Mycosis fungoides is cancer of a person's skin. It is very disfiguring and also life-threatening. Treatments will be adapted to the severity of the disease. A cure; however, remains a challenging goal for members of the pharmaceutical industry.
Mycosis fungoides - (Alibert-Bazin Syndrome or Granuloma Fungoides) - is the most common form of cutaneous T-cell lymphoma. It generally affects the skin, but may progress internally over time. Symptoms include rash, tumors, skin lesions, and itchy skin. Typical visible symptoms include rash-like patches, tumors, or lesions. Itching is common, in around 20% of patients, but is not universal.
Mycosis fungoides is a T-cell lymphoma of a person's skin. The disease is caused by the proliferation of T-lymphocytes, also known as, 'T-cells.' The cells bear the T-cell antigen CD4+ and often lack other average T-cell antigens such as CD7. In the year 1806 the term,' mycosis fungoides,' was first used by Jean-Louis Alibert, a French dermatologist, when describing a severe disorder in which tumors resembling mushrooms presented on a person's skin. The term, 'cutaneous T-cell lymphoma (CTCL),' was first used in 1979 to describe a heterogeneous group of malignant T-cell lymphomas with primary manifestation in the skin.
Mycosis fungoides is the most common type of CTCL and represents around two-percent of all lymphomas. It is a highly symptomatic and disfiguring disease which is life-threatening in the advanced stages and there are no spontaneous remissions. The cause remains unknown. Different theories implicate environmental or occupational exposures, viral exposures, or other forms of chronic antigenic stimulation. People usually survive for a number of years following a diagnosis, yet mycosis fungoides is largely incurable, except in a subset of very early stage people who might sustain durable remissions.
People Affected by Mycosis Fungoides
The incidence in Europe is around 1,200 new cases each year, with a prevalence of approximately 16,000 people. In America, the incidence is around 0.4 per 100,000 people and there are about 1,000 new cases every year. The prevalence of the disease is estimated to be 16,000-20,000. Mycosis fungoides manifests in a person's skin as a progressive form of disease which is more common in men with an age range of usually between 45-65. The disease might progress from eczema-like skin lesions to ulcerative tumors. The duration from the onset of a person's skin symptoms to diagnosis is around six years.
Early in the course of the disease, skin lesions might be non-specific, so confusion with benign conditions is common. Over a period of time, mycosis fungoides becomes more aggressive and in around twenty-percent of people will undergo a transformation to highly malignant lymphoma with widespread dissemination into different organs of the body. Late-stage disease is associated with a decline in the person's immune system. Death is often the result of systemic infection, particularly with Staphylococcus aureus, Pseudomonas aeruginosa or other deadly organisms.
Mycosis Fungoides Stages
During stage one of mycosis fungoides, the cancer only affects portions of the person's skin, which has red, scaly and dry patches. The lymph nodes are not larger than average. During stage two either of the following may be true. The person's skin has red, scaly and dry patches – yet no tumors. Lymph nodes are bigger than average, although they do not contain cancer cells. The person may have tumors on their skin. Their lymph nodes are either average or larger than average, yet do not contain cancer cells.
In stage three almost all of the person's skin is dry, red and scaly. The person's lymph nodes are either average or larger than average, although they do not contain cancer cells. During stage four the skin is involved along with either cancer cells being found in the person's lymph nodes, or cancer that has spread to the person's other organs such as lung or liver.
Current Treatments for Mycosis Fungoides
Relief of symptoms and improvement in cosmetics are the goals of treatment because it is generally agreed that mycosis fungoides is not something that is curable with currently available therapies. Standard and experimental forms of treatments include:
Every current form of therapy is associated with several unpleasant side-effects, to include the potential of inducing other forms of cancer. Some treatments have an inadequate efficacy, are time-consuming and/or cannot be repeated more than a few times.
Therapy for mycosis fungoides is stage-related. In early stage plaque disease, topical nitrogen mustard as a daily application to nearly all of the person's skin surfaces for 6-12 months is considered to be a first line therapy, with reported response rates ranging from 30-60%, to include up to 20% long-term complete responses. Responses are observed more commonly in people with few plaques as compared to people with generalized plaque involvement. Topical therapy with corticosteroids to inhibit intercellular adhesion and T-lymphocyte binding to the inner lining of blood vessels is also an approach that is common. Topical treatment with a retinoid gel is another option for treating early stages of the disease.
Photo chemotherapy, which is a combination of psoralen activated by ultraviolet light, is a commonly used form of therapy for stage two. For people with advanced forms, electron beam therapy is an effective initial therapy resulting in long-term remissions for some. The treatment is technically demanding and availability is limited in some treatment centers. In addition, radiation regimes may only be administered a few times due to late radiation effects on the person's skin.
Extracorporeal photo chemotherapy includes the removal of an amount of the person's blood by plasmapheresis, the treatment of the separated leukocytes with PUVA and the re-infusion of treated blood. The approach is thought to reverse the imbalance of T-cells to increase turnover of T-lymphocytes and is generally used for stage three or erythrodermic disease. Studies have shown complete response rates of greater than 50%.
Compounds reported to reveal clinical activity in mycosis fungoides of stage four and refractory forms of the disease include chemotherapeutic agents. Combination chemotherapy regimens such as CVP and CHOP are also applied. Drawbacks of combination chemotherapy are infectious complications. Short response duration often times outweighs the modest response rates. Skin-directed therapy with chemotherapeutic agents is used palliatively in people with advanced mycosis fungoides and induces fairly short-lived, although significant, responses.
'Retinoids,' are vitamin A analogues involved in modulation of cell growth. Their biological effects result from alterations in gene expressions that are mediated through two major types of nuclear receptors – the retinoic acid receptor and the retinoic X receptor. Recently, an orally administered RAR agonist has been approved in Europe as systemic treatment in people with refractory mycosis fungoides. RAR agonists are considered to block proliferation and promote differentiation of T-lymphocytes. Another approach that is new is the use of fusion toxin protein. The compound consists of diphtheria toxin conjugated to interleukin-3. The toxin is released inside of malignant cells expressing interleukin-2.