Celebrate Sweet’s Syndrome UK Day on June 2nd!

June 2nd 2017 is Sweet’s Syndrome UK Day & the 5th anniversary of Sweet’s Syndrome UK.

What can you do to help spread awareness?

  1. Like our Facebook page, and share one of our posts.
  2. Join our HealthUnlocked forum. This is a FREE online community that’s available in English, Spanish, and Portuguese.
  3. Follow this blog.
  4. Follow on twitter @sweetsfiend.
  5. Follow on Google +.
  6. Talk about Sweet’s syndrome: share some posts; comment; blog about your experiences; tag a friend; tweet for Sweet’s.
  7. Share 5 key facts or 10 myths about Sweet’s syndrome.
  8. Make a donation to the Autoinflammatory Alliance. This is a US-based non-profit organization that helps children and adults with autoinflammatory conditions, including Sweet’s syndrome.
  9. Make a donation to Skin Care Cymru. This a Welsh charity that gives a voice to those with skin conditions in Wales.

BEE sweet and buzz for Sweet’s – help us spread the word!

Can vaccination trigger Sweet’s syndrome?

Sweet’s syndrome triggered by vaccination.

There is some medical evidence to show that certain vaccinations can potentially trigger Sweet’s syndrome, but this is incredibly rare, and it is important to take the following information into consideration:

  • Sweet’s syndrome is rare, probably affecting no more than 3 people per 10,000 (Zamanian and Ameri, 2007).
  • It mainly affects adults not children, and only 5% to 8% of cases have been in children (Sharma et al, 2015).
  • In some people, something is needed to trigger the onset of Sweet’s syndrome, but in up to 71% of people with Sweet’s syndrome there is no known trigger (Tam and Ingraffea, 2015).
  • Infection is a more common trigger for Sweet’s syndrome than vaccination, and as a result, Sweet’s syndrome tends to be more common in countries where people are more likely to develop infections (Ginarte and Toribio, 2011: 120). It is most commonly triggered by upper respiratory tract infection, but can be triggered by other infections too.
  • There have only been 10 cases of Sweet’s syndrome triggered by vaccination reported in medical literature in the past 42 years – globally! In some of these cases, a definite connection between the vaccination and Sweet’s syndrome was not established.
  • Sweet’s syndrome has only been associated with certain vaccinations and not others (see below).

Which vaccinations have been associated with Sweet’s syndrome?

Sweet’s syndrome has been associated with the following vaccinations:

  • Bacillus Calmette-Guerin (BCG or tuberculosis) (Carpentier et al, 2002: 82; Cruz-Velasquez et al, 2016). Two cases. One in 1986, occurring 15 days after vaccination, but the authors of the medical article that reported this did not control the tuberculin (Mantoux) test. One reported in 2002, occurring 10 days after vaccination.
  • Streptococcus pneumonia (Carpentier et al, 2002: 82; Cruz-Velasquez et al, 2016; Pedrosa et al, 2013). Two cases. One reported in 1990, occurring 4 days after vaccination following a splenectomy. One reported in 2013, and the first with the 13-valent conjugate vaccine.
  • Smallpox (Carpentier et al, 2002: 82; Cruz-Velasquez et al, 2016). Two cases reported in 1975, occurring 3 days after vaccination.
  • Influenza (Cruz-Velasquez et al, 2016; Hali et al, 2010, Jovanovic et al, 2005; Tan el al. 2006; Wolf et al. 2009). Four cases. One reported in 2005; in 2006, one case of bullous Sweet’s syndrome following vaccination in a HIV-infected patient; in 2009, neutrophilic dermatosis of the hands occurring 12 hours after vaccination; in 2010, one case of Sweet’s syndrome after H1N1 influenza (swine fluvaccination.

Do vaccinations trigger Sweet’s syndrome because they are toxic or contain dangerous chemicals?

No. Vaccinations do not trigger Sweet’s syndrome because they are toxic or contain dangerous chemicals, and anyone who tells you this is either lying to you, trying to scare you, or has no understanding of vaccinations and Sweet’s syndrome.

Why do vaccinations trigger Sweet’s syndrome?

Vaccination can trigger Sweet’s syndrome because of hypersensitivity reaction. This is not the same as allergic reaction.

What is hypersensitivity reaction?

Sweet’s syndrome is caused by errors in the innate immune system  the body’s most primitive, ‘hard-wired’ immune system, and a part of the immune system that doesn’t produce antibodies. Because of these errors, in some people with Sweet’s syndrome, their innate immune system responds to antigens – mainly proteins or sugars on the surface of a cell, or a non-living substance that a part of your immune system called the adaptive immune system sees as a foreign invader and produces antibodies in response to – in a way that it shouldn’t, i.e. is hypersensitive and goes into overdrive, overreacting to the presence of infectious, inflammatory, drug, or tumour cell antigens (Bhat et al, 2015: 257; Kasirye et al, 2011: 135). This means that the presence of antigens associated with certain health conditions, medications and vaccinations can potentially trigger Sweet’s syndrome by causing the innate immune system to unnecessarily activate or activate too many inflammatory cells, mainly white blood cells called neutrophils (Gosheger et al, 2002: 70). This then leads to the symptoms of Sweet’s syndrome.

If I have Sweet’s syndrome should I avoid having vaccinations?

No. Most people with Sweet’s syndrome don’t need to avoid having their vaccinations unless they can’t be vaccinated for other medical reasons, e.g. they are taking certain types of medication or have other health conditions. However, if the Sweet’s syndrome was initially triggered by a particular vaccination, e.g. influenza, then it would not be advisable to have the same kind of vaccination again.

How do I know if vaccination has triggered my Sweet’s syndrome?

Remember, Sweet’s syndrome triggered by vaccination is incredibly rare, but if it does happen, then symptoms usually develop within hours, days or less commonly, a few weeks after vaccination. Skin lesions sometimes appear at the vaccination site, but this can also happen because of the skin damage caused by having the vaccination (puncture wound from the needle) rather than the vaccine itself. This response is known as pathergy.

Are there other triggers for Sweet’s syndrome?

Yes, and aside from the triggers that have already been mentioned (infection, skin damage, and vaccination), other triggers for Sweet’s syndrome include:

  • Cancer and blood disorders in 15-20% of cases, e.g. solid tumours, and myelodysplastic syndrome which may progress to acute myeloid leukaemia (Chen et al, 2016).
  • Inflammatory bowel disease, e.g. Crohn’s disease and ulcerative colitis (Cohen, 2007).
  • Autoimmune conditions, e.g. rheumatoid arthritis and systemic lupus erythematosus.
  • Medications in up to 5% of cases.
  • Pregnancy in up to 2% of cases. This is probably associated with hormonal changes, but further research is required.
  • Overexposure to sunlight or ultraviolet (UV) light. This can sometimes trigger Sweet’s syndrome, but we are not entirely sure why this happens.

References.

Bhat, Y., Hassan, I., Sajad, P., Akhtar, S. and Sheikh, S. (2015) Sweet’s Syndrome: An Evidence-Based Report. Journal of the College of Physicians and Surgeons – Pakistan, Jul;25(7):525-7 (PubMed).

Carpentier, O., Piette, F. and Delaporte, E. (2002) Sweet’s syndrome after BCG vaccination. Acta Dermato-Venereologica;82(3):221 (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).

Cohen, P. (2007) Sweet’s syndrome – a comprehensive review of an acute febrile neutrophilic dermatosis (online).

Cruz-Velásquez, G., Pac Sha, J., Simal Gil, E. and Gazulla, J. (2016). Aseptic meningitis and anti-β2-glycoprotein 1 antibodies in Sweet syndrome. Neurologia (Barcelona, Spain), Jul 21 (0nline). Article in Spanish, use translate

Ginarte, M. and Toribio, J. (2011) Sweet Syndrome. In Dr. Fang-Ping (Ed.) Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights. Croatia or China: Intech, pp. 119-132 (PDF). 

Gosheger, G., Hillman, A., Ozaki, T., Buerger, H. and Winklemann, W. (2002) Sweet’s Syndrome Associated With Pigmented Villonodular Synovitis. Acta Orthopædica Belgica, Feb;68(1):68-71 (PubMed).

Hali, F., Sbai, M., Benchikhi, H., Ouakadi, A. and Zamiati, S. (2010) [Sweet’s syndrome after H1N1 influenza vaccination]. Annales de Dermatologie et de Venereologie,  Nov;137(11):740-1 (PubMed).

Jovanovic, M., Poljacki, M., Vujanovic, L. and Duran, V. (2005) Acute febrile neutrophilic dermatosis (Sweet’s syndrome) after influenza vaccination. Journal of the American Academy of Dermatology, Feb;52(2):367-9 (PubMed).

Kasirye, Y., Danhof, R., Epperla, N. and Garcia-Montilla, R. (2011) Sweet’s Syndrome: One Disease, Multiple Faces. Clinical Medicine & Research, Nov;9(3-4):134-136 (online).

Pedrosa, A., Morais, P., Nogueira, A., Pardal, J. and Azevedo, F. (2013) Sweet’s syndrome triggered by pneumococcal vaccination. Cutaneous and Ocular Toxicology, Sep;32(3):260-1 (PubMed).

Sharma, A., Rattan, R., Shankar, V., Tegta, G. and Verma, G. (2015) Sweet’s syndrome in a 1-year-old child. Indian Journal of  Paediatric Dermatology;16:29-31 (online).

Tam, C. and Ingraffea, A. (2015) Case Letter: Sweet Syndrome Presenting With an Unusual Morphology. Cutis, Aug;96(2):E9-E10 (online).

Tan, A., Tan. H., and Lim, P. (2006) Bullous Sweet’s syndrome following influenza vaccination in a HIV-infected patient. International Journal of Dermatology, Oct;45(10):1254-5 (PubMed). 

Zamanian, A. and Ameri, A. (2007) Acute febrile neutrophilic dermatosis (Sweet’s syndrome): a study of 15 cases in Iran. International Journal of Dermatology, Jun;46(6):571-4 (PubMed).

Wolf, R., Barzilai, A. and Davidovici, B. (2009) Neutrophilic dermatosis of the hands after influenza vaccination. International Journal of Dermatology, Jan;48(1):66-8 (PubMed).

© 2012-2017 Sweet’s Syndrome UK

Can medication trigger Sweet’s syndrome?

Updated 03/03/17.

Can medication trigger Sweet’s syndrome?

Yes. In up to 5% of cases, Sweet’s syndrome is triggered by medication (Cohen, 2007). This is known as drug-induced Sweet’s syndrome.

How will you know if your Sweet’s syndrome has been triggered by medication?

In at least 95% of patients with Sweet’s syndrome, their condition is not triggered by medication. However, drug-induced Sweet’s syndrome should be considered if:

  • Your Sweet’s syndrome developed not long after a particular medication was started.
  • Your Sweet’s syndrome has continued to persist for many months or years, even after treatment.

What will happen if your doctor thinks you have drug-induced Sweet’s syndrome?

Unfortunately, there is no special test to tell you whether or not your Sweet’s syndrome is being triggered by medication. However, if it is suspected that your Sweet’s syndrome is drug-induced, your doctor will:

  • Stop the medication that is possibly causing your Sweet’s syndrome. Your Sweet’s syndrome should then start to settle down, but you may still need treatment.
  • Re-introduce the medication (rechallenge) to see if your Sweet’s syndrome flares-up again. Sometimes, your doctor will decide that this is not necessary.

Why does medication trigger Sweet’s syndrome in some people?

Drug-induced Sweet’s syndrome is often caused by hypersensitivity reaction, but it can sometimes happen for other reasons too, e.g. a treatment that increases white cell production, or causes hormonal changes. Read more here.

What is hypersensitivity reaction, and is it the same as allergic reaction?

No. Hypersensitivity reaction is not the same as allergic reaction.

Hypersensitivity reaction.

Sweet’s syndrome is caused by errors in the innate immune system  the body’s most primitive, ‘hard-wired’ immune system, and a part of the immune system that doesn’t produce antibodies. Because of these errors, in some people with Sweet’s syndrome, their innate immune system responds to antigens – mainly proteins or sugars on the surface of a cell, or a non-living substance that a part of your immune system called the adaptive immune system sees as a foreign invader and produces antibodies in response to – in a way that it shouldn’t, i.e. is hypersensitive and goes into overdrive, overreacting to the presence of infectious, inflammatory, drug, or tumour cell antigens (Bhat et al, 2015: 257; Kasirye et al, 2011: 135). This means that the presence of antigens associated with certain health conditions, medications and vaccinations can potentially trigger Sweet’s syndrome by causing the innate immune system to unnecessarily activate or activate too many inflammatory cells, mainly white blood cells called neutrophils (Gosheger et al, 2002: 70). This then leads to the symptoms of Sweet’s syndrome. Read more here.

Allergic reaction.

The most common type of allergy is an IgE-mediated allergy. This is an adverse reaction that the body has to a particular substance that is foreign to the body, e.g. a food, pollen, or pet hair, that does not normally cause harm. This substance is known as an allergen (a type of antigen). Allergic reaction occurs when the immune system mistakes an allergen for a foreign invader such as a bacteria or virus. The adaptive immune system then quickly produces allergen-specific immunoglobulin E (IgE) antibodies in response to this, in order to fight the allergen off. Chemicals such as histamine are also produced, with the overall immune response causing the symptoms of allergy.

What medications have been reported to have triggered Sweet’s syndrome?

Medications that have been reported to trigger Sweet’s syndrome include:

Analgesics (non-opioids).

  • Paracetamol (triggered a Sweet’s syndrome-like condition) (Culla et al, 2014).

Antibiotics.

  • Amoxicillin (possibly) (Volpe, 2016).
  • Clindamycin (Cruz-Velasquez et al, 2016).
  • Tetracycline.
  • Doxycycline (Ibid).
  • Minocycline (Cohen, 2007).
  • Nitrofurantoin.
  • Norfloxacin.
  • Ofloxacin.
  • Trimethoprim/sulfamethoxazole.
  • Quinupristin/dalfopristin (Ibid).
  • Piperacillin/tazobactam (Cruz- Velasquez et al, 2016).

Anti-epileptics.

  • Carbamazepine (Cohen, 2007).
  • Diazepam.

Anti-hypertensives.

  • Hydralazine (Cohen, 2007).

Anti-malarials.

  • Chloroquine (Cruz-Velasquez et al, 2016).

Anti-manic agents.

  • Lithium (Xenophontos et al, 2016).

Anti-neoplastics.

  • Bortezomib (Llamas-Velasco et al, 2015).
  • Decitabine (Kasirye et al, 2011: 134).
  • Imatinib mesylate (Cohen, 2007).
  • Ipilimumab (Gormley et al, 2014).
  • Lenalidomide (Cohen, 2007).
  • Obinutuzumab (triggered a Sweet’s syndrome-like condition) (Korman et al, 2016).

Anti-viral drugs.

  • Abacavir (Cohen, 2007).
  • Acyclovir (Cruz-Velasquez et al, 2016).
  • Interferon-α.

Colony stimulating factors.

  • Granulocyte-colony stimulating factor (G-CSF). This is the most common treatment to trigger Sweet’s syndrome (Cohen, 2007).
  • Granulocyte-macrophage-colony stimulating factor (GM-CSF).
  • Pegfilgrastim (Ibid).

Contraceptives.

  • Levonorgestrel/ethinyl estradiol (Triphasil) (Cohen, 2007).
  • Levonorgestrel-releasing intrauterine system (Mirena).

Diuretics.

  • Furosemide (Cohen, 2007).

Immunosuppressants.

  • Azathioprine (Salem et al, 2015). Sometimes, azathioprine-induced Sweet’s syndrome can be confused with azathioprine hypersensitivity syndrome (AHS) (Aleissa et al, 2017). This is a rare adverse reaction occurring a few days to weeks after azathioprine has been given. AHS can sometimes mimic Sweet’s syndrome, and an azathioprine rechallenge is not advised, as it may lead to a severe adverse reaction or even death.

Nonsteroidal anti-inflammatory drugs (NSAIDs).

  • Celecoxib (Cohen, 2007; Oh et al, 2016).
  • Rofecoxib (Cruz-Velasquez et al, 2016).
  • Diclofenac (Cohen, 2007; Gupta et al, 2015).

Platelet aggregation inhibitors.

  • Ticagrelor (Ikram and Veerappan, 2016).

Proton-pump inhibitors.

  • Esomeprazole (Cohen, 2015).
  • Omeprazole.

Psychotropics.

  • Clozapine (Cohen, 2007).
  • Amoxapine (Cruz-Velasquez et al, 2016).
  • Diazepam.
  • Lormetazepam (Ibid).

Retinoids.

  • All-trans retinoic acid (Cohen, 2007; Tam and Ingraffea, 2015).
  • 13-cis-retinoic acid (isotretinoin) (Cohen, 2007).

Sulfa drugs.

  • Sulfasalazine (Romdhane et al, 2016).

Thyroid drugs.

  • Propylthiouracil (Cruz-Velasquez et al, 2016).

Vaccinations.

  • Bacillus Calmette-Guerin (BCG or tuberculosis) (Carpentier et al, 2002: 82; Cruz-Velasquez et al, 2016). Two cases. One in 1986, occurring 15 days after vaccination, but the authors of the medical article that reported this did not control the tuberculin (Mantoux) test. One reported in 2002, occurring 10 days after vaccination.
  • Streptococcus pneumonia (Carpentier et al, 2002: 82; Cruz-Velasquez et al, 2016; Pedrosa et al, 2013). Two cases. One reported in 1990, occurring 4 days after vaccination following a splenectomy. One reported in 2013, and the first with the 13-valent conjugate vaccine.
  • Smallpox (Carpentier et al, 2002: 82; Cruz-Velasquez et al, 2016). Two cases reported in 1975, occurring 3 days after vaccination.
  • Influenza (Cruz-Velasquez et al, 2016; Hali et al, 2010, Jovanovic et al, 2005; Tan el al, 2006; Wolf et al. 2009). Four cases. One reported in 2005; in 2006, one case of bullous Sweet’s syndrome following vaccination in a HIV-infected patient; in 2009, neutrophilic dermatosis of the hands occurring 12 hours after vaccination; in 2010, one case of Sweet’s syndrome after H1N1 influenza (swine fluvaccination.

Sweet’s syndrome triggered by vaccination is incredibly rare (only 10 cases reported in medical literature in the past 42 years), and a definite connection has not been established in all the listed cases. Also, as infection is a more common trigger for Sweet’s syndrome than vaccination, you may be more likely to develop Sweet’s syndrome as a result of not having your vaccinations than having them.

If someone tells you that Sweet’s syndrome is triggered by vaccination because they are toxic or poisonous or contain dangerous chemicals, then they either have no understanding of Sweet’s syndrome and vaccinations, are not telling you the truth, or are trying to scare you, and will have no evidence to support their claims. Sweet’s syndrome triggered by vaccination occurs because of errors in the innate immune system, and this part of the immune system responding to antigens in the way that it shouldn’t. It is nothing to do with vaccines containing dangerous chemicals.

Xanthine oxidase inhibitors.

  • Allopurinol (Polimeni et al, 2015).

Other.

  • X-ray contrast agents (Cruz-Velasquez et al, 2016).

References.

Aleissa, M., Nicol, P., Godeau, M., Tournier, E., de Bellissen, F., Robic, M., Livideanu, C., Mazereeuw-Hautier, J. and Paul, C. (2017) Azathioprine Hypersensitivity Syndrome: Two Cases of Febrile Neutrophilic Dermatosis Induced by Azathioprine. Case Reports in Dermatology, Jan 19;9(1):6-11 (0nline).

Bhat, Y., Hassan, I., Sajad, P., Akhtar, S. and Sheikh, S. (2015) Sweet’s Syndrome: An Evidence-Based Report. Journal of the College of Physicians and Surgeons – Pakistan, Jul;25(7):525-7 (PubMed).

Carpentier, O., Piette, F. and Delaporte, E. (2002) Sweet’s syndrome after BCG vaccination. Acta Dermato-Venereologica;82(3):221 (PubMed).

Cohen, P. (2015) Proton pump inhibitor-induced Sweet’s syndrome: report of acute febrile neutrophilic dermatosis in a woman with recurrent breast cancer. Dermatology Practical & Conceptual, April; 5(2):113–119 (online).

Cohen, P. (2007) Sweet’s syndrome – a comprehensive review of an acute febrile neutrophilic dermatosis (online).

Cruz-Velásquez, G., Pac Sha, J., Simal Gil, E. and Gazulla, J. (2016). Aseptic meningitis and anti-β2-glycoprotein 1 antibodies in Sweet syndrome. Neurologia (Barcelona, Spain), Jul 21 (0nline). Article in Spanish, use translate.

Culla, T., Amayuelas, R., Diez-Canseco, M., Fernandez-Figueras, M., Giralt, C. and Vazquez, M. (2014) Neutrophilic dermatosis (Sweet’s syndrome-like) induced by paracetamol. Clinical and Translational Allergy, Jul; 4(Suppl 3): P83 (online).

Gormley, R., Wanat, K., Elenitsas, R., Giles, J., McGettingan, S., Schucher, L. and Takeshita, J. (2014) Ipilimumab-associated Sweet syndrome in a melanoma patient. Journal of the American Academy of Dermatology, Nov;71(5):e211-3 (online).

Gosheger, G., Hillman, A., Ozaki, T., Buerger, H. and Winklemann, W. (2002) Sweet’s Syndrome Associated With Pigmented Villonodular Synovitis. Acta Orthopædica Belgica, Feb;68(1):68-71 (PubMed).

Gupta, S., Bajpai, M. and Uraiya, D. (2015) Diclofenac-induced sweet’s syndrome. Indian Journal of Dermatology;60:424 (online).

Hali, F., Sbai, M., Benchikhi, H., Ouakadi, A. and Zamiati, S. (2010) [Sweet’s syndrome after H1N1 influenza vaccination]. Annales de Dermatologie et de Venereologie,  Nov;137(11):740-1 (PubMed).

Ikram, S. and Veerappan, V. (2016) Ticagrelor-induced Sweet Syndrome: an unusual dermatologic complication after percutaneous coronary intervention. Cardiovascular Intervention and Therapeutics, May 4th (PubMed).

Jovanovic, M., Poljacki, M., Vujanovic, L. and Duran, V. (2005) Acute febrile neutrophilic dermatosis (Sweet’s syndrome) after influenza vaccination. Journal of the American Academy of Dermatology, Feb;52(2):367-9 (PubMed).

Kasirye, Y., Danhof, R., Epperla, N. and Garcia-Montilla, R. (2011) Sweet’s Syndrome: One Disease, Multiple Faces. Clinical Medicine & Research, Nov;9(3-4):134-136 (online).

Korman, S., Hastings, J. and Byrd, J. (2016) Sweet-Like Eruption Associated With Obinutuzumab Therapy for Chronic Lymphocytic Leukemia. JAMA Dermatology, Nov 23 (online).

Llamas-Velasco, M., Concha-Garcon, M., Fraga, J. and Arageus, M. (2015) Histiocytoid sweet syndrome related to bortezomib: A mimicker of cutaneous infiltration by myeloma. Indian Journal of Dermatology, Venereology and Leprology, May;81:305-6 (online).

Oh, E., Shin, J., Hong, J., Kim, J., Ro, Y. and Ko, J. (2016) Drug-induced bullous Sweet’s syndrome by celecoxib. The Journal of Dermatology, Apr 6 (PubMed).

Pedrosa, A., Morais, P., Nogueira, A., Pardal, J. and Azevedo, F. (2013) Sweet’s syndrome triggered by pneumococcal vaccination. Cutaneous and Ocular Toxicology, Sep;32(3):260-1 (PubMed).

Polimeni. G., Cardillo, R., Garaffo, E., Giardina, C., Macrì, R., Sirna, V.,  Guarneri, C. and Arcoraci, V. (2015) Allopurinol-induced Sweet’s syndrome. International Journal of Immunopathology and Pharmacology, Dec 18th (PubMed).

Romdhane, H., Mokni, S., Fathallah, N., Ghariani, N., Sriha, B. and Salem, B. (2016) Sulfasalazine-induced Sweet’s syndrome. Therapie, Jun;71(3):345-347 (PubMed).

Salem, C., Larif, S., Fathallah, N., Slim, R., Aounallah, A. and Hmouda, J. (2015) A rare case of azathioprine-induced Sweet’s syndrome in a patient with Crohn’s disease. Current Drug Safety, July (PubMed online).

Tam, C. and Ingraffea, A. (2015) Case Letter: Sweet Syndrome Presenting With an Unusual Morphology. Cutis, Aug;96(2):E9-E10 (online).

Tan, A., Tan. H., and Lim, P. (2006) Bullous Sweet’s syndrome following influenza vaccination in a HIV-infected patient. International Journal of Dermatology, Oct;45(10):1254-5 (PubMed). 

Volpe, M. (2016) Sweet Syndrome Associated with Upper Respiratory Infection and Amoxicillin Use. Cureus, Apr; 8(4): e568 (online).

Wolf, R., Barzilai, A. and Davidovici, B. (2009) Neutrophilic dermatosis of the hands after influenza vaccination. International Journal of Dermatology, Jan;48(1):66-8 (PubMed).

Xenophontos, E., Ioannou, A., Constantinides, T. and Papanicolaou. E. (2016) Sweet syndrome on a patient with autoimmune hepatitis on azathioprine and CMV infection. Oxford Medical Case Reports, Feb; (2): 24–27 (online).

Other information.

Cetin, G., Sayarlioglu, H., Erhan, C., Kahraman, H., Ciralik, H. and Sayarlioglu, M. (2014) A case of neutrophilic dermatosis who develop palpable purpura during the use of montelukast. European Journal of Dermatology,  Dec; 1(4): 170–171 (online).

© 2012-2017 Sweet’s Syndrome UK

Pregnancy-associated Sweet’s syndrome

Links checked on 30/03/17.

Can Sweet’s syndrome be triggered by pregnancy?

Yes, but it’s rare. Only about 2% of cases of Sweet’s syndrome are associated with pregnancy (Chebbi and Josephine, 2014).

How many cases have been reported?

By the end of 2014, there had been at least 10 cases of pregnancy-associated Sweet’s syndrome reported in literature (Chebbi and Josephine, 2014; Serrano-Falcón and Serrano-Falcón, 2010: 559). However, it is possibly being under-reported and underdiagnosed due to:

  • A lack of awareness and knowledge of pregnancy-associated Sweet’s syndrome.
  • The variability of Sweet’s syndrome symptoms, and on rare occasions, skin lesions not being present. This means that a diagnosis of Sweet’s syndrome may be not be considered or dismissed.
  • Pregnancy affecting blood results (Serrano-Falcón and Serrano-Falcón, 2010: 559). This means that the blood results of someone with pregnancy-associated Sweet’s syndrome might show something different from what you would expect to find.

Can pregnancy-associated Sweet’s syndrome be confused with other skin conditions?

Yes. It may be confused with urticarial vasculitis, eosinophilic panniculitis, and herpes gestationis (Serrano-Falcón and Serrano-Falcón, 2010: 558).

What causes pregnancy-associated Sweet’s syndrome?

We are not entirely sure what causes pregnancy-associated Sweet’s syndrome in some women, but it may be linked to hormonal changes and increased progesterone or oestrogen levels (Serrano-Falcón and Serrano-Falcón, 2010: 558).

What are the symptoms of pregnancy-associated Sweet’s syndrome?

Read about the symptoms of Sweet’s syndrome here.

How  is it diagnosed?

Read about how Sweet’s syndrome is diagnosed here.

How is pregnancy-associated Sweet’s syndrome treated?

  • Systemic corticosteroids (steroids) such as Prednisone are the main form of treatment. Treatment should start with 1mg/kg/day or less, in a single dose taken in the morning, and should be tapered off until the minimum effective dose is determined (Serrano-Falcón and Serrano-Falcón, 2010:559).
  • Steroid creams can be used if the skin lesions are small and in one area, and if there are few other symptoms.
  • Other treatment options to be considered include colchicine and indomethacin.

Are there treatments that should be avoided?

Yes. Certain medications that are sometimes used to treat Sweet’s syndrome are not safe to use during pregnancy. These include:

  • Potassium iodide.
  • Immunosuppressants such as ciclosporin, azathioprine, and methotrexate.
  • Biologics such as infliximab, adalimumab, and etanercept.

Does Sweet’s syndrome cause complications or affect how you will be cared for during pregnancy?

Sweet’s syndrome does not tend to cause complications during pregnancy or affect the baby. However, as a precaution, your doctor or nurse will need to monitor you as for an at-risk pregnancy.

Can pregnancy-associated Sweet’s syndrome come back once it has been treated?

Pregnancy-associated Sweet’s syndrome normally settles after treatment. This may take up to 7 days, weeks or months. Sometimes, the Sweet’s syndrome doesn’t completely settle until delivery of the baby, and may flare-up again with later pregnancies (Chebbi and Josephine, 2014).

N.B. There are some cases of pregnancy-associated Sweet’s syndrome that have not resolved after delivery, but have not been reported in literature. However, this may be for reasons such as infection, underlying illness, or medication.

References.

Chebbi, W. and Josephine M. (2014) Sweet syndrome during pregnancy: a rare entity not to ignore. The Pan African Medical Journal, 18: 185 (online). Article in French. Use translate.

Serrano-Falcón, C. and Serrano-Falcón, M. (2010) Sweet’s syndrome in a pregnant women. Actas Dermo-Sifiliograficas, Jul;101(6):558-9 (online).

Further information.

Giovanna Brunasso, A. and Massone, C. (2008) Clinical images. Sweet syndrome during pregnancy. CMAJ: Canadian Medical Association Journal, Oct 21;179(9):967 (online).

© 2012-2017 Sweet’s Syndrome UK

A wheat-free or gluten-free diet is not a treatment for Sweet’s syndrome

Currently being updated.

Is a wheat-free or gluten-free diet a treatment for Sweet’s syndrome?

It is not unusual for Sweet’s syndrome patients to be given inaccurate, bad or potentially harmful advice about their condition, particularly from non-health professionals. They can also find that they are pressurized into following a wheat-free or gluten-free diet, or some other kind of special diet as a treatment or cure for their Sweet’s syndrome. This is sometimes well-meant, but often, someone is just trying to promote their own agenda, or get people to buy a particular product or service.

Please be aware of the fact that there is absolutely no medical evidence to show that a wheat-free or gluten-free diet, or any other kind of special diet is a treatment or cure for Sweet’s syndrome. Be wary of anyone who makes such claims, particularly if they are trying to sell you something.

Do some patients with Sweet’s syndrome need to follow a wheat-free or gluten-free diet?

Yes. You will need to follow a 100% gluten-free diet if you have developed your Sweet’s syndrome secondary to the autoimmune condition, coeliac disease. This is because in order to bring the Sweet’s syndrome under control you need to manage or treat the underlying condition. However, Sweet’s syndrome developing secondary to coeliac disease is incredibly rare, and only one case has been reported in medical literature (Eubank et al, 2009).

What is coeliac disease?

When people with coeliac disease eat gluten, the surface of the small intestine becomes inflamed, and this affects the body’s ability to digest food. Management or treatment of coeliac disease includes a gluten-free diet, sometimes extra vaccinations and/or supplements, and less commonly, medication. See ‘Further information’ below to learn more.

Do patients with Sweet’s syndrome sometimes need to follow a wheat-free or gluten-free diet for other reasons?

Occasionally, someone with Sweet’s syndrome may need to follow a wheat-free or gluten-free diet for other types of condition that affect the bowel or gut, and a wheat-free diet will be necessary if you have a wheat allergy.

Can a wheat-free or gluten-free diet be harmful?

Eliminating wheat or gluten from your diet shouldn’t be harmful as long as you make sure that you are meeting all of your nutritional requirements. However, these diets aren’t suitable for everyone, and could potentially increase the risk of nutritional deficiency, e.g. calcium, iron, folic acid, or zinc deficiency, in some people. It is also advisable to check the nutritional content of gluten-free substitutes, e.g. bread or pasta, as they sometimes contain more fat or sugar than products containing gluten.


Frequently asked questions.

Question 1: Can a wheat-free or gluten-free diet be used to treat or cure Sweet’s syndrome and other autoinflammatory conditions?

No. Autoinflammatory conditions such as Sweet’s syndrome are not caused by diet, but errors in the innate immune system – the body’s most primitive, ‘hard-wired’ immune system. This then causes the immune system to activate inflammatory cells, often for unknown reasons, which leads to inflammation.

The majority of autoinflammatory conditions are genetic, which means that they occur as a result of gene mutation that affects how the innate immune system works. However, there are some, including Sweet’s syndrome, that are not usually genetic. In such cases, people are more likely to have certain genes that increase their risk of developing a particular autoinflammatory condition, i.e. they are genetically susceptible, but something may be needed to trigger it. Diet is not one of these triggers. Read about triggers for Sweet’s syndrome here.

Alongside genetic susceptibility, other causes for Sweet’s syndrome include hypersensitivity reaction and cytokine dysregulation.

Question 2: People with the autoimmune condition coeliac disease have to follow a gluten-free diet. My nutritional therapist told me that this means that all people with autoinflammatory conditions should be on a gluten-free diet too, even if they don’t have coeliac disease. Is this true?

No. Even though some autoinflammatory conditions, e.g. Sweet’s syndrome, can develop secondary to autoimmune conditions, autoinflammatory and autoimmune conditions are different. Also, gluten cannot play the same kind of role in autoinflammatory conditions as it does in the autoimmune condition, coeliac disease. This is because autoinflammatory conditions are not caused by diet, the wrong part of the immune system is involved, and there is no antibody production in response to certain naturally occurring proteins in the body. See below for further explanation.

Point 1.

Point 2.

  • In people with the autoimmune condition, coeliac disease, a part of the immune system called the adaptive immune system mistakes gliadin (a component of gluten) and tissue transglutaminase or tTG (a multifunctional enzyme or protein that also modifies gliadin so you can digest it) for foreign invaders such as a bacteria or virus. White blood cells called B-lymphocytes then make antibodies in response to the gliadin and tTG, and the antibody production in response to tTG in particular, causes inflammation and damage to the lining of the gut. Antibodies are also produced in response to endomysium (EMA) which is the protective covering of connective tissue that surrounds each individual muscle fibre. However, this does not cause direct symptoms to intestinal muscle.

Sometimes, Sweet’s syndrome can develop secondary to autoimmune conditions other than coeliac disease. However, just because those with coeliac disease have to follow a gluten-free diet, doesn’t mean that people with other autoimmune conditions will benefit from a gluten-free diet. This is because which proteins in the body are targeted will depend on what kind of autoimmune condition you have, e.g. antibodies will be produced in response to proteins other than tTG and EMA.

Point 3.

  • Autoinflammatory conditions involve the innate, and not the adaptive immune system. The innate immune system does not employ B-lymphocytes, and does not produce antibodies. Therefore, the inflammation in the bodies of patients with autoinflammatory conditions cannot be caused by the production of antibodies in response to tTG, EMA or gliadin.

Question 3: Is Sweet’s syndrome an allergic reaction to wheat?

No. Sweet’s syndrome is not an allergic reaction to wheat, and neither autoinflammatory nor autoimmune conditions are caused by allergy. See below for further information, and read Question 1 & 2.

Point 1.

  • The most common type of allergy is an IgE-mediated allergy. This is an adverse reaction that the body has to a particular substance that is foreign to the body, e.g. a food, pollen, or cat hair, that does not normally cause harm. This substance is known as an allergen (a type of antigen). Allergic reaction occurs when the immune system mistakes an allergen for a foreign invader such as a bacteria or virus. The adaptive immune system then quickly produces allergen-specific immunoglobulin E (IgE) antibodies in response to this, in order to fight the allergen off. Chemicals such as histamine are also produced, with the overall immune response causing the symptoms of allergy.
  • Another type of allergic reaction is a non-IgE-mediated allergy, which is believed to be T-cell mediated. This is an immune response that doesn’t involve antibodies and where white blood cells called T-lymphocytes (part of the adaptive immune system) are activated. The symptoms of this type of allergy can take much longer to develop than in IgE-mediated allergy, sometimes up to several days.

Point 2.

  • In autoinflammatory conditions, the innate and not the adaptive immune system is involved, and antibody production does not occur.

Point 3.

  • Despite antibodies being involved in both autoimmune conditions and IgE-mediated allergy, they are not the same thing. In IgE-mediated allergy, allergen-specific IgE antibodies are produced in response to something that is foreign to the body. In autoimmune conditions, antibodies are produced in response to naturally occurring proteins in the body, e.g. tTG and EMA in coeliac disease.

Question 4: I don’t have coeliac disease, but my friend told me that intolerance to gluten is probably causing my Sweet’s syndrome. Is this true?

No. Sweet’s syndrome or other autoinflammatory conditions are not caused by an intolerance to gluten.

What is gluten intolerance?

Gluten intolerance or non-coeliac gluten sensitivity (NCGS) is a sensitivity to gluten in people who do not have the autoimmune condition coeliac disease, and it is not the same as an allergy to wheat, or an autoinflammatory condition. In those who supposedly have NCGS, it causes intestinal and other symptoms as a result of eating foods containing gluten. There is ongoing debate over whether or not NCGS exists, and the stance of the NHS is that most people, unless they have coeliac disease, do not need to cut out gluten from their diet (NHS Choices, 2016).

If NCGS does exist, its exact nature is not fully understood for some of the following reasons:

  • The role of the immune system still remains unclear in NCGS (Catassi et al, 2013: 3849). The intestinal innate immune system seems to play an important role, but the research is ongoing.
  • It has not been determined whether or not symptoms of NCGS relate specifically or always relate to gluten, e.g. some people may be sensitive to other things in food that contain gluten, or have problems digesting certain types of carbohydrate.
  • A person may have irritable bowel syndrome (IBS) and not NCGS, an overlap in symptoms between the two conditions making diagnosis difficult (Catassi et al, 2013: 3841). IBS is a common, long-term condition of the digestive system. It can cause stomach cramps, bloating, diarrhoea and/or constipation. The exact cause of IBS is unknown, but it is probably related to problems with digestion and increased sensitivity of the gut.
  • The placebo effect (Catassi et al, 2013: 3849). This means that when someone strongly believes that they have NCGS even when they don’t, when they start to eat a gluten-free diet they feel better.
  • We do not know whether or not NCGS is always a long-term condition. In some people it may be very short-term, transient or passing.

What are the symptoms of NCGS?

NCGS can cause a number of different symptoms. Gastrointestinal symptoms include bloating, abdominal pain, diarrhoea or constipation (Catassi et al, 2013: 3843). Extra-intestinal symptoms, i.e. symptoms that are not gastrointestinal, include headaches, dermatitis, skin rashes, joint pain, ‘brain-fog’, tiredness and fatigue. NCGS in children is less likely to cause extra-intestinal symptoms than in adults. Overall, the most common extra-intestinal symptom is tiredness, and there are no known major complications of untreated NCGS.

Please note that the symptoms of NCGS are also common symptoms of many other health conditions, and as a result, people sometimes think that they have NCGS when in fact they have another condition, or a minor and passing health problem.

What is the difference between Sweet’s syndrome and NCGS?

Sweet’s syndrome is caused by errors in the innate immune system, resulting in the activation of inflammatory cells, often for unknown reasons (see Question 1). Unlike NCGS, it is not linked to gluten, and symptoms do not stop when gluten is removed from the diet.

Is there a difference between coeliac disease and NCGS?

Yes, and some of the differences between coeliac disease and NCGS include:

  • Coeliac disease is strongly linked to gene mutation which increases your risk of developing the condition. NCGS is not.
  • No production of antibodies in response to tTG, EMA, and modified (deamidated) gliadin in NCGS, but does occur in coeliac disease (see Question 2 & 3) (Catassi et al, 2013:3847).
  • Immunoglobulin G (IgG) antibodies are produced in response to gliadin in 56.4% of NCGS patients, and 81.2% of coeliac disease patients. IgG antibodies are different from IgE antibodies, and are produced in response to pathogens, not antigens. A pathogen is a foreign invader such as a bacteria or virus or other micro-organism that can do harm, while an antigen is a protein or other substance attached to the foreign invader that activates an antibody response.
  • Only 7.7% of NCGS patients produce immunoglobulin A (IgA) antibodies in response to gliadin compared to the majority of those with coeliac disease. IgA antibodies are different from IgE and IgG antibodies, and prevent invading pathogens from attaching to any outer surface that needs to be protected, e.g. the outer surface of an internal organ, or eyes. They are mainly found in the mucous membranes, e.g. nose, breathing passages and digestive tract, but also in other substances such as tears, saliva, and blood. However, a small number of people do not make them.
  •  Unlike in coeliac disease, NCGS does not cause significant or severe inflammation, or damage to the lining of the small intestine.

Is there a difference between wheat allergy and NCGS?

Yes. There is a difference between wheat allergy and NCGS. Unlike in IgE-mediated wheat allergy, there is no production of allergen-specific IgE antibodies in NCGS (Catassi et al, 2013:3847). However, it can be difficult to distinguish between NCGS and  non-IgE-mediated wheat allergy (Catassi et al, 2013: 3842).


I (Michelle Holder) am not a registered dietician. This information has simply been provided to help you make an informed decision about your dietary choices. Please seek further advice about the suitability of a wheat-free or gluten-free diet from a registered dietician or doctor, but not a nutritional therapist.


References.

Catassi, C., Bai, J., Bonaz, B., Bouma, G., Calabrò, A., Carroccio, A., Castillejo, G., Ciacci, C., Cristofori, F., Dolinsek, J., Francavilla, R., Elli, L., Green, P., Holtmeier, W., Koehler, P., Koletzko, S., Meinhold, C., Sanders, D., Schumann, M., Schuppan, D., Ullrich, R., Vécsei, A., Volta, U., Zevallos, V., Sapone, A. and Fasano, A. (2013) Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders. Nutrients, Sept; 5(10):3839-3853 (online).

Eubank, K. , Nash, J. and Duvic, M. (2009) Sweet syndrome associated with celiac disease. American Journal of Clinical Dermatology (PubMed).

NHS Choices (2016) Food Intolerance (online). Last reviewed 11/08/16.

Further information.

NHS Choices (2016) Coeliac Disease (online). Last reviewed 4/12/16.

NHS Choices (2015) ‘Leaky Gut Syndrome’ (online).  Last reviewed 26/02/15. This is a condition that can supposedly be caused by gluten and other things, and lead to the development of certain health problems. It is a condition that is not recognised by the medical community, and there is absolutely no evidence to prove that it exists. PLEASE DO NOT BELIEVE ANYONE WHO TELLS YOU THAT SWEET’S SYNDROME IS CAUSED BY ‘LEAKY GUT SYNDROME’.

NHS Choices (2015) Should you cut out bread to stop bloating? (online). Last reviewed 18/05/16. Includes information on bread-related gut symptoms, health problems caused by wheat, and the anti-bloat FODMAP diet (originally designed for people with IBS).

Tousseau, J. and Durrant, K. (2014) Myth 6: It must be an allergy. Stop eating diary, wheat, gluten, MSG, etc and you will be fine in “It’s Just a Fever,” and Other Myths & Misconceptions About Periodic Fever Syndromes. SAID Support, May 22nd (online).

© 2012-2017 Sweet’s Syndrome UK

Differentiation syndrome and Sweet’s syndrome: is there a connection?

Links checked on 2/03/17.

Is there a connection between differentiation syndrome and Sweet’s syndrome?

By February 2015, only three cases of Sweet’s syndrome had been reported in patients with differentiation syndrome which occurred as a result of treatment with all trans-retinoic acid (ATRA) for acute promyelocytic leukaemia (Salono-Lopez et al, 2015).

What is acute promyelocytic leukaemia?

Acute promyelocytic leukaemia (APL) is a form of blood cancer that affects a type of white blood cell called the myeloid cell. It is more common in older adults than younger adults, and is rare in young children.

What is differentiation syndrome?

Differentiation syndrome, formally known as retinoic acid syndrome, is a potentially life-threatening condition that mainly occurs as a result of treatment with ATRA or arsenic trioxide for APL. It occurs in approximately 25% of patients with APL receiving these treatments during induction therapy – the first phase of chemotherapy where the aim is to get rid of as many leukaemia cells as possible.

What are the symptoms of differentiation syndrome?

Symptoms of differentiation syndrome include fever; low blood pressure; shortness of breath; weight gain of more than 5 kg; abnormal findings in the lungs on chest x-ray or scan (Montesinos and Sanz, 2011). Less common and rare symptoms include swollen feet and ankles as a result of fluid building up in the tissues; bone, muscle or nerve pain; Sweet’s syndrome; kidney or liver problems; fluid around the heart.

Can ATRA therapy also cause Sweet’s syndrome?

Yes.

In up to 5% of cases, Sweet’s syndrome can be triggered by medication (drug-induced). The most common medication is G-CSF (granulocyte-colony stimulating factor), but it can also be triggered by other medications, including ATRA. The reason as to why some medications can trigger Sweet’s syndrome is still poorly understood, buy may involve hypersensitivity reaction.

Is there a connection between differentiation syndrome and Sweet’s syndrome?

Possibly.

There is debate over whether or not differentiation syndrome and Sweet’s syndrome are completely separate conditions or are part of the same disease spectrum. This is because they share some common features. These include fever, white blood cells called neutrophils infiltrating the tissues, and improvement after steroid therapy. However, there are also some differences. Unlike in differentiation syndrome, Sweet’s syndrome does not commonly affect internal organs, and is not associated with capillary leak syndrome. This is a rare and life-threatening condition that has been suggested as a potential cause for differentiation syndrome. It causes endothelial cells lining small blood vessels called capillaries to separate, allowing fluid to leak into the space between the cells. This eventually leads to symptoms such as a rapid drop in blood pressure; shock; sudden swelling of the arms or legs, and other parts of the body; lightheadedness; weakness; fatigue; feeling sick; fluid around the heart and lungs; high percentage of red blood cells in the blood; low levels of protein in the blood.

Further research is required.

Please note that Sweet’s syndrome as a symptom of differentiation syndrome is very rare.

References.

Montisenos, P. and Sanz, M. (2011) The Differentiation Syndrome in Patients with Acute Promyelocytic Leukemia: Experience of the Pethema Group and Review of the Literature. Mediterranean Journal of Hematology and Infectious Diseases, Dec;3(1):e2011059 (online).

Solano-López, G., Llamas-Velasco, M., Concha-Garzón, M. and Daudén, E. (2015) Sweet syndrome and differentiation syndrome in a patient with acute promyelocytic leukemia. World Journal of Clinical Cases, Feb 16;3(2):196-8 (online).

© 2012-2017 Sweet’s Syndrome UK

Myelodysplasia and Sweet’s Syndrome

Updated 19/03/2017.

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, which means that if you have MDS, it’s very important to get an accurate diagnosis in order to get the proper treatment that you need (John Hopkins Medicine, 2017).

Some of these types are referred to as ‘low-risk MDS’. These progress slowly and can cause mild to moderate anaemia, or a decrease in other types of cells. They might also affect a cell’s ability to function.

Other types of MDS called ‘high-risk MDS’ may cause severe problems. In patients with high-risk MDS, 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.

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):

  • Fever.
  • 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. 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?

Doctors are still working on a cure for MDS, though 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.

Immunosuppression treatment.

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.

Chemotherapy.

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.

Biological therapy.

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 is slightly less likely than in SS.
  • No joint pain: joint pain in MASS is 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 settle 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 can be considered as an additional treatment (Gill et al, 2010). Thalidomide has also been used with some success (Browning et al, 2005). 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.


References.

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).

Casarin Costa, J., Virgens, A., Mestre, L., Dias, N., Samorano, L., Valente, N. and Festa Neto, C. (2017) Sweet Syndrome. Journal of Cutaneous Medicine and Surgery, Feb 1 (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).

Cohen, P. (2007) Sweet’s syndrome – a comprehensive review of an acute febrile neutrophilic dermatosis (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).

John Hopkins Medicine (2017) Myelodysplastic Syndrome. The Sidney Kimmel Comprehensive Cancer Center (online). Accessed 19/03/17.

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).

MDS UK Patient Support Group (2013) MDS GP Fact Sheet (online).

NHS Choices (2014) Myelodysplastic syndrome (myelodysplasia) (online). Last reviewed 5/11/14, and accessed 2/03/17.


Other information.

Baking soda is not a treatment for Sweet’s syndrome or myelodysplastic syndromes.

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).

© 2012-2017 Sweet’s Syndrome UK