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Print version ISSN 0365-0596
An. Bras. Dermatol. vol.86 no.4 Rio de Janeiro July/Aug. 2011
Juliano Vilaverde SchmittI; Mariana TavaresII; Felipe Bochnia CerciIII
IDermatologist, Curitiba Evangelical Teaching Hospital, Curitiba, Parana, Brazil
IIPhysician currently undergoing training at the Pro-Hansen Foundation (FPH), Curitiba, Parana, Brazil
IIIResident Physician at the Pro-Hansen Foundation (FPH), Curitiba, Parana, Brazil
There are restrictions associated with the use of isotretinoin because of its effects on the lipid profile. The records of ninety patients treated with this medication were reviewed to identify factors that would predispose patients to these abnormalities. A significant increase in cholesterol and triglyceride levels occurred. Patients in whom triglyceride levels increased were more likely to be female, although this difference was not present at baseline. Women with persistent acne may constitute a risk population for these side effects.
Keywords: Acne vulgaris; Hyperlipidemias; Isotretinoin; Retinoids; Women
Acne is one of the principal complaints in dermatology clinics and although it is self-limiting in the majority of cases, the condition has a significant psychosocial effect on the patient and may leave permanent unsightly scars. 1 Oral isotretinoin is known to be the only medication able to inhibit this pathology; however, its use involves restrictions principally related to its effects on the liver, changes in the lipid profile and its teratogenicity. 2, 3 In routine clinical practice, although discontinuation of the medication due to an increase in triglycerides (TG) is rarely necessary, elevated TG levels constitute a concern, leading to a reduction in the doses used until laboratory tests return to normal. With this in mind, a brief review was made of the medical charts of patients treated in this institution with the objective of identifying factors indicative of a predisposition to alterations in serum lipids with the use of oral isotretinoin.
Data from the medical records of patients to whom oral isotretinoin had been prescribed for the treatment of acne between 2005 and 2009 at the Pro-Hansen Foundation in Curitiba, Parana, Brazil were retrospectively reviewed. Data evaluated consisted of: age at the beginning of use of the drug, duration of the condition of acne, gender, weight, dose used at the time serum lipid tests were conducted, the presence of other pathologies, the use of other medication, the clinical grade of acne at the time oral isotretinoin was prescribed, serum total cholesterol (TC) and TG levels prior to use of the medication and the highest levels registered on the medical charts for the respective lipids for up to nine months after initiation of the medication. TG levels > 150 mg/dl and TC levels > 200 mg/dl were considered abnormal. Fisher's exact test, the chi-square test, Student's t-test and the Mann-Whitney-Wilcoxon test were used in the bivariate analyses depending on the sample size and the non-normality of distribution according to the Lilliefors test (p<0.05). Analysis of covariance (ANCO-VA) was performed, with the highest TG levels registered during treatment as the dependent variable and considering only those patients for whom no data were missing for any of the variables included in the model: gender, age, daily dose of oral isotretinoin according to weight and previous TG levels.
A total of 90 treatments were included, with 5 cases of retreatment (6%). The median age of patients was 19 years, the majority were male (66%) and the median duration of the disease was 4 years. The median dose of the medication per weight was 0.60 mg/kg/day and was significantly higher for the women compared to the men. The most common clinical grade was grade III, with grade IV being more common in the men, while grade II was more common in the women. Likewise, the women tended to be older at the beginning of treatment (Table 1).
TC and TG levels changed significantly from baseline levels during use of the medication. Mean TC levels increased from 152 ± 32 mg/dl prior to treatment to 174 ± 39 mg/dl following the initiation of treatment (mean ± standard deviation), p<0.01; Student's t-test. Median TG levels increased from 72 mg/dl to 102 mg/dl (interquartile difference: 42 and 92, respectively), p<0.01; Mann-Whitney-Wilcoxon test. Of the patients with normal TG levels at baseline, changes occurred in 28% of cases. Of the patients with normal TC levels at baseline, 13% went on to present alterations.
Patients who developed alterations in TG and TC levels during treatment were more likely to be female; however, this difference was not present prior to the use of oral isotretinoin. The difference between genders with respect to the rate of altered TG levels during treatment remained when analysis was restricted to patients over 17 years of age; however, there was no statistically significant difference in the subgroup of patients under 17 years of age (Table 1). In the multivariate analysis by ANCOVA, a positive correlation was found between the maximum TG levels recorded during treatment and baseline values (p<0.01) and being female (coefficient = 32.37; p = 0.04). The latter association appeared to gain strength when analysis was restricted to patients over 17 years of age (coefficient = 49.51; p = 0.02).
These data are in agreement with previous observations on the effects of oral isotretinoin on serum lipids, indicating that baseline levels are the increases are higher in women with acne. The women in this sample developed the condition later, possibly representing cases of female adult acne in part of these cases. Women with persistent acne may constitute a population that is more susceptible to these effects of oral isotretinoin. Retinoid X receptors (RXR) are known to play a role in the control of cell metabolism and have already been implicated in the metabolic syndrome and in triggering polycystic ovary syndrome. 5, 6 Rodondi et al. identified a propensity to develop the metabolic syndrome in patients who had a pronounced elevation in TG levels during use of oral isotretinoin, suggesting the participation of genetic factors.7 These correlations may help explain the apparent propensity of women to develop high TG levels, as found in the present study, particularly in adult women with persistent acne. Possible inconsistencies in data that are inherent to retrospective studies may have affected the present findings. Furthermore, this study was unable to evaluate the role of hormonal contraceptives, often used together with oral isotretinoin, in the abnormal laboratory findings. Nevertheless, further studies with more robust design should be conducted to investigate the observations presented in this report.
1. Schmitt JV, Masuda PY, Miot HA. Padrões clínicos de acne em mulheres de diferentes faixas etárias. An Bras Dermatol. 2009;84:349-54. [ Links ]
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7. Rodondi N, Darioli R, Ramelet AA, Hohl D, Lenain V, Perdrix J, et al. High risk for hyperlipidemia and the metabolic syndrome after an episode of hypertriglyceridemia during 13-cis retinoic acid therapy for acne: a pharmacogenetic study. Ann Intern Med. 2002;136:582-9. [ Links ]
Mailing address: Received on 08.01.2010. * Study carried out at the Pro-Hansen Foundation (FPH), Curitiba, Parana, Brazil.
Juliano Vilaverde Schmitt
Rua Estados Unidos, 1.454 -Ap. 1.202 -Bacacheri
82510-050 Curitiba -PR, Brazil
Approved by the Advisory Board and accepted for publication on 17.06.2010.
Conflict of interest: None
Financial funding: None
Received on 08.01.2010.
* Study carried out at the Pro-Hansen Foundation (FPH), Curitiba, Parana, Brazil.