Topical Chemotherapy and Immunotherapy of Mycosis Fungoides

The therapeutic use of topical contact sensitizers in benign dermatoses

“…5,6 An allergic response to nitrogen mustard (mechlorethamine) increased the likelihood of remission in spontaneously sensitized patients with cutaneous T-cell lymphoma, but sensitization rates were variable; in addition, the drug, when given systemically, is carcinogenic in animals. 7 Poison ivy (containing the allergen urushiol) was occasionally employed to treat AA in the past 8 but is an unsuitable sensitizer as it grows naturally throughout North America and cross-reacts with poison oak and poison sumac. Nickel, formalin and primin have been used for topical immunotherapy of AA and warts in spontaneously sensitized patients 9,10 but are not reliable allergens in the majority of individuals and also occur commonly in the environment.…”

“…In 1965 the alkylating agent tri‐ethyleneiminobenzoquinone (TEIB or Trenimon) was the first topical sensitizer used to treat cutaneous disease, in this case multiple superficial basal and squamous cell carcinomas, but it fell into disfavour when it was found to be mutagenic 5,6 . An allergic response to nitrogen mustard (mechlorethamine) increased the likelihood of remission in spontaneously sensitized patients with cutaneous T‐cell lymphoma, but sensitization rates were variable; in addition, the drug, when given systemically, is carcinogenic in animals 7 …”

“…In the last 30 years it has been widely used to induce hair growth in AA 8,14 and to cause involution of viral warts 10,15 . There have been a number of uncontrolled retrospective studies relating to its use in the treatment of basal and squamous cell carcinoma, 16,17 Bowen's disease and actinic keratoses, 16,18 cutaneous T‐cell lymphoma, 7,19 , 20 primary and secondary malignant melanoma 21–23 and, most recently, in human immunodeficiency virus (HIV) infection to attempt to raise CD4+ T‐lymphocyte counts and decrease the number of opportunistic infections 24 . Other conditions reported to have been treated successfully with DNCB in case reports or case series include lichen nitidus, 25 nodular prurigo, 26 vulvar intraepithelial neoplasia, 27 vulvar Paget's disease, 28 condylomata acuminata, 29 conjunctival squamous papillomata, 30 atopic eczema, 31 and systemic lupus erythematosus, in which it caused an improvement in immune parameters and relief of joint symptoms 32 .…”

Recent clinical evidence for topical mechlorethamine in mycosis fungoides

“…Delayed contact hypersensitivity, that is, allergic contact dermatitis from minor to blistering, is a common complication of topical mechlorethamine [30,43,46,47,50,[60][61][62][63], and more often noted following application of aqueous formulations versus ointmentbased. The recently approved topical mechlorethamine, VALCHLOR, is contraindicated in patients with known severe hypersensitivity to mechlorethamine [35].…”

“…There may be a small increased risk (1-5%) of developing nonmelanoma skin cancers (i.e., squamous cell carcinomas, basal cell carcinomas), especially with concomitant radiation and PUVA, or in areas that are exposed to the sun [30,47,48,60,62]. However, in a 30-year population-based cohort study from Danish registries [48].…”