What is Sweet's syndrome and what causes it?

Sweet's Syndrome: Definition and Etiology

Sweet's syndrome (acute febrile neutrophilic dermatosis) is characterized by tender, red inflammatory nodules or papules typically affecting the upper limbs, face or neck, accompanied by fever and neutrophilia, and is commonly associated with inflammatory bowel disease, malignancies, infections, or medications. 1

Clinical Features

Sweet's syndrome presents with distinctive clinical manifestations:

• Cutaneous lesions:

  • Tender, erythematous papules, nodules, or plaques
  • Predominantly affects upper extremities, face, and neck
  • May have edematous appearance
  • Lesions develop over 24-48 hours 2

• Systemic symptoms:

  • Fever (present in approximately 32% of patients) 2
  • Malaise
  • Neutrophilia (39% of cases) 2
  • Leukocytosis (60% of cases) 2

• Histopathology:

  • Dense dermal infiltrate of mature neutrophils
  • Edema in the upper dermis
  • Absence of vasculitis (though leukocytoclasia may be present) 2, 3
  • Perivascular infiltration

Etiology and Classification

Sweet's syndrome can be classified into three main categories based on etiology:

1. Classical (Idiopathic) Sweet's Syndrome

• Most common in women aged 30-50 years
• Often preceded by upper respiratory tract infection
• Associated with inflammatory bowel disease and pregnancy
• Approximately one-third of patients experience recurrence 3

2. Malignancy-Associated Sweet's Syndrome

• Occurs as a paraneoplastic syndrome
• Most commonly associated with:
  • Acute myelogenous leukemia
  • Other hematologic malignancies
  • Solid tumors
• Can precede, follow, or appear concurrently with cancer diagnosis
• Laboratory markers: higher erythrocyte sedimentation rate and lower hemoglobin levels compared to other forms 2

3. Drug-Induced Sweet's Syndrome

• Most commonly associated with granulocyte-colony stimulating factor
• Other medications may also trigger the condition
• Accounts for approximately 26% of cases 2
• Typically resolves with discontinuation of the offending medication

4. Other Associations

• Inflammatory bowel disease (particularly ulcerative colitis)
• Infections (24% of cases) 2
• Pregnancy (rare)
• Autoimmune disorders

Pathogenesis

The exact pathogenesis remains unclear but is likely multifactorial:

• Cytokines play a significant etiologic role
• Possible hypersensitivity reaction
• Immune complex formation
• Neutrophil dysfunction
• Genetic predisposition

Treatment

Systemic corticosteroids are the gold standard treatment for Sweet's syndrome 3, 4:

• Prompt response with dramatic improvement of symptoms and skin lesions

• First-line alternatives when corticosteroids are contraindicated:

  • Potassium iodide
  • Colchicine

• Second-line agents:

  • Indomethacin
  • Clofazimine
  • Cyclosporine
  • Dapsone

• For localized lesions:

  • Topical high-potency corticosteroids
  • Intralesional corticosteroids

Clinical Pearls and Pitfalls

• Diagnostic pitfall: Sweet's syndrome can be mistaken for infection, drug eruption, or other neutrophilic dermatoses
• Clinical pearl: Patients with leukocytoclasia on biopsy have a higher risk of recurrence 2
• Important consideration: All patients with Sweet's syndrome deserve careful investigation for underlying conditions, particularly malignancies
• Differential diagnosis: Should include pyoderma gangrenosum, erythema multiforme, leukocytoclastic vasculitis, and bowel-associated dermatosis-arthritis syndrome 1
• Monitoring: Higher ESR and lower hemoglobin levels might indicate need for malignancy screening 2

Sweet's syndrome typically responds rapidly to appropriate treatment, but recurrences may occur following either spontaneous remission or therapy-induced clinical resolution.