Sweet Syndrome

Sweet's syndrome (the eponym for acute febrile neutrophilic dermatosis) is characterized by a constellation of clinical symptoms, physical features, and pathologic findings which include fever, neutrophilia, tender erythematous skin lesions (papules, nodules, and plaques), and a diffuse infiltrate consisting predominantly of mature neutrophils that are typically located in the upper dermis. Several hundreds cases of Sweet's syndrome have been published. Sweet's syndrome presents in three clinical settings: classical (or idiopathic), malignancy-associated, and drug-induced. Classical Sweet's syndrome (CSS) usually presents in women between the age of 30 to 50 years, it is often preceded by an upper respiratory tract infection and may be associated with inflammatory bowel disease and pregnancy. Approximately one-third of patients with CSS experience recurrence of the dermatosis. The malignancy-associated Sweet's syndrome (MASS) can occur as a paraneoplastic syndrome in patients with an established cancer or individuals whose Sweet's syndrome-related hematologic dyscrasia or solid tumor was previously undiscovered; MASS is most commonly related to acute myelogenous leukemia. The dermatosis can precede, follow, or appear concurrent with the diagnosis of the patient's cancer. Hence, MASS can be the cutaneous harbinger of either an undiagnosed visceral malignancy in a previously cancer-free individual or an unsuspected cancer recurrence in an oncology patient. Drug-induced Sweet's syndrome (DISS) most commonly occurs in patients who have been treated with granulocyte-colony stimulating factor, however, other medications may also be associated with DISS. The pathogenesis of Sweet's syndrome may be multifactorial and still remains to be definitively established. Clinical and laboratory evidence suggests that cytokines have an etiologic role. Systemic corticosteroids are the therapeutic gold standard for Sweet's syndrome. After initiation of treatment with systemic corticosteroids, there is a prompt response consisting of dramatic improvement of both the dermatosis-related symptoms and skin lesions. Topical application of high potency corticosteroids or intralesional corticosteroids may be efficacious for treating localized lesions. Other first-line oral systemic agents are potassium iodide and colchicine. Second-line oral systemic agents include indomethacin, clofazimine, cyclosporine, and dapsone. The symptoms and lesions of Sweet's syndrome may resolved spontaneously, without any therapeutic intervention; however, recurrence may follow either spontaneous remission or therapy-induced clinical resolution.

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.

Sweet syndrome (SS), originally described as acute febrile neutrophilic dermatosis, is a rare inflammatory skin condition, considered the prototype of neutrophilic dermatoses. It is characterised by the sudden onset of well-defined tender papules, plaques and nodules often accompanied by fever, neutrophilia and elevated markers of inflammation. Several variants have been described both clinically and histopathologically. Classifications include idiopathic, malignancy-associated, and drug-induced SS. The exact pathogenesis of SS is still unclear; however, recent findings have shed light on the role of dermal infiltrating neutrophils-in the context of innate immunity, and signalling pathways related to adaptive immunity. To critically analyse the current molecular landscape of SS and discuss the recent evidence supporting novel potential immune mediators and biological signalling pathways involved in SS pathogenesis. The methodology followed PRISMA guidelines and included two bibliographical databases, searching articles published until 17 December 2023. Titles, abstracts and full text were reviewed independently by two assessors, while other two investigators resolved any opinion differences. Of 3303 records identified through database search, 22 articles met the eligibility criteria for inclusion. We considered experimental studies that performed molecular analysis, in terms of cytokines quantification, gene expression and/or immunofluorescence/immunohistochemistry. As for the latter, only studies aimed at characterising the nature of the inflammatory infiltrate and potential mechanisms leading to distinct forms of cutaneous inflammatory cell influx were included. Overall, we described research on 202 SS patients (177 skin biopsies and 25 blood specimens) revealing the predominant role of neutrophil activation and abnormal proliferation as unifying mechanisms in different SS subtypes. Interestingly, we found that hyperactivation of the IL-1 pathway might occur only in a subset of SS patients and adaptive immunity could also play a role in the pathogenic scenario of SS, with a potential significant role of IL-17 axis. This systematic review provides a wealth of evidence on the molecular landscape of SS, although further research is needed to a deeper understanding of the patho-mechanisms of this rare disease and hopefully lead to targeted therapeutic approaches.

Occult hematologic malignancies can initially present with cutaneous manifestations. We describe a 53-year-old woman with chronic hepatitis C and intravenous drug use presenting with a painful, progressive leg rash and worsening bicytopenias. A skin punch biopsy revealed neutrophilic dermatosis morphologically compatible with Sweet syndrome (SS), along with rare CD117+/CD34 − blastoid cells. Subsequent bone marrow studies revealed acute myeloid leukemia with mutated NPM1. This case highlights the diagnostic challenge of distinguishing SS from leukemia cutis (LC) when skin biopsies demonstrate mixed neutrophilic with rare blastoid cells. LC represents cutaneous infiltration of leukemic blasts, whereas SS represents a non-neoplastic, cytokine-driven process. Prompt immunophenotypic evaluation and genomic testing of myeloid dermatoses, particularly those with blastoid cells, can be critical in distinguishing SS from LC to provide significant insight on prognosis and therapeutic options. This case highlights the clinical and histopathologic spectrum of myeloid dermatoses and further emphasizes the relevance of skin biopsies in the diagnosis of cutaneous involvement by hematologic malignancies, such as myeloid neoplasms.