Folliculotropic mycosis fungoides responding to bexarotene gel

Journal of Drugs in Dermatology, Feb, 2008 by Hobart W. Walling, Brian L. Swick, Pedram Gerami, Richard K. Scupham

Abstract

Folliculotropic mycosis fungoides (FMF) is an uncommon and potentially aggressive form of cutaneous T cell lymphoma (CTCL). Phototherapy, radiotherapy, and systemic chemotherapy are the most commonly employed treatment options, but may have limited success and common adverse reactions. Bexarotene gel is a topical retinoid X receptor (RXR) agonist with activity on the follicular unit that has not been previously reported in the management of FMF. The case of a 73-year-old male with FMF that responded to bexarotene gel is presented.

Introduction

Mycosis fungoides (MF) is the most common form of cutaneous T cell lymphoma (CTCL), with an annual incidence rate approaching 5 cases per 1 million population. (1) Typical progression from patch to plaque to tumor stage is described. (1) Recognized subtypes of MF include hypopigmented, hyperkeratotic, ichthyosis-like, bullous, granulomatous, and follicular. (1,2) Folliculotropic mycosis fungoides (FMF) is a unique clinicopathologic variant that may be associated with ordinary patch-plaque lesions of MF or may occur as the sole disease manifestation. (3) It is considered distinct from MF-associated follicular mucinosis. The case of a 73-year-old male with FMF that responded to the topical retinoid gel bexarotene is presented.

Case Report

A 73-year-old male presented for evaluation of plaques on the arms present for about 1 year. The patient reported a long history of eczema, which had always responded to intermittent applications of a midpotency topical corticosteroid. The plaques on the arms were initially attributed to lichen simplex chronicus, but had not responded to triamcinolone 0.1% cream, were increasingly pruritic, and had developed follicular prominence. The patient also reported the new onset of a pruritic plaque on the left preauricular cheek. The patient's past medical history was remarkable for coronary artery disease and hypertension.

A physical exam showed well-demarcated erythematous comedonal plaques on the forearms, with lichenification and prominent follicular plugging (Figure 1). An erythematous plaque without follicular prominence was also present on the left preauricular cheek. No lymphadenopathy was present.

Punch biopsy specimens from the plaques on the arm and cheek each showed a dense dermal and perifollicular infiltrate of atypical lymphocytes with hyperchromatic and irregularly-contoured cerebriform nuclei (Figure 2a). Atypical lymphocytes infiltrated the epidermis and follicular epithelium (Figure 2b). Multinucleated giant cells were seen surrounding ruptured follicles. T cell receptor gamma chain gene rearrangement studies were positive for a clonal cell population, detected with primer specific for the V1-8 region. Folliculotropic mycosis fungoides (FMF) was diagnosed. The CT of the chest, abdomen, and pelvis were normal. A complete metabolic panel and CBC with Sezary prep were within normal limits. The disease stage was consistent with 1A.

In discussing treatment options, the patient preferred to avoid oral medication or phototherapy, and also refused topical nitrogen mustard. A 4-week trial of clobetasol propionate applied twice daily was ineffective. Bexarotene gel was then prescribed, which the patient was instructed to apply every other day for the first 2 weeks, with emollient applied on the off days. The patient tolerated this treatment well, and was instructed to increase the frequency of bexarotene gel application to twice daily, which he did on weekdays only to avoid the irritation that developed with daily use. After 12 weeks of treatment, the plaques were noticeably less indurated and the follicular plugging had improved (Figure 3). Erythema at the treatment site was consistent with the irritant effect of the medication and improved with continued use. Additional improvement of the disease was seen with continued use of bexarotene gel over the next 4 months. No new lesions had developed and no signs of disease progression were noted.

[FIGURE 1 OMITTED]

Discussion

Folliculotropic mycosis fungoides (FMF) may present with a myriad of clinical findings and may mimic dozens of dermatologic entities. (4-6) It is generally difficult to treat and may be clinically aggressive. (4,7) A recent review of 43 cases of FMF found that 86% of cases involved the face, with a variety of clinical presentations including papules and plaques with follicular prominence with or without alopecia and scarring, as well as comedonal, acneiform, cystic, and prurigoiform lesions. (8) Intractable lesional pruritis is a common feature. (4,7)

[FIGURE 2 OMITTED]

Both conventional MF and FMF are characterized histologically by CD4-positive cerebriform lymphocytes, epidermotropism, and a propensity for Pautrier's microabscesses. It remains unclear whether the folliculotropism of FMF relates to specific T cell surface antigens of the T cells or pathology within the follicular epithelium. Previous studies of FMF have shown high densities of CDla-positive Langerhans cells in the follicular epithelium, and conspicuous eosinophils and plasma cells in the reactive infiltrate, and a tendency toward large cell transformation. (4,7)