Acute Febrile Neutrophilic Dermatosis, commonly known as Sweet Syndrome, is a rare inflammatory condition affecting the skin. This disorder is characterized by the sudden onset of a distinctive skin rash along with a high temperature. It represents a form of reactive inflammation, meaning it is often a response to an underlying process elsewhere in the body.
Defining Sweet Syndrome
Sweet Syndrome is classified as a neutrophilic dermatosis, a group of skin disorders defined by the accumulation of a specific type of white blood cell, called neutrophils, within the skin layers. These neutrophils gather densely in the dermis without any evidence of infection or vasculitis (blood vessel inflammation) at the site. The condition was first described in 1964 by British dermatologist Dr. Robert Douglas Sweet.
The syndrome is uncommon, with only several hundred cases reported in medical literature. It most frequently affects adults, presenting between the ages of 30 and 60. There is a clear predilection for the disorder to occur in women, who account for the majority of reported cases.
Recognizing the Characteristic Symptoms
The clinical presentation involves the abrupt development of a high-grade fever, often exceeding 100.4°F (38°C), that precedes or accompanies the skin eruption. The hallmark of the disorder is the sudden appearance of tender, raised skin lesions that feel hot to the touch. These lesions can begin as small, red bumps (papules) but quickly evolve into larger, painful plaques or nodules.
The color of the lesions ranges from bright red to a dusky, purplish-red, sometimes described as violaceous, and they may occasionally develop a blister-like appearance on the surface, known as pseudovesiculation. These skin plaques most commonly erupt on the upper extremities, including the arms and hands, as well as the face, neck, and trunk. Patients frequently experience a general feeling of being unwell, or malaise.
Beyond the skin and fever, the inflammation can involve other parts of the body. Musculoskeletal involvement is frequent, with patients experiencing joint pain (arthralgia) or even true arthritis. Eye inflammation, such as conjunctivitis or episcleritis, can also occur. In rare instances, neutrophilic infiltration can affect internal organs, including the lungs, liver, or central nervous system.
Understanding the Underlying Triggers
Sweet Syndrome is often categorized based on its suspected cause, though in many cases, the exact trigger remains unknown, classifying it as “classical” or idiopathic. The syndrome is thought to be a hypersensitivity or reactive process driven by an abnormal immune response to an external or internal stimulus. This abnormal reaction leads to the overproduction and activation of immune cells, particularly neutrophils, which then migrate into the skin.
Infection-Associated
One significant category is infection-associated Sweet Syndrome, which commonly follows a recent upper respiratory tract or gastrointestinal infection. These infections are believed to activate the immune system, setting the stage for the subsequent inflammatory skin reaction. The disorder can also occur during pregnancy, an event that alters a woman’s immune state.
Malignancy-Associated
Another classification is malignancy-associated Sweet Syndrome, where the disorder acts as a paraneoplastic syndrome, signaling an underlying cancer. This association is strongest with hematological malignancies, particularly acute myeloid leukemia (AML) and myelodysplastic syndrome. Recognizing this link is important because the skin condition may appear months before the cancer is officially diagnosed.
Drug-Induced
Drug-induced Sweet Syndrome is directly triggered by exposure to certain medications. The most common culprit is granulocyte colony-stimulating factor (G-CSF), a drug used to stimulate the production of white blood cells in patients undergoing chemotherapy. Other medications, including certain antibiotics like co-trimoxazole (Bactrim) and nonsteroidal anti-inflammatory drugs (NSAIDs), have also been implicated in triggering the syndrome.
Diagnosis and Treatment Approach
Diagnosing Sweet Syndrome relies on a combination of clinical findings, laboratory results, and a confirmatory skin biopsy. Clinicians first look for the sudden onset of fever and the characteristic tender skin lesions. Blood tests reveal an elevated white blood cell count (leukocytosis), specifically an increase in the number of circulating neutrophils (neutrophilia).
A skin biopsy is an indispensable tool for confirming the diagnosis. The biopsy specimen will show a dense infiltration of neutrophils within the dermis without evidence of primary blood vessel destruction. This pathological finding distinguishes Sweet Syndrome from other inflammatory skin conditions.
The primary goal of treatment is to rapidly suppress the inflammation and resolve the symptoms. Systemic corticosteroids, such as oral prednisone, are considered the first-line treatment. Patients experience a dramatic and rapid improvement in both fever and skin lesions, often within 48 hours of starting therapy.
To prevent a relapse, the corticosteroid dose is usually tapered slowly over several weeks to months. For patients who cannot tolerate corticosteroids or in cases where the condition recurs, second-line treatments may be used, including potassium iodide, colchicine, or dapsone. If an underlying trigger like an infection, malignancy, or medication is identified, addressing or removing that cause is necessary to achieve a lasting resolution.