07/12/2017 New treatment options for mycosis fungoides :[PAUTHORS], Indian Journal of Dermatology

E-IJD THERAPEUTIC ROUND

Year : 2016 | Volume : 61 | Issue : 1 | Page : 119-

New treatment options for mycosis fungoides

Alexa Rose Shipman, Julia Scarisbrick
Department of Dermatology, University Hospital Birmingham, Birmingham, United Kingdom

Correspondence Address:
Alexa Rose Shipman
Department of Dermatology, University Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB
United Kingdom

Abstract
The article discusses imiquimod treatment for refractory early stage mycosis fungoides, with a review of
the literature and three case studies.

How to cite this article:

Shipman AR, Scarisbrick J. New treatment options for mycosis fungoides.Indian J Dermatol 2016;61:119-119

How to cite this URL:

Shipman AR, Scarisbrick J. New treatment options for mycosis fungoides. Indian J Dermatol [serial online]
2016 [cited 2017 Dec 7 ];61:119-119
Available from: http://www.e-ijd.org/text.asp?2016/61/1/119/174085

Full Text

Introduction

Mycosis fungoides (MF) is the most prevalent cutaneous lymphoma. MF is a difficult disease to treat,
which is incurable and refractory to multiple treatments. Early stage patients present with patches and
plaques in the skin and the disease may progress slowly over many years (10-15 years). Progression to
an advanced stage with tumors, erythroderma, lymph node, or visceral involvement may occur with a
poor prognosis. Skin-directed treatments are preferred in patients with early stage disease, but options
are limited to topical corticosteroids, phototherapy, superficial radiotherapy, and nitrogen mustard
preparations. Patients frequently reach maximal lifetime dose of phototherapy or radiotherapy or
become refractory to the skin-directed therapy. Refractory early stage disease may require systemic
therapies typically used for the advanced stages of MF such as bexarotene, interferon, gemcitabine, or
multiagent chemotherapy. All these systemic therapies have significant adverse effects. Often
treatments that worked initially lose their efficacy over time. Imiquimod is an immune response
modifier that acts through Toll-like receptor 7 (TLR7). Reports of activity in patches and plaques of MF
are appearing in the literature. This article reviews the published literature and presents three cases of
refractory MF treated with topical imiquimod.

Imiquimod

Imiquimod is a synthetic compound belonging to the imidazoquinoline family of compounds and a TLR
agonist. [1] Imiquimod 5% (Aldara TM ) treats genital warts, superficial basal cell carcinomas, and
actinic keratosis, but also used for lentigo maligna, hemangiomas, and molluscum contagiosum.
Publications of use in MF have been single case reports [1],[2],[3],[4],[5],[6],[7] and four small cohort
studies with 3-6 patients [8],[9],[10],[11] [Table 1]. Chong's paper is the only randomized controlled

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07/12/2017 New treatment options for mycosis fungoides :[PAUTHORS], Indian Journal of Dermatology

trial with four patients, using the vehicle as control, and demonstrating an 8.9% decrease in surface
area compared to a 39.9% increase in control patches and plaques. [9]{Table 1}

Imiquimod works by stimulating TLR7 resulting in cytokine release and inflammatory reaction.
Interferon alpha production is increased, and the anti-apoptotic Bcl-2 molecule is suppressed. Studies
have demonstrated the recruitment of dendritic cells, CD8+ T cells, and natural killer cells. The
pathogenesis of cutaneous T-cell lymphoma is being elucidated by genetic and molecular studies and
includes derangements in the Bcl-2 pathway although the exact mechanism of imiquimod's action in
cutaneous lymphoma is still unclear. Resiquimod is another imidazoquinolone, which activates TLRs 7
and 8 and is being investigated in phase 2 trials in actinic keratosis, basal cell carcinoma, and
cutaneous T-cell lymphoma. [12]

We present three patients with refractory 1A-1B MF and combine our cohort with published series
[Table 1]. This gives an overall response rate to imiquimod of 80% (complete response in 9 of 20
patients [45%], partial response in 7/20 [35%]) with no response in 4/20 (20%).

Clinical Experience

A 61-year-old female presented with a 35 years history of refractory Stage IB MF [Figure 1] and [Figure
2]. Previous treatment included narrowband ultraviolet (UVB) B, psoralen and UVA, radiotherapy,
electron beam therapy, topical nitrogen mustard 4%, clobetasone propionate 0.05%, interferon alpha
(3 MU 3 times a week), and bexarotene 375 mg daily. Her treatment was complicated by multiple basal
cell carcinomas and renal cell carcinoma in March 2014. Topical imiquimod, 5%, was initiated
particularly concentrating on the genital area. Imiquimod was applied 5 days a week until clinical
improvement, with regular 4 weekly outpatient appointments. A dramatic improvement was noted
[Figure 3], the patient treated plaques on average for only 3 weeks to achieve prolonged (6 months)
clearance, although treatment caused significant lethargy, aching, and flu-like symptoms. Histological
clearance was demonstrated on repeat biopsy. Response was complete and durable at 9 months.
{Figure 1}{Figure 2}{Figure 3}

The next patient is a 49-year-old man with a 3 years history of a fixed plaque on his left upper thigh,
diagnosed histologically as MF, Stage IA. Previous treatment included clobetasone propionate 0.05%
and tacrolimus 0.1% ointments with progressive disease in the skin. Imiquimod 5% was prescribed,
daily, for 2 months and induced a significant inflammatory reaction but without clearance of the plaque.
Response was a stable disease.

Our final patient is a 49-year-old man who received topical imiquimod, 5%, after having failed
clobetasone propionate 0.05% ointment for the treatment of plaque Stage 1A MF. He was instructed to
use the cream 5 times a week for 16 weeks. After just 5 weeks, he developed an acute inflammatory
reaction and treatment was stopped. The skin healed within 4 weeks with a good response. Response
was a partial response and durable over 6 months.

Conclusion

Early stage MF may have a long course over many years and skin-directed treatments are preferred,
but these are limited in number and either maximal doses or loss of response typically occurs forcing
the use of systemic therapies. Topical imiquimod 5% is an alternative topical agent for early stage
refractory MF and may provide benefit in patients with plaques of MF resistant to other therapies.
Similarly to use in basal cell carcinoma and actinic keratosis an inflammatory reaction occurs. However,
the high response rate (80%) and possibility of durable complete responses in refractory disease make
it a useful addition to our armoury.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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07/12/2017 New treatment options for mycosis fungoides :[PAUTHORS], Indian Journal of Dermatology

References
1 Ariffin N, Khorshid M. Treatment of mycosis fungoides with imiquimod 5% cream. Clin Exp
Dermatol 2006;31:822-3.
2 Suchin KR, Junkins-Hopkins JM, Rook AH. Treatment of stage IA cutaneous T-Cell lymphoma with
topical application of the immune response modifier imiquimod. Arch Dermatol 2002;138:1137-9.
3 Chiam LY, Chan YC. Solitary plaque mycosis fungoides on the penis responding to topical
imiquimod therapy. Br J Dermatol 2007;156:560-2.
4 Soler-Machín J, Gilaberte-Calzada Y, Vera-Alvarez J, Coscojuela-Santaliestra C, Martínez-Morales J,
Osán-Tello M. Imiquimod in treatment of palpebral mycosis fungoides. Arch Soc Esp Oftalmol
2006;81:221-3.
5 Ardigò M, Cota C, Berardesca E. Unilesional mycosis fungoides successfully treated with
imiquimod. Eur J Dermatol 2006;16:446.
6 Dummer R, Urosevic M, Kempf W, Kazakov D, Burg G. Imiquimod induces complete clearance of a
PUVA-resistant plaque in mycosis fungoides. Dermatology 2003;207:116-8.
7 Onsun N, Ufacik H, Kural Y, Topçu E, Somay A. Efficacy of imiquimod in solitary plaques of mycosis
fungoides. Int J Tissue React 2005;27:167-72.
8 Deeths MJ, Chapman JT, Dellavalle RP, Zeng C, Aeling JL. Treatment of patch and plaque stage
mycosis fungoides with imiquimod 5% cream. J Am Acad Dermatol 2005;52:275-80.
9 Chong A, Loo WJ, Banney L, Grant JW, Norris PG. Imiquimod 5% cream in the treatment of
mycosis fungoides - A pilot study. J Dermatolog Treat 2004;15:118-9.
10 Coors EA, Schuler G, Von Den Driesch P. Topical imiquimod as treatment for different kinds of
cutaneous lymphoma. Eur J Dermatol 2006;16:391-3.
11 Martínez-González MC, Verea-Hernando MM, Yebra-Pimentel MT, Del Pozo J, Mazaira M, Fonseca E.
Imiquimod in mycosis fungoides. Eur J Dermatol 2008;18:148-52.
12 Meyer T, Surber C, French LE, Stockfleth E. Resiquimod, a topical drug for viral skin lesions and
skin cancer. Expert Opin Investig Drugs 2013;22:149-59.

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