Sweet syndrome usually presents upwards of age 30 and is characterised by a sudden onset of fever, followed by the breakout of a rash, described as painful red or purple lesions. The rash can be quite dramatic, often appearing on the face, neck or arms.

Constitutional symptoms such as fever, fatigue and general malaise feature in Sweet syndrome as systemic inflammation develops. Other inflammatory symptoms can also appear with Sweet syndrome, such as joint pain and eye inflammation.

The cause of Sweet syndrome is not known, but it has been associated with genetic marker HLA-B54. Having this marker, however, does not mean Sweet syndrome will develop. There are many people in the population with this genetic marker who do not develop Sweet syndrome. Research is ongoing.

Certain triggers have been reported to activate the initial symptoms of Sweet syndrome, which are infection, certain medication, the presence of other inflammatory and/or autoimmune conditions, pregnancy and cancer, particularly blood cancer. There is surprisingly quite a lot of documentation available about these associations.

As the alternative name (acute febrile neutrophilic dermatosis) suggests, neutrophils feature in Sweet syndrome. Neutrophils are a type of white blood cell, involved in an immune response. In Sweet syndrome, it’s not clear what the immune system is responding to and, even when there has been a suspected trigger, the response is too intense, and the body doesn’t switch it off appropriately.

The immune response itself becomes the very thing that’s causing all the symptoms.

There is no definitive test to confirm Sweet syndrome, and doctors must make a clinical diagnosis, based on symptoms, blood tests and histology. The rashes in Sweet syndrome are particularly nasty and can range in presentation and location.

Histology is an important part of the diagnostic process for Sweet syndrome. This involves taking a skin biopsy for testing which can help rule out other conditions and also confirm Sweet syndrome. Conditions that can present similarly and are usually considered before diagnosing Sweet syndrome are things like erythema nodosum, panniculitis, erythema multiforme and vasculitis, plus other late onset autoinflammatory disease including VEXAS, a newly discovered X-linked syndrome.

Clinical diagnostic criteria have been proposed for Sweet syndrome as follows:

Patient must have BOTH of the following MAJOR criteria:

• Sudden onset eruption of tender, painful plaques or nodules.
• Neutrophilic infiltrate in the dermis without vasculitis.

Patient must have TWO of the following MINOR criteria:

• Fever greater than 38ºC.
• Illness preceded by an upper respiratory or gastrointestinal infection, or associated with an underlying typical inflammatory disorder, malignancy, or pregnancy.
• Elevated white cell count with neutrophil predominance and elevated inflammatory markers.
• Positive response to corticosteroids.

While Sweet syndrome has been associated with the genetic marker HLA-B54, many people have this marker and don’t develop the symptoms of Sweet syndrome. Sweet syndrome has also been associated with familial Mediterranean fever (FMF) patients with disease-causing variants in the MEFV gene. There are many ideas in discussion with regard to Sweet syndrome and a number of genes are under consideration, but nothing has been definitively resolved and research in this area is ongoing.

Is Sweet syndrome autoinflammatory or autoimmune?

Autoinflammatory diseases are caused by problems with the innate (non-specific) immune system, while autoimmune diseases involve the adaptive (specific) immune system. Sweet syndrome is considered autoinflammatory because neutrophils are involved and they are considered part of the body’s first response, the innate (non-specific) immune system.

However, the significance of the genetic marker HLA-B54 hasn’t been figured out yet. HLA markers are part of a self-recognition group which are involved in adaptive (specific) immunity. So, if HLA-B54 is eventually found to be directly involved in the cause of Sweet syndrome, then it could end up in the autoimmune camp.

The thing is that our bodies don’t really care about our categories and, in reality, neutrophils play roles in both immune systems. But with all the hyperactive inflammation in Sweet syndrome, we consider it to be autoinflammatory.

Sweet syndrome is treated by corticosteroids which are usually very effective. In most cases, the symptoms resolve and the condition settles but it can take several weeks or sometimes months. In some patients, relapse occurs and symptoms are treated again, the same way. Sometimes ongoing treatment is prescribed to prevent symptoms from coming back.

When corticosteroids do not work, other treatments sometimes used in Sweet syndrome are colchicine, non-steroidal anti-inflammatory drugs (NSAIDs) and sometimes biologics such as anakinra and others that target TNF.

Sweet syndrome is a serious condition that needs medical attention. Symptoms can be debilitating and extremely painful. With the right treatment, in most cases, the symptoms of Sweet syndrome will resolve but when symptoms are active, they can really disrupt a person’s life. The skin lesions can be painful and many patients report feeling self-conscious causing them to withdraw socially. It’s important to address mental health and show care to someone experiencing symptoms of Sweet syndrome.

In some cases, symptoms can become chronic and ongoing maintenance is needed.