Re-evaluating the necessity of routine laboratory monitoring during isotretinoin therapy for acne

Abstract

In this letter, we discuss the topic of necessity of routine laboratory monitoring during isotretinoin treatment for acne. According to Park and colleagues, it is advisable to monitor the levels of triglycerides, alanine aminotransferase, and aspartate aminotransferase every 5 to 6 months. Additionally, the levels of total cholesterol and low-density lipoprotein should be checked within the first two months of treatment. Isotretinoin is a commonly prescribed agent mainly used to treat acne. Despite its high effectiveness, it necessitates regular monitoring of laboratory parameters due to its side effect profile. Currently, there remains a lack of consensus on the appropriate frequency for monitoring these parameters during treatment with isotretinoin. This letter will provide insight into this complex and controversial topic. Based on existing literature, we concluded that the incidence of changes in lipid and liver aminotransferase levels during isotretinoin treatment for acne was low and likely clinically insignificant. For generally healthy people, we recommend testing lipid and liver profiles once at baseline and a second time at the peak dosage. However, frequent testing might still be beneficial in certain populations of patients.

Key Words: Acne, Isotretinoin, Laboratory monitoring, Liver function, Blood lipids

Core Tip: In this letter we comment on the article Park et al. Currently, there is a lack of consensus of the frequency of follow-up of laboratory parameters during isotretinoin treatment. This letter will provide insight into this complex and controversial topic.

TO THE EDITOR

In this letter, we discuss the necessity of routine laboratory monitoring during isotretinoin treatment for acne. According to Park and colleagues[1], it is advisable to monitor the levels of triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) every 5 to 6 months. Additionally, the levels of low-density lipoprotein (LDL) and total cholesterol (TC) should be checked within the first two months of treatment.

Acne vulgaris is a chronic inflammatory condition affecting the pilosebaceous unit[2]. The pathogenesis of acne involves four key factors: Increased sebum production, colonization by Propionibacterium acnes, altered keratinization processes, and inflammatory mediators around the pilosebaceous unit[3]. Recent lipidomic analyses have shed new light on the contribution of disrupted lipid metabolism to acne development[4]. Isotretinoin is a commonly prescribed agent for acne treatment; it is known for its high efficacy but is also associated with side effects such as changes in serum lipids and liver function, necessitating regular laboratory monitoring[5,6].

Currently, there remains a lack of consensus on the appropriate frequency for monitoring these parameters during treatment with isotretinoin. The European guidelines published in 2016 recommend monitoring laboratory parameters, primarily lipids and liver enzymes, before initiating treatment, after 1 month, and then every 3 months[7]. The guidelines from the American Academy of Dermatology in 2024 suggest that monitoring liver function tests and blood lipids should be considered, but the specific frequency of testing is not mentioned[8]. However, a recent study proposed that routine laboratory monitoring for healthy young individuals receiving oral isotretinoin may be unnecessary[9].

RECENT RESEARCHES OF LABORATORY MONITORING DURING TREATMENT WITH ISOTRETINOIN

This letter drew on five recent researches including three retrospective studies, one systematic review, and a Delphi study.

In the first retrospective analysis, Özaslan et al[10] examined changes in laboratory parameters for acne patients treated with isotretinoin. Their investigation revealed the most prevalent abnormality was hypercholesterolemia (LDL-C ≥ 130 mg/dL), affecting 44.1% of patients at the end of the second month and 40.0% at the end of the fourth month. Furthermore, there was a continuous increase in patients with TG abnormalities during the second (23.9%) and fourth (27.2%) months. Additionally, fewer than 2% of patients experienced Grade 3 or higher elevations in AST, ALT, and gamma-glutamyl transferase (GGT) levels during treatment. This study recommended regular monitoring of TG and LDL-C levels, particularly for patients with a high cumulative dosages of isotretinoin.

In the second retrospective study that included 407 patients with acne, Alajaji et al[11] reported that 12.7% of these patients had elevated TG levels at their final visit, whereas 6.5% of patients had elevated TG levels at baseline, which was statistically significant (P < 0.001). 9% of these patients had elevated TC levels at the final visit compared to 10.5% at the baseline. However, the overall frequency of these laboratory abnormalities is minimal and not linked to substantial morbidity. Additionally, the study indicated a link between higher body weight and a greater prevalence of elevated ALT and TG levels, suggesting that such individuals might benefit from more frequent monitoring.

In the third retrospective analysis involving 1015 patients with acne vulgaris received systemic isotretinoin therapy, laboratory investigations revealed elevated TG in 21.8% of patients, ALT in 12.5% of patients, and AST in 11.2% of patients. TG or transaminase elevations resolved after completing the isotretinoin treatment. This study indicated that transient changes in lipid and liver aminotransferase levels are likely clinically insignificant. They recommended monitoring lipid and liver profiles at specific intervals: Initially at baseline, then at 2 to 3 months, after reaching the peak dosage, and once the treatment course is completed[12].

A systematic review conducted by Affleck et al[9] involved four individual systematic searches of the MEDLINE database, via PubMed, from origin to 2 May 2021. In general, adverse events were reported to be very rare (less than 1 in 10000 patients) and were either not preventable by monitoring, or idiosyncratic, or detected in predisposed individuals. The authors suggest that in healthy young people laboratory monitoring for oral isotretinoin is unnecessary. Nevertheless, it is advisable to check baseline TG levels in those who have risk factors for elevated TG, such as family and personal history, signs of insulin resistance, or truncal obesity.

A fundamental group of laboratory assessments recommended for monitoring prior to and throughout isotretinoin therapy was identified by a Delphi study published in 2022. Consensus was achieved as follows: Monitor TG within a month before starting treatment (89.5%) and at peak dosage (78.9%) but not after completing treatment (73.7%) or monthly (84.2%) ; monitor ALT within a month before starting treatment (89.5%) and at peak dosage (89.5%) but not after completing treatment (73.7%) or monthly (76.2%) ; and do not monitor bilirubin (81.0%), GGT (78.9%), high-density lipoprotein (73.7%), LDL (73.7%), albumin (72.7%), or total protein(72.7%)[13].

DISCUSSION: CRITICAL ANALYSIS

The limitations of the initial three studies include their retrospective design and their dependency on electronic medical records for data collection. The systematic review relied on published adverse event data and only identified a limited number of the cases that occurred. For the Delphi study, it was impossible to facilitate live discussions between rounds to aid in reaching consensus. Furthermore, the study was founded on the insights of a limited number of participants, whose views may not represent the perspectives of all clinicians and practice settings.

RECOMMENDATIONS

We recommend that in healthy young people, lipid and liver profiles should be monitored at baseline and after the peak dosage is reached. Frequent testing may still be beneficial for certain populations of patients, such as those with higher body weights, family and personal histories, signs of insulin resistance, and those requiring a high total cumulative dosage of isotretinoin.

CONCLUSION

The incidence of changes in lipid and liver aminotransferase levels during isotretinoin treatment for acne was low and likely clinically insignificant. For generally healthy people, we recommend testing lipid and liver profiles once at baseline and a second time at the peak dosage. However, this recommendation still needs verification by more targeted studies.