Efficacy and safety of diphenylcyclopropenone alone or in combination with anthralin in the treatment of chronic extensive alopecia areata: A retrospective case series

Durdu, Murat; Özcan, Deren; Baba, Mete; Seckın, Denız

doi:10.1016/j.jaad.2015.01.008

Cited by 47 publications

(52 citation statements)

References 31 publications

(19 reference statements)

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“…Besides immunotherapies, various therapeutic approaches including combination therapy have been attempted. Durdu et al . reported that topical application of anthralin has a meaningful adjuvant effect on DPCP monotherapy.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of superficial cryotherapy for alopecia areata: A retrospective, comprehensive review of 353 cases over 22 years

Jun

Lee

2016

The Journal of Dermatology

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Alopecia areata (AA) affects anagen hair follicles, resulting in non-scarring hair loss. Since introduced by Huang et al., superficial cryotherapy has been accepted as a considerable primary therapeutic modality for AA. The aim of this study was to objectively clarify the therapeutic efficacy and safety of superficial hypothermic cryotherapy for treatment of AA. Medical records of 353 patients from 1993 to 2014 were retrospectively analyzed. According to the response to the superficial cryotherapy, patients were categorized into four groups: "marked", "partial", "poor" and "no recovery". The marked and partial recovery groups were considered as responders. The proportions of the responders among patient subgroups which were defined by various patients, disease, and treatment factors were compared. Of the patients, 60.9% were classified as responders after 3 months of superficial hypothermic cryotherapy. The proportion of the responders were higher when the treatment interval was 2 weeks or less and in the incipient disease stage, with statistical significance. No severe side-effects other than mild pain and pruritus were reported. In conclusion, superficial cryotherapy is an effective and safe therapeutic modality for AA. Especially when the treatment interval is 2 weeks or less and in the first occurrence of the disease, the therapeutic outcome is superior.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of superficial cryotherapy for alopecia areata: A retrospective, comprehensive review of 353 cases over 22 years

Jun

Lee

2016

The Journal of Dermatology

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“…TAC in patients with refractory AA to establish its role as a second‐line therapy in the management of refractory AA. Topical immunotherapy with DPCP has been the treatment of choice for adult and pediatric (aged >10 years) patients with severe and/or treatment‐refractory AA . However, relapse is common during long‐term treatment with DPCP.…”

Section: Discussionmentioning

confidence: 99%

Intramuscular triamcinolone acetonide: An undervalued option for refractory alopecia areata

Seo

Lee

Hwang

et al. 2016

The Journal of Dermatology

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Severe alopecia areata (AA) can have an unpredictable clinical course and become refractory to contact immunotherapy. Novel treatment options include low-dose interleukin-2 and Janus kinase inhibitors; however, these treatments are still under investigation. Therefore, we evaluated the efficacy and safety of intramuscular (i.m.) triamcinolone acetonide (TAC) as a rescue therapy for refractory AA. We retrospectively analysed efficacy, adverse effects and relapse rate of i.m. TAC monthly in 27 patients with refractory AA. We defined AA as refractory if the patient showed an unsatisfactory response to both systemic treatment (not i.m. TAC) and the consecutive diphenylcyclopropenone immunotherapy. The initial systemic treatment of other forms of corticosteroids and/or cyclosporin was used to control extensive AA involving more than 25% of the scalp. Administration of i.m. TAC for 3-6 months resulted in a 63.0% response rate, and all patients showed inactive disease after treatment. Final hair regrowth negatively correlated with initial scalp involvement (Spearman r = -0.595, P = 0.001). All patients showed complete recovery of adrenocortical reserve within 3 months after the last injection. Adverse effects of systemic steroid therapy were observed only in female patients (dysmenorrhea and osteoporosis). i.m. TAC may provide a valuable therapeutic option to manage active hair loss and facilitate hair regrowth in refractory AA, especially in male patients.

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“…DPCP therefore may synergize with pembrolizumab therapy. As this contact sensitizer is inexpensive with a favourable safety profile established over decades , it could have great clinical utility to improve the responses of cutaneous metastases seen with the current standard‐of‐care pembrolizumab treatment. In our patient, combination therapy was well tolerated, without any significant systemic toxicity observed.…”

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confidence: 99%

Definite regression of cutaneous melanoma metastases upon addition of topical contact sensitizer diphencyprone to immune checkpoint inhibitor treatment

Gulati

Postow

Wolchok

et al. 2016

Experimental Dermatology

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Abbreviations: DPCP, diphencyprone; PD-1, programmed death-1. Key words: diphencyprone -immunotherapy -melanomapembrolizumab Accepted for publication 31 March 2016The immune checkpoint inhibitor pembrolizumab, which targets programmed death-1 (PD-1) receptor, has recently emerged as the standard-of-care treatment for patients with advanced melanoma, with a response rate of 33% (1). Another agent in the realm of immunotherapy used throughout the world, but not currently approved by the Food and Drug Administration in the United States, is the contact sensitizer diphencyprone (DPCP). Topical DPCP has been used in a 50-patient case series of cutaneously metastatic melanoma, with a response rate of 84%. DPCP also led to nodal or visceral metastasis regression in four of the patients (2), thus suggesting the potential for an abscopal effect with this topically applied immunotherapy. A recent 2-patient case series showed that topical immunotherapy has limited effect on internal disease, but that combined treatment with the PD-1 inhibitor nivolumab led to pronounced internal metastasis regression (3). Within an ongoing trial treating melanoma patients with topical DPCP formulated in a non-volatile, aqueous solvent as an Investigational New Drug (ClinicalTrials.gov number, NCT01711684), we have observed a remarkable tumor response in one patient on concurrent pembrolizumab therapy.The patient is a 93-year-old man who underwent resection of his primary acral melanoma harbouring an exon 13 K642E mutation from his right foot ten years ago. Subsequently, he was treated with ipilimumab as well as imatinib, but ultimately progressed with extensive in-transit metastases throughout his right lower extremity, which is when he presented to our institution, not having been on any medical therapy for 6 months (Fig. 1a). The patient received two months of twice weekly topical DPCP applications (0.4% and 0.04% concentrations were alternately used, with the goal being to maintain a tolerable level of inflammation and change concentration as necessary) while on no other therapies for his melanoma, and inflammation was induced as expected, but tumor response was incomplete, with generally only smaller lesions (<1 cm) responding, and larger lesions expanding (Fig. 1b). At this point, the patient discontinued DPCP applications to begin treatment with pembrolizumab (2 mg/kg as intravenous infusion every 3 weeks), but during the three months on pembrolizumab (the median time to response for this agent), his disease rapidly progressed (Fig. 1c). We then elected to restart DPCP applications (again twice weekly) concurrently with pembrolizumab (again every 3 weeks), first only to a region of skin that selectively responded (Fig. 1d), suggesting a synergistic reaction, but these data do not fully exclude the possibility of a delayed response to pembrolizumab. Then applications were extended throughout the skin areas involved with melanoma, with substantial metastasis regression observed (Fig. 1e). In comparison with single-agent DPCP, combinati...

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Efficacy and safety of diphenylcyclopropenone alone or in combination with anthralin in the treatment of chronic extensive alopecia areata: A retrospective case series

Cited by 47 publications

References 31 publications

Efficacy and safety of superficial cryotherapy for alopecia areata: A retrospective, comprehensive review of 353 cases over 22 years

Efficacy and safety of superficial cryotherapy for alopecia areata: A retrospective, comprehensive review of 353 cases over 22 years

Intramuscular triamcinolone acetonide: An undervalued option for refractory alopecia areata

Definite regression of cutaneous melanoma metastases upon addition of topical contact sensitizer diphencyprone to immune checkpoint inhibitor treatment

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