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

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 infection, Talaromyces 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 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.

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

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

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 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).

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 8^th (J-Stage).

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 had an ischaemic 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, 2018). 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/migraines.

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). Summary in French and English.

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 and C-reactive protein, 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 scan showed that gas had entered the gluteus maximus muscle layer (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).
• 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

Can vaccination trigger Sweet’s syndrome?

Updated 06/09/2022.

If you’re anti-vax, this is not an anti-vax post. If you’re pro-vax, this is not an anti-vax post. Abusive comments and misinformation will not be tolerated.

Sweet’s syndrome triggered by vaccination.

Sweet’s syndrome (SS) can be triggered by vaccination, but it’s important to take the following into consideration:

• SS is rare, probably affecting no more than 3 people per 10,000 (Zamanian and Ameri, 2007).
• It mainly affects adults and only 5-8% of cases have been in children (Sharma et al, 2015).
• Sometimes there’s a trigger for SS, but in 50% of cases there’s no known trigger.
• Infection (mainly upper respiratory tract and gastrointestinal) and cancer are 2 of the commonest triggers. Paediatric cases less likely to be associated with cancer and are more likely post-infectious (Sharma et al, 2015).
• There are 20 cases of SS associated with vaccination, and 9 of these are associated with SARS-CoV2 vaccine – 3 Pfizer, 2 AstraZeneca, 2 Moderna, 1 Janssen, 1 Sinovac-CoronaVac.
• SS has only been associated with certain vaccinations (see below).

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 SS 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 SS following vaccination in a HIV-infected patient; in 2009, neutrophilic dermatosis of the hands occurring 12 hours after vaccination: in 2010, one case of SS after H1N1 influenza (swine flu) vaccination. Additional note: the nasal spray flu vaccine (FluMist) is live attenuated. There are no reported cases of SS 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.
• SARS-CoV2/COVID-19, different types of vaccine (see comments) (Baffa et al, 2021; Darrigade et al, 2021; Hoshina and Orita, 2022; Kinariwalla et al, 2022; Majid and Mearaj, 2021; Pelchat et al, 2022; Salah et al, 2022; Torrealba-Acosta et al, 2021; Zagar et al, 2021). Nine cases – 3 Pfizer, 2 AstraZeneca, 2 Moderna, 1 Janssen, 1 Sinovac-CoronaVac.

Why do vaccinations trigger Sweet’s syndrome?

Possibly hypersensitivity reaction.

What is hypersensitivity reaction?

In SS or those that go on to develop it, the 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 (Bhat et al, 2015: 257; Kasirye et al, 2011: 135). Antigens are molecules that stimulate an immune response.

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

No. Most people with SS 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 SS was triggered by a particular vaccination, then it isn’t advisable to have the same kind of vaccination again (doctor may advise otherwise if benefits of vaccine outweigh risks). Ideally, a vaccination shouldn’t be given during a SS flare-up.

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

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.

References.

Baffa, M., Maglie, R., Giovannozzi, N., Montefusco, F., Senatore, S., Massi, D. and Antiga, E. (2021) Sweet Syndrome Following SARS-CoV2 (COVID-19) Vaccination. Vaccines, Oct 20 (MDPI). Pfizer.

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).

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.

Darrigade, A., Theophile, H., Sanchez-Pena, P., Milpied, B., Colbert, M., Pedeboscq, S., Pistone, T., Jullie, M. and Seneschal, J. (2021) Sweet syndrome induced by SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. European Journal of Allergy and Clinical Immunology, Jun 18 (Wiley).

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.

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).

Hoshina, D. and Orita, A. (2022) Sweet syndrome after severe acute respiratory syndrome coronavirus 2 mRNA vaccine: A case report and literature review. Japanese Dermatological Association: The Journal of Dermatology, Jan 17 (Wiley). Pfizer/tozinameran.

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).

Kinariwalla, N., London, A. O., Soliman, Y. S., Niedt, G. W., Husain, S. and Gallitano, S. M. (2022) A Case of Generalized Sweet’s Syndrome with Vasculitis Triggered by Recent COVID-19 Vaccination. JAAD Case Reports, Jan 2022 (Elsevier). Janssen.

Majid, I. and Mearaj, S. (2021) Sweet Syndrome after Oxford-AstraZeneca COVID-19 vaccine (AZD1222) in an elderly female. Dermatologic Therapy, Sep 29 (Wiley).

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).

Pelchat, F., Fournier, C., Perron, E., Gilbert, M. and Delisle, B. (2022) Sweet Syndrome Following Moderna COVID-19 Vaccine: A Case Report. SAGE Open Medical Case Reports: SAGE Journals, Aug 11 (online).

Salah, N.B., Korbi, M., Fadhel, N.B., Safa, I., Chad, F., Njima, M., Belhadjali, H., Amri, M., Aouem, K. and Zili, J. (2022) Sweet Syndrome following SARS-CoV-2 CoronaVac vaccine. Journal of the European Academy of Dermatology and Venerealogy, Jun 20 (Wiley).

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).

Torrealba-Acosta, G., Martin, J. C., Huttenbach, Y., Garcia, C. R., Sohail, M. R., Agarwal, S. K., Wasko, C., Bershad, E. M. and Hirzallah, M. I. (2021) Acute encephalitis, myoclonus and Sweet syndrome after mRNA-1273 vaccine. British Medical Journal Case Reports, Jul 24 (PMC). Moderna.

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).

Zagar, T., Hlaca, N., Brajac, I., Prpic-Massari, L., Peternel, S. and Kastelan, M. (2021) Bullous Sweet syndrome following SARS-CoV-2 Oxford AstraZeneca vaccine. British Journal of Dermatology, Nov 24 (Wiley).

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

Two neutrophilic dermatoses captured simultaneously on histology (Sweet’s syndrome and neutrophilic eccrine hidradenitis)

Links checked on 15/11/18.

This is the second reported case of Sweet’s syndrome and neutrophilic eccrine hidradenitis occurring in a patient with acute myeloid leukaemia at the same time (Wlodek et al, 2016).

Key points.

• Sweet’s syndrome (SS) is a rare autoinflammatory condition and form of neutrophilic dermatosis (ND), and in approximately 20% of patients can be triggered by cancer, particularly blood cancer.
• Other forms of ND include neutrophilic dermatosis of the dorsal hands, Behcet’s syndrome, pyoderma gangrenosum, neutrophilic eccrine hidradenitis (NEH), erythema elevatum diutinum, bowel-associated dermatitis-arthritis syndrome, and more.
• NDs are conditions affecting the skin that occur as a result of lots of white blood cells called neutrophils accumulating in the tissues. This accumulation is referred to as ‘neutrophilic infiltrate’.
• A number of NDs, and not just SS, are associated with cancer and cancer treatment.
• Rarely, more than one kind of ND can occur in the same patient at the same time.

Case-study.

This is a case of a 72-year-old man who was being treated for acute myeloid leukaemia (AML) with chemotherapy – daunorubicin and cytarabine. Within 48 hours of starting treatment he developed a fever, and two days later, wide-spread non-tender pink plaques (skin lesions that appear in the form of large raised areas) on the limbs and trunk. A skin biopsy showed lots of white blood cells in the tissues – lymphocytes and histiocytoid cells, but mainly neutrophils. Neutrophils had also accumulated in the fatty tissue under the upper 2 layers of skin, and this is known as panniculitis. All of these finding were consistent with SS. In addition, neutrophils and lymphocytes were also present around the sweat glands, and this is consistent with NEH. NEH is commonly caused by chemotherapy, including cytarabine, but can sometimes occur for other reasons.

The authors of this study have proposed that the neutrophilic infiltrate that’s found in a patient with SS has the potential to extend around the sweat glands, thus leading to NEH.

Further information.

Copaescu, A., Castilloux, J., Chababi-Atallah, M., Sinave, C. and Bertand, J. (2013) A Classic Clinical Case: Neutrophilic Eccrine Hidradenitis. Case Reports in Dermatology, Sep-Dec; 5(3): 340–346 (PMC).

Tan, E. (2007) Skin toxicity of chemotherapy drugs. DermNet NZ (online). Accessed 15/11/18.

References.

Wlodek, C., Bhatt, N. and Kennedy, C. (2016) Two neutrophilic dermatoses captured simultaneously on histology. Dermatology Practical & Conceptual, Jul; 6(3): 55–57 (PMC).

2012-present, Sweet’s Syndrome UK