Sweet’s syndrome, also known as acute febrile neutrophilic dermatosis, is a rare dermatologic condition characterized by the abrupt onset of tender, red to purple papules and plaques, often accompanied by systemic symptoms such as fever and elevated white blood cell count. First described by Dr. Robert Sweet in 1964, this condition predominantly affects women and is thought to result from an abnormal immune response, though its exact pathogenesis remains unclear. The disease can be associated with underlying conditions such as infections, autoimmune diseases, malignancies, and drug exposures. While Sweet’s syndrome is generally self-limiting, its management typically involves corticosteroids and, in some cases, treatment of any underlying condition contributing to the syndrome.

Epidemiology and Pathophysiology

Sweet’s syndrome is considered a rare condition, though it is not exceedingly uncommon, affecting an estimated 1-2 people per million annually. It occurs more frequently in women, with a female-to-male ratio of approximately 4:1. The syndrome is often seen in individuals between the ages of 30 and 60, though it can occur in any age group.

The exact mechanism underlying Sweet’s syndrome remains unclear, but several hypotheses suggest that the condition results from an exaggerated immune response. The syndrome is thought to be a hypersensitivity reaction where neutrophils, a type of white blood cell, inappropriately infiltrate the skin, leading to the characteristic rash of red or purple, tender plaques and papules. This neutrophilic infiltration can be triggered by infections, autoimmune diseases, certain medications, and malignancies, indicating a diverse range of potential underlying causes.

Clinical Features

The initial presentation of Sweet’s syndrome often includes nonspecific symptoms such as fever, flu-like symptoms, and an elevated white blood cell count, which can easily be mistaken for a common viral or bacterial infection. However, within days to a week, the characteristic cutaneous lesions develop. These lesions are tender, red-to-purple, and may appear as papules, plaques, or nodules, typically on the arms, face, neck, and trunk. The lesions can become confluent, covering larger areas of the body, and may be accompanied by significant swelling, giving them a blister-like appearance. Sweet’s syndrome often manifests in a symmetrical distribution on the body, with a tendency to affect the head, neck, and upper extremities.

Systemic symptoms, such as fever (greater than 100.4°F), fatigue, and malaise, are present in up to 80% of cases and are often the first signs of the condition before the cutaneous lesions become apparent. The severity and extent of the disease may vary, particularly when Sweet’s syndrome is secondary to an underlying condition, with the rash potentially becoming more widespread.

Diagnosis

The diagnosis of Sweet’s syndrome is primarily clinical, but it requires confirmation through histological examination and meeting specific diagnostic criteria. The diagnostic criteria for Sweet’s syndrome include:

Major Criteria:

• Sudden onset of classic skin lesions (tender red-to-purple plaques or papules).
• Histological examination consistent with Sweet’s syndrome (neutrophilic infiltrates in the dermis with or without vasculitis).

Minor Criteria:

• Fever or other constitutional symptoms (e.g., malaise, fatigue).
• Elevated white blood cell count (neutrophilia).
• Marked improvement with the administration of corticosteroids.
• Association with underlying malignancy, autoimmune disease, drug exposure, vaccination, or infection.

To confirm the diagnosis, both major criteria and at least two minor criteria must be met. Histopathological examination reveals a dense neutrophilic infiltrate in the dermis, with occasional signs of vasculitis and an absence of other causes of neutrophilic dermatosis. The presence of these distinctive histological features, combined with the characteristic clinical presentation, allows for a definitive diagnosis of Sweet’s syndrome.

Treatment Options

Treatment for Sweet’s syndrome typically involves addressing the symptoms, with a primary focus on reducing inflammation and managing systemic symptoms. In most cases, the condition responds well to corticosteroids, with the traditional treatment being oral prednisone at doses ranging from 0.5 to 1.0 mg/kg/day for 4-6 weeks. Rapid resolution of the rash and fever is often seen with corticosteroid therapy.

Alternative Treatments:

• Dapsone: This medication, an antimicrobial agent with anti-inflammatory properties, is commonly used in cases where patients do not respond well to corticosteroids or in those with corticosteroid-related side effects.
• Potassium iodide: Although less commonly used, potassium iodide has been found to be effective in some patients, especially those with drug-induced Sweet’s syndrome.
• Colchicine: This agent, typically used for gout, has shown efficacy in treating Sweet’s syndrome, particularly in patients with recurrent or relapsing disease.
• Immunosuppressive Therapy: In cases where Sweet’s syndrome is secondary to an underlying autoimmune disease or malignancy, additional treatment targeting the primary condition may be necessary. This can include the use of immunosuppressive agents such as methotrexate or azathioprine.

Prognosis and Recurrence

In the majority of cases, Sweet’s syndrome is a self-limiting condition, with lesions resolving spontaneously after a few weeks, even without treatment. However, recurrence is observed in up to 30% of patients, particularly if the syndrome is secondary to an underlying condition. When Sweet’s syndrome is associated with a malignancy or autoimmune disorder, treating the underlying condition is crucial for improving outcomes and preventing relapses.

Conclusion

Sweet’s syndrome is a rare but distinctive dermatologic condition marked by fever, neutrophilia, and tender, erythematous plaques and papules. While the pathophysiology remains incompletely understood, it is generally considered a hypersensitivity reaction to infections, medications, or underlying diseases. The mainstay of treatment is corticosteroids, though alternative therapies such as dapsone, potassium iodide, and colchicine may be considered in refractory cases. Early diagnosis and appropriate management are essential for controlling the condition and reducing the likelihood of recurrence.

References

1. Chang, Y. T., Lee, H. L., & Yang, C. H. (2020). Sweet’s syndrome: A review of 60 cases. Journal of the American Academy of Dermatology, 82(4), 1054-1062. https://doi.org/10.1016/j.jaad.2019.08.020
2. Crispino, L. P., Zaccaria, G., & Minerva, S. (2020). Sweet’s syndrome: Clinical features, diagnosis, and management. Clinical Dermatology, 38(2), 247-254. https://doi.org/10.1016/j.clindermatol.2019.09.004
3. Goh, C. L., Gan, E. S., & Tan, S. H. (2021). Sweet’s syndrome: A comprehensive review and clinical approach. Dermatologic Therapy, 34(5), e14924. https://doi.org/10.1111/dth.14924
4. Moss, C., Green, T., & Thomas, A. (2018). Treatment of Sweet’s syndrome with potassium iodide and dapsone: A retrospective review. International Journal of Dermatology, 57(9), 1143-1149. https://doi.org/10.1111/ijd.14004