Sweet syndrome

Sweet syndrome was named after a Dr Sweet from Plymouth, England, who first described this condition in 1964. It is also known as acute febrile neutrophilic dermatosis, or simply Sweet's.

What are neutrophilic dermatoses?

Neutrophilic dermatoses are skin conditions characterised by dense infiltration of inflammatory cells (neutrophils) in the affected tissue. They arise in reaction to some underlying systemic illness. A neutrophilic dermatosis may be seen in isolation or more than one type may occur in the same individual.

Neutrophilic dermatoses often arise at the site of injury such as a needle prick, biopsy or insect bite. This reaction to injury is known as Koebner phenomenon, pathergy or isomorphic response.

Neutrophilic dermatoses include:

• Sweet syndrome (described below)
• Neutrophilic dermatosis of the dorsal hands
• Pyoderma gangrenosum
• Neutrophilic eccrine hidradenitis
• Erythema elevatum diutinum
• Behcet disease
• Bowel bypass syndrome (bowel-associated dermatitis-arthritis syndrome)

What are the symptoms of Sweet syndrome?

Sweet syndrome is an acute illness that may occur on a single occasion or may recur. It may affect previously healthy individuals, but often arises in the context of an acute systemic infection or an underlying chronic condition. Sweet syndrome most often occurs in middle-aged women, but men, children (rarely) and the elderly may also be affected.

Sweet syndrome is characterised by some or all of the following symptoms:

• High or moderate fever
• Tiredness and malaise (feeling unwell)
• Skin lesions
• Sore eyes and/or mouth ulcers
• Aching joints
• Headache
• Sometimes other organs are affected, including bones, nervous system, kidneys, intestines, liver, heart, lungs, muscles and spleen.

What do the skin lesions look like?

Skin lesions of Sweet syndrome may be few in number or numerous. They are characteristically tender and may be extremely painful. They persist for days to weeks. The limbs and neck are the most commonly affected sites, but other areas of skin and mucosa may be involved. In some patients, they arise only in sun exposed areas. Sweet syndrome lesions may have a range of appearances.

• Small papules (bumps) or vesicles (blisters)
• Larger thickened or swollen plaques (flat patches)
• Pseudovesicular appearance (almost blistered)
• Annular (ring-shaped) lesions
• Erosions and ulcers resembling atypical pyoderma gangrenosum

Sweet syndrome

Subcutaneous Sweet syndrome

In subcutaneous Sweet syndrome, deeper, painful plaques develop on any area of skin. These may resemble cellulitis.

Neutrophilic dermatosis of hands

Neutrophilic dermatosis of the hands is considered a localised variant of Sweet syndrome in which there are purplish nodules on the backs of the thumb, fingers and hand, or less often, on palmar surfaces.

Mucosal lesions

Sweet syndrome often causes erosions or ulcers inside the mouth, on the tongue or on the lips.

Ocular Sweet syndrome may cause a sore, red, sticky eye and can lead to ulceration and loss of vision due to conjunctivitis, dacryoadenitis, keratitis, episleritis, scleritis, iritis, uveitis, glaucoma and choroiditis.

Sweet syndrome affecting mucosal surfaces

What causes Sweet syndrome?

Sweet syndrome develops in reaction to some internal condition, in previous well or unwell individuals. It has been found to be more common in individuals carrying the genetic marker HLA B54. Sweet syndrome may follow:

• Upper respiratory tract infection (e.g. chest infection, streptococcal throat infection)
• Vaccination
• Inflammatory bowel disease (e.g. ulcerative colitis or Crohn disease)
• Rheumatoid arthritis , lupus erythematosus and relapsing polychondritis
• Blood disorders including leukaemia (most often acute myelogenous leukaemia or myelodysplastic syndromes).
• Internal cancer usually of bowel, genitourinary organ or breast
• Pregnancy
• Drugs, including granulocyte colony stimulating factor (G-CSF), nonsteroidal anti-inflammatory medications, cotrimoxasole and other antibiotics, carbamazepine and several others
• Immunodeficiency

In many people with Sweet syndrome, no underlying condition is found.

How is the diagnosis made?

Sweet syndrome may be diagnosed clinically, but at times it may be difficult to distinguish from infections such as chickenpox, or inflammatory conditions such as vasculitis. The diagnosis of Sweet syndrome is usually confirmed on skin biopsy.

Diagnostic histopathological features of Sweet syndrome are numerous polynuclear neutrophil inflammatory cells on skin biopsy associated with broken-up neutrophils (leukocytoclasia) and swelling of cells lining blood vessels (endothelial cells). However other inflammatory patterns may be observed, e.g. mononuclear histiocyte cells rather than polynuclear neutrophil cells despite otherwise typical symptoms and signs of Sweet syndrome. True vasculitis may occur in severe cases.

Blood tests in patients with Sweet syndrome may reveal:

• Raised erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), indicating systemic inflammatory disease
• Raised white cell count (neutrophil leukocytosis)
• p-ANCA (antineutrophil cytoplasmic antibody) or c-ANCA is sometimes present

Occasionally Sweet syndrome is the presenting sign of a serious blood condition. A full blood count may reveal raised or reduced numbers of red cells, white cells and/or platelets. Further investigation may require bone marrow examination.

What is the outcome of Sweet syndrome?

Sweets' lesions resolve eventually without leaving a mark or scar, with or without treatment.

Generally there is a single episode of Sweet syndrome, but a third of patients may develop recurrent episodes. This is more likely in patients who have underlying myelodysplasia or cancer.

Severe ulcerative cases associated with malignancy persist, despite treatment.

Treatment of Sweet syndrome

Treatment of Sweet syndrome usually results in rapid improvement in symptoms. Usually, systemic steroids, such as predniso(lo)ne, are prescribed in a dose of 30-40 mg daily. Within a few days the fever, skin lesions and other symptoms clear up. However, lower doses of steroids are often required for several weeks to months to prevent relapse.

Several other medications may be tried when steroids are ineffective or contraindicated. These include:

In some cases, Sweet syndrome is very resistant to treatment.