Sweet’s Syndrome, formally known as Acute Febrile Neutrophilic Dermatosis, is a rare inflammatory skin condition. It is characterized by the sudden onset of a high fever and the rapid appearance of painful skin lesions. The disorder is the prototype of neutrophilic dermatoses, involving an abnormal accumulation of a specific type of white blood cell in the skin. Sweet’s Syndrome requires a comprehensive evaluation, as it can be a sign of an underlying illness, and understanding its presentation and causes is necessary for effective management.
Clinical Presentation
The onset is typically abrupt, beginning with a high fever that can precede the skin eruption by several days or appear simultaneously. This fever is often accompanied by systemic symptoms like fatigue, headache, and muscle aches. The defining skin lesions present as tender, raised, and swollen plaques or nodules. These lesions are usually bright red or reddish-blue and commonly develop on the face, neck, and upper limbs, often in an asymmetric distribution. Although the lesions are painful and feel hot to the touch, they generally do not itch. Systemic symptoms include common joint involvement, manifesting as arthralgia, and frequent eye inflammation, such as conjunctivitis or episcleritis. If left untreated, the entire episode can persist for weeks to months.
Underlying Causes and Associations
Sweet’s Syndrome is understood to be a hypersensitivity reaction or an abnormal immune response, though the precise trigger is not always identified. The underlying pathology involves a dense infiltration of the dermis by mature neutrophils, a type of white blood cell responsible for fighting infection. This accumulation is believed to be driven by an imbalance of immune system proteins called cytokines. The condition is categorized into three primary forms based on the clinical setting.
Classical or Idiopathic Form
No specific cause is identified, although it is often preceded by an upper respiratory or gastrointestinal infection. This form is also sometimes associated with pregnancy or inflammatory bowel disease.
Malignancy-Associated Form
This form is strongly linked to certain cancers, particularly hematologic malignancies like acute myeloid leukemia (AML). In about two-thirds of these cases, the skin condition may be the first sign of the underlying cancer.
Drug-Induced Form
This form is triggered by exposure to specific medications. A common trigger is Granulocyte Colony-Stimulating Factor (G-CSF), a medication that stimulates the production of neutrophils. Other drugs, including some antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs), have also been implicated. Elevated G-CSF produced by the cancer itself may contribute to the neutrophilic infiltration in the malignancy-associated form.
Diagnosis and Treatment Approaches
A diagnosis of Sweet’s Syndrome requires a combination of clinical findings, laboratory results, and a tissue biopsy. Clinically, the abrupt onset of fever and characteristic skin lesions is suggestive of the condition. Laboratory tests often reveal elevated markers of inflammation, such as a high erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), but most notably, an increase in white blood cells with a predominance of neutrophils, known as neutrophilia.
The definitive step for confirmation is a skin biopsy, which involves taking a small sample of the affected tissue for microscopic examination. This examination will show the dense infiltration of neutrophils in the dermis without evidence of primary blood vessel inflammation (vasculitis). A thorough diagnostic workup also includes screening for potential underlying conditions, especially if blood tests show signs of anemia or other abnormalities that might suggest a hidden malignancy.
The standard first-line treatment for Sweet’s Syndrome is systemic corticosteroids, such as oral prednisone. Patients typically experience a dramatic and rapid improvement in both fever and skin lesions, often within 48 to 72 hours of starting treatment. The medication is usually continued for several weeks and then gradually tapered to prevent a recurrence of symptoms.
For patients who cannot tolerate corticosteroids or have a coexisting infection, alternative first-line agents may be used, including potassium iodide or colchicine. If the condition is persistent or recurs frequently, second-line treatments like dapsone or cyclosporine are considered, though these require careful monitoring. When the syndrome is linked to a drug, stopping the offending medication is essential, and in malignancy-associated cases, treating the underlying cancer is necessary for lasting resolution of the skin condition.