In up to 71% of patients with Sweet’s syndrome (SS) there is no trigger for their condition. This is often referred to as classical (idiopathic) SS.
In 15-20% of cases, SS can develop secondary to blood disorders and cancer (Chen et al, 2016). This is called paraneoplastic or malignancy-associated Sweet’s syndrome (MASS). Myelodysplasia, otherwise known as myelodysplastic syndromes (MDS), is the most common cause of MASS.
Read more about triggers for SS here.
What is MDS?
MDS refers to a group of blood disorders in which the bone marrow produces too few mature and/or functioning red blood cells, white blood cells or platelets. It begins with a change to a normal stem cell in the bone marrow – a stem cell is a cell that has the potential to develop into many different cell types. Depending on what type of MDS you have, MDS may cause problems such as anaemia (a low number of red blood cells) or more severe problems such as leukaemia (a type of blood cancer).
Types of MDS.
There are several different types of MDS, and these types will either be ‘low-risk’ or ‘high-risk’.
Low-risk types of MDS progress slowly and can cause mild to moderate anaemia, or a decrease in other types of cells (John Hopkins Medicine, 2017). They might also affect a cell’s ability to function.
High-risk types of MDS can cause severe problems, and in high-risk patients, under-developed cells called blast cells make up more than 5% of the cells in the bone marrow. In normal conditions, these cells make up less than 5% of all cells in the marrow. The result is that the blast cells created do not develop into normal red cells, white cells and platelets, often causing the number of red blood cells, white blood cells and platelets in the body to fall. The low cell numbers can lead to anaemia, neutropenia (low neutrophil count, which affects the body’s ability to fight infection) or thrombocytopenia (low platelet count, which affects the body’s ability to help blood to clot). When MDS patients develop more than 20% blast cells, they are reclassified as having acute myelogenous/myeloid leukaemia (AML) with trilineage dysplasia (AML-TLD). Although acute leukaemia can progress quickly, many patients that have developed AML as a result of MDS continue to progress slowly. Treatments for MDS/AML patients may be the same as used for patients with other types of high-risk MDS or may be given treatments more typically used to treat AML.
Additional information for doctors: please see ‘Other information’ and read Pourmoussa and Kwan, 2017.
What are the symptoms of MDS?
Some patients with MDS have no symptoms, but symptoms can include (John Hopkins Medicine, 2017; MDS UK Patient Support Group, 2013; NHS Choices, 2014):
- Night sweats.
- Loss of appetite.
- Weight loss.
- Itchy skin.
- Bone pain.
- A shortage of red blood cells causing tiredness, shortness of breath, and pale skin.
- A shortage of normal white blood cells can lead to frequent or severe infections.
- A shortage of blood platelets can lead to easy bruising and bleeding. Some people notice frequent or severe nosebleeds or bleeding from the gums.
How is MDS diagnosed?
If doctors suspect you have MDS, they will need to examine cells from your blood and bone marrow to confirm the diagnosis (John Hopkins Medicine, 2017). A blood test called a full blood count (FBC) measures the amounts of different cells in the blood, such as the red blood cells, the white blood cells, and the platelets. Patients with MDS often have too few red blood cells, and may also have shortages of white blood cells and platelets. Some MDS patients’ blood samples contain blast cells. This is abnormal and often signals a bone marrow problem. Blood cells from MDS patients may also have abnormal sizes, shapes, or other features that can be seen under the microscope.
Doctors also need to do a bone marrow aspiration or a bone marrow biopsy, two tests that involve taking a sample of cells or tissue from the bone marrow to examine for abnormalities under a microscope. The doctors then will look at the size and shape of the cells and determine the percentage of marrow cells that are blasts.
A diagnosis of MDS is based on the presence of at least one of the following:
- More than 5% of the marrow cells are blast cells.
- Genetic abnormalities seen in the cells.
- Abnormal shape of cells in the blood or bone marrow.
How is MDS treated?
Research into a cure for MDS is ongoing, but there are many ways to manage the disease. Patients with very low risk who do not need blood transfusions may be able to go without treatment for years, as long as they are checked regularly by a doctor. Other patients need more aggressive therapies. One treatment regimen that has worked for some patients is high doses of chemotherapy followed by a stem cell transplant. Other MDS treatments aim to reduce the need for blood transfusions, decrease the risk of infection and increase quality of life.
Symptoms of MDS can be controlled with a combination of the following treatments:
- A blood transfusion – the drip may contain red blood cells, white blood cells or platelets, depending on which cells have been affected.
- Drugs to get rid of the excess iron in your blood (which builds up after a lot of blood transfusions).
- Injections of growth factor drugs such as erythropoietin (EPO) which encourages the bone marrow to make more red blood cells, or granulocyte-colony stimulating factor (G-CSF) which encourages the production of white blood cells. Please note that in rare cases, G-CSF can trigger SS.
- Antibiotics to treat infections, if your white blood cell count is low.
Drugs such as anti-thymocyte immunoglobulin (ATG) and ciclosporin reduce the activity of the immune system, allowing your bone marrow to make blood cells, and can help to control symptoms. However, these drugs are not suitable for everyone and work best in those who are young and who do not have a chromosome change associated with their condition.
If your risk of developing cancer is intermediate or high, you will need prompt treatment with chemotherapy or a stem cell transplant. Chemotherapy involves taking drugs that destroy the immature blood cells by disrupting their growth. The drugs are taken either as a tablet or an injection. If you are at higher risk of developing AML, your chemotherapy treatment will probably be similar to that used to treat AML.
Stem cell (bone marrow) transplant.
The only way to cure MDS is to have intensive treatment with a stem cell transplant from a donor – but this is not suitable for everyone. A stem cell transplant is very intense treatment that will generally only be offered if you are young and in reasonably good health (apart from your MDS). It helps if you have a suitable donor in your family (a close relative such as a brother or sister), although some patients can have a stem cell transplant using an unrelated donor with a matching tissue type. Treatment involves destroying your own bone marrow cells with chemotherapy and sometimes radiotherapy, before having stem cells from a donor fed into your bloodstream via a drip.
New biological drugs are being tested all the time. Biological therapies work by affecting the way your immune system works.
Myelodysplasia and Sweet’s syndrome.
Is malignancy-associated Sweet’s syndrome diagnosed in the same way as Sweet’s syndrome? Are there any differences?
Yes. MASS, including SS that has developed secondary to MDS, is diagnosed in the same way as SS. However, there can be some differences in what you might expect to find. For example:
- No fever: fever in MASS slightly less likely than in SS.
- No joint pain: joint pain in MASS less likely than in SS (Marcoval et al, 2016).
- Differences in skin biopsy result: a biopsy taken from a SS lesion commonly shows lots of neutrophils. However, in MASS, other types of cells are frequently seen alongside the neutrophils. Also, histiocytoid Sweet’s syndrome, a histological variant of SS, can sometimes be mistaken for leukaemia cutis. This is when leukaemia cells infiltrate the skin causing skin lesions to develop.
- Higher erythrocyte sedimentation rate (ESR): this is a blood test that detects inflammation in the body. It is commonly raised in both SS and MASS, but tends to be higher in MASS than SS (Casarin Costa et al, 2017).
- Normal to low white blood cell count, including neutrophil count: SS normally causes a raised white blood cell and neutrophil count (neutrophilia). In MASS, this is less likely to happen, and the white blood cell or neutrophil count may be normal or low (Casarin Costa et al, 2017; Cohen, 2007).
- Anaemia: very common in MASS, but uncommon in SS where there is no underlying cause (Cohen, 2007; Marcoval et al, 2016).
- Thrombocytopenia: quite common in MASS, but uncommon in SS (Cohen, 2007; Marcoval et al, 2016).
Can MDS make Sweet’s syndrome more difficult to treat and manage?
Yes, MDS can make SS more difficult to manage. This is mainly because the SS often won’t settle down until the MDS is treated and brought under control, and even then, may not resolve completely.
What is the treatment for MDS-associated Sweet’s syndrome?
Corticosteroids or steroids, e.g. prednisone, is the main form of treatment for both SS and MASS. However, MASS patients, including those with MDS, do not always respond as well to steroids as those with SS. Immunoglobulin therapy, thalidomide, or anakinra can be considered as additional or alternative treatments (Browning et al, 2005; Gill et al, 2010; Passaro et al, 2013). In patients with AML, dapsone, colchicine, and ciclosporin have been used to successfully treat MASS, even when steroids have not been effective (El-Khalawany et al, 2016).
Read more about treatment here.
Browning, C., Dixon, J., Malone, J. and Callen, J. (2005) Thalidomide in the treatment of recalcitrant Sweet’s syndrome associated with myelodysplasia. Journal of the American Academy of Dermatology, Aug; 53 (2 Suppl 1): S 135-8 (PubMed).
Chen, S., Kuo, Y., Liu, Y., Chen, B., Lu, Y. and Miser, J. (2016) Acute Myeloid Leukemia Presenting with Sweet Syndrome: A Case Report and Review of the Literature. Pediatrics and Neonatology (online).
El-Khalawany, M., Aboeldahab, S., Mosbeh, A. and Thabet, A. (2016) Clinicopathologic, immunophenotyping and cytogenetic analysis of Sweet syndrome in Egyptian patients with acute myeloid leukemia. Pathology, research and practice, Oct 26 (PubMed).
Gill, H., Leung, A., Trendell-Smith, N., Yeung, C. and Liang, R. (2010) Case Report. Sweet Syndrome due to Myelodysplastic Syndrome: Possible Therapeutic Role of Intravenous Immunoglobulin in Addition to Standard Treatment. Advances in Hematology. Article ID 328316 (online).
Marcoval, J., Martin-Callizo, C., Valenti-Medina, F., Bonfill-Orti, M. and Martinez-Molina, L. (2016) Sweet syndrome: long-term follow-up of 138 patients. Clinical and Experimental Dermatology, Oct;41(7):741-6 (PubMed).
NHS Choices (2014) Myelodysplastic syndrome (myelodysplasia) (online). Last reviewed 5/11/14, and accessed 2/03/17.
Passaro, G., Cerrito, L., Giovinale, M., Marinaro, A., Soriano, A,. Rigante, D. and Manna, R. (2013) P03-019 – Anakinra for sweet syndrome treatment. Pediatric Rheumatology Online Journal, Nov; 11(Suppl 1).
Hashemi, S., Fazeli , S., Vahedi, A. and Golabchifard, R. (2016) Rituximab for refractory subcutaneous Sweet’s syndrome in chronic lymphocytic leukemia: A case report. Molecular and Clinical Oncology, Mar;4(3):436-440 (online).
MDS UK Patient Support Group. Includes information on MDS symptoms, diagnosis, and treatment. Consultant Haematologist, Dr. Austin Kulasekararaj, Kings College Hospital, London, is associated with this group. He has experience of treating MASS.
Özdoğu, H., Yeral, M., and Boğa, C. (2017) An Unusual Giant Leg Ulcer as a Rare Presentation of Sweet’s syndrome in a Patient with Hairy Cell Leukemia Successfully Managed by Splenectomy. Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology, Mar 8 (PDF).
Rech, G., Balestri, R., La Placa, M., Magnano, M. and Girardelli, C. (2016) Single Nail Involvement as First Sign of Sweet’s Syndrome. Skin Appendage Disorders, Sep;2(1-2):61-62 (online). This is a case of Sweet’s syndrome developing secondary to essential thrombocythaemia.
Yaghmour, G., Wiedower, E., Yaghmour, B., Nunnery, S., Duncavage, E. and Martin, M. (2017) Sweet’s syndrome associated with clonal hematopoiesis of indeterminate potential responsive to 5-azacitidine. Therapeutic Advances in Hematology, Feb;8(2):91-95 (online).
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