1.1.4.3 Sweet's syndrome (acute neutrophilic dermatosis)

EB20

Acute febrile neutrophilic dermatosis.

Worldwide distribution. Usually presenting in middle age women (30-60 years) with a 4:1 female to male ratio. No racial predilection.

Sweet’s syndrome is a disorder characterized by a variety of symptoms,  clinical and histological findings, which include fever, neutrophilia, erythematous plaques or nodules, and a diffuse dermal neutrophilic infiltrate.

Most cases of Sweet’s syndrome are considered to be idiopathic,  but could also be associated with different disorders:

• Malignancy (10-20%): Myeloproliferative disorders but rarely with solid tumors.
• Inflammatory and autoimmune disorders: Inflammatory bowel disease (ulcerative colitis or Crohn disease), rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, thyroid disease ( Graves disease and Hashimoto thyroiditis)
• Infectious diseases:  HIV, viral hepatitis, tuberculosis, Chlamydia infection.
• Drugs:  G-CSF, antibiotics, antihypertensives, NSAIDs, immunosuppressives, antiepileptics, anti-neoplastic, tyrosine-kinase inhibitors, antipsychotics, anti-thyroidals
• Pregnancy

Pathogenesis unknown. Possible hypersensitivity reaction to a variety of eliciting bacterial, viral, or tumor antigens that may trigger neutrophil activation and infiltration. Possible role of activating cytokines and chemokines.

Some genetic factors and  chromosomal abnormalities have been observed in patients with Sweet’s syndrome.

Acute febrile episode associated with well-defined cutaneous eruptions accompanied by fever and constitutional symptoms (myalgia, fatigue, headache).

The lesions appear as solitary or multiple 0,5 to 12 cm, tender (leading symptom), edematous, erythematous plaques or nodules with a pseudovesicular  appearance. They may also have an urticaria-like pattern. The classical (idiopathic)  form is often preceded by an upper respiratory or gastrointestinal tract infection.

In patients with malignancy-associated Sweet's syndrome, the lesions may adopt atypical clinical patterns (bullous, ulcerated or mimicking pyoderma gangrenosum).

Sweet’s syndrome lesions can be associated with extracutaneous systemic manifestations (especially in the setting of an underlying malignancy) including arthralgias and arthritis (30-60%), ocular inflammation, (conjunctivitis, episcleritis, uveitis), myocarditis, alveolitis, hepatitis  and aseptic meningitis.

The eruption is often distributed asymmetrically. The most frequent locations are at the upper extremities, face, and neck.

Sweet's syndrome may occur in three clinical settings:

Classical (idiopathic) Sweet‘s syndrome (50%). It may be associated with infection (upper respiratory tract or gastrointestinal tract), inflammatory bowel disease, or pregnancy.

Malignancy-associated Sweet's syndrome (< 35%) In patients with an established cancer or in individuals with a previous diagnosis of a malignant hematological or solid neoplasm. The dermatosis can precede, follow, or appear concurrent with the diagnosis of the patient's cancer.

Drug-induced Sweet's syndrome

Workup shall include determining the underlying cause if present. Complete blood cell count with leukocyte differentiation. Acute phase reactants (including the erythrocyte sedimentation rate or C-reactive protein), hepatic and renal function tests and urine analysis.  Serologic evaluation for antistreptolysin-O antibody, rheumatoid factor, and thyroid function. Additional tests  if extracutaneous involvement is clinically suspected.

Age-appropriate cancer screening, including colonoscopy, mammography, and PAP smears, should be pursued.

Diffuse dense dermal neutrophilic infiltrates in the upper dermis and marked edema of the papillary dermis. Leukocytoclasia may be present.  No primary vasculitic changes. 

The individual Sweet's syndrome lesions enlarge and may coalesce over a period of days to weeks. Subsequently, either spontaneously or after treatment, the lesions usually resolve without scarring. Recurrences may occur in up to 50% of patients, usually in cases associated with an underlying inflammatory disease or hematologic malignancy.

Depending on the presence of associated disorders or extracutaneous systemic diseases.

The diagnosis is established on the basis of characteristic clinical, blood cell profile and histopathological findings. Histopathology is required for the diagnosis of Sweet’s syndrome.

Diagnostic criteria for Sweet’s syndrome have been proposed.  Diagnosis may be based on fulfilling of both major criteria and two of the four minor criteria.

Major criteria:

(1) sudden onset eruption of tender, painful plaques or nodules,

(2) neutrophilic infiltrate in the dermis without vasculitis

Minor clinical criteria:

(1) fever >38C,

(2) Illness preceded by an upper respiratory or gastrointestinal infection, or associated with an underlying inflammatory disorder, malignancy, or pregnancy,

(3) Elevated white cell count with neutrophil predominance and elevated inflammatory serum markers,

(4) Positive response to systemic glucocorticosteroids.

Febrile infectious disorders (viral, bacterial, fungal, and mycobacterial) with urticaria like pattern. 

Systemic glucocorticosteroids are the treatment of choice often achieving a rapid response. Other oral systemic agents are dapsone and colchicine. If glucocorticosteroids are contraindicated or a recurrence develops after tapering,  a detailed work-up of the diagnoses has to be made. If no underlying diseases are found, several steroid-sparing agents such as methotrexate, doxycycline, indomethacin, and cyclosporine could be prescribed.

Topical high potency or intralesional glucocorticosteroids may be used for localized lesions.

Sweet’s syndrome is the most representative entity of febrile neutrophilic dermatoses. See also chapter Pyoderma gangrenosum. Neutrophilic dermatoses  are a heterogeneous group of inflammatory cutaneous disorders characterized histologically by a neutrophilic infiltrate with no evidence of underlying infection or vasculitis.

Sweet’s syndrome typically follows a benign course and can resolve spontaneously without scarring in 5–12 weeks. Prognosis varies depending on the underlying associated disorder.