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.

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

Autoinflammatory Diseases: Rheumatology and how to avoid diagnostic errors

https://autoinflammatorydiseases.org/rheumatology-2/what-the-heck-is-arthritis/

Mental Health in Rare Disease

May is Mental Health Awareness Month. Taking care of your mental health is key, whether you are the patient or caregiver. Anxiety, stress and depression can all manifest as physical symptoms, including elevated blood pressure, forgetting to take medications, or insomnia, among many other ailments. If you are a caregiver, many in the rare disease…

Mental Health in Rare Disease: Taking Care of Your Mind Is Taking Care of Your Body — Global Genes

Anatomy of a Next Generation Rare Disease Patient Advocate — Global Genes

Patience is not always a virtue. In the world of rare disease, drug developers and patient advocates alike have come to understand that time is more valuable than money. Through ingenuity, determination, and a little luck, additional funding always seems to remain possible, but the incessant advance of time is an ever-present threat for someone…

Anatomy of a Next Generation Rare Disease Patient Advocate — Global Genes

Covid 19 UK Inquiry into the 500k Forgotten immunocompromised patients — MDS UK Patient Support Group

The APPG for Vulnerable Groups to Pandemics UK Inquiry has released their report this month (March 2023) into the Forgotten 500k Immunocompromised Patients. The post Covid 19 UK Inquiry into the 500k Forgotten immunocompromised patients appeared first on MDS UK Patient Support Group.

Covid 19 UK Inquiry into the 500k Forgotten immunocompromised patients — MDS UK Patient Support Group

Sweet‐like syndrome and multiple COVID arm syndrome following COVID‐19 vaccines: ‘specific’ patterns in a series of 192 patients — Wiley: British Journal of Dermatology: Table of Contents

The two clinico-pathological patterns are ‘Sweet-like syndrome’ and ‘Multiple COVID-Arm’. ‘Sweet-like syndrome’ presents clinically as erythematous and oedematous papules or plaques, sometimes developing vesiculation or bullae. Histology shows classical Sweet syndrome with a diffuse dermal neutrophilic infiltrate, or an infiltrate of histiocyte-like immature myeloid cells consistent with a histiocytoid Sweet syndrome. ‘Multiple COVID-arm’ is characterized…

Sweet‐like syndrome and multiple COVID arm syndrome following COVID‐19 vaccines: ‘specific’ patterns in a series of 192 patients — Wiley: British Journal of Dermatology: Table of Contents

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.

Case-study.

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.

References.

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.

Case-study.

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.

References.

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).

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). 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 (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