What is Sezary Syndrome?
Sezary syndrome and mycosis fungoides are the most typical types of a skin condition called cutaneous T-cell lymphoma (CTCL). They can often be mistaken for harmless skin disorders due to their similar appearance, posing a hurdle to doctors trying to diagnose the condition. While mycosis fungoides is the most commonly occurring skin lymphoma, it only constitutes less than 1% of non-Hodgkin lymphomas (a group of cancers that develop in the lymph system). Experts believe that Sezary syndrome may gradually develop from mycosis fungoides or can appear spontaneously. There is substantial evidence showing a close relationship between Sezary syndrome and mycosis fungoides, considering them as parts of the wide variety of skin lymphomas out there.
Primary cutaneous lymphomas (PCL) are a type of non-Hodgkin lymphoma that is limited to the skin at the time of diagnosis, without affecting other parts of the body. They can arise from two types of cells: T-lymphocytes or B-lymphocytes, forming cutaneous T-cell lymphomas or cutaneous B-cell lymphomas respectively. Cutaneous T-cell lymphoma can be seen in two forms:
1. A mild form, which includes mycosis fungoides, lymphomatoid papulosis (a chronic, recurring skin disease), and a specific version of a large T-cell skin lymphoma.
2. A severe form, which consists of Sezary syndrome.
What Causes Sezary Syndrome?
Doctors and scientists haven’t yet determined the exact cause of two skin conditions called mycosis fungoides and Sezary syndrome.
Risk Factors and Frequency for Sezary Syndrome
Mycosis fungoides and Sezary syndrome are conditions that predominantly affect older people, particularly those over the age of 50. These conditions are more common in males than females, with twice as many males affected. Every year in the United States, there are about 0.8 to 0.9 cases of Sezary syndrome per million people. Mycosis fungoides and Sezary syndrome are also more common in Whites than Blacks. However, it’s important to note that there is no genetic link, meaning that having a family member with Sezary syndrome doesn’t increase your risk of developing the condition.
- Mycosis fungoides and Sezary syndrome often affect older people over 50.
- Both conditions are more common in males, with a ratio of 2 males for every female affected.
- In the US, there are about 0.8 to 0.9 cases of Sezary syndrome per million people every year.
- These conditions are more prevalent among Whites than Blacks.
- There is no need to worry about genetic risk, as having a family member with Sezary syndrome doesn’t make it more likely for you to get it.
Signs and Symptoms of Sezary Syndrome
Mycosis fungoides is a skin condition that can look similar to other skin diseases such as psoriasis, chronic eczema, atopic dermatitis, leprosy, or lichenoid pityriasis. Typically, the skin may show reddish patches or flat areas. These patches can appear as single or multiple spots, primarily found on the buttocks or thighs. These areas can be itchy and can stay the same, disappear, or slowly grow over time.
On the other hand, Sezary syndrome is a type of skin cancer with components found in the blood. It causes a wide-spread, intense, itchy skin rash that may either represent new areas of skin disease or progression of earlier patches.
- It is characterized by redness over most of the body (erythroderma), swollen lymph nodes (lymphadenopathy), and unusual circulating blood cells.
- Unlike Mycosis fungoides, which presents as a patch or plaque, Sezary syndrome shows up as a diffused skin rash.
- It typically affects about 80% of the total body surface area.
Sezary syndrome can be considered a stage of skin T-cell lymphoma that does not affect the bone marrow, though in advanced stages, it can involve the bone marrow. There may be other skin signs such as hair loss, thickened skin on the palms and soles (keratoderma), thickened nails, thick and rough skin (lichenification), and an outward turning of the lower eyelid (ectropion). Rarely, it could also affect internal organs. The itching is intense and can be disabling. Standard medication for itching, even in high doses, often doesn’t help. Treatment of the underlying cancer with steroids has been shown to help control the itching. Due to reduced immunity, people with Sezary syndrome are at a higher risk of getting additional infections (bacteria and viruses) and other types of cancer, such as Hodgkin and non-Hodgkin lymphomas.
Testing for Sezary Syndrome
If you’re examined by a doctor and they suspect you might have Sezary syndrome (a type of lymphoma), they might decide to a take a sample of your skin for testing. Although Sezary syndrome can affect large portions of the skin, it’s not as densely packed as mycosis fungoides (another type of skin lymphoma). So, the area of the skin that’s most swollen or thickened will typically be chosen for the biopsy.
In addition to a skin biopsy, your doctor might also recommend an excisional lymph node biopsy. This means they’ll surgically remove a lymph node (small glands that filter your lymph fluid) to examine it more closely. If it shows certain changes, it could suggest the presence of lymphoma.
In some situations, your blood can also be examined for unusual-looking cells known as Sezary or Lutzner cells. It’s worth noting that a smaller version of these cells can sometimes be seen in healthy individuals or those with a known cancer diagnosis.
Your doctor might also run a few more tests to see what types of cells are present in your blood, confirm if they’re T-cells (a type of white blood cell that helps fight disease), and check for other signs supporting a diagnosis of Sezary syndrome. If you have erythroderma, a condition where more than 80% of your body surface is red and itchy, a particular form of T-cell change observed through lab tests, and at least 1000 Sezary cells in each microliter of your blood, it suggests you have this condition.
Your doctor may also check for two other criteria: either a 10-fold or greater increase in your levels of certain T-cells, or higher levels of certain types of T-cells with an abnormal appearance.
All of these tests are part of Fr staging Sezary syndrome and mycosis fungoides (another type of lymphoma). This staging assesses how widespread the disease is, including the condition of your skin, lymph nodes, specific organ involvement, and how much of your blood has been affected by the disease. If you’re diagnosed with Sezary syndrome, you’ll typically be classed as having stage IVA1, IVA2, or IVB disease. Where you fall in this ranking will depend on if your lymph nodes and organs are showing signs of the disease.
Treatment Options for Sezary Syndrome
The treatment for Sezary syndrome, a type of skin cancer, depends on how far along the disease is. Usually, treatments are aimed at the body as a whole rather than just the skin. This could involve using medication on its own, or in combination with skin-specific therapy. Patients who are in stage IVA, which means the disease hasn’t spread to other organs, may receive treatment that involves circulating their blood through a machine that destroys the cancer cells (extracorporeal phototherapy) by using light. This is often combined with drugs that help the body’s immune system fight the cancer (called biological response modifiers), like retinoids and interferons. Other options include low-dose methotrexate and certain drugs that modify gene behavior (histone deacetylase inhibitors), with names like vorinostat and romidepsin. Various combinations of these treatments can be used.
Therapy that targets the skin may involve creams or medications (topical or systemic steroids), a type of chemotherapy cream (topical nitrogen mustard), light therapy (UVB and PUVA), or radiation therapy that treats the entire surface of the skin (total skin electron beam therapy). Additionally, radiation therapy can be used to manage cancer that’s affecting the skin and lymph nodes locally.
Patients in stage IVB, where the disease has spread to other organs, are typically treated with histone deacetylase inhibitors or targeted therapy, which specifically attacks cancer cells. Targeted therapies like brentuximab vedotin and mogamulizumab have been approved for use in these cases. Brentuximab vedotin is a drug that targets a protein on the surface of the cancer cells and blocks their growth. Mogamulizumab is a manufactured protein that helps the immune system kill cancer cells. These drugs are recommended for patients who have already tried other treatments.
If the disease comes back or if it doesn’t respond to treatment, other therapies can be tried, like chemotherapy drugs (like doxorubicin and gemcitabine), or certain drugs that interfere with the replication of cancer cells’ DNA (purine/pyrimidine analogs). Other options include a type of therapy that stimulates the immune system to fight cancer (immunotherapy) with drugs like pembrolizumab, alemtuzumab, bortezomib, and lenalidomide. In some cases, especially in younger patients with a higher risk of the disease getting worse, a procedure called an allogeneic hematopoietic stem cell transplantation can be performed to replace the person’s bone marrow and immune system.
Along with these treatment options, the severe itching (known as pruritis) that typically accompanies Sezary syndrome can be a significant issue. It can be managed with a variety of local or systemic treatments.
What else can Sezary Syndrome be?
Sezary syndrome is a medical condition that needs to be distinguished from several other disorders that may appear similar. These include:
- Mycosis fungoides (a type of skin lymphoma)
- Psoriasis (an autoimmune skin disease)
- Pityriasis rubra pilaris (a rare skin disorder)
- Dermatitis (inflammation of the skin)
- Hypereosinophilic syndrome (an overproduction of eosinophils, a type of white blood cell)
- Adult T-cell leukemia. (a blood cell cancer)
- Scabies (a skin infestation)
- Drug eruption (a skin reaction to medication)
- Graft-versus-host disease (a complication of bone marrow or stem cell transplant).
These are all conditions that doctors would consider when trying to diagnose Sezary syndrome, as symptoms might be similar.
What to expect with Sezary Syndrome
The potential outcome of a disease can be influenced by many factors. For skin conditions such as mycosis fungoides, a kind of skin lymphoma (cancer), certain factors can lead to a poorer prognosis. These include the classification of the patient’s skin, the stage of the disease they are in, elevated levels of the enzyme LDH, older age, concurrent health conditions, being male, belonging to certain racial groups, having an increase in a type of white blood cell called eosinophils, large cell transformation (which is a sign the lymphoma is becoming more aggressive), and a specific variant of mycosis fungoides that involves hair follicles (folliculotropic mycosis fungoides).
All these factors have been combined into various diagnostic tools that help doctors predict the course of the disease and guide treatment decisions. These include the CTCL Severity Index, the Cutaneous Lymphoma International Prognostic Index, and the Cutaneous Lymphoma International Consortium Prognostic Index. These indices help doctors monitor the disease and make the most appropriate decisions for each individual patient.
