Sweet syndrome, also known as Acute Febrile Neutrophilic Dermatosis, is a rare inflammatory disorder affecting the skin and other parts of the body. It is characterized by the sudden development of a high fever and a painful skin rash. This condition belongs to neutrophilic dermatoses, disorders involving an accumulation of neutrophils (a type of white blood cell) in the skin tissue. While the precise mechanism remains unknown, it is believed to represent a hypersensitivity reaction within the immune system. Most cases are considered idiopathic, meaning they occur without an identified cause, though the syndrome can be linked to other health events.
Distinctive Symptoms and Physical Manifestations
The onset of Sweet syndrome is abrupt, with patients first experiencing systemic symptoms that resemble a severe infection. A high fever, often exceeding 100.4°F, is a hallmark feature, frequently accompanied by a general feeling of being unwell (malaise). Many individuals also report muscle aches and joint pain (arthralgia), which can sometimes progress to arthritis in the wrists, ankles, or knees.
The most recognizable feature is the rash, which consists of tender, raised skin lesions. These lesions appear as red or violaceous plaques and nodules, commonly erupting on the face, neck, arms, and upper trunk. They often have a swollen appearance and can sometimes look like blisters or pustules, but their primary characteristic is their painful nature. The individual lesions can rapidly grow and merge together to form larger, irregular patches.
Triggers and Associated Medical Conditions
Sweet syndrome is classified into three primary categories: classical, malignancy-associated, and drug-induced. Classical Sweet syndrome is often preceded by an infection, most commonly an upper respiratory or gastrointestinal illness. It is also seen in association with other inflammatory disorders, such as inflammatory bowel disease, or during pregnancy.
The malignancy-associated form is a paraneoplastic phenomenon, meaning it is a distant effect of an underlying cancer. Hematologic cancers, particularly Acute Myeloid Leukemia (AML) and myelodysplastic syndromes, account for the majority of these cases. In approximately one-fifth of all patients, the syndrome may accompany an established cancer or serve as a first sign of an undiagnosed malignancy.
A number of medications are known to trigger the drug-induced presentation. The most frequently implicated agent is granulocyte-colony stimulating factor (G-CSF), a medication used to stimulate the production of white blood cells. Other associated drugs include:
- Certain antibiotics, like co-trimoxazole.
- Some nonsteroidal anti-inflammatory drugs.
- All-trans-retinoic acid.
- Hypomethylating agents.
Confirmatory Diagnosis and Standard Treatment
Diagnosing Sweet syndrome involves a combination of clinical observation and laboratory confirmation using established criteria. A major criterion is the abrupt appearance of the characteristic tender plaques or nodules on the skin. This clinical finding must be paired with specific microscopic evidence from a skin biopsy for a definitive diagnosis.
The skin biopsy confirms the presence of a dense infiltration of neutrophils within the dermis. This accumulation of white blood cells must occur without evidence of vasculitis (inflammation of the blood vessel walls). Blood tests show an increased white blood cell count (leukocytosis), with a predominance of neutrophils. Other minor criteria include an elevated body temperature and a history of a preceding infection or associated medical condition.
The primary treatment for Sweet syndrome is the administration of systemic corticosteroids. Oral prednisone is the most common first-line therapy, started at a dose between 40 and 60 milligrams per day. Patients experience a rapid improvement in both their fever and skin lesions within days of starting this medication.
The treatment course involves a gradual reduction of the steroid dose over several weeks to prevent a relapse of symptoms. For patients who cannot tolerate steroids or whose condition is unresponsive, second-line treatments may be considered. These alternatives include medications such as dapsone, colchicine, or potassium iodide. When the syndrome is linked to an underlying malignancy, definitive resolution requires successful treatment of the cancer itself.