Insights Into the Pathogenesis of Sweet's Syndrome

Abstract

Sweet's syndrome, also known as Acute Febrile Neutrophilic Dermatosis, is a rare inflammatory condition. It is considered to be the prototype disease of neutrophilic dermatoses, and presents with acute onset dermal neutrophilic lesions, leukocytosis, and pyrexia. Several variants have been described both clinically and histopathologically. Classifications include classic Sweet's syndrome, malignancy associated, and drug induced. The cellular and molecular mechanisms involved in Sweet's syndrome have been difficult to elucidate due to the large variety of conditions leading to a common clinical presentation. The exact pathogenesis of Sweet's syndrome is unclear; however, new discoveries have shed light on the role of inflammatory signaling, disease induction, and relationship with malignancy. These findings include an improved understanding of inflammasome activation, malignant transformation into dermal infiltrating neutrophils, and genetic contributions. Continued investigations into effective treatments and targeted therapy will benefit patients and improve our molecular understanding of inflammatory diseases, including Sweet's syndrome.

Insights Into the Characteristics of Sweet Syndrome in Patients With and Without Hematologic Malignancy

“…A review about Sweet syndrome that was published in 2019 categorized corticosteroids and other agents such as potassium iodide or colchicine as the first-line treatments (20). Tumor necrosis factor α (TNF-α) antagonists and interleukin 1 (IL-1) inhibitors have also been reported to be effective (21)(22)(23)(24)(25)(26)(27).…”

Upper Respiratory Infection Followed by Concurrent Sweet’s Syndrome and Erythema Nodosum

“…Different diseases, including infectious diseases, malignancies and medications are associated with SS. It appears mostly in women between age 30-60 years [3][4][5] . There are major and minor criteria for diagnosis of SS ( Figure 1) 6,7 .…”

“…For the treatment of patients with Sweet's syndrome systemic corticosteroids have been considered the primary option, but iodide or colchicine can also result in rapid resolution symptoms and lesions. In case that corticosteroids are contraindicated, indomethacin, clofazimine, dapsone, and cyclosporine can be administered 3,4 . Erythema nodosum (EN), a form of panniculitis, is manifested as erythematous painful rounded lumps, 1-6 cm in diameter and occurs 3-5 times more often in female patients in all age groups, but mostly between the second and the fourth decades of life.…”

Thalidomide in the Treatment of Sweet's Syndrome and Eosinophilic Folliculitis Associated With Immune Reconstitution Inflammatory Syndrome

“…that can induce cytokine cascade (12). It is classified as classical, drug-induced, and malignancy-associated Sweet's syndrome (14). It has been increasingly reported with co-occurring immunodeficiencies (15,16).…”

“…In addition, the immunohistochemistry and serological tests suggested that Th1 (17) and Th17 cells (18) secreted pro-inflammatory cytokines (IL-2, INF-γ, and IL-17) played a dominant role in the pathogenesis of Sweet's syndrome, which could activate and recruit neutrophils to the site of inflammation. Besides, other neutrophil recruiters and activators, such as TNF-α, IL-6, and IL-8 are potential cytokine candidates in the pathogenesis of Sweet's syndrome (14,19,20). And some authors have speculated that IL-6 may also be a potential target for the treatment of ND (21).…”