A Challenging Question Regarding the Use of Topical Corticosteroids for Mycosis Fungoides

IN THIS issue of the ARCHIVES, Zackheim and coworkers¹ address whether the use of topical corticosteroids is effective in the management of early-stage mycosis fungoides. They provide us with an answer and challenge us with a question! Although Cohen and Baer² and Farber et al^{3 - 4} demonstrated that topical corticosteroid use may be helpful, their trials were modest and incomplete. Zackheim et al¹ demonstrated that topical corticosteroids are effective agents in the treatment of patch-stage mycosis fungoides.

The challenging question that screams for further answer through further trials is "Where and when is the use of topical corticosteroids indicated?" The question can be further subdivided:

The following scenarios may demonstrate the use of topical corticosteroids in specific situations.

After careful explanation about the possible modalities of therapy, the patient decides that the potential adverse effects of radiation or chemical poisons are too foreboding. The therapist, based on the study of Zackheim et al,¹ can confidently begin a specific therapeutic program of topical potent corticosteroids for a set period to assess the response. According to the current study, 63% of such patients should achieve a complete response. This group of patients would lend itself to a long-term study that Zackheim et al would like to see done, and follow-up would be relatively easy with the performance of follow-up clinical examinations and biopsies. Median follow-up would be extended well beyond the 9 months that Zackheim et al documented.

A patient with stage IA or IB mycosis fungoides is anxious for cure. Therapy with electron beam radiation, topical nitrogen mustard, or psoralen–UV-A is initiated and, either concurrently or after treatment, topical corticosteroids are used on persistent as well as involuted areas of cutaneous involvement. This adjuvant use of corticosteroid therapy is easy on the patient and is rational therapy as Zackheim and colleagues clearly point out. With just a few major centers cooperating in a well-planned trial, the question as to whether the use of corticosteroids will prolong a complete response associated with more aggressive therapy should be relatively easily answered.

In the occasional young patient, the debilitated elderly patient, or the patient with minimal (1 or 2 patches) mycosis fungoides, topical corticosteroids could be used with more confidence given the current report.¹

Almost certainly many readers will have already used topical corticosteroids in patients similar to those presented in scenarios A and C. Until now, we have not had enough data on such patients so treated to offer anything more than reports of success.

Scenario B offers to the clinical researchers an ideal situation in which a multicenter cooperative study would be extremely valuable. For example, psoralen–UV-A therapy and concurrent (perhaps on alternate days) topical corticosteroid therapy to active or involuted patches in one center would be compared with a similar group of patients undergoing electron beam therapy who would then receive posttreatment or concurrent topical corticosteroids to all involved areas. To ensure that the patient populations are comparable, biopsy material could be exchanged from one center to another or 2 separate dermatopathologists in the one center would confirm the diagnosis of mycosis fungoides. The performance of posttreatment biopsies would be an essential part of the protocol, and clinical observation by 2 dermatologists would be appropriate.

Zackheim et al readily admit that there are weaknesses in their study, for example, the low percentage of posttreatment biopsy specimens to confirm complete remission and the relatively short median follow-up of 9 months. Nevertheless, the use of topical cotricosteroids clearly works: they are readily available and do not significantly alter the patient's quality of life, and as Zackheim et al point out, compared with other modalities of therapy, such as topical nitrogen mustard or electron beam radiation, corticosteroids have relatively few and minor adverse effects. Interestingly, a recent review⁵ of mycosis fungoides does not even list topical corticosteroids as a therapeutic option. The study by Zackheim et al¹ must alter that perception.

Finally, Zackheim et al ask the eternal question, "Is mycosis fungoides curable?" Jones⁵ suggests that 30% to 50% of patients with stage IA mycosis fungoides are free of disease 8 to 10 years after therapy with electron beam radiation. According to Vonderheid et al,⁶ topical mechlorethamine hydrochloride use may cure as many as 30% of similar patients with early-stage disease. Zackheim et al¹ of course cannot speculate as to whether patients with stage IA mycosis fungoides will be cured by the use of topical corticosteroids. They rightly point out that long-term studies will answer that question.

All of us have intentionally or unintentionally treated patients with early-stage mycosis fungoides with topical potent corticosteroids. The study by Zackheim et al has confirmed our clinical experience, namely, that topical corticosteroids have a place in the management of early-stage mycosis fungoides. Our challenge is to take this study and apply it to the treatment of patients with mycosis fungoides in the framework of our knowledge of other successful therapies.