Febrile Neutrophilic Dermatosis

Synonyms: This is also known as Sweet's syndrome after the dermatologist, Dr Robert Sweet (1917-2001) from Plymouth who described it in 1964.

The disease is characterized by sudden appearance of red tender plaques on the skin, usually on the limbs or neck but sometimes elsewhere.

It usually occurs in middle-aged women, but men, children and the elderly may also be affected. It is very uncommon but not rare. Women exceed men by 2 or 3:1 except in association with malignancy when it is equal. Women are typically 30 to 50 years old but men are typically 50 and older. In the limited number of cases seen in children, there is often disease of the immune system.¹

It appears to be a reaction to a number of possible triggering stimuli. They include:

• Upper respiratory tract infection, including bronchitis and streptococcal sore throat
• Vaccination
• Inflammatory bowel disease
• Rheumatoid arthritis and other inflammatory diseases
• Haematological malignancy, most often acute myelogenous leukaemia or myelodysplasia
• Malignancy of bowel, genitourinary tract or breast
• Pregnancy
• It may occur at the site of trauma of in areas exposed to the sun
• A number of drugs have been implicated, including granulocyte colony stimulating factor (G-CSF), and NSAIDs
• In many cases no cause is found

The patient is usually systemically unwell:

• Moderate to high fever that may occur with the skin lesions or precede them by days or even weeks.
• General malaise
• One or more tender red papules or plaques. They enlarge and persist for several weeks. They may have blisters, pustules or ulcers. Sometimes they appear to clear in the centre.
• Arthralgia and headache
• Conjunctivitis and episcleritis
• Ulcers on lips, buccal mucosa and tongue
• Sometimes other organs are affected including bones, nervous system, kidneys, intestines, liver, heart, lungs, muscles and spleen. There may be pulmonary infiltration causing cough and a shadow on CXR and lesions in the CNS may cause convulsions. These lesions are rare. It has been suggested that the CNS disease is a separate entity.²

There is a variant called "neutrophilic dermatosis of the dorsal hand", in which bluish or grey nodules like abscesses appear on the dorsum of the hands. These nodules may ulcerate. This is sometimes known as "pustular vasculitis" of the hands, because biopsy shows vasculitis with an infiltration of neutrophil white cells.

• Sweet's disease is related to pyoderma gangrenosum, and is sometimes difficult to distinguish from it.
• Behcet's disease
• Erythema nodosum
• Drug reactions

• White cell count is elevated with a neutrophil leukocytosis.
• ESR or C-reactive protein (CRP) is raised.
• Biopsy if often required for confirmation. Numerous neutrophil inflammatory cells are seen with fragmented neutrophils, called leukocytoclasia and swelling of the endothelial lining of blood vessels.

The presence of both major and 2 minor clinical findings have been proposed as criteria for diagnosis, as suggested by Su and Liu³ and revised by von den Driesch.⁴

Major criteria:

• Abrupt onset of tender or painful erythematous plaques or nodules, occasionally with vesicles, pustules, or bullae.
• Predominantly neutrophilic infiltration in the dermis without leukocytoclastic vasculitis.

Minor criteria:

• Preceding nonspecific respiratory or gastrointestinal tract infection or vaccination or associated with inflammatory disease, haemoproliferative disorders, solid malignant tumors, or pregnancy.
• Periods of general malaise and fever with body temperature above 38°C.
• Laboratory values during onset showing ESR greater than 20, positive C-reactive protein, segmented nuclear neutrophils, bands exceeding 70% in peripheral blood smears, and leukocytosis exceeding 8000/μL. At least 3 of these 4 values are necessary.
• Excellent response to treatment with systemic corticosteroids or potassium iodide.

Response to treatment is usually very swift although it will resolve without treatment:

• Prednisolone is given at 30 to 40mg daily and within a few days the fever, skin lesions and other symptoms resolve.
• Maintainance doses of steroids are often required for several weeks to a few months to prevent relapse.
• If steroids are ineffective or contraindicated, other treatments⁵ include:
  • Dapsone
  • Colchicine
  • NSAIDs
  • Potassium iodide
  • Biological response modifiers

The lesion may be the first indication of an underlying malignancy and if the disease is severe this should be considered seriously. Cases associated with malignancy are often bullous or ulcerative and resemble atypical pyoderma gangrenosum. These lesions are often resistant to treatment and recurrent. About 15 to 20% of cases are associated with malignancy.

With or without treatment there is usually complete resolution without any residual scar. There is usually a single episode but in about a third of cases it is recurrent. These tend to be associated with malignancy.