The Open Dermatology Journal




ISSN: 1874-3722 ― Volume 12, 2018
LETTER

0.1MG/ML Tamoxifen Gel Improves Plaque Psoriasis. An Open Study



Ayman Abdelmaksoud1, Angela Filoni2, Domenico Bonamonte2, Giuseppe Giudice3, Azza Abdelaziz4, Mohammed Zaki5, Maurizio Congedo6, Michelangelo Vestita3, *
1 Mansoura Dermatology, Venerology and Leprology Hospital, Mansoura, Egypt.
2 Department of Biomedical Science and Human Oncology University of Bari, Section of Dermatology, 11, Piazza Giulio Cesare, Bari, 70124, Italy
3 Department of Emergency and Organ Transplantation, Section of Plastic and Reconstructive Surgery, University of Bari, 11, Piazza Giulio Cesare, Bari, 70124, Italy
4 Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
5 Department of Pharmacognosy, Faculty of Pharmacy, Alazhar University, Cairo, Egypt.
6 Section of Dermatology, Vito Fazzi Hospital, Piazza Filippo Muratore, Lecce, 73100, Italy


Article Information


Identifiers and Pagination:

Year: 2018
Volume: 12
First Page: 54
Last Page: 58
Publisher Id: TODJ-12-54
DOI: 10.2174/187437220181201054

Article History:

Received Date: 13/12/2017
Revision Received Date: 22/3/2018
Acceptance Date: 16/04/2018
Electronic publication date: 30/04/2018
Collection year: 2018

Article Metrics:

CrossRef Citations:
0

Total Statistics:

Full-Text HTML Views: 622
Abstract HTML Views: 404
PDF Downloads: 353
ePub Downloads: 506
Total Views/Downloads: 1885

Unique Statistics:

Full-Text HTML Views: 276
Abstract HTML Views: 192
PDF Downloads: 184
ePub Downloads: 140
Total Views/Downloads: 792
Geographical View

© 2018 Abdelmaksoud et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the Department of Emergency and Organ Transplantation, Section of Plastic and Reconstructive Surgery, University of Bari, Michelangelo Vestita, Piazza Giulio Cesare, Bari, 70124, Italy; Tel: +393384718333; E-mail: michelangelovestita@gmail.com




DEAR EDITOR,

From September to October 2016, we have treated 6 patients affected by plaque psoriasis with 0.1mg/ml tamoxifen gel. The characteristics of the study population are summarized in Table 1. Mean PASI was 15.5. Each patient had undergone mainstay topical and systemic therapy with lack of a clinically significant response as per physician assessment (no decrease in PASI). No patient had systemic comorbidities, and the two female patients included were in menopause. In each case, psoriasis diagnosis had been confirmed by histological examination (Fig. 1).

Fig. (1)
Histological view of patient 2 incisional biopsy. H&E 10x.


Being a case series study, we obtained IRB waivers; all patients were required to sign an informed consent. Topical 0.1mg/ml tamoxifen gel in the liposomal base (Supplementary File S1) was applied twice/day to the affected skin for 15 days, with a dosage of 1 fingertip unit per 120 cm2 (half of one hand palm). All patients were followed up at 1 and 3 months; 2 patients reached the 5 months follow up. Tamoxifen and its metabolites (N-desmethyl tamoxifen; E and Z isoforms of 4-hydroxytamoxifen; N-desmethyl 4-hydroxytamoxifen) serum concentrations were assessed at 15 days of therapy in each patient. No other psoriasis treating drugs (topical or systemic) were administered during the study period.

Mean PASI, as assessed by a blinded dermatologist after 15 days, 1 and 3 months were 7.5, 8 and 9.8 (Table 1), Figs. (2-5), respectively. The response was sufficiently sustained over time, with moderate signs of recurrence at 3 months. The two patients followed up for 5 months showed complete recurrence. No systemic or local adverse events were noted in any of the patients.

Table 1
Characteristics of the study group and results.


Fig. (2)
Patient 5. Plaque psoriasis. Dorsal aspect of the trunk.


Sex hormone receptors are known to be present in the skin, as epidermal cells metabolize estrogen and progesterone, even if their specific effects are unclear [1Lin X, Huang T. Impact of pregnancy and oestrogen on psoriasis and potential therapeutic use of selective oestrogen receptor modulators for psoriasis. J Eur Acad Dermatol Venereol 2016; 30(7): 1085-91.[http://dx.doi.org/10.1111/jdv.13661] [PMID: 27072912] ]. Estrogen receptors are also present on T cells, especially in the CD8 subset, where they have been shown to decrease T-helper cell activity (CD4), as well as on vascular smooth muscle and endothelium [1Lin X, Huang T. Impact of pregnancy and oestrogen on psoriasis and potential therapeutic use of selective oestrogen receptor modulators for psoriasis. J Eur Acad Dermatol Venereol 2016; 30(7): 1085-91.[http://dx.doi.org/10.1111/jdv.13661] [PMID: 27072912] ]. These receptors further control the immune response through macrophages and thymocytes. The role of estrogens in psoriasis is complex, as they suppress the T-cell response, reduce cytokine production, stimulate keratinocytes proliferation and promote angiogenesis. Therefore, they may ultimately improve or worsen the dermatosis [1Lin X, Huang T. Impact of pregnancy and oestrogen on psoriasis and potential therapeutic use of selective oestrogen receptor modulators for psoriasis. J Eur Acad Dermatol Venereol 2016; 30(7): 1085-91.[http://dx.doi.org/10.1111/jdv.13661] [PMID: 27072912] ].

As an anti-estrogen, tamoxifen has been shown capable of inducing a shift from Th1 to Th2 immunity and exerts an anti-angiogenic action in different tissues [2Behjati S, Frank MH. The effects of tamoxifen on immunity. Curr Med Chem 2009; 16(24): 3076-80.[http://dx.doi.org/10.2174/092986709788803042] [PMID: 19689284] ]. Previous favorable response to oral administration of tamoxifen has been reported in two dated cases of plaque psoriasis [3Boyd AS, King LE Jr. Tamoxifen-induced remission of psoriasis. J Am Acad Dermatol 1999; 41(5 Pt 2): 887-9.[http://dx.doi.org/10.1016/S0190-9622(99)70356-7] [PMID: 10534679] , 4Ferrari VD, Jirillo A. Psoriasis and tamoxifen therapy: A case report. Tumori 1996; 82(3): 262-3.[PMID: 8693608] ]. Recently, Bhatia et al. [5Bhatia A, Singh B, Wadhwa S, Raza K, Katare OP. Novel phospholipid-based topical formulations of tamoxifen: Evaluation for antipsoriatic activity using mouse-tail model. Pharm Dev Technol 2014; 19(2): 160-3.[http://dx.doi.org/10.3109/10837450.2013.763260] [PMID: 23369039] ] used a mouse-tail model to evaluate the anti-psoriatic activity of topical tamoxifen encapsulated in the new generation phospholipid-based vesicular and micellar systems. The results of this study demonstrated the potential usefulness of topical tamoxifen in psoriasis.

Fig. (3)
Patient 5. Dorsal aspect of the trunk, after 15 days topical tamoxifen.


Fig. (4)
Patient 1. Plaque psoriasis. Frontal aspect of the trunk.


In our observation, topical 0.1mg/ml tamoxifen gel was effective in a 15 days application regimen and provided a sufficiently sustained response up to 3 months in all patients, considering that just one 15 days trial was performed. While precise therapeutic protocols are yet to be defined, topical 0.1mg/ml tamoxifen may represent a novel option to manage hard-to-treat chronic plaque psoriasis; this may allow for an effective therapeutic response while avoiding the potential toxicity associated to conventional systemic therapies in patients showing an insufficient response to such treatments. To avoid complications from systemic absorption, we enrolled two female patients in menopause. As a matter of fact, tamoxifen serum metabolites were undetectable in all of our patients, indicating the safety of topical tamoxifen application, and reflected those of another experience in ductal carcinoma in situ of the breast [6Lee O, Page K, Ivancic D, et al. A randomized phase II presurgical trial of transdermal 4-hydroxytamoxifen gel versus oral tamoxifen in women with ductal carcinoma in situ of the breast. Clin Cancer Res 2014; 20(14): 3672-82.[http://dx.doi.org/10.1158/1078-0432.CCR-13-3045] [PMID: 25028506] ]. However, the rate of absorption could, of course, vary based on the integrity and inflammatory status of the skin, as well as depending on the amount of gel used (some patients tend to apply more or less than prescribed). Therefore, at present, the definite conclusion regarding systemic absorption cannot be drawn. Further controlled studies are needed to confirm our observation and possibly to extend the therapeutic indication to other forms of psoriasis.

Fig. (5)
Patient 1. Frontal aspect of the trunk, after after 15 days of topical tamoxifen.


ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The author obtained IRB waiver for this study.

HUMAN AND ANIMAL RIGHTS

Not applicable.

CONSENT FOR PUBLICATION

All patients were required to sign an informed consent.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

SUPPLEMENTARY MATERIAL

Supplementary material is available on the publishers Website along with the published article.

Download File


REFERENCES

[1] Lin X, Huang T. Impact of pregnancy and oestrogen on psoriasis and potential therapeutic use of selective oestrogen receptor modulators for psoriasis. J Eur Acad Dermatol Venereol 2016; 30(7): 1085-91.[http://dx.doi.org/10.1111/jdv.13661] [PMID: 27072912]
[2] Behjati S, Frank MH. The effects of tamoxifen on immunity. Curr Med Chem 2009; 16(24): 3076-80.[http://dx.doi.org/10.2174/092986709788803042] [PMID: 19689284]
[3] Boyd AS, King LE Jr. Tamoxifen-induced remission of psoriasis. J Am Acad Dermatol 1999; 41(5 Pt 2): 887-9.[http://dx.doi.org/10.1016/S0190-9622(99)70356-7] [PMID: 10534679]
[4] Ferrari VD, Jirillo A. Psoriasis and tamoxifen therapy: A case report. Tumori 1996; 82(3): 262-3.[PMID: 8693608]
[5] Bhatia A, Singh B, Wadhwa S, Raza K, Katare OP. Novel phospholipid-based topical formulations of tamoxifen: Evaluation for antipsoriatic activity using mouse-tail model. Pharm Dev Technol 2014; 19(2): 160-3.[http://dx.doi.org/10.3109/10837450.2013.763260] [PMID: 23369039]
[6] Lee O, Page K, Ivancic D, et al. A randomized phase II presurgical trial of transdermal 4-hydroxytamoxifen gel versus oral tamoxifen in women with ductal carcinoma in situ of the breast. Clin Cancer Res 2014; 20(14): 3672-82.[http://dx.doi.org/10.1158/1078-0432.CCR-13-3045] [PMID: 25028506]

Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


Browse Contents



Advertisements


Webmaster Contact: info@benthamopen.com
Copyright © 2018 Bentham Open