A retrospective chart review was performed on the laboratory results of 246 patients who were treated with isotretinoin for acne over a 9-year period.1 The study suggested that alanine transaminase (ALT) and aspartate transaminase (AST) are not useful for monitoring isotretinoin therapy and that gamma glutamyltransferase (GGT) and creatine kinase (CK) may be of greater value in managing patients. Moreover, elevated CK results are likely a finding of muscle CK and not necessarily that of a hepatic source implying that these values were not providing information on liver functioning. Instead, GGT is a liver specific enzyme and GGT testing level is more representative of liver function than others and should be utilized to monitor hepatic function.
After an informal review of more than 100 cases of patients on isotretinoin (0.5 mg/kg/day – 1.0 mg/kg/day),2 52 patients, all males known to be on varsity teams, had elevated levels of CK at baseline (mean 490 U/L, normal levels <200 U/L). Over a 7-month period, 45 out of 52 patients had consistently elevated CK levels on every test with a mean of 525 U/L. These findings suggest that a CK of 200 U/L is likely not “normal” for athletic teenage boys. Note that these results only related to males and CK abnormalities were not found in females on isotretinoin. Therefore, baseline CK values should be obtained in athletic patients, particularly males. Additionally, the timing of the test is important as CK usually peaks 24-96 hours after activity and normalizes over 4-10 days of rest. If patients have elevated CK levels, it is important to advise them to increase their water intake and limit the amount of exercise.
Scar formation may occur with any degree of acne but is more commonly associated with moderate to severe and very severe form. Although, scar formation is somewhat individual and sometimes unpredictable for every patient with vast range of severity in scarring. The likelihood of acne scarring has also shown to increase when there is a delay in treatment.3 There is a limited amount of time to delay the formation of scars, usually 1-2 years, thus, it is important to provide treatment as soon as possible in these patients. Topical treatments should be initiated with progression toward oral therapy, and finally isotretinoin to be considered on as needed basis for effectiveness.
In a split face study of adapalene (A) 0.3%/benzoyl peroxide (BPO) 2.5% vs vehicle over 24 weeks, patients on A/BPO had 4 fewer total atrophic acne scars on the treated side compared to placebo at week 24 (P<0.0001).4In addition, the placebo arm continued to develop scars while those in the treated arms saw resolution of scars, signaling a remediation in the skin. At the close of the study, the difference in the mean percent change in scars was 29.9% in the A/BPO treated group compared to placebo.
There is increasing evidence that acne pathophysiology may include a skin barrier defect which may lead to alterations in P. acnes and the healthy microbiome. In addition, traditional acne medications are often drying in nature, which may lead to decreased medication use. When reviewing transepidermal water loss (TEWL) and ceramide levels in patients with moderate/mild acne against healthy skin, patients with healthy skin had less TEWL than their acne counterparts and also had higher levels of total ceramides in the stratum corneum (P<0.01).5 These results suggest that an impaired skin barrier function and transepidermal water loss caused by decreased amounts of ceramides may be responsible for comedo formation, since barrier dysfunction is accompanied by hyperkeratosis of the follicular epithelium.
Seasonal changes appear to have some form of correlation as well. In the winter months, patients appeared to have lower ceramide levels and increased TEWL compared to healthy skin.6 Interestingly, this difference partly resolved in the summer months with increased levels of ceramide in the epidermis.
Changes in the facial skin of children (6-13) was also studied.5 Findings demonstrated that skin barrier damage, as measured by TEWL, increased significantly with age. Girls demonstrated skin barrier damage sooner, than males. However, the boys had a larger magnitude of skin barrier damage by the age of 13. This same pattern was observed with free fatty acids increasing with increasing age, as well as with sebaceous lipid profiles. Levels of both aerobic and anaerobic bacterial also increased with age for both males and females. The actual microbiome of healthy vs acne prone skin was also significantly different lending to the theory that the microbiome does play a role in acne.
The effects of acne medications on the stratum corneum also induce alteration of the microbiome.7
Many patients have been shown to have some of the following effects, dependent on the type of medication:
Present disclosure: The presenter has reported that there are no conflicts of interest for this presentation.
Written by: Debbie Anderson, PhD
Reviewed by: Victor Desmond Mandel, MD