Accutane (Isotretinoin) Hair and Skin Changes: What Patients and Clinicians Need to Know

What isotretinoin does to oil glands

Isotretinoin is a retinoid that inhibits sebaceous gland function and keratinization, and the exact mechanism of action is unknown [1]. Clinical improvement in nodular acne occurs together with a fall in sebum secretion. That fall is temporary and reflects a reduction in sebaceous gland size and an inhibition of sebaceous gland differentiation, and the older-format label ties it to dose and duration of treatment [2].

The Accutane label notes that many reactions to isotretinoin resemble those of very high doses of vitamin A: dryness of the skin and mucous membranes, including the lips, nasal passage and eyes [2].

Dry lips, dry skin and the rest of the skin list

A retrospective review of 3,525 patients treated with oral isotretinoin in Poland and Romania between 2012 and 2016 reported that dry lips affected 100% of users, followed by xerosis at 94.97% and facial erythema at 66.21% [3].

The Absorica/Absorica LD label lists dry lips, dry skin, chapped lips, cheilitis, dermatitis and dry eye among the most common adverse reactions, defined as occurring in 5% or more of patients [1]. Cheilitis is the skin reaction the label specifically calls dose related, along with hypertriglyceridemia [1].

The longer adverse-reaction list includes peeling of palms and soles, eczema, contact dermatitis, skin fragility, pyogenic granuloma, seborrhea, hyperpigmentation, hypopigmentation, nail dystrophy, paronychia and abnormal wound healing, described as delayed healing or exuberant granulation tissue with crusting [1]. Separately, the label warns about serious skin reactions: prescribers are told to monitor for Stevens-Johnson syndrome, toxic epidermal necrolysis and other serious skin reactions and to discontinue treatment if they occur [1].

Sunlight and photosensitivity

The older-format Accutane label says patients should be advised to avoid prolonged exposure to UV rays or sunlight [2]. The Medication Guide says: avoid sunlight and ultraviolet lights as much as possible, noting that tanning machines use ultraviolet lights and that isotretinoin may make your skin more sensitive to light [1][2]. The adverse-reaction lists include photoallergic and photosensitizing reactions and increased sunburn susceptibility [1].

Hair loss: alopecia and hair abnormalities

Alopecia is a listed reaction, and the label says it persisted in some cases. Hair abnormalities and hirsutism are also listed [1]. The abstract of the 3,525-patient review does not report a hair-loss rate [3].

Seborrhea

Seborrhea appears in the label's skin reaction list alongside facial erythema and eczema, as part of the rash group [1]. It is listed as a reported reaction, not as an improvement.

Eyes, nose and contact lenses

Dry eye is one of the most common reactions, at 5% or more, and epistaxis and nasal dryness appear in the same labeling [1]. The older-format label also cautions that patients may have decreased tolerance to contact lenses during and after therapy [2].

A review of 1,741 case reports of ocular effects, together with manufacturer data and the published literature, classified abnormal meibomian gland secretion, meibomian gland atrophy, ocular sicca, decreased tolerance to contact lenses and photophobia as certainly associated with isotretinoin use [5].

Waxing, lasers, dermabrasion and wound healing

The labels say to avoid wax epilation and skin resurfacing procedures such as dermabrasion and laser during treatment and for at least 6 months afterward because of the risk of scarring [1][2]. Abnormal wound healing is itself a listed adverse reaction [1].

A 2017 systematic review and consensus statement complicates the blanket waiting period. Reviewing 32 publications that reported 1,485 procedures, the panel found insufficient evidence to support delaying manual dermabrasion, superficial chemical peels, cutaneous surgery, laser hair removal, and fractional ablative and nonablative laser procedures in patients currently taking or recently finished with isotretinoin. It did conclude that mechanical dermabrasion and fully ablative laser are not recommended during systemic isotretinoin treatment [6]. The label's instruction is broader than that review's conclusions [1][6].

Dose and how much the skin effects change with it

Absorica is dosed at 0.5 to 1 mg/kg/day in two divided doses for 15 to 20 weeks, with up to 2 mg/kg/day for adults with very severe disease, and once-daily dosing is not recommended [1]. Cheilitis is dose related according to the label [1].

The classic dose-response trial complicates the assumption that a lower dose means fewer skin problems. In a double-blind study of 150 patients with treatment-resistant nodulocystic acne, three equal groups received 0.1, 0.5 or 1 mg/kg/day. All three doses produced a highly significant clinical response with no significant difference in response between them, but 42% of the 0.1 mg/kg/day group needed retreatment. The authors reported only minor differences in clinical side effects and laboratory abnormalities across doses, and concluded that higher doses were indicated [7].

Neither the Absorica label nor the older-format isotretinoin label states a cumulative mg/kg target [1][2]. The 120 mg/kg figure comes from the medical literature, where it is described as the standard cumulative dose [8]. A single-centre, randomized single-blind trial compared 120 and 150 mg/kg cumulative dosing in moderate-to-severe cystic acne and found no significant difference in lesion counts or severity (p > 0.20). Twelve-month relapse was 26.7% in the 120 mg/kg group and 32.3% in the 150 mg/kg group (p = 0.619), and adverse events were mild and comparable [8].

After the course

The older-format Accutane label states that a single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients, without giving a remission rate [2]. If a second course is needed, the Absorica label does not recommend starting it before a 2-month waiting period, because acne may continue to improve after a course ends [1].

The older-format Accutane label notes that most adverse reactions reported in clinical trials were reversible when therapy was discontinued, though some persisted after cessation [2].