What is Sweet syndrome (acute febrile neutrophilic dermatosis)?

Sweet Syndrome (Acute Febrile Neutrophilic Dermatosis)

Sweet syndrome is a rare inflammatory skin condition characterized by sudden onset of fever, neutrophilia, and painful erythematous skin lesions with a dense neutrophilic infiltrate in the upper dermis that responds dramatically to systemic corticosteroid therapy.

Clinical Presentation

Key Features

• Fever and malaise (often prodromal)
• Tender, erythematous skin lesions:
  • Papules, nodules, or plaques
  • Typically on upper limbs, face, neck, and trunk
  • May have a pseudovesicular appearance
• Prominent cutaneous pain
• Elevated inflammatory markers (ESR, CRP)
• Peripheral blood neutrophilia (in most cases)
• Mucosal involvement may occur

Clinical Variants

Sweet syndrome presents in three main clinical settings:

1. Classical (Idiopathic) Sweet Syndrome:

   • Most common in women aged 30-50 years
   • Often preceded by upper respiratory tract infection
   • May be associated with inflammatory bowel disease and pregnancy
   • Approximately one-third experience recurrence 1

2. Malignancy-Associated Sweet Syndrome:

   • Occurs as paraneoplastic syndrome
   • Most commonly associated with acute myelogenous leukemia
   • Can precede, follow, or appear concurrent with cancer diagnosis
   • May be the first sign of an undiagnosed malignancy or cancer recurrence 1, 2

3. Drug-Induced Sweet Syndrome:

   • Most commonly associated with granulocyte-colony stimulating factor
   • Other medications may also trigger the condition
   • Typically resolves with drug withdrawal 1, 3

Extracutaneous Manifestations

Sweet syndrome can involve multiple organ systems:

• Ocular: conjunctivitis, episcleritis, uveitis
• Musculoskeletal: arthralgia, myalgia
• Pulmonary: neutrophilic infiltrates
• Renal: neutrophilic infiltration
• Neurologic: encephalitis, aseptic meningitis
• Hepatic: neutrophilic infiltration

Diagnosis

Diagnostic Criteria

Diagnosis is based on clinical and histopathological findings:

1. Major criteria:

   • Abrupt onset of painful erythematous plaques or nodules
   • Histopathology showing dense neutrophilic infiltrate without vasculitis

2. Minor criteria:

   • Fever >38°C
   • Association with underlying malignancy, inflammatory disease, pregnancy, or preceding infection
   • Excellent response to systemic corticosteroids
   • Abnormal laboratory values (elevated ESR/CRP, leukocytosis)

Histopathology

• Dense, diffuse neutrophilic infiltrate in the upper dermis
• Absence of vasculitis
• Edema of the papillary dermis
• May have fragmented neutrophil nuclei (leukocytoclasia)

Differential Diagnosis

• Pyoderma gangrenosum
• Erythema multiforme
• Erythema nodosum
• Bowel-associated dermatosis-arthritis syndrome
• Neutrophilic dermatoses associated with IBD
• Infection (bacterial, fungal)
• Vasculitis

Treatment

First-Line Therapy

• Systemic corticosteroids are the gold standard treatment 1, 3
  • Prednisone 0.5-1 mg/kg/day
  • Dramatic improvement typically occurs within 48-72 hours
  • Gradual taper over 2-4 weeks to prevent relapse

Alternative First-Line Options

• Potassium iodide: 300 mg three times daily
• Colchicine: 0.5 mg 2-3 times daily

Second-Line Therapies

• Indomethacin
• Clofazimine
• Cyclosporine
• Dapsone

Treatment Considerations

• Treat underlying malignancy if present
• Discontinue suspected causative medications
• In drug-induced cases, withdrawal of the offending agent may lead to resolution
• Approximately one-third of patients with classical Sweet syndrome experience recurrence 1
• Some cases may resolve spontaneously without treatment

Association with Inflammatory Bowel Disease

Sweet syndrome is recognized as an extraintestinal manifestation of inflammatory bowel disease (IBD), particularly ulcerative colitis 4. In patients with IBD, Sweet syndrome:

• Often correlates with disease activity
• May respond to treatment of the underlying IBD
• Typically presents with the characteristic rash on upper limbs, face, or neck
• Responds well to systemic corticosteroids

Prognosis

The prognosis for Sweet syndrome is generally good:

• Rapid response to appropriate therapy
• Skin lesions typically heal without scarring
• Recurrence is common in classical form (approximately one-third of cases)
• Prognosis in malignancy-associated cases depends on the underlying malignancy
• Drug-induced cases usually resolve with discontinuation of the offending agent

Key Points for Clinicians

• Always evaluate for underlying malignancy, particularly hematologic
• Consider medication review to identify potential triggers
• Prompt initiation of systemic corticosteroids leads to rapid improvement
• Monitor for recurrence after treatment discontinuation
• Consider steroid-sparing agents for maintenance therapy in recurrent cases
• Biopsy is essential for diagnosis and to rule out infection or vasculitis

Sweet syndrome, while rare, represents an important neutrophilic dermatosis that may signal underlying systemic disease. Prompt recognition and treatment are essential to relieve symptoms and identify potentially serious associated conditions.