Acne vulgaris is one of the most frequently seen skin conditions by GPs in adolescents and young adults. It is a risk factor for depression, anxiety, suicidal ideation, and social isolation. Oral isotretinoin is highly effective, and in many cases a permanent treatment for severe acne. It is recommended as a first line treatment. At present, few GPs in Ireland initiate isotretinoin treatment.
Isotretinoin is a vitamin A derivative inducing oil glands to die via apoptosis, initially licensed in 1982. Duration of treatment is typically for four to six months. Side effects include dry skin and lips, rise in transaminase concentrations, teratogenic effects and rarely, severe mood disturbance. With patient education, monitoring and planned care, side effects can largely be prevented or mitigated.1
Comparing rare incidence of severe mood disturbance from isotretinoin with far commoner and sometimes serious social, psychological and psychiatric complications prevalent in younger people with acne, easier access to oral isotretinoin in the community, preferably without cost barriers, is desirable.
In considering this, GPs have an opportunity to connect with younger patients by addressing health concerns that are pertinent to them, including acne vulgaris. Suboptimal treatment of acne is a contributor to poor health outcomes and a strain on the healthcare system, as a result of ongoing downstream costs and complications of acne, including mental health impacts and scarring.
We present a case of a 24-year-old female from general practice, with a preceding 12-year history of sub-optimal treatment for cystic acne.
Clinical presentations of case study
A 24-year-old woman presented to her GP with a 12-year history of cystic acne on chin, neck and cheeks. She had previously used treatments including oral antibiotics (doxycycline and erythromycin), topical benzoyl peroxide with clindamycin, and hormonal treatment (Dianette), with no long-term success, disease persistence, and treatment side effects.
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Assessment was performed using telemedicine. The patient initially scored 27 out of 30 on the Dermatology Life Quality Index (DLQI) questionnaire.2 Prior to initiating treatment she was given written information about isotretinoin, including use, side effects, concomitant contraceptive use, and an agreed schedule of check-ups at intervals. Baseline bloods were taken, and she was commenced on 1/mg/kg/day of oral isotretinoin.
DLQI reduced to 8/30 as cystic acne subsided, with sustained improvement. The patient reported a higher quality of life, with minimal and tolerable side effects (dry lips and skin).
Focused literature review
Focused literature review was conducted using EMBASE and Medline, utilising terms ‘isotretinoin AND primary care AND acne vulgaris,’ for studies from the previous 10 years. On reviewing titles and abstracts (eight articles from Medline and 24 from EMBASE), a total of 13 articles (four from Medline and nine from EMBASE) were included.
Primary outcome measures of the review were to determine safety and feasibility of prescribing isotretinoin in general practice.
Three barriers to prescribing isotretinoin in the GP setting were identified: education, adverse side effects, and willingness to monitor.
A majority of GPs (61%) were concerned about medico-legal risk, while 55% of GPs were unaware they were able to prescribe isotretinoin to their patients.
From a medico-legal perspective, there are well known side effects, most commonly dry lips and skin. Impaired liver functions or hyperlipidemia can occur, resolving over time, sometimes even during the period of therapy. These do highlight the importance of monitoring liver function tests to prevent lasting damage. Severe mood disturbance rarely occurs, including depression. Isotretinoin causes teratogenic effects in 25-35% of embryos exposed, interfering with development of neural crest tissues, causing permanent craniofacial, cardiovascular, and central neurological malformations.
According to the European Union directive3 the following are required: liver functions, full blood count, fasting lipids, and pregnancy test. This testing should be conducted prior to the start of treatment to establish baselines, and then at one, three, and six months during treatment. A monthly negative pregnancy test is needed for females, in order to safely refill the prescription. In addition, mood and mental health evaluations should be conducted at interval, checking for depression and suicidality. Shared documentation of the management plan, and informed written consent to include these elements is advisable for safe prescribing by the GP; the plan stipulating from the outset when reviews are scheduled, and who conducts them with the patient.
There is a role for general practice in prescribing isotretinoin, and overcoming the three main barriers identified here, thereby enabling more people to access what is clearly a life-changing treatment for many.
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Delays in accessing public dermatology outpatients typically take up to 6-18 months, exacerbating inequality in provision of essential healthcare. Further, given the shift of care from secondary to primary care, shifting isotretinoin prescribing from hospitals and OPDs into GP-led care is in keeping with Slaintecare, and also with the important principle of treating the right patient, in the right way, in the right place (ie. the community), and at the right time. Taking this work on in general practice is likely to be helpful in increasing the time available to specialists in dermatology for even more serious time-sensitive conditions. Finally, care provided in the GP setting is likely to be less expensive than that provided in hospital/OPD setting.
Online education module
To address gaps in knowledge about isotretinoin in primary care, a brief and focused online module, educating GPs, practice nurses and community pharmacists on administration, use and monitoring of isotretinoin would be useful, ensuring awareness and safety of this drug is optimised by GP prescribers. Given that dermatology is a well-established special interest within general practice, expert knowledge of GPs with a special interest in dermatology could be utilised as content experts in delivering such a module.
Medico-legal and safety concerns due to side effects are a deterrent for GPs. However, GPs and many practice nurses are already skilled in both mental health and contraception management, the two key areas of expertise to consider when administering isotretinoin.
Isotretinoin and depression
The relationship between isotretinoin and depression has been thoroughly investigated. A meta-analysis of 31 controlled studies found no evidence of increased depression or suicide rates during isotretinoin treatment.4 It is salutary to note that in the subgroup of patients most likely to benefit from isotretinoin (adolescents and young adults), there is already an important and pre-existing incidence of significant depression and anxiety.
Withholding appropriate access to isotretinoin is likely to worsen this for an important proportion of these patients, given that severe cystic acne is a well-documented cause of social isolation, and at times intense levels of distress, at a time of life when many individuals experience vulnerability and are struggling with adjustment reaction in establishing themselves as fully functioning adults.
While studies indicate there is no causal relationship between isotretinoin and depression, it is important to evaluate the patient’s mood and overall well being. GPs have long term relationships with patients, which are beneficial when evaluating a patient’s mental health.
To prevent teratogenic effects, a negative pregnancy test is required at outset, and monthly for women of childbearing age, as well as clear guidance and implementation of effective contraception. It is advisable to consider informed written consent, up to and including anticipatory advice for early medical termination of pregnancy in the event of unplanned pregnancy. Following preparation for and initiation of a prescription, at least some of the reviews can be provided by the practice nurse, depending on practice circumstances. There is no known risk of teratogenic effects from males using isotretinoin.5
Cost is a barrier for a large proportion of patients, and for general practices, for payment for time, in planning and in delivering care.
Our patient, suffering from acne vulgaris, tried numerous forms of treatment for several years, with no long term relief of suffering. Upon starting isotretinoin in the general practice, the patient quickly experienced significant and lasting improvement, with enhanced confidence and quality of life.
Our case report highlights the importance of isotretinoin and its life-changing effects, provided in the general practice setting.
This case report was originally presented at the ROI Faculty RCGP 2021 All- Island Clinical Case Presentation Competition.
Landis MN. Optimizing isotretinoin treatment of acne: update on current recommendations for monitoring, dosing, safety, adverse effects, compliance, and outcomes. American journal of clinical dermatology. 2020 Jun;21(3):411-9
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994 May;19(3):210-6. doi: 10.1111/j.1365-2230.1994.tb01167.x. PMID: 8033378
EU directive https://www.ema.europa.eu/en/documents/referral/isotretinoin-article-29-referral-annex-i-ii-iii_en.pdf
Huang YC, Cheng YC. Isotretinoin treatment for acne and risk of depression: A systematic review and meta-analysis. Journal of the American Academy of Dermatology. 2017 Jun 1;76(6):1068-76
Draghici CC et al. Teratogenic effect of isotretinoin in both fertile females and males (review). Exp Ther Med 2021 May; 21(5): 534. www.ncbi.nlm.nih.gov/pmc/articles/PMC8014951/