Sweet's syndrome; acute febrile neutrophilic dermatosis

Introduction

Uncommon, recurrent skin disease characterized by painful inflammatory papules & plaques associated with fever, arthralgia & leukocytosis.

Etiology

• idiopathic
• possibly hypersensitivity reaction to an underlying inflammatory, infectious, or neoplastic condition
• some cases associated with Yersinia infection
• associated disorders
  • febrile upper respiratory tract infection
  • hematopoietic disorders (most common)
    • acute myeloid leukemia (AML)
    • myelodysplastic syndrome
    • transient myeloid proliferation
    • hairy-cell leukemia
    • chronic leukemias
    • multiple myeloma
  • other malignant tumors
    • breast cancer
    • gastrointestinal cancer
    • urogenital neoplasms
  • benign monoclonal gammopathy
  • ulcerative colitis
  • Behcet syndrome
  • relapsing polychondritis
  • rheumatoid arthritis
  • thyroid disease
• pharmaceutical agents
  • G-CSF, all trans retinoic acid, Bactrim, hydralazine, lithium carbonate, furosemide, minocycline, BCG vaccine
  • other vaccines ?
  • chemotherapy
• pregnancy (1st or 2nd trimester)

Epidemiology

• majority of patients are 30-60 years of age
• females > males
• rare disorder

Pathology

• epidermis generally normal, but may show subcorneal pustulation
• massive edema of papillary dermis
• dense leukocytic infiltrate of lower dermis
  • diffuse or perivascular
  • neutrophils with occasional eosinophils &/or lymphocytes
  • leukocytoclasia leading to nuclear dust
• may be neutrophilic infiltrates in subcutaneous tissues
  • perivascular & interstitial lymphohistiocytic & neutrophilic infiltration

Clinical manifestations

• prodome 1-3 weeks prior to skin lesions
  • febrile upper respiratory tract infection
  • diarrhea
  • tonsillitis
  • flu-like syndrome
• systemic manifestations may precede skin lesions
  • fever
  • headache
  • arthralgia, myalgia
  • malaise
• skin lesions
  • papules or nodules that coalesce to form irregular, sharply demarcated inflammatory plaques
  • intense edema gives the appearance of vesiculation
    • red to purple
    • semi-translucent appearance due to intense dermal edema
    • described in as 'juicy'
  • tiny pustules many or may not be present
  • bullous lesions may occur if associated with leukemia
  • lesions red or blueish red in color
  • lesions are tender or painful
  • central clearing may lead to annular appearance
  • single or multiple lesions distributed asymmetrically
  • lesions grow rapidly & may become blisters that burn or itch
  • lesions almost always present in setting of fever
  • distribution
    • most commonly:
      • face, neck, upper trunk & upper extremities
    • less commonly lower extremities
    • generalized form may occur
  • pathergy: development of lesions in areas of minor trauma
  • lesions heal without scarring
• lesions of the oral mucosa
• eye: conjunctivitis/episcleritis
• lungs: alveolitis
• bone: sterile osteomyelitis
• involvement of liver, mucsle, pancreas, cardiovascular system & CNS may occur

* images

Diagnostic criteria

• 2 major criteria & at least two of 4 minor criteria
• major criteria
  • abrupt onset of painful or tender erythematous plaques or nodules
  • histologic findings that reveal a dense neutrophilic infiltration in the dermis without leukocytoclastic vasculitis
• minor criteria
  • malaise and fever > 38 C
  • association with an underlying cancer, inflammatory disease, pregnancy, vaccine administration, or nonspecific infection
  • response to treatment with systemic glucocorticoids or 2nd-line agents such as dapsone, colchicine, or potassium iodide
  • 3 of the following abnormal laboratory values:
    • ESR> 20 mm per hour
    • elevated serum C-reactive protein
    • leukocytosis with WBC count > 8000/uL
    • neutrophil count > 70% on a peripheral-blood smear

Laboratory

• complete blood count (CBC)
  • neutrophilia
  • leukocytosis may be absent in patients with underlying hemotologic malignancy
• elevated erythrocyte sedimentation rate (ESR) & elevated serum C-reactive protein
• blood cultures to rule out sepsis
• skin biopsy

Differential diagnosis

• erythema multiforme
• erythema nodosum
• prevesicular Herpes simplex
• pyoderma gangrenosum
  • may occur in conjection with pyoderma gangrenosum
• bowel-bypass syndrome
• urticaria
• serum sickness
• SLE panniculitis
• other vasculitides

Management

• rule out sepsis
• prednisone
  • 30-60 mg PO QD
  • taper in 2-3 weeks
  • patients often note improvement after first dose
• dapsone 100 mg QD
• KI, colchicine, NSAIDs, clofazimine, pentoxifylline
• steroid-sparing agent for chronic or severe disease
  • cyclosporine
  • mycophenolate
  • TNF-alpha inhibitor
• antibiotic therapy for Yersinia infection
  • useless for other forms of Sweet's syndrome
• prognosis
  • untreated lesions evolve over a period of days to weeks & eventually resolve without scarring after weeks to months
  • lesions treated with prednisone resolve within a few days
  • recurrences occur in 50% of patients

More general terms

• neutrophilic dermatosis
• syndrome