Sweet Syndrome (Acute Febrile Neutrophilic Dermatosis)

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Introduction

Sweet Syndrome is a rare inflammatory condition characterized by sudden onset of painful, erythematous plaques, nodules, or papules, accompanied by fever and neutrophilia. First described by Dr. Robert Douglas Sweet in 1964.

Key Points

• Rare in children compared to adults
• Female predominance (4:1 female to male ratio)
• Peak incidence: 30-60 years
• Often associated with underlying conditions
• Excellent response to systemic corticosteroids

Pathophysiology

• Neutrophil dysfunction
• Cytokine dysregulation (particularly IL-1β, IL-6, IL-8, IL-17, TNF-α)
• Hypersensitivity reaction
• Genetic factors (HLA-B54)

Classification

Three Clinical Variants:

1. Classical (Idiopathic) Sweet Syndrome
   • Most common form
   • Often preceded by upper respiratory infection
   • Associated with inflammatory bowel disease
2. Malignancy-Associated Sweet Syndrome
   • 20-25% of cases
   • Most commonly associated with acute myeloid leukemia
   • Can precede, follow, or present simultaneously with malignancy
3. Drug-Induced Sweet Syndrome
   • Most commonly by G-CSF
   • Other drugs: all-trans retinoic acid, trimethoprim-sulfamethoxazole
   • Typically resolves with drug discontinuation

Clinical Features

Cutaneous Manifestations

• Primary Lesions:
  • Tender erythematous plaques
  • Pseudovesicular appearance
  • Mammillated surface
  • Assymetric distribution
  • Predilection for upper extremities, face, and neck
• Characteristics:
  • Painful and tender to touch
  • May have vesicular or pustular appearance
  • Can develop target-like appearance
  • Individual lesions enlarge rapidly
  • Healing without scarring

Extracutaneous Manifestations

• Constitutional Symptoms:
  • High fever (>38°C)
  • General malaise
  • Arthralgia
  • Myalgia
  • Headache
• Organ Involvement:
  • Eyes (conjunctivitis, episcleritis)
  • Joints (arthritis)
  • Oral mucosa (aphthous ulcers)
  • Lungs (neutrophilic infiltrates)
  • Bones (osteomyelitis-like lesions)
  • Central nervous system (aseptic meningitis)

Associated Conditions

• Infections:
  • Upper respiratory tract infections
  • Gastrointestinal infections
  • Mycobacterial infections
• Inflammatory Conditions:
  • Inflammatory bowel disease
  • Rheumatoid arthritis
  • Behçet's disease
• Pregnancy
• Medications
• Vaccinations

Diagnosis & Workup

Diagnostic Criteria (Modified Su and Liu Criteria)

Major Criteria (Both Required):

1. Abrupt onset of painful erythematous plaques or nodules
2. Histopathologic evidence of dense neutrophilic infiltrate without vasculitis

Minor Criteria (At least 2 Required):

1. Preceded by fever or infection
2. Accompanied by:
   • Fever >38°C
   • Arthralgias
   • Conjunctivitis
   • Malignancy
3. Excellent response to systemic corticosteroids
4. Abnormal laboratory values at presentation:
   • ESR >20 mm/hr
   • Positive CRP
   • Leukocytosis
   • >70% neutrophils

Laboratory Studies

• Complete blood count with differential
• Comprehensive metabolic panel
• ESR and CRP
• Blood cultures if fever present
• Age-appropriate malignancy screening
• Chest X-ray
• Skin biopsy (essential for diagnosis)

Histopathology

• Dense neutrophilic infiltrate in upper dermis
• Edema in superficial dermis
• No evidence of vasculitis
• Fragmentation of neutrophil nuclei (karyorrhexis)

Management

First-Line Treatment

• Systemic Corticosteroids:
  • Prednisone 0.5-1.0 mg/kg/day
  • Rapid response within 48-72 hours
  • Gradual taper over 4-6 weeks

Alternative Therapies

• First-line alternatives:
  • Potassium iodide
  • Colchicine
  • Dapsone
• Second-line options:
  • Indomethacin
  • Cyclosporine
  • TNF-α inhibitors
  • IVIG

Treatment of Special Cases

• Drug-induced:
  • Discontinuation of offending drug
  • May still require systemic steroids
• Malignancy-associated:
  • Treatment of underlying malignancy
  • May require more aggressive therapy

Complications & Prognosis

Potential Complications

• Local Complications:
  • Secondary infection
  • Scarring (rare)
  • Post-inflammatory hyperpigmentation
• Systemic Complications:
  • Ocular involvement
  • Musculoskeletal manifestations
  • Neurologic involvement

Prognosis

• Classical Form:
  • Excellent response to therapy
  • May recur in 30% of cases
  • No long-term sequelae
• Malignancy-Associated:
  • Prognosis depends on underlying malignancy
  • Higher recurrence rate
  • May require longer treatment

Further Reading

• Medscape - Sweet Syndrome
• NORD - Sweet Syndrome
• DermNet NZ - Sweet Syndrome
• American College of Rheumatology - Sweet Syndrome
• StatPearls - Sweet Syndrome