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

Old blog. Most new information is now posted on our HealthUnlocked community and Facebook page (21/11/20).

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 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.


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

Summary of Genetic Alliance UK’s Good Diagnosis report — Beacon

As many in the rare community already know, nothing is worse than having to fight for your care when you are physically and emotionally drained. The diagnostic odyssey (the time between experiencing symptoms and receiving an accurate, final diagnosis) is long, strenuous and overwhelming. 2,427 more words

Summary of Genetic Alliance UK’s Good Diagnosis report — Beacon

Blood Cancer: The Forgotten Fifth — MDS UK Patient Support Group

Blood cancer patients are less likely to see their needs fully met than patients with the four most common cancers – breast, colorectal, lung and prostate. The blood cancer community, via the umbrella group Blood Cancer Alliance, has launched an important new campaign, called the Forgotten Fifth, pointing out that blood cancer is just as…

Blood Cancer: The Forgotten Fifth — MDS UK Patient Support Group

Sweet Syndrome and Hashimoto Thyroiditis: A Case Report and Review of the Literature.

Posted on FB 23/07/20.


This is a rare case of a 57-year-old man who developed Sweet’s syndrome (SS) secondary to Hashimoto thyroiditis (HT). He was initially misdiagnosed with cellulitis (a bacterial skin infection). HT is an autoimmune condition that causes an underactive thyroid.

Thyroid function tests should be part of the diagnostic examination of a patient with possible SS. These tests look at levels of thyroid-stimulating hormone (TSH) and thyroxine (T4) in the blood. A high level of TSH and a low level of T4 can indicate an underactive thyroid. It may also be appropriate to test for thyroid peroxidase (TPO) antibodies even when there are no obvious signs or symptoms of thyroid dysfunction. Additional note: approx. 95% of patients with HT are positive for TPO antibodies.

The exact relationship between SS and HT is not understood. The two conditions may share a trigger or SS may stimulate the immune system in such a way that it leads to the development of HT.

POSSIBLE ROLE OF T-HELPER CELLS: T and B cells are immune cells/white blood cells called lymphocytes. T-helper cells are a type of T cell that provide help to other cells in the immune response by recognizing foreign invaders and secreting substances called cytokines. These cytokines then activate other T and B cells. There are different types of T-helper cell which can be placed into at least 2 main classes, Th1 and Th2.

Studies have suggested that Th1 cells play a greater role than Th2 cells in the development of SS. T-helper cells are also thought to be involved in the development of HT. A recent study showed that proportions of Th1 cells were significantly higher with overt hypothyroidism (increased TSH and low T4) compared to subclinical hypothyroidism (TSH slightly raised, but normal T4). This suggests that a greater amount of Th1 cells in SS may act as a trigger, ‘pushing’ a susceptible individual into clinical thyroid disease.


Goodwin, J., Ives, S. and Hashmi, H. (2020) Sweet Syndrome and Hashimoto Thyroiditis: A Case Report and Review of the Literature. American Association of Clinical Endocrinologists: Clinical Case Reports, Jul-Aug; 6(4): e179–e182 (PMC).

2012-present, Sweet’s Syndrome UK

COVID-19 presenting with atypical Sweet’s syndrome

Posted on FB 02/06/20.


A 61-year-old woman was admitted to hospital with a one week history of skin lesions on her face and fever. She was also experiencing fatigue, muscle aches and joint pain. There were more lesions on her scalp, extremities, trunk, and mouth ulcers (aphthous). Blood tests showed a raised white blood cell count, including neutrophil count (83%), and raised ESR and CRP, indicating increased levels of inflammation in the body. The first CORONAVIRUS (SARS-Cov-2) test from a nose and throat swab was negative, but CT scan of the chest showed lung involvement. The patient was given hydroxychloroquine, azithromycin and Tamiflu (not proven treatments for COVID-19). The results of a skin biopsy from the right elbow (diffuse neutrophilic infiltrate in upper dermis, but also some subcutaneous involvement) alongside the clinical findings were interpreted as an ERYTHEMA NODOSUM – LIKE SWEET’S SYNDROME (see notes).

A repeat SARS-Cov-2 test was positive. A second CT was given due to prolonged fever, showing a diffuse bilateral parenchymal lung infiltration above 30% (associated with infectious disease affecting the lungs, e.g. pneumonia). Intravenous TOCILIZUMAB, a biologic, was given once. This is a drug that works by blocking INTERLEUKIN 6 (IL-6), a protein and CYTOKINE that is part of the body’s inflammatory and immune processes. Too much IL-6 can cause inflammation and tissue damage (see notes). Favipiravir, an antiviral, was started for 5 days (not a proven treatment for COVID-19). Fever subsided within 24 hours, and the skin lesions resolved.

SS can be reactive, an immune reaction against drugs, tumours or microbial agents such as a virus. This may start a CYTOKINE CASCADE resulting in SS – an overproduction of immune cells and their activating compounds (cytokines). In this case, SARS-Cov-2 was the most likely SS trigger. The patient’s abnormal immune response to COVID-19 has been proposed to be centred around neutrophils, and neutrophils and NETs (neutrophil extracellular traps) have been seen in the lungs in COVID 19. NETs are mesh or web-like structures released by neutrophils to trap and eliminate microbes. Cells in oral aphthous ulcers are also predominately neutrophils.

Overlapping symptoms of SS with COVID 19 made diagnosis difficult. Skin lesions can be a symptom of COVID 19 (see notes).

Additional notes.

1. Erythema nodosum is a skin condition that causes inflammation of the subcutaneous fat – fatty tissue under the two upper layers of the skin. It can look like SS, particularly a variant of SS called subcutaneous SS or Sweet’s panniculitis.

2. “A multicentre, randomised controlled trial of tocilizumab (IL-6 receptor blockade, licensed for cytokine release syndrome), has been approved in patients with COVID-19 pneumonia and elevated IL-6 in China (Mehta et al, 2020).”

3. IL-6 has been shown to play a role in SS.

4. Dermatological symptoms of COVID-19: an erythematous exanthem; livedo reticularis; cutaneous vasculitis; acute urticaria; chickenpox-like blisters; ‘COVID toes’, – like pernio/chilblains or frostbite.


Mehta et al (2020) COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet, Mar 28;395(10229):1033-1034.

Taşkın, B., Vural, S., Altuğ, E., Demirkesen, C., Kocatürk, E., Çelebi, İ., Ferhanoğlu, B. and Alper, S. (2020) COVID-19 presenting with atypical Sweet’s syndrome. Journal of the European Academy of Dermatology and Venereology, May 26. doi: 10.1111/jdv.16662 (Wiley).

2012-present, Sweet’s Syndrome UK

Atypical bortezomib-induced neutrophilic dermatosis

Image: Understanding Velcade, Velcade (bortezomib) for Injection (16/11/18). Link no longer available.

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).


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). 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.


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 (PDF).

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 26/07/20.

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).


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 a raised white blood cell count, including neutrophil 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, 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.


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.

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

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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.


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 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. 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). 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).


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).

2012-present, Sweet’s Syndrome UK