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August 1996 • Volume 1 • Number 6

Contents: (Full text available in print edition.)

Comedone Extraction - Not Effective in Acne

The manual extraction of open and closed comedones has a long tradition in the treatment of acne and continues to be listed amongst treatments for the disease.1,2 However, some dermatologists questioned its utility as long ago as 1984,3 and recent histopathological data support the assertion that extraction does not greatly influence the course of the disease and can cause scarring.4

Extraction of comedones is cosmetically gratifying and therefore seems worthwhile in comedonal acne. Open comedones (blackheads) are usually directly extracted with a comedo extractor, while closed comedones (whiteheads) must usually be punctured with a sharp blade or point before the extraction is performed.

In a recent clinical and histopathological study4, comedones were squeezed out with comedo extractors and studied immediately. In addition, skin biopsies were studied after 2-20 minutes, one hour, and between 1-105 days thereafter. Despite careful extraction, common histopathological features were epithelial defects and inflammatory and granulomatous foreign body reactions. Even if not clinically evident, there were always inflammatory reactions, and scarring was often found. Comedones started to return and became visible within 4-6 weeks, unless the epithelial capsule was delivered during the extraction. However, the comedonal epithelium was rarely expelled in toto or the follicle and comedo permanently removed.

References

  1. Ho V, ed. Acne management for the 90s: current treatment guidelines. Can J Diagn 1995; December supplement.
  2. Drake LA, et al. Guidelines for the care of acne vulgaris. J Am Acad Dermatol 1990; 22: 676-680.
  3. Maddin S. Acne surgery. In: Epstein E, ed. Controversies in dermatology. Philadelphia: WB Saunders, 1984: 286-287.
  4. Jansen T, Plewig G. Komedonenentfernung: eine klinische und histopathologische Studie. Z Hautkr 1995; 70: 177-180.

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Treatment of Alopecia Areata (AA) with Special Emphasis on Topical Immunotherapy with Diphenylcyclopropenone (DCP)

The lifetime risk of men or women developing alopecia areata (AA) is estimated at 1.7%. Although the condition usually resolves spontaneously, approximately 7% of patients may suffer severe and chronic hair loss, which can be psychosocially devastating.1 Topical immunotherapy is the best overall treatment for chronic severe (more than 50% hair loss) AA. Systemic steroids would be more effective, but their side effects are unacceptable.2

Treatment of Alopecia Areata3

With Dr. Jerry Shapiro as Director, The University of British Columbia Hair Clinic (UBCHC) is an acknowledged leader in AA therapy. The clinic's recommended treatments, in order of preference, are:

  • In patients with less than 50% hair loss.
    1. Intralesional corticosteroids
    2. Minoxidil solution
    3. Anthralin
    4. Minoxidil solution plus anthralin
    5. Minoxidil solution plus superpotent topical corticosteroid
    6. Topical immunotherapy if above do not work
  • In patients with more than 50% hair loss.
    1. Topical immunotherapy with DCP to the whole area is the treatment of choice at the UBCHC, according to Dr. Shapiro.
    2. Intralesional corticosteroids can be used on limited resistant patches.
    3. Non-responders can receive PUVA, although this is not always effective; regrown hair falls out when treatment is stopped.
    4. Minoxidil solution, with or without anthralin or superpotent topical steroids. Dr Shapiro prefers 5% minoxidil to the 2% solution, especially in patients with more than 50% hair loss.
    5. Systemic corticosteroids
  • Topical Immunotherapy with DCP
  • Diphenylcyclopropenone (diphencyprone; DCP) treatment of AA should only be used under the supervision of dermatologists. In a study by van der Steen and colleagues, 139 patients with severe AA were treated with DCP for one year. Response in 50.4% was either excellent with total regrowth or satisfactory with only a few remaining bald patches.6 At UBCHC, in severe AA the response rate to DCP is 50-60%.5 The main factor influencing the therapeutic result is the extent of hair loss.4 When treating alopecia universalis or alopecia totalis, the success rate is only 25%.5 Response rates are lower in patients with a long duration of the disease before therapy.4,5 While treatment results may be seen in eight weeks, they are usually apparent in 14 weeks, but may take up to 24 weeks.5

    Hair growth often remains unaffected by gradual discontinuation of DCP treatment.6 In a study of 19 patients, 37% showed no hair loss six months after cessation of treatment and the appearance of the scalp was cosmetically acceptable in 68%. However, 53% developed patchy alopecia, and 10% lost all regrown hair.8 When hair loss recurs, there is a good chance that patients will respond to further DCP treatment.6

    Topical immunotherapy is not approved by the FDA in the USA or the Health Protection Branch of Canada. In the USA, the first official trial of DCP for alopecia areata patients has only just been commenced by the National Institute of Health. Since DCP treatment is experimental, a local ethics committee should approve the treatment protocol.9

  • Practice Tips2
    1. DCP application should be done by trained personnel in a hospital or university-based skin care centre. Treatment should NEVER be self-applied.2, 5
    2. DCP should be applied in well-ventilated conditions, and treatment staff should wear protective garments to guard against allergic reactions.10
    3. DCP solution should not be washed off for 48 hours.
    4. As DCP degrades when exposed to light, the patient must protect the scalp from light, preferably for 48 hours.
    5. Treat half the scalp first. If regrowth occurs, then treat the other side.
    6. Titrate the dose to produce redness. Without redness and itch, treatment will not be effective.
    7. Use topical corticosteroids ONLY if the skin reaction is excessive.
  • Treatment Exclusions
  • Pregnant patients and patients with malignancies or blood dyscrasias of any sort are excluded from treatment. Dark-skinned patients are more difficult to treat as they are more prone to pigment changes.5 There is little experience with DCP treatment of children with AA; one study demonstrated that DCP is effective, but long-term effects are unknown. Parents must be aware of all possible side-effects.11 The UBCHC does not treat children younger than 12 years of age.
  • Side Effects
  • Lymphadenopathy occurs in virtually all patients. Other frequent side effects are more severe eczematous reactions with blistering, spreading of the induced contact eczema, and sleep disturbances. Vitiligo, hyper- and hypopigmentation can also occur.5, 6 Treatment staff can also develop adverse reactions when applying the product.10

    Patients should understand that the allergic contact dermatitis induced by DCP is expected and required for treatment to be successful. They should also be informed about the experimental nature of immunotherapy.9

  • Supply and Cost
  • DCP is readily available through chemical suppliers. Ensure that DCP does not contain dibenzyldibromoketones, precursors of DCP that are positive in the Ames test for mutagenicity.2 Weekly treatments applied to the whole head cost about US$2.25 for materials.

    Mechanism of Action

    Antigenic competition has been proposed as a mechanism of action. The generation of nonspecific T suppressor cells into the area may inhibit the autoimmune reaction to the hair-associated antigen and, thus, allow hair to regrow.12

  • Alternatives to DCP
  • Dinitrochlorobenzene (DNCB) has been in use since 1976.13 DNCB is rapidly absorbed and produces a positive Ames test. Because of safety concerns, it is no longer recommended for use in AA. Squaric acid dibutyl ester (SADBE) is a strong topical sensitizer that is not found naturally and is used only rarely in industry. It is used for treating AA in some centres as an alternative to DCP.14 It is less stable than DCP.2

    References

    1. Safavi KH, Muller SA, Suman VJ, et al. Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989. Mayo Clin Proc 1995; 70: 628-633.
    2. Shapiro J. Topical immunotherapy in the treatment of chronic severe alopecia areata. Dermatol Clinics 1993; 11: 611-617.
    3. Shapiro J. Alopecia areata: update on therapy. Dermatol Clinics 1993; 11: 35-46.
    4. van der Steen PH, van Baar HM, Happle R, et al. Prognostic factors in the treatment of alopecia areata with diphenylcyclopropenone. J Am Acad Dermatol 1991; 24: 227-230.
    5. Shapiro J. Personal communication. April 1996.
    6. van der Steen PH, van Baar HM, Perret C, et al. Treatment of alopecia areata with diphenylcyclopropenone. J Am Acad Dermatol 1991; 24: 253-257.
    7. van Baar HM, van der Vleuten CJM, van der Kerkhof PCM. Dapsone versus topical immunotherapy in alopecia areata. Brit J Dermatol 1995;133: 270-274.
    8. MacDonald -Hull S, Cunliffe W. Post therapy relapse rate in alopecia areata after successful treatment with diphencyprone. J Dermatol Treat 1989; 1: 71.
    9. Perret C, Happle R. Treatment of alopecia areata. In: Orfanos C, Happle R (eds). Hair and hair diseases. New York: Springer-Verlag, 1990: 571-586.
    10. Shah M, Lewis FM, Messenger AG. Hazards in the use of diphencyprone. Brit J Dermatol 1996; 134: 1163.
    11. Hull SM, Pepall L, Cunliffe WJ. Alopecia areata in children: response to treatment with diphencyprone. Br J Dermatol 1991; 164-168.
    12. Happle R. Antigenic competition as a therapeutic concept for alopecia areata. Arch Dermatol Res 1981; 26: 285.
    13. Rosenberg E, Drake L. Letter, Arch Dermatol 1976; 112: 256.
    14. Happle R. Personal communication. June 1996.
    Outlook for the Future
    At present, treatment for severe AA is very non-specific and has considerable side effects. A lot of work is going into researching normal hair biology looking for the events that control the hair cycle. Hopefully, once the trigger for AA is found, more specific, more effective and better tolerated treatments will be developed. Due to the heterogeneous nature of AA, we will find that combination treatments utilizing more than one treatment approach will increase our success rate in treating AA.
    Dr. J. Shapiro, Vancouver, Canada

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    Update on Drugs

    Class Name/Company Approval Dates and Comments
    Anti-acne retinoid Adapalene
    Differin®
    Galderma Laboratories    		 Gel and solution (both 0.1%) of this retinoid-like compound were approved by the FDA on the May 31, 1996 for the topical treatment of acne. Adapalene is already available in several other countries. See the review of adapalene in Issue Four.
    Antipsoriatic Calcipotriol
    Dovonix® Scalp Solution
    Leo Laboratories    		 Dovonex® is now available in Canada in a scalp solution as well as a cream and ointment. The solution formulation is already available in the UK, Western Europe, and Denmark, and is awaiting approval in the USA. This non-steroidal vitamin D analogue is indicated for the topical management of mild to moderate psoriasis.

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    Skin Therapy Letter. (ISSN 1201-5989) Copyright 1996 by International Skin Therapy Newsletter Inc. All rights reserved. Reproduction in whole or in part by any process in whole or in part is strictly forbidden without prior consent of the publisher in writing.

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