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Diphenylcyclopropenone

Author: Dr Chin-Yun Lin, Dermatology Registrar, and Dr.Monisha Gupta, MD, FACD, Dermatologist, Sydney, Australia, 2012.


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What is diphenylcyclopropenone?

Diphenylcyclopropenone (DPCP), also known as diphencyprone, is an experimental sensitising agent used by some dermatology centres to treat skin conditions by contact immunotherapy. Diphenylcyclopropenone is most often used to treat alopecia areata.

Diphenylcyclopropenone is made up in acetone. It should be stored in a dark glass bottle in a cupboard away from sunlight and kept secure from access by children. The compounded preparation has a shelf-life of around 6 months.

How does diphenylcyclopropenone work?

Application of diphenylcyclopropenone to the skin results in allergic contact dermatitis. In alopecia areata, it is believed to work by redirecting the autoimmune attacks on the hair follicles, allowing for re-growth

How to use diphenylcyclopropenone

Initial sensitisation to diphenylcyclopropenone is required for the treatment to work. The clinician applies a small test patch of high-concentration diphenylcyclopropenone (2%) and left in place for 2–3 days to induce contact allergy.

The patient or assistant then applies a weaker concentration of diphenylcyclopropenone to the affected areas once weekly, using up to 1 ml per session. The solution should remain on the skin for 6–24 hours or as directed and is then washed off. The area of application should be physically covered during the first 24 hours, as diphenylcyclopropenone is degraded by sunlight.

Great care should be taken to avoid diphenylcyclopropenone touching other areas of the body. Gloves should be worn by the patient and/or assistant for each application. There is a risk that the patient's partner or health care worker may also become sensitised and develop dermatitis.

What to expect with diphenylcyclopropenone treatment? What are the side effects?

As diphenylcyclopropenone causes contact allergy, local dermatitis is an expected part of treatment. A mild reaction with redness and itching is desirable and usually lasts for 24–48 hours.

Some patients may experience severe itching, burning, blistering or swelling of treated areas. As diphenylcyclopropenone is most often applied to the scalp, the reaction may make wearing wigs or headwear uncomfortable. Swollen lymph nodes may be noticeable behind the ears.

These side effects generally clear up promptly when treatment is stopped.

After initial sensitisation, a very low diphenylcyclopropenone concentration is often chosen to reduce the severity of dermatitis, for example, 0.001%. The strength is gradually increased over time, for example, 0.01%, 0.1%, 0.2%, 0.5%, 1% and 2%.

Other side effects may include:

What is the treatment for diphenylcyclopropenone-induced dermatitis?

Severe contact reactions and blistering may be treated with potent topical steroids, cool compresses, and if necessary, a short course of oral corticosteroids (eg, prednisone).

What success rates are reported with diphenylcyclopropenone?

In a retrospective study involving 54 patients with alopecia areata, terminal hair regrowth on the scalp was excellent (76–100%) in 40.7%, good (51–75%) in 14.8%, moderate (26–50%) in 14.8% and mild (< 25%) in 29.6% of patients. The overall response rate in that study was 55%.

Diphenylcyclopropenone is not effective for everyone. A response is more likely in those who have had alopecia areata for less than 10 years and have limited hair loss at baseline. Poorer outcomes are reported if the extent of the hair loss is 50% or greater, in patients who also have atopic dermatitis, and who have nail involvement. 

It is recommended that treatment should be continued for 6 months before declaring treatment failure.

Diphenylcyclopropenone treatment is usually continued weekly until the hair is re-grown, which may take up to 12 months. Treatment is stopped upon hair regrowth and patients are monitored for relapse. Relapse with further hair loss is common, with one study reporting a rate of 33%, and another study 68.9%. However, most patients benefit from another course of treatment.

Safety of diphenylcyclopropenone in children and during pregnancy

Two studies of contact immunotherapy in children with alopecia areata reported response rates of 33% and 32%.

There are no data on the safety of contact immunotherapy during pregnancy and it should not be used in pregnant women nor in women intending to become pregnant.

There are safety concerns about diphenylcyclopropenone. Although diphenylcyclopropenone is non-mutagenic in the Ames test, its precursor and possible contaminant during commercial production, α,α'-dibromodibenzyl ketone, can be mutagenic.

Other indications for diphenylcyclopropenone

Diphenylcyclopropenone may be useful in treating recalcitrant viral warts. One centre in Melbourne, Australia, reported an 88% success rate in clearing palmoplantar warts with 0.1% diphenylcyclopropenone and 15% salicylic acid in white soft paraffin. The salicylic acid reduced thick scale build-up over warts, thus allowing improved absorption of the diphenylcyclopropenone.

Diphenylcyclopropenone has also been used to treat extensive or locally advanced cutaneous melanoma metastases that are unsuitable for other therapies. A recent case series of seven patients treated with diphenylcyclopropenone demonstrated complete responses of cutaneous metastatic melanoma in four cases, and three had partial responses. The treatment was well tolerated by all patients. See Topical and intralesional immunotherapy for melanoma.

Other topical sensitisers

Topical immunotherapy can be undertaken using other sensitising chemicals such as dinitrochlorobenzene (DNCB) or squaric acid. Published data on the efficacy of dinitrochlorobenzene in alopecia areata is currently limited to case reports and small trials, and there is no convincing evidence that it is beneficial in the long term.

Dithranol is an irritant chemical usually used in the treatment of psoriasis; it has also been applied to areas of alopecia areata to induce contact irritant dermatitis with the hope of stimulating hair to grow. Its efficacy is uncertain.

New Zealand approved datasheets are the official source of information for these prescription medicines, including approved uses and risk information. Check the individual New Zealand datasheet on the Medsafe website.

 

References

  • Pires MC, Martins JM, Montealegre F, Gatti FR. Vitiligo after diphencyprone for alopecia areata. Dermatol Res Pract. 2010;2010:171265. doi:
    10.1155/2010/171265. Epub 2010 May 11. PubMed PMID: 20585597; PubMed Central PMCID: PMC2879911.
  • DCP therapy for alopecia areata. Patient information Sheet, Skin and Cancer Foundation Australia, 277 Bourke Street, Darlinghurst, NSW, Australia.
  • MacDonald Hull SP, Wood ML, Hutchinson PE, Sladden M, Messenger AG; British Association of Dermatologists. Guidelines for the management of alopecia areata. Br J Dermatol. 2003 Oct;149(4):692–9. PubMed PMID: 14616359.
  • Armour K, Orchard D. Treatment of palmoplantar warts with a diphencyprone and salicylic acid ointment. AJD 2006; 47,182–85. PubMed.
  • Avgerinou G, Gregoriou S, Rigopoulos D et al. Alopecia areata: topical immunotherapy treatment with diphencyprone. Journal of the European Academy of Dermatology and Venereology 2008; 22, 320–23. PubMed.
  • Akhyani M, Hassan S, Farshad F et al. The efficacy of topical diphencyprone in the treatment of alopecia areata. Indian J Dermatol 2009; 54, 88–9. PubMed.
  • Damian DL, Saw RP, Thompson JF. Topical immunotherapy with diphencyprone for in transit and cutaneously metastatic melanoma. J Surg Oncol. 2014 Mar;109(4):308–13. doi: 10.1002/jso.23506. Epub 2013 Nov 19. Review. PubMed PMID:24522938.
  • Lee S, Kim BJ, Lee YB, Lee W. Hair Regrowth Outcomes of Contact Immunotherapy for Patients With Alopecia Areata A Systematic Review and Meta-analysis. JAMA Dermatol. Published online August 01, 2018. doi:10.1001/jamadermatol.2018.2312. PubMed.

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