What is Sweet syndrome, its causes, symptoms, and treatment options in a female patient between 30-60 years old?

What is Sweet Syndrome?

Sweet syndrome (acute febrile neutrophilic dermatosis) is a rare inflammatory skin condition characterized by the sudden onset of tender, erythematous papules, nodules, or plaques accompanied by fever and neutrophilia, most commonly affecting women aged 30-60 years. 1, 2, 3

Clinical Presentation

Classic Triad

• Tender, erythematous skin lesions (papules, nodules, or plaques) that develop rapidly over 24-48 hours 1, 3
• Fever (>38°C), present in approximately 32% of patients 2
• Neutrophilia with leukocytosis (observed in 60% of cases) 2

Skin Lesion Characteristics

• Distribution: Predominantly affects upper extremities, trunk, and head/neck regions 1, 2
• Appearance: Erythematous and edematous plaques that are tender to touch 2, 3
• Timing: Lesions develop rapidly and have potential for recurrence 1
• Key distinguishing feature: Absence of ulceration and necrosis (unlike pyoderma gangrenosum) 1

Causes and Associated Conditions

Three Clinical Settings 3, 4

Classical (Idiopathic) Sweet Syndrome (most common in women 30-50 years):

• Often preceded by upper respiratory tract infection 3, 4
• Associated with inflammatory bowel disease 1, 3
• Can occur during pregnancy (though rare, only 2% in one series) 2
• Recurrence occurs in approximately one-third of patients 3

Malignancy-Associated Sweet Syndrome (14-21% of cases):

• Most commonly associated with acute myelogenous leukemia 3, 4
• Can be the first sign of undiagnosed malignancy or cancer recurrence 3, 4
• Clinical clue: Lower hemoglobin levels and higher erythrocyte sedimentation rate compared to other forms 2
• Associated with hematologic disorders and solid tumors 2, 4

Drug-Induced Sweet Syndrome (26% of cases):

• Most commonly caused by granulocyte-colony stimulating factor (G-CSF) 3, 4
• Other implicated medications include anticancer agents (all-trans-retinoic acid, proteasome inhibitors, tyrosine kinase inhibitors, lenalidomide) 4
• Recent infection noted in 24% of cases 2

Underlying Systemic Disorders

• 50-70% of cases are associated with underlying systemic conditions, requiring thorough evaluation 1
• Inflammatory bowel disease (particularly ulcerative colitis and Crohn's disease) forms part of the spectrum of neutrophilic dermatoses 1

Diagnostic Approach

Clinical Examination

• Thorough assessment of skin lesion distribution and morphology to distinguish from other neutrophilic dermatoses 1
• Upper limb distribution and lack of ulceration help differentiate from bowel-associated dermatosis-arthritis syndrome 1

Essential Diagnostic Tests

• Skin biopsy from an active lesion is essential for definitive diagnosis 1
• Histopathology shows dense dermal neutrophilic infiltrate, distinguishing it from erythema multiforme and leukocytoclastic vasculitis 1, 2
• Neutrophilic and lymphohistiocytic infiltrate with edema are the most frequent findings 2

Laboratory Evaluation

• Complete blood count with differential (assessing for leukocytosis and neutrophilia) 2, 3
• Erythrocyte sedimentation rate (elevated ESR may indicate need for malignancy screening) 2
• Hemoglobin level (lower levels associated with malignancy-associated form) 2

Differential Diagnosis 1

The differential must include:

• Drug eruption
• Cutaneous infiltration with underlying malignancy
• Chemotherapy or radiation-induced skin reactions
• Erythema multiforme
• Leukocytoclastic vasculitis
• Infection (bacterial, fungal, viral, or parasitic)

Critical pitfall: Failure to perform skin biopsy can lead to misdiagnosis 1

Treatment Options

First-Line Therapy

Systemic corticosteroids are the therapeutic gold standard 3, 5

• Prompt and dramatic improvement of symptoms and skin lesions after initiation 3, 5
• Excellent response observed in the majority of patients 2

Alternative First-Line Agents 3, 5

• Potassium iodide (oral systemic)
• Colchicine (oral systemic)
• Topical high-potency corticosteroids or intralesional corticosteroids for localized lesions 3

Second-Line Agents 3, 5

• Indomethacin
• Clofazimine
• Cyclosporine
• Dapsone

Special Considerations for Women 30-60 Years

Malignancy screening is essential when higher ESR and lower hemoglobin levels are present 2

Evaluation for inflammatory bowel disease should be performed, as recommended by the American Gastroenterological Association 1

Leukocytoclasia on histopathology is associated with higher risk of recurrence (P = 0.01), demanding closer and longer follow-up 2

Treatment of underlying conditions is crucial, as the syndrome may resolve with management of associated malignancy, infection, or inflammatory disease 3, 4

Natural History

• Symptoms and lesions may resolve spontaneously without therapeutic intervention 3, 5
• However, recurrence may follow either spontaneous remission or therapy-induced resolution 3, 5

Key Clinical Pearls

All patients with Sweet syndrome deserve careful investigation of possible underlying conditions, particularly malignancy, inflammatory bowel disease, and recent infections 2, 3

Mycoplasma pneumoniae has been specifically associated with a variant involving predominantly mucous membranes in patients with upper respiratory tract infections 1

The condition can be distinguished from Stevens-Johnson syndrome/toxic epidermal necrolysis by the characteristic neutrophilic infiltrate rather than epidermal necrosis 6