What Causes Sweet Syndrome? (2024)

Sweet syndrome (acute febrile neutrophilic dermatosis) is a rare disorder that causes a sudden onset of a tender skin rash along with fever. It is categorized as classical, malignancy-associated, or drug-induced.

A rise in white blood cells may also be present, as well as neutrophils (a type of white blood cell) infiltrating the upper layer of skin. Sweet syndrome is usually treated with systemic corticosteroids (steroids taken orally or by injection that work throughout the body).

This article will discuss the symptoms of Sweet syndrome, what causes it, who is most at risk, how it is diagnosed and treated, and possible complications that can arise.

Sweet Syndrome Symptoms

Sweet syndrome presents with a sudden onset of skin lesions that can have a range of characteristics. These lesions may:

• Be tender (common) to extremely painful
• Persist for days to weeks
• Be small papules (bumps) or vesicles (blisters)
• Be pseudovasicular (almost blistered)
• Be larger thickened or swollen plaques (flat patches) or nodules (lumps)
• Be annular (ring-shaped)
• Be erosions and ulcers that resemble atypical pyoderma gangrenosum (an inflammatory skin condition)
• Occur on the limbs, neck, inside the mouth (including tongue and lips), and other areas of skin and mucosa
• Be few or numerous
• Start at millimeters to centimeters in diameter and up to 1 inch in diameter
• Grow slowly, eventually joining together
• Develop as pustules (pus-filled blisters)

In Sweet syndrome, neutrophils accumulate in the dermis, but for some people, they can accumulate in the subcutaneous fat (fatty layer of tissue just below the skin).

Other symptoms of Sweet syndrome may include:

• Moderate to high fever
• Feeling tired or unwell
• Aching joints
• Sore eyes
• Headache

Sweet syndrome can also affect other organs, including:

• Bones
• Kidneys
• Liver
• Nervous system
• Heart
• Lungs
• Intestines
• Muscles
• Spleen
• Eyes

The symptoms of Sweet syndrome may go away on their own, or they may persist for weeks or months if left untreated.

What Causes Sweet Syndrome?

In up to 50% of cases, Sweet syndrome is driven by an underlying condition. It is typically considered a reactive condition. Symptoms of Sweet syndrome can appear before an underlying cause is identified.

The exact cause of Sweet syndrome is not known, but it may be associated with:

• Sun exposure
• Inflammatory bowel disease
• Upper respiratory tract infections
• Blood disorders, including blood cancers such as leukemia
• Pregnancy
• Autoimmune disorders such as rheumatoid arthritis, lupus erythematosus, and relapsing polychondritis
• Cancers such as bowel, genital/urinary, or breast
• Gastrointestinal infection
• Vaccination
• Certain medications
• Immunodeficiency

Often, no underlying condition is found.

Who Is Most at Risk for Sweet Syndrome?

Classical Sweet syndrome is up to 15 times more common in women than men. It typically affects women between the ages of 30 and 50, though it can affect people of any age or sex.

There is no apparent racial disparity. It appears to be more common in people who carry the HLA-B54 genetic marker.

About one-third of people who experience classical Sweet syndrome will have a recurrence.

How Do You Treat Sweet Syndrome?

Sweet syndrome may resolve without treatment, but this could take weeks to months.

In cases of malignancy-associated Sweet syndrome, treatment of the underlying cancer often resolves the symptoms from Sweet syndrome. With drug-induced Sweet syndrome, stopping the medication that is causing the issue can resolve the Sweet syndrome.

All forms of Sweet syndrome are typically treated with corticosteroids, such as methylprednisolone or prednisone. Symptoms can resolve quickly with this treatment.

Other first-line treatments include colchicine (medication used to treat gout) and potassium iodide (a type of non-radioactive iodine).

Sweet syndrome may also be treated with medications such as:

• Anti-infective agents, such as dapsone, clofazimine, metronidazole, or doxycycline
• Retinoids, such as isotretinoin
• Pentoxifylline (a hemorrheologic agent that improves the flow of blood through blood vessels)
• Thalidomide (an immunomodulatory agent)
• Immunosuppressive and cytotoxic agents, such as methotrexate, cyclosporine, or chlorambucil
• Biologic agents
  

How Is Sweet Syndrome Diagnosed?

To make a diagnosis of Sweet syndrome, your healthcare provider may:

• Take a detailed health history
• Do a physical examination
• Order blood tests
• Order a skin biopsy (examination of removed tissue under a microscope) to look for inflammation that is mainly composed of neutrophils without vasculitis (inflammation of the blood vessels)
• Order a bone marrow examination (less common)
• Order other tests, such as a urine test, cancer screening, or imaging studies

Complications Associated With Sweet Syndrome

Sweet syndrome usually resolves without leaving a scar, but complications are possible. These may include:

• Dents in the skin, if there is involvement of subcutaneous fat
• Recurrent episodes (more common with those who have underlying myelodysplasia or cancer)
• Persistence despite treatment with severe ulcerative cases associated with malignancy
• Hyperpigmentation (brown marks) that can take several months to fade
  
• Outcomes associated with underlying conditions
  

Reports of fatalities from Sweet syndrome are uncommon.

Summary

Sweet syndrome is a rare condition that causes a tender rash due to neutrophils infiltrating the upper layer of skin and can cause a rise in white blood cells. It can also cause other symptoms, such as a fever, aching joints, headache, feeling unwell, and sore eyes.

Sweet syndrome may be associated with an underlying cause, such as an infection, pregnancy, or illness, or it may have no known cause.

This condition is classified into three types. Classic Sweet syndrome affects mostly women in their 30s to 50s. Malignancy-associated is associated with cancer, particularly blood cancers. Drug-induced is associated with taking certain medications, especially granulocyte colony-stimulating factor.

Sweet syndrome is usually treated with corticosteroids, but other medications may be used. The condition usually clears without issue, but recurrences are common. Complications such as lasting pigmentation marks may occur.