Acute Febrile Neutrophilic Dermatosis

Updated: Mar 31, 2016
  • Author: Yoon-Soo (Cindy) Bae, MD; Chief Editor: William D James, MD  more...
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Overview

Background

Acute febrile neutrophilic dermatosis, also termed Sweet syndrome, is a reactive process characterized by the abrupt onset of tender, red-to-purple papules, and nodules that coalesce to form plaques. The plaques usually occur on the upper extremities, face, or neck and are typically accompanied by fever and peripheral neutrophilia. [1]

Described in 1964 by Robert Sweet, the entity currently recognized as Sweet syndrome ranges from classic Sweet disease, which occurs in young women after a mild respiratory illness, to a more aggressive neutrophilic process, which may be associated with other inflammatory diseases or malignancy. [1, 2, 3] In fact, the lesions may be the first evidence of an underlying disorder and should prompt further investigation. A drug-induced variant due to the administration of various medications has been recognized, and a pregnancy-associated form has also been reported. [1, 4, 5, 6]

In general, Sweet syndrome responds dramatically to oral corticosteroids and may improve or resolve with treatment of the underlying condition. Without treatment, the syndrome may persist for weeks or months and then improves without leaving scars. Recurrences are common. In rare cases, crops of lesions reappear and the condition persists indefinitely. Cases associated with malignancy can be bullous or ulcerative and resemble atypical pyoderma gangrenosum. These lesions are often recalcitrant to treatment. [1, 7, 8, 9]

The diagnosis of Sweet syndrome is based on both clinical and histopathologic findings. Characteristics that distinguish the lesions of Sweet syndrome from other neutrophilic dermatosis are healing of the lesions without scarring and an absence of vasculitis. However, recent reports suggest that vasculitis should not exclude the diagnosis since it has been shown to occur in many patients with Sweet syndrome, which may represent an epiphenomenon instead of a primary immune-mediated process. [10]

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Pathophysiology

Acute febrile neutrophilic dermatosis (Sweet syndrome) is a reactive process (a hypersensitivity reaction) that occurs in response to systemic factors, such as hematologic disease, infection, inflammation, vaccination, or drug exposure. [11] The condition is neutrophil mediated, as evidenced by its histopathologic appearance, associated neutrophilia, and response to medications that affect neutrophil activity. [1]

The association of exogenous granulocyte colony-stimulating factors (G-CSF) with the development of Sweet syndrome also supports the importance of neutrophils and related endogenous cytokines in the underlying process. G-CSF suppresses apoptosis and prolongs the survival of neutrophils in vivo in a CD34+ cell population. G-CSF levels in peripheral blood are increased in patients with active Sweet syndrome, suggesting that high levels of G-CSF may one day be a useful indicator of activity level of the disease. The functional properties of neutrophils, rather than the absolute number, is thought to be significant because patients with Sweet syndrome due to G-CSF develop lesions as the neutrophil count rapidly increases, despite the absolute neutrophil count being low. [8, 12, 13] See the Absolute Neutrophil Count calculator.

In addition, some studies have suggested a role for tumor necrosis factor, and others have suggested an imbalance of type 1 helper T cells. Although the skin is the primary organ affected, other systems, most notably the lungs and kidneys, can also be involved. Other reactive neutrophilic disorders, such as neutrophilic eccrine hidradenitis, are closely related and may represent a spectrum with related pathogenesis. [9]

A possible genetic link with HLA-B54 has been observed in the Japanese population. A report of 2 brothers who developed Sweet syndrome in the neonatal period also supports a genetic predisposition. Structural alterations in the long arm of chromosome 3 (3q) have been seen in association with Sweet syndrome; these changes involve genes that affect the regulation of granulopoiesis and neutrophil migration. [14]

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Epidemiology

Frequency

Acute febrile neutrophilic dermatosis (Sweet syndrome) is uncommon but not rare. In several series, 10 -20% of cases have occurred in a setting of malignancy, though most are idiopathic or associated with benign conditions. [6, 7]

Race

Acute febrile neutrophilic dermatosis (Sweet syndrome) has no known racial predilection. [1]

Sex

The common reactive variant of acute febrile neutrophilic dermatosis (Sweet syndrome) does have a female predominance, with a female-to-male ratio of 15:1. [15] However, this predilection was not noted in series of cases associated with malignancy. [16] No sex predisposition has been observed in children. [17]

Age

Typically, women with acute febrile neutrophilic dermatosis (Sweet syndrome) are aged 30-50 years. [1] However, cases in neonates as young as 5 days have been described. [18] In children, Sweet syndrome is extremely rare and generally associated with infection. [17]

Sweet syndrome occurring in an infant should prompt a workup for immunodeficiency, as well as a review of the peripheral blood smear to rule out the rare case of malignancy.

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