ACUTE FEBRILE NEUTROPHILIC DERMATOSIS (SWEET’S SYNDROME)
Acute febrile neutrophilic dermatosis is an uncommon rash that most often is secondary to an underlying infection or malignancy. The diagnosis is made by fulfilling a constellation of criteria. Both clinical findings and pathology results are required to make the diagnosis in a patient with a consistent history.
Clinical Findings: Acute febrile neutrophilic dermatosis is often associated with a preceding infection. The infection can be located anywhere but most commonly is in the upper respiratory system. Females appear to be more likely to be afflicted, and there is no race predilection. Patients present with fever and the rapid onset of juicy papules and plaques. Because the papules can look as if they are fluid filled, they are given the descriptive term juicy papules. They can occur anywhere on the body and can be mistaken for a varicella infection. Patients also have neutrophilia and possibly arthritis and arthralgias. If this condition is associated with a preceding infection, it is usually self-limited and heals without scarring, unless the papules and plaques are excoriated or ulcerated by scratching. Variable amounts of pruritus and pain are associated with this skin disease. When one is evaluating a patient with this condition, a thorough history is required. A skin biopsy must be performed. A chest radiograph, throat culture, and urinalysis should be performed to assess for the possibility of bacterial infection.
Lymphoproliferative malignancies have also been seen in association with Sweet’s syndrome. The malignancy often precedes the rash, and the skin disease is believed to be a reaction to the underlying malignancy. It is important to obtain specimens from these patients for histological evaluation and culture for aerobic, anaerobic, mycobacterial, and fungal organisms. The main differential diagnosis is between an infection and Sweet’s syndrome in cases associated with a malignancy. The most common malignancy associated with acute febrile neutrophilic dermatosis is acute myelogenous leukemia. The prognosis in these cases is directly related to the underlying malignancy. Often, the skin disease continues to recur unless the malignancy is put into remission.
A few medications have also been shown to induce Sweet’s syndrome, including granulocyte colonystimulating factor (G-CSF), lithium, all-trans-retinoic acid, minocycline, and oral contraceptives.
Pathogenesis: The pathomechanism of Sweet’s syndrome is theorized to involve the secretion of a neutrophilic chemoattractant factor, which causes massive amounts of neutrophils to migrate into the skin. The exact molecule responsible for the recruitment of neutrophils into the skin is unknown. Reports of exogenous use of G-CSF have led to the theory that it is responsible for the chemoattraction of neutrophils. Other chemoattractants are possible players in the pathogenesis, including interleukin-8.
Histology: Histological examination shows massive dermal edema with a dense infiltrate composed entirely of neutrophils. Varying amounts of leukocytoclasis are present. Subepidermal bulla formation is possible because of the extensive dermal edema. Special stains for microorganisms must be negative to exclude an infectious process, and these must be backed up with cultures to help disprove an infection, because the histological picture can mimic an infectious process.
Treatment: Treatment should be directed at the causative agent. Supportive care is needed for those with postinfectious Sweet’s syndrome. Topical and oral steroids can dramatically shorten the course of the disease. Sweet’s syndrome that develops as a paraneoplastic process secondary to underlying leukemia should be treated with oral or intravenous steroids once an infectious process has been ruled out. This can result in a rapid response, but it is short lived once the steroids are removed. True remission occurs only if the cancer is treated and put into remission.