What are the causes of Sweet's syndrome?

Causes of Sweet's Syndrome

Sweet's syndrome (acute febrile neutrophilic dermatosis) is primarily caused by inflammatory bowel disease, malignancies (especially hematologic), medications, and infections, with the rash typically being associated with active disease in IBD patients.

Clinical Presentation and Classification

Sweet's syndrome is characterized by:

• Tender, red inflammatory nodules or papules, usually affecting the upper limbs, face, or neck
• Acute fever
• Neutrophilia
• Histopathology showing neutrophilic infiltration in the upper dermis without vasculitis

Sweet's syndrome presents in three main clinical settings:

1. Classical (Idiopathic) Sweet's Syndrome

• Most common in women between 30-50 years of age 1
• Often preceded by upper respiratory tract infections (15.4% of cases) 2
• Associated with inflammatory bowel disease, particularly ulcerative colitis 3
• May occur during pregnancy

2. Malignancy-Associated Sweet's Syndrome

• Accounts for approximately 21-35% of cases 4, 5
• Most commonly associated with:
  • Hematologic malignancies (especially acute myelogenous leukemia)
  • Myeloproliferative/myelodysplastic disorders
  • Less commonly with solid tumors

3. Drug-Induced Sweet's Syndrome

• Medications implicated include:
  • Granulocyte-colony stimulating factor (most common) 3
  • Cancer chemotherapeutics
  • All-trans-retinoic acid
  • Proteasome inhibitors
  • Hypomethylating agents
  • Tyrosine kinase inhibitors
  • Lenalidomide 4

Key Diagnostic Features

Laboratory findings that may help identify the underlying cause:

• Anemia is significantly more common in malignancy-associated Sweet's syndrome compared to other types 5
• Neutrophilia is typically present
• Skin biopsy showing neutrophilic infiltrate in the upper dermis without vasculitis

Specific Associations with Inflammatory Bowel Disease

Sweet's syndrome is recognized as an extraintestinal manifestation of inflammatory bowel disease:

• More common in Crohn's disease than ulcerative colitis
• Strong predilection for:
  • Female patients
  • Patients with colonic involvement
  • Active IBD 6
• The rash is mostly associated with active disease 3

Treatment Approach

Systemic corticosteroids are the gold standard treatment for Sweet's syndrome 1:

• Prompt response with dramatic improvement of symptoms and skin lesions
• For IBD-associated Sweet's syndrome, treating the underlying IBD flare is essential 3
• For localized lesions, topical high-potency corticosteroids or intralesional corticosteroids may be effective
• Other first-line oral agents include potassium iodide and colchicine
• Second-line agents include indomethacin, clofazimine, cyclosporine, and dapsone 1

Important Clinical Considerations

• Patients presenting with Sweet's syndrome and anemia should be evaluated for underlying malignancy 5
• Sweet's syndrome may be the first sign of an undiagnosed malignancy or disease recurrence
• The condition may resolve spontaneously but recurrence is common (approximately one-third of patients with classical Sweet's syndrome) 1
• In IBD patients, Sweet's syndrome is a marker of disease activity and should prompt evaluation of IBD control

Sweet's syndrome represents a reactive process that can be triggered by various underlying conditions, making identification and treatment of the underlying cause essential for proper management.