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


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© 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.
Sex Age Psoriasis onset (years before) Previous therapies * Baseline PASI PASI at the end of the therapy
(15 days)
PASI at 1 month follow-up PASI at 3 month follow-up PASI at 5 month follow-up
Patient 1 M 21 2 1, 2, 4 13 6 6 8
Patient 2 F 53 15 1, 2, 4 15 5 6 8
Patient 3 M 46 20 1, 2, 3 14 7 7 9 13
Patient 4 F 56 24 1, 2, 5 20 10 12 14
Patient 5 M 24 6 1, 2, 3, 4 18 10 10 12 15
Patient 6 M 52 28 1, 2, 3, 5, 6 13 7 7 8
*: 1: topical steroids; 2: topical vitamin D analogues; 3: nbUVB; 4: methotrexate; 5: cyclosporine; 6: acitretin
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 [1]. 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 [1]. 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 [1].

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 [2]. Previous favorable response to oral administration of tamoxifen has been reported in two dated cases of plaque psoriasis [3, 4]. Recently, Bhatia et al. [5] 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 [6]. 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.

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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.
[2] Behjati S, Frank MH. The effects of tamoxifen on immunity. Curr Med Chem 2009; 16(24): 3076-80.
[3] Boyd AS, King LE Jr. Tamoxifen-induced remission of psoriasis. J Am Acad Dermatol 1999; 41(5 Pt 2): 887-9.
[4] Ferrari VD, Jirillo A. Psoriasis and tamoxifen therapy: A case report. Tumori 1996; 82(3): 262-3.
[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.
[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.