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Don't Cede Early-Stage Mycosis Fungoides


 

Early stages of mycosis fungoides should be managed by dermatologists, not ceded to oncologists, as often happens. I would hate to see our great specialty demoted to the treatment of acne warts and cosmetic conditions. Let's not give away this disease, too. It belongs to us.

Especially early on, there's a very important role for skin-directed therapy—and we dermatologists are the experts, not the oncologists.

Abundant evidence shows that pathogenetic events leading to tumor progression in myosis fungoides (MF) occur in the skin, and that skin-directed therapy can induce prolonged remissions.

That's a point particularly worth emphasizing in light of the European Organisation for Research and Treatment of Cancer's current recommendation that "expectant management" is a legitimate option in patients with stage IA disease because they have a normal life expectancy. This recommendation is based on a misinterpretation of the data. What the guideline writers failed to realize is that these stage IA MF patients in the major reported series who are doing so well are actually receiving skin-directed treatment. We really don't have good data on the natural history of mycosis fungoides without treatment, so their conclusions are based on faulty information.

Patients with cutaneous T-cell lymphoma (CTCL) face numerous problems in which dermatologists have special expertise: severe pruritus, xerosis, cosmetic issues, an increase in skin cancers, and numerous cutaneous infectious complications.

In one study of 356 patients with MF or Sézary syndrome, the incidence of cutaneous bacterial infection was 17% per year (JAMA 1992;267:1354–8). The combined annual rate of cutaneous herpes simplex and herpes zoster infections was 3.8%. Extracutaneous CTCL involvement independently predicted a 12-fold increased risk of recurrent bacterial skin infection, a 28-fold increase in disseminated herpesvirus infection, and a rather remarkable 15-fold increase in death from infection.

We, as dermatologists, are very well qualified to manage these infections.

A study recently completed at Northwestern University in Chicago showed roughly a 40% Staphylococcus aureus colonization rate in CTCL patients. Worsening of the skin lesions or a new flare of erythroderma in CTCL patients may be related to a cutaneous infection rather than tumor progression.

At Northwestern, we recommend culturing patients often and utilizing frequent dilute bleach baths to help control S. aureus colonization levels. That's important because S. aureus superantigen has been shown to stimulate tumor-infiltrating lymphocytes, thus encouraging growth of malignant T cells. Treating a concurrent S. aureus skin infection may be sufficient to curtain a Sézary syndrome crisis, for example.

The quality of life issues raised by CTCL are often striking and here again dermatologists can be uniquely helpful. A survey of the Mycosis Fungoides Foundation membership found that 62% of respondents indicated their disease made them feel unattractive. A profound distress over health concerns was nearly universal (Cancer 2006;107:2504–11).

With skin-directed therapies, it is important to apply agents such as topical steroids, nitrogen mustard, and retinoids not only to the actual lesions but for a few centimeters beyond the actual clinical borders. Oncologists generally handle systemic therapies for CTCL, but there has been considerable interest among dermatologists in vorinostat (Zolinza), an oral inhibitor of histone deacetylase (HDAC) approved by the Food and Drug Administration in 2006 for the treatment of CTCL.

I have been less than favorably impressed by the low response rates—24% and 30% in two published trials—as well as the short duration of response and extensive side effects. In general, I think dermatologists feel comfortable prescribing oral treatment, but I would recommend caution on its use. The risk-benefit ratio is not that great, and in any case new HDACs with perhaps a better safety profile and efficacy are in the pipeline.

Dermatology has lost control of too many important diseases like sexually transmitted diseases, connective vascular conditions, and other allergy/immunology conditions. We should not lose track of mycosis fungoides, too.

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