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Thread: Accutane: Why to Use it & How to Use it for Rosacea

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    Default Accutane: Why to Use it & How to Use it for Rosacea

    Isotretinoin (Accutane®, Roche Laboratories) is a vitamin A analog that has been used with great success in treating severe nodulocystic acne and various inflammatory skin disorders. Oral isotretinoin has potent anti-inflammatory properties, suppresses abnormal immune responses of the skin, and physically shrinks sebaceous glands. (25) For these reasons, isotretinoin is now being recommended for the treatment of moderate to severe rosacea sufferers with facial papules, pustules, redness, inflammation, burning, swelling, and rhinophyma. In many cases, isotretinoin’s beneficial actions are long lasting. Some synopses of important articles are included below:



    General Findings on Isotretinoin:
    Effect on Skin Inflammation

    •Oral isotretinoin has potent anti-inflammatory actions in the skin. (26-29) In an excellent review article, “Evidence for Anti-inflammatory Activities of Oral Synthetic Retinoids: Experimental Findings and Clinical Experience”, Drs. Orfanos and Bauer detail some important clinical findings on isotretinoin. In this review, they present clinical research demonstrating that oral isotretinoin decreases skin inflammation in patients with inflammatory skin disorders. (29) The medical researchers found that oral isotretinoin actually lowered skin temperature in these patients -- within 3 days of oral isotretinoin treatment, skin temperatures decreased significantly by 0.5° to 1° Celsius. (29) During a separate series of studies on patients with inflammatory skin disorders, Drs. Orfanos and Bauer documented that oral isotretinoin markedly decreased the size of dilated skin blood vessels within 3 weeks of treatment. (29)

    •Studies by Dr. Nikolowski and colleagues, “In-Vivo Testing of Anti-Inflammatory Effects caused by 13-cis-Retinoic Acid”, (30) and Drs. Plewig and Wagner, “Anti-Inflammatory Effects of 13-cis Retinoic Acid: An In Vivo Study”, (31) both demonstrate oral isotretinoin’s powerful anti-inflammatory actions. In a study on 16 patients with inflammatory skin disorders, Drs. Plewig and Wagner found that oral isotretinoin cleared most signs of skin inflammation including redness, swelling, papules, and pustules. (31)

    There is clinical evidence demonstrating that isotretinoin can successfully treat skin inflammation associated with lupus erythematosus. (32, 33) In a clinical case study on a lupus sufferer, medical investigators documented that oral isotretinoin greatly reduced facial inflammation and redness; these physicians included an impressive series of colored photographs showing the patient before treatment (with a severe fire-red face), and after treatment (with a completely normal, white-face). (32) In a second clinical study on a lupus patient who suffered with severe cutaneous inflammation for 15 years, four weeks of low-dose isotretinoin resulted in remarkable clearance of skin inflammation. (33)



    General Findings on Isotretinoin:
    Effect on Rosacea

    •Dr. Shalita and colleagues report that most rosacea sufferers respond very well to oral isotretinoin. In their experience, oral isotretinoin treatment results in dramatic clearance of moderate to severe rosacea. (34) They have also found that this treatment greatly reduces the bulbous red nose of rhinophyma. They state, “A 4- to 5-month course characteristically results in a striking involution of the disease process followed by remissions, even though therapy is discontinued”.

    •Dr. Orfanos reports that oral isotretinoin is extremely effective in treating severe rosacea cases with inflammatory papules, pustules, nodular lesions, redness, swelling, and rhinophyma. (25) He has found that most patients notice dramatic improvement within 4 to 8 weeks of treatment.

    •Drs. Nikolowski and Plewig report excellent success with isotretinoin in 13 patients with severe rosacea (inflammatory papules, pustules, swelling and rhinophyma). (35) Within 2 weeks of treatment, 50% of the inflammatory lesions were healed; after 8 weeks, over 95% of the lesions were completely gone. In this study, most patients also reported significant reductions in facial swelling. All patients (including rhinophyma patients) were in full remission at the 12-month follow up interview.

    •In a clinical study on 6 rosacea sufferers, oral isotretinoin treatment resulted in excellent clearance of inflammatory papules and pustules. (36) In this study, all patients were symptom free at a follow-up interview, 14.8 months later. (36)

    • Numerous other clinical studies demonstrate that oral isotretinoin is a safe and effective form of treatment for rosacea sufferers. (37-45)



    Low-Dose Isotretinoin:
    Effect on Rosacea


    •In a superb clinical study, medical experts demonstrate that low-dose isotretinoin has potent anti-inflammatory actions on rosacea patients. (46) These specialists stated that isotretinoin, “Controlled rosacea in every single patient faster and better than any other previously administered drug. The erythema and edema became much less prominent, and rhinophyma shrank an appreciable amount. Histologically, the severe inflammation in the upper dermis and the accompanying edema disappeared. The first patients on this protocol were in full remission for over 15 months at the time of writing.” (46) In these patients, the average number of papules and pustules per face was 16 prior to treatment, and 0 during treatment. The mean scores for erythema and edema were 2.8 before treatment, and 0.6 after treatment. The physicians conclude, “These results indicate that inflammation was almost completely blocked by isotretinoin therapy”. (46)

    •In a study performed on 47 rosacea patients treated with low-dose isotretinoin for 5 months, very good to excellent clearance was achieved in all patients. At follow-up examinations over a year later, 40 of 47 patients were found to be symptom free. (47)

    •A multicenter clinical trial on 92 rosacea patients was undertaken to evaluate the effectiveness of a 5-month course of low-dose isotretinoin on rosacea symptoms. (48) Isotretinoin was found to be extremely effective in clearing papules and pustules in most patients. Facial swelling and redness also improved considerably in most sufferers. In this study, sebaceous gland abnormalities (hyperplasia) disappeared, and rhinophyma shrank remarkably. (48)

    •In a clinical study on 18 patients with severe rosacea, excellent results were achieved with low-dose isotretinoin. (49)

    •In a small clinical study, low-dose isotretinoin resulted in excellent clearance in 8 patients with rosacea. (50)

    •In an interesting clinical study performed on 12 patients with vascular rosacea, low-dose isotretinoin was shown to decrease facial blood flow. (51) In this study, physicians measured cutaneous blood flow (via laser doppler) on the facial cheeks of all patients before and after isotretinoin treatment. They measured blood flow during normal room temperatures and high room temperatures (93.2 degrees Fahrenheit); they found that after 10 weeks of isotretinoin treatment, blood flow through the rosacea cheeks decreased by an average of 40%.



    Very-Low-Dose Isotretinoin:
    Effect on Rosacea



    •In a clinical study on 22 rosacea patients, very-low-dose isotretinoin (10 milligrams per day taken immediately after breakfast) was shown to significantly decrease facial redness, papules and pustules. (52) Furthermore, burning sensations that had been reported by 18 patients at the beginning of the study were significantly decreased in all patients by the sixth week of treatment. In patients with rhinophyma, isotretinoin caused regression of at least 50% during treatment. No significant side effects were noted at this dosage.

    •In a second study on 8 rosacea subjects, very-low-dose isotretinoin (10 milligrams per day) resulted in significant clearance of facial papules, pustules and facial redness. (53) In this study, the medical experts speculate that a dose as low as 5 milligrams per day may be extremely beneficial to rosacea patients (with very little chance for side effects).

    •In a third study on 6 rosacea patients very-low-dose isotretinoin resulted in significant reductions in facial papules, pustules and rhinophyma. (54) In this study, the remissions were long lasting and no significant side effects were observed.

    •In a clinical study performed on 20 rosacea patients, very-low-dose isotretinoin treatment for 3 to 6 months resulted in good to excellent clearance of papules, pustules and facial redness. (17) After one year, 17 out of 20 patients remained in full remission demonstrating that isotretinoin has long-lasting favorable effects on rosacea.

    •Drs. Jansen and Plewig recommend very-low dose isotretinoin (2.5 or 5.0 milligrams daily, not adjusted to body weight) for the treatment of rosacea. (55) They state, “This dose is surprisingly helpful in many forms of the disease”. Patients on very-low-dose isotretinoin may respond slower than those on higher starting doses, and may need to take isotretinoin for longer periods of time, but the side effects are greatly reduced, and the anti-inflammatory actions are substantial.

    •Dr. Richard Odom, chair and professor of dermatology at the University of California, San Francisco, uses very-low-dose isotretinoin to treat facial papules, pustules, and redness of moderate to severe rosacea sufferers. (56) For certain patients, he suggests using, “10 milligrams of oral isotretinoin 2 to 3 times a week, or 20 milligrams 2 times per week.” Dr. Odom gives oral isotretinoin for up to a year, at which point he likes to cut back the dosage and eventually discontinue the drug. Noteworthy is the fact that side effects at this dosage are minimal to non-existent.

    •In the 1999 medical textbook, “Primary Dermatologic Care”, medical specialists recommend the use of long-term, very-low-dose isotretinoin for the treatment of rosacea. They state, “Very-low-dose therapy of 10 milligrams every other day may suppress the extent of disease when used over a long period (years) and may also be helpful in the treatment of rhinophyma.” (7)

    •Consistent with the above reports, several medical experts are now recommending very-low-dose isotretinoin for the treatment of facial redness, inflammation, swelling, and inflammatory lesions associated with rosacea. (46, 57, 58)


    Isotretinoin dosage: It is important for rosacea sufferers and their physicians to understand that there is a significant difference between very-high-dose isotretinoin treatment (i.e., used for nodulocystic acne), high-dose isotretinoin treatment (for moderate acne or disorders of keratinization), and very-low-dose isotretinoin (now recommended for rosacea). At the high dosages, isotretinoin may actually worsen facial redness and flushing; while at the very low dosages, isotretinoin is a potent anti-inflammatory that usually decreases facial redness and flushing.


    Below is a general guideline for isotretinoin treatment (dosages are based on body weight). The dosages are given for the average male weight (150 pounds = 68 kilograms), and average female weight (100 pounds = 45 kilograms). Rosacea sufferers should focus on the low- and very-low-dosages:


    Very-High Dose Isotretinoin
    (2.0 milligrams/kilogram)

    Average male = 136 milligrams per day
    Average female = 90 milligrams per day



    High-Dose Isotretinoin
    (1.0 milligrams/kilogram)

    Average male = 68 milligrams per day
    Average female = 45 milligrams per day


    ***Low-Dose Isotretinoin***
    (0.5 milligrams/kilogram)

    Average male = 34 milligrams per day
    Average female = 22.5 milligrams per day



    ***Very-Low-Dose Isotretinoin***
    (0.2 milligrams/kilogram)

    Average male = 14 milligrams per day
    Average female = 9 milligrams per day



    ***Very-Low-Dose Isotretinoin***
    (0.1 milligrams/kilogram)

    Average male = 6.8 milligrams per day
    Average female = 4.5 milligrams per day



    As the reader can appreciate, very-high doses of 136 milligrams per day for an average male (which causes facial redness), is quite different from very-low doses of 6.8 milligrams per day (which usually decreases facial redness).


    Note on isotretinoin dosage: In some areas of Europe, oral isotretinoin is available in 2.5 and 5.0 milligrams capsules. In the United States and Canada, the smallest pre-made dose is 10 milligrams; however, all compounding pharmacies are able to make 2.5 or 5.0-milligram capsules.


    My personal experience with isotretinoin: I was treated with very-low-dose isotretinoin for 1 year for my facial papules, swelling, redness, burning, and rhinophyma. Oral isotretinoin was extremely effective on my facial papules, swelling and rhinophyma, and moderately effective on my facial redness and burning sensations. This was a true godsend for me because I could not treat my face with any topical medication due to extreme facial skin sensitivity, and because standard oral antibiotics were not very effective for my case. Oral isotretinoin broke the vicious inflammatory cycle, and has resulted in long-lasting improvement in many aspects of my rosacea. Consistent with my experience, medical experts are now finding that 1 or 2 courses of low-dose (long-term) isotretinoin may decrease the entire disease process.


    Isotretinoin side effects: Oral isotretinoin is a serious medication that comes with a long list of potential side effects, some minor and others major. Some common side effects include dry lips and skin, a transient elevation in cholesterol and triglyceride levels, mild headaches, and dry eyes. (59, 60) One serious side effect, and the one that causes most physicians to not use this medication, is that it can cause severe deformities to the unborn fetus. Thus, its use is contraindicated in women who are trying to get pregnant, or who are not using birth control (at least two forms) while sexually active. All patients considering this medication should sit down with their physicians and thoroughly discuss the most common side effects and the ‘worst case scenarios’ before starting treatment.


    In a recent medical review in Dermatology titled, “How Safe is Oral Isotretinoin”, noted dermatologist Dr. Meigel thoroughly reviews isotretinoin including dosing, duration of treatment, and new insights into optimal treatment. (59) In this article Dr. Meigel emphasizes several important points. First, he stresses that side effects such as dry lips (chelitis), nasal mucosa and eyes are the most common side effects. In his experience, “Pretreatment counseling and concomitant use of moisturizing agents usually manage these side effects effectively; in unusual cases of particularly poor tolerability, dose adjustments suffice”. All of these side effects are reversible upon discontinuation of the drug. (59) Second, systemic side effects, which are much less frequent, can include joint and muscle stiffness, skeletal changes, and transient elevations in cholesterol and lipids. (59) Third, Dr. Meigel indicates that isotretinoin is generally safe when used in moderation; in fact, he states, “Patients with serious concomitant disease, such as insulin-dependent diabetes, epilepsy, spina bifida, transplant patients, renal failure patients, multiple sclerosis motor neuron disease, and others can safely be treated with isotretinoin at a standard cumulative dose of 120 milligrams/kilograms per treatment course.” (59)


    A special warning must also be given to those rosacea sufferers taking isotretinoin who are planning on undergoing laser surgery for removal of blood vessels or rhinophyma. Facial surgery should not be performed while on this medication because there is an increased chance of poor wound healing and scarring. (5) Patients are usually instructed to wait at least 6 months after stoppage of medication before undergoing any form of surgery.

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    This is great info! Thanks for posting up all this info!!

    Also, what would be the deciding factors in drawing the line between low dose and very low dose treatment?

    Thanks

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    Thanks so much for posting this. Very interesting and helpful.
    Orion
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    10mg's of Singulair daily (bonus that it helps with my asthma! lol)

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    OMG - This is what I've been wanting. Someone to "dumb-down" Accutane for me! I get so confused by all of this.

    Thanks, Dr. Nase!

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    Accutane is the only drug that eliminates the severe burning sensations that I have. This drug has given me part of my life back. I was on low dose Accutane for almost 6 years. I have been off of this drug now for almost a year. My symptoms have gradually returned over the past few months. They're definitely not as severe as they were before I started the Accutane, especially the burning. I still have to avoid certain triggers that can exacerbate the neural pain. I'm extremely thankful that this drug is available. THANK YOU Dr. Nase for this informative post on Accutane.

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    Quote Originally Posted by googoo
    Accutane is the only drug that eliminates the severe burning sensations that I have. This drug has given me part of my life back. I was on low dose Accutane for almost 6 years. I have been off of this drug now for almost a year. My symptoms have gradually returned over the past few months. They're definitely not as severe as they were before I started the Accutane, especially the burning. I still have to avoid certain triggers that can exacerbate the neural pain. I'm extremely thankful that this drug is available. THANK YOU Dr. Nase for this informative post on Accutane.
    what dosage were you on and did you get into remission? if not, how much was redness / flushing reduced by?

    Thanks

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    Default Ocular?

    Ocular rosacea is not mentioned in the above info regarding isoretinone. I remember from your book you recommend it also for that?

    Please elaborate as I'm suffering greatly in one eye currently and need some advice to take to my opth.

    LaurieD

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    Default Accutane: why and how to use it

    is it still considered an "off label" use to prescribe for rosacea? my derm would not even discuss it because he said it was off label and the fda was very strict.

    I had a full dose, 6 mo course, 20 yrs ago for acne, skin was great for 15 yrs, then the oil came back and P&P's, sensitivity, in other words rosacea. My derm back then said I might need another course someday. My skin changes could have been hormonal too, got R in my 40's.

    I have considered taking lo dose accutane, but I am already medicated for cholesterol and am taking an estrogen suppresant since I had an early Breast C (sorry, I know you hate the word, therefore the C). I am leery of another strong medication.

    What do you think Dr Nase?
    **Graphic used with permission from Terry Moore, Strangers in Paradise comics.**

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    Senior Member IowaDavid's Avatar
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    Is there a subtype/symptom of rosacea that low-dose accutane treats better than others? Does it work best on phymous and papulopustular rosacea? Or does it vary too much between individuals? Interested if this would help suppress the flushing/redness.

    Thanks.

    David
    35 year-old male
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    Please feel free to PM me with your low-level red light therapy (LLRLT) questions. I'm happy to help if I can.

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    Librarylady,
    That argument by your doctor doesn't make sense to me. You have P&P, just its associated with rosacea. So, can't the doctor say that he is treating P&P, but has to be administered at a lower dose because of the potential complication with rosacea otherwise (i.e. if given at a higher dose, your rosacea would get worse). Seems to me, those rosacea suffers with P&P would have a significantly easier time and better case for being prescribed accutane. Or, is the doctor just so conservative that he doesn't want to open himself/herself to any remote liabilities.

    Best,
    Trey

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