Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Mycosis Fungoides

This rare disease is also known as granuloma fungoides or Alibert-Bazin syndrome.

What is Mycosis Fungoides?

• Mycosis Fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). Because of that, the terms MF and CTCL are often used interchangeably, and sometimes imprecisely. This can be a source of confusion. All cases of MF are CTCL, but not all CTCL cases are MF​
• MF-CTCL is a disease in which lymphocytes (a type of white blood cell) become malignant (cancerous) and affect the skin.​
• The disease affect males at twice the rate of females
• While the number of new cases diagnosed each year is relatively low (about 3,000), it is estimated that, since patients have a very long survival, there may be as many as 30,000 patients living with cutaneous lymphoma in the United States and Canada.​
• Due to the difficulty of diagnosing the disease in its early stages and the lack of an accurate reporting system, these numbers are estimates.​

How Do You Get It?

• Although there is continuing research, at this time no single factor has been proven to cause this disease. There is no supportive research indicating that it is genetic or hereditary in the vast majority of cases. Studies have failed to show connections between chemical exposure, environment, pesticides, radiation, allergies and occupations. ​
• Exposure to Agent Orange may be a risk factor for developing CTCL for veterans of the Vietnam War, but no direct cause-effect relationship has been established. 
• Very uncommon before age 20; most cases are diagnosed between 45-55 years old
• Males are more likely to be affected than females​

What Are the Symptoms?

Mycosis fungoides may go through the following phases:​

• Premycotic phase: A scaly, red rash in areas of the body that usually are not exposed to the sun. This rash does not cause symptoms and may last for months or years. It is hard to diagnose the rash as mycosis fungoides during this phase.​
• Patch phase: Thin, reddened, eczema -like rash. The rash may have a yellow color in darker skinned people.​
• Plaque phase: Small raised bumps (papules) or hardened lesions on the skin, which may be reddened.​ in darker skinned people, these raised areas may be silver or grayish colored.
• Tumor phase: Tumors form on the skin in the form of large, irregular lumps. These tumors may develop ulcers and the skin may get infected. Any area of skin may be affected.​

How Is It Treated?

• Expectant Policy
  • Usually suitable for those with stage IA disease in conjunction with symptomatic treatment if required; patients with single lesion may be considered for “curative therapy” with radiation therapy​
• PUVA
  • For patch/plaque disease; requires regular 2 or 3 times/week treatment; there may be limited availability of PUVA in nonmetropolitan areas; can be combined with retinoids/rexinoids. This is the most common first line treatment.​
• UVB
  • For patch stage disease as skin penetration not as deep as PUVA; requires regular 2 or 3 times/week treatment and generally more often considered in pediatric cases​
• Topical corticosteroids
  • Simple therapy; toxicities if extensive skin application for long periods​
• Bexarotene
  • Topical form is for limited sites of disease; simple therapy; local reactions may occur​
  • Oral bexarotene is generally well tolerated and convenient (oral capsule); some responses can be very durable; most common side effects are hypertriglyceridemia and hypothyroidism that usually require treatment; other relatively common side effects are rash and headache; can be used in conjunction with other therapies​
• Topical NM
  • For limited sites of disease or generalized involvement; local reactions occasionally problematic; ointment causes fewer reactions; availability of NM worldwide has been a problem recently​
• Topical carmustine
  • Rarely used now; for limited sites of disease; local reactions may occur; causes telangiectasias​
• Localized radiotherapy
  • Especially for patients with limited number of lesions and/or thickened plaques; durable remissions achieved
• TSEB
  • Patients with stage IB disease with relatively slow progression; limited availability; can take 6 to 10 weeks to complete​
• IFN-α monotherapy
  • Major difficulty is tolerance and compliance; some responses can be very durable; somewhat inconvenient (daily subcutaneous injection); most common side effect is fatigue, particularly in older patients; requires moderately high doses aiming for 3 to 5+ MU/day; monitor FBC and thyroid function; IFN-α can also be combined with PUVA, retinoids, bexarotene​
• Low-dose MTX
  • Generally well tolerated and convenient (oral weekly); dose-response effect is common and usually starts at 20 to 30 mg/week (up to 60-70 mg/week); some responses can be very durable; most common side effects are cytopenias and long-term risk of liver disease; very effective in patients with coexistent lymphomatoid papulosis; can be used in conjunction with other therapies, such as steroids, ECP, PUVA, IFN-α​
• Vorinostat
  • Only approved HDACi currently; generally well tolerated and convenient (oral daily); there appears to be a dose-response effect in some patients; most common SEs are fatigue, lethargy, mild/moderate thrombocytopenia and elevated creatinine and taste changes; can improve itch even when skin lesions remain; some responses can be very durable; virtually no data on use in combination with other therapies, such as PUVA, IFN-α, MTX, chemotherapy​
• Denileukin diftitox
  • Generally considered after trial of bexarotene and/or HDACi; inconvenient administration requiring daily dosing times 5 days every 3 weeks (6-8 courses); patient’s tumor must express CD25 (although responses are observed in patients with CD25− lesions); there can be substantial supportive care requirements for some patients during therapy who develop capillary leak syndrome; some responses can be very durable even in heavily pretreated patients​

Where Can I Learn More???

• Check out our cornerstone on this disease here.