Diphencyprone

(USAN, rINN)
Diphencyprone Chemical formula
Synonyms: Difenciprona. 2,3-Diphenylcyclopropenone-1.
Cyrillic synonym: Дифенципрон.

Chemical information

Chemical formula: C15H10O = 206.2.
CAS — 886-38-4.

Profile

Diphencyprone has been applied as a contact sensitiser for the treatment of alopecia. It has also been tried in warts.

Adverse effects.

Diphencyprone is considered to lack serious adverse effects but some patients may not be able to tolerate the induced hypersensitivity reaction. There have been reports of generalised urticaria and dermographism, sometimes severe, following the use of diphencyprone.1-5 In another case, a severe reaction of urticaria and dermographism, which lasted several months, occurred after the initial sensitisation dose.6 Allergy to diphencyprone has been reported in medical and nursing staff in spite of taking protective precautions during its application.7 A patient who received diphencyprone treatment for warts developed a widespread pruritic rash and palpitations due to ventricular extrasystoles.1 Vitiligo has also been reported in patients treated with diphencyprone8-10 and it has been suggested that this might be due to unmasking of subclinical vitiligo.8,9 Erythema multiforme-like eruptions have been associated with the topical application of diphencyprone.11,12
1. Lane PR, Hogan DJ. Diphencyprone. J Am Acad Dermatol 1988; 19: 364–5
2. Tosti A, et al. Contact urticaria during topical immunotherapy. Contact Dermatitis 1989; 21: 196–7
3. Skrebova N, et al. Severe dermographism after topical therapy with diphenylcyclopropenone for alopecia universalis. Contact Dermatitis 2000; 42: 212–15
4. Francomano M, Seidenari S. Urticaria after topical immunotherapy with diphenylcyclopropenone. Contact Dermatitis 2002; 47: 310–11
5. Short KA, Higgins EM. Urticaria as a side-effect of diphencyprone therapy for resistant viral warts. Br J Dermatol 2005; 152: 583–5
6. Alam M, et al. Severe urticarial reaction to diphenylcyclopropenone therapy for alopecia areata. J Am Acad Dermatol 1999; 40: 110–12
7. Shah M, et al. Hazards in the use of diphencyprone. Br J Dermatol 1996; 134: 1153
8. Hatzis J, et al. Vitiligo as a reaction to topical treatment with diphencyprone. Dermatologica 1988; 177: 146–8
9. Duhra P, Foulds IS. Persistent vitiligo induced by diphencyprone. Br J Dermatol 1990; 123: 415–16
10. Henderson CA, Ilchyshyn A. Vitiligo complicating diphencyprone sensitization therapy for alopecia universalis. Br J Dermatol 1995; 133: 496–7
11. Perret CM, et al. Erythema multiforme-like eruptions: a rare side effect of topical immunotherapy with diphenylcyclopropenone. Dermatologica 1990; 180: 5–7
12. Oh C-W, et al. Bullous erythema multiforme following topical diphenylcyclopropenone application. Contact Dermatitis 1998; 38: 220–1.

Alopecia.

Diphencyprone has been used as a contact sensitiser in the treatment of various forms of alopecia including areata, totalis, and universalis. Case series reports generally describe treatment of adults, but some groups have also included adolescents and children, and some have reported solely on treatment in children.1,2 Initial sensitisation is usually achieved by applying a 2% solution of diphencyprone in acetone to a small area of scalp, which may be repeated if necessary beneath plastic occlusion if adequate sensitisation is not produced. Thereafter, weaker concentrations are applied once weekly and gradually increased in strength to produce erythema and pruritus for 36 to 48 hours post-therapy. Concentrations that have been used vary between reports and the first treatment application may be as dilute as 0.00001%, with further applications gradually increased to up to 2%. Only one side of the scalp is treated until the optimum concentration is found, in order to prevent a widespread adverse reaction. Once hair regrowth has started on the treated side the applications may be extended to the entire scalp.1-8 As well as erythema and pruritus, patients usually experience transient eczema and regional lymph node swelling.2,5,7,8 Hair regrowth may not start for several months,4,6,8 and the required duration of therapy can vary considerably; at least 8 months of treatment may be required,3,6 and up to 12 months1,2or more4,6 has been reported. Not all patients will respond to treatment and reported response rates vary, although these have probably been influenced by the different definitions used for complete, partial, and no response. Overall, however, regrowth of hair can occur in up to about 70% of patients, with around half of these having complete regrowth.1,4,6-8 Some reports have attempted to determine which factors might be associated with clinical response to diphencyprone. There is disagreement between studies but some possible unfavourable prognostic factors include extensive involvement,4,6,8 younger age at onset,8 longer disease duration before treatment,5,7 and a history of atopic eczema.4,7 The need for high diphencyprone concentrations and prolonged therapy have also been associated with a less favourable outcome.8 Despite these rates of response a significant number of patients will relapse, either during or after stopping treatment, and retreatment may be considered.4,6,7 The time to relapse can be variable. Remission in a small group of complete responders ranged from 1 month to 2 years after stopping therapy.4 Another group of patients who achieved total regrowth of hair were able to stop treatment with diphencyprone for a mean of 15 months without relapse9 while a further group maintained satisfactory hair growth for a mean follow-up period of 19.8 months.5
1. MacDonald Hull S, et al. Alopecia areata in children: response to treatment with diphencyprone. Br J Dermatol 1991; 125: 164–8
2. Schuttelaar M-L, et al. Alopecia areata in children: treatment with diphencyprone. Br J Dermatol 1996; 135: 581–5
3. MacDonald Hull S, Cunliffe WJ. Successful treatment of alopecia areata using the contact allergen diphencyprone. Br J Dermatol 1991; 124: 212–13
4. Hoting E, Boehm A. Therapy of alopecia areata with diphencyprone. Br J Dermatol 1992; 127: 625–9
5. Gordon PM, et al. Topical diphencyprone for alopecia areata: evaluation of 48 cases after 30 months’ follow-up. Br J Dermatol 1996; 134: 869–71.
6. Pericin M, Trüeb RM. Topical immunotherapy of severe alopecia areata with diphenylcyclopropenone: evaluation of 68 cases. Dermatology 1998; 196: 418–21
7. Cotellessa C, et al. The use of topical diphenylcyclopropenone for the treatment of extensive alopecia areata. J Am Acad Dermatol 2001; 44: 73–6
8. Wiseman MC, et al. Predictive model for immunotherapy of alopecia areata with diphencyprone. Arch Dermatol 2001; 137: 1063–8
9. van der Steen PHM, et al. Topical immunotherapy for alopecia areata: re-evaluation of 139 cases after an additional follow-up period of 19 months. Dermatology 1992; 184: 198–201.

Warts.

Diphencyprone has been tried in the treatment of recalcitrant warts. The successful treatment of digital or plantar warts in 42 of 60 patients has been described.1 The patients were initially sensitised with a 2% topical solution of diphencyprone in acetone, then the warts treated every 1 to 4 weeks with solutions ranging from 0.01 to 6%. In another series,2 diphencyprone in a paraffin ointment was effective in the clearance of palmar, plantar, palmoplantar, and periungual warts in 135 of 154 patients. A concentration of diphencyprone 2% was used for the initial sensitisation, and concentrations of 0.5 to 4% were used for treatment once every 3 weeks. After initial sensitisation with diphencyprone 2% in acetone, a preparation of diphencyprone with salicylic acid in white soft paraffin applied every night as tolerated was reported to be successful in 44 of 50 patients treated for palmoplantar warts.3 The concentration of diphencyprone in the ointment ranged from 0.01 to 0.2%, and the concentration of salicylic acid was 15%.
1. Buckley DA, et al. Recalcitrant viral warts treated by diphencyprone immunotherapy. Br J Dermatol 1999; 141: 292–6
2. Upitis JA, Krol A. The use of diphenylcyclopropenone in the treatment of recalcitrant warts. J Cutan Med Surg 2002; 6: 214–17
3. Armour K, Orchard D. Treatment of palmoplantar warts with a diphencyprone and salicylic acid ointment. Australas J Dermatol 2006; 47: 182–5.
Published November 29, 2018.