Article

Effects of Oral Isotretinoin on Lipids and Liver Enzymes in Acne Patients

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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 and P<.001, respectively), while HDL levels were shown to decrease (P<.001). Statistically significant increases in AST levels also were noted (P=.016). Although ALT levels also increased, the changes were not statistically significant increases in AST levels also were noted (P=.016). Although ALT levels also increased, the changes were not statistically significant (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.

Practice Points

  • ­Isotretinoin is recommended for treatment of severe inflammatory acne and for cases resistant to prior treatment with antibiotics or topical agents; however, it may cause alterations in lipids and liver enzymes.
  • In our study, liver enzymes were less affected than lipids in patients who were treated with isotretinoin.
  • ­Use caution when administering isotretinoin in patients with a history of abnormal findings.


 

References

Acne is a chronic inflammatory condition of the pilosebaceous unit affecting approximately 79% to 95% of adolescents in the Western world.1 Treatment of acne depends on its severity. Topical tretinoin, adapalene, benzoyl peroxide, azelaic acid, and topical antibiotics generally are used in cases of noninflammatory or mild inflammatory disease. Isotretinoin is recommended for treatment of severe inflammatory acne (eg, nodulocystic or conglobata acne) and for cases of acne that have proven to be resistant to prior treatment with antibiotics or topical agents. Dosages of isotretinoin range from 0.5 to 2 mg/kg daily for 16 to 24 weeks.1 Isotretinoin reduces the activity and size of the sebaceous glands, normalizes keratinization of the sebaceous follicles, and decreases the number of Propionibacterium acnes. Isotretinoin also may cause clinical side effects and laboratory changes, the most important being teratogenicity. It also may cause mucocutaneous side effects including cracked lips, dryness of the skin and nasal mucosa, skin redness, eye dryness, and eye irritation.1 It also may cause blepharoconjuctivitis, photosensitivity, asteatotic dermatitis, pruritus, telogen effluvium, secondary bacterial colonization, nail fragility, periungual pyogenic granuloma, paronychia, myalgia, intracranial hypertension, nausea, headache, vomiting, depression, psychosis, suicide, constipation, and allergic reactions.2 Isotretinoin treatment may increase serum levels of liver enzymes, triglyc-erides (TGs), and low-density lipoprotein (LDL) cholesterol, and reduce the level of high-density lipoprotein (HDL) cholesterol.1 This retrospective study sought to evaluate the effect of isotretinoin on liver enzymes and lipids over 6 months.

Materials and Methods

Our retrospective study was conducted at the Hospital of Atatürk University in Erzurum, a city located in eastern Turkey. All patients who were treated in the department of dermatology and had received oral isotretinoin between June 2009 and June 2012 were included in the study. The study was based on an evaluation of the patients’ medical records. All patients received oral isotretinoin 0.5 to 1 mg/kg daily; the majority of patients received 30 to 40 mg daily. Patient medical records included age; gender; white blood cell (WBC) count; red blood cell (RBC) count; hemoglobin count; and aspartate aminotransferase (AST), alanine aminotransferase (ALT), TG, LDL, and HDL levels at the beginning of treatment. Aspartate aminotransferase, ALT, TG, LDL, and HDL levels also were measured at 3- and 6-month follow-up. Analysis of AST, ALT, TG, LDL, and HDL levels was based on the National Cholesterol Education Program guidelines.3 Aspartate aminotransferase and ALT levels were classified as normal (<40 U/L) and high (≥40 U/L). Triglyceride levels were classified as normal (<150 mg/dL), borderline high (150–199 mg/dL), high (200–499 mg/dL), and very high (≥500 mg/dL). Low-density lipoprotein levels were classified as optimal (<100 mg/dL), above optimal (100–129 mg/dL), borderline high (130–159 mg/dL), high (160–189 mg/dL), and very high (≥190 mg/dL). High-density lipoprotein levels were classified as low (<40 mg/dL), normal (40–59 mg/dL), and high (≥60 mg/dL). Normal WBC was defined as 3.5 to 12.5×103/mL. Normal hemoglobin count was defined as 11.5 to 15.0×106/mL for women and 13 to 17×106/mL for men. Normal RBC was defined as 4.0 to 5.2×106/mL for women and 4.5 to 5.9×106/mL for men. Statistical analysis was performed using SPSS version 17.0. Repeated measures analysis of variance was used to compare means between 3 groups (baseline, 3-month, and 6-month values). A paired sample t test was used to compare means between any 2 groups. Results with P<.05 were considered statistically significant.

Results

Treatment with oral isotretinoin was initiated in 349 patients at our institution from June 2009 to June 2012. Twenty-seven of these patients were excluded from the study because their medical records were not available. Medical records from 322 patients were obtained. The study population consisted of 226 (70.2%) women and 96 (29.8%) men. Patients ranged in age from 17 to 64 years, with a mean age of 23.9 years. The mean (standard deviation [SD]) age of the women was 23.9 (5.4) years and the mean (SD) age of the men was 23.8 (7.02) years. Most of the patients were on a regimen of 30 or 40 mg of isotretinoin daily. Differences between dosages and laboratory values were not analyzed because we assumed there would not be a significant difference, as most patients received the same dose. The mean (SD) WBC was 8.4 (3.5)×103/mL. The mean (SD) RBC was 4.9 (0.5)×106/mL. The mean (SD) hemoglobin count was 14.3 (1.7)×106/mL (women, 13.6 [1.5]×106/mL; men, 15.9 [1.1]×106/mL).

The study evaluated the effects of isotretinoin on liver enzymes (AST and ALT) and lipids (TGs, LDL, and HDL). Nearly all of the patients (>95%) had normal AST and ALT levels at baseline. The results are outlined in the Table. Some values were not recorded for all patients at each follow-up.

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