Tretinoin

Tretinoin is the acid form of vitamin A and so also known as all-trans retinoic acid or ATRA. It is a drug commonly used to treat acne vulgaris and keratosis pilaris. It is available as a cream or gel (brand name Retin-A). It is also used to treat acute promyelocytic leukemia (APML).

Dermatology
Tretinoin is most commonly used as a form of acne treatment. It was the first retinoid developed for this type of topical use. Tretinoin is the best studied retinoid in the treatment of photoaging. It is used by some as a hair loss treatment and also a component of many commercial products that are advertised as being able to slow skin aging or remove wrinkles. Topical tretinoin is also used to treat and reduce the appearance of stretch marks by increasing collagen production in the dermis.

Leukemia
In addition, tretinoin (marketed as Vesanoid) is also used to treat at least one form of cancer (acute promyelocytic leukemia (APML), also called acute myeloid leukemia subtype M3), usually together with other drugs, by causing the immature blood cells to differentiate (i.e. mature) and die. The pathology of the leukemia is due to the highly proliferative immature cells; retinoic acid drives these cells to develop into functional cells, which helps to alleviate the disease. It is usually prescribed over 3 months at about 8 capsules per day.

Clinical pharmacology
Although the exact mode of action of tretinoin is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of follicular epithelial cells with decreased blackhead formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the blackheads (comedones).

Its success in treating acute promyelocytic leukemia was a major breakthrough in the treatment of this type of leukemia. It works in APML because the majority of cases involve a chromosomal translocation of chromosomes 15 and 17, which causes genetic fusion of the retinoic acid receptor (RAR) gene to the promyelocytic leukemia (PML) gene. This fusion PML-RAR protein is responsible for preventing immature myeloid cells from differentiating into more mature cells. This block in differentiation is thought to cause leukemia. ATRA acts on PML-RAR to lift this block, causing the immature promyelocytes to differentiate to normal mature blood cells.

In dermatological use
When used, dryness of the affected skin may occur. More sensitive patients may also experience redness, scaling, itching, and burning. A gradual increase in the frequency and amount of tretinoin application is best, as this allows one's skin to adequately adjust to the drug. Patients should be careful to follow their physician's recommendations when beginning a round of treatment.

This product increases the risk of extreme sunburn; care should be taken (shade, sunscreen, etc.) to protect treated skin from overexposure to ultraviolet light.

Because usage of tretinoin may cause thinning of the skin, it is strongly recommended that patients who are using the drug abstain from hair removal waxing. The wax will, when removed, pull off the top level of epithelium (skin) with it, leaving a red, inflamed, sore, and unattractive mark for several days. Tweezing or threading (epilation) is a viable option for hair removal while using tretinoin. The recommended timeframe to wait for a waxing treatment after using tretinoin varies from source to source; anywhere from 5 days to 3 months have been reported. Patients should consult with their aesthetician and dermatologist to discuss the best hair removal options during or after tretinoin use.

In leukemia use
There is a unique complication of retinoic acid syndrome in patients with acute promyelocytic leukemia. This is associated with the development of dyspnea, fever, weight gain, peripheral edema and is treated with dexamethasone. The etiology of retinoic acid syndrome has been attributed to capillary leak syndrome from cytokine release from the differentiating promyelocytes.

Teratogenicity
It is a teratogen, and therefore can cause birth defects and tests have shown increases in foetal skull abnormalities in rats. Women who are or may be pregnant, or who are seeking to become pregnant, are therefore warned against using it. This teratogenic effect is caused by the interference of the exogenous retinoic acid with endogenous retinoic acid signaling, which plays a role in patterning the developing embryo. However the risks of topical tretinoin to the unborn child seems to be limited.

Research uses
A study published by the European Respiratory Journal in 2002 suggested that tretinoin can reverse the effects of emphysema in mice by returning elasticity (and regenerating lung tissue through gene mediation) to the alveoli. Studies suggested that this might form a promising treatment in human emphysema patients, A newer follow-up study done in 2006 found inconclusive results("no definitive clinical benefits") using Vitamin A (retinoic acid) in treatment of emphysema in humans and stated that further research is needed to reach conclusions on this treatment.