Sweet Syndrome: Acute Febrile Neutrophilic Dermatosis

Clinical Overview

Sweet syndrome, also termed acute febrile neutrophilic dermatosis (AFND), represents a rare systemic inflammatory condition characterized by acute onset of painful erythematous plaques and papules accompanied by fever, elevated inflammatory markers, and peripheral blood neutrophilia. The condition demonstrates strong association with malignancy in 10-50% of adult cases, particularly hematologic malignancies including acute myeloid leukemia, and with inflammatory bowel disease in 5-15% of cases. Sweet syndrome may be idiopathic, malignancy-associated (paraneoplastic), or medication-induced, with distinctions important for prognostic and management implications. Rapid diagnosis through skin biopsy demonstrating dense neutrophilic infiltration without vasculitis enables prompt systemic corticosteroid therapy achieving rapid disease resolution. Early recognition of associated malignancy drives appropriate cancer screening and treatment coordination.

Epidemiology

Sweet syndrome represents rare condition with annual incidence estimated at 0.5-5 per million population. Peak incidence occurs in adults aged 40-60 years though pediatric cases reported. Females demonstrate 1.5-2 fold higher incidence than males. Approximately 35-50% of adult Sweet syndrome cases associate with underlying malignancy, with acute myeloid leukemia (AML) most frequent (15-20% of cases), followed by other hematologic malignancies and solid tumors. Inflammatory bowel disease (Crohn disease more than ulcerative colitis) associates with Sweet syndrome in 5-15% of IBD patients. Idiopathic Sweet syndrome accounts for 40-50% of cases. Drug-induced Sweet syndrome occurs with oral contraceptives, trimethoprim-sulfamethoxazole, and G-CSF. Pediatric Sweet syndrome represents distinct entity with lower malignancy association (3-5%) compared to adults.

Pathophysiology

Sweet syndrome develops through innate immune dysregulation with abnormal neutrophil recruitment, activation, and tissue infiltration. The primary pathogenic mechanism involves disrupted balance of pro-inflammatory and anti-inflammatory cytokines with marked elevation of TNF-alpha, IL-8, IL-6, and GM-CSF. Neutrophil recruiting factors including CXCL8 (IL-8) drive massive neutrophilic infiltration into dermis creating characteristic histologic picture. Abnormal neutrophil apoptosis impairment prolongs neutrophil survival and tissue accumulation. Underlying malignancy may trigger Sweet syndrome through production of cytokine-secreting cells driving neutrophilic inflammation. Medications including G-CSF and trimethoprim-sulfamethoxazole directly stimulate neutrophil mobilization and activation. Myeloperoxidase (MPO) and ANCA-like antibodies present in variable percentages of patients. The exact trigger for aberrant neutrophil recruitment remains incompletely understood but likely involves combination of genetic predisposition and environmental triggers.

Clinical Presentation

Sweet syndrome typically presents with acute onset (often over 24-72 hours) of tender, erythematous papules and plaques frequently with pseudovesiculation. The lesions demonstrate predilection for face, neck, upper trunk, and upper extremities though can develop anywhere. The plaques demonstrate irregular borders with shiny appearance and characteristic "boggy" or edematous appearance. Fever (often high, exceeding 38.5°C) accompanies skin manifestations in 90% of cases. Constitutional symptoms including malaise, arthralgia, and myalgia occur in 60-75% of cases. Lesions remain painful and tender but typically do not itch. Systemic manifestations may include polyarthritis, conjunctivitis, oral ulceration, and rarely internal organ involvement. The clinical course typically follows rapid onset and resolution with appropriate therapy or spontaneous remission over 2-3 weeks in idiopathic cases.

Diagnosis

Diagnosis of Sweet syndrome depends on clinical presentation combined with histopathology, as skin biopsy represents diagnostic gold standard. Histopathologic examination demonstrates dense perivascular and interstitial neutrophilic infiltrate in dermis without vasculitis or leukocytoclasia. Neutrophils demonstrate preservation of nuclear morphology without significant karyorrhexis distinguishing from leukocytoclastic vasculitis. Variable degree of epidermal involvement including edema or papillomatosis. Bacterial cultures negative. Direct and indirect immunofluorescence negative. Laboratory findings supporting diagnosis include elevated white blood cell count with left shift (neutrophilia), elevated C-reactive protein and erythrocyte sedimentation rate, and mildly elevated liver function tests. Skin biopsy remains essential for diagnosis as clinical features overlap with other conditions.

Treatment Algorithm

Treatment of Sweet syndrome requires systemic corticosteroids as first-line therapy with excellent response rates. Oral prednisone 0.5-1 mg/kg daily (typically 40-60 mg) achieves rapid improvement within 24-48 hours with complete resolution of skin lesions within 1-2 weeks. Intravenous methylprednisolone 1 gram daily for 3-5 days followed by oral prednisone represents alternative for severe disease. Gradual corticosteroid taper over weeks prevents relapse. Prednisone taper can be more rapid than autoimmune bullous diseases due to transient nature. Alternative therapies for corticosteroid-intolerant patients include potassium iodide (SSKI) 300 mg three times daily achieving response in 60-75% of patients. Dapsone 100-150 mg daily provides adjunctive therapy with 50-60% response rates. Colchicine 1-2 mg daily demonstrates efficacy in some cases. Indomethacin 50 mg three times daily provides symptomatic relief. Systemic corticosteroids remain standard therapy due to rapid onset of action and high efficacy.

Prognosis

Prognosis for Sweet syndrome is excellent regarding the dermatologic manifestations with rapid response to systemic corticosteroids and low rate of permanent complications. However, prognosis depends significantly on presence or absence of underlying malignancy. Idiopathic Sweet syndrome typically resolves completely with corticosteroid therapy with low recurrence risk (10-20%). Malignancy-associated Sweet syndrome prognosis depends on underlying malignancy, with AML-associated Sweet syndrome demonstrating variable outcomes dependent on leukemia treatment response. Complete resolution of skin manifestations often parallels successful malignancy treatment. Mortality relates primarily to underlying malignancy rather than Sweet syndrome itself.

When to See a Dermatologist

Patients with suspected Sweet syndrome require prompt dermatology evaluation and skin biopsy for diagnostic confirmation. Cancer screening is essential in all adult patients.

Frequently Asked Questions

Q: Is Sweet syndrome cancer?
A: No, Sweet syndrome is a skin manifestation of systemic inflammation that occurs with cancer in 35-50% of adult cases. Malignancy screening is essential.

Q: Will Sweet syndrome return?
A: Idiopathic Sweet syndrome recurs in 10-20% of cases. Malignancy-associated recurrence depends on cancer control.

References

  1. Sweet RD. An acute febrile neutrophilic dermatosis. Br J Dermatol. 1964;76(8):349-356.
  2. Requena L, Kutzner H, Escalonilla-Rubio MJ, et al. Acute febrile neutrophilic dermatosis (Sweet's syndrome). Pathologic study of clinically typical and atypical cases. Am J Dermatopathol. 2003;25(5):379-388.
  3. Cohen PR. Sweet's syndrome--a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007;2:34.
  4. Roth D, Van Laer C, Cohen PR. Sweet's syndrome: systemic manifestations and associated conditions. Int J Dermatol. 1993;32(6):405-415.
  5. Su WP, Liu HN. Diagnostic criteria for Sweet's syndrome. Cutis. 1986;37(2):167-174.
  6. Marbini A, Fini N, Ferrero A, et al. Acute febrile neutrophilic dermatosis (Sweet's syndrome) and malignancy. J Clin Oncol. 1990;8(3):385-389.
  7. Roenigk HH Jr, Weston WL. A useful measure for the diagnosis of Sweet's syndrome. J Am Acad Dermatol. 1994;30(5 Pt 2):880-882.
  8. Howlett DC, Mackey D, Drinkwater K. Sweet's syndrome (acute febrile neutrophilic dermatosis). J R Soc Med. 1995;88(3):153-156.
  9. Hönig PJ, Rabin BS, Dimond RL. Sweet's syndrome in a child: association with upper respiratory tract infection. J Am Acad Dermatol. 1980;3(3):275-278.
  10. Requena L. Vasculitis and vasculopathy in systemic disease. Semin Cutan Med Surg. 2007;26(2):86-99.