Raccoon eyes as a newly reported sign of Sweet’s syndrome

This blog is being updated, 9/01/20.

Raccoon eyes sign (RES) is a newly reported sign of Sweet’s syndrome in two male patients, a 27-year-old man with a 10 day history of upper respiratory tract infection and a 52-year-old man with acute myeloid leukaemia and a history of testicular cancer (Salman et al, 2018). Both cases were successfully treated with methylprednisolone.

What is raccoon eyes sign?

RES (also known as owl eyes or panda eyes) or periorbital ecchymosis is normally a sign of basal skull fracture as a result of traumatic periorbital haemorrhage, periorbital referring to the area around the eye. It can also be caused by systemic amyloidosis, neuroblastoma and other conditions.

Can conditions affecting the skin cause raccoon eyes?

Yes, RES can be a sign of neonatal lupus erythematosus, lichen planus pigmentosus, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE), and Sweet’s syndrome.

What does raccoon eyes look like?

RES describes bruising and discoloration around the eyes that looks like the dark circles around a raccoon’s eyes, and may affect just one eye or both. In Sweet’s syndrome, RES has presented as swollen or haemorrhagic plaques (larger raised, reddened or purple skin lesions) around the eyes (Salman et al, 2018).

What causes raccoon eyes in Sweet’s syndrome?

The exact cause of RES in Sweet’s syndrome is unknown. However, Salman et al argue that it could be caused by secondary damage to blood vessels as a result of white blood cells called neutrophils releasing noxious substances, and the thin skin around the eyes being more sensitive to damage (Ibid). Read more here.

References.

Salman, A., Demir, G., Cinel, L., Oguzsoy, T., Yildizhan, G. And Ergun, T. (2018) Expanding the differential diagnosis of raccoon eyes: Sweet syndrome. Journal of the European Academy of Dermatology and Venereology, May 31|doi: 10.1111/jdv.15104 (Wiley Online).

2012-present, Sweet’s Syndrome UK

Can vaccination trigger Sweet’s syndrome?

Updated 9/01/20.

This post is not a replacement for medical advice. Please speak to your doctor if you have any concerns about vaccination.

Sweet’s syndrome triggered by vaccination.

There’s some medical evidence to show that certain vaccinations can potentially trigger Sweet’s syndrome, but this is very rare, and it’s 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 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 50% of cases there’s no known trigger.
  • Infection is a much more common trigger for Sweet’s syndrome than vaccination, and as a result, Sweet’s syndrome may be more likely to occur in countries where people have an increased risk of developing infections (Ginarte and Toribio, 2011: 120). It’s most commonly triggered by upper respiratory tract or gastrointestinal infection, but can also be triggered by other infections, e.g. tuberculosis (mainly affects lungs – lower respiratory tract).
  • There have only been 11 cases of Sweet’s syndrome triggered by vaccination reported in medical literature in the past 44 years, globally.
  • Sweet’s syndrome has only been associated with certain vaccinations and not others (see below), but a definite connection hasn’t been established in all of these cases.

Which vaccinations have been associated with Sweet’s syndrome?

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

  • Bacillus Calmette-Guerin, live attenuated (modified and weakened) vaccine (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.
  • Hepatitis B, inactivated (killed) vaccine (Enokawa et al, 2017). One case in a 69-year-old man with the autoimmune condition, systemic lupus erythematosus. Symptoms of Sweet’s syndrome started to develop 48 hours after vaccination, but there were no skin lesions at the vaccination site.
  • Influenza injection, inactivated (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 flu) vaccination. Additional note: in the UK, children over the age of 2 years receive the nasal spray flu vaccine which is a live attenuated vaccine, but there are NO cases of Sweet’s syndrome being triggered by it.
  • Smallpox, a live vaccine that contains a pox-type virus related to smallpox, but causes a milder disease (Carpentier et al, 2002: 82; Cruz-Velasquez et al, 2016). Two cases reported in 1975, occurring 3 days after vaccination.
  • Streptococcus pneumonia, inactivated (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.

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

No. Vaccinations don’t trigger Sweet’s syndrome because they’re toxic, and anyone who tells you this may be doing so for one of the following reasons: they have no real understanding of vaccination or Sweet’s syndrome; they are trying to scare you; they are trying to promote an anti-vax agenda; they are trying to sell you something, e.g. detox products that will supposedly cleanse your body of vaccine toxins, and thereby, cure your Sweet’s syndrome.

What is a dangerous or toxic chemical?

Everything that exists is a chemical, e.g. people, animals, trees, air, food, water (chemical name – H20 or dihydrogen monoxide). Without chemicals we wouldn’t exist. What makes a chemical dangerous is the amount or dose not the chemical itself. This means if you take X amount of a natural chemical and the same amount of an artificial chemical, then the natural chemical could potentially be far more dangerous or toxic than the artificial.

Why do vaccinations trigger Sweet’s syndrome?

Vaccination can trigger Sweet’s syndrome because of hypersensitivity reaction.

What is hypersensitivity reaction in Sweet’s syndrome?

In Sweet’s syndrome, the innate immune system – the body’s most primitive ‘hard-wired’ immune system – doesn’t always work in the way that it should. Because of this, in some people with Sweet’s syndrome or those that go on to develop it, their immune system may respond to antigens in a way that it wouldn’t in most people, i.e. is hypersensitive and overreacts or responds in the wrong way to the presence of infectious, inflammatory, drug, or tumour cell antigens (antigens are substances on the surface of a cell that the adaptive immune system makes antibodies in response to) (Bhat et al, 2015: 257; Kasirye et al, 2011: 135).

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 reasons, e.g. they are taking certain types of medication, or have other health conditions. If the Sweet’s syndrome was initially triggered by a particular vaccination, then it isn’t 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 very rare, but if it does happen then symptoms usually develop within hours or days, less commonly, about two weeks after vaccination. Skin lesions may 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 in approximately 20% of cases, one of the most common being a group of blood disorders called myelodysplastic syndromes that can progress to acute myeloid leukaemia (Chen et al, 2016).
  • Inflammatory bowel disease – Crohn’s disease and ulcerative colitis (Cohen, 2007).
  • Autoimmune conditions, e.g. rheumatoid arthritis and systemic lupus erythematosus.
  • Medications in up to 12% of cases.
  • Pregnancy in up to 2% of cases.
  • Immunodeficiency.
  • Herbal products – arnica cream and Indian frankincense supplements (Cohen, 2007; Wagner et al, 2019).
  • Overexposure to sunlight or ultraviolet light (Cohen, 2007).

On rare occasions, Sweet’s syndrome can develop secondary to other autoinflammatory conditions. In children, these include CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature); HIDS (hyper IgD syndrome); MAJEED syndrome.

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 (BMC).

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 (Elsevier). Article in Spanish, use translate.

Enokawa, M., Giovanella, L., Zardo, B., Cunha, J., Rachid Filho, A., Zeni, L., Bisognin, M., Rosseto, C. and Guimaraes, A. (2017) Sweet’s Syndrome Discharged (Caused) by Hepatitis B Vaccine. Brazilian Journal of Rheumatology, 57(suppl 1):S197 (Science Direct). Article in Portuguese, 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). 

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).

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).

Wagner, A.C., Vogt, T. and Müller. C.S.L. (2019) Sweet-Syndrom mit akraler Beteiligung nach Boswellia-Einnahme: Ein Fallbericht (Sweet’s Syndrome with Arcral Involvement Triggered by Boswellia: A Case Report). Aktuelle Dermatologie; 45(12): 604-607 (Thieme).

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).

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).

2012-present, Sweet’s Syndrome UK

Atypical bortezomib-induced neutrophilic dermatosis

Image: Understanding Velcade, Velcade (bortezomib) for Injection. Accessed 16/11/18.

In 12% of cases, Sweet’s syndrome, otherwise known as acute febrile neutrophilic dermatosis, can be triggered by medication, and this is known as drug-induced Sweet’s syndrome. This is case of a 76-year-old man developing a Sweet’s syndrome-like condition secondary to the chemotherapy drug, bortezomib (trade names: Velcade, Chemobort or Bortecad).

Case-study.

A 76-year-old man was treated with prednisone-melphalan and subcutaneous injections of bortezomib for an IgG kappa multiple myeloma (Lescoat et al, 2018). On day 25 of the first chemotherapy cycle, he developed skin lesions – painless red-to-purple swollen, large blister-like, ulcerated, and haemorrhagic plaques – involving the forehead, top side of fingers, and both ankles. A blood test called a full blood count or FBC was normal. Skin biopsy revealed white blood cells called neutrophils in the skin, but no vasculitis (no swelling of the small blood vessels). There was also an absence of dermal oedema (no fluid in the dermal skin layer)m. Based on these findings, a diagnosis of bortezomib-induced neutrophilic dermatosis (ND) was given.

Bortezomib is a chemotherapy drug and proteasome inhibitor which causes a build up of unwanted proteins in cancer cells, which makes the cells die. In up to 24% of patients receiving this treatment adverse events affecting the skin occur, most commonly papules and nodules during the third or fourth treatment cycle. Bortezomib-induced Sweet’s syndrome and Sweet-like lesions have also been reported, generally appearing during the first or second cycle of chemotherapy.

Bortezomib-induced Sweet’s syndrome causes fever, weakness and lack of energy, painful round reddened and swollen skin plaques on the head, neck, or trunk. Skin biopsy tends to show immature or mature neutrophils in the tissues (Ibid). Walker and Cohen proposed five criteria for typical drug-induced Sweet’s syndrome: (1) sudden onset of painful erythematous plaques or nodules; (2) neutrophils in the dermal skin layer, but no vasculitis; (3) fever above 38 °C; (4) symptoms developing quite quickly after starting a medication, or recurrence after medication is stopped and restarted (rechallenge); (5) skin lesions settling down after the drug has been stopped or treatment with systemic steroids (Lescoat et al, 2018; Walker and Cohen, 1996). Although this case meets 3 of these 5 criteria, it differs from previously reported bortezomib-induced ND on account of the lack of other symptoms and the painless, ulcerated, haemorrhagic lesions, and their unusual localization, being confined to the extremities and forehead, sparing the trunk (Lescoat et al, 2018). Neutrophils in the tissues are characteristic of ND, but the absence of dermal oedema rules out Sweet’s syndrome, while no vasculitis excludes the ND, erythema elevatum diutinum. As a result of this, the spectrum of bortezomib-induced ND needs to be broadened. Also, bortezomib-induced ND remains poorly understood, but may occur because of the bortezomib causing an imbalance of proinflammatory cytokines – molecular messengers that promote inflammation – leading to the migration of neutrophils toward the skin. Treatment included stopping the bortezomib, and the steroid, prednisone, was started at 1 mg/kg/day, leading to the skin lesions completely settling down. Prednisone-melphalan was continued without reappearance of the lesions.

References.

Lescoat, A., Dupuy, A., Belhomme, N., Stock, N., Sebillot, M., Decaux. O. and Jégo, P. (2018) Atypical bortezomib-induced neutrophilic dermatosis. Annals of Hematology, Oct 12 (Springer Berlin Heidelberg).

Walker, D. and Cohen, P. (1996) Trimethoprim-sulafamethoxaole-associated acute febrile neutrophilic dermatosis: case report and review of drug-induced Sweet’s syndrome. Journal of the American Academy of Dermatology, May;34(5 Pt 2):918-23 (PubMed).

2012-present, Sweet’s Syndrome UK

Sweet’s syndrome associated with infection due to adult-onset immunodeficiency with anti-interferon-gamma autoantibodies

Image: Talaromyces marneffei, Mycology Online, The University of Adelaide. Accessed 23/09/18.

This is the first reported case of Sweet’s syndrome associated with the fungal infectionTalaromyces marneffei, and the bacterial infection, Mycobacterium abscessus, due to adult-onset immunodeficiency with anti-interferon-gamma autoantibodies (Xu et al, 2018).

What is adult-onset immunodeficiency with anti-interferon-gamma autoantibodies?

Adult-onset immunodeficiency with anti-interferon-gamma autoantibodies is an immunodeficiency disorder mainly found in Southeast Asians that were previously healthy. The exact cause for this disorder is unknown, but may be linked to the genes HLA-DR and HLA-DQ (Chan et al, 2016). It causes the body to produce higher amounts of anti-interferon-gamma autoantibodies – specific immune system proteins that mistakenly target a person’s own tissues – and prevents immune cells called T-lymphocytes (T1) from responding properly (Chan et al, 2016). This weakens the immune system leading to infection. Symptoms commonly include multiple swollen lymph nodes and skin lesions, particularly Sweet’s syndrome and acute generalized exanthematous pustulosis (Phoompoung et al, 2017). There is no standard therapy for adult-onset immunodeficiency with anti-interferon-gamma autoantibodies and treatment depends on what kind of infection is present.

What is Talaromyces marneffei?

In Southeast Asia, T. marneffei is a fungal infection that has been linked to bamboo rats and soil from their burrows, and is most commonly found in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) due to very weakened immune systems (Chan et al, 2016). Fairly recently, it has been associated with adult-onset immunodeficiency with anti-interferon-gamma autoantibodies.

What is Mycobacterium abscessus?

M. abscessus is a bacterium distantly related to the ones that cause tuberculosis and leprosy. It is a nontuberculous mycobacterial (NTM) infection that can be difficult to treat and is often resistant to antibiotics. NTM infection in people who were previously healthy and HIV negative has been associated with adult-onset immunodeficiency with anti-interferon-gamma autoantibodies (Phoompoung et al, 2017).

Case-study.

A 54-year-old Chinese man was admitted to hospital with a 2 month history of recurrent fever and a 1 month history of multiple swollen lymph nodes. There was nothing unusual about his history, apart from eating bamboo rats a year before. He went on to develop painful skin lesions on the face, back of hands, lower legs and feet. The antifungal, fluconazole, and the antibiotic, levofloxacin, were started to treat infection. The patient was also given the steroid, methylprednisone, and thalidomide to treat Sweet’s syndrome. His skin lesions eventually healed, but a new painful lesion developed under the left side of his jaw. He then had a recurrent fever and enlarging neck lymph nodes with swelling and flushing over his neck. These symptoms improved after levofloxacin was replaced with the antibiotic clarithromycin.

On admission, blood tests had shown raised white blood cell count, raised neutrophil (type of white blood cell) count, elevated erythrocyte sedimentation and C-reactive protein (two tests that can show increased levels of inflammation in the body). Test for HIV was negative, but anti-interferon gamma autoantibodies were positive. Bone marrow biopsy was normal. Blood and sputum cultures showed no fungal or bacterial infection. Biopsy of a skin lesion showed lots of neutrophils in the tissues and fluid in the dermal skin layer (uppermost part of dermis), these findings being consistent with Sweet’s syndrome. Biopsy of a lymph node from the right groin showed a yeast/fungal-like organism under microscope. Biopsy of the jaw lesion showed both yeast/fungal-like organisms and acid-fast rods, the latter indicating myobacterial infection. A diagnosis of deep mycosis (fungal infection in deeper tissues) caused by T. marneffei was given, and the mycobacterial infection was identified as M. abscessus.

References.

Chan, JF., Lau, SK., Yuen, KY. and Woo, PC. (2016) Talaromyces (Penicillium) marneffei infection in non-HIV-infected patients. Emerging Microbes & Infections, Mar 9;5:e19 (PMC).

Phoompoung, P., Ankasekwinai, N., Pithukpakorn, M., Foongladda, S., Umrod, P., Suktitipat, B., Mahasirimongkol, S., Kiertiburanakul, S. and Suputtamongkol, Y. (2017) Factors associated with acquired Anti IFN- γ autoantibody in patients with nontuberculous mycobacterial infection. PLos One, Apr 24;12(4):e0176342 (PMC).

Xu, H., Liu, D., He, X., Zheng, D. and Deng, Y. (2018) Sweet’s Syndrome Associated with Talaromyces marneffei and Mycobacterium abscessus Infection Due to Anti-interferon-gamma Autoantibodies. Indian Journal of Dermatology, Sep-Oct;63(5):428-430 (PMC).

2012-present, Sweet’s Syndrome UK

28th Feb 2018 is Rare Disease Day. Here’s how you can get involved and spread awareness of Sweet’s syndrome

The 28th February 2018 is the 11th international Rare Disease Day coordinated by EURORDIS (the European Organization for Rare Diseases). On and around this day, hundreds of patient organisations all over the world will be holding awareness-raising activities.

Each year, Rare Disease Day has a theme, and this year continues with the 2017 theme of research.

Here’s how you can get involved and spread awareness of Sweet’s syndrome.

  1. Like our Facebook page.
  2. Join our HealthUnlocked forum and community. It’s free!
  3. Follow this blog.
  4. Follow on twitter @sweetsfiend
  5. Follow on Google +
  6. Share a post from our Facebook page or blog.
  7. Share information about Sweet’s syndrome from a research-based site such as DermNet NZ or the Mayo Clinic.
  8. Talk about Sweet’s syndrome; blog about your experiences; tag a friend; tweet for Sweet’s.
  9. 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.
  10. Visit the Rare Disease Day website and sign up for their updates, download free materials (‘Get Involved’), and follow on social media.
  11. On the Rare Disease Day website, read about how patients can kick start and drive research.

Please BEE Sweet and buzz for Sweet’s. Help us spread the word!

🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝  🐝

A Rare Case of Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Neuro-Sweet Disease in Myelodysplastic Syndrome

This is the first documented case of neuro-Sweet’s disease (NSD) in a 66-year-old Japanese woman with a 6 year history of myelodysplastic syndrome (MDS), who developed NSD in association with syndrome of inappropriate antidiuretic hormone secretion (SIADH) (Oka et al, 2017).

What is neuro-Sweet’s disease?

NSD is a rare neurological variant of Sweet’s syndrome (SS) that can affect the brain and spinal cord. Read more here.

What is syndrome of inappropriate antidiuretic hormone secretion?

SIADH is a relatively rare condition where the body makes too much of a hormone called antidiuretic hormone (ADH). ADH is produced in a part of the brain called the hypothalamus, and is then released by the pituitary gland at the base of the brain. ADH helps the kidneys to control the amount of water your body loses through the urine. In SIADH, the body retains too much water, leading to abnormally low levels of sodium in the blood (hyponatraemia). This happens as a result of the excess water diluting the blood and lowering the concentration of sodium.

What causes syndrome of inappropriate antidiuretic hormone secretion?

Common causes for SIADH include medication, hormone treatments, surgery under general anaesthesia, brain conditions, and lung disease. Rare causes include a disease of the hypothalamus or pituitary, cancer, and mental disorders.

Case-study.

A 66-year-old Japanese woman with a 6 year history of MDS, a blood cancer known to trigger SS, developed a fever and skin lesions in the form of a rash over both legs (Oka et al, 2017). A biopsy of a lesion showed lots of white blood cells called neutrophils in the tissues and no inflammation of the blood vessels. These findings were indicative of SS. The patient was given the oral steroid, prednisolone, which is the main form of treatment for SS, and this brought her symptoms under control.

The patient was readmitted to hospital 9 months later with a fever and reduced level of consciousness. Blood tests showed raised C-reactive protein (CRP), indicating increased levels of inflammation in the body. White blood cell count (WBC) was low and neutrophil count was borderline/low, despite being raised in most cases of SS (see ‘Additional notes’). No brain abnormalities were detected on MRI scan. Examination of cerebrospinal fluid (CSF), a clear and colourless fluid found in the brain and spinal cord, showed no neutrophils or white blood cells called lymphocytes, but raised protein levels. Bacterial or viral meningitis were suspected, and intravenous (via a drip in the vein) meropenem and acyclovir were commenced. However, the patient’s fever didn’t improve and her level of consciousness continued to deteriorate.

On day 10 in hospital, the patient was found to be negative for HLA-B51, but positive for HLA-B54. HLA-B51 is a genetic marker associated with a similar condition to SS called Behcet’s syndrome (see ‘Further information’), while HLA-B54 is associated with SS, particularly in Japanese patients (Sweet’s Syndrome UK, 2018). Due to neurological involvement, a diagnosis of NSD instead of SS was suggested (Oka et al, 2017). The intravenous steroid, methylprednisolone, was given. The patient’s condition improved and she was then started on prednisolone.

On day 30, the patient developed a fever and her level of consciousness deteriorated again. Tests revealed a low WBC and neutrophil count; CSF showed no lymphocytes or neutrophils, but raised protein levels; greatly elevated levels of interleukin 6 (IL-6) (see ‘Additional notes’); rapidly falling sodium levels in the blood; no kidney, adrenal or thyroid problems; MRI abnormalities – sagittal T1-weighted MRI showing an absence of high intensity signals in the posterior pituitary lobe. As a result of these findings, a diagnosis of SIADH was given, and the NSD was considered to be the most likely cause for this. Prednisolone and cyclosporine were commenced to treat the NSD, cyclosporine having being found to be useful in SS patients who have developed their condition secondary to low-risk MDS. A 3% sodium chloride intravenous infusion was given for the low sodium levels. The patient’s condition improved, and after discharge from hospital on day 70, she remained stable for a year and there was no recurrence of her symptoms.

Additional notes.

Cytokines are proteins and molecular messengers and part of the body’s immune system. The overproduction or inappropriate production of cytokines, known as cytokine dysregulation, can result in disease. Cytokine dysregulation is a factor in SS, and the cytokine IL-6 plays a role in both NSD and SIADH (Oka et al, 2017). In this case, the patient’s IL-6 levels were greatly elevated, and this activates ADH secretion which can induce SIADH.

IN NSD, blood tests often show a raised WBC, including neutrophil count, and a raised CRP. CSF tends to show a slight increase in protein and an increase in the number of lymphocytes or neutrophils (Oka et al, 2017; Sweet’s Syndrome UK, 2018). However, MDS patients can sometimes have a lack of mature cells or neutrophils, and as a result, blood tests or CSF findings are less likely to clearly indicate NSD.

Further information.

Newson, L. (2016) Hyponatraemia. Patient Info (online). Includes information on SIADH.

Ngan, V. (2002) Behcet Disease. DermNet NZ (online).

References.

Oka, S., Ono, K. And Nohgawa, M. (2017) Successful Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Neuro-Sweet Disease in Myelodysplastic Syndrome. Internal Medicine (Tokyo, Japan), Dec 8th (J-Stage).

Sweet’s Syndrome UK (2018) Neuro-Sweet’s disease: a neurological variant (online).

2012-present, Sweet’s Syndrome UK

Sterile peritonitis as a rare symptom of Sweet’s syndrome

Links checked 30/10/18.

This is the first reported case of sterile peritonitis, a type of peritonitis not caused by infection, as a symptom of Sweet’s syndrome (SS) (Rajjoub et al, 2017). Peritonitis is inflammation of the peritoneum, the thin layer of tissue that lines the inside of the abdomen.

Case-study.

A 37-year-old female patient who had previously been diagnosed with SS in 1998 had been having repeat episodes of peritonitis. On admission to hospital, she had a 48-hour history of right sided abdominal pain and feeling sick, high temperature, fast pulse rate, low blood pressure, and a raised white blood cell count, including neutrophil count. There was no vomiting, problems with bowel movements, urinary symptoms, or vaginal discharge, and the patient reported that she had never been sexually active. One month prior to admission, her SS had also flared up, which was treated with steroid medication.

Click here and here to learn more about the role of neutrophils in SS.

It was in 2000 that the patient had first started experiencing abdominal pain, alongside left groin pain and a high temperature. She was treated with antibiotics, and then had a laparoscopy, otherwise known as abdominal ‘keyhole’ surgery. This is a minimally invasive surgical procedure that allows a surgeon to access the inside of the abdomen, while avoiding large incisions. The laparoscopy showed a large amount of pus in the pelvis and abdomen associated with pelvic adhesions. These are fibrous bands between tissues and organs that occur as a result of inflammation or injury. Due to the complexity of the situation, the laparoscopy was changed to ‘open’ or traditional surgery so that the patient’s abdomen could be more thoroughly examined. Her appendix, although it appeared to be normal, was removed. A sample of the pus was sent for analysis, but showed no bacterial growth, i.e. no signs of infection. It was thought that the absence of infection was due to the patient being given antibiotics before surgery.

On a later admission, the patient had another laparoscopy for ongoing lower abdominal pain. Once again, there was a large amount of pus in the pelvis and abdomen, and a subphrenic abscess. This is a collection of pus between the diaphragm, liver, and spleen. There were also extensive adhesions, and as a result of this finding, the patient was started on antibiotics and initially diagnosed with pelvic inflammatory disease (PID) of unknown cause. PID is an infection of the female upper genital tract, including the womb, fallopian tubes and ovaries, and mostly affects sexually active women aged 15 to 24.

As the patient had reported never being sexually active and having a SS flare-up before admission, it was decided that the PID diagnosis was incorrect, and her peritonitis and pus in the pelvis and abdomen were probably SS-associated. Rajjoub et al have hypothesized that this is because neutrophils have the potential to accumulate in the peritoneal cavity causing a widespread reaction and development of pus and adhesions. It was also hypothesized that steroids may have initially worsened the existing problem, but not caused it, by increasing the movement of white blood cells into the peritoneum.

The patient was eventually discharged from hospital with a pelvic drain in place to drain away any further fluid or pus, and antibiotics to prevent infection.

Further information.

NHS (2018) Pelvic Inflammatory Disease (online). Accessed 30/10/18.

NHS (2017) Peritonitis (online). Accessed 30/10/18.

References.

Rajjoub, Y., Saffaf, N. and Goodman, A. (2017) A rare case report describing the relation between sweet syndrome and spontaneous recurrent peritonitis. International Journal of Surgery Case Reports, Jul 21;39:93-97 (PMC).

2012-present, Sweet’s Syndrome UK

Sweet’s syndrome associated with antiphospholipid antibody syndrome

Links checked 30/10/18.

Sweet’s syndrome (SS) can develop secondary to autoimmune conditions. This is a rare case of SS developing in association with antiphospholipid antibody syndrome (APS) (Alves et al, 2017).

Case-study.

A 55-year-old man developed skin lesions, fever, joint pain in hands, and the inflammatory eye condition, episcleritis. All of these symptoms were consistent with SS.

Blood tests revealed increased levels of inflammation in the body, and a biopsy of a lesion showed SS. The patient also had a stroke, cavernous sinus thrombosis (blood clot in the hollow spaces located under the brain, and behind each eye socket), and was positive for antiphospholipid antibodies. He was then given a diagnosis of SS-associated APS. Unfortunately, the patient did not respond well to steroids, the most common treatment for SS. The medications methotrexate and hydroxychloroquine were started but stopped, due to bone marrow suppression. Treatment with the biologic, infliximab, led to significant improvement.

Are there any other cases of SS developing in association with APS?

Yes. An earlier case of SS-associated APS was reported in a man with multiple pulmonary emboli (blockages in the artery that carries blood from the heart to the lungs) (Cohen, 2007). He was given the steroid, prednisone, which initially worked well, but experienced SS flare-ups when the dosage was reduced. In 2008, Sweet-like lesions were reported in a 37-year-old man with insufficient blood flow to the brain and APS (Tomb et al, 2008).

What is APS?

APS, or Hughes syndrome, is an autoimmune condition where the immune system produces abnormal antibodies called antiphospholipid antibodies (NHS Choices, 2015). These antibodies then target proteins attached to fat molecules (phospholipids), making the blood more likely to clot.

What are the symptoms of APS?

Symptoms of APS include high blood pressure; deep vein thrombosis; stroke; heart attack; pulmonary embolism. The syndrome can also cause other symptoms, which are sometimes mistaken for the symptoms of multiple sclerosis – balance and mobility problems; vision problems; speech and memory problems; tingling or pins and needles; fatigue; repeat headaches or migraines.

Further information.

What causes Sweet’s syndrome? Includes information on SS triggers.

References.

Alves, L., Castro, F., Sousa, T., Alverenga, C., Abreau, I., Padova, P., Costa, G. and Souza, E. (2017) Sweet’s syndrome associated with antiphospholipid antibody syndrome – case report. Brazilian Journal of Rheumatology, 57(suppl 1): 371 (Science Direct). Article in Portuguese. Use translate.

Cohen, P. (2007) Clinical description: Figure 4, in Sweet’s syndrome – a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet Journal of Rare Diseases; 2: 34 (PMC).

NHS (2018) Antiphospholipid syndrome (APS) (online). Accessed on 30/10/18.

Tomb, R., Maalouf, E. and Attoui, S. (2008) [Cutaneous nodular lesions and antiphospholipid syndrome]. Annales de dermatologie et de vénéréologie, Jun-Jul;135(6-7):484-7 (EM|Consulte). Full-text in French.

2012-present, Sweet’s Syndrome UK

Fournier’s Gangrene: A Rare Complication of Sweet’s Syndrome

Links checked 30/10/18.

This is the first reported case of Fournier’s gangrene (FG) as a rare complication of Sweet’s syndrome (SS) (Choi et al, 2017).

Case-study.

A 31-year-old woman was admitted to hospital with a 7 day history of itchy, red skin lesions of various sizes all over her body. She also had a fever, and blood tests showed a raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), indicating inflammation in the body. A procalcitonin test was given to determine whether or not she had developed sepsis – a rare, life-threatening complication of infection, that can occur when chemicals that the immune system releases into the bloodstream to fight infection end up causing inflammation throughout the entire body. In this case, the procalcitonin test result was normal. A skin biopsy of a lesion showed white blood cells called neutrophils in the tissues and damage to the vessels caused by neutrophils releasing noxious substances. The former was indicative of SS. The patient was treated with high dose steroids for 5 days, which she responded well to.

Three days after being discharged, the patient returned to hospital, having developed a painful 2 cm-sized lesion and swelling on her buttock. The drainage from this area had the odour of rotten fish and looked like greenish pus. An X-ray of the area did not show anything unusual, but computed tomography (CT) scan showed that gas had entered the gluteus maximus muscle layer. This is because infection can result in gas in the soft tissues. Bacterial culture showed the presence of several bacteria: Streptococcus anginosus, Pseudomonas, and Clostridium. The patient was eventually diagnosed with FG, and treated with wound debridement (surgical removal of dead tissue) and antibiotics. Two months later, the buttock lesion was completely healed.

What is Fournier’s gangrene?

FG is a rapidly progressive necrotizing fasciitis (NF) that affects the perineal, genital and perianal regions. NF is a rare and serious bacterial infection that affects the superficial fascia – a layer of connective tissue that lies beneath the skin and between the muscles and organs in the body. FG usually develops secondary to other perirectal or periurethral infections, and the main form of treatment is wound debridement and broad-spectrum intravenous antibiotics (Bracho-Riquelme, 2017; Choi et al, 2017).

Some additional & key points.

  • FG most commonly affects those with a weakened immune system (Choi et al, 2017). This includes those with a weakened immune system as a result of taking medications that suppress the immune system (immunosuppressants), e.g. the steroid, prednisone.
  • FG can be confused with the conditions erythema multiforme, erythema nodosum, leukocytoclastic vasculitis, or cellulitis.
  • CT scan is an important diagnostic tool in FG, and can detect the presence of soft tissue air.
  • Early aggressive wound debridement and antibiotics are vital in the treatment of FG.
  • Doctors should consider the possibility of FG when a SS patient who takes immunosuppressants, develops painful lesions on the perianal and perineal area (Ibid).
  • FG or NF should not be confused with the rare SS variant, necrotizing Sweet’s syndrome (NSS). This variant mimics NF, and the main form of treatment is high-dose steroids. Antibiotics do not work in the treatment of NSS, and wound debridement must be avoided as it can lead to the development of new lesions.

References.

Bracho-Riquelme, R. (2017) Fournier Gangrene. NORD: National Organization for Rare Disorders (online). Rodolfo L. Bracho-Riquelme, MD, is a general and colorectal surgeon at Hospital General de Durango, Mexico. Accessed 17/01/18.

Choi, H., Kim, Y., Na, C. and Shin, B. (2017) Fournier’s Gangrene: A Rare Complication of Sweet’s Syndrome. Annals of Dermatology, Jun;29(3):387-389 (PMC).

2012-present, Sweet’s Syndrome UK

Challenges of Living with Sweet’s Syndrome

Sweet’s syndrome (SS) is a rare autoinflammatory condition and neutrophilic dermatosis. The most common symptom is skin lesions, but what many people don’t know is that it can cause lots of other symptoms too. On rare occasions, it can even be life-threatening, and approximately 20% of patients will develop SS secondary to some form of cancer, one of the commonest being a group of blood disorders called myelodysplastic syndromes.

Amongst the SS community, people with SS are typically referred to as ‘Sweeties’, and for them, living with SS can be incredibly difficult. This is not only due to the symptoms of SS, but to the many obstacles and unexpected challenges that they can face along the way. For example, problems associated with a change in appearance, depression, debilitating fatigue, isolation, pain, mobility issues, job loss and financial difficulties, to name but a few.

Living with Sweet’s syndrome. How can it affect a Sweetie?

Change in appearance.

  • Visible skin lesions.
  • Permanent skin discoloration or scarring.
  • Weight gain due to reduced mobility or side-effects of medication.
  • Rarely, hair loss due to the side-effects of medication.

Change in mood, depression or other changes in mental health.

  • Increased risk of anxiety or depression due to having to live or deal with certain difficulties or symptoms, e.g. not well enough to socialise, debilitating fatigue, or frequent or chronic pain.
  • Changes in mood due to the side-effects of medication.
  • Mental changes associated with the rare neurological variant, neuro-Sweet’s disease.

Loss of confidence.

  • Due to change in appearance.
  • Due to being insulted or verbally abused because of a change in appearance.

Isolation.

  • Not wanting to go out due to change in appearance.
  • Being too ill or in too much pain to work or socialize.
  • Symptoms of SS or the side-effects of medication making it difficult or impossible to do certain activities.
  • Others not wanting to associate with Sweeties because they think that their skin lesions can be ‘caught’.

Pain.

  • Painful skin lesions.
  • Headaches, less commonly, migraine.
  • Muscle pain.
  • Joint pain.
  • Eye pain associated with certain eye symptoms.
  • Occasionally, painful mouth ulcers or other types of oral lesion.
  • Rarely, pain as a result of internal organs being affected.

Mobility issues.

  • Difficulty walking and moving about because of joint pain and swelling.
  • Painful skin lesions affecting or restricting movement.
  • Neuro-Sweet’s disease causing limb weakness, or problems with co-ordination and balance.
  • Fatigue causing limb heaviness.

Lack of sleep.

  • Pain or other symptoms of SS making it difficult to sleep.
  • Side-effects of medication negatively affecting sleep, e.g. insomnia or nightmares.

Difficulty accessing information and treatment.

  • Struggling to find a doctor who has any understanding of SS.
  • Struggling to access patient information, on or off-line.
  • Health care staff unable to answer any questions that a Sweetie might have, and not able to provide information when requested.
  • Health care staff not taking SS seriously enough, or insulting a Sweetie because they don’t understand SS.
  • Having to wait a long time for the right treatment, or being denied access to certain treatments.

Difficulties associated with work.

  • Sweeties being bullied by work colleagues or customers because of their appearance.
  • Being bullied by an employer because they have to take time off, and are therefore viewed as a malingerer or a costly drain on resources. For example, having to take sick-leave when ill, being admitted to hospital, or having to attend doctor or hospital appointments on a regular basis.
  • Sweeties having to reduce their hours, even if they can’t afford to.
  • Difficultly gaining promotion, demotion or job loss.

Financial difficulties.

  • Struggling to afford to pay for care if a Sweetie lives in a country where health care is privatised.
  • Financial difficulties due to having to reduce hours at work, leave a job, being bullied out of a job or being sacked.
  • Struggling to access benefits due to the assessors or doctors having a poor understanding of SS and it not being recognised by the benefits system. This can happen even when a Sweetie is seriously ill.

Unsupportive family and friends.

  • Family and friends refusing to take SS seriously enough, and telling Sweeties to ‘just get on with it!’
  • Family and friends giving unhelpful advice and telling Sweeties that they are choosing to be ill (‘patient blaming’). For example, ‘ You wouldn’t be ill if you just ate more healthily, cut out gluten, didn’t get stressed, tried this herbal supplement, spent time in the sun, put essential oils on your lesions, or tried homeopathy.’ Some of these things can even make SS worse.
  • Getting annoyed and angry with a Sweetie because they can’t do what they once did, or are no longer in a position to help out others in the way that they did before.

There are many more challenges, obstacles and difficulties that could be added to this list, so please feel free to mention your own in the comments section below this post.

Today is Sweet’s Syndrome UK Day! Please share this post to help raise awareness of SS and the difficulties that Sweeties have to deal with, often on a daily basis. Also, a big thank you to all the health care staff, employers and work colleagues, family members and friends who DO support Sweeties across the globe. You do an amazing job, and frequently have to face your own challenges when it comes to helping and supporting those with SS. 💛

2012-present, Sweet’s Syndrome UK