Acute febrile neutrophilic dermatosis

Background

• Also known as Sweet syndrome
• Characterized by painful nodules/plaques and fever

Epidemiology

• Rare
• More often in women, though not entirely clear
• More often in adults aged 30 to 60 years

Etiologies

• Primary/idiopathic
• Secondary
  • Infectious/post-infectious
    • Upper respiratory tract infections
    • GI infections
    • NTM
    • Also melioidosis, Erysipelothrix rhusiopathiae, tuberculosis, syphilis, HIV, HCV, COVID-19, sporotrichosis, coccidiomycosis, histoplasmosis
    • Possibly also toxoplasmosis and enterobiasis
  • Hematologic malignancies, particularly AML but also MDS, hairy cell leukemia, and myelofibrosis
  • Solid-organ malignancies, including cervical cancer, cholangiocarcinoma, colon cancer, gastric cancer, and lung cancer
  • Drug-induced
    • Antibiotics: nitrofurantoin, nofloxacin, ofloxacin, minocycline, quinupristin/dalfopristin, cotrimoxazole
    • Antivirals: abacavir
    • Antiepileptics: carbamazepine, diazepam
    • Antineoplastics: bortezomib, imatinib, lenalidomide
    • Antihypertensives: hydralazine
    • Antipsychotics: clozapine
    • Antithyroid medications: propylthiouracil
    • GCSF, GMCSF
    • Levonorgestrel contraceptives
    • Diuretics: furosemide
    • NSAIDs: celecoxib, diclofenac
    • ATRA

Clinical Manifestations

• Sudden onset edematous, erythematous lesions (can be papules, nodules, or plaques)
  • Most commonly on the upper extremities, face, and neck
• Fever, leukocytosis

Clinical Variants

• Bullous: flaccid or tense blisters on extremities, trunk, face, and acral surfaces
• Cellulitis-like: tender, erythematous, edematous lesions identical to cellulitis
• Necrotizing: rapidly-progressive lesions with necrosis of underlying soft tissues, similar appeareance to necrotizing fasciitis

Diagnostic Criteria

Classical Sweet Syndrome

• Requires both major criteria and at least 2 minor criteria
• Major criteria:
  • Abrupt onset of painful erythematous plaques or nodules
  • Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis
• Minor criteria:
  • Fever greater than 38 Celsius
  • Underlying hematologic or solid-organ malignancy, inflammatory disease, or pregnancy; or preceded by an upper respiratory or GI infection or vaccination
  • Excellent response to systemic corticosteroids or potassium iodide
  • Abnormal bloodwork at presentation, with at least 3 of: ESR >20 mm/h, elevated CRP, WBC >8, neutrophils >70%

Drug-Induced Sweet Syndrome

• Requires the presence of all five criteria
• Criteria:
  • Abrupt onset of painful erythematous plaques or nodules
  • Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis
  • Fever greater than 38 Celsius
  • Temporal relationship between drug ingestion and clinical presentation, or temporally-related recurrence after oral challenge
  • Temporal relationship between drug withdrawal or treatment with systemic corticosteroids and resolution of lesions

Further Reading

• Sweet's syndrome - a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007;2:34. doi: 10.1186/1750-1172-2-34.