What are the causes of Sweet syndrome?

Causes of Sweet Syndrome

Sweet syndrome (acute febrile neutrophilic dermatosis) is primarily caused by three major etiological factors: idiopathic/classical, malignancy-associated, and drug-induced causes, with infections also playing a significant role in many cases. 1

Major Etiological Categories

1. Classical/Idiopathic Sweet Syndrome

• Most commonly affects women between 30-50 years of age 1
• Often preceded by upper respiratory tract infections 1, 2
• Associated with inflammatory bowel disease and pregnancy 1
• Approximately one-third of patients experience recurrence of the dermatosis 1

2. Malignancy-Associated Sweet Syndrome

• Accounts for approximately 21% of Sweet syndrome cases 3
• Most commonly associated with hematologic malignancies, particularly acute myelogenous leukemia 1
• Can occur as a paraneoplastic syndrome in patients with established cancer 1
• May be the first sign of an undiagnosed malignancy or cancer recurrence 1
• Laboratory findings: patients with malignancy-associated Sweet syndrome typically have significantly lower hemoglobin levels compared to those with classical or drug-induced forms 4

3. Drug-Induced Sweet Syndrome

• Most commonly associated with granulocyte-colony stimulating factor (G-CSF) 1
• Other implicated medications include:
  • All-trans-retinoic acid 3
  • Proteasome inhibitors 3
  • Hypomethylating agents 3
  • Tyrosine kinase inhibitors 3
  • Lenalidomide 3

4. Infection-Associated Sweet Syndrome

• Upper respiratory tract infections are the most common infectious triggers 1, 5
• Mycoplasma pneumoniae has been specifically associated with a variant involving predominantly mucous membranes 6
• Various bacterial, fungal, viral, and parasitic infections should be considered in the differential diagnosis 2

Pathophysiological Mechanisms

• The pathogenesis remains multifactorial and not definitively established 1
• Cytokines appear to play a significant etiologic role based on clinical and laboratory evidence 1
• Aberrant activation, proliferation, and skin homing of neutrophils is a unifying mechanism across different causes 7
• Recent evidence suggests both innate and adaptive immunity may play roles in the pathogenesis 7
• The incidence of drug-induced Sweet syndrome has been increasing due to frequent use of growth factors in cancer patients 3

Clinical Presentation

• Characterized by tender, erythematous papules, nodules, or plaques 2, 5
• Lesions commonly appear on upper limbs, trunk, and head/neck 2, 5
• Accompanied by fever and neutrophilia 2
• Various clinical and histopathological variants have been described, highlighting the heterogeneity of the condition 7

Diagnostic Approach

• Skin biopsy is essential for definitive diagnosis and should be performed on an active lesion 2
• Failure to perform skin biopsy can lead to misdiagnosis 2
• Thorough evaluation for underlying malignancy is warranted, especially in patients with anemia 4

Management Considerations

• Systemic corticosteroids are the therapeutic gold standard with prompt response 1, 7
• Alternative first-line agents include potassium iodide and colchicine 1
• Second-line agents include indomethacin, clofazimine, cyclosporine, and dapsone 1
• Some cases may resolve spontaneously without treatment, though recurrence is possible 1

Understanding the various causes of Sweet syndrome is essential for appropriate management, as treatment may need to address not only the skin manifestations but also any underlying conditions.