DEPIGMENTATION (1) Monobenzyl ether of hydroquinone (2) Bleaching cream formulation (3) Azelaic acid ------------------------------------------------------- -------------------------------- MONOBENZYL ETHER OF HYDROQUINONE -------------------------------- I have a 43 year old white female with extensive vitiligo; essentially covering 70 percent body surface. She may be a candidate for depigmentation, and she has expressed cautious interest. Does anyone have information as to where I may obtain 20% monobenzyl ether of hydroquinone? Any contraindications in patients with nephrotic syndrome of uncertain etiology? Any words of advice from those experienced in the procedure? Warren J. Winkelman, MD, FRCPC Department of Dermatology Montreal General Hospital ------------------------- Basically, we make it up in our pharmacy as it is difficult to obtain it from ICN. I do not think that the nephrotic syndrome should interfere. However, is she a transplant candidate? There are anecdotal reports of people repigmenting, after depigmentation, upon systemic immunosuppression. This may not be uniform color and thus the procedure which involves starting with a small area twice a day for some weeks, because of the potential allergic reaction, and then using more extensively, and eventually the process goes on its own in areas that have not been treated, must be evaluated carefully. Ethan Lerner MD --------------- I have used the 20% monobenzyl ether of hydroquinone, once, many years ago, with excellent results...a blonde lady with extensive vitiligo became pure white, and was quite happy... but as there is documented systemic absorption...I was always worried about damage to pigmented cells in the retina/brain etc...anyone have any information on this? Steven D. Emmet, M.D. | Assoc.Prof.Derm. UCSD --------------------- As usual, the use of Benoquin is a challenge. It is AGAIN on a manufacturing hiatus, due to FDA concerns regarding viscosity standards, I am told. The upshot is that for the second time in the last few years it is UNAVAILABLE. Unlike last time, there is no remaining store of Benoquin, which means that as of today at least there is no compassionate need emergency IND by which Benoquin can be obtained from ICN. Their comment to me was to check again in mid-April, to see if they get limited approval to start manufacturing. Other alternatives are not great, at least from my perspective, as my compounding pharmacist checked the recipe and it's much too complex for someone to extemporaneously compound. It's a waiting game. Other comments: it can be a great treatment in Caucasians, where the net cosmetic result is often excellent. It is very slow, and very expensive, and my patients have typically chosen to treat only face and hands/arms. If it hits the market again I'll try to remember to post the info. Mark Ling, M.D., Ph.D. Emory University Department of Dermatology Clinical Pharmacology Unit Atlanta, GA ----------- --------------------------- BLEACHING CREAM FORMULATION --------------------------- For some time dermatologists have been mixing hydroquinone powder, Retin-A cream, and Lidex cream to prepare a stronger bleaching cream than the commercially available hydroquinones. I believe the originator of this formula was Al Kligman. I have noticed that the mixture separates if Lidex-E is used instead of regular Lidex cream. Pehaps there is a unique emulisifier or stabilizer in the Lidex cream (hexanetriol, polyethylene glycol 8000?). I would be interested in what compounding formulas are being used by others now that brand name Lidex cream is becoming difficult to obtain. Are there other topical steroid creams that work well? Walter H. Wood, M.D. -------------------- In Al Kligman's original bleaching formulation the steroid was dexamethasone, not Lidex. 1 or 21/2% hydrocortisone is usued the morning after to decrease the irritation produced by Retin A. One can apply Retin A .05 over 4%hydroquinone H.S., apply the steroid in the am. I prefer Azeleic acid over the Retin A H.S. Haines Ely MD ------------- I believe the original "trihydroret" formulation by Kligman did not use such a potent steroid: indeed during my residency at Penn, Albert was quite clear that he no longer feels the corticosteroid is necessary to achieve hypopigmentation and does not use it anymore. I'd certainly be cautious when using Lidex on the face, if that's the indication pursued. Mark Ling, M.D., Ph.D. Emory University Department of Dermatology Clinical Pharmacology Unit Atlanta, GA ----------- Kligman's original forumula was indeed: Hydroquinone powder 5% Dexamethasone powder 0.1% Tretinoin powder 0.1% Hydrophilic ung qs ad 60gm The reference is O.H. Mills and A.M. Kligman, J. Soc. cosmet. Chem., 1978, 29, 147. There are of course other variations. One pharmacist I know dissolves the HQ powder in propylene glycol prior to mixing in hydrocortisone powder, tretinoin powder, and then blending with Unibase cream. I credit Kligman with all variations of the concept of hydroquinone, tretinioin, steroid creams. The exact method of preparation of what I was using with great success was combining in order Water 3ml Hydroquinone powder (Kodak) 5gm Retin A 0.05% cream (DNS) 15gm Lidex cream (DNS) 15gm Eucerin cream (DNS) qs ad 50 gm The HQ is dissolved in the water first, then the creams are combined, and finally all are mixed thourougly by hand. This makes 50gm of a very nice stable bleaching cream which emulsifies nicely. The fluocinonide content is 0.015% and use is carefully monitored by giving the patient 10gm jars at a time. I have never seen atrophy or steroid induced rosacea from use of this, but it is a concern of course. The patient is instructed to apply at hs and use high SPF sunscreen every AM. The advantages are: 1) Patients love it, a prescription made just for them by the dermatologist, and they don't have to pay for it. NO prescription cost to the patient 2) minimal cost to the dermatologist since ingredients are free samples exept for the HQ powder which is inexpensive 3) very individualized treatment with control of supply by the dermatologist. The problem is that samples of Lidex cream (DNS) are no longer available, and I have had problems with the emulsification of other steroid creams (they tend to separate in a few days). Horror of horrors, I may actually have to buy ingredients? All of this raises the question: how many dermatolgists and pharmacists are doing traditional compounding? What are favorite recipes for various things? Is traditional compounding becoming a lost art? Walter H. Wood, M.D. -------------------- In our setting, we have tried from low potency: hydrocortisone to mid potency fluocinonide or betamethasone combination in our bleaching preparation. We find the combination hydroquinone + Tretinoin .05 + hydrocortisone to be the most effective in terms of effect and cost. Hydrocortisone is cheaper in Manila. Lately we are trying to use desonide cream (DesOwen) to see if it is better than hydrocortisone. In regards to separation in your Lidex E, how to you prepare your Hydroquinone powder? Do you use propylene glycol to dissolve it? It might be the diluent that is reacting with the emollient base of Lidex E. Jonathan Yu, MD Skin & Cancer Foundation Makati, Philippines ------------------- Perhaps I should try propylene glycol instead of water. There does seem to be something very unique about the emulsification of regular Lidex cream that made everything work. Mixing already optimized creams is definitely tricky. Walter H. Wood, M.D. -------------------- ------------ AZELAIC ACID ------------ How about asking the company which makes azelaic acid for acne to supply some to you on an investigative basis for depigmentation? Dr. Nazzaro-Poro in Italy reported its use for depigmentation about 10 years ago. If Benoquin is unavailable, there might be a good market for azelaic acid as a substitute. Yelva Lynfield, MD ------------------ In the literature at least, azeleic acid is about as effective as hydroquinone for melasma, therefore I have not considered it an effective substitute for the much more potent benoquin. Mark Ling, M.D., Ph.D. Emory University Department of Dermatology Clinical Pharmacology Unit Atlanta, GA ----------- Azeleic acid will not depigment normal skin and only works well on areas where the pigment is active, ie melasma. Old post inflammatory pigment or deep dermal pigment isn't touched.However, melanex applied first, followed by azeleic acid, is better than melanex alone by quite a bit. Haines ELy MD ------------- ------- 4.17.96