Dr. Ron’s Research Review – September 6, 2016

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This week’s research review focuses on preventing the side effects of Isotretinoin.

Isotretinoin (13-cis-retinoic acid, an isomer of vitamin A) is an medication primarily used to treat severe acne.
Isotretinoin was first marketed as Accutane, but after juries had awarded millions of dollars in damages to former Accutane users over inflammatory bowel disease claims, it was removed from the market and became generic. As of 2017 it is marketed under many brand names worldwide.

Adverse Effects

As a retinoid, isotretinoin has a wide spectrum of side effects, including reproductive, cutaneous, ocular, neurological, musculoskeletal, and hepatic. As long as patients are able to tolerate these side effects, it can be a very effective treatment option. (Brelsford and Beute, 2008)
The most common adverse effects are a transient worsening of acne (lasting 2–3 weeks), dry lips (cheilitis), dry and fragile skin, and an increased susceptibility to sunburn. It is also associated with psychiatric side effects, including depression. Uncommon and rare side effects include muscle aches and pains (myalgias), and headaches. Isotretinoin is known to cause birth defects due to in utero exposure because of the molecule's close resemblance to retinoic acid, a natural vitamin A derivative that controls normal embryonic development.
Overall, isotretinoin is a very well tolerated medication. The most common side effects include mucocutaneous events and myalgias. Long-term side effects are infrequent, occurring in less than 10% of the patient population, and they are usually mild, requiring little to no treatment. (Brelsford and Beute, 2008)

Reducing Side Effects

A study examined a dietary supplement, based on gamma linolenic acid, vitamin E, vitamin C, beta-carotene, coenzyme Q10 and Vitis Vitifera, to reduce side effects, in particular the dry skin, erythema and desquamation, due to treatment with oral isotretinoin, and evaluate the ability of the product to increase adherence to therapy in patients with acne.  Forty-eight patients with nodular acne (32 females and 16 males) were randomly divided into 2 groups: 24 received isotretinoin therapy (20-30 mg/day) for 6 months associated to dietary supplement (twice a day), while the other 24 patients received only isotretinoin (20-30 mg/day) for 6 months. For all patients the degree of acne severity, through GAGS (Global Acne Grading System), the sebum production by Sebutape, the hydration by Corneometer and the erythema by Mexameter, were measured. Patients treated with dietary supplement had lower side effects, with a less degree of erythema and dryness, and greater degree of hydration; a greater adherence to therapy was also reported. (Fabbrocini et al., 2014)

Vitamin E

Two studies found no effect with vitamin E (800 IU/day).
Eighty two patients were randomly assigned to one of two treatment groups with isotretinoin (1 mg/kg/day) alone or combined with vitamin E (800 IU/day) for 16 weeks. Mucocutaneous side-effects such as facial erythema, facial dryness, cheilitis and serum lipid and liver enzyme profiles were assessed.  There was no difference in the incidence and severity of side-effects related to isotretinoin between the two treatment groups. (Kus et al., 2005)
One hundred forty subjects were randomly assigned to one of two treatment programs with isotretinoin (1 mg/kg) together with either vitamin E (800 IU/day) or a vitamin E placebo for 20 weeks. The incidence, severity, and duration of the side effects (eg, dry eyes, dry lips) were assessed. A fixed 800 IU/day dose of vitamin E did not improve the incidence, severity, or duration of side effects associated with isotretinoin (1 mg/kg per day). (Strauss et al., 2000)

 

Dr. Ron


 

Articles

Preventing and managing the side effects of isotretinoin.
            (Brelsford and Beute, 2008) Download
Isotretinoin (13-cis-retinoic acid) is widely used for the treatment of severe acne as well as for disorders of conification, for psoriasis, and for skin cancer prevention. As a member of the retinoid family, it has a wide spectrum of side effects, including reproductive, cutaneous, ocular, neurological, musculoskeletal, and hepatic. As long as patients are able to tolerate these side effects, it can be a very effective treatment option. This article examines both the most common and the most concerning side effects as well as ways in which providers and patients may best manage them to be able to benefit from isotretinoin treatment.

A dietary supplement to reduce side effects of oral isotretinoin therapy in acne patients.
            (Fabbrocini et al., 2014) Download
AIM:  The purpose of the study was to analyze the potential capacity of a dietary supplement, based on gamma linolenic acid, vitamin E, vitamin C, beta-carotene, coenzyme Q10 and Vitis Vitifera, to reduce side effects, in particular the dry skin, erythema and desquamation, due to treatment with oral isotretinoin, and evaluate the ability of the product to increase adherence to therapy in patients with acne. METHODS:  Forty-eight patients with nodular acne (32 females and 16 males) were randomly divided into 2 groups: 24 received isotretinoin therapy (20-30 mg/day) for 6 months associated to dietary supplement (twice a day), while the other 24 patients received only isotretinoin (20-30 mg/day) for 6 months. For all patients the degree of acne severity, through GAGS (Global Acne Grading System), the sebum production by Sebutape, the hydration by Corneometer and the erythema by Mexameter, were measured. We have also evaluated the adherence to treatment, asking to patients how many days a week they follow the therapy. RESULTS:  Patients treated with dietary supplement had lower side effects, with a less degree of erythema and dryness, and greater degree of hydration; a greater adherence to therapy was also reported. CONCLUSION:  Thanks to antioxidant and moisturizing properties, the dietary supplement containing gamma linolenic acid, vitamin E, vitamin C, betacarotene, coenzyme Q10 and Vitis Vitifera, can be considered a useful supplement in the treatment and prevention of dry skin associated with the use of oral isotretinoin.


 

Vitamin E does not reduce the side-effects of isotretinoin in the treatment of acne vulgaris.
            (Kus et al., 2005) Download
BACKGROUND:  Isotretinoin is widely used in the treatment of severe, recalcitrant, nodular acne. Mucocutaneous side-effects are seen in the great majority of patients and some of them have elevations in their serum lipid and liver enzyme profiles. Recently, it has been shown that addition of vitamin E decreased the toxicity of high-dose retinoids. OBJECTIVE:  The purpose of this investigator-blinded, randomized study was to assess whether vitamin E would reduce the side-effects of isotretinoin in the treatment of acne vulgaris. METHODS:  Eighty two patients were randomly assigned to one of two treatment groups with isotretinoin (1 mg/kg/day) alone or combined with vitamin E (800 IU/day). The treatment duration was 16 weeks. Mucocutaneous side-effects such as facial erythema, facial dryness, cheilitis and serum lipid and liver enzyme profiles were assessed. RESULTS:  There was no difference in the incidence and severity of side-effects related to isotretinoin between the two treatment groups. CONCLUSION:  Eight hundred IU/day vitamin E did not improve the side-effects of 1 mg/kg/day of isotretinoin in the treatment of acne vulgaris.

Concomitant administration of vitamin E does not change the side effects of isotretinoin as used in acne vulgaris: a randomized trial.
            (Strauss et al., 2000) Download
BACKGROUND:  Isotretinoin treatment is frequently associated with reversible, dose-related side effects. Recent studies claimed that combining vitamin E with high-dose isotretinoin ameliorated isotretinoin-induced side effects. OBJECTIVE:  The purpose of this double-blind, randomized study was to determine the effects of a fixed dose of vitamin E on the side effects of isotretinoin for treatment-resistant acne vulgaris. METHODS:  One hundred forty subjects were randomly assigned to one of two treatment programs with isotretinoin (1 mg/kg) together with either vitamin E (800 IU/day) or a vitamin E placebo for 20 weeks. The incidence, severity, and duration of the side effects (eg, dry eyes, dry lips) were assessed. RESULTS:  A fixed 800 IU/day dose of vitamin E did not improve the incidence, severity, or duration of side effects associated with isotretinoin (1 mg/kg per day). CONCLUSION:  Vitamin E did not significantly ameliorate retinoid side effects when combined with 1 mg/kg of isotretinoin in the treatment of acne.


 

References

Brelsford, M and TC Beute (2008), ‘Preventing and managing the side effects of isotretinoin.’, Semin Cutan Med Surg, 27 (3), 197-206. PubMed: 18786498
Fabbrocini, G, et al. (2014), ‘A dietary supplement to reduce side effects of oral isotretinoin therapy in acne patients.’, G Ital Dermatol Venereol, 149 (4), 441-45. PubMed: 25068233
Kus, S, et al. (2005), ‘Vitamin E does not reduce the side-effects of isotretinoin in the treatment of acne vulgaris.’, Int J Dermatol, 44 (3), 248-51. PubMed: 15807739
Strauss, JS, et al. (2000), ‘Concomitant administration of vitamin E does not change the side effects of isotretinoin as used in acne vulgaris: a randomized trial.’, J Am Acad Dermatol, 43 (5 Pt 1), 777-84. PubMed: 11050580