IJD
Indian Journal of Dermatology
  Publication of IADVL, WB
  Official organ of AADV
Indexed with Science Citation Index (E) , Web of Science and PubMed
 
Users online: 594  
Home About  Editorial Board  Current Issue Archives Online Early Coming Soon Guidelines Subscriptions  e-Alerts    Login  
    Small font sizeDefault font sizeIncrease font size Print this page Email this page


 
Table of Contents 
E-IJD THERAPEUTIC ROUND
Year : 2016  |  Volume : 61  |  Issue : 1  |  Page : 119
New treatment options for mycosis fungoides


Department of Dermatology, University Hospital Birmingham, Birmingham, United Kingdom

Date of Web Publication15-Jan-2016

Correspondence Address:
Alexa Rose Shipman
Department of Dermatology, University Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB
United Kingdom
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.174085

Rights and Permissions

   Abstract 

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


Keywords: Cutaneous T-cell lymphoma, imiquimod, mycosis fungoides


How to cite this article:
Shipman AR, Scarisbrick J. New treatment options for mycosis fungoides. Indian J Dermatol 2016;61:119

How to cite this URL:
Shipman AR, Scarisbrick J. New treatment options for mycosis fungoides. Indian J Dermatol [serial online] 2016 [cited 2020 Sep 26];61:119. Available from: http://www.e-ijd.org/text.asp?2016/61/1/119/174085

What was known?
Standard treatments for cutaneous T-cell lymphoma are super potent topical steroids, topical nitrogen mustard surgery, and radiotherapy. For more extensive disease phototherapy, electron beam therapy, or systemic agents such as interferon alpha, bexarotene, or methotrexate can be used.



   Introduction Top


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 Top


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 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: Case series' reported results on the use of imiquimod 5% cream on mycosis fungoides


Click here to view


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 Top


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: Biopsy demonstrating dermal and follicular infiltrate (H and E, ×10) (a) with epidermotropism and  Pautrier microabscess More Details (H and E, ×40) (b) and mycosis fungoides cells with cerebriform nuclei (H and E, ×100) (c)

Click here to view
Figure 2: Images of patient's mycosis fungoides on the left groin (a and b) and natal cleft (c)

Click here to view
Figure 3: Images of patient's mycosis fungoides after 3 weeks of topical imiquimod treatment showing left groin (a) and natal cleft (b)

Click here to view


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 Top


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.

 
   References Top

1.
Ariffin N, Khorshid M. Treatment of mycosis fungoides with imiquimod 5% cream. Clin Exp Dermatol 2006;31:822-3.  Back to cited text no. 1
[PUBMED]    
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.  Back to cited text no. 2
    
3.
Chiam LY, Chan YC. Solitary plaque mycosis fungoides on the penis responding to topical imiquimod therapy. Br J Dermatol 2007;156:560-2.  Back to cited text no. 3
    
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.  Back to cited text no. 4
    
5.
Ardigò M, Cota C, Berardesca E. Unilesional mycosis fungoides successfully treated with imiquimod. Eur J Dermatol 2006;16:446.  Back to cited text no. 5
    
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.  Back to cited text no. 6
    
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.  Back to cited text no. 7
    
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.  Back to cited text no. 8
    
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.  Back to cited text no. 9
[PUBMED]    
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.  Back to cited text no. 10
    
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.  Back to cited text no. 11
    
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.  Back to cited text no. 12
    

What is new?
Topical imiquimod is a new option for treatment of refractory patches and plaques of MF.


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]



 

Top
Print this article  Email this article
 
 
  Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (869 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
   Imiquimod
   Clinical Experience
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed5566    
    Printed31    
    Emailed0    
    PDF Downloaded103    
    Comments [Add]    

Recommend this journal