to understand the exact clinical decision making when clinicians encountered abnormal laboratory values.. Although laboratory abnormalities are rare and often do not influence management, frequent laboratory monitoring remains a common practice. There are opportunities to improve the quality of care among patients being treated with isotretinoin for acne by reducing the frequency of lipid and liver function monitoring and by eliminating complete blood count monitoring.

Topics: Acne Vulgaris; Administration, Oral; Adolescent; Cohort Studies; Databases, Factual; Dermatologic Agents; Facial Dermatoses; Female; Humans; Hyperlipidemias; Isotretinoin; Liver Function Tests; Male; Monitoring, Physiologic; Poisson Distribution; Prognosis; Retrospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome; Triglycerides; Young Adult

To determine the incidence of abnormal laboratory test results among isotretinoin users.. Retrospective cohort.. Comprehensive managed care health plan in Northern California.. The study population comprised 13 772 patients aged 13 to 50 years with acne, undergoing oral isotretinoin therapy between March 1995 and September 2002.. Laboratory values for serum triglyceride, total cholesterol, and liver transaminase levels; white blood cell count, hemoglobin level, and platelet count; and frequency of abnormal laboratory results by severity grade as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0.. Substantial increases in the cumulative incidence of abnormalities were seen in serum lipid and transaminase levels, but not in hematologic parameters, during isotretinoin treatment compared with the baseline period. The cumulative incidence of new abnormalities in patients with normal values at baseline was 44% for triglyceride level, 31% for total cholesterol level, and 11% for transaminase level. Moderate to severe abnormalities in lipid and transaminase levels were generally transient and reversible. New abnormalities in hematological test results were uncommon.. The incidence of abnormally high serum lipid levels during isotretinoin treatment may be greater than previously estimated. Elevations in transaminase level are generally mild. Normal baseline values of serum lipid and transaminase levels do not preclude the development of new abnormalities during isotretinoin treatment. Routine monitoring of white blood cell count, hemoglobin level, and platelet count during isotretinoin therapy may be of little utility without clinical suspicion of an abnormality. The clinical significance of laboratory abnormalities during isotretinoin therapy remains to be determined.

Topics: Acne Vulgaris; Administration, Oral; Adolescent; Adult; Blood Chemical Analysis; California; Cholesterol; Cohort Studies; Female; Humans; Hyperlipidemias; Incidence; Isotretinoin; Keratolytic Agents; Liver Function Tests; Male; Managed Care Programs; Middle Aged; Retrospective Studies; Triglycerides

Isotretinoin is well recognised to cause hyperlipidaemia. This is most obvious during the second month of a 4-month course. Since there are no long-term data on lipid profiles, we have identified 30 subjects who have received 3 or more courses of isotretinoin. They had been exposed to a median of 24.5 months (range 12-103) isotretinoin therapy with a median total cumulative dose of 350 mg/kg (range 152-1221). The median serum cholesterol pre-treatment was 4.6 mmol/L (range 3-6.4). This compared to a median of 4.5 mmol/L (range 3-6.4) just prior to starting the final course. The median triglyceride levels before treatment and pre-final course were 0.8 mmol/L (range 0.3-1.7) and 0.92 mmol/L (range 0.4-2.6) respectively, indicating no significant change in cholesterol or triglyceride concentrations when measured prior to the first and last courses. In addition there was no correlation between cholesterol or triglyceride concentration before the final course of isotretinoin and the total cumulative dose of isotretinoin. We conclude that there appears to be little risk of causing hyperlipidaemia by prolonged therapy with isotretinoin in patients with acne.

Topics: Acne Vulgaris; Adolescent; Adult; Age Distribution; Child; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hyperlipidemias; Incidence; Isotretinoin; Lipoproteins; Male; Middle Aged; Probability; Retrospective Studies; Risk Assessment; Sensitivity and Specificity; Sex Distribution; Statistics, Nonparametric

Isotretinoin is a vitamin-A derivative most commonly utilized in the treatment of severe recalcitrant nodulocystic acne. Derangement of lipid metabolism leading to increased triglyceride and cholesterol level has been reported after taking this drug. We report the case of a 43-year-old female with no identifiable risk factor for pancreatitis who developed acute pancreatitis associated with hyperlipidemia while being treated with isotretinoin for hidradenitis suppurativa. To our knowledge, this is the third reported case of isotretinoin-induced hyperlipidemia leading to acute pancreatitis.

Topics: Acute Disease; Adult; Female; Hidradenitis Suppurativa; Humans; Hyperlipidemias; Isotretinoin; Pancreatitis

Administration of 13-cis retinoic acid (isotretinoin) for acne is occasionally accompanied by hyperlipidemia. It is not known why some persons develop this side effect.. To determine whether isotretinoin triggers a familial susceptibility to hyperlipidemia and the metabolic syndrome.. Cross-sectional comparison.. University hospital in Lausanne, Switzerland.. 102 persons in whom triglyceride levels increased at least 1.0 mmol/L (> or =89 mg/dL) (hyperresponders) and 100 persons in whom triglyceride levels changed 0.1 mmol/L (< or =9 mg/dL) or less (nonresponders) during isotretinoin therapy for acne. Parents of 71 hyperresponders and 60 nonresponders were also evaluated.. Waist-to-hip ratio; fasting glucose, insulin, and lipid levels; and apoE genotype.. Hyperresponders and nonresponders had similar pretreatment body weight and plasma lipid levels. When reevaluated approximately 4 years after completion of isotretinoin therapy, hyperresponders were more likely to have hypertriglyceridemia (triglyceride level > 2.0 mmol/L [>177 mg/dL]; odds ratio [OR], 4.8 [95% CI, 1.6 to 13.8]), hypercholesterolemia (cholesterol level > 6.5 mmol/L [>252 mg/dL]; OR, 9.1 [CI, 1.9 to 43]), truncal obesity (waist-to-hip ratio > 0.90 [OR, 11.0 (CI, 2.0 to 59]), and hyperinsulinemia (insulin-glucose ratio > 7.2; OR, 3.0 [CI, 1.6 to 5.7]). In addition, more hyperresponders had at least one parent with hypertriglyceridemia (OR, 2.6 [CI, 1.2 to 5.7]) or a ratio of total to high-density lipoprotein cholesterol that exceeded 4.0 (OR, 3.5 [CI, 1.5 to 8.0]). Lipid response to isotretinoin was closely associated with the apoE gene.. Persons who develop hypertriglyceridemia during isotretinoin therapy for acne, as well as their parents, are at increased risk for future hyperlipidemia and the metabolic syndrome.

Topics: Acne Vulgaris; Adolescent; Adult; Apolipoproteins E; Body Weight; Cross-Sectional Studies; Dermatologic Agents; Female; Genetic Predisposition to Disease; Genotype; Glucose Tolerance Test; Humans; Hyperlipidemias; Insulin; Isotretinoin; Lipids; Male; Metabolic Syndrome; Middle Aged; Pharmacogenetics; Retrospective Studies; Risk Factors

Topics: Acne Vulgaris; Adolescent; Adult; Apolipoproteins E; Body Weight; Cross-Sectional Studies; Dermatologic Agents; Female; Genetic Predisposition to Disease; Genotype; Glucose Tolerance Test; Humans; Hyperlipidemias; Insulin; Isotretinoin; Lipids; Male; Metabolic Syndrome; Middle Aged; Pharmacogenetics; Retrospective Studies; Risk Factors

A significant rise in plasma triacylglycerols from the control level of 0.89 mmol/l to 1.88 mmol/l (P less than 0.001) was observed in male Sprague-Dawley rats treated for 11 days with isotretinoin (oral dosing; 10 mg/day). This rise was due to an increased level of plasma very low density lipoproteins (VLDL). When VLDL from untreated rats were labeled with 125I-labeled tyramine-cellobiose and injected intravenously into rats treated for 10 days with isotretinoin (n = 6) and in control rats (n = 6), it was found that the disappearance of radioactivity from the blood was dramatically retarded in the treated animals. The disappearance could be divided into two phases, a rapid (alpha) phase dominated the first 5 min and was followed by a slower (beta) phase. The half-life of the beta-phase increased significantly from 53 +/- 7 min in the controls, to 120 +/- 62 min after isotretinoin. VLDL prepared from isotretinoin-treated animals (n = 6) had about the same half-life in control animals (62 +/- 8 min) as had ordinary VLDL. The elimination of tracer from the blood was mainly due to uptake by the liver. The amount of radioactivity in the liver after 30 min of circulation was significantly reduced from 34 +/- 7% of injected dose in controls to 24 +/- 5% in the isotretinoin group (P = 0.013). The uptake in other organs was less than 3% per organ and was essentially unaffected by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Biological Transport, Active; Hyperlipidemias; Isotretinoin; Lipoproteins, VLDL; Liver; Male; Rats; Rats, Inbred Strains; Triglycerides

Treatment with retinoids results in increased serum triglyceride and cholesterol and reduced HDL-cholesterol; dietary supplementation with fish oil lowers serum lipids. Therefore combining retinoids with fish oil may reduce retinoid hyperlipidaemia. Increased triglyceride due to isotretinoin was reduced by 70% (P less than 0.05) and cholesterol by 45% (P less than 0.05) after addition of fish oil; placebo oil had no effect. These decreases were not associated with changes in levels of HDL-cholesterol or reduction of increased levels of apoprotein B. Increased triglyceride due to etretinate was reversed after the addition of fish oil (P less than 0.01), but cholesterol levels did not change. Therefore fish oil inhibits hypertriglyceridaemia due to isotretinoin and etretinate and reduces increased cholesterol levels due to isotretinoin; this effect is likely to be due to altered lipoprotein composition.

Topics: Acne Vulgaris; Adolescent; Adult; Aged; Cholesterol; Etretinate; Female; Fish Oils; Humans; Hyperlipidemias; Isotretinoin; Male; Middle Aged; Psoriasis; Tretinoin; Triglycerides

Topics: Adult; Estrogens, Conjugated (USP); Female; Humans; Hyperlipidemias; Isotretinoin; Pancreatitis; Plasmapheresis; Tretinoin; Triglycerides